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The impact of LRRK2 variants on the risk of Parkinson's disease in Egyptians remains unknown. We examined 1210 Egyptians (611 PD patients and 599 controls) from 16 governorates across Egypt for 12 LRRK2 pathogenic variants. The p.Gly2019Ser was the only variant detected, with a prevalence of 4.1% in sporadic cases, 6.5% in familial cases, and 0.68% in controls. Among p.Gly2019Ser carriers, all were heterozygous bar one homozygous patient, and all shared the common haplotype 1. Demographics and UPDRS scores did not differ between carriers and non-carriers, with most patients being males and developed PD in their fifties. Young and Early-onset PD prevalence was 37.5% in carriers and 33% in non-carriers. Familial cases were 16.6% in carriers and 11.5% in non-carriers. This study affirms that like other Mediterranean populations, Egyptians with PD have a higher prevalence of the p.Gly2019Ser variant compared to the global average. LRRK2 inhibitors could be promising therapeutic options for further exploration in this population., (© 2024. The Author(s).)

Objectives: The aim of the current study was to assess the therapeutic impact of repeated low frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (rDLPFC) on sleep problems in patients with fibromyalgia., Methods: Forty two patients with fibromyalgia who had sleep difficulties were randomly assigned to receive either real or sham rTMS treatment. Patients received 20 treatment sessions (5 sessions per week) in which 1200 rTMS pulses were applied over the rDLPFC using a frequency of 1 Hz and an intensity of 120 % of the resting motor threshold. All participants were evaluated at baseline, and then 1 month and 3 months after treatment using the Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Sleep Scale (MOS-SS) and polysomnography (PSG)., Results: There were significant time (pre, 1month, and 3 months)X group (real versus sham group) interactions in all 3 clinical rating scales; FIQ (Df = 1.425, F = 237.645, P = 0.001), PSQI (Df = 2, F = 64.005, P = 0.001), MOS-SS (Df = 2, F = 28.938, P = 0.001) due to the fact that the real group improved significantly more over time than the sham group. Similarly, the real group improved more on the PSG parameters than the sham group. The effect sizes were large both in the rating scales and PSG, indicating a substantial clinical improvement. Correlation as an exploratory analysis between the changes (pre - post 3 months) in MOS-SS and PLMs index (/h) showed significant negative correlation (r = -0.643, P = 0.002)., Conclusions: 20 sessions of LF-rTMS over rDLPFC can improve sleep quality in both subjective (PSQI and MOSS) as well as objective (PSG) rating scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.NONE., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: None.

Background: Avoidant Restrictive Food Intake Disorder (ARFID) is a newly classified eating disorder that requires further understanding of its presentation. There is no previous report of ARFID in a child post-tonsillectomy. ARFID may be a potential negative outcome for children following oropharyngeal surgery., Case Presentation: A female child aged 10 years and 2 months presented with ARFID associated with depression, anxiety and nutritional deficiency following tonsillectomy. She had more difficulty in swallowing solids than fluids and had repeated vomiting and spitting food after chewing it. She became dehydrated and malnourished with a BMI of 10.5 and was misdiagnosed with myasthenic gravis., Conclusions: To our knowledge, this is the first case report of ARFID in a child post-tonsillectomy. We discuss the pathophysiology of ARFID, which remains elusive, and recommend psychiatric assessment when evaluating children post operative tonsillectomy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ahmed, Karim, Khedr, Elbeh, Moheb, Abokresha and Haridy.)

This study aimed to evaluate the efficacy of rTMS in treating sleep disorders in PD. It included 24 patients with PD who had sleep disorders. Group allocations (active or sham with a ratio of 2:1) were placed in serially numbered closed envelopes. Each patient was evaluated with the following: MDS-UPDRS, Parkinson's Disease Sleep Scale (PDSS), Beck Depression Inventory (BDI), and polysomnography (PSG) before and 10 days after the treatment sessions. Each session consisted of 10 trains, 20 Hz, 10 sec for each, over the parietal cortex (bilaterally). Scores of UPDRS, BDI, and PDSS improved significantly in the active group but not in the sham group. The PSG data showed that sleep onset and rapid eye movement (REM) latencies (min), REM duration, and time spent awake (both as %TST) were improved after rTMS in the active group compared with the sham group. The number of awakenings, the wake-after-sleep onset index, the arousal index, and periodic leg movements (PLMs) were all significantly reduced in the active group but not in the sham group. Ten sessions of 20 Hz rTMS over parietal cortexes improved sleep quality and PLMs in patients with PD. The improvement in PSG and PDSS were correlated with improvements in UPDRS and BDI scores.

Few randomized controlled trials have reported that repetitive transcranial magnetic stimulation (rTMS) has controversial results for managing multiple domains of fibromyalgia-related symptoms. This work aimed to evaluate the effect of low-frequency rTMS over the right dorsolateral prefrontal area (DLPFC) on the Fibromyalgia Impact Questionnaire (FIQ) concerning psychiatric and cognitive disorders. Forty-two eligible patients with fibromyalgia (FM) were randomized to have 20 sessions of active or sham rTMS (1 Hz, 120% of resting motor threshold with a total of 1200 pules/session) over the right DLPFC. All participants were evaluated at baseline, post sessions, and 3 months after sessions with the FIQ, Hamilton depression, and anxiety rating scales (HDRS and HARS), Montreal Cognitive Assessment (MoCA), Rey Auditory Verbal Learning Test (RAVLT), Tower of London test (TOL), the Trail Making, and Digit Span Tests. Both groups showed improvement in most rating scales at 1 and 3 months follow-up, with greater improvement in the active group, with significant correlation between FIQ cognitive rating scales, including RAVLT and TOL. Twenty sessions of low-frequency rTMS over the right DLPFC can improve FIQ scores regarding the psychiatric and cognitive symptoms of medicated patients with FM to a greater extent than sham. Changes in RAVLT and TOL correlated with changes in FIQ results.

Despite the proven efficacy of the disease-modifying therapy (DMT) for multiple sclerosis (MS), the rates of non-adherence are frequently high. We aimed to evaluate the rate of non-adherence to the first DMT in Upper Egypt and identify different contributing factors. Out of 310 patients, ninety-seven adult patients with RRMS were recruited from three MS units located in Upper Egypt and were subjected to the following: complete clinical history, expanded disability status score (EDSS), Eight-item Morisky Medication Adherence Scale (MMAS-8), abbreviated Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9), Hamilton depression scale, Fatigue Severity Scale (FSS) and the Pittsburgh Sleep Quality Index (PSQI). According to MMAS-8 scores, 63 (64.9%) of patients were non-adherent to their first DMT. Non-adherent patients are more likely to have longer disease duration (p = 0.002), longer duration on first DMT (p = 0.030), first DMT-start date before 2019 (p = 0.040), and lower treatment satisfaction scores (p = 0.016). However, there was no significant relation with physical disability, depression, fatigue, or sleep quality. On the regression analysis model, a lower treatment satisfaction score was the only predictor of DMT non-adherence (p = 0.012). Despite expanding DMT options, non-adherence among MS patients in Upper Egypt is high. Treatment satisfaction with DMT is the only predictor of adherence among MS patients of Upper Egypt. Adherence and satisfaction with the prescribed DMT should be assessed carefully to maximize DMT benefits., (© 2024. The Author(s).)

