In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

In January 2018, the American Academy of Dermatology (AAD) released its first guidelines of care for the management of nonmelanoma skin cancer (NMSC), which established official recommendations for the treatment of basal cell carcinoma (BCC)¹ and cutaneous squamous cell carcinoma (cSCC).² The guidelines will help dermatologists address the growing health concern of skin cancer, which remains the most common of any type of cancer in the United States.³ Affecting more than 3 million Americans every year, NMSC is the most common type of skin cancer, and its incidence has continued to increase every year over the past few decades.^3,4 During the past 30 years, the incidence of both BCC and cSCC has more than doubled.⁵

Commonly used guidelines for the management of NMSC are available from the National Comprehensive Cancer Network (NCCN).^6,7 Although the NCCN aimed to develop multidisciplinary guidelines, the new AAD guidelines were established primarily by dermatologists for dermatologists. The NCCN guidelines frequently are referenced throughout the new AAD guidelines, which also recognize the importance of multidisciplinary care. The authors of the AAD guidelines noted that, although many of the NCCN recommendations reiterated prevailing knowledge or current practice, some recommendations highlighted alternative tenets that were not as widely considered or were supported by insufficient evidence.

The AAD guidelines address the complete management of NMSC, which includes biopsy technique, staging, treatment, follow-up, metastatic disease, and prevention.^1,2 Also included are evidence tables evaluating the current literature and available recommendations.

BCC Guidelines

For suspected BCCs, the recommended biopsy techniques are punch biopsy, shave biopsy, and excisional biopsy, all of which can detect the most aggressive histology subtypes.¹ Rebiopsy is recommended if the initial specimen is inadequate. The pathology report should include histologic subtype, invasion beyond the reticular dermis, and perineural involvement. The AAD guidelines do not include a formal staging system for risk stratification but rather refer to the NCCN guidelines, which take both clinical and pathologic parameters into account. The AAD treatment recommendations are based on this stratification.¹

Treatment of BCC includes a broad range of therapeutic modalities. Recurrence rate, preservation of function, patient expectations, and potential adverse effects should be considered in the treatment plan.¹ Curettage and electrodessication may be considered for low-risk tumors in nonterminal hair-bearing locations. Surgical excision with 4-mm margins is recommended for low-risk primary tumors. For high-risk BCC, Mohs micrographic surgery is recommended, although standard excision along with attention to margin control may also be considered. Nonsurgical treatments also may be considered when more effective surgical therapies are contraindicated or impractical. If surgical therapy is not feasible or preferred, other treatment options for low-risk BCCs include cryotherapy, topical 5-fluorouracil, topical imiquimod, photodynamic therapy, or radiation therapy; however, the cure rates for these modalities may be lower than with surgical treatment. The AAD guidelines also note that there is insufficient evidence to recommend routine use of laser or electronic surface brachytherapy.¹

Multidisciplinary consultation is recommended in patients with metastatic BCCs along with first-line treatment with a smoothened inhibitor.¹ Alternative treatment options include platinum-based chemotherapy and/or supportive care. For locally advanced disease, surgery and radiation therapy remain the initial treatments, but smoothened inhibitors and supportive care are suitable alternative treatments.¹

The AAD guidelines also offer recommendations for follow-up and reducing future risk of skin cancer. After the first diagnosis of BCC, a skin cancer screening should be performed at least annually, and patients should be counseled about self-examinations and sun protection.¹ Topical and oral retinoids are not recommended for the prevention of additional skin cancers, nor is dietary supplementation with selenium or beta-carotene. There also is insufficient evidence regarding the use of oral nicotinamide, celecoxib, or α-difluoromethylornithine for chemoprevention of disease.¹

cSCC Guidelines

For suspected cSCCs, no single optimal biopsy technique is recommended, but repeat biopsy may be considered if the initial biopsy is insufficient for diagnosis.² The guidelines further recommend an extensive list of elements to be included in the final pathology report (eg, lesion size, immunosuppression, depth of invasion, degree of differentiation). There is no universally recognized stratification for localized cSCC; therefore, the AAD guidelines refer to the framework provided by the NCCN. Also mentioned is the recent release of the American Joint Committee on Cancer’s staging manual,⁸ which includes the management of cSCC in conjunction with all SCCs of the head and neck. The Brigham and Women’s system⁹ was considered as an alternative classification system; however, the NCCN guidelines were chosen because they primarily provide clinical guidance for treatment of cSCC rather than provide accurate prognostication or outcome assessment.

Considerations for surgical treatment of cSCC are similar to those for BCC.² In low-risk tumors, surgical excision with 4- to 6-mm margins to the midsubcutaneous fat or curettage with electrodessication may be considered. Mohs micrographic surgery or standard excision with attention to margin control may be considered for high-risk tumors. Nonsurgical therapies generally are not recommended as a first-line treatment, particularly in cSCC, due to possible recurrence and metastasis. When nonsurgical therapies are preferred, options may include cryosurgery or radiation therapy, with the understanding that cure rates may be lower than with surgical options. Topical therapy with imiquimod or 5-fluorouracil as well as photodynamic or laser therapy are not recommended for cSCCs.²

For patients with metastatic cSCC or locally advanced disease, multidisciplinary consultation is recommended.² In cSCCs with regional lymph node metastases, the recommended approach includes surgical resection with possible adjuvant radiation therapy and/or systemic therapy. For inoperable disease, combination chemoradiation may be considered. Epidermal growth factor inhibitors and cisplatin may be considered in metastatic disease, although there are limited data to support their efficacy. As with BCC, all patients with cSCCs should receive supportive and palliative care to optimize quality of life.²

Recommendations for follow-up after the first diagnosis of cSCC are the same as those for BCC.² Additionally, acitretin is the only therapy that may be beneficial in the reduction of recurrent skin cancer in patients who are solid-organ transplant recipients.

Final Thoughts

A comprehensive understanding of the management of NMSC and the evidence on which recommendations are based is critically important for optimal patient care. These guidelines are an efficient way for dermatologists and their colleagues to understand the latest evidence and recommendations. The AAD guidelines provide support for clinical decision making with standardized approaches to the diagnosis, care, and prevention of NMSC that are consistent with established practice patterns.

With few exceptions, surgical therapy is the most effective approach for the treatment of BCC and cSCC; however, the AAD guidelines include an important review on nonsurgical management options.^1,2 The AAD guidelines help to highlight where data on evidence-based outcomes exist and reveal where data remain insufficient. This is illustrated by the guideline recommendations for providing additional histopathologic characteristics in the pathology reports, which will likely produce future data to enhance the prognosis and eventual treatment of patients with NMSC.^1,2 Future guidelines also may include newer technologies (eg, gene expression profiling).

The guidelines do not cover the management of premalignant and in situ lesions, nor do they provide details on the management of metastatic or locally advanced disease. These topics certainly will require a similar critical review and may be addressed separately. The guidelines are identifying unanswered questions about patient care and are concurrently establishing the collection of appropriate data to answer these questions in the future.

Official guidelines often become the primary source for the measured standard of both treatment and outcomes in patient care; therefore, it is critical that dermatologists and the AAD take the lead in creating these guidelines so that we can provide our patients with the best evidenced-based comprehensive care.

The AAD guidelines emphasize the importance of considering the patient perspective in determining how to treat BCCs and cSCCs.^1,2 It is important for patients to understand the available treatment options and participate in their own medical care. The AAD work group for these guidelines included patient advocates to ensure that the guidelines would promote further dialogue between physicians and their patients.

The AAD guidelines for the management of NMSC were developed by board-certified dermatologists and other experts in the field. They allow dermatologists to work with patients diagnosed with NMSC to determine the treatment option that is best for each individual patient.

You are on the front lines of the prevention, screening, and treatment decisions for adolescent substance use disorders. You often must choose whether to disclose information about substance use to parents and other concerned adults.

The risk of developing a substance use disorder increases dramatically the earlier an individual begins using a given substance.¹ The neurobiology behind this risk is becoming increasingly clear. Young brains are undergoing crucial developmental processes, including synaptic pruning and myelination. The brain increasingly becomes more efficient in a staggered pattern, with limbic regions preceding frontal and executive regions, so we see adolescents with “more gas than brakes.” This has wisely been identified as developmentally appropriate, and even beneficial, rather than evidence that adolescents are somehow broken.²

SolStock/Getty Images

Steve Debenport/Getty Images

In most cases, adolescents should be informed of a decision to disclose substance use to their parents. Inviting adolescents to discuss how this will be done, including if the adolescent will be present, and whether you or the adolescent will disclose the use can be an opportunity to discuss their concerns. You should seek to understand if an adolescent has specific fears related to such a disclosure including careful consideration of any history of domestic violence or abuse.

Although adolescents increasingly identify with the opinions and values of their peers, it is a mistake to assume that they therefore do not value the opinions of their parents and the concerned adults in their lives. Parents play an integral role in preventing and treating adolescent substance use disorders. Except in rare instances of severe parent-child relationship problems or abuse, parents can and should be engaged as invaluable participants

Dr. Jackson is a child and adolescent psychiatrist at the University of Vermont, Burlington.

References

1. “Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings.” NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013).

2. “The Amazing Teen Brain,” Jay N. Geidd, Scientific American, May 2016.

3. Pediatrics 2011 Oct. doi: 10.1542/peds.2011-1754.

4. Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide.

