The prevalence and major determinants of non-compliance with anti-seizure medication among children.

Background: A wide range of adherence to the use of anti-seizure medications has been reported among children with the disease, and accordingly, various factors on the degree of adherence to the drug have been reported. But in our society, there is no clear picture of drug adherence and related factors among children with seizures. We evaluated the frequency of adherence to anti-seizure medication as well as related factors. Methods: This cross-sectional study was conducted on 120 children with epilepsy who referred to Ali Asghar Hospital in Tehran, Iran, during 2019 and 2020. Along with demographic characteristics, adherence to antiepileptic medications was assessed by the Modified Morisky Scale (MMS). Results: The overall frequency of adherence to anti-seizure medications among children was reported to be about 41.7%. Among all baseline characteristics, much higher adherence was revealed in patients with educated parents. The rate of drug adherence in children with a history of perinatal morbidities was much lower than in other patients. The type of seizure could also affect the rate of drug adherence as the highest and the lowest adherence was found concerning focal impaired awareness seizure (57.1%) and atonic seizures (11.1%) indicating a significant difference (P = 0.022). The most common causes of non-adherence to treatment were expressing inability to treat the patient (23.0%), parents' forgetfulness to give medicine to the child (18.3%), and not taking medication when traveling or leaving home (16.7%). Conclusion: The lower level of education of the parents, type of seizure, as well as the presence ofunderlying perinatal morbidity in the child can predict non-compliance with anticonvulsant medication regimens among affected children.

Frequency of neurological involvement in patients with/without diarrhea hemolytic uremic syndrome: A Systematic review and meta-analysis.

Background: Diarrhea-associated-hemolytic-uremic-syndrome (D+HUS) is a common from of HUS. Central-nervous-system (CNS) involvement is one of the most common extrarenal organ involvements in children with D+HUS. This systematic review and meta-analysis aim to recognize the frequency of neurological complications in pts with HUS. Methods: Databases of PubMed, Embase, and Web of Science were searched systematically to find the papers on neurological involvement in HUS pts. Two researchers independently assessed the papers' quality and extracted data. CMA v. 2.2.064. was used for data analysis. Heterogeneity was evaluated using the I-squared (I2) test, and a fixed/random-effects model was used when appropriate. Results: In this review, 21 studies including 2,189 participants with a median age between 1.3-40-year-old, entered the meta-analysis. The meta-analysis in D+HUS patients indicated 27.0% with neurological complications (95% CI, 22.0%-32.6%), 25.5% of symptoms weren't categorized (95% CI, 15.9%-38.3%), 20.8% of them developed the seizures (95% CI, 2.3%-74.4%). In D-HUS pts, 20.8% of them were presented neurological symptoms (95% CI, 17.9%-24.0%), of which 29.0% weren't categorized (95% CI, 19.2%-41.2%), 17.5% of pts got into coma (95% CI, 9.6%-29.7%), 5.6 % showed hemiparesis (95% CI, 2.8%-10.9%), 17.2% experienced lethargy (95% CI, 5.2%-44.1%), 30.5% developed the seizures (95% CI, 18.2%-46.2%), 7.4% manifested speech abnormalities (95% CI, 0.2%-7.22%), 6.4% of D-HUS pts presented visual-disturbances (95% CI, 3.4%-11.6%). Conclusion: This systematic review and meta-analysis indicated more than one-fourth of both D+HUS and D-HUS patients were presented with neurological symptoms, and the most prevalent symptoms were seizures, which can lead to an epilepsy sequel.

A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.

BACKGROUND: Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. CASE PRESENTATION: A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. CONCLUSION: The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.

Chronic Neurological Complications in Hemolytic Uremic Syndrome in Children.

