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.

Narrative review based on fingolimod therapy in pediatric MS.

The course of pediatric-onset multiple sclerosis and adult multiple sclerosis shows some clinical differences. The rate of having a second attack after the first clinical event is 80% in children and around 45% in adults but the time to the second event is similar in all age groups. The pediatric group usually has a more aggressive onset than adults. On the other hand, a higher rate of complete recovery is observed in pediatric-onset multiple sclerosis after the first clinical event compared to the adult group. Despite a highly active initial disease course, pediatric-onset multiple sclerosis patients show a slower increase in disability than patients with adult-onset disease. This is thought to be due to greater remyelination capacity and plasticity of the developing brain. The management of pediatric-onset multiple sclerosis includes safety issues as well as effective disease control. In the pediatric-onset multiple sclerosis group, similar to adult multiple sclerosis, injectable treatments have been used for many years with reasonable efficacy and safety. Since 2011, oral treatments and then infusion treatments have been approved and used effectively in adult multiple sclerosis and have gradually entered clinical use in the pediatric-onset multiple sclerosis group. However, clinical trials are fewer, smaller, and include shorter follow-up due to the much lower prevalence of pediatric-onset multiple sclerosis than adult multiple sclerosis. This is particularly important in the era of recent disease-modifying treatments. This review of the literature presents existing data on the safety and efficacy of fingolimod, pointing to a relatively favorable profile.

Clinically important intracranial abnormalities in children presenting with first focal seizure.

BACKGROUND: Management of pediatric patients presenting with first seizure is challenging, especially with regards to emergent neuroimaging. The rate of abnormal neuroimaging findings is known to be higher in focal seizures than in generalized seizures, but those intracranial abnormalities are not always clinically emergent. In this study, we aimed to determine the rate and indicators for clinically important intracranial abnormalities that change acute management in children presenting with a first focal seizure to the pediatric emergency department (PED). METHODS: This study was conducted retrospectively in the PED at a University Children`s Hospital setting. The study population consisted of patients aged between 30 days and 18 years with first focal seizure and who had emergent neuroimaging at the PED between the years 2001 and 2012. RESULTS: There were 65 eligible patients meeting the study criteria. Clinically important intracranial abnormalities requiring emergent neurosurgical or medical intervention were detected in 18 patients (27.7%) at the PED. Four patients (6.1%) underwent emergent surgical procedures. Seizure recurrence and the need for acute seizure treatment in the PED were significantly associated with clinically important intracranial abnormalities. CONCLUSIONS: Neuroimaging study yielding of 27.7% shows that first focal seizure must be evaluated meticulously. From the emergency department`s point of view; we suggest that first focal seizures in children should be evaluated with emergent neuroimaging, if possible with magnetic resonance imaging. Especially patients with recurrent seizures at presentation requires more careful evaluation.

Triggers and clinical changes of childhood primary headache characteristics during COVID-19 pandemic lockdown.

OBJECTIVE: Children with primary headache are particularly vulnerable to the negative impacts of the pandemic due to factors like increased social isolation, disruption of sleep and impairment of healthy diet. We aimed to investigate the clinical changes and triggering factors for childhood primary headaches to demonstrate the impact of the pandemic lockdown. METHOD: Children aged between 60 months and 18 years with headache complaint attending the general outpatient clinic between December 2019 and December 2020 were included in the study. Patients were classified according to ICHD-3 regarding clinical and laboratory data. Primary headaches diagnosed before (December 2019-March 2020) and during the pandemic lockdown (April 2020-December 2020) were divided into two groups as migraine and tension-type headache (TTH). Clinical picture and triggering factors were compared between groups to illustrate the effect of the lockdown. RESULTS: The study included 612 subjects, with 463 patients (76%) classified in the primary headache group and 149 (24%) in the secondary headache group. Among the first group, 267 patients (58%) had migraine and 196 patients (42%) had TTH. Comparisons between before and during the pandemic lockdown showed significant increased frequency of TTH, but no difference in the frequency and duration of migraine. Both screen exposure and sleep pattern changes were found to be significantly increased in the TTH group during the pandemic lockdown. DISCUSSION: We found a significant increase in the attack frequency for TTH patients during the pandemic lockdown. Reduction in screen time is an important strategy in preventing primary headache attacks in children.

