Correlation between cognitive changes and neuroradiological changes over time in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: While many studies have examined relationships of neuroimaging variables to cognitive measures in multiple sclerosis (MS), longitudinal studies are lacking. The relationship of cognitive changes to neuroradiological changes in MS is thus incompletely understood. The present study systematically reviews all studies reporting a relationship between MRI changes and cognitive changes after at least one year of follow-up. METHOD: An extensive and methodical search of online databases was conducted to identify qualified studies until August 2023. Among various cognitive tests and magnetic resonance imaging (MRI) measures, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), verbal fluency, T2 lesion volume (T2LV), white matter lesion volume (WML), and grey matter volume (GMV) qualified for inclusion in a meta-analysis investigating the association of cognitive changes to neuroradiological changes. RESULTS: We identified 35 studies that explored the link between MRI changes and changes in cognitive outcomes. Of these, twenty studies (57.14%) investigated the association between SDMT/PASAT and MRI metrics. Eleven studies (31.42%) focused on the relationship between MRI metrics and verbal learning and memory, while ten studies (28.57%) reported associations with visuospatial learning and memory. Furthermore, eight studies (22.85%) analyzed the correlation between verbal fluency and MRI measures. Only 5 were eligible for inclusion in the meta-analysis. The meta-analysis evaluated correlations between SDMT/PASAT and GMV (rs = 0.67, 95% CI 0.44-0.91), and verbal fluency and T2LV (rs = 0.35, 95% CI 0.09-0.60). CONCLUSION: In this rigorously conducted systematic review, we found a significant association of cognitive changes, specifically SDMT/PASAT and verbal fluency, to changes in T2LV and atrophy in individuals with MS. Findings should be interpreted cautiously due to the limited amount of high-quality research, small sample sizes, and variability in study methodologies.

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.

Polymorphism of glucocorticoid receptor gene (rs41423247) in functional seizures (psychogenic nonepileptic seizures/attacks).

OBJECTIVE: We investigated the association between the glucocorticoid receptor (GR) gene, also known as the nuclear receptor subfamily 3, group C, member 1 (NR3C1), rs41423247 polymorphism, and functional seizures (psychogenic nonepileptic seizures/attacks) in a case-control study. We hypothesized that the tested polymorphism has significant associations with functional seizures (psychogenic nonepileptic seizures/attacks) independent from comorbid depression. METHODS: Seventy patients with functional seizures (psychogenic nonepileptic seizures/attacks), 70 with major depressive disorder (MDD), and 70 healthy controls (HCs) were studied. Their DNAs were analyzed for NR3C1 rs41423247 polymorphism. RESULTS: Genotype and allele frequencies of rs41423247 were different between the three groups. G allele carriers were more frequent in patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD compared to HCs (p = 0.0001). However no significant difference was observed with respect to allele distributions between functional seizures (psychogenic nonepileptic seizures/attacks) and MDD groups (p = 0.391). CC genotype was less often associated with functional seizures (psychogenic nonepileptic seizures/attacks) versus HC: Codominant model; p = 0.001, OR = 0.11, 95% CI = 0.05-0.24, and -2loglilkelihood = 231.7. In comparison between functional seizures (psychogenic nonepileptic seizures/attacks) group and other (MDD + HC) groups, we observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks) (Codominant model; p = 0.001, OR = 5.63, 95% CI = 2.60-12.40 and -2loglikelihood = 245.99). SIGNIFICANCE: Patients with functional seizures (psychogenic nonepileptic seizures/attacks) and those with MDD were significantly more often G allele carriers in rs41423247 compared with HCs. We observed a significant association between CG genotype and functional seizures (psychogenic nonepileptic seizures/attacks). However, we could not exclude the possibility of confounding effects of depression. Future genetic studies of patients with functional seizures (psychogenic nonepileptic seizures/attacks) should include a comparison group with depression in addition to a comparison group of HCs.

The Possible Role of COVID-19 in the Triggering of Underlying Mitochondrial Dysfunction in MELAS Syndrome, A Brief Report of three cases.

