A 22-year-old student was brought in to a college student health center in a wheelchair by campus safety personnel. She appeared drowsy and was crying softly. She complained of a severe headache and said she was “tired of going through this all the time.” The woman said she had seen spots and become dizzy, then had gotten “the worst headache of my life” while sitting in class. She rated the headache pain at 8 on a 10-point scale and also complained of nausea and photophobia.

The history revealed dizziness that made her “feel as if I’m tipping over” and similar headaches during the previous year. The patient said she had seen “a few doctors” for her symptoms, but that they “could never find anything.” The headaches usually occurred on the left side of her head, lasted hours to days, and were only partially relieved with acetaminophen. The patient could not remember whether she had eaten breakfast and was unsure of what day it was. She described herself as frustrated and began to weep again.

She was currently under the care of a psychologist but seemed uncertain why; she said that she was sexually active and used condoms. She had undergone an appendectomy at age 12. She denied taking any medications besides acetaminophen. She denied smoking or drug use, history of migraine headaches, vision or hearing changes, facial weakness, depression, or anxiety. Her family history included a grandfather with diabetes and hypertension and an uncle with heart disease. The family history was negative for migraine or psychiatric illness.

Because of the patient’s weakness, she was assisted onto the examination table by a nurse. Physical exam revealed a pale, slightly sweaty, overweight, tearful young woman who was slow to respond. Her blood pressure was measured at 134/104 mm Hg; pulse, 100 beats/min; respirations, 14 breaths/min; and temperature, 97.0ºF. Point-of-care testing of blood glucose was 91 mg/dL, and hemoglobin was measured at 12.3 g/dL. The ophthalmologic exam was positive for photophobia and revealed slightly disconjugate gaze with horizontal nystagmus during testing of cranial nerves (CN) III, IV, and VI. The otoscopic exam revealed a slightly injected right tympanic membrane, and there were no apparent hearing deficits.

The neurologic exam showed patellar and brachial deep tendon reflexes equal, grips weak and equal, and the pupillary response intact. The patient was able to stand without assistance, although her gait was slightly unsteady. Because the patient was of college age, the clinician ruled out meningitis by negative Kernig’s and Brudzinski’s signs and absence of fever. Subarachnoid hemorrhage was also a concern when the patient mentioned the “worst headache of my life,” indicating the need for emergent imaging.

The patient’s presentation, it was felt, warranted a 911 call. The emergency medical team arrived, and its members began to question the patient. Discrepancies in the patient’s history during the paramedics’ reexamination led them to question whether an emergency department (ED) visit was necessary, but at the clinician’s insistence, they agreed to transport the student to the ED.

The following day, the student health center clinician was contacted by a member of the hospital ED staff with an update on the patient’s status. Shortly after her arrival at the hospital, she underwent MRI and was diagnosed with a vestibular schwannoma. She had surgery that same evening, during which the surgeon removed most of the tumor. Although the ED staff was not at liberty to provide more complete information, they did inform the clinician that the patient would require radiation for the remainder of the tumor.

DISCUSSION
Vestibular schwannoma is also known as acoustic schwannoma, acoustic neuroma, acoustic neurinoma, or vestibular neurilemmoma. These tumors arise from perineural elements of Schwann cells, which commonly form and lead to myelination in the vestibular area of CN VIII¹ (see figure). They occur with equal frequency on the superior and inferior branches of the vestibular nerve and originate only rarely at the cochlear portion of the eighth cranial nerve. Vestibular schwannomas represent approximately 8% to 10% of brain tumors and 80% to 90% of tumors in the cere­bellopontine angle in adults.² Tumors are distributed evenly across genders, but the majority of diagnosed patients are white.³

Most likely because of improvements in diagnostic technology, the incidence of vestibular schwannoma has increased over the past 30 years. One British research team predicts that one in 1,000 persons will receive a diagnosis of vestibular schwannoma in their lifetime.⁴ These tumors are most commonly diagnosed in people ages 30 to 60, with a median age of 55.⁵

A relationship has been demonstrated between neurofibromatosis type 2 (NF2), an autosomal-dominant disease, and the development of vestibular schwannomas.^6,7 NF2 has a birth prevalence of one in about 25,000 persons,^4,8 and those who inherit the responsible gene inevitably develop vestibular schwannomas.⁹ Patients with a confirmed diagnosis of vestibular schwannoma should be screened by a geneticist for the NF2 gene; although the tumors are benign, they can cause compression of the vestibular nerve, leading to deafness and balance disorders.¹⁰ Schwannomas of the spinal nerves can also occur in persons with NF2.¹¹ Compression of the spinal nerves in these patients can lead to significant morbidity and a shortened average life span.¹⁰

NF2 is diagnosed using the following criteria:

1) Bilateral vestibular schwan­nomas

2) Diagnosis of a family member with either NF2 or unilateral vestibular schwannoma, and

3) Juvenile posterior subscapular lens opacities.^9,12,13

Because schwannomas grow slowly, the vestibular system can adapt to the slow destruction of CN VIII. For this reason, patients typically present with unilateral deafness or hearing impairment rather than dizziness.¹¹ Many patients also present with tinnitus and/or vertigo.^14,15

Some vestibular tumors remain stable or even regress; others progress, in some cases causing life-threatening complications.¹⁶ An extremely rare complication of a vestibular schwannoma was reported in one patient: an intratumoral hemorrhage that led to acute neurologic deterioration and death.¹⁷

Since the case patient underwent immediate surgical intervention, it appears she was experiencing significant involvement and it was likely anticipated that without surgical intervention, clinical progression would occur. Her young age could be considered a risk factor for a faster-growing neuroma.¹⁸

Clinical Presentation and Diagnosis
Primary care clinicians commonly see patients with complaints of dizziness, lightheadedness, faintness, or a sensation of spinning or tilting. Vestibular schwannoma should be considered in the differential diagnosis of the patient who presents with these complaints, as well as tinnitus or hearing loss.⁹ The patient with vestibular schwannoma may also have a history of headache, unsteady gait, facial pain, and numbness.¹⁹ A partial differential diagnosis is listed in the table^20,21). The astute clinician will systematically rule out many of these conditions, since certain other features that may be present (eg, rapid onset, vomiting, fever) do not typically occur in the patient with vestibular schwannoma.

Because the symptoms typically associated with vestibular schwannoma are likely to occur bilaterally in patients with other conditions, unilateral symptoms should alert the clinician to investigate further. The patterns and growth rates of vestibular schwannomas are highly variable and currently unpredictable¹⁸ (according to Fortnum et al,¹⁴ at least 50% of tumors do not grow within several years after diagnosis); thus, no clear predictors of tumor growth have been identified to assist in the evaluation of an affected patient,¹⁶ although faster tumor growth rates have been reported in young patients, and Baser et al¹⁸ have called for additional research involving younger persons with vestibular schwannomas.

Standard testing is audiometry followed by MRI, which is considered the most effective means to confirm a diagnosis of vestibular schwannoma.^5,14,22

Treatment for Vestibular Schwannoma
Treatment, whether with surgery or radiation, is associated with significant morbidity and possibly decreased quality of life.¹⁶ Therefore, distinguishing patients whose tumors will grow and pose a threat to them from those whose tumors are likely to remain stable is central to appropriate management.²³

Treatment modalities are considered based on tumor size, growth, presence or absence of tinnitus, and the patient’s preferences and life expectancy.²³ In most cases, decision making is complex and should be customized to meet the patient’s individual circumstances. Patients with similar clinical scenarios have been reported to opt for different treatment choices.²⁴

Four treatment options are currently available for patients with vestibular schwannoma:

Serial observation with periodic MRI studies. Since vestibular schwannomas are benign and slow-growing, conservative manage­ment can be a reasonable option, particularly if the patient is elderly, the tumor is small, and/or little hearing loss has taken place. However, use of observation is associated with a risk for progressive and permanent hearing loss.² Between 15% and 50% of patients who opt for serial observation will undergo subsequent surgical intervention, particularly in cases involving worsening tinnitus, balance problems, or hearing loss.^23-25

Chemotherapy. Agents including bevacizumab (a humanized monoclonal antibody against vascular endothelial growth factor)^8,26,27 and erlotinib (an epidermal growth factor receptor inhibitor) may delay progression or even facilitate regression of vestibular schwannomas.²⁸ Hearing improvement has also been reported in patients with NF2 who were treated with bevacizumab⁸; research is ongoing.²⁶

Fractionated radiotherapy. Hearing may be preserved in 60% to 95% of patients, depending on levels of dosing to the cochlea, but 3% to 7% of patients will need further treatment.^29-31 Radiation treatment is a likely choice in patients with tumors measuring 2.0 cm or less. Larger tumors are considered a surgical disease, and directed radiotherapy may be administered postoperatively (as in the case patient) for residual portions of the tumor.¹⁶

Microsurgery. Compared with other treatment modalities, the emphasis of microsurgery is on removing tumors (particularly larger tumors) rather than controlling their growth.²⁹ The three common approaches are retrosigmoid, middle fossa, or translabyrinthine.^32-34 Preservation of hearing is reportedly better following retrosigmoid or middle fossa microsurgery, compared with a translabyrinthine procedure (because in the latter, the tumor cannot be exposed without damage to the inner ear).^32,35

With any such surgery, risks include cranial nerve damage, leakage of cerebrospinal fluid, and infection.^29,32 Postsurgically, about half of patients report frequent headaches, which are persistent in about half of these cases.^36-38 Another concern is preservation of the facial nerves, with a risk for temporary facial weakness or dysfunction.^3,24,39 Less than 2% of patients who undergo microsurgery require additional treatment.²⁹

Stereotactic radiosurgery. These procedures, which are performed using the Gamma Knife,^® the CyberKnife, or the linear accelerator,^29,40,41 are considered appropriate for patients with smaller tumors and those who are not candidates for conventional surgery.¹ Trigeminal neuropathy, injury to the facial nerves, and hydrocephaly are reported complications of Gamma Knife radiosurgery, but improvements in these technologies are ongoing.^1,2,40

Patient Outcomes
The outcome in a patient with vestibular schwannoma depends on the treatment administered, but prolonged follow-up is typically necessary. For patients being managed through observation, annual brain scans are recommended for 10 years, with subsequent scans every three to five years if no tumor growth is seen. For patients who have had surgery, annual brain scans are advised for the successive eight to 10 years, with decreasing frequency if no tumor remains. In patients who undergo radiation, annual scans are recommended for 10 years, then every two years if no tumor growth is detected.³⁶

Psychosocial experiences vary widely among patients who have undergone treatment for vestibular schwannomas. Some are unable to perform necessary or recreational activities, and others must retire early from work.⁴² Others, however, have minimal disruption in their lives and enjoy a good quality of life. The most difficult consequence of vestibular schwannoma and its treatment, according to patients, is the associated hearing loss.^8,19

THE CASE PATIENT
The 22-year-old patient in this case had an atypical presentation of vestibular schwannoma. Although she did present with vertigo, she also complained of headache, nausea, and photophobia—which are rarely reported in investigations of these tumors. She was also younger than the typical patient and did not report tinnitus.

The case patient reportedly underwent surgery and subsequent radiation to treat the remaining portion of her tumor. She suspended her attendance at the college and, as of this writing, has not re-enrolled. She was lost to follow-up.

CONCLUSION
For the primary care provider, diagnostic challenges require great clinical acumen. Vertigo, headache, hearing loss, and tinnitus are all symptoms seen in the primary care setting; when they occur together, the clinician should be alerted to investigate further. A high level of suspicion is appropriate when a patient complains of longstanding auditory symptoms, with or without headache. Unilateral hearing loss is a common symptom in patients with vestibular schwannomas, although some may present with facial weakness or pain, imbalance, and/or vertigo.

In addition to the history and physical exam, experts recommend that audiometry and MRI be considered, particularly if hearing loss is unilateral. Genetic screening for NF2 should be performed if vestibular schwannoma is found on MRI. Referral to a neurologist, a neurosurgeon, or an otolaryngologist is appropriate.

REFERENCES
1. Arthurs BJ, Lamoreaux WT, Giddings NA, et al. Gamma Knife radiosurgery for vestibular schwannoma: case report and review of the literature. World J Surg Oncol. 2009 Dec 18;7:100.

2. Mohammed TA, Ahuja MS, Ju SS, Thomas J. Normal pressure hydrocephalus after Gamma Knife radiosurgery for vestibular schwannoma. J Postgrad Med. 2010;56(3):213-215.

3. Gal TJ, Shinn J, Huang B. Current epidemiology and management trends in acoustic neuroma. Otolaryngol Head Neck Surg. 2010;142(5):677-681.

4. Evans DG, Moran A, King A, et al. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol. 2005;26(1):93-97.

5. Haynes D. Acoustic neuroma diagnosis and treatment options. Hearing Health. 2009;25(3):32. www.drf.org/magazine/36/Summer+2009+Issue/article/272. Accessed May 16, 2011.

6. Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol. 1993;52(2):106-113.

7. Evans DG, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med. 1992;84(304):603-618.

8. Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361(4):358-367.

9. Evans DGR, Sainio M, Baser E. Neurofibromatosis type 2. J Med Genet. 2000:37(11):897-904.

10. Gusella JF, Ramesh V, MacCollin M, Jacoby LB. Neurofibromatosis 2: loss of Merlin’s protective spell. Curr Opin Genet Dev. 1996;6(1):87-92.

11. Sagar SM, Israel MA. Ch 374. Primary and metastatic tumors of the nervous system. In: Kasper DL, Braunwald E, Fauci AS, et al. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill Companies, Inc; 2008:2601-2610.

12. Evans DGR. Neurofibromatosis 2 [bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med. 2009;11(9):599-610.

13. Arya R, Sahu JK, Kabra M. Neurofibromatosis type II (Wishart type). J Pediatr Neurol. 2009;7(3): 333-335.

14. Fortnum H, O’Neill C, Taylor R, et al. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and cost effectiveness and natural history. Health Technol Assess. 2009;13(18):iii-iv, ix-xi, 1-154.

15. Forton GE, Cremers CW, Offeciers EE. Acoustic neuroma ingrowth in the cochlear nerve: does it influence the clinical presentation? Ann Otol Rhinol Laryngol. 2004;113(7):582-586.

16. Nikolopoulos TP, Fortnum H, O’Donoghue G, Baguley D. Acoustic neuroma growth: a systematic review of the evidence. Otol Neurotol. 2010;31(3):478-485.

17. Yates CW, Weinberg M, Packer MJ, Jacob A. Fatal case of tumor-associated hemorrhage in a large vestibular schwannoma. Ann Otol Rhinol Laryngol. 2010;119(6):402-405.

18. Baser ME, Mautner VF, Parry DM, Evans DGR. Methodological issues in longitudinal studies; vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet. 2005;42(12):903-906.

19. Brooker J, Burney S, Fletcher J, Dally M. A qualitative exploration of quality of life among individuals diagnosed with an acoustic neuroma. Br J Health Psychol. 2009;14(pt 3):563-578.

20. Strupp M, Brandt T. Diagnosis and treatment of vertigo and dizziness. Dtsch Arzetbl Int. 2008;105(10):173-180.

21. Kerber KA. Dizziness and vertigo. In: Andreoli TE, Griggs RC, Benjamin I , Wing EJ, eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 8th ed. Philadelphia, PA: Elsevier Inc; 2010:1104-1105.

22. Gimsing S. Vestibular schwannoma: when to look for it? J Laryngol Otol. 2010;124(3):258-264.

23. Agrawal Y, Clark JH, Limb CJ, et al. Predictors of vestibular schwannoma growth and clinical implications. Otol Neurotol. 2010;31(5):807-812.

24. Cheung SW, Aranda D, Driscoll CLW, Parsa AT. Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management. Otol Neurotol. 2010;31(2):284-293.

25. Myrseth E, Pedersen PH, Møller P, Lund-Johansen M. Treatment of vestibular schwannomas: why, when and how? Acta Neurochir (Wien). 2007;149(7):647-660.

26. Sidney Kimmel Comprehensive Cancer Center, Massachusetts General Hospital, National Cancer Institute. Bevacizumab for symptomatic vestibular schwannoma in neurofibromatosis type 2 (NF2). http://clinicaltrials.gov/ct2/show/NCT01207687. Accessed May 16, 2011.

27. Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12(1):14-18.

28. Plotkin SR, Halpin C, McKenna MJ, et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010;31(7):1135-1143.

29. Arthurs BJ, Fairbanks RK, Demakas JJ, et al. A review of treatment modalities for vestibular schwannoma. Neurosurg Rev. 2011 Feb 9; [Epub ahead of print].

30. Andrews DW, Werner-Wasik M, Den RB, et al. Toward dose optimization for fractionated stereotactic radiotherapy for acoustic neuromas: comparison of two dose cohorts. Int J Radiat Oncol Biol Phys. 2009;74(2):419-426.

31. Thomas C, Di Maio S, Ma R, et al. Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose. J Neurosurg. 2007;107(5):917-926.

32. Samii M, Gerganov V, Samii A. Improved preservation of hearing and facial nerve function in vestibular schwannoma surgery via the retrosigmoid approach in a series of 200 patients. J Neuro­surg. 2006;105(4):527-535.

33. Shiobara R, Ohira T, Inoue Y, et al. Extended middle cranial fossa approach for vestibular schwannoma: technical note and surgical results of 896 operations. Prog Neurol Surg. 2008;21:65-72.

