Epidemiology north-east (Grampian Region) of Scotland-an · Epidemiology ofmultiple sclerosis in the north-east (Grampian Region) ofScotland-an update Table 2 Prevalence ofmultiplesclerosis

Journal of Epidemiology and Community Health, 1987, 41, 5-13

Epidemiology of multiple sclerosis in the north-east(Grampian Region) of Scotland-an updateJAYANT G PHADKE AND ALLAN W DOWNIEFrom the Department of Neurology, Aberdeen Royal Infirmary

SUMMARY The north-east of Scotland (Grampian Region) has undergone three incidence andprevalence surveys, including the present one, since 1970. Results from these indicate a true increasein the prevalence ofthe disease in the region. The incidence of the disease has remained continuouslyhigh and shows a slightly upward trend. Literature on the subject of repeated surveys in differentregions ofthe world has been reviewed in detail. The need for a prevalence study from the south oftheBritish Isles has been emphasised in order to enable one to judge if the increase in Scotland is inkeeping with the pattern in the whole of the British Isles. The familial incidence of the disease wasnoted to be virtually unchanged between the three surveys. Certain other aspects of aetiologicalsignificance have been analysed, viz, clustering of patients at birth or at onset of the disease; ages ofoccurrence of childhood viral infections such as measles, mumps, chickenpox and rubella; and therole of canine distemper infection.

The area now known as the Grampian Region has been 7previously reported I

2 to have the highest prevalence ofmultiple sclerosis (MS) compared to any other surveyedarea of comparable population (471 000). We havecarried out a further study of incidence and prevalenceof the disease as at December 1980 to assess the

present situation. In addition, historical details ofpossible aetiological relevance were enquired about,foreudarexample, age of occurrence of certain childhood viral MorY Buchaninfections, degree ofexposure to dogs as domestic pets,and family history of neurological disease or of Go ,autoimmune diseases. The clinical features of the berdeen

disease, with particular attention to its course and ide ondprognosis, were also studied and will form subjects oflater publications.

Materials and methods Fio Iictritc11 7ii.Unfrnmninn Roia5nn JiU5l A07YI

Due to administrative reorganisation since 1975, thenorth-east area has been reformed as GrampianRegion. This corresponds closely with the areapreviously surveyed, but minor and appropriateadjustments had to be made in some boundary areas.A breakdown into the 28 areas containing apopulation of 10 000 or more as carried cwt in theprevious two surveys' 2 to allow comparisons ofprevalence in these small sub-units was not possiblebecause of the reorganisation, but the new sub-division ofthe region into five districts still allowed forsome comparisons between the three surveys. The

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1980 series was made up of the nucleus of those foundin the earlier studies who were known not to have diedor left the area, and to this were added all the newpatients ascertained from a variety of sources sincethat time. These sources included hospital diagnosticrecord index, neurology departmental records,including the records of patients referred for visualevoked responses, patients found in long-stay wards,patients found in the local branch of the MultipleSclerosis Society, and patients under care of theCommunity Nursing Services. After preliminary

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6screening of case notes of all the patients compiledfrom the above sources (1200), lists of suspectedpatients known to be cared for by individual generalpractices were prepared. National Health Servicenumbers, present address, and name of the generalpractitioner for each patient were personally obtainedfrom records of the local Primary Care Department,and this made the tracing of patients much easier. Thelist of patients known to be in each general practicewas then submitted to the practice with a request, asbefore, that they notify any other cases known to thembut not to us, and remove any patients who were nolonger on their lists. Information about currentdisability status (using McAlpine's Disability Scale3),about the number of relapses since the patient was lastseen in the hospital, and also about other possiblerelevant factors, as mentioned above, was requested.The returned questionnaires from the general

practitioners added 13 further cases of multiplesclerosis to the number about whom information hadalready been available, but six cases had to be removedfrom our preliminary lists as notice of their death sincethe previous survey had not been received from othersources. In ten patients identified in the 1973 survey,further events had made the diagnosis ofMS no longertenable, and in two of these another diagnosis hadbeen established at necropsy.The 'balance sheet' showing the change between

1973 and 1980 is shown in table 1. All except fivepatients were examined at least once, and a largenumber had been examined several times by a memberof the Neurological Services in Aberdeen.

