Review Article

Neurological Manifestations of Primary Immunodeficiencies

Zahra Chavoshzadeh, Amir Hashemitari, Sepideh Darougar

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 7-23

Primary immunodeficiencies (PID) are a heterogeneous group of disorders  with a variable clinical spectrum of manifestations. The central nervous system may be involved in PIDs with symptoms which may present initially or develop at later stages. Neurological manifestations of primary immunodeficiencies are common with diverse pathologic mechanisms. Neurological deficits may be mild or they may greatly influence the course of the disease with major impacts on the quality of life of the patients. Physical examination may give the clinician valuable clues to the cause of PIDs that underlie the neurological signs. Certain neurological abnormalities may later signify a PID. Therefore physicians should be aware of the neurological features accompanying immunodeficiencies.  Neuromascular abnormality presenting with ataxia(ataxia-telangiectasia) , flaccid paralysis after live poliovirus immunization (combined or antibody deficiencies) ,pernicious anaemia (CVID), cognitive impairment, nystagmus and cerebellar, spinal and peripheral neuropathies(Chediac-Higashi syndrome), seizures, ataxia and occulomotor and reflex abnormalities(Griscelli syndrome) are examples of neurologic features seen in different immunodeficiency syndromes. Early recognition and treatment is important to prevent or reduce future irreversible neurological sequelae. The aim of this study is to review the neurological manifestations of different primary immunodeficiency syndromes.

Research Article

Serum Total Antioxidant Capacity of Epileptic Children before and after Monotherapy with Sodium Valproate, Carbamazepine,

Mahmoud Reza Ashrafi, Reza Azizi Malamiri, Sedigheh Shams, Neda Rashidi Ranjbar, Sara Ebrahimi Nasrabadi, Mohammad Taghi Haghi Ashtiani, Nargess Saladjegheh, Varasteh Vakili Zarch

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 24-31

Background: Brain is highly vulnerable to free radical damage due to a large quantity of mitochondria, a considerable amount of oxidizable polyunsaturated fatty acids, a ratio of high oxygen consumption, and less antioxidant capacity. The experimental and clinical data suggest a putative role of oxidative stress in the pathophysiology of seizures and epileptic syndromes.

Objectives: A case-control study was carried out to compare serum total antioxidant capacity in the newly diagnosed children with epilepsy and that of a control group of healthy children at the same age.

Patients and Methods: A total of 130 participants (65 in each group) aged between 1 and 17 years participated in this study. Serum total antioxidant capacity was compared between two groups before drug administration. The effect of antiepileptic therapy on the serum total antioxidant capacity also was studied in children with epilepsy before and 3 months after antiepileptic drug administration. Serum total antioxidant capacity values were measured based on Erel's method using an automated commercial kit. This method is based on the bleaching of the characteristic color of a more stable 2,2’‑azinobis‑(3‑ethylbenzothiazoline‑6‑sulfonic acid) radical cation by antioxidants. The results were expressed in mmol Trolox equivalent/l

Results: Serum total antioxidant capacity values was significantly lower in the patients group before drug administration [mean (SD): 1.31 (0.19) mmol/L] than that of the control group [mean (SD): 1.46 (0.21) mmol/L] (P < 0.001). In the patients group, no differences were found in the serum total antioxidant capacity before and 3 months after anticonvulsant monotherapy.

Conclusion: Reduced serum total antioxidant capacity, and an increased vulnerability to oxidative stress should be considered in the children with epilepsy.

Effect of Multi-sensory Stimulation on Neuromuscular Development of Premature Infants

Hossein Zeraati, fatemeh Nasimi, Javad Shahinfar, maryam ghorban zadeh

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 32-39

Background: preterm birth is considered as a risk factor for developmental disabilities, which can lead to long-term effects on the nervous system of children.

Objectives: The aim of this study was to determine the effect of multi-sensory stimulation on neurodevelopment of premature infants.

