Multiple Sclerosis Females Research Articles

Preliminary Analysis of Brain Footprints in Multiple Sclerosis Females With Detrusor Sphincter Dyssynergia: A Concurrent Urodynamic and Functional Magnetic Resonance Imaging Study.

PurposeThis study evaluates the grey and white brain matter characteristics in women with multiple sclerosis (MS) and detrusor sphincter dyssynergia (DSD). Grey matter is assessed via the functional connectivity (FC) of brain regions activated during voiding, using functional magnetic resonance imaging (fMRI). Two white matter tracts involved in bladder function, the anterior thalamic radiation (ATR) and superior longitudinal fasciculus (SLF), were evaluated using diffusion tensor imaging.MethodsTwenty-seven women with MS (2 groups: no-DSD [n=23] or DSD [n=4]), and 8 healthy controls (HCs) underwent concurrent urodynamic-fMRI evaluation with 4 cycles of bladder filling and emptying. A FC similarity measure (FC_sim) was calculated for each subject to express the similarity of individual FC at voiding initiation compared to all FC patterns. ATR and SLF tracts were traced and their fractional anisotropy (FA) and mean diffusivity (MD) were recorded.ResultsMean FC_sim values were significantly different among the 3 groups indicating distinct FC patterns; however, no significant difference was found between DSD and no-DSD groups. DSD group showed trends of lower FA and higher MD— indicating loss of coherence—in all tracts compared to HCs, and in the left and right ATR when compared to MS women with neither DSD nor voiding dysfunction (VD), suggesting more damage in these tracts for MS women with DSD.ConclusionsWomen with MS show distinctly different FC patterns compared to HCs. There are trends showing more damage in the ATR in women with MS and DSD compared to those with neither DSD nor VD.

Sex differences in brain atrophy in multiple sclerosis

BackgroundWomen are more susceptible to multiple sclerosis (MS) than men by a ratio of approximately 3:1. However, being male is a risk factor for worse disability progression. Inflammatory genes have been linked to susceptibility, while neurodegeneration underlies disability progression. Thus, there appears to be a differential effect of sex on inflammation versus neurodegeneration. Further, gray matter (GM) atrophy is not uniform across the brain in MS, but instead shows regional variation. Here, we study sex differences in neurodegeneration by comparing regional GM atrophy in a cohort of men and women with MS versus their respective age- and sex-matched healthy controls.MethodsVoxel-based morphometry (VBM), deep GM substructure volumetry, and cortical thinning were used to examine regional GM atrophy.ResultsVBM analysis showed deep GM atrophy in the thalamic area in both men and women with MS, whereas men had additional atrophy in the putamen as well as in localized cortical regions. Volumetry confirmed deep GM loss, while localized cortical thinning confirmed GM loss in the cerebral cortex. Further, MS males exhibited worse performance on the 9-hole peg test (9HPT) than MS females. We observed a strong correlation between thalamic volume and 9HPT performance in MS males, but not in MS females.ConclusionMore regional GM atrophy was observed in men with MS than women with MS, consistent with previous observations that male sex is a risk factor for worse disease progression.

