Congenital myasthenic syndrome in Turkey: clinical and genetic features in the long-term follow-up of patients.

Congenital Myasthenic Syndromes (CMS) are rare disorders that occur as a result of defects in the structure and in the function of neuromuscular junctions. Molecular genetic diagnosis is important to select the most suitable therapeutic option and treatment. Eight patients with congenital myasthenic syndromes who presented to the Çukurova University Pediatric Neurology Department Outpatient Clinic between June 2015 and May 2018 were reviewed. Mutations in the acetylcholine receptor (subunits in epsilon) (CHRNE) in three and mutations in the collagenic tail of endplate acetylcholinesterase (COLQ) gene in five patients were identified; p.W148 mutation was detected to be homozygous in four, c.1169A > G novel mutation in COLQ gene was homozygous in one, c452_454delAGG mutation was homozygous in the other patient, IVS7 + 2T > C(c.802 + 2T > C) mutation was homozygous in a patient and compound heterozygous mutations of c.865C > T(p.Leu289Phe) and c.872C > G(p.A2916)(p.Arg291Gly) in the CHRNE gene in the last patient. The parents of all the evaluated patients were consanguineous. Ptosis, ophthalmoplegia, generalized hypotonia, bulbar weakness, and respiratory crisis were the main findings at the time of presentation. Pyridostigmine is the first-line drug therapy in primary AChR deficiency. Beta adrenergic agonists, ephedrine, and albuterol are the other treatment options for CMS subtypes caused by mutations in COLQ. This study points out the genetic and phenotypic features of CMS patients in the Turkish population and it also reports previously unreported mutations in the literature. CHRNE and COLQ gene mutations are common in the Turkish population. Patients can get serious benefits and recover after the treatment. The treatment should be planned according to genetic tests and clinical findings.

Optic Nerve Sheath Diameter and Retinal Artery Resistive Index Measurements with Bedside Ophthalmic Ultrasound in Pediatric Patients with Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome (PTCS) is characterized by raised intracranial pressure (ICP) with no neuroradiological abnormalities. Ocular ultrasound has been in use to measure optic nerve sheath diameter (ONSD), and retinal artery Doppler indices have been used for indirect assessment of ICP by pediatric intensivists. Here, we aimed to evaluate the correlation of the lumbar puncture (LP) opening pressure with the ultrasonographic ONSD and retinal resistive index (RRI) measures in patients with PTCS. And we wanted to find an answer to the following question: Can ultrasonographic ONSD measures serve as a follow-up tool in patients with PTCS? A prospective, single-center, case-control study was performed by pediatric intensive care and pediatric neurology departments. A total of 7 patients with PTCS were evaluated as patient group and 15 healthy children were evaluated as control group. The mean age of patient group was 138.8 ± 43.7 months. The mean right ONSD was 6.7 ± 0.5 mm and the mean left ONSD was 6.7 ± 0.6 mm. The mean right RRI value was 0.73 ± 0.03 and the mean left RRI was 0.73 ± 0.09. For the patient group, ONSD and RRI values of both eyes were statistically significant higher values than for the control group. The mean LP opening pressure was 56.57 ± 16.36 cmH 2 O. We detected strong, positive, and statistically significant correlations between the LP opening pressure and ONSD baseline measures for both the right eye ( r = 0.882, p = 0.009) and the left eye ( r = 0.649, p = 0.004). There was no correlation between opening pressure in LP and RRI measurements. We detected a statistically significant decrease in the right ONSD and left ONSD values and visual analog scale scores at the third-month follow-up. Our study results demonstrate that ultrasonographic ONSD measurements can be used as a noninvasive tool for assessment of the ICP at first admission and can be used as a follow-up tool in PTSC patients.

Dynamic thiol/disulphide homeostasis in children with neurofibromatosis type 1 and tuberous sclerosis.

Neurofibromatosis type 1 (NF1) and tuberous sclerosis (TSC) are autosomal dominant neurocutaneous diseases. Epilepsy, malignancy and other neurological complications are common in both diseases. We aimed to investigate the thiol/disulphide balance as an oxidative stress marker in children who suffer from NF1 and TSC. Twenty-two patients with NF1, 20 TCS, and 22 healthy control subjects were included in the study. The total thiol, native thiol, and disulphide levels were measured and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated and compared in three groups. The mean age and sex distribution of the patients with TSC and NF1 and the healthy control were similar. The total thiol, native thiol, and disulfide level was lower in TSC and NF1 group than the healthy control group. There were no significant differences among disulphide/native thiol and disulphide/total thiol ratios of three groups. We detected that the total thiol, native thiol, and disulfide levels were lower in TSC and NF1 group than the healthy control group. These results indicate that dynamic thiol-disulphide homeostasis can be used as a marker of oxidative stress in clinical trials with TSC and NF1.