Materials & Methods: In this two-group double-blind clinical trial conducted from June to August 2016 in Iran, 80 preterm infants were randomly divided into two groups. The Intervention group received multisensory stimulation for 12 min per session, 5 sessions per wk along with routine NICU care the control group received ward's routine care. Neuromuscular Maturity each infant was assessed by New Ballard Score.

Results: The intervention group showed higher Neuromuscular Maturity compared to the control group. The Posture, Arm Recoil, Popliteal angle and Heel to ear were statistically significant between the groups.

Conclusions: The results shows that Multi-sensory stimulation can have beneficial effects on the development of neuromuscular in premature infants.

Keyword: Multisensory stimulation. Neurodevelopmen. premature infants

Validation of the Comprehensive ICF Core Set for young Children with Cerebral Palsy: An Occupational Therapy Perspective from Iran

Parvin Raji, Afsoon Hassani Mehraban, Faranak Aliabadi, Maryam Ahmadi, Veronica Schiariti

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 40-58


Evidence has shown that because of the multiplicity and diversity of the symptoms of cerebral palsy, integration between different specialists in evaluating the function of this population does not exist. Comprehensive ICF Core Set of cerebral palsy including a set of functions of these children and the aim of this study was to determine the validity of this version based on Iranian Occupational Therapists’ perspectives.

 Materials & Methods

This study was a qualitative study using expert panels and Delphi survey. Experts were the academic staff of the universities that were selected through convenience sampling. Content validity was done by them. Then a Delphi survey was used for generating consensus on the final version. Participants were 50 clinical Occupational Therapists who were invited via email from across the country. An agreement of 75% was considered as the cut-off for inclusion of each code-category. 


After expert panels and rounds of Delphi, 60% of the code–categories of comprehensive version of ICF Core Set of cerebral palsy approved by Occupational Therapists. In the final version, 82 code-categories were listed that included 21 code-categories for Body Functions, 40 for Activity/Participation, and 21 for Environmental Factors. This indicates that Occupational Therapists pay more attention to the activity/ participation component.


The validity of the Iranian ICF Core Set for children with CP aged 0–6 years was supported by Iranian Occupational Therapists. It could be the basis for evaluation of this population in Occupational Therapy.



Causes and Factors Associated with Neonatal Seizure and its Short-term Outcome; A Retrospective Prognostic Cohort Study

Hamid Nemati, Parvaneh Karimzadeh, Minoo Fallahi

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 59-68


Background: Neonatal seizures are common, difficult to diagnose and treat, and associated with a great mortality rate and long-term risk of neurodevelopmental impairments. We aimed to determine the etiology, clinical presentation, and neurodevelopmental outcome of neonatal seizures.

Methods: In this cross-sectional study, 88 neonates, aged < 28 days, who were admitted to Mofid Children’s Hospital, Tehran, Iran, from September 2011 to 2013 with the initial diagnosis of seizure were included by convenient sampling method. Data, including age, gestational age, birth weight, Apgar of the fifth minute, neonatal intensive care unit (NICU) admission, family history, type, cause, and age of seizure, EEG and paraclinic findings, anticonvulsant used for treatment, neurodevelopmental status, and the final outcome, were collected from medical records and the missed cases were completed by phone calls. The frequency and association of variables were analyzed using SPSS software.

Results: Among neonates with seizures, 67% were male, 79.5% were born term, and 72.7% had normal birth weight. The most common type of seizure was multifocal clonic seizures (45.5%). The main diagnosis in neonates with seizures was hypoxic-ischemic encephalopathy (HIE) (23.9%) and hypoglycemia (10.22%). The mortality rate was 11.36% during a mean follow-up period of 21.4±6.4 months. Neurodevelopmental assessments showed that 64% were normal, 27% had global delay, and 9% had motor delay. Positive family history of epilepsy (P=0.006), low Apgar score (P=0.002) and epilepsy (P<0.001) were significantly associated with adverse neurodevelopmental outcome.

Conclusion: Since HIE and hypoglycemia were the most common cause of neonatal seizures in the present study, efforts should be made to improve care during delivery and early breastfeeding.