Body Composition In Persons With Multiple Sclerosis Vs. Healthy Controls

Multiple Sclerosis (MS) is an autoimmune disease that attacks the myelin sheath and impedes proper conduction of action potentials through the central nervous system. As a result, persons with MS (PwMS) can experience symptoms of fatigue, muscular weakness, spasticity, and balance or gait issues. Such symptoms may reduce physical activity, negatively affecting body composition and predisposing PwMS to obesity, sarcopenia and osteoporosis. PURPOSE: The aim of the current study was to compare the body composition of PwMS and controls using DXA. METHODS: Six males and 13 females with relapsing-remitting MS and 19 Age/Sex/BMI matched healthy controls were recruited for this study. Extended disability status score (EDSS) in PwMS ranged 0 to 6 (x̄=3.1 ± 2.2). DXA scans were used to assess whole body and limb specific contents of fat, muscle and mineral content. Two-way ANOVAs (Group x Sex) with post hoc comparisons were run to assess differences across group and sex. RESULTS: Compared to male controls, MS males had a reduced whole body % lean mass (%LMWB) (60.9 ± 6.3% vs. 74.0 ± 11.0%, p=0.02), %LMARMS (66.7 ± 8.5 vs. 79.0 ± 8.6%, p=0.03), %LMLEGS (61.8 ± 6.2 vs. 75.2 ± 9.9%, p=0.02), % appendicular lean mass (aLM) (28.1 ± 5.1 vs. 35.3 ± 5.8%, p=0.03), and aLM/BMI (90.0 ± 21.10 vs. 115.8 ± 21.9, p=0.04) Similarly, the % body fat (%BF) was higher in MS males (36.7 ± 7.0%) compared to male controls (23.1 ± 11.7% and p=0.02). No between group differences were found for bone mineral content (p>0.05). When collapsed across sex, group differences disappeared in all measures except android fat mass, which was higher in PwMS (35.0 ± 16.0 kg) than controls (23.8 ± 16.3 kg, p=0.04). Interestingly, the Pearson’s r correlation between BMI and BF% was significant for the MS group (r=0.715, p<0.01) but not for the control group (r=0.347, p=0.15). EDSS scores in PwMS did not significantly correlate with any variables (p>0.05). CONCLUSIONS: Expected sex differences in body composition occurred regardless of group. MS males tended to have lower LM and higher %BF than controls, which was not seen in MS females. Significance in MS males may be explained by differences in sample size (n=6) or sex differences in MS symptom or disease progression. It is furthermore unclear to what extent individual differences in physical activity or medication may influence results.

Are White Matter Tract Integrities Different in Multiple Sclerosis Women With Voiding Dysfunction?

Two white matter tracts (WMTs) are proposed to be involved in bladder function: anterior thalamic radiation and superior longitudinal fasciculus. Multiple sclerosis (MS) patients with voiding dysfunction (VD) may have distinct changes in these 2 WMTs. This study aims to compare the fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging of MS females with and without VD versus healthy controls (HCs). Prospective observational cohorts of 28 female MS patients and 11 HCs were recruited. Multiple sclerosis patients were divided into 2 groups: voiders (patients without VD, n = 14) and VD (patients with VD, n = 14). Diffusion tensor imaging of each subject was obtained, from which FA and MD maps were generated. The mean FA and MD of each WMT on both sides were analyzed using one-way analysis of variance and pairwise comparison with adjusted P values. Overall MS patients had significantly lower mean FA (loss of coherence) and significantly higher mean MD (increased free diffusion) than HCs in both WMTs, indicating more damage. Furthermore, VD showed a trend of loss of integrity in both WMTs when compared with voiders with lower FA and higher MD. There is damage reflected by lower FA and higher MD values in the proposed WMTs involved in bladder function in MS women. Voiding dysfunction in this patient population can be attributed to these damages considering women with VD demonstrated a trend of deterioration in these WMTs compared with women without VD. Future studies with larger sample sizes should be done to further confirm this correlation.

Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

BackgroundInflammatory cytokines contribute to proatherogenic changes in lipid metabolism by reduction of HDL-cholesterol (HDL-C) levels, impairment of its antiinflammatory and antioxidant functions. Therefore, the protective actions of HDL-C can be limited in chronic inflammatory diseases such as multiple sclerosis (MS). The aim of this study was to assess the association between lipoprotein subfractions and inflammatory status in early stages of multiple sclerosis.MethodsPolyacrylamide gel electrophoresis Lipoprint© System was used for lipoprotein profile analysis in 19 newly diagnosed MS patients, and in matched 19 healthy controls. Serum levels of interleukin (IL) 1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, interferon-γ and TNF-α were measured by multiplex bead assay.ResultsConcentrations of the measured cytokines and lipoprotein subclasses were comparable between MS patients and controls. Male, but not female MS patients had significantly higher total HDL-C and small HDL-C subfraction than healthy controls. Large HDL-C negatively correlated with all measured cytokines except IL-17 in MS but not in controls. Intermediate HDL-C subfractions correlated positively with all measured cytokines except G-CSF in MS females but not in MS males or controls.ConclusionOur results of higher HDL-C and mainly its small HDL-C subfraction suggest that male MS patients are at higher risk of atherosclerosis and the subtle dyslipidemia is present in early stages of the disease. The correlations between specific HDL-C subfractions and the inflammatory cytokines demonstrate mutual links between systemic inflammation and lipid metabolism in MS.Trial registrationClinicalTrials.gov, Identifier: NCT 03052595 Registered on Feb 14, 2017.

