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Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive inborn error of creatine synthesis that results in intellectual disability, epilepsy, expressive language delay, and dystonia. We report data from two siblings with an uncommon GAMT deficiency phenotype and their clinical, biochemical, imaging, and treatment findings. The older sibling had intellectual disability, epilepsy, and generalized dystonia. The younger sibling had intellectual disability and generalized dystonia. After treatment with creatine, verbal fluency improved, as well as dystonia and aggression. This study confirms that in patients with unexplained intellectual disability, epilepsy, and/or movement disorders, GAMT deficiency should be considered. GAMT-associated cerebral creatine deficiency syndrome is a potentially treatable condition and can be identified by elevated levels of guanidinoacetate in plasma or urine or by a significantly decreased creatine peak on magnetic resonance spectroscopy.

Objective Cognitive impairment (CI) and executive dysfunction (ED) are prevalent in patients with multiple sclerosis (PwMS). The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is the gold standard neuropsychological battery (NPB) for detecting CI. Delis-Kaplan Executive Function System (DKEFS) NPB evaluates ED. We aimed to find practical test(s) from DKEFS with acceptable diagnostic utility for early detection of impairment in cognitive and executive domains. Methods Cognitive and executive tasks, physical disability, and depression scores of 30 PwMS were assessed (17 women, age: 38.1). Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Controlled Oral Word Association Test (COWAT) from MACFIMS and Trail Making Test (TMT), Design Fluency Test (DFT), and Verbal Fluency Test (VFT) from DKEFS were selected. The association between patients' characteristics and performance in tests, and diagnostic accuracy of DKEFS tests in detecting impairment in cognitive tasks were evaluated, using Pearson correlation and receiver operator characteristic curve analyses, respectively. Results A significant correlation was found between disease duration and SDMT and TMT subtests. Expanded Disability Status Scale was significantly related to SDMT, VFT-switching, and TMT subtests. Beck Depression Inventory was significantly related to DFT. TMT-switching detected abnormalities in SDMT and PASAT with 100% sensitivity, 93.3% (for SDMT), and 85.7% specificity (for PASAT). TMT-letter showed 100% sensitivity and 90% specificity in identifying abnormalities in COWAT. Conclusions TMT, particularly the switching condition, is a practical paper-based test that could predict impairment in cognitive tasks. Clinicians may use TMT as a screening tool among PwMS.

Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury.We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests.The current study showed significant (p 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Background: The non-motor symptoms (NMS) of Parkinson’s disease (PD) and their potential role in early diagnosis are recent debates. Herein, we aimed to investigate the association between depression and non-motor symptoms of PD including sleep disorders, hyposexuality, hyposmia, constipation, and orthostatic hypotension. Methods: After obtaining written informed consent, the diagnosis was confirmed using the criteria developed by the United Kingdom PD Society Brain Bank for the clinical diagnosis of PD. The stage and the severity of the disease were determined using the UPDRS and Hoehn & Yahr criteria. Demographics as well as the family history, habitual history, and past medical history data were obtained. Depression was determined through a psychiatric consultation based on DSMV criteria and Beck Depression Inventory (BDI). Sleep quality was assessed using the Pittsburgh Sleep Quality (PSQ), and Epworth and REM Sleep Behavior Disorder Sleep Questionnaire (RBDSQ) was applied to investigate daytime sleepiness and REM sleep disorders, respectively. Cognitive disorders were also investigated using Montreal cognitive assessment (MoCA).Results: 93 patients were enrolled. The BDI score was significantly correlated with hyposexuality, MoCA scores, and PSQ scores. Depression was significantly more severe in those with hyposexuality (p-value = 0.018). After adjustments, a significant association existed between the BDI score and the MoCA score and hyposexuality.Conclusions: Besides the known correlations of depression with cognitive decline in PD, depression is also significantly associated with hyposexuality in these patients. The etiological underpinnings of these associations are to be explored in the future.

Background Regardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases. Case presentation In this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn’t help finding the source of occult bleeding. Conclusion SS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intracranial surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.

