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Often difficult to diagnose, CNS vasculitis is a serious condition that can be treated effectively if addressed early.
HILTON HEAD, SC—Vasculitis is a general term for a group of uncommon diseases involving inflammation of blood vessels, which can lead to the occlusion or destruction of the vessels and to ischemia of the tissues supplied by those vessels. CNS vasculitis can be a primary disease or occur secondary to infections or as part of a systemic vasculitis or systemic inflammatory (eg, rheumatologic) disease. Without prompt diagnosis and treatment, patients are at high risk of permanent neurologic disability or death, according to a presentation at the 41st Annual Contemporary Clinical Neurology Symposium. 
If diagnosed and treated early, CNS vasculitis has a good prognosis, but delayed intervention can result in severe morbidity or mortality, said Siddharama Pawate, MD, Associate Professor of Neurology at the Vanderbilt University Medical Center in Nashville. “You have to do extensive workups sometimes before you can make a diagnosis,” he said, citing the need for neurology, rheumatology, and infectious disease input. “Investigations include serologic testing, CSF analysis, MRI, and brain biopsy.”
Rare But With a High Risk of Morbidity
The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitis adopted an extensive list of names for the numerous manifestations of vasculitis. These include the following:
• Large-vessel vasculitis (eg, giant cell arteritis [GCA])
• Medium-vessel vasculitis (eg, polyarteritis nodosa)
• Small-vessel vasculitis (eg, microscopic polyangiitis and granulomatosis with polyangiitis [Wegener’s granulomatosis])
• Variable-vessel vasculitis (eg, Behçet’s disease)
• Single-organ vasculitis (eg, primary CNS vasculitis)
• Vasculitis associated with systemic disease (eg, rheumatoid vasculitis)
• Vasculitis associated with probable etiology (eg, hepatitis B virus-associated or cancer-associated vasculitis).
CNS vasculitis may be grouped into two larger categories—infectious CNS vasculitis and immune-mediated CNS vasculitis. Dr. Pawate provided a brief overview of infectious causes of vasculitis including bacteria, mycobacteria, varicella-zoster, fungi, and neurocysticercosis, but devoted the main part of his presentation to the latter of the two categories, including a focus on primary CNS vasculitis (PCNSV), which is also known as primary angiitis of the CNS (PACNS). Dr. Pawate offered an analysis of what is entailed in the recognition, diagnosis, and treatment of CNS vasculitis in general and its immune-mediated variants more specifically.
CNS vasculitis may occur as part of a broader systemic vasculitis. GCA is a medical emergency that can cause permanent visual loss if not diagnosed and treated early. Vision loss occurs most often due to anterior ischemic optic neuropathy but also central retinal artery occlusion and posterior ischemic optic neuropathy. The American College of Rheumatology criteria for GCA diagnosis include three of the five following core features: age 50 or older at onset, new-onset headaches, temporal artery abnormality, elevated erythrocyte sedimentation rate of at least 50 mm/h, and abnormal temporal artery biopsy. High-dose steroids should be started if there is suspicion, without waiting for biopsy results. Recently, the anti-IL6 monoclonal antibody tocilizumab was approved by the FDA as a treatment for GCA. Granulomatosis with polyangiitis most often causes peripheral neuropathy, but can cause a small or medium vessel CNS vasculitis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is characterized by the triad of asthma, hypereosinophilia, and necrotizing vasculitis, usually in that order. CNS involvement is common as part of the vasculitis. CNS vasculitis may also be seen in Behçet’s disease manifesting as dural sinus thrombosis and arterial occlusion or aneurysm.
In systemic lupus erythematosus, vasculitis has a prevalence ranging between 11% and 36%, but CNS involvement is much less common. Case reports of CNS vasculitis in patients with rheumatoid arthritis are rare.
