Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis.

INTRODUCTION: Treatment with disease-modifying therapies (DMT) in patients with clinically isolated syndrome (CIS) represents standard care in multiple sclerosis (MS) patients nowadays. Since a proportion of patients may show no evidence of disease activity (NEDA) after some time of treatment, the question might arise about the risks of stopping DMT. METHODS: We present a cohort of 49 patients who started DMT immediately after CIS and had no evidence of disease activity (NEDA-3) for at least five years before discontinuation of therapy. Thereafter, patients underwent clinical and MRI follow-up for at least five consecutive years. RESULTS: Of 49 patients discontinuing DMT, 53% (n = 26) had NEDA for at least further five years, while 47% (n = 23) showed either a relapse/disease progression (18.4%, n = 9), MRI activity (14.3%, n = 7) or both (14.3%, n = 7). The main predictive factor for sustained NEDA was age at DMT termination. Patients aged > 45 years had a significantly lower risk of disease reactivation (13% vs. 54% in patients aged < 45 years, p < 0.001) after DMT discontinuation. DISCUSSION: In CIS patients with immediate DMT after their first clinical episode, older age at the time of DMT discontinuation is the main predictive factor for sustained NEDA status.

Medication overuse headache in 787 patients admitted for inpatient treatment over a period of 32 years.

BACKGROUND: Definitions of medication overuse headache have changed over time. OBJECTIVE: To evaluate the clinical characteristics of medication overuse headache patients admitted for inpatient withdrawal therapy over a period of 32 years. METHODS: We included all patients with medication overuse headache treated from 1 January 1984 to 31 December 2015. We obtained all data from the medical reports and defined three periods, P1 (1984-1993), P2 (1994-2003), and P3 (2004-2015). The p-value adjusted for multiple comparisons was set to 0.005. RESULTS: Within 32 years, a total of 787 patients accounted for 904 admissions for MOH. From P1 to P3, the proportion of patients with preexisting migraine increased from 44.3% to 53.3% (chi2 = 9.0, p = 0.01) and that with preexisting tension-type headache decreased from 47.9% to 34.6% (chi2 = 9.3, p < 0.01). The median time since onset of headache and medication overuse headache decreased from 20 to 15 years (p < 0.001) and from 3 to 2 years (p < 0.001). The median cumulative number of single doses decreased from 120 to 90 per month (p = 0.002). Overuse of triptans, non-opioid analgesics, and opioids increased, whereas overuse of ergotamines decreased over time (p < 0.001 for all tests). The use of prophylactic medication before admission increased from 8.3% to 29.9% (chi2 = 89.5, p < 0.001). CONCLUSION: This retrospective study in a large number of patients with medication overuse headache admitted for inpatient withdrawal therapy over a period of 32 years shows a trend towards changes in the preexisting headache type, a decrease in the time since onset of headache and medication overuse headache, a decrease in the number of drug doses used per month, changes in the type of drugs overused, and an increase in, but still low rate, of prophylactic medication prior to admission.

Do elevated autoantibodies in patients with multiple sclerosis matter?

OBJECTIVES: The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort. MATERIAL & METHODS: In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels. RESULTS: The 18.8% of the MS cohort showed elevated serum autoantibody levels, but only 10.2% of all MS patients were diagnosed with a further autoimmune disease (AI). Patients with elevated serum autoantibodies (AABS) were not significantly more often diagnosed with a clinical manifest AI as compared to patients with negative autoantibodies (P = 0.338). MS patients with disease duration of more than 10 years showed no significant increase of positive autoantibodies as compared to patients with a more recent disease onset (P = 1). MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease course (P = 0.428). CONCLUSIONS: According to our data, elevated serum autoantibodies do not have the potential to serve as a prognostic tool for disease severity in patients with MS Since MS patients with positive serum AABS did not significantly more often suffer from clinical manifest AIs than MS patients with negative serum AABS, the role of routine testing of serum AABS in MS patients should be critically called into question.

Month-of-birth-effect in multiple sclerosis in Austria.

BACKGROUND: The month-of-birth-effect (MoBE) describes the finding that multiple sclerosis (MS) patients seem to have been born significantly more frequently in spring, with a rise in May, and significantly less often in autumn and winter with the fewest births in November. OBJECTIVES: To analyse if the MoBE can also be found in the Austrian MS population, and if so, whether the pattern is similar to the reported pattern in Canada, United Kingdom, and some Scandinavian countries. METHODS: The data of 7886 MS patients in Austria were compared to all live births in Austria from 1940 to 2010, that is, 7.256545 data entries of the Austrian birth registry and analysed in detail. RESULTS: Patterns observed in our MS cohort were not different from patterns in the general population, even when stratifying for gender. However, the noticeable and partly significant ups and downs over the examined years did not follow the distinct specific pattern with highest birth rates in spring and lowest birth rates in autumn that has been described previously for countries above the 49th latitude. CONCLUSION: After correcting for month-of-birth patterns in the general Austrian population, there is no evidence for the previously described MoBE in Austrian MS patients.

