Dual positivity for anti-MOG and oligoclonal bands: Unveiling unique clinical profiles and implications.

BACKGROUND: Distinguishing between MOG-associated disease (MOGAD) and multiple sclerosis (MS) presents a considerable challenge, as there are instances of overlapping clinical presentations. This complexity is further magnified in cases where patients concurrently exhibit both anti-myelin oligodendrocyte glycoprotein (anti-MOG) positivity and detectable oligoclonal bands (OCBs) This retrospective study investigates the clinical and imaging attributes of dual-positive patients, those with both anti-MOG positivity and OCBs, The study aims to show potential areas of overlap between multiple sclerosis (MS) and MOGAD. METHODS: Utilizing data gathered from three medical centers, we evaluated a cohort of 45 patients, stratifying them into two groups: those exclusively positive for anti-MOG antibodies and those displaying dual positivity. Our analysis encompassed a wide range of clinical and imaging parameters. The statistical techniques employed comprised Fisher's Exact Test along with Benjamini-Hochberg correction to ensure robustness of the findings. RESULTS: The study involved 45 patients with anti-MOG antibodies; 30 exhibited isolated anti-MOG positivity without OCBs, while 15 were dual-positive. The first group's average age was 10±7 years, compared to 28±17 years in the double-positive group (p = 0.001). CSF analysis showed no significant differences in pleocytosis, protein levels, or opening pressure between the groups. In the exclusive anti-MOG positivity cohort, 9 out of 15 patients received IVIG treatment; a larger subgroup with dual positivity chose anti-CD20 treatment. Notably, papilledema incidence was higher in the single-positive group (p = 0.014). Optic nerve enhancement (p = 0.0038) and nerve thickening (p = 0.0017) were markedly elevated in the single-positive population, with a trend towards pre-chiasmatic lesions (p = 0.06). Double-positive cases exhibited more polyfocal presentation (p = 0.013) and higher attacks per case (p = 0.002, HR=10.2, 95 % CI: 2.19 to 49.23). The double-positive group had more brain lesions (p = 0.0063) but no significant distinctions in other aspects. CONCLUSION: The results emphasize the challenges inherent in differentiating between MS and a more MOGAD. While the data suggest two plausible scenarios-either falling within the spectrum of MS or representing an intensified MOGAD-we recognize the need for stronger evidence to definitively classify these instances. This study underscores the imperative for thorough investigations to ascertain whether these cases align with the MS spectrum or denote an inflammatory variant of MOGAD.

The consequences of switching from Gilenya® to generics for fingolimod.

BACKGROUND: On May 2017, two generic drugs for fingolimod were introduced into the market in Israel, and most MS patients treated with Gilenya® (Novartis) were switched to fingolimod (Teva), or to Finolim (Rafa). In this study we analyzed the consequences of switching to generic fingolimod in a single MS center. METHODS: Study population included relapsing MS patients who were treated with Gilenya® for at least two year before May 2017, switched to generic fingolimod and remained on treatment for at least 2 years thereafter. Data before and after the switch were compared. RESULTS: Twenty-seven patients fulfilled the inclusion criteria (F = 20, RRMS=20, SPMS=7, average age 49±11.4 years, average disease duration=16.6 ± 7.6 years). Seventeen patients had to be switched back to the original Gilenya® due to intolerable new or worsening clinical adverse events (n = 9), clinical relapse (n = 1), clinical relapse with adverse events (n = 3), elevation of liver enzymes > X3 ULN (n = 3) and elevation of amylase (n = 1). Expanded Disability Status Scale (EDSS) score increased in 4 patients during the year before the switch, and in 12 patients during the year of treatment with generic fingolimod (p = 0.036). CONCLUSION: The tolerability, retention rate and probably efficacy of generic fingolimod seems to be lower than the original Gilenya®.

COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review.