Diverse psychological consequences of the COVID-19 pandemic have been reported for 6 months after infection. We conducted a prospective study to evaluate the psychological impact of COVID-19 infection in newly diagnosed cases that were followed up at 1, 6, and 9 months after infection. 137 people were recruited and divided into four groups based on the COVID-19 Treatment Guidelines. They were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Post-traumatic stress disorder Checklist for DSM-5 (PCL-5), and Symptom Checklist 90 (SCL-90). We found that 9 months after infection, patients continued to report poor sleep (74.5%), PTSD (78.3%), somatization (17%), anxiety (17%), aggression (5.7%), phobic anxiety (4.7%), psychoticism (1.9%), paranoid (3.8%), and obsessive-compulsive (9.4%) symptoms, as well as depression and interpersonal sensitivity. The most significant risk factors for psychiatric complications were older age, level of education, smoking, hospitalization duration, hypertension, and critical severity. The negative mental health effects of COVID-19 persist after hospital discharge, and many patients continue to experience moderate-to-severe issues that may endure for 9 months. Notably, there was a progressive improvement in these symptoms over that time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: This study aimed to determine the impact of patients' baseline clinical, neurophysiological data, and management plan of Guillain-Barré syndrome (GBS) on long-term quality of life (QoL) and to identify its potential predictors., Methods: Seventy-nine GBS patients were recruited. On admission, participants were evaluated using the Medical Research Council (MRC) sumscore, GBS disability scale (GDS), and Erasmus GBS Respiratory Insufficiency Score (EGRIS). Neurophysiological data were collected, and a management plan was devised. MRC sumscore was repeated at nadir. MRC, GDS and Short Form Survey (SF-36) were assessed at first-year follow-up., Results: The mean age was 37.84 ± 17.26 years, with 43 male patients (54.4%). QoL at one year correlated significantly with baseline clinical variables (age, number of days between weakness and admission, MRC sumscore at onset and nadir, high GDS, and EGRIS scores). Antecedent events, especially diarrhoea, neck muscle weakness, autonomic dysfunction, cranial nerve involvement, and mechanical ventilation (MV), associated with worse QoL. Axonal GBS patients had lower QoL than AIDP patients, and PE patients exhibited lower QoL than IVIG patients. Multiple regression analysis showed that older age, diarrhoea, number of days between weakness and admission, neck muscle weakness, cranial nerve involvement, autonomic dysfunction, early MV, and MRC at onset and nadir and high GDS could predict poor QoL., Conclusion: Older age, more days between weakness and admission, neck muscle weakness, cranial nerve involvement, autonomic dysfunction, early MV, diarrhoea, low MRC at onset and nadir, high GDS at onset, axonal type, and PE treatment were potential predictors of poor QoL in GBS., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest concerning this article’s research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study compared the clinical outcomes of the two main neurophysiological types of Guillain-Barré Syndrome (GBS). Sixty-two GBS patients were examined clinically at onset using Medical Research Council (MRC), Hughes disability scales (HDS), and nerve conduction studies were evaluated in four limbs. The Modified Erasmus GBS outcome score (MEGOS) was assessed 2 weeks after onset. Outcomes were measured after 3 months using MRC and HDS scores. According to electrophysiological data two main groups identified acute inflammatory demyelinating polyneuropathy (AIDP = 31 cases) or acute axonal GBS including inexcitable forms (26 cases). The number of days between onset of weakness and admission was significantly shorter, and gastrointestinal symptoms were significantly higher among the axonal type than AIDP. MRC sum scores at onset and at nadir were significantly worse in the axonal type than in AIDP. Neck muscle weakness, impaired cough reflex, the need for mechanical ventilation, hypoalbuminemia, and hypernatremia were more common in the axonal type. At outcome, 74% of the AIDP were healthy/minor symptoms versus 38.46% of the axonal type. There was a high prevalence of the axonal variant (41.9%) compared with European and North American populations. The axonal type had a significantly worse outcome than AIDP type., (© 2023. Springer Nature Limited.)

Fatigue is a common disabling symptom of relapsing remitting multiple sclerosis (RRMS). Many studies have linked grey matter atrophy to fatigue, but white matter lesion load (WM-LL) has received less attention. Here we assess the relation between fatigue and regional WM-LL volumetric measures. 63 patients with RRMS participated in this study; mean age was 31.9 ± 8.1 years. Each patient provided demographic details and was scored on the expanded disability status scale (EDSS) and fatigue severity scale (FSS). VolBrain, a fully automated, operator-independent tool was used to assess WM-LL and whole brain volume. The patients were classified into three groups: no fatigue (FSS < 4), low to moderate fatigue (FSS ≥ 4 ≤ 5) and high fatigue (FSS > 5). 33.3% of patients had no significant fatigue, 25.4% had mild-to-moderate fatigue, and 41.3% had significant fatigue. Age, disease duration, relapses, and EDSS were positively correlated to fatigue severity (P = 0.034, 0.002, 0.009 and 0.001 respectively). Whole brain volume, total and regional WM-LL (juxtacortical, periventricular, infratentorial) were also correlated with fatigue severity. Ordinal regression analysis for fatigue severity showed EDSS and infratentorial lesion volume were the best predictors. In conclusion, EDSS and infratentorial lesion volume (cerebellar and brainstem) are the best predictors of fatigue severity., (© 2023. The Author(s).)

Objectives: Cerebrovascular stroke (CVS) is one of the well-known complications of coronavirus-2019 (Covid-19), but less is known about the outcome and safety of thrombolytic therapy in these patients. In this study we compare the efficacy and safety of Tissue plasminogen activator (rTPA) in acute ischemic stroke (AIS) patients with or without Covid-19 infection., Materials and Methods: A comparative prospective study in which all patients who presented with AIS and eligible for rTPA were recruited from the emergency department and classified into 2 groups (AIS with Covid-19 infection and AIS without Covid-19 as controls). Demographic data, symptoms of Covid-19, clinical examination, neuroimaging, and laboratory investigations were obtained in each patient. National Institute of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS) were assessed before, immediately after rTPA, and 3 months later., Results: There were 22 patients in the COVID-19 group and 25 control patients. Those with COVID-19 were more likely to have a history of smoking and Diabetes Mellitus than controls. On admission, motor symptoms were more severe in patients with COVID-19. COVID-19 patients were more likely to have symptomatic intra-cerebral hemorrhage and radiological hemorrhagic transformation than controls. Onset to door time (ODT) and onset to successful reperfusion time were significantly longer in Covid-19 patients than controls. Clinical improvement and frequency of re-occlusion and recurrent ischemic stroke at 3 months follow-up did not differ between groups, although there was higher number of deaths (27.3%) in the Covid-19 group than controls (16%)., Conclusions: Using rTPA is safe and effective in patients with AIS with or without COVID-19 infection despite the high frequency of hemorrhagic transformation and high number of deaths., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Previous studies in headache patients measured the cerebrovascular reactivity (CVR) in response to photic stimulation but they have yielded contradictory results. The purpose of study was to measure CVR of both migraine and chronic tension headache (TTH) patients in response to photic stimulation., Methods: The study included 37 migraineurs and 24 chronic TTH patients compared with 50 age- and sex-matched healthy volunteers. Peak systolic, end diastolic, mean flow velocities and CVR (PSV, EDV, MFV, and CVR) were measured using TCD ultrasonography of the middle, anterior, posterior cerebral and vertebral arteries (MCA, ACA, PCA, and VA) before and after 100 s of 14 Hz photic stimulation., Results: A three-way repeated measures ANOVA interaction with main factors of Vessels (MCA, ACA, PCA, VA), Time (pre-post photic) and Groups (migraine, TTH, and control group) revealed significant 3-way interactions for measures of PSV (P = 0.012) and MFV (P = 0.043). In the migraine patients there was significantly higher PSV, EDV, and MFV in the MCA, ACA, and PCA after photic stimulation compared with baseline. The CVR of the MCA was also significantly higher in migraineurs than controls. In the TTH group, there was significantly higher PSV, EDV, and MFV (P = 0.003, 0.012, 0.002 respectively) in the VA after photic stimulation than at baseline. The CVR was significantly higher in the VA of TTH patients than controls., Conclusion: Compared with controls after photic stimulation, the higher CVR of the MCA in migraineurs and of the VA in TTH patients could be used as diagnostic tool to differentiate between the two types of headaches., (© 2023. The Author(s).)

