Motor Dysfunction as a Prodrome of Parkinson’s Disease

Alarcón, Fernando; MALDONADO, J; Cañizares, M.A.; Molina, José Antonio; Noyce, Alastair J.; Lees, Andrew J.

doi:10.3233/jpd-191851

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…A longitudinal study conducted in Spain showed that after 3-years of follow-up, people with essential tremor were four times more likely to develop PD than those without tremor [34] . Similar results were found in another longitudinal study, where isolated tremor was associated with a doubling of the risk of PD [35] . Rigidity is a sign not a symptom explaining why it is rarely reported by patients.…”

Section: Discussionsupporting

confidence: 90%

Risk factors, early presentations, and clinical markers of Parkinson’s disease in Primary Care in a diverse UK population

Simonet

Bestwick

Jitlal

et al. 2021

Preprint

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Importance: Predictors of future Parkinson′s disease (PD) have been suggested through population-based studies, but these studies over–represent white, affluent groups and may not be generalisable. Objective: To investigate the association between risk factors and pre–diagnostic presentations of PD in a uniquely diverse UK population, with universal access to health care. Design, Setting, and Participants: A case–control study was conducted in East London, using primary care health records. Main outcomes and Measures: Logistic regression was used to determine associations between risk factors and pre–diagnostic presentations of PD with final diagnosis. Three periods (recorded <2 years, 2–5 years, and 5–10 years prior to diagnosis) were analysed. Results: Primary care records were available for 1,055 patients with PD and 1,009,523 controls. The strongest associations were found for tremor (OR, 181.69; 95% CI, 151.91–217.31) and ′memory complaints′ (OR, 9.84; 95% CI, 7.39–13.11), <2 years before PD diagnosis. However, associations for both complaints persisted up to 10 years prior to PD diagnosis. Shoulder pain was more common in those who developed PD, emerging 5 to 10 years prior to diagnosis (OR, 2.54; 95% CI, 1.77–3.65), and may be a surrogate marker for rigidity. Epilepsy showed a strongest association with subsequent PD (OR, 5.14; 95% CI, 1.26–21.0), and associations were also found for hypertension (OR, 1.71; 95% CI, 1.34–2.17) and type 2 diabetes (OR, 1.57; 95% CI, 1.31–1.87) 5 to 10 years before diagnosis. We replicated several known associations with early non motor features including hypotension, constipation, and depression. A weak but novel association was observed with prodromal hearing loss and subsequent PD, which appeared up to 10 years prior to diagnosis. No associations with future PD diagnosis were found for ethnicity or deprivation index. Conclusions and relevance: This study provides further evidence that a range of comorbidities and pre-diagnostic presentations are encountered in primary care prior to PD diagnosis, but for the first time in such a diverse and deprived population. Convincing temporal associations were observed for epilepsy and hearing loss with subsequent PD. The predominance of ′memory symptoms′ hints at an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally under–represented groups.

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Section: Discussionsupporting

confidence: 90%

Risk factors, early presentations, and clinical markers of Parkinson’s disease in Primary Care in a diverse UK population

Simonet

Bestwick

Jitlal

et al. 2021

Preprint

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“…Of the prediagnostic clinical manifestations, tremor showed the highest association with subsequent PD, which was also found up to 10 years before diagnosis. Various studies have reported that tremor may be an early feature of PD . In people reporting tremor years before diagnosis, one must consider the possibility that diagnosis is simply delayed in primary care.…”

