Fatigue at enrollment predicts EDSS worsening in the New York State Multiple Sclerosis Consortium.

BACKGROUND: Fatigue is one of the most common and distressing symptoms among persons with multiple sclerosis (pwMS). OBJECTIVE: The aim of this study is to evaluate fatigue as a predictor for disease worsening among pwMS. METHODS: In this retrospective cohort study of New York State MS Consortium (NYSMSC) registry, MS patients reporting moderate-to-severe fatigue at study enrollment (n = 2714) were frequency matched to less-fatigued subjects (n = 2714) on age, baseline Kurtzke Expanded Disability Status Scale (EDSS), disease duration, and MS phenotype. Change from baseline patient-reported outcomes (PROs), as measured by LIFEware™, categorized participants into two groups: those with stable/improved outcomes and those who worsened. In a subgroup of patients with longitudinal data (n = 1951), sustained EDSS worsening was analyzed using Cox proportional hazards modeling to explore the effect of fatigue. RESULTS: The median survival time from study enrollment to sustained EDSS worsening was 8.7 years (CI: 7.2-10.1). Participants who reported fatigue at baseline were more likely to experience sustained EDSS worsening during follow-up (HR: 1.4, 95% CI: 1.2-1.7). Patients who were fatigued at baseline were also more likely to report worsening psychosocial limitations (all ps ⩽ 0.01). CONCLUSION: In addition to being a common symptom of MS, severe fatigue was a significant predictor for EDSS worsening in the NYSMSC.

Factors associated with benign multiple sclerosis in the New York State MS Consortium (NYSMSC).

BACKGROUND: This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up. METHODS: Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale ≤2 and disease duration ≥10 years). RESULTS: Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were followed for a median of 4 years to explore effect of disease-modifying treatment (DMT) on benign status. DMT (p = 0.009) and longer disease duration (p = 0.007) were the only significant positive predictors of maintaining BMS at follow-up. The protective effect was stronger for patients taking DMT at both enrollment and follow-up (OR = 0.71; p = 0.006). CONCLUSIONS: There is a need for development of more reliable prognostic indicators of BMS. Use of DMT was significantly associated with maintaining a benign disease state.

Predictive immunophenotypes: disease-related profile in chronic fatigue syndrome.

BACKGROUND: There is a growing body of evidence supporting the theory that problems with immune function play an important role in chronic fatigue syndrome (CFS). METHODS: We studied 90 CFS cases and 50 healthy controls from two different areas of upstate New York to determine whether there were differences in the absolute number and pattern of natural killer (NK) and cytotoxic T-cell phenotypes between CFS cases and healthy controls in the two regions. One group was from a small town where a cluster of cases existed; the other was from a large metropolitan area where there was not a known cluster. RESULTS: The number of CD56+CD3+CD8+ and CD56+CD3+CD8- cells in cases from the two areas were both significantly elevated over that of controls from the metropolitan area (P < 0.03). The number of CD56+CD3-CD8+ and CD56+CD3-CD8- cells was significantly reduced in the two case groups compared to that of controls from the metropolitan area (P = 0.04). However, controls who were from the same town as the cluster cases had numbers of CD56+CD3+CD8+, CD56+CD3+CD8-, and CD56+CD3-CD8- cells that were more like that of cases than controls. Only the number of CD56+CD3-CD8+ cells (an NK cell subset) was significantly different in cases versus controls from the cluster area (P = 0.022). CONCLUSIONS: These data suggest that differences in controls from cluster and noncluster areas may be responsible for some of the inconsistencies in results from other studies. Furthermore, they suggest the possibility that NK cell function may play an important role in preventing the development of CFS in individuals who live in a community where a cluster of cases have been identified.

Cancer mortality following radiotherapy for benign gynecologic disorders.

