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PubMed1976

Multiple sclerosis and Hodgkin's disease in Denmark.

There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Detweeen 1943-62, the average annual incidence rate for Hoadgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951-69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). The average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128.86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rate for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25-29 and the other at age 70-74; this was found for each sex, with male rates consistently higher than female. The age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25-29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. The geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology.

Adolescent↗
PubMed1980

Multiple sclerosis in North-West India.

Fifty-four patients, with multiple sclerosis from North-West India are described. This included two pathologically proven cases of multiple sclerosis. Five patients conformed to the definition of neuromyelitis optica (Devic's syndrome). This study is in agreement with the other series reported from Asia regarding the special clinical features of multiple sclerosis described from this part of the world. There is more common occurrence of visual impairment at onset, predominant involvement of optic nerves and spinal cord and higher incidence of classical neuromyelitis optica. There is no relationship of any or all cerebro spinal fluid abnormalities with the type of multiple sclerosis, duration of an attack and disability, except for the possible relation between the type of colloidal gold reaction pattern and the type of multiple sclerosis.

Adolescent↗
PubMed1986

Interferon induction, 2'-5' oligo A synthetase and lymphocyte subpopulations in out-patients with multiple sclerosis in a longitudinal study.

Nine patients with multiple sclerosis, four with relapsing-remitting disease, and five with chronic progressive disease, together with eight healthy control, were followed for nearly a year with monthly clinical and laboratory examinations. Alpha- and gamma-interferon was induced in lymphocytes with different viruses and PHA, no differences were found between healthy controls and multiple sclerosis patients. The alpha- and gamma-interferon induced enzyme 2'-5' oligo A synthetase in lymphocytes was found to have a tendency to be lower in multiple sclerosis patients than in healthy controls. When medians of ratios of helper/suppressor blood lymphocytes in multiple sclerosis patients were compared with healthy controls, the same results were found, although higher values of ratios were found among the patients and the highest value was found in a patient with chronic progressive disease. No correlation to disease activity could be found in interferon inductions, 2'-5' oligo A synthetase concentrations and ratios of OKT4/OKT8. In particular no change in ratio was found in relation to five exacerbations taking place in the four multiple sclerosis patients with acute relapses.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Heart rate variability in multiple sclerosis during a stable phase.

OBJECTIVES: Multiple sclerosis (MS) frequently causes disturbances of autonomic functions. Cardiovascular dysautonomia has been studied by classic autonomic tests and, recently, by heart rate variability analysis in some isolated periods. Multiple authors recommended performing heart rate variability analysis with a 24 h ECG recording to increase its sensitivity. MATERIAL AND METHODS: We analyzed the heart rate variability in time and frequency domains in 34 MS patients and 24 age and sex-matched healthy control subjects, in order to evaluate the effects of MS on sympathetic and parasympathetic cardiovascular regulatory functions measured from 24-h electrocardiogram. RESULTS: Low frequency power (0.01) and low frequency/high frequency power (0.01) were significantly higher in multiple sclerosis patients independently, all together or in subgroups. Very low frequency (0.01) and high frequency (0.001) power were higher in less affected multiple sclerosis patients. Variability in time domain (0.05) were lower in most affected multiple sclerosis patients. CONCLUSIONS: These results suggest that multiple sclerosis causes cardiovascular autonomic dysregulation manifesting as impaired heart rate variability. This illness seems to cause an increase in sympathetic cardiovascular tone; the parasympathetic tone is most variable and depends on clinical and paraclinical findings, but the illness progression seems to provoke a decrease in it.

Adult↗
PubMed2003

Multiple sclerosis and glutamate.

Experimental autoimmune encephalomyelitis reproduces in rodents the features of multiple sclerosis, an immune-mediated, disabling disorder of the human nervous system. No adequate therapy is available for multiple sclerosis, despite anti-inflammatory, immunosuppressive, and immunomodulatory measures. Increasingly glutamate is implicated in the pathogenesis of neurodegenerative diseases. Here we (1) review changes in the glutamatergic system in multiple sclerosis and (2) reveal the effects of glutamate AMPA antagonists in acute and chronic rodent models of multiple sclerosis. Administration of structurally diverse competitive and non-competitive AMPA antagonists reduces neurologic disability in rodents subjected to acute experimental autoimmune encephalomyelitis. In addition, AMPA antagonists are active in both the adoptive transfer and in chronic models of experimental autoimmune encephalomyelitis in rats and mice and affect both the acute and chronic relapsing phases. Moreover, short-term therapy with AMPA antagonists leads to sustained benefit well into the progressive phases. These results imply that therapeutic strategies for multiple sclerosis should be complemented by glutamate AMPA antagonists to reduce neurologic disability.

