Review Article

Pulmonary Involvement in Neuromuscular Diseases: A review

Ghamartaj Khanbabaee, Parvaneh Karim Zadeh, Mohammad Mahdi Nasehi, Seyed Ahmad Tabatabaii, Matin pourghasem, Fariba Alaei, Saeed Sadr, Nazanin Farahbakhsh, Seyedeh Zalfa Modarresi, Fatemeh Khazaii, Maedeh Soflaee, Abdolhamid taghizadeh behbahani, Nafiseh Fadavi, Mahsa Pourghasem

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 9-17

Neuromuscular diseases (NMDs) affect muscle function directly or indirectly by affecting nerves or neuromuscular junctions. One of the leading causes of death in patients with NMD is respiratory muscle
weakness (RMW). Respiratory involvement in patients with NMD can manifest widely, from mild failure that may initially affect only sleep to severe failure that can be life-threatening. Care approaches include arranged and precise clinical follow-ups of signs of sleep-disordered breathing, daytime hypoventilation, coughing, and swallowing disturbances. This manuscript will review the mechanisms and abnormalities of respiratory function in patients with NMD and help optimize NMD management.

Research Article

The Efficacy and Safety of Rapamycin in Children with Tuberous Sclerosis: A Cross-sectional Study

Fateme Tehrani , Nahideh Khosroshahi , Zarrin Keihanidoust , Soheila Dabiran, Mohammad Reza Zarkesh

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 19-29



Mutations in TSC1 or TSC2 genes have been proposed as the main causative factors responsible for developingTuberous Sclerosis Complex (TSC). Given the effect of these two genes on the mTOR pathway,rapamycin hasemerged as a novel therapeutic agent.The present study evaluated the effectiveness and safety of rapamycin on the multiple manifestations of TSC.

Materials & Methods

Twenty-three eligible children were enrolled in the present crosssectional study. They were prescribed rapamycin1mg tablet twice daily for the first two weeks of treatment and then once daily for at least one year.Periodicevaluations through follow-up visits were performed Besides, growth and developmental statuses wereevaluated. All data, including the number and size of brain tuberomas, size of renal angiomyolipomas, and skinlesions, were gathered and recorded, and then analyzed.


During the study period, the mean number of epileptic episodes significantly reduced (p<0.0001), and nine cases were seizure-free at the final visit. The mean number of brain tuberomas decreased from 19.3±11.0 at the initial visit to 11.1±5.6 and 8.2±3.2 in the subsequent visits (p<0.001). The mean size of brain tuberomas similarly decreased from 17.9±18.5 cm at enrollment to 13.7±5.1 cm and 6.9±5.1 cm in the second and third visits, respectively (p=0.029). The mean size of renal angiomyolipomas significantly decreased (p<0.001). A significant trend toward a decrease in the number of skin lesions was observed (p<0.0001). No relationship was observed between the effects of rapamycin and the patient’s age or sex (p>0.05). Changes in patients’ growth and developmental features were not statistically significant through subsequent visits (p=0.507).


This study revealed the effectiveness and safety of rapamycin on TSC among our patients



Vitamin D insufficiency/rickets is a metabolic bone disease that leads to insufficient mineralization of bone. Chronic neurological diseases, including cerebral palsy (CP), convulsive disorders, neural tube defects, myopathy, immobility, lack of sun exposure, inadequate nutrition, and antiepileptic drugs (AEDs) can cause vitamin D insufficiency and osteopenia in children.

Materials & Methods

In this study, the authors searched the frequency and causative factors of vitamin D insufficiency in children with chronic neurological diseases such as CP, hypoxic-ischemic encephalopathy, mental motor retardation, epilepsy, neurodegenerative and neuromuscular diseases, meningitis-encephalitis sequelae, neural tube defects, paralysis, and paresis. This cross-sectional study included 108 children (forty-five [41.6%] females; sixty-three [58.4%] males), aged between one and 18 years with chronic neurological diseases, and a control group of thirty age-matched healthy children (16 [53.3%] females; 14 [46.7%] males.