INTRODUCTION: The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world. This pandemic has had a significant impact on patients with chronic diseases. Among patients with demyelinating diseases of the central nervous system (CNS), such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), concerns remain about the potential impact of COVID-19 on these patients given their treatment with immunosuppressive or immunomodulatory therapies. In this study, we review the existing literature investigating the impact of disease-modifying therapies(DMT) on COVID-19 risks in this group of patients. METHOD: For this systematic review, we searched PubMed from January 1, 2020, to December 3, 2020. The following keywords were used: "COVID-19" AND "Multiple Sclerosis" OR "Neuromyelitis Optica." Articles evaluating COVID-19 in patients with demyelinating diseases of CNS were included. This study evaluates the different aspects of the DMTs in these patients during the COVID-19 era. RESULTS AND CONCLUSION: A total of 262 articles were found. After eliminating duplicates and unrelated research papers, a total of 84 articles met the final inclusion criteria in our study. Overall, the experiences of 2493 MS patients and 37 NMOSD patients with COVID-19 were included in this review. Among them, 46(1.8%) MS patients died(the global death-to-case ratio of Covid-19 was reported about 2.1%). Among DMTs, Rituximab had the highest mortality rate (4%). Despite controversies, especially concerning anti-CD20 monoclonal antibody therapies, a relation between DMT-use and COVID-19 disease- course was not found in many studies. This observation reinforces the recommendation of not stopping current DMTs. Other variables such as age, higher expanded disability status scale (EDSS) scores, cardiac comorbidities, and obesity were independent risk factors for severe COVID-19. Despite the risks of infection, most patients were willing to continue their DMT during the pandemic because of more significant concern about the risk of relapse or worsening MS symptoms. After the infection, an immune response's attenuation was seen in the patients on Fingolimod and anti-CD20 monoclonal antibodies. This may be a critical finding in future vaccinations.

Association between cervical disc disease and lesions of multiple sclerosis.

BACKGROUND: Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. METHODS: Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1-C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher's exact test was used to test the association between demyelinating lesions and disc pathology. RESULTS: Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease (p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). CONCLUSION: Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.

Neurological complications of coronavirus infection; a comparative review and lessons learned during the COVID-19 pandemic.

INTRODUCTION: Coronavirus disease-19 (COVID-19) pandemic continues to grow all over the world. Several studies have been performed, focusing on understanding the acute respiratory syndrome and treatment strategies. However, there is growing evidence indicating neurological manifestations occur in patients with COVID-19. Similarly, the other coronaviruses (CoV) epidemics; severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) have been associated with neurological complications. METHODS: This systematic review serves to summarize available information regarding the potential effects of different types of CoV on the nervous system and describes the range of clinical neurological complications that have been reported thus far in COVID-19. RESULTS: Two hundred and twenty-five studies on CoV infections associated neurological manifestations in human were reviewed. Of those, 208 articles were pertinent to COVID-19. The most common neurological complaints in COVID-19 were anosmia, ageusia, and headache, but more serious complications, such as stroke, impairment of consciousness, seizures, and encephalopathy, have also been reported. CONCLUSION: There are several similarities between neurological complications after SARS-CoV-1, MERS-CoV and COVID-19, however, the scope of the epidemics and number of patients are very different. Reports on the neurological complications after and during COVID-19 are growing on a daily basis. Accordingly, comprehensive knowledge of these complications will help health care providers to be attentive to these complications and diagnose and treat them timely.

Familial Creutzfeldt-Jakob disease homozygous to the E200K mutation: clinical characteristics and disease course.

OBJECTIVE: To characterize the demographic, clinical features and disease course of familial Creutzfeldt-Jakob disease (fCJD) patients homozygous to the E200K mutation. METHODS: The Israeli National CJD Database was screened for patients homozygous to the E200K mutation. Patients' demographic data, clinical presentation and neurological findings, tau protein levels in the cerebrospinal fluid (CSF) and EEG, were assessed. RESULTS: Ten homozygous E200K patients were identified (80% males). Average age of onset was 47.5 ± 6.1 years (range 40-56) and the average age of death was 49.3 ± 7. 7 years (range 42-63) with average disease duration of 27.7 ± 9.7 months (range 2-97). Initial clinical presentation included behavioral change in 4/10 patients, cognitive decline in 3/10 patients and focal neurological deficits in 2/10 patients. Throughout the disease course, the clinical signs in descending order of prevalence included cerebellar (70%), brainstem (60%), extrapyramidal (50%), pyramidal (50%), frontal lobe signs (30%), and disturbances of ocular motility (30%) Compared to the 228 heterozygous E200K fCJD patients, the 10 homozygous patients were significantly younger at disease onset (47.5 vs 59.7 years, p < 0.001), had a longer disease duration (27.7 vs 8.5 months, p < 0.001) and presented more frequently with behavioral changes as initial manifestation (4/10 vs. 34/228, p = 0.05). CONCLUSIONS: Homozygous E200K fCJD patients are characterized by a relatively younger age of onset and longer disease duration. Behavioral changes as a presenting symptom were more common in homozygous patients and cerebellar dysfunction was the most common neurological manifestation throughout the disease course.

