The natural course of clinically isolated syndrome in pediatric patients.

BACKGROUND: The first episode of central nervous system (CNS) symptoms with a presumed inflammatory demyelinating cause is defined as clinically isolated syndrome (CIS) according to the 2007 consensus of the International Pediatric Multiple Sclerosis Study Group, which developed diagnostic criteria for CNS demyelination disease in children. Using this definition of CIS, we attempted to identify the natural course of pediatric patients with CIS in a single Korean institution and to determine the factors affecting their prognosis. METHODS: We retrospectively reviewed the medical records of all pediatric patients (age <18 years old) who presented with clinical symptoms of CNS events between 1997 and 2008. RESULTS: We identified 32 patients with CIS. Their mean age with standard deviation was 10.0±4.1 years. The most common type of presentation of CIS was optic neuritis (ON). Sixteen (16/32, 50%) patients experienced a second demyelinating event. The mean interval between the first event and the recurrent episode was 21±20 months. The mean follow-up was 6.1±1.6 years. Eleven (34%) patients developed childhood onset multiple sclerosis (MS). In contrast to previous studies, asymptomatic brain lesions on magnetic resonance imaging (MRI) and the presence of cerebrospinal fluid (CSF) oligoclonal bands (OCBs) were not predictors of conversion to MS. CONCLUSION: In our study, a second relapse and initial presentation with brain stem, cerebellar, cerebral dysfunction, or multifocal CIS were strongly associated with the development of MS (p=0.002). Despite clinical definitions and increased understanding of CIS in children, challenges remain in predicting its progression to a chronic demyelinating disease.

Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

BACKGROUND: Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. METHODS: We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. RESULTS: Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. CONCLUSION: This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization.