Basic CSF parameters and MRZ reaction help in differentiating MOG antibody-associated autoimmune disease versus multiple sclerosis

BackgroundMyelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.MethodsThis is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (QAlb), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).ResultsMOGAD patients with myelitis were more likely to have a pleocytosis, a QAlb elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, QAlb>10×10-3, as well as higher mean QAlb values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were QAlb>10×10-3 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).ConclusionBasic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but QAlb>10×10-3 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria

Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report

BACKGROUND Severe acute respiratory syndrome virus 2 (SARS-CoV-2) is spreading globally and causes most frequently fever and respiratory symptoms, i.e. Coronavirus disease 2019 (COVID-19), however, distinct neurological syndromes associated with SARS-CoV-2 infection have been described. Among SARS-CoV-2-infections-associated neurological symptoms fatigue, headache, dizziness, impaired consciousness and anosmia/ageusia are most frequent, but less frequent neurological deficits such as seizures, Guillain-Barré syndrome or ataxia may also occur. CASE PRESENTATION Herein we present a case of a 62-year-old man who developed a subacute cerebellar syndrome with limb-, truncal- and gait ataxia and scanning speech 1 day after clinical resolution of symptomatic SARS-CoV-2 infection of the upper airways. Apart from ataxia, there were no signs indicative of opsoclonus myoclonus ataxia syndrome or Miller Fisher syndrome. Cerebral magnetic resonance imaging showed mild cerebellar atrophy. SARS-CoV-2 infection of the cerebellum was excluded by normal cerebrospinal fluid cell counts and, most importantly, absence of SARS-CoV-2 RNA or intrathecal SARS-CoV-2-specific antibody production. Other causes of ataxia such as other viral infections, other autoimmune and/or paraneoplastic diseases or intoxication were ruled out. The neurological deficits improved rapidly after high-dose methylprednisolone therapy. CONCLUSIONS The laboratory and clinical findings as well as the marked improvement after high-dose methylprednisolone therapy suggest a post-infectious, immune-mediated cause of ataxia. This report should make clinicians aware to consider SARS-CoV-2 infection as a potential cause of post-infectious neurological deficits with an atypical clinical presentation and to consider high-dose corticosteroid treatment in case that a post-infectious immune-mediated mechanism is assumed

Glial Fibrillary Acidic Protein Autoimmunity After Aseptic Meningitis: A Report of 2 Cases

Bien C, Büttner T, Reichen I, et al. Glial Fibrillary Acidic Protein Autoimmunity After Aseptic Meningitis: A Report of 2 Cases. Neurology: Neuroimmunology & Neuroinflammation. 2024;11(1): e200180.OBJECTIVES: We describe 2 patients with glial fibrillary acidic protein (GFAP) autoimmunity secondary to aseptic viral meningitis or meningoencephalomyelitis.; METHODS: This study involved a retrospective chart review.; RESULTS: Two female patients, 45 and 55 years of age, developed aseptic meningoencephalomyelitis or meningitis; in one patient, it was likely caused by herpes simplex virus 2. The patients were recovering from the infectious condition when they, 51 and 5 days after onset, had new symptoms with detection of GFAP antibodies in the CSF; CSF and serum samples from the initial lumbar punctures had been negative for GFAP antibodies. Both patients recovered with steroid treatment (in one case, plus rituximab; in the other, plus azathioprine) including resolution of MRI and CSF abnormalities.; DISCUSSION: These 2 patients had GFAP autoimmunity secondary to viral meningoencephalomyelitis or meningitis. This suggests that GFAP astrocytopathy might not always be a primary disease entity; it may follow another brain injury that triggers this autoimmune response. Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

The role of neuronal antibodies in cryptogenic new‐onset refractory status epilepticus