Primary CNS Vasculitis
Primary CNS vasculitis causes inflammation of mostly small- to medium-sized leptomeningeal and parenchymal arterial vessels. It is rare—a 2007 retrospective analysis by Salvarani et al of 101 cases estimated the average annual incidence to be 2.4 cases per one million person-years. Onset tends to occur in middle age, with a median age at diagnosis of 50 and a similar frequency in males and females.
Clinical presentation of PCNSV can be acute, subacute, chronic, or recurrent. Depending on the area of the brain or spinal cord that is affected, patients can present with a wide variety of neurologic complaints. Headache is the most common symptom—found in 50% to 78% of patients—followed by altered cognition and persistent neurologic deficits. Stroke and transient ischemic attack involving multiple vascular areas occur in 30% to 50% of patients.
The diagnostic gold standard for PCNSV is brain parenchymal/leptomeningeal biopsy. The most common diagnoses are granulomatous angiitis of the CNS (58%), lymphocytic PACNS (28%), and necrotizing vasculitis (14%). More than 90% of patients have abnormalities on MRI, and the most common imaging findings are cortical and subcortical infarcts, leptomeningeal enhancement, intracranial hemorrhage, and areas of increased signal on FLAIR and T2-weighted sequences. It has been increasingly recognized that differential diagnosis for PCNSV should include reversible cerebral vasoconstriction syndrome (RCVS), which is characterized by reversible multifocal narrowing of the cerebral arteries—typically preceded by sudden, severe thunderclap headaches with or without associated neurologic deficits. RCVS typically resolves in approximately 12 weeks.
Regarding treatment for PCNSV, Dr. Pawate recommended starting with high-dose steroids—eg, IV methylprednisolone, 1,000 mg daily for five days, with a prolonged oral prednisone taper starting at 1 mg/kg/day—and six to nine months of IV cyclophosphamide pulse therapy, 500–750 mg/m2 every two to four weeks for more severe cases. Case studies have shown rituximab and mycophenolate to be effective. “I had one patient initially on cyclophosphamide for six months who we [then] maintained on mycophenolate for five years and then stopped immunosuppression,” Dr. Pawate said. “She did quite well.”
—Fred Balzac
Suggested Reading
Abdel Razek AA, Alvarez H, Bagg S, et al. Imaging spectrum of CNS vasculitis. Radiographics. 2014;34(4):873-894.
Chow FC, Marra CM, Cho TA. Cerebrovascular disease in central nervous system infections. Semin Neurol. 2011;31(3):286-306.
Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun. 2014;48-49:149-152.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442-451.
Scolding NJ. Central nervous system vasculitis. Semin Immunopathol. 2009;31(4):527-536.
Often difficult to diagnose, CNS vasculitis is a serious condition that can be treated effectively if addressed early.
Often difficult to diagnose, CNS vasculitis is a serious condition that can be treated effectively if addressed early.
HILTON HEAD, SC—Vasculitis is a general term for a group of uncommon diseases involving inflammation of blood vessels, which can lead to the occlusion or destruction of the vessels and to ischemia of the tissues supplied by those vessels. CNS vasculitis can be a primary disease or occur secondary to infections or as part of a systemic vasculitis or systemic inflammatory (eg, rheumatologic) disease. Without prompt diagnosis and treatment, patients are at high risk of permanent neurologic disability or death, according to a presentation at the 41st Annual Contemporary Clinical Neurology Symposium.
If diagnosed and treated early, CNS vasculitis has a good prognosis, but delayed intervention can result in severe morbidity or mortality, said Siddharama Pawate, MD, Associate Professor of Neurology at the Vanderbilt University Medical Center in Nashville. “You have to do extensive workups sometimes before you can make a diagnosis,” he said, citing the need for neurology, rheumatology, and infectious disease input. “Investigations include serologic testing, CSF analysis, MRI, and brain biopsy.”