34. Schmerber S, Palombi O, Boubagra K, et al. Long-term control of vestibular schwannoma after a translabyrinthine complete removal. Neurosurgery. 2005;57(4):693-698.

35. Phillips DJ, Kobylarz EJ, De Peralta ET, et al. Predictive factors of hearing preservation after surgical resection of small vestibular schwannomas. Otol Neurotol. 2010;31(9):1463-1468.

36. Park JK, Black MP, Vernick DM, Ramakrishna N. Vestibular schwannoma (acoustic neuroma) (2010). www.uptodate.com/contents/vestibular-schwannoma-acoustic-neuroma. Accessed May 16, 2011.

37. Schankin CJ, Gall C, Straube A. Headache syndromes after acoustic neuroma surgery and their implications for quality of life. Cephalalgia. 2009;29(7):760-761.

38. Ryzenman JM, Pensak ML, Tew JM Jr. Headache: a quality of life analysis in a cohort of 1,657 patients undergoing acoustic neuroma surgery: results from the Acoustic Neuroma Association. Laryngoscope. 2005;115(4):703-711.

39. Sriskandan N, Connor SE. The role of radiology in the diagnosis and management of vestibular schwannoma. Clin Radiol. 2010;66(4):357-365.

40. Yang I, Sughrue ME, Han SJ, et al. Facial nerve preservation after vestibular schwannoma Gamma Knife surgery. J Neurooncol. 2009;93(1): 41-48.

41. Unger F, Dominikus K, Haselsberger K. Stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neuromas [in German]. HNO. 2011;59(1):31-37.

42. Tos T, Caye-Thomasen P, Stangerup SE, et al. Long-term socio-economic impact of vestibular schwannoma for patients under observation and after surgery. J Laryngol Otol. 2003;117(12):955-964.

A 22-year-old student was brought in to a college student health center in a wheelchair by campus safety personnel. She appeared drowsy and was crying softly. She complained of a severe headache and said she was “tired of going through this all the time.” The woman said she had seen spots and become dizzy, then had gotten “the worst headache of my life” while sitting in class. She rated the headache pain at 8 on a 10-point scale and also complained of nausea and photophobia.

The history revealed dizziness that made her “feel as if I’m tipping over” and similar headaches during the previous year. The patient said she had seen “a few doctors” for her symptoms, but that they “could never find anything.” The headaches usually occurred on the left side of her head, lasted hours to days, and were only partially relieved with acetaminophen. The patient could not remember whether she had eaten breakfast and was unsure of what day it was. She described herself as frustrated and began to weep again.

She was currently under the care of a psychologist but seemed uncertain why; she said that she was sexually active and used condoms. She had undergone an appendectomy at age 12. She denied taking any medications besides acetaminophen. She denied smoking or drug use, history of migraine headaches, vision or hearing changes, facial weakness, depression, or anxiety. Her family history included a grandfather with diabetes and hypertension and an uncle with heart disease. The family history was negative for migraine or psychiatric illness.

Because of the patient’s weakness, she was assisted onto the examination table by a nurse. Physical exam revealed a pale, slightly sweaty, overweight, tearful young woman who was slow to respond. Her blood pressure was measured at 134/104 mm Hg; pulse, 100 beats/min; respirations, 14 breaths/min; and temperature, 97.0ºF. Point-of-care testing of blood glucose was 91 mg/dL, and hemoglobin was measured at 12.3 g/dL. The ophthalmologic exam was positive for photophobia and revealed slightly disconjugate gaze with horizontal nystagmus during testing of cranial nerves (CN) III, IV, and VI. The otoscopic exam revealed a slightly injected right tympanic membrane, and there were no apparent hearing deficits.

The neurologic exam showed patellar and brachial deep tendon reflexes equal, grips weak and equal, and the pupillary response intact. The patient was able to stand without assistance, although her gait was slightly unsteady. Because the patient was of college age, the clinician ruled out meningitis by negative Kernig’s and Brudzinski’s signs and absence of fever. Subarachnoid hemorrhage was also a concern when the patient mentioned the “worst headache of my life,” indicating the need for emergent imaging.

The patient’s presentation, it was felt, warranted a 911 call. The emergency medical team arrived, and its members began to question the patient. Discrepancies in the patient’s history during the paramedics’ reexamination led them to question whether an emergency department (ED) visit was necessary, but at the clinician’s insistence, they agreed to transport the student to the ED.

The following day, the student health center clinician was contacted by a member of the hospital ED staff with an update on the patient’s status. Shortly after her arrival at the hospital, she underwent MRI and was diagnosed with a vestibular schwannoma. She had surgery that same evening, during which the surgeon removed most of the tumor. Although the ED staff was not at liberty to provide more complete information, they did inform the clinician that the patient would require radiation for the remainder of the tumor.

DISCUSSION
Vestibular schwannoma is also known as acoustic schwannoma, acoustic neuroma, acoustic neurinoma, or vestibular neurilemmoma. These tumors arise from perineural elements of Schwann cells, which commonly form and lead to myelination in the vestibular area of CN VIII¹ (see figure). They occur with equal frequency on the superior and inferior branches of the vestibular nerve and originate only rarely at the cochlear portion of the eighth cranial nerve. Vestibular schwannomas represent approximately 8% to 10% of brain tumors and 80% to 90% of tumors in the cere­bellopontine angle in adults.² Tumors are distributed evenly across genders, but the majority of diagnosed patients are white.³

Most likely because of improvements in diagnostic technology, the incidence of vestibular schwannoma has increased over the past 30 years. One British research team predicts that one in 1,000 persons will receive a diagnosis of vestibular schwannoma in their lifetime.⁴ These tumors are most commonly diagnosed in people ages 30 to 60, with a median age of 55.⁵

A relationship has been demonstrated between neurofibromatosis type 2 (NF2), an autosomal-dominant disease, and the development of vestibular schwannomas.^6,7 NF2 has a birth prevalence of one in about 25,000 persons,^4,8 and those who inherit the responsible gene inevitably develop vestibular schwannomas.⁹ Patients with a confirmed diagnosis of vestibular schwannoma should be screened by a geneticist for the NF2 gene; although the tumors are benign, they can cause compression of the vestibular nerve, leading to deafness and balance disorders.¹⁰ Schwannomas of the spinal nerves can also occur in persons with NF2.¹¹ Compression of the spinal nerves in these patients can lead to significant morbidity and a shortened average life span.¹⁰

NF2 is diagnosed using the following criteria:

1) Bilateral vestibular schwan­nomas

2) Diagnosis of a family member with either NF2 or unilateral vestibular schwannoma, and

3) Juvenile posterior subscapular lens opacities.^9,12,13

Because schwannomas grow slowly, the vestibular system can adapt to the slow destruction of CN VIII. For this reason, patients typically present with unilateral deafness or hearing impairment rather than dizziness.¹¹ Many patients also present with tinnitus and/or vertigo.^14,15

Some vestibular tumors remain stable or even regress; others progress, in some cases causing life-threatening complications.¹⁶ An extremely rare complication of a vestibular schwannoma was reported in one patient: an intratumoral hemorrhage that led to acute neurologic deterioration and death.¹⁷

Since the case patient underwent immediate surgical intervention, it appears she was experiencing significant involvement and it was likely anticipated that without surgical intervention, clinical progression would occur. Her young age could be considered a risk factor for a faster-growing neuroma.¹⁸

Clinical Presentation and Diagnosis
Primary care clinicians commonly see patients with complaints of dizziness, lightheadedness, faintness, or a sensation of spinning or tilting. Vestibular schwannoma should be considered in the differential diagnosis of the patient who presents with these complaints, as well as tinnitus or hearing loss.⁹ The patient with vestibular schwannoma may also have a history of headache, unsteady gait, facial pain, and numbness.¹⁹ A partial differential diagnosis is listed in the table^20,21). The astute clinician will systematically rule out many of these conditions, since certain other features that may be present (eg, rapid onset, vomiting, fever) do not typically occur in the patient with vestibular schwannoma.

Because the symptoms typically associated with vestibular schwannoma are likely to occur bilaterally in patients with other conditions, unilateral symptoms should alert the clinician to investigate further. The patterns and growth rates of vestibular schwannomas are highly variable and currently unpredictable¹⁸ (according to Fortnum et al,¹⁴ at least 50% of tumors do not grow within several years after diagnosis); thus, no clear predictors of tumor growth have been identified to assist in the evaluation of an affected patient,¹⁶ although faster tumor growth rates have been reported in young patients, and Baser et al¹⁸ have called for additional research involving younger persons with vestibular schwannomas.

Standard testing is audiometry followed by MRI, which is considered the most effective means to confirm a diagnosis of vestibular schwannoma.^5,14,22

Treatment for Vestibular Schwannoma
Treatment, whether with surgery or radiation, is associated with significant morbidity and possibly decreased quality of life.¹⁶ Therefore, distinguishing patients whose tumors will grow and pose a threat to them from those whose tumors are likely to remain stable is central to appropriate management.²³

Treatment modalities are considered based on tumor size, growth, presence or absence of tinnitus, and the patient’s preferences and life expectancy.²³ In most cases, decision making is complex and should be customized to meet the patient’s individual circumstances. Patients with similar clinical scenarios have been reported to opt for different treatment choices.²⁴

Four treatment options are currently available for patients with vestibular schwannoma:

Serial observation with periodic MRI studies. Since vestibular schwannomas are benign and slow-growing, conservative manage­ment can be a reasonable option, particularly if the patient is elderly, the tumor is small, and/or little hearing loss has taken place. However, use of observation is associated with a risk for progressive and permanent hearing loss.² Between 15% and 50% of patients who opt for serial observation will undergo subsequent surgical intervention, particularly in cases involving worsening tinnitus, balance problems, or hearing loss.^23-25

Chemotherapy. Agents including bevacizumab (a humanized monoclonal antibody against vascular endothelial growth factor)^8,26,27 and erlotinib (an epidermal growth factor receptor inhibitor) may delay progression or even facilitate regression of vestibular schwannomas.²⁸ Hearing improvement has also been reported in patients with NF2 who were treated with bevacizumab⁸; research is ongoing.²⁶

Fractionated radiotherapy. Hearing may be preserved in 60% to 95% of patients, depending on levels of dosing to the cochlea, but 3% to 7% of patients will need further treatment.^29-31 Radiation treatment is a likely choice in patients with tumors measuring 2.0 cm or less. Larger tumors are considered a surgical disease, and directed radiotherapy may be administered postoperatively (as in the case patient) for residual portions of the tumor.¹⁶

Microsurgery. Compared with other treatment modalities, the emphasis of microsurgery is on removing tumors (particularly larger tumors) rather than controlling their growth.²⁹ The three common approaches are retrosigmoid, middle fossa, or translabyrinthine.^32-34 Preservation of hearing is reportedly better following retrosigmoid or middle fossa microsurgery, compared with a translabyrinthine procedure (because in the latter, the tumor cannot be exposed without damage to the inner ear).^32,35

With any such surgery, risks include cranial nerve damage, leakage of cerebrospinal fluid, and infection.^29,32 Postsurgically, about half of patients report frequent headaches, which are persistent in about half of these cases.^36-38 Another concern is preservation of the facial nerves, with a risk for temporary facial weakness or dysfunction.^3,24,39 Less than 2% of patients who undergo microsurgery require additional treatment.²⁹

Stereotactic radiosurgery. These procedures, which are performed using the Gamma Knife,^® the CyberKnife, or the linear accelerator,^29,40,41 are considered appropriate for patients with smaller tumors and those who are not candidates for conventional surgery.¹ Trigeminal neuropathy, injury to the facial nerves, and hydrocephaly are reported complications of Gamma Knife radiosurgery, but improvements in these technologies are ongoing.^1,2,40

Patient Outcomes
The outcome in a patient with vestibular schwannoma depends on the treatment administered, but prolonged follow-up is typically necessary. For patients being managed through observation, annual brain scans are recommended for 10 years, with subsequent scans every three to five years if no tumor growth is seen. For patients who have had surgery, annual brain scans are advised for the successive eight to 10 years, with decreasing frequency if no tumor remains. In patients who undergo radiation, annual scans are recommended for 10 years, then every two years if no tumor growth is detected.³⁶

Psychosocial experiences vary widely among patients who have undergone treatment for vestibular schwannomas. Some are unable to perform necessary or recreational activities, and others must retire early from work.⁴² Others, however, have minimal disruption in their lives and enjoy a good quality of life. The most difficult consequence of vestibular schwannoma and its treatment, according to patients, is the associated hearing loss.^8,19

THE CASE PATIENT
The 22-year-old patient in this case had an atypical presentation of vestibular schwannoma. Although she did present with vertigo, she also complained of headache, nausea, and photophobia—which are rarely reported in investigations of these tumors. She was also younger than the typical patient and did not report tinnitus.

The case patient reportedly underwent surgery and subsequent radiation to treat the remaining portion of her tumor. She suspended her attendance at the college and, as of this writing, has not re-enrolled. She was lost to follow-up.

CONCLUSION
For the primary care provider, diagnostic challenges require great clinical acumen. Vertigo, headache, hearing loss, and tinnitus are all symptoms seen in the primary care setting; when they occur together, the clinician should be alerted to investigate further. A high level of suspicion is appropriate when a patient complains of longstanding auditory symptoms, with or without headache. Unilateral hearing loss is a common symptom in patients with vestibular schwannomas, although some may present with facial weakness or pain, imbalance, and/or vertigo.

In addition to the history and physical exam, experts recommend that audiometry and MRI be considered, particularly if hearing loss is unilateral. Genetic screening for NF2 should be performed if vestibular schwannoma is found on MRI. Referral to a neurologist, a neurosurgeon, or an otolaryngologist is appropriate.

REFERENCES
1. Arthurs BJ, Lamoreaux WT, Giddings NA, et al. Gamma Knife radiosurgery for vestibular schwannoma: case report and review of the literature. World J Surg Oncol. 2009 Dec 18;7:100.

2. Mohammed TA, Ahuja MS, Ju SS, Thomas J. Normal pressure hydrocephalus after Gamma Knife radiosurgery for vestibular schwannoma. J Postgrad Med. 2010;56(3):213-215.

3. Gal TJ, Shinn J, Huang B. Current epidemiology and management trends in acoustic neuroma. Otolaryngol Head Neck Surg. 2010;142(5):677-681.

4. Evans DG, Moran A, King A, et al. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol. 2005;26(1):93-97.

5. Haynes D. Acoustic neuroma diagnosis and treatment options. Hearing Health. 2009;25(3):32. www.drf.org/magazine/36/Summer+2009+Issue/article/272. Accessed May 16, 2011.

6. Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol. 1993;52(2):106-113.

7. Evans DG, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med. 1992;84(304):603-618.

8. Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361(4):358-367.

9. Evans DGR, Sainio M, Baser E. Neurofibromatosis type 2. J Med Genet. 2000:37(11):897-904.

10. Gusella JF, Ramesh V, MacCollin M, Jacoby LB. Neurofibromatosis 2: loss of Merlin’s protective spell. Curr Opin Genet Dev. 1996;6(1):87-92.

11. Sagar SM, Israel MA. Ch 374. Primary and metastatic tumors of the nervous system. In: Kasper DL, Braunwald E, Fauci AS, et al. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill Companies, Inc; 2008:2601-2610.

12. Evans DGR. Neurofibromatosis 2 [bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med. 2009;11(9):599-610.

13. Arya R, Sahu JK, Kabra M. Neurofibromatosis type II (Wishart type). J Pediatr Neurol. 2009;7(3): 333-335.

14. Fortnum H, O’Neill C, Taylor R, et al. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and cost effectiveness and natural history. Health Technol Assess. 2009;13(18):iii-iv, ix-xi, 1-154.

15. Forton GE, Cremers CW, Offeciers EE. Acoustic neuroma ingrowth in the cochlear nerve: does it influence the clinical presentation? Ann Otol Rhinol Laryngol. 2004;113(7):582-586.

16. Nikolopoulos TP, Fortnum H, O’Donoghue G, Baguley D. Acoustic neuroma growth: a systematic review of the evidence. Otol Neurotol. 2010;31(3):478-485.

17. Yates CW, Weinberg M, Packer MJ, Jacob A. Fatal case of tumor-associated hemorrhage in a large vestibular schwannoma. Ann Otol Rhinol Laryngol. 2010;119(6):402-405.

18. Baser ME, Mautner VF, Parry DM, Evans DGR. Methodological issues in longitudinal studies; vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet. 2005;42(12):903-906.

19. Brooker J, Burney S, Fletcher J, Dally M. A qualitative exploration of quality of life among individuals diagnosed with an acoustic neuroma. Br J Health Psychol. 2009;14(pt 3):563-578.

20. Strupp M, Brandt T. Diagnosis and treatment of vertigo and dizziness. Dtsch Arzetbl Int. 2008;105(10):173-180.

21. Kerber KA. Dizziness and vertigo. In: Andreoli TE, Griggs RC, Benjamin I , Wing EJ, eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 8th ed. Philadelphia, PA: Elsevier Inc; 2010:1104-1105.

