Electroencephalographic abnormalities in children with type 1 diabetes mellitus: a prospective study.

Background/aim: The aim herein was to investigate epileptiform discharges on electroencephalogram (EEG), their correlation with glutamic acid decarboxylase 65 autoantibody (GAD-ab) in newly diagnosed pediatric type 1 diabetes mellitus (T1DM) patients and interpret their medium-term utility in predicting epilepsy. Materials and methods: Children presenting with T1DM between July 2018 and December 2019 were included in this prospective longitudinal study. Patients with a history of head injury, chronic illness, neurological disorder, seizure, autism, or encephalopathy were excluded. EEGs were obtained within the first 7 days of diagnosis and later reviewed by a pediatric neurologist. All of the children were clinically followed-up in pediatric endocrinology and neurology clinics for 2 years after their diagnosis. Results: A total of 105 children (46 male, 43.8%) were included. The mean age at the time of diagnosis was 9.6 ± 4.1 years (range: 11 months-17.5 years). At the time of admission, 24 (22.9%), 29 (27.6%), and 52 (49.5%) patients had hyperglycemia, ketosis, and diabetic ketoacidosis, respectively. GAD-ab was positive in 55 children (52.4%). No background or sleep architecture abnormalities or focal slowing were present on the EEGs. Of the patients, 3 (2.9%) had focal epileptiform discharges. The mean GAD-ab levels of the remaining 102 patients were 7.48 ± 11.97 U/mL (range: 0.01-50.54) (p = 0.2). All 3 children with EEG abnormality had higher levels of GAD-ab (3.59 U/mL, 31.3 U/mL, and 7.09 U/mL, respectively). None of the patients developed epilepsy during the follow-up, although 1 patient experienced Guillain-Barré syndrome (GBS). Conclusion: The prevalence of epileptiform discharges in the patients was similar to those of previous studies, in which healthy children were also included. No relationship was found between the epileptiform discharges and GAD-ab, and none of the patients manifested seizures during the first 2 years of follow-up of T1DM. These data support the findings of previous studies reporting that T1DM patients with confirmed electroencephalographic abnormalities do not have an increased risk of epilepsy. On the other hand, GBS might be considered as another autoimmune disease that may be associated with T1DM in children.

Ifosfamide-induced Encephalopathy With Rapid Response to Thiamine: A Pediatric Case.

Ifosfamide is an important chemotherapeutic agent used in the therapeutic protocols of many malignant tumors. Central nervous system toxicity of ifosfamide manifests with encephalopathy in 10% to 30% of patients treated with ifosfamide. Thiamine and methylene blue have been reported beneficial in the treatment and prevention of ifosfamide-induced encephalopathy (IIE). We describe an episode of encephalopathy developed at the third cycle of ifosfamide treatment in a child with Ewing sarcoma. With the administration of thiamin, the encephalopathy resolved and no episode was noted during subsequent courses of ifosfamide. Previous use of cisplatin, concomitant use of opioids, low levels of serum albumin and hemoglobin, and elevated levels of serum creatinine are potential risk factors for IIE. The current case illustrates the possibility of IIE even in the absence of such additional risk factors, treated successfully with thiamin and draws attention to the need for close neurological monitorization of patients treated with ifosfamide.

Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study.

