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.

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.

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.

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.

Hashimoto's encephalopathy: four cases and review of literature.

Hashimoto's encephalopathy is a rare clinically heterogenous condition consisting of encephalopathy, seizures and variable neurological and psychiatric manifestations, accompanied by high titres of serum antithyroid antibodies. We described the clinical and laboratory findings of four children (aged 8-17 years) with Hashimoto's encephalopathy. The clinical features of three patients at presentation included refractory epilepsy, and confusion, and one patient presented with behavioral and cognitive changes. During their presentation, two of them were in euthyroid, and the others were in hypothyroid status. All patients manifested increased antithyroid antibodies. Two patients improved with steroid treatment. The others responded to plasmapheresis instead of corticosteroid treatment. Physicians' awareness of this complication is of great importance because most patients respond dramatically to the treatment.

Fatal encephalitis associated with novel influenza A (H1N1) virus infection in a child.

A 4-year-old girl presented with fever, coughing, and vomiting; followed by unconsciousness. Magnetic resonance imaging showed hyperintense changes in the thalami bilaterally, brain stem, cerebellum, and subcortical cortex. Novel influenza A (H1N1) virus was identified by polymerase chain reaction in patient's nasopharyngeal swab specimen. We reported a rare case of clinically severe, novel influenza A-associated encephalitis. Novel influenza A should be considered in the differential diagnosis in patients with seizures and mental status changes, especially during an influenza outbreak.

Hypohidrosis and hyperthermia during topiramate treatment in children.

Topiramate is one of the newer generation antiepileptic drugs with a beneficial clinical effect on various seizure types. In this study, we present the clinical findings of hypohidrosis and hyperthermia with topiramate in pediatric patients. The data were collected retrospectively on 173 patients diagnosed as epilepsy on topiramate treatment, and hypohidrosis-related symptoms induced by topiramate were found in 22 patients. Their mean age was 64.45 +/- 56.63 months. The mean duration of topiramate treatment was 7.09 +/- 2.46 months, and the mean dose was 5.37 +/- 1.75 mg/kg/day. All of the patients complained of hypohidrosis and hyperthermia. Six (27.2%) of them had facial flushing, 4 (18.1%) had heat sensation and only 1 (4.5%) had lethargy. Hypohidrosis-related symptoms resolved after discontinuation of the medication. In conclusion, children treated with topiramate should be cautioned regarding these potential adverse effects and advised to avoid its use during the hot summer season.

Guillain-Barré syndrome in children.

Guillain-Barré syndrome (GBS) is one of the reasons of acute polyneuropathy causing severe morbidity and mortality. Forty-six patients with GBS were included in our study. Clinical, laboratory, electrophysiological and prognostic features of the patients were evaluated retrospectively. Patients were divided into two groups. Group A consisted of children who attained a full recovery within 2 months from onset of the disease; group B consisted of children who experienced complete or partial recovery beyond 2 months from onset of the disease. Acute inflammatory demyelinating polyradiculoneuropathy was found in 56.5% of patients and axonal form in 43.5% patients. Antecedent events were found in 28 (60.9%) patients. Five patients (10.8%) needed mechanical ventilation and one patient (2.1%) died. Poor outcome was related with clinic stage and electrophysiological subtypes (axonal form). In our study, poor prognostic factors were related with clinic stage and electrophysiological subtypes (axonal form).

Evaluation of sixteen children with pseudotumor cerebri.

Pseudotumor cerebri (PTC) is a clinical condition characterized by signs and symptoms of increased intracranial pressure, such as headache and papilledema. A total of 16 patients diagnosed with PTC [12 (75%) female; 4 (25%) male] were included in the study. The age of onset of symptoms was 123.4 +/- 34.3 months (range: 60-168 months). Obesity was found in four (25%) of them. Two patients had venous sinus thrombosis, two had corticosteroid withdrawal, and one had posttraumatic PTC. The most common symptom was headache, recorded in 93.8% of the patients. All patients were treated medically. Two patients in our group also required a lumboperitoneal shunt. In conclusion, PTC in children is rare. Both papilledema and sixth nerve palsy resolved rapidly with treatment. However, children can sustain loss of visual field and visual acuity despite treatment.

Albendazole-induced dystonic reaction: a case report.

Drug-induced dystonic reactions are a common presentation to the emergency department and typically occur with drugs like chlorpromazine, haloperidol and metoclopramide. There are no reports in the literature of dystonic reaction caused by albendazole. We report a case of albendazole-induced acute dystonic reaction whose symptoms completely resolved after the discontinuation of the drug. Even though dystonia side effects of albendazole are rare, it can induce an alarming dystonia in some sensitive children. The mechanism of dystonia is unclear.

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.

Pseudotumor cerebri in a child with hyperimmunoglobulin E syndrome.

Hyperimmunoglobulin E syndrome (HIES) is recognized as a multisystem disorder with various connective tissue, skeletal and immunologic abnormalities. Central nervous system abnormalities have been considered a feature of HIES. Pseudotumor cerebri (PTC) is a condition characterized by increased intracranial pressure in the absence of any intracranial mass lesion or ventricular dilatation, with normal neurology and cerebral spinal fluid composition. PTC without papilledema is rarely reported in children. We describe an atypical presentation of PTC in a child with HIES.

Neurologic findings of nutritional vitamin B12 deficiency in children.

