Abnormal multisensory temporal discrimination in Parkinson's disease.

Cognitive deficits are prevalent in Parkinson's disease (PD), ranging from mild deficits in perception and executive function to severe dementia. Multisensory integration (MSI), the ability to pool information from different sensory modalities to form a combined, coherent perception of the environment, is known to be impaired in PD. This study investigated the disruption of audiovisual MSI in PD patients by evaluating temporal discrimination ability between auditory and visual stimuli with different stimulus onset asynchronies (SOAs). The experiment was conducted with Fifteen PD patients and fifteen age-matched healthy controls where participants were requested to report whether the audiovisual stimuli pairs were temporal simultaneous. The temporal binding window (TBW), the time during which sensory modalities are perceived as synchronous, was adapted as the comparison index between PD patients and healthy individuals. Our results showed that PD patients had a significantly wider TBW than healthy controls, indicating abnormal audiovisual temporal discrimination. Furthermore, PD patients had more difficulty in discriminating temporal asynchrony in visual-first, but not in auditory-first stimuli, compared to healthy controls. In contrast, no significant difference was observed for auditory-first stimuli. PD patients also had shorter reaction times than healthy controls regardless of stimulus priority. Together, our findings point to abnormal audiovisual temporal discrimination, a major component of MSI irregularity, in PD patients. These results have important implications for future models of MSI experiments and models that aim to uncover the underlying mechanism of MSI in patients afflicted with PD.

A decision support system based on recurrent neural networks to predict medication dosage for patients with Parkinson's disease.

Using deep learning has demonstrated significant potential in making informed decisions based on clinical evidence. In this study, we deal with optimizing medication and quantitatively present the role of deep learning in predicting the medication dosage for patients with Parkinson's disease (PD). The proposed method is based on recurrent neural networks (RNNs) and tries to predict the dosage of five critical medication types for PD, including levodopa, dopamine agonists, monoamine oxidase-B inhibitors, catechol-O-methyltransferase inhibitors, and amantadine. Recurrent neural networks have memory blocks that retain crucial information from previous patient visits. This feature is helpful for patients with PD, as the neurologist can refer to the patient's previous state and the prescribed medication to make informed decisions. We employed data from the Parkinson's Progression Markers Initiative. The dataset included information on the Unified Parkinson's Disease Rating Scale, Activities of Daily Living, Hoehn and Yahr scale, demographic details, and medication use logs for each patient. We evaluated several models, such as multi-layer perceptron (MLP), Simple-RNN, long short-term memory (LSTM), and gated recurrent units (GRU). Our analysis found that recurrent neural networks (LSTM and GRU) performed the best. More specifically, when using LSTM, we were able to predict levodopa and dopamine agonist dosage with a mean squared error of 0.009 and 0.003, mean absolute error of 0.062 and 0.030, root mean square error of 0.099 and 0.053, and R-squared of 0.514 and 0.711, respectively.

Sex hormone therapy in Multiple Sclerosis: A systematic review of randomized clinical trials.

Background: In spite of the observed immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) in different investigations, to date, there has been no study to systematically review the documents to add more powerful data to the field. Objectives: Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. Design: A comprehensive search of electronic databases including PubMed, EMBASE, and Scopus was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. Data sources and methods: In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. Two reviewers also assessed the quality of each study independently using PEDro scale. Results: We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. Conclusion: In conclusion, the existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

Immunomodulatory properties of different sex hormones on Multiple Sclerosis (MS) have been proposed. Therefore, in this paper we aim to systematically review clinical and randomized controlled trials (RCT) assessing the effect of sex hormone therapies on individuals with MS. A comprehensive search of electronic databases was conducted. Clinical trials and RCTs that assessed the impact of sex hormones on individuals with MS were selected and included in the systematic review. In the final phase of the search strategy, 9 papers reached the criteria for entering in the systematic review. Two independent reviewers extracted the relevant data from each article according to the standardized data extraction form. We categorized three different classifications of outcomes including clinical, MRI, and immune system findings and put each measured outcome in the category which matched best. The existed investigations on the effect of sex hormones on inflammatory and neurodegenerative components of MS are promising particularly in relapsing-remitting MS (RRMS).