5. Pediatrics. 2016 Jul 1. doi: 10.1542/peds.2016-1211.

6. J Fam Commun. 2014 Jan 1:14(4):328-51.

7. J Clin Child Adolesc. Psychol. 2008;37(1):236-59.

8. J Child Adolesc Subst Abuse. 2015 May 4;24(3):155-65.

9. Arch Pediatr Adolesc Med. 2012;166(12):1132-9.

You are on the front lines of the prevention, screening, and treatment decisions for adolescent substance use disorders. You often must choose whether to disclose information about substance use to parents and other concerned adults.

The risk of developing a substance use disorder increases dramatically the earlier an individual begins using a given substance.¹ The neurobiology behind this risk is becoming increasingly clear. Young brains are undergoing crucial developmental processes, including synaptic pruning and myelination. The brain increasingly becomes more efficient in a staggered pattern, with limbic regions preceding frontal and executive regions, so we see adolescents with “more gas than brakes.” This has wisely been identified as developmentally appropriate, and even beneficial, rather than evidence that adolescents are somehow broken.²

SolStock/Getty Images

Steve Debenport/Getty Images

In most cases, adolescents should be informed of a decision to disclose substance use to their parents. Inviting adolescents to discuss how this will be done, including if the adolescent will be present, and whether you or the adolescent will disclose the use can be an opportunity to discuss their concerns. You should seek to understand if an adolescent has specific fears related to such a disclosure including careful consideration of any history of domestic violence or abuse.

Although adolescents increasingly identify with the opinions and values of their peers, it is a mistake to assume that they therefore do not value the opinions of their parents and the concerned adults in their lives. Parents play an integral role in preventing and treating adolescent substance use disorders. Except in rare instances of severe parent-child relationship problems or abuse, parents can and should be engaged as invaluable participants

Dr. Jackson is a child and adolescent psychiatrist at the University of Vermont, Burlington.

References

1. “Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings.” NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013).

2. “The Amazing Teen Brain,” Jay N. Geidd, Scientific American, May 2016.

3. Pediatrics 2011 Oct. doi: 10.1542/peds.2011-1754.

4. Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide.

5. Pediatrics. 2016 Jul 1. doi: 10.1542/peds.2016-1211.

6. J Fam Commun. 2014 Jan 1:14(4):328-51.

7. J Clin Child Adolesc. Psychol. 2008;37(1):236-59.

8. J Child Adolesc Subst Abuse. 2015 May 4;24(3):155-65.

9. Arch Pediatr Adolesc Med. 2012;166(12):1132-9.

You are on the front lines of the prevention, screening, and treatment decisions for adolescent substance use disorders. You often must choose whether to disclose information about substance use to parents and other concerned adults.

The risk of developing a substance use disorder increases dramatically the earlier an individual begins using a given substance.¹ The neurobiology behind this risk is becoming increasingly clear. Young brains are undergoing crucial developmental processes, including synaptic pruning and myelination. The brain increasingly becomes more efficient in a staggered pattern, with limbic regions preceding frontal and executive regions, so we see adolescents with “more gas than brakes.” This has wisely been identified as developmentally appropriate, and even beneficial, rather than evidence that adolescents are somehow broken.²

SolStock/Getty Images

Steve Debenport/Getty Images

In most cases, adolescents should be informed of a decision to disclose substance use to their parents. Inviting adolescents to discuss how this will be done, including if the adolescent will be present, and whether you or the adolescent will disclose the use can be an opportunity to discuss their concerns. You should seek to understand if an adolescent has specific fears related to such a disclosure including careful consideration of any history of domestic violence or abuse.

Although adolescents increasingly identify with the opinions and values of their peers, it is a mistake to assume that they therefore do not value the opinions of their parents and the concerned adults in their lives. Parents play an integral role in preventing and treating adolescent substance use disorders. Except in rare instances of severe parent-child relationship problems or abuse, parents can and should be engaged as invaluable participants

Dr. Jackson is a child and adolescent psychiatrist at the University of Vermont, Burlington.

References

1. “Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings.” NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. (Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013).

2. “The Amazing Teen Brain,” Jay N. Geidd, Scientific American, May 2016.

3. Pediatrics 2011 Oct. doi: 10.1542/peds.2011-1754.

4. Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide.

5. Pediatrics. 2016 Jul 1. doi: 10.1542/peds.2016-1211.

6. J Fam Commun. 2014 Jan 1:14(4):328-51.

7. J Clin Child Adolesc. Psychol. 2008;37(1):236-59.

8. J Child Adolesc Subst Abuse. 2015 May 4;24(3):155-65.

9. Arch Pediatr Adolesc Med. 2012;166(12):1132-9.

BOSTON – It’s been just a year since Bani Chander Roland, MD, FACG, was awarded the 2017 AGA-Medtronic Research and Development Pilot Award in Technology, and her team already has recruited 30 patients with irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) for a study of the gut microbiome and functioning. Interim data from her grant will be presented at Digestive Disease Week® 2018 in June in Washington, D.C., as a poster of distinction.

Dr. Roland and her team are testing the hypothesis that IBS and SIBO result from several distinct pathophysiologic mechanisms, each of which are associated with their own distinct microbial and inflammatory profile. For the study, they are using the Wireless Motility Capsule (WMC, SmartPill) to assess alterations in gastrointestinal pathophysiology in patients with suspected IBS and SIBO – just the sort of innovative technology that the AGA Center for GI Innovation and Technology (CGIT) has fostered. They also are obtaining microflora from oropharyngeal, gastric, small bowel, and fecal samples for DNA sequencing. In addition, the team is beginning to study serum samples to test the hypothesis that patients with IBS and SIBO have increased expression of pro-inflammatory markers compared to those with only IBS; they are attempting to correlate the inflammatory markers to specific bacteria.

“IBS is a very common gastrointestinal disorder, and we’re continuing to see an increase in prevalence in Western countries, without understanding the etiology for this syndrome,” said Dr. Roland, director of gastrointestinal motility at Lenox Hill Hospital and Northwell Health System in New York. “Unfortunately, we don’t have any specific or targeted therapies for this patient population because the underlying physiological mechanisms that cause IBS are not very well understood. When we treat these patients with antibiotics, often their symptoms come right back. If we can target the causes of disease in subsets of these patients, we may be able to successfully treat them.”

“We’re very excited to see what changes in the microbiome exist in this patient population, to determine if the microbiome may be another potential area that we can target for treatment,” she added.

In data to be presented in the DDW poster, Dr. Roland’s team used the SmartPill to measure the gastrointestinal transit times, pH, and ileocecal junction pressures of patients with IBS and SIBO as compared to patients with IBS without evidence of SIBO. “Interestingly, patients who had IBS and SIBO had significantly higher contraction frequency in the stomach and small bowel compared to patients with IBS alone,” Dr. Roland said. Those with both conditions also had lower ileocecal junction pressures. “These are physiological mechanisms that have not been well understood before,” Dr. Roland said. “We have been able to begin delineating some of the underlying physiological mechanisms in this challenging patient population for the first time, using a noninvasive, wireless motility capsule.”

Dr. Roland’s team is now partnering with the hospital’s endocrinology division to compare the circulating inflammatory markers in patients with IBS and SIBO, such as TNF (tumor necrosis factor)-alpha and IL (interleukin)-6, to patients with IBS alone. They will use their data to apply for future funding.

BOSTON – It’s been just a year since Bani Chander Roland, MD, FACG, was awarded the 2017 AGA-Medtronic Research and Development Pilot Award in Technology, and her team already has recruited 30 patients with irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) for a study of the gut microbiome and functioning. Interim data from her grant will be presented at Digestive Disease Week® 2018 in June in Washington, D.C., as a poster of distinction.

Dr. Roland and her team are testing the hypothesis that IBS and SIBO result from several distinct pathophysiologic mechanisms, each of which are associated with their own distinct microbial and inflammatory profile. For the study, they are using the Wireless Motility Capsule (WMC, SmartPill) to assess alterations in gastrointestinal pathophysiology in patients with suspected IBS and SIBO – just the sort of innovative technology that the AGA Center for GI Innovation and Technology (CGIT) has fostered. They also are obtaining microflora from oropharyngeal, gastric, small bowel, and fecal samples for DNA sequencing. In addition, the team is beginning to study serum samples to test the hypothesis that patients with IBS and SIBO have increased expression of pro-inflammatory markers compared to those with only IBS; they are attempting to correlate the inflammatory markers to specific bacteria.

“IBS is a very common gastrointestinal disorder, and we’re continuing to see an increase in prevalence in Western countries, without understanding the etiology for this syndrome,” said Dr. Roland, director of gastrointestinal motility at Lenox Hill Hospital and Northwell Health System in New York. “Unfortunately, we don’t have any specific or targeted therapies for this patient population because the underlying physiological mechanisms that cause IBS are not very well understood. When we treat these patients with antibiotics, often their symptoms come right back. If we can target the causes of disease in subsets of these patients, we may be able to successfully treat them.”

“We’re very excited to see what changes in the microbiome exist in this patient population, to determine if the microbiome may be another potential area that we can target for treatment,” she added.

In data to be presented in the DDW poster, Dr. Roland’s team used the SmartPill to measure the gastrointestinal transit times, pH, and ileocecal junction pressures of patients with IBS and SIBO as compared to patients with IBS without evidence of SIBO. “Interestingly, patients who had IBS and SIBO had significantly higher contraction frequency in the stomach and small bowel compared to patients with IBS alone,” Dr. Roland said. Those with both conditions also had lower ileocecal junction pressures. “These are physiological mechanisms that have not been well understood before,” Dr. Roland said. “We have been able to begin delineating some of the underlying physiological mechanisms in this challenging patient population for the first time, using a noninvasive, wireless motility capsule.”