Epidemiology of Multiple Sclerosis in Austria.

BACKGROUND: To assess the incidence rate and prevalence ratio of multiple sclerosis (MS) in Austria. METHODS: Hospital discharge diagnosis and MS-specific immunomodulatory treatment prescriptions from public health insurances, covering 98% of Austrian citizens with health insurance were used to extrapolate incidence and prevalence numbers based on the capture-recapture method. RESULTS: A total of 1,392,629 medication prescriptions and 40,956 hospitalizations were extracted from 2 data sources, leading to a total of 13,205 patients. The incidence rate and prevalence ratio of MS in Austria based on the capture-recapture method were 19.5/100,000 person-years (95% CI 14.3-24.7) and 158.9/100,000 (95% CI 141.2-175.9), respectively. Female to male ratio was 1.6 for incidence and 2.2 for prevalence. CONCLUSIONS: Incidence rates and prevalence ratios of MS in our study are within the upper range of comparable studies across many European countries as well as the United States.

Similar impact of multiple sclerosis and migraine on sexual function in women : Is the multiple sclerosis impact scale questionnaire useful?

BACKGROUND: Sexuality is an integral part of overall health but the impact of neurological diseases on sexual function still receives too little attention. AIM: The aim of this case control study was to compare frequencies and characteristics of sexual dysfunction in women with stable relapsing-remitting multiple sclerosis (MS) and migraine. METHODS: Sexually active women aged 18-50 years were recruited at the MS and headache outpatient clinics of a university hospital and asked to complete questionnaires on sexual function using the multiple sclerosis intimacy and sexuality questionnaire (MSISQ-19) adapted for patients with migraine, depression using the Beck depression inventory (BDI-II) and quality of life using the short form-36 questionnaire (SF-36). RESULTS: At least one symptom of sexual dysfunction was "almost always" or "always" present in 35.7 % of 42 patients with MS and in 22.6 % of 30 patients with migraine (p = 0.3). The MSISQ-19 total score did not differ between the two groups (31.6 ± 10.8 vs. 28.2 ± 11.6, respectively, p = 0.2). Sexual dysfunction was categorized as primary, secondary and tertiary in 66.7 %, 40 % and 33.3 % of MS patients and in 57.1 % (p = 0.7), 71.4 % (p = 0.2) and 71.4 % (p = 0.1) of migraine patients, respectively. Depressive symptoms were more common in women with sexual dysfunction than in those without both in MS (p = 0.001) and migraine (p = 0.006). The SF-36 showed decreasing quality of life with increasing MSISQ-19 sum scores (mental subscale p < 0.001 and physical subscale p = 0.04). CONCLUSIONS: Sexual dysfunction is a major problem both in women with MS and in women with migraine and is strongly associated with comorbid depression and impaired quality of life. Thus, categorizing sexuality as done by MSISQ-19 is limited by its complex biopsychosocial interactions.

Do nocturnal headaches matter? A prospective diary study on subjective sleep parameters in snorers and their bed partners.

BACKGROUND: The objective of this study was to assess the influence of nocturnal headaches (NH) on subjective sleep parameters prospectively in habitual snorers and their bed partners. METHODS: We recruited habitual snorers and their bed partners via newspaper articles. The participants completed a semistructured interview, filled in questionnaires about quality of sleep (PSQI), daytime sleepiness (ESS), depression (SDS) and anxiety (SAS) and they kept a 90-day headache and sleep diary. RESULTS: Seventy-six snorers (25 female) and 41 bed partners (31 female) completed the study recording a total of 6690 and 3497 diary days, respectively. NH were recorded on 222 (3.3%) and 79 (2.2%) days in 32 (42%) snorers and 17 (41%) bed partners, respectively. Snorers with NH showed significantly higher PSQI (5 ± 3 vs. 4 ± 2, p = 0.004), SAS (38 ± 11 vs. 31 ± 10, p = 0.011) and SDS scores (39 ± 12 vs. 34 ± 10, p = 0.048) than snorers without NH. For bed partners with NH we found a significant female predominance (sex ratio f:m = 16:1 vs. 12:12, p = 0.005) and significantly higher SAS scores (38 ± 6 vs. 33 ± 8, p = 0.030) compared with bed partners without NH. The subjective quality of sleep in habitual snorers (p < 0.001) as well as their bed partners (p = 0.017) was negatively influenced by NH, but not total sleep time. DISCUSSION: NH occurred in around 40% of snorers and their bed partners at least once during the 90-day observation period. Our results confirmed a negative impact on the subjective quality of sleep in both groups.