INTRODUCTION: Central nervous system (CNS) involvement is the most common extrarenal involvement in hemolytic uremic syndrome (HUS). There are limited reports on clinical cause of chronic neurologic problems in HUS. We evaluated residual neurologic involvement in children with HUS. MATERIALS AND METHODS: This cross-sectional study was conducted on 58 patients with a diagnosis of HUS referred to 2 tertiary pediatric centers. Neurological examinations was performed on all of the patients and they were followed up between 2001 and 2015. Data including demographic variables, type of HUS, neurological symptoms, and other complications were recorded. Neurological involvements that occurred after 6 months from the acute phase of HUS were considered as chronic neurological involvement. RESULTS:  Among 58 patients who were included in the study, 31 (53.4%) had neurological manifestations (31 with acute and 19 with chronic complications). There was no significant difference in acute neurological manifestations between typical and atypical HUS, while chronic neurological manifestations were more frequents in patients with atypical HUS (P = .05). The most common presentations were seizure and decreased level of consciousness. Chronic neurologic problems were found in follow-up visits of 11 patients with acute and 8 without acute involvement. Hypertension was associated with chronic manifestations (P = .01). CONCLUSIONS: According to our results, residual neurological problems were not infrequent in HUS and they were more related with atypical form of disease. Evidence of hypertension is a significant variable for persistence of neurologic problems.

The Association between Failure to Thrive or Anemia and Febrile Seizures in Children between 6 Months to 6 Years Old Age.

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 investigated the association between febrile seizures and anemia or failure to thrive. MATERIALS AND METHODS: This case-control study was performed on 307 children 6 months to 6 yr old age hospitalized at the Ali Asghar Children`s Hospital, Tehran, Iran from 2011 to 2014 divided into two groups as follows: 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 data 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 cases 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.

Acute Transverse Myelitis in Children, Literature Review.

OBJECTIVE: Acute transverse myelitis (ATM) is a rare inflammatory demyelinating disorder characterized by relatively acute onset of motor, sensory, and autonomic dysfunction. Children comprise 20% of total cases of ATM. In this review, we described the current literature on childhood ATM, focusing on the epidemiology, pathogenesis, clinical presentation, approach to diagnosis, differential diagnosis, treatment and outcome in the pediatric population. MATERIALS &METHODS: We searched the related articles in electronic databases such as Scopus, EMBASE, Google Scholar, and PubMed. All study designs were included and the essential key words for searching were myelitis, acute transverse myelitis, childhood transverse myelitis, and acquired demyelinating syndromes. RESULTS: The related data focusing on the epidemiology, pathogenesis, clinical presentation, diagnostic approach and differential diagnosis, treatment and outcome of pediatric ATM were gathered and described. CONCLUSION: ATM is a heterogeneous disorder in children with a broad spectrum of clinical presentation, etiology, and outcome. It may be the first presentation of relapsing acquired demyelinating syndromes and also must be distinguished from compressive and noninflamatory myelopathies. Correct diagnosis is crucial for treatment and prognosis.

The prevalence of hypertension in children with renal scars.

BACKGROUND: Hypertension (HTN) is a late outcome of congenital or acquired renal scar. We used ambulatory blood pressure to assess the early blood pressure abnormalities in children with history of urinary tract infection with various degrees of renal scars. METHODS: Between 2009 and 2011, 60 (45 females, 15 males) children aged 5-15 years and height equal or more than 120 cm with previous history of febrile urinary tract infection were entered into the study. All children went on 24-hour ambulatory blood pressure monitoring (24-H ABPM). Updated classification of 24-H ABPM was used to interpret the results. RESULTS: Masked hypertension was detected in 5% of cases, hypertension in 8.4%, and white coat hypertension in 11.7%. Pre-hypertension was seen in 23.3% of children. There was significant correlation between abnormal blood pressure and the severity of renal parenchymal scar (r=0.39, P value=0.004), vesicoureteral reflux (r= 0.34, P value=0.009), microalbuminuria (r= 0.39, P value=0.004), and carotid intima media thickness (r=0.41, P value=0.006). CONCLUSIONS: This study revealed the utility of 24-H ABPM in early detection of hypertension and pre-hypertension in children with severe renal scars and past history of urinary tract infection.

A rare case of Sjogren-Larsson syndrome with recurrent pneumonia and asthma.

