Iranian Journal of Child Neurology

The immune system and metabolic pathways are strongly interconnected, influencing each other in both physiological and pathological contexts.  Nutrient signaling and cellular energy levels have a significant impact on the functioning of the immune system, in processes ranging from activation to differentiation and survival. In children, where both the immune and metabolic systems are still developing, disturbances in this balance can markedly influence disease manifestation and treatment response. Recent advances in immunometabolism have revealed that metabolic dysfunction is not merely a consequence of inflammation but can also serve as a primary driver of immune dysregulation. This review explores how metabolic problems may mimic or modify rheumatic diseases, and conversely, how immune-mediated disorders can disturb metabolic homeostasis. Understanding this bidirectional relationship provides novel insights into pathogenesis and opens avenues for metabolism-based diagnostic and therapeutic strategies in pediatric rheumatology.

Objectives:

Understanding normative biometric data of the posterior fossa is imperative to elucidate pathological alterations. Consequently, a reference for normative biometric data on posterior fossa structures in pediatric populations is essential for diagnosing cerebellar hypoplasia and other associated anomalies. However, a comprehensive set of objective, age-stratified biometric ratios for key posterior fossa structures is lacking, limiting diagnostic precision. To the best of our knowledge, only one study has evaluated the biometric data of the posterior fossa components in children.

Materials & Methods:

The current study is a cross-sectional study conducted among children hospitalized at Imam Hossein Children’s Hospital in Isfahan, Iran, in 2022-2023. All magnetic resonance imaging (MRI) examinations, including midline sagittal sections, performed in children ≤ 15 years of age, were included. Patients with a clinical history of posterior fossa involvement or MRI abnormalities were excluded from this study. Two-dimensional (2D) parameters, including the height of the vermian (H-V), anterior-posterior diameter of the vermis (APD-V), anterior-posterior diameter of the midbrain-pons junction (APD-MP), and anterior-posterior diameter of the midpons, were all measured. Four biometric ratios were calculated to normalize posterior fossa morphology across age groups, accounting for individual size variability and providing objective criteria.

Results: Four hundred twenty patients, with a mean age of 5.79 ± 4.02 years, were investigated, of whome 222 (52.9%) were boys. All parameters, except APD-V, were significantly higher in boys than in girls. Although boys had a higher mean APD-V than girls, this difference was not statistically significant. In addition, all studied parameters had the fastest growth rates in the first year and continued to grow more slowly until the end of the 15th year. Key findings reveal a mean APD-P/APD-V ratio of 0.77 ± 0.09. The ratio was generally higher in older children, indicating that pontine growth outpaces vermian expansion during development—values near or above 1.00 may suggest pontocerebellar hypoplasia. The H-V/APD-V ratio (mean 1.72 ± 0.18) shows a dip in early childhood, particularly at 1-3 years, suggestingtransient vermian flattening. The H-V/APD-P ratio declines from ~2.30 in infancy to ~2.11 in adolescence, reflecting posterior fossa maturation. Meanwhile, the APD-P/APD-MP ratio remains consistently around 1.91-1.95, aligning with the expected 2:1 anatomical norm, and serving as a reliable reference across age and sex groups.

Conclusion: The present study showed that all posterior fossa parameters, except APD-V, were significantly higher in boys. This study establishes normative reference values for key posterior fossa ratios. The APD-P/APD-V ratio (mean 0.77 ± 0.09) increases with age, while the H-V/APD-P ratio declines from ~2.30 to ~2.11. The APD-P/APD-MP ratio remains stable at ~1.91, consistent with the 2:1 anatomical norm. These objective criteria provide quantifiable thresholds for detecting anomalies like pontocerebellar hypoplasia.

Objectives:

Traumatic Brain Injury (TBI) is a significant public health problem. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor regulating oxidative stress and inflammation after TBI. This study examined the neuroprotective potential of Nebivolol in a rat model of moderate TBI, with a focus on implications for pediatric therapy.

Materials & Methods:

Twenty-one male Wistar rats (230 ± 10 g) were included. The animals were trained using the Morris Water Maze (MWM) test, and mTBI was induced using a pendulum-based method. Nebivolol was administered at a dose of 0.05 mg/kg daily from day 8 to day 21 post-injury. Behavioral assessments were performed using the MWM, while structural brain changes were evaluated via micro-computed tomography (micro-CT). Inflammatory biomarkers were also analyzed.