Vitamin D levels were significantly lower, and parathyroid hormone (PTH) levels were significantly higher in the patient group than in the control group (p<0.05). The patient group was divided into four subgroups: (i) Epilepsy (n=41; 38%), (ii) Neural tubedefects (n=14; 13%), (iii) CP (n=21; 19%), and (iv) other diseases (neurodegenerative and neuromuscular diseases, meningitis sequelae, intracranial hemorrhage, psychomotor retardation, hypoxic-ischemic encephalopathy) (n=32; 30%) to identify any differences in the measured levels. In the patient group, eighty-three (76.9%) had vitamin D deficiency, and 17 (15.7%) had vitamin D insufficiency, while in the control group, twenty-one (70%) had vitamin D insufficiency. The use of AEDs had no significant effect on serum Ca, P, ALP, PTH, orvitamin D levels (p>0.05), and serum Ca levels were significantly higher in ambulant patients than in non-ambulant patients (p<0.05). Vitamin D levels were significantly higher in the non-ambulant than in the ambulant patients (p<0.05). No rickets was determined in the control group, while in the patient group, nine (8.3%) had level-1 rickets, six (5.6%) had level-2 rickets, and two (1.9%) had level-3rickets.


Children with chronic neurological diseases have low serum vitamin D levels, and vitamin D prophylaxis is essential in this group


This study investigates the impact of modified constraint-induced movement therapy (m-CIMT), accompanied by occupation-based and activity analysis, on the participation of children with hemiplegia.

Materials & Methods

Twenty-three participants were randomly assigned to the intervention and control groups. The intervention group received occupation-based m-CIMT (m-CIMT along with occupation-based and activity analysis), while the control group received m-CIMT without occupation-based and activity analysis. The intervention was conducted one hour perday, three days a week, for four weeks.


The primary outcomes revealed no significant differences between groups in promoting the participation of children with hemiplegia in the activities of daily living (ADL). However, scores were higher in the intervention group with a medium to large effect size (Canadian occupational performance measure: F(1,19)=2.14, P=0.160, η2 P=0.101, Canadian occupational performance measure-satisfaction: F(1,19)=1.53,P=0.231, η2 P=0.075, Goal attainment scaling: F(1,19)=5.55, P=0.029, η2 P=0.226). This effect remained during the follow-up period. The secondary outcomes indicated no significant differences between groups in improving the manual ability of the children. However, scores were higher in the intervention group with a medium to large effect size (ABILHAND-Kids: F(1,19)=0.64, P=0.434, η2 P=0.033, pediatric motor activity log- how long: F(1,19)=3.53, P=0.076, η2 P=0.157, pediatric motor activity log- how well: F(1,19)=2.59, P=0.124, η2 P=0.120). This effect was sustainable during the follow-up period.


m-CIMT accompanied by occupation-based and activity analysis and the client-centered paradigm substantially enhances the manual ability of children with hemiplegia and their participation in the ADL.

The relationship between anxiety and salivary alpha amylase levels in mothers of neonates admitted to neonatal intensive care unit

fateme eghbalian, Mohammad Ahmadpanah , Mohammad Ali Seif Rabiei , Parya Khadem, Mohammad Hasan Saati Asr

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 55-61



Anxiety is a significant health issue in mothers who give birth to unhealthy neonates. Different studies have investigated the relationship between anxiety and alpha-amylase. According to the necessity for psychological care of mothers whose infants are hospitalized in intensive care units and consequently the anxiety that is imposed on mothers due to the condition, this study aims to assess anxiety in these mothers and the relationship between this anxiety and salivary alpha-amylase.

Materials & Methods

This study was a cross-sectional study conducted at Besat Hospital in Hamadan in 2021. Thirty mothers were enrolled in the study through a census method sampling. The Hamilton questionnaire measured maternal anxiety during the children’s hospitalization period. Salivary alpha-amylase samples were taken from all mothers according to the scientific method, and mothers’ salivary alphaamylase levels were measured. All the gathered data were analyzed using SPSS 21 software. The significant level was considered 0.05 in all comparisons.


The mean age of the 30 mothers was 29.27+6.24 years. The mean score of maternal anxiety was 16.27 + 6.78, and the mean salivary amylase level was 33.02 ± 16.22 U / ml. Fourteen mothers obtained low anxiety scores, 14 had moderate anxiety, and two had severe anxiety. No significant relationship was found between the mean of salivary alpha-amylase at the three levels and anxiety. There was no significant relationship between anxiety level with parent location,age, mother’s level of education, infant gender, and child rank.


According to the results of the present study, there was no significant relationship between the level of alpha-amylase and the level of anxiety in mothers of neonates admitted to the neonatal intensive care unit (NICU), so further researches in similar groups that are in anxious conditions seem necessary.

Awareness of Nigerian Mothers on the Risk Factors, Prevention and Management of Seizures in Newborns

Oluwatosin Olarinde, Bayo Lawal Ajibade, Cynthia Adaku Attah, Oluwadamilare Akingbade

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 63-73


The study aimed to assess the awareness of mothers on the risk factors, prevention, and management of seizures in newborns.

