Effect of Early Levodopa Treatment on Mortality in People with Parkinson's Disease.

BACKGROUND: The ideal timing for initiating levodopa in newly diagnosed people with Parkinson's disease (PD) is uncertain due to limited data on the long-term effects of levodopa. OBJECTIVE: The aim was to investigate whether early levodopa initiation postpones mortality (primary outcome), the requirement of device-aided therapies, and the incidence of PD-related complications, such as fall-induced injuries. METHODS: Using nationwide claims data from Dutch hospitals (2012-2020), we grouped newly diagnosed PD individuals as "early initiators" (initiating levodopa within 2 years of diagnosis) or "nonearly initiators." We used the national death registry to assess mortality and health-care claims to assess PD-related complications and device-aided therapies. We used marginal structural models to compare mortality and device-aided therapy rates between groups, and a Poisson regression model to compare PD-related complication rates. RESULTS: Among 29,943 newly diagnosed PD individuals (mean age at diagnosis: 71.6, 38.5% female), there were 24,847 early and 5096 nonearly levodopa initiators. Over a median 4.25 years, 8109 (27.1%) died. The causal risk ratio for mortality was 1.04 (95% confidence interval [CI] 0.92-1.19) for early versus nonearly initiators. The risk ratio of receiving any device-aided therapy was 3.19 (95% CI 2.56-5.80). No association was observed with incidence of PD-related complications (incidence rate ratio: 1.00, 95% CI 0.96-1.05). CONCLUSIONS: Early levodopa initiation in PD does neither postpone nor accelerate mortality or PD-related complications, nor does it precipitate earlier occurrence of PD-related complications or mortality. However, we cannot exclude that the results were influenced by residual confounding due to unmeasured risk factors of mortality.

[Risk factors for Parkinson's disease: possibilities for prevention and intervention]. / Risicofactoren voor de ziekte van Parkinson.

Considering age to be the primary risk factor for developing Parkinson's disease and the observation that the Dutch population is rapidly aging, the parkinson prevalence is expected to increase over the coming years, as there is still no cure available for the disease. This has been confirmed by epidemiological data, which show a steady increase of the disease prevalence in the Netherlands for the period 2010-2021. Genetic risk factors only partially explain the disease pathogenesis. Environmental factors, such as exposure to pesticides and trichloroethylene are associated with a higher risk for developing Parkinson's disease. Lifestyle factors such as exercise, caffeine intake and the Mediterranean diet are associated with a lower risk for developing the disease and possibly delay the disease progression. Policy makers and healthcare providers should employ stricter regulations for pesticide use and should stimulate a healthy lifestyle to slow down the increasing prevalence.

Proactive and Integrated Management and Empowerment in Parkinson's Disease protocol for a randomised controlled trial (PRIME-UK) to evaluate a new model of care.

BACKGROUND: People living with Parkinson's disease experience progressive motor and non-motor symptoms, which negatively impact on health-related quality of life and can lead to an increased risk of hospitalisation. It is increasingly recognised that the current care models are not suitable for the needs of people with parkinsonism whose care needs evolve and change as the disease progresses. This trial aims to evaluate whether a complex and innovative model of integrated care will increase an individual's ability to achieve their personal goals, have a positive impact on health and symptom burden and be more cost-effective when compared with usual care. METHODS: This is a single-centre, randomised controlled trial where people with parkinsonism and their informal caregivers are randomised into one of two groups: either PRIME Parkinson multi-component model of care or usual care. Adults ≥18 years with a diagnosis of parkinsonism, able to provide informed consent or the availability of a close friend or relative to act as a personal consultee if capacity to do so is absent and living in the trial geographical area are eligible. Up to three caregivers per patient can also take part, must be ≥18 years, provide informal, unpaid care and able to give informed consent. The primary outcome measure is goal attainment, as measured using the Bangor Goal Setting Interview. The duration of enrolment is 24 months. The total recruitment target is n=214, and the main analyses will be intention to treat. DISCUSSION: This trial tests whether a novel model of care improves health and disease-related metrics including goal attainment and decreases hospitalisations whilst being more cost-effective than the current usual care. Subject to successful implementation of this intervention within one centre, the PRIME Parkinson model of care could then be evaluated within a cluster-randomised trial at multiple centres.

Specialized Versus Generic Allied Health Therapy and the Risk of Parkinson's Disease Complications.