Animals↗
PubMed2006

Apolipoprotein E-derived peptides ameliorate clinical disability and inflammatory infiltrates into the spinal cord in a murine model of multiple sclerosis.

Apolipoprotein E (apoE), well known to play a role in lipid transport and cholesterol metabolism, also exerts anti-inflammatory and neuroprotective effects in the central nervous system. Recent clinical and genetic studies display an association between apoE genotype (APOE) and the progression and severity of multiple sclerosis, raising the possibility that modulation of apoE may be a novel treatment for multiple sclerosis. Using a murine experimental autoimmune encephalomyelitis (EAE) model of human multiple sclerosis, we found that a peptidomimetic of apoE protein, COG133, substantially reduces the clinical symptoms of EAE and promotes remission from the disability when administered before or after onset of disease. Most notably, fusion of COG133 to a protein transduction domain creates COG112, a modified apoE-mimetic peptide with significantly enhanced anti-inflammatory bioactivities in vitro, and improved therapeutic effects on EAE in vivo, which renders a nearly full remission from the disability. Histopathological analysis showed that COG112 and COG133 attenuated demyelination and significantly diminished the number of peripheral cells infiltrating into the spinal cord. ApoE mimetics also interfered with several mechanisms relevant to the pathogenesis of EAE and multiple sclerosis, including activation of macrophages, subsequent production of nitric oxide and inflammatory cytokines, and lymphocyte proliferation. These data suggest that apoE mimetics represent a multidimensional therapeutic for multiple sclerosis capable of inhibiting the inflammatory cascade, modulating immune cell function, and reducing clinical signs, which may have novel utility for the treatment of inflammatory autoimmune diseases.

Amino Acid Sequence↗
PubMed1993

Cardiac rhabdomyomas and their association with tuberous sclerosis.

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.

Echocardiography↗
PubMed1991

Prevalence of multiple sclerosis in five rural Suffolk practices.

OBJECTIVE: To determine a point prevalence of multiple sclerosis in part of Suffolk. DESIGN: Multiple source search for patients with multiple sclerosis in five general practices. Patients were reviewed and categorised by using general practice notes. SETTING: Five rural general practices in Suffolk, 12 May 1988. SUBJECTS: 31,379 patients registered with five practices. MAIN OUTCOME MEASURES: Multiple sclerosis diagnosed by a specialist. RESULTS: The search produced a provisional list of 62 eligible patients with multiple sclerosis. Review of case notes showed that 48 had probable disease, 10 early disease, and four possible disease. The probable cases gave a crude prevalence of 153/100,000 population (95% confidence interval 109/100,000 to 196/100,000). CONCLUSIONS: Although the results should be interpreted cautiously because of the small sample size, they suggest that the prevalence of multiple sclerosis in Suffolk is higher than has been estimated from hospital data.

Age Factors↗
PubMed1995

"Abnormal" illness behaviour in chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome. DESIGN: A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis. SETTING: A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic. SUBJECTS: 98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis. MAIN OUTCOME MEASURE: Responses to the 62 item illness behaviour questionnaire. RESULTS: 90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles. CONCLUSION: Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome.

Adult↗
PubMed1997

Doctors and patients don't agree: cross sectional study of patients' and doctors' perceptions and assessments of disability in multiple sclerosis.

OBJECTIVES: To compare the judgments of clinicians on which domains of health in the short form questionnaire (SF-36) would be most important to patients with multiple sclerosis with the opinions of patients themselves; to compare assessment of physical disability in multiple sclerosis by a clinician using Kurtzke's expanded disability status scale and a non-clinically qualified assistant using the Office of Population Census and Surveys' (OPCS) disability scale with self assessment of disability and other domains of health related quality of life by patients using the SF-36 and the EuroQol questionnaire; and to compare the scores of patients for each domain of the SF-36 with control data matched for age and sex. DESIGN: Cross sectional study. SETTING: Clinical department of neurology, Edinburgh. SUBJECTS: 42 consecutive patients with multiple sclerosis attending a neurology outpatient clinic for review or a neurology ward for rehabilitation. MAIN OUTCOME MEASURES: Scores on the SF-36; EuroQol; Kurtzke's expanded disability status scale; the OPCS disability scale. RESULTS: Patients and clinicians disagreed on which domains of health status were most important (chi 2 = 21, df = 7, P = 0.003). Patients' assessment of their physical disability using the physical functioning domain of the SF-36 was highly correlated with the clinicians' assessment (r = -0.87, P < 0.001) and the non-clinical assessment (r = -0.90, P < 0.001). However, none of the measures of physical disability correlated with overall health related quality of life measured with EuroQol, Quality of life correlated with vitality, general health, and mental health in the SF-36, each of which patients rated as more important than clinicians and for each of which patients scored lower than the controls. CONCLUSIONS: Patients with multiple sclerosis and possibly those with other chronic diseases are less concerned than their clinicians about physical disability in their illness. Clinical trials in multiple sclerosis should assess the effect of treatment on the other elements of health status that patients consider important, which are also affected by the disease process, are more closely related to overall health related quality of life, and may well be adversely affected by side effects of treatment.