Factors affecting epilepsy prognosis in patients with tuberous sclerosis.

PURPOSE: We aimed to determine the characteristics of epileptic seizures that significantly affect the cognitive functions of 83 patients followed with tuberous sclerosis complex (TSC), their resistance to treatment and risk factors causing this resistance. MATERIALS-METHODS: In order to determine the prognosis, the seizure-free/seizure-controlled group and the group with refractory seizures were compared. In addition, risk factors affecting cognitive functions in the patients were determined. RESULTS: There was a statistical significance between the presence of a history of seizures in the neonatal period, the age of onset of seizures being less than 2 years of age, autism, status epilepticus, Lennox-Gastaut syndrome (LGS), presence of infantile spasm, generalization of the electroencephalography (EEG) findings, the number of tubers in cerebral imaging being more than three and refractory seizures (p < 0.05). Statistically significant relationship was found between presence of a history of seizures in the neonatal period, the age of onset of seizures, autism, LGS, presence of infantile spasm, presence of status epilepticus history, history of using more than three antiepileptic drugs, generalization of EEG findings, presence of SEGA in cerebral imaging, number of tubers being more than three and the patient's mental retardation (p < 0.05). CONCLUSION: In logistic regression analysis, the age of the seizure onset being less than 2 years of age, the presence of autism and number of tubers being more than three in cerebral magnetic resonance imaging (MRI) are determined to be the risk factors that most likely to increase the seizures to be more resistant.

Retrospective analysis of children with myelin oligodendrocyte glycoprotein antibody-related disorders.

BACKGROUND: Knowledge has been expanding on myelin oligodendrocyte glycoprotein (MOG) antibody-associated central nervous system disorders. We delineate the clinical and paraclinical findings and outcome of our pediatric patients with MOG antibody seropositive disease. METHODS: We retrospectively analyzed the clinical presentation, cerebrospinal fluid findings, magnetic resonance imaging (MRI) studies, course and outcome of children seropositive for anti-MOG IgG. RESULTS: Total 20 children with neurological symptoms and serum anti-MOG IgG were identified from six centers in Turkey. Median age at onset was 9 years (mean 8.8 ±â€¯5.0 years, range: 1.5-16.5 years). Final diagnoses were acute disseminated encephalomyelitis (ADEM) (n = 5), ADEM + optic neuritis (n = 4), neuromyelitis optica spectrum disorder (NMOSD) (n = 3), myelitis (n = 2), relapsing optic neuritis (n = 2), multiphasic DEM (n = 3), and unclassified relapsing demyelinating disease (n = 1). Seven/20 (35%) children experienced a single episode while 13/20 (65%) had a least one relapse during follow-up. On MRI, subcortical white matter, brainstem, and corpus callosum were preferentially involved regions. Full recovery was observed in 15/20 (75%) children. CONCLUSION: MOG autoimmunity in children has a wide clinical spectrum, tendency to relapse, and a favourable outcome compared with other relapsing demyelinating diseases.

Risk factors affecting prognosis in infantile spasm.

AIM: To assess risk factors that affect epilepsy prognosis and neurodevelopmental outcome and response to treatment in patients diagnosed with infantile spasm. METHODS: In this study, demographics, treatment modalities, etiologies, risk factors affecting neurodevelopmental outcome and epilepsy prognosis were assessed retrospectively at the end of a minimum 24-months follow-up of 104 patients diagnosed with infantile spasm from May 2012 to October 2015. RESULTS: Neonatal seizure during neonatal period, abnormal head circumference, young age at the time of presentation and early gestational age, symptomatic etiology, abnormal initial examination and abnormal development test at the time of diagnosis, consanguinity, the medical center where treatment was started in the second center or beyond and magnetic resonance imaging finding were found to be statistically significant for poor prognosis in terms of neurodevelopment (p < 0.05). Abnormal initial examination and abnormal development test both at the time of diagnosis and at the end of follow-up, consanguineous parents, young age at the time of presentation, symptomatic etiology, a family history of mental retardation and epilepsy were found to be statistically significant for poor prognosis in terms of epilepsy. Administration of adrenocorticotropic hormone (ACTH) for seizure control was statistically significant compared to other antiepileptic drugs (p < 0.05). CONCLUSION: Infantile spasm is an age-related epileptic encephalopathy, and it was observed that it is still catastrophic, and that the most important factor affecting prognosis of epilepsy is etiology, age at the time of presentation and the medical center where treatment was started in the second center or beyond.

Guillain-Barré syndrome with hyperreflexia and bilateral papillitis in a child.

