Validity and reliability of the Persian version of Recce stigma scale in people with multiple sclerosis and its impact on quality of life.

BACKGROUND: There is often a fear of social stigma experienced by people with multiple sclerosis (pwMS), which negatively impacts the quality of their lives (QoL). Currently, no Persian-validated questionnaire is available to assess this issue in pwMS. This study aimed to assess the validaty and reliability of the Persian version of Reece Stigma Scale Multiple Sclerosis (RSS-MS) questionnaire for pwMS. METHOD: This cross-sectional was conducted between January and February 2023 in Isfahan, Iran. The demographic and clinical information and the RSS-MS and Multiple Sclerosis Impact Scale-29 (MSIS-29) questionnaires were recorded from pwMS. The content validity index (CVI) and content validity ratio (CVR) have been used to evaluate validity. To identify the factors supporting the MS-related stigma, an exploratory factor analysis (EFA) was conducted. RESULTS: The present study recruited 194 pwMS. Based on factor analysis, only two factors had eigenvalues ≥ 1.0 and exhibited high internal consistency. The Cronbach's α coefficient for internal consistency of the RSS-MS scale was 0.822. More evidence for the construct validity suggested that having higher levels of stigma is significantly correlated with psychological (r = 0.468, p-value < 0.001) and physical dimensions (r = 0.585, p-value < 0.001) of MSIS-29. Expanded Disability Status Scale, disease duration, and treatment duration did not show a significant correlation with stigma (p-value > 0.05). CONCLUSION: This study indicated that the modified version of the RSS-MS scale in the Persian language showed acceptable validity and reliability for evaluating the stigma among Persian pwMS. Furthermore, this study emphasizes the cruciality of monitoring and addressing stigma among pwMS, as it can potentially enhance medical, psychological, physical, and QoL outcomes.

Minimal important differences and self-identifying treatment response in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIM: The use of outcome measures is recommended for chronic inflammatory demyelinating polyneuropathy (CIDP). Implications of minimal important differences (MID) to ascertain responder status are unknown. The reliability of patient-reported treatment-response in relation to clinically relevant change is also unknown. METHODS: We retrospectively studied 72 subjects with "definite" or "probable" CIDP evaluated at pre-specified time-intervals pre- and post-treatment. We derived MID and the minimum detectable change with 95% confidence intervals (MDC95 ) for four scales. Scale sensitivities were determined with applicable MID-defined cutoffs (aMIDc), to detect subjects with self-identifying treatment response through a single question. RESULTS: The use of MID was not valid for the Medical Research Council Sum Score, as MDC95 > MID. The aMIDc for the Overall Neuropathy Limitation Score (ONLS) was 1 (sensitivity: 84.7%). The aMIDc for the centile Inflammatory Rasch-built Overall Disability Scale (cI-RODS) was 8 (sensitivity: 62.3%). The aMIDc for grip strength was 4 kg (sensitivity: 79.1%). MID-defined amelioration of any one scale among ONLS, cI-RODS, or grip strength, significantly improved sensitivity to detect treatment-responders compared with the ONLS alone (McNemar test: P = .008, odds ratio: 3.36 [95% confidence interval: 1.44-7.86]). Patient-reported improvement was highly reliable in relation to MID-defined amelioration on any one scale. DISCUSSION: In subjects with CIDP, MID-defined amelioration of any one of three commonly used outcome measures offers optimum relevance and sensitivity to detect self-identifying treatment-responders. Patient reliability to single-question ascertainment of response is high in relation to MID-defined clinical relevance. These findings support use of multiple outcome measures in CIDP monitoring and justify enhanced patient involvement in the process.

Comparative value and determinants of suitability of outcome measures in treated chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: The comparative value and suitability of outcome measures are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We studied 35 patients with CIDP using the Overall Neuropathy Limitation Scale (ONLS), the inflammatory Rasch-built Overall Disability Scale (I-RODS), and the Medical Research Council Sum Score (MRCSS). RESULTS: Significant associations were determined between initial deficit and ONLS score (P = .002) and MRCSS improvement (P = .001) but not I-RODS score. A strong inverse correlation was observed between disease duration and I-RODS score(P = .002) but not ONLS/MRCSS improvement. A strong association was observed between age ≤ 40 years and I-RODS score (P = .001) but not ONLS/MRCSS improvement. When minimum important differences were used, ONLS and I-RODS sensitivities were comparable (P = .19). DISCUSSION: Overall Neuropathy Limitation Scale and I-RODS are equally sensitive in identifying change. Ease of administration, better ability to detect improvement in severe disease, and greater amplitude responses throughout the disease and in older patients favor the ONLS. The I-RODS appears more useful in early disease/younger patients.