Results:

The results revealed significant post-TBI increases in inflammatory markers (CRP, cortisol) and decreases in prolactin levels in control animals (p<0.01). Nebivolol treatment attenuated these biochemical changes while maintaining cardiovascular stability. The MWM demonstrated improved late-phase cognitive recovery in Nebivolol-treated subjects despite initial learning impairment. Nebivolol treatment significantly attenuated these biochemical changes. While early learning in the MWM was impaired, animals treated with Nebivolol established superior late-phase cognitive recovery. It suggests enhanced neuroplasticity. Nebivolol also maintained cardiovascular stability without inducing bradycardia.

Conclusion:

The results demonstrated that Nebivolol treatment significantly modulates TBI-induced physiological changes, such as CRP and cortisol, while maintaining cardiovascular stability. Although it showed protective effects against TBI-related stress responses, the observed neuroendocrine alterations suggest complex systemic interactions. Nebivolol reduces inflammation, stabilizes cardiovascular function, and finally promotes cognitive rehab. The pleiotropic profile of Nebivolol promises reliable research in pediatric-focused models and forthcoming clinical trials.

Objectives:

Pediatric epilepsy is a neurological condition that could be associated with structural brain abnormalities. Although the common magnetic resonance imaging (MRI) technique is a standard tool for detecting these abnormalities, its diagnostic utility remains unclear compared to advanced neuroimaging techniques. This study aimed to evaluate the effectiveness of the common brain MRI technique in identifying structural lesions in pediatric epilepsy.

Materials & Methods: In this cross-sectional investigation, 337 patients with pediatric epilepsy underwent a common brain MRI. The scans were examined for abnormal lesions and assessed for their connections with neurological characteristics. Chi-square tests were used in statistical analysis to detect essential connections.

Results:

Brain MRI scans revealed abnormalities in 20.7% of patients. These abnormalities included white matter lesions (72%), gray matter lesions (22%), hippocampal lesions (12.8%), ventricular lesions (7%), and vascular lesions (2.8%). A significant relationship was found between abnormal neurological exam results and brain MRI findings (p < 0.001).

Conclusion:

While standard brain MRI can help identify structural abnormalities in pediatric epilepsy, it is not the most sensitive method, particularly compared to advanced neuroimaging techniques. Higher-resolution imaging and advanced modalities such as diffusion tensor imaging (DTI) and functional MRI (fMRI) may enhance diagnostic accuracy and improve outcomes in pediatric epilepsy management

Objectives:

The increasing rates of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) underscore the need to focus on how parents adopt strategies associated with these challenges.

Material & Methods:

This study presents the “Contingent Parental Metamorphosis Theory” formulated through grounded theory methodology, focusing on the adaptive processes of 27 parents of children with NDDs. The participants were selected through theoretical sampling and purposive sampling. The data were obtained using interviews, observations, field notes, and memos. The information analysis was based on Corbin and Strauss’s 2015 approach, and the MAXQDA 2010 programwas utilized for information management.

Results:

The data revealed 38 undercategories, 12 subcategories, and six major categories: (1) perceived parental crisis in the diagnostic-treatment process, (2) duality of parental grief, (3) hierarchical support, (4) organization of financial-motivational resources, (5) conscious parental strategies, and (6) commitment to parental adherence.

Conclusion:

The findings indicate a theory of Contingent Parental Metamorphosis, elucidating how parents adjust to the challenges posed by their offspring’s conditions. This theory highlights the duality of parental grief, illustrating the complex emotional landscape parents navigate. The theory offers a multivariate framework capturing the dynamic nature of the adjustment process, encompassing both the stress and the fulfillment that parents experience, ultimately fostering a renewed sense of purpose

Objectives: Sleep disturbance is a common difficulty in children with autism spectrum disorder that can affect daily functioning and quality of life. Research has established an association between the severity of autism and the severity of sleep problems. But the assessment and intervention in this issue are less noticed by therapists. This study aimed to investigate the psychometric properties of the Children’s Sleep Habits Questionnaire (CSHQ) including content validity, factor analysis, internal consistency, and test-retest reliability in children with autism aged 4–10 years.