Keywords:  Newborn; Seizure; Etiology; Neurodevelopmental outcome



Background and Objective: Febrile seizures are the most common type of convulsions. Medicinal prophylaxis is sometimes used for children at high risk of recurrent febrile seizure. In certain circumstances, conventional drugs such as diazepam and phenobarbital cannot be used and the need for alternative medicines is felt. This study set out to compare the effectiveness of topiramate and diazepam in preventing the risk of recurrent febrile seizure in children under the age of 2 years.

Methodology: This was a randomized controlled trial. The research sampleincluded 54 patients, at risk of recurrent febrile seizure,who were inhibited from taking phenobarbital. After selection, they were randomly divided into two groups. The first group received diazepam treatment during fever episodes and the second group received daily dose of topiramate.  A one-year follow-up of recurrent febrile seizure and its complications was also conducted.

Findings: Thirty four patients (17 patients in each group) completed the one-year course of the trial. Recurrent febrile seizure was not observed in the course of preventive treatment. The prevalence of minor complications was 29.4% in the diazepam group and 48.5% in the topiramate group.No major complication was observed in among the subjects

Conclusion: Topiramate can be recommended for preventing recurrent febrile seizure when the use of front line medicines is not possible.

"Investigating Brain MRI Findings in Children with Migraine

ali Abbaskhanian

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 78-85

Purpose: migraine is a common headache associated with structural changes in brain. The purpose of this study was to evaluate brain MRI findings in children with migraine.

Methods:  this study was cross-sectional. With respect to the exclusion and inclusion criteria, participants with headache and age between 5 and 15 years were evaluated with MRI and their headache type was diagnosed by the standard criteria. The findings of the MRI were interpreted by a radiologist who was blinded to the diagnoses.

Results: 81 individuals with the mean age of 9.56±3.25 years participated in the study. 66.7% of them were male. 20 patients with the mean age of 9.65±2.75 years were diagnosed with migraine without aura. Among the 54 male patients, 8 patients (14.8%) were diagnosed with migraine; and among the 27 female patients, 12 patients (44.4%) were diagnosed with migraine (RR: 1.5, 95%CI: 1.07-2.18, P=0.004). 10 migraine patients had abnormal MRI findings (50%), including 8 cases with high signal with matter lesion (3 patients in the frontal periventricular, 2 patients in semiovale centrum, 2 patients in periventricular at trigone area and 1 patient in periventricular at trigone area and semiovale centrum), and 2 cases with empty sella. The occurrence of the high signal white matter lesions was significantly greater in the migraine patients (RR: 3.91, 95% CI: 2.10-7.25, P=0.001).

Conclusions: the results revealed that the possibility of occurrence of the high signal white matter lesions in the brain MRI of children with migraine was significantly higher compared with other headache types.

Objectives: Febrile seizure is the most common seizure disorder in childhood. Anemia or failure to thrive can predispose children to Febrile seizure by affecting the nervous system function. The current study investigates the association between febrile seizures and Anemia or failure to thrive.

Materials and Methods: This case-control study was performed on 307children 6 months to 6 years old age hospitalized at the Ali Asghar children`s Hospital from 2011 to 2014 divided into two groups: a case group including 158 children with febrile seizures and a control group including 149 febrile children without seizure. The amount of Hgb, Hct, RBC count, MCV, MCH, and MCHC was recorded and weight-for-age and weight-for-height was calculated based on the WHO Z-Score charts.The date were compared between two groups.

Results: There were no differences regarding  age and sex between the groups. Statistically significant differences were found regarding the mean RBC count between the case group (4.38×106 ± 0.72×106) and the control group (4.24×106 ± 0.84×106) (p=0.013), as well as about the mean MCV that was 78.73 ± 0.97 and 76.78 ± 1.00 in the case and control groups respectively(p=0.005). Anemia was seen in 28.5% of the case and 42.3% of control group which was statistically significant (p=0.012). There was not statistically significant difference regarding  failure to thrive between two groups.

Conclusion: in children with febrile seizures anemia was lower comparing with febrile children without seizure. Moreover, there was not any association between failure to thrive and febrile seizures. 

