ABSTRACT
To date, pharmacological treatment options for progressive supranuclear palsy (PSP), a neurodegenerative tauopathy, are limited. The MAO-B inhibitor rasagiline has shown neuroprotective effects in preclinical models of neurodegeneration. To evaluate the safety, tolerability and therapeutic effect of rasagiline on symptom progression in PSP. In this 1-year randomized, double-blind, placebo-controlled trial, 44 patients fulfilling the NINDS-PSP criteria were randomized to 1 mg/d rasagiline or placebo. The combined primary endpoint included symptom progression as measured by the PSP rating scale (PSP-RS) and the requirement of L-dopa rescue medication. Secondary endpoints included Schwab and England Activities of Daily Living (SEADL), Montgomery-Åsberg Depression Rating Scale, Mini Mental State Examination, Frontal Assessment Battery and posturographic measurements. Of the 44 patients randomized, 26 completed the trial per protocol. Rasagiline was well tolerated, with a slight increase of known side effects (hallucinations, ventricular extrasystoles). No effect on the primary endpoint (p = 0.496) was detected. Symptom progression averaged at 11.2 (rasagiline) and 10.8 (placebo) points per year (ΔPSP-RS). No difference was seen in SEADL, depression, cognitive function, frontal executive function and posturographic measurements. Post hoc analyses of PSP-RS subdomains indicate a potential beneficial effect in the "limb motor" subdomain, whereas performance appeared lower in the "mentation" and "history" subdomains in the treatment group. While rasagiline is well tolerated in PSP, a beneficial effect on overall symptom progression was not detected. Post hoc analyses suggest the implementation of more specific endpoints in future studies.
Subject(s)
Indans/therapeutic use , Monoamine Oxidase Inhibitors/therapeutic use , Supranuclear Palsy, Progressive/drug therapy , Aged , Area Under Curve , Cognition Disorders , Depression/etiology , Disease Progression , Double-Blind Method , Electrocardiography , Executive Function/drug effects , Female , Follow-Up Studies , Humans , Male , Mental Status Schedule , Middle Aged , Postural Balance/drug effects , Sensation Disorders/drug therapy , Sensation Disorders/etiology , Supranuclear Palsy, Progressive/complicationsABSTRACT
Amyotrophic lateral sclerosis (ALS) is predominantly characterized by a progressive loss of motor function. While autonomic dysfunction has been described in ALS, little is known about the prevalence of lower urinary tract symptoms (LUTS) and intestinal dysfunction. We investigated disease severity, LUTS and intestinal dysfunction in 43 patients with ALS attending our outpatient department applying the ALS functional rating scale, the International Consultation on Incontinence Modular Questionnaire, the Urinary Distress Inventory and the Cleveland Clinic Incontinence Score. Results were compared to the German population of a cross-sectional study assessing LUTS in the healthy population, the EPIC study. Results showed that urinary incontinence was increased in patients with ALS aged ≥ 60 years compared to the EPIC cohort (female: 50%/19% (ALS/EPIC), p = 0.026; male: 36%/11% (ALS/EPIC), p = 0.002). No difference was seen at 40-59 years of age. Urge incontinence was the predominant presentation (73% of symptoms). A high symptom burden was stated (ICIQ-SF quality of life subscore 5.5/10). Intake of muscle relaxants and anticholinergics was associated with both urinary incontinence and severity of symptoms. Furthermore, a high prevalence of constipation (46%), but not stool incontinence (9%), was noted. In conclusion, the increased prevalence of urge incontinence and high symptom burden imply that in patients with ALS, LUTS should be increasingly investigated for.
Subject(s)
Amyotrophic Lateral Sclerosis/complications , Intestinal Diseases/epidemiology , Intestinal Diseases/etiology , Urination Disorders/epidemiology , Urination Disorders/etiology , Adult , Aged , Aged, 80 and over , Amyotrophic Lateral Sclerosis/epidemiology , Female , Germany , Humans , Intestinal Diseases/classification , Male , Middle Aged , Prevalence , Retrospective Studies , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
This exploratory study investigated meaning in life (MiL) in patients with progressive supranuclear palsy (PSP). In the "Schedule for Meaning in Life Evaluation" (SMiLE), respondents list individual MiL areas before rating their current satisfaction and importance with them (index of weighting [IoW], index of satisfaction [IoS], and index of weighted satisfaction [IoWS], range 0-100). A total of 38 patients with PSP completed the SMiLE (IoS: 68.6 ± 25.6, IoW: 79.6 ± 12.6, and IoWS: 69.2 ± 26.1). A representative sample of healthy participants (n = 977) scored significantly higher in the IoS (82.8 ± 14.7, P < .001), the IoW (85.6 ± 12.3, P = .006), and the IoWS (83.3 ± 14.8, P < .001). Compared to healthy individuals, patients with PSP were less likely to list health (P = .001) and more likely to list partner (P = .04), leisure (P = .01), home/garden (P = .01), and pleasure (P = .02). Patients with PSP seem to focus on supportive relationships and leisure, while the decreasing health status is becoming less important to them.
