Tülay Kamaşak

Leukoencephalopathy with thalamus and brainstem involvement and high lactate caused by novel mutations in the EARS2 gene in two siblings

Leukoencephalopathy with thalamus and brainstem involvement, and high lactate (LTBL) is a recently identified disease related to mutations in the EARS2 gene encoding glutamyl-tRNA synthetase. We report clinical and radiological findings for two siblings with new pathogenic mutations in the EARS2 gene. Both patients showed symptoms of mild-type disease, but there were clinical differences between the two siblings. While the older brother had hypotonia and delayed developmental milestones, the younger brother had seizures and spasticity in the lower extremities. Brain magnetic resonance imaging (MRI) findings were quite similar for the two siblings. MRI findings were specific to LTBL. MRI lesions of the older sibling had regressed over time. Clinical and radiological improvement, as in the previously reported patients with LTBL, may be an important clue for diagnosis.

Comparison of the serum cytokine levels before and after adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasm

PURPOSE Infantile spasm is an age-dependent epileptic syndrome seen in infancy or early childhood. Although studies have investigated the epilepsy-cytokine relationship, there has been insufficient research into the relation between cytokines and infantile spasm. The purpose of this study was to examine the role of cytokines in the pathogenesis of infantile spasm by investigating cytokine levels before and 1month after adrenocorticotropic hormone (ACTH) therapy in patients diagnosed with the condition. METHOD Twenty patients aged between 1month and 2years and diagnosed with infantile spasm at the Karadeniz Technical University Medical Faculty Department of Child Health and Diseases Pediatric Neurology Clinic, Turkey, and 20 healthy children were included in the study. Patients received 11 doses of ACTH on 2days a week. Levels of TNF-alpha and IL-2, the main cytokines involved in inflammation and recently associated with infantile spasm, and of IL-1beta, IL-6 and IL-17A, associated with epileptic seizures, and serum levels of the IL-17A activator IL-23 were investigated in all patients at the start of treatment and 1month after completion of treatment. RESULTS No statistically significant difference was observed between pre- and post-treatment patient group and control group IL-1beta, IL-2, IL-23 or TNF-alpha levels. Pre-treatment IL-6 and IL-17A levels were significantly higher in the untreated patient group compared to the healthy control group (p<0.001 and p=0.002). CONCLUSION Our study supports the recent idea that IL-6 and IL-17A are cytokines involved in the pathogenesis of infantile spasm.

A rare cause of chronic ataxia in childhood: ganglioneuroma

Ganglioneuroma is an extremely rare cause of ataxia in childhood, the only descriptions of which are in the form of case reports [1, 2]. Ganglioneuroma can be asymptomatic in the abdominal and thoracic region, or else can be symptomatic with abdominal pain, scoliosis, opsomyoclonus and ataxia. It may cause dysphonia and stridor in a cervical location [1]. While chronic ataxia with associated findings such as opsoclonus and cerebellar atrophy are rare in ganglioneuromas [3–5], isolated pure chronic ataxia is exceedingly unusual [2]. A 4-year-old-boy presented with wide-base gait over the previous 2 years. He recently described hand tremor when reaching out for an object. There was no infection history prior to the symptoms. His personal medical history was uneventful, and there was no family history of ataxia or other movement disorder. Neurological examination revealed gait ataxia and dysmetria. Physical examination revealed no opsoclonus-myoclonus, nystagmus or oculomotor apraxia. Alpha fetoprotein level was borderline at 0.98 mg/dL (range 0–0.9 mg/dL). Metabolic screening, electromyography, cranial neuroimaging findings and aprataxin and senataxin gene analysis were normal. Spinal magnetic resonance imaging (MRI) revealed a mass lesion on the right adrenal gland. Abdominal MRI revealed a mass lesion 21 × 18 mm in size in the right adrenal gland with homogeneous contrast enhancement (Fig. 1). Surgery was performed following consultation with the pediatric surgery department. The right adrenal mass was excised totally. Pathological examination identified the tumor as ganglioneuroma (Fig. 2). Peripheral neuroblastic tumors are tumors of the neural crest. They are classified into three histological types: neuroblastoma, ganglioneuroblastoma and ganglioneuroma. They derive from the sympathetic ganglia or adrenal medulla and exhibit a broad spectrum of differentiation and neuronal maturation [6]. Neuroblastoma is the most common and most highly malignant form. This exhibits a histological pattern of abundant neuroblasts and scarce stroma. Opsoclonus-myoclonus ataxia syndrome is the most common paraneoplastic manifestation, being reported in 2–4% of children with neuroblastoma [7]. Ganglioneuromas are rarer and generally benign. These are stroma-predominant tumors, with more or less mature ganglion cells. Pure ganglioneuroma does not contain immature elements, such as neuroblasts, intermediate cells, or mitotic figures [1, 8, 9]. Ganglioneuromas most commonly occur in the mediastinum, retroperitoneum, cervical region and abdominal region. Although they can cause symptoms such as abdominal pain, scoliosis, and stridor, they can also be asymptomatic. Although clinical data concerning neurological symptoms during childhood are limited, these tumors may cause opsoclonus-myoclonus ataxia as they originate from the neural crest [1]. Since there is no treatment for the majority of progressive hereditary ataxias, it is important for treatable causes not to be overlooked [10, 11]. Following complete resection of the tumor, the gait ataxia in this case resolved in a few days. Ataxia and dysmetria had resolved completely at neurological examination 1 month * Elif Acar Arslan elifacararslan@gmail.com