BACKGROUND: During corona virus pandemic, various neurological complications of COVID-19 have been reported. Recent studies demonstrated different pathophysiology for neurological manifestations of COVID-19 such as mitochondrial dysfunction and damage to cerebral vasculature. In addition, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder with a variety of neurological symptoms. In this study, we aim to assess a potential predisposition in mitochondrial dysfunction of COVID-19, leading to MELAS presentation. METHODS: We studied three previously healthy patients with the first presentation of acute stroke-like symptoms, following COVID-19 infection. We analyzed the patients' clinical data and brain magnetic resonance imaging (MRI) lesions that presented to the neurological center of a university-affiliated hospital in Tehran, Iran, from September 2020 to August 2021. RESULTS: All cases are characterized by a temporoparietal abnormality in imaging studies and electroencephalogram (EEG). Based on electrodiagnostic tests, three patients were diagnosed with myopathy. In two brothers with relatively the same symptoms, one performed muscle biopsy finding myopathic process, and genetic testing confirmed a 3243A>G point mutation in a heteroplasmic state in one of our patients. CONCLUSION: Although MELAS is not a prevalent condition, the recent increase in the number of these patients in our center might indicate the potential role of COVID-19 in triggering the silent pre- existing mitochondrial dysfunction in these patients.

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.

Increased levels of neurofilament light chain in suicide attempters' serum.

Background: A specific biological vulnerability underlies suicidal behavior. Recent findings have suggested a possible role of inflammation and neuroaxonal injury. However, the relationship between inflammation and clinical symptoms in this disorder is still unclear. The objective of this study is applying novel blood markers of neuroaxonal integrity such as neurofilament light chain (NfL) and comparing the results with the healthy control subjects. Methods: In this cross-sectional study patients with suicide attempts were evaluated. The serum concentration of NfL on admission was measured by enzyme-linked immunosorbent assays. Results: A total of 50 patients with a suicide attempts and 35 healthy controls were included in the study. The levels of NfL in attempted suicide patients were significantly higher in comparison with healthy controls (40.52 ± 33.54 vs 13.73 ± 5.11, P < 0.001). A significant association between serum levels of NfL and risk factors for suicide was not found. Conclusion: These findings indicate that axonal damage may be an underlying neuropathological component of suicide attempt patients, although no correlation was observed with clinical features. This line of work could lead to new horizons in understanding the neurobiology of suicidal attempts and the development of better management strategies for these patients.

Altered serum and cerebrospinal fluid TNF-α, caspase 3, and IL 1ß in COVID-19 disease.

Background: We evaluated the levels of the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and caspase-3 in the cerebrospinal fluid (CSF) and serum of COVID-19 patients to improve our knowledge about underlying mechanisms caused by this virus in central nervous system involvement. Case Presentation: This case series study included six COVID-19 patients from March 26, 2020, to April 17, 2020, and six healthy control patients. CSF and serum levels of TNF-α, IL-1ß, and caspase-3 have been assayed using monoclonal antibodies-based ELISAs.Patients with COVID-19 had significantly higher level of IL-1ß, TNF-α, and caspase-3 in serum (239.16±35.73 pg/ml, 100.50±12.49 pg/ml, 3.58±0.11pg/ml, p < 0.001) and CSF (146.66±17.55 pg/ml, 63.16±14.68 pg/ml,3.22±0.03pg/ml, p<0.001), respectively as compared to control. In addition, our results showed that these biomarkers were significantly higher in serum compared with CSF of the COVID-19 patients (p<0.001). Conclusion: This study provides essential information for understanding the pathogenesis of COVID-19 infection and sheds light on the potential mechanisms of virus transmission. The obtained data could be useful for designing new prevention and treatment strategies for COVID-19.

The impact of brain lesions on sexual dysfunction in patients with multiple sclerosis: A systematic review of magnetic resonance imaging studies.

BACKGROUND: Sexual dysfunction is common but underestimated clinical symptom in MS patients. A growing body of evidence has been suggested the link between brain lesions and sexual dysfunction (SD) in patients with multiple sclerosis (MS). However, the clinical research investigating this relationship have shown inconsistent results. Here, we aimed to systematically review the magnetic resonance imaging (MRI) studies evaluating the association between the brain lesions and SD in MS patients. METHODS: This study was provided according to the recommendations of the preferred reporting items for systematic reviews and meta-analyses statement. A comprehensive systematic search of online databases was performed to find eligible studies up to December 2020. The quality of studies was methodologically assessed using Newcastle-Ottawa Scale score. RESULTS: We identified eight articles regarding MS brain lesions and SD through the search strategy. Seven studies showed significant associations between SD and brain lesions. Three studies investigated the brain stem, two studies the insular and occipital region, one study the frontal lobe, prefrontal cortex, and temporal lobe and one study the parietal area. CONCLUSION: The results of this systematic review showed that lesions in different brain areas are correlated with SD in MS patients. Plaques in the occipital and hippocampus areas, as well as left insula appear to be related to dysfunction of sexual arousability or lubrication/erection in MS patients. Orgasmic dysfunction in MS patients may be associated with brain lesions in pons, left temporal periventricular, and right occipital areas.