The earlier the diagnosis of multiple sclerosis (MS), the sooner disease-modifying treatments can be initiated. However, significant delays still occur in developing countries. We aimed to identify factors leading to delayed diagnosis of MS in Upper Egypt. One hundred forty-two patients with remitting relapsing MS (RRMS) were recruited from 3 MS units in Upper Egypt. Detailed demographic and clinical data were collected. Neurological examination and assessment of the Disability Status Scale (EDSS) were performed. The mean age was 33.52 ± 8.96 years with 72.5% of patients were females. The mean time from symptom onset to diagnosis was 18.63 ± 27.87 months and the median was 3 months. Seventy-two patients (50.7%) achieved diagnosis within three months after the first presenting symptom (early diagnosis), while seventy patients (49.3%) had more than three months delay in diagnosis (delayed diagnosis). Patients with a delayed diagnosis frequently presented in the period before 2019 and had a significantly higher rate of initial non-motor presentation, initial non-neurological consultations, prior misdiagnoses, and a higher relapse rate. Another possible factor was delayed MRI acquisition following the initial presentation in sixty-six (46.5%) patients. Multivariable logistic regression analysis demonstrated that earlier presentation, initial non-neurological consultation, and prior misdiagnosis were independent predictors of diagnostic delay. Despite advances in MS management in Egypt, initial non-neurological consultation and previous misdiagnoses are significant factors responsible for delayed diagnosis in Upper Egypt., (© 2023. The Author(s).)

Background: Most previous studies comparing the effectiveness of Plasma Exchange (PE) or intravenous immunoglobulin (IVIG) in treating Guillain-Barre syndrome (GBS) have focused on the short-term outcome at around 1 month., Objective: To compare the long-term efficacy of PE and IVIG at one year in adult patients with GBS., Methods: Eighty-one adult patients with acute GBS were randomized into two groups with a ratio of 2 : 1: PE (N = 54) and IVIG (N = 27). Patients were assessed with the Medical Research Council sum score (MRC sum score), GBS Disability Scale (GDS), and Functional assessment of acute inflammatory neuropathy (FAAIN) at baseline, ten days, one month, three months, and one year. Neurophysiological examinations were performed at baseline and three months following treatment., Results: There were no significant differences between groups in demographic, clinical, and laboratory data. Both treatments produced a significant improvement in all clinical rating scales in both groups that continued up to one year. There were significant differences in the time course of recovery in the MRC and FAAIN scales, with significantly more improvement in the IVIG group at 1 and 3 months, although there was no significant difference in outcome at one year. However the effect size showed measurable differences between the PE and IVIG groups across the different measures at one-year. Electrophysiological studies showed equal improvement in most measures in both groups at three months, with a slightly greater effect in the IVIG group., Conclusion: long term outcomes of IVIG and PE were equivalent. However the effect size showed measurable differences between the PE and IVIG groups across the different measures at one-year follow-up that indicate the superiorty of IVIG. There was also a tendency for improvement to be slightly faster in the IVIG group.

Purpose: Using constrained spherical deconvolution (CSD)-based tractography, we aimed to obtain conjoint analysis of diffusion measures of major language white matter (WM) tracts in post-stroke aphasic patients bilaterally, and to correlate the measures of each tract to the different language deficits., Material and Methods: 17 aphasic patients with left hemispheric stroke, at the subacute stage, and ten age- matched controls underwent diffusion MRI examination. CSD-based tractography was performed. Diffusion measures [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were extracted after dissection of major language tracts bilaterally. Aphasia was assessed using language subset of hemispheric stroke scale. Comparisons of diffusion measures, for all tracts, between the two groups were performed. Partial correlations between the diffusion measures and different language components were obtained., Results: In the left hemisphere, significant lower FA and or higher MD with higher RD of patients' WM tracts compared to the control group. Significant differences of diffusion measures were also evident in the right hemisphere yet, less prominent. All changes reflected damage of the tracts' integrity. Significant correlations were found between comprehension and FA of the left arcuate fasciculus (AF) and left inferior longitudinal fasciculus. Additionally, a significant correlation was found between MD of the right AF and repetition., Conclusion: Conjoint analysis of diffusion measures, based on CSD tractography, can provide important markers for the underlying WM changes bilaterally. Moreover, our findings emphasize that language processing can be mediated by both ventral and dorsal streams and further highlight the contribution of the right AF in repetition., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Background: Stroke rehabilitation interventions are routinely personalized to address individuals' needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias., Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database., Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori . Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild-moderate/ moderate-severe based on language outcomes' median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness., Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants' greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3-4 SLT-h/week; ⩾ 50 hours). For moderate-severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild-moderate participants' greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males' greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week., Conclusions: We observed a treatment response in most subgroups' overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild-moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate-severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.

