Life-threatening focal status epilepticus due to occult cortical dysplasia.

OBJECTIVE: Neuronal migration disorders are usually, but not necessarily, demonstrated by magnetic resonance imaging. Preoperative suspicion of these anomalies in the presence of normal magnetic resonance studies has important practical implications. This study delineates some clinical features that permit early suspicion of focal cortical dysplasia localized in the central and precentral regions. DESIGN: In a retrospective case series, we studied the clinical presentation of four consecutive patients with normal preoperative magnetic resonance images in whom focal cortical dysplasia was found in the surgical specimen. SETTING: Patients were seen in three referral centers specializing in epilepsy surgery. PATIENTS: Four patients (three female), between the ages of 4 and 21 years, had intractable partial seizures leading to resective brain surgery. INTERVENTION: Three patients had corticectomies in the central (two patients) or frontal (one patient) regions. One underwent an en bloc resection of the central area after two unsuccessful corticectomies and cortical transection. RESULTS: Three patients presented with life-threatening focal motor status epilepticus necessitating intubation, and one had epilepsia partialis continua. All had had seizures previously, and the attacks progressed to intractability after 1 1/2 to 3 years. Surgery led to control of the seizures, but only two patients became seizure free (mean follow-up, 15.7 months). All but one developed a postoperative deficit, which eventually improved. CONCLUSIONS: Focal cortical dysplasia should be suspected when life-threatening focal motor status epilepticus or epilepsia partialis continua occur in children or young persons without another obvious cause. Normal magnetic resonance studies do not exclude neuronal migration disorders.

Genetic linkage studies in familial frontal epilepsy: exclusion of the human chromosome regions homologous to the El-1 mouse locus.

Familial frontal epilepsy has been recently described in six pedigrees. All families reported show autosomal dominant inheritance with incomplete penetrance. Affected individuals develop predominantly nocturnal seizures with frontal lobe semiology. In 1959, a genetic mouse model for partial epilepsy, the El mouse, was reported. In the El mouse, a major seizure susceptibility gene, El-1, segregates in an autosomal dominant fashion and has been localized to a region distal to the centromere of mouse ch 9. Comparative genetic maps between man and mouse have been used to predict the location of several human disease genes. The El-1 locus in the mouse is homologous to human chromosomes 3p23-p21.2, 3p11.2-q11.2, 3q21-q25.3, 6p12-q12 and 15q24. Polymorphic microsatellite markers covering these candidate regions were used for genotyping individuals in the three larger families ascertained, one of which is French-Canadian and two are Australian. Significant negative two-point and multipoint lod scores were obtained separately for each family, thus excluding linkage with the candidate regions on chromosomes 3, 6 and 15.

Scalp EEG in temporal lobe epilepsy surgery.

Electroencephalography (EEG) with standard scalp and additional noninvasive electrodes plays a major role in the selection of patients for temporal lobe epilepsy surgery. Recent studies have provided data supporting the value of interictal and postictal EEG in assessing the site of ictal onset. Scalp ictal rhythms are morphologically complex but at least one pattern (a five cycles/second rhythm maximum at the sphenoidal or anterior temporal electrode) occurs in >50% of patients and has a high predictive value and interobserver reliability for temporal lobe originating seizures. Thorough interictal and ictal scalp EEG evaluation, in conjunction with modern neuroimaging, is sufficient for proceeding to surgery without invasive recordings in some patients. Further studies are required to define the scalp ictal characteristics of mesial vs. lateral temporal lobe epilepsy.

Current educational issues in the clinical neurosciences.

OBJECTIVE: Canadian training in the clinical neurosciences, neurology and neurosurgery, faces significant challenges. New balances are being set by residents, their associations and the Royal College of Physicians and Surgeons of Canada between clinical service, education and personal time. The nature of hospital-provided medical service has changed significantly over the past decade, impacting importantly on resident training. Finally, future manpower needs are of concern, especially in the field of neurosurgery, where it appears that soon more specialists will be trained than can be absorbed into the Canadian health care system. METHODS: A special symposium on current challenges in clinical neuroscience training was held at the Canadian Congress of Neurological Sciences in June 2000. Representatives from the Canadian Association of Interns and Residents, the Royal College of Physicians and Surgeons of Canada and English and French neurology and neurosurgery training programs made presentations, which are summarized in this report. RESULTS: Residency training has become less service-oriented, and this trend will continue. In order to manage the increasingly sophisticated hospital services of neurology and neurosurgery, resident-alternatives in the form of physician "moonlighters" or more permanent hospital-based clinicians or "hospitalists" will be necessary in order to operate major neuroclinical units. Health authorities and hospitals will need to recognize and assume this responsibility. As clinical experience diminishes during residency training, inevitably so will the concept of the fully competent "generalist" at the end of specialty training. Additional subspecialty training is being increasingly sought by graduates, particularly in neurosurgery. CONCLUSIONS: Training in neurology and neurosurgery, as in all medical specialties, has changed significantly in recent years and continues to change. Programs and hospitals need to adapt to these changes in order to ensure the production of fully qualified specialists in neurology and neurosurgery and the provision of optimal care to patients in clinical teaching units.

