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.

Neuromuscular disease genetics in under-represented populations: increasing data diversity.

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.

High diagnostic yield with algorithmic molecular approach on hereditary neuropathies.

OBJECTIVE: Charcot-Marie-Tooth disease covers a group of inherited peripheral neuropathies. The aim of this study was to investigate the effect of targeted next-generation sequencing panels on the molecular diagnosis of Charcot-Marie-Tooth disease and its subtypes in routine clinical practice, and also to show the limitations and importance of next-generation sequencing in the diagnosis of Charcot-Marie-Tooth diseases. METHODS: This is a retrospective study. Three different molecular methods (multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing) were used to detect the mutations related to Charcot-Marie-Tooth disease. RESULTS: In total, 64 patients (33 males and 31 females) with suspected Charcot-Marie-Tooth disease were analyzed for molecular etiology. In all, 25 (39%) patients were diagnosed by multiplex ligation probe amplification. With an extra 11 patients with normal PMP22 multiplex ligation probe amplification results that were consulted to our laboratory for further genetic analysis, a total of 50 patients underwent next-generation sequencing for targeted gene panels associated with Charcot-Marie-Tooth disease. Notably, 18 (36%) patients had pathogenic/likely pathogenic variants. Whole-exome sequencing was performed on five patients with normal next-generation sequencing results; the diagnostic yield by whole-exome sequencing was 80% and it was higher in the childhood group. CONCLUSION: The molecular etiology in Charcot-Marie-Tooth disease patients can be determined according to pre-test evaluation, deciding the inheritance type with pedigree analysis, the clinical phenotype, and an algorithm for the genetic analysis. The presence of patients without a molecular diagnosis in all the literature suggests that there are new genes or mechanisms waiting to be discovered in the etiology of Charcot-Marie-Tooth disease.

High diagnostic yield with algorithmic molecular approach on hereditary neuropathies

SUMMARY OBJECTIVE: Charcot-Marie-Tooth disease covers a group of inherited peripheral neuropathies. The aim of this study was to investigate the effect of targeted next-generation sequencing panels on the molecular diagnosis of Charcot-Marie-Tooth disease and its subtypes in routine clinical practice, and also to show the limitations and importance of next-generation sequencing in the diagnosis of Charcot-Marie-Tooth diseases. METHODS: This is a retrospective study. Three different molecular methods (multiplex ligation probe amplification, next-generation sequencing, and whole-exome sequencing) were used to detect the mutations related to Charcot-Marie-Tooth disease. RESULTS: In total, 64 patients (33 males and 31 females) with suspected Charcot-Marie-Tooth disease were analyzed for molecular etiology. In all, 25 (39%) patients were diagnosed by multiplex ligation probe amplification. With an extra 11 patients with normal PMP22 multiplex ligation probe amplification results that were consulted to our laboratory for further genetic analysis, a total of 50 patients underwent next-generation sequencing for targeted gene panels associated with Charcot-Marie-Tooth disease. Notably, 18 (36%) patients had pathogenic/likely pathogenic variants. Whole-exome sequencing was performed on five patients with normal next-generation sequencing results; the diagnostic yield by whole-exome sequencing was 80% and it was higher in the childhood group. CONCLUSION: The molecular etiology in Charcot-Marie-Tooth disease patients can be determined according to pre-test evaluation, deciding the inheritance type with pedigree analysis, the clinical phenotype, and an algorithm for the genetic analysis. The presence of patients without a molecular diagnosis in all the literature suggests that there are new genes or mechanisms waiting to be discovered in the etiology of Charcot-Marie-Tooth disease.

High diagnostic yield of targeted next-generation sequencing panel as a first-tier molecular test for the patients with myopathy or muscular dystrophy.

