Progressive Myoclonus Epilepsy and Beyond: Systematic Review of SEMA6B-Related Disorders.

Progressive myoclonus epilepsy (PME) is a rare, clinically and genetically heterogeneous epilepsy syndrome, and pathogenic variants in the SEMA6B gene have recently been reported to be among the causes of PME. Cases with pathogenic variants in the SEMA6B gene are extremely rare, only a limited number of cases have been reported in the literature. In this systematic review, we aimed to present a summary of a PME case in which a heterozygous nonsense variant of c.2086C>T p.(Gln696*) in the SEMA6B gene was detected in the etiology and other cases with SEMA6B pathogenic variant in the literature. Except our case, 35 cases from 12 studies were included. The main clinical findings of this patients were cognitive problems, seizures, gait and speech disturbances, and cognitive and/or motor regression, and they had a wide spectrum of severity. Response to antiseizure medications was also highly variable, almost half of the patients had pharmacoresistant seizures. Patients were divided into four different phenotypic groups according to their clinical presentations: PME (18/36), developmental and epileptic encephalopathy (DEE) (13/36), neurodevelopmental disorder (NDD) (4/36), and epilepsy (1/36), respectively. In conclusion, although SEMA6B has been associated with PME, it may actually cause a much broader phenotypic spectrum. Due to their extreme rarity, our knowledge of SEMA6B-related disorders is limited. As with all other rare diseases, each new SEMA6B-related disorder case of could contribute to a better understanding of the disease. And a better understanding of the disease may allow the development of specific treatment options in the future.

Correlation between early computed tomography findings and neurological outcome in pediatric traumatic brain injury patients.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. Head computed tomography (CT) is frequently utilized for evaluating trauma-related characteristics, selecting treatment options, and monitoring complications in the early stages. This study assessed the relationship between cranial CT findings and early and late neurological outcomes in pediatric TBI patients admitted to the pediatric intensive care unit (PICU). The study included children aged 1 month to 18 years who were admitted to the PICU due to TBI between 2014 and 2020. Sociodemographic data, clinical characteristics, and cranial CT findings were analyzed. Patients were categorized based on their Glasgow Coma Scale (GCS) score. Of the 129 patients, 83 (64%) were male, and 46 (36%) were female, with a mean age of 6.8 years. Falls (n = 51, 39.5%) and in-vehicle traffic accidents (n = 35, 27.1%) were the most common trauma types observed. Normal brain imaging findings were found in 62.7% of the patients, while 37.3% exhibited intracranial pathology. Hemorrhage was the most frequent CT finding. Severe TBI (n = 26, p = 0.032) and mortality (n = 9, p = 0.017) were more prevalent in traffic accidents. The overall mortality rate in the study population was 10.1%. In children with TBI, cranial CT imaging serves as an essential initial method for patients with neurological manifestations. Particularly, a GCS score of ≤ 8, multiple hemorrhages, diffuse cerebral edema, and intraventricular bleeding are associated with sequelae and mortality.

VAMP1-Related Congenital Myasthenic Syndrome: A Case Report and Literature Review.

Congenital myasthenic syndrome-25 (CMS-25) is an autosomal recessive neuromuscular disorder caused by a homozygous mutation in VAMP1 gene. To date, only eight types of allelic variants in VAMP1 gene have been reported in 12 cases of CMS-25. Here, we report on an 8-year-old boy with motor developmental delay, axial hypotonia, myopathic face, muscle weakness, strabismus, ptosis, pectus carinatum, kyphoscoliosis, joint contractures, joint laxity, seizures, and recurrent nephrolithiasis. He also had feeding difficulties and recurrent aspiration pneumonia. Brain magnetic resonance imaging at 20 months of age showed left focal cerebellar hypoplasia. Genetic analysis revealed a homozygous missense variant of c.202C > T (p.Arg68Ter) in the VAMP1 gene. Treatment with oral pyridostigmine was started, which resulted in mild improvement in muscle strength. Salbutamol syrup was added a few months later, but no significant improvement was observed. This case report presents novel findings such as focal cerebellar hypoplasia and nephrolithiasis in VAMP1-related CMS-25. Consequently, this case report extends the clinical spectrum. Further studies are needed to expand the genotype-phenotype correlations in VAMP1-related CMS-25.