Pregnancy outcomes amongst multiple sclerosis females with third trimester natalizumab use

BackgroundNatalizumab, a monoclonal antibody directed against alpha-4-integrin, is an efficacious treatment used in Multiple Sclerosis (MS). Use in early pregnancy is safe but information in the third trimester is limited. Ceasing natalizumab is often associated with an increased risk in MS relapse and in some instances natalizumab continuation during pregnancy may be required. However natalizumab crosses the placenta in late pregnancy and has been associated with hematological abnormalities. We present clinical and hematological outcome data of newborns from a series of MS patients who received natalizumab during their second and third pregnancy trimesters. We describe possible methods to mitigate risks to the fetus. MethodsRetrospective chart review of 15 births from mothers receiving natalizumab throughout pregnancy. ResultsThirteen mothers with third-trimester exposure to natalizumab were identified. Median age at conception was 34 years (26–40) and median disease duration was 53.5 months (11–204). The 13 mothers gave birth to 15 newborns (2 mothers each with 2 individual births), median (SD) birth weight was 2778 gs (2100 – 3790). Congenital or laboratory abnormalities were identified in 5 which included anemia (n = 2) and thrombocytopenia (n = 3). ConclusionsComplications following natalizumab administration during the second and third trimester of pregnancy occurred in 33% of newborns. However, did not result in mortality or morbidity. Dose alterations during the third trimester, pre-delivery umbilical cord sampling and IVIG administration may reduce hematological effects on newborns. Prospective studies with larger numbers of patients are required to provide further evidence regarding the safety of Natalizumab use in pregnancy.

Differential Transcription of SOCS5 and SOCS7 in Multiple Sclerosis Patients Treated with Interferon Beta or Glatiramer Acetate.

The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing–remitting phase, treated with IFN-β or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-β (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0–160) than in healthy subjects (0 range, 0–106). The same pattern was observed in MS patients treated with IFN-β (68 pg/mL, range 0–160) compared to patients treated with GA (51 pg/mL, range 0–114), and in MS females (64 pg/mL, range 0–161) compared to healthy females (0, range 0–99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.

Does pregnancy affect women with multiple sclerosis? A prospective study in Western China

Objectives: Pregnancy is considered to be protective for multiple sclerosis (MS) but little is known about Asian MS women. Our study aimed to investigate whether pregnancy affects the course of MS and whether MS affects pregnancy in a Chinese cohort.Methods: We established a database (2009–2016) of 94 females with MS in the Department of Neurology at West China Hospital. From this database, we enrolled females who had been pregnant before or after the clinical onset of MS and consecutively followed up the patients and their offspring for at least one year after delivery. We registered their demographic, clinical and pregnancy-related information, as well as the annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score.Results: We enrolled 55 females with MS and 126 pregnancies. Among them, 14 females had 15 deliveries after MS onset. In these 15 full-term pregnancies after MS onset, the average ARR decreased from 0.46 ± 0.52 in the year before pregnancy to 0.07 ± 0.26 (P = .034) during pregnancy and no drug exposure were observed during pregnancy. The average EDSS score at one year after delivery (1.50 ± 1.72) was higher than that at conception (0.77 ± 1.35; P = .045).Conclusions: The natural history of MS during pregnancy suggests that full-term pregnancy protects MS females from relapse. However, the disability of MS females may develop after delivery.

PLXNA3 Variant rs5945430 is Associated with Severe Clinical Course in Male Multiple Sclerosis Patients.

