Migration and multiple sclerosis in United Kingdom and Ireland immigrants to Australia: a reassessment. II. Characteristics of early (pre-1947) compared to later migrants.

In our recent reassessment we explored the risk of MS by age at immigration in 258 migrants from United Kingdom and Ireland (UKI) to four states of Australia (New South Wales, Queensland, South Australia, and Western Australia) in the period 1947-1981 (Group II). In the present report we have compared their characteristics with 44 cases who migrated before 1947 (Group I), divided into two subsets: Group Ia (15 cases) was rather similar to Group II in age at immigration (means of 20 and 23 years), age at onset (39 and 33 years), and duration from immigration to onset (19 and 10 years). Group Ib (29 cases) was significantly different from Group II, with mean ages of 4 years at immigration and 40 years at onset, for a mean interval of some 35 years between immigration and onset. All onsets in Group Ib occurred after 1947. We concluded that the Group Ib cases had most probably acquired their MS in Australia. Immigrants from high MS risk countries, including UKI, were modest in number before 1947, but some 770,000 entered from 1947-1981. They may have been the source of MS for the Group Ib migrants.

Migration and multiple sclerosis in immigrants to Australia from United Kingdom and Ireland: a reassessment. I. Risk of MS by age at immigration.

A previous study of the prevalence of multiple sclerosis (MS) in 1981 among immigrants from the United Kingdom and Ireland to Australia found that the prevalence for those with age at immigration (AAI) under 15 years of age did not differ from the older immigrants. We have reanalysed the original materials as well as census data for 1901-1981 for UKI and other high MS risk country immigrants. There was a highly significant trend in the prevalence rates of all Australians from New South Wales (NSW) to South Australia (SA) to Western Australia (WA) to Queensland (QLD). Rates by state among the Australian-born were almost identical to these, but there was no prevalence gradient for the UKI-born. The denominator population at risk of MS by AAI was calculated from special census tables of length of residence in Australia by age 0-79 in 1981 for UKI immigrants 1947-1981. The numerator was limited to the subset of 258 MS (Group II) also immigrating in 1947 and later, and age 0-79 in 1981. The absolute risk of MS for these migrants to the four states entering at age 0-14 was 22/100,000, significantly less than for all older age groups; age 15-39 immigrants had a risk of 54/100,000. Similar risk ratios for 0-14 versus 15-39 by state were 31 versus 61 (NSW), 29 versus 44 (QLD), 11 versus 50 (SA), 15 versus 51 (WA).

Multiple sclerosis in Australia: prognostic factors.

In order to determine the influence of age of onset, sex, onset symptoms, clinical course and interval from onset to first relapse on the subsequent outcome of multiple sclerosis (MS), data from 2934 cases of MS documented in a large population based study undertaken in Australia have been analysed. Disability on prevalence day (30 June 1981) was defined on the Kurtzke disability scale as mild (DSS 0-3), moderate (DSS 4-6) and severe (DSS 7-9). Prognostic factors associated with mild vs moderate/severe, and moderate vs severe disability on prevalence day were identified by logistic regression analysis. A worse prognosis was significantly associated with older age of onset, progressive disease course, onset symptoms that were multiple, pyramidal or cerebellar, and a short interval between onset and first relapse.

The age-range of risk of developing multiple sclerosis: evidence from a migrant population in Australia.

The prevalence of multiple sclerosis in the Australian-born population in five different regions of Australia has a strong correlation with latitude, the disease becoming increasingly prevalent with increasing south latitude. In this study, the prevalence in the migrant population from the UK and Ireland (UKI) in the different regions also showed a significant correlation with latitude, but this relationship was strongly influenced by the high prevalence in Hobart. Except for Hobart, the prevalence in migrants was considerably less than that in their countries of origin. The prevalence of multiple sclerosis among those migrating before the age of 15 years from the high-risk UKI to lower-risk Australia was not significantly different to that among those migrating at or after that age, and this finding was confirmed in a case-control study which demonstrated little association between age at migration and risk of developing multiple sclerosis. These findings suggest that the risk from environmental factors in multiple sclerosis may operate over a period of many years and not only in childhood and early adult life.

Multiple sclerosis in Australia: socioeconomic factors.

