Clinical, electrophysiological and genetic characteristics of childhood hereditary polyneuropathies.

BACKGROUND: Hereditary polyneuropathies are heterogeneous group of diseases of the peripheral nervous system. In this study, we investigated the demographic, clinical, electrophysiological, and genetic characteristics of hereditary polyneuropathy patients diagnosed and followed up in our tertiary center clinic in Izmir, Turkey. METHODS: Patients who were diagnosed with hereditary polyneuropathies during nerve conduction studies in our center were evaluated retrospectively. RESULTS: In a total of 1484 nerve conduction studies, 207 patients were diagnosed with polyneuropathy. Ninety-nine of those patients were determined to have hereditary polyneuropathy, 52 of which were male and 47 were female. Sixty-nine patients with hereditary polyneuropathy were compatible with axonal and 30 were compatible with demyelinating polyneuropathy. Genetic analysis was performed in 69 patients, and 49 of those patients were genetically diagnosed, leading to a diagnosis rate of 71%. CONCLUSIONS: Advances in genetics have led to an increase in the heterogeneity of hereditary polyneuropathies, causing difficulties in the use of existing classifications. Although typical mutations expected in childhood-onset polyneuropathies are seen less frequently, polyneuropathies are frequently encountered as findings of complex, multisystemic diseases.

Successful treatment of intractable epilepsy with ketogenic diet therapy in twins with ALG3-CDG.

BACKGROUND: Congenital disorders of glycosylation (CDG) is a heterogeneous group of congenital metabolic diseases with multisystem clinical involvement. ALG3-CDG is a very rare subtype with only 24 cases reported so far. CASE: Here, we report two siblings with dysmorphic features, growth retardation, microcephaly, intractable epilepsy, and hemangioma in the frontal, occipital and lumbosacral regions. RESULTS: We studied two siblings by whole exome sequencing. A pathogenic variant in ALG3 (NM_005787.6: c.165C > T; p.Gly55=) that had been previously associated with congenital glycolysis defect type 1d was identified. Their intractable seizures were controlled by ketogenic diet. CONCLUSION: Although prominent findings of growth retardation and microcephaly seen in our patients have been extensively reported before, presence of hemangioma is a novel finding that may be used as an indication for ALG3-CDG diagnosis. Our patients are the first reported cases whose intractable seizures were controlled with ketogenic diet. This report adds ketogenic diet as an option for treatment of intractable epilepsy in ALG3-CDG.

Clinical, pathological and radiological survey of patients with Leigh syndrome.

AIM: The aim of this study was to evaluate the clinical, pathological and radiological survey of patients affected by Leigh syndrome. METHODS: Eleven patients with Leigh disease were evaluated at Dokuz Eylül University, School of Medicine, Department of Pediatric Neurology. All patients underwent neurological evaluation with detailed medical and family history. Muscle biopsy from quadriceps muscle, brain magnetic resonance imaging and brain magnetic spectroscopy were obtained. RESULTS: The patients were aged between 1 month and 8 years (mean age: 2.29+/-2.58 years). The most common presentation findings were psychomotor retardation and acute metabolic encephalopathy. All patients had elevated lactate in the blood and/or cerebrospinal fluid. Except in two patients, brain magnetic resonance imaging revealed abnormal symmetrical lesions in the brainstem and basal ganglia. Brain magnetic resonance spectroscopy revealed abnormal lactate peak in all patients. The muscle biopsy of two patients showed cytocrom-c oxidase deficiency and measurement of respiratory chain complex in one patient revealed complex I and IV deficiency. One patient was found to carry mitochondrial T8993C mutation. CONCLUSIONS: There are no specific markers for Leigh disease which lead to extensive work-up. The disease should be considered in patients who present progressive neurologic symptoms involving brainstem and basal ganglia.

Protective effects of topiramate against hyperoxic brain injury in the developing brain.

Recent studies have shown that exposure to hyperoxia in infant rats leads to extensive apoptotic degeneration in the cortex and white matter of the developing brain. Besides its antiepileptic effects, topiramate exerts neuroprotective effects in animal models of stroke, hypoxia ischemia, excitotoxic insults, and status epilepticus. In the present study, we investigated the effects of topiramate against hyperoxia-induced neurodegeneration in the developing brain. Eighteen Wistar rat pups were divided into three groups: control group, hyperoxia+phosphate buffered saline treated group and hyperoxia+topiramate treated group. Hyperoxia groups were exposed to 80% oxygen (n=12) in plexiglas chambers in which the oxygen concentration was monitored twice daily from birth until postnatal day five. The hyperoxia+topiramate group received an intraperitoneal injection of topiramate at a dose of 80 mg/kg/day. At postnatal day 5, all animals were killed. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that topiramate significantly diminished apoptosis in the CA1 region and dentate gyrus of hippocampus. Topiramate may offer a therapeutic potential for neuroprotection under conditions of hyperoxic brain injury.