Dr. Roland’s team is now partnering with the hospital’s endocrinology division to compare the circulating inflammatory markers in patients with IBS and SIBO, such as TNF (tumor necrosis factor)-alpha and IL (interleukin)-6, to patients with IBS alone. They will use their data to apply for future funding.

BOSTON – It’s been just a year since Bani Chander Roland, MD, FACG, was awarded the 2017 AGA-Medtronic Research and Development Pilot Award in Technology, and her team already has recruited 30 patients with irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) for a study of the gut microbiome and functioning. Interim data from her grant will be presented at Digestive Disease Week® 2018 in June in Washington, D.C., as a poster of distinction.

Dr. Roland and her team are testing the hypothesis that IBS and SIBO result from several distinct pathophysiologic mechanisms, each of which are associated with their own distinct microbial and inflammatory profile. For the study, they are using the Wireless Motility Capsule (WMC, SmartPill) to assess alterations in gastrointestinal pathophysiology in patients with suspected IBS and SIBO – just the sort of innovative technology that the AGA Center for GI Innovation and Technology (CGIT) has fostered. They also are obtaining microflora from oropharyngeal, gastric, small bowel, and fecal samples for DNA sequencing. In addition, the team is beginning to study serum samples to test the hypothesis that patients with IBS and SIBO have increased expression of pro-inflammatory markers compared to those with only IBS; they are attempting to correlate the inflammatory markers to specific bacteria.

“IBS is a very common gastrointestinal disorder, and we’re continuing to see an increase in prevalence in Western countries, without understanding the etiology for this syndrome,” said Dr. Roland, director of gastrointestinal motility at Lenox Hill Hospital and Northwell Health System in New York. “Unfortunately, we don’t have any specific or targeted therapies for this patient population because the underlying physiological mechanisms that cause IBS are not very well understood. When we treat these patients with antibiotics, often their symptoms come right back. If we can target the causes of disease in subsets of these patients, we may be able to successfully treat them.”

“We’re very excited to see what changes in the microbiome exist in this patient population, to determine if the microbiome may be another potential area that we can target for treatment,” she added.

In data to be presented in the DDW poster, Dr. Roland’s team used the SmartPill to measure the gastrointestinal transit times, pH, and ileocecal junction pressures of patients with IBS and SIBO as compared to patients with IBS without evidence of SIBO. “Interestingly, patients who had IBS and SIBO had significantly higher contraction frequency in the stomach and small bowel compared to patients with IBS alone,” Dr. Roland said. Those with both conditions also had lower ileocecal junction pressures. “These are physiological mechanisms that have not been well understood before,” Dr. Roland said. “We have been able to begin delineating some of the underlying physiological mechanisms in this challenging patient population for the first time, using a noninvasive, wireless motility capsule.”

Dr. Roland’s team is now partnering with the hospital’s endocrinology division to compare the circulating inflammatory markers in patients with IBS and SIBO, such as TNF (tumor necrosis factor)-alpha and IL (interleukin)-6, to patients with IBS alone. They will use their data to apply for future funding.

Rare genetic variants that affect the maturation, migration, and death of neurons appear to be responsible for about 7% of cases of juvenile myoclonic epilepsy.

Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles (UCLA), and her colleagues reported in the March 15 issue of the New England Journal of Medicine.

But among these 34 patients, the variants manifested as different epileptic phenotypes, suggesting genetic pleiotropism, the investigators said.

Clinical Heterogeneity

“We report striking variation with respect to epilepsy phenotypes both within and among families,” the researchers said. “Of 34 affected nonproband family members, five (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, four (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, four (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”

ICK “is expressed in all tissues,” said senior study author Antonio Delgado-Escueta, MD, Professor of Neurology at UCLA. The subtle brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy is “diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain,” he said. “The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”

The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binding protein, has been implicated in juvenile myoclonic epilepsy. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.

An Epilepsy Database

The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study analyzed information from 334 families with genetic generalized epilepsies. Among these families, 310 patients had adolescent-onset myoclonic seizures and polyspike waves or had a diagnosis of juvenile myoclonic epilepsy.

The investigators first performed an exome-wide analysis of four affected members of a large family with genetic juvenile myoclonic epilepsy. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for juvenile myoclonic epilepsy.

A linkage analysis confirmed two candidate genes on chromosome 6p12.2. Further analyses pinpointed a single variant: K305T on the ICK gene. This trait was present in each of the 12 affected members and three unaffected members of the initial family examined. Of those affected, three had juvenile myoclonic epilepsy, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.

“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.

ICK variants were also present in 24 of the 310 database patients who had juvenile myoclonic epilepsy (8%). Of these, nine belonged to families with other affected members. The researchers tested 24 ICK variants for pathogenicity and determined that 13 exerted significant juvenile myoclonic epilepsy risk, with odds ratios exceeding 5.0.

When the researchers looked for these variants in the Genome Aggregation Database (gnomAD), they found that 12 of the variants were present but extremely rare, and eight were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. That variant was a benign polymorphism in Africans.

Dr. Bailey and her colleagues thus concluded that 21 ICK variants in 22 patients with juvenile myoclonic epilepsy accounted for 7% of the juvenile myoclonic epilepsy among the 310 cases examined.

Experiments in Mice

The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice during light sleep displayed muscle movements similar to human myoclonic seizures. These mice also displayed diffuse polyspike brain waves on EEG recordings.

“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.

The study was funded by private and public grants. Several authors are coholders of patents on EFHC1-based diagnostics and therapeutics that have been licensed to Athena Diagnostics.

—Michele G. Sullivan

Suggested Reading

Bailey JN, de Nijs L, Bai D, et al. Variant intestinal-cell kinase in juvenile myoclonic epilepsy. N Engl J Med. 2018; 378(11): 1018-1028.

Rare genetic variants that affect the maturation, migration, and death of neurons appear to be responsible for about 7% of cases of juvenile myoclonic epilepsy.

Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles (UCLA), and her colleagues reported in the March 15 issue of the New England Journal of Medicine.

But among these 34 patients, the variants manifested as different epileptic phenotypes, suggesting genetic pleiotropism, the investigators said.

Clinical Heterogeneity

“We report striking variation with respect to epilepsy phenotypes both within and among families,” the researchers said. “Of 34 affected nonproband family members, five (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, four (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, four (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”

ICK “is expressed in all tissues,” said senior study author Antonio Delgado-Escueta, MD, Professor of Neurology at UCLA. The subtle brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy is “diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain,” he said. “The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”

The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binding protein, has been implicated in juvenile myoclonic epilepsy. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.

An Epilepsy Database

The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study analyzed information from 334 families with genetic generalized epilepsies. Among these families, 310 patients had adolescent-onset myoclonic seizures and polyspike waves or had a diagnosis of juvenile myoclonic epilepsy.

The investigators first performed an exome-wide analysis of four affected members of a large family with genetic juvenile myoclonic epilepsy. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for juvenile myoclonic epilepsy.

A linkage analysis confirmed two candidate genes on chromosome 6p12.2. Further analyses pinpointed a single variant: K305T on the ICK gene. This trait was present in each of the 12 affected members and three unaffected members of the initial family examined. Of those affected, three had juvenile myoclonic epilepsy, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.

“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.

ICK variants were also present in 24 of the 310 database patients who had juvenile myoclonic epilepsy (8%). Of these, nine belonged to families with other affected members. The researchers tested 24 ICK variants for pathogenicity and determined that 13 exerted significant juvenile myoclonic epilepsy risk, with odds ratios exceeding 5.0.

When the researchers looked for these variants in the Genome Aggregation Database (gnomAD), they found that 12 of the variants were present but extremely rare, and eight were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. That variant was a benign polymorphism in Africans.

Dr. Bailey and her colleagues thus concluded that 21 ICK variants in 22 patients with juvenile myoclonic epilepsy accounted for 7% of the juvenile myoclonic epilepsy among the 310 cases examined.

Experiments in Mice

The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice during light sleep displayed muscle movements similar to human myoclonic seizures. These mice also displayed diffuse polyspike brain waves on EEG recordings.

“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.

The study was funded by private and public grants. Several authors are coholders of patents on EFHC1-based diagnostics and therapeutics that have been licensed to Athena Diagnostics.

—Michele G. Sullivan

Suggested Reading

Bailey JN, de Nijs L, Bai D, et al. Variant intestinal-cell kinase in juvenile myoclonic epilepsy. N Engl J Med. 2018; 378(11): 1018-1028.

Rare genetic variants that affect the maturation, migration, and death of neurons appear to be responsible for about 7% of cases of juvenile myoclonic epilepsy.

Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles (UCLA), and her colleagues reported in the March 15 issue of the New England Journal of Medicine.

But among these 34 patients, the variants manifested as different epileptic phenotypes, suggesting genetic pleiotropism, the investigators said.

Clinical Heterogeneity

“We report striking variation with respect to epilepsy phenotypes both within and among families,” the researchers said. “Of 34 affected nonproband family members, five (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, four (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, four (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”

ICK “is expressed in all tissues,” said senior study author Antonio Delgado-Escueta, MD, Professor of Neurology at UCLA. The subtle brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy is “diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain,” he said. “The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”

The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binding protein, has been implicated in juvenile myoclonic epilepsy. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.