After all the available information from the familydoctor and from the hospital case notes had beenentered on a patient's card, questionnaires were sent toeach patient asking for details of the ages at which theyhad suffered from the various infective illnesses(mumps, measles, chickenpox, rubella, and herpeszoster). They were also asked for their address at thepresumed onset of their disease, at their birth, and

Table I Analysis and details of 1980 survey

Number ofpatientsSource Female Male Total

1973 Survey 402 232 634Deaths between 1973 and 1980from the 1973 Survey 77 42 119Left area between 1973 and 1980 24 9 33Cases rejected from 1973 Survey 8 2 10

Remaining cases from 1973 Survey 293 179 472Migration into Grampian afteronset of disease elsewhere 20 5 25New cases since 1973 Survey(alive on prevalence day I Dec. 1980) 236 106 342

Total cases in 1980 survey 549 290 839

Jayant G Phadke and Allan W Downieduring the major part of their childhood, and theiroccupation at the presumed onset.From all these and other clinical and social details

from the assembled data, patients were classified intopossible and probable MS categories as in the earlierseries' 2 in which Broman et ars (1965)4 modificationsofAllison and Millar's (1954)5 classification was used,although on this occasion the categories previouslylabelled probable (group 1) and early probable andlatent (group 2) were merged, while the categorypossible was retained as before. Probable MStherefore included patients with a history and physicalsigns of a central nervous system disease disseminatedin time and place, in whom other neurologicalconditions had been excluded as far as possible. Alsoincluded in this category were patients at an earlierstage of the disease with a relapsing remitting course,who had few persisting physical signs of centralnervous system lesion, but in whom diagnosis wassupported by paraclinical evidence such as elevatedimmunoglobulin G in the CSF, prolonged visualevoked response latency or an abnormal CT scan.Possible MS included patients with a history andexamination compatible with MS in whom otherdiagnoses had been excluded as far as possible.Evidence of multiplicity of lesions was sometimeslacking in these patients. This group included somepatients with progressive spastic paraparesis wherefull investigations, including myelography, hadexcluded other likely causes of such a picture. Patientswith optic neuritis alone were not included.

Finally, because of easy storage, ready access, andability to carry out complete correlations andstatistical analyses, all the above data were coded andentered on a main line computer. As in the 1973study,2 all patients were 'flagged' in the centralRegistrar's Office at Edinburgh by sending that officeeach patient's full name, age, National Health Servicenumber, and address. This has proved to be invaluablein reliable ascertainment of deaths in the past.

Results

In all, 839 patients thought to have the disease werepresent in the region on the prevalence day, 1December 1980. Six hundred and eighty-two were inthe probable and 157 in the possible category.

DISEASE PREVALENCEDespite stringent and only slightly altered selectioncriteria, the prevalence figures indicate a markedincrease between 1970, 1973, and the present survey(table 2).The new administrative districts created in the

reorganisation of 1975 are shown in figure 1. The totalpopulation rose by 44 000 between the 1971 and 1981



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Epidemiology of multiple sclerosis in the north-east (Grampian Region) of Scotland-an updateTable 2 Prevalence ofmultiple sclerosis in the Granpian Region of Scotland (1970,.1973 and 1980)

No ofpatients Prevaknce rate/lOO 000Year Mak Femaak Total Probabk Possible M.:F ratio Probable All cases

1970 215 342 557 464 95 1:1-59 106 1271973 232 402 634 517 117 1:1-73 117 1441980 290 549 839 682 157 1:1-89 145 178

NB. The prevalence rates have been rounded up to the nearest whole number

census.6 Figures obtained in the 1973 survey from thesmall sub-units were rearranged to allow acomparison, and an excess noted in 1973 in the areanow known as Gordon District has disappeared, whilethe neighbouring City ofAberdeen District has shownan apparent disproportionate increase. Apart fromGordon District, all the districts in the region haveshown an absolute increase in numbers ofcases whichis statistically highly significant (p < 0-001) (table 3).The change in Gordon District may have been due

partly to boundary changes or in part to a true increasein prevalence in the City of Aberdeen.

