Early clinical response and complications of therapeutic plasma exchange in central nervous system demyelinating diseases.

Background: Appropriate treatment reduces the severity and duration of relapses in demyelinating diseases of Central Nervous System (CNS). If high-dose corticosteroids treatment fails, therapeutic plasma exchange (TPE) is considered as a rescue treatment. Objectives: This study aimed to investigate early clinical response and complications of TPE and prognostic factors in CNS demyelinating relapses. Design: This prospective observational study was designed in a tertiary center during one year. Methods: All adult patients diagnosed corticosteroid-resistant Multiple Sclerosis (MS), NeuroMyelitis Optica Spectrum Disorder (NMOSD), idiotypic Transverse Myelitis or Clinical Isolated Syndrome relapses, were eligible. Clinical response is defined based on Expanded Disability Status Scale (EDSS) at discharge. Clinical and laboratory complications recorded. Results: Seventy-two patients were analyzed which 58.3% patients were female. MS was diagnosed for 61.1% of cases. Thirty-five patients (48.6%) responded and the mean differences of EDSS significantly decreased 0.60 score (CI95%:0.44-.77). Electrolyte imbalances and thrombocytopenia occurred in 80.6% and 55.6% of cases respectively and 40.3% of patients had systemic reactions. However, 26.4% patients experienced moderate to severe complications. In patients with moderate to severe disability, responders were younger (MD: 8.42 years, CI95%: 1.67-15.17) and had lower EDSS score at admission (median:6, IQR: 5.5-6 against 7.5 IQR: 6.5-8). The risk of failure was higher in active progressive MS patients compared with RRMS patients (OR: 6.06, CI 95%:1.37-26.76). Patients with thrombocytopenia were hospitalized more than others (MD: 1.5 days, CI 95%: 0-3). Females were more prone to hypokalemia and systemic reactions (OR: 3.11, CI 95%:1.17-8.24 and OR: 6.67, CI 95%:2.14-20.81 respectively). Conclusion: The most common indication of TPE was corticosteroid-resistant severe MS relapses. About half of the patients presented an early clinical response. Lower disability, younger age and RRMS diagnosis are prognostic factors of better response. One out of four patients experienced moderate to severe complications, mainly electrolyte imbalances and systemic reactions. Appropriate interventions against these complications should be considered during TPE, especially in females.

Plasmapheresis and IVIG for Treatment of Non-Tumor Anti-Tr/DNER Antibody-Associated Ataxia: A Case Report.

Autoimmune cerebellar ataxia (ACA) is a condition characterized by progressive ataxia resulting from an immune-mediated attack on cerebellar structures. The presence of anti-Tr/DNER antibodies, strongly associated with Hodgkin lymphoma, has been identified in ACA. However, cases with no underlying malignancy are rare. We report the case of a 49-year-old woman presenting with progressive ataxia, slurred speech, and dizziness over three months. The patient exhibited significant cerebellar symptoms, including dysarthria and limb ataxia, without signs of other systemic illnesses. Comprehensive investigations, including imaging, lumbar puncture, and autoantibody testing, were performed. The cerebrospinal fluid (CSF) sample revealed positivity for Tr/DNER antibodies, leading to a diagnosis of autoimmune cerebellar ataxia. The patient underwent nine sessions of plasmapheresis, followed by six doses of intravenous immunoglobulin (IVIG), resulting in significant clinical improvement. Despite extensive cancer screening, no underlying malignancy was detected, suggesting a non-tumor origin of anti-Tr/DNER antibodies. The patient's gait improved, ataxia resolved, and cerebellar tests normalized following treatment. The patient was further managed with rituximab treatment every six months. This case represents a presentation of anti-Tr/DNER-associated autoimmune cerebellar ataxia without malignancy. The successful treatment with plasmapheresis and IVIG suggests that these interventions may be effective in managing autoimmune cerebellar ataxia associated with anti-Tr/DNER antibodies. Further research is needed to understand the underlying mechanisms of this condition and to determine the optimal treatment strategies.

The benefit of intravenous immune globulin in the treatment of delayed radiation myelopathy.

Delayed radiation myelopathy (DRM) is a rare yet severe complication of radiotherapy. This condition has a progressive pattern that is often irreversible. Several therapeutic strategies have been introduced to alleviate disease complications, including corticosteroids, hyperbaric oxygen, anticoagulants, and antivascular endothelial growth factor (VEGF) agents. However, despite their beneficial effect, they have not been the definitive treatments for DRM. Here we present the case of a 55-year-old woman with a history of multiple myeloma who developed neurological complications 11 months after radiation therapy. As her radiologic findings demonstrated transverse myelitis, based on the DRM diagnostic criteria, the diagnosis of delayed radiation myelitis was reached. Therefore, methylprednisolone pulse therapy was initiated, resulting in the complete resolution of her neurological symptoms. However, on her follow-up examination, although she did not have new neurological complications, magnetic resonance imaging (MRI) demonstrated a residual enhancement in the thoracic spinal cord area. Hence, due to the possibility of myelitis progression and spinal cord atrophy, intravenous immune globulin (IVIG) was administered, resulting in the resolution of lesion enhancement. Considering this outcome and the immunomodulatory properties of IVIG, it could be regarded as a potential therapeutic option in the case of DRM activity.