22. Gimsing S. Vestibular schwannoma: when to look for it? J Laryngol Otol. 2010;124(3):258-264.

23. Agrawal Y, Clark JH, Limb CJ, et al. Predictors of vestibular schwannoma growth and clinical implications. Otol Neurotol. 2010;31(5):807-812.

24. Cheung SW, Aranda D, Driscoll CLW, Parsa AT. Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management. Otol Neurotol. 2010;31(2):284-293.

25. Myrseth E, Pedersen PH, Møller P, Lund-Johansen M. Treatment of vestibular schwannomas: why, when and how? Acta Neurochir (Wien). 2007;149(7):647-660.

26. Sidney Kimmel Comprehensive Cancer Center, Massachusetts General Hospital, National Cancer Institute. Bevacizumab for symptomatic vestibular schwannoma in neurofibromatosis type 2 (NF2). http://clinicaltrials.gov/ct2/show/NCT01207687. Accessed May 16, 2011.

27. Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12(1):14-18.

28. Plotkin SR, Halpin C, McKenna MJ, et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010;31(7):1135-1143.

29. Arthurs BJ, Fairbanks RK, Demakas JJ, et al. A review of treatment modalities for vestibular schwannoma. Neurosurg Rev. 2011 Feb 9; [Epub ahead of print].

30. Andrews DW, Werner-Wasik M, Den RB, et al. Toward dose optimization for fractionated stereotactic radiotherapy for acoustic neuromas: comparison of two dose cohorts. Int J Radiat Oncol Biol Phys. 2009;74(2):419-426.

31. Thomas C, Di Maio S, Ma R, et al. Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose. J Neurosurg. 2007;107(5):917-926.

32. Samii M, Gerganov V, Samii A. Improved preservation of hearing and facial nerve function in vestibular schwannoma surgery via the retrosigmoid approach in a series of 200 patients. J Neuro­surg. 2006;105(4):527-535.

33. Shiobara R, Ohira T, Inoue Y, et al. Extended middle cranial fossa approach for vestibular schwannoma: technical note and surgical results of 896 operations. Prog Neurol Surg. 2008;21:65-72.

34. Schmerber S, Palombi O, Boubagra K, et al. Long-term control of vestibular schwannoma after a translabyrinthine complete removal. Neurosurgery. 2005;57(4):693-698.

35. Phillips DJ, Kobylarz EJ, De Peralta ET, et al. Predictive factors of hearing preservation after surgical resection of small vestibular schwannomas. Otol Neurotol. 2010;31(9):1463-1468.

36. Park JK, Black MP, Vernick DM, Ramakrishna N. Vestibular schwannoma (acoustic neuroma) (2010). www.uptodate.com/contents/vestibular-schwannoma-acoustic-neuroma. Accessed May 16, 2011.

37. Schankin CJ, Gall C, Straube A. Headache syndromes after acoustic neuroma surgery and their implications for quality of life. Cephalalgia. 2009;29(7):760-761.

38. Ryzenman JM, Pensak ML, Tew JM Jr. Headache: a quality of life analysis in a cohort of 1,657 patients undergoing acoustic neuroma surgery: results from the Acoustic Neuroma Association. Laryngoscope. 2005;115(4):703-711.

39. Sriskandan N, Connor SE. The role of radiology in the diagnosis and management of vestibular schwannoma. Clin Radiol. 2010;66(4):357-365.

40. Yang I, Sughrue ME, Han SJ, et al. Facial nerve preservation after vestibular schwannoma Gamma Knife surgery. J Neurooncol. 2009;93(1): 41-48.

41. Unger F, Dominikus K, Haselsberger K. Stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neuromas [in German]. HNO. 2011;59(1):31-37.

42. Tos T, Caye-Thomasen P, Stangerup SE, et al. Long-term socio-economic impact of vestibular schwannoma for patients under observation and after surgery. J Laryngol Otol. 2003;117(12):955-964.

A 22-year-old student was brought in to a college student health center in a wheelchair by campus safety personnel. She appeared drowsy and was crying softly. She complained of a severe headache and said she was “tired of going through this all the time.” The woman said she had seen spots and become dizzy, then had gotten “the worst headache of my life” while sitting in class. She rated the headache pain at 8 on a 10-point scale and also complained of nausea and photophobia.

The history revealed dizziness that made her “feel as if I’m tipping over” and similar headaches during the previous year. The patient said she had seen “a few doctors” for her symptoms, but that they “could never find anything.” The headaches usually occurred on the left side of her head, lasted hours to days, and were only partially relieved with acetaminophen. The patient could not remember whether she had eaten breakfast and was unsure of what day it was. She described herself as frustrated and began to weep again.

She was currently under the care of a psychologist but seemed uncertain why; she said that she was sexually active and used condoms. She had undergone an appendectomy at age 12. She denied taking any medications besides acetaminophen. She denied smoking or drug use, history of migraine headaches, vision or hearing changes, facial weakness, depression, or anxiety. Her family history included a grandfather with diabetes and hypertension and an uncle with heart disease. The family history was negative for migraine or psychiatric illness.

Because of the patient’s weakness, she was assisted onto the examination table by a nurse. Physical exam revealed a pale, slightly sweaty, overweight, tearful young woman who was slow to respond. Her blood pressure was measured at 134/104 mm Hg; pulse, 100 beats/min; respirations, 14 breaths/min; and temperature, 97.0ºF. Point-of-care testing of blood glucose was 91 mg/dL, and hemoglobin was measured at 12.3 g/dL. The ophthalmologic exam was positive for photophobia and revealed slightly disconjugate gaze with horizontal nystagmus during testing of cranial nerves (CN) III, IV, and VI. The otoscopic exam revealed a slightly injected right tympanic membrane, and there were no apparent hearing deficits.

The neurologic exam showed patellar and brachial deep tendon reflexes equal, grips weak and equal, and the pupillary response intact. The patient was able to stand without assistance, although her gait was slightly unsteady. Because the patient was of college age, the clinician ruled out meningitis by negative Kernig’s and Brudzinski’s signs and absence of fever. Subarachnoid hemorrhage was also a concern when the patient mentioned the “worst headache of my life,” indicating the need for emergent imaging.

The patient’s presentation, it was felt, warranted a 911 call. The emergency medical team arrived, and its members began to question the patient. Discrepancies in the patient’s history during the paramedics’ reexamination led them to question whether an emergency department (ED) visit was necessary, but at the clinician’s insistence, they agreed to transport the student to the ED.

The following day, the student health center clinician was contacted by a member of the hospital ED staff with an update on the patient’s status. Shortly after her arrival at the hospital, she underwent MRI and was diagnosed with a vestibular schwannoma. She had surgery that same evening, during which the surgeon removed most of the tumor. Although the ED staff was not at liberty to provide more complete information, they did inform the clinician that the patient would require radiation for the remainder of the tumor.

DISCUSSION
Vestibular schwannoma is also known as acoustic schwannoma, acoustic neuroma, acoustic neurinoma, or vestibular neurilemmoma. These tumors arise from perineural elements of Schwann cells, which commonly form and lead to myelination in the vestibular area of CN VIII¹ (see figure). They occur with equal frequency on the superior and inferior branches of the vestibular nerve and originate only rarely at the cochlear portion of the eighth cranial nerve. Vestibular schwannomas represent approximately 8% to 10% of brain tumors and 80% to 90% of tumors in the cere­bellopontine angle in adults.² Tumors are distributed evenly across genders, but the majority of diagnosed patients are white.³

Most likely because of improvements in diagnostic technology, the incidence of vestibular schwannoma has increased over the past 30 years. One British research team predicts that one in 1,000 persons will receive a diagnosis of vestibular schwannoma in their lifetime.⁴ These tumors are most commonly diagnosed in people ages 30 to 60, with a median age of 55.⁵

A relationship has been demonstrated between neurofibromatosis type 2 (NF2), an autosomal-dominant disease, and the development of vestibular schwannomas.^6,7 NF2 has a birth prevalence of one in about 25,000 persons,^4,8 and those who inherit the responsible gene inevitably develop vestibular schwannomas.⁹ Patients with a confirmed diagnosis of vestibular schwannoma should be screened by a geneticist for the NF2 gene; although the tumors are benign, they can cause compression of the vestibular nerve, leading to deafness and balance disorders.¹⁰ Schwannomas of the spinal nerves can also occur in persons with NF2.¹¹ Compression of the spinal nerves in these patients can lead to significant morbidity and a shortened average life span.¹⁰

NF2 is diagnosed using the following criteria:

1) Bilateral vestibular schwan­nomas

2) Diagnosis of a family member with either NF2 or unilateral vestibular schwannoma, and

3) Juvenile posterior subscapular lens opacities.^9,12,13

Because schwannomas grow slowly, the vestibular system can adapt to the slow destruction of CN VIII. For this reason, patients typically present with unilateral deafness or hearing impairment rather than dizziness.¹¹ Many patients also present with tinnitus and/or vertigo.^14,15

Some vestibular tumors remain stable or even regress; others progress, in some cases causing life-threatening complications.¹⁶ An extremely rare complication of a vestibular schwannoma was reported in one patient: an intratumoral hemorrhage that led to acute neurologic deterioration and death.¹⁷

Since the case patient underwent immediate surgical intervention, it appears she was experiencing significant involvement and it was likely anticipated that without surgical intervention, clinical progression would occur. Her young age could be considered a risk factor for a faster-growing neuroma.¹⁸

Clinical Presentation and Diagnosis
Primary care clinicians commonly see patients with complaints of dizziness, lightheadedness, faintness, or a sensation of spinning or tilting. Vestibular schwannoma should be considered in the differential diagnosis of the patient who presents with these complaints, as well as tinnitus or hearing loss.⁹ The patient with vestibular schwannoma may also have a history of headache, unsteady gait, facial pain, and numbness.¹⁹ A partial differential diagnosis is listed in the table^20,21). The astute clinician will systematically rule out many of these conditions, since certain other features that may be present (eg, rapid onset, vomiting, fever) do not typically occur in the patient with vestibular schwannoma.

Because the symptoms typically associated with vestibular schwannoma are likely to occur bilaterally in patients with other conditions, unilateral symptoms should alert the clinician to investigate further. The patterns and growth rates of vestibular schwannomas are highly variable and currently unpredictable¹⁸ (according to Fortnum et al,¹⁴ at least 50% of tumors do not grow within several years after diagnosis); thus, no clear predictors of tumor growth have been identified to assist in the evaluation of an affected patient,¹⁶ although faster tumor growth rates have been reported in young patients, and Baser et al¹⁸ have called for additional research involving younger persons with vestibular schwannomas.

Standard testing is audiometry followed by MRI, which is considered the most effective means to confirm a diagnosis of vestibular schwannoma.^5,14,22

Treatment for Vestibular Schwannoma
Treatment, whether with surgery or radiation, is associated with significant morbidity and possibly decreased quality of life.¹⁶ Therefore, distinguishing patients whose tumors will grow and pose a threat to them from those whose tumors are likely to remain stable is central to appropriate management.²³

Treatment modalities are considered based on tumor size, growth, presence or absence of tinnitus, and the patient’s preferences and life expectancy.²³ In most cases, decision making is complex and should be customized to meet the patient’s individual circumstances. Patients with similar clinical scenarios have been reported to opt for different treatment choices.²⁴

Four treatment options are currently available for patients with vestibular schwannoma:

Serial observation with periodic MRI studies. Since vestibular schwannomas are benign and slow-growing, conservative manage­ment can be a reasonable option, particularly if the patient is elderly, the tumor is small, and/or little hearing loss has taken place. However, use of observation is associated with a risk for progressive and permanent hearing loss.² Between 15% and 50% of patients who opt for serial observation will undergo subsequent surgical intervention, particularly in cases involving worsening tinnitus, balance problems, or hearing loss.^23-25

Chemotherapy. Agents including bevacizumab (a humanized monoclonal antibody against vascular endothelial growth factor)^8,26,27 and erlotinib (an epidermal growth factor receptor inhibitor) may delay progression or even facilitate regression of vestibular schwannomas.²⁸ Hearing improvement has also been reported in patients with NF2 who were treated with bevacizumab⁸; research is ongoing.²⁶

Fractionated radiotherapy. Hearing may be preserved in 60% to 95% of patients, depending on levels of dosing to the cochlea, but 3% to 7% of patients will need further treatment.^29-31 Radiation treatment is a likely choice in patients with tumors measuring 2.0 cm or less. Larger tumors are considered a surgical disease, and directed radiotherapy may be administered postoperatively (as in the case patient) for residual portions of the tumor.¹⁶

Microsurgery. Compared with other treatment modalities, the emphasis of microsurgery is on removing tumors (particularly larger tumors) rather than controlling their growth.²⁹ The three common approaches are retrosigmoid, middle fossa, or translabyrinthine.^32-34 Preservation of hearing is reportedly better following retrosigmoid or middle fossa microsurgery, compared with a translabyrinthine procedure (because in the latter, the tumor cannot be exposed without damage to the inner ear).^32,35

With any such surgery, risks include cranial nerve damage, leakage of cerebrospinal fluid, and infection.^29,32 Postsurgically, about half of patients report frequent headaches, which are persistent in about half of these cases.^36-38 Another concern is preservation of the facial nerves, with a risk for temporary facial weakness or dysfunction.^3,24,39 Less than 2% of patients who undergo microsurgery require additional treatment.²⁹

Stereotactic radiosurgery. These procedures, which are performed using the Gamma Knife,^® the CyberKnife, or the linear accelerator,^29,40,41 are considered appropriate for patients with smaller tumors and those who are not candidates for conventional surgery.¹ Trigeminal neuropathy, injury to the facial nerves, and hydrocephaly are reported complications of Gamma Knife radiosurgery, but improvements in these technologies are ongoing.^1,2,40

Patient Outcomes
The outcome in a patient with vestibular schwannoma depends on the treatment administered, but prolonged follow-up is typically necessary. For patients being managed through observation, annual brain scans are recommended for 10 years, with subsequent scans every three to five years if no tumor growth is seen. For patients who have had surgery, annual brain scans are advised for the successive eight to 10 years, with decreasing frequency if no tumor remains. In patients who undergo radiation, annual scans are recommended for 10 years, then every two years if no tumor growth is detected.³⁶

Psychosocial experiences vary widely among patients who have undergone treatment for vestibular schwannomas. Some are unable to perform necessary or recreational activities, and others must retire early from work.⁴² Others, however, have minimal disruption in their lives and enjoy a good quality of life. The most difficult consequence of vestibular schwannoma and its treatment, according to patients, is the associated hearing loss.^8,19

THE CASE PATIENT
The 22-year-old patient in this case had an atypical presentation of vestibular schwannoma. Although she did present with vertigo, she also complained of headache, nausea, and photophobia—which are rarely reported in investigations of these tumors. She was also younger than the typical patient and did not report tinnitus.

The case patient reportedly underwent surgery and subsequent radiation to treat the remaining portion of her tumor. She suspended her attendance at the college and, as of this writing, has not re-enrolled. She was lost to follow-up.

CONCLUSION
For the primary care provider, diagnostic challenges require great clinical acumen. Vertigo, headache, hearing loss, and tinnitus are all symptoms seen in the primary care setting; when they occur together, the clinician should be alerted to investigate further. A high level of suspicion is appropriate when a patient complains of longstanding auditory symptoms, with or without headache. Unilateral hearing loss is a common symptom in patients with vestibular schwannomas, although some may present with facial weakness or pain, imbalance, and/or vertigo.

In addition to the history and physical exam, experts recommend that audiometry and MRI be considered, particularly if hearing loss is unilateral. Genetic screening for NF2 should be performed if vestibular schwannoma is found on MRI. Referral to a neurologist, a neurosurgeon, or an otolaryngologist is appropriate.

REFERENCES
1. Arthurs BJ, Lamoreaux WT, Giddings NA, et al. Gamma Knife radiosurgery for vestibular schwannoma: case report and review of the literature. World J Surg Oncol. 2009 Dec 18;7:100.

2. Mohammed TA, Ahuja MS, Ju SS, Thomas J. Normal pressure hydrocephalus after Gamma Knife radiosurgery for vestibular schwannoma. J Postgrad Med. 2010;56(3):213-215.

3. Gal TJ, Shinn J, Huang B. Current epidemiology and management trends in acoustic neuroma. Otolaryngol Head Neck Surg. 2010;142(5):677-681.

4. Evans DG, Moran A, King A, et al. Incidence of vestibular schwannoma and neurofibromatosis 2 in the North West of England over a 10-year period: higher incidence than previously thought. Otol Neurotol. 2005;26(1):93-97.

5. Haynes D. Acoustic neuroma diagnosis and treatment options. Hearing Health. 2009;25(3):32. www.drf.org/magazine/36/Summer+2009+Issue/article/272. Accessed May 16, 2011.

6. Sobel RA. Vestibular (acoustic) schwannomas: histologic features in neurofibromatosis 2 and in unilateral cases. J Neuropathol Exp Neurol. 1993;52(2):106-113.

7. Evans DG, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. Q J Med. 1992;84(304):603-618.

8. Plotkin SR, Stemmer-Rachamimov AO, Barker FG 2nd, et al. Hearing improvement after bevacizumab in patients with neurofibromatosis type 2. N Engl J Med. 2009;361(4):358-367.

