CSF Oligoclonal Bands Research Articles

Clinical laboratory test utilization of CSF oligoclonal bands and IgG index in a tertiary pediatric hospital

BackgroundCriteria developed for the diagnosis of multiple sclerosis (MS) in adults are also used in the pediatric setting. However, differential diagnosis in pediatric-onset MS (POMS) is distinct from that of adult-onset MS. There is little literature characterizing the utility of oligoclonal bands (OCB) and IgG index in differentiating POMS from other childhood diseases with overlapping clinical presentation which can require immediate treatment. MethodsA retrospective review of all MS panels resulted between March 2022 and May 2023 on patients age ≤ 18 years at one tertiary care pediatric hospital in the northeastern United States was performed with pediatric neurology collaboration to characterize clinical utility (n = 85 cases). ResultsDemyelinating diseases accounted for 31 of 85 total cases (36.5%), 12 of these cases were POMS (14%). Other diagnoses consisted of psychiatric etiologies (17.6%), infectious meningitis/encephalitis (5.9%), and migraine (5.9%). Elevated IgG index was seen in 67% of those with demyelinating diseases, versus only 13% of those with other conditions. Unique OCBs were found in 41% of those with demyelinating diseases, versus only 9% of those with other conditions. Fourteen of 15 patients (93.3%) with psychiatric conditions had normal MS panels. ConclusionsPatients with demyelinating diseases were more likely to have elevated IgG index and unique OCBs versus patients with other conditions. For pediatric hospitals without in-house OCB evaluation, implementation of an in-house IgG index may serve as a rapid screen for differentials that include demyelinating diseases while awaiting OCB results, in the appropriate clinical context. Impact statementIgG index and CSF oligoclonal bands are important tools in the diagnosis of patients with suspected Multiple Sclerosis (MS). In the pediatric population, these markers are used to differentiate pediatric-onset MS (POMS) from other neurologic, psychiatric, and inflammatory diseases that display clinical overlap. The use of these markers in differentiating these conditions has not been thoroughly investigated. We examined the associations between abnormal markers and final diagnoses in pediatric patients undergoing testing for POMS in order to identify trends that may enhance ordering and reporting practices.

Multiple sclerosis in Central America and Caribbean countries: frequency and clinical characterization of an emergent disease.

Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.

Charcot-Marie-Tooth Type 2 Disease and Relapsing Remitting Multiple Sclerosis Coexistence

Multiple sclerosis (MS) and Charcot-Marie-Tooth disease (CMT) association has been reported, namely in CMTX and CMT1A. A 37-year-old woman with CMT type 2 (MFN2 mutation) developed subacute brainstem syndrome (left internuclear ophthalmoplegia, facial palsy and ataxia). Brain magnetic resonance imaging revealed infratentorial, periventricular and subcortical lesions, typical of MS (positive CSF oligoclonal bands, negative anti-aquaporin 4 and anti-MOG antibodies). Patient underwent natalizumab, reaching NEDA-3 – no evidence of disease activity - (3-years follow-up). Patients with MFN2 mutations may disclose optic atrophy and periventricular white matter T2 signal changes mimicking MS. Notwithstanding, this is, probably, the first report of proven concomitance between both conditions.

Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

African American patients with Multiple Sclerosis (MS) have higher proportions of CD19+ and CD20+ B-cell lineage cells in their cerebrospinal fluid than White MS patients

ObjectivesTo compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-American (AA) and White (W) patients with MS. BackgroundAA MS patients are more likely to have oligoclonal bands in CSF, higher IgG index in CSF, and higher circulating plasmablasts in blood than W MS patients. It is unknown whether the proportion of B-cells in CSF differs between AA and W patients in MS. MethodsDemographics, disease-related information, treatment history were retrospectively collected on patients with MS who self-identified as AA or W and underwent flow cytometry of CSF during diagnostic work-up. Proportion of B-lymphocytes, T-lymphocytes, NK cells, monocytes, and plasma cells were analyzed with flow cytometry. Results20 AA and 56 W MS patients fulfilled our inclusion criteria. The groups had similar demographics, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (1.08 vs. 0.85, p = 0.031). AA had higher proportions of CD19+ (5.46 % AA vs. 2.26 % W, p = 0.006) and CD20+ (4.64 % AA vs. 1.91 % W, p = 0.004) cells but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. ConclusionsB-cells are overrepresented in the CSF of African American patients with MS relative to Whites.

