Daniel Keene

Severe Myoclonic Epilepsy of Infancy: Extended Spectrum of GEFS+?

Summary:  Purpose: Severe myoclonic epilepsy of infancy (SMEI) is an intractable epilepsy of early childhood of unknown etiology. It is often associated with a family history of seizure disorders, but epilepsy phenotypes have not been well described. We sought to characterize the seizure phenotypes of relatives to better understand to the genetic basis of SMEI.

SCN1A duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis

Objective:  We aimed to determine the type, frequency, and size of microchromosomal copy number variations (CNVs) affecting the neuronal sodium channel α 1 subunit gene (SCN1A) in Dravet syndrome (DS), other epileptic encephalopathies, and generalized epilepsy with febrile seizures plus (GEFS+).

The efficacy and efficiency of a self-administered treatment for adolescent migraine☆

&NA; Migraine headaches are frequent in adolescents. Although many adolescents are adequately treated palliatively with analgesics, an important subgroup requires prophylactic treatment. Medical treatments for adolescents with frequent severe headaches is often problematic. Prophylactic pharmacological treatments are often shunned by adolescents and their parents because of concern over drug usage. Moreover, propranolol, the most widely used prophylactic drug with adults, is frequently not effective. Psychological interventions are effective but are costly and often not available. A randomized controlled trial was undertaken to evaluate the efficacy and efficiency of a predominantly self‐administered treatment that could be delivered in a very cost‐efficient format. Eighty seven adolescents (63 females and 24 males) ranging in age from 11 to 18 years were randomly assigned to receive a self‐administered treatment, the same treatment delivered by a therapist or a control treatment. Self‐administered and clinic treatment were equally effective and superior to the control treatment. However, the self‐administered treatment was substantially more efficient. Both active treatments were durable at 1‐year follow‐up.

Cognitive and relaxation treatment of paediatric migraine

&NA; The present study compared the efficacy of two active treatments, relaxation training and cognitive coping, with a non‐specific placebo control in the treatment of 42 children and adolescents with migraine. The first treatment is a simplified version of progressive deep muscle relaxation; the second, a form of cognitive restructuring involving the alteration of dysfunctional thought processes. The results demonstrated that each active treatment was superior to the non‐specific intervention in reducing overall headache activity and frequency but not duration or intensity. There were no differences between the experimental groups, and both continued to improve through a 16‐week follow‐up period, but the control group did not. Initial level of headache severity was an important factor in treatment outcome, with children with severe headaches responding better than those with milder headaches. Possible reasons for the differential treatment effects are discussed, and the implications for future research are considered.

RELAXATION PROPHYLAXIS FOR CHILDHOOD MIGRAINE: A RANDOMIZED PLACEBO-CONTROLLED TRIAL

A randomized controlled trial was used to evaluate the effectiveness of relaxation training in the treatment of paediatric migraine. Relaxation training was compared with two control groups (psychological placebo and ‘own best efforts’) in a total of 99 children and adolescents with frequent migraine. Daily recording of the headaches following treatment, three months after treatment and at the one‐year follow‐up indicated that all three treatments were equally effective. The importance of the use of adequate control conditions which generate equivalent expectancies in pain treatment research was confirmed.

Cognitive Changes in Children Treated for Acute Lymphoblastic Leukemia With Chemotherapy Only According to the Pediatric Oncology Group 9605 Protocol

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Childrens Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 ± 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 ± 15.69 and 84.83 ± 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 ± 15.46 and 88.30± 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity. (J Child Neurol 2005;20:129—133).

Brain tumors in childhood and adolescence

Brain tumors are the second most common neoplasm in childhood and adolescence. With the recent advances in technology, changes in tumor incidence have been reported. This study examines this statement. A 19-year retrospective case review of primary brain tumors in persons younger than 18 years of age at time of diagnosis, who had permanent residence in our catchment area, was performed. Data were examined for changes in presenting symptoms and signs and incidence rates for tumors on the basis of anatomic location and histologic tumor type. An incidence rate of 2.76 per 100,000 people younger than 18 years of age was found. During the period of this study a small, but significant, trend toward increasing incidence was evident. No changes in patterns of presentation or duration of symptoms before diagnosis was observed. The incidence rate based on histologic tumor diagnosis remained fairly constant during the study period.

Monoclonal antibodies and progressive multifocal leukoencephalopathy.

Monoclonal antibodies have become an important treatment option for a number of serious conditions. Concerns have arisen about the potential association of these products with progressive multifocal leukoencephalopathy (PML). A list of monoclonal antibodies authorized for sale was derived from the Health Canada Drug Product Database. Case reports of PML after exposure to a monoclonal antibody authorized for use in Canada were retrieved by searching Canada Vigilance and WHO adverse event databases and through a Pub MED/Medline literature search. 182 adverse event case reports were retrieved (adalimumab -1 case, alemtuzumab-14, bevacizumab -3, cetuximab -1, efalizumab - 8, ibritumomab tiuxetan-5, infliximab-4, natalizumab-32, and rituximab-114). The Canadian Product Monographs for natalizumab and ritiximab contain box warnings for PML. A natalizumab registry has been established.

Bone marrow metastasis in astrocytic gliomata

With the increasing survival time of many pediatric patients with malignancies, unexpected symptoms or signs require diligent search for rare complications or second cancers related to the disease or treatment. We recently encountered a patient with extensive glioblastoma multiforme who developed pancytopenia six months after completion of treatment with craniospinal radiation and chemotherapy with etoposide and cyclophosphamide. Bone marrow aspirate and biopsy confirmed bone marrow metastasis from the brain tumor. He showed good partial remission with chemotherapy with carmustine and cis-platinum as demonstrated by serial bone marrow aspirate for cytology and cytogenetics and enjoyed good quality of life for eight months. 14 other patients with astrocytic glioma, two of whom are children, are reported in the literature to have diffuse bone marrow metastasis. Therefore, in patients with malignant astrocytic tumor, bone marrow metastasis, though not common, should be considered when bone pain or cytopenias occur, especially when prolonged.

Isolated angiitis of the central nervous system in childhood

Isolated angiitis of the central nervous system, a rare inflammatory condition of the nervous system, characterized by vasculitis of the small vessels, has not, to the best of our knowledge, been described in childhood. It usually presents with a diversity of neurological symptoms in the fifth to eighth decades of life. We reviewed the case of an 8 year old male with autopsy proven isolated cerebral angiitis, to encourage the consideration of this disorder in children; and to emphasize the lack of sensitivity of present modalities of neurological investigation in the diagnosis.