A Review of Ocular Movement Abnormalities in Hereditary Cerebellar Ataxias.

Cerebellar ataxias are a wide heterogeneous group of disorders that may present with fine motor deficits as well as gait and balance disturbances that have a significant influence on everyday activities. To review the ocular movements in cerebellar ataxias in order to improve the clinical knowledge of cerebellar ataxias and related subtypes. English papers published from January 1990 to May 2022 were selected by searching PubMed services. The main search keywords were ocular motor, oculomotor, eye movement, eye motility, and ocular motility, along with each ataxia subtype. The eligible papers were analyzed for clinical presentation, involved mutations, the underlying pathology, and ocular movement alterations. Forty-three subtypes of spinocerebellar ataxias and a number of autosomal dominant and autosomal recessive ataxias were discussed in terms of pathology, clinical manifestations, involved mutations, and with a focus on the ocular abnormalities. A flowchart has been made using ocular movement manifestations to differentiate different ataxia subtypes. And underlying pathology of each subtype is reviewed in form of illustrated models to reach a better understanding of each disorder.

International Genetic Testing and Counseling Practices for Parkinson's Disease.

BACKGROUND: There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct-to-consumer testing. OBJECTIVES: The aim is to determine the international landscape of genetic testing in PD to inform future worldwide recommendations. METHODS: A web-based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership. RESULTS: Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region-dependent differences in access to and availability of testing and counseling were most notable in Africa. High-income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan-American and Asian countries. CONCLUSIONS: This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.

Genetic Testing in Parkinson's Disease.

Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily available in clinical, research, and direct-to-consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene-targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long-term outcomes of consumer- and research-based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost-benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A review on approach to a twitchy tongue in neurology.

BACKGROUND: Several etiologies are responsible for presentation of a twitching tongue in clinical practice. Some of these etiologies cause an isolated hyperkinetic tongue muscle, and some others cause it along with other signs and symptoms. OBJECTIVES: The present paper aims to review the causes, pathology, and presentations reported with twitchy tongue. An anatomical basis of the etiologies responsible for presentation of a twitchy tongue and hyperkinetic movement disorders of this muscle is pursued. METHOD: The reporting of this systematic review was guided by the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement. All of the research papers conducted with keywords described in the method section between 2000 and 2022 were used, and review articles and articles without any human subject and without any described hyperkinetic movement disorders of the tongue were excluded. RESULTS: All of the etiologies responsible for hyperkinetic movement disorders of tongue were listed in the basis of their anatomical site of effect; cortical region, basal ganglia, cerebellum, brain stem, nucleus and nerve, and neuromuscular junction. One last remained part is the "not classified" section, which contains the etiologies with no particular anatomical origin. CONCLUSION: There are a variety of responsible etiologies for presentation of a twitchy tongue, and in the matter of a complaint of hyperkinetic tongue presentation, physicians should consider anatomical, functional, and psychological etiologies and other signs and symptoms must be participated in the diagnosis process to achieve a proper medical decision.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis.

Studies among people with multiple sclerosis (pwMS) receiving disease-modifying therapies (DMTs) have provided adequate evidence for an appraisal of COVID-19 vaccination policies among them. To synthesise the available evidence addressing the effect of MS DMTs on COVID-19 vaccines' immunogenicity and effectiveness, following the Cochrane guidelines, we systematically reviewed all observational studies available in MEDLINE, Scopus, Web of Science, MedRxiv and Google Scholar from January 2021 to January 2022 and extracted their relevant data. Immunogenicity data were then synthesised in a quantitative, and other data in a qualitative manner. Evidence from 28 studies suggests extensively lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM) treated and anti-CD20 (aCD20) treated, and lower T-cell responses in interferon-treated, S1PRM-treated and cladribine-treated pwMS-although most T cell evidence currently comprises of low or very low certainty. With every 10-week increase in aCD20-to-vaccine period, a 1.94-fold (95% CI 1.57 to 2.41, p<0.00001) increase in the odds of seroconversion was observed. Furthermore, the evidence points out that B-cell-depleting therapies may accelerate postvaccination humoral waning, and boosters' immunogenicity is predictable with the same factors affecting the initial vaccination cycle. Four real-world studies further indicate that the comparative incidence/severity of breakthrough COVID-19 has been higher among the pwMS treated with S1PRM and aCD20-unlike the ones treated with other DMTs. S1PRM and aCD20 therapies were the only DMTs reducing the real-world effectiveness of COVID-19 vaccination among pwMS. Hence, it could be concluded that optimisation of humoral immunogenicity and ensuring its durability are the necessities of an effective COVID-19 vaccination policy among pwMS who receive DMTs.

