Short- and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome: a systematic review of randomised controlled trials and network meta-analysis.

BACKGROUND: Beta-interferon (IFN-ß) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. METHODS: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-ß and GA. Main outcomes were time to CDMS, and discontinuation due to adverse events (AE). We compared interventions using random-effect network meta-analyses (NMA). We also reported outcomes from long-term open-label extension (OLE) studies. RESULTS: We identified five primary studies. Four had open-label extensions following double-blind periods comparing outcomes between early vs delayed DMT. Short-term clinical results (double-blind period) showed that all drugs delayed CDMS compared to placebo. Indirect comparisons did not suggest superiority of any one active drug over another. We could not undertake a NMA for discontinuation due to AE. Long-term clinical results (OLE studies) showed that the risk of developing CDMS was consistently reduced across studies after early DMT treatment compared to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of DMTs in reducing the time to, and magnitude of, disability progression. CONCLUSIONS: Meta-analyses confirmed that IFN-ß and GA delay time to CDMS compared to placebo. In the absence of evidence that early DMTs can reduce disability progression, future research is needed to better identify patients most likely to benefit from long-term DMTs.

Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls.

BACKGROUND: The best data on prognosis comes from population-based incident cohorts but few such cohorts exist for Parkinson's disease and atypical parkinsonism. METHODS: The PINE study is a prospective follow-up study of an incident cohort of people with degenerative or vascular parkinsonism and age-sex matched controls. Participants have annual follow-up from diagnosis until death with review of primary/secondary care records and linkage to the UK death register. Data are collected on survival, disability (dependency on others for activities of daily living) and institutionalization. Research criteria are used to guide the clinical diagnosis, which is updated annually. We compared all-cause mortality, disability and institutionalization in patients (subdivided by diagnosis) and controls, adjusted for important confounders. RESULTS: 323 incident parkinsonian patients (199 Parkinson's disease, 124 atypical parkinsonism, mean age at diagnosis 75yrs) and 262 controls (mean age 75yrs) had 1349 and 1334 person-years follow-up respectively (maximum follow-up 10 years). All outcomes were worse in parkinsonian patients than controls, especially in atypical parkinsonism (adjusted mortality hazards ratios Parkinson's disease 2.49, 95%CI 1.72-3.58, atypical parkinsonism, 6.85, 95%CI 4.78-9.81). Median survival times for Parkinson's disease and atypical parkinsonism were 7.8 and 2.7 years respectively but were very age-dependent. At three years the rates of death or dependency were controls 21%, Parkinson's disease 46%, atypical parkinsonism 96% whilst overall institutionalization rates were 5%, 15% and 55% respectively. CONCLUSION: The prognosis of Parkinson's disease and atypical parkinsonism in this unselected incident cohort was significantly worse than previously reported. This has important implications for patient management.

Motor complications in an incident Parkinson's disease cohort.

BACKGROUND AND PURPOSE: Levodopa treatment in Parkinson's disease (PD) causes motor fluctuations and dyskinesias, but few data describe their development or severity in unselected incident cohorts. METHODS: Demographic, clinical, treatment, smoking, caffeine and alcohol data from 183 people with PD were gathered from the Parkinsonism Incidence in Northeast Scotland (PINE) study, a community-based, incident cohort. With Kaplan-Meier survival analysis and Cox regression modelling the development, and severity, of dyskinesias and motor fluctuations and which factors independently influenced their onset were assessed. RESULTS: After a mean follow-up of 59 months, 39 patients (21.3%) developed motor fluctuations and 52 (28.4%) developed dyskinesias. Kaplan-Meier estimates of the probability of motor fluctuations and dyskinesias after 5 years of dopaminergic treatment were 29.2% [95% confidence interval (CI) 21.5%-38.8%] and 37.0% (95% CI 28.5%-47.1%) respectively. 19.8% developed motor fluctuations requiring treatment changes but only 4.0% (95% CI 1.5%-10.4%) developed dyskinesias requiring treatment changes by 5 years. Cumulative levodopa dose [hazard ratio (HR) 1.38 (95% CI 1.19-1.60)], female sex [HR 2.41 (1.19-4.89)] and younger age at diagnosis [HR 1.08 (1.04-1.11)] were independently associated with development of motor fluctuations. Cumulative levodopa dose [HR 1.23 (1.08-1.40)] and female sex [HR 2.51 (1.40-4.51)] were independently associated with dyskinesias. In exploratory analyses, moderate caffeine exposure was associated with fewer motor fluctuations, longer symptom duration with more dyskinesias, and tremor at diagnosis with higher rates of both complications. CONCLUSIONS: In this community-based incident PD cohort, severe dyskinesias were rare. Cumulative levodopa dose was the strongest predictor of both dyskinesias and motor fluctuations.

