Infantile spasms: Knowledge, attitude, and practice of pediatricians in Turkey.

BACKGROUND: Infantile Spasms Syndrome (ISS) encompasses both West syndrome (WS), comprising epileptic spasms, psychomotor stagnation or regression and hypsarrhythmia, and also infants presenting with epileptic spasms who do not fulfill the triad of WS. OBJECTIVE: To investigate the knowledge, attitude, and practice regarding ISS among Turkish pediatricians and pediatric residents. METHODS: A cross-sectional study was conducted among pediatricians and pediatric residents from all regions of Turkey. Knowledge, attitude, and practice (KAP) about ISS were assessed using a questionnaire including 45 questions. RESULTS: Out of 174 participants, 91.4% of respondents thought that ISS was a type of epilepsy. The two most recognized etiologic causes were structural abnormalities (90.8%) and genetic disorders (90.2%). Infantile colic (78.7%) and gastroesophageal reflux (75.9%) were reported to be the most common confusing diagnoses in this study. Almost all the respondents agreed that EEG recordings should be obtained for a patient with suspected ISS. Half of the participants stated that steroids were the first choice for treatment. Nearly all participants agreed on referring a pediatric patient with suspected ISS to a pediatric neurologist. CONCLUSION: Our findings highlight the importance of medical education as awareness is critical for diagnosing ISS. To facilitate rapid diagnosis, it is also important to combine medical education with public action. To ensure a sufficient level of knowledge about epileptic spasms and ISS, a strategy based on the socio-cultural characteristics of each population should be developed.

Effect of Chronic Valproic Acid Use on Anterior Cerebral Blood Flow of Children with Idiopathic Generalized Epilepsy.

OBJECTIVE: Cerebral blood flow has been blamed as a factor in the negative effect of antiepileptic drugs on neurocognition. This study aimed to investigate whether valproic acid (VPA), used for the treatment of idiopathic generalized epilepsy (IGE), causes a change in cerebral blood flow in children. METHODS: Included in this study were 33 children who were receiving VPA for IGE and 34 age-matched controls. Doppler and spectral measurements in common carotid artery (CCA), left and right internal CA (ICA) and external CA (ECA), anterior cerebral artery (ACA) and middle cerebral artery (MCA) were performed and the maximum velocity (VM), end-diastolic velocity (EDV), resistive index (RI), pulsatility index (PI) and flow rate (FR) were calculated. RESULTS: The mean age of drug and control groups were 9.33 plus or minus 2.11, and 9.74 plus or minus 2 years, respectively. Follow-up of patients was 17.7 plus or minus 3.2 months. The period of VPA treatment was 17.4 plus or minus 3.4 months. No statistically significant differences were found between control and VPA group for the VM, EDV, RI, PI, and FR values obtained from the bilateral ICA, ACA, and MCA. CONCLUSIONS: The results showed that VPA in therapeutic doses did not affect anterior cerebral blood flow. However according to result, it is still difficult to conclude that neurocognitive deterioration is not observed in patients receiving VPA.

Significant neuropsychiatric symptoms: three mucopolysaccharidosis type IIIB cases, two of whom were siblings with a novel NAGLU gene mutation.

Mucopolysaccharidosis (MPS) type IIIB patients present with marked neurodevelopmental and neuropsychiatric problems and not with typical MPS symptoms such as coarse facial features, organomegaly, or short body height, especially at the first presentation. We present three pediatric cases, two of which are sisters with novel NAGLU gene mutations, to emphasize that diagnosis of MPS type IIIB should be remembered in patients presenting with neurodevelopmental and neuropsychiatric problems such as delayed speech, autistic-like symptoms, severe behavioral and sleep problems, motor deterioration or idiopathic intellectual disability with or without refractory epilepsy, especially if there is aconsanguineous marriage.

Impact of COVID-19 on serum melatonin levels and sleep parameters in children

Background/aim: This study aimed to analyze the serum melatonin levels and changes in sleep patterns in pediatric patients with coronavirus disease 2019 (COVID-19). Materials and methods: This study was designed as a descriptive, cross-sectional study. Serum melatonin levels and sleep parameters of children with the diagnosis of COVID-19 who had mild and moderate disease (i.e., COVID-19 group) were compared with those of children admitted with non-COVID-19 nonspecific upper respiratory tract infection (i.e., control group). The sleep disturbance scale for children (SDSC) questionnaire was applied to the participants> primary caregivers to analyze their sleep patterns at present and six months before symptom onset and to investigate the impact of COVID-19 on sleep patterns. Results: The entire study cohort consisted of 106 patients. The COVID-19 group included 80 patients, while the control group consisted of 26 patients. The mean serum melatonin levels were 136.72 pg/mL and 172.63 pg/mL in the COVID-19 and control groups, respectively (p = 0.16). There was no significant difference between the groups in terms of 6 subcategories of the SDSC questionnaire regarding the present time and 6 months before symptom onset. The total SDSC scores were also similar in two different evaluation time points described above (p = 0.99) Conclusions: We conclude that COVID-19 did not impact the sleep parameters of children. Serum melatonin levels of all patients were higher than the reference range; however, they were higher in the non-COVID-19 patient group than the COVID-19 group. Since serum melatonin levels were higher than the reference values in children with COVID-19, and this disease is significantly less morbid in children, melatonin may have protective effects against COVID-19.