9. Evans DGR, Sainio M, Baser E. Neurofibromatosis type 2. J Med Genet. 2000:37(11):897-904.

10. Gusella JF, Ramesh V, MacCollin M, Jacoby LB. Neurofibromatosis 2: loss of Merlin’s protective spell. Curr Opin Genet Dev. 1996;6(1):87-92.

11. Sagar SM, Israel MA. Ch 374. Primary and metastatic tumors of the nervous system. In: Kasper DL, Braunwald E, Fauci AS, et al. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill Companies, Inc; 2008:2601-2610.

12. Evans DGR. Neurofibromatosis 2 [bilateral acoustic neurofibromatosis, central neurofibromatosis, NF2, neurofibromatosis type II]. Genet Med. 2009;11(9):599-610.

13. Arya R, Sahu JK, Kabra M. Neurofibromatosis type II (Wishart type). J Pediatr Neurol. 2009;7(3): 333-335.

14. Fortnum H, O’Neill C, Taylor R, et al. The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and cost effectiveness and natural history. Health Technol Assess. 2009;13(18):iii-iv, ix-xi, 1-154.

15. Forton GE, Cremers CW, Offeciers EE. Acoustic neuroma ingrowth in the cochlear nerve: does it influence the clinical presentation? Ann Otol Rhinol Laryngol. 2004;113(7):582-586.

16. Nikolopoulos TP, Fortnum H, O’Donoghue G, Baguley D. Acoustic neuroma growth: a systematic review of the evidence. Otol Neurotol. 2010;31(3):478-485.

17. Yates CW, Weinberg M, Packer MJ, Jacob A. Fatal case of tumor-associated hemorrhage in a large vestibular schwannoma. Ann Otol Rhinol Laryngol. 2010;119(6):402-405.

18. Baser ME, Mautner VF, Parry DM, Evans DGR. Methodological issues in longitudinal studies; vestibular schwannoma growth rates in neurofibromatosis 2. J Med Genet. 2005;42(12):903-906.

19. Brooker J, Burney S, Fletcher J, Dally M. A qualitative exploration of quality of life among individuals diagnosed with an acoustic neuroma. Br J Health Psychol. 2009;14(pt 3):563-578.

20. Strupp M, Brandt T. Diagnosis and treatment of vertigo and dizziness. Dtsch Arzetbl Int. 2008;105(10):173-180.

21. Kerber KA. Dizziness and vertigo. In: Andreoli TE, Griggs RC, Benjamin I , Wing EJ, eds. Andreoli and Carpenter’s Cecil Essentials of Medicine. 8th ed. Philadelphia, PA: Elsevier Inc; 2010:1104-1105.

22. Gimsing S. Vestibular schwannoma: when to look for it? J Laryngol Otol. 2010;124(3):258-264.

23. Agrawal Y, Clark JH, Limb CJ, et al. Predictors of vestibular schwannoma growth and clinical implications. Otol Neurotol. 2010;31(5):807-812.

24. Cheung SW, Aranda D, Driscoll CLW, Parsa AT. Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management. Otol Neurotol. 2010;31(2):284-293.

25. Myrseth E, Pedersen PH, Møller P, Lund-Johansen M. Treatment of vestibular schwannomas: why, when and how? Acta Neurochir (Wien). 2007;149(7):647-660.

26. Sidney Kimmel Comprehensive Cancer Center, Massachusetts General Hospital, National Cancer Institute. Bevacizumab for symptomatic vestibular schwannoma in neurofibromatosis type 2 (NF2). http://clinicaltrials.gov/ct2/show/NCT01207687. Accessed May 16, 2011.

27. Mautner VF, Nguyen R, Kutta H, et al. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 2010;12(1):14-18.

28. Plotkin SR, Halpin C, McKenna MJ, et al. Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients. Otol Neurotol. 2010;31(7):1135-1143.

29. Arthurs BJ, Fairbanks RK, Demakas JJ, et al. A review of treatment modalities for vestibular schwannoma. Neurosurg Rev. 2011 Feb 9; [Epub ahead of print].

30. Andrews DW, Werner-Wasik M, Den RB, et al. Toward dose optimization for fractionated stereotactic radiotherapy for acoustic neuromas: comparison of two dose cohorts. Int J Radiat Oncol Biol Phys. 2009;74(2):419-426.

31. Thomas C, Di Maio S, Ma R, et al. Hearing preservation following fractionated stereotactic radiotherapy for vestibular schwannomas: prognostic implications of cochlear dose. J Neurosurg. 2007;107(5):917-926.

32. Samii M, Gerganov V, Samii A. Improved preservation of hearing and facial nerve function in vestibular schwannoma surgery via the retrosigmoid approach in a series of 200 patients. J Neuro­surg. 2006;105(4):527-535.

33. Shiobara R, Ohira T, Inoue Y, et al. Extended middle cranial fossa approach for vestibular schwannoma: technical note and surgical results of 896 operations. Prog Neurol Surg. 2008;21:65-72.

34. Schmerber S, Palombi O, Boubagra K, et al. Long-term control of vestibular schwannoma after a translabyrinthine complete removal. Neurosurgery. 2005;57(4):693-698.

35. Phillips DJ, Kobylarz EJ, De Peralta ET, et al. Predictive factors of hearing preservation after surgical resection of small vestibular schwannomas. Otol Neurotol. 2010;31(9):1463-1468.

36. Park JK, Black MP, Vernick DM, Ramakrishna N. Vestibular schwannoma (acoustic neuroma) (2010). www.uptodate.com/contents/vestibular-schwannoma-acoustic-neuroma. Accessed May 16, 2011.

37. Schankin CJ, Gall C, Straube A. Headache syndromes after acoustic neuroma surgery and their implications for quality of life. Cephalalgia. 2009;29(7):760-761.

38. Ryzenman JM, Pensak ML, Tew JM Jr. Headache: a quality of life analysis in a cohort of 1,657 patients undergoing acoustic neuroma surgery: results from the Acoustic Neuroma Association. Laryngoscope. 2005;115(4):703-711.

39. Sriskandan N, Connor SE. The role of radiology in the diagnosis and management of vestibular schwannoma. Clin Radiol. 2010;66(4):357-365.

40. Yang I, Sughrue ME, Han SJ, et al. Facial nerve preservation after vestibular schwannoma Gamma Knife surgery. J Neurooncol. 2009;93(1): 41-48.

41. Unger F, Dominikus K, Haselsberger K. Stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neuromas [in German]. HNO. 2011;59(1):31-37.

42. Tos T, Caye-Thomasen P, Stangerup SE, et al. Long-term socio-economic impact of vestibular schwannoma for patients under observation and after surgery. J Laryngol Otol. 2003;117(12):955-964.

This issue includes a Priority Update from the Research Literature (PURL) that evaluates the results of 2 studies concerning PSA screening.^1,2 No sooner had this PURL been completed than The New England Journal of Medicine (NEJM) published the results of a randomized controlled trial of radical prostatectomy vs watchful waiting in early prostate cancer,^3- accompanied by an editorial titled, “Effective treatment for early-stage prostate cancer—possible, necessary, or both?”⁴ Meanwhile, we await the results of 2 trials being touted as definitive: the Prostate cancer Intervention Versus Observation Trial (PIVOT)⁵ and the Prostate testing for cancer and Treatment (ProtecT) trial.⁶

Keeping up with this area of practice is beginning to feel like a full-time job.

But I am going to go out on a limb here and suggest that, until we have fundamentally changed strategies for targeted case finding or early intervention (think genomic and proteomic markers), it is time to stop this screening nonsense. The facts speak for themselves: A trial of 182,000 patients finds in a post hoc analysis of a very narrow population that death can be averted in one of 723 individuals who are screened.² What about the complications associated with diagnosis, work-up, and treatment?

It is time for urologists and primary care physicians to tell patients that PSA screening is unlikely to benefit them.

Some of you will suggest that we counsel patients about PSA testing to facilitate informed decision-making. But do we advise patients to play the lottery or try futile therapies?

The only men who stand to get even a small benefit from PSA screening are those in excellent health, and it is pretty darn hard to improve on that. I urge all of us to stop offering routine PSA testing and, when asked, to advise against this risky intervention.

This issue includes a Priority Update from the Research Literature (PURL) that evaluates the results of 2 studies concerning PSA screening.^1,2 No sooner had this PURL been completed than The New England Journal of Medicine (NEJM) published the results of a randomized controlled trial of radical prostatectomy vs watchful waiting in early prostate cancer,^3- accompanied by an editorial titled, “Effective treatment for early-stage prostate cancer—possible, necessary, or both?”⁴ Meanwhile, we await the results of 2 trials being touted as definitive: the Prostate cancer Intervention Versus Observation Trial (PIVOT)⁵ and the Prostate testing for cancer and Treatment (ProtecT) trial.⁶

Keeping up with this area of practice is beginning to feel like a full-time job.

But I am going to go out on a limb here and suggest that, until we have fundamentally changed strategies for targeted case finding or early intervention (think genomic and proteomic markers), it is time to stop this screening nonsense. The facts speak for themselves: A trial of 182,000 patients finds in a post hoc analysis of a very narrow population that death can be averted in one of 723 individuals who are screened.² What about the complications associated with diagnosis, work-up, and treatment?

It is time for urologists and primary care physicians to tell patients that PSA screening is unlikely to benefit them.

Some of you will suggest that we counsel patients about PSA testing to facilitate informed decision-making. But do we advise patients to play the lottery or try futile therapies?

The only men who stand to get even a small benefit from PSA screening are those in excellent health, and it is pretty darn hard to improve on that. I urge all of us to stop offering routine PSA testing and, when asked, to advise against this risky intervention.

This issue includes a Priority Update from the Research Literature (PURL) that evaluates the results of 2 studies concerning PSA screening.^1,2 No sooner had this PURL been completed than The New England Journal of Medicine (NEJM) published the results of a randomized controlled trial of radical prostatectomy vs watchful waiting in early prostate cancer,^3- accompanied by an editorial titled, “Effective treatment for early-stage prostate cancer—possible, necessary, or both?”⁴ Meanwhile, we await the results of 2 trials being touted as definitive: the Prostate cancer Intervention Versus Observation Trial (PIVOT)⁵ and the Prostate testing for cancer and Treatment (ProtecT) trial.⁶

Keeping up with this area of practice is beginning to feel like a full-time job.

But I am going to go out on a limb here and suggest that, until we have fundamentally changed strategies for targeted case finding or early intervention (think genomic and proteomic markers), it is time to stop this screening nonsense. The facts speak for themselves: A trial of 182,000 patients finds in a post hoc analysis of a very narrow population that death can be averted in one of 723 individuals who are screened.² What about the complications associated with diagnosis, work-up, and treatment?

It is time for urologists and primary care physicians to tell patients that PSA screening is unlikely to benefit them.

Some of you will suggest that we counsel patients about PSA testing to facilitate informed decision-making. But do we advise patients to play the lottery or try futile therapies?

The only men who stand to get even a small benefit from PSA screening are those in excellent health, and it is pretty darn hard to improve on that. I urge all of us to stop offering routine PSA testing and, when asked, to advise against this risky intervention.

ILLUSTRATIVE CASES

A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?

A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?

Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.^3,4

Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.⁵ Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.

By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.⁶ Two large RCTs, both published in 2009, reported conflicting results.^7,8

The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.⁷

The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.⁸

PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.⁶ In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.⁹

Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.

STUDY SUMMARY: Widespread screening doesn’t save lives

Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.¹ Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.

Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.² Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.

Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.

Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.

However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).

WHAT’S NEW: At best, screening has a small benefit

These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.¹⁰ The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.¹

Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.

CAVEATS: Study limitations, some unknowns

These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.

Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.

In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.

In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.

What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.

CHALLENGES TO IMPLEMENTATION: Old habits die hard

Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)

Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.¹¹

Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.¹²

Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASES

A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?

A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?

Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.^3,4

Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.⁵ Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.

By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.⁶ Two large RCTs, both published in 2009, reported conflicting results.^7,8

The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.⁷

The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.⁸

PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.⁶ In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.⁹

Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.

STUDY SUMMARY: Widespread screening doesn’t save lives

Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.¹ Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.

Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.² Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.

Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.

Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.

However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).

WHAT’S NEW: At best, screening has a small benefit

These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.¹⁰ The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.¹

Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.

CAVEATS: Study limitations, some unknowns

These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.

Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.

In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.

In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.

What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.

CHALLENGES TO IMPLEMENTATION: Old habits die hard

Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)

Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.¹¹

Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.¹²

Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASES

A 65-year-old obese man with high blood pressure comes in for a complete physical and asks if he should have the “blood test for cancer.” He had a normal prostate specific antigen (PSA) the last time he was tested, but that was 10 years ago. What should you tell him?

A 55-year-old man schedules a routine check-up and requests a PSA test. His last test, at age 50, was normal. The patient has no known medical problems and no family history of prostate cancer, and he exercises regularly and doesn’t smoke. How should you respond to his request for a PSA test?

Prostate cancer is the second leading cause of cancer deaths among men in the United States, after lung cancer. One in 6 American men will be diagnosed with prostate cancer; for about 3% of them, the cancer will be fatal.^3,4

Widespread testing without evidence of efficacy
The PSA test was approved by the US Food and Drug Administration (FDA) in 1986.⁵ Its potential to detect early prostate cancer in the hope of decreasing morbidity and mortality led to widespread PSA screening in the 1990s, before data on the efficacy of routine screening existed.

By 2002, only one low-quality RCT that compared screening with no screening had been published. The investigators concluded that screening resulted in lower mortality rates, but a subsequent (and superior) intention-to-treat analysis showed no mortality benefit.⁶ Two large RCTs, both published in 2009, reported conflicting results.^7,8

The European Randomized Study of Screening for Prostate Cancer (ERSPC) enrolled 182,000 men ages 50 to 74 years and randomized them to either PSA screening every 4 years or no screening. Prostate cancer-specific mortality was 20% lower for those in the screening group compared with the no-screening group; however, the absolute risk reduction was only 0.71 deaths per 1000 men.⁷

The US Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) Screening Trial randomized 77,000 men ages 55 to 74 years to either annual PSA and digital rectal examination (DRE) screening or usual care. After 7 years of follow-up, no significant difference was found in prostate cancer deaths or all-cause mortality in the screening group vs the control group. It is important to note, however, that 52% of the men in the control group had ≥1 PSA screening during the study period, which decreased the researchers’ ability to fully assess the benefits of screening.⁸

PSA’s limitations and potential harmful effects
The PSA test’s significant limitations and potentially harmful effects counter the potential benefits of screening. About 75% of positive tests are false positives, which are associated with psychological harm in some men for up to a year after the test.⁶ In addition, diagnostic testing and treatment for what may be nonlife-threatening prostate cancer can cause harm, including erectile dysfunction (ED), urinary incontinence, bowel dysfunction, and death. Rates of ED and incontinence 18 months after radical prostatectomy are an estimated 59.9% and 8.4%, respectively.⁹

Do the benefits of PSA testing outweigh the harms—and for which men? The meta-analysis and post hoc analysis detailed in this PURL help clear up the controversy.

STUDY SUMMARY: Widespread screening doesn’t save lives

Djulbegovic et al examined 6 RCTs, including the ERSPC and PLCO studies described earlier, that compared screening for prostate cancer (PSA with or without DRE) with no screening or usual care.¹ Together, the studies included nearly 390,000 men ages 45 to 80 years, and had 4 to 15 years of follow-up. The results showed that routine screening for prostate cancer had no statistically significant effect on all-cause mortality (relative risk [RR]=0.99; 95% confidence interval [CI], 0.97-1.01), death from prostate cancer (RR=0.88; 95% CI, 0.71-1.09), or diagnosis of stage III or IV prostate cancer (RR=0.94; 95% CI, 0.85-1.04). Routine screening did, however, increase the probability of being diagnosed with prostate cancer at any stage, especially at stage I. For every 1000 men screened, on average, 20 more cases of prostate cancer were diagnosed.

Healthy men may benefit from screening
Crawford et al conducted a post hoc analysis of the PLCO trial, which had found no benefit to annual PSA testing and serial DRE compared with usual care for the general population.² Their analysis compared the mortality benefits (both prostate cancer–specific and overall) of annual PSA screening for healthy men with no or minimal comorbidities vs the mortality benefits for men with any risk factor for the 2 leading causes of death: cancer and cardiovascular disease.

Annual PSA testing yielded more diagnoses of prostate cancer in both healthy and at-risk men. Deaths from prostate cancer were infrequent in both groups, occurring in 0.22% (164/73,378) of all participants.

Men with ≥1 risk factor had similar prostate cancer–specific deaths with both yearly screening and usual care (62 vs 42 deaths, adjusted hazard ratio [AHR]=1.43; 95% CI, 0.96-2.11); their prostate cancer–specific mortality rate was 0.27% (95% CI, 0.21-0.34) and 0.19% (95% CI, 0.14-0.25), respectively.

However, healthy men younger than 75 years had fewer prostate cancer–specific deaths with annual PSA screenings (22 vs 38; AHR=0.56; 95% CI, 0.33-0.95; P=.03). Specifically, the prostate cancer mortality rate was 0.17% (95% CI, 0.11-0.25) in the group that received screening vs 0.31% (95% CI, 0.22-0.42) in the usual care group. Thus, the absolute risk reduction for prostate cancer-specific mortality in men without comorbidities who received yearly screening instead of usual care was 0.14% (0.31% vs 0.17%, P=.03), with a number needed to screen of 723 to prevent one death from prostate cancer. There was a non-significant reduction in all-cause mortality in the intervention group vs the control group (AHR=0.93; 95% CI, 0.86-1.02; P=.11).