Most cases with new‐onset refractory status epilepticus (NORSE) remain cryptogenic despite extensive diagnostic work‐up. The aim of this study was to analyse the etiology and clinical features of NORSE and investigate known or potentially novel autoantibodies in cryptogenic NORSE (cNORSE). We retrospectively assessed the medical records of adults with status epilepticus at a Swiss tertiary referral center between 2010 and 2021. Demographic, diagnostic, therapeutic and outcome parameters were characterized. We performed post‐hoc screening for known or potentially novel autoantibodies including immunohistochemistry (IHC) on rat brain with CSF and serum samples of cNORSE. 20 patients with NORSE were identified. Etiologies included infections (n=4), Creutzfeld‐Jakob disease (n=1), CASPR2 autoimmune encephalitis (n=1), and carotid artery stenosis with recurrent perfusion deficit (n=1). Thirteen cases (65%) were cryptogenic despite detailed evaluation. A posteriori IHC for neuronal autoantibodies yielded negative results in all available serum (n=11) and CSF (n=9) samples of cNORSE. Our results suggest that neuronal antibodies are unlikely to play a major role in the pathogenesis of cNORSE. Future studies should rather focus on other – especially T‐cell‐ and cytokine‐mediated – mechanisms of autoinflammation in this devastating disease, which is far too poorly understood so far

Cerebrospinal fluid findings in COVID-19: a multicenter study of 150 lumbar punctures in 127 patients

BACKGROUND Comprehensive data on the cerebrospinal fluid (CSF) profile in patients with COVID-19 and neurological involvement from large-scale multicenter studies are missing so far. OBJECTIVE To analyze systematically the CSF profile in COVID-19. METHODS Retrospective analysis of 150 lumbar punctures in 127 patients with PCR-proven COVID-19 and neurological symptoms seen at 17 European university centers RESULTS: The most frequent pathological finding was blood-CSF barrier (BCB) dysfunction (median QAlb 11.4 [6.72-50.8]), which was present in 58/116 (50%) samples from patients without pre-/coexisting CNS diseases (group I). QAlb remained elevated > 14d (47.6%) and even > 30d (55.6%) after neurological onset. CSF total protein was elevated in 54/118 (45.8%) samples (median 65.35 mg/dl [45.3-240.4]) and strongly correlated with QAlb. The CSF white cell count (WCC) was increased in 14/128 (11%) samples (mostly lympho-monocytic; median 10 cells/µl, > 100 in only 4). An albuminocytological dissociation (ACD) was found in 43/115 (37.4%) samples. CSF L-lactate was increased in 26/109 (24%; median 3.04 mmol/l [2.2-4]). CSF-IgG was elevated in 50/100 (50%), but was of peripheral origin, since QIgG was normal in almost all cases, as were QIgA and QIgM. In 58/103 samples (56%) pattern 4 oligoclonal bands (OCB) compatible with systemic inflammation were present, while CSF-restricted OCB were found in only 2/103 (1.9%). SARS-CoV-2-CSF-PCR was negative in 76/76 samples. Routine CSF findings were normal in 35%. Cytokine levels were frequently elevated in the CSF (often associated with BCB dysfunction) and serum, partly remaining positive at high levels for weeks/months (939 tests). Of note, a positive SARS-CoV-2-IgG-antibody index (AI) was found in 2/19 (10.5%) patients which was associated with unusually high WCC in both of them and a strongly increased interleukin-6 (IL-6) index in one (not tested in the other). Anti-neuronal/anti-glial autoantibodies were mostly absent in the CSF and serum (1509 tests). In samples from patients with pre-/coexisting CNS disorders (group II [N = 19]; including multiple sclerosis, JC-virus-associated immune reconstitution inflammatory syndrome, HSV/VZV encephalitis/meningitis, CNS lymphoma, anti-Yo syndrome, subarachnoid hemorrhage), CSF findings were mostly representative of the respective disease. CONCLUSIONS The CSF profile in COVID-19 with neurological symptoms is mainly characterized by BCB disruption in the absence of intrathecal inflammation, compatible with cerebrospinal endotheliopathy. Persistent BCB dysfunction and elevated cytokine levels may contribute to both acute symptoms and 'long COVID'. Direct infection of the CNS with SARS-CoV-2, if occurring at all, seems to be rare. Broad differential diagnostic considerations are recommended to avoid misinterpretation of treatable coexisting neurological disorders as complications of COVID-19