PREVALENCE BY AREA OF BIRTH PLACENearly three-quarters of the patients were born in theregion (616 patients), about one-fifth outside theregion (169), and the address at birth was unknown inthe case of 54 patients. If MS was the result ofexposure to an environmental agent in childhood, adegree of clustering of patients for their birth-andchildhood addresses might have been noticeable in arelatively static population such as ours. Patients werearranged in different groups by age, year ofonset, andthe place of residence during childhood. On statisticalanalysis using the x2 test, however, no difference was

Table 3 Comparison ofdisease prevalence between 1973 and1980 surveys in different districts of Grampian Region

No of cases No of cases Prevaknce rateDistrict Year observed expected X2 /100 000

City of 1973 284 287 004 142Aberdeen 1980 407 363 533 200Kincardine & 1973 52 48 0-32 156Deeside 1980 76 75 001 180

Gordon 1973 108 85 6-3 183Gordon ~~1980 93 III 2-8 149

Banff& 1973 104 112 0-54 134Buchan 1980 134 145 0-86 164

Moray ~ 1973 81 97 2-60 120Moray 1980 129 115 1 74 159

Total ~1973 6290Total 1980 839

There were significant differences between the prevalence rates in differentdistricts.This is true in both surveys- 1973-x22= 9-29 p<005

1980-X = 1081 p<0-05*5 cases originally observed in the 1973 survey were omitted because ofadjustment for boundary changes

noted between any of the districts. No trend wasnoticeable either on arranging the figures for theaddress at onset in a similar way.

AGE AT ONSET AND DURATION OF DISEASEMean age at onset was noted to be similar in the 1973and the present survey (males= 34-1 years and females34-7 years; all patients 34-5 years). Mean age on theprevalence day was 45 1 (range 11-94) years. Theproportions of patients in different age groups at theonset of disease have been shown in figure 2. Thisshows that the largest percentage ofpatients had onsetof disease in the third decade. Mean duration of thedisease was also similar to that in the 1973 survey2(14-8 years). Ninety-two patients (11%) had survivedfor more than 30 years after the onset of the diseasewith a slight male preponderance in this group(M:F= 1.19:1).

AGE AND SEX SPECIFIC PREVALENCE RATESUsing the 1981 census6 figures for distribution by ageand sex of the Scottish population, the specificprevalence rates were calculated. The overallprevalence rate was highest for the age group 45-54years at 412/100 000; that for females in the same agegroup was 494 3/100 000, and for males 324 7/100 000.In actual numerical terms, therefore, 1 in 200 womenand 1 in 300 men between the ages of 45 and 54 yearswere affected by the disease (fig 3).

40-35-

30(25-20-15-10

5-

O-

* Males (372)1° lFems(683)1

nill ~~~IMon0-9 10-19 20-29 30-39 40-49 50-59 >60

Age at onset of diseaseFig 2 Age at onset by sex (all patients observed between1970 and 1980).

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8500-50- o-o Females f

Fi*3Ae pcioMatesaec ae

300

u00

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0i<~15 16--24 25-34 35-44 45-54 55-'64 65-'74 75+

Age on prevalence day

Fig 3 Age specific prevalence rates

INCIDENCE OF DISEASEIncidence of the disease was calculated in three year

periods between 1960 and 1980. This was done bydividing the number of patients whose disease beganwhile they were living in the Grampian Region by theestimated population in each three year period.7 Thisincluded not only those patients who were living in theregion at the time of the present survey but also thosewho had died or had left the area before the prevalenceday but whose disease had begun while they were

living in the region during the respective three year

periods (fig 4).Increased local interest and awareness following the

1970 survey might have contributed to the apparentincrease in incidence recorded in 1973. The increasinguse of investigations such as visual evoked responses,CT scanning, and CSF IgG estimation may also haveincreased diagnostic certainty between 1973 and 1980,but the overall trend of the disease in the decade doesseem to be an upward one (fig 4). Incidence figures

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8-18- 7.2

6-0 6-0 /7 0

2

I

0 -

1959-61 62-64 65-67 68-70 71-73 74-76 77-80

Fig 4 Incidence rates for three year periods, 1959-80

Jayant G Phadke and Allan W Downieprior to 1959 are not so reliable, as accurate data aboutdeaths and migration were not available. The slightfall off in incidence rates after the peak recorded in1970-73 is unlikely to be very significant as somepatients who have been seen only in recent years mayhave had only a single episode of neurologicalsymptoms so that as yet they have not been classifiedeven as possible cases of multiple sclerosis. Thedifference in the incidence figures for the period1970-73 as shown in the report of the previous survey2compared with the present one is due to the latepresentation of a number of patients whose diseasehad begun during that period but who were similarlynot recorded at that time as established cases ofmultiple sclerosis.