Small fiber neuropathy in unexpected clinical settings: a review.

Small fiber neuropathy (SFN) is being recognized with increasing frequency in neuromuscular practice due to improved diagnostic techniques. Although there are some common etiologies, up to one-third of cases are considered idiopathic. In recent years, several disorders have unexpectedly been reported in association with SFN, on clinical grounds and complementary investigations, including quantitative sensory testing, intraepidermal nerve fiber density and confocal corneal microscopy. Knowledge of these disorders is important in clinical practice as increased awareness enables prompt diagnosis of SFN in these settings and early optimal therapeutic management of affected patients. Furthermore, these new developments may lead to a better understanding of the pathophysiologic mechanisms underlying SFN in these different disorders as well as, in some cases, an expanded spectrum of affected organs and systems. This article reviews these reported associations, their possible pathophysiologic bases, and the potential resulting management implications.

The Effect of Functional Stretching Exercises on Neural and Mechanical Properties of the Spastic Medial Gastrocnemius Muscle in Patients with Chronic Stroke: A Randomized Controlled Trial.

BACKGROUND: Following spasticity, neural and mechanical changes of the paretic muscle often occur, which affect the muscle function. The aim of this study was to investigate the effect of functional stretching exercises on neural and mechanical properties of the spastic muscle in patients with stroke. MATERIALS AND METHODS: This study was a single-blinded, randomized control trial. Forty five patients with stroke (experimental group: n = 30; control group: n = 15) participated in this study. Subjects in the experimental group participated in a functional stretching program 3 times a week for 4 weeks. Subjects in both groups were evaluated before the training, at the end of training, and then during a 2-month follow-up. Neural properties, including H-reflex latency and Hmax/Mmax ratio, were acquired. Mechanical properties, including fascicle length, pennation angle, and muscle thickness in the spastic medial gastrocnemius muscle, were evaluated. Repeated measure analysis of variance was used in the analysis. RESULTS: Time by group interaction in the pennation angle (P = .006), and in muscle thickness (P = .030) was significant. The results indicated that the H-reflex latency (P = .006), pennation angle (P < .001), and muscle thickness (P = .001) were altered after stretching training program and these changes were at significant level after 2-month follow-up. CONCLUSION: The results indicated that the use of functional stretching exercises can cause significant differences in neural and mechanical properties of spastic medial gastrocnemius muscle in patients with chronic stroke.

The effects of intradermal botulinum toxin type a injections on pain symptoms of patients with diabetic neuropathy.

BACKGROUND: Considering the dramatic increasing rate of diabetes and consequently its related complications, most importantly diabetic peripheral neuropathy (DPN), challenges regarding proper treatment of DPN and its effect on the quality-of-life and care of diabetic patients, the aim of this current study is to evaluate the effect of intradermal botulinum toxin type A (BTX-A) injections on pain symptoms of patients with diabetic neuropathic pain. MATERIALS AND METHODS: In this randomized double-blind placebo-controlled clinical trial study, diabetic patients aged <70 years with neuropathic pain in both feet were enrolled. Diabetic neuropathy (DN) in selected patients was diagnosed using DN4 questionnaire and nerve conduction velocity examinations. They randomized in two intervention (BTX-A injection/100 unit, N = 20) and placebo groups (normal saline injection, N = 20). The outcome of injection on diabetic neuropathic pain was assessed using neuropathy pain scale (NPS) and visual analog scale (VAS) score and compared in two studied groups. RESULTS: There was no significant difference in DN4, NPS and VAS scales of studied population after intervention in the placebo group. Intradermal injection of BTX-A reduced NPS scores for all items except cold sensation (P = 0.05). It reduced DN4 scores for electric shocks, burning, pins and needles and brushing (P < 0.05). According to VAS scale 30% and 0% of patients in intervention and placebo groups have no pain after intervention (P = 0.01). CONCLUSION: Intradermal injection of BTX-A is a well-tolerated agent that has a significant effect on DPN pain.