In Alzheimer's disease (AD), the most common form of dementia, microtubules (MTs) play a pivotal role through their highly dynamic structure and instability. They mediate axonal transport that is crucial to synaptic viability. MT assembly, dynamic instability and stabilization are modulated by tau proteins, whose detachment initiates MT disintegration. Albeit extensive research, the role of GTPase activity in molecular mechanism of stability remains controversial. We hypothesized that GTPase activity is altered in AD leading to microtubule dynamic dysfunction and ultimately to neuronal death. In this paper, fresh tubulin was purified by chromatography from normal young adult, normal aged, and Alzheimer's brain tissues. Polymerization pattern, assembly kinetics and dynamics, critical concentration, GTPase activity, interaction with tau, intermolecular geometry, and conformational changes were explored via Förster Resonance Energy Transfer (FRET) and various spectroscopy methods. Results showed slower MT assembly process in samples from the brains of people with AD compared with normal young and aged brains. This observation was characterized by prolonged lag phase and increased critical and inactive concentration of tubulin. In addition, the GTPase activity in samples from AD brains was significantly higher than in both normal young and normal aged samples, concurrent with profound conformational changes and contracted intermolecular MT-tau distances as revealed by FRET. These alterations were partially restored in the presence of a microtubule stabilizer, paclitaxel. We proposed that alterations of both tubulin function and GTPase activity may be involved in the molecular neuropathogenesis of AD, thus providing new avenues for therapeutic approaches.

Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints.This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3 mg/day, clonazepam 1 mg/day, or trazodone 50 mg/day for 4 weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures.A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4 weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group.Trazodone 50 mg/day, clonazepam 1 mg/day, and melatonin 3 mg/day were all tolerable and effective in improving sleep quality in patients with PD.Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Posterior Cortical Atrophy (PCA) is a rare neuropsychiatric syndrome characterized by the dominancy of visuospatial impairments due to bilateral parieto-occipital divesting with the most common pathological changes presented in typical Alzheimer’s Disease (AD). We reported 3 cases with similar diagnoses and interesting manifestations in this study. Gradual onset and progression of visual deficits without underlying ophthalmologic disease accompanied by intact memory and fluent speech and also the presence of simultagnosia, optic ataxia, oculomotor apraxia, dyscalculia, finger agnosia, and environmental disorientation, and the absence of any history of related diseases; all of them strongly suggesting posterior cortical atrophy.

Functional neuroimaging modalities have enhanced our understanding of juvenile myoclonic epilepsy (JME) underlying neural mechanisms. Due to its non-invasive, sensitive and analytical nature, functional magnetic resonance imaging (fMRI) provides valuable insights into relevant functional brain networks and their segregation and integration properties. We systematically reviewed the contribution of resting-state and task-based fMRI to the current understanding of the pathophysiology and the patterns of seizure propagation in JME Altogether, despite some discrepancies, functional findings suggest that corticothalamo-striato-cerebellar network along with default-mode network and salience network are the most affected networks in patients with JME. However, further studies are required to investigate the association between JME's main deficiencies, e.g., motor and cognitive deficiencies and fMRI findings. Moreover, simultaneous electroencephalography-fMRI (EEG-fMRI) studies indicate that alterations of these networks play a role in seizure modulation but fall short of identifying a causal relationship between altered functional properties and seizure propagation. This review highlights the complex pathophysiology of JME, which necessitates the design of more personalized diagnostic and therapeutic strategies in this group.

Neurofilament light chain (NFL) has been recently introduced as a biomarker of early dementia. 18-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is a proxy for regional hypometabolism in Alzheimer disease (AD). Globally normalized 18F-FDG-PET values and levels of NFL and tau were obtained from 149 patients with mild cognitive impairment (MCI) from the baseline cohort of the Alzheimer’s Disease Neuroimaging Initiative database. We adopted a stepwise partial correlation model using plasma NFL, plasma tau, CSF NFL, and regional cerebral metabolic rate of glucose (CMRGlc) as main variables, and age, sex, and Alzheimer’s Disease Rating Scale (ADAS) as covariates. Significant regions were entered into a stepwise multiple regression analysis to investigate the independent correlation of each biomarker to baseline regional CMRGlc and its progression in patients with MCI. Higher baseline CSF NFL levels correlated with hypometabolism in bilateral precuneal and posterior cingulate cortex. After correction for age, sex, and ADAS score, plasma NFL levels correlated with hypometabolism in bilateral parahippocampal and middle temporal gyri. Cortical hypometabolism in bilateral parahippocampal gyri and right fusiform and middle temporal gyri was independently predicted by higher baseline plasma NFL levels in a multiple regression model. Plasma NFL promises to be an early biomarker of cortical hypometabolism in MCI and for MCI progression to AD.

