The radiologically isolated syndrome: revised diagnostic criteria.

The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.

Erdheim-Chester disease of brain parenchyma without any systemic involvement: A case report and review of literature.

Erdheim-Chester disease is a non-Langerhans cell histiocytosis syndrome characterised by histiocytic infiltration of different organs and systems in the body. Erdheim-Chester disease with isolated central nervous system (CNS) involvement causes diagnostic difficulties due to the absence of systemic findings and may result in misdiagnosis and inaccurate treatment choices. The case discussed in this report exemplifies how challenging it is to diagnose Erdheim-Chester disease with isolated CNS involvement. This case, which presented with progressive pyramidocerebellar syndrome, was clinically and radiologically resistant to all immunosuppressive and immunomodulatory treatments administered. The presence of false negative results in repeated histopathological investigations and the absence of evidence for systemic disease hindered the diagnosis and treatment work-up. In this study, we reviewed and discussed the prominent features of the presented case in light of the relevant literature.

Ataxia in a Movement Disorders Outpatient Clinic: a Single-Center Experience in Turkey.

The etiology may not be determined in patients with ataxia despite detailed evaluations. The aim of this study was to investigate the clinical and laboratory characteristics of a large cohort of patients with adult-onset ataxia of different etiologies, particularly, undetermined etiologies despite extensive clinical, genetic, laboratory, electrophysiological, and imaging investigations. The medical records of all patients diagnosed with ataxia of subacute-chronic onset between January 2011 and March 2021 were reviewed retrospectively. The records of patients with symptom onset after 16 years of age were included in the study. In all patients, clinical and demographic findings were noted. Etiologies were classified as acquired, hereditary, degenerative (multiple system atrophy-cerebellar, MSA-C), functional, and undetermined. During the study period, we determined 74 patients with ataxia and 59 (35 males) patients met the study criteria. The age range was 22-87 years. The etiologies were hereditary (n = 19), acquired (n = 14), MSA-C (n = 9), functional (n = 2), and undetermined (n = 15). The patients with hereditary etiologies and undetermined causes were significantly younger at admission and at symptom onset (p = 0.001 and p = 0.000). There was a significant delay until diagnosis in patients with hereditary etiologies compared to other etiologies. In acquired etiologies, axial findings (71.4%) were more prominent whereas extremity and axial findings were more common in patients with hereditary etiologies (83.3%, p = 0.030). There were systemic and radiological indicators such as hearing loss, juvenile cataract, or dentate hyperintensity in certain disorders. Hereditary etiologies are as common as acquired or degenerative etiologies in adults. However, they have an earlier onset and delayed diagnosis. Therefore, we should recognize the extracerebellar neurological, systemic, and neuroimaging findings.

Impact of COVID-19 vaccination or infection on disease activity in a radiologically isolated syndrome cohort: The VaxiRIS study.

BACKGROUND: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised. OBJECTIVES: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS). METHODS: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients' history of COVID-19 infection. RESULTS: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients. CONCLUSION: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation. METHODS: A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow-up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non-rebound group. Clinical and demographic data and 5-year clinical outcomes of both groups were prospectively examined. RESULTS: At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non-rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5-year follow-up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non-rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow-up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non-rebound group (52.4%, p = 0.05). CONCLUSION: When rebound activity is well-monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long-term follow-up.

Parainfectious autoimmune encephalitis related to SARS-CoV-2 infection, presenting with catatonia.

OBJECTIVE: SARS-CoV-2 infection commonly affects both the central and peripheral nervous systems, resulting in a variety of neurological and psychiatric symptoms. Whereas the effects of SARS-CoV-2 on neuronal structures in the short and long-term are still controversial, neurological involvement secondary to SARS-CoV- 2 is heterogeneous in terms of clinical presentation, treatment response, and prognosis. METHOD: A case of autoimmune encephalitis developing after SARS-CoV-2 is described in this article. RESULTS: The patient was admitted to the clinic with classical signs of catatonia and encephalopathy. The emergence of neuropsychiatric problems after the relief of SARS-CoV-2 symptoms suggests that symptoms were primarily related to immune processes. This patient demonstrated a good clinical response to symptomatic catatonia treatment and immune-modulatory agents and recovered both physically and cognitively without sequelae. CONCLUSION: SARS-CoV-2 infection may involve encephalitic involvement and psychological symptoms (including catatonia) after the infection by triggering autoimmune pathways.

