High genetic heterogeneity of leukodystrophies in Iranian children: the first report of Iranian Leukodystrophy Registry.

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children.

Economic evaluation of next-generation sequencing techniques in diagnosis of genetic disorders: A systematic review.

In recent years, massively parallel sequencing or next generation sequencing (NGS) has considerably changed both the research and diagnostic fields, and rapid developments have led to the combination of NGS techniques in clinical practice, ease of analysis, and detection of genetic mutations. This article aimed at reviewing the economic evaluation studies of the NGS techniques in the diagnosis of genetic diseases. In this systematic review, scientific databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA registry) were searched from 2005 to 2022 to identify the related literature on the economic evaluation of NGS techniques in the diagnosis of genetic diseases. Full-text reviews and data extraction were all performed by two independent researchers. The quality of all the articles included in this study was evaluated using the Checklist of Quality of Health Economic Studies (QHES). Out of 20 521 screened abstracts, 36 studies met the inclusion criteria. The mean score of the QHES checklist for the studies was 0.78 (high quality). Seventeen studies were conducted based on modeling. Cost-effectiveness analysis, cost-utility analysis, and cost-minimization analysis were done in 26 studies, 13 studies, and 1 study, respectively. Based on the available evidence and findings, exome sequencing, which is one of the NGS techniques, could have the potential to be used as a cost-effective genomic test to diagnose children with suspected genetic diseases. The results of the present study support the cost-effectiveness of exome sequencing in diagnosing suspected genetic disorders. However, the use of exome sequencing as a first- or second-line diagnostic test is still controversial. Most studies have been conducted in high-income countries, and research on the cost-effectiveness of NGS methods is recommended in low- and middle-income countries.

The effects of ketogenic diet on beta-hydroxybutyrate, arachidonic acid, and oxidative stress in pediatric epilepsy.

The exact mechanism of a ketogenic diet (KD) as a suitable alternative therapeutic approach for drug-resistant epilepsy (DRE) in alleviating seizures is not yet fully understood. The present study aimed to evaluate the role of the KD in reducing oxidative stress (OS) by increasing the ketone body beta-hydroxybutyrate (BHB) and Arachidonic acid (ARA), an essential polyunsaturated fatty acid, as a possible mechanism in relieving seizure attacks in children with DRE. Forty children with refractory epilepsy were included in the present study. The serum levels of BHB, ARA, and OS markers, malondialdehyde (MDA), and 8-hydroxyl-deoxyguanosine (8-OHdG), were evaluated in children with DRE and compared before and after the three months of KD therapy. Thirty-four of 40 included children could complete the three-month KD therapy. Twenty-one (61.76%) patients had more than a 50% reduction in seizure frequency after the KD (responders). The remaining 13 children were considered non-responders to the diet. The serum levels of ARA and BHB significantly (p < 0.05) increased after the KD therapy. The serum levels of OS parameters MDA and 8-OHdG before the diet therapy were significantly (p < 0.05) higher than those after the administration. The serum levels of BHB and MDA after the KD therapy in the responders were respectively higher and lower than those in the non-responders (p < 0.001). Ketogenic diet might reduce brain OS by increasing BHB and ARA. The role of BHB in diminishing OS and seizure might be more remarkable than ARA.

A report on the blended short-term supplementary course on "Developmental Care for infants and toddlers" taught with a multidisciplinary approach for pediatricians -qualitative and quantitative study.

