Brain stimulation for patients with multiple sclerosis: an umbrella review of therapeutic efficacy.

Multiple sclerosis patients often experience various symptoms that can greatly impact their quality of life. There are various brain stimulation techniques that have been evaluated for their ability to reduce the symptoms of multiple sclerosis. However, there is inconsistency in the specific stimulation methods used and the symptoms targeted in the existing research. This umbrella review conducted in order to evaluate the effectiveness of brain stimulation and identify limitations and gaps for further research. In this umbrella review, we conducted a searched on Web of Knowledge, PubMed, and Scopus database. We specifically looked for reviews, with or without meta-analyses, that have investigated the effects of brain stimulation methods on symptoms of multiple sclerosis. All articles were examined by AMSTAR 2 (A Measure Tool to Assess Systematic Review 2). We identified 155 articles, of which 14 were eligible for inclusion. Of those, five were qualitative studies and nine were meta-analyses. Among the included studies, four examined the use of deep brain stimulation, while ten investigated the therapeutic potential of noninvasive brain stimulation. Considering the heterogeneity of studies, the current evidence suggests that repetitive transcranial magnetic stimulation may be effective in treating pain and improving motor function, while transcranial direct current stimulation may be useful in alleviating fatigue and enhancing certain aspects of cognitive performance. Deep brain stimulation, on the other hand, appears to be effective in reducing tremors. However, further research is warranted to validate these findings and address the existing limitations in the field.

The outbreak of methanol intoxication during COVID-19 pandemic: prevalence of brain lesions and its predisposing factors.

During the COVID-19 pandemic, methanol-containing beverages' consumption has risen because people mistakenly believed that alcohol might protect them against the virus. This study aimed to evaluate the prevalence and predisposing factors of brain lesions in patients with methanol toxicity and its outcome. A total of 516 patients with confirmed methanol poisoning were enrolled in this retrospective study, of which 40 patients underwent spiral brain computed tomography (CT) scan. The presence of unilateral or bilateral brain necrosis was significantly higher in the non-survival group (p = 0.001). Also, intracerebral hemorrhage (ICH) and brain edema were prevalent among patients that subsequently died (p = 0.004 and p = 0.002, respectively). Lower Glasgow Coma Scale (GCS) was related to a higher mortality rate (p = 0.001). The mortality rate in chronic alcohol consumption was lower than the patients who drank alcohol for the first time (p = 0.014). In conclusion, increasing the number of methanol poisoning and its associated mortality and morbidity should be considered a threat during the COVID-19 pandemic.

Neurological manifestations as the predictors of severity and mortality in hospitalized individuals with COVID-19: a multicenter prospective clinical study.

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. RESULTS: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. CONCLUSION: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

Neurochemicals of limbic system and thalamofrontal cortical network: Are they different between patients with idiopathic generalized epilepsy and psychogenic nonepileptic seizure?

OBJECTIVE: Thalamofrontal cortical network and limbic system are proposed to be involved in psychogenic nonepileptic seizure (PNES) and idiopathic generalized epilepsy (IGE). This study aimed to investigate neurochemical changes in prefrontal cortex, thalamus, and limbic circuits in patients with PNES and IGE. We also analyzed the interaction between cognitive functions and neurochemical changes in both groups. METHODS: Hydrogen proton magnetic resonance spectroscopy (1H-MRS) was used to measure N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), glutamate-glutamine (Glx), and myo-inositol (MI). The voxels were placed on the bilateral dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), anterior cingulate cortex (ACC), and thalamus. Attention and inhibitory control, as well as general intelligence status, were investigated using the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) and the Wechsler Adult Intelligence Scale (WAIS), respectively, in patients with PNES and IGE, as well as healthy volunteers. RESULTS: The 1H-MRS showed a decreased ratio of NAA/Cr in the right and left thalamus, right DMPFC, and right ACC in patients with IGE and PNES. Furthermore, a decrease of the NAA/Cr ratio in the left DMPFC and an increase of NAA/Cr ratio in the right DLPFC were observed in patients with PNES compared with the controls. The patient groups had a decreased ratio of Cho/Cr in right ACC compared with the healthy subjects. Moreover, the NAA/Cr ratio in the left thalamus and left DMPFC was correlated with seizure frequency in patient groups. Reduced NAA/Cr ratio in the right ACC and left DLPFC were also correlated with poor IVA-CPT scores. CONCLUSION: This study highlighted the dysfunction in prefrontal-thalamic-limbic circuits and impairment in neurocognition in patients with PNES and IGE.