Materials and Methods: In this descriptive and cross-sectional study, 306 parents of children with autism were selected by convenience sampling. They answered the Persian version of the CSHQ. The content validity index and ratio were assessed through opinions of 11 autism experts. Confirmatory factor analysis was conducted. Cronbach's alpha coefficient was used for internal consistency, and the intraclass correlation coefficient was calculated for test-retest reliability. Data were analyzed by and LISREL 88 and SPSS 26.

Results: The content validity index (0.81-1) and ratio (0.63–1) were confirmed. The confirmatory factor analysis results (RMSEA = 0.74; P < 0.001; Chi-Square =596.85; df = 224) confirmed the model obtained. The total Cronbach's alpha was 0.83. The intraclass correlation coefficient for the test-retest reliability was 0.90 in total and 0.82-0.91 for the domains of the questionnaire.

Conclusion: The Persian version of CSHQ in children with autism has acceptable validity and reliability and can be used by autism therapists as a suitable tool in research and clinical practice.

Objectives:

Children with autism spectrum disorder (ASD) frequently experience sensory processing difficulties that interfere with daily functioning, particularly self-care, yet their specific relationships remain underexplored. Therefore, this study aimed to investigate the relationship between sensory processing patterns and self-care skills in children with ASD aged 3-6 years, examining sensory quadrants, sensory sections, and behavioral domains based on the Sensory Profile-second edition (SP-2).

Materials & Methods:

A cross-sectional design was employed, involving 93 children with ASD. Sensory processing patterns were assessed using the SP-2, while self-care skills were evaluated with the Pediatric Evaluation of Disability Inventory (PEDI). Researchers conducted multiple linear regression analyses to investigate how sensory processing patterns relate to self-care skills.

Results:

The analysis revealed prevalent sensory processing difficulties in sensory sensitivity (M = 42.2, SD = 13.1), low registration (M = 46.0, SD = 14.4), touch (M = 23.0, SD = 9.2), movement (M = 18.1, SD = 7.4), and body position (M = 16.0, SD = 8.0). Regression analyses showed that overall sensory processing patterns significantly predicted self-care skills (R² = 0.151, p = 0.030). Among specific sensory patterns, the movement domain approached significance (β = -0.289, p = 0.063), suggesting its potential importance in predicting self-care abilities.

Conclusion:

Sensory processing difficulties may predict self-care skills in young children with ASD. Motor-related sensory challenges seem particularly significant, but it is crucial to approach these findings carefully due to the study’s cross-sectional design and dependence on parents’ reports. Future research should include longitudinal studies with objective measurements to provide more definitive insights.

Objectives:

Although COVID-19 primarily affects the respiratory system, the central and peripheral nervous system may be involved. Neurological manifestations of COVID-19 infection occur in acute or post-acute stages and may persist as long-lasting symptoms known as “long-COVID“ or “post-COVID-19”. This study aimed to investigate the clinical profile, outcomes, and management of neurological manifestations after COVID-19 infection in children.

Materials & Methods:

A retrospective chart review was conducted of all pediatric patients admitted to our tertiary pediatric center with neurological symptoms following COVID-19, meeting criteria for long COVID-19/post-COVID-19, from December 2020 through the end of 2021, with a one-year follow-up period.

Results:

Eighty-four patients were included (median age 12.7 years; range, 0.5-18 years). Girls were more affected than the boys (female n = 51; 60.7%, χ2 = 3, 86; p = 0,049). The most common neurological manifestation were headache (n = 47; 55.95%), dizziness (n = 19; 22.6%), visual disturbances (n = 9; 10.7%), afebrile seizures (n = 6; 7.1%), and anosmia/hyposmia (n = 4; 4.7%). Overall, 19 (22.6%) patients required psychological support, of whom 4 (4.8%) patients required psychiatric consultation due to suspected mental disorder. The most significant number of patients with neurological symptoms after COVID-19 was observed between October 2020 and March 2021 (n=44, 52.4%).

Conclusion:

The obtained findings align with the results from similar studies and show that neurological manifestations after COVID-19 infection appear more frequently in school-aged children, predominantly in female patients. Neurological post-COVID-19 symptoms require medical attention to exclude more severe conditions.

Objectives:

Febrile seizures (FS) are among the most common neurological emergencies in children aged 6 months to 6 years, yet their risk factors remain poorly defined in Iran. This study aimed to identify and analyze the demographic, clinical, and laboratory factors associated with the first episode of febrile convulsion (FC) in children admitted to a major pediatric hospital in Tehran, Iran.