Materials & Methods

This descriptive cross-sectional study was conducted on 359 mothers using simple random sampling. The data were collected using questionnaires that included general awareness, awareness of the causes, risk factors, prevention, and management. The data collected were analyzed using frequencies and percentages. Null hypotheses were tested using chi-square at 0.05 level of significance


Two hundred seventy-four mothers (76.3%) had high awareness of seizures in newborns, thirty-four (9.5%) had average awareness, and fifty-one (14.2%) had low awareness. Two hundred and seventythree mothers (76%) had high awareness of the risk factors, and eighty-six (24%) had low awareness, meaning that although some respondents had misconceptions, awareness of the risk factors and causes was good. Two hundred twenty-three (62.1%) respondents had high awareness of preventing seizures in newborns, while 136 (37.9%) had low awareness. The awareness of respondents on managing seizures in newborns is positive, as 291 (81.1%) had high awareness of managing seizures in newborns, while sixty-eight (18.9%) had low awareness. There was a significant relationship between age (p =0.000), marital status (p=0.018), level of education (p =0.000), and awareness of risk factors of seizures in the newborn


A high awareness of neonatal seizures was found among mothers because of their high educational level, although some still had some misconceptions. Improving maternal neonatal seizure awareness and appropriate educational interventions to correct misconceptions are needed.

Walking Ability, Participation, and Quality of Life in Children with Spastic Diplegic Cerebral Palsy: A Path Analysis Study

Roshanak Vameghi, Seyed Ali Hoseini, Samira Heydarian, Hossein Azadeh, Masoud Gharib

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 75-91



This study aims to design a conceptual model for the effect of various factors on walking ability, participation, and quality of life in children with spastic diplegic cerebral palsy (SDCP) and test it based on field data using path analysis.

Materials & Methods

This cross-sectional study was performed on 181 children with SDCP. The following were used to measure each of the variables: the Modified Ashworth Scale, the Micro Manual Muscle Tester, the Timed Up and Go Test (TUG), the Boyd and Graham test, the goniometer, weight and height, the Gross Motor Function Classification System, the Life Habits Questionnaire, and cerebral palsy Quality of Life Questionnaire for Children. The structural model was tested in Amos 17.


All paths of the proposed model were significant (P <0.05). Among evaluated variables, muscle strength (B = -0.466), balance (B = 0.326), and spasticity (B = 0.143) affected walking ability. Moreover, as an intermediate factor, walking ability affected the subjects’ participation (B = -0.819) and quality of life (B = -0.183).


Muscle strength, balance, and spasticity are the most influential factors in the walking ability of children with SDCP. Furthermore, walking ability and participation are two critical factors in promoting the quality of life of these children.

The Effect of an Exercise Package for Students with Intellectual Disability on Motor and Social Development

Ali Kashi, Helen Dawes , Maedeh Mansoubi , Zahra Sarlak

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 93-110



Physical activity and reducing inactivity improve health, well-being and benefits the social development of young people with intellectual disability (ID) lasting into adulthood. Therefore, given the importance of encouraging an active lifestyle in adolescents, researchers developed and evaluated the feasibility and potential effect of a novel “Sport Science Research Institute (SSRI) exercise package for young people with intellectual disability” to improve the motor and social development of these individuals.

Materials & Methods

In a Randomised controlled trial between October 2019 to February-2020, Thirty-six 7-18-year-old students with mild intellectual disabilities who were studying in a special school in Tehran received the invitation to the study. Students were randomly divided into intervention (18 students) and control (18 students) groups. Before and after the exercise program, three sessions per week for 12 weeks, motor proficiency was measured using the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), and social development was measured using the Vineland Social Maturity Scale (VSMS).


Pupils in the intervention group completed 92% of the sessions. The results of the ANCOVA test showed that the exercise program led to a statistically significant improvement in total motor proficiency (P<0.01) and total social maturity score (P<0.015).


According to this study the, SSRI training package achieved good adherence and increased physical activity and showed potential to improve motor and social skills in young people with intellectual disability.

Prevalence of positive findings of brain computed tomography scans in pediatric population

Amirreza Jahanshahi, Shahram Sadeghvand, Mohammad Khalafi, Alireza Jafarzadeh, Armin Zarrintan

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 111-117



Computed tomography (CT) scans are used more frequently in medical centers, increasing unnecessary requests for it as a first-line evaluation. This study aimed to investigate the rate and prevalence of abnormal findings in a brain CT scan in children at the Children’s Hospital of Tabriz, Iran.