A comparison of the ultrasonographic median nerve cross-sectional area at the wrist and the wrist-to-forearm ratio in carpal tunnel syndrome.

BACKGROUND: Electrophysiologic (EDX) study is the most valuable method in grading the severity of carpal tunnel syndrome (CTS), but it is invasive and painful. We evaluated the efficacy of ultrasound for this purpose. MATERIALS AND METHODS: Eighty-one wrists of 52 consecutive patients with clinical evidences of CTS, confirmed and graded by EDX as mild, moderate, and severe, were examined by ultrasonography. Cross-sectional area (CSA) of the median nerve was measured at the distal wrist (CSA-D), and proximal forearm (CSA-P), and wrist-to-forearm ratio (WFR) was calculated for each hand. RESULTS: The mean CSA-D was 0.12 cm(2) ± 0.03, 0.15 cm(2) ± 0.03 and 0.19 cm(2) ± 0.06 and the mean WFR was 2.77 ± 1.14, 3.07 ± 1.07 and 4.07 ± 1.61 in mild, moderate and severe groups respectively. WFR showed significant differences between the severe and none severe CTS groups (P < 0.001), but there was no significant difference between mild and moderate CTS groups (P < 0.381). CSA-D showed a significant difference between all groups (P < 0.0001). In the Receiver Operating Characteristic curve analysis, the optimal cut-off value of the CSA-D and WFR for detecting severe CTS were 0.15 (area under the curve 0.784, 95% confidence interval (CI): 0.662-0.898, P < 0.001, sensitivity of 68.2% and specificity of 70.9%) and 3 (area under the curve 0.714, 95% CI: 0.585-0.84, P = 0.001, sensitivity of 68.2% and specificity of 64.8%) respectively. All values were superior in CSA-D. CONCLUSION: Ultrasonography, can be complementary but not conclusive to the classification of CTS severities. CSA-D and WFR both increased in proportion to CTS severity, but neither parameter exhibited excellent performance in grading the severities.

Small fiber neuropathy in irritable bowel syndrome.

Aim: In this study, we intend to evaluate the occurrence of small fiber neuropathy in patients with irritable bowel syndrome (IBS). Background: Small fiber neuropathy (SFN) is a sensory neuropathy that results from the degeneration of small Aδ and unmyelinated C fibers. SFN manifests positive symptoms, such as tingling, burning, prickling, and aching, and negative symptoms, including numbness, tightness, and coldness. The SFN coexistence with other comorbidities (e.g., fibromyalgia, inflammatory bowel disease, celiac disease) has been reported in previous studies. Methods: We conducted a cross-sectional study to assess the coexistence of SFN and IBS. Forty-two IBS patients and forty-three healthy individuals were asked to complete the Michigan Neuropathy Screening Instrument (MNSI) questionnaire. Results greater than three (>3) were considered positive. Participants with positive MNSI questionnaire results were examined for any neuropathy signs according to the Utah Early Neuropathy Scale (UENS) examination. The participants with positive results for the questionnaire and examination were checked for the sural and the superficial peroneal nerve conduction study (NCS). Normal NCS represented intact large fibers and the diagnosis of SFN. Results: Ten participants, 7 (16.7 %) in the IBS group and 3 (6.9 %) in the healthy group, had positive results for the questionnaire. Four participants were positive for the examination, with normal NCS, and were classified as SFN-positive. All four SFN diagnoses were from the IBS group. No one in the healthy group was diagnosed with SFN. We could find a significant statistical difference (p<0.05) between the IBS and healthy groups regarding the prevalence of SFN diagnosis. Conclusion: The co-occurrence of SFN and IBS suggests the possibility of a generalized neuropathy syndrome characterized by widespread neuronal impairment. Thus, any peripheral neuropathy symptom in IBS patients (and potentially other chronic pain disorders) should be evaluated for SFN since timely diagnosis and proper treatment result in a better quality of life for the patients.

Multiple sclerosis and personality traits: associations with depression and anxiety.

