The occurrence of multiple sclerosis in the Hutterites of North America.

OBJECTIVE: To report the occurrence, clinical characteristics and genealogical analysis of multiple sclerosis in the Hutterites of North-Western United States and Western Canada. BACKGROUND: The incidence of multiple sclerosis is reported to be lower or rare in certain ethnic groups and genetic isolates and was previously observed to be absent in the Hutterite population. METHODS: After long-term surveillance, six patients were identified and clinical examinations and laboratory investigations including VER and MRI were completed. RESULTS: The six cases included two brothers, two first cousins, male and female, another male and female, all representing two of the three endogamous groups of Hutterites, are linked to two common ancestors through lines of descent dating to 1723. The individual pedigrees were analyzed from extensive genealogical records covering eight generations. CONCLUSION: The incidence of multiple sclerosis in Hutterites is low in a high risk area of North America. A specific mode of inheritance pattern has not been established and a common founder effect may play a role in the development of multiple sclerosis. The genetic contribution of the Hutterites seems greater than previously recognized.

A prevalence study of multiple sclerosis in the Crowsnest Pass region of southern Alberta.

Reports of a high prevalence rate for multiple sclerosis in Southern Alberta led to an epidemiologic study of this disease in the Crowsnest Pass and Cardston regions. In Cardston, the prevalence rate for multiple sclerosis was 88 per 100,000. In the Crowsnest Pass, the prevalence rate was 217 per 100,000. Previous epidemiologic studies of the prevalence rate of multiple sclerosis in Western Canada have shown rates between 93 and 111 per 100,000. Two prevalence studies of multiple sclerosis in Barrhead County, Alberta and Westlock County, Alberta show prevalence rates of 196 and 201 per 100,000. The prevalence rate in the Crowsnest Pass is comparable to the prevalence in Barrhead County and Westlock County, Alberta. However, there is no statistically significant difference between prevalence rates in the Cardston and Crowsnest Pass regions and our overall feeling is that the results of studies of small populations should be interpreted with caution.

Differences in illness intrusiveness across rheumatoid arthritis, end-stage renal disease, and multiple sclerosis.

Illness intrusiveness derives from illness-induced lifestyle disruptions that interfere with continued involvements in valued activities and interests and is hypothesized to represent a fundamental determinant of the psychosocial impact of chronic conditions. The present investigation compared reported levels of illness intrusiveness across 305 individuals from three chronically ill populations: rheumatoid arthritis (N = 110), end-stage renal disease (N = 101), and multiple sclerosis (N = 94). Although multiple sclerosis was significantly more intrusive, overall, into lifestyles, activities, and interests as compared with rheumatoid arthritis and end-stage renal disease (which did not differ), a significant illness group x life domain interaction indicated that intrusiveness into eight individual life domains differed significantly across the groups and that the pattern of differences varied as a function of the particular life domain involved. Differences in the constellations of signs, symptoms, and treatment regimens associated with a given condition were hypothesized to account for observed differences in illness intrusiveness.

Restless sleep, illness intrusiveness, and depressive symptoms in three chronic illness conditions: rheumatoid arthritis, end-stage renal disease, and multiple sclerosis.

Restless sleep was compared across 110 out-patients with rheumatoid arthritis (RA), 101 with end-stage renal disease (ESRD), 94 with multiple sclerosis (MS), and an unselected control group of 176 individuals attending their family practitioners (FP). It was also investigated in the three chronic illness groups as a contributor to illness intrusiveness--the extent to which one's illness and/or its treatment interfere with continued involvements in valued activities and interests--a determinant of depression and emotional distress in chronic conditions. Reported frequencies of restless sleep were highest in RA, lower in ESRD, and lowest in MS; FP patients reported frequencies that were similar, overall, to those observed in MS. These differences were evident among nondepressed, (chi 2 9, N = 309, p < 0.0001), but not depressed, individuals. The occurrence of restless sleep correlated significantly with increased illness intrusiveness, r (279) = 0.31, p < 0.001, in RA, ESRD, and MS. Results supported the hypothesis that the relation between restless sleep and emotional distress is mediated by illness intrusiveness. Treatment of restless sleep may offer the added benefit of diminishing illness intrusiveness and may, thereby, enhance quality of life in chronic physical illness.

