This article is a Letter to the Editor and does not include an Abstract.
Background: Stroke is a multifactorial disorder and a major cause of morbidity and mortality around the world. There are growing numbers of candidate gene pathways which are thought to be associated with stroke. Genes involved in lipid metabolism are important issues in stroke studies. Studying different polymorphisms in these genes are becoming an interest for researchers. 5-lipoxygenase activating protein (ALOX5AP) is one of these genes. Different studies have provided different relations between ALOX5AP promoter polymorphism (rs17222919) and stroke. In the present study, we have evaluated this gene polymorphism in a population in north east of Iran. Methods: This case-control study took place in Ghaem Hospital, Mashhad, Iran. Patients with computed tomography (CT) or magnetic resonance imaging (MRI) confirmation for ischemic stroke were enrolled in this study and considered as case group. Healthy persons without ischemic stroke were control group. During 1-year period of this study, ALOX5AP gene polymorphism in 200 healthy patients (control group) as well as 228 patients with stroke (case group) was evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: All of 428 persons (228 cases and 200 healthy controls) enrolled in this study. The genotype and allele frequency was significantly different between both groups (P = 0.001 and P = 0.003, respectively). A total number of 54 patients had G allele in case group in contrast to 27 ones in control group. Also, 174 patients in case group had T allele and 173 persons had this allele in control group. In compression of TT genotype, the risk of developing stroke in GG and TG genotypes increased by 3.998 and 1.643, respectively. Also the risk of ischemic stroke with G allele would increase by 2.128. Conclusion: According to our results, ALOX5AP promoter polymorphism (rs17222919) is related to increased ischemic stroke in Iranian population.
Motor unit number index (MUNIX) is an electrophysiological technique to give an estimate of functioning motor neurons in a muscle. For any given neurophysiological technique for the use in clinical or research studies, reproducibility between different operators and in a single operator in different times is one of the most important qualities, which must be evaluated and approved by different examiners and centers. After its introduction, testing the reproducibility of MUNIX was the aim of many studies to show this quality of the technique. In this review, we aimed to summarize all the studies, which have been performed up to now to approve MUNIX reproducibility in amyotrophic lateral sclerosis comparing healthy individuals.
Hemifacial spasm (HFS) is characterized by irregular involuntary tonic or clonic contractions of muscles innervated by the seventh cranial nerve. Patients usually need long-term treatment, as spontaneous remission is infrequent. Repeated botulinum toxin injection has been shown as a safe and successful treatment for symptomatic relief in patients with HFS.1 Side effects are usually mild and transient. Ptosis has been reported in about 24% of patients with HFS probably due to diffusion of toxin to levator palpebrae superioris muscle.2 However, the frequency of ptosis in patients with HFS has not been addressed yet, due to causes other than botulinum toxin side effect. Herein, we present a case of HFS who presented to our clinic with complaint of complete ptosis and progressive pain early after botulinum toxin injection. Despite initial negative evaluations, further work up revealed a compressive lesion. A 75-year-old man presented with left severe ptosis since 3 weeks ago (Figure 1). He was known case of left HFS since 4 years ago, and botulinum toxin had been regularly injected for his symptom relief in orbicularis oculi, corrugator, and procerus muscles. Figure 1. Left Blepharoptosis one week after botulinum toxin injection The patient stated that this new ptosis had begun within a week after his last Dysport (Ipsen, Ltd., Slough, Berkshire, UK) injection while he had no ptosis in his previous injections. In past medical history, he had ischemic heart disease, hypertension, cataract extraction of both eyes, and glaucoma surgery on his right eye. He had been admitted to the neurology ward of a general hospital.