Children with chronic neurological diseases, including cerebral palsy (CP), are especially susceptible to vaccine-preventable infections and face an increased risk of severe respiratory infections and decompensation of their disease. This study aims to examine age-appropriate immunization status and related factors in the CP population of our country. This cross-sectional prospective multicentered survey study included 18 pediatric neurology clinics around Turkey, wherein outpatient children with CP were included in the study. Data on patient and CP characteristics, concomitant disorders, vaccination status included in the National Immunization Program (NIP), administration, and influenza vaccine recommendation were collected at a single visit. A total of 1194 patients were enrolled. Regarding immunization records, the most frequently administrated and schedule completed vaccines were BCG (90.8%), hepatitis B (88.9%), and oral poliovirus vaccine (88.5%). MMR was administered to 77.3%, and DTaP-IPV-HiB was administered to 60.5% of patients. For the pneumococcal vaccines, 54.1% of children received PCV in the scope of the NIP, and 15.2% of children were not fully vaccinated for their age. The influenza vaccine was administered only to 3.4% of the patients at any time and was never recommended to 1122 parents (93.9%). In the patients with severe (grades 4 and 5) motor dysfunction, the frequency of incomplete/none vaccination of hepatitis B, BCG, DTaP-IPV-HiB, OPV, and MMR was statistically more common than mild to moderate (grades 1-3) motor dysfunction (p = 0.003, p < 0.001, p < 0.001, p < 0.00, and p < 0.001, respectively). Physicians' influenza vaccine recommendation was higher in the severe motor dysfunction group, and the difference was statistically significant (p = 0.029).Conclusion: Children with CP had lower immunization rates and incomplete immunization programs. Clinicians must ensure children with CP receive the same preventative health measures as healthy children, including vaccines. What is Known: • Health authorities have defined chronic neurological diseases as high-risk conditions for influenza and pneumococcal infections, and they recommend vaccines against these infections. • Children with CP have a high risk of incomplete and delayed immunization, a significant concern given to their increased healthcare needs and vulnerability to infectious diseases. What is New: • Influenza vaccination was recommended for patients hospitalized due to pneumonia at a higher rate, and patients were administered influenza vaccine more commonly. • Children with CP who had higher levels of motor dysfunction (levels 4 and 5) were more likely to be overdue immunizations.

Etiological and Clinical Profile of Acute Nonbacterial Encephalitis in Children: A Single-Center Prospective Study.

Encephalitis is a serious neurological syndrome caused by inflammation of the brain. The diagnosis can be challenging and etiology remains unidentified in about half of the pediatric cases. We aimed to investigate demographic, clinical, laboratory, electroencephalographic and neuroimaging findings, and outcome of acute encephalitis of nonbacterial etiology. This prospective study included children hospitalized with the diagnosis of acute encephalitis between 2017 and 2019. Microbiological investigations of the cerebrospinal fluid (CSF) were recorded. All CSF specimens were tested for anti-N methyl D-aspartate receptor (NMDAR) antibodies. In total, 31 children aged 10 months to 17 years (median = 6 years) were included. Pathogens were confirmed in CSF in three patients (9.7%): varicella zoster virus, herpes simplex virus type 1 (HSV-1), and both HSV-1 and NMDAR antibodies. Presenting features included encephalopathy (100%), fever (80.6%), seizure (45.2%), focal neurological signs (29%), and ataxia (19.4%). On clinical follow-up of median 9 (6-24) months, six patients showed neurological deficits: together with two patients who died in hospital, total eight (25.8%) patients were considered to have unfavorable outcome. Need for intubation, receiving immunomodulatory treatment, prolonged hospitalization, and high erythrocyte sedimentation rate at admission were associated with unfavorable outcome. The etiology of encephalitis remains unexplained in the majority of children. HSV-1 is the most frequently detected virus, consistent with the literature. The fact that anti-NMDAR encephalitis was detected in one child suggests autoimmune encephalitis not being rare in our center. The outcome is favorable in the majority while about one-fifth of cases suffer from sequelae.

International consensus classification of hippocampal sclerosis and etiologic diversity in children with temporal lobectomy.