Visual accommodation and sustained visual resolution in multiple sclerosis.

Many multiple sclerosis (MS) patients frequently experience transient blurring. We investigated the possibility that this symptom is due to the inability of patients to sustain an accommodative response to stimuli viewed at distances nearer than or farther from the individual tonus position of accommodation. In a group of MS patients and age-matched healthy control subjects, we measured (1) accommodative range and tonus position; (2) reaction time (RT) to detect a change in a small optotype (viewed in a Badal lens system) as a function of viewing distance; and (3) contrast sensitivity at a fixed viewing distance. MS patients did not differ significantly from healthy controls on near point, far point, pupil size, accommodative range, or tonus position measures. However, as a group, MS patients showed significantly slower RTs than controls to detect optotype changes for stimuli viewed at distances nearer to or farther from the individual tonus position of accommodation. All subjects showed significantly slower RTs to detect changes in optotypes viewed at extreme near and far optical distances compared to RTs to detect changes in stimuli viewed at the tonus position. This difference was significantly larger for MS patients than for controls. These data also suggest that dynamic dioptric factors contribute to the magnitude of contrast sensitivity deficits in this patient population and indicate that the relationship between the individual tonus accommodation position and viewing distance is an important variable in CS testing.

Multiple sclerosis: the impact of MR imaging.

MR imaging has had a significant impact on the understanding of multiple sclerosis. The procedure now plays an important role in initial diagnostic workup, replacing some other radiologic and paraclinical tests and often confirming clinically suggested locations of lesions. It also has contributed greatly to the understanding of the natural history of this disease, allowing objective assessment of disease load, detection of asymptomatic lesions, and differentiation between acute and chronic lesions. MR imaging is highly sensitive to inflammation and demyelination caused by multiple sclerosis, and although there is a long differential diagnosis for some of the MR findings, increasing experience has defined a number of relatively specific criteria for multiple sclerosis. Recent advances may allow faster imaging and highly objective lesion quantification, which will aid in therapeutic trials.

Response of non-migrainous headaches to chlorpromazine.

Chlorpromazine, given intravenously, is a useful agent in the treatment of acute migraine headaches. Patients with more serious conditions, however, may also respond to this medication. In this paper we report two patients who were initially diagnosed as having migraine headaches and treated with chlorpromazine. Both experienced temporary pain relief and it was only after repeated presentations to the emergency department that their conditions--a subarachnoid hemorrhage and a subdural hematoma--were accurately diagnosed. Because of this, caution must be exercised before re-treating within a short period of time, a patient with recurrent headache. Strong consideration must be given to an alternate diagnosis and such a diagnosis should be actively sought should there be any suspicion of a non-migrainous cause for headache. It is only by doing so that we may avoid missing more serious and life-threatening conditions such as those with which our patients presented.

An analysis of the frequency of Sjogren's syndrome in a population of multiple sclerosis patients.

We have studied 42 unselected patients with a clinical diagnosis of multiple sclerosis (MS) for clinical and laboratory features of Sjogren's syndrome (SS). The MS patients in this study had similar demographic/epidemiologic features as those previously reported in the literature. The most striking features of the MS patients suggesting a SS diathesis was the presence of dry eyes (xeropthalmia) in six (14%). Although 2/6 of the symptomatic patients and 6/36 of the asymptomatic patients had abnormal tear production (Schirmer's test) this was accounted for by the concomitant use of anti-cholinergic medication. None of the MS patients had autoantibodies (SS-A/Ro, SS-B/La, rheumatoid factor) thought to be characteristic of SS. We conclude that SS, either in isolation or occurring in combination with MS, is uncommon in an MS outpatient setting.

gamma-Aminobutyric acid (GABA) and sepsis-related encephalopathy.