Background: Multiple sclerosis (MS) is a neurologic disorder with a considerable global burden. During the last decades, some pharmaceutical treatments have been approved for patients with MS. Dimethyl fumarate (DMF) is one of these drugs which has been reported to have early promising results in recent studies, but the efficacy of this drug in patients with MS is still being studied in different parts of the world. In the present study, we evaluated the effectiveness of DMF therapy on reducing relapses, lesions, and disability in Iranian patients with MS. Methods: The present single-arm before-after study was approved by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran [Iranian Registry of Clinical Trial (IRCT) code: IRCT20190121042439N1]. Every patient who was diagnosed with relapsing MS was considered eligible to enroll in the present clinical trial. Before receiving DMF therapy, the baseline liver function tests and complete blood count were obtained from all individuals. Also, a baseline brain magnetic resonance imaging (MRI) was obtained and Expanded Disability Status Scale (EDSS) was documented from all patients. After receiving 240 mg DMF twice daily for 12 months, the laboratory and imaging measurements as well as EDSS were repeated. Furthermore, the total number of relapses within the study period was recorded. Satisfaction with DMF treatment was determined by answering a yes-no question. Results: A total number of 50 patients enrolled in the study and most of them were female (80%). There was a significant decrease in EDSS score and gadolinium (GD)-enhancing lesions after the study period (P < 0.001 for each). Moreover, the attacks significantly dropped after the study period (P < 0.001) and 86% of patients were satisfied with their treatment. Conclusion: The findings of this study showed that 240 mg DMF administered twice daily can effectively reduce disability and provide satisfaction within the first year of therapy in patients with MS.
Although various advancements have been made to control incidence of stroke, the overall incidence, and the rate of morbidity of stroke, still increase in developing countries.1-3 In last years, the epidemiologic studies on ischemic stroke have been widely increased in Turkey and Iran.1-3 These two countries are located in similar geography with a similar historical background, though the environmental factors and lifestyle of general population in these two neighboring countries show peculiar differences. In this study, we aimed to make a comparison between data from Turkey and from Iran, in terms of etiologies and risk factors of ischemic stroke, to reveal region-related similarities or country-related differences. We reviewed the files of 2534 patients with ischemic stroke followed up for 15 years in our Cerebrovascular Outpatient Clinics in Faculty of Neurology, Istanbul University (Cerrahpasa), Istanbul, Turkey. Data collection in Iran was made from 2314 patients with ischemic stroke followed up for 6 years in Stroke Unit, Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. In the etiological classification, both centers used the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria4 upon clinical data, neurological examinations findings, and neuroimaging characteristics. Risk factors were recorded in detail, the statistical analyses were performed with the SPSS software (version 21, IBM Corporation, Armonk, NY, USA). Statistical tests used in the analysis were as χ2 or Fisher’s test for independent categorical variables, Student’s t test for normally distributed independent numerical variables, and Mann-Whitney U for not normally distributed independent numerical variables. The effects of covariates and independent variables were investigated by logistic regression.
Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are both demyelinating disorders and oxidative stress is suggested to have a role in their pathogenesis. Glucose-6-phosphate dehydrogenase (G6PD) produces nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. NADPH is not only involved in the synthesis of fatty acids necessary for myelination, but also it is involved in the defense against oxidative stress. Prescribing supplementary vitamin D as a part of the MS treatment plan can increase G6PD gene expression. The aim of this study was to determine the serum level of G6PD in patients with MS and NMO and its relationship with vitamin D, since it is yet to be explored thoroughly. Methods: In this case-control study, subjects were divided into three experimental and control groups. The experimental groups comprised 50 patients with relapsing-remitting MS (RRMS) who had a history of vitamin D consumption, 50 newly-diagnosed MS patients, and 50 patients with NMO. Control group included 65 healthy individuals. Serum level of G6PD was measured and compared among these groups. Results: No significant difference was seen between the G6PD level in patients with MS and NMO, but it should be noted that this level was significantly lower than the healthy group. G6PD serum level was significantly higher in patients with MS who had previously consumed supplementary vitamin D compared to those who had not. Conclusion: G6PD deficiency is observed in patients with MS and NMO. Also, supplementary vitamin D may induce favorable results on the G6PD level.
Driving restriction is a well-known undesirable consequence of epilepsy and causes significant problems regarding independence and employment for epileptic patients. Many countries all over the world have provided comprehensive protocols in this regard with the aim of providing the possibility of less restricted, but safe driving for epileptic patients and also providing the opportunity for uniform decision-making for clinicians. However, the available fitness to drive protocol in Iran still lacks sufficient details and clinicians might encounter serious problems in terms of the driving issue in epileptic patients. In order to provide a uniform protocol containing adequate practical data, a systematic review of literature addressing guidelines about driving and epilepsy and driving laws of different countries for epileptic patients was performed and, after consideration of cultural issues, a practical protocol for Iranian neurologists was suggested.