An Epilepsy Database

The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study analyzed information from 334 families with genetic generalized epilepsies. Among these families, 310 patients had adolescent-onset myoclonic seizures and polyspike waves or had a diagnosis of juvenile myoclonic epilepsy.

The investigators first performed an exome-wide analysis of four affected members of a large family with genetic juvenile myoclonic epilepsy. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for juvenile myoclonic epilepsy.

A linkage analysis confirmed two candidate genes on chromosome 6p12.2. Further analyses pinpointed a single variant: K305T on the ICK gene. This trait was present in each of the 12 affected members and three unaffected members of the initial family examined. Of those affected, three had juvenile myoclonic epilepsy, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.

“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.

ICK variants were also present in 24 of the 310 database patients who had juvenile myoclonic epilepsy (8%). Of these, nine belonged to families with other affected members. The researchers tested 24 ICK variants for pathogenicity and determined that 13 exerted significant juvenile myoclonic epilepsy risk, with odds ratios exceeding 5.0.

When the researchers looked for these variants in the Genome Aggregation Database (gnomAD), they found that 12 of the variants were present but extremely rare, and eight were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. That variant was a benign polymorphism in Africans.

Dr. Bailey and her colleagues thus concluded that 21 ICK variants in 22 patients with juvenile myoclonic epilepsy accounted for 7% of the juvenile myoclonic epilepsy among the 310 cases examined.

Experiments in Mice

The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice during light sleep displayed muscle movements similar to human myoclonic seizures. These mice also displayed diffuse polyspike brain waves on EEG recordings.

“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.

The study was funded by private and public grants. Several authors are coholders of patents on EFHC1-based diagnostics and therapeutics that have been licensed to Athena Diagnostics.

—Michele G. Sullivan

Suggested Reading

Bailey JN, de Nijs L, Bai D, et al. Variant intestinal-cell kinase in juvenile myoclonic epilepsy. N Engl J Med. 2018; 378(11): 1018-1028.

LAS VEGAS – To appropriately manage patients on opioids who develop constipation, one of the most important distinctions to make is whether the condition was caused by the pain treatment or was just exacerbated by it, according to Darren M. Brenner, MD.

Because of the rampant use of opioids, the answer to that question is increasingly relevant to clinical practice, said Dr. Brenner, associate professor of medicine (gastroenterology and hepatology) and surgery at Northwestern University, Chicago.

Andrew D. Bowser/MDedge News

“From my own clinical experience, you will miss a third of your population that has constipation,” Dr. Brenner said, noting that some patients will instead think of their condition in terms of incomplete evacuation or decreased stool frequency.

Step 2 of the algorithm, therefore, is to assess for signs and symptoms of functional constipation in all patients, regardless of whether they report the condition.

The recently published Rome IV diagnostic criteria included a new category for opioid-induced constipation. According to the new definition, opioid-induced constipation must include new or worsening symptoms, such as fewer than three solid bowel movements per week, and straining, blockage sensation, or manual maneuvers on at least 25% of bowel movements, among other symptoms listed in the report.

If patients do have constipation meeting these criteria, then step 3 of the algorithm is to determine whether the symptoms were present prior to taking opioids.

If onset of constipation is related to the start of opioid treatment, options may include prescribing peripherally acting mu-opioid receptor antagonists (PAMORAs). By contrast, onset unrelated to the start of opioids, also known as opioid-exacerbated constipation, may require treatment according to the underlying cause. For example, slow-transit constipation may respond to laxatives, while evacuation disorders may be treated with surgery, biofeedback, or physical therapy.

The hardest group to identify, according to Dr. Brenner, is individuals whose symptoms were so minor that they didn’t even realize they had constipation symptoms prior to opioids.

Because treatment protocols for opioid-induced and opioid-exacerbated constipation are so different, “we must tease these people out,” Dr. Brenner said.

Global Academy and this news organization are owned by the same parent company.

Dr. Brenner reported disclosures related to Allergan, Daiichi Sankyo, Ironwood Pharmaceuticals, Prius Medical, Salix Pharmaceuticals, Synergy Pharmaceuticals, Shionogi, and others.

LAS VEGAS – To appropriately manage patients on opioids who develop constipation, one of the most important distinctions to make is whether the condition was caused by the pain treatment or was just exacerbated by it, according to Darren M. Brenner, MD.

Because of the rampant use of opioids, the answer to that question is increasingly relevant to clinical practice, said Dr. Brenner, associate professor of medicine (gastroenterology and hepatology) and surgery at Northwestern University, Chicago.

Andrew D. Bowser/MDedge News

“From my own clinical experience, you will miss a third of your population that has constipation,” Dr. Brenner said, noting that some patients will instead think of their condition in terms of incomplete evacuation or decreased stool frequency.

Step 2 of the algorithm, therefore, is to assess for signs and symptoms of functional constipation in all patients, regardless of whether they report the condition.

The recently published Rome IV diagnostic criteria included a new category for opioid-induced constipation. According to the new definition, opioid-induced constipation must include new or worsening symptoms, such as fewer than three solid bowel movements per week, and straining, blockage sensation, or manual maneuvers on at least 25% of bowel movements, among other symptoms listed in the report.

If patients do have constipation meeting these criteria, then step 3 of the algorithm is to determine whether the symptoms were present prior to taking opioids.

If onset of constipation is related to the start of opioid treatment, options may include prescribing peripherally acting mu-opioid receptor antagonists (PAMORAs). By contrast, onset unrelated to the start of opioids, also known as opioid-exacerbated constipation, may require treatment according to the underlying cause. For example, slow-transit constipation may respond to laxatives, while evacuation disorders may be treated with surgery, biofeedback, or physical therapy.

The hardest group to identify, according to Dr. Brenner, is individuals whose symptoms were so minor that they didn’t even realize they had constipation symptoms prior to opioids.

Because treatment protocols for opioid-induced and opioid-exacerbated constipation are so different, “we must tease these people out,” Dr. Brenner said.

Global Academy and this news organization are owned by the same parent company.

Dr. Brenner reported disclosures related to Allergan, Daiichi Sankyo, Ironwood Pharmaceuticals, Prius Medical, Salix Pharmaceuticals, Synergy Pharmaceuticals, Shionogi, and others.

LAS VEGAS – To appropriately manage patients on opioids who develop constipation, one of the most important distinctions to make is whether the condition was caused by the pain treatment or was just exacerbated by it, according to Darren M. Brenner, MD.

Because of the rampant use of opioids, the answer to that question is increasingly relevant to clinical practice, said Dr. Brenner, associate professor of medicine (gastroenterology and hepatology) and surgery at Northwestern University, Chicago.

Andrew D. Bowser/MDedge News

“From my own clinical experience, you will miss a third of your population that has constipation,” Dr. Brenner said, noting that some patients will instead think of their condition in terms of incomplete evacuation or decreased stool frequency.

Step 2 of the algorithm, therefore, is to assess for signs and symptoms of functional constipation in all patients, regardless of whether they report the condition.

The recently published Rome IV diagnostic criteria included a new category for opioid-induced constipation. According to the new definition, opioid-induced constipation must include new or worsening symptoms, such as fewer than three solid bowel movements per week, and straining, blockage sensation, or manual maneuvers on at least 25% of bowel movements, among other symptoms listed in the report.

If patients do have constipation meeting these criteria, then step 3 of the algorithm is to determine whether the symptoms were present prior to taking opioids.

If onset of constipation is related to the start of opioid treatment, options may include prescribing peripherally acting mu-opioid receptor antagonists (PAMORAs). By contrast, onset unrelated to the start of opioids, also known as opioid-exacerbated constipation, may require treatment according to the underlying cause. For example, slow-transit constipation may respond to laxatives, while evacuation disorders may be treated with surgery, biofeedback, or physical therapy.

The hardest group to identify, according to Dr. Brenner, is individuals whose symptoms were so minor that they didn’t even realize they had constipation symptoms prior to opioids.

Because treatment protocols for opioid-induced and opioid-exacerbated constipation are so different, “we must tease these people out,” Dr. Brenner said.

Global Academy and this news organization are owned by the same parent company.

Dr. Brenner reported disclosures related to Allergan, Daiichi Sankyo, Ironwood Pharmaceuticals, Prius Medical, Salix Pharmaceuticals, Synergy Pharmaceuticals, Shionogi, and others.

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – A revised hematopoietic stem cell transplantation comorbidity index developed for adolescents and young adults is useful for predicting nonrelapse mortality in this specific population, according to Brian Friend, MD.

In a retrospective study of 241 patients aged 15-39 years who underwent a first allogeneic hematopoietic stem cell transplant (HCT) between 2005 and 2015 at the University of California, Los Angeles, nonrelapse mortality incidence was particularly high, with rates of 26%, 28%, and 30% at 1, 2, and 3 years, respectively, Dr. Friend, a clinical research fellow at the David Geffen School of Medicine, Los Angeles, reported in a poster at the Acute Leukemia Forum of Hemedicus.

Sharon Worcester/MDedge News

“We sought to develop a modified HCT-CI that would be more practical and efficient in predicting outcomes of adolescent and young adult patients,” he wrote.

Data were collected on 15 comorbidities included in the original HCT-CI study, as well as the psychosocial risk factors. The relationship between multiple variables and the incidence of nonrelapse mortality was investigated via the Fine and Gray competing risk model with adjustments for patient- and transplant-specific factors.