In order to determine whether disturbances in GABA homeostasis might play a role in the pathogenesis of sepsis-related encephalopathy, serum and brain tissue GABA concentrations from six areas of the brain (cortex, diencephalon, striatum, hippocampus, midbrain, and pons-medulla) were determined in a rat model of bacterial sepsis (cecal ligation and perforation). The results were compared to those obtained from sham operated control animals. All septic animals demonstrated clinical signs of encephalopathy and had elevated serum GABA levels (0.92 +/- 0.3 uM versus 0.48 +/- 0.15 in controls, p less than 0.01). GABA content in the specific subcompartments of the brain, however, were similar in the two groups. These results indicate that although serum GABA levels are elevated during sepsis, GABA is unlikely to play an important role in the pathogenesis of sepsis-related encephalopathy.

Juvenile dermatomyositis induced by toxoplasmosis.

A 10-year-old girl from southern Alberta, Canada, who had close contact with cats, developed typical features of dermatomyositis. The diagnosis was confirmed by muscle biopsy. A toxoplasmosis titer was 1:16,384 by indirect fluorescent antibody technique, and the IgM response to toxoplasma was positive. Only minimal improvement followed prednisone and azathioprine administration, but she rapidly improved after 4 weeks of treatment for toxoplasmosis with pyrimethamine and sulfadiazine. A year after the onset of dermatomyositis, she showed no weakness or cutaneous lesions, and a repeat muscle biopsy no longer showed inflammation, perifascicular atrophy, or regeneration of myofibers. She remains asymptomatic more than 2 years after discontinuation of all medications. Investigation for immune deficiency disease 1 year after therapy revealed that lymphocytic response to T-cell and B-cell mitogens was normal, as were immunoglobulin and complement levels. She had mild impairment of natural killer cell activity and a positive antinuclear factor. Her rapid improvement on specific therapy and lack of significant long-term immune deficiency is consistent with acute toxoplasmosis infection in an immunologically competent child.

A population-based study of multiple sclerosis in twins.

Results from studies of twin concordance in multiple sclerosis have not conclusively differentiated between environmental and genetic factors that determine susceptibility to the disease. Published studies that have been based on case finding by public appeal have been characterized by difficulties in ascertainment. The data reported here are from a large population-based study of multiple sclerosis in twins, in which ascertainment has been relatively unbiased and the cooperation of patients nearly complete. A total of 5463 patients attending 10 multiple sclerosis clinics across Canada were surveyed. Twenty-seven monozygotic and 43 dizygotic twin pairs were identified, and the diagnosis of multiple sclerosis was verified by examination and laboratory investigation. Seven of 27 monozygotic pairs (25.9 percent) and 1 of 43 dizygotic pairs (2.3 percent) were concordant for multiple sclerosis. The concordance rate for 4582 nontwin siblings of patients at two multiple sclerosis clinics was 1.9 percent, closely paralleling the concordance rate in dizygotic twins. To the extent that the difference in concordance rates between monozygotic and dizygotic twins indicates genetic susceptibility, the results of this study show a major genetic component in susceptibility to multiple sclerosis.

Occlusive cerebrovascular disease in young adults.

This retrospective study documents the experience of two large Canadian teaching hospitals with occlusive cerebrovascular disease in young adults. Chart review disclosed 76 patients aged 15-40 years during a recent six year period. An apparent cause, or significant coincident risk factors were found in 51 patients (67%). The most prevalent recognized causes were atherosclerosis, emboli from cardiac sources or intracranial aneurysms, and complicated migraine. Pregnancies or use of oral contraceptives were apparent coincident risk factors.