Multiple sclerosis (MS) exhibits sex bias in disease clinical course as male MS patients develop severe, progressive clinical course with accumulating disability. So far, no factors have been found associating with this sex bias in MS severity. We set out to determine the genetic factor contributing to MS male-specific progressive disease. This is an MS cross-sectional study involving 213 Kuwaiti MS patients recruited at Dasman Diabetes Institute. Exome sequencing was performed on 18 females and 8 male MS patients' genomic DNA. rs5945430 genotyping was performed using Taqman genotyping assay. Estradiol levels were determined by enzyme-linked immunosorbent assay. Exome analysis revealed a missense variant (rs5945430) in Plexin A3 (PLXNA3) gene (Xq28) associated with male-specific MS severity. Genotyping of 187 MS patients for rs5945430 confirmed the association of rs5945430G with increased disease severity in MS males (p=0.013; OR 3.8; 95% CI 1.24-11.7) and disability (p=0.024). Estradiol levels shown to effect PLXNA3 expression were lower in MS males compared to MS females, and they were lower than control rs5945430G males (p=0.057), whereas MS females had similar estradiol levels to healthy females reducing the level of expressed PLXNA3 GG in MS females. PLXNA3 rs5945430G is associated with increased disease severity in MS male patients. Estradiol is a possible protective factor against the expression of rs5945430G in MS females.

Multiple Sclerosis impact on employment and income in New Zealand.

We investigated the demographic, social and clinical characteristics associated with employment status and income for people with multiple sclerosis (MS) in New Zealand (NZ). The NZ National MS Prevalence study included all persons resident in NZ on census day 2006 diagnosed with MS (96.7% coverage). Factors associated with employment and income status among the working age population (25-64years) were identified by linear regression. Over 90% of working age people with MS (n=1727) had a work history, but 54% were not working. Work loss occurred early in the disease course, and at low disability (P<.001). Advancing age, progressive disease, longer disease duration, higher disability levels, partner loss and lower education were associated with work loss (P<.001). Working age people with MS had lower income than the NZ population (P<.0001). Higher qualifications yielded no additional income for MS females and about half the additional income for MS males (P<.0001). MS profoundly reduces employment and income early in the disease course, and at low levels of disability, however, unemployment is not entirely accounted for by clinical, social and demographic factors. These findings suggest social supports should be explored early in the disease course to reduce loss of income and unemployment for people with MS.

Feasibility study for remote assessment of cognitive function in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

Sex differences and subclinical retinal injury in pediatric-onset MS

Objective: To assess retinal ganglion cell (RGC) injury and sex differences in axon loss in pediatric multiple sclerosis (MS). Methods: This is a cross-sectional evaluation of consecutive pediatric MS subjects and controls. Eyes with acute optic neuritis (ON) within 6 months of visit were excluded. Spectral domain optical coherence tomography (OCT) included peripapillary ring and macular scans with post-acquisition segmentation of retinal layers using automated software (Heidelberg v1.8.6.0). Generalized estimating equations (GEEs) measured associations of sex, history of ON, disease duration, and age with OCT outcomes. Results: In all, 53 MS subjects (100 eyes, median disease duration = 1.0 years, interquartile range (IQR) = 0.3, 2.5) were compared to 19 control subjects (38 eyes). Eyes with history of ON showed reduced retinal nerve fiber layer (RNFL: −26.8 µm, 95% confidence interval (CI) = −38.9, −14.8, p < 0.001) and 26% lower ganglion cell layer (GCL) volumes (−0.12 mm3, 95% CI = −0.16, −0.072, p < 0.001) compared to control eyes. Non-ON MS eyes had lower temporal RNFL (−11.9 µm, 95% CI = −18.6, −5.3, p < 0.001) and GCL volumes (−0.036 mm3, 95% CI = −0.06, −0.011, p = 0.004) than control eyes. In MS eyes, males versus females had lower global RNFL (−9.4 µm, 95% CI = −17.4, −1.33, p = 0.022) and in ON eyes had lower temporal quadrant RNFL (−9.6 µm, 95% CI = −15.1, −4.15, p = 0.001). Conclusion: Subclinical retinal injury occurs in pediatric-onset MS patients without a history of ON. As in adult-onset MS, substantial GCL thinning is present in eyes with prior ON. Finally, greater retinal axonal injury occurs in boys compared to girls.

