The diagnostic performance of AI-based algorithms to discriminate between NMOSD and MS using MRI features: A systematic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging [MRI] findings in Neuromyelitis optica spectrum disorder [NMOSD] and Multiple Sclerosis [MS] patients could lead us to discriminate toward them. For instance, U-fiber and Dawson's finger-type lesions are suggestive of MS, however linear ependymal lesions raise the possibility of NMOSD. Recently, artificial intelligence [AI] models have been used to discriminate between NMOSD and MS based on MRI features. In this study, we aim to systematically review the capability of AI algorithms in NMOSD and MS discrimination based on MRI features. METHOD: We searched PubMed, Scopus, Web of Sciences, Embase, and IEEE databases up to August 2023. All studies that used AI-based algorithms to discriminate between NMOSD and MS using MRI features were included, without any restriction in time, region, race, and age. Data on NMOSD and MS patients, Aquaporin-4 antibodies [AQP4-Ab] status, diagnosis criteria, performance metrics (accuracy, sensitivity, specificity, and AUC), artificial intelligence paradigm, MR imaging, and used features were extracted. This study is registered with PROSPERO, CRD42023465265. RESULTS: Fifteen studies were included in this systematic review, with sample sizes ranging between 53 and 351. 1,362 MS patients and 1,118 NMOSD patients were included in our systematic review. AQP4-Ab was positive in 94.9% of NMOSD patients in 9 studies. Eight studies used machine learning [ML] as a classifier, while 7 used deep learning [DL]. AI models based on only MRI or MRI and clinical features yielded a pooled accuracy of 82% (95% CI: 78-86%), sensitivity of 83% (95% CI: 79-88%), and specificity of 80% (95% CI: 75-86%). In subgroup analysis, using only MRI features yielded an accuracy, sensitivity, and specificity of 83% (95% CI: 78-88%), 81% (95% CI: 76-87%), and 84% (95% CI: 79-89%), respectively. CONCLUSION: AI models based on MRI features showed a high potential to discriminate between NMOSD and MS. However, heterogeneity in MR imaging, model evaluation, and reporting performance metrics, among other confounders, affected the reliability of our results. Well-designed studies on multicentric datasets, standardized imaging and evaluation protocols, and detailed transparent reporting of results are needed to reach optimal performance.

Whole spinal transverse myelitis in neuromyelitis optica spectrum disorder.

BACKGROUND: Spinal cord is one of the prominent targets of autoimmune mechanisms in Neuromyelitis Optica Spectrum Disorder (NMOSD). Rarely, NMOSD causes damage to the entire length of the spinal cord, from cervical segments to conus medullaris, which has not been characterized in the existing literature. MATERIAL AND METHOD: We reviewed medical records, demographic information, and magnetic resonance imaging (MRI) sequences of 174 NMOSD patients from January 2011 to January 2023 who were admitted to Isfahan Multiple Sclerosis center to find patients with whole spinal transverse myelitis (TM). RESULTS: Whole spinal TM was present in five patients (2.9 %). Three patients were seropositive for Aquaporin-4 (AQP4) antibody; Myelin Oligodendrocyte Glycoprotein antibody (MOG IgG) tested negative for all of them. Lower limb weakness was the most frequent clinical complaint. Two patients presented with optic neuritis; One patient reported having episodes of nausea and vomiting. These patients, overall, yielded a higher expanded disability status scale (EDSS) score than the other NMOSD patients. CONCLUSION: Whole spinal TM is a rare finding in NMOSD, which is strongly associated with a higher severity and a worse outcome of the disease. The role of anti-AQP4 antibodies in the extent of myelitis in NMOSD has yet to be investigated.

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.

Dietary approach to stop hypertension (DASH), but not Mediterranean and MIND, dietary pattern protects against Parkinson's disease.

