Predicting accidental falls in people with multiple sclerosis -- a longitudinal study.

OBJECTIVE: To investigate accidental falls and near fall incidents in people with multiple sclerosis with respect to clinical variables and the predictive values of four tests. DESIGN: A longitudinal, multi-centred cohort study with prospectively collected falls. PROCEDURES: Self-reported incidents during the three months following a standardized test procedure. SUBJECTS: Seventy-six people with multiple sclerosis and an Expanded Disability Status Scale score between 3.5 and 6.0. MAIN OUTCOME MEASURES: Berg Balance Scale, Timed Up and Go cognitive, Four Square Step Test (FSST) and 12-item Multiple Sclerosis Walking Scale. RESULTS: Forty-eight people (63%) registered 270 falls. Most falls occurred indoors during activities of daily life. We found a correlation of r(s)=0.57 between near falls and falls, and of r(s) = 0.82 between registered and retrospectively recalled falls. Fallers and non-fallers differed significantly regarding Expanded Disability Status Score (odds ratio (OR) 1.99, 95% confidence interval (CI) 1.22; 3.40), spasticity (OR 1.14, CI 1.02; 1.31), proprioception (OR 2.50, CI 1.36; 5.12) and use of walking aids (OR 2.27, CI 1.23; 4.37). Reported use of walking aids both indoors and outdoors increased the odds of falling fivefold while disturbed proprioception increased the odds 2.5-15.6 times depending on severity. The odds of falling were doubled for each degree of increased Expanded Disability Status Score and more than doubled for each degree of increased spasticity. The Berg Balance Scale, use of walking aids and Timed Up and Go cognitive best identified fallers (73-94%) and proprioception, Expanded Disability Status Score, 12-item Multiple Sclerosis Walking Scale and Four Square Step Test best identified non-fallers (75-93%). CONCLUSIONS: In clinical practice, looking at the use of walking aids, investigating proprioception and spasticity, rating Expanded Disability Status Score and using Berg Balance Scale or Timed Up and Go cognitive all contribute when identifying fallers.

A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy.

OBJECTIVE: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. DESIGN: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. SETTING: Two different counties in Sweden, being either study or control setting. SUBJECTS: The study group comprised 37 adults (21 women, 16 men; mean age 50 years), while the control group comprised 39 people (25 women, 14 men; mean age 46 years). INTERVENTIONS: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. MAIN MEASURES: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. RESULTS: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P= 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P= 0.073) when being compared to the study group. CONCLUSIONS: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial.

A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia.

OBJECTIVE: To perform genetic linkage analysis in a family affected with ALS and frontotemporal dementia (FTD). METHODS: The authors performed a genome-wide linkage analysis of a four-generation, 50-member Scandinavian family in which five individuals were diagnosed with ALS and nine with FTD. Linkage calculations assuming autosomal dominant inheritance of a single neurodegenerative disease manifesting as either ALS or FTD with age-dependent penetrance were performed. Further analyses for ALS alone and FTD alone were performed. A parametric logarithm of odds (lod) score of 2.0 or greater was required for further study of a potential locus and crossover (haplotype) analysis. RESULTS: A new ALS-FTD locus was identified between markers D9s1870 and D9s1791 on human chromosome 9p21.3-p13.3. A maximum multipoint lod score of 3.00 was obtained between markers D9s1121 and D9s2154. Crossover analysis indicates this region covers approximately 21.8 cM, or 14Mb. CONCLUSIONS: A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.

Quality of life and impairment in patients with multiple sclerosis.