Prediction of response to treatment in children with epilepsy

Mohammad Ghofrani, mohammad mehdi nasehi, Sasan Saket, Mohsen Mollamohammadi, Mohammad Mahdi Taghdiri, Parvaneh Karimzadeh, Seyed Hassan Tonekaboni, Mohsen Javadzadeh, Narjes Jafari, Azadeh Zavehzad, Masoud Hasanvand Amouzadeh, Mahsa Beshrat, Meysam Babaei

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 94-100

Objective: Predicting the response to treatment in patients treated  with anti-epilepsy drugs are always a major challenge. This study was conducted to predict the response to treatment in patients with epilepsy.

Material and Methods: This analytical questionnaire-based study was conducted in 2014 among patients with epilepsy admitted to Mofid Children's Hospital. The inclusion criteria were children 2 months to 12 years of age with epilepsy and patients who experienced fever and seizure attacks at least once were excluded from the study. After the initial recording of patient information, patients were followed up for 6 months and the response to their treatment was recorded. The response to good treatment was defined as the absence of maximum seizure with two drugs during follow up.

Result: This study was conducted among 128 children with seizure. 72 patients (56.3%) were boys. The age of the first seizure was under 2 years old in 90 patients (70.3%). History of febrile convulsion, family history of seizure and history of asphyxia was found in 16 patients (12.5%), 41 patients (32%), 27 (21.1%), respectively.  IQ was decreased in 79 patients (61.7%). Seizure etiology was idiopathic in 90 patients (70.3%), and the number of seizures was 1 - 2 in 36 patients (28.1%). 57 patients (44.5%) had cerebral lesion according to CT scan or MRI, and EEG was normal in 21 patients (16.4%) and abnormal in 101 patients (78.9%). In 6-month follow-up, 40 patients (31.3%) responded well to the treatment and 88 patients (68.8%) responded poorly to the treatment. The results of multivariate analysis demonstrated that history of asphyxia (OR = 6.82), neonatal jaundice (OR = 2.81) and abnormal EEG (OR = 0.19) were effective factors in response to treatment.

Conclusion: Results of univariate and multivariate analysis indicated that abnormal EEG is an effective factor in treatment response in the children studied.

As there were a few studies about the mental disorders resulting from diabetes in children, this study aimed at investigating the prevalence of psychological disorders among children.

the studied samples included 323 children with diabetes type 1 aged 5-12 years old referring to Endocrinology clinic of Mofid Hospital in 2014-2015. Also, 317 healthy children were considered as control group. The materials used for data analysis were information form and questionnaire CSI-4 filled out by their parents. The filled questionnaires were rated in that day and then analyzed and diagnosed by the Pediatric Psychiatry in order to determine the type and intensity of psychological disorder. Results were analyzed using SPSS 20. T tests, Scheffe post hoc test and Pearson’s correlation test were used for analysis of data. The amounts were significantly different at P<0.05.

In terms of Neuro-Evolutionary disorders, Attention-deficit (ADD), hyperactivity (HD) and Attention-deficit hyperactivity disorders (ADHD) in children with diabetes were significantly higher than those in healthy children (P=0.001). Intense/ fundamental Depressive disorders were higher in diabetic children (P=0.001). In terms of anxiety disorder, a specific phobia and panic was significantly higher in diabetic children (P=0.005). In terms of aggressive behaviors, diabetic children were more disobedient and stubborn than the others.

this study showed that prevalence of psychological disorders among diabetic children was higher than the others. As psychological disorders will effect on the life quality of children, improvement of life quality of diabetic children and adolescents, on-time diagnosis and treatment of psychological disorders in these patients seems essential

Neurometabolic Disorder Articles

A novel mutation of Beta-ketothiolase deficiency: The first report from Iran and review of literature

Rahim Vakili, Somayyeh Hashemian

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 113-121


Beta-ketothiolase deficiency is a rare autosomal recessive disorder characterized by an inborn error of isoleucine catabolism and affecting ketone body metabolism. Clinical features characterized by intermittent keto acidotic episodes associated with clinical signs and symptoms of toxic encephalopathy such as lethargy, hypotonia, vomiting, tachypnea, and coma in some patients, with an onset during infancy or toddler-hood.