Association of Changed Serum Brain Biomarkers With Perihematomal Edema and Early Clinical Outcome in Primary ICH Patients.

BACKGROUND: Perihematomal edema (PHE) following primary intracranial hemorrhages (ICHs) affects the patient outcome. Also, serum biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) have been associated with ICHs outcome. We aimed to investigate the association between these biomarkers and PHE in ICH patients. METHODS: In this cross-sectional study, patients with primary ICH between January 2020 and August 2020 were evaluated. All participants underwent spiral brain computed tomography scans upon admission, and 48 to 72 hours later and quantification of initial hematoma volume was performed. Serum level of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), GFAP, and S100B on admission were measured by enzyme-linked immunosorbent assays. Acute clinical outcome was assessed by the modified-Rankin scale, National Institute of Health Stroke Scale (NIHSS), and ICH score. RESULTS: Thirty-seven ICH patients (21 patients with a favorable outcome and 16 unfavorable) were studied. Compared with survival patients, nonsurvivor patients showed a higher serum level of MMP-9, VEGF, GFAP, and S100B ( P <0.05). Scores of absolute PHE, edema expansion distance, and PHE growth rate in the nonsurvivor group were higher than the survivors ( P <0.001). The regression model revealed that MMP-9, VEGF, ICH score, and hematoma volume were associated with the PHE growth rate. S100B and ICH score were associated with edema expansion distance. CONCLUSIONS: Our data showed that the serum level of molecular biomarkers was associated with higher PHE volume and PHE scores were higher in nonsurvival patients, suggesting it may have a pathogenic role in developing PHE after ICH.

Factors predisposing patients with temporal lobe epilepsy to seizure cluster.

Background: We aimed to identify the potential risk factors associated with seizure clusters in patients with temporal lobe epilepsy (TLE). Methods: This retrospective cross-sectional study was performed on all the consecutive patients with TLE, who were admitted to the Epilepsy Monitoring Unit (EMU), Loghman-Hakim Hospital, Tehran, Iran. Seizure cluster was defined as three or more habitual seizures occurring within 24 hours, in over 50% of ictal events, with inter-seizure interval of less than 8 hours. The patients' demographic data, epilepsy duration, seizure frequency, frequency of interictal epileptiform discharges (IEDs), and brain magnetic resonance imaging (MRI) findings were collected. Results: Among a total number of 124 patients with TLE, 62 (50.0%) patients reported seizure clusters. In addition, 44 (37.9%), 42 (36.2%), and 30 (25.9%) patients had normal-appearing brain MRI, mesial temporal sclerosis (MTS), and other brain pathologies, respectively. In terms of IEDs frequency, 35 (29.4%), 43 (36.1%), 17 (14.3%), and 24 (20.2%) patients had respectively frequent, occasional, rare, and no spikes in one-hour of interictal scalp electroencephalography (EEG) recording. In our study, seizure clusters were not associated with the epilepsy duration (P = 0.100), the amount of IEDs (P = 0.764), or MRI findings (P = 0.112). Conclusion: In patients with TLE, seizure clustering had no correlation with the epilepsy duration, the amount of IEDs, or brain MRI findings.

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.

Is Selenium Supplementation Beneficial in Acute Ischemic Stroke?