Thalamic asymmetry in Multiple Sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic neuroinflammatory disease that affects the central nervous system. Asymmetry is one of the finding in brain MRI of these patients, which is related to the debilitating symptoms of the disease. This study aimed to investigate and compare the thalamic asymmetry in MS patients and its relationship with other MRI and clinical findings of these patients. METHODS: This cross-sectional study conducted on 83 patients with relapse-remitting MS (RRMS), 43 patients with secondary progressive MS (SPMS), and 89 healthy controls. The volumes of total intracranial, total gray matter, total white matter, lesions, thalamus, and also the thalamic asymmetry indices were calculated. The 9-hole peg test (9-HPT) and Expanded Disability Status Scale (EDSS) were assessed as clinical findings. RESULTS: We showed that the normalized whole thalamic volume in healthy subjects was higher than MS patients (both RRMS and SPMS). Thalamic asymmetry index (TAI) was significantly different between RRMS patients and SPMS patients (p = 0.011). The absolute value of TAI was significantly lower in healthy subjects than in RRMS (p < 0.001) and SPMS patients (p < 0.001), and SPMS patients had a higher absolute TAI compared to RRMS patients (p = 0.037). CONCLUSIONS: In this cross-sectional study we showed a relationship between normalized whole thalamic volume and MS subtype. Also, we showed that the asymmetric indices of the thalamus can be related to the progression of the disease. Eventually, we showed that thalamic asymmetry can be related to the disease progression and subtype changes in MS.

Familial Mediterranean Fever and Transverse Myelitis: A Causal Relation?

Familial Mediterranean fever (FMF) is a rare autoinflammatory disorder characterized mainly by recurrent self-limited episodes of fever and polyserositis. FMF-related neurologic complication is an old debate, and the correlation between FMF and demyelinating disorders has been a matter of dispute for a long time. Few reports demonstrated a relationship between FMF and multiple sclerosis; however, the existence of a causal relationship between FMF and demyelinating disorders is still a puzzle. This report presents the first case of transverse myelitis following FMF attacks in which neurologic manifestations were resolved using colchicine treatment. Due to relapses of FMF, which were accompanied by transverse myelitis, rituximab was administered, which resulted in stabilizing disease activity. Accordingly, in the case of colchicine-resistant FMF and FMF-related demyelinating conditions, rituximab could be considered as a potential therapeutic option to alleviate both polyserositis and demyelinating manifestations.

Effect of deep gray matter atrophy on information processing speed in early relapsing-remitting multiple sclerosis.

BACKGROUND: Cognitive dysfunction, including reduced Information processing speed (IPS), is relatively common in multiple sclerosis(MS). IPS deficits have profound effects on several aspects of patients' life. Previous studies showed that deep gray matter atrophy is highly correlated with overall cognitive impairment in MS. However, the effect of deep gray matter atrophy on IPS deficits is not well understood. In this study, we evaluated the effects of deep gray matter volume changes on IPS in people with early relapse-remitting MS (RRMS) compared to healthy control. METHODS: In this case-control study, we enrolled 63 case with RRMS and 36 healthy controls. All patients were diagnosed within 6 years. IPS was evaluated using the Integrated Cognitive Assessment (ICA) test. We also performed a 1.5T MRI to evaluate deep gray matter structures. RESULTS: People with RRMS had lower accuracy in the ICA test (p = .01). However, the reaction time did not significantly differ between RRMS and control groups (p = .6). Thalamus volume was significantly lower in the RRMS group with impaired IPS compared to the RRMS with normal IPS and control groups (p < 10-4). Other deep gray matter structures were not significantly different between the RRMS with impaired IPS group and the RRMS with normal IPS group. CONCLUSION: Some people with MS are impaired in IPS even in the early stages of the disease. Thalamic atrophy affected IPS in these patients, however atrophy in other deep gray matter structures, including caudate, putamen, globus pallidus, hippocampus, amygdala, accumbens, and cerebellum, were not significantly correlated with IPS impairment in early RRMS.

Fulminant neuromyelitis optica spectrum disorder (NMOSD) following COVID-19 vaccination: A need for reconsideration?

During the coronavirus disease 2019 (COVID-19) pandemic, mass vaccination was a beneficial strategy in many countries. Nevertheless, reports of serious complications such as postvaccination neuromyelitis optica spectrum disorder (NMOSD) raised concerns about the safety of vaccines. Anamnart and colleagues explained postvaccination NMOSD following different vaccines, including COVID-19. To emphasize the message of this article, in this letter, we present a unique case of postvaccination NMOSD with a fulminant and fatal course, which may show a plausible relationship between COVID-19 vaccination and triggering anti-aquaporin-4 antibody (AQP4-Ab).