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy characterized by rapidly progressive symmetric weakness, and areflexia. Areflexia is necessary for the diagnosis of GBS. However, recently there have been studies of hyperreflexia with axonal neuropathy form of GBS. We report a 14-year-old boy with GBS, who presented with hyperreflexia and bilateral papillitis. To the best of our knowledge, this is the first pediatric patient presenting with papillitis and hyperreflexia with acute motor and sensory axonal neuropathy form of GBS.

Intravenous levetiracetam in critically ill children.

BACKGROUND: To report the effectiveness and safety of intravenous (IV) levetiracetam (LEV) in the treatment of critically ill children with acute repetitive seizures and status epilepticus (SE) in a children's hospital. MATERIALS AND METHODS: We retrospectively analyzed data from children treated with IV LEV. RESULTS: The mean age of the 108 children was 69.39 ± 46.14 months (1-192 months). There were 58 (53.1%) males and 50 (46.8%) females. LEV load dose was 28.33 ± 4.60 mg/kg/dose (10-40 mg/kg). Out of these 108 patients, LEV terminated seizures in 79 (73.1%). No serious adverse effects were observed but agitation and aggression were developed in two patients, and mild erythematous rash and urticaria developed in one patient. CONCLUSION: Antiepileptic treatment of critically ill children with IV LEV seems to be effective and safe. Further study is needed to elucidate the role of IV LEV in critically ill children.

Neurofibromatosis type 1 and cardiac manifestations.

OBJECTIVE: Cardiac manifestations of neurofibromatosis type 1 (NF1) may include hypertension, congenital heart disease, and hypertrophic cardiomyopathy. The aim of this study was to evaluate cardiac abnormalities in patients with NF1. METHODS: Sixty-five NF1 patients (mean age: 9±4.48 years) were retrospectively studied. Standard electrocardiography and echocardiography were performed in all patients. RESULTS: Cardiac abnormalities were found in 11 of the 65 patients (15.3%). Five patients had mitral valve regurgitation, 2 patients had secundum atrial septal defect, 1 patient had pulmonary valvular stenosis, 1 patient had ventricular septal defect, 1 patient had tricuspid valve regurgitation, and 1 patient had aortic valve regurgitation. CONCLUSION: Cardiac abnormalities have potential long-term hemodynamic consequences that justify an early diagnosis. Thus, for any patient with NF1, a cardiologic assessment is mandatory at the time of diagnosis and with regular follow-up intervals.

A Multinational Survey on Actual Diagnostics and Treatment of Subacute Sclerosing Panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a chronic infection of the central nervous system caused by the measles virus (MV). Its prevalence remains high in resource poor countries and is likely to increase in the Northern Europe as vaccination rates decrease. Clinical knowledge of this devastating condition, however, is limited. We therefore conducted this multinational survey summarizing experience obtained from more than 500 patients treated by 24 physicians in seven countries. SSPE should be considered in all patients presenting with otherwise unexplained acquired neurological symptoms. In most patients, the diagnosis will be established by the combination of typical clinical symptoms (characteristic repetitive myoclonic jerks), a strong intrathecal synthesis of antibodies to MV and typical electroencephalogram findings (Radermecker complexes). Whereas the therapeutic use of different antiviral (amantadine, ribavirin) and immunomodulatory drugs (isoprinosine, interferons) and of immunoglobulins has been reported repeatedly, optimum application regimen of these drugs has not been established. This is partly due to the absence of common diagnostic and clinical standards focusing on neurological and psychosocial aspects. Carbamazepine, levetiracetam, and clobazam are the drugs most frequently used to control myoclonic jerks. We have established a consensus on essential laboratory and clinical parameters that should facilitate collaborative studies. Those are urgently needed to improve outcome.

First-drug treatment failures in 42 Turkish children with idiopathic childhood occipital epilepsies.

BACKGROUND: The early and late benign occipital epilepsies of childhood (BOEC) are described as two discrete electro-clinical syndromes, eponymously known as Panayiotopoulos and Gastaut syndromes. The purpose of this study was to identify predictors of failure to respond to the initial antiepileptic drug (AED). MATERIALS AND METHODS: A total of 42 children with BOEC were enrolled. Predictive factors were analyzed by survival methods. RESULTS: Among the 42, 25 patients (59.5%) were boys and 17 (40.5%) were girls and the mean age at the seizure onset was 7.46 ± 2.65 years (4-14 years). Of the 42 patients, 34 (81.0%) were treated relatively successfully with the first AED treatment, and 8 (19.0%) were not responded initial AED treatment. There was no correlation between response to initial AED treatment and sex, consanguinity, epilepsy history of family, age of seizure onset, frequency of seizures, history of status epilepticus, duration of starting first treatment, findings on electroencephalogram. However, history of febrile seizure and type of BOEC were significantly associated with failure risk. CONCLUSIONS: Factors predicting failure to respond to the AED were history of febrile seizure and type of BOEC in children with BOEC.