Frequency of myelin oligodendrocyte glycoprotein antibodies in pediatric onset multiple sclerosis.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are associated with acute demyelinating syndromes and only rarely detected in multiple sclerosis (MS). As MOG-Ab associated disease is common in childhood, we speculated young patients might be more likely to produce MOG-Ab and investigated the frequency of MOG-Ab seropositivity in pediatric onset MS (POMS). MATERIAL AND METHODS: Patients who experienced their first acute demyelinating event before age 18 years and were diagnosed with MS during follow-up were included in this single-center study. Patient data were retrieved from clinical records. Serum samples obtained and frozen at clinical visits were analyzed for MOG-Ab by a live cell-based assay (CBA) measuring delta mean fluorescence intensity (MFI) and MFI ratio. The control group consisted of patients referred to pediatric neurology for headache or vertigo and who had no neurological disorder (n = 48). Another control group consisted of patients with systemic inflammatory disorders systemic lupus erythematosus (n = 17) and juvenile idiopathic arthritis (n = 13) diagnosed in the rheumatology clinic. RESULTS: The patient group (n = 122, F/M: 90/32, mean age 17.8 ± 2.6 years) were initially diagnosed as: MS, 62/122 (50.8%), clinically isolated syndrome, 43/122 (35.2%), radiologically isolated syndrome, 9/122 (7.3%), and acute disseminated encephalomyelitis 8/122 (6.5%). All received the final diagnosis of POMS. Serum was sampled 22.4 ± 29.2 (0-132) months after the first episode. None of the control groups had MOG-Ab positivity while 2/122 (1.6%) POMS cases had MOG-Abs, and a third patient had positive MFI and a MFI ratio slightly below the cut-off. These three patients' initial and final diagnoses were MS, their annualized relapsing rates (ARRs) were 0.4-0.6, and most recent Expanded Disability Status Scale was 0. CONCLUSION: Low titers of MOG-Ab can be detected in a small number of POMS patients at similar frequency with adult MS. Our POMS cases with MOG-Abs presented brainstem-cerebellar findings or seizures and had low ARR. Further series and longer follow-up will define whether these cases differ significantly from MOG-Ab negative POMS cases.

Synthetic MRI in children with tuberous sclerosis complex.

OBJECTIVE: The generation of numerous sequences and quantitative data in a short scanning time is the most potential advantage of Synthetic MRI (SyMRI). We aimed to test detection of the tubers and to determine underlying tissue characteristics, and morphometric alterations in the brain of pediatric tuberous sclerosis complex (TSC) patients, using SyMRI. METHODS: Conventional brain MRI (cMRI) and SyMRI were prospectively obtained from 10 TSC patients and 18 healthy control subjects (HCs). Two neuroradiologists independently evaluated tubers on both scans. Additionally, automatically segmented volume calculation and myelin quantification, including the subcortical part of the tubers and normal-appearing brain parenchyma (NABP) of patients, were carried out using SyMRI. RESULTS: The cMRI and SyMRI comparison showed a very good correlation on the detection of the tubers (k = 0.82-0.94). Automatic segmentation of Non-gray matter/white matter/cerebrospinal fluid (Non), %Non/brain parenchymal volume, and %Non/intracranial volume was significantly higher; however, %Myelin/intracranial volume and %Myelin/brain parenchymal volume were significantly lower in the TSC patients (p < 0.05). The proton density values were significantly increased, and myelin fraction volume and myelin-correlated compound values were significantly decreased in the NABP in TSC patients on myelin maps (p < 0.05). The white-matter volume, myelin and white-matter fractional volume, longitudinal relaxation rate, transverse relaxation rate, and myelin-correlated compound values were significantly decreased in the subcortical part of tubers on quantification maps (p < 0.001) in TSC patients. CONCLUSION: SyMRI enables the detection of cortical tubers and is a developing tool in the quantification of morphometric and tissue alterations in pediatric TSC patients with a rational scanning time.