In whom does horizontal canal BPPV recur?

PURPOSE: The objective of this study is to examine the rate of horizontal canal BPPV recurrence of the same type and search for predisposing factors.

Mycosis fungoides - A cutaneous lymphoproliferative disorder in a patient treated with fingolimod for multiple sclerosis.

Fingolimod was the first oral disease-modifying drug approved for the treatment of relapsing-remitting multiple sclerosis (MS). It has previously been associated with rare cases of lymphoma. Here we describe the first case of mycosis fungoides - a cutaneous lymphoproliferative disorder, in an MS patient treated with fingolimod. who developed histologically confirmed mycosis fungoides 3 years after starting fingolimod. The drug was withdrawn and the patient was treated with radiotherapy and surgical excision with remission. This report points to a possible association between fingolimod and skin lymphoproliferative disorder and emphasizes the need for periodic skin examination.

Daclizumab for the treatment of adults with relapsing forms of multiple sclerosis.

INTRODUCTION: The goal of the article is to review the mechanism of action and the use of daclizumab, a humanized monoclonal antibody (mAb) against the alpha subunit of the high affinity interleukin-2 (IL-2) receptor, in the treatment of Multiple Sclerosis (MS). Areas covered: PubMed was searched for the terms 'daclizumab' and 'multiple sclerosis'. The mechanisms of action, pharmacokinetics and pharmacodynamics, major studies, side effects and drug interactions of daclizumab in MS are discussed. Expert commentary: Monthly daclizumab-beta [DAC-beta, formerly daclizumab high yield process (DAC HYP), approved as ZINBRYTA®, which has a different form and structure than an earlier form of daclizumab], is an effective and convenient treatment option for patients with relapsing forms of MS who have failed other treatment, or as a first-line option in highly active MS patients. IL-2 signaling modulation by daclizumab constitutes a novel mechanism of action which may also underlie the adverse and serious adverse events and risk profile of the drug that requires appropriate patient selection, monitoring and risk-mitigation programs.

Magnetic resonance brain imaging in patients with visual vertigo.

INTRODUCTION: Patients with visual vertigo (VV) report dizziness provoked by moving visual surroundings. It has been suggested that these subjects develop a compensation strategy for a vestibulo-proprioceptive deficit and rely excessively on visual input. We have postulated that patients with VV might have brain abnormalities that interfere with appropriate processing of visual stimulation and performed a brain MRI study to verify this hypothesis. MATERIALS AND METHODS: Patients with VV of more than 3 months duration were included. They were asked to complete the Situational Characteristic Questionnaire (SCQ) that scores for the symptoms of VV. Dizzy patients without VV served as controls. A brain MRI was performed with a Siemens 1.5 Tesla scanner in patients and controls. RESULTS: Twenty-four patients with VV were included. Their mean SCQ score was 1.45 ± 0.9 (normal 0.16 ± 0.28). In 50% of patients, abnormalities in MRI imaging were found. Thirty-three percent of 27 controls demonstrated an abnormal brain MRI. The two groups were similar in respect to the prevalence of a localized hemispheric or posterior fossa lesion (P = 0.13), but VV patients had more unspecific white matter brain changes than controls (P = 0.009). Patients and controls did not differ in age and gender distribution (P = 0.9) or the history of a neurotological event preceding their symptoms (P = 0.3). CONCLUSIONS: Our study suggests that multiple white matter lesions might contribute to occurrence of the phenomenon of VV. Future prospective large-scale studies by specific MR techniques are indicated to validate our preliminary findings and elucidate the pathological mechanism of VV.