We compared the effectiveness of low frequency repetitive transcranial magnetic stimulation over right dorsolateral prefrontal cortex (DLPFC), right orbitofrontal cortex (OFC) and sham for treatment of obsessive-compulsive disorder (OCD) and sought to determine possible predictors of effective treatment. Sixty OCD patients participated and were randomly allocated to one of the 3 treatment groups. Treatment was administered daily for 10 days. Assessments were made at the beginning and end of therapy as well as three months later using the Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory (BDI), and Clinical Global Impression - Severity scale (CGI-S). There were no significant demographic or clinical differences between the groups at baseline. One-way repeated measures ANOVA showed that participants in all 3 groups improved their scores on all rating scales following treatment. A two-way repeated measures ANOVA revealed a significant time and group interaction due to the fact that both active treatment groups outperformed the sham group, although there was no significant difference between the two. Percent improvement had significant negative correlations with the following factors: duration of illness, baseline Y-BOCS, HAM-A, and BDI. We conclude that rTMS over either right DLPFC or OFC has a therapeutic effect on OCD symptoms. Patients with lower Y-BOCS and fewer comorbidities responded best to rTMS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Out of 75 cases of OCD were recruited from Aswan University Hospital (AUH) only 60 were participated in the study and classified randomly into 3 groups (each 20 patients). All patients completed the sessions and included in the analysis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The aim of the current study was to determine whether tension-type headache (TTH) and migraine with or without aura have altered anterior and posterior circulation compared with normal volunteers as assessed by Transcranial Doppler (TCD) ultrasonography. The study included 24 patients with chronic TTH and 37 patients with migraine (16 with aura and 21 without aura) classified according to the diagnostic criteria of the International Headache Society 2018. They were compared with a control group of 50 age- and sex-matched healthy volunteers. Each participant was examined with TCD ultrasonography of the middle, anterior and posterior cerebral and vertebral arteries (MCA, ACA, PCA, and VA) at rest. Patients in the TTH group had a significantly lower peak systolic velocity (PSV) and mean flow velocity (MFV) in the MCA compared with controls, whereas EDV and MFV in the ACA were significantly higher in the migraine without aura group than controls. Within the 3 groups of patients, the TTH group had significantly lower PSV in the MCA and PCA than the group of migraine with aura. In addition, the TTH group had significantly lower PSV and MFV in the MCA and a lower EDV in the VA than migraine patients without aura. In conclusion, the possibility of cerebrovascular changes is confirmed in the present study in both TTH and migraine without aura. The former has a low MFV in the MCA whereas the latter has a high MFV in the ACA., (© 2022. The Author(s).)

Background: Transcranial direct current stimulation (tDCS) has shown promising results in alleviating different types of pain. The present study compares the efficacy of three sessions of anodal tDCS applied over primary motor area (M1) or the left dorsolateral prefrontal cortex (DLPFC) or sham on reducing pain and the total opioid consumption in postoperative spine surgery patients., Materials: Sixty-seven out of 75 eligible patients for postoperative spine surgery were randomly allocated into one of the three experimental groups. Group A received anodal tDCS applied over M1 cortex, group B over left DLPF cortex (2 mA, 20 min) and group C received sham tDCS, all for 3 consecutive postoperative days. Patients were evaluated using a visual analogue scale (VAS) and adynamic visual analogue scale (DVAS) at baseline, and on each of the treatment days. The total morphine consumption over the 3 postoperative days was assessed., Results: Two-way repeated measures ANOVA showed no statistically significant difference in resting VAS between the three groups. However, there was significant pain improvement (P < 0.001) in DVAS in both active groups (group A and B) compared to the sham group (group C) in the postoperative period, with no significant difference between the active groups. Morphine consumption was significantly reduced in both active groups compared with the sham group, but there was no difference in consumption between the active groups., Conclusion: There was a significant postoperative reduction in morphine consumption and DVAS scores after three sessions of active tDCS., Significance: tDCS is a promising tool for alleviating pain in the field of postoperative spine surgery., (© 2022 European Pain Federation - EFIC®.)

Background: Fatigue is the most troublesome symptom in relapsing remitting multiple sclerosis (RRMS). It starts early in the disease course, escalates with disease progression and impacts the patients` quality of life. The aim of this work was to estimate the frequency of fatigue and to evaluate the relationship between severity of fatigue, clinical data, level of disability and volumetric brain atrophy in RRMS., Methods: 43 RRMS patients with 40 age- and sex-matched normal volunteers were recruited. Demographic and clinical data were recorded. Each participant was assessed with the Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS), Brief Cognitive Assessment for Multiple Sclerosis (BICAMS) and a variety of brain volumetric measures., Results: 31 (72.1%) of RRMS patients were found to have fatigue. There were no significant differences in demographic data between patients with or without fatigue according to FSS. However, patients with fatigue had a higher number of attacks, and higher scores in the EDSS and BICAMS than non-fatigued patients. There was a greater reduction in total brain volume, cerebral grey matter, and brain stem, thalamic and caudate volumes in fatigued compared with the non-fatigued patients and controls. FSS was significantly correlated with patients' age, duration of illness, total number of attacks, EDSS, and BICAMS. Total brain, cerebral grey matter and thalamic volumes all had negative correlations with fatigue severity. Regression analysis showed that EDSS accounted for 46% of the variance in fatigue scores while thalamic and brainstem atrophy accounted for 50.7%., Conclusion: Fatigue was fairly common in RRMS patients. Level of disability and atrophy of the thalamus and brain stem were the best predictors of fatigue., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Dysbiosis of gut microbiota has been reported to be enrolled in the pathogenesis of Alzheimer's disease (AD). However, there is a lack of relevant studies on this topic in Egyptian patients with AD., Objective: To investigate different species of gut microbiota in Egyptian patients with AD and correlate microbiota bacterial abundance with clinical data., Methods: The study included 25 patients with AD and 25 healthy volunteers as age and sex-matched controls. Clinical data was taken for each patient, including medical history and examination; Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were assessed for each participant. Bacterial DNA was extracted from stool, and abundance quantified via qPCR using 16S rRNA group-specific primers., Results: Akkermansia, Enterobacteria, Bacteroidetes, Bacillus cereus, Prevotella, and Clostridium cluster IV were more abundant in the AD group than in the control group, although there was significantly less abundance of Bifidobacterium spp., Firmicutes, and Actinobacteria in patients with AD than in controls, whereas no such significance was found for lactic acid bacteria between both groups. Lactic acid bacteria and Prevotella abundance was negatively correlated with cognitive impairment (p = 0.03 with MMSE, and p = 0.03 with MoCA). Prevotella abundance was positively correlated with age of onset and duration of illness and negatively correlated with smoking and coronary heart disease (p = 0.007, p = 0.03, p = 0.035, and p = 0.047, respectively)., Conclusion: The current work highlighted a significant relationship between AD and gut microbiota dysbiosis. A higher abundance of Prevotella species and lactic acid bacteria was correlated with cognition.

Background: The coronavirus disease 19 (COVID-19) pandemic has spread rapidly around the globe with considerable morbidity and mortality. Coexistence of comorbidities with COVID-19 had consistently been reported as risk factors for unfavorable outcome. We aimed to evaluate the impact of comorbidities in COVID-19 patients on the outcome and determine predictors of prolonged hospital stay, requisite for intensive care unit (ICU) admission. Four hundred and thirty-nine adult patients who are admitted through (June and July 2020) in our University Hospitals were included in the study. All participants were diagnosed with COVID-19 according to Egyptian Ministry of Health guidance as definite case or probable case., Results: Patients with comorbidities represented 61.7% of all cases. Constitutional symptoms especially myalgia and lower respiratory tract (LRT) symptoms such as dyspnea were significantly higher in patients with comorbidities ( P  < 0.05). Patients with comorbidities had significantly worse laboratory parameters. ICU admission was higher in patients with comorbidities (35.8%). Among different comorbidities 45.4% of cardiovascular diseases (CVD) cases were admitted in ICU followed by diabetes mellitus (DM) cases (40.8%). Also, patients with comorbidities needed invasive mechanical ventilation more than those without comorbidity (31 versus 10.7%, P  < 0.001). Significant lower frequency of recovery was found in COVID-19 patients with comorbidities (59% versus 81%, P  < 0.001) and death rate was significantly higher in cases with comorbidities ( P  < 0.001) . The survival rates in cases with pre-existing CVD and neurological diseases were lower than those without disease ( P  < 0.002 and 0.001, respectively)., Conclusions: Association of cardiovascular comorbid conditions including hypertension or neurological diseases including old cerebrovascular strokes together with COVID-19 infections carries higher risks of mortality. However, other comorbidities such as diabetes mellitus, chronic pulmonary or kidney diseases may also contribute to increased COVID-19 severity., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