Treatment of multiple sclerosis-related trigeminal neuralgia with onabotulinumtoxinA.

BACKGROUND: The effectiveness of onabotulinumtoxinA (BTX-A) has been established in primary trigeminal neuralgia (TN). However, to the best of our knowledge, the efficacy of BTX-A in secondary TN has not yet been studied. OBJECTIVE: This study aimed to investigate the efficacy of BTX-A treatment in patients with multiple sclerosis-related trigeminal neuralgia (TN-MS) and compare the efficacy of BTX-A treatment between patients with primary trigeminal neuralgia (TN-P) and patients with TN-MS. METHODS: This was a retrospective medical record-review study. Demographic and clinical features and severity and frequency of pain before and 2 weeks after the BTX-A administration were extracted from the patient files. BTX-A was injected into the painful area subcutaneously and/or submucosally. BTX-A injections were performed by the same physician using the same methods. A reduction in severity and/or frequency of pain ≥50% was considered therapeutic efficacy. RESULTS: Fifty-three patients were included in this study. We classified 22 (42%) as TN-P and 31 (58%) as TN-MS. Treatment with BTX-A was effective in 16 of 31 (52%) patients with TN-MS and 10 of 22 (45%) with TN-P. BTX-A treatment was less effective in patients with a history of interventional treatments and more effective in patients with concomitant continuous pain (p = 0.007; odds ratio [OR]: 0.020-0.53 and p = 0.047; OR: 0.046-0.98, respectively). CONCLUSION: The BTX-A treatment was found to be effective in at least half of our cohort with TN-MS. Concomitant continuous pain and history of interventional treatments to the trigeminal nerve or ganglion might be predictive factors for the efficacy of BTX-A treatment.

A novel diagnostic method for myasthenia gravis.

INTRODUCTION/AIMS: Videonystagmography (VNG) which directly records eye movements using infrared video goggles with mini-cameras, is used to measure nystagmus. Our aim is to explore whether VNG can be used to detect a decrement in the extraocular muscle (EOM) activity of patients with myasthenia gravis (MG). METHODS: Thirty-four patients with MG, including 13 with ocular-predominant and 21 with generalized MG, and 23 healthy controls participated. Using VNG we recorded the velocity of the eye movements of the patients as they followed a moving target. We then calculated the gain by dividing the eye movement velocity (degrees/second) by the target velocity (degrees/second). RESULTS: In MG subjects, the mean initial gain (maximum gain) was 1.23 ± 0.31 (range: 0.63-2.15) for the right eye and 1.22 ± 0.37 (range; 0.60-2.28) for the left eye. The mean minimum gain was 0.11 ± 0.12 (0.01-0.58) for the right and 0.14 ± 0.5 (0.02-0.55) for the left. Due to fatigue, the movement gain was reduced by 91.7% in the right eye and 88.2% in the left eye. After reaching minimum velocity, gain remained at a minimum for a mean of 1.08 ± 0.52 (0.3-2.4) s for the right and 1.49 ± 0.85 (0.4-3.6) s for the left, before the velocity increased again. There was no fatigue-induced decrement in healthy subjects. DISCUSSION: Our study documents a decrement in EOM activity recorded by VNG in patients with MG which begins to improve within 1-2 s after reaching minimum velocity, analogous to traditional low-frequency repetitive nerve stimulation testing and its U-shaped pattern. Thus, VNG may be a promising diagnostic test for MG.