Pre-hospital notification is associated with improved stroke thrombolysis timing.

Intravenous thrombolysis increases disability-free survival after acute ischaemic stroke in a time-dependent fashion. We aimed to determine whether pre-hospital notification, introduction of a CT scanner near to assessment site and introduction of out-of-hours thrombolysis services affect thrombolysis timing. Methods Timings related to thrombolysis were collected between May 2012 and June 2014 at a single hospital site; these included time to stroke physician assessment, time to cranial CT imaging and door to needle time. All thrombolysed ischaemic stroke patients admitted via the emergency department were included. Ambulance services were asked to pre-notify the emergency department of any suspected stroke patient during this period. Results We studied 182 patients (48% female; mean age 74 years; 59% pre-notified). Pre-hospital notification was associated with a significantly higher rate of CT scanning within 25 minutes (60% vs 24%, odds ratio [OR] 4.7, 95% confidence interval [CI] 2.4-9.0; p<0.001), earlier stroke physician assessment (median 6 vs 32 minutes; p<0.001) and receiving thrombolysis within 60 minutes (89% vs 49%, OR 8.0, 95% CI 3.8-16.9; p<0.001). Being treated outside normal working hours did not alter thrombolysis timing. Logistic regression identified the introduction of a near-site CT scanner (OR 4.6 [95% CI 1.7-12.5]) and pre-hospital notification (OR 4.7, [95% CI 2.3-9.6]) as independent predictors of door to CT time less than or equal to 25 minutes, and pre-hospital notification (OR 11.6, [95% CI 4.9-30.3]) and stroke severity (OR 1.15 per point of NIHSS scale, [95% CI 1.08-1.23]) as predictors of door to thrombolysis time less than or equal to 60 minutes. The most common perceived timing delays were radiology-related (33%), the need to acutely lower blood pressure (15%) and obtaining consent (12%). Conclusion Pre-hospital notification is associated with earlier stroke physician review, CT imaging and delivery of thrombolysis. Referral to an out of hours thrombolysis service was not associated with additional delay.

Statistical analysis, trial design and duration in Alzheimer's disease clinical trials: a review.

BACKGROUND: The social and economic burden of Alzheimer's disease (AD) and its increasing prevalence has led to much work on new treatment strategies and clinical trials. The search for surrogate markers of disease progression continues but traditional parallel group trial designs that use well-established, but often insensitive, clinical outcome measures predominate. METHODS: We performed a systematic search across the Cochrane Library and PubMed abstracts published between January 2004 and August 2009. Information regarding the clinical trial methodology, outcome measures, intervention type and primary statistical analysis techniques was extracted and categorized, according to a standard protocol. RESULTS: We identified 149 papers describing results from clinical trials in AD containing sufficient detail for our purposes. The largest proportion (38%) presented results of trials based on tests of cognition as the primary outcome measure. The primary analysis in most papers (85%) was a univariate significance test of a single primary outcome measure. CONCLUSIONS: The majority of trials reported a comparison of baseline and end-point assessment over relatively short patient follow-up periods, using univariate statistical methods to compare differences between intervention and control groups in the primary analysis. There is considerable scope to introduce newer statistical methods and trial designs in treatment evaluations in AD.

Seizure risk from cavernous or arteriovenous malformations: prospective population-based study.

OBJECTIVES: To determine the risk of epileptic seizures due to a brain arteriovenous malformation (AVM) or cavernous malformation (CM). METHODS: In a prospective population-based study of new diagnoses of AVMs (n = 229) or CMs (n = 139) in adults in Scotland in 1999-2003, we used annual medical records surveillance, general practitioner follow-up, and patient questionnaires to quantify the risk of seizures between clinical presentation and AVM/CM treatment, last follow-up, or death. RESULTS: The 5-year risk of first-ever seizure after presentation was higher for AVMs presenting with intracranial hemorrhage or focal neurologic deficit (ICH/FND: n = 119; 23%, 95% confidence interval [CI] 9%-37%) than for incidental AVMs (n = 40; 8%, 95% CI 0%-20%), CMs presenting with ICH/FND (n = 38; 6%, 95% CI 0%-14%), or incidental CMs (n = 57; 4%, 95% CI 0%-10%). For adults who had never experienced ICH/FND, the 5-year risk of epilepsy after first-ever seizure was higher for CMs (n = 23; 94%, 95% CI 84%-100%) than AVMs (n = 37; 58%, 95% CI 40%-76%; p = 0.02). Among adults who never experienced ICH/FND and presented with or developed epilepsy, there was no difference in the proportions achieving 2-year seizure freedom over 5 years between AVMs (n = 43; 45%, 95% CI 20%-70%) and CMs (n = 35; 47%, 95% CI 27%-67%). CONCLUSIONS: AVM-related ICH confers a significantly higher risk of a first-ever seizure compared to CMs or incidental AVMs. Adults with a CM have a high risk of epilepsy after a first-ever seizure but achieve seizure freedom as frequently as those with epilepsy due to an AVM.