A few things were “looked at differently,” he said, explaining, for example, that multiple cardiovascular risk factors were combined into one since they are rare in younger patients.

The study demonstrated that an index including only a few comorbidities important in adolescents and young adults is more predictive in these younger patients vs. adults, suggesting that a simpler model is more practical and useful, Dr. Friend said.

A larger study is planned in conjunction with the Center for International Blood and Marrow Transplant Research (CIBMTR). The researchers for that study will take an in-depth look at this younger population in an effort to develop a novel risk score for them. Other future efforts will focus on developing interventions to target high risk patients – and in particular, modifiable risk factors – with a focus on preventive measures, he said.

Dr. Friend reported having no financial disclosures.

[email protected]

WASHINGTON, DC—Neuroimaging is a core competency for epileptologists, according to an overview presented at the 71st Annual Meeting of the American Epilepsy Society. Neurologists trained in this subspecialty must bring “value-added” skills to the routine reports that radiologists provide—ensuring that both a proper diagnostic protocol and a quality-assurance mindset are in place so that when images are used, they are of sufficient quality to exclude wrong diagnoses.

Ultimately, it is the role of the epileptologist to review these images in the context of other localizing data and to work with radiologists in an integrative way, said Graeme Jackson, MD, Senior Deputy Director of the Florey Institute of Neuroscience and Mental Health in Melbourne.

What Is the Protocol?

In a presentation comprised largely of imaging studies in cases across the lifespan—infant, young child, teenager, adult, and senior citizen—Dr. Jackson discussed the diagnostic information essential for all patients with epilepsy: a clinical history for context, an EEG for function, and structural MRI with an epilepsy protocol for structure.

To map out the proper protocol, clinicians have to contend with many choices for MRI studies. Eventually, the process results in images. One pathway leads to a report from the radiologist, and another pathway leads to the epileptologist’s review.

Epileptologists are responsible for obtaining images that are adequate—not just taking what they get, said Dr. Jackson. “The radiologist is sitting there—[with] probably 2,000 images … a couple of minutes and a lot of cases.” As the “epileptologist, you have the advantage of having other information. You have the focus [and] the hypotheses.… It is critical that they be reviewed and iterated, particularly in difficult cases.”

Four “Can’t Miss” Imaging Diagnoses

The top four missed imaging diagnoses in epilepsy are obvious abnormalities, hippocampal sclerosis, malformations of cortical development, and a diagnosis of nothing, in which the clinician must be confident because the implicit observation is that the brain is completely structurally normal. Clinicians sometimes miss subtle things that can only be identified by looking correctly in the proper location, said Dr. Jackson.

In contrast to the four “can’t miss” diagnoses, focal cortical dysplasia, bilateral hippocampal sclerosis, temporal encephalocele, and parahippocampal dysplasia are among the many subtle lesions that clinicians can easily miss.

Examining a Case Study

Dr. Jackson assessed the case of Rachel, age 17, who has BOSD. This form of dysplasia encompasses localized seizures and can present at any time from infancy to adulthood. Although these entities are often intractable, 90% of patients who undergo resection of the cortical BOSD remain seizure-free.

Rachel had her first seizure at age 15. It lasted a few seconds and caused her to drop her ice cream. Her facial appearance was blank and she was pointing her right index finger, said Dr. Jackson. Her condition evolved into intractable tonic-clonic seizures at night, resulting in multiple medication use and side effects. After imaging revealed that Rachel—a left-dominant-language individual with aspirations to be a teacher—had a tiny abnormality at the base of the sulci, she underwent surgery.

“Before surgery, we could never convince our radiologist that this was abnormal,” said Dr. Jackson. “But because we believe these small BOSDs could cause this sort of epilepsy, we convinced our surgeon to take a tiny resection … that just took out [an] area of abnormal connectivity.”

The surgery was so precise that Rachel has been seizure-free for nearly three years, reported Dr. Jackson. “We did quite a remarkable job of taking out exactly that bit and only that bit within the middle of her language area,” he said. “When [Rachel] came out of the anesthetic, she was much more interactive, and [we] noticed the personality change.… She did not have that delay we often see in patients, even though she was on the same medications.”

“Really tiny bits of the brain can drive pretty nasty epilepsy,” said Dr. Jackson. Since Rachel’s procedure, she has graduated college and earned her first degree. “I published this [research] just to make the point that not all epilepsy [cases] are like this, but there are some, and we should try to find them.”

—Fred Balzac

Suggested Reading

Abou-Hamden A, Lau M, Fabinyi G, et al. Small temporal pole encephaloceles: a treatable cause of “lesion negative” temporal lobe epilepsy. Epilepsia. 2010;51(10):2199-2202.

Hofman PA, Fitt GJ, Harvey AS, et al. Bottom-of-sulcus dysplasia: imaging features. AJR Am J Roentgenol. 2011;196(4):881-885.

Jackson GD, Pedersen M, Harvey AS. How small can the epileptogenic region be?: a case in point. Neurology. 2017;88(21):2017-2019.

Jackson GD, Berkovic SF, Duncan JS, et al. Optimizing the diagnosis of hippocampal sclerosis using MR imaging. AJNR Am J Neuroradiol. 1993;14(3):753-762.

Jackson GD, Berkovic SF, Tress BM, et al. Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Neurology. 1990;40(12):1869-1875.

Pillay N, Fabinyi GC, Myles TS, et al. Parahippocampal epilepsy with subtle dysplasia: A cause of “imaging negative” partial epilepsy. Epilepsia. 2009;50(12):2611-2618.

WASHINGTON, DC—Neuroimaging is a core competency for epileptologists, according to an overview presented at the 71st Annual Meeting of the American Epilepsy Society. Neurologists trained in this subspecialty must bring “value-added” skills to the routine reports that radiologists provide—ensuring that both a proper diagnostic protocol and a quality-assurance mindset are in place so that when images are used, they are of sufficient quality to exclude wrong diagnoses.

Ultimately, it is the role of the epileptologist to review these images in the context of other localizing data and to work with radiologists in an integrative way, said Graeme Jackson, MD, Senior Deputy Director of the Florey Institute of Neuroscience and Mental Health in Melbourne.

What Is the Protocol?

In a presentation comprised largely of imaging studies in cases across the lifespan—infant, young child, teenager, adult, and senior citizen—Dr. Jackson discussed the diagnostic information essential for all patients with epilepsy: a clinical history for context, an EEG for function, and structural MRI with an epilepsy protocol for structure.

To map out the proper protocol, clinicians have to contend with many choices for MRI studies. Eventually, the process results in images. One pathway leads to a report from the radiologist, and another pathway leads to the epileptologist’s review.

Epileptologists are responsible for obtaining images that are adequate—not just taking what they get, said Dr. Jackson. “The radiologist is sitting there—[with] probably 2,000 images … a couple of minutes and a lot of cases.” As the “epileptologist, you have the advantage of having other information. You have the focus [and] the hypotheses.… It is critical that they be reviewed and iterated, particularly in difficult cases.”

Four “Can’t Miss” Imaging Diagnoses

The top four missed imaging diagnoses in epilepsy are obvious abnormalities, hippocampal sclerosis, malformations of cortical development, and a diagnosis of nothing, in which the clinician must be confident because the implicit observation is that the brain is completely structurally normal. Clinicians sometimes miss subtle things that can only be identified by looking correctly in the proper location, said Dr. Jackson.

In contrast to the four “can’t miss” diagnoses, focal cortical dysplasia, bilateral hippocampal sclerosis, temporal encephalocele, and parahippocampal dysplasia are among the many subtle lesions that clinicians can easily miss.

Examining a Case Study

Dr. Jackson assessed the case of Rachel, age 17, who has BOSD. This form of dysplasia encompasses localized seizures and can present at any time from infancy to adulthood. Although these entities are often intractable, 90% of patients who undergo resection of the cortical BOSD remain seizure-free.

Rachel had her first seizure at age 15. It lasted a few seconds and caused her to drop her ice cream. Her facial appearance was blank and she was pointing her right index finger, said Dr. Jackson. Her condition evolved into intractable tonic-clonic seizures at night, resulting in multiple medication use and side effects. After imaging revealed that Rachel—a left-dominant-language individual with aspirations to be a teacher—had a tiny abnormality at the base of the sulci, she underwent surgery.

“Before surgery, we could never convince our radiologist that this was abnormal,” said Dr. Jackson. “But because we believe these small BOSDs could cause this sort of epilepsy, we convinced our surgeon to take a tiny resection … that just took out [an] area of abnormal connectivity.”

The surgery was so precise that Rachel has been seizure-free for nearly three years, reported Dr. Jackson. “We did quite a remarkable job of taking out exactly that bit and only that bit within the middle of her language area,” he said. “When [Rachel] came out of the anesthetic, she was much more interactive, and [we] noticed the personality change.… She did not have that delay we often see in patients, even though she was on the same medications.”

“Really tiny bits of the brain can drive pretty nasty epilepsy,” said Dr. Jackson. Since Rachel’s procedure, she has graduated college and earned her first degree. “I published this [research] just to make the point that not all epilepsy [cases] are like this, but there are some, and we should try to find them.”

—Fred Balzac

Suggested Reading

Abou-Hamden A, Lau M, Fabinyi G, et al. Small temporal pole encephaloceles: a treatable cause of “lesion negative” temporal lobe epilepsy. Epilepsia. 2010;51(10):2199-2202.

