Raphe Nuclei Echogenicity and Diameter of Third Ventricle in Schizophrenia Measured by Transcranial Sonography.

Introduction: Serotonergic system hyperactivity at 5-HT2A receptors on glutamate neurons in the cerebral cortex is one of the pathways that is theoretically linked to psychosis. In addition to neurotransmitter dysfunction, volumetric studies have revealed the loss of cortical gray matter and ventricular enlargement in patients with schizophrenia, although there is no case-control research on patients with schizophrenia to evaluate echogenicity of raphe nuclei (RN) or diameter of the third ventricle (DTV). To address these issues, the present study assessed midbrain RN, as the main source of brain serotonin, and DTV, as an index of atrophy, by transcranial sonography (TCS) in a group of patients with schizophrenia. Methods: Thirty patients with schizophrenia and 30 controls were assessed by TCS for RN echogenicity and DTV. TCS was done through a temporal bone window via a phased-array ultrasound using a 2.5 MHz transducer in a depth of 14-16 cm. RN echogenicity was assessed by a semi-quantitative visual scale and DTV was measured in the thalamic plane. Results: Twenty-three patients (76.5%) and 15 controls (50 %) showed hypoechogenicity of RN, which was marginally significant (P=0.06). DTV was on average larger in the experimental group (0.388 cm vs 0.234 cm, P<0.001). Conclusion: Increased DTV in patients with schizophrenia is consistent with previous neuroimaging findings. However, marginally lower echogenicity of midbrain RN on TCS in schizophrenia is a new finding that supports the serotonin hypothesis of schizophrenia. Highlights: 30 patients with schizophrenia and 30 controls were assessed by TCS for RN echogenicity and diameter of the third ventricle (DTV).23 patients (76.5%) and 15(50 %) controls showed hypoechogenicity of RN which was marginally significant (P=0.06)DTV was in average larger in the patient's group (0.388 cm vs 0.234 cm, P<0.001).Increased DTV in the patients with schizophrenia is consistent with previous neuroimaging findingsMarginally lower echogenicity of midbrain RN on TCS in schizophrenia is a new finding that supports the serotonin hypothesis of schizophrenia. Plain Language Summary: Schizophrenia is a disabling psychiatric disorder. Various neurotransmitters have a role in the pathophysiology of schizophrenia including Serotonin and dopamine. This study assessed the echogenicity of raphe nuclei (RN), as the main source of brain serotonin, and the diameter of the third ventricle (DTV), as an index of atrophy, by transcranial sonography (TCS) method in 30 patients with schizophrenia and 30 healthy controls. Based on the results, 23 patients (76.5%) and 15 controls (50%) showed decreased echogenicity of RN. There was a significant difference between the two groups in terms of the echogenicity of RN. Moreover, the DTV diameter was significantly larger in patients compared to controls.

Posterior reversible encephalopathy syndrome in SARS-CoV-2 infection: A case report and review of literature.

Consider PRES in SARS-CoV-2 infected patients who develop encephalopathy, seizures or impaired vision; especially if the disease is complicated by respiratory distress and need for mechanical ventilation.

Salivary levels of disease-related biomarkers in the early stages of Parkinson's and Alzheimer's disease: A cross-sectional study.

Introduction: Finding a non-invasive and repeatable tool has been recommended to make an accurate diagnosis of Alzheimer's disease (AD) and Parkinson's disease (PD). Methods: 70 volunteers participated in three groups: 24 with mild dementia of AD, 24 in the first and second stages of PD, and 22 healthy controls. After valuing the scores of cognitive tests, the salivary levels of phosphorylated tau (p-tau), total alpha-synuclein (α-syn), and beta-amyloid 1-42 (Aß) proteins have been evaluated. Finally, the cutoff points, receiver operating characteristic (ROC), sensitivity, and specificity have been calculated to find accurate and detectable biomarkers. Results: Findings showed that the salivary level of Aß was higher in both PD (p < 0.01) and AD (p < 0.001) patients than in controls. Moreover, the level of α-syn in both PD and AD patients was similarly lower than in controls (p < 0.05). However, the level of p-tau was only higher in the AD group than in the control (p < 0.01). Salivary Aß 1-42 level at a 60.3 pg/ml cutoff point revealed an excellent performance for diagnosing AD (AUC: 0.81). Conclusion: Evaluation of p-tau, α-syn, and Aß 1-42 levels in the saliva of AD and PD patients could help the early diagnosis. The p-tau level might be valuable for differentiation between AD and PD. Therefore, these hopeful investigations could be done to reduce the usage of invasive diagnostic methods, which alone is a success in alleviating the suffering of AD and PD patients. Moreover, introducing accurate salivary biomarkers according to the pathophysiology of AD and PD should be encouraged.