Attention and inhibitory control deficits in patients with genetic generalized epilepsy and psychogenic nonepileptic seizure.

This study aimed to evaluate the attention and inhibitory control functions in patients with genetic generalized epilepsy (GGE) and psychogenic nonepileptic seizure (PNES) and compare the results with the healthy control subjects. A total of 30 patients with GGE, 30 patients with PNES, and 32 healthy control subjects were included in the study. The severity of attention and inhibitory control deficit, general intelligence status, and psychopathology screening in all subjects were respectively investigated with the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), the Wechsler Adult Intelligence Scale (WAIS), and the Symptoms Checklist 90-revised (SCL-90-R). Patients with PNES had severe impairments in all performed tasks compared with the control group and the group with GGE (p < 0.01), whereas patients with GGE had significantly lower attention quotient versus healthy subjects (p < 0.01). The full-scale attention quotient (FSAQ) and full-scale response control quotient (FSRCQ) in patients with PNES were significantly lower in comparison with GGE (47.83 ±â€¯32.68, 60.18 ±â€¯35.35, p < 0.01), respectively. Multiple regression analysis did not demonstrate any significant effect of seizure frequency or epilepsy duration on attention and inhibitory control deficits, but patient's intelligence quotient (IQ) showed a significant effect on FSAQ and FSRCQ (ß: 0.997, p < 0.001; ß: 0.933, p < 0.001, respectively). Attention and inhibitory control are significantly impaired in patients with GGE and PNES. The cognitive deficits in patients with GGE and PNES have potentially important clinical implications in planning their neuropsychological rehabilitation.

Correlation between neurofilament, HMGB1, MMP9, ds DNA blood levels and cognitive impairment in patients with neuropsychiatric systemic lupus erythematosus.

Background: Diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is challenging due to nonspecific biomarkers. High serum levels of neurofilament protein light subunit (NFL), high mobility group box 1 (HMGB1), Matrix metalloproteinase-9 (MMP-9) and have been reported in several autoimmune diseases. The aim of this study was to examine whether their plasma levels could serve as a diagnostic or prognostic biomarker for NPSLE. Methods: There were 90 SLE patients enrolled in this cross-sectional study (87.8% women and 12.2% men with a mean age of 41.67±11.05 years). We assessed the mental status of patients, also we measured the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ACR (SLICC/ ACR) Damage Index or SDI scores. Serum levels of NFL, HMGB1, MMP9, and ds-DNA were investigated to find a role in the pathophysiology of NPSLE. Results: Among the 90 patients with SLE, 63 (70%) met the criteria of NPSLE syndrome. Our results have shown a notable difference concerning SEDIAC-2k score, SDI score, PANS, MoCA, and Beck anxiety depression, between the two groups (p < 0.05). Although serum level of all measured serum biomarkers (NFL, MMP-9, HMGB1, dsDNA) were higher in patients with NPSLE, the difference was not statistically significant. Interestingly, our results showed that the serum level of NFL was correlated with the serum level of HMGB-1 and MMP-9. (r: 0.411, P=0.003). Conclusion: Serum level of NFL, HMGB-1 and MMP-9 may be used to detect abnormal mental status in patients with SLE.

Cognitive deficits in multiple sclerosis: Auditory and visual attention and inhibitory control.

BACKGROUND: A growing body of evidence has been paid to the cognitive impairment in patients with multiple sclerosis (MS). However, studies concerning cognitive functions in MS have also yielded conflicting results. This study investigates the attention and inhibitory control functions in patients with MS and their relationship with other clinical features, such as depression and fatigue in these patients. METHODS: Participants included 80 patients with MS and 60 healthy controls. The attention and inhibitory control, fatigue, and psychiatric screening in all subjects were studied, respectively with the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), Fatigue Severity Scale (FSS), and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Patients with MS performed the IVA-CPT task more poorly than the healthy control group (p < 0.001). However, multiple regression analysis did not show any significant relationship between disease duration, FSS, and HADS on attention and inhibitory control. CONCLUSION: Inhibitory control and attention are significantly impaired in patients with MS. Finding the basics of cognitive deficits in MS have potentially important clinical implications for developing better cognitive rehabilitation strategies.