Hofman PA, Fitt GJ, Harvey AS, et al. Bottom-of-sulcus dysplasia: imaging features. AJR Am J Roentgenol. 2011;196(4):881-885.

Jackson GD, Pedersen M, Harvey AS. How small can the epileptogenic region be?: a case in point. Neurology. 2017;88(21):2017-2019.

Jackson GD, Berkovic SF, Duncan JS, et al. Optimizing the diagnosis of hippocampal sclerosis using MR imaging. AJNR Am J Neuroradiol. 1993;14(3):753-762.

Jackson GD, Berkovic SF, Tress BM, et al. Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Neurology. 1990;40(12):1869-1875.

Pillay N, Fabinyi GC, Myles TS, et al. Parahippocampal epilepsy with subtle dysplasia: A cause of “imaging negative” partial epilepsy. Epilepsia. 2009;50(12):2611-2618.

WASHINGTON, DC—Neuroimaging is a core competency for epileptologists, according to an overview presented at the 71st Annual Meeting of the American Epilepsy Society. Neurologists trained in this subspecialty must bring “value-added” skills to the routine reports that radiologists provide—ensuring that both a proper diagnostic protocol and a quality-assurance mindset are in place so that when images are used, they are of sufficient quality to exclude wrong diagnoses.

Ultimately, it is the role of the epileptologist to review these images in the context of other localizing data and to work with radiologists in an integrative way, said Graeme Jackson, MD, Senior Deputy Director of the Florey Institute of Neuroscience and Mental Health in Melbourne.

What Is the Protocol?

In a presentation comprised largely of imaging studies in cases across the lifespan—infant, young child, teenager, adult, and senior citizen—Dr. Jackson discussed the diagnostic information essential for all patients with epilepsy: a clinical history for context, an EEG for function, and structural MRI with an epilepsy protocol for structure.

To map out the proper protocol, clinicians have to contend with many choices for MRI studies. Eventually, the process results in images. One pathway leads to a report from the radiologist, and another pathway leads to the epileptologist’s review.

Epileptologists are responsible for obtaining images that are adequate—not just taking what they get, said Dr. Jackson. “The radiologist is sitting there—[with] probably 2,000 images … a couple of minutes and a lot of cases.” As the “epileptologist, you have the advantage of having other information. You have the focus [and] the hypotheses.… It is critical that they be reviewed and iterated, particularly in difficult cases.”

Four “Can’t Miss” Imaging Diagnoses

The top four missed imaging diagnoses in epilepsy are obvious abnormalities, hippocampal sclerosis, malformations of cortical development, and a diagnosis of nothing, in which the clinician must be confident because the implicit observation is that the brain is completely structurally normal. Clinicians sometimes miss subtle things that can only be identified by looking correctly in the proper location, said Dr. Jackson.

In contrast to the four “can’t miss” diagnoses, focal cortical dysplasia, bilateral hippocampal sclerosis, temporal encephalocele, and parahippocampal dysplasia are among the many subtle lesions that clinicians can easily miss.

Examining a Case Study

Dr. Jackson assessed the case of Rachel, age 17, who has BOSD. This form of dysplasia encompasses localized seizures and can present at any time from infancy to adulthood. Although these entities are often intractable, 90% of patients who undergo resection of the cortical BOSD remain seizure-free.

Rachel had her first seizure at age 15. It lasted a few seconds and caused her to drop her ice cream. Her facial appearance was blank and she was pointing her right index finger, said Dr. Jackson. Her condition evolved into intractable tonic-clonic seizures at night, resulting in multiple medication use and side effects. After imaging revealed that Rachel—a left-dominant-language individual with aspirations to be a teacher—had a tiny abnormality at the base of the sulci, she underwent surgery.

“Before surgery, we could never convince our radiologist that this was abnormal,” said Dr. Jackson. “But because we believe these small BOSDs could cause this sort of epilepsy, we convinced our surgeon to take a tiny resection … that just took out [an] area of abnormal connectivity.”

The surgery was so precise that Rachel has been seizure-free for nearly three years, reported Dr. Jackson. “We did quite a remarkable job of taking out exactly that bit and only that bit within the middle of her language area,” he said. “When [Rachel] came out of the anesthetic, she was much more interactive, and [we] noticed the personality change.… She did not have that delay we often see in patients, even though she was on the same medications.”

“Really tiny bits of the brain can drive pretty nasty epilepsy,” said Dr. Jackson. Since Rachel’s procedure, she has graduated college and earned her first degree. “I published this [research] just to make the point that not all epilepsy [cases] are like this, but there are some, and we should try to find them.”

—Fred Balzac

Suggested Reading

Abou-Hamden A, Lau M, Fabinyi G, et al. Small temporal pole encephaloceles: a treatable cause of “lesion negative” temporal lobe epilepsy. Epilepsia. 2010;51(10):2199-2202.

Hofman PA, Fitt GJ, Harvey AS, et al. Bottom-of-sulcus dysplasia: imaging features. AJR Am J Roentgenol. 2011;196(4):881-885.

Jackson GD, Pedersen M, Harvey AS. How small can the epileptogenic region be?: a case in point. Neurology. 2017;88(21):2017-2019.

Jackson GD, Berkovic SF, Duncan JS, et al. Optimizing the diagnosis of hippocampal sclerosis using MR imaging. AJNR Am J Neuroradiol. 1993;14(3):753-762.

Jackson GD, Berkovic SF, Tress BM, et al. Hippocampal sclerosis can be reliably detected by magnetic resonance imaging. Neurology. 1990;40(12):1869-1875.

Pillay N, Fabinyi GC, Myles TS, et al. Parahippocampal epilepsy with subtle dysplasia: A cause of “imaging negative” partial epilepsy. Epilepsia. 2009;50(12):2611-2618.

Patients with multiple sclerosis (MS) who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions on MRI, yet have undetectable JC virus (JCV) DNA in their CSF, according to a cross-sectional, retrospective study published online ahead of print March 12 in JAMA Neurology.

The findings show that for some people with MS, PML diagnosis could be delayed if CSF sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to Martijn T. Wijburg, MD, a neurologist at the MS Center at VU University Medical Center in Amsterdam, and colleagues.

The study also described a potential correlation between PML lesion volume and JCV copy numbers. “To our knowledge, this is the first study that shows an association between total PML lesion volume measured by brain MRI and CSF JCV polymerase chain reaction [PCR] results in patients with [natalizumab-associated PML]. This finding may have considerable implications for patient care,” said the authors.

A Retrospective Study

PML, a lytic infection of glial and neuronal cells by the JCV, can be diagnosed when a patient exhibits clinical symptoms, when JCV DNA is detected in CSF by PCR, and when specific brain lesions are seen on MRI, according to a consensus statement from the Neuroinfectious Disease section of the American Academy of Neurology.

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab-associated PML between January 2007 and December 2014. Patients were required to meet one of the following criteria:

• Definite or probable PML, based on positive PCR and MRI findings suggestive of PML, with or without PML symptoms.
• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), nine patients (16.1%) had undetectable JCV DNA in CSF, and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45, and the median natalizumab treatment duration was 43 months. Patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs 6.7 mL). Logistic regression showed that a smaller PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers. PML lesion volume was greater in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

Results Suggest Need for Pharmacovigilance

The findings suggest that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay diagnosis.

“This [finding] can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (eg, when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” said the authors.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume.... As a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR.”

Strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative PCR results, which hampers a formal diagnosis of [PML] and may complicate patient treatment,” said the authors.

Meticulous clinical and MRI follow-up, in combination with repeated CSF JCV PCR testing, was warranted in these patients, they added. Complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future.”

MRI Alone Cannot Yet Support Diagnosis

“Dr. Wijburg and colleagues raise an important point in our understanding of the development of PML by showing that small brain lesions may be present at what may be the start of JCV infection when the virus is still undetectable in CSF,” said Eugene O. Major, PhD, a consultant in the Division of Neuroimmunology and Neurovirology at NINDS in Bethesda, Maryland, in an accompanying editorial. “However, it is not yet clear how well the relationship between viral load in CSF and MRI brain lesions approximates the stages of the disease and the processes with which it affects its target brain cells.”

Repeat testing may be worthwhile when CSF testing is negative, because some patients test positive weeks after testing negative, he added. “Suspicion for PML may be increased when MRI shows signs of PML despite negative CSF testing, but it is too early to rely on MRI alone for diagnosis.”

Dr. Major has received consulting fees while serving on independent adjudication committees for Takeda/Millennium, Roche/Genentech, and GlaxoSmithKline.He has patent rights at the NIH as coinventor of the Ultrasensitive Quantitative PCR Multiplex assay for the detection of JCV DNA–distinguishing viral variants.

—Nicola Garrett

Suggested Reading

Major EO. Progressive multifocal leukoencephalopathy lesions and JC virus: the limits and value of imaging. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Wijburg MT, Kleerekooper I, Lissenberg-Witte BI, et al. Association of progressive multifocal leukoencephalopathy lesion volume with JC virus polymerase chain reaction results in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Patients with multiple sclerosis (MS) who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions on MRI, yet have undetectable JC virus (JCV) DNA in their CSF, according to a cross-sectional, retrospective study published online ahead of print March 12 in JAMA Neurology.

The findings show that for some people with MS, PML diagnosis could be delayed if CSF sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to Martijn T. Wijburg, MD, a neurologist at the MS Center at VU University Medical Center in Amsterdam, and colleagues.