INTRODUCTION: The distribution of hippocampal sclerosis (HS) subtypes, according to the classification of the International League Against Epilepsy (ILAE), has been reported mainly in adult patients. We aimed to review the pathological findings in children who had anterior temporal lobectomy accompanied with amygdalohippocampectomy, in view of the current classification, and evaluate postsurgical outcome with respect to HS subtypes in childhood. METHODS: Seventy children who underwent temporal resections for treatment of medically refractory epilepsy, with a minimum follow-up of 2 years, were included; the surgical hippocampus specimens were re-evaluated under the HS ILAE classification. RESULTS: Neuropathological evaluations revealed HS type 1 in 38 patients (54.3%), HS type 2 in 2 (2.8%), HS type 3 in 21 patients (30%), and no HS in 9 patients (12.9%). Of 70 patients, 23 (32.9%) had dual pathology, and the most common pattern was HS type 3 with low-grade epilepsy-associated brain tumors (LEAT). The distribution of HS types with respect to age revealed that HS type 3 and no HS subgroups had significantly more patients younger than 12 years, compared with those of HS type 1 (90.5%, 77.8% vs 47.4%, respectively). History of febrile seizures was higher in HS type 1. Prolonged/recurrent febrile seizures were most common in patients 12 years and older, whereas LEAT was the most common etiology in patients under 12 years of age (p < 0.001). Patients with HS type 1 had longer duration of epilepsy and an older age at the time of surgery compared with patients with HS type 3 and no HS (p: 0.031, p: 0.007). At final visit, 74.3% of the patients were seizure-free. Seizure outcome showed no significant difference between pathological subtypes. CONCLUSIONS: Our study presents the distribution of HS ILAE subtypes in an exclusively pediatric series along with long-term seizure outcome. The study reveals that the leading pathological HS subgroup in children is HS type 1, similar with adult series. Hippocampal sclerosis type 2 is significantly less in children compared with adults; however, HS type 3 emerges as the second most predominant group because of dual pathology, particularly LEAT. Further studies are required regarding clinicopathological features of isolated HS in pediatric cohort. Seizure-free outcome was favorable and similar in all HS types in children. The proportion of HS types may be better defined in pediatric patients with temporal resections, as the current HS ILAE classification becomes more widely used, and may help reveal the surgical and cognitive outcome with respect to HS types.

Behavioral problems of preschool children with new-onset epilepsy and one-year follow-up - A prospective study.

OBJECTIVES: Childhood emotional/behavioral problems in children with epilepsy have been reported to be higher compared with those with typical development or with other nonneurologic health conditions. Increasing interest towards understanding these behavioral comorbidities is reflected in literature. However, longitudinal investigations regarding the course of behavioral problems in children with newly diagnosed epilepsy and normal development are rare, and majority of them involve school-aged children. We aimed to study the behavioral comorbidities of preschool children with newly diagnosed epilepsy and to explore the changes of behavioral problems after one year from the diagnosis in comparison with the healthy group and subsequently, to elucidate the potential developmental, neurologic, and social risk factors associated with these difficulties. METHODS: Participants were 83 patients, aged between 18 and 59 months, 43 of them were children with new-onset epilepsy, and 40 of them were healthy children as the comparison group. The Child Behavior Check List-1 1/2-5 (CBCL) was used to evaluate emotional/behavioral problems of the children. Maternal anxiety was analyzed by The State-Trait Anxiety Inventory (STAI). The general development of children was evaluated by the Denver-II-Developmental Screening Test (D-II-DST). Sociodemographic characteristics were also collected for all participants. Each evaluation was repeated after one year from the diagnosis. RESULTS: Internalizing, externalizing, and total problem scores were higher in children with epilepsy than the control group at baseline, and despite some reduction in several scales, the differences continued across groups after one year. The analysis for the course revealed that behavior problem scores reduced in children with new-onset epilepsy over a year, but it did not change in healthy children. Among the possible factors related to behavior problem scores, in correlation analysis, the duration of screen viewing, socioeconomic status, and maternal education were associated with behavior problem scores. There was no significant association between epilepsy-related variables and the behavior problem scores and the course. Among all possible risk factors in the regression analyses, maternal trait anxiety level was found to be significantly related to the total problems, internalizing, and externalizing scores in the group with epilepsy. CONCLUSION: Behavioral comorbidities of epilepsy are present very early and can be seen at the time of the diagnosis, however, they do not worsen over time in preschool children. Maternal anxiety should be considered as a risk factor for behavioral problems in preschool children with epilepsy. Assisting children and parents and ensuring necessary guidance and support should be a crucial part of epilepsy treatment initiated as soon as the time of diagnosis.

Susceptibility-Weighted Magnetic Resonance Imaging Findings of Two Pediatric Migraine Patients with Aura.

