Embryonal tumors in Canadian children less than 36 months of age: results from the Canadian Pediatric Brain Tumor Consortium (CPBTC).

Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors whose subgroups have varying incidence and outcome. Despite these differences, they are often grouped as a single entity for study purposes. To date, there are no Canadian multi-institutional studies examining the incidence and outcome of all embryonal subtypes. The current study is an observational study reviewing embryonal tumors in all patients less than 36 months of age diagnosed with a CNS tumor in Canada from 1990 to 2005. Embryonal tumors accounted for 26.9% of all CNS tumors. Medulloblastomas were the highest proportion of the embryonal tumors at 61.5%. Atypical teratoid/rhabdoid tumors (AT/RT) had the second highest proportion of embryonal tumors at 18%. The proportion of primitive neuroectodermal tumors (PNET) was 16%, with 2.6 and 1.9% for congenital medulloepithelioma and ependymoblastoma tumors, respectively. AT/RT and PNET were more common in younger age groups. Medulloblastoma became more prevalent with increasing age, with its highest prevalence in the 25 to 36 month age group. Survival rates for our Canadian population at 18 and 24 months were 0.74 and 0.68 for medulloblastoma, 0.64 and 0.60 for PNET, and 0.36 and 0.29 for AT/RT, respectively. Overall, our data are comparable with published international rates for embryonal tumors. These incidence and outcome figures can guide future research into these rare tumors.

Brainstem compression: a predictor of postoperative cerebellar mutism.

PURPOSE: Cerebellar mutism is a common complication of posterior fossa tumor resection. We observed marked, preoperative brainstem compression on MR imaging, among patients who developed postoperative mutism. This study was designed to investigate if an association was indeed present. MATERIALS AND METHODS: Patients (18 months-18 years) undergoing resection of a midline, posterior fossa tumor were retrospectively reviewed. Demographic data, tumor pathology, mutism onset and duration, and postoperative complications were obtained from hospital records. Pre- and postoperative MR images were studied to assess tumor size and the severity of pons compression (an estimate of the mechanical and distortional forces imparted by the tumor). RESULTS: Patients with mutism showed greater preoperative pons compression and a greater increase in postoperative pons diameter. CONCLUSION: We predict that brainstem compression may represent white-matter injury from (1) surgical manipulation and traction, and (2) axonal damage caused by the release of the tumor's compressive force and ensuing axon distortion and dysfunction. The results provide support that mutism may be largely caused by white-matter damage disrupted axon integrity and function.

Ophthalmoplegic migraine: inflammatory neuropathy with secondary migraine?

BACKGROUND: This critical review provides a summary of the clinical presentation, neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM). The features of OM are not in keeping with its classification as a migraine-variant. METHOD: We review 3 new and 37 reported pediatric OM cases. RESULTS: Headache was an inconsistent feature, with 25% patients showing no evidence of pain at the initial OM episode. Patients demonstrated: 1) prolonged time for symptom resolution to occur (median time 3 weeks); 2) tendency for recurrent episodes to have more severe and persistent nerve involvement; 3) evidence of permanent neurological sequelae with recurrent episodes (30% of patients); 4) rapid improvement and shortened duration with corticosteroid therapy and; 5) transient, reversible MRI contrast enhancement of the affected cranial nerve (86% of patients). These features would not be expected in primary migraine headache. CONCLUSION: A detailed understanding of the natural history of OM is essential for the clinical. This review provides support that OM may result from cranial nerve inflammation with headache a secondary and later feature of this condition.

Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment.

We retrospectively studied 12 consecutive patients with gelastic seizures and hypothalamic hamartomas who, because of intractable epilepsy, underwent chronic intracranial EEG monitoring or epilepsy surgery. All patients had medically refractory seizures that included laughter as an ictal behavior (gelastic seizures). The hypothalamic hamartomas were identified with neuroimaging studies (12 of 12) and by pathologic verification (four of 12). Associated clinical features included behavioral disorders (n = 5), developmental delay (n = 4), and precocious puberty (n = 2). Interictal extracranial EEG predominantly showed bi-hemispheric epileptiform changes suggesting a secondary generalized epileptic disorder. Intracranial EEG recordings, performed in eight patients, indicated the apparent focal onset of seizure activity (anterior temporal lobe [n = 7] and frontal lobe [n = 1]). None of the seven patients who underwent a focal cortical resection, however, experienced a significant reduction in seizure tendency. An anterior corpus callosotomy, performed in two patients with symptomatic generalized epilepsy, resulted in a worthwhile reduction in drop attacks. Results of this study may modify the surgical strategies in patients with gelastic seizures and hypothalamic hamartomas.