The study also described a potential correlation between PML lesion volume and JCV copy numbers. “To our knowledge, this is the first study that shows an association between total PML lesion volume measured by brain MRI and CSF JCV polymerase chain reaction [PCR] results in patients with [natalizumab-associated PML]. This finding may have considerable implications for patient care,” said the authors.

A Retrospective Study

PML, a lytic infection of glial and neuronal cells by the JCV, can be diagnosed when a patient exhibits clinical symptoms, when JCV DNA is detected in CSF by PCR, and when specific brain lesions are seen on MRI, according to a consensus statement from the Neuroinfectious Disease section of the American Academy of Neurology.

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab-associated PML between January 2007 and December 2014. Patients were required to meet one of the following criteria:

• Definite or probable PML, based on positive PCR and MRI findings suggestive of PML, with or without PML symptoms.
• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), nine patients (16.1%) had undetectable JCV DNA in CSF, and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45, and the median natalizumab treatment duration was 43 months. Patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs 6.7 mL). Logistic regression showed that a smaller PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers. PML lesion volume was greater in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

Results Suggest Need for Pharmacovigilance

The findings suggest that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay diagnosis.

“This [finding] can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (eg, when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” said the authors.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume.... As a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR.”

Strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative PCR results, which hampers a formal diagnosis of [PML] and may complicate patient treatment,” said the authors.

Meticulous clinical and MRI follow-up, in combination with repeated CSF JCV PCR testing, was warranted in these patients, they added. Complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future.”

MRI Alone Cannot Yet Support Diagnosis

“Dr. Wijburg and colleagues raise an important point in our understanding of the development of PML by showing that small brain lesions may be present at what may be the start of JCV infection when the virus is still undetectable in CSF,” said Eugene O. Major, PhD, a consultant in the Division of Neuroimmunology and Neurovirology at NINDS in Bethesda, Maryland, in an accompanying editorial. “However, it is not yet clear how well the relationship between viral load in CSF and MRI brain lesions approximates the stages of the disease and the processes with which it affects its target brain cells.”

Repeat testing may be worthwhile when CSF testing is negative, because some patients test positive weeks after testing negative, he added. “Suspicion for PML may be increased when MRI shows signs of PML despite negative CSF testing, but it is too early to rely on MRI alone for diagnosis.”

Dr. Major has received consulting fees while serving on independent adjudication committees for Takeda/Millennium, Roche/Genentech, and GlaxoSmithKline.He has patent rights at the NIH as coinventor of the Ultrasensitive Quantitative PCR Multiplex assay for the detection of JCV DNA–distinguishing viral variants.

—Nicola Garrett

Suggested Reading

Major EO. Progressive multifocal leukoencephalopathy lesions and JC virus: the limits and value of imaging. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Wijburg MT, Kleerekooper I, Lissenberg-Witte BI, et al. Association of progressive multifocal leukoencephalopathy lesion volume with JC virus polymerase chain reaction results in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Patients with multiple sclerosis (MS) who are treated with natalizumab can have small progressive multifocal leukoencephalopathy (PML) lesions on MRI, yet have undetectable JC virus (JCV) DNA in their CSF, according to a cross-sectional, retrospective study published online ahead of print March 12 in JAMA Neurology.

The findings show that for some people with MS, PML diagnosis could be delayed if CSF sampling is negative and patients are asymptomatic, potentially resulting in worse functional outcomes and survival rates, according to Martijn T. Wijburg, MD, a neurologist at the MS Center at VU University Medical Center in Amsterdam, and colleagues.

The study also described a potential correlation between PML lesion volume and JCV copy numbers. “To our knowledge, this is the first study that shows an association between total PML lesion volume measured by brain MRI and CSF JCV polymerase chain reaction [PCR] results in patients with [natalizumab-associated PML]. This finding may have considerable implications for patient care,” said the authors.

A Retrospective Study

PML, a lytic infection of glial and neuronal cells by the JCV, can be diagnosed when a patient exhibits clinical symptoms, when JCV DNA is detected in CSF by PCR, and when specific brain lesions are seen on MRI, according to a consensus statement from the Neuroinfectious Disease section of the American Academy of Neurology.

Dr. Wijburg and his coinvestigators reviewed data from Dutch and Belgian patients considered to have natalizumab-associated PML between January 2007 and December 2014. Patients were required to meet one of the following criteria:

• Definite or probable PML, based on positive PCR and MRI findings suggestive of PML, with or without PML symptoms.
• In the absence of a positive PCR, the presence of all four of the following features: high risk of PML development, such as positive anti-JCV serostatus and natalizumab treatment duration greater than 12 months; no MS disease activity prior to PML suspicion; MRI lesions highly suggestive of PML, with lesion characteristics as previously reported and absence of lesion characteristics suggestive of other diseases, as judged by an experienced neuroradiologist; and a lesion evolution on follow-up MRI scans suggestive of PML, including development of immune reconstitution inflammatory syndrome.

In the study of 56 patients (37 women), nine patients (16.1%) had undetectable JCV DNA in CSF, and 14 (25%) were asymptomatic for PML. At the time of PML diagnosis, the median age was 45, and the median natalizumab treatment duration was 43 months. Patients with a positive PCR had larger total PML lesion volumes than did those with undetectable JCV DNA (median volume, 22.9 mL vs 6.7 mL). Logistic regression showed that a smaller PML lesion volume significantly increased the probability for undetectable JCV DNA.

The research team also observed a positive correlation between PML lesion volume and JCV copy numbers. PML lesion volume was greater in patients with PML symptoms and in patients with more widespread lesion dissemination. But no association was found between PCR results and PML lesion dissemination, signs of inflammation, or PML symptoms.

Results Suggest Need for Pharmacovigilance

The findings suggest that patients with a smaller PML lesion volume were more likely to have a negative test result for JCV, which may lead to a delayed diagnosis of PML. Patients with smaller lesion volume were also more likely to be asymptomatic, which may further delay diagnosis.

“This [finding] can result in a therapeutic dilemma. Unjustly excluding PML may have serious consequences (eg, when switching from [natalizumab] to even more potent immunosuppressive treatments, such as alemtuzumab),” said the authors.

“In patients with [natalizumab-associated PML], both the probability for a positive CSF JCV PCR result and the JCV viral load are associated with the total PML lesion volume.... As a consequence, patients with smaller PML lesion volumes are more likely to have undetectable JCV DNA, and PML can thus not reliably be excluded based on a negative PCR.”

Strict pharmacovigilance by MRI “will lead to identification of smaller [PML] lesions that associate with a higher likelihood of negative PCR results, which hampers a formal diagnosis of [PML] and may complicate patient treatment,” said the authors.

Meticulous clinical and MRI follow-up, in combination with repeated CSF JCV PCR testing, was warranted in these patients, they added. Complementary PML diagnostic approaches, such as assessing intrathecal antibody synthesis to JCV by determining the CSF JCV antibody index, may also be of additional value.

“Furthermore, undetectable JCV DNA does not completely preclude the presence of JCV DNA. Further development and improvement of ultrasensitive PCR assays may improve the diagnostic accuracy in the future.”

MRI Alone Cannot Yet Support Diagnosis

“Dr. Wijburg and colleagues raise an important point in our understanding of the development of PML by showing that small brain lesions may be present at what may be the start of JCV infection when the virus is still undetectable in CSF,” said Eugene O. Major, PhD, a consultant in the Division of Neuroimmunology and Neurovirology at NINDS in Bethesda, Maryland, in an accompanying editorial. “However, it is not yet clear how well the relationship between viral load in CSF and MRI brain lesions approximates the stages of the disease and the processes with which it affects its target brain cells.”

Repeat testing may be worthwhile when CSF testing is negative, because some patients test positive weeks after testing negative, he added. “Suspicion for PML may be increased when MRI shows signs of PML despite negative CSF testing, but it is too early to rely on MRI alone for diagnosis.”

Dr. Major has received consulting fees while serving on independent adjudication committees for Takeda/Millennium, Roche/Genentech, and GlaxoSmithKline.He has patent rights at the NIH as coinventor of the Ultrasensitive Quantitative PCR Multiplex assay for the detection of JCV DNA–distinguishing viral variants.

—Nicola Garrett

Suggested Reading

Major EO. Progressive multifocal leukoencephalopathy lesions and JC virus: the limits and value of imaging. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Wijburg MT, Kleerekooper I, Lissenberg-Witte BI, et al. Association of progressive multifocal leukoencephalopathy lesion volume with JC virus polymerase chain reaction results in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis. JAMA Neurol. 2018 Mar 12 [Epub ahead of print].

Medical students and nurses who listen to 15 seconds of single-channel sonified EEGs may detect seizures with 95% to 98% sensitivity, thus outperforming neurologists who review traditional visual EEG displays, according to the results of a single-center study published in the April issue of Epilepsia.

“Individuals without EEG training can detect ongoing seizures or seizurelike rhythmic and periodic patterns by merely listening to short clips of sonified EEG,” said Josef Parvizi, MD, PhD, Professor of Neurology at Stanford University Medical Center in California, and his associates. “Ours is also the first study to test the capability of a sonification method to detect a range of significant abnormalities when it is used by clinical staff (eg, physicians, nurses, and students).”

—Amy Karon

Suggested Reading

Parvizi J, Gururangan K, Razavi B, Chafe C. Detecting silent seizures by their sound. Epilepsia. 2018;59(4):877-884.