Medication management in people with Parkinson's disease during surgical admissions.

BACKGROUND: Patients with Parkinson's disease (PD) may experience problems in hospital, with their medication being withheld or inappropriate medication being prescribed. Since surgical admissions present particular risks, the authors examined the management of patients with PD on surgical wards. METHODS: All patients with PD admitted to surgical departments in Aberdeen Royal Infirmary during an 18-month period were identified. Medical and nursing notes were reviewed retrospectively, and drug prescription and administration were studied in detail. All documented complications were recorded. RESULTS: 59 surgical admissions (51 receiving PD medication, median duration 6 days) were studied. 71% had missed doses of PD medication, with 34% missing over 10% of prescribed doses. Values were similar for levodopa and agonists. Overall, 12% of all prescribed PD medication was missed (mean 0.7 missed doses per patient per day). No reason for missed doses was recorded in 64% of cases, while inappropriate reasons included 'out of stock' (12%) and 'nil by mouth' (8%). Centrally acting antidopaminergic drugs (mainly antiemetics) were prescribed in 41% of cases, and administered in 22%. Complications, most commonly neuropsychiatric, were documented in 69% of non-day-case admissions. CONCLUSION: Poor prescribing and incomplete drug administration are common in patients with PD on surgical wards. Measures to improve management are identified.

Documentation of cerebrospinal fluid opening pressure and other important aspects of lumbar puncture in acute headache.

BACKGROUND: Measuring cerebrospinal fluid (CSF) opening pressure by lumbar puncture (LP) is an essential tool in the investigation of patients with acute headache. AIM: To assess documentation of opening CSF pressure in those with acute headache undergoing LP. General documentation of the procedure and CSF investigations was also assessed. METHODS: Retrospective review of medical records of patients admitted to a teaching hospital Acute Medical Admissions Unit over a three-month period with a presenting complaint of headache. RESULTS: A total of 106 patients presented with headache of whom 48 patients had at least one LP attempted. Only 41 patients (85%, 95% CI 72-94) had their LP documented. Of 47 patients that had a successful LP, 22 (47%) had a recorded opening pressure. Eighteen (32%) of all patients had their position recorded, with seven (15%) patients having had position and opening pressure documented. Twenty patients (43%) had the appropriate results documented. Twelve patients (31%) had paired serum glucose measured. CONCLUSIONS: Documentation of a LP for headache in the acute setting was generally poor. CSF opening pressure measurement was frequently omitted and no appropriate action taken if high. Paired serum glucose was rarely measured. Acute physicians may benefit from a proposed protocol and documentation sticker.

'Not taken in by media hype': how potential donors, recipients and members of the general public perceive stem cell research.

BACKGROUND: Views of embryo donors, scientists and members of the general public on embryonic stem cell research (eSCR) have been widely reported. Less is known about views of potential beneficiaries of stem cell therapy and the influence of media 'hype' on perceptions of eSCR among different groups of stakeholders. This study aimed to examine the perceptions of members of the general public as well as two patient groups likely to benefit from eSCR and to explore the role of the media in shaping these views. METHODS: A qualitative study carried out in Aberdeen, Scotland included 15 people living with Parkinson's disease (PD), 15 people living with diabetes mellitus (DM), 15 couples with infertility and 21 members of the general public who volunteered for the study. Interview transcripts were analysed thematically using grounded theory. RESULTS: The two patient groups likely to benefit from eSCR in the future differed in their knowledge (mainly gained from the media) and understanding of eSCR. Those living with PD were older, more debilitated and better informed than those with DM who showed limited interest in potential future benefits of eSCR. Infertile couples learnt about eSCR from health professionals who explained the process of embryo donation to them, and had sought no further information. Most of the general public had accessed information on eSCR and believed themselves to be more discerning than others because of their objectivity, intelligence and 'scientific awareness'. Although, the media and internet were primary sources of information for all except couples with infertility, members of all four groups claimed not to be taken in by the media 'hype' surrounding eSCR. CONCLUSIONS: Those who expected to benefit from eSCR in the future as well as members of the general public differ in their susceptibility to media 'hype', while believing that they are not taken in by exaggerated claims of benefits. As respondents were a selected group who were not drawn from a representative sample, the findings cannot be generalized to a wider population.