OBJECTIVE: Migraine with aura is considered common during the pediatric age and in some cases it could be hard to distinguish migraine from mimicking conditions. We would like to emphasize the role of susceptibility-weighted imaging (SWI) in pediatric migraine patients with aura. METHODS: We retrospectively reviewed the clinical and SWI findings of two pediatric migraine patients with aura. RESULTS: Initial SWI of two pediatric migraine patients with aura demonstrated venous conspicuity in the left cerebral hemisphere and follow-up SWI of them showed normal findings with symmetrical venous vasculature. CONCLUSION: Beyond routine work-up techniques, SWI in combination with diffusion-weighted imaging is helpful for differentiation from acute ischemic stroke, especially in the setting of acephalgic migraine. Multimodality imaging may also be helpful in elucidating the underlying pathophysiologic mechanisms of migraine in the pediatric age group.

Dihydropyrimidinase deficiency with atrioventricular septal defect: a case report.

OBJECTIVES: Dihydropyrimidinase deficiency is a rare autosomal recessive disorder of the pyrimidine degradation pathway, with fewer than 40 patients published. Clinical findings are variable and some patients may remain asymptomatic. Global developmental delay and increased susceptibility to 5-fluorouracil are commonly reported. Here we present atrioventricular septal defect as a novel feature in dihydropyrimidinase deficiency. CASE PRESENTATION: A four-year-old male with global developmental delay, dysmorphic facies, autistic features and a history of seizures was diagnosed with dihydropyrimidinase deficiency based on strikingly elevated urinary dihydrouracil and dihydrothymine and a homozygous pathogenic nonsense variant in DPYS gene. He had a history of complete atrioventricular septal defect corrected surgically in infancy. CONCLUSIONS: This is the second report of congenital heart disease in dihydropyrimidinase deficiency, following a single patient with a ventricular septal defect. The rarity of the disease and the variability of the reported findings make it difficult to describe a disease-specific clinical phenotype. The mechanism of neurological and other systemic findings is unclear. Dihydropyrimidinase deficiency should be considered in patients with microcephaly, developmental delay, epilepsy and autistic traits. We suggest that congenital heart disease may also be a rare phenotypic feature.

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

Glucose-6-phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experience.

AIM: The aim of this study was to investigate the prevalence of glucose-6-phospate dehydrogenase (G6PD) deficiency in newborn infants with neonatal hyperbilirubinaemia and to compare the clinical features of G6PD-deficient and G6PD-normal newborn infants. METHODS: A total of 4906 term and preterm neonates with indirect hyperbilirubinaemia were retrospectively evaluated according to demographic, neonatal features, bilirubin levels, erythrocyte G6PD levels, other risk factors and treatments. RESULTS: Among 4906 newborn infants with indirect hyperbilirubinaemia, 55 (1.12%) neonates were G6PD-deficient. In our study, no statistically significant difference was detected between G6PD-deficient and G6PD-normal infants in relation to the time of onset of jaundice, bilirubin levels and duration of phototherapy. However, the incidence of exchange transfusion in G6PD-deficient infants was 16.4% while it was only 3.3% in G6PD normal infants (P < 0.05). CONCLUSION: Testing for G6PD must be ordered to all newborns who are receiving phototherapy and especially to those who are coming from the high incident geographical regions and less responsive to phototherapy.

Non-epileptic paroxysmal events at pediatric video-electroencephalography monitoring unit over a 15-year period.