Adult↗
PubMed1982

Clinical detection of the hepatic lesion of pericentral sclerosis in chronic alcoholics.

It has been shown that a specific liver lesion--that is, pericentral sclerosis associated with pericellular fibrosis--is the precursor of alcoholic liver sclerosis. It is, however, difficult to diagnose this hepatic lesion in chronic alcoholics, using only clinical data without liver biopsy. To investigate the possibility of a clinical test reflecting the presence of this hepatic lesion, ethanol (0.75 g/kg body weight) was given orally to chronic alcoholics, and serum glycoprotein levels (prealbumin, alpha HS glycoprotein, haptoglobin, alpha 2-macroglobulin) were measured before and six hours after. Chronic alcoholics were divided into three groups according to the histological findings in the liver at the time of study. Group I (alcoholic fatty liver or non-specific change) consisted of seven cases without pericentral sclerosis. Group II (alcoholic hepatic fibrosis or alcoholic hepatitis) consisted of five cases with pericentral sclerosis and pericellular fibrosis. Group III consisted of five cases with alcoholic liver cirrhosis. After the ethanol administration, serum glycoprotein levels decreased significantly in group I (P less than 0.05), whereas they increased in group II and group III. Their alternative ratios (see text) apparently differed (P less than 0.005) between group I and group II, and between group I and group III. These results indicate that the determination of serum glycoprotein levels before and after oral ethanol administration is useful way of discriminating alcoholic patients with hepatic pericentral sclerosis and pericellular fibrosis from alcoholics without such lesions.

Adult↗
PubMed1994

Pelvic floor function in multiple sclerosis.

The aim of this study was to define pelvic floor function in patients with multiple sclerosis and bowel dysfunction, either incontinence (MSI) or defecation difficulties without incontinence (MSC). Normal controls and patients with idiopathic neurogenic faecal incontinence without multiple sclerosis (FI, disease controls) were also studied. Thirty eight multiple sclerosis patients (20 incontinent, 18 incontinent) 73 normal controls, and 91 FI patients were studied. The FI group showed the characteristic combined sensorimotor deficit previously described in these patients of low resting and voluntary contraction and pressures, increased sensory threshold to mucosal stimulation, and increased pudendal nerve terminal motor latencies and fibre densities. MSI patients had significantly lower anal resting pressures (80 (30-140) cm H2O, median (range) v 98 (30-200), normal controls, p = 0.002) and both MSC and MSI patients had significantly lower anal maximum voluntary contraction pressures (65 (0-260) cm H2O, MSC and 25 (0-100), MSI v 120 (30-300), normal controls, p = < 0.0004) and higher external anal sphincter fibre densities (1.7 (1.1-2.6), MSC and 1.7 (1.1-2.4), MSI v 1.5 (1.1-1.75), normal controls, p < 0.006) compared with normal controls but pudendal nerve terminal motor latencies were similar and no sensory deficit was found. This contrasted with the idiopathic faecal incontinent patients who, in addition to significantly higher fibre densities (1.8 (1.1-3), p = 0.001) had increased pudendal latencies (2.5 (1.1-5.5) mS v 2.08 (1.4-2.6), p = 0.001) compared with normal controls. The idiopathic faecal incontinent group had significantly lower resting anal pressures (50 (10-160) cm H2O, p=0.02) than the MSI group. Comparison with the incontinent and continent multiple sclerosis groups showed that incontinence was associated with lower voluntary anal contraction pressures (25 (0-100) v 65 (0-260), p=0.03) but that there were no other differences between these two groups. Pelvic floor function is considerably disturbed in multiple sclerosis, showing muscular weakness with preservation of peripheral motor nerve conduction, providing indirect evidence that this is mainly a result of lesions within the central nervous system.

Adult↗
PubMed1991

On the incidence of fits and mental retardation in tuberous sclerosis.

OBJECTIVES: To establish the frequency of fits and mental retardation in an unbiased group of tuberous sclerosis patients. METHODS: Known tuberous sclerosis families with more than one affected person were ascertained for a genetic linkage study. A number of members were born after genetic counselling had been given after identification of the proband. These subjects were then carefully examined clinically and in many cases with cranial computerised tomography, renal ultrasound, and skeletal survey but not echocardiography. They provide an unbiased group of tuberous sclerosis patients and allow affected patients with normal intellect to be diagnosed. PATIENTS: Thirty-seven tuberous sclerosis families were ascertained and 26 patients born after the family proband were identified. RESULTS: Sixteen of these 26 patients suffered fits (62%) and 10 patients were mentally retarded (38%). CONCLUSIONS: A lower incidence of fits and mental retardation has been found in an unbiased sample of tuberous sclerosis patients. The lifetime risk for fits might be higher had we been able to follow the patients for longer. However, we believe these are more appropriate figures to use in genetic counselling for this disease.