"Split-day syndrome", a patient with frontotemporal dementia who lives two days in the span of one: a case report and review of articles.

Frontotemporal dementia (FTD) is among the most prevalent causes of young-onset dementia  . Along with the frontotemporal and striate atrophy, dopamine dysregulation is also present in FTD. The dopamine system controls mechanisms of time perception. Its depletion can cause miscalculations in the perception of time. We present a 72-year-old man with a unique profile of disorientation in time, such that he split each day into two, 12-h intervals. Although through each 12-h period, he went by his daily activities as if a complete day had passed, e.g., he had two sets of breakfast, lunch, and dinner  , hence the designated "split-day syndrome."

Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention. Here we conducted a meta-analysis of 12 circulating miRNA profiling studies using the robust rank aggregation (RRA) method, followed by enrichment analysis and experimental verification. We identified miR-451a and let-7f-5p as meta-signature miRNAs whose targets are involved in critical pathogenic pathways underlying ALS, including 'FoxO signaling pathway', 'MAPK signaling pathway', and 'apoptosis'. A systematic review of 7 circulating gene profiling studies elucidated that 241 genes up-regulated in sALS circulation with concomitant being targets of the meta-signature miRNAs. Protein-protein interaction (PPI) network analysis of the candidate targets using MCODE algorithm revealed the main subcluster is involved in multiple cascades eventually leads apoptosis, including 'positive regulation of neuron apoptosis. Besides, we validated the meta-analysis results using RT-qPCR. Indeed, relative expression analysis verified let-7f-5p and miR-338-3p as significantly down-regulated and up-regulated biomarkers in the plasma of sALS patients, respectively. Receiver operating characteristic (ROC) analysis also highlighted the let-7f-5p and miR-338-3p potential as robustness plasma biomarkers for diagnosis and potential therapeutic targets of sALS disease.

The prevalence and major determinants of non-compliance with anti-seizure medication among children.

Background: A wide range of adherence to the use of anti-seizure medications has been reported among children with the disease, and accordingly, various factors on the degree of adherence to the drug have been reported. But in our society, there is no clear picture of drug adherence and related factors among children with seizures. We evaluated the frequency of adherence to anti-seizure medication as well as related factors. Methods: This cross-sectional study was conducted on 120 children with epilepsy who referred to Ali Asghar Hospital in Tehran, Iran, during 2019 and 2020. Along with demographic characteristics, adherence to antiepileptic medications was assessed by the Modified Morisky Scale (MMS). Results: The overall frequency of adherence to anti-seizure medications among children was reported to be about 41.7%. Among all baseline characteristics, much higher adherence was revealed in patients with educated parents. The rate of drug adherence in children with a history of perinatal morbidities was much lower than in other patients. The type of seizure could also affect the rate of drug adherence as the highest and the lowest adherence was found concerning focal impaired awareness seizure (57.1%) and atonic seizures (11.1%) indicating a significant difference (P = 0.022). The most common causes of non-adherence to treatment were expressing inability to treat the patient (23.0%), parents' forgetfulness to give medicine to the child (18.3%), and not taking medication when traveling or leaving home (16.7%). Conclusion: The lower level of education of the parents, type of seizure, as well as the presence ofunderlying perinatal morbidity in the child can predict non-compliance with anticonvulsant medication regimens among affected children.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Sour aversion in frontotemporal dementia: a case report and review on physiologic-anatomic mechanisms.

Frontotemporal dementia (FTD) is a common cause of early-onset dementia characterized by behavioral and personality changes, as well as, altered eating habits. FTD is associated with complex changes in neural networks of gustatory processing which may be responsible for eating abnormalities. Here, we present a 66-years-old lady suffered from behavioral variant of FTD with an interesting symptom of food aversion, typically sour foods.

Description of clinical features and genetic analysis of one ultra-rare (SPG64) and two common forms (SPG5A and SPG15) of hereditary spastic paraplegia families.