Changes in diagnosis with follow-up in an incident cohort of patients with parkinsonism.

BACKGROUND: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation, but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria. METHODS: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patient records at baseline and the latest yearly follow-up. RESULTS: Of 82 incident patients, 66 underwent at least 1 year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a "probable" diagnosis in 71% of parkinsonian patients at follow-up but in only 15% at the initial assessment. DISCUSSION: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson's disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis, even after a median of 29 months of follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.

Recruitment bias resulted in poorer overall health status in a community-based control group.

OBJECTIVE: During a prospective community-based incidence study of parkinsonism, a control group was recruited for comparison with the incident patients. This study compared the demographic and health status of recruited vs. nonrecruited controls. STUDY DESIGN AND SETTING: For each incident patient, attempts were made to recruit an age-gender matched control from the same general practice or, failing that, from a previously identified community cohort of people aged over 64 years who had expressed an interest in taking part in future research. Recruited controls were compared with those who were approached but not recruited in terms of age, socioeconomic status, gender, several measures of health status, and survival. RESULTS: A total of 74 controls (40%) were recruited out of 186 potential controls who were approached. Recruited controls scored slightly worse than nonrecruited controls on every measure of health status, which reached statistical significance for numbers of acute prescriptions and major surgical procedures. There were no significant differences in age, gender, socioeconomic status, or survival. CONCLUSION: The control cohort was affected by recruitment bias, which suggested that recruited controls had slightly poorer health compared to nonrecruited controls. This bias may reduce differences in health when comparisons are made between the controls and the parkinsonian patients.

Changes in quality of life in people with Parkinson's disease left untreated at diagnosis.

BACKGROUND: The issue of whether to adopt a "wait and watch" strategy or to initiate drug therapy soon after diagnosis in Parkinson's disease (PD) has been the subject of some debate. A recent observational study supported early treatment by demonstrating deterioration in self-reported health status in those left untreated, but not those who received therapy. We aimed to replicate this observation. METHODS: People with PD from a prospective incidence study underwent follow-up with yearly clinical assessment of parkinsonian impairment (Unified Parkinson's Disease Rating Scale (UPDRS)) and self-reported health status (Parkinson's Disease Questionnaire (PDQ-39)). Two year outcomes were compared with those who started treatment within 1 year of diagnosis and those left untreated. RESULTS: 42 patients with PD were followed-up for 2 years, of whom 26 started treatment during the first year and 16 remained untreated. Those receiving treatment had significantly higher UPDRS and PDQ-39 scores at baseline. There was no significant deterioration in PDQ-39 score in either group (median change untreated 0.8 vs treated 4.0; p = 0.47), despite a significant difference in the change in motor UPDRS scores (untreated 6.0 vs treated -6.0; p = 0.03). CONCLUSION: Given the lack of significant deterioration in the PDQ-39 in untreated patients, we believe a "wait and watch" strategy for the treatment of newly diagnosed PD remains a credible approach unless randomised trials prove otherwise.

Differences between intracranial vascular malformation types in the characteristics of their presenting haemorrhages: prospective, population-based study.

OBJECTIVE: To determine the imaging and demographic characteristics of intracranial haemorrhages, which are subsequently found to be due to an underlying intracranial vascular malformation (IVM). METHODS: We compared the demographic and brain imaging characteristics of adults presenting with intracranial haemorrhage, subsequently found to be due to a brain arteriovenous malformation (BAVM), dural arteriovenous fistula (DAVF) or cavernous malformation (CM) in a prospective, population-based cohort of adults diagnosed for the first time with an IVM (The Scottish IVM Study (SIVMS)). RESULTS: Of the 141 adults in SIVMS who presented with intracranial haemorrhage, those with CMs presented at a younger age and were less handicapped. A total of 115 (82%) had intracerebral haemorrhage (ICH) with or without subarachnoid, intraventricular or subdural extension. ICH without extension into other compartments accounted for all CM bleeds, but only 50% of BAVM and DAVF bleeds. Median haematoma volumes differed (Kruskal-Wallis, p<0.0001): ICH due to BAVM (16.0 cm3, inter-quartile range (IQR) 4.7 to 42.0) and DAVF (14.1 cm3, IQR 4.9 to 21.5) were similar, but CM haematoma volumes were smaller (median 1.8 cm3, IQR 1.3 to 4.3). These findings were robust in sensitivity analyses. Small haematoma volumes occurred among all IVM types; the largest haematoma volume due to CM was 12 cm3, and volumes of >34 cm3 were only due to BAVM. CONCLUSIONS: Intracranial haemorrhages found to be due to IVMs differ in adults' age of presentation and clinical severity, as well as the volume and distribution of the haematoma within the brain compartments.