BACKGROUND: Depression and anxiety are commonly observed in people with multiple sclerosis (pwMS). There is a growing body of literature supporting the hypothesis that personality traits can influence the mood disorders. This study aimed to investigate the personality traits and their relationships with depression and anxiety among pwMS. METHODS: 234 pwMS were involved in this cross-sectional study. Personality traits, depression, and anxiety were assessed using the NEO Five-Factor Inventory (NEO-FFI) and Hospital Anxiety and Depression Scale (HADS), respectively. Pearson's correlation coefficient and generalized linear model were employed to evaluate the relationships between demographic and clinical characteristics, NEO-FFI, and HADS subscales. RESULTS: In pwMS, longer disease duration was significantly associated with lower level of conscientiousness (ß = - 0.23, p = 0.008) and agreeableness (ß = - 0.2, p = 0.01). Moreover, higher expanded disability status scale (EDSS) of pwMS had a significant relationship with higher level of neuroticism (ß = 0.89, p = 0.01). Increased level of neuroticism was significantly correlated with lower level of extraversion (r = - 0.28, p < 0.001), openness (r = - 0.37, p < 0.001), agreeableness (r = - 0.31, p < 0.001), and conscientiousness (r = - 0.45, p < 0.001). PwMS with higher level of conscientiousness showed more extraversion (r = 0.23, p < 0.001), openness (r = 0.61, p < 0.001), and agreeableness (r = 0.41, p < 0.001). Elevated level of neuroticism was significantly associated with higher level of anxiety (ß = 0.47, p < 0.001) and depression (ß = 0.11, p < 0.001) among pwMS. CONCLUSION: The co-occurrence of depression and anxiety is probably associated with neuroticism among pwMS. Additionally, the impact of personality traits extends to influencing key disease aspects such as physical disability and disease duration in MS.

Biallelic variation in the choline and ethanolamine transporter FLVCR1 underlies a pleiotropic disease spectrum from adult neurodegeneration to severe developmental disorders.

FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. While Flvcr1 knockout mice die in utero with skeletal malformations and defective erythropoiesis reminiscent of Diamond-Blackfan anemia, rare biallelic pathogenic FLVCR1 variants are linked to childhood or adult-onset neurodegeneration of the retina, spinal cord, and peripheral nervous system. We ascertained from research and clinical exome sequencing 27 individuals from 20 unrelated families with biallelic ultra-rare missense and predicted loss-of-function (pLoF) FLVCR1 variant alleles. We characterize an expansive FLVCR1 phenotypic spectrum ranging from adult-onset retinitis pigmentosa to severe developmental disorders with microcephaly, reduced brain volume, epilepsy, spasticity, and premature death. The most severely affected individuals, including three individuals with homozygous pLoF variants, share traits with Flvcr1 knockout mice and Diamond-Blackfan anemia including macrocytic anemia and congenital skeletal malformations. Pathogenic FLVCR1 missense variants primarily lie within transmembrane domains and reduce choline and ethanolamine transport activity compared with wild-type FLVCR1 with minimal impact on FLVCR1 stability or subcellular localization. Several variants disrupt splicing in a mini-gene assay which may contribute to genotype-phenotype correlations. Taken together, these data support an allele-specific gene dosage model in which phenotypic severity reflects residual FLVCR1 activity. This study expands our understanding of Mendelian disorders of choline and ethanolamine transport and demonstrates the importance of choline and ethanolamine in neurodevelopment and neuronal homeostasis.

Oral prednisolone in the treatment of cervical radiculopathy: A randomized placebo controlled trial.

BACKGROUND: Steroids are commonly used in the treatment of cervical radiculopathy (CR), but there is limited information in this regard. We evaluated the efficacy of oral prednisone in the treatment of CR. MATERIALS AND METHODS: This randomized, double-blinded, placebo-controlled trial was conducted on adult patients with neck/shoulder pain for at least 1 month with no alarm symptoms/sings of malignancy, infection, or severe myelopathy, and no contraindication for corticosteroid use. Patients were allocated to receive prednisolone 50 mg/day for 5 days that was tapered within the following 5 days, or placebo. All patients also received acetaminophen 325 mg three times a day and ranitidine 150 mg two times a day. Neck disability index (NDI) and the verbal rating scale (VRS) were used to evaluate the outcomes. RESULTS: A total of 59 patients (31 female, mean ± SD age = 46.2 ± 9.0 years) completed the study. A significant decrease was observed regarding the NDI and VAS scores from baseline to the end of study in both groups (P < 0.001). However, for both the NDI (35.7 ± 21.4 vs. 12.9 ± 10.2) and VRS (4.4 ± 2.7 vs. 1.6 ± 1.2), the amount of decrease was greater in the prednisone compared with the placebo group (P < 0.001). Based on the clinically important change in NDI, pain was improved in 75.8% (22/29) of the prednisolone and 30% (9/30) of the placebo group (P < 0.001). CONCLUSION: A short course of oral steroid therapy with prednisolone is highly effective in reducing pain in patients referring with uncomplicated CR. Further studies are warranted on dosing, duration, and long-term efficacy and safety of oral steroid therapy, compared with injection approach.