Rare But With a High Risk of Morbidity
The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitis adopted an extensive list of names for the numerous manifestations of vasculitis. These include the following:
• Large-vessel vasculitis (eg, giant cell arteritis [GCA])
• Medium-vessel vasculitis (eg, polyarteritis nodosa)
• Small-vessel vasculitis (eg, microscopic polyangiitis and granulomatosis with polyangiitis [Wegener’s granulomatosis])
• Variable-vessel vasculitis (eg, Behçet’s disease)
• Single-organ vasculitis (eg, primary CNS vasculitis)
• Vasculitis associated with systemic disease (eg, rheumatoid vasculitis)
• Vasculitis associated with probable etiology (eg, hepatitis B virus-associated or cancer-associated vasculitis).
CNS vasculitis may be grouped into two larger categories—infectious CNS vasculitis and immune-mediated CNS vasculitis. Dr. Pawate provided a brief overview of infectious causes of vasculitis including bacteria, mycobacteria, varicella-zoster, fungi, and neurocysticercosis, but devoted the main part of his presentation to the latter of the two categories, including a focus on primary CNS vasculitis (PCNSV), which is also known as primary angiitis of the CNS (PACNS). Dr. Pawate offered an analysis of what is entailed in the recognition, diagnosis, and treatment of CNS vasculitis in general and its immune-mediated variants more specifically.
CNS vasculitis may occur as part of a broader systemic vasculitis. GCA is a medical emergency that can cause permanent visual loss if not diagnosed and treated early. Vision loss occurs most often due to anterior ischemic optic neuropathy but also central retinal artery occlusion and posterior ischemic optic neuropathy. The American College of Rheumatology criteria for GCA diagnosis include three of the five following core features: age 50 or older at onset, new-onset headaches, temporal artery abnormality, elevated erythrocyte sedimentation rate of at least 50 mm/h, and abnormal temporal artery biopsy. High-dose steroids should be started if there is suspicion, without waiting for biopsy results. Recently, the anti-IL6 monoclonal antibody tocilizumab was approved by the FDA as a treatment for GCA. Granulomatosis with polyangiitis most often causes peripheral neuropathy, but can cause a small or medium vessel CNS vasculitis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is characterized by the triad of asthma, hypereosinophilia, and necrotizing vasculitis, usually in that order. CNS involvement is common as part of the vasculitis. CNS vasculitis may also be seen in Behçet’s disease manifesting as dural sinus thrombosis and arterial occlusion or aneurysm.
In systemic lupus erythematosus, vasculitis has a prevalence ranging between 11% and 36%, but CNS involvement is much less common. Case reports of CNS vasculitis in patients with rheumatoid arthritis are rare.
Primary CNS Vasculitis
Primary CNS vasculitis causes inflammation of mostly small- to medium-sized leptomeningeal and parenchymal arterial vessels. It is rare—a 2007 retrospective analysis by Salvarani et al of 101 cases estimated the average annual incidence to be 2.4 cases per one million person-years. Onset tends to occur in middle age, with a median age at diagnosis of 50 and a similar frequency in males and females.
Clinical presentation of PCNSV can be acute, subacute, chronic, or recurrent. Depending on the area of the brain or spinal cord that is affected, patients can present with a wide variety of neurologic complaints. Headache is the most common symptom—found in 50% to 78% of patients—followed by altered cognition and persistent neurologic deficits. Stroke and transient ischemic attack involving multiple vascular areas occur in 30% to 50% of patients.
The diagnostic gold standard for PCNSV is brain parenchymal/leptomeningeal biopsy. The most common diagnoses are granulomatous angiitis of the CNS (58%), lymphocytic PACNS (28%), and necrotizing vasculitis (14%). More than 90% of patients have abnormalities on MRI, and the most common imaging findings are cortical and subcortical infarcts, leptomeningeal enhancement, intracranial hemorrhage, and areas of increased signal on FLAIR and T2-weighted sequences. It has been increasingly recognized that differential diagnosis for PCNSV should include reversible cerebral vasoconstriction syndrome (RCVS), which is characterized by reversible multifocal narrowing of the cerebral arteries—typically preceded by sudden, severe thunderclap headaches with or without associated neurologic deficits. RCVS typically resolves in approximately 12 weeks.
