A Case of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Optic Neuritis Responsive to Intravenous Immunoglobulin (IVIG) Therapy in a Pediatric Patient.

We present a case of an eight-year-old boy who presented with complaints of headache, blurry vision, and eye pain. Ophthalmological exams and magnetic resonance imaging confirmed the presence of optic neuritis. Initial cerebrospinal fluid analysis was negative for all antibodies (Abs) associated with optic neuritis and other acute demyelinating syndromes, including anti-myelin oligodendrocyte glycoprotein Ab (anti-MOG-Ab). The child was treated with a course of pulse methylprednisolone therapy for five days, with significant improvement in his symptoms. However, the child went on to have a recurrent episode of optic neuritis one month after his initial presentation. Hence, investigations targeting immunological biomarkers were repeated and turned out to be positive for anti-MOG-Abs with elevated titers. The child was diagnosed with MOG-Ab-associated optic neuritis presenting as chronic relapsing inflammatory optic neuropathy (CRION). He was then started on maintenance intravenous immunoglobulin (IVIG) therapy as a disease-modifying therapy, following which he has not had any further relapses over two years.

Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients.

BACKGROUND: The ring chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism. METHODS: To understand the structure and composition of the ring chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis. RESULTS: These studies revealed two distinct groups of patients. Group 1 (N=21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N=7) had non-mosaic ring chromosomes with a deletion at one or both ends of the chromosome, near the ring fusion point. The non-mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non-mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities. CONCLUSIONS: These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.

Topiramate for the treatment of infantile spasms.

Topiramate is a new antiepileptic drug with a broad spectrum of efficacy. Reports on the use of topiramate for treatment of infantile spasms are limited. We prospectively followed 15 children with recently diagnosed infantile spasms treated with topiramate for efficacy and tolerability. Twelve patients had symptomatic infantile spasms, and two patients had cryptogenic infantile spasms. Topiramate was started at a dose of 3 mg/kg/day and titrated up to a dose of 27 mg/kg/day in 2 to 3 weeks. The primary efficacy measure was comparison of the seizure rate during the 2-week baseline with the median seizure rate during the first 2 months of treatment with topiramate. We also compared baseline electroencephalograms (EEGs) with post-treatment EEGs. The median seizure rate reduction during the first 2 months of treatment was 41% (P = .002). Three patients became spasm free (20%), five had > 50% reduction, and three had at least 25% reduction. Four patients did not respond. Three of 15 patients had clearing of hypsarrhythmia. Topiramate was generally well tolerated, with irritability being the most common side effect. Topiramate was efficacious and well tolerated; one patient discontinued the medication because of adverse effects. (J Child Neurol 2006;21:17-19).

Confronting the issues of therapeutic misconception, enrollment decisions, and personal motives in genetic medicine-based clinical research studies for fatal disorders.

Genetic medicine-based therapies have unlocked the potential for ameliorating diseases previously considered inevitably fatal. Inherent in the clinical trials of genetic medicines are ethical issues of therapeutic misconception, enrollment decisions as they relate to the risks and benefits of research, and the complex relationships among funding sources, investigators, and the families of affected individuals. The purpose of this paper is to help define these complex issues relevant to the use of genetic medicines and to describe the strategy we have used to confront these issues in a phase I trial of adeno-associated virus-mediated gene transfer to the central nervous system of children with late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal lysosomal storage disease associated with progressive neurodegeneration and death by mid-childhood. Our approach to these challenges should provide a useful paradigm for investigators initiating other genetic medicine- based studies to treat inevitably fatal diseases.

Electroencephalographic patterns in unresponsive pediatric patients.

To study the occurrence and incidence of various electroencephalographic patterns, the electroencephalograms of unresponsive pediatric patients admitted to the intensive care unit were analyzed. The interpreters were unaware of the patients' clinical diagnoses. A total of 178 electroencephalographic studies performed on unresponsive patients were analyzed over a period of 3 years. The mean age of the study patients was 7.9 years. Sixty-six patients were less than 1 year old. The following electroencephalographic patterns were observed: 58 patients (33%) manifested electroencephalographic patterns consistent with nonconvulsive status epilepticus. Of the patients with nonconvulsive status epilepticus, 32 patients (18%) had generalized nonconvulsive status epilepticus and 26 patients (14%) manifested partial nonconvulsive status epilepticus. The remaining 120 patients (67%) manifested diffuse cerebral dysfunction, with the majority having severe diffuse cerebral dysfunction. Only 4 patients (2%) had triphasic waves, suggesting a metabolic encephalopathy. Thirty-six percent of the patients under the age of 1 year had electroencephalographic patterns consistent with nonconvulsive status epilepticus. Nonconvulsive status epilepticus is a relatively common electroencephalographic pattern in unresponsive pediatric patients. Metabolic encephalopathy is uncommon in this patient group.

Ketogenic diet in pediatric epilepsy patients with gastrostomy feeding.

Ketogenic diet is effective in the control of intractable seizures. Poor compliance is a major limiting factor. In one study, only 50% of children receiving the oral ketogenic diet remained on the diet after 1 year. Twelve children with static encephalopathy and intractable symptomatic epilepsy were given the ketogenic diet via gastrostomy tube. Mean age was 3 years (range, 7 months to 6.5 years). Mean seizure frequency at baseline was 199/month. Seizure frequency after 12 and 18 months of diet was compared with baseline. After 12 months on the diet, the number of antiepileptic drugs was compared with baseline. Median seizure reduction at 1 year and 18 months was 61% and 66%, respectively (P = 0.02). Individually, six patients had 90% seizure reduction, one had 75% reduction, three had 50% reduction, and two patients did not improve. Mean antiepileptic drugs at baseline was 2.8; at 12 months 1.6 (49% reduction). Three patients had weight loss. Two patients discontinued the diet at 13 months and 21 months, respectively, because of diarrhea and weight loss. Compliance with diet was 100% during treatment. This study suggests that the ketogenic diet via gastrostomy feeding tube is safe and effective in children with intractable seizures and ensures compliance.

Nitrazepam for the treatment of Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome is a severe childhood epileptic syndrome with encephalopathy and multiple seizure types, which are often intractable to treatment. Most of these children will ultimately become mentally retarded and dependent on others for their daily care. Antiepileptic drugs are the mainstay of treatment, however, no particular drug is entirely effective. Apart from the use of antiepileptic drugs, nonpharmacologic treatments are also considered (i.e., callosotomy, ketogenic diet, and vagus nerve stimulation), which have proven to be partially effective. We prospectively studied 14 children (11 months-8 years of age) with medication-resistant Lennox-Gastaut syndrome, being treated with nitrazepam (open-label compassionate protocol). We compared the 1-month baseline seizure frequency with the median seizure rate reduction during the first 12 months of treatment with nitrazepam. The median seizure rate reduction during the first 12 months of treatment with nitrazepam was 41% (P = 0.001), with more than 50% seizure reduction in 60% of patients. Two patients became seizure free, five patients demonstrated at least 50% reduction in seizure rates, six patients had at least 25% seizure rate reduction, and one patient did not respond. No patient had any serious adverse effects. Side effects included sedation in six children (40%) and drooling in nine patients (60%).