OBJECTIVES: The aims of this study were to describe the quality of life in patients with multiple sclerosis (MS) given immunological treatment and in those not given immunological treatment and to investigate the relationship between impairment and quality of life. METHODS: Twenty nine patients given immunological treatment were matched with the same number of patients not given such treatment. Matching variables were sex, Kurtzke's Expanded Disability Status Scale (EDSS), years since diagnosis, and age (total n = 58). The patients were interviewed using the self-reported impairment checklist and they answered two questionnaires on quality of life, the 36-Item Short-Form Health Survey (SF-36) and the Subjective Estimation of Quality of Life (SQoL). RESULTS: The self-reported impairment checklist captured a more differentiated picture of the patients' symptoms of MS than the EDSS. Health related quality of life was markedly reduced, while the subjective quality of life was less affected. There was a stronger association between self-reported ratings of impairment and health related quality of life on the SF-36 than between impairment and global ratings of quality of life on the SQoL. Subjective quality of life on the SQoL was not directly dependent on impairment expressed in physical limitations. There were no statistically significant differences between the treated and untreated groups. A non-significant trend towards better health related quality of life was found in favour of the treated group with respect to emotional role, physical role, and social function on the SF-36. CONCLUSIONS: The self-reported impairment checklist and SF-36 proved to be valuable complements to the well established EDSS in describing the diverse symptoms of MS. Measuring both health related quality of life and subjective wellbeing provides valuable knowledge about the consequences of MS.

Mercury intolerance and lymphocyte transformation test with nickel sulfate, palladium chloride, mercuric chloride, and gold sodium thiosulfate.

The peripheral lymphocytes of 10 patients referred to as mercury intolerant and 9 patients referred to as tolerant with regard to presence or absence of psychosomatic symptoms when percutaneously exposed to low patch test doses of mercury were stimulated in vitro with four metal salts. In addition, cells from 7 subjects with no anamnestic mercury intolerance or allergy to metals as well as free from dental alloys were included as controls. Lymphocyte transformation test was done by in vitro challenge with five concentrations of gold sodium thiosulfate, nickel chloride, palladium chloride, and seven concentrations of mercuric chloride. Stimulation with palladium chloride and mercuric chloride showed a difference between the mercury-intolerant and -tolerant patients on one hand and the controls on the other, but there was no difference between the two patient groups. With regard to nickel sulfate, there was a significant dose-dependent stimulation in all the three groups but no difference between the groups could be seen. Gold sodium thiosulfate did not stimulate the lymphocytes at all. Based on these results, we therefore conclude that lymphocyte transformation test performed with the four metal salts cannot be used to further differentiate between mercury-intolerant and -tolerant patients.

Serotonin production in lymphocytes and mercury intolerance.

Patients with suspected illness due to mercury in dental amalgam were classified as tolerant or intolerant depending on their psychosomatic responses following in vivo epicutaneous provocation with low doses (patch test doses) of metallic mercury and phenylmercuric acetate. Ten intolerant patients and nine tolerant patients plus seven healthy amalgam-free and metal non-allergic controls were recruited to the study. Peripheral blood lymphocytes were exposed in vitro to three concentration of mercuric chloride (0.92, 1.83 and 3.68 microM) with and without 10 microg phytohaemagglutinine (PHA)/ml and the release of serotonin into the supernatant was measured. Lymphocytes exposed only to HgCl(2) showed no significant dose-dependent increase of serotonin, but the response of the tolerant patients was significantly higher compared with the controls. No other differences were found. Co-culture with mercuric chloride and PHA showed a statistically significant dose-dependant release of serotonin, but no differences between the three clinical groups could be detected. Thus, our results could not validate the concept of mercury tolerance and intolerance.

Disability, coping and quality of life in individuals with muscular dystrophy: a prospective study over five years.