Sjogren-Larsson syndrome (SLS) is a rare autosomal recessive neurocutaneous disorder with worldwide incidence of 0.4 per 100,000 people. It is characterized by the triad of congenital ichthyosis, spastic diplegia or quadriplegia, and mental retardation. Herein we report a 2-year-old male child with SLS, asthma, and recurrent pneumonia. SLS was confirmed by a molecular genetics study that revealed a deletion mutation in the ALDH3A2 gene. An ALDH3A2 gene mutation results in dysfunction of the microsomal enzyme fatty aldehyde dehydrogenase and impaired metabolism and accumulation of leukotriene B4, which is a key molecule and a pro-inflammatory mediator in developing allergic diseases, especially asthma. An increased level of leukotriene B4 has been reported in SLS patients. As far as we are aware, this is the first report of SLS associated with asthma and recurrent pneumonia. In conclusion, pediatricians should be aware of and evaluate patients with SLS for possible associated asthma and allergic disorders.

Sleep Symptoms and Polysomnographic Patterns of Obstructive Sleep Apnea in Obese Children.

OBJECTIVE: This study was conducted to investigate the sleep symptoms and polysomnographic patterns of obstructive sleep apnea in overweight and obese children. MATERIALS & METHODS: Overweight or obese children aging 6-18 yr old referred during 2010 to Endocrinology Clinic of Ghods Hospital in Ghazvin, central Iran were enrolled in the study. Polysomnography was done for the diagnosis of obstructive sleep apnea and the BEARS and Children's Sleep Habits questionnaires were used to survey sleep behaviors. RESULTS: We enrolled 30 children (14 males, 16 females). Twenty-one cases had body mass index (BMI) >95% and 9 had 85%

Kleine-Levin Syndrome in an 8-Year-Old Girl with Autistic Disorder: Does Autism Account a Primary or Secondary Cause?

Objective Kleine-Levin syndrome (KLS) is a rare disorder with an unknown etiology. Autism spectrum disorder is characterized by various degrees of impairment in social communication, repetitive behavior and restricted interests. Only four patients of KLS with autistic spectrum disorder (ASD) have been reported so far. This report presents an 8-year-old girl with history of autistic disorder and epilepsy that superimposed KLS. Because of the rarity of KLS and related studies did not address whether autism accounts for a primary or secondary cause, the area required attention further studies.

Reliability and validity of the Peabody Developmental Motor Scales-second edition for assessing motor development of low birth weight preterm infants.

BACKGROUND: Motor developmental impairment is a common symptom in low birth weight neonates. The Peabody Developmental Motor Scales-second edition is an instrument for measuring motor abilities in these infants. This study aimed to validate the Peabody Developmental Motor Scales-second edition in Iran. METHODS: This was a prospective clinical validation study. The reliability and validity of the original measure were performed in accordance with published guidelines. To collect data, a total of 88 infants including 58 LBW infants and 30 normal birth weight control patients were included in the study, and the measure was completed for them. The Bayley Scales of Infant Development, second edition, and the Motor Scale (Psychomotor Development Index) also were completed for the study samples. To test reliability, the internal consistency was assessed by Cronbach alpha coefficient. Test-retest reliability was performed using Intraclass Correlation Coefficient at 1-week interval. Validity was evaluated using known groups comparison and criterion validity (convergent validity). RESULTS: The Cronbach alpha coefficient for the Peabody Developmental Motor Scales-second edition was 0.92. Further analysis also indicated that test-retest reliability was excellent (Intraclass Correlation Coefficient = .98). Validity as performed by known groups comparison indicated satisfactory result. The instrument well discriminated among subgroups of the study samples that differed in birth weight. The Psychomotor Development Index score correlated strongly with the Peabody Developmental Motor Scales-second edition (r for Fine Motor Scale = .91, P < 0.001 and r for the Peabody Developmental Motor Scales-second edition Gross Motor Scale = .93, P < 0.001). CONCLUSIONS: The findings suggest that the Iranian version of Peabody Developmental Motor Scales-second edition is a reliable and valid measure. It can now be used in clinical settings for assessing motor development in low birth weight infants.

Renal function in children with febrile convulsions.