The data from an epidemiological study on multiple sclerosis in Australia have been analysed to determine the relation between the prevalence of the disease and educational level, and the association between level of disability and employment status. There was a significantly higher frequency of multiple sclerosis in those who left school at an older age and achieved a higher educational level. The explanation of this finding remains speculative and may be related to genetic or environmental factors. The study confirmed the recognised association between moderate-severe disability and divorce-separation and lower rates of employment.

Epidemiology of multiple sclerosis in Australia. With NSW and SA survey results.

OBJECTIVES: (i) To determine the prevalence of multiple sclerosis (MS) in New South Wales and South Australia; (ii) to compare these prevalences with those in other areas of Australia and to determine the relationship between prevalence and latitude; (iii) to examine the relative contribution of genetic and environmental factors in the aetiology of the disease in Australia; and (iv) to ascertain whether there had been a change in the frequency of the disease since 1961. RESULTS: The crude prevalence of MS in New South Wales on prevalence day (National Census Day, 30 June 1981) was 37.2/100,000 and the age-standardised prevalence 36.6/100,000. The female:male ratio was 2.3:1. The crude prevalence in South Australia was 29.4/100,000 and the age-standardised prevalence 28.8/100,000. The female:male ratio was 2.4:1. No Aborigines or Torres Strait Islanders with MS were identified. There was a significant increase in the prevalence with increasing south latitude in Australia, MS being about seven times more frequent in Hobart than in tropical Queensland, but no genetic differences were found in the surveyed population in different parts of Australia. A significant increase in the prevalence of MS occurred in most areas of Australia between 1961 and 1981, but this may not reflect a true increase in incidence. CONCLUSION: The increasing prevalence with increasing south latitude cannot readily be explained by genetic susceptibility, and suggests that environmental factors are important for expression of the disease.

Multiple sclerosis in Australia and New Zealand: are the determinants genetic or environmental?

The prevalence of multiple sclerosis (MS) has been recently reported from nine regions of Australia and New Zealand. There is a marked variation of prevalence with latitude. MS is seven times more common in southern New Zealand than in tropical Queensland. On current evidence, it is suggested that in both countries this variation is predominantly due to environmental rather than genetic factors.

The contribution of mortality statistics to the study of multiple sclerosis in Australia.

Mortality statistics provided a valuable source of support for data obtained from prevalence surveys of multiple sclerosis in Australia. Firstly, multiple sclerosis mortality data for the decade 1971-80 in the States of Australia confirmed the relationship between increasing disease frequency and increasing south latitude shown by State and regional point prevalence surveys based on the national census day 30 June 1981. Secondly, a comparison with mortality data from the decade 1950-59 showed that in most States there had been a substantial fall in multiple sclerosis mortality in the more recent decade and this was clearly an important contributing factor to the rise in prevalence noted between the morbidity surveys of 1961 and 1981. Thirdly, multiple sclerosis mortality in the UK-born migrant population dying in Australia was found to be similar to that of the Australian-born population and very much lower than that found in the UK. This observation corroborated evidence from the 1981 morbidity surveys and suggested that migration from the UK to Australia may lower the risk of developing multiple sclerosis either through a reduction in disease incidence or the operation of environmental factors curbing disease expression.

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 three Australian cities: Perth, Newcastle and Hobart.

An epidemiological survey of multiple sclerosis (MS) in three Australian cities, Perth, Newcastle and Hobart, was undertaken with its prevalence day being the national census day on June 30, 1981, exactly twenty years after a previous survey of the same cities. The relationship between increasing prevalence and increasing south latitude found in the 1961 survey was confirmed in this present study. Prevalence rates had increased significantly over the twenty years between the studies. Over the same time period incidence rates had also increased in Newcastle and Hobart but had remained essentially stable in Perth although these changes were not significant. The rise in prevalence was due to a combination of factors of differing importance in each city. These factors included better case ascertainment, increased recognition of the less severely disabled patient, increased survival time and differential immigration of a population at a higher risk of developing MS than the indigenous population. Finally, analysis of MS prevalence rates amongst migrant populations in Perth and Hobart suggested that either the risk of acquisition of MS may extend over a wider age range than is generally accepted or that environmental factors prevalent in the former city have modified disease expression there.

The interaction between sex and click polarity in brain-stem auditory potentials evoked from control subjects of Oriental and Caucasian origin.

