Figure 1
Flow diagram summarizing the steps involved in the literature search.
Figure 2
Cerebral neuronal and neurochemical basis of tremor in Parkinson’s Disease. The figure shows the main circuits of the dimmer-switch model (A), which includes the cerebello-thalamo-cortical circuit (in red) and the basal ganglia-cortical circuit (in green). The basal ganglia (B) is the key structure that triggers the initiation of tremor. The striatum increases inhibitory output to the globus pallidus internus (Gpi), which in turn stimulates the anterior ventrolateral (VLa) nucleus of the thalamus. This trigger further propagates to the cerebral cortex, where convergence of both circuits occurs. This convergence stimulates the cerebello-thalamo-cortical circuit, which alters tremor amplitude. The figure also shows the main nuclei proposed to have major neurochemical role in tremor pathogenesis: 1. Degeneration in the retrorubral area (RRA) leads to reduced dopaminergic projections to the subthalamic region, the basal ganglia, and the ventrolateral thalamus 2. Reduced serotonergic projections result from degenerative raphe nuclei (RN). 3. Increased noradrenergic projection from the locus coeruleus (LC).
Table 1
Pharmacotherapeutic options in the treatment of Parkinson’s disease tremor.
| MEDICATION | MECHANISM OF ACTION | STARTING DOSAGE (MG) | TITRATION | MAXIMUM (MG) | SIDE EFFECTS | COMMENTS |
|---|---|---|---|---|---|---|
| Levodopa | Metabolic precursor of dopamine | Levodopa-carbidopa 100/25 mg TID | Increase by 1–2 tablets every week | 1200–1500 mg/day in 3–4 divided doses | Nausea, vomiting, postural hypotension, confusion or hallucinations | Dose and frequency can be increased as tolerated |
| Levodopa-benserazide 100/25 mg TID | ||||||
| Dopamine Agonists | Stimulate dopamine receptors | Pramipexole 0.125 mg TID | Slow titration every 5–7 days | 4.5 mg/day | Somnolence, constipation, dizziness, hallucinations, sleep attacks and ICD. | |
| Pramipexole ER 0.375 mg TID | ||||||
| Rotigotine transdermal patch 2 mg/24 hours | May increase by 2 mg/24 hours at weekly intervals | 8 mg/24 hours | ||||
| Ropinirole 0.25 mg TID | Slow titration at weekly intervals | 24 mg/day | ||||
| Ropinirole ER 2 mg OD | ||||||
| MAOB-I | Inhibits monoamine oxidase enzyme | Selegiline 2.5–5 mg OD | Slow titration at weekly intervals | 10 mg/day in 2 divided doses | Headache, dizziness, insomnia, nausea | |
| Rasagiline 0.5 mg OD | 1 mg/day | |||||
| Anticholinergics | Antagonise the effects of acetylcholine at muscarinic receptors postsynaptic to striatal interneurons | Benztropine 0.5mg/day | Increase by 0.5 mg every 5–7 days | 6 mg/day in 2 to 4 divided doses | Memory impairment, confusion, and hallucinations plus peripheral antimuscarinic side effects. | Rapid withdrawal can result in exacerbation of parkinsonism |
| Trihexyphenidyl 1 mg/day | Gradual increase by 2 mg at 3–5 days interval | 12–15 mg/day in 3 to 4 divided doses | ||||
| Clozapine | Has anticholinergic and anti-serotonergic properties | 12.5 mg | Add 12.5mg every 1 to 2 weeks | 75–100 mg/day | Agranulocytosis, sedation, hypotension, hypersalivation and fever have been reported. | Requires routine blood monitoring for blood count |
| Clonazepam | Enhances GABA activity | 0.5mg OD | Increase by 0.5 mg every 3–4 days | 6 mg/day | sedation, memory loss and confusion. | |
| Propranolol | β1- and β2-receptor blocker | Regular 10–20 mg BID | Titration at 3–7 days interval | 320 mg/day | Sedation, insomnia, depression, hypotension, diarrhea, constipation and impotence | Rapid withdrawal can result in arrythmias |
| ER 60–80 mg OD |
[i] GABA: gamma-aminobutyric acid; OD: once daily, BID: twice per day. TID: three times per day; ER: Extended Release; ICD: Impulse Control Disorder.
Figure 3
Algorithm for the treatment of Parkinson Disease with predominant symptomatic tremor. † No strong evidence to support long term, sustained efficacy, and safety. Currently, the modality is mostly applied within the scope of clinical trials and registries.
Table 2
Advanced surgical modalities for Parkinson’s Disease tremor.
| MODALITY | SELECTION CRITERIA | TARGETS | ADVERSE EVENTS |
|---|---|---|---|
| A. DBS |
| STN, GPi, Vim, PSA | Cognitive decline, cerebral hemorrhage, infection, hardware failure, delayed lead migration, and death |
| B. Lesioning therapies | |||
| MRgFUS |
| Thalamotomy, Subthalamotomy, Pallidotomy | Headache, dizziness and vertigo, transient ataxia, paresthesia, and weakness |
| GK | Thalamotomy, Subthalamotomy | Transient paresthesia and hemiparesis, dysphagia, and death | |
| RF | Thalamotomy | Transient paresthesia, hemiparesis, dysarthria, ataxia, confusion, cognitive decline, and intracerebral hemorrhage | |
[i] IPD: Idiopathic Parkinson’s Disease; * No consensus agreement; ** May not be reliable indicator in the case of tremor-dominant PD.