Abrupt bilateral blindness as a rare post-acute demyelinating consequence of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could prompt various neurological complications. Abrupt visual disturbance was reported as a rare severe manifestation of post-coronavirus disease 2019 (COVID-19). Autoimmune conditions were assumed to have an undeniable role in creation of such circumstances. This report presents a 69-year-old woman with sudden bilateral blindness three weeks after recovering from a SARS-CoV-2 infection. Demyelination due to COVID-19-related autoimmune disorder of the central nervous system (CRAD-C) was considered to be the etiology of her bilateral blindness. Due to her progressive demyelination, immunosuppressive treatments were administered, which resulted in stabilizing post-COVID-19 demyelinating lesions. Accordingly, in the case of COVID-19-related neurological deficits, especially the acute and progressive symptoms, there should be great consideration of autoimmune response to prevent serious complications; hence early diagnosis, treatment, and long-term assessment of patients are necessitated.

Safety of Sinopharm vaccine for people with Multiple Sclerosis: Study of adverse reactions and disease activity.

BACKGROUND: The aim of this study was to evaluate the safety of Sinofarm vaccine (BBIBP-CorV) in patients with multiple sclerosis (pwMS). METHODS: This study was conducted on pwMS patients in Isfahan, Iran. All participants received two doses of BBIBP-CorV (Sinopharm vaccine). Demographic information and data on vaccine side effects were collected after each dose using questionnaires. All patients that recorded worsening of MS symptoms were evaluated and those with true relapse were treated with IV methyl prednisolone. RESULTS: Of the 1538 patients, 1151 (74.8%) were female and the mean age was 40.45 ± 9.74. The average disease duration was 10.38±6.81 years and 76.1% of participants had RRMS. 92.8% of the participants were using DMTs and mean EDSS was 2.06 ± 3.16. 54.2% (833 patient) reported at least one adverse event after the first dose of vaccine and 46.8% (720 patient) after the second dose; in both cases going away in a few days. Most prevalent adverse events after both doses were injection site pain, headache, myalgia, fever and fatigue. Adverse events were more prevalent in younger and less prevalent in mildly disabled patients. There were seven cases of Covid-19 infection between the first and second vaccination dose, and eight cases during one-month follow -up after the second dose, none of whom needed mechanical ventilation. Ten patients after first dose and thirteen patients after the second dose experienced acute relapse. A patient had two relapses, one after each vaccine dose that were clinically and radiologically confirmed. The first relapse occurred seven days after the first vaccination with hemiparesis and other relapse, 14 days after the second dose with diplopia, hemiparesis and ataxia. CONCLUSION: Adverse events in pwMS following vaccination with Sinopharm vaccine was similar to the general population, which were more common in younger patients and less common in those with mild disability. As no increase in relapse rate after vaccination was detected, Sinopharm vaccine was safe in MS patients.

COVID-19 infection and hospitalization rate in Iranian multiple sclerosis patients: What we know by May 2021.

BACKGROUND: Despite investigations on the effect of disease modifying therapies (DMTs) used in multiple sclerosis (MS) on coronavirus disease 2019 (COVID-19); there are still controversies. OBJECTIVE: We designed this study to evaluate the epidemiological features of covid-19 in a large sample of people with MS (pwMS) in Isfahan, Iran, as well as the association between DMTs, risk of COVID-19 infection and hospitalization. METHODS: In an observational pwMS, we interviewed subjects on their MS and COVID-19 history. RESULTS: 3050 subjects were included (74% female) with a mean age of 41.36. 423 (13.8%) had confirmed COVID-19 which shows that pwMS are at a higher risk of infection compared to the general population, No significant relationship was observed in COVID-19 infection when individual drugs. Dimethyl fumarate and rituximab had the lowest and the highest relative risks for hospitalization rate compared to other drugs, respectively. CONCLUSION: We found no evidence supporting a higher prevalence of COVID-19 in pwMS compared to the general population. However, our results show pwMS to be more prone to hospitalization compared to the general population, Therefore, it is advised to use safer treatment if possible until complete vaccination, and to postpone the use of rituximab.

Rivaroxaban in Recurrent Ischemic Stroke Due to Protein S Deficiency: A Case Report.

Protein S deficiency is a thrombophilia associated with an increased risk of thromboembolism. Previous studies have shown its role as a predisposing factor for venous thromboembolism, but its role in recurrent arterial ischemic stroke remains uncertain. Here we report a patient with recurrent ischemic stroke due to protein S deficiency. Oral anticoagulant treatment with vitamin K antagonist (VKA) drugs is used to treat and prevent thromboembolic events caused by thrombophilia, but it has many limitations, especially in the case of recurrent thromboembolic events. Direct oral anticoagulants (DOACs) have many advantages over VKA. Previous studies have shown that they are safe in cases of thrombophilia, but they are not well studied in recurrent ischemic stroke due to protein S deficiency. In this study our patient was treated with rivaroxaban. Protein S deficiency may be a predisposing factor in recurrent ischemic stroke, and rivaroxaban can be a safe and effective treatment option. Further studies are needed to confirm our findings.