Materials & Methods:

This retrospective cross-sectional study was conducted at a large pediatric hospital in Tehran, Iran, from 2019 to 2021. A total of 305 children who met the predefined inclusion criteria were included. Data were extracted from medical records and supplemented by interviews with caregivers. Collected variables included seizure type, perinatal history, family history of febrile seizures, serum biomarkers (e.g., hemoglobin, sodium), cause of fever, and other relevant clinical factors.

Results:

Of the seizures, 85.2% were simple and predominantly occurred within the first 24 hours of fever onset. Complex seizures showed a significant association with preterm delivery (P=0.02) and a positive family history of febrile seizures (P=0.01). Anemia was significantly more common in girls (P=0.027), and hemoglobin levels tended to be lower in children with complex seizures, although this difference was not statistically significant (P=0.06). Serum sodium levels remained within the normal range in all groups. Routine electroencephalography (EEG) showed abnormal findings in only 0.66% of cases, questioning its routine diagnostic value in first febrile seizures. Antihistamine use was uncommon and showed no association with seizure characteristics. The most frequent underlying causes of fever were upper respiratory tract infections, viral gastroenteritis, and post-vaccination fever.

Conclusion:

This study provides novel regional insights into the pathophysiological and epidemiological features of first febrile seizures in Iranian children. The findings highlight specific risk factors for complex seizures (preterm birth and family history) and suggest that targeted screening and preventive strategies could benefit high-risk pediatric populations. The very low yield of routine EEG supports a more selective approach to its use in this setting

Objectives:

Approximately 3% of newborns worldwide are affected by Congenital Anomalies (CAs) with or without Intellectual Disability (ID)/Developmental Delay (DD), often caused by genetic factors such as single-gene disorders or chromosome aberrations. Whole Exome Sequencing (WES) has become a highly effective first-tier test for identifying these genetic factors, detecting both Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms (SNPs)/Insertion/Deletion Polymorphisms (INDELs), while conventional cytogenetic analysis can provide additional valuable information to confirm results where applicable.

Materials & Methods:

The proband DNA was extracted and subjected to WES. Genetic variants were analyzed using the Genome Analysis Toolkit (GATK) following the American College of Medical Genetics and Genomics (ACMG) guidelines. Additionally, karyotyping of the child and her parents was conducted with high-resolution CTG banding after harvesting conventional cell cultures and performing Giemsa banding on metaphase spreads of cultured leukocytes.

Results:

This study describes a patient with microcephaly, mild intellectual disability, and specific facial features, where initial WES did not identify any causative SNPs/INDELs. However, subsequent WES-based analysis for CNVs revealed the presence of dup (9) (q21.11q22.32). Further chromosomal analysis uncovered unique karyotypes for the patient [46, XX, t (5; 9) (p15.1; q22.1), add (14) (p11.1)] and her father [46, XY, t (5;9)(p15.1;q22.1)], and a normal karyotype for the mother.

Conclusion:

The present study confirms the effectiveness of utilizing WES-based analysis of CNVs and SNPs/INDELs as the primary diagnostic test for identifying patients with CAs/ID/DD.

Acute flaccid paralysis (AFP) may arise due to various underlying factors, such as acute poliomyelitis caused by poliovirus or other neurotropic viruses, vaccine-associated paralytic poliomyelitis (VAPP), acute myelopathy, Guillain-Barré syndrome (GBS), systemic illnesses, disorders affecting the neuromuscular junction, or muscular conditions.¹

Iran has played a significant role in worldwide polio eradication effort, successfully eliminating locally transmitted wild virus. The country’s last recorded indigenous case dates back to 1997.^2,3 Importation of wild poliovirus from neighboring endemic countries, Afghanistan and Pakistan, was halted by December 2000.⁴ Despite this success, VAPP remains a rare, yet significant condition linked to the oral polio vaccine (OPV). A limited number of genetic substitution that lead to minor changes can result in an attenuated phenotype during OPV replication in humans. Theses mutations are responsible for the rare instances of VAPP in OPV recipients and their close contacts.^5,6