BACKGROUND: The implementation of follow-up programs for high-risk infants and toddlers aimed to promptly diagnose developmental delays and disorders and initiate early intervention to help improve their developmental status, reduce their care costs in the future, as well as improve their productivity as members of society. There is a lack of qualified specialists in the infant and toddler development field in Iran. To compensate for the lack of training in this area, for the first time, Tabriz University of Medical Sciences has designed a short-term supplementary course of "Developmental Care for Infants and Toddlers". Due to the multidisciplinary nature of the field of child development, this course has been designed as such. The current study aimed to evaluate this course and explain the graduates' relevant experiences using a multidisciplinary approach. METHODS: The current study is a quantitative/qualitative study conducted in two phases. In the first step, the learners were asked to assess the teaching quality of the short-term supplementary course of "Developmental Care for Infants and Toddlers" in 5 areas of "educational design," "course administrators' support", " learners' motivation ", "acquisition of general learning and specialized skills" using the Australian Course Experience Questionnaire (CEQ). All graduates completed the questionnaires. The data from the questionnaires were analyzed using descriptive statistics of medians, and interquartile ranges in SPSS software. The second step was a qualitative study to explain the graduates' experiences of this course with a multidisciplinary approach. The samples were selected using a purposive sampling technique. The samples were those who had completed the course mentioned above, had rich experiences in this field, and were willing to share them. The data were collected through semi-structured interviews and analyzed using conventional content analysis. RESULTS: In general, the graduates' satisfaction with the course in terms of the five areas studied was evaluated as follows: Educational design, motivating participants to do their best had the greatest median. 5(4-5), Learning objectives; in all items, the median was 4. Course content and resources; all items median were 4 .Relevant learner assessment methods; in all items, the median was 4.The median learners' satisfaction in the areas of "course administrators' support" in all items was 4 and "learners' motivation ", was 5. Learner's motivation" in all items it was 4, indicating the highest level of satisfaction with the "acquisition of specialized skills". In the area of education design, the highest satisfaction was found with the appropriateness of teaching strategies. The codes extracted from the analysis of interviews with the graduates, are divided into four categories: "Ethical and professional commitment of course teachers", "Being a role model in the observance of patients and their caregivers' rights", "Course planning with a multidisciplinary approach and teamwork" as well as "The use of virtual platforms to strengthen and maintain team communication between learners". CONCLUSION: This course was the first experience of applying a multidisciplinary approach in an interprofessional course. Ideally, it is indispensable for the Iranian medical education system to move away from specialization and connect all related specialties and disciplines to achieve its educational and therapeutic goals. Therefore, the design of this course can be applied as an educational model for other disciplines and clinical courses.

Ketogenic diet: overview, types, and possible anti-seizure mechanisms.

The ketogenic diet (KD) has been used for a long time as a therapeutic approach for drug-resistant epilepsy. It is a high-fat, low-carbohydrate, and adequate protein diet. There are various types of KD with some differences in their compositions that mainly include classic KD, medium-chain triglyceride diet, modified Atkins diet, and low glycemic index treatment. The anti-seizure mechanisms of KDs have not yet completely understood but, some possible mechanisms can be theorized. The aim of the present study was to review the various types of KD and explain the probable biochemical mechanisms involved in its anti-seizure property.

Predictive factors for achieving independent walking in children with Guillain-Barre syndrome.

BackgroundTo determine the predictors of achieving independent walking at 2 and 6 months after onset of weakness in children with Guillain-Barre syndrome (GBS).MethodsChildren with GBS admitted to the Tabriz Children's Hospital were studied prospectively. All patients had frequent clinical evaluations until achieving independent walking. Unaided walking at 2 and 6 months and factors influencing these outcomes were determined using both univariate and multiple analyses.ResultsBetween 2003 and 2014, 324 children (mean age: 5.3±3.66 years) were admitted. The mean duration to independent walking was 2.97±3.02 months; 90.5% of patients could walk independently at 6 months. In the univariate analysis, disability score of >3 (P=0.03), autonomic nerve involvement (P=0.003), cranial nerve involvement (P=0.008), and absent compound muscle action potential (CMAP; P=0.048) were found to be significantly associated with poor walking outcome at 6 months. In the multivariate analysis, cranial nerve involvement (P=0.008) and absence of CMAP (P=0.022) were independently associated with poor functional outcome.ConclusionDisability score >3, cranial and autonomic nerve involvement, and absence of CMAP were predictors of independent walking in childhood GBS in this study; early rehabilitation program may prevent further impairments secondary to immobility in these patients.

Differential fatty acid analysis of cerebrospinal fluid in infants and young children with suspected meningitis.