Case presentation:

A two months old girl presented with acute episode of fever and toxic encephalopathy with attack of vomiting, hypotonia, lethargy, tonic clonic seizures and then a day in coma, few days after vaccination .After then similar episodes happened until 7 months age.  . Biochemical tests that suggested diagnose of beta ketothiolase deficiency were attacks of ketoacidosis with urinary exertion of 2-methyl-3-hydroxybutric acid 2-methyl aceto acetic acid tiglylglycine. In genetic assessment we detected a novel homozygous mutation c.664A> C (p. Ser 222 Arg) in ACAT gene. This is a first report of beta ketothiolase deficiency confirmed by molecular analysis from Iran.

Conclusion: we report on a homozygous variant in the ACAT1 gene that is the first time we detect this variant and is a novel mutation. According to the obtained result and patient’s phenotype, we recommended carrier testing for all informative family members to recognize mutations in asymptomatic family members.

Case Report

Chronic Myelogenous leukemia with cranial neuropathy report of one case in childhood

ali khajeh, mahsa tajik, gholamreza solemani, ghasem miri aliabad, afshin fayyazi, majid naderi

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 122-125

Pediatric neurologist usually is the first physician in a child with cranial nerve palsy and bulging fontanel should be consulted to examine the cause of increased intracranial pressure. In  this article we report a child with chronic myelogenous leukemia(CML) for the one time that presented with 7 cranial nerve palsy and bulging fontanel and leukemic infiltration of the central nervous system. In this patient chromosomal study and peripheral blood smear confirmed the diagnosis. unfortunately the child eventually died.

Early onset cerebral infarction in Schimke immuno-osseous dysplasia: A case report

Amir Hossein Babaei, Soroor Inaloo, Mitra Basiratnia, Ali Derakhshan

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 126-132

Schimke Immuno-Osseous Dysplasia is a rare autosomal recessive disease caused by a biallelic mutation in SMARCAL1 gene. Typical findings in Schimke Immuno-Osseous Dysplasia include spondylo-epiphyseal dysplasia, steroid resistance nephrotic syndrome, progressive renal failure, T-cell immunodeficiency, bone marrow failure, and cerebral infarction. In this case report, we described a 9-year-old girl who presented with failure to thrive in infancy. Nephrotic syndrome was diagnosed at the age of four years. She had three episodes of admission with cerebral stroke due to moyamoya syndrome. In the last admission, she had new cerebral ischemia, developed seizure, and finally died.

Guillain-Barré syndrome in a child with ongoing Hepatitis A viral infection

Ivan Baltadzhiev

Iranian Journal of Child Neurology, Vol. 12 No. 3 (2018), 26 June 2018, Page 133-138

Guillain-Barré syndrome (GBS) belongs to the group of peripheral immune-mediated neuropathies and is often preceded by an inflammatory episode. GBS is rarely associated with hepatitis A viral (HAV) infection, the latter as a rule antecedent of the neurological disorders. This association is quite rare in childhood, and only isolated cases have been described. We report an unusual case of pediatric GBS which development coincided with the development of HAV IgM (+) acute hepatitis A. From the 2nd to the 14th day after admission to hospital for mild jaundice of the skin and sclera in 12-year-old boy, the following neurological disorders have developed: absent Achilles and knee jerk reflexes, diminished brachioradialis reflex, moderately decreased muscle power in the upper extremities, and more pronounced power loss in the lower extremities. Facial palsy developed bilaterally, more expressed to the right. There was albuminocytologic dissociation of the cerebrospinal fluid and stimulation electromyography (EMG) showed findings compatible with the GBS subdivision - Acute inflammatory demyelinating polyneuropathy (AIDP). Our case report has shown that hepatitis A virus can trigger GBS in the very beginning of HAV infection in children, and this may be due to some common pathogenic mechanisms shared by both diseases.

Letter to Editor