Comparison of serum anti-neuronal antibody levels in patients having autism spectrum disorder with and without regression.

BACKGROUND: Autism Spectrum Disorders (ASD) may present with a delay in social and communication development, or less frequently, with regression in social and language skills. The reasons for this difference in clinical presentation are unknown, and the regressive symptoms in the second group suggest an acquired process. METHODS: We investigated serum autoantibodies in these two types of ASD in a cross-sectional design in a total of 50 children, 24 with autistic regression and 26 with classical ASD according to the DSM-5 criteria. Clinical assessment by the Childhood Autism Rating Scale (CARS) and Ankara Developmental Screening Test (ADST), parental questionnaires consisting of the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AuBC) were completed. Serum samples were tested for anti-neuronal antibodies including anti-N-methyl-Daspartate receptor (NMDAR), anti-contactin-associated protein (CASPR2), anti-leucine rich glioma inactivated 1 (LG1), anti-glutamate type 2-amino-3-propionic Acid (AMPA) 1-2, anti-gamma amino butyric acid (GABA) B, anti-dipeptidyl aminopeptidase-like protein 6 (DPPX) and anti-glutamic acid decarboxylase 65(GAD). RESULTS: Serum anti-GAD antibodies were at detectable levels in five (20.8%) patients with autistic regression, of whom three had 2 to 4-fold increased titers, and in none of the patients with classical ASD. The age of the father at the patient`s birth and the duration of autistic regression correlated with anti-GAD IgG levels (P: 0,045, P: 0.855 respectively) in the ASD-regression group. No other antibodies were detected in either group. CONCLUSIONS: Our results do not suggest a causative role of anti-neuronal antibodies, but the possibility of an autoimmune process accompanying regressive symptoms in a small subgroup of ASD.

Impairment of vestibulo-collic reflex and linear vestibulo-ocular reflex in pediatric-onset multiple sclerosis patients.

OBJECTIVES: This study aimed to examine the vestibulo-collic reflex (VCR) and linear vestibulo-ocular reflex (lVOR) and their correlation with brain lesions in pediatric-onset multiple sclerosis (POMS). METHODS: The study group consisted of 17 patients (34 ears) with POMS (mean age 18.73 ±â€¯2.02, mean age at disease onset 14.64 ±â€¯1.36 years), and the control group included 11 age-matched healthy subjects (22 ears). Ocular and cervical Vestibular Evoked Myogenic Potentials (oVEMP and cVEMP) were performed to assess IVOR and VCR pathways. Magnetic Resonance Imaging was evaluated in the study group. RESULTS: In the POMS group, 47.05 % of oVEMPs and 17.64 % of the cVEMPs were abnormal, while all VEMPs were normal in the control group. The oVEMP amplitude was associated with infratentorial lesion volume (r = -0.459, p = 0.01) and total lesion volume of the brainstem and cerebellum (r = -0.450, p = 0.01). The cVEMP asymmetry ratio was correlated with the deep white matter lesion volume (r = 0.683, p < 0.001). The MVEMP scores were found to correlate only with lesion volumes in the cerebellum (r = 0.488, p = 0.04) and infratentorial region (r = 0.573, p = 0.01). CONCLUSIONS: Ocular and cervical VEMP abnormalities confirm that lVOR and VCR pathways may be affected in early POMS. SIGNIFICANCE: Routine use of the VEMP test, especially the oVEMP test is recommended as a useful tool in the follow-up of POMS patients.

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.

Comprehensive clinical, biochemical, radiological and genetic analysis of 28 Turkish cases with suspected metachromatic leukodystrophy and their relatives.