Clobazam as an add-on drug in the treatment of refractory epilepsy of childhood.

We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur.

Anoxic tonic seizures due to asthma; a serious complication in adults.

Anoxic tonic seizures are reported as a complication of severe asthma in two adults. The nature of these attacks can be misinterpreted. They do not indicate the presence of a recurrent seizure problem unconnected to the episodes of anoxia caused by asthma. These attacks do not respond to antiepileptic medication, but cease if the asthma can be controlled. One of our patients developed an anoxic encephalopathy and the other died. The need for prompt diagnosis and appropriate treatment is emphasized.

Sodium valproate in the treatment of the intractable childhood epileptic.

Sixty-five children with seizure disorders, who had been treated with multiple anticonvulsants but were poorly controlled, were selected from the Montreal Children's Hospital Convulsive Disorder Clinic and Neurology Service and were treated with sodium valproate (valproate). All types of seizure disorders were included in the group. Rapid oral absorption of the drug lead to peak plasma levels in one to three hours (later peaks occurring if administered after meals). A mean plasma half-life of 12.8 hours was calculated. Correlation between oral dose and plasma levels was poor. The side effects which occurred in this study were trivial. Drug interactions occurred with phenobarbital, diphenylhydantoin and clonazepam. Sixty percent of patients had a greater than 50% reduction in seizure frequency with sodium valproate, but the best response was in generalized absence seizures. Since all types of seizures responded to some degree, a trial of sodium valproate is warranted in intractable seizure disorders of childhood regardless of classification.

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.

Alfentanil mediated activation of epileptiform activity in the electrocorticogram during resection of epileptogenic foci.

PURPOSE: Alfentanil is a potent, short-acting opioid agent which has been used during balanced anaesthesia in children undergoing the surgical excision of epileptic foci. After the observation that this agent had the potential to induce epileptic seizures, we questioned the frequency of this occurrence in this group of patients. METHOD: Twelve patients (6 males, 6 females) undergoing surgical excision of an epileptic foci were prospectively followed. For each patient an electrocorticogram was recorded for 30 minutes before and after receiving alfentanil 20 micrograms/kg intravenously. The frequency of epileptiform abnormalities before and after drug administration was evaluated. When the electrocorticogram no longer showed the effects of alfentanil administration, methohexital 0.5 microgram/kg was given intravenously. RESULTS: Alfentanil induced significant activation of epileptiform discharges among 83% of these patients. Twenty-five per cent had an electrographic seizure. In comparison, methohexital induced significant activation of epileptiform discharges in 50% of these patients. None experienced electrographic seizures. CONCLUSIONS: As alfentanil can induce electrographic seizures in patients known to have epilepsy, caution is advised in its use in this group of patients.

EEG abnormalities and convulsions in juvenile diabetes mellitus.

The clinical and EEG findings were reviewed for 270 juvenile children from the Montreal Children's Hospital Diabetic Clinic in an attempt to correlate the EEG findings at the onset of diabetes mellitus with the future risk of having a convulsion with a hypoglycemic reaction. Compared to a non-diabetic control population, the number of epileptiform EEG abnormalities was significantly increased in the initial EEG of diabetic patients who later had a hypoglycemic convulsion. The initial epileptiform EEG did not help to differentiate those diabetics with recurrent hypoglycemic induced convulsions from diabetics who would have only a single convulsion.

Fulminating haemophilus influenzae b meningitis.

Haemophilus influenzae type b (HIb) is the most common cause of bacterial meningitis in children with a mortality rate ranging from 1.6% to 14%. Most patients have a 2-3 day history of symptoms prior to admission. A few have fulminating disease with rapid neurological deterioration. Review of 191 cases of HIb meningitis revealed a mortality rate of 2.1% but all who died had fulminating meningitis (FM). Four of six patients with FM died. FM patients had symptoms for less than 24 hours before rapid neurological deterioration with increased ICP, seizures, coma and/or respiratory arrest. Review of 10 FM cases revealed that on admission, 5 had hypotension, 3 had thrombocytopenia, and 8 had coma. Typical CSF changes were seen in only 7. All fatal cases died within 24 hours. Brain swelling and tonsillar herniation were found at autopsy. SDS-PAGE outer membrane protein subtyping did not show one "killer strain". Animal and autopsy data suggest that diminished CSF outflow and cerebral edema contribute to increased ICP. To improve survival of FM patients, initial treatment must (1) decrease ICP below levels impairing cerebral perfusion, (2) maintain adequate ventilation and blood pressure, and include (3) LP when stable, (4) antibiotics, and (5) close monitoring. Utilizing these principles, two FM patients survived without major sequelae.