PURPOSE: The present study investigates progressive muscular dystrophy over a five year period. The purpose is twofold: to describe changes over time and to investigate relations between disability, coping and quality of life. METHOD: The study group comprised 45 adults (16 men and 29 women), with an average age of 44 years. All were assessed in 1991 and 1996, with the following instruments: the ADL staircase, the Self-report ADL, the Mental Adjustment to Cancer scale, the Sickness Impact Profile and the Psychosocial well-being questionnaire (Kaasa). RESULTS: Increasing disability was accompanied by an increase in dependence on others and a significant deterioration of health-related quality of life and with regard to 'Satisfaction'. The predominant type of coping was 'Fighting spirit', whilst 'Fatalism' showed the greatest decline over time. 'Ambulation' and the ADL staircase correlated with 'Physical index' on the SIP. Correlations between disability, coping and quality of life were moderate. The results can serve as a basis for planning and evaluation of recurring rehabilitation for persons with MD.

Muscular dystrophy in adults: a five-year follow-up.

The aim was to describe the natural history of adults with hereditary muscular dystrophies, including myotonic dystrophy, with respect to muscular function, ventilation and electrocardiogram. In a prospective study, 46 subjects were followed over a period of five years. In 1991 and 1996, their muscle function was assessed according to an observation scheme and their lung vital capacity was measured by spirometer. Electrocardiograms were obtained in 1991, 1993 and 1996. Deterioration of muscular function was seen with regard to both the functional muscle tests and the vital capacity. The proportion of pathological electrocardiograms increased from 38% in 1991 to 54% in 1996 in the 26 patients with myotonic dystrophy without an increase in clinically detected cardiac abnormalities. Timely examinations using standard methods can reveal medically important information on deterioration, which often passes clinically unnoticed because of the insidious progress of the diseases.

In vitro lymphoproliferative assays with HgCl2 cannot identify patients with systemic symptoms attributed to dental amalgam.

Dental amalgam is suspected, by some exposed individuals, to cause various systemic psychological, sensory, and neurological symptoms. Since not all amalgam-bearers experience such reactions, an individual characteristic--for example, a susceptible immune system--might explain these conditions. In vitro lymphocyte proliferation is a valuable tool in the diagnosis of allergy. With HgCl2 as the antigen, however, the test is hampered, because Hg2+ can cause unspecific lymphocyte proliferation, optimal at 1.4 to 9.5 micrograms HgCl2/mL. Recently, the use of suboptimal HgCl2 concentrations (< or = 0.5 microgram/mL) has been suggested to circumvent these problems. The main aim of this study was to investigate whether patients with systemic symptoms alleged to result from the presence of dental amalgam differ from healthy controls, with reference to in vitro lymphoproliferative responses to HgCl2 < or = 0.5 microgram/mL. Three different test protocols--lymphocyte transformation test (LTT) in micro- and macro-cultures, and the memory lymphocyte immunostimulation assay (MELISA)--were used. Other immune parameters--such as a standard patch test for dental materials, the number of T- and B-lymphocytes, monocytes, granulocytes, and NK cells in peripheral blood, allergic symptoms, and predisposition--were also investigated. Twenty-three amalgam patients, 30 healthy blood donors with amalgam, ten healthy subjects without amalgam, and nine patients with oral lichen planus (OLP) adjacent to dental amalgam and a positive patch test to Hg0 were tested. None of the investigated immune parameters revealed any significant differences between amalgam patients and controls. The sensitivity of in vitro lymphocyte proliferation ranged from 33 to 67%, with the OLP patients as a positive control group, and the specificity from 0 to 70% for healthy controls with a negative patch test to Hg0. Thus, despite the use of HgCl2 < or = 0.5 microgram/mL, a high frequency of positive results was obtained among healthy subjects with or without dental amalgam. Consequently, in vitro lymphocyte proliferation with HgCl2 cannot be used as an objective marker for mercury allergy in dental amalgam-bearers.

Autosomal dominant myopathy with proximal weakness and early respiratory muscle involvement maps to chromosome 2q.