OBJECTIVE: Non-epileptic paroxysmal events (NEPEs) are common in pediatric patients and may be misdiagnosed as epileptic seizures. We aimed to study the distribution of NEPEs across age groups and with different comorbidities, and to correlate the patients' presenting symptoms with their final diagnosis after video-EEG. METHODS: We retrospectively analyzed video-EEG recordings of children aged one month to 18 years who were admitted between March 2005 and March 2020. Patients who experienced any NEPE while under video-EEG monitorization were evaluated in this study. Subjects with concomitant epilepsy were also included. The patients were first divided into 14 groups according to the basic characteristics of symptoms they reported at admission. The events captured on video-EEG were then classified into six NEPE categories based on the nature of the events. These groups were compared according to video-EEG results. RESULTS: We retrospectively evaluated 1338 records of 1173 patients. The final diagnosis was non-epileptic paroxysmal event in 226 (19.3%) of 1173 patients. The mean age of the patients was 105.4 ± 64.4 months at the time of the monitoring. The presenting symptoms were motor in 149/226 (65.9%) patients, with jerking being the most common (n = 40, 17.7%). Based on video-EEG, the most common NEPE was psychogenic non-epileptic seizures (PNES) (n = 66, 29.2%), and the most common PNES subtype was major motor movements (n = 19/66, 28.8%). Movement disorders (n = 46, 20.4%) were the second most common NEPE and the most common NEPE (n = 21/60, 35%) in children with developmental delay (n = 60). Other common NEPEs were physiological motor movements during sleep (n = 33, 14.6%), normal behavioral events (n = 31, 13.7%), and sleep disorders (n = 15, 6.6%). Almost half of the patients had a prior diagnosis of epilepsy (n = 105, 46.5%). Following the diagnosis of NEPE, antiseizure medication (ASM) was discontinued in 56 (24.8%) patients. CONCLUSION: Non-epileptiform paroxysmal events can be difficult to distinguish from epileptic seizures in children, especially in patients with developmental delay, epilepsy, abnormal interictal EEG, or abnormal MRI findings. Correct diagnosis of NEPEs by video-EEG prevents unnecessary ASM exposure in children and guides appropriate management of NEPEs.

Role of serostatus in pediatric neuromyelitis optica spectrum disorders: A nationwide multicentric study.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system (CNS) mostly presenting as optic neuritis and acute myelitis. NMOSD can be associated with seropositivity for aquaporin 4 antibody (AQP4 IgG), myelin oligodendrocyte glycoprotein antibody (MOG IgG), or can be seronegative for both. In this study, we retrospectively examined our seropositive and seronegative pediatric NMOSD patients. METHOD: Data were collected from all participating centres nationwide. Patients diagnosed with NMOSD were divided into three subgroups according to serology: AQP4 IgG NMOSD, MOG IgG NMOSD, and double seronegative (DN) NMOSD. Patients with at least six months of follow-up were compared statistically. RESULTS: The study included 45 patients, 29 female and 16 male (ratio:1.8), mean age 15.16 ± 4.93 (range 5.5-27) years. Age at onset, clinical manifestations, and cerebrospinal fluid findings were similar between AQP4 IgG NMOSD (n = 17), MOG IgG NMOSD (n = 10), and DN NMOSD (n = 18) groups. A polyphasic course was more frequent in the AQP4 IgG and MOG IgG NMOSD groups than DN NMOSD (p = 0.007). The annualized relapse rate and rate of disability were similar between groups. Most common types of disability were related to optic pathway and spinal cord involvement. Rituximab in AQP4 IgG NMOSD, intravenous immunoglobulin in MOG IgG NMOSD, and azathioprine in DN NMOSD were usually preferred for maintenance treatment. CONCLUSION: In our series with a considerable number of double seronegatives, the three major serological groups of NMOSD were indistinguishable based on clinical and laboratory findings at initial presentation. Their outcome is similar in terms of disability, but seropositive patients should be more closely followed-up for relapses.

Lesional resective epilepsy surgery in childhood: Comparison of two decades and long-term seizure outcome from a single center.

OBJECTIVE: Epilepsy surgery has shown efficacy in children. We aimed to assess long-term seizure outcome in children who underwent epilepsy surgery and determine predictive factors for seizure freedom. METHODS: This is a retrospective study of 196 children who underwent epilepsy surgery between 1994 and 2015 and had a minimum postoperative follow-up of 5 years. RESULTS: The median age at the time of surgery was 9.5 (0.08-19.8) years; 110 (56.1%) had temporal, 62 (31.6%) had extratemporal resections, and 24 (12.2%) had hemispheric surgery. The duration of postsurgical follow-up was between 5 and 20 years (mean±SD: 7 ± 3.2). Overall, 129 of 196 (65.8%) patients had Engel class I outcome at final visit. Among patients who underwent temporal, extratemporal and hemispheric surgery; 84 of 110 (76.4%), 34 of 62 (54.8%), and 11 of 24 (45.8%) patients had complete seizure freedom, respectively (p: 0.016). Patients with tumors had the best outcome, with 83.1% seizure freedom. The number of preoperative antiseizure medications (OR 3.19, 95% CI 1.07-9.48), the absence of postoperative focal epileptiform discharges (OR 8.98, 95% CI 4.07-19.79) were independent predictors of seizure freedom. Across two decades, the age at surgery was decreased (p: 0.003), overall seizure freedom (61.8% vs 68%) did not differ. In the past decade, a higher proportion of malformations of cortical development was operated (14.7% vs 35.9%, p: 0.007). SIGNIFICANCE: Our findings showed favorable long-term seizure outcome in children who underwent epilepsy surgery. The results are encouraging for developing centers with limited resources to establish pediatric epilepsy programs.

