In vitro quantitative autoradiography of [3H]-L-deprenyl and [3H]-PK 11195 binding sites in human epileptic hippocampus.

Distribution of the enzyme monoamine oxidase B (MAO-B) and the peripheral benzodiazepine binding site (omega 3 site) was studied by quantitative autoradiography using [3H]L-deprenyl and [3H]PK 11195, two tentative glial markers, as ligands. Sclerotic hippocampus from seven patients who had had anterotemporal lobe resection because of intractable complex partial epilepsy were investigated and compared with postmortem hippocampus from three nonepileptic controls. A significantly higher degree of L-deprenyl and PK 11195 binding was observed in the epileptic cases. The increased binding of both ligands correlated to extent of neuronal loss, but only PK 11195 showed correlation to degree of gliosis. We concluded that both ligands could provide useful markers for quantitating the degree of gliosis in pathologic states such as epilepsy. They may be applicable in future in vivo studies with positron emission tomography (PET).

Functional and pharmacokinetic studies of tetrahydroaminoacridine in patients with amyotrophic lateral sclerosis.

Assuming the presence of clinically significant cholinergic hypofunction in amyotrophic lateral scleroses (ALS), seven patients with ALS were treated with 100-200 mg tetrahydroaminoacridine (THA) together with 11 g lecithin daily for up to 7 weeks. In a separate experiment pharmacokinetics and effects on muscle strength and neurophysiological parameters were studied following the injection of 30 mg THA intravenously. Following the injection of THA an increase in muscle strength was observed in two patients. There were no consistent pharmacokinetic differences that could explain the effect on intravenous THA on muscle strength in these two patients. The plasma clearance of THA was high and the oral bioavailability low with large interindividual differences (6-36%). No beneficial effect was seen during oral medication and side-effects were common. There were no conclusive changes observed regarding neurophysiological parameters after drug administration. THA has probably no place in the treatment of ALS.

Relationship of intraindividual dose to plasma concentration of carbamazepine: indication of dose-dependent induction of metabolism.

The effect of a dose change on the plasma concentration of carbamazepine (CBZ) was studied in 13 epileptic patients, all with a CBZ dose of at least 800 mg/day. A disproportionately small rise in the plasma concentration of CBZ was found in 10 of the patients. The ratio between the final metabolite 10,11-dihydro-10,11-trans-dihydroxy-CBZ and CBZ in plasma was higher after dose increase in the 10 patients with a small rise in CBZ levels, indicating a dose-dependent autoinduction of CBZ metabolism. The ratio between the active intermediary metabolite, CBZ-epoxide, and CBZ was unaltered by the dose change in all patients. This indicates that CBZ plasma level determinations can be used for prediction of the total effect of CBZ treatment during high as well as low dosage.

Afferent projections to human tibialis anterior motor units active at various levels of muscle contraction.

The synaptic efficacy of muscle and cutaneous afferents on single tibialis anterior motoneurones in man was derived from changes in the firing probability of single, voluntarily activated, motor units in response to electrical stimulation of peripheral nerves or skin. The motor units were recorded with a Macro EMG electrode. The Macro motor unit potential (Macro MUP) recorded with this electrode reflects the electrical activity of all of the muscle fibres in a single motor unit. The amplitude of the Macro MUP is positively correlated with the recruitment threshold of the unit. Motor units with different Macro MUP amplitudes were examined at approximately the same level of voluntary contraction (less than 20% of maximum). The synaptic efficacy of muscle and cutaneous afferents was similar for units with small and with large Macro MUP amplitudes. Single motor units were examined at several different levels of muscle contraction. There was no consistent change in the facilitation from muscle afferents but there was less facilitation from cutaneous afferents during stronger contractions. This was not simply a consequence of the units faster firing rate. It is concluded that, with increasing voluntary drive to tibialis anterior motoneurones in man, there is a reduction in transmission in the pathways from cutaneous afferents to tibialis anterior motoneurones. There is no evidence that low and high threshold units (judging from their Macro MUP amplitudes) have different afferent connections.

Cholinesterase inhibitors lack therapeutic effect in amyotrophic lateral sclerosis. A controlled study of physostigmine versus neostigmine.

Seven patients with amyotrophic lateral sclerosis participated in a double-blind cross-over trial of oral physostigmine and neostigmine (10 and 45 mg/day, respectively, for 3 days). Six of the patients were also given intravenous injections (1 and 1.5 mg, respectively) of the drugs in an open trial. No significant effects on muscle strength or neurophysiological parameters were observed.

Causes of the increased fiber density in muscular dystrophies studied with single fiber EMG during electrical stimulation.

The impulse transmission in motor end-plates and along muscle fibers was studied with single fiber EMG in 13 patients with muscular dystrophy during intramuscular nerve stimulation and direct muscle fiber stimulation. For comparison, three patients with spinal muscular atrophy (SMA) and five normal subjects were studied. At nerve stimulation, 25% of the recordings in the patients with muscular dystrophy showed "increased" jitter (> 55 microsec), 48% "normal" (10-55 microsec), and 27% "abnormally low" jitter (< 5 microsec). At direct muscle fiber stimulation, the jitter was "abnormally low" in 91% of the recordings; 9% of the recordings had normal jitter. In SMA, no abnormally low jitter values were found. Increased jitter is a sign of impaired impulse transmission in immature intramuscular nerves and motor end-plates. "Abnormally low jitter" suggests the presence of branched muscle fibers and ephaptic transmission between hyperexcitable fibers.

The motor unit in muscular dystrophy, a single fibre EMG and scanning EMG study.

Dystrophic muscle shows increase in fibre density, abnormally low jitter in some recordings and more often increased jitter. The cross section of the motor unit has normal length. There are no signs of abnormal volume conduction characteristics. The increased fibre density is believed to be due to localised increase in the number of muscle action potential generators. The findings are compatible with a remodeling of the motor unit due to fibre loss and a reparative process with fibre regeneration and reinnervation.

Motor unit size in muscular dystrophy, a macro EMG and scanning EMG study.

Patients with muscular dystrophy were investigated with Macro EMG to study activity from whole individual motor units, and with Scanning EMG to study the distribution of activity within the motor unit. Macro motor unit potentials were normal or only slightly reduced in amplitude. In Scanning EMG the units had unchanged mean length compared with normal, but an uneven distribution of the activity. This was also seen in severely weak muscles. The findings are interpreted to be the result of degenerative and regenerative processes, giving rise to remodelling of the motor unit.

Effect of occupational exposure to organophosphorus insecticides on neuromuscular function.

Neurophysiological investigations and determinations of cholinesterase activity on plasma and erythrocytes were carried out on 11 Swedish spraymen exposed to bromophos, diazinon, dursbane, and malathion. Plasma cholinesterase activity was significantly reduced after work, while erythrocyte cholinesterase activity was unchanged. In none of the workers with a decreased plasma cholinesterase activity after work could any related acute neuromuscular disturbance be detected when the men were tested with repetitive nerve stimulation and with single fiber electromyography. Signs of subclinical neuropathy were present as a slight reduction in sensory conduction velocity and increased fiber density in some workers.

The motor unit in psychotic patients: a single fibre EMG study.

Single fibre EMG recording from extensor digitorum communis muscle is described in patients with psychotic illness. The fibre density, or average number of single muscle fibre action potentials belonging to the same motor unit within the uptake area of the electrode, was higher in the patient group than in normal controls. Increased jitter was occasionally seen. Motor and sensory nerve conduction velocity values were within the normal range. The results indicate that psychosis is associated with denervation and reinnervation by collateral sprouting.