rimary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown cause. The mean age of onset is 50 years, and men are affected twice as often as women. Headache and encephalopathy are the most frequent initial symptoms. Stroke or focal symptoms develop in less than 20% of patients at the onset of disease and are uncommon in the absence of headache or encephalopathy. Symptoms or signs of vasculitis outside of the central nervous system are rare; serologic markers of inflammation are typically normal. Magnetic resonance imaging of the brain is abnormal in more than 90% of patients, but the pattern of abnormal findings is not specific. Cerebrospinal fluid analysis is also usually abnormal because of modest, nonspecific elevations in total protein level or white blood cell count. Angiography has a low sensitivity and low specificity. Most patients suspected of having PACNS have another disease. The diagnosis of PACNS is established by brain biopsy. The differential diagnosis of PACNS is broad and includes reversal cerebral vasoconstriction. In contrast to patients with PACNS, patients with reversal cerebral vasoconstriction are more often young women who experience a thunderclap headache and have a normal cerebrospinal fluid analysis. Patients with biopsyproven PACNS are treated with cyclophosphamide and prednisone.

Objective. Myelitis causes pain, weakness, and sphincteric deficits, and is 1,000-fold more prevalent in patients with systemic lupus erythematosus (SLE) than in the general population. For the last century, descriptions of SLE myelitis have been primarily limited to case reports. In contrast, larger-scale cohort studies have revealed that myelitis occurring in the idiopathic demyelinating diseases (i.e., multiple sclerosis versus neuromyelitis optica) represents distinct syndromes. This study was undertaken to determine whether SLE myelitis similarly encapsulates distinct syndromes.Methods. We analyzed a cohort of 22 patients with SLE and myelitis. Patients were assessed for neurologic variables related to myelitis and for clinical and serologic features of SLE. Magnetic resonance images of the spine, cerebrospinal fluid profiles, and autoantibody profiles were obtained.Results. Eleven patients presented with signs of gray matter dysfunction (i.e., flaccidity and hyporeflexia), whereas 11 patients presented with signs of white matter dysfunction (i.e., spasticity and hyperreflexia). Patients with gray matter dysfunction were more likely to have irreversible paraplegia (P < 0.01), despite presenting with a monophasic versus polyphasic course (P ‫؍‬ 0.01), higher levels of SLE activity (mean SLE Disease Activity Index 9.8 versus 2.0; P ‫؍‬ 0.01), and a cerebrospinal fluid profile indistinguishable from bacterial meningitis. Prior to irreversible paraplegia, these patients presented with prodromes of fever and urinary retention, but were misdiagnosed by physicians of different specialties as having urinary tract infections. Patients with white matter dysfunction were more likely to meet criteria for neuromyelitis optica (P ‫؍‬ 0.04) and were also more likely to have antiphospholipid antibodies (lupus anticoagulant) (P ‫؍‬ 0.01). Conclusion. Our findings indicate that SLE myelitis encapsulates 2 distinct and previously unrecognized syndromes that can be distinguished clinically by gray matter versus white matter findings. Recognition of fever and urinary retention as prodromes of irreversible paraplegia may allow earlier diagnosis and treatment in SLE patients presenting with gray matter findings.Myelitis is a devastating inflammatory syndrome of the spinal cord, causing weakness, numbness, and sphincteric deficits. Myelitis is estimated to affect 1-2% of patients with systemic lupus erythematosus (SLE) (1), more than 1,000 times greater than the prevalence of idiopathic myelitis in the general population (2). Despite this disproportionate morbidity affecting SLE patients, the last century has witnessed mostly isolated case reports of myelitis in SLE patients.SLE myelitis is traditionally regarded as a single diagnostic entity (3-5). However, subsuming all cases of myelitis in SLE patients under a unifying diagnostic rubric may be incorrect. Forms of SLE myelitis may have distinct clinical patterns, relationships to SLE activity, cerebrospinal fluid (CSF) profiles, and mechanisms of action. Such heterogeneity is di...

Objective. To characterize peripheral neuropathy subtypes, ancillary studies, and immunologic profiles associated with peripheral neuropathies in patients with systemic lupus erythematosus (SLE).Methods. In this 25-year study of 2,097 SLE patients, we characterized peripheral neuropathies due to SLE and compared clinical and SLE-related features in patients with versus those without neuropathy.Results. The prevalence of peripheral neuropathies was 5.9% (123 of 2,097 patients), and 66.7% of these patients (82 of 123) had peripheral neuropathies attributable to SLE. We noted that 17.1% of the patients with peripheral neuropathies due to SLE (14 of 82 patients) had small-fiber neuropathy, which is a painful neuropathy not included in the American College of Rheumatology (ACR) neuropsychiatric SLE (NPSLE) case definitions. SLE patients with small-fiber neuropathies could present with unorthodox neuropathic pain patterns not consistent with a stocking-glove distribution and had associated skin biopsy results suggestive of dorsal root ganglion neuronal cell loss. Compared to SLE patients without peripheral neuropathies, those with peripheral neuropathies had lower mean disease activity (P ‫؍‬ 0.01) and higher disease damage (P < 0.01) and were more likely to have a history of herpes zoster virus infection (P < 0.01), osteoporotic fractures (P < 0.01), and opportunistic infections (P < 0.01).Conclusion. Our findings indicate that smallfiber neuropathy is a frequently occurring peripheral neuropathy. The skin biopsy findings in small-fiber neuropathy patients support the notion that distinct mechanisms target the dorsal root ganglia as well as distal axons. SLE patients with peripheral neuropathy have lower mean disease activity scores and higher disease damage. Our findings suggest that revision of the ACR NPSLE case definitions, which currently do not include small-fiber neuropathies, is warranted.Peripheral neuropathies cause severe pain, weakness, and psychosocial morbidity (1). In the past decade, many studies of central nervous system (CNS) manifestations associated with systemic lupus erythematosus (SLE) have been conducted (2-5). Such studies have provided valuable insight into the spectrum of CNS manifestations and the association of distinct CNS syndromes with autoantibodies, immunologic markers, and aspects of SLE activity (5-7). In contrast, there have been a limited number of studies of the association of peripheral neuropathies with autoantibody patterns and aspects of SLE activity (8). However, such studies have, importantly, begun to emphasize that peripheral neuropathies in SLE may occur with equal or greater frequency compared to some CNS syndromes (2-5,8), and therefore constitute an important although poorly understood cause of morbidity.The 1999 American College of Rheumatology (ACR) case definitions for neuropsychiatric SLE (NPSLE) were an important advance in providing standardized definitions for both CNS and peripheral ner-

The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.