Materials &Methods

This study was a cross-sectional descriptive-analytical study that included all children under 15 years old undergoing a brain CT scan at the Children’s Hospital of Tabriz, Iran. All patients who fulfilled the inclusion criteria and were referred to the Children’s Hospital of Tabriz during the spring of 2018 entered the study. Age, gender, patient history, and clinical findings were examined. In the next step, the results of each patient’s CT scan were evaluated.


In this study, 108 patients were studied with a median age of 18.0 months. CT scan results were normal in seventy-four cases (68.5%), hydrocephalus was seen in 15 (13.9%), and benign infantile hydrocephalus was seen in eight (7.4%). The study revealed a statistically significant relationship between patient history and CT scan results (p=0.017). A statistically significant relationship was observed between the clinical findings and CT scan results (p=0.042).


Brain CT scans have more abnormal findings in patients with positive clinical findings. Although a CT scan is a highly sensitive and specifimodality in diagnosing central nervous system (CNS) abnormalities, its value depends on the underlying medical history and physical exam.

The Effect of Probiotics on Headaches in Children with Migraine Treated with Sodium Valproate A Randomized Controlled Clinical Trial

Elham Bidabadi, Mitra Elyasi, Afagh Hassanzadeh Rad, Ehsan Kazemnezhad

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 119-126



Migraine is one of the most common complaints in children. This study aimed to determine the effect of probiotics (KidiLact) on headaches in children aged six to 15 years with migraine treated with sodium valproate.

Materials & Methods

This double-blind, randomized controlled clinical trial was performed on eighty children with migraine treated with sodium valproate. Patients were divided into two groups. All patients in the intervention and control groups received two sachets of probiotics and a placebo daily for four months, respectively. They were compared in terms of frequency and severity of headaches and painkiller consumption before and two and four months after initiating probiotics.


The mean number of headaches in the second and third visits in the probiotic group was 1.27 and 1.18, and 2 and 1.50 per month in the placebo group, respectively. The authors observed a significant difference between the two groups in the second (P = 0.010) and the third visit (P = 0.019). Moreover, the mean severity of headache in the second and third visits in the probiotic group was 1.38 and 1.23, and 1.60 and 1.53 in the placebo group, respectively. The authors demonstrated that the daily consumption of painkillers in the probiotic group was significantly reduced compared to the placebo Received: 23-Des-2022 group (P = 0.007).


Using probiotic supplements seems to significantly affect the severity and frequency of migraine headaches compared to the placebo, and daily consumption of painkillers was significantly reduced in the probiotic group compared to the placebo group

Neurometabolic Disorder Articles

A Novel Mutation in the OXCT1 Gene Causing Succinyl-CoA:3-Ketoacid CoA Transferase (SCOT) Deficiency Starting with Neurologic Manifestations

Davoud Amirkashani, Mostafa Asadollahi, Rozita Hosseini, Saeed Talebi, Zahra Golchehre, Mohammad Keramatipour

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 127-133


Succinyl-CoA:3-oxoacid CoA-transferase (SCOT) deficiency is an inborn error of ketone body utilization characterized by intermittent ketoacidosis crises. This study reports the first Iranian patient with SCOT deficiency who presented with seizure and hypotonia at birth.
Accordingly, she was consequently re-hospitalized due to hypotonia and respiratory distress. Laboratory tests revealed hyperammonemia, ketonuria, and metabolic acidosis. Besides, the plasma glucose level was normal without any other abnormality. Despite treatment with high-dose bicarbonate, severe acidosis persisted. Poor response to treatment raised a significant diagnostic challenge among specialists until genetic investigation identified a homozygous nonsense mutation (c.79G>T; p.Gly27*) in the OXCT1 gene (NM_000436), causing SCOT deficiency. Genetic studies help clinicians achieve a definite diagnosis of such metabolic disorders. In this case, the accurate and early diagnosis of SCOT deficiency opened new therapeutic possibilities, including frequent carbohydrate-rich meals and low fat and protein diet. Moreover, our findings expand the mutational and clinical spectrum of SCOT deficiency.

Case Report

Autoimmune Encephalitis Due to COVID-19 in a Young Patient

Forough Derakhshani, Mohammadreza Ghazavi, Neda Hosseini

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 135-142


Autoimmune encephalitis is an inflammatory condition caused by different factors including viral infections that is diagnosed after ruling out other causes of encephalitis. In the current study, we reported a novel case of autoimmune encephalitis in an 11-year-old girl that presented with seizure, cognitive dysfunction and neurological impairments. During the admission, we observed high levels of anti- N-methyl-D-aspartate receptor (NMDAR) antibody in the cerebrospinal fluid (CSF). She had also positive anti COVID-19 IgG. Therefore, the diagnosis of COVID-19 induced autoimmune encephalitis was certain. The patient received anti-epileptic and anti-viral drugs and also IVIG and rituximab and was discharged with remission. The diagnosis of the case was made by anti-NMDAR antibodies that highlights the importance of this diagnostic tool. Similar cases have been reported earlier but the point of this case was her younger age compared to the previous cases and development of neurological deficit before COVID-19 presentations.