Seizure characteristics in multiple sclerosis patients.

BACKGROUND: To evaluate seizure characteristic among multiple sclerosis patients with coexistent seizure activity compared to control group. MATERIALS AND METHODS: This study is a cross-sectional study which was conducted by reviewing the clinical records of patients with definite diagnosis of MS according to McDonald's criteria from March 2007 to June 2011, who referred to the MS clinic of the university. RESULTS: A total of 920 patients with a diagnosis of MS were identified, among whom 29 patients (3.15%) with seizure activity (case) due to MS with the mean age of 32.6 ± 6.23 years were analyzed. Also, fifty MS patients without any seizure occurrence with the mean age of 33.7 ± 7.4 years were used as our control group. In case group, seizure was general tonic clonic in 23 patients (79.3%), complex partial in four (13.8%), and simple partial in two (5.9%). The 26 available interictal EEGs in MS patients showed abnormal EEG pattern in 22 (84.6%) of them, including focal epileptic form discharge or focal slowing in 10 (38.5%), generalized discharge (spike-wave, polyspike, or general paroxysmal fast activity) in 10 (38.5%), and general slowing activity in 10 record (38.5%). MRI reviews of the 26 available brain MRIs showed subcortical white mater lesions in 22 (84.6%) of patients with seizure. All MRIs were performed within one month after the first seizure episode. Amongst 48 available MRIs in our control group, 91.7% (44 cases) showed periventricular lesions and in 8.3% (4 cases) subcortical white matter lesions were reported. CONCLUSION: The result of this study demonstrated the higher rate of subcortical whit matter lesion in MS patients with seizure occurrence compared to control group.

Speed of word retrieval in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a common inflammatory - degenerative disease of myelin sheet of central nervous system that affects more young people. These patients show some degrees of cognition problems such as memory and processing disorders. The aim of this study was to evaluate the speed processing ability by word finding assessment in three categories include fruits, animals and objects in MS patients. MATERIALS AND METHODS: This study carried out as case-control and descriptive-analytic on 47 MS patients and 29 healthy controls. We measured the reaction time (RT) in three stages. Each stage includes 25 words (animals, fruits and objects words with high familiarity) that were presented randomly. In each stage, the subject should press a key when recognized the target category. Collected data analyzed with repeated measure ANOVA, two-way ANOVA test, and independent-samples t-test. RESULTS: MS patients in comparison to normal healthy subjects show delay in speed of processing in which there was significant difference between MS patients and control subjects in mean reaction time in all three categories (P < 0.001). CONCLUSION: The speed of processing is impaired in MS patients. Consequently, more evaluation and planning treatment programs based of speed processing for memory in these patients are necessary for them because of the role of memory in daily activities of life.

Seizure in Iranian patients with multiple sclerosis.

BACKGROUND: There is a broad variation in reported frequencies of seizure in multiple sclerosis (MS). In this study, the seizure and its characteristics analyzed among a large group of patients with MS. PATIENTS AND METHODS: We reviewed the medical records of all definite MS patients referred to the MS Clinic of Kashani hospital, Isfahan, Iran, between 2007 and 2011. RESULTS: Altogether, 34 cases with seizure activity identified among the 920 definite MS subjects (3.69%). Five excluded due to the other probable etiologies rather than MS. In the remained 29 patients (3.15%), the type of seizure was mostly generalized (79.3%); interictal electroencephalography showed an abnormal pattern in 84.6%, brain magnetic resonance imaging revealed subcortical white mater lesions in 84.6% of patients. The mean duration of MS onsets was 8.17 years and the mean interval between MS onset and the first seizure occurrence was 3.7 years. In general, response to antiepileptic treatment was excellent. CONCLUSION: Seizures can occur at any stage during the course of MS, but it is more common during the early stages.