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study.

BACKGROUND: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated. OBJECTIVE: To detect possible changes in MS clinical disease activity after COVID-19. METHODS: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS). RESULTS: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved. CONCLUSION: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS.

Cutaneous adverse events related to COVID-19 vaccines: A cross-sectional questionnaire-based study of 867 patients.

Considering the emergency approval of the Food and Drug Administration for widespread use of coronavirus disease 2019 (COVID-19) vaccines, evaluating potential vaccine-related adverse effects is critical as it will allow physicians to diagnose and manage these complications properly. In this descriptive cross-sectional questionnaire-based study, we evaluated the possible side effects of the COVID-19 vaccine from June 1, 2021 to June 21, 2021. The Iranian population is generally vaccinated with AstraZeneca, Sputnik V, Sinopharm, and Bharat vaccines. The continuous and categorical variables were described and data analyzed by the SPSS software version 25. Cutaneous reactions occurred in 30% of individuals vaccinated against COVID-19. The most common cutaneous complications were focal injection site reaction, exanthematous rash, and urticaria. There were infrequent cutaneous adverse events that included vesicular eruption, pernio-like lesions, angioedema, erythema multiforme-like eruption, and zoster. Acquainting physicians with COVID-19 vaccine-related cutaneous complications will assist them in detection and management. In addition, introducing these complications to individuals might improve acceptance of vaccine-related adverse effects in the general population.

Autoimmune encephalitis: the first observational study from Iran.

BACKGROUND: Even within the most populous countries in the Middle East, such as Iran, autoimmune encephalitis cases have been rarely reported. OBJECTIVE: We aimed to describe the demographic, clinical, and paraclinical characteristics of Iranian patients with autoimmune encephalitis positive for anti-neuronal autoantibodies. METHODS: This cross-sectional study included all patients diagnosed with autoimmune encephalitis and referred to our hospital, in Isfahan, Iran, from March 2016 to May 2020. Patients' demographic, clinical, laboratory, radiological, and electroencephalographic features were obtained from their medical records. RESULTS: We identified a total of 39 (21 females, 53.8%) patients with autoimmune encephalitis (mean age = 34.9 ± 12.8 years). The most commonly detected antibody was anti-NMDAR (n = 26, 66.7%), followed by anti-GABABR (n = 8, 20.5%), anti-Zic4 (n = 4, 10.3%), and anti-GAD65 (n = 1, 2.6%) antibodies, in descending order of frequency. Two anti-NMDAR-positive patients had a history of systemic lupus erythematosus (SLE), and four had a prior history of herpes simplex encephalitis. Clinical presentations in patients positive for anti-Zic4 antibodies included cognitive decline (n = 4, 100%), seizures (n = 3, 75%), parkinsonism (n = 1, 25%), and stiff-person syndrome (n = 1, 25%). CONCLUSION: This was the first case series of Iranian patients with autoimmune encephalitis with some interesting observations, including SLE-associated anti-NMDAR encephalitis, as well as an unusual concurrence of anti-Zic4 antibody positivity and cognitive problems, seizures, parkinsonism, and stiff-person syndrome.

MiR-193b deregulation is associated with Parkinson's disease.