OBJECTIVE: Febrile convulsions (FC) are the most frequent seizure disorder in children. Some studies have detected serum electrolyte disturbances in patients with FC. This study determines serum electrolytes, renal function tests, and frequency of urinary tract infection in hospitalized children with FC. MATERIALS & METHODS: In this descriptive, cross sectional study, we evaluated 291 children with FC admitted to the Neurology ward of Ali-Asghar Children's Hospital from 2008- 2013. Data was recorded on age, sex, type (simple, complex), and recurrence of seizures, family history of FC and epilepsy, serum electrolytes, renal function tests, and urinary tract infections. RESULTS: A total of 291 patients with diagnosis of FC were admitted to our center. Of these 291 patients, 181 (62.2%) were male. The mean age was 24.4 ± 14.6 months. There were simple, complex, and recurrent FCs in 215 (73.9%), 76 (26.1%) and 61 (21%) of patients, respectively. Urinary tract infections (UTI) were found in 13 (4.5%) patients, more present in females (p-value = 0.03) and under 12 months of age (p-value = 0.003). Hyponatremia, hypocalcemia, and hypokalemia was detected in 32 (11%), 16 (5.5%), and 4 (1.4%) of cases, respectively. Twentyfour (8.2%) patients had a glomerular filtration rate less than 60 ml/min/1.73m2. There were no abnormalities in serum magnesium, BUN, and creatinine levels. CONCLUSION: During FCs, mild changes may occur in renal function but a serum electrolyte evaluation is not necessary unless patients are dehydrated. In children with FC, urinary tract infections should be ruled out.

Frequency of Meningitis in Children Presenting with Febrile Seizures at Ali-Asghar Children's Hospital.

OBJECTIVE: Febrile seizures (FS) are the most common type of childhood seizures, affecting 2-5% of children. As the seizure may be the sole presentation of bacterial meningitis in febrile infants, it is mandatory to exclude underlying meningitis in children presenting with fever and seizure. To determine the frequency of meningitis in children with FS and related risk factors, the present study was conducted at Ali-Asghar Children's Hospital. MATERIALS & METHODS: The records of children aged from 1-month-6 years of age with fever and seizure admitted to the hospital from October 2000-2010 were studied. The charts of patients who had undergone a lumbar puncture were studied and cases of meningitis were selected. The related data was collected and analyzed with SPSS version 16. RESULTS: A total of 681 patients with FS were known from which 422 (62%) lumbar punctures (LP) were done. Meningitis (bacterial or aseptic) was identified in 19 cases (4.5%, 95% CI 2.9-6.9 by Wilson- Score internal) and bacterial meningitis in 7 (1.65%, 95% CI 0.8-3.3). None of the patients with bacterial meningitis had meningeal irritation signs. Complex FS, first attack of FS, and impaired consciousness were more common in patients with meningitis when compared to non- meningitis patients. CONCLUSION: Meningitis is more common in patients less than 18 months presenting with FS; however, complex features of seizures, first attack of FS, or impaired consciousness seem significant risk factors for meningitis in these children and an LP should be considered in this situation.

Motor developmental status of moderately low birth weight preterm infants.

OBJECTIVE: Motor development is frequently reported to be impaired in very low birth weight (VLBW) infants, but little is known about the moderately low birth weight (MLBW) infants. The aim of this study was to investigate whether MLBW preterm infants present developmental delay. METHODS: In a historical cohort study, 18±2 month-old infants with a history of low birth weight (LBW) were identified. All infants with complications of LBW with negative effects on development were excluded. Healthy infants with normal birth weight (2500-4000 g) were included as controls. All infants were evaluated by the Peabody Developmental Motor Scale II (PDMS-2) test and final scores compared between the two groups. FINDING: 88 infants including 58 MLBW and 30 NBW with a mean birth weight of 1900±382.4 g and 3150±473.5 g respectively, were studied. In the MLBW group, gross and fine motor skill scores were below average in 6 (6.8%) and 10 (17%) infants, respectively. There were no significant differences between the two groups according to gross motor quotient (102.5±5.5 in NBW vs 100.1±7.2 in MLBW; P=0.1), but MLBW infants achieved significantly lower scores in fine motor (93.3±5.4 vs 99.6±5.0; P=0.001) and total motor quotient (97.0±5.9 vs 101.53±5.0; P=0.001). CONCLUSION: The finding of this study show developmental defects in fine motor skills in MLBW infants. Accurate monitoring of the developmental status of this population should be emphasized for an earlier recognition and intervention.