Background: A number of patients with symptoms of acute cerebral ischemia may have other causes called stroke mimics (SM). The prevalence of SM can be as high as 31% in some reports, and these patients are potentially at the risk of intravenous thrombolysis (IVT) therapy and its complications. This study was designed to determine the prevalence of our center’s SM (Firoozgar Hospital) among patients who received IVT, their baseline characteristics, final diagnoses, and outcomes. Methods: We reviewed the medical records of all patients who received IVT between June 2015 and May 2018. The following variables were collected: demographic characteristics, past medical history, onset-to-needle (OTN) time, door-to-needle (DTN) time, National Institutes of Health Stroke Scale (NIHSS) score at admission, brain imaging, and all paraclinic findings. Functional outcome at discharge based on modified Rankin Scale (mRS) was also assessed. Results: 10 out of 165 (6.0%) patients including 8 men and 4 women were finally diagnosed with SM. The median age and NIHSS score at presentation were 60 years and 7, respectively. Final diagnoses were seizure (n = 6), hemiplegic migraine (n = 2), conversion (n = 1), and alcohol intoxication (n = 1). All patients were discharged with a mRS score of 0 and 1 without experiencing any thrombolytic adverse effects. Conclusion: None of the patients with SM experienced any adverse effect of tissue plasminogen activator (tPA) including hemorrhage and all of them reached good mRS score. This shows that tPA is generally safe and the risk of treating patients with SM is very low and making a vital treatment decision may outweigh the risk of neglected cases in a time-sensitive setting.
Dopa-responsive dystonia (DRD) belongs to combined dystonia syndrome (dystonia-plus syndrome)1 which encompasses non-degenerative and neurometabolic disorders characterized by combination of dystonia as the prominent sign, with another movement manifestation. Parkinsonism and myoclonus are the main disturbances accompany dystonia in the combined dystonia syndrome. Dystonia with parkinsonism includes DRD [DYT5, tyrosine hydroxylase (TH), and sepiapterin reductase (SPR)], dopamine agonist-responsive dystonia, rapid-onset dystonia parkinsonism (DYT12), and early-onset dystonia with parkinsonism (DYT16). However, dystonia combined with myoclonus is just classified as myoclonus dystonia (DYT11).2 DRD can be inherited in either autosomal dominant or autosomal recessive patterns. The autosomal dominant inheritance results in the typical phenotype of DRD, known as DYT5 or Segawa disease, which is caused by heterozygous mutations of guanosine triphosphate (GTP) cyclohydrolase I gene (GCH1). Mutations of the TH and SPR genes are responsible for autosomal recessive types of DRD.3 DYT5 is represented as progressive lower limbs dystonia with childhood-onset at the common age of 2-5 years. It shows diurnal fluctuations, which are aggravated toward the evening and alleviated by sleeping. Excellent and sustained response to the low dose of levodopa is the marked feature of DYT5 disease. Additional parkinsonism and spasticity may present later in life.4 Moreover, hemiatrophy of the brain, body, or both has been reported in patients with DRD, associated with a biochemical lesion located in basal ganglia.5 However, focal atrophy and muscle weakness rarely accompanies DRD. Interestingly, we aimed to introduce weakness and focal muscle atrophy as the onset manifestations of DRD in an elderly man misdiagnosed for about 70 years.