BACKGROUND: Specialized versus generic physiotherapy (PT) reduces Parkinson's disease (PD)-related complications. It is unclear (1) whether other specialized allied heath disciplines, including occupational therapy (OT) and speech and language therapy (S<), also reduce complications; (2) whether there is a synergistic effect among multiple specialized disciplines; and (3) whether each allied health discipline prevents specific complications. OBJECTIVES: To longitudinally assessed whether the level of expertise (specialized vs. generic training) of PT, OT, and S< was associated with the incidence rate of PD-related complications. METHODS: We used claims data of all insured persons with PD in the Netherlands between January 1, 2010, and December 31, 2018. ParkinsonNet-trained therapists were classified as specialized, and other therapists as generic. We used mixed-effects Poisson regression models to estimate rate ratios adjusting for sociodemographic and clinical characteristics. RESULTS: The population of 51,464 persons with PD (mean age, 72.4 years; standard deviation 9.8) sustained 10,525 PD-related complications during follow-up (median 3.3 years). Specialized PT was associated with fewer complications (incidence rate ratio [IRR] of specialized versus generic = 0.79; 95% confidence interval, [0.74-0.83]; P < 0.0001), as was specialized OT (IRR = 0.88 [0.77-0.99]; P = 0.03). We found a trend of an association between specialized S< and a lower rate of PD-related complications (IRR = 0.88 [0.74-1.04]; P = 0.18). The inverse association of specialized OT persisted in the stratum, which also received specialized PT (IRR = 0.62 [0.42-0.90]; P = 0.001). The strongest inverse association of PT was seen with orthopedic injuries (IRR = 0.78 [0.73-0.82]; P < 0.0001) and of S< with pneumonia (IRR = 0.70 [0.53-0.93]; P = 0.03). CONCLUSIONS: These findings support a wider introduction of specialized allied health therapy expertise in PD care and conceivably for other medical conditions. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cost-Effectiveness and Cost-Utility of Early Levodopa in Parkinson's Disease.

BACKGROUND: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start). OBJECTIVE: This paper reports the results of the economic evaluation performed alongside the LEAP-study. METHODS: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up. RESULTS: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of € 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated. CONCLUSION: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa.

Dance classes improve self-esteem and quality of life in persons with Parkinson's disease.

INTRODUCTION: Dance can reduce motor symptoms in persons with Parkinson's disease (PD). However, the effect on psychosocial wellbeing, including self-esteem and quality of life is less clear. METHODS: Forty-nine persons with PD (Hoehn and Yahr stage 1-4) participated in weekly dance classes for a consecutive period of 22 weeks, 36 participants completed the classes. Two baseline measurements (T1a and T1b) were performed during a 2-week control period prior to the dance classes. Post-measurements (T2) were performed immediately after 22 weeks of dance classes. Primary outcome was self-esteem as measured with the Rosenberg Self-Esteem Score. RESULTS: Self-esteem scores were stable across the two baseline measurements and improved significantly after the dance classes (1.5 points improvement between T1b and T2, 95% CI 0.3, 2.7; p = 0.012). Additionally, quality of life as measured with the Parkinson's Disease Questionnaire 39 improved significantly (3.4 points reduction between T1b and T2, 95%CI - 5.7, - 1.2; p = 0.003) as did motor symptoms as measured with the Movement Disorders Society-Unified Parkinson's Disease Rating Scale-part III (6.2 points reduction between T1b and T2, 95%CI - 10.1, - 2.4; p = 0.002). Balance confidence as measured with the Activities-Specific Balance Confidence Scale did not change. DISCUSSION AND CONCLUSIONS: Dance classes seem to improve self-esteem, quality of life and motor symptoms in persons with PD. These effects should be investigated further in a randomized clinical trial. CLINICAL MESSAGE: Dance classes may be a valuable complementary treatment option in people with PD to improve not only motor symptoms, but also self-esteem and quality of life.

Characteristics of Patients with Late-Stage Parkinsonism Who are Nursing Home Residents Compared with those Living at Home.

OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder.

Neurovestibular Dysfunction and Falls in Parkinson's Disease and Atypical Parkinsonism: A Prospective 1 Year Follow-Up Study.