Metachromatic leukodystrophy (MLD) is a glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ASA) or its activator protein saposin B. MLD can affect all age groups in severity varying from a severe fatal form to milder adult onset forms. Diagnosis is usually made by measuring leukocyte ASA activity. However, this test can give false negative or false positive laboratory results due to pseudodeficiency of ASA and saposin B deficiency, respectively. Therefore, we aimed to evaluate patients with suspected MLD in a Turkish population by comprehensive clinical, biochemical, radiological, and genetic analyses for molecular and phenotypic characterization. We analyzed 28 suspected MLD patients and 41 relatives from 24 families. ASA activity was found to be decreased in 21 of 28 patients. Sixteen patients were diagnosed as MLD (11 late infantile, 2 juvenile and 3 adult types), 2 MSD, 2 pseudodeficiency (PD) and the remaining 8 patients were diagnosed as having other leukodystrophies. Enzyme analysis showed that the age of onset of MLD did not correlate with residual ASA activity. Sequence analysis showed 11 mutations in ARSA, of which 4 were novel (p.Trp195GlyfsTer5, p.Gly298Asp, p.Arg301Leu, and p.Gly311Asp), and 2 mutations in SUMF1 causing multiple sulfatase deficiency, and confirmed the diagnosis of MLD in 2 presymptomatic relatives. All individuals with confirmed mutations had low ASA activity and urinary sulfatide excretion. Intra- and inter-familial variability was high for the same ARSA missense genotypes, indicating the contribution of other factors to disease expression. Imaging findings were evaluated through a modified brain MRI scoring system which indicated patients with protein-truncating mutations had more severe MRI findings and late-infantile disease onset. MRI findings were not specific for the diagnosis. Anti-sulfatide IgM was similar to control subjects, and IgG, elevated in multiple sulfatase deficiency. In conclusion, the knowledge on the biochemical, clinical and genetic basis of MLD was expanded, a modified diagnostic laboratory algorithm for MLD based on integrated evaluation of ASA activity, urinary sulfatide excretion and genetic tests was devised.

Long-term effects of vagus nerve stimulation in refractory pediatric epilepsy: A single-center experience.

INTRODUCTION: Vagus nerve stimulation (VNS) has been used as an adjunctive therapy for both children and adults with refractory epilepsy, over the last two decades. In this study, we aimed to evaluate the long-term effects and tolerability of VNS in the pediatric drug-resistant epilepsy (DRE) and to identify the predictive factors for responsiveness to VNS. METHODS: We retrospectively reviewed the medical records of pediatric patients who underwent VNS implantation between 1997 and 2018. Patients with ≥50% reduction of seizure frequency compared with the baseline were defined as "responders". The clinical characteristics of responders and nonresponders were compared. RESULTS: A total of 58 children (male/female: 40/18) with a mean follow-up duration of 5.7 years (3 months to 20 years) were included. The mean age at implantation was 12.4 years (4.5 to 18.5 years). Approximately half (45%) of our patients were responders, including 3 patients (5.8%) who achieved seizure freedom during follow-up. The age of seizure-onset, duration of epilepsy, age at implantation, and etiologies of epilepsy showed no significant difference between responders and nonresponders. Responders were more likely to have focal or multifocal epileptiform discharges (63%) on interictal electroencephalogram (EEG), when compared to nonresponders (36%) (p = .07). Vocal disturbances and paresthesias were the most common side effects, and in two patients, VNS was removed because of local reaction. CONCLUSION: Our series had a diverse etiological profile and patients with transition to adult care. Long-term follow-up showed that VNS is an effective and well-tolerated treatment modality for refractory childhood onset epilepsy. Age at implantation, duration of epilepsy and underlying etiology are not found to be predictors of responsiveness to VNS. Higher response rates were observed for a subset of patients with focal epileptiform discharges.