Elevated levels of carbonyl proteins in cerebrospinal fluid of patients with neurodegenerative diseases.

The importance of oxidative stress in the pathogenesis of neuroimmunological and neurodegenerative diseases, such as multiple sclerosis (MS), has been discussed for a long time. However, markers for oxidative stress in cerebrospinal fluid are hardly detected. The aim of the present study is to assess whether carbonyl proteins as end products of metabolic processes may serve as a marker for oxidative stress in the cerebrospinal fluid (CSF) of patients with neuroimmunological and neurodegenerative diseases. Levels of carbonyl proteins in the CSF were assessed in 15 patients suffering from MS, four patients with neurodegenerative diseases, including one patient with dementia complicated by carcinomatous meningitis due to breast cancer, and four control subjects with no established neurological disease. Levels of carbonyl proteins were measured with a commercially available KIT. A significant difference (P = 0.025) was shown for mean values of various subgroups with highest levels for patients with neurodegenerative diseases (756.1 pmol/mg), followed by the MS (630.8 pmol/mg) and the control group (356.5 pmol/mg). Post-hoc pair wise comparisons showed significant differences between the MS group and healthy controls (P = 0.016) as well as for patients with neurodegenerative diseases and healthy controls (P = 0.02). This pilot trial showed that carbonyl proteins might serve as measure for oxidative stress in the CSF of relapsing as well as progressive MS patients and in patients with neurodegenerative diseases. Larger trials have to show whether they may serve as biomarkers and be helpful in monitoring patients with MS or neurodegenerative diseases.

Benefits of inpatient multidisciplinary rehabilitation in multiple sclerosis.

BACKGROUND: Rehabilitation is often recommended to MS-patients but data on its efficacy is limited. OBJECTIVE: To evaluate the benefit of inpatient multidisciplinary rehabilitation. METHODS: A rater-blinded, randomized, waiting list controlled exploratory study. 19 participants completed the study with ten allocated to the intervention and nine to the waiting list group. Assessment of outcome-parameters was done at baseline and after 3 months. Time Walking Tests (TWTs) and 9 Hole Peg Test were used to objectively assess the level of activity, Functional-Assessment-in-MS and MS-Self Efficacy-Scale to assess participation and quality of life and Expanded Disability Status Scale (EDSS) to assess bodily function. Additionally Rivermead Mobility Index, Berg Balance Scale, Tinetti-Test, MS-Functional Composite and a rater-blinded evaluation of a video-analysis on walking performance was done. RESULTS: Mean change scores of Timed 50 meter Walk (p = 0.014), walking speed (p = 0.034), 2- (p = 0.204) and 6-Minute Walk (p = 0.027) indicated an improvement favoring inpatient multidisciplinary rehabilitation. We could not demonstrate a benefit for upper limb function and some improvement was seen in other outcome-parameters without reaching statistical significance. EDSS remained unchanged. CONCLUSION: Inpatient multidisciplinary rehabilitation is effective in MS patients with positive impact on the level of activity as measured by TWTs covering both short and long distance ambulation.

Prospective analysis of factors related to migraine aura--the PAMINA study.

OBJECTIVES: The aim of this study was to examine factors increasing and decreasing the risk of occurrence of migraine aura and of headache and migraine not associated with aura (HoA, MoA) prospectively by means of a daily diary. METHODS: Of 327 patients with migraine completing a comprehensive diary up to 90 days, we selected all patients who recorded at least 1 episode of migraine aura. To find risk indicators and triggers of aura, HoA, and MoA, we analyzed 56 variables and calculated univariate and multivariate generalized linear mixed models. RESULTS: Fifty-four patients recorded a total of 4562 patient days including 354 days with migraine aura. In the multivariate analysis, the risk of aura was statistically significantly increased by smoking, menstruation, and hunger, and it was decreased by holidays and days off. The risk of HoA and/or MoA was increased during menstruation, by psychic tension, tiredness, and odors, and it was decreased by smoking. CONCLUSION: Menstruation is the most prominent factor increasing the risk of aura as well as that of HoA and MoA. Smoking shows the most striking difference increasing the risk of aura, but decreasing the risk of HoA and MoA.