First-drug treatment failures in children with typical absence epilepsy.

BACKGROUND: Childhood absence epilepsy (CAE) is a well-known syndrome with onset in middle childhood and is characterized by multiple typical absences per day. Pharmacological treatment is specific and usually successful with a single medication. The goal of the study was to assess on risk factors associated with failure to respond to the initial antiepileptic drug (AED). METHODS: Fifty-two children with CAE were enrolled. Predictive factors were analyzed by survival methods. RESULTS: Among 52 patients, 32 patients (61.5%) were girls and the remaining 20 (38.5%) were boys and the mean age at the seizure onset was 6.5±1.78 years old (3-11.5 years). Of the 52 patients, 42 (80.8%) were treated relatively successfully with the first AED treatment (Group A), and 10 (19.2%) were not responsed (Group B). Age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response were significantly associated with failure risk according to univariate analysis. In the multivariate analysis, only photoconvulsive EEG response was the risk factor influencing poor response to initial AED treatment. CONCLUSION: Factors predicting failure to respond to the AED were age of seizure onset, coexisting other types of seizures, and photoconvulsive EEG response in children with CAE.

Prognostic significance of failure of the initial antiepileptic drug in children with benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: Benign epilepsy with centrotemporal spikes is the most common partial epilepsy syndrome in children. The long-term prognosis for children with BECTS is believed to be generally excellent with seizures usually responding well to AEDs. The goal of the present study was to determine the risk factors associated with a poor prognosis. METHODS: Eighty-four children with BECTS were retrospectively analyzed. Fifty-four (64.3%) were boys and 30 (35.7%) were girls with the mean age at seizure onset 7.1 ± 2.01 years (range: 3-12 years). RESULTS: Of the 84 patients, 72 (85.7%) were treated successfully with the first AED (Group A), and 12 (14.3%) failed to responded to the initial AED treatment (Group B [poor prognosis]). Univariate analyses suggested that younger age of seizure onset, presence of generalized seizures, and frequent seizures (>3 prior to the initial treatment) were associated with failure to control seizures with the initial AED. Multivariate analysis suggested that younger age of seizure onset was the independent risk factor predicting a poor response to initial AED treatment. CONCLUSION: About 14% of our cohort of children with BECTS continued to have seizures following the initial AED treatment. Further prospective studies are warranted to determine how well prognosis can be predicted by age of seizure onset, type of seizures, and frequency of pre-existing seizures in children with BECTS.

Giant axonal disease: Report of eight cases.

BACKGROUND: Giant axonal neuropathy (GAN) is an autosomal recessive inherited progressive motor and sensory neuropathy with typical onset in early childhood. The disease is caused by GAN gene mutations on chromosome 16q24.1. To determine clinical and genetic results in Turkish patients with GAN. METHODS: Eight children with GAN were retrospectively analyzed. Five (62.5%) were girls and 3 (37.5%) were boys with the mean age on admission 10.13±3.8 years (range: 5-15 years). RESULTS: Parental consanguinity was found in all the families. The patients had the classical clinical phenotype characterized by a severe axonal neuropathy with kinky hair. Two patients had contractures of extremities, and not walking. One patient was walking with aid. The other patients were walking without aid. Mutation analysis was performed in two patients and IVS9 (+1G>T) (homozygous) mutation was detected. CONCLUSION: The classical clinical findings allowed considering the GAN diagnosis, but, in atypical cases and milder phenotypes, the presence of giant axons in nerve biopsy was helpful to specify molecular analysis.

Pyridoxine-dependent epilepsy in two Turkish patients in Turkey and review of the literature.

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive enzyme defect in the vitamin B6 metabolism characterized by intractable seizures which are usually resistant to all antiepileptic drugs but respond to pharmacological doses of pyridoxine. We present the clinical and molecular genetic findings of two patients with c.1597_1597delG mutations in ALDH7A1 gene. There are different clinical phenotypes in PDE: patients with complete seizure control with pyridoxine and normal development (group 1), patients with complete seizure control with pyridoxine and development delay (group 2), and patients with persistent seizures despite pyridoxine treatment and with development delay (group 3). Our two patients have persistant seizure despite pyridoxine treatment and with development delay. Pyridoxine-dependent epilepsy can be identified in any neonate with signs of encephalopathy and refractory seizures, with no evidence of hypoxic-ischemic damage or other underlying metabolic disturbance. Neurodevelopmental outcomes of patients with PDE is multifactorial; early diagnosis and treatment of these patients is vital.