PIP: The charts of patients between the ages of 15-40 years admitted to the Foothills or Calgary General Hospitals in Alberta, Canada between January 1, 1976 and December 31, 1981 and discharged with a diagnosis of reversible ischemic neurological deficits (RIND) or transient ischemic attacks (TIA) were reviewed. A basic work-up was done in almost every instance. 76 patients ranging in age from 16 to 40 years were identified -- 30 male and 46 female. 12 patients (16%) had angiographic evidence of atherosclerosis at a site appropriate to their symptoms, and atheroslerosis was therefore assumed to be the cause of the occlusive cerebrovascular event. 11 (14.5%) were believed to have cardiac sources for emboli and 4 (5%) were thought to have emoblized from intracranial aneurysms. 6 (8%) had a stroke or RIND associated with complicated migraine. 12 patients were pregnant or taking oral contraceptives (OCs) at the time of their illness and in 7 (15% of the female group) this was apparently the only significant coincident risk factor. 11 (14.5%) had other causes for their ischemic episodes, and in 25 instances (33%) no cause was identified. 56 patients (73.5%) had a cranial tomography (CT) scan, 55 (72.5%) had cerebral angiography, and 44 (58%) underwent echocardiography. Only 23 (30%) had all 3 tests. Of 12 patients with atherosclerosis, 7 were male and 5 female. These persons tended to be at the upper end of the age range for the study with a mean age of 36 years. Almost all had 1 or more risk factors for atherosclerosis, such as hypertension, diabetes mellitus, hyperlipidemia, obesity, or smoking. 11 patients had an identified cardiac source for an embolous. 55 patients (72.5%) in this series had cerebral angiograms and 4 of these demonstrated intracranial aneurysms. In 7 females with no direct discernible cause for an ischemic event, 6 were using OCs and 1 was pregnant. A variety of other causes were detected in 11 patients. A total of 25 individuals had no cause identified for their illness. Occlusive cerebrovascular disease is not uncommon in young adults. OCs are seldom implicated, and a high yield of identifiable treatable lesions justifies extending conventional screening investigations to include echocardiography and cerebral angiography.

The diagnostic challenge of multiple sclerosis.

Multiple sclerosis is a common cause of many neurological complaints and disabilities among young, adult Canadians. In the absence of a reliable and specific laboratory test for the disease, the diagnosis is established primarily by clinical criteria, which are outlined in this article. Recent advances in immunology, neurophysiology and neuroimaging have provided techniques to improve diagnostic confidence, particularly in early or atypical cases.

Binding of 125I-labelled encephalitogenic basic protein to normal lymphocytes. Inhibition with multiple sclerosis serum.

A sheep lymphocyte 125I-labelled human encephalitogenic basic protein (125I-BP) binding assay was used to study the correlation of 125I-BP binding with the diagnosis and status of multiple sclerosis (MS) patients. MS serum generally caused significant inhibition of binding, and serum from MS patients in remission caused significantly more inhibition than serum from MS patients in relapse. Serum inhibition increased in association with improvement in neurological status in three out of four MS patients studied for more than 10 months.

Radioimmunoassay of CSF for encephalitogenic basic protein: a diagnostic test for MS?

Competitive inhibition of binding between radioiodine-labelled encephalitogenic basic protein from human myelin ((125)I-HEProt) and normal human alpha-2 macroglobulin and between (125)I-HEProt and rabbit antiHEProt serum was used to study concentrated cerebrospinal fluid (CSF) under "blind" control for cross-reactivity with HEProt. Samples of CSF from patients meeting the standard criteria for definite MS and possible MS, and from patients with optic neuritis and "other" diagnoses were studied. CSF from patients in all four groups was shown to have an inhibitor cross-reactive with HEProt when studied by the (125)I-HEProt/alpha-2 macroglobulin test, but the amount was significantly greater in the definite MS group than in the "other" group. Results of the two tests on CSF from MS patients correlated, suggesting that the tests were identifying the same inhibitor. It was concluded that CSF contains an inhibitor similar to HEProt and that the amount present in CSF could be a useful diagnostic marker of MS.