PGC-1α/FNDC5/BDNF has found to be a critical pathway in neurodegeneration. MicroRNAs (miR(NA)s) are non-coding regulatory RNAs whose dysregulation has been observed in multiple neurological disorders, and miRNA-mediated gene deregulation plays a decisive role in PD. Here, candidate miRNA was chosen based on the literature survey and in silico studies. Chronic and acute models of PD were created using MPP+-treated SH-SY5Y cells. Twenty PD patients and 20 healthy volunteers were recruited. RT-qPCR was performed to assess the expression of miRNA and genes. Severe mitochondrial dysfunction induced by acute MPP+ treatment instigated compensatory mechanisms through enhancing expression of PGC-1α/FNDC5/BDNF pathway genes, while chronic MPP+ toxicity led to down-regulated levels of the genes in SH-SY5Y cells. PD peripheral blood mononuclear cells (PBMCs) also showed decreased expression of target genes. There were significant changes in the level of miR-193b in both models, as well as PD PBMCs. Moreover, miR-193b overexpression significantly affected PGC-1α, FNDC5 and TFAM levels. Interestingly, down-regulations of PGC-1α, FNDC5, BDNF and TFAM were inversely correlated with miR-193b up-regulation in PD PBMCs. This study showed the deregulation of PGC-1α/FNDC5/BDNF pathway in PD models and PBMCs, verifying its importance in neurodegeneration. Our findings also revealed that miR-193b functions in PD development, possibly through regulating PGC-1α/FNDC5/BDNF pathway, suggesting miR-193b as a potential biomarker for PD diagnosis.

"NMDA receptor spectrum disorder" in the differential diagnosis of demyelinating disorders of the CNS: optic neuritis and myelitis.

OBJECTIVE: The aim of this study was to investigate the frequency of anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody positivity in patients presenting with transverse myelitis (TM) and/or optic neuritis (ON), to describe their neurologic and radiological characteristics, and to compare these characteristics with those reported in previous studies. MATERIAL AND METHODS: This study included 179 patients (ON: 96, TM: 74, ON and TM: 9) who visited Isfahan Multiple Sclerosis Center from January 2017 to September 2019, for approximately 32 months. The respective neurological examinations were performed. Demographic data of the patients, as well as findings from radiological and serological investigations were obtained. RESULTS: Frequencies of anti-NMDAR seropositivity in patients with TM, ON, and concurrent TM and ON were approximately 3.4%, 1.4%, and 11.1%, respectively. None exhibited any psychiatric symptoms. CONCLUSION: Based on the frequency of seropositivity for anti-NMDAR antibody in our patients, positivity for this antibody appears to be more frequent than previously anticipated in patients presenting with these conditions. We recommend that the anti-NMDAR antibody presence in CSF/serum be checked and considered in addition to the routine examinations performed upon confronting demyelinating conditions such as TM and ON. We suggest considering the term "NMDAR spectrum disorder" to more clearly distinguish the potentially overlapping conditions with different etiologies in patients with CNS disorders.

Pneumocephalus as a rare complication: a systematic review plus clinical vignette.

INTRODUCTION: Pneumocephalus is a clinical entity characterised by the presence of gas in the intracranial space. It can result from many different causes. The most common cause is head or facial trauma. Other causes include neoplasms, infections, and surgical or diagnostic procedures. Spontaneous non-traumatic pneumocephalus is a rare condition caused by bone defects, malformations, infections, tumours, intravenous air injection, and other causes. This review, supplemented with a case presentation, aims to summarise the current state of knowledge regarding non-traumatic pneumocephalus. METHODOLOGY: This review involved an electronic search (PubMed, Scopus, Embase, and Web of Science) to identify studies regarding non-traumatic pneumocephalus. In addition, reference lists of identified articles were screened for other potentially relevant papers. RESULTS: In total, 1,107 articles were retrieved by searching databases with the selected query. Based on the selection process, 134 articles were included. These articles were then classified into 'otogenic', 'bone defect', 'malformations', 'infectious', 'tumours', 'associated with intravenous air injection', and other categories. CONCLUSION: Spontaneous non-traumatic pneumocephalus is a rare condition. Symptoms, clinical courses, and prognoses vary depending on the underlying cause of the disease. To the best of our knowledge, this review's example is the first case report of spontaneous pneumocephalus due to air embolism secondary to lung cancer.