CSF oligoclonal IgG bands are not associated with ALS progression and prognosis.

Amyotrophic Lateral Sclerosis (ALS) is characterized by progressive motoneuron degeneration through cell autonomous and non-cell autonomous mechanisms; and the involvement of the innate and adaptive immune system has been hypothesized based on human and murine model data. We have explored if B-cell activation and IgG responses, as detected by IgG Oligoclonal bands (OCB) in serum and cerebrospinal fluid, were associated with ALS or with a subgroup of patients with distinct clinical features. IgG OCB were determined in patients affected by ALS (n=457), Alzheimer Disease (n=516), Mild Cognitive Impairment (n=91), Tension-type Headache (n=152) and idiopathic Facial Palsy (n=94). For ALS patients, clinico-demographic and survival data were prospectively collected in the Register Schabia. The prevalence of IgG OCB is comparable in ALS and the four neurological cohorts. When the OCB pattern was considered (highlighting either intrathecal or systemic B-cells activation), no effect of OCB pattern on clinic-demographic parameters and overall. ALS patients with intrathecal IgG synthesis (type 2 and 3) were more likely to display infectious, inflammatory or systemic autoimmune conditions. These data suggest that OCB are not related to ALS pathophysiology but rather are a finding possibly indicative a coincidental infectious or inflammatory comorbidity that merits further investigation.

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Paraneoplastic and non-paraneoplastic limbic encephalitis: distinguishing features and outcomes (P7-5.031)

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response

BackgroundAntibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. MethodsAll patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. ResultsOne-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. ConclusionsOverall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.

A Severe Case of Lupus Cerebritis

Objective Lupus cerebritis is a rare but potentially fatal complication of SLE. Prompt diagnosis and rapid initiation of therapy can prove lifesaving. Background We present the case of a 31-year-old woman who presented to the emergency department with one week of fevers, headaches and confusion. Review of systems was notable for diffuse muscle and joint pains, weakness and a rash. SLE and Sjogren's were both diagnosed six months prior to admission and treatment included prednisone, methotrexate, and hydroxychloroquine. She self-discontinued therapy six weeks prior to seek natural remedies in her native Ecuador. Vitals on admission were 102.2 F, 111 beats/min, 96/67 mmHg, 16 breaths/min and 95% SO2 on 2 L/min via nasal cannula. Physical exam was notable for conjunctival injection, hypopyon (OD), and oral ulcers with visible bleeding. Pelvic exam showed shallow ulcerations of the vaginal mucosa. Neurological exam was significant for diffuse weakness. There were punched-out ulcers on the digits of both hands. Laboratory markers of lupus disease activity were markedly abnormal. An MRI of the brain showed numerous punctate foci of restricted diffusion in the supra and infratentorial brain parenchyma. Few of the lesions showed subtle rim-enhancement and microhemorrhagic foci. CSF analysis showed 220 WBC/mL (70% PMNs), glucose 13 mg/dL and protein 63.7 mg/dL. No CSF oligoclonal bands were detected. CSF/serum albumin index showed mild impairment of the blood brain barrier. Cultures of CSF, blood, urine and sputum showed no growth. Design/Methods NA. Results The patient improved significantly upon initiation of pulsed corticosteroids, plasma exchange, and cyclophosphamide. She was transitioned to steroid-sparing agents and is doing well. Conclusions Lupus cerebritis can be the dominant syndrome in a patient presenting with uncontrolled SLE. Imaging and CSF findings can be dramatic and evoke infectious syndromes. Once alternative diagnoses have been ruled out lupus cerebritis should be managed aggressively to ensure good outcomes.

Unmasking of a Relapsing Encephalomyelitis After SARS-CoV-2 Infection and COVID-19 Vaccination