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder, characterized by lower-limb spasticity and weakness. To date, more than 82 loci/genes (SPG1-SPG82) have been identified that contribute to the cause of HSP. Despite the use of next-generation sequencing-based methods, genetic-analysis has failed in the finding of causative genes in more than 50% of HSP patients, indicating a more significant heterogeneity and absence of a given phenotype-genotype correlation. Here, we performed whole-exome sequencing (WES) to identify HSP-causing genes in three unrelated-Iranian probands. Candidate variants were detected and confirmed in the probands and co-segregated in the family members. The phenotypic data gathered and compared with earlier cases with the same sub-types of disease. Three novel homozygous variants, c.978delT; p.Q327Kfs*39, c.A1208G; p.D403G and c.3811delT; p.S1271Lfs*44, in known HSP-causing genes including ENTPD1, CYP7B1, and ZFYVE26 were identified, respectively. Intra and interfamilial clinical variability were observed among affected individuals. Mutations in CYP7B1 and ZFYVE26 are relatively common causes of HSP and associated with SPG5A and SPG15, respectively. However, mutations in ENTPD1 are related to SPG64 which is an ultra-rare form of HSP. The research affirmed more complexities of phenotypic manifestations and allelic heterogeneity in HSP. Due to these complexities, it is not feasible to show a clear phenotype-genotype correlation in HSP cases. Identification of more families with mutations in HSP-causing genes may help the establishment of this correlation, further understanding of the molecular basis of the disease, and would provide an opportunity for genetic-counseling in these families.

The role of transcranial sonography in differentiation of dementia subtypes: an introduction of a new diagnostic method.

PURPOSE: Transcranial sonography (TCS) is increasingly used for the diagnosis of neurodegenerative disorders. We assessed the role of third ventricle width (TVW), midbrain area (MA), and midbrain circumference (MC) by TCS for diagnosis and differentiation of dementia. METHODS: A cross-sectional study was designed in 59 patients with dementia including 19 patients with Alzheimer's disease (AD), 10 Dementia with Lewy bodies (DLB), 23 Frontotemporal dementia (FTD) and 7 Vascular dementia (VaD), and 22 normal-cognition individuals. Both case and control groups were matched by age, sex, and educational level. The dementia patients were divided into two subgroups: cortical-dominant dementia (CDD) including AD and FTD; and subcortical-dominant dementia (SDD) including DLB and VaD. TCS was performed through a temporal window, in which the size of TVW and midbrain was measured by trans-thalamic and trans-mesencephalic planes, respectively. RESULTS: The mean TVW was 0.85 ± 0.3 cm and 0.66 ± 0.2 cm in dementia patients and the control group, respectively (p < 0.01). The MA/MC were smaller in dementia patients compared with the control group (p < 0.05 and p < 0.01). The TVW in CDD (p = 0.003) and SDD (p = 0.027), but only MA/MC in SDD (p < 0.05), was statistically different compared with the control group. CONCLUSION: The measurement of TVW and midbrain size by TCS can be used for diagnosis and differentiation of dementia. Patients with CDD and SDD have larger TVW than the control group, whereas patients with SDD have smaller midbrain sizes.

CAPN1 and hereditary spastic paraplegia: a novel variant in an Iranian family and overview of the genotype-phenotype correlation.

PURPOSE: SPG76 is one of the rare forms of hereditary spastic paraplegia (HSP) which causes by mutations in the CAPN1 gene. The mode of inheritance of SPG76 is autosomal recessive (AR) and so far, only 24 families and 25 mutations in this gene have been reported worldwide. These mutations have been associated with a spectrum of disorders from pure HSP to spastic ataxia. HSP genetically is one of the most heterogeneous neurological disorders and to date, 79 types of HSP (SPG1-SPG79) have been identified, however, it has been suggested that many HSP-genes, particularly in AR-HSPs, remained unknown. AR-HSPs clinically overlap with other neurodegenerative disorders, making an accurate diagnosis of the disease difficult. Therefore, in addition to clinical examination, a high throughout genetic method like whole exome sequencing (WES) may be necessary for the diagnosis of this type of neurodegenerative disorders. METHODS AND RESULTS: Herein, we present the clinical features and results of WES in the first Iranian family with a novel CAPN1 variant, c.C853T:p.R285* and pure HSP. CONCLUSION: Some of the previous studies have mentioned that the "spasticity-ataxia phenotype might be conducted to the diagnosis of SPG76" but recently the number of pure HSP patients with CAPN1 mutation is increasing. The present study also expands the mutation spectrum of pure CAPN1-related SPG76; emphasizing that CAPN1 screening is required in both pure HSP and spasticity-ataxia phenotypes. As noted in some other literature, we suggest the clinical spectrum of this disorder to be considered as "CAPN1-associated neurodegeneration".