WHAT’S NEW: At best, screening has a small benefit

These trials indicate that only a small group of men will potentially benefit from PSA screening. Prior to this meta-analysis, a Cochrane review published in 2006 had concluded that there was insufficient evidence to support or refute the routine use of mass screening for prostate can-cer.¹⁰ The meta-analysis by Djulbegovic et al, which included 4 additional trials, 2 of them large, found no benefit of PSA screening in reducing mortality from prostate cancer for the general population.¹

Annual screening does appear to provide a small reduction in prostate cancer deaths but no significant reduction in all-cause mortality in men younger than age 75 who have no risk factors for cancer or cardiovascular disease.

CAVEATS: Study limitations, some unknowns

These studies did not address whether certain groups at higher risk of developing prostate cancer, such as African American men and those with a family history of prostate cancer, would benefit from PSA screening. In addition, both of the studies detailed in this PURL had substantive weaknesses.

Methodological limitations of the studies in the meta-analysis included the lack of intention-to-treat analysis and allocation concealment, which favors finding a benefit for the screening arm, and PSA screening in the nonscreening arm, which biases the results toward not finding a screening benefit that might exist. Despite these weaknesses, this meta-analysis brings together the best available evidence of the value of screening for prostate cancer.

In addition, there was no quantitative assessment of complication rates included in the meta-analysis. None of the 6 trials collected data on the effect of screening or treatment on participants’ quality of life.

In the post hoc study showing a benefit for screening healthy men, the decrease in prostate cancer deaths was small in magnitude, did not have an impact on all-cause mortality, and was of marginal statistical significance. Although the data came from the largest multicenter study to date of prostate cancer screening, the results of a post hoc analysis of a single trial should be interpreted with caution. The study was initially designed to test the effect of screening on a general population. Whenever a study deviates from the original hypothesis to evaluate a subset of the study population, the investigators increase the risk of finding a difference where none exists. Thus, it is possible that the findings of benefit for healthy men may not truly be present.

What’s more, the risk factors identified by the authors could be interpreted as arbitrary. They included diverticulosis, which is not known to increase the likelihood of cancer or heart disease, as a risk factor. By the same token, smoking—a known risk factor for both cancer and cardiovascular disease—was not addressed. Finally, potential harms associated with false-positive tests and prostate cancer treatment were not addressed in these studies.

CHALLENGES TO IMPLEMENTATION: Old habits die hard

Clinicians have recommended PSA screening for men >50 years, and men have requested such screening, for more than 2 decades. Physicians often opt to order a PSA test rather than to take the time to explain potential harms and benefits and listen to the patient’s thoughts and feelings about the value of screening. In addition, physicians who believe the lack of benefit from screening does not apply to their patients will continue to order the PSA test. (See “The perils of PSA screening”.)

Patients may opt to continue to be screened although they have developed a risk factor for cardiovascular disease. Also, a decision not to screen directly contradicts the recommendation of the American Urological Association, which calls for annual PSA testing for asymptomatic men with a life expectancy >10 years starting at 40 years of age.¹¹

Shared decision-making
The US Preventive Services Task Force (USPSTF) provides a basis for shared decision-making between physicians and patients concerning prostate cancer screening. The USPSTF states that there is insufficient evidence to recommend for or against prostate cancer screening for the general male population younger than age 75 and recommends against screening men age 75 and older or those with a life expectancy of less than 10 years.¹²

Decisions regarding PSA screening should be shared and documented for all men between the ages of 50 and 75 years. Advise patients with risk factors that the evidence shows little value and possible harm from screening. Tell healthier men that PSA testing appears to offer a small benefit, at best.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources; the grant is a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

CASE: Abnormal movements

Pregnant and unsure of her due date, Ms. A, age 35, presents to the emergency room complaining of hourly uterine contractions for the last 3 days and new onset vaginal bleeding. Ms. A is admitted to the obstetrics (OB) service for preterm labor at 34 and 3/7 weeks as dated by a triage ultrasound.

During initial examination by the OB service, Ms. A’s blood pressure is 155/112 mm Hg with a pulse of 126. Her cervix is dilated to 4 centimeters. Her physical exam is notable for rapid, repetitive, involuntary movements in her upper extremities and to a lesser degree in lower extremities. Ms. A is started on IV fluids and hydralazine, 10 mg/d, for elevated blood pressure. Later that day, she delivers a preterm female weighing 2,360 grams in a spontaneous vaginal delivery without any complications.

After delivery, the OB service requests a psychiatric consultation to evaluate Ms. A’s “blunted affect,” history of heavy alcohol use, and abnormal movements. During examination, Ms. A is alert and oriented to her surroundings. She states that this was her eleventh pregnancy; however, she is unable to recall details of most previous pregnancies. She also cannot remember any significant medical, surgical, or mental health history. Ms. A appears distracted, has difficulty participating in the interview, and gives contradictory histories to different team members. She is well groomed but shows repetitive circular movements of her hands, feet, and jaw that are nearly continuous. In addition, Ms. A has intermittent lip biting and smacking. Her speech is delayed, with increased latency of her responses to basic questions.

Her mood is neutral, her affect is blunted, and she denies any current suicidal or homicidal ideations, delusions, and auditory or visual hallucinations. Although her chart indicates a history of alcohol abuse, she denies this history and current drug or alcohol use. Her Mini-Mental State Exam score is a 22/30, missing points in her ability to copy shapes and write a sentence, complicated by her chorea-like upper body movements. She also demonstrates marked inattentiveness and is unwilling to cooperate with spelling “world.” On physical exam, her gait is wide-based but steady.

The authors’ observations

Determining the cause of Ms. A’s abnormal movements, delayed speech, and neutral mood initially proves difficult because she is minimally cooperative with the interview and we find discrepancies between information she provides and her medical records from previous OB admissions. It is unclear whether these inconsistencies are because of her faltering memory—which she admits has worsened in the last year—or unwillingness to provide a complete medical history.

We consider possible substance intoxication given her documented history of substance use. However, an extended drug screen is negative and her laboratory values do not suggest heavy alcohol use.

HISTORY: Depression and confusion

The next day, Ms. A is more cooperative with the interview. She says that she began feeling depressed 8 years ago, around the time her brother was killed in a violent crime. She denies previous psychiatric hospitalizations, but says she attempted suicide 4 years ago by stabbing herself in the throat with a fork. After that attempt, she was referred to an outpatient psychiatrist whom she continues to see intermittently. She says that her abnormal movements started 2 years before she first saw her outpatient psychiatrist.

She says she has been prescribed several medications, but remembers only taking quetiapine for depressive symptoms and insomnia. After a discussion with her psychiatrist about the possible effects of quetiapine on the fetus, she discontinued the drug approximately 8 weeks into her pregnancy. Quetiapine decreased her movement symptoms slightly, and she feels her movements have become uncontrollable since discontinuing it.

She reports increased feelings of sadness, worthlessness, guilt, decreased energy, irritability, and difficulty sleeping during her pregnancy. She denies current or past psychotic symptoms or mania. Ms. A says she has noticed problems with her memory as well as increased confusion over recent months. She often gets lost and cannot remember where she lives after leaving her home.

Based on hospital records, we learn that an MRI of the brain without contrast was completed 1 year ago to “evaluate choreiform movements.” The scan showed mild atrophy and abnormal signal within the caudate and putamen, as well as volume loss. We consult with the neurology service to evaluate Ms. A’s abnormal movements and her previous abnormal brain imaging. The neurologic exam notes that Ms. A has orofacial dyskinesias and near-continuous choreiform movements in her arms and hands. Her gait remains wide-based and she is unable to tandem walk. Because Ms. A shows no new neurologic symptoms, the neurology service does not feel that additional neuroimaging is indicated.

The authors’ observations

In consultation with neurology, the leading differential diagnoses include tardive dyskinesia, chorea gravidarum, and Huntington’s disease. See the Table^1,2 for the differential diagnosis of chorea.

Ms. A reports taking quetiapine for 3 years, which suggests possible tardive dyskinesia. Although second-generation antipsychotics have a lower incidence of movement disorders than first-generation antipsychotics, the risk still exists. Withdrawal dyskinesias can occur after suddenly stopping or tapering antipsychotics and appear as extrapyramidal symptoms, including choreoathetosis similar to what Ms. A experienced.^3,4 This type of dyskinesia is thought to be secondary to chronic dopamine antagonism leading to increased postsynaptic receptors and dopamine hypersensitivity.⁵ Because Ms. A discontinued quetiapine early in her pregnancy, withdrawal dyskinesias are less likely.

Because Ms. A presented with a movement disorder while pregnant, the neurology service considers chorea gravidarum, the term given to chorea occurring during pregnancy. This syndrome is thought to be caused by the effects of pregnancy on the basal ganglia.⁶ Historically, chorea gravidarum was associated with rheumatic fever (RF); however, with the decline in prevalence of RF, most choreiform movements that appear during pregnancy typically are caused by other diseases, such as systemic lupus erythematosus or Huntington’s disease. Approximately one-half of chorea gravidarum cases are idiopathic, with RF and antiphospholipid syndrome accounting for the remainder.⁷ Huntington’s disease during pregnancy is rare because it tends to present in women beyond childbearing age.

Based on Ms. A’s symptoms and previous MRI findings, we ask her if she has a known family history of Huntington’s disease. She denies this, but says she has not seen her father since she was very young and is uncertain of his medical history.

Table

Differential diagnosis for chorea

TREATMENT: Restart medication

Ms. A’s laboratory results show a slightly low hemoglobin of 10.5 g/dL and hematocrit of 32.8%. Her mean corpuscular volume is slightly decreased at 77 fL. Her urinalysis is negative, and blood glucose and thyroid-stimulating hormone are within normal limits. Rapid plasma regain, anti-nuclear antibody, and human immunodeficiency virus (HIV) are negative. Based on hospital records, we learn that during the previous admission a year ago a serum ceruloplasmin and serum copper were drawn and were normal.

We contact Ms. A’s outpatient psychiatrist for collateral information. The psychiatrist says he first evaluated Ms. A 3 years ago after a friend brought her in because of strange behavior, including talking to herself, making odd facial gestures, and laughing inappropriately. Although Ms. A denies past psychiatric hospitalizations, her psychiatrist states that she was hospitalized for 1 week after the suicide attempt 4 years ago and prescribed lorazepam and sertraline during that admission. He speculates that the suicide attempt may have been related to 5 of her children being taken from her by the Department of Family and Child Services after police raided her home to search for drugs. Custody was awarded to their respective fathers, causing Ms. A to “snap,” according to her friend.

Since then, neither Ms. A nor her psychiatrist have reported any further psychotic symptoms. Her psychiatrist confirms that Ms. A’s abnormal movements were present before her first appointment with him. He says that he referred Ms. A to a local hospital for a neurology work-up, but she did not schedule an appointment.

When we follow up with Ms. A 2 days after delivery, she continues to deny depressive symptoms, although her affect remains blunted. She says she is looking forward to going home with the baby, whom she plans to bottle feed. Her choreiform movements appear unchanged. She also continues to experience lip smacking. Although Ms. A recognizes that she has some movements, she minimizes them and says they do not bother her. She continues to demonstrate latency in her verbal responses to questions. Based on the collateral history and positive response with quetiapine, we recommend that Ms. A be restarted on quetiapine, 200 mg/d.

The authors’ observations

Ms. A’s choreiform movements started before her psychotic symptoms and subsequent usage of neuroleptic medication, which makes tardive dyskinesia less likely. Laboratory studies rule out systemic lupus erythematosus, HIV, and Wilson’s disease as the cause of her abnormal movements.

Ms. A’s history is highly suggestive of Huntington’s disease. She exhibits classic motor signs, including involuntary choreiform movements in her extremities. She also has psychiatric symptoms that are commonly associated with Huntington’s disease, including depression—which preceded her motor symptoms—cognitive decline, apathy, and psychotic symptoms. In addition, her MRI findings of volume changes in the caudate nucleus and the putamen and inability to rule out a family history make Huntington’s disease more likely (Box).^1,8-11

Box

Psychiatric symptoms

Psychiatric symptoms frequently are evident in the early stages of Huntington’s disease, often before onset of motor symptoms.¹ Depression is the most common sign, and can be difficult to diagnose because weight loss, apathy, and inactivity also occur in Huntington’s disease. Feelings of low self-esteem, guilt, and anxiety can help distinguish depression from symptoms of Huntington’s disease. Cognitive decline also may present before the first motor symptoms occur. Cognitive changes typically are related to executive functions and affected individuals may develop impairments in organization and planning. Psychotic symptoms may be present, but are more common in later stages of the disease.¹

Ms. A reported that quetiapine seemed to lessen her choreiform movements, and dopamine receptor blocking agents (ie, antipsychotics) often are considered for managing chorea and psychosis in Huntington’s disease. However, there are few double-blind, placebo-controlled studies evaluating the efficacy of these agents.¹² Small, uncontrolled, nonrandomized trials found quetiapine has some efficacy for both motor and psychiatric symptoms in Huntington’s disease.^12-15

OUTCOME: Lost to follow-up

Ms. A is discharged from the hospital 3 days after she delivers her daughter and is given an appointment in 6 weeks at an affiliated movement disorders clinic. Before discharge, she is tested for the Huntington’s disease gene mutation with a plan to receive her results during her follow-up visit. During the informed consent process for the genetic testing, Ms. A states that she was tested previously and was quite sure that the test was positive for Huntington’s disease, although she could not recall where or when this testing was completed.

Ms. A also is scheduled to follow up with her obstetrician for a 6-week postpartum check-up and tubal ligation. We encourage Ms. A to make an appointment with her psychiatrist soon after discharge. We also make a referral to the Department of Family and Children Services to provide adequate support and resources to her and her children because of her physical and psychiatric issues.

Ms. A does not show up for her follow-up appointment at the movement disorders clinic. The genetic test is not completed during this admission because of a clerical error, and the serum sample subsequently expires.

The authors’ observations

Although Huntington’s disease is the most likely cause of Ms. A’s presentation, we were unable to confirm the diagnosis with genetic testing. If Ms. A returns to the neurology service and the genetic test is negative for Huntington’s disease, other causes of chorea must be investigated.

Related Resources

• De Marchi N, Mennella R. Huntington’s disease and its association with psychopathology. Harv Rev Psychiatry. 2000; 7(5):278-289.
• Revilla FJ, Grutzendler J, Larsh TR. Huntington disease. Medscape. http://emedicine.medscape.com/article/1150165-overview.

Drug Brand Names

• Hydralazine • Apresoline
• Lithium • Eskalith, Lithobid, others
• Lorazepam • Ativan
• Quetiapine • Seroquel
• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Abnormal movements

Pregnant and unsure of her due date, Ms. A, age 35, presents to the emergency room complaining of hourly uterine contractions for the last 3 days and new onset vaginal bleeding. Ms. A is admitted to the obstetrics (OB) service for preterm labor at 34 and 3/7 weeks as dated by a triage ultrasound.

During initial examination by the OB service, Ms. A’s blood pressure is 155/112 mm Hg with a pulse of 126. Her cervix is dilated to 4 centimeters. Her physical exam is notable for rapid, repetitive, involuntary movements in her upper extremities and to a lesser degree in lower extremities. Ms. A is started on IV fluids and hydralazine, 10 mg/d, for elevated blood pressure. Later that day, she delivers a preterm female weighing 2,360 grams in a spontaneous vaginal delivery without any complications.

After delivery, the OB service requests a psychiatric consultation to evaluate Ms. A’s “blunted affect,” history of heavy alcohol use, and abnormal movements. During examination, Ms. A is alert and oriented to her surroundings. She states that this was her eleventh pregnancy; however, she is unable to recall details of most previous pregnancies. She also cannot remember any significant medical, surgical, or mental health history. Ms. A appears distracted, has difficulty participating in the interview, and gives contradictory histories to different team members. She is well groomed but shows repetitive circular movements of her hands, feet, and jaw that are nearly continuous. In addition, Ms. A has intermittent lip biting and smacking. Her speech is delayed, with increased latency of her responses to basic questions.

Her mood is neutral, her affect is blunted, and she denies any current suicidal or homicidal ideations, delusions, and auditory or visual hallucinations. Although her chart indicates a history of alcohol abuse, she denies this history and current drug or alcohol use. Her Mini-Mental State Exam score is a 22/30, missing points in her ability to copy shapes and write a sentence, complicated by her chorea-like upper body movements. She also demonstrates marked inattentiveness and is unwilling to cooperate with spelling “world.” On physical exam, her gait is wide-based but steady.

The authors’ observations

Determining the cause of Ms. A’s abnormal movements, delayed speech, and neutral mood initially proves difficult because she is minimally cooperative with the interview and we find discrepancies between information she provides and her medical records from previous OB admissions. It is unclear whether these inconsistencies are because of her faltering memory—which she admits has worsened in the last year—or unwillingness to provide a complete medical history.

We consider possible substance intoxication given her documented history of substance use. However, an extended drug screen is negative and her laboratory values do not suggest heavy alcohol use.