Outcome of COVID-19 infection in multiple sclerosis patients receiving disease-modifying therapies.

BACKGROUND: With the spread of COVID-19, treatment of diseases such as multiple sclerosis (MS) should be resumed with caution due to the disease-modifying therapies (DMTs) used in this subset of patients and the immunoregulatory effects of these drugs. We aim to assess the outcome of COVID-19 infection in MS patients receiving DMTs. MATERIALS AND METHODS: This is a cross-sectional study involving 45 COVID-19-infected patients previously diagnosed with MS. The data regarding their MS status and the type of DMT taken by the patients were extracted from the Isfahan MS Institute registry and were summarized. Diagnosis of MS was based on the 2017 McDonald Criteria, and the diagnosis of COVID-19 was based on computed tomography scan and polymerase chain reaction of nasopharyngeal swabs. RESULTS: Out of the 45 MS patients infected with COVID-19, 5 had unfavorable outcomes. Two patients deceased and the other three had persistent respiratory complications on the 4-week follow-up visit. Hypertension, diabetes, seizures, and rheumatoid arthritis were among the comorbidities that the patients reported. Both patients who died received rituximab as part of their MS treatment. All other patients recovered completely. CONCLUSION: Each different drug category may possess a distinct risk for infection, therefore until robust evidence are available, the safest drug should be utilized or the therapy should be postponed, if possible, to minimize patient risk. Disease-modifying therapy use in MS patients should be cautiously applied as their effect on COVID-19 infection prognosis is not yet studied.

Incidence of anxiety in epilepsy during coronavirus disease (COVID-19) pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has affected people globally, and people with chronic diseases are suffering more in maintaining their mental and physical health. METHOD: This cross-sectional, case-control study assessed the anxiety level in people with epilepsy compared with the general population. RESULTS: The results showed that 13.5% of patients had experienced a severe level of anxiety, but the mean anxiety level between groups did not show significant difference. CONCLUSION: Although still many aspects of the pandemic on people with epilepsy are yet to be determined, active investigation of psychological sequels of the pandemic is demanded.

Fulminant encephalitis as a sole manifestation of COVID-19.

Novel coronavirus (SARS-CoV-2) occurred in December 2019 in Wuhan, China, and has become a global health emergency. Coronavirus primarily is a respiratory virus, but it has been detected in the brain and cerebrospinal fluid of infected individuals. The present report describes a case of fulminant encephalitis in a patient affected by COVID-19.

COVID-19-related strokes in adults below 55 years of age: a case series.

BACKGROUND: Coronavirus infection is a novel respiratory disease affecting people across the world. Although the majority of patients present with fever, dyspnea, cough, or myalgia, various signs and symptoms have been reported for this disease. Recently, neurological symptoms have been noticed in patients with COVID-19 with unknown etiology. However, the occurrence of strokes in young and middle aged patients with COVID-19 is not fully explained. METHODS: In this series, six patients younger than 55 years of age with diagnosis of stroke and a confirmed diagnosis of COVID-19 were evaluated for symptoms, lab data, imaging findings, and outcomes from March 2020 to the end of April 2020 from all stroke cases in a tertiary academic hospital. Patients older than 55 and all others who had evidence of cardiac abnormalities (arrhythmia/valvular) were excluded. RESULTS: Fever, myalgia, cough, and dyspnea were the most common clinical symptoms noted in 66.66% (4/6), 66.66% (4/6), 50% (3/6), and 50% (3/6) of the patients, respectively. The mean ± standard deviation (SD) of National Institutes of Health Stroke Scale (NIHSS) for the patient was 10.16 ± 7.13 (ranged 5-24). The most involved area was middle cerebral artery (MCA) (five in MCA versus one in basal ganglia) and the majority of our patients had a low lung involvement score (mean ± SD: 13.16 ± 6.49 out of 24). Finally, one patient was deceased and rest discharged. CONCLUSION: Stroke may be unrelated to age and the extent of lung involvement. However, different factors may play roles in co-occurrence of stroke and COVID-19 and its outcome. Future studies with long-term follow-up and more cases are needed to assess prognostic factors.