Relationship among four functional classification systems and parent interpredicted intelligence level in children with different clinical types of cerebral palsy.

OBJECTIVE: To investigate the relationships between four functional classification systems in children with cerebral palsy (CP) and parent-interpredicted intelligence level, and the functional status in clinical types of CP. METHODS: Two hundred and twenty-five children with CP ages between 2 and 18 (mean age 6.5 ± 4.4) years included using the Surveillance of CP in Europe (SCPE) database in Turkey. Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS) and Eating and Drinking Classification System (EDACS) levels were classified by clinical observation, and intelligence quotient (IQ) was determined by parent reports. RESULTS: Correlations were found between all functional levels; the strongest were between GMFCS-MACS (r = 0.784, p < .001), CFCS-EDACS (r = 0.772, p < .001). Strong correlations were found for the IQ-CFCS (r = 0.762, p < .001) and IQ-EDACS (r = 0.634, p < .001). Correlations were stronger in children with bilateral CP and IQ level <70. CONCLUSIONS: Taken together, these four classification systems and reported IQ levels can adequately describe overall functioning for children with CP. Our results can guide clinicians in the rehabilitation of children with CP.

Myelin oligodendrocyte glycoprotein antibodies in genetic leukodystrophies.

Accumulation of intermediate metabolites due to enzyme deficiencies and demyelination can provoke inflammation in genetic leukodystrophies. Thirty patients with genetic leukodystrophy and 48 healthy control sera were tested for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies by fixed and/or live cell-based assays. MOG-IgG was detected in two late infantile metachromatic leukodystrophy (MLD) cases, both of which were also weakly positive for IgG1, and one with IgG3 as the dominant anti-MOG IgG subclass. MOG-IgG was borderline positive in a vanishing white matter (VWM) disease patient. These results suggest that inherited metabolic or degenerative processes can have an autoimmune component, possibly as an epiphenomenon.

Neurologic manifestations in children with COVID-19 from a tertiary center in Turkey and literature review.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a global pandemic caused by highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although respiratory disease and multisystem inflammatory syndrome in children (MIS-C) are main clinical presentations in children, numerous neurological manifestations are being described increasingly. We aimed to investigate new onset neurological symptoms associated with SARS-CoV-2 in pediatric patients in order to establish a possible relationship as well as to understand the underlying pathophysiological mechanisms between SARS-CoV-2 infection and neurological findings. METHODS: We analyzed retrospectively children who had neurologic manifestations temporally associated with SARS-CoV-2 infection at Hacettepe University Ihsan Dogramaci Children's Hospital. We performed a literature search between March 20, 2020 and March 30, 2021. Articles that report children with COVID-19 related neurological manifestations were included. RESULTS: We have observed 15 consecutive cases with new onset neurological manifestations along with confirmed SARS-CoV-2 infection. Age at hospitalization ranged from three months to 17 years. Ten patients had central nervous system involvement, and most common manifestation was encephalopathy (5/10), which is also one of the most common manifestations of the patients mentioned in the relevant 39 articles we reviewed. CONCLUSION: Children with COVID-19 can present with neurologic findings such as encephalopathy, seizures, cerebrovascular events as well as abnormal eye movements. Clinical suspicion and awareness are required to show the association between neurologic manifestations and COVID-19.

