Idiopathic Central Nervous System Research Articles

Patterns and utility of myelin oligodendrocyte glycoprotein (MOG) antibody testing in cerebrospinal fluid.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associateddisease (MOGAD) is an idiopathic central nervous system (CNS) demyelinating disease gaining recognition with wider availability of cell-based assay (CBA) testing and recently published diagnostic criteria. However, uncertainty remains regarding the interpretation of antibody titers, particularly cerebrospinal fluid (CSF) MOG antibody titers. All MOG IgG CBA results performed by the provincial MitogenDx laboratory in Alberta from July 2017 to July 2023 were retrieved. Chart review was performed in patients with both serum and CSF testing and ≥ 1 positive MOG antibody result. Demographics, antibody titers, clinical and imaging features, treatment, and diagnosis were analyzed based on serum/CSF status. Among 4494 MOG CBA assays, there were 413 CSF samples in 402 patients, and 268 patients had at least one associated serum sample. Mean time between CSF and serum testing was 20.9days (range 0-870days), most with testing within 30days. Five of the 268 patients had serum positive/CSF positive MOG antibodies, 4 with acute disseminated encephalomyelitis and 1 with longitudinally extensive transverse myelitis. Twenty-three patients had serum positive/CSF negative MOG and 13/23 with optic neuritis. CSF MOG antibody positive patients were younger, and more likely to remain MOG seropositive versus CSF negative patients. No seronegative patient had MOG antibodies in CSF. In province-wide testing, CSF MOG antibodies were rare, only in MOG seropositive patients and none with optic neuritis. Our study does not support a clear role for CSF MOG antibody testing in the majority of patients, although further study is required.

Vaccination coverage in patients with idiopathic inflammatory central nervous system demyelinating diseases at Siriraj Hospital, a single-center experience

Vaccination coverage in patients with idiopathic inflammatory central nervous system demyelinating diseases at Siriraj Hospital, a single-center experience

Vaccination Coverage in Patients with Idiopathic Inflammatory Central Nervous System Demyelinating Diseases at Siriraj Hospital, A Single-center Experience

Objective: Individuals with Idiopathic Inflammatory Central Nervous System Demyelinating Diseases (CNS-IIDDs) have an elevated risk for infection. Vaccination is key to reducing infection. This study aimed to determine vaccination coverage, the adverse effects of vaccination, and general vaccination knowledge in the patients. Methods and Methods: A single-center cross-sectional study in the Multiple Sclerosis Clinic at Siriraj Hospital, Thailand, was performed using the designed questionnaires. Results: Of 100 participants, 90% were female, with a mean (SD) age of 46.2 (12.9). Overall, all received compulsory vaccine coverage. For optional vaccines, the coverage was lower-than-expected, with rates of 3%, 4%, and 3% for human papilloma virus, pneumococcal, and zoster vaccines, respectively. Only 28% of participants received the 2021/2022 seasonal influenza vaccine. The only factor associated with the uptake of the influenza vaccination was the participants’ health coverage. By asking questions to evaluate general vaccination knowledge, two questions related to vaccination and immuno-suppressive agents received the highest percentage of ‘not sure’ responses. Conclusion: Vaccination coverage was lower than expected among Thai CNS-IIDDs patients, both for optional and seasonal influenza vaccines. Vaccination in these groups of patients should be encouraged to prevent potential infections.

Management of Idiopathic CNS inflammatory diseases during the COVID-19 pandemic: Perspectives and strategies for continuity of care from a South East Asian Center with limited resources.

The Covid-19 pandemic poses a grave health management challenge globally of unprecedented nature. Management of idiopathic Central Nervous system inflammatory disorders (iCNSID) such as Multiple sclerosis, Neuromyelitis optica and its spectrum disorders and related conditions during this pandemic needs to be addressed with affirmative and sustainable strategies in order to prevent disease related risks, medication related complications and possible COVID-19 disease associated effects.Global international iCNSIDs agencies and recent publications are attempting to address this but such guidance is not available in South East Asia. Here we outline prospectively qualitatively and quantitatively novel strategies at a tertiary center in Malaysia catering for neuroimmunological disorders despite modest resources during this pandemic.In this retrospective study with longitudinal follow-up, we describe stratification of patients for face to face versus virtual visits in the absence of formal teleneurology, stratification of patients for treatment according to disease activity, rescheduling, deferring initiation or extending treatment intervals of certain disease modifying therapies(DMT's) or immunosuppressants(IS), especially those producing lymphocyte depletion in MS and the continuation of IS in patients with NMO/NMOSD.Furthermore, we highlight the use off-label treatments such as Intravenous immunoglobulins/rituximab,bridging interferons/Teriflunomide temporarily replacing more potent DMT choices,supply challenges of IS/DMT's and tailoring blood watches and neuroimaging surveillance based on the current health needs to stave off the pandemic and prevent at risk patients with iCNSID/health care workers from possibly being exposed to the COVID-19.