Our primary aim was to determine whether neurovestibular laboratory tests can predict future falls in patients with either Parkinson's disease (PD) or atypical parkinsonism (AP). We included 25 healthy subjects, 30 PD patients (median Hoehn and Yahr stage 2.5, range 1-4), and 14 AP patients (6 multiple system atrophy, 3 progressive supranuclear palsy, and 5 vascular parkinsonism) in a case-control study design (all matched for age and gender). At baseline, all subjects underwent clinical neurological and neurotological assessments, cervical and ocular vestibular evoked myogenic potentials (VEMP), brainstem auditory evoked potentials (BAEP), subjective visual vertical measurements (SVV), and video nystagmography with caloric and rotary test stimulation. After 1 year follow-up, all subjects were contacted by telephone for an interview about their fall frequency (based upon fall diaries) and about their balance confidence (according to the ABC-16 questionnaire); only one participant was lost to follow-up (attrition bias of 1.4%). Cervical and ocular VEMPs combined with clinical tests for postural imbalance predicted future fall incidents in both PD and AP groups with a sensitivity of 100%. A positive predictive value of 68% was achieved, if only one VEMP test was abnormal, and of 83% when both VEMP tests were abnormal. The fall frequency at baseline and after 1 year was significantly higher and the balance confidence scale (ABC-16) was significantly lower in both the PD and AP groups compared to healthy controls. Therefore, VEMP testing can predict the risk of future fall incidents in PD and AP patients with postural imbalance.

Optimizing Treatment in Undertreated Late-Stage Parkinsonism: A Pragmatic Randomized Trial.

BACKGROUND: Treatment of patients with late-stage parkinsonism is often sub-optimal. OBJECTIVE: To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. METHODS: Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted. RESULTS: Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = -1.2, p = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = -3.7, p = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. CONCLUSIONS: The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes.

Telemedicine for Hyperkinetic Movement Disorders.

Telemedicine is the use of electronic communication technology to facilitate healthcare between distant providers and patients. In addition to synchronous video conferencing, asynchronous video transfer has been used to support care for neurology patients. There is a growing literature on using telemedicine in movement disorders, with the most common focus on Parkinson's disease. There is accumulating evidence for videoconferencing to diagnose and treat patients with hyperkinetic movement disorders and to support providers in remote underserviced areas. Cognitive testing has been shown to be feasible remotely. Genetic counseling and other counseling-based therapeutic interventions have also successfully performed in hyperkinetic movement disorders. We use a problem-based approach to review the current evidence for the use of telemedicine in various hyperkinetic movement disorders. This Viewpoint attempts to identify possible telemedicine solutions as well as discussing unmet needs and future directions.

Slave to the rhythm: Seasonal differences in non-motor symptoms in Parkinson's disease.

INTRODUCTION: Although circadian variation of (motor) symptoms in Parkinson disease (PD) patients has been described, it remains unclear what effect seasonal variation may have on non-motor symptoms (NMS). METHODS: Cross-sectional retrospective study on 372 consecutive PD patients taking part in the Non-motor Longitudinal International Study at King's College Hospital London between November 2011 and July 2018. Patients were divided into three groups based on their date of assessment, using a simplified seasonal model: group 1: November-February (n = 107); group 2: March-15 June (n = 107); and group 3: 16 June-October (n = 158). Primary outcome was a seasonal difference in NMS scale (NMSS) total scores (higher scores reflecting greater disability). We hypothesized that PD patients exhibit circannual NMS burden patterns. RESULTS: All groups were identical concerning disease onset and duration, HY stage, Levodopa equivalent dose, and gender. There was a seasonal difference in NMSS total scores (p = 0.040), with the highest scores (57.1 ±â€¯42.5) in season 1 (winter months) and the lowest (45.1 ±â€¯34.4) in season 3 (summer months) (p = 0.037). Seasonal differences were observed in NMSS domain 1 (cardiovascular symptoms) (p = 0.011), domain 4 (perceptual problems) (p = 0.017) and domain 9 (miscellaneous symptoms) (p = 0.009). A trend was observed for domain 2 (sleep) (p = 0.057). CONCLUSION: NMS in PD fluctuate throughout the year, with worsening of symptoms in the winter months compared to the summer months suggestive of dysfunction of the body's master clock, the suprachiasmatic nuclei. Such variations must be accommodated in daily care to ascertain appropriate changes in medication regimes and in clinical trials for the interpretation of outcomes.

Randomized Delayed-Start Trial of Levodopa in Parkinson's Disease.