Regarding treatment for PCNSV, Dr. Pawate recommended starting with high-dose steroids—eg, IV methylprednisolone, 1,000 mg daily for five days, with a prolonged oral prednisone taper starting at 1 mg/kg/day—and six to nine months of IV cyclophosphamide pulse therapy, 500–750 mg/m2 every two to four weeks for more severe cases. Case studies have shown rituximab and mycophenolate to be effective. “I had one patient initially on cyclophosphamide for six months who we [then] maintained on mycophenolate for five years and then stopped immunosuppression,” Dr. Pawate said. “She did quite well.”
—Fred Balzac
Suggested Reading
Abdel Razek AA, Alvarez H, Bagg S, et al. Imaging spectrum of CNS vasculitis. Radiographics. 2014;34(4):873-894.
Chow FC, Marra CM, Cho TA. Cerebrovascular disease in central nervous system infections. Semin Neurol. 2011;31(3):286-306.
Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun. 2014;48-49:149-152.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442-451.
Scolding NJ. Central nervous system vasculitis. Semin Immunopathol. 2009;31(4):527-536.
HILTON HEAD, SC—Vasculitis is a general term for a group of uncommon diseases involving inflammation of blood vessels, which can lead to the occlusion or destruction of the vessels and to ischemia of the tissues supplied by those vessels. CNS vasculitis can be a primary disease or occur secondary to infections or as part of a systemic vasculitis or systemic inflammatory (eg, rheumatologic) disease. Without prompt diagnosis and treatment, patients are at high risk of permanent neurologic disability or death, according to a presentation at the 41st Annual Contemporary Clinical Neurology Symposium.
If diagnosed and treated early, CNS vasculitis has a good prognosis, but delayed intervention can result in severe morbidity or mortality, said Siddharama Pawate, MD, Associate Professor of Neurology at the Vanderbilt University Medical Center in Nashville. “You have to do extensive workups sometimes before you can make a diagnosis,” he said, citing the need for neurology, rheumatology, and infectious disease input. “Investigations include serologic testing, CSF analysis, MRI, and brain biopsy.”
Rare But With a High Risk of Morbidity
The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitis adopted an extensive list of names for the numerous manifestations of vasculitis. These include the following:
• Large-vessel vasculitis (eg, giant cell arteritis [GCA])
• Medium-vessel vasculitis (eg, polyarteritis nodosa)
• Small-vessel vasculitis (eg, microscopic polyangiitis and granulomatosis with polyangiitis [Wegener’s granulomatosis])
• Variable-vessel vasculitis (eg, Behçet’s disease)
• Single-organ vasculitis (eg, primary CNS vasculitis)
• Vasculitis associated with systemic disease (eg, rheumatoid vasculitis)
• Vasculitis associated with probable etiology (eg, hepatitis B virus-associated or cancer-associated vasculitis).
CNS vasculitis may be grouped into two larger categories—infectious CNS vasculitis and immune-mediated CNS vasculitis. Dr. Pawate provided a brief overview of infectious causes of vasculitis including bacteria, mycobacteria, varicella-zoster, fungi, and neurocysticercosis, but devoted the main part of his presentation to the latter of the two categories, including a focus on primary CNS vasculitis (PCNSV), which is also known as primary angiitis of the CNS (PACNS). Dr. Pawate offered an analysis of what is entailed in the recognition, diagnosis, and treatment of CNS vasculitis in general and its immune-mediated variants more specifically.