Diagnosis and long-term outcome in dogs with acute onset intracranial signs.

To investigate dogs with acute onset of intracranial signs suspected of stroke by primary veterinary clinicians, and establish possible differential diagnoses and long-term outcome. In addition, serum C-reactive protein and plasma cytokines were investigated as potential biomarkers of disease. All cases were evaluated by neurologic examination, routine haematology and biochemistry and measurement of serum C-reactive protein, plasma cytokine concentrations (interleukin-2, -6, -8, -10, tumour necrosis factor) and low-field MRI. Primary veterinarians contacted the investigators with 85 suspected stroke cases. Only 20 met the inclusion criteria. Of these, two were diagnosed with ischaemic stroke. Other causes were idiopathic vestibular syndrome (n=6), brain tumour (n=5) and inflammatory brain disease (n=2); in five cases a precise diagnosis could not be determined. Median survival times were: brain tumour, 3 days, idiopathic vestibular syndrome, 315 days, ischaemic stroke, 365 days and inflammatory central nervous system (CNS) disease, 468 days. The median plasma concentrations of interleukin-2, -6, -8, -10 or tumour necrosis factor were not significantly increased in any of the diagnosis groups compared to healthy controls. Serum C-reactive protein was higher in dogs with brain tumours and inflammatory brain disease but not above the upper bound of the reference interval. Dogs that present with acute onset intracranial disease may have ischaemic stroke but are more likely to have other causes. Many dogs with such acute onset of neurological dysfunction (brain tumours excluded) may recover within a couple of weeks despite their initial severe clinical appearance.

Idiopathic Central Nervous System Inflammatory Disease in the Setting of HLA-B27 Uveitis

ABSTRACTPurpose: The purpose of the article is to describe a novel case of idiopathic central nervous system inflammatory disease with bilateral human leukocyte antigen (HLA)-B27-positive anterior uveitis.Methods/Results: A 15-year-old African American boy with bilateral HLA-B27-positive anterior uveitis controlled with topical and oral steroids for 8 months acutely developed headaches, left eyelid ptosis, and binocular diplopia. Imaging showed lesions in the right midbrain, superior colliculus, cerebellar peduncles, and cerebellar vermis and leptomeningeal enhancement along the vermian foliae. Cerebral spinal fluid tests showed mild lymphohistiocytic pleocytosis with negative cytology; inflammatory and infectious workup were negative. He received intravenous methylprednisolone without initial symptomatic improvement; repeat magnetic resonance imaging (MRI) showed reduced lesion burden. Oral steroids were continued; his symptoms resolved in 1 month. Repeat MRI 2 months after presentation showed almost complete lesion resolution.Conclusions: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was diagnosed. HLA-B27 positivity may represent a novel association with CLIPPERS.

Central nervous system granulomastous phlebitis with limited extracranial involvement of the heart and lungs: An autopsy case

Primary angiitis of the central nervous system is a rare condition, usually with an insidious onset. There is a wide variety of histological types (granulomatous, lymphocytic or necrotizing vasculitis) and types of vessel involved (arteries, veins or both). Most cases are idiopathic. We describe a first case of idiopathic granulomatous central nervous system phlebitis with additional limited involvement of the heart and lung, exclusively affecting small and medium sized veins in a 22-year-old woman, presenting as a sub acute headache. The reasons for this peculiar limitation of inflammation to the veins and the involvement of the heart and lungs are unknown.