External validation of a six simple variable model of stroke outcome and verification in hyper-acute stroke.

We aimed to validate a previously described six simple variable (SSV) model that was developed from acute and sub-acute stroke patients in our population that included hyper-acute stroke patients. A Stroke Outcome Study enrolled patients from 2001 to 2002. Functional status was assessed at 6 months using the modified Rankin Scale (mRS). SSV model performance was tested in our cohort. 538 acute ischaemic (87%) and haemorrhagic stroke patients were enrolled, 51% of whom presented to hospital within 6 h of symptom recognition. At 6 months post-stroke, 42% of patients had a good outcome (mRS < or = 2). Stroke patients presenting within 6 h of symptom recognition were significantly older with higher stroke severity. In our Stroke Outcome Study dataset, the SSV model had an area under the curve of 0.792 for 6 month outcomes and performed well for hyper-acute or post-acute stroke, age < or > or = 75 years, haemorrhagic or ischaemic stroke, men or women, moderate and severe stroke, but poorly for mild stroke. This study confirms the external validity of the SSV model in our hospital stroke population. This model can therefore be utilised for stratification in acute and hyper-acute stroke trials.

Environmental risk factors for Parkinson's disease and parkinsonism: the Geoparkinson study.

OBJECTIVE: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. METHODS: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. RESULTS: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) = 1.13, 95% CI 0.82 to 1.57, high vs no exposure, OR = 1.41, 95% CI 1.06 to 1.88) and ever knocked unconscious (once vs never, OR = 1.35, 95% CI 1.09 to 1.68, more than once vs never, OR = 2.53, 95% CI 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% CI 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. CONCLUSIONS: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.

Screening for undiagnosed parkinsonism in people aged 65 years and over in the community.

We screened a random sample of 2449 people aged 65 years and over for undiagnosed parkinsonism, using a postal screening questionnaire followed by clinical neurological assessment. Amongst the 1556 (63.5%) patients who responded, four patients with previously undiagnosed parkinsonism were identified, suggesting a prevalence of 257 per 100,000 (95% CI 70, 658) in this age-group. Although only small, the numbers were sufficient to significantly increase the incidence of parkinsonism in an incidence study. Two simple screening questions achieved a high sensitivity for newly diagnosed parkinsonism of 95%, but a low specificity of 28%.

Monoamine oxidase B inhibitors for early Parkinson's disease.

BACKGROUND: It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD). Clinical trials have produced conflicting results. OBJECTIVES: To assess the evidence from randomized controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD. SEARCH STRATEGY: We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (last searched 18th August 2004) and EMBASE (last searched 18th August 2004). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. SELECTION CRITERIA: We sought to include all unconfounded randomized controlled trials that compared a MAO-B inhibitor with control, in the presence or absence of levodopa or dopamine agonists, in patients with early PD and where treatment and follow up lasted at least one year. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. A small amount of additional data was provided by the original authors. Random-effects models were used to analyse results, where appropriate. MAIN RESULTS: Ten trials were included (a total of 2422 patients), nine using selegiline, one using lazabemide. The methodological quality was reasonable although concealment of allocation was definitely adequate in only four trials. The mean follow up was for 5.8 years. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.15; 95% confidence interval (CI) 0.92 to 1.44). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score was 3.81 points less with MAO-B inhibitors; 95% CI 2.27 to 5.36) and disability (WMD for change in UPDRS ADL score was 1.50 less; 95% CI 0.48 to 2.53) at one year which, although statistically significant, were not clinically significant. There was a marked levodopa-sparing effect with MAO-B inhibitors which was associated with a significant reduction in motor fluctuations (OR 0.75; 95% CI 0.59 to 0.94) but not dyskinesia (OR 0.97; 95% CI 0.76 to 1.25). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. Although adverse events were generally mild and infrequent, withdrawals due to side-effects were higher (OR 2.36; 95% CI 1.32 to 4.20) with MAO-B inhibitors. AUTHORS' CONCLUSIONS: MAO-B inhibitors do not appear to delay disease progression but may have a beneficial effect on motor fluctuations. There was no statistically significant effect on deaths although the confidence interval does not exclude a small increase with MAO-B inhibitors. At present we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease but further randomized controlled trials should be carried out to clarify, in particular, their effect on deaths and motor complications.