Objective NA. Background Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask neuroinflammatory conditions. We present a case of relapsing steroid-responsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. Design/Methods NA. Results A 47-year-old man with a history COVID-19 presented with subacute lower extremity weakness, erectile dysfunction, and gait instability with falls. His symptoms started several weeks after COVID-19 vaccination which he underwent 3 months after COVID-19 infection. His initial exam demonstrated weakness at the knees and ankles and extensor plantar responses. MRI demonstrated innumerable enhancing lesions involving the subcortical white matter, basal ganglia, thalami, brainstem, cerebellum, and the entire spinal cord parenchyma. CSF testing revealed a lymphocytic pleocytosis (10 WBC, 88% lymphocytes), and transient matched serum and CSF oligoclonal bands. Testing was unremarkable for infections, malignancies, primary demyelinating conditions, etc. He responded dramatically to five days of high dose methylprednisolone but had recurrence of symptoms with weaning of oral prednisone, requiring another pulse of IV steroids. After 2 months, his steroids were weaned again, with clinical and radiographic recurrence, requiring another course of IV steroids. He was subsequently transitioned to mycophenolate as a steroid-sparing agent. Literature review identified 20 additional cases of CNS neuroinflammatory disease after either SARS-CoV-2 infection or vaccination (11 transverse myelitis, 6 optic neuritis, 3 encephalomyelitis). Conclusions Our patient's steroid-dependency and relapsing course suggests unmasking of an underlying CNS neuroinflammatory condition. Temporal associations of neurological conditions with vaccinations or infections do not prove causality despite previous reports of such sequelae. Vaccines containing SARS-CoV-2 antigens may enhance autoimmunity by mechanisms including polyclonal activation, epitope spreading, or molecular mimicry. This case highlights that the resulting inflammation may be insidious and extensive, though treatable. As COVID-19 constitutes a life-threatening infection in some patients, the benefits of vaccination outweigh the smaller risk of unmasking an immune-related condition.

Autoimmune Encephalitis Misdiagnosis: A Review of Reported Cases

Objective To identify autoimmune encephalitis (AE) mimics and clinical features reported in the literature. Background Recent evidence suggesting that AE is as frequent as infectious encephalitis has increased awareness and testing for immune-mediated causes of neurological impairment. Consistent with this theme, several publications have focused on patients in whom a diagnosis of AE was initially overlooked. On the contrary, AE remains a rare diagnosis in clinical practice, opening up the possibility for symptoms, signs, and test findings associated with other etiologies to be misattributed to AE. Design/Methods Case reports published in PubMed in English language before 04/2022 were reviewed. Cases in whom AE was clearly suspected during the diagnostic work-up or misdiagnosed were included. Results A total of forty-five patients with a final diagnosis different from AE were included from 40 reports. Median age was 52 (range 5-86) years; 30/45 (67%) were male. Twenty-eight patients fulfilled the criteria for possible AE (62%), five for definite AE (11%), and twelve neither (27%). Features suggestive of AE were acute/subacute altered mental status (ranging from abnormal behavior to coma), (82%); new-onset refractory status epilepticus, (7%); CSF pleocytosis (42%) or oligoclonal bands (9%), and apparent response to immunotherapy (38%). In 26 cases, imaging corresponded to the anatomical classification of limbic encephalitis, 15 had one or more cortical/subcortical T2-abnormalities, one meningeal involvement, one brainstem involvement, and two had normal MRI. In 12 patients, clinically not relevant neural autoantibodies were detected in serum and/or CSF, including GAD, Anti-Zic4, CASPR2, VGKC, anti-N-type calcium channel antibody, anti-LGI1, and GQ1B. We identified four common AE mimic categories: neoplasms (15 patients), infectious diseases (9 patients), genetic diseases (9 patients), and neurodegenerative diseases (7 patients). Five patients had other etiologies. Conclusions Despite well-defined clinical diagnostic criteria, the misdiagnosis of AE encompasses atypical presentation of common disorders and less likely rare diagnoses.

One Case of POMES Syndrome with “Limb Pain” As the Main Presentation

Objective: To summarize the clinical manifestations, imaging features and gene mutation sites of a patient with pomes syndrome with “limb pain” as the main manifestation, so as to improve the understanding of this rare disease. Medical History: The patient was a 34 year old male with limb pain and fatigue for more than 20 days. Symptoms and Signs: The tongue is in the middle, the uvula is in the middle, the bilateral pharyngeal reflex disappears, the neck is soft, the muscle strength of both upper limbs is grade 5, the proximal muscle strength of both lower limbs is grade 4, and the distal muscle strength is grade 5. The muscle tension of the extremities is normal, the tendon reflex of the extremities disappears, and no obvious abnormalities are found in the examination of deep and shallow sensation and ataxia. The diagnostic method bone marrow puncture showed thrombocytosis. The pathological results showed that the hematopoietic cells of the three lines were proliferative, the oligoclonal bands in CSF were positive, and the oligoclonal bands in serum were positive. Serum immunofixation electrophoresis (March 30, 2018): IgG λ Abnormal monoclonal bands were found in the lane, and the type of monoclonal immunoglobulin was IgG- λ Type. Blood analysis suggested thrombocytosis (738 × 10°several L). There is no specific therapeutic drug, but hormone and hydroxyurea are effective. The clinical outcome was improved and the disease was gradually alleviated. The clinical conclusion is that poems syndrome is a rare clinical syndrome with various forms. Early intervention is effective for the prognosis of patients.

