What causes resting tremor?

From the Guidelines

Tremor at rest is primarily caused by Parkinson's disease, a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra, leading to an imbalance in the neural pathways that regulate movement. This condition is the most common cause of Parkinsonism, with an annual incidence estimated at 10 to 18/100,000 in the total population and a peak age of onset between 60 to 70 years 1. The clinical presentation of Parkinson's disease is characterized by resting tremor, bradykinesia, and rigidity, which are related to the progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum.

Other causes of tremor at rest include:

• Progressive supranuclear palsy (PSP), a tauopathy characterized by the abnormal accumulation of tau proteins in different regions of the brain
• Multiple system atrophy (MSA), a synucleinopathy characterized by the abnormal accumulation of alpha-synuclein in oligodendroglia
• Corticobasal degeneration (CBD), a tauopathy characterized by the abnormal accumulation of tau proteins in different regions of the brain
• Vascular Parkinsonism, a condition caused by vascular disease affecting the brain

These conditions are considered "Parkinson-plus" syndromes or atypical Parkinsonisms and demonstrate the classic findings of Parkinson's disease, including bradykinesia and rigidity, with additional clinical features 1. The diagnosis of Parkinsonian syndromes can be challenging, and imaging remains an essential diagnostic tool in the evaluation of a patient presenting with Parkinsonian symptoms 1.

The estimated interval between initial loss of dopaminergic neurons and the appearance of symptoms in Parkinson's disease is approximately 5 years, after approximately 40% to 50% of the dopaminergic neurons in the substantia nigra have been lost 1. Other features of Parkinson's disease include autonomic dysfunction, behavioral changes, and dementia. Treatment depends on the underlying cause, with Parkinson's disease typically managed with medications that increase dopamine activity.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanism of Action Parkinson's disease is a progressive, neurodegenerative disorder of the extrapyramidal nervous system affecting the mobility and control of the skeletal muscular system. Its characteristic features include resting tremor, rigidity, and bradykinetic movements. Current evidence indicates that symptoms of Parkinson's disease are related to depletion of dopamine in the corpus striatum.

The cause of tremor at rest is related to the depletion of dopamine in the corpus striatum, a characteristic feature of Parkinson's disease 2.

From the Research

Causes of Tremor at Rest

• Tremor at rest is a common symptom in Parkinson's Disease (PD) and is characterized by a rhythmical, involuntary oscillatory movement of a body part 3
• The underlying pathophysiology of tremor in PD remains complex and incompletely understood, but neurodegeneration of dopaminergic neurons in the retrorubral area, high-power neural oscillations in the cerebello-thalamo-cortical circuit and the basal ganglia, play a major role 4, 5
• Rest tremor is also found in other disorders such as dystonic tremor, essential tremor with a rest component, Holmes tremor, and a few even rarer conditions 3
• Dopamine transporter imaging and several electrophysiological methods provide additional clues for tremor differential diagnosis 3

Pathophysiology of Parkinson's Disease Tremor

• Clinical and experimental observations suggest that tremor in PD cannot be interpreted merely as an expression of dopaminergic denervation of the basal ganglia 5
• Other neurotransmitter systems and brain areas are involved, including altered oscillations and synchronization in two partially overlapping central motor circuitries, e.g., the cerebello-thalamo-cortical and the basal ganglia-cortical loops 5
• The abnormal interplay between the two systems has pathophysiological consequences, and a better understanding of this issue is likely to facilitate future therapeutic approaches to PD patients based on medications and invasive and non-invasive stimulation techniques 5

Treatment of Tremor at Rest

• Levodopa is the first-line therapeutic option for all motor symptoms, including tremor, and the addition of dopamine agonists or anticholinergics can lead to further tremor reduction 4, 6
• Botulinum toxin injection is an effective alternative for patients with pharmacological-resistant tremor who are not seeking advanced therapies 4
• Deep brain stimulation is the most well-established advanced therapy owing to its long-term efficacy, reversibility, and effectiveness in other motor symptoms and fluctuations 4, 6