The long-term impact of the COVID-19 infection on mental health in people and its relation to the severity is unclear. We aimed to study the long-term effect of post-COVID-19 disease on sleep and mental health and to detect possible relationship between severity of COVID-19 at onset and sleep and mental illness. We enrolled 182 participants 6 months post COVID-19 infection and grouped into non-severe(101),severe(60) and critical(20) according to according to WHO guidance. All participants were assessed using Pittsburgh Sleep Quality Index ", Post traumatic stress disorder (PTSD) Checklist for DSM-5, and Symptom Checklist90 test. Only 8.8% had no psychiatric symptoms while 91.2% had psychiatric symptoms as follow (poor sleep (64.8%), PTSD (28.6%), somatization (41.8%), obsessive-compulsive (OCD) (19.8%), depression (11.5%), anxiety (28%), phobic-anxiety (24.2%), psychoticism (17.6%)). Diabetes, oxygen support or mechanically ventilated were a risk for sleep impairment, while high Neutrophil/lymphocyte ratio(NLR) was the only risk factor for PTSD. Other psychiatric illnesses had several risk factors: being female, diabetes, oxygen support or mechanically ventilated. Abnormal sleep, somatization and anxiety are the most common mental illnesses in Post-Covid19. The critical group is common associated with PTSD, anxiety, and psychosis. Being female, diabetic, having oxygen support or mechanically ventilated, and high NLR level are more vulnerable for mental illness in post COVID19., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To assess by transcranial magnetic stimulation (TMS) the excitability of various cortical circuits in akinetic-rigid and tremor-dominant subtypes of Parkinson's disease (PD)., Methods: The study included 92 patients with PD according to UK Brain Bank criteria, with akinetic-rigid (n = 64) or tremor-dominant (n = 28) subtype. Cortical excitability study, including resting and active motor thresholds (rMT and aMT), input-output curve of motor evoked potentials, contralateral and ipsilateral silent periods (cSP and iSP), short and long-interval intracortical inhibition (SICI and LICI), and intracortical facilitation (ICF) were measured. The results obtained were compared to a control group of 30 age- and sex-matched healthy subjects., Results: The patients in the tremor group had significantly lower rMT and aMT compared to controls and akinetic-rigid patients and significantly shorter iSP duration compared to akinetic-rigid patients, while iSP latency tended to be longer in akinetic-rigid patients compared to controls. There were no significant differences between the two PD subgroups regarding other cortical excitability parameters, including paired-pulse TMS parameters., Conclusions: Only subtle differences of cortical excitability were found between patients with akinetic-rigid vs. tremor-dominant subtype of PD., Significance: The clinical heterogeneity of PD patients probably has an impact on cortical excitability measures, far beyond the akinetic-rigid versus tremor-dominant profile., Competing Interests: Declaration of Competing Interest None of the authors have potential conflicts of interest to be disclosed., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Healthcare workers (HCWs) are at a high risk for disease exposure. Given the limited availability of nucleic acid testing by PCR in low resource settings, serological assays can provide useful data on the proportion of HCWs who have recently or previously been infected. Therefore, in this study, we conducted an immunologic study to determine the seroprevalence of anti-SARS-CoV-2 antibodies in two university hospitals in Egypt., Methods: in this cross sectional study, HCWs who were working in SARS-CoV-2 Isolation Hospitals were interviewed. Estimating specific antibodies (IgM and IgG) against SARS-CoV-2 was carried out using an enzyme-linked immunosorbent assay targeting the Spike antigen of SARS-CoV-2 virus., Results: Out of 111, 82 (74%) HCWs accepted to participate with a mean age of 31.5 ± 8.5 years. Anti-SARS-COV2 antibodies were detected in 38/82 (46.3%) of cases with a mean age of 31 years and female HCWs constituted 57.6% of cases. The highest rate of seropositivity was from the nurses (60.5%), and physicians (31.6%) with only (7.9%) technicians. Only 28/82 (34.1%) HCWs reported previous history of COVID19. We reported a statistically significant difference in the timing of exposure (p = 0.010) and the frequency of contact with COVID-19 cases (p = 0.040) between previously infected and on-infected HCWs. Longer time of recovery was reported from IgG positive HCWs (p = 0.036)., Conclusion: The high frequency of seropositive HCWs in investigated hospitals is alarming, especially among asymptomatic personnel. Confirmation of diseased HCWs (among seropositive ones) are warranted., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Gut microbiota is assumed to play an essential role in the pathogenesis of multiple sclerosis (MS). This study aimed to investigate the abundance of some gut microbiota among Egyptian patients with relapsing remitting multiple sclerosis (RR-MS)., Materials and Methods: Forty cases of RR-MS diagnosed according to McDonald diagnostic criteria (2017) were recruited consecutively from the Department of Neurology, Assiut University Hospitals. The results were compared with 22 healthy age and sex matched control subjects. DNA was extracted from stool and measures made of concentration and copy number of bacterial organisms by real-time PCR using group specific primers for 16S rRNA targeting predominant genera of gut microbiota previously hypothesized to participate in MS pathogenesis., Results: The mean age was 31.4 ± 8.8 yrs; 75% of the patients were women. The mean and SD of EDSS score was 3.43 ± 1.35. Seven cases had cervical cord plaques (17%). There were significantly increased copy numbers of Desulfovibrio, Actinobacteria, Firmcutes, and Lactic acid bacteria in patients compared with the control group. In contrast there was a significantly lower level of Clostridium cluster IV in the patients. Patients who had EDSS < 3.5 had a significantly higher copy number of Actinobacteria, Bacteroidetes, and Bifidobacterium , compared with patients who had EDSS > 3.5. There was a significant negative correlation between duration of illness and copy number of Firmcutes, Akkermansia, and Lactic acid bacteria (P = 0.01, 0.04, and 0.004 respectively)., Conclusion: The changes in gut microbiota are associated with exacerbation of MS disease. Disruption of the intestinal microbiota results in the depletion or enrichment of certain bacteria that may affect the immune balance leading to predisposition to MS., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Objectives: In this pilot study we investigated the effects of transcranial direct current stimulation (tDCS) on language recovery in the subacute stage of post-stroke aphasia using clinical parameters and diffusion imaging with constrained spherical deconvolution-based tractography. Methods: The study included 21 patients with subacute post-stroke aphasia. Patients were randomly classified into two groups with a ratio of 2:1 to receive real tDCS or sham tDCS as placebo control. Patients received 10 sessions (5/week) bi-hemispheric tDCS treatments over the left affected Broca's area (anodal electrode) and over the right unaffected Broca's area (cathodal stimulation). Aphasia score was assessed clinically using the language section of the Hemispheric Stroke Scale (HSS) before and after treatment sessions. Diffusion imaging and tractography were performed for seven patients of the real group, both before and after the 10th session. Dissection of language-related white matter tracts was achieved, and diffusion measures were extracted. A paired Student's t -test was used to compare the clinical recovery and diffusion measures of the dissected tracts both pre- and post- treatment. The partial correlation between changes in diffusion measures and the language improvements was calculated. Results: At baseline assessment, there were no significant differences between groups in demographic and clinical HSS language score. No significant clinical recovery in HSS was evident in the sham group. However, significant improvements in the different components of HSS were only observed in patients receiving real tDCS. Associated significant increase in the fractional anisotropy of the right uncinate fasciculus and a significant reduction in the mean diffusivity of the right frontal aslant tract were reported. A significant positive correlation was found between the changes in the right uncinate fasciculus and fluency improvement. Conclusions: Aphasia recovery after bi-hemispheric transcranial direct current stimulation was associated with contralesional right-sided white matter changes at the subacute stage. These changes probably reflect neuroplasticity that could contribute to the recovery. Both the right uncinate fasciculus and right frontal aslant tract seem to be involved in aphasia recovery.