Unraveling neuronal ceroid lipofuscinosis type 2 (CLN2) disease: A tertiary center experience for determinants of diagnostic delay.

OBJECTIVE: To evaluate the clinical phenotype, disease course, laboratory, and genetic features of patients with CLN2 disease over a 20 year period with a special emphasis on risk factors for diagnostic delay. METHODS: Thirty patients (23 families) with CLN2 disease, evaluated between 1996 and 2019 in a tertiary referral center in Turkey, were included. Clinical features, diagnostic pathway, disease course, genetic data, electrophysiological, and neuroimaging findings were analyzed, retrospectively. The patients diagnosed between 1996 and 2009, and 2010-2019 were defined as group 1 (G1), and group 2 (G2), respectively. Patients in these two groups were also compared. RESULTS: The median age at symptom-onset was 36 months (20 months-7 years). Most common presenting symptoms were seizures (70%), followed by language delay (43%), and psychomotor regression (27%). Median age at diagnosis was 5.2 years (1.6-11 years) with a median 27 months (1 month-7 years) of diagnostic delay. Age at diagnosis was earlier in G2 (4.6 years vs 7 years, p = 0.002), with a shorter time to diagnosis (21 months vs 39 months, p = 0.004). Median time between the onset of first symptoms and death was 8.3 years (SE 1.0). Electroencephalograms (EEG) revealed abnormal features predominantly in posterior hemispheral regions and a photoparoxysmal response to intermittent photic stimulation was detected in 53% of the patients. Cerebellar (96%)/cerebral atrophy (83%), and white matter changes (57%) were the most common radiological abnormalities. CONCLUSIONS: Most of our patients presented with late-infantile onset seizures. Despite increased availability of enzymatic and molecular testing, there is still a considerable diagnostic delay.

Basal Serum Thyroxine Level should Guide Initial Thyroxine Replacement Dose in Neonates with Congenital Hypothyroidism

Objective: Initial high-dose sodium levothyroxine (Na-LT4) (10-15 µg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels. Methods: Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups. Results: Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 µg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016). Conclusion: Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pre-treatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.

Biallelic mutations in ELFN1 gene associated with developmental and epileptic encephalopathy and joint laxity.

ELFN1, a transmembrane leucine rich repeat protein, is involved in signal transduction in both neural cells and ROD ON-bipolar synaptogenesis. We present three siblings with developmental and epileptic encephalopathy and co-morbidities due to ELFN1 gene mutation; this is the first report in literature defining the human phenotype of ELFN1 gene mutation. Clinical, electrophysiological, and radiological findings along with comprehensive genetic studies of the patients and their family members are presented. Developmental and epileptic encephalopathy, autistic features, pyramidal signs, joint laxity, and dysmorphic features are the characteristic findings of this new clinical entity, involving mainly nervous system and possibly connective tissue. Whole exome sequence analysis followed by Sanger sequencing in all family members revealed disease-causing 8 bp frameshift mutation depicted as NM_001128636.2: c.42_49delGGCCGCCA; p. (Ala15Profs*241) in ELFN1. The variant, located in the signal peptide domain in the ELFN1 gene, was found to be homozygous in three patients, and heterozygous in the parents and three healthy siblings. Segregation analysis in family members together with pathogenicity assessment tools strongly supported the damaging effect of the frameshift variant on the function of the ELFN1 protein. Mutations in ELFN1 gene may be considered in patients with neonatal and infantile-onset epileptic encephalopathy before the full clinical picture is apparent.

Optic neuropathies in childhood: a review of etiology and treatment.

Günbey C, Konuskan B. Optic neuropathies in childhood: a review of etiology and treatment. Turk J Pediatr 2019; 61: 471-476. Optic neuropathy (ON) is a common problem in childhood resulting from various causes including ischemic, metabolic, hereditary, traumatic and inflammatory events. The latter represents the most prevalent group; the term `optic neuritis` is generally used for this group which can manifest as part of a systemic inflammatory disease, a central nervous system disorder, or as an isolated entity. The aim of this review is to highlight the clinical characteristics and treatments of ON for pediatricians, focusing on optic neuritis.