Muscular dystrophies are a heterogeneous group of neuromuscular disorders with a wide range of the clinical and genetic spectrum. Whole-exome sequencing (WES) has been on the rise to become the usual method of choice for molecular diagnosis in patients presenting with muscular dystrophy or congenital or metabolic myopathy phenotype. Here, we used a panel with 47 genes including not only muscular dystrophy but also myopathy-associated genes that had been used as a first-tier approach. A total of 146 patients who were referred to our clinic with the prediagnosis of muscular dystrophy and/or myopathy were included in the study. Dystrophin gene deletion/duplication was ruled out on the patients with a preliminary diagnosis of Duchenne muscular dystrophy. In this study, the molecular etiology of 67 patients was proved with the gene panel with a diagnostic yield of 46%. Causal variants were identified in 23 genes including CAPN3(11), DYSF(9), DMD(8), SGCA(5), TTN(4), LAMA2(3), LMNA(3), SGCB(3), COL6A1(3), DES (2), CAV3(2), FKRP(2), FKTN(2), ANO5, COL6A2, CLCN1, GNE, POMGNT1, POMGNT2, POMT2, SYNE1, TCAP, and FLNC with 16 novel variants. There were 27 patients with uncertain molecular results including the ones who had a variant of uncertain significance, who had only one heterozygous variant for an autosomal recessive disease, and the ones who had two variants in different genes. Molecular diagnosis in muscular dystrophy is essential to plan clinical management and choosing treatment options. Also, the results will affect the reproduction options. Targeted next-generation sequencing is a cost-effective method that reduces the WES requirements with a significant diagnostic rate.

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.

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.

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.

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.

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.

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.

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.

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.

Risk of recurrence after antiepileptic withdrawal: Was it a good decision or not?

Background: The aim of this study was to identify the demographic-clinical variables affecting idiopathic epilepsy (IE) [called genetic generalized epilepsy (GGE)] recurrence and determine cut-off values that can be used in pediatric neurology practice for children with IE/GGE. Methods: A total of 250 children and adolescents with IE/GGE were included and retrospectively evaluated. The patients' hospital records were examined in order to identify possible electro-clinical features affecting epilepsy recurrence. Results: The overall rate of recurrence in the patients was 46%; the age at onset of seizures in recurrence group was lower (P = 0.040) and the age at last seizure was higher in the recurrence group (P < 0.001) than that in the non-recurrence group. Other factors found to be related to recurrence were the shorter duration of the seizure-free period (P = 0.030), shorter interval between the last seizure and antiepileptic drug (AED) withdrawal (P = 0.003), shorter duration of AED withdrawal (P = 0.005), and the existence of abnormalities on sleep electroencephalogram (EEG) during AED withdrawal (P = 0.010) and at the 6th month of withdrawal (P < 0.001). According to receiver operating characteristic (ROC) analysis, the risk of IE recurrence was higher in children who were younger than 3.6 years old (sensitivity: 65.6%, specificity: 62.7%), children with a seizure-free period that was shorter than 35.5 months (sensitivity: 89.6%, specificity: 32.8%), and children whose drug withdrawal period was shorter than 4.5 months (sensitivity: 56.3%, specificity: 71.6%). Conclusion: This study defined some electro-clinical factors that could guide clinicians when deciding to withdraw AEDs with regard to recurrence risk after evaluating a homogenous population of children with a diagnosis of IE/GGE.

Neurologic Manifestations of COVID 19 in Children: Prospective Study in a Single Center.

Background: The data related to the neurologic manifestations of coronavirus disease 2019 (COVID-19) in children are limited. The frequency of the neurologic manifestations and the risk factors in the development of these symptoms are not clear. Objectives: We aimed to determine the exact frequency of the neurological symptoms in pediatric patients with confirmed COVID-19 and to identify the risk factors for the development of neurological manifestations. Materials and Methods: We included pediatric Covid-19 patients admitted to the Children's Hospital of Ankara City Hospital between March 22 and June 1, 2020. Neurological findings were questioned by interviewing the patients and their families and detailed neurologic examinations were performed within protection measures. Results: A total of 312 pediatric patients with the diagnosis of COVID-19 were enrolled in the study. Sixty-six participants (21.15%) showed neurologic symptoms during COVID-19. Headache was the most common neurologic symptom and present in 14% (n: 44) of the cases. The other neurologic symptoms were myalgia (n: 30, 9.6%), anosmia/hyposmia (n: 6, 1.9%), ageusia (n: 2, 0.6%), and vertigo (n: 1, 0.3%). Neutrophil-to-lymphocyte ratio (NLR) (P = 0.002) and platelet-to-lymphocyte ratio (PLR) (P = 0.001) were significantly elevated in patients with neurological symptoms when compared to the patients without the symptoms. Conclusions: Physicians should be alert to the neurologic involvement of COVID-19 disease in children. NLR and PLR ratios could have a predictive value for the development of neurological manifestations.

