Comparative efficacy of risdiplam and nusinersen in Type 2 and 3 spinal muscular atrophy patients: A cohort study using real-world data Mahmoud Reza Ashrafi, Marzieh Babaee, Seyed Saeed Hashemi Nazari, Mohammad Barzegar, Mohammadreza Ghazavi, Mehran Beiraghi Toosi, Shahriar Nafissi, Soroor Inaloo, Gholamreza Zamani Ghaletaki, Farzad Fatehi, Ramin Heshmat, Masood Ghahvechi Akbari, Alireza Abdi, Hassan Bakhtiary, Hadi Montazerlotfelahi, Ali Abbaskhanian, Seyed Ahmad Hosseini, Hossein Farshadmoghadam, Seyyed Mohammad Mahdi Hosseiny, Fakhreddin Shariatmadari, Bentolhoda Ziaadini, Meisam Babaei, Azita Tavasoli, Sedighe Nikbakht, Aliakbar Momen, Ali Khajeh, Vahid Aminzadeh, Mohsen Mollamohammadi, Mohammad Mehdi Taghdiri, Mohammad Mehdi Nasehi, Sara Memarian, Reza Shervin Badv, Morteza Heidari, Narjes Jafari Journal of Neuromuscular Diseases, 2024 Background Three medications have been approved for spinal muscular atrophy (SMA) treatment. No head-to-head clinical trials have directly compared the efficacy of nusinersen and risdiplam. We compare the efficacy of them in Type 2 and 3 SMA patients, with 6 months of follow-up. Methods A multicenter cohort study was conducted. Demographic, genetic and clinical findings containing Hammersmith Functional Motor Scale Expanded (HFMSE) and revised upper limb module (RULM) scales were gathered. An increase of at least 3 points in HFMSE and RULM scores was considered a positive response. Results 73 (58.4%) children received risdiplam, and 52 (41.6%) received nusinersen non-randomly, based on clinical decision. The difference in HFMSE and RULM scores compared to the baseline was significant in both groups (P-value <0.001). However, there was no significant difference between mean difference changes in HFMSE and RULM scores between the two groups. 80.4% of patients in the risdiplam group and 72% in the nusinersen group achieved the 3-point cutoff after 6 months, and there is no significant difference between the two groups (P-Value:0.33). Conclusions This study showed that both medications significantly changed the HFSME and RULM after 3 and 6 months of follow-up. However, there was no significant difference between the two drugs according to the HFSME.
Clinical and Genetic Characteristics of Limb-Girdle Muscular Dystrophy in Iranian Patients Hossein Farshadmoghadam, Gholamreza Zamani, Mahmoud Reza Ashrafi, Ali Reza Tavasoli, Morteza Heidari Iranian Journal of Pediatrics, 2023 Background: Limb-girdle muscular dystrophy (LGMD) is a bothersome muscle disease associated with weakness of the shoulder and pelvic girdle. Objectives: The study aimed to determine the genetic diversity and relative frequency of various forms of LGMD in Iranian children. Methods: In this descriptive research, 60 children referred to the neurology or emergency department of the Pediatric Medical Center were studied from April 2019 to April 2020. Additional tests (muscle biopsy and genetic testing) were performed to confirm the diagnosis of LGMDs. Quantitative data such as disease level, motor, respiratory, and cardiac functions, and molecular data underwent statistical analysis. Results: A total of 41 patients with a mean age of 11.1 were studied. Twenty-two patients were diagnosed with genetic tests and 19 with muscle biopsies. Also, there were 26.8% cases of alpha sarcoglycanopathy, 24.4% beta sarcoglycanopathy, 17.1% gamma sarcoglycanopathy, 7.3% calpainopathy, 7.3% dysferlinopathy, 7.3% dystroglycanopathy, 7.3% titinopathy, and one case of laminopathy. Among genetically confirmed individuals, 27.3% had SGCB mutation, and 18.2% had SGCA mutation. A significant relationship was seen between the mutation type and creatine phosphokinase (CPK) levels (P < 0.05). Conclusions: The prevalence of alpha and beta sarcoglycanopathy phenotypes in the study population showed that the severity of clinical involvement may be predicted by SGCB gene mutation and sarcoglycan expression.
The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy Vahid Mansouri, Morteza Heidari, Maryam Bemanalizadeh, Reza Azizimalamiri, Shahriar Nafissi, Masood Ghahvechi Akbari, Mohammad Barzegar, Ali Reza Moayedi, Reza Shervin Badv, Mahmood Mohamadi, Ali Reza Tavasoli, Susan Amirsalari, Ali Khajeh, Soroor Inaloo, Farzad Fatehi, Sareh Hosseinpour, Meisam Babaei, Seyed Ahmad Hosseini, Seyyed Mohammad Mahdi Hosseiny, Afshin Fayyazi, Firoozeh Hosseini, Mehran Beiraghi Toosi, Nahid Khosroshahi, Homa Ghabeli, Habibeh Nejad Biglari, Simin Khayatzadeh Kakhki, Seyed Hossein Mirlohi, Elham Bidabadi, Bahram Mohammadi, Abdolmajid Omrani, Mostafa Sedighi, Mohammad Vafaee-Shahi, Maryam Rasulinezhad, Seyyed Mohamad Hoseini, Mojtaba Movahedinia, Zahra Rezaei, Parviz Karimi, Hossein Farshadmoghadam, Saeed Anvari, Omid Yaghini, Jafar Nasiri, Gholamreza Zamani, Mahmoud Reza Ashrafi Journal of Neuromuscular Diseases, 2023 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.