PURPOSE: Meningitis is relatively common in infants and young children and can cause permanent brain damage. The aim of this study was to determine whether meningitis is associated with fatty acids in cerebrospinal fluid (CSF). METHODS: CSF samples from children between 3 months and 6 years of age admitted to the Tabriz public hospitals who met clinical criteria of meningitis were collected at enrollment. A total of 81 samples were analyzed for fatty acid profile by gas-liquid chromatography. RESULTS: Children with a purulent meningitis demonstrated a higher percentage of oleic acid (p < 0.05, >10 %) and lower percentages of omega-3 polyunsaturated fatty acids (p < 0.001, <-40 %) than aseptic meningitis and nonmeningitis groups did. There was an inverse relationship between CSF long-chain omega-3 fatty acids and the total number of leukocytes and differential counts of neutrophils and lymphocytes in the purulent meningitis group. Moreover, significantly lower omega-3 fatty acids (p = 0.001, -37 %) and higher ratio of n-6/n-3 (p = 0.02, -29 %) were found in patients with purulent meningitis with sepsis than in those with meningitis and no sepsis. CONCLUSIONS: This study provides evidence that purulent meningitis and its complication with sepsis are associated with important disturbances in CSF fatty acids, mainly deficiency in long-chain omega-3 polyunsaturated fatty acids.

Evaluating the status of antiganglioside antibodies in children with Guillain-Barré syndrome.

OBJECTIVE: Antiganglioside antibodies have been reported to play a role in the pathophysiology of Guillain-Barré syndrome (GBS). METHODS: This case-control study was designed to evaluate the status of antiganglioside antibodies in children with GBS. The study included 50 patients suffering from GBS as the case group and 30 children as the control group. Clinical information such as demographic data and recent digestive or respiratory infection (within the last month) was collected for all patients, and paraclinical studies including cerebrospinal fluid examination and electrophysiology were conducted by a subspecialized physician. Anti-GM1, anti-GQ1 and anti-GD1a antibodies were measured with ELISA and the EUROLINE method. RESULTS: The mean age of patients in the case and control groups was 5.3 ± 3.8 and 5.4 ± 3.4 years, respectively. With the EUROLINE method, the results obtained for anti-GM1 were significant (p = 0.007); however, the p values for anti-GQ1a and anti-GQ1b were not significant (0.051 vs. 0.94), while with ELISA, comparing all three antibodies in both the case and control groups showed statistically significant results, with a p < 0.05. CONCLUSION: EUROLINE is a new method used to evaluate antibodies in immune system diseases, but it is not useful for all antibodies specific to GBS, as the analysis was significant with a p value of 0.007 for anti-GM2.

Economic evaluation of stereotactic radiotherapy and stereotactic radiosurgery technologies in the treatment of cancers: a systematic review.

INTRODUCTION: This systematic review study investigated the cost-effectiveness of stereotactic radiotherapy (SRT) and stereotactic radiosurgery (SRS) for treatment of various types of cancers. METHODS: PubMed, Scopus, and Web of Science were searched from 30 December 1990 to 1 January 2023. The entered studies were screened in accordance with the inclusion criteria. The inclusion criteria encompassed all types of economic evaluation studies that investigated SRT/SRS technologies in the treatment of various cancers. RESULTS: A total of 47 articles were included in the review. The findings suggest that the use of Linear accelerator technology for the treatment of lung cancer (8 out of 12 studies) and prostate cancer (4 out of 5 studies) was a cost-effective strategy. Linear accelerator was found to be cost-effective in the treatment of liver metastases and liver cancer (2 out of 5 studies). All of the included studies that used Gamma Knife technology in brain metastases reported Gamma-Knife was a cost-effective treatment. Furthermore, in the treatment of prostate and liver cancer, proton therapy was identified as a cost-effective option than other treatments. CONCLUSIONS: This study confirms that SRT/SRS is a cost-effective procedure for the treatment of various types of cancers. Therefore, it is recommended to use SRT/SRS technology for optimal use of resources.

The relationship between psychosocial care and attitudes toward illness in adolescents with epilepsy.