We report herein our interesting case series of 15 infants admitting with neurological symptoms who were found to have vitamin B12 deficiency. Infants who were admitted to our hospital between 2004 and 2007 with neurological symptoms and were found to have vitamin B12 deficiency were included in this study. Data regarding clinical and laboratory features were obtained. Of 15 infants, 9 were boys (60%) and 6 were girls (40%). The mean age was 11.7 months. Anorexia, pallor, hypotonia, and neurodevelopmental retardation were present in all infants. Seizures and tremor were observed in 46.6% (7/15) and 33% (5/15) of patients, respectively. Seizures were generalized tonic-clonic in 4 patients, generalized tonic in 1 patient and focal in 2 patients. Four patients had tremor on admission and 1 patient had occurrence after vitamin B12 treatment. Vitamin B12 deficiency may lead to serious neurological deficits in addition to megaloblastic anemia. Persistent neurological damage can be prevented with early diagnosis and treatment. We believe that a thorough clinical and neurological assessment might prevent failure to notice rare but possible vitamin B12 deficiency in infants with neurological deficits and neurodevelopmental retardation.

Hypokalemic periodic paralysis due to the SCN4A R672H mutation in a Turkish family.

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disorder characterized by episodic attacks of muscle weakness associated with a decrease in blood potassium levels. Recently, mutations in the gene coding for the skeletal muscle voltage-gated sodium channel alpha subunit (SCN4A) have been reported. We detected the R672H mutation in one HypoPP Turkish family.

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.

Cognitive functions in neurofibromatosis type 1 patients and unaffected siblings.

Attention, learning, and perceptual problems have been reported at various degrees and rates in neurofibromatosis type 1 (NF1). We aimed to define the cognitive profiles frequently associated with NF1. Children and adolescents with NF1 (n=58) were tested using Wechsler Intelligence Scales for Children-Revised (WISC-R), Judgment of Line Orientation, and Bender Visual-Motor Gestalt tests. Comparison groups were unaffected siblings of NF1 patients (n=20), children with attention deficit and hyperactivity disorder (ADHD, n=40), and normal children (n=40). No difference was found between familial or sporadic NF1 cases. Seventeen/58 (29%) of NF1 cases had a full scale IQ<70. The subgroup of NF1 patients with full scale IQ>80 (n=27) scored lower in WISC-R subtests measuring visual perception when compared to a healthy control group of similar intelligence, and lower in arithmetic but better in Bender-Gestalt and Judgment of Line Orientation tests when compared to an ADHD group of similar intelligence. These results indicate a high prevalence of mental retardation in a clinical NF1 series. NF1 patients who have normal intelligence may have impaired visual perception, but their visual perceptual problems are less than in ADHD. The tendency of unaffected siblings of NF1 patients to have mildly but consistently low test scores compared to healthy controls needs to be studied further for underlying genetic or environmental factors.

Evaluation of nine children with reversible posterior encephalopathy syndrome.

BACKGROUND: Reversible posterior leukoencephalopathy syndrome (PRES) is a neurological disorder characterized by signs of posterior cerebral edema upon radiographic examination. MATERIALS AND METHODS: We retrospectively analyzed the records of nine children with the diagnosis of PRES. RESULTS: Of the nine patients, seven were receiving immunosuppressive therapy and two were acute hypertensive crisis associated with renal disease. Immunosupressive drugs were intrathecal methotrexate in two patients, cyclosporine in two patients, intrathecal cytarabine in one patient, cyclophasphamide in one patient, and intravenous immunoglobulin (IVIg) in another one patient. The most presenting symptoms were seizure, headache, and altered consciousness. Six patients had seizures. Altered consciousness was present in four patients. Headache and nausea or vomiting was present also in six patients. Visual abnormalities were noted in two patients. Magnetic resonance imaging (MRI) studies showed white-matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres, but the changes often involved other cerebral areas, the brain stem, basal ganglia or the cerebellum. The patients were treated with antihypertensive medications, and immunosuppressive therapy was withdrawn. In all the patients, the clinical and radiological findings resolved more completely. CONCLUSION: Reversible posterior leukoencephalopathy may develop in patients who have renal insufficiency or hypertension or who are immunosuppressed. This syndrome should be recognized immediately and trigger agents can be discontinued to prevent long-term sequelae.

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.

Clinical characteristics of 10 patients with continuous spikes and waves during slow sleep syndrome.

Continuous spikes and waves during slow sleep syndrome is characterized by the presence of spike-and-wave discharges in at least 85% of non-rapid eye movement sleep. Associated clinical features vary. Here, features of 10 patients with this syndrome are compared to those in the literature. Patients ranged in age from 4 to 11 years. All patients had predominantly nocturnal partial motor or generalized tonic-clonic seizures; four patients also had daily atonic seizures. All 10 patients had different degrees of neuropsychologic disturbances: 9 patients had low intelligence quotient scores (the 10th, diagnosed attention deficit and hyperactivity disorder, had normal intelligence quotient score); 4 patients had autistic-like features. Apart from mental retardation (7 of 10), physical and neurologic findings were normal. Significant pyramidal signs and microcephaly were detected in two patients, and hypotonia, ataxia, and bilateral pyramidal signs were found in one other. Cranial magnetic resonance imaging findings were normal for 6 patients; the other 4 had some abnormal findings. Continuous spikes and waves during slow sleep syndrome is a rare epileptic syndrome in childhood. A variety of clinical and neurocognitive features were found in patients with continuous spikes and waves during slow sleep syndrome.