Patient and caregiver outcomes after 6 +/- 1.5-months of rivastigmine therapy for mild-to-moderate Alzheimer's disease: the Belgian FExT study.

OBJECTIVE: Despite response variability, cholinesterase inhibitors are recommended in mild to moderate Alzheimer's disease. Dose titration is common; however randomized controlled trials (RCTs) have mainly investigated fixed-dose regimens. We examined practice patterns and outcomes of 6 +/- 1.5-month rivastigmine therapy. METHODS: Prospective, pharmacoepidemiologic, naturalistic study of 175 evaluable patients with mild to moderate Alzheimer's disease (+ 151 caregivers) from 52 centers in Belgium on 6 +/- 1.5 month (titrated) rivastigmine treatment. MAIN OUTCOME MEASURES: Measured at baseline (enrollment) and follow-up (6 +/- 1.5 months). For patients: Mini-Mental State Exam (MMSE), Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS) scores; treatment response (improvement, maintenance, or decline less than normative slope). For caregivers: hours/week spent caring; Zarit Caregiver Burden Scale (ZCBS), 12-item version of General Health Questionnaire (GHQ-12), Instrumental Activities of Daily Living (IADL) scores. RESULTS: Patients' MMSE and NPI scores (p < 0.001) improved from baseline to follow-up, but not ADL and GDS scores. Treatment response was 89.1% of patients for MMSE (including 60.6% with improvement) and 77.7% for NPI (including 57.1% with improvement). Quadratic curves were fitted for the average daily dose and the MMSE and NPI scores; with a trend towards average daily dose of 6.0 +/- 3.0 mg/day. Caregivers' ZCBS (p = 0.036) and GHQ-12 (p = 0.029) scores improved, but not IADL scores and time spent caring. CONCLUSIONS: Patients' MMSE and ADL scores confirmed the meta-analyses of rivastigmine efficacy trials, while NPI scores exceeded efficacy results. Proportionately more patients responded to (titrated) treatment than in fixed-dose RCTs. Caregivers reported less burden (similar to meta-analysis) and better general health over the study period. Where efficacy and effectiveness results diverge, the benefit is in 'real-world' effectiveness. Large sample, multi-country replications, less sensitive to censoring secondary to missing data and powered to permit advanced modeling, as well as RCTs with adaptive designs to accommodate titration, are needed. The profile of patients most likely to benefit from treatment or most vulnerable to treatment outcome must be studied, as must the impact of physician- and center-related variables on outcomes.

A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis.

BACKGROUND: Impaired mitochondrial phosphorylation potential may play a role in migraine pathogenesis. Metabolic enhancers, such as riboflavin or coenzyme Q, are effective in migraine prophylaxis and quasi-devoid of adverse effects. Thioctic acid (-lipoic acid) is another substance known to enhance energy metabolism in mitochondria and to be beneficial in diabetic neuropathy. OBJECTIVE: After an open pilot study suggesting its therapeutic antimigraine potentials, we embarked therefore in a randomized controlled trial of thioctic acid (Thioctacid) in migraine prophylaxis steered by the Belgian Headache Society. METHODS: Five Belgian centers recruited 54 migraineurs (43 migraine without aura, 11 with aura; mean age 38 +/- 8 years; 7 males). After a 1-month single-blinded run-in period, 44 patients received either placebo (n = 18) or thioctic acid 600 mg p.o./day (n = 26) for 3 months. RESULTS: Statistical analysis was carried out on an intention-to-treat basis. Monthly attack frequency tended to be reduced between run-in and the 3rd month of treatment in the thioctic acid group compared to placebo (P= .06). The proportion of 50% responders was not significantly different between thioctic acid (30.8%) and placebo (27.8%). Within-group analyses showed a significant reduction of attack frequency (P= .005), headache days (P= .009), and headache severity (P= .03) in patients treated with thioctic acid for 3 months, while these outcome measures remained unchanged in the placebo group. No adverse effects were reported. For logistical reasons this trial was interrupted before the planned 80 patients were enrolled. CONCLUSION: Albeit underpowered, this study tends to indicate that thioctic acid may be beneficial in migraine prophylaxis. Before any firm conclusion can be drawn, however, a large multicenter trial is necessary.

A unique episode of REM sleep behavior disorder triggered during surgery for Parkinson's disease.

REM sleep behavior disorder (RBD) is characterized by vigorous movements during REM sleep. Here, the authors report the case of a patient who presented such a disorder immediately after the implantation of the definitive electrode for left subthalamic stimulation. Interestingly, this was and has remained a unique episode in his medical history. It was found that a microlesion in or near the upper part of the pars compacta of the substantia nigra was very likely responsible for this phenomenon.