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.

EEG and CT findings in patients with panic disorder.

Fifty-four patients with panic disorder were investigated using extensive electroencephalographic (EEG) recordings and computerized tomography (CT). Fifteen (28%) of these patients had previously been treated for temporal lobe epilepsy or were considered to have another neurological disorder. EEG recordings showed increased slow-wave activity in 13 (24%) patients and CT scan revealed incidental abnormalities in 6 (20%) of the 30 patients investigated. Taking into account the limitations of the methods applied, the present results indicate that clear-cut epileptic EEG patterns only rarely occur in panic disorder: the vast majority of panic patients exhibit normal EEG and CT findings.

Efficacy of a 1- to 3-day ambulatory electroencephalogram in recording epileptic seizures.

The duration of an ambulatory electroencephalogram (aEEG) necessary to record epileptic seizures was studied in neurological patients. A total of 2221 aEEG recordings were made for 2035 inpatients. Ambulatory EEG lasting 1 to 8 days (mean, 1.6 days) included seizures or typical undiagnosed symptomatic attacks in 750 recordings (34%), and 266 of them were epileptic in origin. Symptomatic attacks without simultaneous EEG discharges were exhibited in 27% of the epileptic patients. Of the total number of epileptic seizures, 81% were encountered during the first 24 hours, an additional 10% during the next 24 hours, and 7% during the third 24-hour period. Our conclusion was that, in patients exhibiting epileptic seizures during the aEEG recording, the diagnosis will be confirmed by a 2-day recording in the vast majority of the cases.

The importance of the electrocardiogram in ambulatory electroencephalographic recordings.

The role of an ambulatory electroencephalogram performed simultaneously with an electrocardiogram was studied in 861 neurologic inpatients. In total, 123 patients (14%) had interictal cardiac rhythm abnormalities, and 31 (4%) had neurologic symptoms considered to be of cardiac origin. The occurrence of cardiac arrhythmias was related to medical history of cardiovascular disease, but not to organic cerebral disorders. The ictal increase of heart rate was significantly higher and more abrupt in epileptic seizures than in psychogenic attacks. The ictal electroencephalogram/electrocardiogram may thus be applicable to the differential diagnosis between the epileptic and psychogenic seizures.

End-plate spikes in electromyography are fusimotor unit potentials.

Spontaneous negative-positive potentials (NPPs) in electromyography were often activated by movement of the needle electrode or by tetanic stimulation. Coactivation of NPPs was sometimes observed in voluntary effort. Circulatory arrest or hyperventilation had no consistent effect. These facts and the differences of firing of NPPs from usual ectopic firing patterns indicate that NPPs are not driven by ectopic activity of motor axons. Instead, the firing of NPPs is similar to activity of muscle spindle afferents during fusimotor drive. We believe that NPPs are action potentials of intrafusal muscle fibers driven by gamma motor neurons.

Sweat gland vacuoles in Unverricht-Lundborg disease: a clue to diagnosis?

There has been no reported pathologic abnormality outside the central nervous system in patients with Unverricht-Lundborg disease (ULD). We report membrane-bound vacuoles with clear contents in eccrine clear cells and dark cells in five of seven patients with ULD, as well as in one clinically unaffected sibling. Vacuoles were not seen in the biopsies of two patients and of eight controls with Lafora's disease. These findings, though not entirely specific, suggest that skin biopsy may serve as a diagnostic aid to give supportive evidence for ULD.

Cardiac arrhythmias in the differential diagnosis of epilepsy.

Symptomatic attacks or seizures associated with cardiac arrhythmias may cause difficulty in differential diagnosis. Two patients are reported in whom disturbances of cardiac conduction induced attacks which clinically resembled attacks of psychogenic and epileptic origin and were abolished after implantation of a demand-type pacemaker. A third patient is described who had epileptic seizures resulting in cardiac arrhythmias. In the differential diagnosis of these cases, simultaneous ambulatory EEG and ECG recording was essential.

Motor unit potentials in a mildly affected muscle in amyotrophic lateral sclerosis.