Seizure severity has been increasingly gaining attention as a complementary assessment to seizure frequency for the measurement of treatment responses. This study aimed to assess the reliability and external validity and of the Persian version of the Seizure Severity Questionnaire (SSQ).The study sample was recruited from 126 patients with epilepsy who attended the neurology outpatient clinic at Imam Khomeini and Roozbeh hospitals, Tehran, Iran. The Forward-Backward technique was applied to translate the questionnaire. The reliability of SSQ was assessed by Cronbach's alpha coefficient. The external validity of SSQ was assessed by correlating SSQ scores with Quality of Life in Epilepsy Inventory-31 (QOLIE-31) subscales.The sample comprised 63 women (50%) and 63 men (50%) aged 13-76 years. The mean scores of SSQ items ranged from 3.46 to 5.48. Distribution was skewed for all component scores, with a tendency for the item scores to concentrate toward the highest scores. Reliability for almost all domains were moderate to good, with Cronbach's alpha ranging from 0.615 to 0.770. Component B to D and total score of SSQ had weak-to-moderate inverse correlation with QOLIE-31 subscale scores. However, the result showed no significant correlation with age, sex, or education.With some limitations, the Persian version of the SSQ shows relatively good reliability and content validity, supporting its use as a specific measure of seizure severity in epilepsy in Iran.

This cross-sectional study is aimed at assessing the effects of opium use disorder (OUD) on attention, working memory, and information-processing speed. Thirty outpatients with OUD and 20 healthy controls (HCs) were assessed using a neuropsychological battery consisted of Auditory Verbal Learning Test-Revised (AVLT-R), Brief Visuospatial Memory Test-Revised (BVMT-R), Digit Forward and Backward Tests (DFT and DBT), and WAIS-R Digit Symbol Substitution Test (DSST). The most affected cognitive functions in patients with OUD were detected by DBT and DSST. However, we found no significant difference between patients according to the route of administration. Within patients with OUD, DBT score was associated with opium use quantity (OUQ) ( r = − 0.385 ), and DBT ( r = 0.483 ) and DSST ( r = 0.542 ) scores were correlated with duration of use. Our findings indicated that working memory and information-processing speed are the most affected domains of cognitive functioning. DBT and DSST could be used as brief assessments in clinical settings to screen for cognitive deficits in patients with OUD.

The 2019 novel coronavirus pandemic, severe acute respiratory syndrome CoV-2 (COVID-19), has been a worldwide urgent public health threat, resulting in six-hundred seventy thousand deaths to date. The COVID-19 pandemic has led to a series of public health challenges. One such challenge is the management of diseases such as chronic neurological diseases during an epidemic event. COVID-19 affects all kinds of people, including older people with chronic underlying diseases, who are particularly at risk of severe infection or even death. Chronic neurological diseases such as epilepsy, dementia, Parkinson’s disease (PD), and multiple sclerosis (MS) are frequently associated with comorbidities; thus, these patients are in the high-risk category. Therefore, in this article, we review associations and challenges the people with epilepsy, dementia, PD, and MS faces during the COVID-19 pandemic and suggest approaches to provide consensus recommendations on how to provide the best possible care.

Dysregulation of cation-chloride cotransporters NKCC1 and KCC2 expression was shown to be related to drug-resistant epilepsy. Previous studies suggested that bumetanide, an inhibitor of NKCC1, might have antiepileptic effects.The aim of this study was to investigate the safety and efficacy of bumetanide add-on therapy in patients with drug-resistant epilepsy and its relation to cation-chloride cotransporters NKCC1 and KCC2.We conducted an open-label, single-arm clinical trial in drug-resistant temporal lobe epilepsy (TLE) patients. This study consisted of three phases: pretreatment (3 months), titration (3 weeks), and active treatment (6 months). During the pretreatment phase, the dose of antiepileptic drugs was stabilized, and bumetanide was then added at an initial dose of 0.5 mg/day, increasing by 0.5 mg/week until a target dose of 2 mg/day was achieved. Bumetanide treatment was then continued for 6 months. Seizure frequency and adverse events were assessed at every monthly visit. Blood samples were collected from patients and 12 healthy controls were used for polymerase chain reaction and Western blot analyses. Primary clinical outcomes were drug safety and change in seizure frequency. Changes in NKCC1 and KCC2 expression were the non-clinical endpoints.A total of 30 patients were enrolled, 27 of whom completed the study. The mean duration of epilepsy was 16.5 years. Median seizure frequency per month was 9 [interquartile range (IQR) 7-14.5] at baseline, 3.67 (IQR 1.84-6.17) at the first 3 months, and 2 (IQR 0.84-4.34) at the last 3 months (p 0.001). Five adverse events were detected in six patients. The reported adverse events were anorexia in four patients, nausea and vomiting in two patients, and agitation, headache and increased seizure frequency in one patient each. The level of NKCC1 and KCC2 gene transcripts and KCC2 protein did not change significantly following treatment (p 0.05); however, we observed a significant reduction in NKCC1 protein levels (p = 0.042).Bumetanide might be an effective and relatively tolerable drug in patients with drug-resistant TLE. Downregulation of NKCC1 protein following bumetanide treatment may be responsible for its antiepileptic effects.IRCT 201012115368N1.

