No abstract

The clinical and electrophysiological features of 50 consecutive patients with the Lambert-Eaton myasthenic syndrome (LEMS) have been analysed. Carcinoma was detected (CD group) in 25, of whom 21 had small cell lung cancer (SCLC). SCLC was evident within 2 yrs of onset of LEMS symptoms in 20/21 cases, and at 3.8 yrs in 1/21. In the cases in whom no carcinoma was detected (NCD group), 14/25 had a history of LEMS greater than 5 yrs. The dominant neurological features were similar in the CD and NCD groups, and consisted of proximal lower limb weakness (100%), depressed tendon reflexes (92%) with posttetanic potentiation (78%), autonomic features, especially dryness of the mouth (74%) and mild/moderate ptosis (54%). The compound evoked muscle action potential amplitude in abductor digiti minimi was below the lower limit of control values in 48/50, and the increment following maximum voluntary contraction above the upper limit of control values in 48/50. Single fibre electromyographic abnormalities were found in 29/29 cases. The analysis indicates that a patient presenting with LEMS has a 62% risk of an underlying SCLC, and that this risk declines sharply after 2 yrs, becoming very low at 4 to 5 yrs. It is argued that in SCLC cases antigenic determinants on tumour cells initiate the autoimmune response, often early in the course of the malignancy, but that the association of LEMS with tumours other than SCLC may be fortuitous. In the latter, and in NCD patients, the initiating factor(s) are unknown.

SUMMARY1. The magnetic field generated by a brief current in a 9 cm diameter flat circular coil varies rapidly with time and when applied over the human scalp it is capable of exciting motor structures subserving the small hand muscles. With a peak magnetic field at the centre of the coil of 09-1-6 Tesla, single scalp stimuli produced twitches in the right abductor digiti minimi (a.d.m.), first dorsal interosseous (f.d.i.) and adductor pollicis muscles. Compound muscle action potentials (c.m.a.p.s) and single motor units from these muscles were recorded.2. The twitch force and corresponding c.m.a.p. were greatly enhanced by voluntary background contraction of the muscle and depended on the direction and intensity of the magnetic field. Response amplitude was maximal with the stimulating coil centred near the vertex but precise coil position was not critical.3. When the orthodromic volley set up in the peripheral nerve by magnetic stimulation of the brain collided with a maximal antidromic volley set up by stimulation at the wrist, remaining electromyographic (e.m.g.) activity gave evidence of multiple firing of some spinal motoneurones, provided that the muscle exerted a slight voluntary background contraction and the stimulus intensity was above threshold for relaxed muscle.4. When the muscle changed from total relaxation to a slightly contracted state the onset latency of the c.m.a.p. was shortened by about 3 ms without further change when the background contraction increased. In slightly contracted muscle, c.m.a.p. onset latency was little affected over a wide range of stimulus intensities and was unaffected by the position of the stimulating coil within an area of 6 x 6 cm over the vertex. 7. It is likely that the enhancement of responses by voluntary background contraction is caused by additional recruitment of higher-threshold motor units in the motoneurone pool and by multiple firing of some motor units.8. There may be two mechanisms of enhancement of responses to cortical stimulation, one related to a rise in excitability of homologous spinal motoneurone pools on the two sides, and a second operating at a higher level when the subject focuses his attention on the motor performance of a particular hand. The latter mechanism can be seen more easily with magnetic than with electrical brain stimulation, probably because the latter in part bypasses intracortical neuronal elements.

Fatigue is a common and disabling symptom in multiple sclerosis but is poorly understood. We investigated 'physiological' fatigue in 21 patients with multiple sclerosis who complained of disabling fatigue by measuring the decline in strength during a 45 s maximal contraction of the adductor pollicis muscle. The results were compared with those from a control group of 19 healthy subjects. The strength of control subjects declined by approximately 20% during the contraction; twitch interpolation showed central drive remained almost maximal throughout, and therefore that the fatigue was peripheral in origin. Patients had normal baseline strength, but developed greater fatigue (approximately 45%), which was central in origin. In both cases, the decline in strength followed a roughly linear time course suggesting that the patients, like the normals, were trying to maintain a maximum voluntary effort. Evidence for frequency-dependent conduction block (FDCB) in the patients' central motor pathways was sought by measuring the EMG responses to single and paired transcranial magnetic stimuli. Fatigue had no effect on the latency or size of EMG responses to transcranial magnetic stimulation, suggesting that FDCB was unlikely to have occurred. This was supported by measurements of the maximum speed of voluntary muscle contraction; although the patients showed relatively slow speeds before exercise, the decline in speed after fatigue was no greater than in normal subjects. We conclude that excessive 'physiological' fatigue contributes to the symptom of fatigue in multiple sclerosis and is central in origin. However, since the degree of exercise-induced fatigue did not correlate with the baseline complaint of fatigue, other factors must also be operating to produce the full range of clinical symptoms. We found no conclusive evidence that central fatigue is related to increased dysfunction in the primary central motor pathways and no evidence that FDCB is the pathophysiological mechanism. We postulate that central fatigue in multiple sclerosis is due to impaired drive to the primary motor cortex and several lines of evidence strongly suggest that this is not due to a lack of motivation.