The role and therapeutic applications of exosomes in multiple sclerosis disease Khalil Komlakh, Seyed Hossein Aghamiri, Hossein Farshadmoghadam Clinical and Experimental Pharmacology and Physiology, 2022 A range of the central nervous system (CNS) and immune cells are affected by multiple sclerosis (MS), a complex autoimmune disease of the CNS. Chronic neuroinflammation, demyelination, and neuronal death are all features of MS, but the disease's molecular mechanisms are unknown. Exosomes are small, membrane‐bound extracellular vesicles with a crucial role in cell communication. They are stable in biological fluids and emerge from the cell membrane during endocytic internalization. It might be possible to recognize better the mechanisms involved in the development and progress of illnesses by understanding the variety of exosomal contents and their associated targets, like neurologic disorders. In this review, we sought to bring together important data on the biology of exosomes in MS and highlight discoveries on these nanoparticles' prognostic, diagnostic and therapeutic potential.
Novel Missense Variation in NDUFA9 Gene in an Iranian Patient with Fatal Leigh Syndrome Pourandokht Gholamipour Shirazi, Abolfazl Heidari, Hossein Farshadmoghadam Iranian Journal of Pediatrics, 2022 : Mitochondrial diseases are caused by disturbances in the oxidative phosphorylation (OXPHOS) system. Leigh syndrome encompasses a spectrum of mitochondrial diseases characterized by necrotizing encephalopathy. Thus far, two cases carrying a variant in NDUFA9 with a diagnosis of Leigh syndrome have been reported. NDUFA9 is a subunit involved in the assembly and stability of the mitochondrial respiratory complex I. We present a lethal phenotype of Leigh syndrome in a four-month-old boy born to a consanguineous (first cousins) Iranian couple. The patient’s clinical course was notable for episodes of cyanosis, seizures, lactic acidosis, nystagmus, spastic paraplegia, apnea, and respiratory arrest. Due to high branched-chain amino acids, an initial diagnosis of maple syrup urine disease was considered; however, the patient did not respond to treatment. Via exome sequencing, we identified a novel homozygous missense variation in NDUFA9 (c.1069C>G, p.Arg357Gly), and a posthumous diagnosis of Leigh syndrome was made. This report highlights the potential differential diagnosis of Leigh syndrome and further describes the phenotypic spectrum of NDUFA9 defects.
Triosephosphate Isomerase Deficiency: The First Case Report from I.R. Iran Majid Vafaie, Manoochehr Mahram, Hossein Farshadmoghadam Iranian Journal of Pediatrics, 2022 Introduction: Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disease and the most severe form of glycolytic enzymopathies, characterized by hemolytic anemia, neurological disorders, infections, and muscle weakness that can affect breathing and heart function. Signs and symptoms include anemia, pallor, jaundice, fatigue, shortness of breath, muscle weakness, atrophy, movement problems, dystonia, tremors, seizures, cardiomyopathy, and diaphragm weakness. Case Presentation: A three-day female newborn was admitted because of hemolytic anemia. All usual assessments for hemolysis, G6PD, osmotic fragility, RBC morphology and cell panel, minor blood groups, antibody screening, and echocardiography were normal. Neurological manifestations appeared after six months of age, including some seizure-like movements, dystonia, and opisthotonus. Whole exome sequencing confirmed the diagnosis of TPI deficiency with the variant NM-000365.5:c.315G>C chr12-6978338(hg19) which revealed the mutation of p.Glu105Asp. By the age of two years, in addition to some drugs for neurologic manifestations and folic acid, the patient was hospitalized every 30 - 45 days for blood transfusion or because of pneumonia. The episodes of pneumonia increased after 24 months of age, and finally, the child expired at the age of 34 months due to pneumonia and respiratory failure. Conclusions: Triosephosphate isomerase deficiency should be considered in all neonates with hemolytic anemia without usual causes.
Brain on FIRES: Super refractory seizure in a 7 yr old boy Iranian Journal of Child Neurology, 2016
Be careful of lies: A 6 years old boy with respiratory distress and decreased level of consciousness Acta Medica Iranica, 2014
Human herpesvirus 6 infection in febrile children: Frequency in an Iranian referral hospital H. Farshadmoghadam, B. Pourakbari, S. Mahmoud, R. H. Sadeghi, S. Mamishi British Journal of Biomedical Science, 2014 Polymerase chain reaction (PCR) tests for virus in blood and saliva are frequently positive in persons with past infection, re-infection with new strains or latency with or without repeated reactivation of human herpesvirus 6 (HHV6). The aim of this study is to determine the frequency of HHV6 infections in children aged two years or under with an initial diagnosis of fever during an evaluation in the paediatric emergency department of the Children’s Medical Center, an Iranian referral hospital, using PCR methodology. In all children, the clinical characteristics noted at the initial evaluation as well as demographic and laboratory findings were obtained. Among 150 patients (91 male, 59 female) admitted to the paediatric emergency department, HHV6 was found in 49 (33%; 14 female [29%] and 35 male [71%]). Rash was seen in 14/49 (29%) of HHV6-positive cases, while 35 cases without rash had a positive PCR test (71%). Seizures were found in 78/150 (52%) patients. There was no significant association between seizures and positive HHV6 results (43% in patients without seizure; 57% in cases that developed seizure). Although standard PCR on samples including blood cannot discriminate between latent and active HHV6 infection, nearly a third of patients (mainly children less than one year old) had HHV6 infection.
Sudden impolite behavior in a polite girl: A case report Acta Medica Iranica, 2014
A neonate with indurate dermal papules and nodules and pneumonia: A Case Report Acta Medica Iranica, 2014