Background Brain-derived neurotrophic factor (BDNF) is an abundant neurotrophin in the adult brain. Serum BDNF levels might be used as a proxy for its central expression. Considering conflicting reports, we aimed to answer “How do serum/CSF levels of BDNF change in patients with PD?”. Methods We conducted a comprehensive search in MEDLINE, EMBASE and SCOPUS databases including 12 eligible studies. Five studies compared BDNF in serum of PD patients versus healthy controls (HC) and 3 studies provided BDNF levels in sera of non-depressed and depressed PD patients (NDPD and DPD). Review Manager and Software version 3.0 were used for meta-analysis and meta-regressions. Mean difference (MD) was used for measurement of effect size. Results PD patients had reduced serum BDNF levels compared to HC (MD = - 2.99 ng/mL). Serum BDNF was highest in DPD patients compared to HC (MD = - 4.83 ng/mL), with no difference between DPD and NDPD patients in serum BDNF levels. Among co-variates that were eligible for meta-regression, age, sex, and Hoehn and Yahr (H&Y) motor stage had significant positive associations with the effect size in the difference of serum BDNF between patients and HC. Conclusions PD patients had reduced serum BDNF levels compared to HC, regardless of presence of co-morbid depression. PD is at least equally effective in reducing serum BDNF levels as depression. Motor progression predicts serum BDNF downregulation in PD. Acute exercise improves motor function and depressive symptoms in PD probably via BDNF upregulation. The paradoxical rise in serum BDNF in advance PD is probably compensatory in nature.

Objectives Clinical difficulty to discriminate between the Alzheimer disease (AD) and dementia with Lewy bodies (DLB) has led researchers to focus on highly sensitive functional imaging modalities. The aim of the present study was to assess 131I-MIBG cardiac imaging to distinguish between AD and DLB. Patients and methods Seventeen patients who were known cases of dementia underwent 131I-MIBG myocardial scintigraphy to differentiate AD from DLB. Planar and 131I-MIBG SPECT were obtained 2 h after the injection of 1 mCi 131I-MIBG on a dual head gamma camera. The visual assessment of the heart uptake compared with lungs and the quantification based on the heart to mediastinal ratio (HMR) were done. The cardiac receiver operating characteristic (ROC) curve was designed for the optimal HMR cut-off values to predict the diagnoses of the patients. The diagnoses were clinically confirmed during the follow up of 14 ± 8.2 months. Results Out of 17 patients (13 males; 76.5%), 10 patients had AD (7 males; 70%) and 7 patients had DLB (6 males; 85%). The pooled HMR was 1.74 ± 0.33 in the study population; with 1.95 ± 0.22 in the AD group and 1.43 ± 0.20 in the DLB group to demonstrate significantly different HMR scores between patients with AD and DLB (p value = 0.001). The visual interpretation was positive in 10 patients (accuracy of 88.2%). The shortest distance on the ROC curve to the optimal value corresponding to HMR = 1.57 identified 10 patients with a high HMR (positive cardiac uptake) and 7 patients with a low HMR (negative cardiac uptake), the accuracy calculated at 88.2%. Conclusion 131I-MIBG myocardial scintigraphy is a potential alternative diagnostic modality for discrimination between AD and DLB when 123I is not available.

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.