Migraine and tension-type headache in children and adolescents presenting to neurology clinics.

OBJECTIVE: Headache is one of the most common neurologic problems in children and adolescents. Primary headache including migraine and tension-type headache comprises the vast majority of headaches and are associated with marked incidence, prevalence, and individual and social cost. We aimed to assess demographic characteristics and to compare some factors related to primary headaches in children/ adolescents presented to neurology clinics of Tabriz University of Medical Sciences. METHODS: Children from 4 to 15 years of age with the diagnosis of primary headache (migraine or tension-type headaches) who presented to the neurology clinics affiliated to Tabriz University of Medical Sciences, Tabriz, Iran from March 2009 to October 2011 are included in this cross-sectional study. Data regarding the type of headache, history of atopy, peripartum asphyxia, and breast feeding, family history of headache and the socioeconomic status of the family were collected. The diagnosis was based on the international headache society diagnostic criteria for the primary headache disorders. FINDINGS: One hundred ninety children (107 females) with primary headache (88 patients with migraine and 102 patients with tension type headache) enrolled in the study. Peripartum asphyxia, history of atopy, family history of headache and low socioeconomic status (SES) were more common in patients with migraine (P-values: 0.007, 0.01, 0.001, 0.003; respectively). CONCLUSION: Physicians need to extent their knowledge regarding the primary headaches. Peripartum asphyxia, history of atopy, headache in parents and low SES have been shown in the present study to be more prevalent in patients with migraine as compared to tension-type headache.

Severe hypertension and encephalopathy due to Renin-producing hepatoblastoma.

Paraneoplastic syndromes result from secretion of hormones, peptides or cytokines by tumor or immune cross-reactivity between malignant and normal tissues. These conditions are rare in children, but when the clinical presentation of patients with a tumor is unusual, these syndromes should be emphasized. Extrarenal tumors with renin-secretion are rare in children. They may be related to paraneoplastic syndromes. We report a 22-month-old infant with hepatoblastoma presented with severe hypertension and related neurologic symptoms due to high plasma renin activity. To the best of our knowledge, this is the second report of renin producing hepatoblastoma in the literature. However, due to lack of laboratory facilities such as immunohistochemical study or polyclonal antibody for human renin activity, we could not prove the secretion of renin just by tumor tissue cells, but this potentiality is very likely. Other intensive investigations did not show any other origin for rennin secretion or hypertension in this patient.

Neuroimaging findings in first unprovoked seizures: a multicentric study in tehran.

OBJECTIVE: Seizure is an emergency in pediatrics. It really matters to the parents of the involved child to have information about the causes, management and prognosis. First unprovoked seizures (FUS) are seizures that occur in patients without fever, trauma or infection. Due to the rapid improvement in diagnostic techniques in the last few decades, the etiology will be revealed and this term will no longer exist. This Study was designed to evaluate brain imaging findings in FUS patients. MATERIALS & METHODS: Ninety-six children with FUS, who were admitted in three major children's hospitals in Tehran, underwent brain imaging and were enrolled into the study. The decision about the type of imaging (CT or MRI) was based on the patient's medical and financial conditions. An expert radiologist in the field of pediatric neuroimaging interpreted the images. RESULTS: Altogether, 27.1% had abnormal findings of which 29.2% were in the brain MRI group and 14.3% were in the brain CT scan group. Abnormal results were gliosis (10.4%), hemorrhage (4.2%), dysgenesis (2.1%), dysmyelination (7.3%), encephalomalacy (1%), atrophy (5.2%) and infarction (2.1%). In some patients, the lesions were in 2 or 3 sites and some had more than one type of lesion. There was no association between the duration, age and type of seizure and imaging abnormlities. However, we found an association between the location of the lesion and the type of seizure. CONCLUSION: We recommend brain imaging in all patients with FUS and apart from some exceptions, brain MRI is superior to CT.