What kept back on the mirror of COVID-19 related transverse myelitis? A genetic background!

Reza Sinaei, Sara Pezeshki, Roya Sinaei

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 143-147


The acute transverse myelitis associated with COVID-19 cases have been reported worldwide. Nevertheless, Iran, Italy and USA are the most affected countries, witnessing the possibility that genetic factors might be associated with this susceptibility. The genetic variants of the coronavirus-2 entry mechanisms and host innate immune response related genes like interferons, interleukins, Toll-like receptors, human leukocyte antigen, blood groups, and some risk loci may be accountable. Here, we have a description of the compatibility of the geographical distribution between ATM and the Neanderthal core haplotype that confers risk for severe COVID-19, as well as some possible culprit genes.

The Gross, Fine, and Oral Motor Functions in a Patient with Megalencephalic Leukoencephalopathy with Subcortical Cyst A Case Report

reihane sabermoghadam, Toktam Maleki Shahmahmood , Pooria Sarvghadi , Mehran Beiraghi Toosi

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 149-157


Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC) is a rare autosomal recessive neurodegenerative disorder. As motor deficits are a core feature of MLC, we reported on the gross, fine and oral motor functions in a MLC1 patient. Our patient demonstrated macrocephaly, deterioration of motor functions with ataxia, spasticity and intellectual disability. In addition to medical interventions, the patient received rehabilitation interventions of occupational therapy and speech therapy. Brain structures were analyzed with magnitude resonance imaging (MRI), and gross, fine and oral motor functions were analyzed with Gross Motor Function Measurement (GMFM), Purdue Pegboard Test (PPT) and Oral Motor Assessment Scale (OMAS) at age 2, as well as after interventions at age 5. The results showed that although the motor functions did improve due to the interventions, the patient still had weaknesses in gross, fine and oral motor functions when compared to his peers. These findings emphasize the importance of early referral for rehabilitation of motor function in order to increase their independence, participation in daily life and quality of life.

The Association of Acute Motor Axonal Neuropathy (Guillain-Barre’ Syndrome Variant) with Coronavirus (SARS-Cov-2) in a Child: A Case Report

Alireza Nateghian, Mozhde Mohammadpour, Naseh Yousefi, Mohammad Sadegh Khabbaz, Katayoun Moradi

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 159-166


Various reports of neurological manifestations of SARS-COV-2 infection after the virus outbreak are available, including anosmia, seizures, acute flaccid myelitis, Guillain-Barré syndrome (GBS), and encephalitis. Most of the literature has focused on the respiratory manifestation of SARS-CoV-2 infection in adults, but recent evidence showed that it is not confined to the respiratory tract. This report is about a rare variant of GBS acute motor axonal neuropathy (AMAN) in a child due to COVID-19 infection An 11 years old boy was referred to the hospital with a history of three-day lasting mild fever, and gastroenteritis, two weeks before starting symptoms. He was presented with progressive ascending weakness, paresthesia, and areflexia in four limbs four days ago. Nasopharyngeal swab polymerase chain reaction (PCR) was positive for SARS-CoV-2. The electrodiagnostic finding was compatible with acute generalized axonal motor neuropathy, and imaging revealed thoracolumbar syrinx and nerve root enhancement in lumbosacral MRI. Other lab tests were normal. GBS and its variant are one of the manifestations of SARS-CoV-2 in children. Children with an unexplained neurological process should be tested for SARS-CoV-2.

Post Herpetic Anti-NMDA- Receptor Encephalitis in an 18-month-old Infant

Hossein Eslamiyeh, Reihane Ranjbar Jamalabadi, Mohsen Askarbioki

Iranian Journal of Child Neurology, Vol. 17 No. 2 (2023), , Page 167-171


Herpes simplex encephalitis (HSE), caused by herpes simplex virus type 1 (HSV-1), is the most common cause of severe sporadic encephalitis worldwide.
HSE is occasionally accompanied by the recurrence of clinical symptoms that usually occur a few weeks following the initial infection. According to recent studies, the recurrence can be due to a secondary autoimmune mechanism rather than the virus invasion.
One of the most common etiologies for autoimmunity is Anti-NMethyl D-Aspartate receptor encephalitis. This disorder is a treatable autoimmune encephalitis manifesting as movement disorder or neuropsychological involvement