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• Neurologic involvement in progressive systemic sclerosis is considered uncommon. We retrospectively examined the prevalence and nature of neurologic complications in 50 patients with progressive systemic sclerosis. In 20 (40%), neurologic abnormalities were detected, with a total of 28 neurologic manifestations. All levels of the central and peripheral nervous system were affected: muscle (22%), peripheral nerve (18%), spinal cord (8%), and brain (6%). Of note were the presence of myelopathy in four patients and inclusion-body myositis in two. In 10 patients (20%), no definable cause of the neurologic dysfunction could be identified, apart from progressive systemic sclerosis. Thus, neurologic presentations of progressive systemic sclerosis are much more common than previously reported and may be due to direct involvement of the nervous system by a primary pathologic process in a significant number of patients.

Background Although overt involvement of the central nervous system (CNS) in myasthenia gravis (MG) is considered rare, hyperreflexia is a common and yet unexplained finding. Aquaporin 4 (AQP4), the target autoantigen in neuromyelitis optica, is expressed both in the CNS and in the neuromuscular junction. Objectives To evaluate the prevalence of even mild CNS involvement in patients with MG and to identify features indicative of neuromyelitis optica–like disease. Design Cohort study. Setting Outpatient clinic. Patients A cohort of 164 patients with MG. Methods In 24 patients with MG, signs of CNS involvement were detected; 15 of these patients had at least 1 additional paraclinical indication of neuromyelitis optica–like disease (presence of antibodies against AQP4, pathological visual evoked potentials, or white matter lesions detected on brain and/or spinal magnetic resonance imaging scans) and fulfilled the inclusion and exclusion criteria for our study. Results Of the 15 patients who had at least 1 additional paraclinical indication of neuromyelitis optica–like disease, 14 had abnormal visual evoked potentials, and in 6 of 9 patients in whom magnetic resonance imaging was performed, there was evidence of lesions in the white matter of the brain and/or spinal cord. Anti-AQP4 antibodies were detected in 7 patients (out of the 14 tested). Thymic enlargement (hyperplasia or thymoma) was more frequent in patients with MG who had signs of CNS involvement than in patients with MG who did not. Conclusions The incidence of CNS involvement in MG is higher than previously reported and is expressed predominantly as a pyramidal syndrome accompanied by optical tract involvement (frequently subclinical). These features bear some resemblance to neuromyelitis optica spectrum disease, supported also by the presence of anti-AQP4 antibodies in 7 of the 14 patients tested. This association may represent a new nosological entity or may indicate that an autoimmune process targeting AQP4 is an integral part of the immunopathogenetic mechanisms in MG.

Background A possible role of autoimmunity in Alzheimer disease pathogenesis has recently attracted increasing attention. Vaccination with amyloid-β peptide was reported to cause marked reduction in amyloid deposition, but it also induced encephalitis. Not much is known regarding neurofibrillary tangle–related autoimmune effects. Objective To use the main component of tangles—microtubule-associated tau protein—to test the feasibility of active induction of a neuroautoimmune disorder in mice. Design Prospective, randomized controlled animal study. Setting University medical center research laboratory. Subjects Female C57BL/6 mice. Interventions Inoculation with recombinant human tau protein emulsified in complete Freund adjuvant and with pertussis toxin. Main Outcome Measures Clinical, immunologic, pathologic, and behavioral evaluations were performed. Results Vaccination with tau protein induced histopathologic features of Alzheimer disease and tauopathies, indicated by the presence of neurofibrillary tangle–like structures, axonal damage, and gliosis. Also, mononuclear infiltrates without demyelination in the central nervous system, accompanied by neurologic deficits (such as a limp tail and limb paralysis), were observed. Anti–tau antibodies were detected in the serum of tau-immunized mice. Conclusions These results provide a link between tau autoimmunity and tauopathy-like abnormalities and indicate potential dangers of using tau for immunotherapy. This experimental autoimmune tauopathy-like model is due to a pathogenic immune response against an intraneuronal antigen and is not related to myelin antigens.

Background Choreoacanthocytosis (CHAC) is a slowly progressive multisystem disorder with involuntary movements, cognitive decline, behavioral changes, seizures, and polyneuropathy caused by mutations in the VPS13A gene. Objective To describe the early clinical features and possible genotype-phenotype correlation in CHAC. Design and Setting Case series in a tertiary care center. Patients and Main Outcome Methods Choreoacanthocytosis was diagnosed in 3 patients of Jewish origin from 3 unrelated families. We reviewed their medical histories and performed molecular analysis by screening all 73 exons of VPS13A . Results Trichotillomania, hypertrophic cardiomyopathy, and idiopathic hyperCKemia, in 1 patient each, preceded the development of the full clinical spectrum of CHAC by 2 to 20 years. At diagnosis, 2 patients manifested signs of overt neuromuscular involvement and were homozygous for the 6059delC mutation, whereas 1 patient had only hyporeflexia and was homozygous for the EX23del mutation. Because only 1 of the 2 patients with 6059delC had cardiomyopathy, its relevance to CHAC is unclear. Conclusions These findings extend the knowledge of significant early clinical heterogeneity in CHAC and suggest a possible genotype-phenotype correlation. Awareness of the early manifestations may prevent misdiagnosis and enable appropriate genetic counseling.