HISTORY: Depression and confusion

The next day, Ms. A is more cooperative with the interview. She says that she began feeling depressed 8 years ago, around the time her brother was killed in a violent crime. She denies previous psychiatric hospitalizations, but says she attempted suicide 4 years ago by stabbing herself in the throat with a fork. After that attempt, she was referred to an outpatient psychiatrist whom she continues to see intermittently. She says that her abnormal movements started 2 years before she first saw her outpatient psychiatrist.

She says she has been prescribed several medications, but remembers only taking quetiapine for depressive symptoms and insomnia. After a discussion with her psychiatrist about the possible effects of quetiapine on the fetus, she discontinued the drug approximately 8 weeks into her pregnancy. Quetiapine decreased her movement symptoms slightly, and she feels her movements have become uncontrollable since discontinuing it.

She reports increased feelings of sadness, worthlessness, guilt, decreased energy, irritability, and difficulty sleeping during her pregnancy. She denies current or past psychotic symptoms or mania. Ms. A says she has noticed problems with her memory as well as increased confusion over recent months. She often gets lost and cannot remember where she lives after leaving her home.

Based on hospital records, we learn that an MRI of the brain without contrast was completed 1 year ago to “evaluate choreiform movements.” The scan showed mild atrophy and abnormal signal within the caudate and putamen, as well as volume loss. We consult with the neurology service to evaluate Ms. A’s abnormal movements and her previous abnormal brain imaging. The neurologic exam notes that Ms. A has orofacial dyskinesias and near-continuous choreiform movements in her arms and hands. Her gait remains wide-based and she is unable to tandem walk. Because Ms. A shows no new neurologic symptoms, the neurology service does not feel that additional neuroimaging is indicated.

The authors’ observations

In consultation with neurology, the leading differential diagnoses include tardive dyskinesia, chorea gravidarum, and Huntington’s disease. See the Table^1,2 for the differential diagnosis of chorea.

Ms. A reports taking quetiapine for 3 years, which suggests possible tardive dyskinesia. Although second-generation antipsychotics have a lower incidence of movement disorders than first-generation antipsychotics, the risk still exists. Withdrawal dyskinesias can occur after suddenly stopping or tapering antipsychotics and appear as extrapyramidal symptoms, including choreoathetosis similar to what Ms. A experienced.^3,4 This type of dyskinesia is thought to be secondary to chronic dopamine antagonism leading to increased postsynaptic receptors and dopamine hypersensitivity.⁵ Because Ms. A discontinued quetiapine early in her pregnancy, withdrawal dyskinesias are less likely.

Because Ms. A presented with a movement disorder while pregnant, the neurology service considers chorea gravidarum, the term given to chorea occurring during pregnancy. This syndrome is thought to be caused by the effects of pregnancy on the basal ganglia.⁶ Historically, chorea gravidarum was associated with rheumatic fever (RF); however, with the decline in prevalence of RF, most choreiform movements that appear during pregnancy typically are caused by other diseases, such as systemic lupus erythematosus or Huntington’s disease. Approximately one-half of chorea gravidarum cases are idiopathic, with RF and antiphospholipid syndrome accounting for the remainder.⁷ Huntington’s disease during pregnancy is rare because it tends to present in women beyond childbearing age.

Based on Ms. A’s symptoms and previous MRI findings, we ask her if she has a known family history of Huntington’s disease. She denies this, but says she has not seen her father since she was very young and is uncertain of his medical history.

Table

Differential diagnosis for chorea

TREATMENT: Restart medication

Ms. A’s laboratory results show a slightly low hemoglobin of 10.5 g/dL and hematocrit of 32.8%. Her mean corpuscular volume is slightly decreased at 77 fL. Her urinalysis is negative, and blood glucose and thyroid-stimulating hormone are within normal limits. Rapid plasma regain, anti-nuclear antibody, and human immunodeficiency virus (HIV) are negative. Based on hospital records, we learn that during the previous admission a year ago a serum ceruloplasmin and serum copper were drawn and were normal.

We contact Ms. A’s outpatient psychiatrist for collateral information. The psychiatrist says he first evaluated Ms. A 3 years ago after a friend brought her in because of strange behavior, including talking to herself, making odd facial gestures, and laughing inappropriately. Although Ms. A denies past psychiatric hospitalizations, her psychiatrist states that she was hospitalized for 1 week after the suicide attempt 4 years ago and prescribed lorazepam and sertraline during that admission. He speculates that the suicide attempt may have been related to 5 of her children being taken from her by the Department of Family and Child Services after police raided her home to search for drugs. Custody was awarded to their respective fathers, causing Ms. A to “snap,” according to her friend.

Since then, neither Ms. A nor her psychiatrist have reported any further psychotic symptoms. Her psychiatrist confirms that Ms. A’s abnormal movements were present before her first appointment with him. He says that he referred Ms. A to a local hospital for a neurology work-up, but she did not schedule an appointment.

When we follow up with Ms. A 2 days after delivery, she continues to deny depressive symptoms, although her affect remains blunted. She says she is looking forward to going home with the baby, whom she plans to bottle feed. Her choreiform movements appear unchanged. She also continues to experience lip smacking. Although Ms. A recognizes that she has some movements, she minimizes them and says they do not bother her. She continues to demonstrate latency in her verbal responses to questions. Based on the collateral history and positive response with quetiapine, we recommend that Ms. A be restarted on quetiapine, 200 mg/d.

The authors’ observations

Ms. A’s choreiform movements started before her psychotic symptoms and subsequent usage of neuroleptic medication, which makes tardive dyskinesia less likely. Laboratory studies rule out systemic lupus erythematosus, HIV, and Wilson’s disease as the cause of her abnormal movements.

Ms. A’s history is highly suggestive of Huntington’s disease. She exhibits classic motor signs, including involuntary choreiform movements in her extremities. She also has psychiatric symptoms that are commonly associated with Huntington’s disease, including depression—which preceded her motor symptoms—cognitive decline, apathy, and psychotic symptoms. In addition, her MRI findings of volume changes in the caudate nucleus and the putamen and inability to rule out a family history make Huntington’s disease more likely (Box).^1,8-11

Box

Psychiatric symptoms

Psychiatric symptoms frequently are evident in the early stages of Huntington’s disease, often before onset of motor symptoms.¹ Depression is the most common sign, and can be difficult to diagnose because weight loss, apathy, and inactivity also occur in Huntington’s disease. Feelings of low self-esteem, guilt, and anxiety can help distinguish depression from symptoms of Huntington’s disease. Cognitive decline also may present before the first motor symptoms occur. Cognitive changes typically are related to executive functions and affected individuals may develop impairments in organization and planning. Psychotic symptoms may be present, but are more common in later stages of the disease.¹

Ms. A reported that quetiapine seemed to lessen her choreiform movements, and dopamine receptor blocking agents (ie, antipsychotics) often are considered for managing chorea and psychosis in Huntington’s disease. However, there are few double-blind, placebo-controlled studies evaluating the efficacy of these agents.¹² Small, uncontrolled, nonrandomized trials found quetiapine has some efficacy for both motor and psychiatric symptoms in Huntington’s disease.^12-15

OUTCOME: Lost to follow-up

Ms. A is discharged from the hospital 3 days after she delivers her daughter and is given an appointment in 6 weeks at an affiliated movement disorders clinic. Before discharge, she is tested for the Huntington’s disease gene mutation with a plan to receive her results during her follow-up visit. During the informed consent process for the genetic testing, Ms. A states that she was tested previously and was quite sure that the test was positive for Huntington’s disease, although she could not recall where or when this testing was completed.

Ms. A also is scheduled to follow up with her obstetrician for a 6-week postpartum check-up and tubal ligation. We encourage Ms. A to make an appointment with her psychiatrist soon after discharge. We also make a referral to the Department of Family and Children Services to provide adequate support and resources to her and her children because of her physical and psychiatric issues.

Ms. A does not show up for her follow-up appointment at the movement disorders clinic. The genetic test is not completed during this admission because of a clerical error, and the serum sample subsequently expires.

The authors’ observations

Although Huntington’s disease is the most likely cause of Ms. A’s presentation, we were unable to confirm the diagnosis with genetic testing. If Ms. A returns to the neurology service and the genetic test is negative for Huntington’s disease, other causes of chorea must be investigated.

Related Resources

• De Marchi N, Mennella R. Huntington’s disease and its association with psychopathology. Harv Rev Psychiatry. 2000; 7(5):278-289.
• Revilla FJ, Grutzendler J, Larsh TR. Huntington disease. Medscape. http://emedicine.medscape.com/article/1150165-overview.

Drug Brand Names

• Hydralazine • Apresoline
• Lithium • Eskalith, Lithobid, others
• Lorazepam • Ativan
• Quetiapine • Seroquel
• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Abnormal movements

Pregnant and unsure of her due date, Ms. A, age 35, presents to the emergency room complaining of hourly uterine contractions for the last 3 days and new onset vaginal bleeding. Ms. A is admitted to the obstetrics (OB) service for preterm labor at 34 and 3/7 weeks as dated by a triage ultrasound.

During initial examination by the OB service, Ms. A’s blood pressure is 155/112 mm Hg with a pulse of 126. Her cervix is dilated to 4 centimeters. Her physical exam is notable for rapid, repetitive, involuntary movements in her upper extremities and to a lesser degree in lower extremities. Ms. A is started on IV fluids and hydralazine, 10 mg/d, for elevated blood pressure. Later that day, she delivers a preterm female weighing 2,360 grams in a spontaneous vaginal delivery without any complications.

After delivery, the OB service requests a psychiatric consultation to evaluate Ms. A’s “blunted affect,” history of heavy alcohol use, and abnormal movements. During examination, Ms. A is alert and oriented to her surroundings. She states that this was her eleventh pregnancy; however, she is unable to recall details of most previous pregnancies. She also cannot remember any significant medical, surgical, or mental health history. Ms. A appears distracted, has difficulty participating in the interview, and gives contradictory histories to different team members. She is well groomed but shows repetitive circular movements of her hands, feet, and jaw that are nearly continuous. In addition, Ms. A has intermittent lip biting and smacking. Her speech is delayed, with increased latency of her responses to basic questions.

Her mood is neutral, her affect is blunted, and she denies any current suicidal or homicidal ideations, delusions, and auditory or visual hallucinations. Although her chart indicates a history of alcohol abuse, she denies this history and current drug or alcohol use. Her Mini-Mental State Exam score is a 22/30, missing points in her ability to copy shapes and write a sentence, complicated by her chorea-like upper body movements. She also demonstrates marked inattentiveness and is unwilling to cooperate with spelling “world.” On physical exam, her gait is wide-based but steady.

The authors’ observations

Determining the cause of Ms. A’s abnormal movements, delayed speech, and neutral mood initially proves difficult because she is minimally cooperative with the interview and we find discrepancies between information she provides and her medical records from previous OB admissions. It is unclear whether these inconsistencies are because of her faltering memory—which she admits has worsened in the last year—or unwillingness to provide a complete medical history.

We consider possible substance intoxication given her documented history of substance use. However, an extended drug screen is negative and her laboratory values do not suggest heavy alcohol use.

HISTORY: Depression and confusion

The next day, Ms. A is more cooperative with the interview. She says that she began feeling depressed 8 years ago, around the time her brother was killed in a violent crime. She denies previous psychiatric hospitalizations, but says she attempted suicide 4 years ago by stabbing herself in the throat with a fork. After that attempt, she was referred to an outpatient psychiatrist whom she continues to see intermittently. She says that her abnormal movements started 2 years before she first saw her outpatient psychiatrist.

She says she has been prescribed several medications, but remembers only taking quetiapine for depressive symptoms and insomnia. After a discussion with her psychiatrist about the possible effects of quetiapine on the fetus, she discontinued the drug approximately 8 weeks into her pregnancy. Quetiapine decreased her movement symptoms slightly, and she feels her movements have become uncontrollable since discontinuing it.

She reports increased feelings of sadness, worthlessness, guilt, decreased energy, irritability, and difficulty sleeping during her pregnancy. She denies current or past psychotic symptoms or mania. Ms. A says she has noticed problems with her memory as well as increased confusion over recent months. She often gets lost and cannot remember where she lives after leaving her home.

Based on hospital records, we learn that an MRI of the brain without contrast was completed 1 year ago to “evaluate choreiform movements.” The scan showed mild atrophy and abnormal signal within the caudate and putamen, as well as volume loss. We consult with the neurology service to evaluate Ms. A’s abnormal movements and her previous abnormal brain imaging. The neurologic exam notes that Ms. A has orofacial dyskinesias and near-continuous choreiform movements in her arms and hands. Her gait remains wide-based and she is unable to tandem walk. Because Ms. A shows no new neurologic symptoms, the neurology service does not feel that additional neuroimaging is indicated.

The authors’ observations

In consultation with neurology, the leading differential diagnoses include tardive dyskinesia, chorea gravidarum, and Huntington’s disease. See the Table^1,2 for the differential diagnosis of chorea.

Ms. A reports taking quetiapine for 3 years, which suggests possible tardive dyskinesia. Although second-generation antipsychotics have a lower incidence of movement disorders than first-generation antipsychotics, the risk still exists. Withdrawal dyskinesias can occur after suddenly stopping or tapering antipsychotics and appear as extrapyramidal symptoms, including choreoathetosis similar to what Ms. A experienced.^3,4 This type of dyskinesia is thought to be secondary to chronic dopamine antagonism leading to increased postsynaptic receptors and dopamine hypersensitivity.⁵ Because Ms. A discontinued quetiapine early in her pregnancy, withdrawal dyskinesias are less likely.

Because Ms. A presented with a movement disorder while pregnant, the neurology service considers chorea gravidarum, the term given to chorea occurring during pregnancy. This syndrome is thought to be caused by the effects of pregnancy on the basal ganglia.⁶ Historically, chorea gravidarum was associated with rheumatic fever (RF); however, with the decline in prevalence of RF, most choreiform movements that appear during pregnancy typically are caused by other diseases, such as systemic lupus erythematosus or Huntington’s disease. Approximately one-half of chorea gravidarum cases are idiopathic, with RF and antiphospholipid syndrome accounting for the remainder.⁷ Huntington’s disease during pregnancy is rare because it tends to present in women beyond childbearing age.

Based on Ms. A’s symptoms and previous MRI findings, we ask her if she has a known family history of Huntington’s disease. She denies this, but says she has not seen her father since she was very young and is uncertain of his medical history.

Table

Differential diagnosis for chorea

TREATMENT: Restart medication

Ms. A’s laboratory results show a slightly low hemoglobin of 10.5 g/dL and hematocrit of 32.8%. Her mean corpuscular volume is slightly decreased at 77 fL. Her urinalysis is negative, and blood glucose and thyroid-stimulating hormone are within normal limits. Rapid plasma regain, anti-nuclear antibody, and human immunodeficiency virus (HIV) are negative. Based on hospital records, we learn that during the previous admission a year ago a serum ceruloplasmin and serum copper were drawn and were normal.

We contact Ms. A’s outpatient psychiatrist for collateral information. The psychiatrist says he first evaluated Ms. A 3 years ago after a friend brought her in because of strange behavior, including talking to herself, making odd facial gestures, and laughing inappropriately. Although Ms. A denies past psychiatric hospitalizations, her psychiatrist states that she was hospitalized for 1 week after the suicide attempt 4 years ago and prescribed lorazepam and sertraline during that admission. He speculates that the suicide attempt may have been related to 5 of her children being taken from her by the Department of Family and Child Services after police raided her home to search for drugs. Custody was awarded to their respective fathers, causing Ms. A to “snap,” according to her friend.

Since then, neither Ms. A nor her psychiatrist have reported any further psychotic symptoms. Her psychiatrist confirms that Ms. A’s abnormal movements were present before her first appointment with him. He says that he referred Ms. A to a local hospital for a neurology work-up, but she did not schedule an appointment.

When we follow up with Ms. A 2 days after delivery, she continues to deny depressive symptoms, although her affect remains blunted. She says she is looking forward to going home with the baby, whom she plans to bottle feed. Her choreiform movements appear unchanged. She also continues to experience lip smacking. Although Ms. A recognizes that she has some movements, she minimizes them and says they do not bother her. She continues to demonstrate latency in her verbal responses to questions. Based on the collateral history and positive response with quetiapine, we recommend that Ms. A be restarted on quetiapine, 200 mg/d.

The authors’ observations

Ms. A’s choreiform movements started before her psychotic symptoms and subsequent usage of neuroleptic medication, which makes tardive dyskinesia less likely. Laboratory studies rule out systemic lupus erythematosus, HIV, and Wilson’s disease as the cause of her abnormal movements.