PSYCHOSIS OR ENCEPHALITIS? HAVE A LOW INDEX OF SUSPICION FOR ANTI-N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ENCEPHALITIS

PSYCHOSIS OR ENCEPHALITIS? HAVE A LOW INDEX OF SUSPICION FOR ANTI-N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ENCEPHALITIS

Anti-N-methyl-D-aspartate receptor encephalitis: characteristics and rapid diagnostic approach in the emergency department

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common type of autoimmune encephalitis. Patients with this condition are frequently very ill but are often misdiagnosed in the Emergency Department (ED). The objective of this study was to analyze the clinical characteristics of anti-NMDAR patients in the ED and to identify any associations with a diagnosis of anti-NMDAR encephalitis.MethodsWe performed a retrospective analysis of a prospectively obtained cohort of ED patients from May 2011 to December 2017. We identified patients diagnosed with anti-NMDAR encephalitis in this cohort and extracted key patient characteristics and clinical data, including patient gender, age, presentation, modified Rank Score (m-RS), laboratory test results, significant treatments, and mortality.ResultsEighty-seven patients with anti-NMDAR encephalitis were identified. 54 (62.1%) were female, 23 (26.4%) were < 18 years old, 14 (16.1%) had teratoma, and 45 (51.7%) had an m-RS ≥ 4. Fever, altered mental status, and seizures were the most common symptoms, with a > 50% incidence of each symptom in the cohort. The sensitivity of CSF oligoclonal band (OB) testing was 78.9%. 22 (25.3%) were admitted to the ICU, 20 (23.0%) patients were intubated, but only one patient died (1.1%). 47 (54.0%) were misdiagnosed prior to ED arrival. All patients underwent immunotherapy as first-line treatment for anti-NMDAR encephalitis.ConclusionsA majority of anti-NMDAR encephalitis patients presenting to the ED were female and were likely to be misdiagnosed prior to arrival. Patients with symptoms of fever, altered mental status, and seizures need a lumbar puncture, including CSF OB testing, for definitive diagnosis.

Repeated lumbar puncture in search of oligoclonal bands – What is the yield?

BackgroundCerebrospinal fluid (CSF) oligoclonal bands (OCBs) are immunoglobulins that represent intrathecal synthesis during central nervous system infection or inflammation. As repeated lumbar puncture (LP) is usually not performed unless clinically indicated, there is very limited data on the natural history and course of OCBs status in the CSF, its relation to disease activity, duration of persistence, and the rate of either CSF conversion of OCBs or disappearance. MethodsWe retrospectively collected data from adult patients with various neurological syndromes who had repeated CSF samplings. OCBs were analyzed by agarose gel electrophoresis or by isoelectric focusing. ResultsDuring the years 2010–2020, we identified 48 patients with at least two CSF OCBs results in Rabin Medical Center. These included 11 patients with Multiple Sclerosis, ADEM and NMOSD (one patient each), 7 patients with unspecified demyelinating disease, 4 with optic neuropathy, 15 patients with unknown diagnosis. Overall, 6/48 (12.5%) patients had change in OCBs status between first and second LP's. Four (8.33%) patients changed OCBs from positive to negative, and two patients (4.2%) from negative to positive. There was no significant difference in demographic, disease category, CSF constituents or time interval to second LP between patients who changed their OCBs status to those who did not. ConclusionRepeated LP for OCBs analysis in our cohort did not yield a practical benefit. The conversion rate of OCBs status was low (12.5%) and in most cases did not lead to a change in the final diagnosis or patient's clinical management.

Pure Relapsing Short Myelitis: Part of the Multiple Sclerosis Spectrum or New Entity?