BACKGROUND: Levodopa is the main treatment for symptoms of Parkinson's disease. Determining whether levodopa also has a disease-modifying effect could provide guidance as to when in the course of the disease the treatment with this drug should be initiated. METHODS: In a multicenter, double-blind, placebo-controlled, delayed-start trial, we randomly assigned patients with early Parkinson's disease to receive levodopa (100 mg three times per day) in combination with carbidopa (25 mg three times per day) for 80 weeks (early-start group) or placebo for 40 weeks followed by levodopa in combination with carbidopa for 40 weeks (delayed-start group). The primary outcome was the between-group difference in the mean change from baseline to week 80 in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS; scores range from 0 to 176, with higher scores signifying more severe disease). Secondary analyses included the progression of symptoms, as measured by the UPDRS score, between weeks 4 and 40 and the noninferiority of early initiation of treatment to delayed initiation between weeks 44 and 80, with a noninferiority margin of 0.055 points per week. RESULTS: A total of 445 patients were randomly assigned: 222 to the early-start group and 223 to the delayed-start group. The mean (±SD) UPDRS score at baseline was 28.1±11.4 points in the early-start group and 29.3±12.1 points in the delayed-start group. The change in UPDRS score from baseline to week 80 was -1.0±13.1 points and -2.0±13.0 points, respectively (difference, 1.0 point; 95% confidence interval [CI], -1.5 to 3.5; P=0.44); this finding of no significant between-group difference at week 80 implies that levodopa had no disease-modifying effect. Between weeks 4 and 40, the rate of progression of symptoms, as measured in UPDRS points per week, was 0.04±0.23 in the early-start group and 0.06±0.34 in the delayed-start group (difference, -0.02; 95% CI, -0.07 to 0.03). The corresponding rates between weeks 44 and 80 were 0.10±0.25 and 0.03±0.28 (difference, 0.07; two-sided 90% CI, 0.03 to 0.10); the difference in the rate of progression between weeks 44 and 80 did not meet the criterion for noninferiority of early receipt of levodopa to delayed receipt. The rates of dyskinesia and levodopa-related fluctuations in motor response did not differ significantly between the two groups. CONCLUSIONS: Among patients with early Parkinson's disease who were evaluated over the course of 80 weeks, treatment with levodopa in combination with carbidopa had no disease-modifying effect. (Funded by the Netherlands Organization for Health Research and Development and others; LEAP Current Controlled Trials number, ISRCTN30518857 .).

Physical Exercise Modulates L-DOPA-Regulated Molecular Pathways in the MPTP Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas. MPTP reduced the number of DA neurons in the SNpc, whereas physical exercise improved beam walking, rotarod performance, and motor behavior in the open field. Further, enrichment analyses of the RNA-sequencing data revealed that in the MPTP-treated mice physical exercise predominantly modulated signaling cascades that are regulated by the top upstream regulators L-DOPA, RICTOR, CREB1, or bicuculline/dalfampridine, associated with movement disorders, mitochondrial dysfunction, and epilepsy-related processes. To elucidate the molecular pathways underlying these cascades, we integrated the proteins encoded by the exercise-induced differentially expressed mRNAs for each of the upstream regulators into a molecular landscape, for multiple key brain areas. Most notable was the opposite effect of physical exercise compared to previously reported effects of L-DOPA on the expression of mRNAs in the SN and the ventromedial striatum that are involved in-among other processes-circadian rhythm and signaling involving DA, neuropeptides, and endocannabinoids. Altogether, our findings suggest that physical exercise can improve motor function in PD and may, at the same time, counteract L-DOPA-mediated molecular mechanisms. Further, we hypothesize that physical exercise has the potential to improve non-motor symptoms of PD, some of which may be the result of (chronic) L-DOPA use.

ParkinsonNet: A Low-Cost Health Care Innovation With A Systems Approach From The Netherlands.

ParkinsonNet, a low-cost innovation to optimize care for patients with Parkinson disease, was developed in 2004 as a network of physical therapists in several regions in the Netherlands. Since that time, the network has achieved full national reach, with 70 regional networks and around 3,000 specifically trained professionals from 12 disciplines. Key elements include the empowerment of professionals who are highly trained and specialized in Parkinson disease, the empowerment of patients by education and consultation, and the empowerment of integrated multidisciplinary teams to better address and manage the disease. Studies have found that the ParkinsonNet approach leads to outcomes that are at least as good as, if not better than, outcomes from usual care. One study found a 50 percent reduction in hip fractures and fewer inpatient admissions. Other studies suggest that ParkinsonNet leads to modest but important cost savings (at least US$439 per patient annually). These cost savings outweigh the costs of building and maintaining the network. Because of ParkinsonNet's success, the program has now spread to several other countries and serves as a model of a successful and scalable frugal innovation.