The neuroprotective effects of dietary patterns have been reported in previous studies. This study aimed to examine the association between the dietary approach to stop hypertension (DASH), the Mediterranean diet (MeDi), and the Mediterranean-DASH intervention for neurodegenerative delay (MIND) with the severity and risk of Parkinson's disease (PD). In this comparative cross-sectional study, 120 patients with PD and 50 healthy participants participated. Adherence to DASH, MeDi, and MIND dietary patterns was determined according to the dietary intake data using a food frequency questionnaire (FFQ). The Severity of PD was determined by the Unified Parkinson's Disease Rating Scale (UPDRS). The mean score of the DASH was significantly lower in the PD group compared to the healthy group (p = .006), but the mean score of MeDi and MIND did not significantly differ between the two groups (p > .05). Also, the mean score of the DASH was significantly lower in men than in women in the healthy group (p = .018). High adherence to the DASH diet decreased the risk of PD by 15% (OR = 0.856, 95% CI: 0.751, 0.976, p = .020). Participants in quartiles 3 and 4 of the DASH dietary pattern had 86% (p = .003) and 87% (p = .007), respectively, lower risk of PD. MeDi and MIND diets were not significantly associated with the risk of PD. There was no significant association between dietary patterns and the severity of PD. The findings indicate that high adherence to the DASH dietary pattern may protect against PD.

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.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Balance rehabilitation for patients with Multiple Sclerosis using a Kinect®-based virtual training program.

BACKGROUND: Patients with multiple sclerosis (MS) often experience balance issues during physical activities. Traditional rehabilitation exercises such as stretching, resistance, and aerobic training have been found to be effective, but can be repetitive and tedious, leading to reduced patient motivation and adherence. Furthermore, direct supervision by a therapist is not always possible. METHODS: The aim of this study was to develop and evaluate the effectiveness of a virtual training program incorporating visual feedback from the Kinect® sensor in male patients with multiple sclerosis. Forty-five participants, with an age range of 22-56 years (mean age = 39), were randomly assigned to one of three equal groups, including two experimental groups and one control group. The experimental groups participated in eight-week exercise interventions, with each session lasting 20 to 30 min and occurring three times per week. In contrast, the control group received no interventions. Within the experimental groups, one was exposed to conventional balance exercises, whereas the other engaged in the proposed virtual training program. Both of these groups undertook three balance exercises, namely the single-foot stance, lunge maneuvers, and arm/leg stretching routines. The assessment encompassed diverse facets of balance, including parameters of 10 Meter Walk Time, Berg Balance Scale, Static Balance Score, and Time-Up and Go Scale, as well as the quality of life, gauged through the Multiple Sclerosis Quality of Life (MSQOL)-54 Questionnaire. The effect of test variables was investigated using analysis of covariance (ANCOVA), while the independent samples t-test was used to check for significant differences among the groups. The effects of the groups were compared using a paired samples t-test. RESULTS: The findings revealed that both rehabilitation programs positively affected the dependent variables compared to the control group. However, the significant difference between the pre-test and post-test scores of the experimental groups indicated the effectiveness of the proposed program compared to the traditional method. CONCLUSIONS: Entertaining virtual training programs utilizing visual feedback can be effective for rehabilitating patients with MS. The proposed method enables patients to perform rehabilitation exercises at home with high motivation, while accurate information about the treatment process are provided to the therapist.

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.

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.

Evaluation of the prevalence of bovine leukemia virus DNA in peripheral blood mononuclear cells of multiple sclerosis patients.

Multiple sclerosis (MS) is an immune system-mediated neurodegenerative disease. Recent studies suggest that viral agents, especially the Epstein Barr virus (EBV), are etiological agents for MS. The roles of other viruses in MS have been investigated. Studies have shown an increase in the level of antibodies against bovine leukemia virus (BLV) in patients with MS. In this regard, our study aimed to examine the presence of BLV DNA in peripheral blood mononuclear cells (PBMCs) of MS patients in Iran. In this cross-sectional study, the presence of BLV in 109 Iranian MS patients and 60 healthy controls was evaluated. The isolated PBMCs were used for DNA extraction and PCR, using specific primers for two distinct genes. The mean age of the participants was 39 ± 9.5 years, and 27 (24.77%) of them were male. Clinical evaluation of these patients showed the most frequent MS type to be relapsing-remitting MS (RRMS) (71; 65.14%). BLV evaluation did not show any BLV DNA presence in the PBMCs of individuals in either the MS or healthy control groups. Therefore, our study showed no evidence of BLV infection in Iranian MS patients.