Epilepsy is a significant health problem in Iran and other countries. Previous epilepsy studies conducted in Iran have often focused on physiological aspects and pharmacological therapy, and little attention has been paid to the psychological and social aspects of care, particularly in adolescence. This paper aims to fill this gap by assessing the relationship between psychosocial care and attitudes toward illness in adolescents with epilepsy. A descriptive correlational design was adopted, and 74 adolescents who experienced generalized seizures and were treated at the neurology clinic affiliated with the Tabriz University of Medical Sciences in 2010 were examined. The data were collected using instruments including (1) the patient demographic characteristics, (2) the Child Report of Psychosocial Care Scale, and (3) the Child's Attitude Toward Illness Scale. There was a significant positive correlation between psychosocial care and attitudes toward illness (p<.05). There is no evidence for routine psychological consultation for our sample; it would be helpful if psychological consultation with and without parents made available to adolescents with epilepsy.

Identification of a novel mutation in the HACD1 gene in an Iranian family with autosomal recessive congenital myopathy, with fibre-type disproportion.

Congenital fibre-type disproportion (CFTD) with myopathy, is a genetically heterogeneous disease in which there is relative hypotrophy of type-1-muscle-fibres compared to type-2-fibres on skeletal muscle biopsy. The classical characteristics of CFTD are infantile hypotonia and nonprogressive muscle weakness with a broad range of clinical manifestations. Pathogenic mutations in the HACD1 gene encoding 3-hydroxyacyl-CoA-dehydratase-1 have recently been reported to be associated with this disease. Whole-exome sequencing (WES) was conducted in a 12-year-old girl born to consanguineous parents from the Iranian-Azeri-Turkish population. She was diagnosed with congenital myopathy at the age of 4-month-old due to hypotonia and abnormal electromyography. DNAs were extracted from the blood samples of the proband and her parents, and subjected to PCR-Sanger-sequencing to confirm the WES result. WES data analysis identified a homozygous single nucleotide change (A>T) at position c.785-2 located in intron 6 of the HACD1 gene (NC_000010.11(NM_014241.4):c.785-2A>T). This novel mutation located at the splice-acceptor site is disturbing the splicing procedure. The absence of this mutation among our control group (100 normal healthy adults from the same ethnic group) and not being reported in any other population database confirms the pathogenicity of this mutation. Bioinformatics analysis also classified this variant as a pathogenic mutation. PCR-Sanger-sequencing data analysis confirmed the WES result in the proband and showed that the parents were carriers for the mutation. A substitution (NC_000010.11(NM_014241.4):c.785-2A>T) mutation resulted in the removal of the splicing acceptor site at the HACD1 gene. This pathogenic mutation is associated with CFTD disease.

Economic evaluation of ferric carboxymaltose compared with placebo in iron-deficient patients with heart failure: a systematic review.

BACKGROUND: It has been shown that ferric carboxymaltose (FCM) improves symptoms and quality of life in iron-deficient patients with heart failure (HF). AIM: We aimed to systematically review studies conducted on the cost-effectiveness of FCM compared to placebo in iron-deficient patients with HF. METHOD: We searched PubMed, EMBASE, Scopus, and Web of Science to find the relevant studies. After removing duplicates, two authors independently evaluated the titles, abstracts, and full texts. We included studies that investigated the full economic evaluations of FCM in HF patients with iron deficiency (cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis) and used the CHEERS tool to evaluate the quality of the studies. RESULTS: Seven studies were included which evaluated the economic analysis of treatments with FCM in iron-deficient patients with HF. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF. CONCLUSION: FCM is a cost-effective treatment for iron-deficient patients with HF. Considering the fact that all the included studies in the present systematic review took place in high-income countries, we recommend further studies investigating the cost-effectiveness of FCM in low- and middle-income countries.

Cost Effectiveness of Adding Dapagliflozin to Standard Care in Heart Failure Patients with Reduced Ejection Fraction: A Systematic Review.