Aprepitant in the Treatment of Subacute Sclerosing Panencephalitis: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant in patients with subacute sclerosing panencephalitis. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with subacute sclerosing panencephalitis assigned to receive two courses of aprepitant 250 mg/day orally or placebo for 15 days with an interval of two months between courses. Primary end points were safety and tolerability, and secondary end point was clinical improvement or stabilization assessed by subacute sclerosing panencephalitis scoring system. Electroencephalography (EEG), brain magnetic resonance imaging, and cerebrospinal fluid measles-specific immunoglobulin G index were evaluated before and after treatment. RESULTS: Sixty-two patients with subacute sclerosing panencephalitis were allocated to aprepitant (n = 31, median age 18 years) or placebo (n = 31, median age 22 years) group. Fifteen patients left the study within the first six months and 12 patients left between six and 12 months. Aprepitant was well tolerated and treatment-associated adverse events were similar to those described in the treatment of nausea. Clinical status at six and 12 months' follow-up did not differ between aprepitant and placebo groups. Post-treatment EEG scores at 12 months were better in the aprepitant group (P = 0.015). Cerebral atrophy on magnetic resonance imaging increased in both groups, whereas measles-specific immunoglobulin G index decreased in the placebo group. CONCLUSIONS: In this first clinical trial of aprepitant treatment in patients with subacute sclerosing panencephalitis, the drug was safe and well tolerated. No clinical effect was observed. A modest improvement in EEG findings might justify trials for longer periods because EEG changes can precede clinical findings in subacute sclerosing panencephalitis.

Vestibulo-ocular reflex involvement in childhood-onset multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS), an autoimmune demyelinating disease of the central nervous system, is an important cause of disability in young adults. The purpose of this cross-sectional study was to evaluate the vestibular system with video Head Impulse Test (vHIT) and determine the impairment of the Vestibulo-ocular Reflex (VOR) in childhood-onset MS. METHODS: The study group, 20 persons with MS (pwMS) with onset before 18 years of age (6 M, 14 F; mean age 19.06 ± 1.66) and the control group, 20 healthy, age- and sex-matched individuals were retrieved from vHIT recordings. The mean age of MS onset in the study group was 14.60 ± 1.53 years. The VOR pathway was evaluated using vHIT. RESULTS: The median VOR gains of right anterior (1.00), left lateral (0.96) and left posterior (0.91) semicircular canals were significantly lower in the pwMS group than those of the healthy control group (1.05, 1.00, 0.98 respectively, p < 0.05). Four of pwMS (20%) had abnormal VOR gains. The pwMS with dizziness had significantly lower VOR gains (median 0.91) compared with pwMS without dizziness (median 1.01, p < 0.05). CONCLUSION: This study demonstrates vestibulo-ocular system can be affected in patients with childhood-onset MS and suggests using vHIT especially in the follow-up of pwMS with dizziness.

Acute Cerebellitis or Postinfectious Cerebellar Ataxia? Clinical and Imaging Features in Acute Cerebellitis.

Acute cerebellitis is a rare condition often considered within the group of acute postinfectious cerebellar ataxia despite its distinctive clinical and imaging features. We retrieved clinical, laboratory, and follow-up data of 15 children diagnosed with acute cerebellitis in our department between 2011 and 2019. There were 10 boys and 5 girls aged 3-15 years, median 9.5 years. The most common first symptoms were ataxia, vomiting, and headache. Magnetic resonance imaging (MRI) generally showed bilateral symmetrical T2 hyperintense changes with moderate swelling in the cerebellar cortex. Tonsillar herniation was present in 73.3% and obstructive hydrocephalus in 26.6%. Etiologic workup for infectious pathogens revealed Mycoplasma pneumoniae, influenza A virus, cytomegalovirus, and varicella zoster virus in 1 case each. Fourteen of 15 patients were treated with intravenous and/or oral steroids and 8 cases with intravenous immunoglobulin. No patient required surgical decompression. Neurologic examination median 12 months later revealed ataxia and dysmetria in 4 cases (27%), accompanied by memory difficulties, dysarthria or tremor. Follow-up magnetic resonance imaging (MRI; n = 12) showed diffuse cerebellar cortical T2-hyperintense signal changes in 11 cases and cerebellar atrophy in 9. The diagnosis of acute cerebellitis rather than acute postinfectious cerebellar ataxia should be considered when headache and vomiting accompany ataxia in a child. Acute cerebellitis heals with sequelae in about one-third of cases. The absence of fatalities in our series suggests early diagnosis, and steroid treatment can increase the chance of recovery. MRI results were not found to be predictive of outcome.

