The clinical profile of MS in Australia: a comparison between medium- and high-frequency prevalence zones.

Recent epidemiologic studies of multiple sclerosis (MS) in Australia defined the State of Queensland as a medium-frequency zone and the more southerly placed cities of Perth, Newcastle, and Hobart as high-frequency zones. Clinical profiles in the patient populations of both frequency zones were remarkably similar in most respects to each other and to MS populations in the northern hemisphere. However, male patients in Queensland differed from their counterparts in the three cities by showing a greater tendency to develop a progressive disease course and, hence, more disability. The explanation for these observations is uncertain; we speculate that the hotter climate in Queensland may be relevant.

The epidemiology of multiple sclerosis in Queensland, Australia.

An epidemiological survey of multiple sclerosis (MS) in the State of Queensland was undertaken with its prevalence day being the national census day on June 30th, 1981, 20 years after a regional survey within the State. The relationship between increasing prevalence of MS and increasing south latitude within the State of Queensland which was suggested by the 1961 study was confirmed in the present study. The prevalence rate had increased significantly over the 20-year period between the studies but the State remained a medium frequency zone for MS (prevalence rate between 5 and 29 per 100,000 of population). Although a real increase in disease frequency could not be excluded as a contributing factor to the rise in prevalence, it was most likely due predominantly to an increase in life expectancy amongst the MS population and also in differential migration of a population at a greater risk of developing MS than the indigenous population. The proportions of Australian-born patients who had migrated to Queensland from the higher risk southern regions of Australia or travelled overseas to countries known to be high-risk for MS prior to disease onset, had fallen between the two surveys thus exerting, if anything, a negative influence on the change in prevalence. Analysis of MS prevalence rates amongst migrant populations in Queensland as compared to the more southerly city of Perth in Western Australia, suggested that the risk of acquisition of MS may extend over a wider age range than is generally accepted. Finally, there was an absence of MS cases amongst the Aboriginal population in Queensland but it can only cautiously be concluded from this study that the disease is rare in these peoples.

Neuromuscular effects of chronic administration of two organophosphorus insecticides to rats.

Groups of rats were fed chlorfenvinphos (at two dose levels) or dicrotophos. Whole blood and plasma cholinesterase activity was markedly reduced. Compared with control animals there was no change in muscle action potential amplitude (M response) to a single stimulus for periods of up to 3 months. Exposed animals developed a prolonged negative potential at the end of the spike potential, lasting up to 15 ms. Superimposed on this, repetitive activity (RA) developed with latency of approximately 4.5 ms. These abnormalities became more marked with time, even on constant dosing. Double and repetitive stimulation reduced or abolished the prolonged negative potential and RA.

Effects of edrophonium bromide on neuromuscular transmission in a healthy human subject.

Regional intravenous injections of different amounts (1-3 mg) of edrophonium were given to the hand of a healthy subject. The earliest change was a small negative deflection occurring at the end of the muscle response evoked by nerve stimulation, due to repetitive activity. It did not occur after a second stimulus at 30 ms or immediately after 10 s maximum voluntary contraction. Repetitive stimulation at 0.5 Hz reduced the repetitive activity. With a higher dose of edrophonium the response to a second shock (M2) at 30 ms was reduced in amplitude, but M2 at 80 ms was unaffected. An even larger dose caused depression of M2 at 80 ms also and a decremental response to 50 Hz stimulation. The amplitude of the response to a single shock was unchanged throughout.

Effect on neuromuscular transmission of repeated administration of an organophosphorus compound, metrifonate, during treatment of children with urinary schistosomiasis.

Muscle action potential amplitude recorded from abductor pollicis brevis in response to nerve stimulation was measured in 55 children during treatment of urinary schistosomiasis with metrifonate (3 doses at 2 weekly intervals). Mean erythrocyte cholinesterase activity was 52-75% of pretreatment value in different groups when examined electrophysiologically. Twenty-six children acted as controls. There was no difference in amplitude between control and exposed subjects 2 weeks after the 2nd dose. Six hours after the 3rd dose, amplitude was larger in some subjects. This effect was not related to dose or degree of cholinesterase inhibition and was thought unlikely to be the result of treatment. Three children who received the highest dose of metrifonate had developed repetitive activity 6 hr later. The criteria for its identification are described.

Transient facial sensory symptoms following exposure to synthetic pyrethroids: a clinical and electrophysiological assessment.

Amongst twenty-three workers exposed to synthetic pyrethroids, ninteen had experienced one or more episodes of abnormal facial sensation, developing between thirty min and three hr after exposure and persisting for thirty min to eight hr. There were no abnormal neurological signs and electrophysiological studies were normal in the arms and legs. It is concluded that the symptoms are most likely to be due to transient lowering of the threshold of sensory nerve fibres or sensory nerve endings following exposure of the facial skin to pyrethroids, similar to the phenomena that have been described following exposure of animal nerves to pyrethroids.

Effect of metrifonate on neuromuscular transmission.

The least detectable effect of acute cholinesterase inhibition (produced by edrophonium) in a normal subject is described. It consists of repetitive activity following the muscle response to a single nerve stimulus. Repetitive activity does not follow a second response at an interval of 30 msec. or 80 msec. There is no change in amplitude of the response to a single stimulus; nor to a second stimulus with the smallest dose of edrophonium. With higher doses of edrophonium the amplitude of the second response is reduced. 55 children were studied during treatment of urinary schistosomiasis with metrifonate (3 doses at 2 weekly intervals). No change in evoked muscle action potential amplitude attributable to treatment was detected. 3 children developed some repetitive activity 6 hours after their third dose, when erythrocyte cholinesterase inhibition was approximately 50%.

Conduction velocity in hexachlorophane neuropathy: correlation between electrophysiological and histological findings.

After 2-3 weeks exposure to hexachlorophane, maximum motor nerve conduction velocity in sciatic nerves of rats was reduced by 7.5% and evoked muscle action potential amplitude by 9%. Histological examination at this stage showed intramyelin oedema affecting some fibres and axonal degeneration of other fibres. After longer periods of exposure velocity and amplitude fell further. Velocity was reduced by 27% after 6-7 months treatment. In addition to intramyelin oedema and axonal degeneration, segmental demyelination was present in animals intoxicated for more than three months. There was no correlation between the degree of oedema and reduction of conduction velocity. It is concluded that intramyelin oedema has little or no effect on conduction velocity. Nodes of Ranvier are normal in the early stages of the lesion and this may contribute to the preservation of normal conduction. The electrophysiological findings can be attributed to secondary changes of axonal degeneration and segmental demyelination.