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.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Rituximab-associated PRES in antibody-mediated kidney rejection: A case report.

Posterior Reversible Encephalopathy Syndrome (PRES) is a rare neurological disorder with a wide range of neurological symptoms. Different risk factors are known for PRES in patients with a history of kidney transplantation; these patients developing PRES were associated with immunosuppressants and cytotoxic drug therapies, including reports of rituximab therapy. Herein, we report a case of rituximab-associated PRES in the context of antibody-mediated kidney allograft rejection. A 29-year-old male patient with antibody-mediated kidney rejection was treated with rituximab, and then he developed PRES. The patient, who was transplanted with a kidney allograft five years earlier, was continuously treated with standard tacrolimus and mycophenolate mofetil therapy without any symptoms of PRES. Rituximab treatment was started to block an ongoing kidney rejection, and the patient received a second dose of rituximab four days prior to the hospital admission. At admission, the patient demonstrated symptoms of headache, nausea, and photophobia. The brain magnetic resonance imaging (MRI) showed changes consistent with PRES. After 12 days of hospitalization, he was discharged with a complete cessation of the initial symptoms. We postulate that possible endothelial dysfunction caused by rituximab may explain the condition leading to PRES. It is unclear whether rituximab, when used in kidney rejection patients who receive other immunosuppressants, may contribute to PRES.

Patent foramen ovale leading to mismanagement in a mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes patient.

Key Clinical Message: The stroke-like episodes and brain MRI lesions in MELAS usually have a nonischemic pattern, are resolved over time, and have a migrating pattern that helps us distinguish them from ischemic cerebral infarcts. Nevertheless, conditions such as intracardiac thromboses, PFO, and hypercoagulable state may be present concomitantly, leading to mismanagement. Therefore, further investigation and echocardiography are suggested in MELAS patients. Abstract: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is the most common maternally-inherited mitochondrial disorder presenting by stroke-like episodes, seizures, encephalopathy and muscle weakness. We report the clinical, imaging, echocardiography and muscle biopsy findings of a patient presenting by unique characteristics which have not been reported in previous cases of MELAS. The reported case is a 34 year old man with the history of three times hospitalization due to muscle weakness, encephalopathy, progressive cognitive decline, and gradual visual loss. Muscle biopsy revealed Ragged Red Fibers concomitant with mitochondrial disorders. PFO was found in echocardiography leading to mismanagement of this patient and MR imaging showed ischemic lesions with a progressive pattern. This is the first reported case of MELAS accompanying with PFO. All previous reported cases of MELAS have mentioned a fluctuating characteristic for the ischemic lesions; hence this is the first case of MELAS with the progressive pattern of ischemic lesions.

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.

Neuromyelitis optica spectrum disorder in a patient with ankylosing spondylitis: A case report.

Neuromyelitis optica spectrum disorder is an autoimmune disease which tends to have other coexisting autoimmune or connective tissue diseases. However, coexisting with ankylosing spondylitis is rare. Here, we report a 57-year-old man with concomitant autoantibodies against aquaporin 4-positive neuromyelitis optica spectrum disorder and HLA-B27-positive ankylosing spondylitis.

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.

Third COVID-19 vaccine dose for people with multiple sclerosis who did not seroconvert following two doses of BBIBP-CorV (Sinopharm) inactivated vaccine: A pilot study on safety and immunogenicity.

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines. Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine. Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine. Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year ß: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 ß: -8.36, P <0.01; fingolimod ß: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated ß: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose. Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used.

A case of glial fibrillary acidotic protein (GFAP) meningoencephalitis with rheumatoid arthritis.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory disease of the central nervous system (CNS), which affects various regions in the CNS, presenting by variable clinical manifestations. Meningoencephalitis is the most common clinical presentation and association with autoimmune disorders has been reported in about 20% of these patients. Diagnosis is confirmed by the presence of CSF or serum immunoglobulin-G (IgG) against GFAP. The reported case is a 53-year-old woman with the history of long-standing rheumatoid arthritis who first presented with acute-onset dizziness and gait disturbance, periventricular linear and radial enhancement pattern on MRI, and normal CSF analysis, successfully treated with an increase in the dose of oral steroids. After a year she had a subacute-onset, moderate to severe holocephalic headache, normal neurologic examination and CSF analysis, and bilateral diffuse, pachymeningeal, and leptomeningeal enhancement on MRI. According to her Brain MRI imaging with relapsing remitting course steroid responsive ataxia and aseptic meningitis, her serum was tested for GFAP IgG antibodies which was positive. The reported patient is the first in the literature reported pachymeningitis in GFAP astrocytopathy. This case highlights the co-occurrence of rheumatoid arthritis with GFAP-associated astrocytopathy, and expands on the previously reported cases with similar association. This might also suggest a common immune pathogenesis.