Metabolic etiologies in children with infantile epileptic spasm syndrome: Experience at a tertiary pediatric neurology center.

OBJECTIVE: Infantile epileptic spasm syndrome (IESS), including West syndrome (WS) and infantile spasm (IS), causes a challenging prognosis, particularly when associated with metabolic etiologies. METHODS: This study, conducted at a tertiary pediatric neurology center, explored the prevalence and clinical features of inborn errors of metabolism in 112 children with IESS over 10 years. RESULTS: Most patients presented with seizures, primarily flexor spasms, and the median age at onset was 5 months. Comprehensive clinical evaluation and neuroimaging revealed structural-acquired causes as the most common etiology. Notably, inborn errors of metabolism were identified in 5.4 % of cases, with six distinct diagnoses including nonketotic hyperglycinemia, pyridoxine-dependent epilepsy, primary coenzyme Q10 deficiency 7, congenital disorder of glycosylation type IIM, 6-pyruvoyl tetrahydrobiopterin synthase deficiency, and argininosuccinate lyase deficiency. The prevalence of inborn errors of metabolism in this cohort was consistent with global variations reported in the literature. Genetic testing, including karyotype analysis and whole exome sequencing, was performed in a subset of cases with no clear diagnosis, revealing abnormalities in approximately 50 % of cases. Adrenocorticotropic hormone emerged as the most frequently prescribed antiseizure medication. CONCLUSION: This study provides insight into the diagnostic challenges associated with IESS and highlights the importance of metabolic investigations, especially in cases without a clear etiology. The findings emphasize the need for further genetic and metabolic studies to enhance prognostic accuracy and guide potential treatment options for children with IESS, particularly in populations with high rates of consanguinity.

Predictors of medical intractability in children with epilepsy onset during the first two years of life, excluding infantile epileptic spasm syndrome.

PURPOSE: Early childhood epilepsy presents a significant challenge, with approximately 30 % of individuals experiencing treatment failure. This study aimed to identify predictors of medical intractability in children with epilepsy onset during the first two years of life, excluding infantile epileptic spasm syndrome. METHODS: A total of 323 children were retrospectively evaluated. The analyses included a review of medical records for demographic, laboratory, radiological, and electroencephalographic (EEG) findings. Children were diagnosed with drug-resistant epilepsy (DRE) according to the ILAE diagnostic criteria. Twenty-one potential prognostic predictors were examined in relation to medical intractability. RESULTS: Among the 323 children (56.7 % male), 119 (36.8 %) had unknown epilepsy, 131 (40.6 %) had structural epilepsy, 53 (16.4 %) had genetic epilepsy, and 20 (6.2 %) had metabolic epilepsy. Over a median follow-up of 68 months, 55.4 % of the children achieved ≥6 months of seizure freedom, 33.1 % developed DRE, and the remaining 11.5 % had rare ongoing seizures but did not meet the criteria for DRE because they were only treated with one antiseizure medication at the last follow-up. Univariate logistic regression analyses identified ten risk factors significantly associated with DRE. Multivariate logistic regression analyses revealed that the presence of developmental delay at epilepsy onset (p = 0.000; OR 7.890; 95 %CI 2.713 to 22.945), history of status epilepticus (p = 0.000; OR 8.247; 95 %CI 3.619 to 18.793), number of antiseizure medications (ASMs) at the sixth month of diagnosis (p = 0.000; OR 20.585; 95 %CI 8.993 to 47.117), and initial EEG findings (p = 0.046; OR 2.366; 95 %CI 1.015 to 5.518) were predictors of medical intractability. Nineteen (5.9 %) children died during follow-up for various reasons, including progressive neurogenetic or neurodegenerative disorders. CONCLUSION: Developmental delay at epilepsy onset, a history of status epilepticus, the use of two or more ASMs in the sixth month of diagnosis, and abnormal initial EEG findings were associated with medical intractability.

