Tremor in Parkinson’s Disease: From Pathophysiology to Advanced Therapies

Abstract

Background: Tremor is one of the most prevalent symptoms in Parkinson's Disease (PD). The progression and management of tremor in PD can be challenging, as response to dopaminergic agents might be relatively poor, particularly in patients with tremordominant PD compared to the akinetic/rigid subtype. In this review, we aim to highlight recent advances in the underlying pathogenesis and treatment modalities for tremor in PD.Methods: A structured literature search through Embase was conducted using the terms "Parkinson's Disease" AND "tremor" OR "etiology" OR "management" OR "drug resistance" OR "therapy" OR "rehabilitation" OR "surgery." After initial screening, eligible articles were selected with a focus on published literature in the last 10 years. Discussion:The underlying pathophysiology of tremor in PD remains complex and incompletely understood. Neurodegeneration of dopaminergic neurons in the retrorubral area, in addition to high-power neural oscillations in the cerebello-thalamo-cortical circuit and the basal ganglia, play a major role. Levodopa is the first-line therapeutic option for all motor symptoms, including tremor. The addition of dopamine agonists or anticholinergics can lead to further tremor reduction. Botulinum toxin injection is an effective alternative for patients with pharmacological-resistant tremor who are not seeking advanced therapies. Deep brain stimulation is the most well-established advanced therapy owing to its longterm efficacy, reversibility, and effectiveness in other motor symptoms and fluctuations. Magnetic resonance-guided focused ultrasound is a promising modality, which has the advantage of being incisionless. Cortical and peripheral electrical stimulation are noninvasive innovatory techniques that have demonstrated good efficacy in suppressing intractable tremor.

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort

“…Over 75% of people with Parkinson's disease (PD) develop tremor, which can greatly impact their quality of life 1 . Patients with tremor‐dominant PD (TdPD) often have delayed onset of rigidity and bradykinesia and less severe non‐motor symptoms, but the tremor can be very resistant to medical therapy 2 . For those patients with significant tremor that is medically refractory, neurosurgical intervention is a treatment option.…”

Parkinson disease following COVID‐19: Report of six cases

“…The available evidence does not allow us to draw a well‐defined hypothesis on the dominance of tremor as an early symptom in these cases. In principle, there is no need to suspect pathophysiological mechanisms other than those already well described, which include both imbalance in basal ganglia neurochemistry and a synchronous oscillatory activity in cerebellothalamocortical and basal ganglia–cortical loops [25]. One of the possible interpretations lies in the role of stress in patients who have experienced COVID‐19.…”

Association of 7-Day Profiles of Motor Activity in Marital Dyads with One Component Affected by Parkinson’s Disease

“…Freezing of gait [ 5 ], festination [ 6 ], gait initiation [ 7 ] and termination deficits [ 8 ], poor dynamic balance [ 9 , 10 ], difficulty in negotiating turning [ 11 ], tremor [ 12 ], and upper limb locomotor synergies [ 13 ] are among the typical motor signs affecting persons with PD. More generally, PD impacts many aspects of daily life, including sleep and diet [ 14 ].…”