INTRODUCTION: Dapagliflozin, a new treatment option for heart failure, leads to a significant reduction in the hospitalization of patients with heart failure. We aimed to review studies on the economic evaluation of adding dapagliflozin to standard care compared with standard care alone in heart failure patients with reduced ejection fraction (HFrEF). METHODS: For this systematic review, the PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA Registry scientific databases were searched from 1 January 2020 to 25 March 2022. Two of the present researchers screened titles and abstracts, extracted data from full-text articles, and evaluated their quality using the Quality of Health Economic Studies (QHES) checklist for the quality assessment of health economic studies. RESULTS: Of the 456 abstracts screened, 19 studies met the inclusion criteria. The mean QHES score for the studies was 0.87 (high quality). Eight studies on cost-effectiveness analysis, ten studies on cost-utility analysis, and one study on cost-minimization analysis were conducted. Based on the available evidence and the present findings, the addition of dapagliflozin to standard care in patients with HFrEF was cost effective in most countries. CONCLUSIONS: Based on the results of the present study, the addition of dapagliflozin to standard care in patients with HFrEF was cost effective. More studies investigating the cost effectiveness of dapagliflozin in patients with HFrEF are required in light of the actual epidemiological data of countries in the relevant input parameters. It is also recommended to conduct cost-effectiveness studies of dapagliflozin taking into account costs and benefits from a societal perspective.

The Effects of Vitamin B-Complex Supplementation on Serum Homocysteine Levels and Migraine Severity in Children A Randomized Controlled Trial.

Objectives: Given that deficiency in B vitamins can lead to the accumulation of homocysteine (Hcy), and hyperhomocysteinemia may have a role in migraine pathogenesis, the present prospective randomized double-blinded placebo-controlled trial aimed to evaluate the effect of vitamin B-complex supplementation on the alleviation of migraine in children through a possible reduction in Hcy levels. Materials & Methods: Ninety children under 15 years of age suffering from typical migraine were included in the present trial. They were randomly assigned into two groups (forty-five patients in each group) to receive either vitamin B-complex or a matching placebo for six months. Serum Hcy levels and headache characteristics were evaluated and compared before and after administering vitamin B-complex or placebo. Results: Unlike the placebo group, the monthly headache frequency, severity of headache, headache disability, and serum Hcy levels were significantly decreased after the vitamin administration. The headache duration was not significantly different before and after the treatment. In the vitamin group, there were significant positive correlations between the frequency and severity, frequency and disability, and severity and disability of headaches. Hcy also had significant positive correlations with the frequency and disability of headaches. In the placebo group, the only found significant correlation was between headache frequency and disability. Conclusion: The administration of vitamin B-complex might effectively relieve migraine severity in children by reducing serum Hcy. However, further studies are needed to confirm the results.

Cost-effectiveness of remdesivir for the treatment of hospitalized patients with COVID-19: a systematic review.

BACKGROUND: Remdesivir is being studied and used to treat coronavirus disease 2019 (COVID-19). This study aimed to systematically identify, critically evaluate, and summarize the findings of the studies on the cost-effectiveness of remdesivir in the treatment of hospitalized patients with COVID-19. METHODS: In this systematic review, PubMed, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched for studies published between 2019 and 2022. We included all full economic evaluations of remdesivir for the treatment of hospitalized patients with COVID-19. Data were summarized in a structured and narrative manner. RESULTS: Out of 616 articles obtained in this literature search, 12 studies were included in the final analysis. The mean score of the Quality of Health Economic Studies (QHES) for the studies was 87.66 (high quality). All studies were conducted in high-income countries (eight studies in the USA and one study in England), except for three studies from middle-to-high-income countries (China, South Africa, and Turkey). Six studies conducted their economic analysis in terms of a health system perspective; five studies conducted their economic analysis from a payer perspective; three studies from the perspective of a health care provider. The results of five studies showed that remdesivir was cost-effective compared to standard treatment. Furthermore, the therapeutic strategy of combining remdesivir with baricitinib was cost-effective compared to remdesivir alone. CONCLUSIONS: Based on the results of the present study, remdesivir appears to be cost-effective in comparison with the standard of care in China, Turkey, and South Africa. Studies conducted in the United States show conflicting results, and combining remdesivir with baricitinib is cost-effective compared with remdesivir alone. However, the cost-effectiveness of remdesivir in low-income countries remains unknown. Thus, more studies in different countries are required to determine the cost-effectiveness of this drug.