Relevance of endoglin, IL-1α, IL-1β and anti-ovarian antibodies in females with multiple sclerosis

Few studies support the concept of reduced fertility in females with multiple sclerosis (MS). Recently we reported on reduced serum levels of Anti-Müllerian Hormone (AMH) in reproductive-age females with MS, suggestive of reduced ovarian reserve. The cause for this observation is not evident and remains speculative. The aim of the study is to examine possible immunological mechanisms interfering with fertility, as well as ovarian reserve that might affect the reproductive potential in women with MS.ELISA experiments were done to detect anti-ovarian antibodies (AOA), endoglin and interleukin (IL)-1α/-1β in sera of 85 MS females, including 15 women with known low AMH level as a marker of ovarian reserve, compared to 63 healthy controls.Groups did not differ with respect to age, smoking habits, BMI, and use of oral contraceptives. MS females showed significantly increased endoglin values compared to healthy controls. Remarkable, the highest endoglin values were found in subjects with low AMH. AOA were neither detectable in MS patients nor control subjects. IL-1α and IL-1β levels did not differ between groups.Our data established no relevance of IL-1α/-1β or AOA in ovarian insufficiency/dysfunction but suggests the involvement of endoglin in RRMS.

Determinants of Independent Living Optimism among Adults with Multiple Sclerosis

This study investigated the relationship between cognitive, psychological and physical symptoms of multiple sclerosis (MS) and independent living optimism among a sample of 5,082 adults with MS (females = 77.8%; Whites = 96.1%, age range 20 to 91 years). Data on physical, cognitive and psychological function were collected utilising standardised clinical measures including the Multiple Sclerosis Impact Scale-29, Perceived Deficits Questionnaire-5-Item version, and the Independent Living Optimism scale. Multiple regression analysis indicated that specific physical, psychological and cognitive factors contributed to the overall prediction model. The combined variables explained approximately 33% of the variance in independent living optimism. This study enables a specific, item-level understanding of the relationship between MS-related symptoms and independent living optimism, and provides important information for the development of targeted rehabilitation interventions.

Distortion of Birth Distribution in Multiple Sclerosis: Relation to Season, Gender and Residential Province

Introduction. Season of birth may influence risk of multiple sclerosis (MS) in higher geographic latitudes. Aim of the study is to determine if seasonal birth distribution of MS people is associated with risk of the disease in Poland. Material and method . This study included 436 MS patients (M - 171, F - 265) who were born in the years 1918-1995 and died in the year 2007 in Poland. Data on month of birth, gender, diagnosis and place of the last residence were obtained from the Central Statistical Office. Monthly birth distribution in registered MS cohort was compared to month of birth in expected MS people from collected group and from the general population. Analysis was carried out using chi square test and Fisher’s exact test. Results . The greatest number of birth in observed MS cohort was found in April as compared to the number of expected MS group (59 vs. 36.3; p=0.001) or to expected MS assemblage from the general population (59 vs. 40.2; p=0.003). Observed monthly birth distribution was different from the expected monthly birth pattern in MS cohort (p=0.008), but not from the expected distribution in MS assemblage from the general population (p=0.223). April/November birth ratio (59:28) significantly increased; p=0.001. Seasonal birth distribution was significantly different in MS females (p=0.019), but not in MS males (p=0.476). The greater number of provinces was resided by April born than by November born MS patients (p=0.037 for M and p=0.025 for F). Conclusions . Higher MS risk was associated with birth in April. Difference in seasonal birth distribution of MS patients indicates association of spring born women with development of the disease.

Serum levels of estradiol correlate with disability in men with multiple sclerosis (MS) (129.20)

Abstract MS occurs more frequently in women compared to men, however men are thought to deteriorate more rapidly. The underlying reasons for a sex bias in MS may relate to sex hormone effects. To determine whether hormone levels correlate with disease disability, we tested 51 untreated relapsing-remitting MS patients (31F, 20M) and 71 controls (38 F, 33M). Serum was tested for hormones (estrogen, testosterone, progesterone) and disability was assessed by the Multiple Sclerosis Functional Composite (MSFC). Testosterone (T) levels were significantly elevated in women with MS compared to female controls (p = 0.0005). 17-beta-estradiol (E2) levels strongly trended towards lower levels in male MS patients compared to male controls (p = 0.06). E2 was significantly positively correlated with T levels in all subjects except the MS males. In males with MS, E2 levels correlated with the MSFC (p = 0.011). T levels did not correlate with disability in men or women. Thus, E2 levels appear decreased in males with MS, which strongly correlates with greater disease disability. Interestingly, we observed that T levels were significantly increased in MS females and did not correlate with disability. Our findings suggest interference in hormone metabolism in patients with MS, which may contribute to altered clinical responses depending on the sex of the patient. Supported by: NIH, NMSS, and CCF GCRC.