The effects of valproate and topiramate use on serum insulin, leptin, neuropeptide Y and ghrelin levels in epileptic children

PURPOSE Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group. METHOD 48 patients (25 VPA, 23 TPM) aged between 6 and 15.5 years, presenting to the Karadeniz Technical University Medical Faculty Pediatric Neurology Clinic, diagnosed with idiopathic epilepsy or location-related idiopathic epilepsy, and receiving VPA or TPM monotherapy for at least 6 months were included in the study. Twenty-five healthy subjects with similar demographic characteristics were enrolled as the control group. Blood samples were collected from the patient and control groups after fasting for at least 10-12 h and again 1 and 2 h postprandially. Body mass index (BMI) values were calculated for all cases. VPA levels, glucose, insulin, leptin, neuropeptide Y and ghrelin were investigated in all three separate blood samples. RESULTS Age, height, weight and BMI were similar between the patient and control groups. Significant weight gain was observed throughout treatment in the VPA group compared to the TPM group. High fasting and postprandial insulin levels were observed in the VPA group. VPA group leptin and neuropeptide Y (NPY) levels were also higher than in the TPM and control groups. No significant difference was determined in ghrelin levels in the patient groups compared to the controls. CONCLUSION Low blood sugar not being observed, even though insulin levels are high, after fasting and in the postprandial period in epileptic children receiving VPA is indicative of insulin resistance. The elevation in leptin and neuropeptide Y levels observed in the VPA group also suggest this.

Are diagnostic magnetic resonance patterns life-saving in children with biotin-thiamine-responsive basal ganglia disease?

BACKGROUND Biotin-thiamine responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder caused by mutations in the SLC19A3 gene and characterized by recurrent sub-acute episodes of encephalopathy that typically starts in early childhood. This study describes characteristic clinical and magnetic resonance imaging (MRI) findings of six cases of BTBGD diagnosed with newly identified mutations and genetically confirmed, with very early and different presentations compared to cases in the previous literature. METHODS Six patients referred from different centers with similar clinical findings were diagnosed with BTBGD with newly identified mutations in the SLC19A3 gene. Two novel mutations in the SLC19A3 gene were identified in two patients at whole exome sequencing analysis. The clinical characteristics, responses to treatment, and electroencephalography (EEG) and MRI findings of these patients were examined. The other four patients presented with similar clinical and cranial MRI findings. These patients were therefore started on high-dose biotin and thiamine therapy, and mutation analysis concerning the SLC19A3 gene was performed. Responses to treatment, clinical courses, EEG findings and follow-up MRI were recorded for all these patients. RESULTS Age at onset of symptoms ranged from 1 to 3 months. The first symptoms were generally persistent crying and restlessness. Seizures occurred in five of the six patients. Cranial magnetic resonance imaging revealed involvement in the basal ganglia, brain stem, and the parietal and frontal regions in general. The first two patients were siblings, and both exhibited a novel mutation of the SLC19A3 gene. The third and fourth patients were also siblings and also exhibited a similar novel mutation of the SLC19A3 gene. The fifth and sixth patients were not related, and a newly identified mutation was detected in both these subjects. Three novel mutations were thus detected in six patients. CONCLUSION BTBGD is a progressive disease that can lead to severe disability and death. Early diagnosis of treatable diseases such as BTBGD is important in order to prevent long-term complications and disability.

P201 – 2862: Tetraparesis secondary to superior sagittal sinus thrombosis related antithrombin III deficiency in a child

Objective Cerebral venous infarction is rare comparing to arterial occlusion. Antithrombin III deficiency can lead to deep vein thrombosis in early adulthood, but is rare as a cause of cerebral infarction. Herein a pediatric case with acute tetraparesis was presented because of improvement within 3 weeks. Methods The case was presented. Results A 15-year-old girl was referred to our hospital with the complaints of tetraparesis and dysarthria developed within 1 day following left hemiparesis. Her vital signs were normal, but drowsiness, tetraparesis and bilateral Babinskis sign were present. His muscle strength was1/5 in the distal and proximal of the extremities. In laboratory examination, except anemia and increased D-dimer, other biochemical, hematological and blood gas analysis were normal. Brain magnetic resonance (MR) imaging showed venous infarction in the bilateral frontal regions. MR venography revealed thrombosis in the superior sagittal sinus and cortical veins. Enoxaparin and acetylsalicylic acid were initiated. Dexamethasone, mannitol and furosemide were added for 5 days. Oral iron supplementation was given for iron deficiency anemia. The consciousness returned to normal in the second day, and dysarthria disappeared in the 4th day. Motor movement began in the hands at the end of the first week, and later muscle strength was 4–5/5 in the whole upper extremities within 1 week. The next week, motor movement began in the lower extremities and reached full recovery within one week. At the end of the 3 weeks, she began walking with assistance and later without assistance in a few days. Antithrombin III levels were decreased in repeated controls. Conclusion Increased intracranial pressure and alteration in vascular supply may lead to the ischemic and hemorrhagic lesions in cerebral sinus-vein thrombosis (CSVT). It may be thought that venous infarction, even with large parenchymal changes, may show good outcome, especially in the patients with well controlled intracranial pressure.