The efficacy of rituximab in patients with neuromyelitis optica spectrum disorder: A real-world study from Turkey.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are a group of antibody-mediated chronic inflammatory diseases of the central nervous system. Rituximab is a monoclonal antibody that leads to a reduction in disease activity. OBJECTIVE: To evaluate the efficacy of rituximab as monotherapy in NMOSD and to determine whether the efficacy varies depending on the presence of antibodies in this cohort. METHOD: This multicentre national retrospective study included patients with NMOSD treated with rituximab at least for 12 months from Turkey. The primary outcomes were the change in the annualised relapse rate, the Expanded Disability Status Scale (EDSS), the number of relapse and radiological activity-free patients. RESULTS: A total of 85 patients with NMOSD were included in the study. Of 85 patients, 58 (68.2%) were seropositive for anti-Aquaporin4-IgG (antI-AQP4-IgG). All patients were Anti-Myelin Oligodendrocyte Glycoprotein IgG (anti-MOG-IgG) negative. The median follow-up for rituximab treatment was 21 months (Q1 16-Q3 34.5). During rituximab treatment, the mean annualised relapse rate (ARR) significantly decreased from 1.45 ± 1.53 to 0.15 ± 0.34 (P < .001). In subgroup analyses, the mean ARR decreased from 1.61 ± 1.65 to 0.20 ± 0.39 in the seropositive group and 1.10 ± 1.19 to 0.05 ± 0.13 in the seronegative group. The mean EDSS improved from 3.98 ± 2.04 (prior to treatment onset) to 2.71 ± 1.59 (at follow-up) (P < .001). In the seropositive group, mean EDSS decreased from 3.94 ± 1.98 to 2.67 ± 1.54, and in the seronegative group, mean EDSS decreased from 4.07 ± 2.21 to 2.79 ± 1.73. There was no significant difference between anti-AQP4-IgG (+) and (-) groups in terms of ARR and EDSS. Sixty-four patients (75.2%) were relapse-free after the initiation of treatment. Seventy patients (82.3%) were radiological activity-free in the optic nerve, area postrema and brainstem. Additionally, 78 patients (91.7%) showed no spinal cord involvement after the treatment. CONCLUSION: Rituximab therapy is efficacious in the treatment of Turkish NMOSD patients independent of the presence of the anti-AQP4-IgG antibody.

Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection.

Online supplemental material is available for this article.

The effect of vitamin D on restless legs syndrome: prospective self-controlled case study.

PURPOSE: To evaluate the effect of vitamin D on severity of restless legs syndrome in patients with idiopathic restless legs syndrome (RLS). METHODS: Patients with idiopathic RLS completed questionnaires including the International Restless Legs Severity Scale (IRLSS) and were evaluated for vitamin D deficiency. Patients with deficiency of vitamin D were treated with 50,000 units per week for 2 months. At the end of the 2 months, vitamin D levels were re-measured and disease severity was re-evaluated in patients who reached adequate vitamin D level. Subgroups of IRLSS questionnaire were also analyzed. RESULTS: Of 35 patients enrolled, 21 (60%) had vitamin D deficiency and received vitamin D therapy. In 2 patients, vitamin D levels did not rise to sufficient levels with supplementation and these 2 patients were excluded from analysis. The remaining 19 patients showed vitamin D levels increased from 13.2 ± 4.0 to 42.8 ± 9.6 ng/mL while IRLSS improved from 24.9 ± 5.1 to 21.1 ± 2.9 points (p <0.001). Selected subscores of the IRLSS were also improved including symptom severity (p <0.001), impact on sleep (p <0.001), symptom measures (p =0.002), and disease impact measures (p <0.001). There were trends toward improvement in subscores of frequency (p =0.11) and mood (p =0.051). CONCLUSIONS: The findings suggest that vitamin D levels should be evaluated in patients with RLS and if vitamin D deficiency is revealed, consideration should be given to replacement therapy.u.

Electrophysiological Investigations in Orthostatic Myoclonus: Preliminary Findings.

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Microstructural analysis of verbal fluency performance in relapsing-remitting multiple sclerosis based on the impact of disability level.

Verbal fluency (VF) evaluates language and cognitive abilities. This study compared VF in Relapsing-Remitting Multiple Sclerosis (RRMS) and healthy controls (HC), examining variables including correct responses (CR), mean cluster size (MCS), switches (S), and fluency difference score (FDS). RRMS participants were subgrouped by Expanded Disability Status Scale (EDSS), to explore the relationship between MS severity and VF. Twenty-four RRMS participants and matched HCs underwent Mini-Mental State Exam and VF Test. Statistical analysis compared VF between RRMS subgroups based on severity levels, and in HC. RRMS significantly impacted the CR, and S (CRSF p = 0.01, SSF p = 0.002; CRPF=0.002, SPF p = 0.002), while there was no significant difference in FDS between RRMS groups (p = 0.9). No significant relationship was found between EDSS scores, and VF subtests (CRSF p = 0.061, MCSSF p = 0.46, SSF p = 0.051, CRPF p = 0.521, MCSPF p = 0.966, SPF p = 0.599). In RRMS, our results demonstrate impairments in all VF parameters except the MCSSF+PF, and FDS. This study suggests that intact MCSSF+PF may reflect preserved verbal memory and word recall, while significant switching differences may indicate impaired cognitive flexibility. Similar FDS to those of HC suggest that no performance discrepancy in subtests in RRMS. Intact MCS might be a distinctive pattern in the early clinical stage of MS.

Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.

BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Understanding the features of posterior auricular muscle response in a facial nerve disease prototype.

OBJECTIVES: This study aims to compare and investigate the changes of posterior auricular muscle response (PAMR) following peripheral facial nerve palsy (PFP) with blink reflex (BR). PATIENTS AND METHODS: A total of 75 idiopathic PFP patients and age and sex-matched 38 healthy volunteers were included. Patients with PFP were classified into two groups including early (≤6 months) and late (>6 months) based on the duration of symptoms. Following clinical evaluation, PAMR and BR were recorded. A comparison was performed among the early PFP group (n=52), late PFP group (n=23) and healthy volunteers (n=38). RESULTS: We obtained PAMR in 78.9% (n=30) of healthy volunteers, in 60.9% (n=14) of late and in only 38.5% (n=20) of early PFP patients (p=0.001). No habituation was observed following repeated stimuli. The mean latencies were 9.1±1.6, 10.9±1.9 and 12.3±2.0 msec., respectively (p=0.000). R1 and R2 latencies were longer in the early PFP group, compared to other groups (p=0.000). CONCLUSION: Posterior auricular muscle response exhibits changes in a manner similar to R1 and R2 of BR in early and late PFP. The occurrence rate of PAMR seems to be lowest or its latency is prolonged in the early PFP.

Ocrelizumab in pediatric multiple sclerosis.

BACKGROUND: Ocrelizumab is a recombinant humanized anti-CD20 monoclonal IgG1, approved by FDA and EMA for adult patients with multiple sclerosis (MS). The data on the efficacy and safety of Ocrelizumab for pediatric MS cases are limited. OBJECTIVE: Here, we describe pediatric relapsing-remitting MS (P-RRMS) cases who were treated with Ocrelizumab as a disease-modifying drug. METHOD: P-RRMS cases who were started Ocrelizumab below 18 years-of-age and followed-up >12 months with Ocrelizumab treatment were included. The primary end-points were annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity (new/enlarging T2 lesions and new gadolinium (Gd) enhancing lesions). The secondary end-points were the percentage of patients who remain relapse-free and/or free from Gd enhancing lesions, Expanded Disability Status Scale (EDSS) score, and the safety profile of Ocrelizumab. RESULTS: Of 18 P-RRMS cases receiving Ocrelizumab, 10 patients fulfilled the inclusion criteria for our study. The median duration of follow-up under Ocrelizumab was 28,3 months (min: 15 months, max: 46 months). Mean ARR decreased from 2.01 (±0.71) to 0 during the follow-up of Ocrelizumab treatment (P < 0.0001). None of the patients had MRI activity during the treatment. Mean EDSS decreased from 1.75 (±1.09) to 1.20 (±0.63) from the initiation of Ocrelizumab to the last follow-up of the patients (P = 0.024). None of the patients had serious side effects, except one patient who experienced anaphylaxis. CONCLUSION: Ocrelizumab can be considered a safe and effective treatment option in highly active P-RRMS.

Analysis of determinants of treatment change in adult paediatric-onset MS patients.

BACKGROUND: Paediatric-onset multiple sclerosis (POMS) is increasing worldwide and represents approximately 5% of all MS cases. Although this patient group has similar characteristics to the adult group, it is important for this patient group to receive effective treatment due to the early onset of cognitive involvement, higher lesion burden, and secondary progression at an earlier age than adults. In this study, we aimed to evaluate the factors that cause treatment change in POMS patients. MATERIAL AND METHOD: Adult patients with a first MS attack at age 18 years or younger who were followed up with the diagnosis of MS at the Clinical Neuroimmunology and Demyelinating Diseases outpatient clinic of Cerrahpasa Medical School between 1987 and 2020 were included in our study. Patient files were reviewed retrospectively, and demographic and clinical characteristics, imaging, first attack characteristics, and treatment change were noted. We included 269 patients with a definite diagnosis of MS in the study, and these patients were evaluated in two groups: negative for treatment change and positive for treatment change. RESULTS: Multifocal involvement was detected more frequently in the group with treatment change (p = 0,049). Cerebellar involvement as a first attack symptom was more common in male patients (p = 0,023) The age at first MS attack was found to be younger (p = 0,006), and the disease duration was longer in the positive for treatment change group (p = 0,003). Spinal cord involvement was more common in the positive for treatment change group (p = 0,016). Abnormal VEP findings were observed more frequently in the group without treatment change (p = 0.018). In multivariant analysis, spinal cord involvement, younger age at first attack, and abnormal VEP findings in the group without treatment change were found to be significant. Among the reasons for treatment change, the most common reason was radiological and clinical progression. CONCLUSION: The higher inflammatory load in POMS patients compared with adults necessitates early initiation of treatment in this group and timely treatment change to prevent disability. Furthermore, this patient group should be followed closely and receive effective treatment.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