Brain-stem auditory evoked potentials (BAEPs) were performed on 30 male and 30 female young normal Oriental subjects, using both condensation and rarefaction stimulation. The effects of sex and click polarity on the BAEP latencies and amplitudes were studied. Females had shorter absolute and interpeak latencies and higher absolute amplitudes than the males. These sex-related BAEP differences were independent of the click polarity. Rarefaction clicks produced shorter wave I latency and longer I-III interpeak latency, but the differences were significant in the female only. The polarity-related BAEP amplitude differences were essentially independent of the sex. BAEPs performed on 60 sex- and age-matched young Caucasian subjects produced similar results. The importance of establishing control BAEP values according to the sex and click polarity is emphasised.

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.

The relevance of contralateral recordings and patient disability to assessment of brain-stem auditory evoked potential abnormalities in multiple sclerosis.

Brain-stem auditory evoked responses (BAER) were recorded in a group of 83 patients with a diagnosis of clinically definite or probable multiple sclerosis to assess the relevance of recording contralateral responses simultaneously with ipsilateral responses and to correlate patients disability with the detection of abnormalities. The contralateral responses generally mirrored the ipsilateral responses, but in seven patients the responses differed, mainly involving the presence or absence of wave V. However, contralateral recordings did not contribute significantly to the sensitivity of lesion detection, and their main value was to aid in the recognition of waves when they were not clearly seen in the ipsilateral recordings. The BAER abnormality rates were found to be significantly correlated with disability, and it is suggested that this is an important variable to consider when undertaking or comparing results of BAER studies in patients with multiple sclerosis.

Variability on serial testing of pattern reversal visual evoked potential latencies from full-field, half-field and foveal stimulation in control subjects.

The change in pattern reversal visual evoked potential (PRVEP) latency over time (test-retest variability, TRV) was assessed in 30 (16 males, 14 females) adult control subjects using full-field (FF), half-field (HF) and foveal (central-field, CF) stimulation. The mean test-retest interval (TRI) was 20.5 months with a range of 18-21.5 months. There were no significant test-retest latency differences in either sex and furthermore there were no significant inter-sex differences in any of the test-retest parameters. Because of the latter finding the test-retest upper limit of normal for each parameter as defined by the mean value + 2.5 S.D. was taken as the largest value obtained in either sex. Thus the test-retest upper limits of normal for absolute latency from FF, right HF, left HF and CF stimulation were 6, 7, 9 and 7 msec, respectively; for interocular latency differences (ILD) from FF and CF stimulation were 4 and 5 msec respectively; and for right HF to left HF intraocular latency difference (IOLD) was 7 msec. It is concluded that the TRV was sufficiently small in our control group with each of the stimulus techniques to make all of them potentially useful in serial PRVEP studies. Furthermore the extra information provided by CF and HF stimulation may increase the sensitivity and accuracy with which change can be monitored.

Contribution of pattern reversal foveal and half-field stimulation to analysis of VEP abnormalities in multiple sclerosis.

Multichannel pattern reversal visual evoked potentials (PRVEPs) from full-field (FF), half-field (HF) and foveal (central-field, CF) stimulation were recorded in 112 mildly disabled multiple sclerosis (MS) patients with the aim of evaluating the contribution of HF and CF stimulation in this disease. CF stimulation was marginally more sensitive in detecting abnormalities (75% of patients) than FF stimulation (71% of patients). However, more importantly the two techniques were found to be complementary with the maximum number of abnormalities (79% of patients) resulting from a combination of the results. Abnormal FF responses were further evaluated by HF responses. P100 latency prolongation indicative of conduction delay was the most common finding but one-third of abnormalities consisted of disturbances of wave form relating to conduction block predominantly in macular fibres. Furthermore 34% of patients had an absent or indeterminate response to CF stimulation thus providing electrophysiological confirmation of the preferential involvement of macular fibres in MS. Although electrophysiological abnormalities were localised to the optic nerve in the majority of cases, some patients also had evidence of retrochiasmatic and chiasmatic lesions. In the majority of cases CF stimulation proved to be a useful alternative to HF stimulation in evaluating FF responses with abnormal wave forms. The study also suggested that an important factor determining whether a central scotoma will disturb the morphology of the FF VEP in the midline recording channel is the position of the macular representation in the occipital cortex. It is concluded that with multichannel recording and the additional use of CF and HF stimulation it is possible to increase the yield of PRVEP abnormalities found in MS and to define their nature with considerably greater precision.