Focality in childhood absence epilepsy.

BACKGROUND AND PURPOSE: Childhood absence epilepsy (CAE) has a typical electroencephalography (EEG) pattern of generalized 3 Hz spike and wave discharges (SWD). Focal interictal discharges were also documented in a small number of documents. The aim was to investigate the amplitudes of interictal 3 Hz SWD within the 1st second in drug-naïve CAE patients. In this way, areas with maximal electronegativity at the beginning of clinically generalized discharges will be documented. METHODS: The EEG records of children with drug-naïve CAE were evaluated retrospectively by two child neurologists first for 3 Hz SWD. Then, a machine-learning model evaluated the amplitudes of 3 Hz in the 1st second of SWD. Maximum electronegativity areas were documented and classified as focal, bilateral, and generalized. RESULTS: One hundred and twelve 3 Hz SWD were evaluated in 11 patients. Among discharges within the 1st second, maximum electronegativity areas were documented as focal for 44 (39.2%), bilateral for 8 (7.1%), generalized for 60 (53.5%). Among focal electronegativity areas, mostly right central, left occipital and midline parietal areas were documented in 12 (10.7%), 7 (6.2%), and 6 (5.3%), respectively. Eight (7.1%) of the maximum electronegativity areas were detected bilaterally, of which 7 (6.2%) originated from the frontopolar areas. CONCLUSIONS: Focal maximal electronegativity areas were frequently observed in drug-naïve CAE patients, comprising approximately half of non-generalized discharges. Focal discharges might be misleading in diagnosis. Focal areas within the brain may be responsible for and contribute to absence seizures that appear bilaterally symmetrical and generalized clinically. Although its clinical implication is unknown, this warrants further study.

Sleep quality and daytime sleepiness amongst family caregivers of children with Spinal Muscular Atrophy.

BACKGROUND: While there are limited studies focusing on sleep quality of family caregivers of children with Spinal Muscular Atrophy (SMA), there are no studies on daytime sleepiness in SMA. AIMS: This study aimed a) to compare the sleep quality and daytime sleepiness between caregivers of children with SMA and those of healthy peers and b) to investigate the sleep quality and daytime sleepiness of family caregivers of children with different types of SMA. METHODS AND PROCEDURES: This study included 30 family caregivers of children with SMA (SMA Type 1:12, SMA Type 2:10, and SMA Type 3:8) and 31 family caregivers of healthy peers. Sleep quality and daytime sleepiness of family caregivers were evaluated using the Pittsburg Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (EPS), consecutively. OUTCOMES AND RESULTS: Demographic characteristics of children with SMA and healthy peers were similar (p > 0.05). The mean ages of family caregivers of children with SMA and healthy peers were 36.07 ± 5.84 and 35.26 ± 5.02 years, respectively (p = 0.6). The PSQI scores of family caregivers of children with SMA (7.50 ± 3.90 points) were lower than those of healthy peers (4.09 ± 1.97 points) (p < 0.001). There was no difference in PSQI scores between SMA types (p = 0.8). Also, no difference was found between SMA types and between SMA and healthy peers in terms of EPS (p > 0.05). CONCLUSIONS AND IMPLICATIONS: Family caregivers of children with SMA had poor sleep quality but similar daytime sleepiness compared with those of healthy peers. Among SMA types, family caregivers had similar sleep quality and daytime sleepiness. It was demonstrated that the sleep quality of family caregivers should be taken into consideration in the disease management of SMA.

A Near-Global Slowing of Background Activity and Epileptic Discharges in Children With Mild to Moderately Symptomatic COVID-19 Infection: An Electro-Neurophysiological Study.