Validating the Persian version of the amyotrophic lateral sclerosis-specific quality of life-revised instrument.

Background: Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) encompasses 50 items which assess quality of life (QOL) in patients with amyotrophic lateral sclerosis (ALS) in six major domains. This study aims to translate the ALSSQOL-R into Persian and evaluate its reliability and validity among Iranian patients. Methods: ALSSQOL-R was translated by the standard multi-step forward-backward method. Content validity was calculated using item content validity index (I-CVI). Three items in the "intimacy" domain were deleted considering Iranian culture. Cronbach's alpha was used for all 6 dimensions to calculate the internal consistency reliability. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC) with one-month interval. Concurrent validity was measured by the validated version of 36-Item Short Form Health Survey (SF-36) questionnaire. Results: Sixty-three patients with ALS were enrolled in the study. I-CVI was 70%, promoted to 85% after modifications (acceptable). Regarding internal consistency reliability, Cronbach's alpha in all six domains was 0.70 and total Cronbach's alpha was 0.89 which is assumed as good. In terms of test-retest reliability, ICC [95% confidence interval (CI)] was 0.91 (91%) and Pearson correlation coefficient (r) was 0.90 (P < 0.001), all indicating an excellent reliability. The concurrent validity was established based on a strong correlation with SF-36 (r = 0.744, P < 0.001). Conclusion: The findings show that the modified Persian version of ALSSQOL-R is a valid and reliable QOL questionnaire which can be used for Iranian patients with ALS in both clinical and research settings.

The association between serum 25-hydroxyvitamin D level and subclinical atherosclerosis in healthy population.

Background: Subclinical atherosclerosis is the asymptomatic phase of carotid atherosclerosis, and its early diagnosis is important to prevent cerebrovascular diseases. Although the vitamin D plays a role in the structure of vessels, the association between the serum level of vitamin D and subclinical atherosclerosis has not been well-studied. We aimed to investigate the association between serum vitamin D level and carotid artery intima-media thickness (CIMT) in Iranian population. Methods: One hundred individuals with the age range from 20 to 50 years with no history of cardiovascular risk factors were selected for the analysis. Measurements of serum 25-hydroxyvitamin D3 [25(OH) D3] concentration and CIMT were made. Confounding factors such as diabetes, hypertension (HTN), smoking, alcohol, tobacco, dyslipidemia, cardiovascular disease (CVD), high body mass index (BMI), history of drug intake especially calcium, vitamin D, statins, and anti-hypertensive drugs were considered and then excluded from our study. Results: The mean serum vitamin D level was 15.55 ± 0.42 ng/ml, whereas in the increased intima-media thickness (IMT), it was 12.50 ± 9.50 ng/ml. 55% of the subjects were diagnosed with subclinical atherosclerosis (IMT ≥ 0.75 mm). Mean IMT was 0.74 ± 0.12 mm; however, it was higher (0.86 ± 0.30) in severe vitamin D deficiency group. The analysis showed an association between serum 25(OH) D3 level and CIMT (P = 0.002). 44% of those participants with subclinical atherosclerosis had also a severe vitamin D deficiency, while only 13% of normal people had a severe vitamin D deficiency. Also, a correlation was observed between severe vitamin D deficiency and the presence of plaque or higher IMT. Conclusion: Serum 25(OH) D3 level was inversely correlated with CIMT in our investigated subjects with no cardiovascular risk factor.

Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis.

AIM: Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population. METHODS: PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals. RESULTS: Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel (n = 14, 293) or aspirin (n = 15, 064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53-0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups. CONCLUSIONS: The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke.

Effects of treadmill training on the balance, functional capacity and quality of life in Parkinson's disease: A randomized clinical trial.