BACKGROUND: Selenium (Se) plays a significant role in brain physiology. The existing human data demonstrate that stroke is associated with significantly reduced Se levels and glutathione peroxidase (GPx) activity. This study proposed to investigate the effect of intravenous Se (Selenase) administration in patients with acute ischemic stroke (AIS) on neurological outcomes, antioxidant enzyme activity, and inflammatory marker levels. METHODS: AIS patients (n=50) were recruited from a neurology unit of a university-affiliated hospital. Patients were randomly assigned to receive either Selenase or placebo (saline) for 5 days. The modified ranking scale, the national institute of health stroke scale, and the mini-mental state examination, as primary outcomes, and the serum GPx concentration, total antioxidant activity, and tumor necrosis factor-α levels, as secondary outcomes, were measured at the baseline and on day 30. RESULTS: Eventually, 44 patients with AIS completed the intervention study. A notable increase in GPx and total antioxidant activity levels was detected in the treatment group compared with the placebo group (110.63±52.48 m/mL, 1.34±0.30 mmol/L, P<0.05), whereas the serum tumor necrosis factor-α level in the Selenase group was significantly lower than that of the placebo group (58.58±61.33 pg/mL, P<0.05). In addition, Selenase improved the modified ranking scale and national institute of health stroke scale scores significantly (P<0.05 and <0.04, respectively), but no statistical difference was observed between the 2 groups in the mini-mental state examination score. CONCLUSION: Selenase, plausibly due to its antioxidant function, results in positive outcomes in terms of neurological deficits, antioxidant enzyme activity, and inflammatory marker levels.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19.

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

Apelin-13 prevents apoptosis in the cochlear tissue of noise-exposed rat via Sirt-1 regulation.

Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 µg/kg, ip), and noise exposure groups without any treatment or were administered apelin-13 (50 or 100 µg/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 µg/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

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.

Epilepsy syndromes in Iran: A systematic review.

This study aimed to systematically review the literature on the epidemiology of epilepsy in Iran and to provide analytical estimates of the prevalence of various epilepsy syndromes. MEDLINE, Scopus, and Embase from inception to 30 July 2020 were systematically searched. These key words were used: "epilepsy" OR "seizure" AND "Iran." In the second part of the study, the prevalence of various epilepsy syndromes in Iran was estimated based on the data from previous studies. We could identify 17 related articles. Three studies had class 2, and the rest provided class 4 of evidence. Two population-based studies provided the prevalence rate of epilepsy in Iran: 0.8% and 1.2%. In one clinic-based study, 20.2% of the patients were diagnosed as having idiopathic generalized epilepsy (IGE). In another clinic-based study, 5.4% of the patients were diagnosed to have Lennox-Gastaut syndrome. No study has provided data on focal epilepsy syndromes other than temporal lobe epilepsy (TLE) in Iran. While high-quality data from Iran on the epidemiology of epilepsy syndromes are scarce, based on the available data and extrapolations form other data from other world regions, we can estimate that the prevalence of epilepsy in Iran is about 1% and about 840,000 people currently have active epilepsy. From the whole population of people with epilepsy in Iran, about 168,000 people have IGEs, tens of thousands suffer from symptomatic generalized epilepsies, and approximately, 126,000-226,800 people suffer from TLE. There is a need for well-designed population-based epidemiological studies on the topic.

COVID-19, de novo seizures, and epilepsy: a systematic review.

OBJECTIVE: We discuss the evidence on the occurrence of de novo seizures in patients with COVID-19, the consequences of this catastrophic disease in people with epilepsy (PWE), and the electroencephalographic (EEG) findings in patients with COVID-19. METHODS: This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Scopus, and Embase from inception to August 15, 2020 were systematically searched. These key words were used: "COVID" AND "seizure" OR "epilepsy" OR "EEG" OR "status epilepticus" OR "electroencephalography". RESULTS: We could identify 62 related manuscripts. Many studies were case reports or case series of patients with COVID-19 and seizures. PWE showed more psychological distress than healthy controls. Many cases with new-onset focal seizures, serial seizures, and status epilepticus have been reported in the literature. EEG studies have been significantly ignored and underused globally. CONCLUSION: Many PWE perceived significant disruption in the quality of care to them, and some people reported increase in their seizure frequency since the onset of the pandemic. Telemedicine is a helpful technology that may improve access to the needed care for PWE in these difficult times. De novo seizures may occur in people with COVID-19 and they may happen in a variety of forms. In addition to prolonged EEG monitoring, performing a through metabolic investigation, electrocardiogram, brain imaging, and a careful review of all medications are necessary steps. The susceptibility of PWE to contracting COVID-19 should be investigated further.