Enalapril protects endothelial cells against induced apoptosis in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease in which endothelial cell (EC) can be affected. In brain, functional changes in ECs contribute to reductions in resting blood flow. Furthermore, angiotensin-converting enzyme inhibitors (ACE-I) have beneficial effects on endothelial dysfunction. This is the first study that presents direct experimental evidence associating endothelial apoptosis as a basis of AD pathogenesis and response to an ACE-I therapy. MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were treated with sera from AD patients and sera from healthy volunteers (each group, n = 10). Apoptosis was determined by annexin V-propidium iodide staining and cell death detection kit. The effect of 50 µM enalapril on endothelial apoptosis was assessed. Nitrite (NO2 (-)) levels were determined in the culture supernatants. RESULTS: Enalapril suppressed the induction of apoptosis by the serum of patients only when used before treating HUVECs with the sera of AD. Mean ± SD of apoptosis induction in the control group was 6.7 ± 3.69; in the group treated with sera of AD for 24 h was 47.78 ± 0.65; in the group wherein sera from AD was added (pretreatment) after exposure of HUVECs by 50 µM enalapril for 24 h was 26.6 ± 2.63; and in the group wherein HUVECs were exposed in the sera of AD for 24 h and then 50 µM enalapril was added to these cells for another 24 h (post-treatment) was 56.87 ± 5.51. Also, the mean ± SD of NO2 (-) concentration showed significantly greater levels of dissolved NO2/NO3 metabolite in the culture media of untreated HUVECs by enalapril (1.03 ± 0.06) as compared with control (0.26 ± 0.13; P < 0.05), while the rate of nitric oxide (NO) significantly decreased when enalapril was presented in culture both in the pretreatment (0.07 ± 0.003) and in the post-treatment group (0.06 ± 0.005; P < 0.05). CONCLUSION: It could be concluded that EC treated with sera from AD patients activates apoptosis in HUVECs; this effect was reversed by enalapril pretreatment. This can be proposed as a therapeutic approach for Alzheimer's patients.

The value of provocative tests in diagnosis of cervical radiculopathy.

BACKGROUND: This study was aimed at assessing the accuracy of provocative tests in diagnosis of acute or chronic Cervical Radiculopathy (CR) based on an electrodiagnostic reference criterion. MATERIALS AND METHODS: Shoulder Abduction Test (SAT), Spurling Test (ST), Upper Limb Tension Test (ULTT), and electromyography were done on 97 patients who referred to Electrodiagnostic center in the university hospital from January 2010 to March 2011. All of the participants had neck and radicular pain for at least 3 weeks. They were classified according to electrodiagnostic findings. Then diagnostic values of provocative tests were assessed in diagnosis of acute or chronic CR on the basis of reference criterion. RESULTS: SAT and ST were more specific (85%) compared to ULTT, while ULTT was more sensitive (60.46% in acute and 35.29% in chronic) than the other two. SAT and ST had a significant accuracy for comparison between acute and chronic CR (P < 0.05). CONCLUSION: ULTT is suitable for screening of CR, while SAT and ST can support diagnosis. SAT and ST are good diagnostic tests for comparison between acute and chronic CR.

On genotype-phenotype relationship of dystrophinopathies among Iranian population.

Background: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are inherited X-linked disorders resulting from alterations in the dystrophin gene. Genotype-phenotype matching studies have revealed a link between disease severity, the amount of muscle dystrophin, and the extent of mutation/deletion on the dystrophin gene. This study aimed to assess the relationship between genetic alterations in the dystrophin gene and the clinical status of patients with dystrophinopathies among the Iranian population. Methods: This cross-sectional study examined 54 patients with muscle weakness caused by abnormalities in the dystrophin gene at a hospital affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, in 2021. The participants' demographic information, including age, family history of muscle dystrophies, and family history of other medical diseases as well as the type of muscular dystrophy were recorded. Furthermore, the number and region of deleted exons based on dystrophy types were also evaluated using multiplex ligation-dependent probe amplification (MLPA). The patients' gaits were also assessed as using a wheelchair, the presence of waddling gaits, or toe gaits. The patients' clinical status and the coexistence of pulmonary, bulbar, and mental conditions were also examined and compared between the two groups of dystrophinopathies. Results: In this study, 54 patients with dystrophinopathy with the mean age of 16.63 ± 12.10 years were evaluated, of whom 22 (40.7%) and 30 (55.6%) patients were classified as BMD and DMD, respectively. The most affected regions with deleted exons were exons 45-47 (n = 5) and 45-48 (n = 4) in patients with BMD, while exons 45, 48-52, 51-55, and 53 (2 cases per exon) were the most common affected exons in patients with DMD. Further analyses revealed that deletions in exons 45-47 and 51-55 were significantly associated with older and younger ages at the onset of becoming wheelchair-bound in patients with dystrophy, respectively. The hotspot range in both BMD and DMD was within exons 45-55 (n = 15 for each group); 63% of the patients had alterations on the dystrophin gene within this range [30 patients (68.18%) in the BMD group, 15 patients (53.57%) in the DMD group]. Conclusion: Exon deletion was the most common genetic alteration in patients with dystrophinopathies. No significant difference was observed between DMD and BMD regarding the number of deleted exons. Deletions in exons 45-47 and 51-55 were linked to later and earlier onset of becoming wheelchair-bound, respectively.