BACKGROUND: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. OBJECTIVE: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. METHODS: Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. RESULTS: CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. CONCLUSION: The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.

Severe disease reactivation in seropositive neuromyelitis optica spectrum disorders patients after stopping eculizumab treatment.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune, inflammatory disease of the central nervous system affecting the optic nerves and spinal cord. Most NMOSD patients have autoantibodies against the astrocyte water channel protein aquaporin-4 (AQP4). Eculizumab treatment is used effectively and safely in AQP4-IgG+ NMOSD. Our study evaluated the prognosis and outcomes of all clinical trial (PREVENT) patients from Turkey who received eculizumab treatment for AQP4-IgG+ NMOSD. METHOD: Clinical and demographic data of all patients enrolled in the PREVENT and OLE clinical trial in Turkey were analyzed during the study period and after the study ended. Clinical follow-up results were recorded in detail in patients who had to discontinue eculizumab treatment. RESULTS: The study included 10 patients who participated in PREVENT and OLE. Seven patients completed the studies, three patients did not continue the study and were switched to other treatments. Only one of the seven patients was able to continue treatment after eculizumab was approved in AQP4-IgG+NMOSD. The other six patients could not continue treatment due to reimbursement conditions. Four of the six patients who could not continue eculizumab treatment experienced early relapse (within the first three months after stopping the drug). All of these patients had high disease activity before eculizumab and had never relapsed under eculizumab treatment over the long term. CONCLUSION: Eculizumab was used effectively and safely in Turkish AQP4-IgG+NMOSD patients with high disease activity. Disease reactivation and relapse may occur after discontinuation of eculizumab treatment in patients with a long-term stable course. In these cases, close monitoring for disease reactivation is recommended.

The Effect of Smoking on Inactivated and mRNA Vaccine Responses Applied to Prevent COVID-19 in Multiple Sclerosis.

Introduction: Coronavirus disease 2019 (COVID-19) is the biggest health challenge of recent times. Studies so far reveal that vaccination is the only way to prevent this pandemic. There may be factors that decrease or increase vaccine effectiveness. In multiple sclerosis (MS), some of these factors may cause changes in the effectiveness of the vaccine, depending on the nature of the disease and disease-modifying treatments (DMT). In this study, we aimed to investigate the relationship between antibody titer and smoking in non-treated and DMT-treated MS patients who received inactivated vaccine (Sinovac) and messenger RNA BNT162b2 (BioNTech) mRNA vaccines. Method: Vaccine antibody responses were measured between 4-12 weeks after two doses of inactivated vaccine and mRNA vaccines. Patients were separated into 6 groups as: patients with MS without treatment PwMS w/o T, ocrelizumab, fingolimod, interferons (interferon beta-1a and interferon beta-1b), dimethyl fumarate, and teriflunomide. Antibody titers of smokers and non-smokers were compared for both vaccines and for each group. Results: The study included 798 patients. In the mRNA vaccine group, smokers (n=148; 2982±326 AU/mL) had lower antibody titers compared to the non-smokers (n=244; 5903±545 AU/mL) in total (p=0.020). In the inactivated vaccine group, no significant difference was detected between smokers (n=136; 383±51 AU/mL) and non-smokers (n=270; 388±49 AU/mL) in total (p=0.149). In both vaccine groups, patients receiving ocrelizumab and fingolimod had lower antibody titers than those receiving other DMTs or PwMS w/o T. In untreated MS patients, antibody levels in smokers were lower than in non-smokers in the mRNA vaccine group. No difference was found between antibody levels of smokers and non-smokers in any of the inactivated vaccine groups. Conclusion: Ocrelizumab and fingolimod have lower antibody levels than PwMS w/o T or other DMTs in both mRNA and inactivated vaccine groups. Smoking decreases antibody levels in the mRNA vaccine group, while it has no effect in the inactivated vaccine group.