CNS vasculitis may occur as part of a broader systemic vasculitis. GCA is a medical emergency that can cause permanent visual loss if not diagnosed and treated early. Vision loss occurs most often due to anterior ischemic optic neuropathy but also central retinal artery occlusion and posterior ischemic optic neuropathy. The American College of Rheumatology criteria for GCA diagnosis include three of the five following core features: age 50 or older at onset, new-onset headaches, temporal artery abnormality, elevated erythrocyte sedimentation rate of at least 50 mm/h, and abnormal temporal artery biopsy. High-dose steroids should be started if there is suspicion, without waiting for biopsy results. Recently, the anti-IL6 monoclonal antibody tocilizumab was approved by the FDA as a treatment for GCA. Granulomatosis with polyangiitis most often causes peripheral neuropathy, but can cause a small or medium vessel CNS vasculitis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) is characterized by the triad of asthma, hypereosinophilia, and necrotizing vasculitis, usually in that order. CNS involvement is common as part of the vasculitis. CNS vasculitis may also be seen in Behçet’s disease manifesting as dural sinus thrombosis and arterial occlusion or aneurysm.
In systemic lupus erythematosus, vasculitis has a prevalence ranging between 11% and 36%, but CNS involvement is much less common. Case reports of CNS vasculitis in patients with rheumatoid arthritis are rare.
Primary CNS Vasculitis
Primary CNS vasculitis causes inflammation of mostly small- to medium-sized leptomeningeal and parenchymal arterial vessels. It is rare—a 2007 retrospective analysis by Salvarani et al of 101 cases estimated the average annual incidence to be 2.4 cases per one million person-years. Onset tends to occur in middle age, with a median age at diagnosis of 50 and a similar frequency in males and females.
Clinical presentation of PCNSV can be acute, subacute, chronic, or recurrent. Depending on the area of the brain or spinal cord that is affected, patients can present with a wide variety of neurologic complaints. Headache is the most common symptom—found in 50% to 78% of patients—followed by altered cognition and persistent neurologic deficits. Stroke and transient ischemic attack involving multiple vascular areas occur in 30% to 50% of patients.
The diagnostic gold standard for PCNSV is brain parenchymal/leptomeningeal biopsy. The most common diagnoses are granulomatous angiitis of the CNS (58%), lymphocytic PACNS (28%), and necrotizing vasculitis (14%). More than 90% of patients have abnormalities on MRI, and the most common imaging findings are cortical and subcortical infarcts, leptomeningeal enhancement, intracranial hemorrhage, and areas of increased signal on FLAIR and T2-weighted sequences. It has been increasingly recognized that differential diagnosis for PCNSV should include reversible cerebral vasoconstriction syndrome (RCVS), which is characterized by reversible multifocal narrowing of the cerebral arteries—typically preceded by sudden, severe thunderclap headaches with or without associated neurologic deficits. RCVS typically resolves in approximately 12 weeks.
Regarding treatment for PCNSV, Dr. Pawate recommended starting with high-dose steroids—eg, IV methylprednisolone, 1,000 mg daily for five days, with a prolonged oral prednisone taper starting at 1 mg/kg/day—and six to nine months of IV cyclophosphamide pulse therapy, 500–750 mg/m2 every two to four weeks for more severe cases. Case studies have shown rituximab and mycophenolate to be effective. “I had one patient initially on cyclophosphamide for six months who we [then] maintained on mycophenolate for five years and then stopped immunosuppression,” Dr. Pawate said. “She did quite well.”
—Fred Balzac
Suggested Reading
Abdel Razek AA, Alvarez H, Bagg S, et al. Imaging spectrum of CNS vasculitis. Radiographics. 2014;34(4):873-894.
Chow FC, Marra CM, Cho TA. Cerebrovascular disease in central nervous system infections. Semin Neurol. 2011;31(3):286-306.
Hajj-Ali RA, Calabrese LH. Diagnosis and classification of central nervous system vasculitis. J Autoimmun. 2014;48-49:149-152.
Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
Salvarani C, Brown RD Jr, Calamia KT, et al. Primary central nervous system vasculitis: analysis of 101 patients. Ann Neurol. 2007;62(5):442-451.
Scolding NJ. Central nervous system vasculitis. Semin Immunopathol. 2009;31(4):527-536.