CERTAIN AETIOLOGICAL CONSIDERATIONSEnvironmental factorsSocial class Nearly two-thirds of the patientsbelonged to social classes I to III. This was similar tothe findings of the earlier survey in this region.8 Thispreponderance of the higher social class is highlysignificant (p<0 001) when compared to thedistribution in the general Scottish population.9

Occupation In the 1973 survey,2 an excess of woodworkers, nurses, and doctors was noted among thepatients. This observation was, however, notconfirmed in the present survey. In this survey, anumber of other occupations, such as clerk, shopassistant, typist, and teacher, was noted to becommon.

Although the differences from the generalpopulation were statistically significant, no firmconclusions could be drawn because the numbers ineach occupation group were small.

Exposure to dogs In view of the renewed interest inthe possible role of canine distemper virus in theaetiology of MS, patients were questioned aboutcontact with dogs as domestic pets. Out of697 patientswho answered this question, just over half had neverkept a dog as a pet. Of the ones who had, only aboutone-sixth reported that their dogs had suffered fromcanine distemper. Without control values from thegeneral population no firm conclusions can be drawn.

Age of occurrence of childhood viralinfections Epidemiological data on the age ofoccurrence of childhood viral infections, in particular,measles, suggests that it is earlier in low MS frequencycompared to high frequency regions.'10 Our figuresare in keeping with this (table 4). The age ofoccurrenceof measles was more than five years in two-thirds ofthe patients (64 35%). In comparison to the controlpopulation the age of occurrence was later in the MS



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Epidemiology of multiple sclerosis in the north-east (Grampian Region) of Scotland-an updateTable 4 Frequency and age of occurrence of certain virus infections

Measles Herpes zosterChicken pox Mwnps Rubella MS patients Controls MS patients tControls

Number of patientswith no history of 220 253 358 92 - 551 48infection (34-9) (39-6) (58-3) (14-0) (85-7) (96)with history of 411 385 256 567 - 92 2infection (65-1) (60-4) (41-7) (86 0) - (14 3) (4)

Age of occurrence0-4 years 89 64 39 186 12,578 1

(21-7) (16-6) (152) (357) (393) (1 1)5 years & over 285 290 192 335 19,407 85

(69 3) (74 4) (75-0) (64 3) (60 7) (94-4)Age unknown 37 31 25 46 - 6

(9 0) (8 0) (9-8) (6-5)

Total number with 631 638 614 659 31,985 643history available (100 0) (100 0) (100 0) (100) (76 6)

P> 05 X2=3 02 p<007

* Figures showing ages of reported measles cases in the City of Aberdeen between 1911 and 1973.Data for war years (1914-1918 and 1940-1944) not available.

t Control figures from Ref 42. Pleas see text.Figures in brackets are percentages.

patients, but the difference was only marginallysignificant at the 5% level (table 4). Herpes zosteroccurred in 14-3% compared to 4% in the controls(p< 002). Control figures for other childhoodinfections were not available.

Genetic factorsFamilial incidence of multiple sclerosis Ninety-threepatients had one or more than one first degree relativeaffected with the disease. Sixteen of these were, in fact,present in the present survey, thus constituting 77families (77/284 = 9.3%). This figure is similar to thatin the two earlier studies in this region when a familialincidence of 9-2% and 9-6% was noted.8

Familial incidence of other neurological andautoimmune disease There is increasing evidencenow that MS has an autoimmune basis. An increasedfamilial incidence of diseases with an autoimmunebasis has been reported in a number of conditions, forexample, thyroid disease, pernicious anaemia, etc,where an autoimmune pathogenesis is suspected. Wedecided to see if a similar pattern of increasedincidence of other autoimmune diseases existed in thefamilies of MS patients in this region. In addition tothe incidence of the autoimmune diseases we alsoinquired about the occurrence of certain otherneurological disease in the families. Apart frommultiple sclerosis itself, 21 cases ofParkinson's diseaseand ten cases of poliomyelitis were found in therelatives of 778 cases of multiple sclerosis. Seven casesof rheumatoid arthritis out of 375 cases were alsofound. In 11 other diseases enquired about(neurological and autoimmune) no obvious increase in

numbers was noted. In the absence of control valuesfor the population under study no firm conclusionscan be drawn but the incidence ofrheumatoid arthritisand Parkinson's disease does seem greater thanexpected.