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.

Neuromuscular Electrical Stimulation in Conjunction with Conventional Swallowing Therapy in the Treatment of Dysphagia Caused by Multiple Sclerosis: A Single-Case Experimental Design.

INTRODUCTION: Dysphagia as a consequence of multiple sclerosis (MS) puts individuals at higher risk of dehydration, malnutrition, and aspiration pneumonia. This study intended to investigate the effects of a combined program of neuromuscular electrical stimulation (NMES) and conventional swallowing therapy to improve swallow safety and efficiency, oral intake, and physical, emotional, and functional impacts of dysphagia in people with dysphagia and MS. METHODS: In this single-case experimental study with ABA design, two participants with dysphagia caused by MS underwent 12 sessions therapy during 6 weeks following a baseline of 4 evaluation sessions. They were evaluated 4 more times in the follow-up phase after therapy sessions. Scores of Mann Assessment of Swallowing Ability (MASA), DYsphagia in MUltiple Sclerosis (DYMUS), and timed test of swallowing capacity were obtained at baseline, during treatment, and in the follow-up phases. The Dysphagia Outcome and Severity Scale (DOSS) based on videofluoroscopic swallow studies, Persian-Dysphagia Handicap Index (Persian-DHI), and Functional Oral Intake Scale (FOIS) were also completed before and after treatment. Visual analysis and percentage of nonoverlapping data were calculated. RESULTS: MASA, DYMUS, FOIS, and DHI scores indicated significant improvement in both participants. Although the scores of the timed test of swallowing capacity in participant 1 (B.N.) and DOSS in participant 2 (M.A.) showed no changes, considerable improvements including reducing the amount of residue and the number of swallows required to clear bolus were seen in the posttreatment videofluoroscopic records of both participants. CONCLUSION: NMES in conjunction with conventional dysphagia therapy based on motor learning principles could improve the swallowing function and decrease disabling effects of dysphagia on different aspects of life in participants with dysphagia caused by MS.

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.

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.

Human exposure to dust and heavy metals in industrial regions and its relationship with the prevalence of multiple sclerosis disease.

In recent decades, multiple sclerosis (MS) diseases have been significantly prevalent in some industrial areas of Iran, such as steel industrial areas in Isfahan province (central Iran). In this study, the environmental impacts of two steel mill factories in Isfahan province and their effects on the spread of MS in the region were investigated. To examine the extent of exposure, seasonal dust samples were collected from 15 sites around the two investigated factories. The annual dust deposition rate (DDR) was then determined and the concentrations of lead (Pb), cadmium (Cd), nickel (Ni), cobalt (Co), and manganese (Mn) in the dust samples were measured. Furthermore, the concentration of the mentioned elements was determined in the nail samples taken from 40 MS patients and 40 healthy people (control) living in the study region. The interpolated map extracted from the DDR values showed the highest dust deposition around the two studied steel factories, which decreases with increasing distance from them. The enrichment factor (EF) of heavy metals was the highest at the distance between the two steel factories, decreasing by moving away from them which indicate that these two steel factories are the source of investigated heavy metals in the region. The statistical analysis also revealed significant differences (P < 0.01) between the concentration of heavy metals measured in nail samples taken from MS patients and healthy people. The mean Pb concentration measured in the nail sample taken from MS patients was more than 18 times that of healthy people (93.45 and 5.02 mg/kg, respectively). These results revealed a buildup of heavy metals in the body of MS patients much more than usual, originating from the activities of two investigated steel companies in the region.

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.