The possible anti-seizure properties of Klotho.

Recurrent seizures in epilepsy may lead to progressive neuronal damage, which can diminish health-related quality of life. Evaluation and control of pathological processes in the brain is valuable. It seems imperative that new markers and approaches for seizure alleviation be discovered. Klotho (Kl), an antiaging protein, has protective effects in the brain against neurological disorders. It may also have antiseizure effects by improving creatine transfer to the brain, upregulating excitatory amino acid transporters, and inhibiting insulin/insulin-like growth factor-1 (IGF-1), Wingless (Wnt), transforming growth factor-beta (TGF-ß), and retinoic-acid-inducible gene-I (RIG-I)/nuclear translocation of nuclear factor-κB (NF-κB) pathways. Stimulation and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and apoptosis signal-regulating kinase 1 (ASK1)/p38 mitogen­activated protein kinase (MAPK) signaling pathways could also be considered other possible antiseizure mechanisms of Kl. In the present review, the roles of Kl in the central nervous system as well as its possible anti-seizure properties are discussed for the first time.

The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy.

BACKGROUND: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. OBJECTIVE: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). METHODS: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. RESULTS: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. CONCLUSIONS: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Peripheral neuropathy as a very rare symptom in a patient with Niemann-Pick type C with negative enzymatic evaluation: a case report.

BACKGROUND: Niemann-Pick is a rare metabolic disease distinguished by lysosomal storage defects. This disease is characterized by sphingomyelinase acid deficiency, causing its accumulation in various organs such as the kidneys, spleen, liver, brain, and nerves. Niemann-Pick disease is categorized into four groups: A, B, C, and D. Peripheral neuropathy is an extremely rare complication in patients with Niemann-Pick type C, which certainly leads to neurologic deterioration. CASE PRESENTATION: We report a case of Niemann-Pick type C disease in a 3-year-old Iranian Azeri female patient who was hospitalized twice. The first time was at 1 month of age with symptoms of splenomegaly, jaundice, and elevated liver enzymes, and the second time was at around age 2 for loss of mental and physical abilities. The patient presented with failure to thrive. According to paraclinical examinations, mildly delayed myelination along with a nonspecific periventricular hypersignal intensity was seen. Interestingly, the patient's Niemann-Pick type C enzymatic function was evaluated twice and was negative on both occasions, while she was positive for NPC1 and NPC2 gene examinations. CONCLUSIONS: In this study, despite the enzymatic study being negative, Niemann-Pick type C disease was finally confirmed, revealing the importance of mutations in Niemann-Pick type C pathogenesis. Besides, peripheral neuropathy was diagnosed in this patient as a very rare symptom of Niemann-Pick type C.

Clinical presentation, electrodiagnostic findings and outcomes of acute flaccid myelitis: A brief review and case series.

Acute flaccid myelitis (AFM) is an acute condition occurring mostly in children. Although affected patients can show a broad spectrum of symptoms, it is mainly characterized by the progressive onset of focal limb weakness, presenting over a period of hours to a week, with or without pain, and spinal cord gray matter involvement on magnetic resonance imaging (MRI). There is compelling evidence to support the role of viruses, in particular enteroviruses. Studies describing electrodiagnostic (EDX) abnormalities and long-term outcomes in AFM are limited. In this report, the clinical presentation, EDX and MRI findings, and long-term outcomes in three children with AFM who presented with progressive and asymmetric weakness of the limbs are described. MRI showed a long segment cervicothoracic lesion with vertical expansion in all three cases. Patients do recover in time, but many continue to have permanent muscle weakness in the worst affected part(s), and complete recovery is rare. Follow-up of these three cases at 18 months demonstrated a partial recovery in the motor system.