Investigating the Impact on Long-Term Outcomes and the Necessity of Hereditary Thrombophilia Screening in Presumed or Perinatal Arterial Ischemic Stroke.

This study aimed to investigate the influence of prothrombotic risk factors on long-term outcomes of patients with perinatal arterial ischemic stroke. The study was conducted through an analysis of monitoring results that were regularly maintained for approximately 20 years at a tertiary stroke-monitoring center. The study assessed prothrombotic risk factors, radiological area of involvement, clinical presentation, treatments, clinical outcomes, and long-term outcomes of the 48 patients included in the study, with a mean monitoring time of 77.6 ± 45.7 months (range: 6-204). Our results showed that the presence of prothrombotic risk factors did not affect long-term outcomes. However, patients with middle cerebral artery infarction had the highest risk of developing cerebral palsy, whereas those with presumed stroke had the highest risk of developing epilepsy. This study suggests that prothrombotic risk factors should not be evaluated during the acute stage unless there is a strong suspicion of the patient's history, and prevention or early diagnosis of presumed stroke patients will positively impact their long-term prognosis.

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.

A multicenter study of radiologically isolated syndrome in children and adolescents: Can we predict the course?

OBJECTIVES: To evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up. METHODS: Demographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings. RESULTS: There were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up. CONCLUSION: Children and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

Ketogenic diet-responsive drug-resistant epilepsy in a case of asparagine synthetase deficiency with a novel compound heterozygous missense variant.

Asparagine synthetase deficiency (ASNSD) is a rare autosomal recessive neurometabolic disorder caused by homozygous or compound heterozygous mutations in the ASNS gene. Most of the patients have early-onset intractable seizures. A 7-year-old boy was first admitted to our clinic with intractable febrile and afebrile seizures that started when he was 6 months old. He had axial hypotonia with spastic quadriparesis, mild facial dysmorphism, and acquired microcephaly at 1 year-old. Metabolic tests showed a borderline-low serum asparagine level. The electroencephalogram demonstrated epileptic discharges with a high incidence of multifocal spike-wave activity. Brain MRI showed mild cerebral atrophy. His seizures continued despite combinations of multiple antiseizure agents. Whole-exome sequencing (WES) revealed a novel compound heterozygous missense variant of the ASNS gene, and the variants were confirmed by Sanger sequencing. He was started on a ketogenic diet at five years and six months of age. In the first month of the ketogenic diet, we observed that the frequency of seizures significantly decreased. He showed a remarkable improvement in seizures and milder improvement in cognitive skills. To our knowledge, our case is the first report describing significant improvement with a ketogenic diet in intractable seizures due to ASNSD.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with Sjögren`s syndrome in a child.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nervous system disease associated with polyautoimmunity. CASE: We report a previously healthy 13-year old boy who was referred to our outpatient clinic with gait disturbance and distal lower limb weakness that had been increasing for six months. The patient had decreased deep tendon reflexes in the upper extremities and absence in the lower extremities, reduced muscle strength in the distal and proximal lower extremities, muscle atrophy, drop foot, and normal pinprick sensations. The patient was diagnosed with CIDP as a result of clinical findings and electrophysiological studies. Autoimmune diseases and infectious agents were investigated in terms of triggering CIDP. Although there was no clinical sign other than polyneuropathy, he was also diagnosed with Sjögren`s syndrome due to positive antinuclear antibodies and antibodies against Ro52, and with autoimmune sialadenitis. After six months of monthly intravenous immunoglobulin and oral methylprednisolone treatments, the patient was able to dorsiflex his left foot and walk without support. CONCLUSIONS: To our knowledge, our case is the first pediatric case with the coexistence of Sjögren`s syndrome and CIDP. Therefore, we suggest investigating children with CIDP in terms of underlying autoimmune diseases such as Sjögren`s syndrome.

A Case of Multidrug-Resistant Lance-Adams Syndrome Successfully Treated With Phenobarbital.