Demographic and Clinical Characteristics of Familial and Sporadic Multiple Sclerosis Patients.

Background: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, immune-mediated disease of the central nervous system. It is still unestablished whether heredity correlates with the disease's progression and severity. Methods: This study includes the patients with MS seen in the MS clinic of Kashani Hospital, affiliated with Isfahan University of Medical Sciences, from January 2019 to January 2020. We gathered data regarding the demographic and clinical characteristics, such as type of disease and family history of MS. Patients were grouped based on having relatives with MS. We compared demographic and clinical characteristics between those with a family history of MS (familial MS: FMS) and those without a family history of MS (sporadic MS: SMS). Results: We included 2,929 MS patients, 523 (17.2%) with FMS and 2,406 (82.8%) with SMS. Patients with FMS were found to have active lesions in the thoracic spine more frequently than those with SMS (P = 0.022). We also found differences in the distribution of gender (P = 0.036) and the frequency of having active brain lesions (P = .024) among patients with FMS and SMS. No difference was found between the demographic/clinical characteristics and the number of affected relatives in the family. Conclusions: Significant differences were found among different groups of patients in terms of demographical and clinical characteristics.

Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants.

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a non-syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next-generation sequencing (NGS) a necessary approach for the proper diagnosis of LGMD. METHODS: In this article, 26 Iranian patients with LGMD criteria were diagnosed with disease variants in the genes encoding calpain3, dysferlin, sarcoglycans and Laminin α-2. Patients were referred to the hospital with variable distribution of muscle wasting and progressive weakness in the body. The symptoms along with biochemical and EMG tests were suggestive of LGMD; thus the genomic DNA of patients were investigated by whole-exome sequencing including flanking intronic regions. The target genes were explored for the disease-causing variants. Moreover, the consequence of the amino acid alterations on proteins' secondary structure and function was investigated for a better understanding of the pathogenicity of variants. Variants were sorted based on the genomic region, type and clinical significance. RESULTS: In a comprehensive investigation of previous clinical records, 6 variations were determined as novel, including c.1354-2 A > T and c.3169_3172dupCGGC in DYSF, c.568 G > T in SGCD, c.7243 C > T, c.8662_8663 insT and c. 4397G > C in LAMA2. Some of the detected variants were located in functional domains and/or near to the post-translational modification sites, altering or removing highly conserved regions of amino acid sequence.

Iranian clinical practice guideline for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegeneration involving motor neurons. The 3-5 years that patients have to live is marked by day-to-day loss of motor and sometimes cognitive abilities. Enormous amounts of healthcare services and resources are necessary to support patients and their caregivers during this relatively short but burdensome journey. Organization and management of these resources need to best meet patients' expectations and health system efficiency mandates. This can only occur in the setting of multidisciplinary ALS clinics which are known as the gold standard of ALS care worldwide. To introduce this standard to the care of Iranian ALS patients, which is an inevitable quality milestone, a national ALS clinical practice guideline is the necessary first step. The National ALS guideline will serve as the knowledge base for the development of local clinical pathways to guide patient journeys in multidisciplinary ALS clinics. To this end, we gathered a team of national neuromuscular experts as well as experts in related specialties necessary for delivering multidisciplinary care to ALS patients to develop the Iranian ALS clinical practice guideline. Clinical questions were prepared in the Patient, Intervention, Comparison, and Outcome (PICO) format to serve as a guide for the literature search. Considering the lack of adequate national/local studies at this time, a consensus-based approach was taken to evaluate the quality of the retrieved evidence and summarize recommendations.