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.

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.

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.

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.

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.

Management of neurological problems in children on home invasive mechanical ventilation.

INTRODUCTION: Home invasive mechanical ventilation (HIMV) has become a crucial long-term respiratory support for children with neurological disorders, but requires advanced technological skills and 24-h care. The increasing global population of children on HIMV is attributed to advancements in intensive care and improved survival rates. METHOD: The manuscript will review the most common neurological problems encountered in children on HIMV. CONCLUSION: The manuscript emphasizes the multidisciplinary nature of managing these patients, involving pediatric pulmonologists, pediatric neurologists, pediatric intensivists, nurses, therapists, dietitians, psychologists, and caregivers. The manuscript outlines the challenges posed by neurological disorders, such as spinal muscular atrophy, muscular dystrophy, cerebral palsy, spinal cord injuries, and neurodegenerative disorders, which may result in respiratory muscle weakness and impaired ventilation. The importance of individualized assessments, appropriate ventilator mode and equipment selection, training of caregivers, airway clearance techniques, nutritional support, regular follow-up visits, psychological and educational support, and addressing specific neurological issues such as involuntary movement disorders, prolonged seizures, sleep disorders, pain, sialorrhea, and immobilization-related complications are discussed. The treatment options for these specific challenges are outlined. This review highlights the complex nature of managing children with neurological disorders on HIMV and the importance of a collaborative approach among healthcare professionals and caregivers to optimize care and improve the quality of life for these children.

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.

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 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.

Intracranial Calcification Associated with 3-Methylcrotonyl-CoA Carboxylase Deficiency.

3-methylcrotonyl-CoA carboxylase (3-MCC) deficiency is the most frequent organic aciduria detected in newborn screening programs. It demonstrates a variable heterogeneous clinical phenotype, ranging from neonatal onset with severe neurological disorders to asymptomatic adult forms. Herein, we report the first 2 related cases of 3-MCC deficiency presenting with intracranial calcification in the literature. A girl and a boy aged 3 years, 9 months and 4 years were included in the study. The main clinical manifestations were acquired microcephaly, global developmental delay, intractable seizures, mild feeding difficulty, and intermittent dystonic contractions. On physical and neurological examinations, their weights, heights, and head circumferences were below the 3rd percentile, they had acquired microcephaly, truncal hypotonia, upper and lower limb spasticity, hyperreflexia, positive bilateral Babinski signs, and clonus. The detailed biochemical and metabolic tests were unremarkable, except blood 3-hydroxyisovalerylcarnitine (C5OH) was slightly increased in case 1. Cranial computed tomography demonstrated mild cerebral and cerebellar atrophy as well as bilateral periventricular and thalamic calcifications in both cases. We identified a homozygous mutation of c.1015G>A (p.V339M) in the MCCC2gene, and the mutation was confirmed by Sanger sequencing. To the best of our knowledge, our cases are the first reported describing intracranial calcification in cases with 3-MCC deficiency. This report expands on the underlying causes of intracranial calcifications and suggests that 3-MCC deficiency may have intracranial calcifications on bilateral thalamus and periventricular white matters. If clinical findings show intracranial calcification, 3-MCC deficiency should also be kept in mind.

Mild congenital myopathy due to a novel variation in SPEG gene.

Centronuclear myopathies (CNMs) are a subgroup of congenital myopathies (CMs) characterized by muscle weakness, genetic heterogeneity, and predominant type 1 fibers and increased central nuclei in muscle biopsy. Mutations in CNM-causing genes such as MTM1, DNM2, BIN1, RYR1, CACNA1S, TTN, and extraordinary rarely SPEG (striated muscle preferentially expressed protein kinase) have been identified for about 60-80% of patients. Herein, we report a case of CM due to a novel variation in the SPEG gene, manifested by mild neonatal hypotonia, muscle weakness, delayed motor milestones, and ophthalmoplegia, without dilated cardiomyopathy. We identified a novel variation [c.153C>T (p.Asn51=) in exon 1] in the SPEG gene with whole-exome sequencing and confirmed by Sanger sequencing. Mild intellectual disability has not been associated with SPEG-related CM in the previous reports. We suggest that this report expands the phenotypic spectrum of SPEG-related CM, and further case reports are required to expand the genotype-phenotype correlations.

Therapeutic plasma exchange in clinical pediatric neurology practice: Experience from a tertiary referral hospital.

OBJECTIVE: This study aims to retrospectively evaluate the long-term efficacy, tolerability, and safety of therapeutic plasma exchange (TPE) in children with various neuroimmunological disorders. METHODS: This analysis was a single-center, retrospective cohort study of pediatric patients with neuroimmunological events undergoing TPE procedures in a tertiary referral center. RESULTS: There were 23 patients, 14 boys (60.9%), aged at diagnosis onset 8 months to 16.8 years. The main indications of TPE were Guillain-Barré syndrome (GBS, n = 8), autoimmune encephalitis (n = 5), febrile infection-related epilepsy syndrome (FIRES, n = 4), and acute disseminated encephalomyelitis (ADEM, n = 3). There was no life-threatening complication due to the TPE procedures. Eight (34.8%) of 23 patients experienced 13 (7%) complications in 186 TPE procedures, mostly electrolyte disturbances (n = 5). None of patients discontinued TPE due to complications. Two (8.7%) of 23 patients had marked improvement, 6 (26.1%) had moderate and 11 (47.8%) had mild improvement after TPE. The last follow-up visit revealed neurological sequelae in 12 (52.2%) patients. Therapeutic plasma exchange was found to be more effective on GBS, autoimmune encephalitis and myasthenia gravis, less effective on ADEM and FIRES. There was no correlation between improvement with TPE and clinical parameters, including age, sex, diagnosis, disease duration before TPE, presence of intubation, and length of stay in the intensive care unit and hospital. CONCLUSION: Therapeutic plasma exchange was found to be effective and well-tolerated in children with various types of neuroimmunological disorder, with at least mild improvement in approximately 80% of the patients and no life-threatening complications.

A homozygous mutation in the POMT2 gene in four siblings with limb-girdle muscular dystrophy 2N.

Mutations in protein O-mannosyltransferase 2 can cause a wide spectrum of clinical phenotypes from severe congenital muscular dystrophy such as Walker-Warburg syndrome to milder limb-girdle muscular dystrophy 2N. We aimed to describe the clinical and paraclinical features, laboratory tests, and molecular findings of four siblings with a homozygous mutation in the protein O-mannosyltransferase 2 gene. There were two sisters and two brothers, aged 4 to 17 years, with an age of onset symptoms at 3 to 12 years. The main neurologic findings were mild intellectual disability, hypoactive deep tendon reflexes, symmetrical weakness of the proximal lower and/or upper limbs, and difficulties in walking on heels and/or toes. The scoliosis found in two siblings has not been associated with protein O-mannosyltransferase 2 gene mutations related to limb-girdle muscular dystrophy 2N in previous reports. This report expands the phenotypic spectrum of protein O-mannosyltransferase 2 gene mutation-related limb-girdle muscular dystrophy 2N.