OBJECTIVE: Lance-Adams syndrome is a rare but devastating disorder characterized by rest, action, and stimulus-sensitive myoclonus after cardiorespiratory arrest. We aimed to present a case of multidrug-resistant Lance-Adams syndrome that was successfully treated with oral phenobarbital therapy. METHOD AND RESULTS: We report a previously healthy 11-year, 6-month-old boy was referred to our pediatric intensive care unit because of severe hypoxic ischemic brain injury due to sudden cardiorespiratory arrest. On the 15th day of hospitalization, he developed myoclonic jerks involving his limbs, trunk, and eyes. Despite many antiseizure medications in different combinations, myoclonic jerks persisted. Then, phenobarbital was started, and myoclonic jerks disappeared the next day. At the final evaluation, additional phenobarbital treatment was continued for 6 months and the patient remained myoclonus-free during this time. CONCLUSIONS: To the best of our knowledge, this case is the first report describing significant improvement with phenobarbital in a patient with multidrug-resistant Lance-Adams syndrome. We suggest that phenobarbital is an effective option and should be kept in mind in patients with multidrug-resistant Lance-Adams syndrome.

Clinical and Imaging Clues of Arteriopathy-Related Pediatric Arterial Ischemic Stroke: A Single Center Experience.

Background and Purpose: Arteriopathy is a common etiology for childhood arterial ischemic stroke (AIS). In this study, we aimed to address clinical, demographic, and neuroimaging characteristics and the reversibility of vasculopathy in patients with childhood stroke due to arteriopathy by classifying them according to Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria. Methods: We included 15 patients with AIS due to arteriopathy presented between 2013 and 2018. All patients were diagnosed and followed up using magnetic resonance imaging (MRI) studies. All acute AIS patients were classified by acute CASCADE criteria (1-4). Moreover, each group was categorized according to the chronic CASCADE criteria, including progressive, stable, reversible, and indeterminate courses. Results: In the study population, CASCADE 2 patients were the most common group, and basal ganglia involvement was the most common involvement in CASCADE 2 patients. Of CASCADE 2 patients, 71.4% received steroids, which was compatible with a favorable outcome. In the study, trauma was present in 33.3% of patients, 60% of which was related to CASCADE 4. In the control visit on month 24, there were neuromotor sequelae of 60%, including hemiparesis, facial paralysis, and decreased fine motor skills; furthermore, the recurrence rate was 20%. Conclusion: We strongly emphasize that arteriopathy should be kept in mind in school-age children presenting with hemiparesis and headache. Moyamoya disease must be considered in the differential diagnosis with anterior circulation involvement, while focal cerebral arteriopathy (FCA) in patients with basal ganglia involvement was detected on MRI and dissection in the patients with a history of head-neck injury. We think that steroids have positive influences on neurologic prognosis in patients with FCA.

Clinical features and outcomes of children admitted to the pediatric intensive care unit due to posterior reversible encephalopathy syndrome.

OBJECTIVE: The aim of this study is to analyze the clinical features, neuroimaging findings and outcomes of the children admitted to our tertiary pediatric intensive care unit (PICU) due to posterior reversible encephalopathy syndrome (PRES). METHODS: This was a retrospective study where the hospital records of children admitted to PICU due to PRES between January 1, 2011 and January 1, 2021 were reviewed. RESULTS: We enrolled 14 patients with a median age of 8 years (IQR 2.2-14.2) to study. Eight (57 %) patients were male. All patients had comorbid illnesses such as hemophagocytic lymphohistiocytosis in 3, Β-cell acute lymphoblastic leukemia in 2, and different diagnosis in other patients as one one. Three patients had cardiac arrest, 9 patients had seizures, 5 patients had SE, 12 patients had altered mental status, 8 patients had hypertensive crisis, 1 patient had visual impairment. Thirteen patients had occipital involvement, 11 had parietal involvement, 4 had temporal involvement, 1 had thalamic involvement, 2 had cerebellar involvement, 1 had involvement of the corpus callosum, 1 had brainstem involvement, 1 had hippocampus involvement and 1 had involvement of the basal ganglia. Fourteen patients had supratentorial involvement while 3 had infratentorial involvement. Electroencephalogram was performed for 7 patients, out of which 6 revealed encephalopathy. Median PICU LOS was 19.5 days (IQR 13.2-49.2, minimum 2 - maximum 84 days). Five patients had neurologic sequelae. Four (28.5 %) patients died and ten patients survived. CONCLUSION: Co-occurence of hypertension and seizures should prompt consideration of PRES and urgent neuroimaging, particularly in patients on immunosuppressants or chemotherapeutics. Hypertension should be addressed aggressively in patients with PRES. Electroencephalographic monitoring should be performed if there is suspicion of SE or nonconvulsive SE. Despite its usually good prognosis, PRES can cause serious morbidity and mortality with delay in diagnosis or treatment.