Background. To assess the functional involvement of the central nervous system (CNS) via quantitative electroencephalography (EEG) analysis in children with mild to moderate COVID-19 infection who were otherwise previously healthy children. Methods. This prospective, case-control study was conducted between June and September 2020. Sleep EEG records of at least 40 min were planned for children who tested positive for COVID-19 using real-time PCR analysis and within 4-6 months post-recovery. All of the EEG analyses in this study were performed on an Ubuntu 20.04.2 LTS Operating System with the developed software using Python 3.7.6. The quantitative analysis of the epileptic discharges within the EEG records was performed using random forest after elimination of the artifacts with a model training accuracy of 98% for each sample data point. The frequency analysis was performed using the Welch method. Results. Among the age and sex-matched groups, the global mean frequency was significantly lower among the COVID-19 patients, with a P-value of 0.004. The spike slow-wave and sharp slow-wave indices were significantly higher in the patients when compared to the controls. The mean frequency values were significantly lower in almost all of the electrodes recording the frontal, central, and occipital areas. For the temporal and parietal areas, those significantly low mean frequencies were limited to the right hemisphere. Conclusion. A near-global involvement of background activity with decreased frequency, in addition to epileptic discharges, was recorded in mild to moderately COVID-19 infected children post-infection.

KMT2B-Related Dystonia: Challenges in Diagnosis and Treatment.

In this study, we report the first known Turkish case of a novel nonsense mutation c.2453dupT (p.M818fs*28) in the KMT2B (NM_014727.2) gene diagnosed in a male patient with KMT2B-related dystonia (DYT-KMT2B, DYT-28, Dystonia*-28), which is a complex, childhood-onset, progressive, hereditary dystonia. The patient, who is followed up from 9 to 13 years of age, had dysmorphic features, developmental delay, short stature, and microcephaly, in addition to focal dystonia and hemichorea (in the right and left lower extremities). Generalized dystonia involving bulbar and cervical muscles, in addition to dystonic cramps, myoclonus, and hemiballismus, were also observed during the course of the follow-up. While he was able to perform basic functions like eating, climbing stairs, walking, and writing with the aid of levodopa and trihexyphenidyl treatment, his clinical status gradually deteriorated secondary to progressive generalized dystonia in the 4-year follow-up. Deep brain stimulation has been shown to be effective in several patients which could be the next preferred treatment for the patient.

Spike-Wave Index Assessment and Electro-Clinical Correlation in Patients with Encephalopathy Associated with Epileptic State During Slow Sleep (ESES / CSWS); Single-Center Experience.

PURPOSE: This study aimed to describe the electroclinical spectrum and neurocognitive outcome in children with epileptic encephalopathy with status epilepticus during sleep (ESES) according to the EEG patterns. METHODS: Records of 48 (19 males, 29 females) patients with ESES/CSWS syndrome were retrospectively evaluated for data on sleep and awake EEGs, psychometric tests, and brain MRI. Patients with a spike-wave index (SWI) of at least 50 % in the NREM sleep EEG were included in the study. Electrophysiologic findings were separated into two groups based on SWI: SWI>85-100 % (typical ESES) and SWI < 85 % (atypical ESES). The neurocognitive prognosis was also evaluated in two groups; favorable and unfavorable. RESULTS: The median age at the onset of ESES was 6 years and 5 months and ranged from 3 to 13 years. The median duration of follow-up after the ESES diagnosis was 57 months (range 24-150 months). Etiology was evaluated in three groups: symptomatic/structural, idiopathic, and unknown (cryptogenic). Twenty-seven (56.25 %) patients had atypical ESES patterns and 21 patients (43.75 %) had typical ESES patterns. Twenty-eight patients (58.3 %) had cognitive deterioration. Long term neurocognitive outcome was unfavorable in half of the patients. Symptomatic/structural etiology was more common in patients with unfavorable (p < 0.001) outcomes. The median age at the diagnosis of ESES (p < 0.001) was significantly earlier in the patients with unfavorable neurocognitive outcomes. The longer duration of ESES(p < 0.001), and the longer time between the onset of epilepsy and ESES (p = 0.039) was significantly associated with unfavorable outcomes. We found that patients with typical ESES had a higher risk for poor neurocognitive outcomes than patients with atypical ESES (OR: 31.096 [1.565-617.696]). CONCLUSION: The long-term outcome of ESES is exceedingly variable. An unfavorable neurocognitive outcome seems to be related to ESES with a long-duration and early-onset epileptic activity, SWI ≥ 85 %, and etiology.

Sleep: How is it affected in patients with DMD and their mothers?