[Two cases of benign polypes of the ureter (author's transl)].

The polyp of the ureter is a tumour which originates in the connective tissue and is covered by normal urothelium. Radical surgery is justified in some of these urothelial tumours but one should also consider a more conservative attitude when one deals with a benign fibro-epithelial polyp of the ureter especially when they are located in the lower or upper third of the ureter. We present two cases, one which represents the eleventh case of benign fibro-epithelial polyp described in children in the literature.

Stages and patterns of centrifugal arrest of diffuse neuronal migration disorders.

Centrifugal migration of newly generated neuroblasts toward the cortical surface can be arrested at different levels, resulting in anatomically different disorders. This is illustrated by three patients with diffuse or generalized neuronal migration disorders (NMDs): pachygyria, subcortical laminar heterotopia ('double-cortex' syndrome), and periventricular laminar heterotopia. All had medically intractable partial and generalized epileptic seizures, but there was no close correlation between the type of dysplasia and intelligence or clinical pattern. The low intelligence found in these patients may relate to the epileptic syndrome, rather than to the NMDs alone. MRI suggested that in this spectrum of disorders the migration process was arrested at different stages, depending on the extent, timing and site of damage to radial glial fibres.

Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder.

The disorder of autosomal dominant nocturnal frontal lobe epilepsy has recently been identified, and is now delineated in detail. A phenotypically homogeneous group of five families from Australia, Britain and Canada, containing 47 affected individuals, was studied. The largest family contained 25 affected individuals spanning six generations. This disorder is characterized by clusters of brief nocturnal motor seizures, with hyperkinetic or tonic manifestations. Subjects often experienced an aura, and remained aware throughout the attacks. Seizures occurred in clusters (mean eight attacks/night) typically as the individual dozed, or shortly before awakening. The epilepsy usually began in childhood, and persisted through adult life, with considerable intra-family variation in severity. Seizures were often misdiagnosed as benign nocturnal parasomnias, psychiatric and medical disorders. Interictal EEG studies were unhelpful. Ictal video-EEG studies showed that the attacks were partial seizures with frontal lobe seizure semiology. Neuro-imaging was normal. Carbamazepine monotherapy was frequently effective. This disorder showed autosomal dominant inheritance. Recognition of this entity is clinically important for diagnosis, appropriate therapy and genetic counselling. Moreover, this disorder now offers an opportunity to identify a gene for partial epilepsy.

Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder.

We describe a distinctive epilepsy syndrome in six families, which is the first partial epilepsy syndrome to follow single gene inheritance. The predominant seizure pattern had frontal lobe seizure semiology with clusters of brief motor attacks occurring in sleep. Onset was usually in childhood, often persisting through adult life. Misdiagnosis as night terrors, nightmares, hysteria, or paroxysmal nocturnal dystonia was common, and the inheritance pattern was often not appreciated. This autosomal dominant epilepsy syndrome is ideal for identification of partial epilepsy genes.

Mapping of a gene determining familial partial epilepsy with variable foci to chromosome 22q11-q12.

We identified two large French-Canadian families segregating a familial partial epilepsy syndrome with variable foci (FPEVF) characterized by mostly nocturnal seizures arising from frontal, temporal, and occasionally occipital epileptic foci. There is no evidence for structural brain damage or permanent neurological dysfunction. The syndrome is inherited as an autosomal dominant trait with incomplete penetrance. We mapped the disease locus to a 3. 8-cM interval on chromosome 22q11-q12, between markers D22S1144 and D22S685. Using the most conservative diagnostic scheme, the maximum cumulative LOD score was 6.53 at recombination fraction (straight theta) 0 with D22S689. The LOD score in the larger family was 5.34 at straight theta=0 with the same marker. The two families share an identical linked haplotype for >/=10 cM, including the candidate interval, indicating a recent founder effect. A severe phenotype in one of the probands may be caused by homozygosity for the causative mutation, as suggested by extensive homozygosity for the linked haplotype and a bilineal family history of epilepsy. An Australian family with a similar phenotype was not found to link to chromosome 22, indicating genetic heterogeneity of FPEVF.