Objective To evaluate the presence and specificity of anti–myelin oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma of patients with multiple sclerosis (MS). Design Case-control study of patients with clinically definite MS compared with patients with other neurologic diseases (ONDs) of the central nervous system and control subjects. Setting Referral center in the Department of Neurology of Hadassah University Hospital, greater Jerusalem area, Israel. Participants Consecutive cerebrospinal fluid samples from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy controls were taken from the cerebrospinal fluid and plasma bank of the Department of Neurology, Hadassah University Hospital. Main Outcome Measures Levels and frequencies of anti-MOG antibody in patients with MS, as defined by enzyme-linked immunosorbent assay. Results Cerebrospinal fluid levels of antibodies to MOG and to myelin basic protein were significantly higher in patients with MS ( P P =.001, respectively) and patients with ONDs ( P =.005 and P =.03, respectively) compared with controls; frequency of antibodies to MOG, but not to myelin basic protein, was higher in patients with MS and patients with ONDs ( P =.01 and P =.003, respectively, for the frequency of anti-MOG antibody, and P =.65 and P =.41, respectively, for the frequency of anti-myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin basic protein were higher in patients with MS compared with patients with ONDs ( P =.003 for both comparisons) and with controls ( P =.03 and P =.04, respectively); however, the frequency of antibodies to MOG and myelin basic protein was similar in patients with MS, patients with ONDs ( P =.54 and P =.82, respectively), and controls ( P =.50 and P =.14, respectively). Conclusions The elevated presence of anti-MOG antibody is not specific for MS because a similar appearance was also demonstrated in patients with ONDs. Therefore, it is not clear whether this antibody is pathogenic in MS or, on the contrary, has a defensive role against further immune-mediated damage after myelin breakdown.

• Subacute sclerosing panencephalitis developed during pregnancy in a 27-year-old woman and immediately after delivery in an 18-year-old woman. In both, disease took an acute and fulminant course culminating in a vegetative state within several weeks. It is suggested that the relative older age of disease presentation and the unusually rapid neurologic deterioration were partially due to immunologic and hormonal alterations of pregnancy.

Of 66 patients (31 female and 35 male) with demyelinating inflammatory polyradiculoneuropathy (DIP), 12% (8/66) had a chronic relapsing and/or progressive course (CR-DIP) and 88% (58/66) had an acute monophasic illness (acute Guillain-Barré syndrome or GBS). Ten (15%) of the 66 had one or more associated putative autoimmune diseases; of these ten, five had CR-DIP and five had GBS. Cell-mediated immune responsiveness (CMI) of 30 cases with DIP was tested in vitro by lymphocyte transformation. Peripheral nervous system neuritogenic protein (NP) and central nervous system encephalitogenic myelin basic protein were the challenge antigens. Eighteen (60%) of the 30 patients had CMI to NP of human peripheral nervous system origin when a stimulation index (SI) of 2 or more was evaluated as positive; eight 27% (1) had CMI to NP when a positive SI was 3 or more. Of the 44 control patients with other neuropathies, only two (4.6%) demonstrated CMI to NP (SI, greater than or equal to 2). The in vitro response of patients with DIP to myelin basic protein (7/30) was not significantly different from that of the control population (16/44). The high incidence of DIP associated with autoimmune diseases and the CMI to NP in this group suggest that DIP may be an autoimmune disease with NP as one possible major antigen.

• Lymphocytes from patients with myasthenia gravis (MG) were transformed when cultured in vitro with an acetylcholine receptor fraction extracted from the electric organ of an electric eel. Marked diminution of the cellular response to acetylcholine receptor was shown in patients who improved clinically with prednisone treatment. The transient clinical deterioration during the first days of prednisone treatment was accompanied by a transient increase in lymphocyte response. These findings suggest that an in vivo sensitization of lymphocytes to self-acetylcholine receptor may occur in MG, and that a cell-mediated autoimmune mechanism may be important in the pathogenesis of the neuromuscular block. The present observations indicate that prednisone provides a measure of immunosuppression in MG. The transient clinical deterioration during the first days of prednisone therapy may reflect an enhancement of cell reactivity by this drug.