Previous studies have demonstrated executive dysfunction in patients with temporal lobe epilepsy (TLE). Frontal assessment battery (FAB) is a short neuropsychological tool that was developed for assessment of frontal lobe function in a clinical setting. The aim of the present study is to evaluate the clinical utility of FAB for detection of executive dysfunction in TLE patients. Forty-eight TLE patients and 48 sex and age-matched healthy controls participated in this study. Compared to healthy participants, the total FAB score was significantly lower among the TLE patients. TLE patients performed significantly worse at the mental flexibility, motor programming, sensitivity to interference and inhibitory control tasks. The duration of time has been passed since the last seizure was the only significant predictor of FAB score and patients who had a seizure less than a week before the evaluation time, had significantly lower FAB scores. The number of antiepileptic drugs (AEDs) did not influence the executive function in this study; however, sodium valproate was found to affect the mental flexibility. In conclusion, impaired executive function is common in TLE patients, and we suggest that FAB is a clinically applicable tool to monitor it. Moreover, we found that the time of the last seizure is a significant predictor of executive functioning and patients' performance may become worse up to seven days after a seizure. We also recommend that clinicians evaluate the cognitive adverse effects of AEDs especially sodium valproate, which was found to affect the mental flexibility in this study.

Background Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS). Currently, there is no approved medication for MS-related fatigue. Objective In this study, we aim to evaluate the safety and efficacy of memantine for improving fatigue in patients with MS. Methods This was a pilot randomized, double-blind, placebo-controlled clinical trial. Eligible patients with relapsing-remitting MS (RRMS) according to the McDonald criteria were randomized to receive either memantine (20 mg/day) or placebo and were assessed at baseline and three months after treatment. The change in the severity of fatigue was determined by the Modified Fatigue Impact Scale (MFIS). Results Sixty-four patients were randomly allocated to the memantine (n = 32) and placebo (n = 32) groups. Sixteen patients in the memantine group and 24 patients in the placebo group completed the study. The mean [95% CI] absolute change in MFIS scores from baseline did not differ significantly between the memantine (−5.8 [−12.7 to 1.0]) and placebo (−4.0 [−10.6 to 2.7]) groups (between-group difference: −1.9 [−11.7 to 7.8], P = .702). No serious adverse events were reported, except for dizziness and sedation in four patients in the experimental arm, which resulted in discontinuation. Conclusion This trial failed to prove any clinical efficacy of memantine for the management of MS-related fatigue. Although memantine was generally well-tolerated, adverse events were among the major causes of dropout in this study.

Introduction: Brucellosis is a zoonotic endemic disease, which is transmitted to the human through occupational exposure or ingestion of contaminated dairy products. Neurobrucellosis has been detected in 5% - 10% of patients with diverse manifestations. Case Presentation: In this study, an atypical case of neurobrucellosis is reported. The patient was a 28-year-old man suffering from psychiatric symptoms and catatonic states. The CSF analysis was unremarkable but the diagnosis was made according to Enzyme-linked Immune Sorbent Assay, other serology tests, and brain MRI findings. Conclusions: It should be mentioned, one of the differential diagnoses in patients with unexplained neurological and psychiatric symptoms in endemic areas is neurobrucellosis and a multidisciplinary approach to these patients is essential.

Ischaemic stroke represents one of the main causes of disability. According to the broad investigations, it is widely assumed that the contribution of inflammatory mediators is strongly involved in its pathogenesis. Hence, it seems that stroke treatment needs more efficient and inflammatory-targeted compounds to modulate inflammatory-related pathways. Such strategies paved the way to achieve better clinical outcomes along with conventional therapies. Boswellic acids (BAs), the main bioactive compounds of Boswellia sp. resin; are triterpenoids with well-documented anti-inflammatory properties. Compared with NSAIDs, BAs cross blood–brain barrier yet they do not cause serious gastrointestinal adverse effects. Considering BAs anti-inflammatory features, we conducted a randomized double-blind placebo-controlled pilot trial of these compounds as a supplementary therapy. This trial randomized 80 ischaemic stroke patients (40–80-years old) with a 4–20 score according to the National Institutes of Health Stroke Scale (NIHSS), within 72 h of neurological sign onset, in 1-month follow-up period. We assessed NIHSS as primary and plasma levels of TNF-α, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, IP-10, MCP-1, 8-isoprostane, and PGE2 as secondary outcomes. According to NIHSS evaluation, patients who were allocated to BA group had a significant recovery in neurological function during the 1-month follow-up, compared with the placebo. The levels of plasma inflammatory markers were significantly decreased in BA group after 7 days of intervention in TNF-α, IL-1β, IL-6, IL-8, and PGE2. As a preliminary controlled trial in ischaemic stroke, BAs could improve clinical outcome in the early phases of stroke along with promising changes in plasma inflammatory factors. Clinical trial registrationhttps://www.irct.ir Unique identifier: IRCT20170315033086N5. IRCT is a primary registry in the WHO registry network (https://www.who.int/ictrp/network/primary/en/)

Introduction Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. Objectives We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. Methods Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. Results The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. Conclusion Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.