Background and ObjectivesPure relapsing short myelitis with clinical and paraclinical features suggesting multiple sclerosis (MS) has been described recently. Here, we evaluated the existence of this potential new form of MS by retrospectively searching for similar cases in the databases of the French tertiary MS centers.MethodsPatients were included based on the present criteria: at least 2 short (<3 vertebral segments) myelitis episodes; minimum follow-up of 3 years; no MS-like brain lesion during all the follow-up; tested negative for both anti–myelin oligodendrocyte glycoprotein and anti–aquaporin 4 antibodies in serum; presence of oligoclonal bands in CSF; and comprehensive workup to exclude alternative diagnoses.ResultsEighteen patients fulfilled all criteria. The sex ratio (females/males) was 5/1; the median (range) age at first relapse was 35.5 (25–54) years, the disease duration was 80.5 (50–308) months, and the annualized relapse rate was 0.36 (0.1–0.5). The median (range) number of relapses per patient was 2 (2–5), and the median (range) Expanded Disability Status Scale score at last follow-up was 1 (0–7.5). In CSF, the median (range) protein level was 0.34 g/L (0.18–0.77), and the median (range) number of mononuclear cells was 3 (0–28). Spinal cord MRI demonstrated a median (range) number of 2 (1–5) lesions per examination and 3 [1–7] on the last examination. Fifty-five percent of lesions involved the cervical levels. Secondary progressive evolution occurred in 3 of 18 (17%) patients.DiscussionPure spinal MS could be a rare entity in the MS disease spectrum. However, the existence of a distinct entity in the inflammatory CNS disorders cannot be excluded.

Immune-Mediated Cerebellar Ataxia Associated With Neuronal Surface Antibodies.

BackgroundImmune-mediated cerebellar ataxias (IMCAs) are common in paraneoplastic cerebellar degeneration (PCD) but rarely occur in patients with neuronal surface antibodies (NSAbs). Although cerebellar ataxias (CAs) associated with anti-NMDAR and anti-CASPR2 have been reported in a few cases, they have never been studied systematically. This study aimed to analyze the characteristics of anti-NSAbs-associated CAs.MethodsA retrospective investigation was conducted to identify patients using the keywords IMCAs and NSAbs. We collected the clinical data of 14 patients diagnosed with anti-NSAbs-associated CAs.ResultsThe median age was 33 years (16-66), and the male-to-female ratio was 4:3. Nine were positive for NMDAR-Ab, two for LGI1-Ab, two for CASPR2-Ab, and one for AMPA2R-Ab. CAs were initial symptoms in three patients and presented during the first two months of the disease course (10 days on average) among the rest of the patients. After the immunotherapy, two cases were free from symptoms, and eight cases recovered satisfactorily (10/14, 71.4%). Compared with other causes of IMCAs, anti-NSAbs were more frequently associated with additional extra-cerebellar symptoms (85.7%), mostly seizures (78.6%) and mental abnormalities (64.3%). In the CSF analysis, pleocytosis was detected in ten patients (71.4%) and oligoclonal bands (OB) were observed in nine patients (64.3%). Moreover, compared with PCD and anti-GAD65-Ab-associated CAs, anti-NSAbs-associated CAs showed a better response to immunotherapy.ConclusionIMCAs are rare and atypical in autoimmune encephalitis with neuronal surface antibodies. Compared with other forms of IMCAs, more symptoms of encephalopathy, a higher rate of pleocytosis and positive OB in CSF, and positive therapeutic effect were the key features of anti-NSAbs-associated CAs.

Smoldering lesions in MS: if you like it then you should put a rim on it.

In multiple sclerosis (MS), chronic active/smoldering white matter lesions presenting with hypointense rims on susceptibility-weighted imaging (SWI) of the brain have been recognized as an important radiological feature. The aim of this work was to study the prevalence of paramagnetic rim lesions (RLs) in MS patients in a clinical setting and to assess differences in demographic and clinical variables regarding the presence of RLs. All 3T brain magnetic resonance (MR) studies performed in MS patients between July 2020 and January 2021 were reviewed. In all patients, RLs were assessed on three-dimensional (3D) SWI images and the T2 FLAIR lesion load volume was assessed. Demographic, laboratory (oligoclonal bands in CSF), and clinical data, including functional status with Expanded Disability Status Scale (EDSS), were retrieved from the clinical files. Of the 192 patients, 113 (59%) presented with at least 1 RL. In the RL-positive group, the mean RL count was 4.81 ranging from 1 to 37. There was no significant difference in the number of RLs between the different types of MS (p = 0.858). Regarding the presence of RLs, there were no significant differences based on gender (p = 0.083), disease duration (p = 0.520), treatment regime (p = 0.326), EDSS score (p = 0.103), and the associated T2 FLAIR lesion load volume. SWI RLs were frequently detected in our cohort regardless of the MS type, T2 FLAIR lesion load volume, demographic features, disease duration, or clinical score. Our results suggest that RLs are not associated with more severe forms of the disease. Today, RLs can be seen on 3T 3D SWI, although this is not a clinical standard sequence yet. Therefore, it should be considered an additional helpful MR sequence in the diagnostic workup of MS, although more studies are warranted to establish the role of RLs as prognostic markers.