Clinical features and outcomes of opsoclonus myoclonus ataxia syndrome.

OBJECTIVES AND METHODS: Opsoclonus myoclonus ataxia syndrome (OMAS) is a rare neuroinflammatory disorder. We aimed to retrospectively evaluate clinical and laboratory data and outcomes of 23 children diagnosed with OMAS in two children's hospitals between 2010 and 2021. RESULTS: There were 14 boys and 9 girls aged 4-113 months, median 24 months. Ten (43.5%) children had paraneoplastic causes: neuroblastoma/ganglioneuroblastoma (n = 9), acute lymphoblastic leukemia (n = 1). Three children had a postinfectious cause (upper respiratory tract infection in 2, EBV infection in 1) and two had a history of vaccination (varicella in 1, hepatitis A and meningococcal in 1). No underlying factor was identified in 8 (34.8%) children. Speech disorders were more frequent in patients with neural tumors than in those without (p = 0.017). Intravenous immunoglobulin and steroids were effective as initial treatment in most children. Rituximab resulted in at least mild improvement in all 6 children with persistent or recurrent symptoms. Nine (39%) children experienced at least one relapse. Neurological sequelae were detected in 13 (57%) children. There was no significant correlation between clinical characteristics and outcome, except for higher risk of relapse in case of incomplete recovery after first attack (p = 0.001). CONCLUSIONS: Acute lymphoblastic leukemia, vaccines against hepatitis A and meningococci can be included among antecedent factors in OMAS. Among clinical symptoms, speech problems might point to the likelihood of an underlying neoplasm in OMAS. Intravenous immunoglobulin and steroids may be chosen for initial treatment while rituximab can increase the chance of recovery in case of persistent or recurrent symptoms. The presence of relapse was associated with poor outcome.

Risk of seizure relapse and long-term outcomes after discontinuation of antiseizure medication in children with epilepsy.

OBJECTIVES: The aims of this study were to evaluate the demographic and clinical characteristics of children with epilepsy who discontinued their antiseizure medication (ASM), to determine potential predictors of seizure relapse, to calculate the rate of seizure relapse, and to detect long-term seizure outcomes. METHODS: A total of 269 seizure-free children with epilepsy who were decided to discontinue their ASM and were followed up for at least 18 months after ASM withdrawal were retrospectively evaluated. RESULTS: The enrolled children had been followed up for a median of 46 months (range 18-126 months; IQR: 29-61) after ASM withdrawal and 90 (33.5%) of their seizures relapsed. The median time to seizure relapse was 8 months (range 0.23-117 months; IQR: 2-25). Seizure relapse occurred in 16.7% of the 90 children at 1 month, 45.6% at 6 months, 62.2% at 1 year, 74.4% at 2 years, and 94.4% at 5 years. Univariate logistic regression analyses revealed six predictors significantly related to relapse: age at first seizure, age at diagnosis of epilepsy, intellectual disability, EEG findings after ASM withdrawal, ASM tapering time, and number of seizures on ASM. In multivariate logistic regression analyses, age at first seizure, intellectual disability, and ASM tapering time were not significantly associated anymore. The other three remained independently predictive. Pharmacological control of seizures with monotherapy was restored in 93.3% of the children with seizure relapse. CONCLUSION: This study evaluated potential predictors of seizure relapse, some of which have rarely been evaluated in previous studies. Adolescent age at diagnosis, abnormal EEG findings after ASM withdrawal, and high number of seizures on ASM were associated with a higher risk of seizure relapse. Abnormal MRI findings such as malformations of cortical development and hydrocephalus may be potential biomarkers for the risk of seizure relapse.