Cognitive functions in pediatric multiple sclerosis: 2-years follow-up.

Objective: To assess the neuropsychological status of pediatric multiple sclerosis (MS) patients and its relationship with clinical variables in a longitudinal study.Methods: Patients with MS (n = 46) and age- and gender-matched healthy control subjects (HCs, n = 53) were given tests of non-verbal reasoning, attention/concentration, visuospatial judgement and verbal fluency at baseline visit and after 2 years of follow-up. Cognitive impairment was defined as a failure on at least three of the four tests. Patients were grouped according to the age of disease onset (≤12 years as group 1 and > 12 years as group 2).Results: Cognitive impairment was detected in 22 of 46 patients at follow-up (47.8%). Patients with cognitive worsening had higher EDSS scores at follow-up compared to cognitively improved/stable group (0.68 ± 1.16 vs 0.04 ± 0.2, p = 0.01). The most affected domains were attention/concentration and non-verbal reasoning. Comparison between baseline and follow-up tests showed impairment in non-verbal reasoning over time in group 1 patients while other functions improved over time in patient and control groups as expected.Conclusion: Pediatric MS is likely to affect patients' cognition concurrently with their disability levels. This effect is significant in the non-verbal reasoning area in patients with disease onset before age 12 years. A practical method assessing this function should be part of these patients' regular follow-up for optimal treatment, prevention and rehabilitation.

Epilepsy in neurofibromatosis type 1: Diffuse cerebral dysfunction?

INTRODUCTION: Neurofibromatosis type 1 (NF1) is accompanied by epileptic seizures in 4-7% of patients. We examined clinical, electrophysiological, and radiological features associated with epilepsy in our NF1 series in order to identify risk factors. METHODS: We reviewed data of 641 pediatric patients with NF1 diagnosis according to National Institutes of Health (NIH) criteria in Hacettepe University records from January 2008-August 2018. Demographic features, NF1-related clinical and imaging characteristics, age at onset of epilepsy, seizure semiology, and frequency, electroencephalogram (EEG) findings, and response to treatment were noted. RESULTS: Twenty-six patients with NF1, 15 male, 11 female, had epilepsy. Age at seizure onset was 6 months to 13 years. Seizure semiology was focal with impaired awareness (n = 9, 34%), focal aware motor (n = 2, 8%), focal to bilateral tonic-clonic (n = 3, 12%), generalized tonic-clonic (n = 7, 28%), absence (n = 3, 12%), infantile spasms (n = 1), and unclassified type (n = 1). None had a history of status epilepticus. The EEG findings were normal for age in ten patients (38%). Others had focal (n = 8, 30%), generalized (n = 7, 27%), or multifocal (n = 1, 4%) discharges. On brain magnetic resonance imaging (MRI) signal intensity changes typical for NF1 (neurofibromatosis bright objects, NBOs) were the most common finding (80%), followed by normal MRI (20%). There was no relation between the localization of NBOs and discharges on EEG. Seventeen patients (65%) were seizure-free at the time of the study; 11 of them still under medication including four on multiple antiepileptic drugs. The rate of learning problems and NBO were significantly higher in patients with NF1 with epilepsy compared to those without. DISCUSSION: Epilepsy in NF1 is associated with relatively infrequent seizures and good response to treatment. Learning disorders are markedly frequent in this group, irrespective of the severity of epilepsy. The absence of correlation between the localizations of epileptiform discharges and lesions on MRI support the role of cellular or synaptic mechanisms rather than structural causes in the pathogenesis of epilepsy.

Treatment in childhood central nervous system demyelinating disorders.