A 23-year-old woman was admitted to the emergency department with the history of headache, serial seizures, and decreased the level of consciousness from a week before. At admission, blood pressure was 230/170 mmHg, and creatinine level was 7.6 mg/dl. Initial brain and cervical magnetic resonance imaging (MRI) revealed hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) in bilateral occipital lobes and a longitudinally extensive lesion in the spinal cord (Figure 1, A-C). In the laboratory investigations, the level of anti-double stranded DNA was 45 IU/ml (normal < 10 IU/ml) and anti-nuclear antibody titer was high (> 1/160). Moreover, in renal biopsy, lupus nephritis was reported. Two weeks later, after hypertension treatment, the hyperintense signals wholly disappeared (Figure 1, D-F). Figure 1. Axial fluid-attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) indicating hypersignal lesions in parieto-occipital areas in favor of posterior reversible encephalopathy syndrome (PRES) at admission (A, B); sagittal T2 cervical MRI demonstrating a longitudinally extensive lesion in the spinal cord at admission (C); two weeks later, the hyperintense signals had completely disappeared on the brain and spinal cord MRIs (D-F).
Multiple sclerosis (MS) is an autoimmune disabling disease of the central nervous system, and can lead to a wide range of symptoms. Although the most common form of MS is relapsing-remitting, most of the patients also will develop disability in the future due to the natural course of the disease.1,2 The disease onset mostly occurs in 27 years of age.3 Therefore, considering the symptoms and complications of the disease, it can virtually affect the whole life of the patient. Unfortunately, there is not any accurate study of the opinions of patients with MS regarding their illness. However, in the daily work of treatment, one of the well-known cases of severe discomfort expressed by patients is the fear of future disability. This issue is aggravated when a person starts to lose abilities. When the patient experiences disability in walking and a decrease in his/her daily activities, thinking about the future becomes one of his/her major concerns. Most patients express these concerns in their visits. However, a patient who has other abilities such as poetry, writing a story, or painting, can more effectively portray concerns. The painting reported here is the allegorical view of a patient about her disability. The patient is a 37-year-old woman who has had MS for 15 years. Her illness started with the right eye optic neuritis. She has had six attacks during this period and, after 9 years, her disease entered the secondary progressive phase. Her symptom in this stage was the weakness of the right lower extremity, which was gradually deteriorating such as difficulty in walking. Now, she is unable to walk without help. This disability has affected all aspects of her life, and has greatly diminished her quality of life. She has been interested in drawing since childhood, and has drawn as a non-professional artist. One of her paintings reported here (Figure 1), according to the patient herself, reflects her perception and grief over her progressive disability. She believes that she should say goodbye to her ability and good days of the past. She painted herself as someone (when she could walk unrestrictedly) moving away along with a balloon
Glatiramer acetate (GA) is one of the well-tolerated disease-modifying therapeutic options, which is commonly administered subcutaneously in patients with multiple sclerosis (MS). The current study aimed at defining a bullous pemphigoid (BP) skin reaction in a patient with MS receiving treatment with GA. A 29-year-old women with MS, receiving GA treatment within the past nine months, November 11, 2018, was admitted to our MS clinic due to itching skin eruptions at the site of injection. Her disease was started at February 12, 2017 with left optic neuritis; and because of six periventricular and eleven juxtacortical brain magnetic resonance imaging (MRI) lesions without any enhancement, lumbar puncture was done for her. Due to positive cerebrospinal fluid (CSF) oligoclonal band, MS was diagnosed for her. At that time, she refused to start disease modifying treatment. GA was started 9 months before admission for her. After dermatologic consultation, the dermatologist defined the lesions as fluid-filled and blistering at the site of injection without mucosal involvement (Figure 1). Figure 1. Large, fluid-filled blisters Timeline: Skin lesions appeared exactly at the GA injection site.
Glioblastoma multiforme (GBM), the most frequent malignant and aggressive primary brain tumor, is characterized by genetically unstable heterogeneous cells, diffused growth pattern, microvascular proliferation, and resistance to chemotherapy. Extensive investigations are being carried out to identify the molecular origin of resistance to chemo-and radio-therapy in GBM and find novel targets for therapy to improve overall survival rate. Dimethyl fumarate (DMF) has been shown to be a safe drug with limited short and long-term side effects, and fumaric acid esters (FAEs), including DMF, present both anti-oxidative and anti-inflammatory activity in different cell types and tissues. DMF has also anti-tumoral and neuroprotective effects and so it could be repurposed in the treatment of this invasive tumor in the future. Here, we have reviewed DMF pharmacokinetics and different mechanisms by which DMF could have therapeutic effects on GBM.