Evaluating the Role of HLA DRB1 Alleles and Oligoclonal Bands in Influencing Clinical Course of Multiple Sclerosis - A Study from the Mangalore Demyelinating Disease Registry.

Background:The possible interaction between genetic and immunological factors in influencing clinical course of multiple sclerosis (MS) has not been studied previously in Indian population.Aim:In this study we evaluated the association of HLA alleles and OCB in affecting clinical course and disability of MS.Methods:Clinical and demographic features of 145 MS patients who had CSF oligoclonal bands (OCB) tested by isoelectric focussing technique were analyzed, disability status estimated, and HLA DRB1 alleles were genotyped.Results:OCBs were positive in 53.8% (78/145) of all MS cases. Patients with CSF OCB had more frequent relapses and an association with HLA DRB1*15. Early disease onset and a high annualized relapse rate was associated with HLA DRB1*03 allele. A relapsing remitting course for MS was seen with HLA DRB1*03 & 15 while a progressive disease was associated with DRB1*01. Presence of both OCB and HLA DRB1*13 was significantly associated with disability in this cohort.Conclusion:The results of our study suggest that an interaction between immunological and genetic factors may influence disease onset, course, and disability in MS.

352. Seronegative Relapse of Brucellosis in the Central Nervous System

BackgroundBrucellosis is the most common zoonotic infection in the world. High risk areas include the Mediterranean Basin, Eastern Europe and the Middle East. Clinical presentation is quite heterogenous.CNS involvement (neurobrucellosis) varies widely, from 0,5 to 25%. This reflects a high prevalence in endemic areas and the lack of established criteria for a diagnosis. We present a patient with a seronegative relapse of brucellosis, confined in the CNS, identified by Brucella IgG ELISA and 16S rRNA sequencing.MethodsCase ReportResultsA 60-year-old man, farmer, with a history of systematic brucellosis two years before admission, presented with high fever, headache and agitation. A serum agglutination test and anti-Brucella IgG ELISA were negative at baseline. Spinal tap revealed lymphocytosis and low glucose. CSF culture was negative. The patient received ceftriaxone, ampicillin and acyclovir with an initial remission. A week later the patient’s symptoms relapsed. Administration of ceftriaxone and acyclovir was reinitiated with clinical improvement, however, lymphocytic meningitis persisted even after 15 days of treatment.Brain MRI demonstrated nonspecific white matter hyperintensities and severe meningitis as identified by contrast-enhanced 3D Flair MRI. CSF oligoclonal bands showed intrathecal immunoglobin synthesis. CSF agglutination tests and CSF IgG ELISA were positive for Brucella. Though CSF PCR for Brucella was negative, 16S rRNA sequencing revealed the presence of Brucella spp. Patient was treated with ceftriaxone and dexamethasone and despite an initial worsening of neurological symptoms of tremor, loss of balance, hearing loss and diplopia, a clinical remission was achieved after a month and a laboratory remission after eight months of treatment.Brain MRI: 3D Flair Sequence with Contrast Enhancement Table. CSF Parameters ConclusionNeurobrucellosis presents with a variety of clinical symptoms and it should always be considered in neurological patients in highly endemic areas. Establishing a diagnosis is challenging. In our patient, CSF oligoclonal bands and the agglutination test in the CSF helped in achieving a diagnosis, suggesting their possible role in the diagnostic criteria. Although still under debate, the use of corticosteroids in our patient as well as the prolonged use of ceftriaxone in the therapeutic regime were crucial.Disclosures All Authors: No reported disclosures