Background and Aim: Several studies have shown the anatomical associations between the vestibular system and cognitive processes, especially spatial memory. One of the first problems that occur in Alzheimer's disease (AD) is spatial memory deficits. The preclinical stage of AD is mild cognitive impairment (MCI). Amnestic type of MCI (aMCI) is more likely to progress to AD. Previous studies have demonstrated high incidence of vestibular disorders in AD patients; however, the balance system of aMCI patients has not been investigated. Therefore, the present study aimed to investigate vestibulo-ocular reflex (VOR) impairments in aMCI patients compared with control group. Methods: In this cross-sectional study VOR gain and catch-up saccades in six semicircular canals were measured in 12 aMCI patients and 12 normal controls using video head impulse test. Results: Vestibulo-ocular reflex gains in direction of all vertical semicircular canals were lower in aMCI- compared with normal-group (right anterior canal 0.74±0.17 vs 0.87±0.12; right posterior canal 0.77±0.10 vs 0.90±0.10; left anterior canal 0.87±0.10 vs 0.97±0.11; left posterior 0.72±0.18 vs 0.87±0.90). Catch-up saccades were found in direction of all canals in aMCI patients while there were no saccades in normal groups. Conclusion: In aMCI patients there was more vestibular dysfunction, which might be associated with cognitive deficits especially spatial type. In brief, vestibular investigation is suggested in aMCI patients.

Background and Aim: Recent studies have reported connections between vestibular function and cognition and also reported more prevalence of vestibular impairment in patients with Alzheimer's disease. Because patients with amnestic mild cognitive impairment (aMCI) are more likely to develop Alzheimer's disease, this study was conducted to evaluate vestibular dysfunction of otolith organs in aMCI patients compared to normal subjects. Methods: In our case-control study, 11 patients (22 ears) with aMCI with mean age of 56.73±8.83 years and 11 normal participants (22 ears) with mean age of 54.30±7.4 years were eva­luated for ocular and cervical vestibular evoked myogenic potentials (o- and cVEMP). Occurrence of VEMP responses, amplitude, latency and threshold of these waves were recorded and compared between the two groups. Results: Ocular VEMP was absent in 63.6% of aMCI patients and in 18.2% of the normal group. The difference was significant (p=0.002), while occurrence rate, amplitude, latencies and threshold of cVEMP were not significantly different between the two groups (p>0.05). McNemar's test showed that there was no significant relationship between occurrences of two potentials in aMCI group. Conclusion: These findings show the presence of vestibular dysfunction, especially in the pathways of ocular vestibular evoked potential, in patients with amnestic mild cognitive impairment. Given that previous studies have shown that cVEMP was absent in Alzheimer's disease, absence of oVEMP can be used as an indicator for predicting future impairment in individuals with amnestic MCI.

The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list. All patients and research investigators were blinded to treatment allocation. The primary outcome was survival, and event was defined to be death or mechanical ventilation dependency. Analysis was by intention-to-treat and included all patients who received at least one dose of study drug. A total of 54 patients were randomized to receive either nanocurcumin (n = 27) or placebo (n = 27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin group and in 6 patients (22.2%) in the placebo group. Kaplan–Meier analysis revealed a significant difference between the study groups regarding their survival curves (p = 0.036). No significant between-group differences were observed for any other outcome measures. No serious adverse events or treatment-related deaths were detected. No patients withdrew as a result of drug adverse events. The results suggest that nanocurcumin is safe and might improve the probability of survival as an add-on treatment in patients with ALS, especially in those with existing bulbar symptoms. Future studies with larger sample sizes and of longer duration are needed to confirm these findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-018-0606-7) contains supplementary material, which is available to authorized users.