Quantitative analysis of motor unit potentials (MUPs) with spike triggering and averaging was performed from the mildly affected brachial biceps muscle of 18 patients with amyotrophic lateral sclerosis (ALS) and of 18 age-matched controls. The total MUP duration was only 6% higher in ALS patients than in controls (P less than 0.05) while the durations of the main MUP and fast components were prolonged by 63% and 194% (P less than 0.001), respectively. The number of satellites, number of fast components and amplitude were also significantly increased in the ALS group. It is concluded that determination of the duration and number of fast components and the MUP amplitude will sensitively pick up mild neurogenic affection of the brachial biceps muscle.

Differential induction of various carboxylesterases by certain polycyclic aromatic hydrocarbons in the rat.

Hepatic and extrahepatic carboxylesterase (EC 3.1.1.1) activities were studied after the exposure of rats to polycyclic aromatic hydrocarbons. In dose- and time-dependent studies, the carcinogens benz[a]anthracene, benzo[a]pyrene and 3-methylcholanthrene moderately induced the hepatic cytosolic and kidney microsomal carboxylesterase activities, while the non-carcinogenic compounds anthracene, phenanthrene and chrysene had no effects on these enzyme activities. The hepatic microsomal and kidney cytosolic enzyme activities were not altered by the polycyclic aromatic hydrocarbons tested. Carboxylesterase activity in the postmitochondrial fraction of the intestinal mucosa decreased the serum enzyme activity slightly increased after the administration of the carcinogenic compounds. Although the in vitro hydrolysis of propanidid by hepatic cytosolic and kidney microsomal preparations was increased, the biological half-life of propanidid in vivo was not changed by 3-methylcholanthrene treatment.

Induction of aldehyde dehydrogenase by polycyclic aromatic hydrocarbons in rats.

Short-term intragastric administration of selected polycyclic aromatic hydrocarbons (100 mg/kg daily for 4 days) to male Wistar rats resulted in marked changes in liver cytosolic aldehyde dehydrogenase activity. Non-carcinogenic anthracene, phenanthrene and chrysene produced a 2.5--3-fold increase in the activity assayed with propionaldehyde as substrate and NAD as coenzyme. Weakly carcinogenic 1,2-benzanthracene enhanced aldehyde dehydrogenase activity 9-fold and the potent carcinogens 3,4-benzpyrene and 3-methylcholanthrene 30-fold. With benzaldehyde as substrate and NADP as coenzyme the differences between the groups were even more pronounced. Somewhat similar but less manifest effects on aldehyde dehydrogenase activity were detected also in the liver microsomes and in the postmitochondrial fractions of the small intestinal mucosa. On the basis of their ability to induce aldehyde dehydrogenase activity the compounds could be divided into three groups. This classification was found to correlate well with the carcinogenic potency of the compounds. It appeared that the exposure to polycyclic aromatic hydrocarbons, especially the carcinogenic ones, was followed by synthesis of a new aldehyde dehydrogenase form. This new form was differentiated from the normally existing cytosolic aldehyde dehydrogenase by its ability to oxidize benzaldehyde in the presence of NADP.

Clinical picture and long-term course of epileptic seizures that occur during clozapine treatment.

Clozapine is an atypical neuroleptic drug that has proved to be effective in alleviating psychotic symptoms refractory to treatment with standard neuroleptic drugs. In addition to hematological side effects, an increased susceptibility to epileptic seizures during clozapine treatment has previously been described. In this report, we describe the clinical picture and electroencephalographic findings of 12 schizophrenic patients who have had from one to six clozapine-associated epileptic convulsions.

Electroneuromyographic findings in patients with Alzheimer's disease.

Electroneurophysiological abnormalities have been reported in some patients with dementia, but the data available is rather limited and controversial. We studied nerve conduction velocities and electromyography in 59 patients with moderate to severe involvement of Alzheimer's disease. Except some occasional mono- and polyneuropathies, the patients showed no systemic dysfunction of the peripheral nervous system.