Bacterial infectious burden and prevalence of idiopathic central nervous system demyelinating diseases in Japanese

Bacterial infectious burden and prevalence of idiopathic central nervous system demyelinating diseases in Japanese

Genetic and environmental factors underlying the rapid changes in epidemiological and clinical features of multiple sclerosis and neuromyelitis optica in Japanese

AbstractThe discovery of a specific biomarker for neuromyelitis optica (NMO), NMO‐immunoglobulin G (IgG)/anti‐aquaporin‐4 (AQP4) antibody, requires us to take it into account when interpreting epidemiological findings on multiple sclerosis (MS). Recent genetic studies showed that HLA‐DRB1*0405 is the most common susceptibility allele for non‐NMO MS in Japanese, and that DRB1*0405 carriers comprise >40% of all Japanese MS patients. Thus, idiopathic central nervous system demyelinating disease in Japanese can be subclassified into DRB1*0405‐positive and ‐negative MS, and anti‐AQP4 antibody‐positive and ‐negative NMO. HLA‐DRB1*0405‐positive MS patients show younger age at onset, fewer brain lesions and a slower progression. The recent increase in the numbers of MS patients in this subgroup could explain the decrease in age at onset, as shown by the fourth nationwide survey in Japanese MS patients. Among HLA‐DRB1*0405‐negative MS patients, DRB1*1501 is a risk factor for MS, and DRB1*1501 carriers have high frequencies of brain lesions fulfilling the Barkhof criteria and cerebrospinal fluid IgG abnormalities. HLA‐DRB1*0405‐negative MS patients have higher frequencies of Epstein–Barr virus infection, but a lower frequency of Helicobacter pylori infection, which reflects improved sanitation in childhood. Anti‐AQP4 antibody‐positive NMO is associated with H. pylori and Chlamydia pneumoniae infections. The effects of improved sanitation on this subgroup might explain the decrease in incidence of opticospinal MS with longitudinally extensive spinal cord lesions, regarded as the same disease as NMO, as suggested by the fourth nationwide survey. Therefore, changes in environmental factors could have differentially influenced susceptibility to each disease subtype in Japanese.

Anti‐KIR4.1 antibodies in Japanese patients with idiopathic central nervous system demyelinating diseases

Anti‐<scp>KIR</scp>4.1 antibodies in <scp>J</scp>apanese patients with idiopathic central nervous system demyelinating diseases

Cerebrospinal fluid interleukin-6 and glial fibrillary acidic protein levels are increased during initial neuromyelitis optica attacks

BackgroundThe current 2006 neuromyelitis optica (NMO) criteria is useful for diagnosing NMO, however this criteria seemed to be insufficient at early stage of NMO. Hence, the development of diagnostic marker besides anti-aquaporin 4 antibody at early stage of NMO may be required. Our main aim of this study is to test the usefulness of measuring cerebrospinal fluid (CSF) interleukin (IL)-6 and glial fibrillary acidic protein (GFAP) concentrations as early diagnostic markers during initial NMO attacks. MethodsWe investigated CSF IL-6 and GFAP concentrations in 13 NMO spectrum disorder (NMOSD) patients at initial attacks, 24 idiopathic central nervous system inflammatory disease patients (9 optic neuritis, 9 myelitis and 6 encephalitis) and 20 other non-inflammatory neurological disorders (ONNDs) patients, retrospectively. ResultsThe mean CSF IL-6 and GFAP concentrations during the initial NMOSD attack were 91.4pg/ml and 369.3ng/ml, respectively, and were significantly higher than in ONNDs, idiopathic optic neuritis and myelitis patients (P<0.01). The sensitivity of high CSF IL-6 during initial NMO attack was 76.9% and that of high CSF GFAP was 84.6%, respectively. ConclusionOur data suggests that CSF IL-6 and GFAP may be useful early diagnostic markers of NMOSD.

Neuromyelitis Optica: Potential Roles for Intravenous Immunoglobulin

Neuromyelitis optica (NMO) is an idiopathic central nervous system inflammatory demyelinating disease that causes optic neuritis, transverse myelitis, and other CNS syndromes. It is distinct from multiple sclerosis and is associated with autoantibodies that target aquaporin-4 (AQP4), an astrocyte water channel. Evidence indicating antibody-mediated immune injury in NMO includes its association with other autoimmune diseases, lesional pathology that reveals prominent complement activation and immunoglobulin deposition, pathogenic potential of AQP4 autoantibodies based on in vitro studies, and reports of putative animal models of the disease. The rationale and potential role for intravenous immunoglobulin in NMO will be discussed in the context of both relapse treatment and relapse prevention.