Potential role of FKBP5 single-nucleotide polymorphisms in functional seizures.

OBJECTIVE: We investigated the associations between FKBP5 single-nucleotide polymorphisms (SNPs) and functional seizures (FS). METHODS: Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3' region and rs9470080 in the 5' region of the FKBP5. Childhood trauma questionnaire and hospital anxiety and depression scale were used. RESULTS: Patients with FS and those with MDD had less GG and more AA genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. Similar results were observed for allelic frequencies. There were no significant differences between FS and MDD groups in terms of genotype and allelic frequencies for both SNPs. The results of multinomial logistic regression analysis showed that FKBP5 polymorphisms were not associated with the diagnosis. SIGNIFICANCE: Patients with FS and those with MDD had significantly different genotypes in both rs9470080 and rs1360780 SNPs compared with those in healthy controls. However, it seems that FKBP5 polymorphisms were not associated with FS in the absence of depression. Further genetic investigations of patients with FS may increase our understanding of the neurobiological underpinnings of this condition, but such studies should be large enough and very well designed; they should include a comparison group with depression in addition to a healthy control group.

The effectiveness of anodal tDCS and cognitive training on cognitive functions in multiple sclerosis; a randomized, double-blind, parallel-group study.

BACKGROUND: Forty to 70% of patients with multiple sclerosis (MS) suffer from cognitive impairment during their illness. Only a few studies have examined the effects of anodal transcranial direct current stimulation (a-tDCS) along with cognitive training on cognitive performance in MS patients. This study aims to determine whether multi-session a-tDCS with or without cognitive training impacts cognitive performance in MS. METHODS: Eighty MS patients received a-tDCS, cognitive training, a-tDCS plus cognitive training, and sham for ten consecutive daily sessions. Cognitive function (including episodic memory, attention, and inhibitory control, working memory, and visuospatial skill) was measured at baseline, week 4, and week 12 after the intervention. RESULTS: All cognitive functions significantly improved after the intervention compared to the sham condition. This effect also showed persistence during follow-up for some cognitive tasks in the a-tDCS and a-tDCS combined cognitive training groups. Although the cognitive training group experienced an immediate improvement in attention and inhibitory control, the difference was not significant at follow-up. Also, there were no significant differences between these three groups in cognitive scores after the intervention. CONCLUSION: a-tDCS alone and a-tDCS paired with or without cognitive training as compared to sham appears to be a promising therapeutic option for cognitive performance in MS patients.

A Case of Fingolimod-associated Cryptococcal Meningitis.

BACKGROUND: Leukopenia, a rare adverse effect of Fingolimod therapy, paves the way for opportunistic infections. In this study, we reported rare fingolimod associated cryptococcal meningitis. CASE PRESENTATION: A 39-year-old woman with RRMS was referred to the emergency department. The patient's major complaints were headache, fever, weakness, and progressive loss of consciousness within the last two days prior to the referral. The patient had a history of hospitalization due to RRMS [two times]. In the second hospitalization, interferon Beta-1a was replaced with Fingolimod. Using polymerase chain reaction, Cryptococcus neoformans was detected in CSF. Liposomal amphotericin B and fluconazole [800 mg per day] were started. Six weeks later, the patient was discharged without any major complaints. CONCLUSION: Albeit fingolimod associated cryptococcal meningitis is a rare event, Fingolimod therapy in patients with MS should be performed cautiously. Regular follow-ups may give rise to a timely diagnosis of probable fingolimod associated cryptococcal meningitis. Fingolimod therapy can lead to lymphocytopenia and various infections. We, therefore, suggest that intermittent blood lymphocyte counts as well as monitoring of clinical manifestations among MS patients treated with Fingolimod to avoid additional neurological and physical disabilities in these patients.

Does vitamin D administration play a role in outcome of patients with acute ischemic stroke? A randomized controlled trial.