Neurological disease contributes significantly to morbidity and mortality in different ages and geographic areas around the world. The purpose of the current study was to investigate the incidence and disability-adjusted life years (DALYs) trend of neurological disease in Iran during 27 years ago. We used the data of the Global Burden of Disease (GBD) Study to estimate the incidence and DALYs of neurological disease in Iran in different age groups between 1990 and 2017. Age groups were defined in 5 groups including < 5 years, 5-14 years, 15-49 years, 50-69 years, and ≥ 70 years. The incidence number of neurological disease during 1990 to 2017 increased from 7.5 million to more than 12 million and the incidence rate grew as much as 1400 per 100000 populations in Iran. Totally, headache, epilepsy, and Alzheimer were the most common neurological diseases according to incidence and had the most values of DALY in Iran. The highest incidence and DALY of neurological disease was observed in the age group of 15-49 years. This study showed that the incidence and burden of neurological diseases had a dramatic increasing trend during 27 years ago in Iran. Consequently, it is necessary to investigate the causes of the growing trend in future studies.
Background: Neuropathic pain is one of the most common problems in patients with diabetes mellitus (DM). In this study, the effect of botulinum toxin type A (BTX-A) on neuropathic pain, quality of sleep, and quality of life of diabetic patients with sensorimotor polyneuropathy was studied. Methods: This randomized placebo-controlled trial study was carried out in a double-blind (patientresearcher) method. The study was performed on 32 patients with type 2 DM. Neuropathy was confirmed by Douleur Neuropathique 4 (DN4) Questionnaire and nerve conduction study (NCS). The patients were randomly assigned to two intervention and control groups based on the random numbers table. After selecting the subjects, we used 36-Item Short Form Health Survey (SF-36), Neuropathic Pain Scale (NPS), Visual Analogue Scale (VAS), and Pittsburgh Sleep Quality Index (PSQI) questionnaires before and after 3 months of 100 units BTX-A injection (as intervention group) or same amount of chloride sodium (as control group) to the subjects' feet. The data were analyzed by SPSS software using independent twosample t-test, chi-square test, and one-way repeated measures analysis of variance (ANOVA). Results: 12 male and 20 female patients participated in this study. There was a significant difference in the mean VAS, PSQI, physical dimension of the SF-36, and some NPS indices over time (12 weeks) (P < 0.001). Conclusion: The results of this study showed that BTX-A reduced neuropathic pain and improved the quality of life and sleep in people with diabetic neuropathy.
Background: There is evidence that supports the neuroprotective effects of dimethyl fumarate (DMF) in stroke. Nuclear factor erythroid 2-related factor 2 (Nrf2) has both anti-oxidant and anti-inflammatory mechanisms. We investigated the neuroprotective effects of DMF via Nrf2 activation in the cortex, striatum, and diencephalon in a middle cerebral artery occlusion (MCAO) model of stroke. Methods: 22 Sprague-Dawley male rats were randomized into 3 groups. In DMF-treated group (n = 8), rats received 15 mg/kg oral DMF twice daily by gavage from day 0 to 14 after a 60-minute MCAO. The vehicle group (n = 7) underwent MCAO and were given methocel/H2O, using the same method and schedule. In the sham group (n = 7), neck was opened, but neither middle cerebral artery (MCA) was occluded nor any drug was administered. After 14 days, the animals were sacrificed. The infarct volume were assessed by stereology method. Nrf2 expression was evaluated in the cortex, striatum, and diencephalon by immunohistochemistry method. Results: Ratio of infarct to total brain volume was significantly lower in the DMF-treated group (5.76%) in comparison with the vehicle group (22.39%) (P < 0.0001). Nrf2 expression was higher in DMFtreated group in comparison with both the vehicle and sham groups in cortex, striatum, diencephalon, and total brain (P < 0.0001). In the DMF-treated group, significant negative correlation between Nrf2 expression and infarct volume was observed in cortex, striatum, diencephalon, and total brain. Conclusion: DMF induces Nrf2 expression and its neuroprotective effects in different brain anatomical regions.