In the history of Polio reports in Iran, Shahmahmoodi et al. documented six cases of paralytic poliomyelitis caused by immunodeficient vaccine-derived polioviruses (iVDPVs), which were diagnosed between 1995 and 2008 in Acute Flaccid Paralysis (AFP) cases. Data from the Iran National Polio Laboratory highlights a significant concern regarding the reversion of the vaccine poliovirus to VDPV, a rare but severe adverse effect associated with the use of the oral polio vaccine.⁷

In line with the aforementioned study in Iran, our hospital-based study investigated the causes of AFP, and the primary objective of the authors was to identify the main diagnoses in children presenting with acute motor limb weakness like acute poliomyelitis, VAPP, acute myelopathy, GBS, acute transverse myelitis (ATM), etc. at the Children’s Medical Center Emergency Room (CMC-ER) in Iran between 2011 and 2016. As stated in the results, the three most common diagnoses were GBS, acute viral myositis, and ATM.

Among the 80% of enrolled patients who underwent stool testing, 97.5% had normal or nonspecific findings, while botulinum toxin was detected in 2.5% of cases."The negative results of the stool tests were related to the wild type of poliovirus, but six cases of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) were found. The authors of this commentary aim to emphasize that the stool test results of six patients were not included in the hospital’s stool test records. In other words, six iVDPV cases reported by the reference laboratory, but these cases were not included in the statistics presented in the referenced article.

As one of the definitions of VAPP is “isolation of vaccine virus (Sabin-Like: SL) from the stool of the paralyzed child, based on the  iVDVP isolation from the stool samples of six patients, a laboratory diagnosis of iVDPV instead of clinical diagnoses of VAPP is proposed.

A VAPP diagnosis requires meeting the following criteria:

1- The paralytic illness must present clinical features consistent with poliomyelitis, including residual paralysis persisting 60 days after onset. Additionally, there should be no epidemiological connection to confirmed cases of wild poliovirus or poliomyelitis outbreaks.

2- At least one adequate stool sample must test negative for wild poliovirus in a WHO-accredited laboratory while testing positive for a Sabin-Like (vaccine) virus.

3- Other potential causes of flaccid paralysis, including GBS, transverse myelitis, neuritis, tumors, and trauma, must be excluded.

1. The patient must be assessed by an expert committee that evaluates supplementary information such as exposure history, clinical findings, virological data, and possible epidemiological connections to confirmed poliomyelitis cases. The diagnosis of VAPP must be confirmed by the National Expert Committee, comprising a pediatrician, neurologist, virologist, and an epidemiologist or public health specialist, for the final classification of AFP cases.^5,6

Adequate specimens for diagnostic purpose consist of two stool samples collected with at least 24-hour interval between collections. These must be obtained within 14 days following paralysis onset and arrive at the laboratory in sufficient volume and proper condition. Good condition ensures no desiccation, proper documentation, and confirmation that the cold chain was maintained. Since 1996, stool samples from all AFP cases in Iran have been sent to the National Polio Laboratory (NPL- Iran) for poliovirus detection, with cell culture serving as the gold standard diagnostic method.⁵

VDPVs are categorized according to their degree of genetic divergence from the original oral polio vaccine strain, as  measured by nucleotide variation in the complete viral protein 1 (VP1) coding sequence. VDPVs are categorized into three types:

• Circulating VDPV (cVDPV) is identified when surveillance confirms community transmission of VDVP stains. Circulation of VDPV occurs when populations are inadequately immunized.
• Immune deficiency associated VDPV (iVDPV) occurs when the VDPV is detected in the stool specimen of a person with primary immune deficiency.
• Ambiguous VDPV (aVDPV) is when the VDPV is detected in sewage or a healthy individual. ⁵

In conclusion, due to the diagnostic significance of poliovirus (either Sabin-Like virus in VAPP cases, or VDPV in AFP cases), it is essential for healthcare centers to collaborate with reference laboratories to ensure accurate poliovirus diagnoses. Among the six cases analyzed in the present study, as well as six additional cases documented between 1995 and 2008, the vaccine-derived poliovirus (VDPV) detected in stool samples was notably consistent with patterns typically associated with immunodeficiency-associated VDPV (iVDPV).

To ensure inclusion of all AFP cases in poliovirus surveillance, it is recommended that care should be taken in registry of AFP cases in the hospitals and healthcare centers. Even when the patient is unconscious, sending a rectal swab can help in detecting Sabin-Like virus in a probable VAPP case, or detecting VDPV in a primary immune deficient paralyzed patient.