MORTALITY RATESOne hundred and fifty-two patients known to us assuffering from possible or probable multiple sclerosisdied between 1974 and 1980. The annual mortalityrate using the 1961 census figurest3 was 5-0/100 000.This figure was strikingly different from the officialfigure of 18 per 100 000 for Grampian Regionreported by the Registrar General's Office for theperiod 1974 to 1981 6This figure, ofcourse, is based ondeath certificates giving multiple sclerosis only as theprimary cause of death. A similar discrepancy in themortality figures for the region from 1971 to 1975 wasnoted by Shepherd.8

Table 5 shows the inadequacy of the official figuresas a true indicator of the number of deaths in patientswith multiple sclerosis. As the official mortality figurefor the Grampian Region was similar to that for therest ofScotland (2-1/100 000),6 it is likely that a similardiscrepancy may have occurred in other regions aswell.Mean duration to death was 24-5 years. This figure

by direct measurement is less than would have beenobtained by the indirect method suggested byPoskanzer et al.'4 This estimation was obtained bydoubling the duration of the disease on prevalenceday, and with our subjects a figure of29-6 years wouldhave been obtained. Females survived slightly longerthan males (F:M=257: 23-5 years), a fact also

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Table 5 MS deaths 1971-80 in the Grampian Region

1971 1972 1973 1974 1975 1976 1977 1978 1979 1980 Total

No of deaths 21 21 19 23 19 27 12 24 17 30 213

Source of information1* 10 5 9 5 15 19 10 19 13 19 124 ( 58%)2* 7 11 10 15 3 5 2 2 0 3 58 ( 27%)3* 4 5 0 3 1 3 0 3 4 8 31 ( 15%)Total 21 21 19 23 19 27 12 24 17 30 213 (100%)

1 * Mortality figures from Registrar General's annual computer printout. These contained patients in whom death had been notified as a contributory as well as aprimary factor.

2* Death certificate copies obtained on cases from General Register Office, Edinburgh, who had been 'flagged' by us from earlier surveys as suffering from multiplesclerosis. These would be notified to us even if multiple sclerosis was not mentioned on the death certificate.

3* Mortality infonnation from local sources including necropsy reports12 and GP questionnaires.

reflected by a lesser ratio of females in the mortalitygroup (M:F=1:1 5) compared to the prevalencegroup (M:F = 1:1 89).

DiscussionThis third survey of MS in the Grampian Region(north-east) of Scotland has reaffirmed that thedisease continues to occur there more frequently thanin any other surveyed area of comparable populationin the world.

There has been a sharp increase in prevalence sincethe 1973 survey (table 2). Increased local interest mighthave played some part in early case referral but is likelyto be of minimal significance and cannot bequantified. No significant changes in the basicdiagnostic criteria have occurred, and the diagnosis isstill based mainly on clinical grounds. Altered criteriafor ascertainment would be unlikely to have playedany major part since one of us (AWD) has beenpresent here since 1965 and has participated in all threesurveys.The mean duration of disease has not significantly

changed between the three surveys. The death rate for1971-74 was 4- 1/100 00015 and is close to (in fact lessthan) the mean annual death rate between 1974 and1980 (5-0/100 000). Increased survival cannottherefore be the cause of the increased prevalence inrecent years. The migration figures suggest no netinflux of patients (table 1). An additional 18 patientswith MS were in fact present in the region at the time ofthe 1973 survey but were missed. The population ofthe region has increased from 438 631 to 470 596between the 1971 and 1981 censuses,6 and if one addsthe number ofpatients in proportion to the populationincrease (56 patients) and the 18 patients who weremissed in 1973 to the total of 634 patients reported inthe 1973 survey, the present survey figure of 839 is stillsignificantly greater than expected (table 2). Otherindicators of a true increase in the number of patientsinclude an overall upward trend of incidence (fig 3) inthe decade 1970-80 and a sharp increase in the number

of female compared to male patients in spite of nogreat difference in their survival. If increased localawareness and interest were to have played a majorrole, the proportion of female to male patients mighthave remained constant, but contrary to that the F:Mratio in the patients diagnosed since 1973 has increasedto 2-22:1 compared to 1 73:1 in 1973.2