Transglutaminase 2: A Novel Autoantigen in Canine Idiopathic Central Nervous System Inflammatory Diseases

Necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE) and granulomatous meningoencephalomyelitis (GME) are common idiopathic inflammatory central nervous system (CNS) diseases with unknown etiology in dogs. We previously showed that IgG autoantibodies in the cerebrospinal fluid (CSF) of NME cases reacted to unknown brain proteins as well as to glial fibrillary acidic protein (GFAP). In the present report, we evaluated the autoantibodies against transglutaminase2 (TG2) in the canine CNS diseases. CSF samples obtained from dogs with NME (n=19), NLE (n=7), GME (n=11) and miscellaneous CNS diseases (n=12) were subjected. CSFs from 20 healthy dogs were used as controls. Indirect fluorescent antibody test on the canine cerebrum revealed astrocyte-binding IgG in the CSF of NME. After absorption of the CSF with bovine GFAP, the CSF still possessed the reactivity to astrocytes. Double-color staining showed clear colocalization of the autoantibodies and anti-human TG2 rabbit polyclonal IgG. An immunoblot assay against human recombinant TG2 revealed anti-TG2 IgG in the CSF from dogs with NME, NLE and GME. The CSF of canine idiopathic encephalitis cases, notably of NME, tended to show high ELISA OD values against human recombinant TG2 compared to healthy controls. The presence of anti-TG2 autoantibodies in the CSF may contribute to the elucidation of the etiology of canine NME, NLE and GME.

Outcome of gonadotropin-releasing analog treatment for children with central precocious puberty: 15-year experience in southern Thailand

Central precocious puberty (CPP) is defined as pubertal development caused by activation of the hypothalamic-pituitary-gonadal axis before 8 years of age in girls and 9 years in boys. Failure to recognize and/or treat this condition can result in short adult stature. To determine the etiology, clinical presentation and near-final height (NFH) of Thai children with CPP with or without gonadotropin-releasing hormone analog (GnRHa) treatment. In a longitudinal observational study, 73 CPP patients who attended Songklanagarind Hospital between 1995 and 2009 were followed up every 3-6 months until they attained their NFH. The etiologies observed were idiopathic CPP, hypothalamic hamartoma and central nervous system diseases. The mean age at time of diagnosis was 6.4 +/- 2.9 years. Bone age was on average 4 years more advanced than chronological age. Of the 52 patients who reached their NFH during the study, 32 were treated with GnRHa and 20 were not. The mean age at menarche was significantly greater for GnRHa-treated than for untreated girls (11.6 +/- 0.8 vs 10.1 +/- 1.1 years, p < 0.001). The median NFH of GnRHa-treated girls was 152.4 +/- 5.2 cm, which was significantly greater than the 144.4 +/- 5.0 cm for untreated girls (p < 0.001). GnRHa treatment can preserve the genetic height potential of children with CPP.

Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese

Background Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease. Objective The objective of the current study was to clarify immunological differences between the two groups of patients. Methods We studied the serum antibody titers against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified their relationships with immunological parameters. Results Anti-AQP4 antibody positivity rate was higher in patients with OSMS (21/58, 36.2%), idiopathic recurrent myelitis (4/17, 23.5%), and recurrent optic neuritis (7/26, 26.9%), than in conventional MS (CMS) patients (6/90, 6.7%) and patients with other diseases (0/87). Anti-AQP4 antibody titer was significantly higher in patients with SS-A/B antibodies than in those without them. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+IFN-γ+IL-4−T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibody-positive patients, anti-AQP4 antibody-negative CMS patients, and healthy controls, and CD4+IFN-γ+IL-4−T cell percentages were negatively correlated with anti-AQP4 antibody titers. Conclusion Anti-AQP4 antibody-positive patients are immunologically distinct from anti-AQP4 antibody-negative OSMS patients owing to a Th2 shift in the former group in comparison to a Th1 shift in the latter.

Association of the HLA‐DPB1*0501 allele with anti‐aquaporin‐4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders

There are two subtypes of multiple sclerosis (MS) in Asians: the opticospinal (OSMS) form that shows a selective involvement of the optic nerve and the spinal cord and the conventional (CMS) form that has disseminated lesions in the central nervous system including the cerebrum, cerebellum and brainstem. Both show distinct human leukocyte antigen (HLA) class II associations. OSMS has similar features to the relapsing form of neuromyelitis optica (NMO) in Western populations. Recently, it was shown that antibodies to aquaporin-4 (AQP4) are specifically detected in NMO patients and in some Japanese patients with OSMS or recurrent optic neuritis or myelitis. To clarify the immunogenetic background of anti-AQP4 antibody production, we studied HLA-DRB1 and -DPB1 gene polymorphisms in anti-AQP4 antibody-positive and -negative patients with idiopathic demyelinating diseases, such as MS, recurrent optic neuritis and recurrent myelitis. The phenotypic frequency of the HLA-DPB1*0501 allele was significantly increased in anti-AQP4 antibody-positive patients (89.5%, odds ratio = 4.8; 95% confidence interval = 1.6-14.3, n = 38, P(corr) = 0.032) compared with controls (64.0%, n = 125) but not in either anti-AQP4 antibody-negative OSMS (75.0%, n = 32) or CMS (69.2%, n = 52) patients. There was no significant correlation between any HLA-DRB1 allele and the existence of anti-AQP4 antibody. These findings suggest that the emergence of anti-AQP4 antibody is reinforced by the presence of the HLA-DPB1*0501 allele in Japanese.