Sumatriptan has been among the top choices in the management of migraine headaches. The association between migraine and epilepsy highlights the possible effect of sumatriptan on seizures. In this regard, we investigated sumatriptan effects on PTZ-induced seizures thresholds and delineated the modulatory role of 5-HT1B/D receptors and NOS/NO pathway. Our data revealed the anti-convulsant effects of lower doses of sumatriptan, and pro-convulsant effects of higher doses of sumatriptan. GR 127935, a selective 5-HT1B/D antagonist, could abolish the sumatriptan anti-convulsant effects, but it was ineffective against the sumatriptan pro-convulsant effects. Serotonin depletion by consecutive administration of p-CPA, a selective irreversible inhibitor of tryptophan hydroxylase, could not affect the anti-convulsant effects of sumatriptan. The anti-convulsant effects of sumatriptan was potentiated by L-NAME, a non-selective NOS inhibitor, 7-NI, a selective nNOS inhibitor, but not AG, an iNOS inhibitor. It was also neutralized by L-ARG, a NO precursor. The pro-convulsant effects of sumatriptan were blocked by L-NAME and AG, but not 7-NI. It was also potentiated by L-ARG. Our data revealed that anti-convulsive effects of sumatriptan is mediated by interaction between non-serotonergic 5-HT1B/D receptors and nNOS/NO pathway. Besides, the pro-convulsive effect of sumatriptan is mediated by iNOS/NO pathway independent of 5-HT1B/D receptors. For the first time, this study reported the biphasic effect of sumatriptan on an animal model of GCS and its modulatory pathways.

Clinical difficulty to discriminate between the Alzheimer disease (AD) and dementia with Lewy bodies (DLB) has led researchers to focus on highly sensitive functional imaging modalities. The aim of the present study was to assessSeventeen patients who were known cases of dementia underwentOut of 17 patients (13 males; 76.5%), 10 patients had AD (7 males; 70%) and 7 patients had DLB (6 males; 85%). The pooled HMR was 1.74±0.33 in the study population; with 1.95±0.22 in the AD group and 1.43±0.20 in the DLB group to demonstrate significantly different HMR scores between patients with AD and DLB (p value=0.001). The visual interpretation was positive in 10 patients (accuracy of 88.2%). The shortest distance on the ROC curve to the optimal value corresponding to HMR=1.57 identified 10 patients with a high HMR (positive cardiac uptake) and 7 patients with a low HMR (negative cardiac uptake), the accuracy calculated at 88.2%.

Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations.We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism.Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members.The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157CT) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes.Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155GA) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.

Urbach-Wiethe disease (UWD) is an autosomal recessive disease characterized by both neurological and dermatological manifestations. Face specially eyelids are commonly involved. Alopecia, nail dystrophy and dental anomalies have been reported as less frequent symptoms. Some patients show evidences of epilepsy and psychiatric symptoms such as schizophrenia, mood disorders, and anxiety due to calcium deposits in different parts of the brain. In this report, we describe the case of a young woman affected by UWD presenting with neurological involvements and no dermatological manifestations. This patient is a unique case of UWD as she has partial seizures and hoarseness. Also we summarize relevant data from the literature.

To compare the sympathetic skin responses (SSRs) in patients with multiple sclerosis (MS), clinically isolated syndrome (CIS), and healthy controls.SSR was recorded on both hands and feet in 30 patients and 20 healthy controls. SSR results (latency measurements) were compared in patients with normal or abnormal brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs).Twenty-three (76.6%) and sixteen patients (53.3%) with MS had abnormal SSR recordings based on 2-standard deviation (SD) or 3-SD (from the mean of the control group) abnormality criteria, respectively. Sixty-six percent and 40 percent of patients had abnormal (2SD) SSR in at least one hand and one foot, respectively. Patients with absent SSR had more severe disease and higher Expanded Disability Status Scale (EDSS) scores. Fourteen patients had an EDSS of zero, of whom nine had abnormal SSR and others had at least one abnormal EP study. Patients with abnormal SSR had significantly more abnormal BAEPs and SEPs than patients with normal SSR. SSR latencies were significantly correlated with EDSS and disease duration (P0.01). All patients had at least one abnormal electrophysiological study. ROC-curve analysis showed that a cut-off score of 7008 ms as the sum of all-4-limb SSR latencies had a 80% sensitivity and 95% specificity for differentiating MS patients from healthy controls.This study suggests that SSR is a useful tool for assessment of autonomic function and can be complementary to EDSS and other electrophysiological studies in patients with MS and CIS.

Background and purpose: Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-A (PDGF-AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF-2 and PDGF-AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RR-MS) and compared these values with control subjects. Methods: Twenty-three patients with RR-MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann–Whitney U-test and Spearman’s rank correlation were used for analysis. P values of