The purpose of this study is to quantify cancer mortality in relationship to organ-specific radiation dose among women irradiated for benign gynecologic disorders. Included in this study are 12,955 women treated for benign gynecologic disorders at hospitals in the Northeastern U.S. between 1925 and 1965; 9,770 women treated by radiation and 3,186 women treated by other methods. The average age at treatment was 45.9 years (range, 13-88 years), and the average follow-up period was 30.1 years (maximum, 69.9 years). Radiation doses to organs and active bone marrow were reconstructed by medical physicists using original radiotherapy records. The highest doses were received by the uterine cervix (median, 120 Gy) and uterine corpus (median, 34 Gy), followed by the bladder, rectum and colon (median, 1.7-7.2 Gy), with other abdominal organs receiving median doses ≤1 Gy and organs in the chest and head receiving doses <0.1 Gy. Standardized mortality rate ratios relative to the general U.S. population were calculated. Radiation-related risks were estimated in internal analyses using Poisson regression models. Mortality was significantly elevated among irradiated women for cancers of the uterine corpus, ovary, bladder, rectum, colon and brain, as well as for leukemia (exclusive of chronic lymphocytic leukemia) but not for cancer of the cervix, Hodgkin or non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Evidence of a dose-response was seen for cancers of the ovary [excess relative risk (ERR) = 0.31/Gy, P < 0.001], bladder (ERR = 0.21/Gy, P = 0.02) and rectum (ERR = 0.23/Gy, P = 0.05) and suggested for colon (ERR = 0.09/Gy, P = 0.10), but not for cancers of the uterine corpus or brain nor for non-chronic lymphocytic leukemia. Relative risks of mortality due to cancers of the stomach, pancreas, liver and kidney were close to 1.0, with no evidence of dose-response over the range of 0-1.5 Gy. Breast cancer was not significantly associated with dose to the breast or ovary. Mortality due to cancers of heavily irradiated organs remained elevated up to 40 years after irradiation. Significantly elevated radiation-related risk was seen for cancers of organs proximal to the radiation source or fields (bladder, rectum and ovary), as well as for non-chronic lymphocytic leukemia. Our results corroborate those from previous studies that suggest that cells of the uterine cervix and lymphopoietic system are relatively resistant to the carcinogenic effects of radiation. Studies of women irradiated for benign gynecologic disorders, together with studies of women treated with higher doses of radiation for uterine cancers, provide quantitative information on cancer risks associated with a broad range of pelvic radiation exposures.

Glatiramer acetate recovers microscopic tissue damage in patients with multiple sclerosis. A case-control diffusion imaging study.

Traditional magnetic resonance imaging (MRI) techniques have contributed to the management of multiple sclerosis (MS) but are limited in their ability to detect neuronal damage. Advanced MRI metrics provide assessment of microscopic neuronal changes; however, few studies have examined the effects of MS therapies on these measures. This prospective, open-label, observational study evaluated the effect of subcutaneous glatiramer acetate (GA) 20mg/day on the 1- and 2-year changes in diffusion-weighted imaging (DWI) measures in patients with relapsing-remitting (RR) MS and in age- and sex-matched healthy controls (HC). Inclusion criteria were age 18-65, RR disease course, expanded disability status scale (EDSS) score ≤5.5 and disease duration<20 years. MS patients and HC underwent 1.5T MRI scans and clinical examinations at baseline and at 1- and 2-year follow-up. Nineteen RRMS patients and 16 HC completed the 1-year follow-up and 16 MS patients and 13 HC the 2-year follow-up of the study. In MS patients, treatment with GA promoted recovery of DWI mean parenchymal diffusivity (MPD) at year 1 (-7.1%, p=0.007) and at year 2 (-10.1%, p=0.028). The recovery of DWI MPD was significantly higher in MS patients compared to HC at year 1 (p=0.01) and year 2 (p<0.001). GA promoted recovery of DWI entropy at 2 years (-1.2%, p=0.018). No significant DWI MPD and entropy changes were observed in HC over the follow-up. No significant deterioration in magnetization transfer ratio occurred over the follow-up in MS patients and HC. Patients on GA and HC did not develop significant global or regional atrophy over 2 years. GA significantly improved microscopic tissue damage in the brain, as measured by DWI over the 1- and 2-year follow-up.