Two Swedish families with autosomal dominant myopathy, who also had proximal weakness, early respiratory failure, and characteristic cytoplasmic bodies in the affected muscle biopsies, were screened for linkage by means of the human genome screening set (Cooperative Human Linkage Center Human Screening Set/Weber version 6). Most chromosome regions were completely excluded by linkage analysis (LOD score <-2). Linkage to the chromosomal region 2q24-q31 was established. A maximum combined two-point LOD score of 4.87 at a recombination fraction of 0 was obtained with marker D2S1245. Haplotype analysis indicated that the gene responsible for the disease is likely to be located in the 17-cM region between markers D2S2384 and D2S364. The affected individuals from these two families share an identical haplotype, which suggests a common origin.

The diagnosis of carpal tunnel syndrome. Sensitivity and specificity of some clinical and electrophysiological tests.

The study group consisted of 100 persons referred with suspected carpal tunnel syndrome. Clinical and neurophysiological examinations were performed blinded from each other. The gold standard for the carpal tunnel syndrome (CTS) diagnosis was based on the results of these examinations but relief of CTS symptoms after surgery was also required. The sensitivity and specificity for the combined results of the clinical examinations were 94% and 80% respectively, and for the neurophysiological examinations, 85% and 87%. Of the neurophysiological methods used, the quotient of sensory nerve conduction velocity between palm to wrist and wrist to elbow was best and the cut-off for this test was studied by means of an ROC-curve. According to our results clinical examination by an experienced doctor seems to be sufficient if there are typical symptoms of carpal tunnel syndrome, but if there is a history of pain, atypical symptoms or earlier fractures in the arm, wrist or hand, it is important to add a neurophysiological examination.

Disability and quality of life in individuals with muscular dystrophy.

In the county of Orebro, Sweden, 32 individuals with myotonic disorders and 25 with other types of muscular dystrophy were examined. Disability was assessed with functional tests and standardized observations of muscle function (mainly based on those proposed by Dr. Brooke), a new self-administered questionnaire regarding the Activities of Daily Living (ADL) and the ADL staircase (based on Katz ADL index). The results of the different tests of disability were highly correlated. The Sickness Impact Profile and the Kaasa test were used for assessing the quality of life, and no significant differences were found between the groups of muscular dystrophy. In an explanatory factor analysis three main factors of disability were found. The factors "walk and move" and "finger function" were fair to good associated with the quality of life. This study offers an approach for research on the consequences of muscular dystrophy using established as well as new methods.

An epidemic-like cluster of motor neuron disease in a Swedish county during the period 1973-1984.

We have tried to find all cases of motor neuron disease (MND) with onset during the study period 1961-1990 in the county of Skaraborg, Sweden, and in this retrospective study we have identified 168 cases, 107 men and 61 women. Fifty percent of them were alive 2 years after onset. The number of MND cases in consecutive 5-year intervals during the study period was shown to be statistically significantly elevated for males in the period 1981-1985 (Knox test disjoint procedure, p = 0.02). During the period 1973-1984, 70 males had onset of MND, corresponding to an average annual incidence of 4 per 100,000 person-years. This epidemic-like cluster was compared to the MND morbidity in a neighbouring county and was shown to be statistically significantly elevated even when the p value was adjusted for multiple comparisons. Agricultural work was significantly more common among the cases compared to the rest of the population.

Rising mortality from motor neurone disease in Sweden 1961-1990: the relative role of increased population life expectancy and environmental factors.

Recent studies of mortality from motor neurone disease (MND) in Sweden have demonstrated rising levels of mortality from the disease, especially amongst older age groups. Case-control investigations have suggested that certain environmental factors are significantly related to variations in mortality from the disease, and are associated with a probable individual susceptibility to MND. This study applies an innovative epidemiological technique to longitudinal and cohort analysis of Swedish mortality from MND during the period 1961 to 1990. Survival modelling shows that a subpopulation susceptible to MND exists in Sweden, as has been demonstrated in other countries. The increased life expectancy of the Swedish population since 1961 has resulted in more of that susceptible population living to the ages at which MND is expressed, explaining the majority of the increase in mortality from the disease. However, environmental factors may play a role in accelerating the course of MND and may affect the timing of death within the susceptible sub-population.