The last two decades witnessed significant advances in the treatment of acquired demyelinating disorders: thirteen new agents have been approved for the treatment of multiple sclerosis in adults by the European Medicines Agency and US Food and Drug Administration in the last twenty years. Although the long-term efficacy and safety profiles of some new drugs are still being assessed in paediatric MS, clinicians may have to use them in the management of paediatric onset MS resistant to first-line medications, based on results obtained in adult-onset disease. This review summarizes the current approach to treatment in children with demyelinating syndromes. WHAT THIS PAPER ADDS: Serological markers affect management in paediatric demyelinating diseases. Antibodies against aquaporin-4 and myelin oligodendrocyte glycoprotein should be tested in children with acute demyelinating disease. New therapeutic agents currently in trial for pediatric disease should be used with close follow-up.

TRATAMIENTO EN LOS TRASTORNOS DESMIELINIZANTES DEL SISTEMA NERVIOSO CENTRAL INFANTIL: Las últimas dos décadas fueron testigos de avances significativos en el tratamiento de los trastornos desmielinizantes adquiridos, como lo demuestra la aprobación de 13 nuevos agentes por parte de la Agencia Europea de Medicamentos y la Administración de Medicamentos y Alimentos de los EE. UU. para el tratamiento de la esclerosis múltiple en adultos. A pesar de ciertas preguntas sobre los perfiles de eficacia y seguridad de los nuevos tratamientos en niños, la expansión de las opciones terapéuticas proporciona flexibilidad en la toma de decisiones basada en la potencia, los riesgos y las preferencias del paciente. En los casos pediátricos resistentes a los medicamentos estándar, los médicos frecuentemente guían su manejo basándose en los resultados obtenidos en la enfermedad de aparición en la edad adulta. Esta revisión resume el enfoque actual del tratamiento en niños con síndromes desmielinizantes.

TRATAMENTO EM DESORDENS DESMIELINIZANTES DO SISTEMA NERVOSO CENTRAL NA INFÂNCIA: As últimas duas décadas testemunharam avanços significativos no tratamento de desordens desmielinizantes adquiridas: 13 novos agentes foram aprovados pela Agência Européia de Medicamentos e a Administração de Alimentos e Medicamentos dos EUA para o tratamento da esclerose múltipla em adultos. Apesar de a eficácia em longo prazo e segurança de novos tratamentos ainda estejam sendo avaliados em EM pediátrica, clínicos podem ter que utilizá-las no manejo de EM de início pediátrico resistente a medicamentos de primeira linha, com base em resultados obtidos em casos de doença de início na vida adulta. Esta revisão sintetiza a abordagem atual para o tratamento de crianças com síndromes desmielinizantes.

Cardiac autonomic function evaluation in pediatric and adult patients with congenital myasthenic syndromes.

Cardiac autonomic dysfunction has been examined in myasthenia gravis but not in congenital myasthenic syndromes (CMS). We aimed to evaluate cardiac autonomic functions in genetically defined CMS. Patients diagnosed with and under treatment for CMS were reviewed for 24-hour cardiac rhythm monitoring. Heart rate variability (HRV) measures were defined as: SDNN, mean of the standard deviations for all R-R intervals; SDNNi, standard deviation of all R-R intervals in successive five-minute epochs; RMSSD, square root of the mean of squared differences between successive R-R intervals. Ten patients with mutations in the epsilon subunit of the acetylcholine receptor (AChRε) and five patients with mutations in the collagen-like tail of asymmetric acetylcholinesterase (ColQ) were included. Median age at evaluation was 17 (2.5-46) years. In the AChRε group, RMSSD values; and in the ColQ group, SDNN, SDNNi and RMSSD values were significantly lower than those of healthy subjects. This first extensive report examining HRV in CMS showed alterations in patients with ColQ mutations and, to a lesser extent, in the group with AChRε mutations. This might indicate an increased risk of cardiac arrhythmias. We suggest cardiological follow-up in CMS, and consideration of any potential cardiovascular effects of therapeutic agents used in management.