Effect of multiple sclerosis disease-modifying therapies on the real-world effectiveness of two doses of BBIBP-CorV (Sinopharm) vaccine.

BACKGROUND: Immunogenicity data shows blunted responses to COVID-19 vaccination among people with MS (pwMS) on certain disease-modifying therapies (DMTs). Still, it is uncertain how this data translates into the clinic. OBJECTIVE: To assess the effect of DMTs and other factors on the effectiveness of inactivated vaccination in pwMS. METHODS: This cohort study was conducted in a period in which Iran experienced two COVID-19 peaks caused by the Delta variant. We used multivariable cox regression to compare COVID-19-free survivals, and an ordinal logistic model to compare COVID-19 severity between vaccinated pwMS on different DMTs. RESULTS: A total of 617 pwMS were included in the final analysis, with a mean [SD] follow-up of 25.59 weeks [5.48] after their second dose. Laboratory/imaging-confirmed breakthrough COVID-19 occurred in 15/277 (5.41%) of injectable-treated (reference), 10/61 (16.39%) of fingolimod-treated (adjusted hazard ratio (aHR) [95% confidence interval (CI)]: 2.80 [1.24, 6.29]; P = 0.01), 9/128 (7.03%) of other oral-treated (aHR [95%CI]: 1.16 [0.50, 2.68]; P = 0.73), 19/145 (13.10%) of anti-CD20-treated (aHR [95%CI]: 2.11 [1.05, 4.22]; P = 0.04), and 6/56 (10.71%) of non-treated pwMS (aHR [95%CI]: 1.52 [0.57, 4.04]; P = 0.40). Age (adjusted Odds Ratio [aOR] [95%CI]: 1.05 [1.00, 1.10], P = 0.05) number of comorbidities (aOR [95%CI]: 2.05 [1.06, 3.96], P = 0.03), fingolimod therapy (aOR [95%CI]: 10.39 [2.47, 43.62], P < 0.01), and anti-CD20 therapy (aOR [95%CI]: 4.44 [1.49, 13.23], P < 0.01) were independently associated with a more severe COVID-19 course. CONCLUSION: The observed results stress the importance of developing personalized vaccination schedules and reservation of COVID-19 treatment resources for older pwMS with comorbidities receiving fingolimod or anti-CD20 therapies.

Diffuse subcortical white matter restriction: An uncommon finding on metronidazole toxicity.

Metronidazole is a common and widely used antibiotic to treat a wide range of infectious diseases and has been associated with serious neurologic disturbances which in some cases were irreversible. We present a metronidazole-induced encephalopathy in a 19-year-old girl after 7 days of metronidazole treatment, with diffusion restricted subcortical white matter lesions along with the corpus callosum involvements. Diverse clinical presentation of a serious neurologic disturbance caused by a common widely used antibiotic should be carefully addressed in the setting of both short- and long-term treatment.

Longitudinal extensive transverse myelitis due to tuberculosis: A case report.

Neurotuberculosis is a potentially fatal disease that can present with upper or lower motor neuron symptoms. Longitudinally extensive transverse myelitis (LETM) is characterized by contiguous inflammatory lesions of the spinal cord extending to three or more vertebral segments. The causes of LETM include infections, neoplasm, and autoimmune diseases. Mycobacterium tuberculosis is a rare cause of transverse myelitis. Here, we report a 21-year-old Afghan female who was referred with chronic progressive quadriparesis and showed LETM on cervical MRI. This report indicates that tuberculosis should be considered as a differential diagnosis of LETM, especially in endemic areas.