Section: Discussionmentioning

confidence: 81%

Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population

et al. 2022

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IMPORTANCEEarly features of Parkinson disease (PD) have been described through population-based studies that overrepresent White, affluent groups and may not be generalizable.OBJECTIVE To investigate the association between risk factors and prediagnostic presentations of PD in an ethnically diverse UK population with high socioeconomic deprivation but universal access to health care. DESIGN, SETTING, AND PARTICIPANTSA nested case-control study was conducted using electronic health care records on 1 016 277 individuals from primary care practices in East London to extract clinical information recorded between 1990 and February 6, 2018. The data were analyzed between September 3, 2020, and September 3, 2021. Individuals with a diagnosis of PD were compared with controls without PD or other major neurological conditions. MAIN OUTCOMES AND MEASURESA matched analysis (10 controls matched for each patient with PD according to age and sex) and an unmatched analysis (adjusted for age and sex) were undertaken using multivariable logistic regression to determine associations between risk factors and prediagnostic presentations to primary care with subsequent diagnosis of PD. Three time periods (<2, 2-<5, and 5-10 years before diagnosis) were analyzed separately and together.RESULTS Of 1 016 277 individuals included in the data set, 5699 were excluded and 1055 patients with PD and 1 009 523 controls were included in the analysis. Patients with PD were older than controls (mean [SD], 72.9 [11.3] vs 40.3 [15.2] years), and more were male (632 [59.9%] vs 516 862 [51.2%]). In the matched analysis (1055 individuals with PD and 10 550 controls), associations were found for tremor (odds ratio [OR], 145.96; 95% CI, 90.55-235.28) and memory symptoms (OR, 8.60; 95% CI, 5.91-12.49) less than 2 years before the PD diagnosis. The associations were also found up to 10 years before PD diagnosis for tremor and 5 years for memory symptoms. Among midlife risk factors, hypertension (OR, 1.36; 95% CI,) and type 2 diabetes (OR, 1.39; 95% CI, 1.19-1.62) were associated with subsequent diagnosis of PD. Associations with early nonmotor features, including hypotension (OR, 6.84; 95% CI, 3.38-13.85), constipation (OR, 3.29; 95% CI, 2.32-4.66), and depression (OR, 4.69; 95% CI, 2.88-7.63), were also noted. Associations were found for epilepsy (OR, 2.5; 95% CI, 1.63-3.83) and hearing loss (OR, 1.66; 95% CI, 1.06-2.58), which have not previously been well reported. These findings were replicated using data from the UK Biobank. No association with future PD diagnosis was found for ethnicity or deprivation index level. CONCLUSIONS AND RELEVANCEThis study provides data suggesting that a range of comorbidities and symptoms are encountered in primary care settings before PD diagnosis in an ethnically diverse and deprived population. Novel temporal associations were observed for epilepsy and hearing loss with subsequent development of PD. The prominence of memory symptoms suggests an excess of cognitive dysfunction in early PD in this population or difficul...

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“…There are, however, many reports of musculoskeletal problems, especially "frozen shoulder," before the onset of classic parkinsonian symptoms that are often attributed to local injury. While it can be argued that those are early symptoms of PD (such as decreased arm swing leading to a "frozen shoulder"), shoulder pain is now well recognized early symptom of PD [90][91][92][93][94]. Although the relationship between shoulder problems and PD is not well understood, we and others have encountered many well-documented cases of parkinsonism with onset within days or weeks following shoulder injury [16].…”

Section: Parkinsonismmentioning

confidence: 96%

Peripherally-induced Movement Disorders: An Update

Lenka¹,

Jankovic

2023

Tremor and Other Hyperkinetic Movements

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Background: Peripherally-induced movement disorders (PIMD) should be considered when involuntary or abnormal movements emerge shortly after an injury to a body part. A close topographic and temporal association between peripheral injury and onset of the movement disorders is crucial to diagnosing PIMD. PIMD is under-recognized and often misdiagnosed as functional movement disorder, although both may co-exist. Given the considerable diagnostic, therapeutic, and psychosocial-legal challenges associated with PIMD, it is crucial to update the clinical and scientific information about this important movement disorder.Methods: A comprehensive PubMed search through a broad range of keywords and combinations was performed in February 2023 to identify relevant articles for this narrative review. Results:The spectrum of the phenomenology of PIMD is broad and it encompasses both hyperkinetic and hypokinetic movements. Hemifacial spasm is probably the most common PIMD. Others include dystonia, tremor, parkinsonism, myoclonus, painful leg moving toe syndrome, tics, polyminimyoclonus, and amputation stump dyskinesia. We also highlight conditions such as neuropathic tremor, pseudoathetosis, and MYBPC1associated myogenic tremor as examples of PIMD.Discussion: There is considerable heterogeneity among PIMD in terms of severity and nature of injury, natural course, association with pain, and response to treatment. As some patients may have co-existing functional movement disorder, neurologists should be able to differentiate the two disorders. While the exact pathophysiology remains elusive, aberrant central sensitization after peripheral stimuli and maladaptive plasticity in the sensorimotor cortex, on a background of genetic (two-hit hypothesis) or other predisposition, seem to play a role in the pathogenesis of PIMD.

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Motor Dysfunction as a Prodrome of Parkinson’s Disease

Cited by 8 publications

References 42 publications

Risk factors, early presentations, and clinical markers of Parkinson’s disease in Primary Care in a diverse UK population

Risk factors, early presentations, and clinical markers of Parkinson’s disease in Primary Care in a diverse UK population

Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population

Peripherally-induced Movement Disorders: An Update

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