BACKGROUND: To investigate whether children with Duchenne muscular dystrophy (DMD) have sleep disorders, and the sleep quality and daytime sleepiness of mothers who are primary caregivers. METHODS: Clinical data and gross motor functional status of 24 patients with DMD were measured using the gross motor function classification system (GMFCS). Sleep Disturbance Scale for Children scores were evaluated to determine their sleep features. The Pittsburgh Sleep Quality Index scores were used to measure sleep quality, and Epworth Sleepiness Scale scores were used to measure daytime sleepiness of 24 mothers. RESULTS: Sleep disturbances were observed in 62.5% (n = 15) of patients, 41.6% (n = 5) of those who were GMFCS I-II-III and in 83.3% (n = 10) who were IV-V level. A disturbed sleep pattern was observed in 3 (33.3%) of 9 patients who were younger than 10 and in 12 (80.0%) of 15 patients who were older than 10. Of mothers, 54.2% had low sleep quality, which was present in 83.3% of mothers with GMFCS IV-V children and 54.2% of those with GMFCS I-II-III children. Ten (41.6%) mothers had increased daytime sleepiness, which was present in 66.6% of mothers with GMFCS IV-V children and 16.6% of mothers with GMFCS I-II-III children. CONCLUSIONS: Sleep disturbances increase in parallel to loss of gross motor functions in patients with DMD, which has had negative impact on the sleep quality and daytime sleepiness of the caregiver.

Pediatric headache: Are the red flags misleading or prognostic?

BACKGROUND: Symptoms and findings called orange or red flags may indicate the etiology of pediatric headaches and may point to a life-threatening situation requiring urgent treatment and thus can alter patient management. These findings can be either misleading or prognostic for clinicians. We aimed to identify the etiology and prognostic value of orange/red flags in pediatric patients. METHODS: This study included 810 children with headaches who underwent neuroimaging due to the existence of orange/red flags. Their hospital records were examined to obtain demographical, clinical, laboratory data, and re-classify the headaches and determine orange/red flags on admission. RESULTS: Secondary causes were identified in 17.0% (n: 138) of patients, however, those who were diagnosed with a life-threatening headache that required emergency treatment were 5.2% of all patients and 30.4% of the patients diagnosed with a secondary headache. Those with secondary headaches and with life threatening secondary headaches which required urgent treatment were younger (p = 0,018, p = 0,022), had more emergency department visits (p < 0,001), and acute onsets (p < 0,001). Red flags, like systemic symptoms (p < 0,001), sudden onset (p = 0,023, p = 0.039), papilledema (p < 0,001), and progressive headaches (p = 0,048, p = 0.006), were more common with secondary headaches and its subgroup, while headache awakening from sleep (p = 0.009) and family history of primary headache (P > 0,001) were more common in primary headaches. No correlation existed between the number of red flags and etiology. However, older age (p = 0,001) and a shorter duration between symptoms and admission (p = 0,032), and the number of emergency service visits (p = 0,020) increased with increasing red flags. CONCLUSIONS: Physicians always look for flags when they encounter patients with headaches, which is a common symptom, so as not to overlook anything. However, red flags do not always mean that the underlying cause requires emergency treatment and the severity of the cause is not correlated with the number of flags.

Prevalence of Obesity and Metabolic Syndrome in Children with Type 1 Diabetes: A Comparative Assessment Based on Criteria Established by the International Diabetes Federation, World Health Organisation and National Cholesterol Education Program

Objective: To determine the prevalence of obesity and metabolic syndrome (MetS) in children and adolescents with type 1 diabetes (T1D) and to compare the widely accepted and used diagnostic criteria for MetS established by the International Diabetes Federation (IDF), World Health Organisation (WHO) and National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII). Methods: We conducted a descriptive, cross sectional study including T1D patients between 8-18 years of age. The three sets of criteria were used to determine the prevalence of MetS and findings compared. Risk factors related to MetS were extracted from hospital records. Results: The study included 200 patients with T1D (52% boys). Of these, 18% (n=36) were overweight/obese (body mass index percentile ≥85%). MetS prevalence was 10.5%, 8.5% and 13.5% according to IDF, WHO and NCEP criteria, respectively. There were no statistically significant differences in age, gender, family history of T1D and T2D, pubertal stage, duration of diabetes, hemoglobin A1c levels and daily insulin doses between patients with or without MetS. In the overweight or obese T1D patients, the prevalence of MetS was 44.4%, 38.8% and 44.4% according to IDF, WHO and NCEP-ATPIII criteria, respectively. Conclusion: Obesity prevalence in the T1D cohort was similar to that of the healthy population of the same age. Prevalence of MetS was higher in children and adolescents with T1D compared to the obese population in Turkey. The WHO criteria include microvascular complications which are rare in childhood and the NCEP criteria do not include a primary criterion while diagnosing non-obese patients according to waist circumference as MetS because the existence of diabetes is considered as a direct criterion. Our study suggests that IDF criteria which allows the diagnosis of MetS with obesity and have accepted criteria for the childhood are more suitable for the diagnosis of MetS in children and adolescents with T1D.