Accuracy of EEG dipole source localization using implanted sources in the human brain.

OBJECTIVES: The location of electrical sources in the brain can be estimated by calculating inverse solutions in which the location, amplitude and orientation of the electrical sources are fitted to the scalp EEG. To assess localization accuracy of the moving dipole inverse solution algorithm (ISA), we studied two patients who had depth electrodes implanted for presurgical planning of epilepsy surgery. METHODS: Artificial dipoles were created by connecting a single sine wave pulse generator to different pairs of electrodes in multiple orientations and depths. Surface EEG recordings of the resulting pulses were evaluated with the ISA using a 4-shell spherical head model and plotted on the subjects' MRI. Dipole localization errors were evaluated with respect to the number of averaged pulses, different electrode montages and different dipole locations and orientations. RESULTS: Dipoles located at 40-57 mm from the scalp surface had localization errors that were greater than those located at 62-85 mm. Localization accuracy improved with increasing numbers of pulses and recording electrodes. Results with a standard 10-20 array of 21 electrodes showed an average localization error of 17 mm, whereas 41 electrodes improved this to 13 mm. Mean angular errors were 31 and 30 degrees, respectively. CONCLUSIONS: The ISA was able to differentiate between tangential and radial dipoles. We conclude that our implementation of the ISA is a useful and sound method for localizing electrical activity in the brain.

Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

Periodic lateralized epileptiform discharges--a critical review.

It is the purpose of this review to critically consider and organize the literature dealing with the ephemeral electroencephalographic (EEG) pattern periodic lateralized epileptiform discharges (PLEDs). Although the retrospective nature of these studies limits their ability to discuss accurately the clinical and pathophysiological aspects of this EEG entity, the available data strongly emphasize stroke as the dominant etiology and its high association with seizures. Recent evidence, particularly from functional neuroimaging studies, strongly suggests that PLEDs might reflect a key pattern for focal hyperexcitability in the penumbra zone of ischemic stroke. The authors prefer to consider PLEDs as an EEG signature of a dynamic pathophysiological state in which unstable neurobiological processes create an ictal-interictal continuum, with the nature of the underlying neuronal injury, the patient's preexisting propensity to have seizures, and the co-existence of any acute metabolic derangements all contributing to whether seizures occur or not. This review underlines the need for further sophisticated prospective controlled studies implementing early continuous EEG monitoring in order to contribute to an understanding of the incidence, dynamics, and relevance of this pattern.

Unverricht-Lundborg disease: absence of nonallelic genetic heterogeneity.

Unverricht-Lundborg disease is a clinically recognizable form of progressive myoclonus epilepsy. Recently, in several families of both Finnish and Mediterranean extraction segregating Unverricht-Lundborg disease, the gene for this disease was linked to the same region of the long arm of chromosome 21. We performed linkage analysis in eight families, including four of neither Baltic nor Mediterranean origin, using a polymorphic (CA)n repeat marker for the human liver-type 6 phosphofructokinase (PFKL) gene, previously mapped to 21q22.3. No recombinations were observed between the disease phenotype and the PFKL marker and a maximum lod score of 5.63 was obtained. These findings confirm tight linkage between PFKL and the gene for Unverricht-Lundborg disease and strongly suggest a lack of nonallelic genetic heterogeneity of the disease.

Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin: a second case.

A 44 year old female presented with a progressive cerebellar disturbance approximately 13 years after receiving human pituitary derived gonadotrophin injections as a treatment for infertility. The patient died approximately nine months later. Creutzfeldt-Jakob disease was confirmed at necropsy. This is the second reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin.

Creutzfeldt-Jakob disease in a recipient of human pituitary-derived gonadotrophin.

A forty-year-old female presented with an unsteady gait 13 years after receiving an eight-month course of human pituitary-derived gonadotrophin injections as treatment for infertility. Over the next ten months the patient subsequently developed generalised myoclonic jerks and dementia and finally died. Neuropathological examination revealed changes in the brain consistent with Creutzfeldt-Jakob disease. This is the first reported case of Creutzfeldt-Jakob disease in a recipient of human derived gonadotrophin.

CNS cryptococcosis: unusual aspects.

Eleven patients with CNS cryptococcal infection are reviewed. The most prominent symptom was headache, present in all patients. The clinical manifestations were the direct result of the meningitis itself or a consequence of intracranial cryptococcal granulomata or hydrocephalus, these latter 2 complications being demonstrable on CT head scan. In the 2 patients who also had MRI scans, additional parenchymal lesions were revealed which had not been detected by CT. Combined amphotericin B and 5-fluorocytosine therapy was the treatment of choice, but in 3 patients fluconazole was also used. Chronic oral therapy with this agent has maintained a good clinical response in one patient who failed to respond to traditional antifungal therapy.