Ms. A’s history is highly suggestive of Huntington’s disease. She exhibits classic motor signs, including involuntary choreiform movements in her extremities. She also has psychiatric symptoms that are commonly associated with Huntington’s disease, including depression—which preceded her motor symptoms—cognitive decline, apathy, and psychotic symptoms. In addition, her MRI findings of volume changes in the caudate nucleus and the putamen and inability to rule out a family history make Huntington’s disease more likely (Box).^1,8-11

Box

Psychiatric symptoms

Psychiatric symptoms frequently are evident in the early stages of Huntington’s disease, often before onset of motor symptoms.¹ Depression is the most common sign, and can be difficult to diagnose because weight loss, apathy, and inactivity also occur in Huntington’s disease. Feelings of low self-esteem, guilt, and anxiety can help distinguish depression from symptoms of Huntington’s disease. Cognitive decline also may present before the first motor symptoms occur. Cognitive changes typically are related to executive functions and affected individuals may develop impairments in organization and planning. Psychotic symptoms may be present, but are more common in later stages of the disease.¹

Ms. A reported that quetiapine seemed to lessen her choreiform movements, and dopamine receptor blocking agents (ie, antipsychotics) often are considered for managing chorea and psychosis in Huntington’s disease. However, there are few double-blind, placebo-controlled studies evaluating the efficacy of these agents.¹² Small, uncontrolled, nonrandomized trials found quetiapine has some efficacy for both motor and psychiatric symptoms in Huntington’s disease.^12-15

OUTCOME: Lost to follow-up

Ms. A is discharged from the hospital 3 days after she delivers her daughter and is given an appointment in 6 weeks at an affiliated movement disorders clinic. Before discharge, she is tested for the Huntington’s disease gene mutation with a plan to receive her results during her follow-up visit. During the informed consent process for the genetic testing, Ms. A states that she was tested previously and was quite sure that the test was positive for Huntington’s disease, although she could not recall where or when this testing was completed.

Ms. A also is scheduled to follow up with her obstetrician for a 6-week postpartum check-up and tubal ligation. We encourage Ms. A to make an appointment with her psychiatrist soon after discharge. We also make a referral to the Department of Family and Children Services to provide adequate support and resources to her and her children because of her physical and psychiatric issues.

Ms. A does not show up for her follow-up appointment at the movement disorders clinic. The genetic test is not completed during this admission because of a clerical error, and the serum sample subsequently expires.

The authors’ observations

Although Huntington’s disease is the most likely cause of Ms. A’s presentation, we were unable to confirm the diagnosis with genetic testing. If Ms. A returns to the neurology service and the genetic test is negative for Huntington’s disease, other causes of chorea must be investigated.

Related Resources

• De Marchi N, Mennella R. Huntington’s disease and its association with psychopathology. Harv Rev Psychiatry. 2000; 7(5):278-289.
• Revilla FJ, Grutzendler J, Larsh TR. Huntington disease. Medscape. http://emedicine.medscape.com/article/1150165-overview.

Drug Brand Names

• Hydralazine • Apresoline
• Lithium • Eskalith, Lithobid, others
• Lorazepam • Ativan
• Quetiapine • Seroquel
• Sertraline • Zoloft

Disclosure

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

This article, with accompanying video footage, is presented with the support of the International Academy of Pelvic Surgery.

The concept of utilizing the uterosacral ligaments to support the vaginal cuff and correct an enterocele is nothing new: As early as 1957, Milton McCall described what became known as the McCall culdoplasty, in which sutures incorporated the uterosacral ligaments into the posterior vaginal vault to obliterate the cul-de-sac and suspend or support the vaginal apex at the time of vaginal hysterectomy.¹

Later, in the 1990s, Richardson promoted the concept that, in patients who have pelvic organ prolapse, the uterosacral ligaments do not become attenuated, instead, they break at specific points.

Shull and colleagues took this idea and described how utilizing uterosacral ligaments to support the vaginal cuff can be performed vaginally—by passing sutures bilaterally through the uterosacral ligaments near the level of the ischial spine.²

Since Shull described this procedure, numerous published studies have demonstrated outcomes similar to other vaginal suspension procedures, such as sacrospinous ligament suspension.^3-5

Potential advantages of a high uterosacral vaginal vault suspension are that:

• it provides good apical support without significantly distorting the vaginal axis, making it applicable to all types of vaginal prolapse
• intraperitoneal passage of sutures can be a lot cleaner and simpler than passing sutures, or anchors, through retroperitoneal structures, such as the sacrospinous ligament (FIGURE 1).

FIGURE 1 Locating intraperitoneal sutures during uterosacral suspension

Cross-section of the pelvic floor shows where sutures are placed as part of McCall culdoplasty (1), traditional uterosacral suspension (2), and modified high uterosacral suspension (3). Note: High uterosacral suspension may involve passing the suture through the sacrospinous ligament–coccygeus (SSL-C) muscle complex (dashed oval) because a segment of the uterosacral ligament inserts into that structure.

A disadvantage of the procedure is that the uterosacral ligament may, at times, lie in close proximity to the ureter. Studies have shown that the ureter can become kinked when sutures in this procedure are passed too far laterally.^2-5

High uterosacral suspension has been our operation of choice for 11 years for patients who have pelvic organ prolapse in which the peritoneum is accessible (see “How this procedure evolved in our hands”). In this article, we provide a step-by-step description of the procedure. Four accompanying videos that further illuminate those steps are noted in the text here at appropriate places.(For example, Video #1, immediately below, sets the stage for the step-by-step discussion by reviewing pertinent pelvic anatomy.)

Details of the procedure

1. Enter the peritoneum

It’s our opinion that, even though extraperitoneal uterosacral suspension procedures have been described, the pertinent anatomic structures (again, see Video #1) are not easily identifiable unless suspension is undertaken intraperitoneally. Entering the peritoneum is, obviously, not a concern if the patient is undergoing vaginal hysterectomy. If the patient has post-hysterectomy prolapse, however, you must be able to isolate an enterocele and enter the peritoneum (follow FIGURE 2, beginning here and through subsequent steps of the procedure).

FIGURE 2 Step by step: High uterosacral vaginal vault suspension

A The most prominent portion of the prolapsed vaginal vault is grasped with two Allis clamps. B The vaginal wall is opened up and the enterocele sac is identified and entered. C The bowel is packed high into the pelvis using large laparotomy sponges. The retractor lifts the sponges out of the lower pelvis, thus completely exposing the cul-de-sac. When appropriate traction is placed downward on the uterosacral ligaments with an Allis clamp, the uterosacral ligaments are easily palpated bilaterally. D Delayed absorbable sutures have been passed through the uppermost portion of the uterosacral ligaments on each side, and have been individually tagged.
E Each end of the previously passed sutures is brought out through the posterior peritoneum and the posterior vaginal wall. (A free needle is used to pass both ends of these delayed absorbable sutures through the full thickness of the vaginal wall.) F Anterior colporrhaphy is begun by initiating dissection between the prolapsed bladder and the anterior vaginal wall. G Anterior colporrhaphy is complete. H The vagina has been appropriately trimmed and closed with interrupted or continuous delayed absorbable sutures. Delayed absorbable sutures that were previously brought out through the full thickness of the posterior vaginal wall are then tied; doing so elevates the prolapsed vaginal vault high up into the hollow of the sacrum.Once you have entered the peritoneum, the cul-de-sac must be relatively free of adhesive disease if you are to be able to continue with this procedure. (See “5 surgical pearls for high ureterosacral vaginal vault suspension”)

2. Pack the bowel; expose the uterosacral ligaments

Next, pack the small bowel out of the cul-de-sac to allow easy access and visualization of the uppermost portions of the uterosacral ligament. This is best accomplished by passing large, moistened laparotomy sponges intraperitoneally and elevating them with a large retractor (e.g., Deaver, Breisky-Navrital, Sweetheart).

When the bowel is appropriately packed, the retractor lifts the intestinal contents out of the pelvis, usually allowing easy access to the proximal or uppermost portion of the uterosacral ligaments (see Video #3, which focuses on the anatomy of the uterosacral ligament).

When performing high uterosacral suspension, it is possible to pass sutures through the coccygeus muscle-sacrospinous ligament complex (arrow) because a segment of the uterosacral ligament inserts into that structure.

3. Palpate the ischial spines bilaterally

It’s important that you palpate the ischial spines. Often, the ureter can be palpated against the pelvic sidewall. If you palpate the ischial spines and continue to palpate medially and cephalad, you can usually palpate the coccygeus muscle-sacrospinous ligament complex transperitoneally because a portion of the uterosacral ligament inserts into the sacrospinous ligament.⁶

If sutures can be passed at this level, the result will (usually) be a vagina that is, at minimum, approximately 9 cm long.

FIGURE 3 Access to the sacrospinous ligament

The sacrospinous ligament can be palpated and exposed along any one of three approaches: anterior paravaginally (A), transperitoneally (B), and posterior pararectally (C).

4. Pass the sutures

We prefer to pass two or three sutures on each side, utilizing a long, straight needle holder. Because we eventually pass the sutures through the full thickness of the posterior vaginal wall, we’ve opted for a delayed absorbable suture—preferably, 0 Vicryl on a CT-2 needle.

A Breisky-Navrital retractor is utilized to retract the sigmoid colon in the opposite direction of the ligament in which the sutures are being passed. At times, attaching a light to a suction device or a retractor is also helpful to visualize this area.

Use an Allis clamp to elevate and apply traction on the distal uterosacral ligament; this facilitates palpation and visualization of the appropriate site for placement of the sutures. The exact area of suture passage is best identified by palpation.

(Note: In early descriptions of this procedure, permanent sutures were utilized; again, we use delayed absorbable sutures because all sutures are brought out through the full thickness of the posterior vaginal wall. Permanent suture in our approach would be unacceptable because the sutures are tied in the lumen of the vagina. In some other modifications of this procedure, sutures are passed through the muscular layer of the vagina to exclude epithelium; under those circumstances, permanent sutures can be utilized.)

Once the sutures are brought through the full thickness of the posterior vaginal wall—including the peritoneum, if possible—tag them individually. If the anterior segment is well-supported, close the vaginal incision with a continuous delayed absorbable suture.

Tie the suspension sutures, elevating the apex into the hollow of the sacrum.

If anterior colporrhaphy is needed, perform that repair. Close the anterior vaginal wall as well as the vaginal cuff before tying off the suspension sutures.

5. Ensure that the ureters are patent

After the sutures are tied, instruct the anesthesiologist to administer 5 cc of indigo carmine dye intravenously. Assuming no renal compromise, you should see dye in the bladder 5 to 10 minutes later. If the patient is elderly or if you want to expedite this step, furosemide, 5 to 10 mg, can be given by IV push.

Next, perform cystoscopy to ensure ureteral patency. You should observe a spill of dye-colored urine out of both ureteral orifices. If dye does not spill from either orifice after a reasonable wait (usually, 20 minutes), assume that the ureter on that side is obstructed.

FIGURE 4 Providing support for the posterior vaginal wall

A View of a posterior vaginal wall defect secondary to an enterocele and rectocele. B After entry into the enterocele sac, intraperitoneal suspension sutures are brought out through the full thickness of the vaginal wall at the level of the apex. C Tying these sutures after the vaginal incision is closed at the apex not only results in greater vaginal length but also contributes to overall support of the entire posterior vaginal wall.

6. Completely reconstruct the vagina

The remainder of steps required to complete the procedure usually involve posterior colporrhaphy and perineoplasty. We also reserve placement of a synthetic midurethral sling (if one is needed) until after the vault procedure is complete.

Refer to FIGURE 2 for a step-by step guide to how best to perform high uterosacral vaginal vault suspension.

Questions often asked about this procedure

What do I do if I can’t isolate an enterocele sac and enter it?

Perform a unilateral or bilateral sacrospinous ligament colpopexy.

Is it always possible to identify a usable uterosacral ligament in patients who have advanced prolapse?

We’ve found it extremely rare not to be able identify a usable and durable structure.

The trick to identifying the ligament is to pass an Allis clamp so that one end is positioned intraperitoneally, as high up as possible, and the other end is on the vaginal mucosa side. Elevating the clamp puts the ligament on tension. These clamps are usually placed between 4 and 5 o’clock on the left side and between 7 and 8 o’clock on the right side.

With appropriate traction, the ligament can usually be easily palpated.

If I don’t see indigo carmine dye spilling from one side during cystoscopy, what sequence of events should I undertake?

If the only sutures placed on that side were the uterosacral ligament sutures, cut them individually. If the ureter spills dye after a suture is cut, decide whether you think it is appropriate to replace that suture. Sometimes, unilateral suspension or a suspension with one remaining suture on the side where you cut a suture or two is sufficient.

If you do want to replace a cut suture, ureteral patency must be confirmed again after it is replaced.

No further management of the ureter is required—that is, it isn’t necessary to catheterize the ureter or perform postoperative imaging studies. If anterior colporrhaphy has also been performed, however, apply your highest index of suspicion to determine the source of the offending suture: the uterosacral suspension or the anterior repair.*

If the patient has severe hip or leg pain postoperatively, what should I suspect is wrong? How should I manage this complication?

The nerve to the levator ani runs within the coccygeus muscle. In a thin patient, in whom deep bites are taken, the nerve is often injured or trapped. Such trauma can cause hip pain that is fairly severe but that is almost always self-limiting and requires only nonsteroidal anti-inflammatory medication. Usually, this complication resolves within 2 weeks after surgery.

Significant postoperative pain that radiates down the back of the thigh or down the leg all the way to the foot is of greater concern because one of the sacral nerve segments has most likely been injured or stretched. Obtain a neurology consult; rarely, it becomes necessary to take the patient back to surgery to cut the offending suture.

*For detailed discussion of this subject, see the International Academy of Pelvic Surgery’s August 2010 “Case of the month” at www.academyofpelvicsurgery.com.

We want to hear from you! Tell us what you think.

This article, with accompanying video footage, is presented with the support of the International Academy of Pelvic Surgery.

The concept of utilizing the uterosacral ligaments to support the vaginal cuff and correct an enterocele is nothing new: As early as 1957, Milton McCall described what became known as the McCall culdoplasty, in which sutures incorporated the uterosacral ligaments into the posterior vaginal vault to obliterate the cul-de-sac and suspend or support the vaginal apex at the time of vaginal hysterectomy.¹

Later, in the 1990s, Richardson promoted the concept that, in patients who have pelvic organ prolapse, the uterosacral ligaments do not become attenuated, instead, they break at specific points.

Shull and colleagues took this idea and described how utilizing uterosacral ligaments to support the vaginal cuff can be performed vaginally—by passing sutures bilaterally through the uterosacral ligaments near the level of the ischial spine.²

Since Shull described this procedure, numerous published studies have demonstrated outcomes similar to other vaginal suspension procedures, such as sacrospinous ligament suspension.^3-5

Potential advantages of a high uterosacral vaginal vault suspension are that:

• it provides good apical support without significantly distorting the vaginal axis, making it applicable to all types of vaginal prolapse
• intraperitoneal passage of sutures can be a lot cleaner and simpler than passing sutures, or anchors, through retroperitoneal structures, such as the sacrospinous ligament (FIGURE 1).

FIGURE 1 Locating intraperitoneal sutures during uterosacral suspension

Cross-section of the pelvic floor shows where sutures are placed as part of McCall culdoplasty (1), traditional uterosacral suspension (2), and modified high uterosacral suspension (3). Note: High uterosacral suspension may involve passing the suture through the sacrospinous ligament–coccygeus (SSL-C) muscle complex (dashed oval) because a segment of the uterosacral ligament inserts into that structure.

A disadvantage of the procedure is that the uterosacral ligament may, at times, lie in close proximity to the ureter. Studies have shown that the ureter can become kinked when sutures in this procedure are passed too far laterally.^2-5

High uterosacral suspension has been our operation of choice for 11 years for patients who have pelvic organ prolapse in which the peritoneum is accessible (see “How this procedure evolved in our hands”). In this article, we provide a step-by-step description of the procedure. Four accompanying videos that further illuminate those steps are noted in the text here at appropriate places.(For example, Video #1, immediately below, sets the stage for the step-by-step discussion by reviewing pertinent pelvic anatomy.)

Details of the procedure

1. Enter the peritoneum

It’s our opinion that, even though extraperitoneal uterosacral suspension procedures have been described, the pertinent anatomic structures (again, see Video #1) are not easily identifiable unless suspension is undertaken intraperitoneally. Entering the peritoneum is, obviously, not a concern if the patient is undergoing vaginal hysterectomy. If the patient has post-hysterectomy prolapse, however, you must be able to isolate an enterocele and enter the peritoneum (follow FIGURE 2, beginning here and through subsequent steps of the procedure).

FIGURE 2 Step by step: High uterosacral vaginal vault suspension

A The most prominent portion of the prolapsed vaginal vault is grasped with two Allis clamps. B The vaginal wall is opened up and the enterocele sac is identified and entered. C The bowel is packed high into the pelvis using large laparotomy sponges. The retractor lifts the sponges out of the lower pelvis, thus completely exposing the cul-de-sac. When appropriate traction is placed downward on the uterosacral ligaments with an Allis clamp, the uterosacral ligaments are easily palpated bilaterally. D Delayed absorbable sutures have been passed through the uppermost portion of the uterosacral ligaments on each side, and have been individually tagged.
E Each end of the previously passed sutures is brought out through the posterior peritoneum and the posterior vaginal wall. (A free needle is used to pass both ends of these delayed absorbable sutures through the full thickness of the vaginal wall.) F Anterior colporrhaphy is begun by initiating dissection between the prolapsed bladder and the anterior vaginal wall. G Anterior colporrhaphy is complete. H The vagina has been appropriately trimmed and closed with interrupted or continuous delayed absorbable sutures. Delayed absorbable sutures that were previously brought out through the full thickness of the posterior vaginal wall are then tied; doing so elevates the prolapsed vaginal vault high up into the hollow of the sacrum.Once you have entered the peritoneum, the cul-de-sac must be relatively free of adhesive disease if you are to be able to continue with this procedure. (See “5 surgical pearls for high ureterosacral vaginal vault suspension”)

2. Pack the bowel; expose the uterosacral ligaments

Next, pack the small bowel out of the cul-de-sac to allow easy access and visualization of the uppermost portions of the uterosacral ligament. This is best accomplished by passing large, moistened laparotomy sponges intraperitoneally and elevating them with a large retractor (e.g., Deaver, Breisky-Navrital, Sweetheart).