Greyhound meningoencephalitis: PCR-based detection methods highlight an absence of the most likely primary inducing agents

Greyhound meningoencephalitis is currently classified as a breed-associated idiopathic central nervous system inflammatory disorder. The non-suppurative inflammatory response can be distinguished from the other breed-associated disorders based on histopathology and lesion topography, however the nature of the response primarily suggests a viral infection. In the present study PCR and RT-PCR technologies were employed on frozen cerebral tissue from confirmed cases of meningoencephalitis to target specific viruses and protozoa likely to be implicated and to exclude the presence of bacterial 16SrRNA. Secondly, degenerate primers were used to detect viruses of the herpesvirus and flavivirus families. In addition cerebral tissues were probed for West Nile Virus. Viral nucleic acid sequences to Borna disease virus, to louping ill, tick borne encephalitis, West Nile and other flaviviruses were not detected. Canine distemper virus was detected in one animal with 97% homology to strain A75/15. Degenerate PCR for herpesviruses detected viral amplification products in one animal with 90% homology to canine herpesvirus DNA polymerase gene. Protozoal amplification products were only detected in a single dog with pathological confirmation of a combination of lesions of greyhound meningoencephalitis and a protozoal encephalomyelitis. Neospora was confirmed with sequence homology to Austrian strain 1. Bacterial 16SrRNA was not detected. The present study supports previous observations that many of the known microbial causes of canine meningoencephalitis are not involved. Findings could reflect that the causal agent was not specifically targeted for detection, or that the agent is at undetectable levels or has been eliminated from brain tissue. The potential roles of genetics and of molecular mimicry also cannot be discounted.

Evidence for humoral autoimmunity in neuromyelitis optica

Neuromyelitis optica (NMO) is an idiopathic central nervous system (CNS) demyelinating syndrome that may be distinguished from typical multiple sclerosis (MS). Although the cause of the disorder is not known, several lines of evidence suggest that the fundamental immunological process is driven by humoral mechanisms. These observations include the frequent coexistence of systemic autoimmune disease or positive serum autoantibodies with NMO, immunopathologic studies that demonstrate prominent complement activation and immunoglobulin deposition and the discovery of the serum autoantibody NMO-IgG, a potential NMO biomarker that targets aquaporin-4. Furthermore, clinical experience suggests that plasmapheresis and immunosuppressive therapies are beneficial for treatment and prevention of acute attacks but that standard MS immunomodulatory drugs may not alter the course of NMO. This evidence is reviewed in the context of its implications for future laboratory and clinical research in NMO.

The neurology of gluten sensitivity: separating the wheat from the chaff.

Coeliac disease is the prototypical gluten-sensitive disease. Clinico-pathological features heal on a gluten-free diet and relapse when gluten is reintroduced. An immunopathology is suspected. A number of neurological syndromes may be associated with coeliac disease but it is unclear whether these are directly or indirectly caused by gluten ingestion. It has been proposed that idiopathic ataxias and central nervous system white matter disease are gluten-sensitive syndromes. This is an exciting hypothesis because it offers new therapeutic possibilities including simple exclusion diets. However, interpretation is difficult because occult sub-clinical coeliac disease occurs commonly and background prevalence needs to be accounted for in population-based studies. This review will attempt to summarize the pertinent literature on this fascinating topic.

Clinical caveat: prior sleep deprivation can affect the MSLT for days

It is common practice to forcibly awaken patients from an all-night polysomnographic study prior to performance of a multiple sleep latency test (MSLT); either for reasons of protocol or for the convenience of the laboratory personnel. We report a case of a young woman who, by formal sleep study criteria, received the erroneous diagnosis of narcolepsy due to the effects of severe sleep deprivation, and document that the effects of prior sleep deprivation require more than one night of ad libitum sleep. Forced awakening prior to MSLT may permit sleep deprivation or delayed sleep phase syndrome to masquerade as narcolepsy or idiopathic central nervous system (CNS) hypersomnia.