From the Guidelines
Parkinson's disease (PD) with myoclonus is most commonly caused by advanced PD itself, medication-induced myoclonus, particularly from levodopa therapy, and certain genetic forms of PD, such as those with PARK2 (parkin) mutations, as well as comorbid conditions like dementia with Lewy bodies or multiple system atrophy. The clinical presentation of PD is characterized by resting tremor, bradykinesia, and rigidity, related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum 1. Myoclonus in PD can be triggered by various factors, including medication, disease progression, and genetic predisposition. According to the most recent study 1, adults with 22q11.2DS have an increased risk of developing Parkinson's disease, particularly early-onset PD, and may also experience myoclonus, motor tics, restless legs, postural and action tremors, and drug-induced movement disorders.
Key factors to consider in the diagnosis and management of PD with myoclonus include:
- Medication-induced myoclonus, particularly from levodopa therapy, especially at peak doses or with long-term use
- Advanced PD itself, reflecting more widespread neurodegeneration beyond the nigrostriatal system
- Certain genetic forms of PD, particularly those with PARK2 (parkin) mutations
- Comorbid conditions like dementia with Lewy bodies or multiple system atrophy
- Underlying metabolic disturbances, such as hypocalcemia, which may induce or worsen movement disorders 1
Management of PD with myoclonus typically involves:
- Adjusting PD medications, such as reducing levodopa doses or switching to extended-release formulations
- Adding antimyoclonic agents, like clonazepam (0.5-2mg daily), valproate (250-1000mg daily), or levetiracetam (500-3000mg daily)
- Treating any underlying metabolic disturbances, such as hypocalcemia or hypomagnesemia 1.
From the Research
Causes of Parkinson's Disease (PD) with Myoclonus
- Myoclonus in PD can be caused by various factors, including neurodegenerative syndromes such as multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, frontotemporal dementia, and Lewy body disorders 2
- The exact source of cortical myoclonus generation is controversial, and increased corticomuscular coherence represents a robust phenomenon that needs to be explained by any model that offers a putative explanation for cortical myoclonus generation 3
- Myoclonus in PD can be classified as a cortical phenomenon, but a subcortical origin cannot always be ruled out 4
- Atypical parkinsonian disorders (APD), including multiple system atrophy and progressive supranuclear palsy, can also present with myoclonus, making diagnosis challenging 5
- Clinicopathological discrepancies can occur in the diagnosis of PD and parkinsonism, highlighting the importance of careful long-term follow-up and postmortem neuropathological evaluation 6
Classification of Myoclonus
- Myoclonus can be classified by examination findings, etiology, or physiological characteristics, including cortical, cortical-subcortical, subcortical, segmental, and peripheral categories 2
- The physiological classification of myoclonus is important for determining the best approach for treatment 3