A Case of Combined Oxidative Phosphorylation Deficiency 35 Associated with a Novel Missense Variant of the TRIT1 Gene.

Combined oxidative phosphorylation deficiency 35 (COXPD35) is a rare autosomal recessive disorder associated with homozygous or compound heterozygous mutations in the tRNA isopentenyltransferase (TRIT1) gene in chromosome 1p34.2. To date, only 10 types of allelic variants in the TRIT1 gene have been previously reported in 9 patients with COXPD35. Herein, we describe a case with a novel homozygous missense variant in TRIT1. A 6-year, 6-month-old boy presented with global developmental delay, microcephaly, intractable seizures, and failure to thrive. The other main clinical manifestations were intellectual disability, spastic tetraparesis, truncal hypotonia, malnutrition, polyuria and polydipsia, ketotic hypoglycemia, dysmorphic facial features, strabismus, bicuspid aortic valve, and nephrolithiasis. The detailed biochemical, radiological, and metabolic evaluations were unremarkable. Chromosomal analysis confirmed a normal male 46,XY karyotype and the array comparative genomic hybridization analysis revealed no abnormalities. We identified a novel homozygous missense variant of c.246G>C (p.Met82Ile) in the TRIT1 gene, and the variant was confirmed by Sanger sequencing. The present case is the first report describing strabismus, ketotic hypoglycemia, nephrolithiasis, and bicuspid aortic valve in TRIT1-related COXPD35. This study expands the genotype-phenotype spectrum of TRIT1-related COXPD35.

A Rare Pediatric Case of Severe Rhabdomyolysis Owing to Dual Infection.

AIM: We aimed to report a severe and rare pediatric rhabdomyolysis case associated with a dual viral infection. CASE: A 13 year-old, healthy girl presented with the complaints of fever, abdominal pain, weakness and dark-colored urine. She was diagnosed with rhabdomyolysis based on clinical signs and laboratory findings. The diagnosis was confirmed by serological tests and real-time polymerase chain reaction for Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Other potential genetic, metabolic and infectious causes were evaluated meticulously but no evidence was found. This case is also important as it is the first reported case to our knowledge on rhabdomyolysis associated with EBV and CMV co-infection in children. CONCLUSION: The presented case experienced tetraplegia due to the severe muscular damage and muscle power returned to normal range after 3 months. This suggests that EBV and CMV may have exert synergistic effects leading to more severe inflammation and degeneration.

Ocular and cerebral causes of visual impairment in young children and a new scoring system to evaluate visual function.

PURPOSE: Childhood blindness is important cause contributing to the burden of blindness. It is necessary to identify the most frequently observed diseases in different populations. We aimed to demonstrate clinical features of low vision children and to evaluate the factors affecting visual function by a new visual function scoring system. METHODS: Two hundred forty nine children between the age of 6 months and 3 years were included. Visual function was scored from 0 to 15 according to; response to threat, light, object, presence of fixation, duration of fixation, following of light and object in horizontal, vertical, oblique, and circular gazes, optokinetic nystagmus. Patients were classified according to neurological diagnosis and cranial magnetic resonance imaging findings. Correlation between visual function score and ocular and neurologic findings were evaluated. RESULTS: While 136 patients (54.6%) had cerebral visual impairment (CVI), 89 (35.7%) had ocular pathology, 24 patients (9.6%) had combined pathology. The most common ocular and cerebral pathologies were oculocutaneous albinism (23.9%) and hypoxic ischemic encephalopathy (HIE) (27.5%), respectively. Patients with CVI had lower visual function than ocular pathologies. Neurological structural disorders and HIE had worse visual function. Widespread involvement of brain had lower visual function score. Seizure negatively affected visual function. CONCLUSIONS: Cerebral causes were found in approximately half of infants and children with low vision who were referred to our center for visual habilitation. The visual function scoring system we developed in this study will provide an opportunity to be objective in the follow-up of babies and in evaluating the effectiveness of visual habilitation programs.