No abstract

Transcranial stimulation has become an established method in the evaluation of corticospinal tract function. Clinical studies mainly address slowing of conduction through measurement of increased central conduction time (CCT) and 'failures' of conduction through observation of marked reductions in the size of the motor evoked potential (MEP). While CCT is of great interest in detecting subclinical slowing of conduction, the method discloses only gross failures of conduction, since the size of the MEP varies markedly between normal subjects and from one stimulus to another, leading to a broad range of normal values. Furthermore, transcranial stimulation does not appear to achieve depolarization of all spinal motor neurons leading to the target muscles, since in most normal subjects MEPs are smaller in amplitude than the responses evoked by peripheral nerve stimulation. We have developed a triple stimulation technique (TST) which, through two collisions, links central to peripheral conduction and suppresses desynchronization of MEPs. This technique shows that transcranial stimulation does achieve depolarization of all, or nearly all, spinal motor neurons supplying the target muscle in healthy subjects. Our data thus demonstrate that the amplitudes of MEPs are (i) smaller than those of peripheral responses, mostly due to phase cancellation of the action potentials caused by the desynchronization occurring within the corticospinal tract or at spinal cell level and (ii) variable between normal subjects and from one stimulus to another, mostly due to variability of this desynchronization. This technique provides new insights into normal corticospinal tract conduction. It will improve detection and quantification of central motor conduction failures.

Amplitudes of motor evoked potentials (MEPs) are usually much smaller than those of motor responses to maximal peripheral nerve stimulation, and show marked variation between normal subjects and from one stimulus to another. Consequently, amplitude measurements have low sensitivity to detect central motor conduction failures due to the broad range of normal values. Since these characteristics are mostly due to varying desynchronization of the descending action potentials, causing different degrees of phase cancellation, we applied the recently developed triple stimulation technique (TST) to study corticospinal conduction to 489 abductor digiti minimi muscles of 271 unselected patients referred for possible corticospinal dysfunction. The TST allows resynchronization of the MEP, and thereby a quantification of the proportion of motor units activated by the transcranial stimulus. TST results were compared with those of conventional MEPs. In 212 of 489 sides, abnormal TST responses suggested conduction failure of various degrees. By contrast, conventional MEPs detected conduction failures in only 77 of 489 sides. The TST was therefore 2.75 times more sensitive than conventional MEPs in disclosing corticospinal conduction failures. When the results of the TST and conventional MEPs were combined, 225 sides were abnormal: 145 sides showed central conduction failure, 13 sides central conduction slowing and 67 sides both conduction failure and slowing. It is concluded that the TST is a valuable addition to the study of MEPs, since it improves detection and gives quantitative information on central conduction failure, an abnormality which appears to be much more frequent than conduction slowing. This new technique will be useful in following the natural course and the benefit of treatments in disorders affecting central motor conduction.

The polymorphic cytochrome P-450 DB1 (P-450 IID6) is responsible for the O-demethylation of codeine to morphine by human liver microsomes. The influence of P-450 DB1 variable activity on the bioactivation of codeine in vivo to morphine and on its analgesic effect was investigated in phenotyped healthy volunteers--7 extensive [EM] and 1 poor [PM] metabolizer of debrisoquine. After pretreatment with oral placebo or quinidine sulphate 50 mg, codeine phosphate 100 mg or placebo were administered orally according to a double-blind randomized crossover design. In EM subjects the plasma morphine Cmax was 17.9 nmol/l, whereas virtually no morphine was detectable after quinidine pretreatment (1.5 nmol/l), and in the PM subject (0.60 nmol/l). In EM codeine significantly increased subjective (VAS) and objective (R-III reflex) pain thresholds in response to selective transcutaneous nerve stimulation, whereas no significant analgesia was detected after placebo, or after codeine with quinidine pretreatment, or in the PM. In PM of genetic origin, or due to environmental alteration of the phenotypic expression (i.e. drug interaction), codeine is not activated into morphine and is an inefficient analgesic.

We describe a patient with chronic asymmetric motor neuropathy, which began in the upper extremity. The paretic muscles showed abundant fasciculations and myokymia but only little amyotrophy. Electrophysiologic examination revealed (1) proximal multifocal persistent conduction block (CB) not located at the usual entrapment sites, and (2) arrhythmic isolated or grouped fasciculation potentials originating distally on blocked axons. Over the years, new CBs developed, which led to tetraplegia, and amyotrophy slowly increased with progressive denervation. This patient differs from the cases of chronic acquired demyelinating polyneuropathy described in the literature by the absence of sensory deficit and the proximal location of CB.