Iranian Journal of Child Neurology (IJCN)
Volume:17 Issue: 2, Spring 2023

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.

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

Twenty-three eligible children were enrolled in the present crosssectional study. They were prescribed rapamycin 1mg tablet twice daily for the first two weeks of treatment and then once daily for at least one year. Periodic evaluations through follow-up visits were performed. Besides, growth and developmental statuses were evaluated. All data, including the number and size of brain tuberomas, size of renal angiomyolipomas, and skin lesions, 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.

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 tube defects (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, or vitamin 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-3 rickets.

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.

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 per day, 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.

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.

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.

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

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.

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.

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.

Physical activity and reducing inactivity improve health and wellbeing and benefit young people’s social development with an 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.

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 the potential to improve motor and social skills in young people with an intellectual disability.

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.

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 specific modality in diagnosing central nervous system (CNS) abnormalities, its value depends on the underlying medical history and physical exam.

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.

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

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.

Autoimmune encephalitis is an inflammatory condition caused by different factors, including viral infections, diagnosed after ruling out other causes of encephalitis. The current study reported novel autoimmune encephalitis in an 11-year-old girl who presented with seizures, cognitive dysfunction, and neurological impairments. During the admission, the researchers observed high levels of anti-N-methyl- D-aspartate receptor (NMDAR) antibodies in the cerebrospinal fluid (CSF). Besides, she had positive anti-COVID-19IgG. Therefore, the diagnosis of COVID-19-induced autoimmune encephalitis was specific. The patient received anti-epileptic, anti-viral drugs, IVIG, and rituximab and was discharged with remission. The case diagnosis was made by anti-NMDAR antibodies, which 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 her developing neurological deficit before COVID-19 presentations.

COVID-19-associated acute transverse myelitis (ATM) cases have been reported worldwide. Nevertheless, Iran, Italy, and the 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, Tolllike receptors, human leukocyte antigens, blood groups, and some risk loci may be accountable. This study describes the compatibility of the geographical distribution between ATM and the Neanderthal core haplotype that confers risk for severe COVID-19 and some possible culprit genes.

Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC) is a rare autosomal recessive neurodegenerative disorder. As motor deficits are a core feature of MLC, the present study reported on an MLC1 patient’s gross, fine, and oral motor functions. 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 magnetic 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 two and after interventions at age five. 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 emphasized the importance of early referral for rehabilitation of motor function in order to increase their independence, participation in daily tasks, and quality of life.

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.

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.

The article pertains to the presentation of an 18-month-old infant with a primary diagnosis of herpetic encephalitis who was readmitted to the hospital shortly after discharge with restlessness, speech disorder, and abnormal movements. The movements were predominantly choreiform and disappeared during sleep. Brain MRI revealed abnormal predominance in the left temporoparietal regions with encephalomalacic changes in some areas in favor of sequella of previous encephalitis in addition to recent right temporal involvement of sequella of previous encephalitis. The polymerase chain reaction test of cerebrospinal fluid for herpes simplex infection was negative. Therefore, the possibility of autoimmune encephalitis was raised. More laboratory examinations revealed that the Anti-N-Methyl- D-Aspartate receptor antibody level was significantly elevated in cerebrospinal fluid. Thus, the diagnosis of Anti-N-Methyl-DAspartate receptor encephalitis was established.

Relapsing symptoms after herpes simplex virus encephalitis, especially with movement disorders, should raise a high clinical suspicion of Anti-N-Methyl-D-Aspartate receptor encephalitis in children. Therefore, clinicians should be cautious of its occurrence in infants; despite its rarity in that age group.