Motor neuron disease and exposure to chemicals--aetiological suggestions from a case-control study.

A recent case-control study indicates that some males are genetically predisposed to develop motor neuron disease if they are exposed to chemicals, particularly solvents. Markers for such a predisposition are hereditary for a neurodegenerative disease and/or a thyroid disease. The reason for this susceptibility might be pharmacogenetic polymorphism, which causes deficient detoxification entailing oxidative stress and cell death.

Respiratory function, electrocardiography and quality of life in individuals with muscular dystrophy.

All individuals in a Swedish county afflicted with any type of hereditary muscular dystrophy (MD) were identified and 57 (85 percent) of eligible individuals in the age range 16 to 64 were included in the study. Respiratory disturbances were estimated by means of spirometry and analysis of arterial blood gases, and 58 percent yielded abnormal results on at least one of these examinations. Elevated PCO2 was found more commonly than reduced forced vital capacity (FVC) and there was a moderate association between these parameters. Respiratory symptoms, most commonly breathlessness, were encountered in 79 percent. Pathologic ECG recordings were found in 21 individuals (37 percent). Conduction disturbances and affection of the myocard were most frequent in myotonic dystrophy. Quality of life was assessed by means of the Sickness Impact Profile instrument and the Kaasa test. The results showed that quality of life was significantly related to FVC and to the symptom of abnormal fatigue. Respiratory and cardiac parameters showed a greater number of significant correlations with measures of functional ability than with subjective well-being.

Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a Swedish county.

The epidemiology of neuromuscular diseases was studied in the county of Orebro, Sweden (study population 270,000). Several different sources of data were utilized, compared and validated. On the prevalence of day (January 1, 1988) 474 patients were identified. The rate per 100,000 population was 92 for the postpolio sequelae (PPS) and 84 for the other neuromuscular diseases (motor neuron disease 9, hereditary neuropathies 9, myoneural disorders 16, myotonic disorders 19, muscular dystrophies 20 and myositis 11). Of the patients with the PPS, 80% reported late-onset symptoms. On the basis of an expanded survey including all medical records in one health care district, the prevalence of the PPS was estimated to be 186/100,000 population.

A case-control study of motor neurone disease: its relation to heritability, and occupational exposures, particularly to solvents.

Motor neurone disease (MND) was studied in relation to various determinants in a case-control study covering nine counties in southern Sweden. A questionnaire about occupational exposures, medical history, lifestyle factors etc was given to all cases in the age range 45-79 and to a random sample of 500 population controls in the same age range. The questionnaires were answered by 92 cases and 372 controls, a response rate of 85% and 75% respectively. Among men high Mantel-Haenszel odds ratios (MHORs) were obtained for electricity work (MHOR = 6.7, 95% confidence interval (95% CI) 1.0-32.1), welding (MHOR = 3.7, 95% CI 1.1-13.0), and impregnating agents (MHOR = 3.5, 95% CI 0.9-13.1). Heritability with regard to a neurodegenerative disease or thyroid disease seemed to predispose to a risk of developing MND (OR = 2.1, 95% CI 1.0-4.3). The highest OR was found for the combination of such heritability, exposure to solvents, and male sex (OR = 15.6, 95% CI 2.8-87.0), a combination that occurred for seven cases and three controls. Hereditary factors and external exposures had a different distribution among cases with the spinal type of MND than among cases with involvement of the pyramidal tract or bulbar paresis also.

Motor neuron disease and dementia reported among 13 members of a single family.

All 49 members of four generations of a family were identified. In the first three generations eight members were afflicted with dementia, whereas in the fourth generation only one was demented but three of four were afflicted with motor neuron disease and they also had slight cognitive deficiencies. The pattern of heredity is compatible with dominant autosomal inheritance. Neuropsychological testing revealed affection mostly of the frontal lobes. A pedigree and six case reports are presented.