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.

Utility of estimated glucose disposal rate for predicting metabolic syndrome in children and adolescents with type-1 diabetes.

Objectives To determine the clinical utility of the estimated glucose disposal rate (eGDR) for predicting metabolic syndrome (MetS) in children and adolescents with type-1 diabetes (T1D). Methods Modified criteria of the International Diabetes Federation were used to determine MetS in children and adolescents between 10 and 18 years of age with T1D. The eGDR, a validated marker of insulin sensitivity, was calculated in two different ways using either the waist-to-hip ratio (WHR) or waist circumference (WC). Receiver operating characteristic (ROC) curve analysis was performed to ascertain cut-off levels of the eGDR to predict MetS. Results A total of 200 patients (52% male) with T1D were enrolled in the study. The prevalence of MetS was 10.5% (n: 21). Lower eGDR levels, indicating greater insulin resistance, were found in T1D patients with MetS when compared to those without (6.41 ± 1.86 vs. 9.50 ± 1.34 mg/kg/min) (p < 0.001). An eGDRWHR cut-off of 8.44 mg/kg/min showed 85.7% sensitivity and 82.6% specificity, while an eGDRWC cut-off of 8.16 mg/kg/min showed 76.1% sensitivity and 92.1% specificity for MetS diagnosis. The diagnostic odds ratio was 28.6 (7.3-131.0) for the eGDRWHR cut-off and 37.7 (10.8-140.8) for the eGDRWC cut-off. Conclusions The eGDR is a mathematical formula that can be used in clinical practice to detect the existence of MetS in children and adolescents with T1D using only the WC, existence of hypertension, and hemoglobin A1c levels. An eGDR calculated using the WC could be a preferred choice due to its higher diagnostic performance.

Benign epilepsy with centrotemporal spikes: Is there a thalamocortical network dysfunction present?

INTRODUCTION: Benign epilepsy of childhood with centrotemporal spikes (BECTS) is one of the most frequently seen epileptic syndromes in childhood. It is characterized by centrotemporal spikes (CTS) on electroencephalography (EEG) that are typically activated by drowsiness and stage N2 sleep. The location, frequency, and amplitude of the spikes may vary in different EEG records of the same patient, supporting the presence of a global pathology rather than a focal one. Despite the well-known relation between BECTS and stage N2 sleep, the results of sleep studies have been diverse and have mainly focused on sleep cycles. The characteristics of sleep spindles in the interictal periods have not been studied well. METHODS: A retrospective study involving patients with BECTS who were admitted to the Gazi University, Faculty of Medicine, Department of Pediatric Neurology from January 2017 to October 2018 was conducted herein. Patients with BECTS and age-matched controls who had stage N2 sleep records of 10 min were enrolled for spindle amplitude (peak-to-peak difference in spindle voltage), frequency (number of waveforms per second), and duration and density (number of spindle bursts/minute of stage N2 sleep). RESULTS: A total of 30 children with BECTS and 20 age-matched healthy peers were enrolled in the study. There were no significant differences between the age and sex of the patients. Statistically significant lower mean values of the amplitude, and duration and density of the spindle activity were observed in patients with BECTS when compared to the controls (P: 0.034, P: 0.016, and 0.020, respectively). Additionally, the risk of epilepsy was found to increase by 1.9 %, by the decrease of the mean amplitude of the spindles by 1 mV when compared to control group. CONCLUSION: The interictal records of stage N2 sleep differed in the patients with BECTS when compared to the controls. Findings related to the stage N2 sleep of the present study may suggest a network problem involving the thalamus and thalamocortical pathways in patients with BECTS.