Background: Clinical studies have reported improved neurological outcomes in patients who were taking vitamin D supplements. This study investigates the effect of intramuscular (IM) vitamin D supplementation in patients with acute ischemic stroke (AIS) on neurological outcomes and inflammatory marker levels. Methods: This study included patients diagnosed with AIS (n = 60) from the Neurology Unit of Loghman Hakim Hospital, Tehran, Iran, during the year 2019. Patients with AIS were allocated randomly into two groups who received a single dose of 300000 IU IM vitamin D and a control group that did not receive vitamin D supplementation. Serum vitamin D concentration, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) levels, as primary outcomes, and the Modified Rankin Scale (MRS), the National Institute of Health Stroke Scale (NIHSS), and the Mini-Mental State Examination (MMSE), as secondary outcomes, were measured at the baseline and the end of the study (6 weeks). Results: Eventually, 59 patients with AIS completed the intervention study. A single dose of 300000 IU increased vitamin D level; moreover, vitamin D supplementation improved MRS and IL-6 levels significantly (P = 0.01, P = 0.02, respectively). There were reverse correlations between serum vitamin D and NIHSS and TNF-α after vitamin D administration. However, no statistically significant effect of vitamin D on the TNF-α or NIHSS and MMSE was seen compared to the control group. Conclusion: Vitamin D probably due to a single dose and short duration of administration, as well as a short follow-up period, had no favorable effects on TNF-α level and NIHSS score.

A case of possible atypical demyelinating event of the central nervous system following COVID-19.

After the novel coronavirus disease outbreak first began in Wuhan, China, in December 2019, the viral epidemic has quickly spread across the world, and it is now a major public health concern. Here we present a 21-year-old male with encephalomyelitis following intermittent vomiting and malaise for 4 days. He reported upper respiratory signs and symptoms 2 weeks before this presentation. Two cerebrospinal fluid (CSF) analyses were notable for mononuclear pleocytosis, elevated protein (more than 100 mg/dl), and hypoglycorrhachia. Brain Magnetic Resonance Imaging (MRI) showed bilateral posterior internal capsule lesions extending to the ventral portion of the pons and a marbled splenium hyperintensity pattern. Cervical and thoracic MRI showed longitudinally extensive transverse myelitis (LETM), none of which were enhanced with gadolinium. Both the AQP4 and MOG antibodies were negative. Spiral chest computed tomography (CT) scan confirmed to COVID-19 as did the high IgG level against coronavirus, but the oropharyngeal swabs were negative. Neurological manifestations of COVID-19 have not been adequately studied. Some COVID-19 patients, especially those suffering from a severe disease, are highly likely to have central nervous system (CNS) manifestations. Our case is a post-COVID-19 demyelinating event in the CNS.

Effect of Various Degrees of Chronic Kidney Disease on Long-term Outcome of Patients with Percutaneous Coronary Intervention.

BACKGROUND: We aimed to identify the association of degree of renal failure in chronic kidney disease patients who underwent percutaneous coronary intervention (PCI) at our center with 5-year major adverse cardiac events (MACE). METHODS: In this cohort study, we enrolled all patients who underwent primary or elective PCI and completed their 5-year followup unless they developed events related to study end-points. Demographic, angiographic and clinical data of the participants were retrieved from our databank. Glomerular filtration rate (GFR) was calculated based on the Cockcroft-Gault equation for men and women, separately. Accordingly, our patients were classified into three groups: GFR ≥ 60, GFR < 60 and ≥30 and GFR < 30 mL/ min. Then, the demographic and clinical data, as well as the frequency of MACE and its elements, were compared between the study groups. RESULTS: We included the data for 5,510 patients. MACE occurred in 891 (16.1%) of the patients. A total of 632 cases (16.7%) occurred in patients with GFR > 60 while 224 cases (18.8%) and 35 events (43.7%) occurred in patients with 30 ≤ GFR < 60 and GFR < 30 mL/min, respectively. So, GFR < 30 mL/min was significant predictor for MACE (hazard ratio [HR] = 3.74, 95% CI: 2.64-5.28; P < 0.001). The prediction effect of GFR < 30 remained significant after adjustment for the confounding variables (HR = 3.43, 95% CI: 2.38-4.94; P < 0.001). CONCLUSION: GFR <30 mL/min was a strong predictor for 5-year MACE. Moreover, in patients with GFR > 30 mL/min, PCI is a more applicable approach.