When the bowel is appropriately packed, the retractor lifts the intestinal contents out of the pelvis, usually allowing easy access to the proximal or uppermost portion of the uterosacral ligaments (see Video #3, which focuses on the anatomy of the uterosacral ligament).

When performing high uterosacral suspension, it is possible to pass sutures through the coccygeus muscle-sacrospinous ligament complex (arrow) because a segment of the uterosacral ligament inserts into that structure.

3. Palpate the ischial spines bilaterally

It’s important that you palpate the ischial spines. Often, the ureter can be palpated against the pelvic sidewall. If you palpate the ischial spines and continue to palpate medially and cephalad, you can usually palpate the coccygeus muscle-sacrospinous ligament complex transperitoneally because a portion of the uterosacral ligament inserts into the sacrospinous ligament.⁶

If sutures can be passed at this level, the result will (usually) be a vagina that is, at minimum, approximately 9 cm long.

FIGURE 3 Access to the sacrospinous ligament

The sacrospinous ligament can be palpated and exposed along any one of three approaches: anterior paravaginally (A), transperitoneally (B), and posterior pararectally (C).

4. Pass the sutures

We prefer to pass two or three sutures on each side, utilizing a long, straight needle holder. Because we eventually pass the sutures through the full thickness of the posterior vaginal wall, we’ve opted for a delayed absorbable suture—preferably, 0 Vicryl on a CT-2 needle.

A Breisky-Navrital retractor is utilized to retract the sigmoid colon in the opposite direction of the ligament in which the sutures are being passed. At times, attaching a light to a suction device or a retractor is also helpful to visualize this area.

Use an Allis clamp to elevate and apply traction on the distal uterosacral ligament; this facilitates palpation and visualization of the appropriate site for placement of the sutures. The exact area of suture passage is best identified by palpation.

(Note: In early descriptions of this procedure, permanent sutures were utilized; again, we use delayed absorbable sutures because all sutures are brought out through the full thickness of the posterior vaginal wall. Permanent suture in our approach would be unacceptable because the sutures are tied in the lumen of the vagina. In some other modifications of this procedure, sutures are passed through the muscular layer of the vagina to exclude epithelium; under those circumstances, permanent sutures can be utilized.)

Once the sutures are brought through the full thickness of the posterior vaginal wall—including the peritoneum, if possible—tag them individually. If the anterior segment is well-supported, close the vaginal incision with a continuous delayed absorbable suture.

Tie the suspension sutures, elevating the apex into the hollow of the sacrum.

If anterior colporrhaphy is needed, perform that repair. Close the anterior vaginal wall as well as the vaginal cuff before tying off the suspension sutures.

5. Ensure that the ureters are patent

After the sutures are tied, instruct the anesthesiologist to administer 5 cc of indigo carmine dye intravenously. Assuming no renal compromise, you should see dye in the bladder 5 to 10 minutes later. If the patient is elderly or if you want to expedite this step, furosemide, 5 to 10 mg, can be given by IV push.

Next, perform cystoscopy to ensure ureteral patency. You should observe a spill of dye-colored urine out of both ureteral orifices. If dye does not spill from either orifice after a reasonable wait (usually, 20 minutes), assume that the ureter on that side is obstructed.

FIGURE 4 Providing support for the posterior vaginal wall

A View of a posterior vaginal wall defect secondary to an enterocele and rectocele. B After entry into the enterocele sac, intraperitoneal suspension sutures are brought out through the full thickness of the vaginal wall at the level of the apex. C Tying these sutures after the vaginal incision is closed at the apex not only results in greater vaginal length but also contributes to overall support of the entire posterior vaginal wall.

6. Completely reconstruct the vagina

The remainder of steps required to complete the procedure usually involve posterior colporrhaphy and perineoplasty. We also reserve placement of a synthetic midurethral sling (if one is needed) until after the vault procedure is complete.

Refer to FIGURE 2 for a step-by step guide to how best to perform high uterosacral vaginal vault suspension.

Questions often asked about this procedure

What do I do if I can’t isolate an enterocele sac and enter it?

Perform a unilateral or bilateral sacrospinous ligament colpopexy.

Is it always possible to identify a usable uterosacral ligament in patients who have advanced prolapse?

We’ve found it extremely rare not to be able identify a usable and durable structure.

The trick to identifying the ligament is to pass an Allis clamp so that one end is positioned intraperitoneally, as high up as possible, and the other end is on the vaginal mucosa side. Elevating the clamp puts the ligament on tension. These clamps are usually placed between 4 and 5 o’clock on the left side and between 7 and 8 o’clock on the right side.

With appropriate traction, the ligament can usually be easily palpated.

If I don’t see indigo carmine dye spilling from one side during cystoscopy, what sequence of events should I undertake?

If the only sutures placed on that side were the uterosacral ligament sutures, cut them individually. If the ureter spills dye after a suture is cut, decide whether you think it is appropriate to replace that suture. Sometimes, unilateral suspension or a suspension with one remaining suture on the side where you cut a suture or two is sufficient.

If you do want to replace a cut suture, ureteral patency must be confirmed again after it is replaced.

No further management of the ureter is required—that is, it isn’t necessary to catheterize the ureter or perform postoperative imaging studies. If anterior colporrhaphy has also been performed, however, apply your highest index of suspicion to determine the source of the offending suture: the uterosacral suspension or the anterior repair.*

If the patient has severe hip or leg pain postoperatively, what should I suspect is wrong? How should I manage this complication?

The nerve to the levator ani runs within the coccygeus muscle. In a thin patient, in whom deep bites are taken, the nerve is often injured or trapped. Such trauma can cause hip pain that is fairly severe but that is almost always self-limiting and requires only nonsteroidal anti-inflammatory medication. Usually, this complication resolves within 2 weeks after surgery.

Significant postoperative pain that radiates down the back of the thigh or down the leg all the way to the foot is of greater concern because one of the sacral nerve segments has most likely been injured or stretched. Obtain a neurology consult; rarely, it becomes necessary to take the patient back to surgery to cut the offending suture.

*For detailed discussion of this subject, see the International Academy of Pelvic Surgery’s August 2010 “Case of the month” at www.academyofpelvicsurgery.com.

We want to hear from you! Tell us what you think.

This article, with accompanying video footage, is presented with the support of the International Academy of Pelvic Surgery.

The concept of utilizing the uterosacral ligaments to support the vaginal cuff and correct an enterocele is nothing new: As early as 1957, Milton McCall described what became known as the McCall culdoplasty, in which sutures incorporated the uterosacral ligaments into the posterior vaginal vault to obliterate the cul-de-sac and suspend or support the vaginal apex at the time of vaginal hysterectomy.¹

Later, in the 1990s, Richardson promoted the concept that, in patients who have pelvic organ prolapse, the uterosacral ligaments do not become attenuated, instead, they break at specific points.

Shull and colleagues took this idea and described how utilizing uterosacral ligaments to support the vaginal cuff can be performed vaginally—by passing sutures bilaterally through the uterosacral ligaments near the level of the ischial spine.²

Since Shull described this procedure, numerous published studies have demonstrated outcomes similar to other vaginal suspension procedures, such as sacrospinous ligament suspension.^3-5

Potential advantages of a high uterosacral vaginal vault suspension are that:

• it provides good apical support without significantly distorting the vaginal axis, making it applicable to all types of vaginal prolapse
• intraperitoneal passage of sutures can be a lot cleaner and simpler than passing sutures, or anchors, through retroperitoneal structures, such as the sacrospinous ligament (FIGURE 1).

FIGURE 1 Locating intraperitoneal sutures during uterosacral suspension

Cross-section of the pelvic floor shows where sutures are placed as part of McCall culdoplasty (1), traditional uterosacral suspension (2), and modified high uterosacral suspension (3). Note: High uterosacral suspension may involve passing the suture through the sacrospinous ligament–coccygeus (SSL-C) muscle complex (dashed oval) because a segment of the uterosacral ligament inserts into that structure.

A disadvantage of the procedure is that the uterosacral ligament may, at times, lie in close proximity to the ureter. Studies have shown that the ureter can become kinked when sutures in this procedure are passed too far laterally.^2-5

High uterosacral suspension has been our operation of choice for 11 years for patients who have pelvic organ prolapse in which the peritoneum is accessible (see “How this procedure evolved in our hands”). In this article, we provide a step-by-step description of the procedure. Four accompanying videos that further illuminate those steps are noted in the text here at appropriate places.(For example, Video #1, immediately below, sets the stage for the step-by-step discussion by reviewing pertinent pelvic anatomy.)

Details of the procedure

1. Enter the peritoneum

It’s our opinion that, even though extraperitoneal uterosacral suspension procedures have been described, the pertinent anatomic structures (again, see Video #1) are not easily identifiable unless suspension is undertaken intraperitoneally. Entering the peritoneum is, obviously, not a concern if the patient is undergoing vaginal hysterectomy. If the patient has post-hysterectomy prolapse, however, you must be able to isolate an enterocele and enter the peritoneum (follow FIGURE 2, beginning here and through subsequent steps of the procedure).

FIGURE 2 Step by step: High uterosacral vaginal vault suspension

A The most prominent portion of the prolapsed vaginal vault is grasped with two Allis clamps. B The vaginal wall is opened up and the enterocele sac is identified and entered. C The bowel is packed high into the pelvis using large laparotomy sponges. The retractor lifts the sponges out of the lower pelvis, thus completely exposing the cul-de-sac. When appropriate traction is placed downward on the uterosacral ligaments with an Allis clamp, the uterosacral ligaments are easily palpated bilaterally. D Delayed absorbable sutures have been passed through the uppermost portion of the uterosacral ligaments on each side, and have been individually tagged.
E Each end of the previously passed sutures is brought out through the posterior peritoneum and the posterior vaginal wall. (A free needle is used to pass both ends of these delayed absorbable sutures through the full thickness of the vaginal wall.) F Anterior colporrhaphy is begun by initiating dissection between the prolapsed bladder and the anterior vaginal wall. G Anterior colporrhaphy is complete. H The vagina has been appropriately trimmed and closed with interrupted or continuous delayed absorbable sutures. Delayed absorbable sutures that were previously brought out through the full thickness of the posterior vaginal wall are then tied; doing so elevates the prolapsed vaginal vault high up into the hollow of the sacrum.Once you have entered the peritoneum, the cul-de-sac must be relatively free of adhesive disease if you are to be able to continue with this procedure. (See “5 surgical pearls for high ureterosacral vaginal vault suspension”)

2. Pack the bowel; expose the uterosacral ligaments

Next, pack the small bowel out of the cul-de-sac to allow easy access and visualization of the uppermost portions of the uterosacral ligament. This is best accomplished by passing large, moistened laparotomy sponges intraperitoneally and elevating them with a large retractor (e.g., Deaver, Breisky-Navrital, Sweetheart).

When the bowel is appropriately packed, the retractor lifts the intestinal contents out of the pelvis, usually allowing easy access to the proximal or uppermost portion of the uterosacral ligaments (see Video #3, which focuses on the anatomy of the uterosacral ligament).

When performing high uterosacral suspension, it is possible to pass sutures through the coccygeus muscle-sacrospinous ligament complex (arrow) because a segment of the uterosacral ligament inserts into that structure.

3. Palpate the ischial spines bilaterally

It’s important that you palpate the ischial spines. Often, the ureter can be palpated against the pelvic sidewall. If you palpate the ischial spines and continue to palpate medially and cephalad, you can usually palpate the coccygeus muscle-sacrospinous ligament complex transperitoneally because a portion of the uterosacral ligament inserts into the sacrospinous ligament.⁶

If sutures can be passed at this level, the result will (usually) be a vagina that is, at minimum, approximately 9 cm long.

FIGURE 3 Access to the sacrospinous ligament

The sacrospinous ligament can be palpated and exposed along any one of three approaches: anterior paravaginally (A), transperitoneally (B), and posterior pararectally (C).

4. Pass the sutures

We prefer to pass two or three sutures on each side, utilizing a long, straight needle holder. Because we eventually pass the sutures through the full thickness of the posterior vaginal wall, we’ve opted for a delayed absorbable suture—preferably, 0 Vicryl on a CT-2 needle.

A Breisky-Navrital retractor is utilized to retract the sigmoid colon in the opposite direction of the ligament in which the sutures are being passed. At times, attaching a light to a suction device or a retractor is also helpful to visualize this area.

Use an Allis clamp to elevate and apply traction on the distal uterosacral ligament; this facilitates palpation and visualization of the appropriate site for placement of the sutures. The exact area of suture passage is best identified by palpation.

(Note: In early descriptions of this procedure, permanent sutures were utilized; again, we use delayed absorbable sutures because all sutures are brought out through the full thickness of the posterior vaginal wall. Permanent suture in our approach would be unacceptable because the sutures are tied in the lumen of the vagina. In some other modifications of this procedure, sutures are passed through the muscular layer of the vagina to exclude epithelium; under those circumstances, permanent sutures can be utilized.)

Once the sutures are brought through the full thickness of the posterior vaginal wall—including the peritoneum, if possible—tag them individually. If the anterior segment is well-supported, close the vaginal incision with a continuous delayed absorbable suture.

Tie the suspension sutures, elevating the apex into the hollow of the sacrum.

If anterior colporrhaphy is needed, perform that repair. Close the anterior vaginal wall as well as the vaginal cuff before tying off the suspension sutures.

5. Ensure that the ureters are patent

After the sutures are tied, instruct the anesthesiologist to administer 5 cc of indigo carmine dye intravenously. Assuming no renal compromise, you should see dye in the bladder 5 to 10 minutes later. If the patient is elderly or if you want to expedite this step, furosemide, 5 to 10 mg, can be given by IV push.

Next, perform cystoscopy to ensure ureteral patency. You should observe a spill of dye-colored urine out of both ureteral orifices. If dye does not spill from either orifice after a reasonable wait (usually, 20 minutes), assume that the ureter on that side is obstructed.

FIGURE 4 Providing support for the posterior vaginal wall

A View of a posterior vaginal wall defect secondary to an enterocele and rectocele. B After entry into the enterocele sac, intraperitoneal suspension sutures are brought out through the full thickness of the vaginal wall at the level of the apex. C Tying these sutures after the vaginal incision is closed at the apex not only results in greater vaginal length but also contributes to overall support of the entire posterior vaginal wall.

6. Completely reconstruct the vagina

The remainder of steps required to complete the procedure usually involve posterior colporrhaphy and perineoplasty. We also reserve placement of a synthetic midurethral sling (if one is needed) until after the vault procedure is complete.

Refer to FIGURE 2 for a step-by step guide to how best to perform high uterosacral vaginal vault suspension.

Questions often asked about this procedure

What do I do if I can’t isolate an enterocele sac and enter it?

Perform a unilateral or bilateral sacrospinous ligament colpopexy.

Is it always possible to identify a usable uterosacral ligament in patients who have advanced prolapse?

We’ve found it extremely rare not to be able identify a usable and durable structure.

The trick to identifying the ligament is to pass an Allis clamp so that one end is positioned intraperitoneally, as high up as possible, and the other end is on the vaginal mucosa side. Elevating the clamp puts the ligament on tension. These clamps are usually placed between 4 and 5 o’clock on the left side and between 7 and 8 o’clock on the right side.

With appropriate traction, the ligament can usually be easily palpated.

If I don’t see indigo carmine dye spilling from one side during cystoscopy, what sequence of events should I undertake?

If the only sutures placed on that side were the uterosacral ligament sutures, cut them individually. If the ureter spills dye after a suture is cut, decide whether you think it is appropriate to replace that suture. Sometimes, unilateral suspension or a suspension with one remaining suture on the side where you cut a suture or two is sufficient.

If you do want to replace a cut suture, ureteral patency must be confirmed again after it is replaced.

No further management of the ureter is required—that is, it isn’t necessary to catheterize the ureter or perform postoperative imaging studies. If anterior colporrhaphy has also been performed, however, apply your highest index of suspicion to determine the source of the offending suture: the uterosacral suspension or the anterior repair.*

If the patient has severe hip or leg pain postoperatively, what should I suspect is wrong? How should I manage this complication?

The nerve to the levator ani runs within the coccygeus muscle. In a thin patient, in whom deep bites are taken, the nerve is often injured or trapped. Such trauma can cause hip pain that is fairly severe but that is almost always self-limiting and requires only nonsteroidal anti-inflammatory medication. Usually, this complication resolves within 2 weeks after surgery.

Significant postoperative pain that radiates down the back of the thigh or down the leg all the way to the foot is of greater concern because one of the sacral nerve segments has most likely been injured or stretched. Obtain a neurology consult; rarely, it becomes necessary to take the patient back to surgery to cut the offending suture.

*For detailed discussion of this subject, see the International Academy of Pelvic Surgery’s August 2010 “Case of the month” at www.academyofpelvicsurgery.com.

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