In most places where the prevalence of MS has beenstudied on more than one occasion, an increase hasbeen reported'$29 with the exception of Winnipeg,30Boston,3t and the Faroes.32 The Mayo Clinic series33provided a 60 year follow-up of incidence andprevalence. Incidence showed a very minimal increase,and the prevalence rate was stable for those who hadbeen resident from the onset of this study. Adisproportionate influx of patients already affectedwith the disease was thought to account for theincrease in prevalence from 46 to 86 per 100 000between 1905 and 1964. The studies from Orkney andShetland,34 covering a period of 20 years, showed arelatively constant incidence rate but a marked rise inprevalence rate from 110 to 309/100 000 between 1954and 1974 in the Orkney Isles. These rates appearslightly less dramatic when one considers that thepopulation at risk was about 20 000. The actualincrease in numbers was from 23 in 1954 to 54 in 1974.The increased prevalence despite a relatively stableincidence was thought to be due in part at least toincreased survival. A more complete ascertainmentand differential emigration of unaffected people wereconsidered as possible contributing factors. Theauthors noted a slight drop-off of incidence rate in thelater years and considered that this was because ofincomplete ascertainment of undiagnosed casesaccentuated by the fact that they did not includepossible cases in their calculations. In studies fromIceland,22 where the population at the time ofthe mostrecent survey (1974) was over 200 000, incidence andprevalence rates were estimated for the period 1904-74. It is doubtful whether much reliance can be placedon the very early figures, but the later studies suggested

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Epidemiology of multiple sclerosis in the north-east (Grampian Region) of Scotland-an updatean abrupt rise in incidence in the post war period1945-54, the rates doubling from 1 6 for 1923-24 to3-2 in the next decade but falling again thereafter.Prevalence rates increased steadily from 10 per 100 000in 1924 to 53 in 1954 and 'essentially stabilisedthereafter'. It was considered that the data suggestedan epidemic ofMS in the post war years similar to thatdescribed in the Faroes.32Our data, although they cover a relatively short

period of 20 years, do show an upward trend inincidence but more importantly a continuing highincidence, about twice the highest rate recorded inIceland at the height of the 'epidemic'. Incidence ratesin the Orkney and Shetland study varied from year toyear from 3 to 12 per 100 000. While this related onlyto probable cases and might seem more reliable, itmust be remembered that one single extra patientdeveloping the disease in any one year increases theincidence rate per 100 000 in such a small populationby about 5. In terms of actual cases in the Orkneys orShetland Isles, the variation in one island from oneyear to another was from nil to four new casesrecorded. In Grampian Region our incidence figure ofaround 7 per 100 000 represents the identification ofapproximately 33 cases of probable or possible newcases per year.

INFECTIONSPrevious epidemiological data on the age ofacquisition ofmeasles suggest that it occurs at a muchearlier age (usually under 5 years) in communities nearthe equator with low MS frequency, compared to onesin northerly regions with higher MS frequency." Atleast in three different studies35-37 an older age ofacquisition of measles has been reported in MSpatients compared to controls, although in none ofthem did the difference reach a highly significantstatistical level. In the present investigaton also anolder age of acquisition of measles was noted amongtheMS patients compared to the general population ofthe region between 1911 and 1973 (table 4). Anotherobservation of interest is that in fatal cases due tomeasles the incidence of central nervous systemcomplications was directly linked to age ofoccurrence,38-39 suggesting an age dependentneurotropism.Our figures show that not only measles but other

viral infections, such as chicken pox, mumps, andrubella, also occur in a high proportion ofMS patientsat an older age, although due to lack ofcontrol figures,firm conclusions about these latter infections cannotbe drawn. Age dependent neurotropism has beenshown in a number of viral infections.'"4' It istherefore tempting to speculate that MS may be theresult of host determined response to measles or

perhaps more than one viral infection acquired at alater age than average.

Herpes zoster was reported by 14-3% of patients(table 4), the majority having had it after the age of 10years. We do not have figures from a controlpopulation in our region, but, using control figuresfrom the study of Lenman and Peters,42 whosepatients came from a geographically adjacent areaonly 70 miles or so away from our region, asignificantly higher incidence ofherpes zoster was alsonoted in our patients (p< 0 02). Their control sampleconsisted of unselected patients attending a neurologyclinic for diseases other than MS. It may be that thedisturbed cell mediated immunity in MS patientsallowed the varicella zoster virus to reactivate. Therelation between animal viruses, particularly caninedistemper and MS, has been recently reviewed.43 Mostof the data do not favour an association betweenexposure to dogs and occurrence ofMS. Although ourdata in the absence of a control population are notconclusive, the figure of more than 50% of non-dogowners is against a causal relation.