Background and Purpose: Post COVID-19 seizures are relatively rare. The aim of the present study was to estimate the frequency of acute symptomatic seizures among patients with COVID-19 and to discuss possible pathophysiological mechanisms., Material and Methods: Out of 439 cases with COVID-19 that were admitted to Assiut and Aswan University hospitals during the period from 1 June to 10 August 2020, 19 patients (4.3 %) presented with acute symptomatic seizures. Each patient underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the brain and conventional electroencephalography (EEG). Laboratory investigations included: blood gases, complete blood picture, serum D-Dimer, Ferritin, C-reactive protein, renal and liver functions, and coagulation profile., Results: Of the 19 patients, 3 had new onset seizures without underlying pathology (0.68 % out of the total 439 patients); 2 others (0.46 %) had previously diagnosed controlled epilepsy with breakthrough seizures. The majority of cases (14 patients, 3.19 %) had primary pathology that could explain the occurrence of seizures: 5 suffered a post COVID-19 stroke (3 ischemic and 2 hemorrhagic stroke); 6 patients had COVID-related encephalitis; 2 patients were old ischemic stroke patients; 1 patient had a brain tumor and developed seizures post COVID-19., Conclusion: acute symptomatic seizure is not a rare complication of post COVID-19 infection. Both new onset seizures and seizures secondary to primary brain insult (post COVID encephalitis or recent stroke) were observed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The aim of the present study was to explore the impact of acute and chronic nicotine consumption on measures of intracortical inhibition and facilitation., Methods: This study involved 50 chronic heavy cigarette smokers and 40 healthy subjects matched for age, sex and educational level, with no history of chronic nicotine intake. Intracortical inhibition and facilitation were assessed using transcranial magnetic stimulation (TMS) measures of motor threshold (MT), short- and long-interval intra-cortical inhibition (SICI, LICI), cortical silent period (CSP) and intra-cortical facilitation (ICF). Basal serum levels of cotinine were measured in the healthy group and at ½ and 2 h after smoking a single cigarette in the chronic smokers., Results: There was enhanced SICI and reduced ICF in smokers (independent of time after smoking) compared with non-smokers. The former suggests a chronic effect of increased nicotine levels on GABA-A neurotransmission whereas the latter suggests an additional effect on glutamatergic transmission. There were no significant differences between smokers and non-smokers in other TMS parameters. There was a significant negative correlation between cotinine levels at ½ h after smoking and SICI at 3 ms ISI (P < 0.001). There were no significant differences in any of the neurophysiological measures between smokers at ½ h versus 2 h after smoking a single cigarette., Conclusion: Chronic nicotine consumption enhances SICI, and reduces ICF, supporting the hypothesis that nicotine acts as a neuromodulator of GABA-A and glutamate neurotransmission., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background and Purpose: There is little information on the acute cerebrovascular complications of coronavirus disease 2019 (COVID-19) in Egypt. The aim of this study was to estimate the proportion of acute cerebrovascular disease (CVD) among COVID-19 patients and evaluate their clinical and radiological characteristics in comparison with non-COVID-19 CVD. Materials and Methods: In a retrospective study, COVID-19 patients whom presented with CVD in Assiut and Aswan University Hospitals were compared with non-COVID-19, CVD patients, admitted to Qena University Hospital, prior to the pandemic. The following data were collected: clinical history and presentation, risk factors, comorbidities, brain imaging (MRI or CT), chest CT, and some laboratory investigations. Results: Fifty-five (12.5%) of the 439 patients with COVID-19 had acute CVD. Of them, 42 (9.6%) had ischemic stroke while 13 patients (2.9%) had hemorrhagic CVD. In the 250 cases of the non-COVID-19 group, 180 had ischemic stroke and 70 had hemorrhagic stroke. A large proportion of patients with COVID-19 who presented with ischemic stroke had large vessel occlusion (LVO), which was significantly higher than in non-COVID-19 patients with CVD (40 vs. 7.2%, P < 0.001). Comorbidities were recorded in 44 (80%) cases. In COVID-19 ischemic stroke patients, risk factors [hypertension and ischemic heart disease (IHD)] and comorbidities (hepatic and renal) were significantly higher than those in non-COVID-19 patients. In addition, 23.5% had hemorrhagic CVD, and six patients with LVO developed hemorrhagic transformation. Conclusion: Acute CVD among patients with COVID-19 was common in our study. LVO was the commonest. Hypertension, IHD, and anemia are the most common risk factors and could contribute to the worsening of clinical presentation. Comorbidities were common among patients with CVD, although a large number had elevated liver enzymes and creatinine that were partially due to COVID-19 infection itself. The current results begin to characterize the spectrum of CVD associated with COVID-19 in patients in Upper Egypt. Registration ID: The ID number of this study is IRB no: 17300470., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khedr, Soliman, Abo-Elfetof, Amin, Mansour, Aly, Zaki and Saber.)

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is a widely applied treatment protocol for chronic smoking and major depressive disorder. However, no previous study has measured the effects of rTMS on both nicotine consumption and anxiety/depression in the same volunteers despite the relationship between them. The aim of this work was to evaluate the efficacy of 10 daily sessions of HF-rTMS over the L-DLPFC in chronic cigarette smokers' addiction and investigate the possible beneficial effects of this treatment procedure on symptoms of depression and anxiety in the same subjects. The study included 40 treatment-seeking nicotine-dependent cigarette smokers. Onset/duration of smoking, number of cigarettes/day, Fagerstrom Test of Nicotine Dependence (FTND), Tobacco Craving Questionnaire-Short Form (TCQ-SF), Hamilton depression and anxiety scales (HAM-D and HAM-A) were recorded. Participants were randomly assigned to the active or the sham treatment group. Those in the active group received 10 trains of 20 Hz stimulation, at 80% of the resting motor threshold (rMT) for 10 consecutive working days over L-DLPFC. Participants were reassessed immediately after treatment, and then 3 months later using all rating scales. There were no differences between active and sham groups at baseline. The cigarette consumption/day, and scores on FTND, and TCQ decreased significantly in both groups (p = 0.0001 for each) immediately after treatment. However, improvement persisted to 3 months in the active group but not in the sham group. Moreover, there was a significant reduction in HAM-D and HAM-A scores immediately after treatment in the active but not the sham group. Subjects with a longer history of smoking had a lower percent improvement in FTND (p = 0.005). Our findings revealed that HF-rTMS over L-DLPCF for 10 days reduced cigarette consumption, craving, dependence, and improved associated symptoms of anxiety and depression.ClinicalTrials.gov Identifier: NCT03264755 registered at 29/08/2017.