A comparison of brainstem auditory evoked responses evoked by rarefaction and condensation stimulation in control subjects and in patients with Wernicke-Korsakoff syndrome and multiple sclerosis.

Brainstem auditory evoked responses (BAER) evoked by rarefaction and condensation stimulation were compared in patients with Wernicke-Korsakoff syndrome (WKS) and multiple sclerosis (MS) and click polarity-related differences in topodiagnosis were found in 24% of the WKS and 40% of the MS patients. These results suggest the need to record BAER routinely with both stimulus polarities separately if practicable. BAER from rarefaction and condensation stimulation were recorded from control subjects of both sexes to provide control data for the patient study and also to investigate the interaction between sex and click polarity. BAER latency and amplitude differences between males and females were found to be independent of click polarity. However, the study did show an interaction between female sex and click polarity-related BAER latency differences although differences in amplitude and waveform morphology were essentially independent of sex. This further emphasises the importance of taking into account the variables of sex and stimulus polarity in establishing BAER control values.

Transfer factor as a therapy for multiple sclerosis: a follow-up study.

The result of a two year, double blind, controlled trial of Transfer Factor (TF) in the treatment of multiple sclerosis (MS) were reported in 1980. It was demonstrated that TF significantly reduced the rate of progression of the disability but the benefit of therapy was not apparent until 18 months after its commencement. After the completion of the trial, TF treatment was offered to all the trial participants. Forty-five of these people accepted TF as treatment and have been followed for the subsequent three years. The twenty-three people who had received TF during the trial, and continued on TF after the trial, consistently had a slower rate of progression of their MS. Although the twenty-two patients initially on placebo had a significantly faster rate of progression during the trial, this slowed with commencement of TF treatment. After 3 years of TF, the rate of progression of disease was similar to that of the group receiving TF continuously for 5 years. In addition, 470 patients with clinically definite MS are being treated in New South Wales in an open study of TF. The rate of progression of the disease is being monitored by neurological assessments and appears to be similar to that of patients who had received TF in the original trial. The follow-up study of the 1980 TF trial patients and the open study of 470 MS patients confirm the original observation that TF has some effect on slowing the course of MS.

Alpha-1 antitrypsin phenotypes in demyelinating disease: an association between demyelinating disease and the allele PiM3.

Alpha-1 Antitrypsin, the major circulating protease inhibitor, has more than thirty alleles that can be identified by electrophoresis. In addition to its role as a protease inhibitor, alpha-1 antitrypsin may regulate the immune response. As there is evidence that both the inflammatory polyneuropathies and multiple sclerosis have an immune basis, and that genetic factors influence susceptibility, we have determined the alpha-1 antitrypsin phenotypes (protease inhibitor types) of 63 patients with Guillain-Barré syndrome, 52 patients with chronic inflammatory demyelinating polyneuropathy, and 178 patients with multiple sclerosis. In all 3 groups there was a significant increase in the proportion of patients with the protease inhibitor type M3 allele.

A clinical and electrophysiological study of neurogenically induced winging of the scapula.

Four cases of neurogenically induced winging of the scapula are described. Systematic clinical evaluation enabled the affected nerve or nerves to be defined in each case, particular attention being directed to the presence or absence of deformity at rest, the direction of rotation of the winging scapula, and the movement of the arm that produced maximal scapular winging. EMG studies were performed on all 4 cases and serial spinal accessory nerve conduction studies on the 2 patients with involvement of this nerve. Both techniques proved useful adjuncts to clinical evaluation and provided confirmatory diagnostic information. The accessory nerve conduction studies were of further value in assessing the extent and type of neural damage, the rate of recovery and the prognosis.

Occipital neuralgia.

The findings in 23 cases of occipital neuralgia are presented. The clinical features of the condition are pain and sensory change in the distribution of the relevant nerve, localised nerve trunk tenderness and a clear response to local forms of therapy. The clinical picture is often complicated by migrainous and trigeminal nerve features and the mechanisms by which these come about are discussed. Occipital neuralgia is generally neglected in both the standard textbooks and the literature. The condition occurs sufficiently commonly to warrant more consideration in the differential diagnosis of head pain than it has received to date.