Complete horizontal gaze palsy due to bilateral paramedian pontine reticular formation involvement as a presentation of multiple sclerosis: a case report.

BACKGROUND: Demyelinating central nervous system diseases include several disorders that multiple sclerosis (MS) is identified as the most common among them. Ocular movement disturbances are a typical presentation in MS patients where lesions affect the complex and interconnected pathways involved in eye motion. Centers for gaze control are located in the pons primarily; therefore, lesions involving these centers can be presented with abnormalities in gaze. However, bilateral lesions in pontine gaze centers are exceptionally rare. CASE PRESENTATION: A 16-year-old girl with bilateral horizontal gaze palsy was referred to the neurology clinic. Magnetic resonance imaging of the patient indicated bilateral hyperintensities in the pons at the level of the paramedian pontine reticular formation. The patient was diagnosed with multiple sclerosis with respect to clinical and imaging findings and managed. CONCLUSION: Ocular movement abnormalities are a commonly encountered manifestation in patients with multiple sclerosis, however, bilateral gaze palsy is an exceptionally rare sign and should guide the physician to contemplate for anticipated lesions in the pons, and suspect MS, especially in childbearing-aged women. Although an extensive workup should also be done to rule out possible mimickers.

Magnetic resonance imaging findings in diagnosis and prognosis of Wilson disease.

Wilson disease (WD) is a rare autosomal recessive disorder characterized by excessive copper deposition in the body, principally in the liver and the brain. There is a wide spectrum of clinical presentations, but the most significant and basic symptoms of the disease can be divided into hepatic, neurologic, and psychiatric manifestations. Magnetic resonance imaging (MRI) provides more detailed anatomical information than computed tomography of the brain, especially of the structure of the basal ganglia and brain stem. In this review, we want to evaluate the correlation between MRI findings and clinical features of WD.

Efficacy and safety of rituximab in neuromyelitis optica: Review of evidence.

Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system with preferential involvement in the optic nerve and spinal cord with a widespread spectrum of clinical features; multiple therapeutic agents have been used with different results. Recent evidence points to B-cell-mediated humoral immunity in the pathogenesis of NMO. Rituximab targets the CD20 antigen on B-cells. Treatment leads to profound B-cell depletion, principally over an antibody-dependent cell cytotoxicity mechanism. The aim of our study was to review clinical trials to elucidate the impact of rituximab on the relapse rate, Expanded Disability Status Scale (EDSS), and progression of disability in NMO. We performed a comprehensive review of all studies that evaluated clinical and paraclinical effects of rituximab on NMO. MEDLINE-PubMed, Web of Sciences, EMBASE, and Cochrane databases up to June 2016 included in our searches. In addition, reference lists from articles identified by search as well as a key review article to identify additional articles included in the study. Rituximab targets the CD20 antigen on B-cells and decreases attack frequency and severity in patients with NMO; however, it does not remove attacks, even when modifying treatment to achieve B-cell depletion. Most of the investigations revealed that EDSS significantly in all patients with rituximab treatment will be decreased after treatment with rituximab. No new or enlarged lesions or pathological gadolinium enhancement was observed in serial brain and spinal cord magnetic resonance imaging, except for those observed concomitantly with clinical relapses and the median length of spinal cord lesions was significantly reduced after therapy. Rituximab targets the CD20 antigen and decreases attack frequency and severity in patients with NMO.