Medical students and nurses who listen to 15 seconds of single-channel sonified EEGs may detect seizures with 95% to 98% sensitivity, thus outperforming neurologists who review traditional visual EEG displays, according to the results of a single-center study published in the April issue of Epilepsia.

“Individuals without EEG training can detect ongoing seizures or seizurelike rhythmic and periodic patterns by merely listening to short clips of sonified EEG,” said Josef Parvizi, MD, PhD, Professor of Neurology at Stanford University Medical Center in California, and his associates. “Ours is also the first study to test the capability of a sonification method to detect a range of significant abnormalities when it is used by clinical staff (eg, physicians, nurses, and students).”

—Amy Karon

Suggested Reading

Parvizi J, Gururangan K, Razavi B, Chafe C. Detecting silent seizures by their sound. Epilepsia. 2018;59(4):877-884.

Medical students and nurses who listen to 15 seconds of single-channel sonified EEGs may detect seizures with 95% to 98% sensitivity, thus outperforming neurologists who review traditional visual EEG displays, according to the results of a single-center study published in the April issue of Epilepsia.

“Individuals without EEG training can detect ongoing seizures or seizurelike rhythmic and periodic patterns by merely listening to short clips of sonified EEG,” said Josef Parvizi, MD, PhD, Professor of Neurology at Stanford University Medical Center in California, and his associates. “Ours is also the first study to test the capability of a sonification method to detect a range of significant abnormalities when it is used by clinical staff (eg, physicians, nurses, and students).”

—Amy Karon

Suggested Reading

Parvizi J, Gururangan K, Razavi B, Chafe C. Detecting silent seizures by their sound. Epilepsia. 2018;59(4):877-884.

PART 1

• Leading best gynecologic surgical care into the next decade
• Optimal surgical management of stage 3 and 4 pelvic organ prolapse
• Patient experience: It’s not about satisfaction

‌

‌

Andrew P. Cassidenti, MD
Chief, Female Pelvic Medicine and Reconstructive Surgery
Kern Medical,
Bakersfield, California

Amanda White, MD
Assistant Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Vivian Aguilar, MD
Assistant Professor, Obstetrics and Gynecology
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Rebecca G. Rogers, MD
Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Associate Chair, Clinical Integration and Operations
Dell Medical School, University of Texas
Austin, Texas

Patrick Culligan, MD
Director, Urogynecology and The Center for Female Pelvic Health
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Sarah Huber, MD
Fellow, Female Pelvic Medicine and Reconstructive Surgery
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Vincent R. Lucente, MD, MBA
Chief, Gynecology, St. Luke’s University Health Network
Medical Director, The Institute for Female Pelvic Medicine and Reconstructive Surgery
Allentown, Pennsylvania

Jessica B. Ton, MD
AAGL Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
Bethlehem, Pennsylvania

James I. Merlino, MD
President and Chief Medical Officer of Advisory and Strategic Consulting
Press Ganey Associates
Cleveland, Ohio

Amy A. Merlino, MD
Maternal Fetal Medicine Specialist
Department of Obstetrics and Gynecology
Enterprise Chief Informatics Officer
Cleveland Clinic, Cleveland, Ohio

PART 2

• Deep infiltrating endometriosis: Evaluation and management
• What’s new in simulation training for hysterectomy

‌

‌

‌

‌

Rosanne M. Kho, MD
Head, Section of Benign Gynecology
Women’s Health Institute
Department of Obstetrics and Gynecology
Cleveland Clinic
Cleveland, Ohio

Mauricio S. Abrão, MD
Associate Professor and
Director, Endometriosis Division
Department of Obstetrics and Gynecology
São Paulo University Medical School
São Paulo, Brazil

Alicia Scribner, MD, MPH
Director, Ob/Gyn Simulation Curriculum
Madigan Army Medical Center
Tacoma, Washington
Clinical Instructor
Department of Obstetrics and Gynecology
University of Washington, Seattle

Christine Vaccaro, DO
Medical Director, Andersen Simulation Center
Madigan Army Medical Center
Tacoma, Washington
Clinical Assistant Professor
Department of Obstetrics and Gynecology
University of Washington, Seattle
Uniformed Services University of Health Sciences
Bethesda, Maryland

PART 1

• Leading best gynecologic surgical care into the next decade
• Optimal surgical management of stage 3 and 4 pelvic organ prolapse
• Patient experience: It’s not about satisfaction

‌

‌

Andrew P. Cassidenti, MD
Chief, Female Pelvic Medicine and Reconstructive Surgery
Kern Medical,
Bakersfield, California

Amanda White, MD
Assistant Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Vivian Aguilar, MD
Assistant Professor, Obstetrics and Gynecology
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Rebecca G. Rogers, MD
Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Associate Chair, Clinical Integration and Operations
Dell Medical School, University of Texas
Austin, Texas

Patrick Culligan, MD
Director, Urogynecology and The Center for Female Pelvic Health
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Sarah Huber, MD
Fellow, Female Pelvic Medicine and Reconstructive Surgery
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Vincent R. Lucente, MD, MBA
Chief, Gynecology, St. Luke’s University Health Network
Medical Director, The Institute for Female Pelvic Medicine and Reconstructive Surgery
Allentown, Pennsylvania

Jessica B. Ton, MD
AAGL Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
Bethlehem, Pennsylvania

James I. Merlino, MD
President and Chief Medical Officer of Advisory and Strategic Consulting
Press Ganey Associates
Cleveland, Ohio

Amy A. Merlino, MD
Maternal Fetal Medicine Specialist
Department of Obstetrics and Gynecology
Enterprise Chief Informatics Officer
Cleveland Clinic, Cleveland, Ohio

PART 2

• Deep infiltrating endometriosis: Evaluation and management
• What’s new in simulation training for hysterectomy

‌

‌

‌

‌

Rosanne M. Kho, MD
Head, Section of Benign Gynecology
Women’s Health Institute
Department of Obstetrics and Gynecology
Cleveland Clinic
Cleveland, Ohio

Mauricio S. Abrão, MD
Associate Professor and
Director, Endometriosis Division
Department of Obstetrics and Gynecology
São Paulo University Medical School
São Paulo, Brazil

Alicia Scribner, MD, MPH
Director, Ob/Gyn Simulation Curriculum
Madigan Army Medical Center
Tacoma, Washington
Clinical Instructor
Department of Obstetrics and Gynecology
University of Washington, Seattle

Christine Vaccaro, DO
Medical Director, Andersen Simulation Center
Madigan Army Medical Center
Tacoma, Washington
Clinical Assistant Professor
Department of Obstetrics and Gynecology
University of Washington, Seattle
Uniformed Services University of Health Sciences
Bethesda, Maryland

PART 1

• Leading best gynecologic surgical care into the next decade
• Optimal surgical management of stage 3 and 4 pelvic organ prolapse
• Patient experience: It’s not about satisfaction

‌

‌

Andrew P. Cassidenti, MD
Chief, Female Pelvic Medicine and Reconstructive Surgery
Kern Medical,
Bakersfield, California

Amanda White, MD
Assistant Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Vivian Aguilar, MD
Assistant Professor, Obstetrics and Gynecology
Female Pelvic Medicine and Reconstructive Surgery
Dell Medical School, University of Texas
Austin, Texas

Rebecca G. Rogers, MD
Professor, Department of Women’s Health
Female Pelvic Medicine and Reconstructive Surgery
Associate Chair, Clinical Integration and Operations
Dell Medical School, University of Texas
Austin, Texas

Patrick Culligan, MD
Director, Urogynecology and The Center for Female Pelvic Health
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Sarah Huber, MD
Fellow, Female Pelvic Medicine and Reconstructive Surgery
Department of Urology
Weill Cornell Medical College, New York Presbyterian/Weill Cornell Medical Center
New York, New York

Vincent R. Lucente, MD, MBA
Chief, Gynecology, St. Luke’s University Health Network
Medical Director, The Institute for Female Pelvic Medicine and Reconstructive Surgery
Allentown, Pennsylvania

Jessica B. Ton, MD
AAGL Fellow, Minimally Invasive Gynecologic Surgery
St. Luke’s University Health Network
Bethlehem, Pennsylvania

James I. Merlino, MD
President and Chief Medical Officer of Advisory and Strategic Consulting
Press Ganey Associates
Cleveland, Ohio

Amy A. Merlino, MD
Maternal Fetal Medicine Specialist
Department of Obstetrics and Gynecology
Enterprise Chief Informatics Officer
Cleveland Clinic, Cleveland, Ohio

PART 2

• Deep infiltrating endometriosis: Evaluation and management
• What’s new in simulation training for hysterectomy

‌

‌

‌

‌

Rosanne M. Kho, MD
Head, Section of Benign Gynecology
Women’s Health Institute
Department of Obstetrics and Gynecology
Cleveland Clinic
Cleveland, Ohio

Mauricio S. Abrão, MD
Associate Professor and
Director, Endometriosis Division
Department of Obstetrics and Gynecology
São Paulo University Medical School
São Paulo, Brazil

Alicia Scribner, MD, MPH
Director, Ob/Gyn Simulation Curriculum
Madigan Army Medical Center
Tacoma, Washington
Clinical Instructor
Department of Obstetrics and Gynecology
University of Washington, Seattle

Christine Vaccaro, DO
Medical Director, Andersen Simulation Center
Madigan Army Medical Center
Tacoma, Washington
Clinical Assistant Professor
Department of Obstetrics and Gynecology
University of Washington, Seattle
Uniformed Services University of Health Sciences
Bethesda, Maryland