Sex differences in cytokine responses to myelin peptides in multiple sclerosis

Many autoimmune diseases preferentially affect women; however, the underlying mechanisms for the sex differences are poorly understood. We examined sex-dependent differences in the immunologic response to myelin proteins in 22 multiple sclerosis (MS) patients and 22 healthy controls. Using ELISA spot assay (ELISPOT) methodology, interferon (IFN) γ and IL-5 secretions were examined at the single cell level in response to overlapping proteolipid protein (PLP) peptides. As previously reported, we observed an overall disease effect in the IFNγ response, such that MS patients were significantly higher than controls. With respect to PLP-induced IFNγ secretion, both MS and control females responded higher than their corresponding males. Female MS patients demonstrated the highest responses compared to MS males or healthy controls of either sex. Although MS females had high IFNγ responses to PLP, they had no IL-5 responses at all, suggesting strong Th1 skewing. In contrast, MS males had more IL-5 than control males, who lacked IL-5 responses. These IL-5 responses suggested that disease and gender are not independent, but rather interact to influence the cytokine response to myelin. The data suggest a gender bias towards Th1 responses in MS, which may contribute to the female predominance in this disease.

Circulating thyroid and gastric parietal cell autoantibodies in patients with multiple sclerosis

Multiple sclerosis (MS) is associated with complex abnormalities of immunoregulation and a role of autoimmunity in its pathogenesis has been accepted. MS is reportedly associated with several autoimmune diseases, but few studies are available on the prevalence of organ-specific autoantibodies in this condition. The aim of this study was to assess the frequency of anti-thyroglobulin (TgAb), anti-thyroid microsomal (MAb) and gastric parietal cell (PCA) antibodies in 113 patients (63 females, 50 males, age ranging 15-62 years) with MS and in 51 neurological controls. The diagnosis of MS was made according to McDonald and Halliday criteria. TgAb and/or MAb were detected by passive hemagglutination in 19 (16.8%) patients with MS and in 3 (5.9%) of the controls. All positive TgAb and/or MAb were observed in MS females (19/63 = 30.1%), with significantly higher frequency than in female controls (X2 = 5.15, p less than 0.025). The presence of circulating thyroid antibodies was higher in patients with clinically definite or progressive probable MS and in those with long standing disease. In contrast with thyroid antibodies, no difference in the frequency of PCA, as assessed by radioimmunoassay, was observed between MS and controls. These data support a specific association between thyroid autoimmunity and MS. The appearance of thyroid autoimmune phenomena seems to be related to the reliability of the diagnosis of MS and the duration of the disease.

Red cell and hemorheological changes in multiple sclerosis

Blood rheology in multiple sclerosis (MS) was investigated in 15 subjects with varying degrees of locomotor difficulties who were members of the local MS Society. Control data were obtained from blood samples from 25 male and 25 female normal blood donors. Whole blood viscosity was measured and blood filterability was assessed. Six MS females provided blood samples for scanning electron microscopy. Erythrocyte membrane fatty acids and phospholipids were assayed. Whole blood viscosity in MS females was higher than controls at 3 of 4 shear rates (p less than 0.001) but in MS males blood viscosity was higher only at shear rate of 1.0 s-1 (p less than 0.05). MS erythrocyte filtration rates were significantly lower than controls (p less than 0.001). Leucocyte counts in MS were greater than controls both in males (p less than 0.01) and females (p less than 0.001). MS erythrocyte morphology was greatly different from controls (p less than 0.0001) and erythrocyte membranes contained less sphingomyelin than controls (p less than 0.01) but more phosphatidylinositol plus phosphatidylserine (p less than 0.02). We conclude that, because our findings indicate an identifiable and potentially correctable abnormality, it is possible to envisage an inhibition of the progressive nature of MS, with the hope of a better prognosis for patients.