FAMILY HISTORYThe numbers of patients with a family history of MShas remained fairly constant in the three surveys in thisregion (9-2% in 1970; 9-8% in 1973; 9-3% in thepresent study). The figures from the Grampian regionare only exceeded by the figures of 16-7% fromDenmark44 and 11 -6% from Orkney and Shetland.4s

OCCUPATIONAL HISTORYThe excess of woodworkers, including joiners, andnurses in the 1970 study8 has not been confirmed in thepresent investigation. Although a number ofoccupations has been noted to be commoner in the MSpopulation in the present study, the results had to beinterpreted with caution, as a bias had been introducedin the controls due to selection of certain occupationsfor the purposes of statistical analysis, necessitated byvery small numbers in many occupations. The excessof clerical staff, however, was highly significant, afinding also noted in 1970,15 although the overallexcess of females in the entire MS group might havebeen responsible for this. A review of the literature inrelation to this subject reveals diverse results, makingit unlikely for MS to be an occupationally linkeddisease.

URBAN/RURAL DISTRIBUTIONConflicting data exist as well about urban versus ruraldistribution of MS patients. Studies from Sweden,46Norway,47 Denmark,48 and Lower Franconia49 showan excess in the rural population, while a strongsupport in favour of urban excess comes from the USVeterans Study50 and from Israel.5' Studies in this

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12region on this occasion (table 3) showed an urbanexcess, but earlier studies'5 in which comparison couldbe made of individual areas within the city showedvariable results, possibly related to varyingproportions ofdifferent social classes in different partsof the city. The area of highest prevalence in 1970 and1973 was in a rural area. Reports fromNorthumberland and Durham,'4 Switzerland,'9Iceland,2' and South Africa52 and a reappraisal offigures from West Australia53 show no significantdifference between urban and rural distribution. Ittherefore seems that no clear pattern exists in theurban versus rural distribution of MS throughout theworld.

SOCIAL CLASSMiller, Ridley, and Schapira54 first drew attention tothe increased frequency of MS in the RegistrarGeneral's social classes I and II compared to classes IVand V. Since then at least three studies,8 14 50 includingone in this region, have also shown an excess inprofessional workers (social classes I and II). The datafrom the present study confirm this. No obviousreason for an excess in social classes I and II, however,is apparent.

MORTALITYMean annual MS mortality in the region has remainedfairly stable in the last decade (table 5). Since theformation of Grampian Region, the RegistrarGeneral's office has been kind enough to send us theannual mortality computer printouts, which are basedon death certification for MS where this appears as theprimary or as an associated cause of death. Table 5shows, however, that 40% of the deaths in this serieswere not obtained from this source and highlights thevalue of flagging cases with the General RegisterOffice in Edinburgh so that notice of death can beobtained even when multiple sclerosis is notmentioned in the death certificate. The mean durationof the disease in the 213 patients who died due to thedisease was 24 5 years (males 23-5 years; females 25-7years) and the M:F ratio was 1:1 57.

ConclusionThe prevalence of MS in the Grampian Region(north-east) of Scotland has increased, due in part tosome increase in the actual incidence of the disease.The familial incidence over a longitudinal period hasnot increased. Further studies about age of childhoodviral infections, perhaps with a follow-up of a cohortfrom childhood, are required. It seems that exposureto dogs is unlikely to be of any aetiologicalsignificance.

Finally, further careful epidemiological studiesfrom comparable areas of England and Wales are

Jayant G Phadke and Allan W Downieurgently needed to show if the apparent highprevalence in the north-east of Scotland representsmore than the fact that the region, for various reasons,has allowed a more complete ascertainment than hasbeen possible elsewhere in the UK, with the exceptionof the Orkney and Shetland Isles.

Financial support for the study was given by theScottish Hospital Endowment Research Trust.

Address for reprints and correspondence: J G Phadke,consultant neurologist, (X976) Riyadh MilitaryHospital, PO Box 7897, Riyadh 11159, Kingdom ofSaudi Arabia.

References

' Shepherd DI, Downie AW. Prevalence of multiple sclerosisin North East of Scotland. Br Med J 1978; 2: 314-6.

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Epidemiology north-east (Grampian Region) of Scotland-an · Epidemiology ofmultiple sclerosis in the north-east (Grampian Region) ofScotland-an update Table 2 Prevalence ofmultiplesclerosis