Adolescent↗
PubMed2004

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis.

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Adolescent↗
PubMed2005

Suicide among Danes with multiple sclerosis.

OBJECTIVE: To compare the suicide risk among Danish citizens with multiple sclerosis with that of the general population, and to evaluate changes over 45 years. METHODS: The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry. It comprised all 10,174 persons in whom multiple sclerosis was diagnosed in the period 1953 to 1996. The end of follow up was 1 January 1999. Standardised mortality ratios (SMRs) were calculated for various times after diagnosis and for age and calendar period of diagnosis. RESULTS: In all, 115 persons (63 men, 52 women) had taken their own lives, whereas the expected number of suicides was 54.2 (29.1 men, 25.1 women). Thus the suicide risk among persons with multiple sclerosis was more than twice that of the general population (SMR = 2.12). The increased risk was particularly high during the first year after diagnosis (SMR = 3.15). CONCLUSIONS: The risk of suicide in multiple sclerosis was almost twice as high as expected more than 20 years after diagnosis. The excess suicide risk has not declined since 1953.

Adult↗
PubMed2006

Clinical and MRI features of Japanese patients with multiple sclerosis positive for NMO-IgG.

This study investigates the relation between the serological status of NMO (neuromyelitis optica)-IgG and the clinical and MRI features in Japanese patients with multiple sclerosis. Serum NMO-IgG was tested in 35 Japanese patients diagnosed with multiple sclerosis, including 19 with the optic-spinal form of multiple sclerosis (OSMS), three with the spinal form of multiple sclerosis (SMS), and 13 with the conventional form of multiple sclerosis (CMS), which affects the brain. NMO-IgG was detected in 14 patients, 12 with OSMS and 2 with CMS. In these patients, longitudinally extensive (> 3 vertebral segments) spinal cord lesions (93% v 57%) and permanent, complete blindness (no perception of light) in at least one eye (50% v 0%) were the noticeable features as compared with NMO-IgG-negative OSMS. The two patients having CMS with NMO-IgG had unusual brain lesions, but in other respects had features suggesting OSMS. NMO-IgG was detected in more than half the number of patients with OSMS and in some patients with CMS. This newly discovered serum autoantibody was markedly associated with longitudinally extensive spinal cord lesions and with complete blindness, suggesting severe optic-spinal disease.

Adult↗
PubMed2006

Is the frequency of abnormalities on magnetic resonance imaging in isolated optic neuritis related to the prevalence of multiple sclerosis? A global comparison.

The link between optic neuritis and multiple sclerosis is well established, as is the increased risk of conversion to multiple sclerosis, with lesions seen at presentation on the magnetic resonance imaging (MRI) scan of the brain. One or more asymptomatic lesions were present in 77% of the optic neuritis cohort from London, UK, a higher proportion than that reported in other large cohorts studied elsewhere, where generally lower prevalence rates for multiple sclerosis are also reported. These observations may support the hypothesis that optic neuritis is more likely to be associated with abnormalities on MRI and to be due to multiple sclerosis in geographical regions where multiple sclerosis is more common.

Adolescent↗
PubMed1983

Lymphocyte subpopulations in patients with multiple sclerosis.

Using monoclonal antibodies, peripheral blood helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) lymphocytes were measured in 14 normal controls, 36 patients with multiple sclerosis at different stages of the disease and 15 patients with isolated optic neuritis. Thirty-four of these individuals were studied on two or more occasions at intervals up to 340 days. Patients with multiple sclerosis in relapse had low levels of OKT8 cells (14.07% +/- 3.79) compared with controls (29.42% +/- 4.69) and this abnormality returned to normal within approximately one month of the onset of new symptoms. Further changes occurred with new relapses. Low OKT8 cells were also found in patients with isolated optic neuritis (18.76 +/- 3.71) or progressive multiple sclerosis (19.91% +/- 7.96); the same pattern of recovery was seen in these two groups as in patients with multiple sclerosis in relapse. In 25% patients studied on two or more occasions after an episode of demyelination abnormalities of lymphocyte subpopulations occurred which were not accompanied by new clinical symptoms or signs. Fluctuations of this kind did not occur in controls. The findings have implications for the pathogenesis and management of patients with multiple sclerosis.

Humans↗