What a neurologist should know about depression in Parkinson's disease.

Depression is a frequent non-motor symptom of Parkinson's disease. Its prevalence varies widely across studies (between 2.7% and 90%); around 35% have clinically significant depressive symptoms. Although depression can have an immense impact on the quality of life of affected patients and their caregivers, depressive symptoms in Parkinson's disease frequently remain unrecognised and, as a result, remain untreated. Here we overview the diagnostic challenges and pitfalls, including the factors contributing to the underdiagnosis of depression. We also discuss current ideas on the underlying pathophysiology. Finally, we offer a treatment approach based on currently available evidence.

Palliative Care for Patients and Families With Parkinson's Disease.

Parkinson's disease is the second most common neurodegenerative disease worldwide. There is widespread consensus that Parkinson patients, their carers, and clinicians involved in their care would benefit from a fully integrated, need-based provision of palliative care. However, the concept of palliative care in Parkinson's disease is still poorly defined and, consequently, poorly implemented into daily clinical practice. A particular challenge is the gradually progressive nature of Parkinson's disease-with insidiously increasing disability-making it challenging to clearly define the onset of palliative care needs for Parkinson patients. As people with Parkinson's disease are now living longer than in the past, future research needs to develop a more robust evidence-based approach to clarify the disease events associated with increased palliative care needs, and to examine these, prospectively, in an integrated palliative care service. The modern palliative care outlook, termed "simultaneous care,",is no longer restricted to the final stage of disease. It involves incorporating a continuity of care, effective management of the chronic-palliative interface, and a multidisciplinary network of professionals working both in the community and in specialized clinics, with active involvement of caregivers. Although promising, there is still a need to demonstrate the effectiveness of palliative care for patients with Parkinson's disease.

Cerebellar function and ischemic brain lesions in migraine patients from the general population.

Objective The objective of this article is to obtain detailed quantitative assessment of cerebellar function and structure in unselected migraine patients and controls from the general population. Methods A total of 282 clinically well-defined participants (migraine with aura n = 111; migraine without aura n = 89; non-migraine controls n = 82; age range 43-72; 72% female) from a population-based study were subjected to a range of sensitive and validated cerebellar tests that cover functions of all main parts of the cerebellar cortex, including cerebrocerebellum, spinocerebellum, and vestibulocerebellum. In addition, all participants underwent magnetic resonance imaging (MRI) of the brain to screen for cerebellar lesions. As a positive control, the same cerebellar tests were conducted in 13 patients with familial hemiplegic migraine type 1 (FHM1; age range 19-64; 69% female) all carrying a CACNA1A mutation known to affect cerebellar function. Results MRI revealed cerebellar ischemic lesions in 17/196 (8.5%) migraine patients and 3/79 (4%) controls, which were always located in the posterior lobe except for one control. With regard to the cerebellar tests, there were no differences between migraine patients with aura, migraine patients without aura, and controls for the: (i) Purdue-pegboard test for fine motor skills (assembly scores p = 0.1); (ii) block-design test for visuospatial ability (mean scaled scores p = 0.2); (iii) prism-adaptation task for limb learning (shift scores p = 0.8); (iv) eyeblink-conditioning task for learning-dependent timing (peak-time p = 0.1); and (v) body-sway test for balance capabilities (pitch velocity score under two-legs stance condition p = 0.5). Among migraine patients, those with cerebellar ischaemic lesions performed worse than those without lesions on the assembly scores of the pegboard task ( p < 0.005), but not on the primary outcome measures of the other tasks. Compared with controls and non-hemiplegic migraine patients, FHM1 patients showed substantially more deficits on all primary outcomes, including Purdue-peg assembly ( p < 0.05), block-design scaled score ( p < 0.001), shift in prism-adaptation ( p < 0.001), peak-time of conditioned eyeblink responses ( p < 0.05) and pitch-velocity score during stance-sway test ( p < 0.001). Conclusions Unselected migraine patients from the general population show normal cerebellar functions despite having increased prevalence of ischaemic lesions in the cerebellar posterior lobe. Except for an impaired pegboard test revealing deficits in fine motor skills, these lesions appear to have little functional impact. In contrast, all cerebellar functions were significantly impaired in participants with FHM1.