Background: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals., Materials and Methods: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated., Results: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection., Conclusion: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis., (© 2021 S. Karger AG, Basel.)

As for hypertension, chronic pain, epilepsy and other disorders with particular symptoms, a commonly accepted and unambiguous definition provides a common ground for researchers and clinicians to study and treat the problem. The WHO's ICD11 definition only mentions tinnitus as a nonspecific symptom of a hearing disorder, but not as a clinical entity in its own right, and the American Psychiatric Association's DSM-V doesn't mention tinnitus at all. Here we propose that the tinnitus without and with associated suffering should be differentiated by distinct terms: "Tinnitus" for the former and "Tinnitus Disorder" for the latter. The proposed definition then becomes "Tinnitus is the conscious awareness of a tonal or composite noise for which there is no identifiable corresponding external acoustic source, which becomes Tinnitus Disorder "when associated with emotional distress, cognitive dysfunction, and/or autonomic arousal, leading to behavioural changes and functional disability.". In other words "Tinnitus" describes the auditory or sensory component, whereas "Tinnitus Disorder" reflects the auditory component and the associated suffering. Whereas acute tinnitus may be a symptom secondary to a trauma or disease, chronic tinnitus may be considered a primary disorder in its own right. If adopted, this will advance the recognition of tinnitus disorder as a primary health condition in its own right. The capacity to measure the incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address acute tinnitus as a symptom but chronic tinnitus as a disorder., (© 2021 Elsevier B.V. All rights reserved.)

Background and Purpose: Successful reperfusion is a significant predictor of a good clinical outcome after mechanical thrombectomy (MT). However, some patients have a poor clinical outcome even with successful reperfusion. We aimed to study factors that predict a poor clinical outcome (90-day modified Rankin Scale ≥ 3) in patients with anterior circulation large vessel occlusion (LVO) treated by successful MT within 6 h of symptom onset. Methods: We performed a retrospective review of a prospectively maintained MT database of all patients who underwent MT within 6 h of symptom onset for an anterior circulation LVO at our institution from May 2016 to June 2018. Uni- and multivariable analyses were performed to identify predictors of poor outcome. Results: A total of 56 patients met the criteria for inclusion in this study. A poor outcome occurred in 31 (55.4%) patients. On univariate analysis, compared to patients with good clinical outcome, patients with poor outcome had higher mean baseline NIHSS scores (23.3 vs. 13.8, P < 0.001), were more likely to have internal carotid artery (ICA) occlusions (38.7 vs. 8%, P = 0.008), and had a higher incidence of distal clot migration (DCM) (48.4 vs. 8%, P = 0.028). Age, gender, other baseline clinical characteristics, MT technique, and incidence of hemorrhagic transformation did not differ between the two cohorts. On multivariable regression analysis, baseline NIHSS score [OR; 1.3, 95%CI [1.11-1.52], P = 0.001], site of occlusion (ICA) [OR; 8.9, 95%CI [1.3-60.9], P = 0.026], and DCM [OR; 5.77, 95%CI [1.09-30.69], P = 0.04] were independent predictors of poor outcome at 90-days. Conclusion: Baseline NIHSS score, ICA occlusion, and DCM are independent predictors of a poor outcome after MT for anterior circulation LVO performed within 6 h of symptoms onset., (Copyright © 2020 Mohammaden, Stapleton, Brunozzi, Hussein, Khedr, Atwal and Alaraj.)

Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by polyarthritis and systemic manifestations. RA-fatigue is a significant problem and adds on disease burden. Sleep disturbance, depression, and disease activity are suggested contributing factors to RA-fatigue; however, their combined role did not examine before among Egyptian RA patients. The objective of the study was to investigate the presence of fatigue, sleep and mood disturbances in RA patients. Also, to evaluate the possible association of poor sleep, depression, and disease activity with RA-fatigue., Methods: This cross-sectional study included 115 RA patients diagnosed according to the 2010 ACR-EULAR criteria and 46 age and sex matched controls. Fatigue using the Multidimensional Assessment of Fatigue-Global Fatigue Index, sleep using the Pittsburgh Sleep Quality Index and mood status using Beck Depression Inventory were assessed for all participants. RA disease activity was evaluated using disease activity score-28 joints., Results: RA patients had higher mean fatigue, sleep disturbance, and depression scores (27.2±8.9, 6.4±3.6, and 12.8±7.3; respectively) than controls (22.7±7, 4.8±3, 7.8±5.9; respectively) (P<.05). Poor sleep, depression and higher disease activity were significantly correlated with fatigue (r=0.4, r=0.65, r=0.55; respectively) (P<.001). The three variables may explain up to 49.1% of the variation in fatigue on multiple regression analysis., Conclusion: Fatigue, poor sleep, and depression are more common in Egyptian patients with RA. A remarkably higher fatigue was associated with poor sleep, depression, and high disease activity, thus monitoring these silent comorbidities in clinical practice is required., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Transcranial magnetic stimulation (TMS) can be used to evaluate the effects of pharmacological interventions. The aim of this study was to assess the impact of the selective serotonin reuptake inhibitor, sertraline, and the atypical antipsychotic drugs quetiapine and olanzapine, on cortical excitability in unmedicated patients with major depressive disorder (MDD). The study included 45 medication-free MDD patients diagnosed according to DSM V. They were divided randomly into three groups who received a single oral dose of one of the three drugs sertraline (50 mg), quetiapine (100 mg) and olanzapine (10 mg). Psychological evaluation was conducted using the Mini-Mental State Examination (MMSE) and Beck Depression Inventory Scale (BDI). Resting and active motor thresholds (rMT and aMT) together with contralateral and ipsilateral cortical silent periods (cSP, and iSP) were measured for each participant before and at the time of maximum concentration of drug intake. There was significant increase in excitability of motor cortex after sertraline without changes in GABA B neurotransmission. Quetiapine and olanzapine potentiated inhibitory GABA B neurotransmission (prolongation of cSP); olanzapine additionally prolonged the iSP. Thus TMS can differentiate between the impact of different psychotropic drugs on excitatory and inhibitory transmission in motor cortex., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Accumulating evidence suggests that major depressive disorders (MDD) are associated with an imbalance of excitation-inhibition within the prefrontal cortex (PFC), generated by a deficit of inhibitory synaptic transmission onto glutamatergic principal neurons. Transcranial magnetic stimulation (TMS) protocols can be used to measure neuronal excitability and GABAergic inhibition and thus provide additional evidence to evaluate this theory., Objective: In the present study, TMS protocols were used to compare GABAergic function and cortical excitability of dominant hemisphere in unmedicated patients with MDD versus a control group of healthy individuals., Methods: The study included 43 MDD patients according to DSM-V and 20 age- and sex- matched healthy volunteers. Psychological evaluation was conducted using the Beck Depression Inventory (BDI). Resting and active motor thresholds (rMT and aMT) together with contralateral and ipsilateral cortical silent periods (cSP, and iSP) were measured for each participant., Results: rMT and aMT were higher in MDD patients compared with the control group, while cSP and iSP were significantly shorter in duration. There were significant positive correlations between the BDI score and rMT, aMT (P=0.001 and 0.002 respectively), and a negative correlation with cSP duration (P=0.001)., Conclusion: Global hypoexcitability of both pyramidal cortical neurons (elevated MTs) and GABAergic controls (shortened SPs) was evidenced within the left/dominant motor cortex in MDD. These results are consistent with previous reports of abnormal glutamate and GABA function in frontal cortex., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease dementia (PDD), and to examine their relationship to levels of transforming growth factor β1 (TGFβ1)., Methods: The study included 15 patients with each type of dementia (AD, VaD, PDD) and 25 control subjects. Dementia patients were diagnosed according to the DiagnosticandStatisticalManualofMentalDisorders4thedition-revised(DSM-IV-R). Modified Mini Mental State Examination (MMMSE), motor cortex excitability including resting and active motor thresholds (rMT, aMT), input-output (I/O) curve, contralateral and ipsilateral silent periods (cSP, iSP), short-interval intracortical inhibition (SICI) at 1,2 and 4ms, and serum levels of TGFβ1 were examined., Results: There were no significant differences between groups with regards to age, sex, education or socioeconomic level. There was significant neuronal hyperexcitability in the form of reduced rMT and aMT and a shallower I/O curve in all three groups of dementia compared with the control group. The durations of cSP and iSP were longer in AD and PDD groups compared with the control group, whereas there were no significant differences in VaD. SICI was less effective in the three dementia groups than in the control group at intervals of 4ms. Serum levels of TGFβ1 were significantly elevated in all dementia groups in comparison with the control group. There was a significant negative correlation between serum level of TGFβ1 and cSP, iSP, and SICI across all patients and a significant negative correlation between serum level of TGFβ1 and iSP duration in AD., Conclusion: Although motor thresholds were reduced in all patients, measures of SICI, cSP and iSP could distinguish between dementia groups. Serum level of TGFβ1 negatively correlated with iSP specifically in the AD group. This suggests that levels of TGFβ1 may relate to GABAergic dysfunction in dementia., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other disease severity parameters., Methods: In the present study, 20 SSc consecutive female patients, who met the 2013 American College of Rheumatology SSc criteria, were compared with 20 healthy age-, gender-, and educational status-matched volunteer hospital workers. Mean age and duration of illness were 41.8 ± 12.52 and 6.9 ± 5.4 years respectively. Mini-Mental State Examination (MMSE), Wechsler Adult Intelligence scale (WAIS-III), and P300 component of event-related potentials (ERPs) were used to evaluate cognitive function in SS subjectively and objectively respectively., Results: Sixty-five percent (13 out of 20) of SSc patients had MMSE score < 25, and cognitive impairment. Despite the lack of clinically apparent neurological manifestations, SSc patients had significantly low MMSE score, high Deterioration Index (DI), and prolonged P300 latency compared with that of the control group (P = 0.0001; 0.010 and 0.008 respectively). A significant positive association was found between (DI) and the Medsger severity vascular score (r = 0.518; P = 0.012).There were few differences between limited and diffuse SSc., Conclusions: To our knowledge, few studies highlighted that subclinical cognitive impairment can occur in the course of SSc disease. Early diagnosis of cognitive impairment should be investigated either subjectively (using psychometrics tests as MMSE or WAIS-III) or objectively using P300 evoked related potentials. Medsger severity vascular score seems to be closely related to cognitive impairment.Key points• Cognitive impairment can be associated with Medsger Vascular severity score and the duration of illness.• Further larger studies will be needed to estimate the effect of disease activity on cognitive function, to further delineate the differences between limited and diffuse SSc in this area, and to understand the underlying pathophysiological mechanisms causing cognitive impairment in patients with SSc.• To investigate impaired cognitive function in patients with SSc, even in the absence of clinically apparent neurological and vascular disease.

Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis., Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke., Methods and Procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions., Outcomes and Results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains., Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke., Systematic Review Registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947).

Objectives: Transcranial magnetic stimulation (TMS) allows exploration of the mode of action of neuroactive substances in the human brain, and allows evaluation of neuronal networks, which might be involved in the action of nicotine. The aim of the present study was to explore motor cortex excitability in chronic smokers and non-smokers using TMS., Methods: The study included 50 healthy subjects, of whom 25 were chronic smokers and 25 were age- and sex-matched non-smokers. Number of cigarettes per day and duration of smoking in years were documented. Serum level of cotinine was measured. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O) were performed to assess corticospinal excitability. The duration of the contralateral silent period (cSP) at different ranges of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition., Results: There were no significant differences either in RMT or AMT between groups. I/O curve showed a significant intensity×group interaction (P=0.008). This was attributable to significantly higher amplitudes of MEP among smokers than non-smokers especially at 130, 140 and 150% of RMT (P=0.0001 and P=0.03 and 0.02 respectively). The mean duration of the cSP at different intensities and iSP duration were similar in both groups. Nicotine level and smoking index were correlated respectively with rMT and iSP (P=0.03 and 0.01)., Conclusion: The present results confirm previous findings by Grundey et al. (2013) that chronic nicotine consumption is characterized by hyperexcitability of corticospinal output. We speculate that it is a secondary adaptation to long-term nicotine use with high inter-individual variance., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The exact mechanism of cognitive impairment in PD is not known. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for cognitive impairment and to treat the motor symptoms in Parkinson's disease (PD) where its effects seem additive to those of dopaminergic medications., Objective: In this pilot study we investigated whether repeated sessions of rTMS have an effect on measures of cognitive impairment in patients with PD dementia., Methods: 33 patients with PD dementia were randomly assigned sham or real rTMS (2000 pulses; 20 Hz; 90% RMT; 10 trains of 10 s with 25 s between each train) over the hand area of each motor cortex (5 min between hemispheres) for 10 days (5 days/week) followed by 5 booster sessions every month for 3 months. Assessments included the Unified Parkinson's Disease Rating Scale part III (UPDRS), Montreal Cognitive Assessment (MoCA); Mini Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR); Memory and Executive Screening (MES) and Instrumental activity of Daily Living (IADL). Event related potentials (P300) and cortical excitability were measured before treatment and after the last session., Results: There were no significant differences in the effects of rTMS between groups. Although rTMS improved motor function in the active group it had only a minor effect on two of the dementia rating scores (the MMSE and MoCA) but not the others (CDR and MES). There was also a reduction in the latency of the P300 in the active group., Conclusions: rTMS over M1 is useful for motor function and may have a small positive effect on cognition. However, better approaches for the latter are necessary, may be require multisite rTMS to target both motor and frontal cortical region.