Background There is growing evidence that exercise modalities have considerable effects on Parkinson's disease (PD). This trial aimed to provide a more detailed viewpoint of short-term and long-term treadmill training (TT) effects on some motor and non-motor features of PD. Methods In this prospective, randomized, single-blind clinical trial, 20 mild to moderate PD patients, admitted in Rasoul-e-Akram hospital in Tehran, Iran, were randomly allocated in case (11) and control (9) groups. Treadmill intervention was performed at moderate intensity with 60% of heart rate reserved (HRR) in two 30-min sessions/week for a duration of 10 weeks. Both the groups were evaluated for three times; at the baseline, 2 months later and then 2 months after the second evaluation. We assigned the Timed Up and Go test (TUG), 6-min walk test (6MW), and the SF-8 healthy questionnaire, for assessment of balance, functional capacity, and Quality of life (QoL), respectively. Results Balance and functional capacity were significantly improved in the case group after the intervention (TUG p-value: 0.003, 6MW p-value: 0.003). Moreover, the long-term analysis revealed significant results as well (TUG p-value: 0.001, 6MW p-value: 0.004). Mental condition's scores of SF-8 in cases were not statistically different in short-term follow-up (F/U). However, analysis illustrated p-value: 0.016 for long-term assessment. The intervention induced significant changes in physical condition's scores in both of the F/Us (PC p-value: 0.013). Conclusions This study provides evidence that a TT of mild to moderate intensity has significant and persistent benefits for the balance, functional capacity, and QoL in PD.

Midbrain area for differentiating Parkinson's disease from progressive supranuclear palsy.

OBJECTIVES: We aimed to investigate the values of midbrain area in diagnosing Parkinson's Disease (PD) and progressive supranuclear palsy (PSP) by using transcranial sonography (TCS). Disease duration effect on brain sonographic findings could decrease the accuracy of TCS in PD and PSP patients. We reduced the disease duration effect on sonographic differences found between PD and PSP patients by using multivariate analysis. PATIENTS AND METHODS: Patients with clinical diagnosis of PSP and PD were recruited. We used SonoSite Edge II Ultrasound system to measure midbrain area, diameter of third ventricle and substantia nigra echogenicity. Diagnostic value of each measured area in sonography was estimated regarding its power for diagnosing PD or PSP. Independent sample t-test, Regression analysis and receiver operating characteristic (ROC) curve were performed using SPSS software. RESULTS: Of 35 patients, 18 were PD and 17 PSP cases. The mean midbrain area was 4.86 ± 0.71cm2 in PD patients and 3.61 ± 0.85cm2 in those with PSP (P < 0.005). Regression for reducing the effect of disease duration on midbrain area variances between patients with PD and PSP revealed a significant P value (P < 0.005, Adjusted R2 = 0.36). The sensitivity and specificity of midbrain area in diagnosing PD were 83.3% and 70.6% respectively. The sensitivity of the third ventricle size in diagnosing PSP was 82% although its specificity was 62%. CONCLUSION: Midbrain area in patients with PD was wider than those with PSP that was not affected by disease duration. Midbrain area was the most accurate index for diagnosing PD by TCS although third ventricle size was the most sensitive one for diagnosing PSP.

Mutation screening of SLC52A3, C19orf12, and TARDBP in Iranian ALS patients.

Mutations in the same gene are sometimes the cause of different clinically diagnosed neurologic disorders; this emphasizes interrelationships between various neurologic diseases. In this light, we screened SLC52A3, which is the cause of Brown-Vialetto-Van Laere syndrome, and C19orf12, which is the cause of neurodegeneration with brain iron accumulation in 60 Iranian amyotrophic lateral sclerosis (ALS) patients without mutations in the 2 most important ALS-causing genes, SOD1 and C9orf72. To the best of our knowledge, neither SLC52A3 nor C19orf12 has been mutation-screened previously in ALS cohorts. Justification for screening SLC52A3 included notable clinical similarities between Brown-Vialetto-Van Laere syndrome and ALS, and justification for screening C19orf12 was known contribution of mitochondrial dysfunction to ALS etiology. Disease-causing variations in the 2 genes were not found among the ALS patients. TARDBP was screened in 107 patients, and a mutation (p.Gly348Cys) was identified in one. Detailed clinical data on the patient are presented. It appears that mutations in TARDBP in ALS patients of Iran are rare and occur at similar frequencies to European populations.