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.

MRI diagnosis of gliomatosis cerebri.

Until recently the diagnosis of gliomatosis cerebri has been made on postmortem examination. This article reviews the use of serial magnetic resonance imaging studies to suggest premorbid diagnosis of this condition. The following is a case report of a 14-year-old female who had a subtotal cortical resection of tumor and several years later developed a progressive dementia. At postmortem examination the diagnosis of gliomatosis cerebri was made. Diffuse progressive white matter changes involving both hemispheres and brainstem, with increased thickness of the corpus callosum and without changes in cortical markings on T2-weighted magnetic resonance images, in this patient were highly suggestive of the diagnosis of gliomatosis cerebri.

Cerebral vascular events associated with ulcerative colitis in children.

Although peripheral vascular thrombic events are recognized as a serious extra-intestinal complication of inflammatory bowel disease, the occurrence of cerebral vascular events in association with acute exacerbations of this group of diseases is rare. In this article, relevant literature is reviewed and three children, 5, 12, and 13 years of age, who presented with clinical and magnetic resonance imaging evidence of an acute cerebrovascular event in association with an acute exacerbation of their inflammatory bowel disease are described. Except for the presence of anemia, hematologic and coagulation studies were unremarkable, and a search for evidence of a systemic vasculitis proved negative.

Iron deficiency: a cause of stroke in infants and children.

Iron deficiency is a common pediatric problem affecting 20%-25% of the world's infants. Most commonly causing anemia, iron deficiency is also implicated in such neurologic sequelae as irritability, lethargy, headaches, developmental delay, and infrequently papilledema, pseudotumor cerebri, and cranial nerve abnormalities. Rarely has iron deficiency been recognized as a significant cause of stroke in the adult or pediatric populations. We report a series of 6 children, 6 to 18 months of age, who presented with an ischemic stroke or venous thrombosis after a viral prodrome. All patients had iron deficiency as a consistent finding among the group, and other known etiologies of childhood stroke were excluded. These patients provide evidence of a strong association between iron deficiency and ischemic events in children between 6 and 18 months of age.

Ketogenic diet in the treatment of refractory epilepsy in childhood.

There has been renewed interest in the ketogenic diet in the treatment of medically refractory seizure disorders in childhood. This article reports the results of a retrospective chart review of 52 patients who were treated with the ketogenic diet. The vast majority (49 of 52) were treated with the classic 4:1 diet. Seizure control improved in 67.3% of patients with complete abolition of seizures in six. Adverse reactions were uncommon and included the development of renal stones, gall bladder stones, and hypoproteinemia in one patient each. Routine biochemical screening during the diet did not identify or prevent adverse events. The authors' experiences with the diet emphasize the need for close ongoing medical and dietary supervision.

Electrocorticography.

Electrocorticography (ECOG), the intra-operative recording of cortical potentials, has played an important role in the surgical management of patients with medically refractory epilepsy. It has been used 1) to localize the epileptogenic tissue; 2) map out cortical functions; and 3) predict the success of the surgery. Despite its common use, few studies have been done to prove its effectiveness in these areas. The technique used in children for recording ECOG is very similar to that used in adults except for the limitations imposed by the child's age. Anaesthesia must often be used. Based upon a computerized medical literature search, a review of this procedure was done. Pre-resection localization, and post-resection prediction of outcome was done for temporal and extra-temporal resection, both lesional and nonlesional. Most of the available studies were in adult patients. All were retrospective in nature. Evidence for the role of pre-resection ECOG in determining the degree of resection felt necessary to obtain good clinical outcome was limited. Similarly the post-resection ECOG predication of surgical outcome was restricted.

The preoperative assessment in the planning of surgical management of medically refractory epilepsy in the pediatric patient.

Surgical intervention in refractory epilepsy in children offers the hope of seizure control. For the patient, the preoperative assessment is a major factor in whether he or she is selected as a patient who will potentially benefit. It also plays an important part in the choice of the surgical intervention to be used. This paper reviews the investigations available and suggests an investigational algorithm for use in the pediatric population.