29th April 2024

Parkinson’s Disease

Background

Idiopathic Parkinson’s disease (PD) is characterised primarily by bradykinesia, the presence of which is key for a confident diagnosis. Bradykinesia is often seen with rigidity, resting tremor, postural instability and gait impairment. PD occurs as a result of degeneration of the dopaminergic neurons in the ventral pars compacta of the substantia nigra. α-synuclein, a protein bound to ubiquitin, aggregates in damaged cells, forming cellular inclusions called Lewy bodies.

Clinical manifestations

Anxiety can precede motor symptoms by decades, whilst anosmia can be an early, though non-specific sign. Early manifestations may also include rapid eye movement (REM) behavioural disorder, which is strongly predictive of future neurodegenerative pathology.

Motor symptoms in PD often develop asymmetrically. This asymmetry often persists as the disease progresses. The resting tremor has a slow frequency (4 – 6 cycles per second), typically with a pill rolling character. It is often a re-emergent tremor, it will subside when the limb is moved to take up a new position but will re-emerge a short time after maintaining the new position. Stress and emotion can also exacerbate the tremor, whilst distraction can reveal the tremor. For instance, asking the patient to perform simple cognitive tasks such as counting backwards may reveal the tremor. Tremors can also affect the legs, chin, lips and trunk.

Increased muscle tone, described as rigidity, is best seen on slow passive movements. This can be described as “lead pipe” unless there is a superimposed tremor as well, in which case it may be described as cogwheeling. Rigidity can be accentuated by asking the patient to move the contralateral limb.

Bradykinesia tends to interfere with voluntary movements. It encompasses a range of movement disturbances, including a breakdown of fine movements, fatiguing and difficulty in gait initiation. Bradykinesia or akinesia accounts for the lack of facial expression (hypomimia), soft, monotonous speech (hypophonia), impaired swallowing, which may result in drooling (sialorrhea), small handwriting (micrographia), reduced arm swing, short strides and shuffling gait.

Postural instability is another feature of PD. Patients are often stooped, with instability resulting in falls. Patients may also report an inability to stop themselves going forward (propulsion) and may have a hurried (festinant) gait.

As the disease progresses, or in late presentations, motor symptoms tend to be more severe and can affect contralateral limbs. In addition, systemic features are common. These include constipation, dysphagia, autonomic problems (orthostatic hypotension, thermodysregulation, constipation) and cognitive disturbances including dementia.

Diagnosis

Diagnosis is primarily clinical, with investigations primarily focused on excluding other causes of parkinsonism. Single-photon emission computed tomography (DaTSCAN) can be used. This involves the injection of a radioisotope with a high affinity for dopamine transporter, particularly in the striatum. SPECT images are then produced with a gamma camera. In PD, patients may demonstrate reduced uptake.

Management

Dopamine replacement using levodopa and a peripheral dopa-decarboxylase inhibitor is the most effective treatment for PD. Levodopa can, however, be associated with the development of dyskinesia, motor fluctuations and hallucinations.

Dopamine agonists can also be used but are associated with impulse control disorders. These, along with Monoamine oxidase-B inhibitors (MAO-B) and Catechol-O-methyltransferase (COMT) inhibitors can be used as an adjunct to levodopa in those who develop dyskinesia or motor fluctuations.

References

• National Institute for Health and Care Excellence (UK). Parkinson’s disease in adults: diagnosis and management. London: National Institute for Health and Care Excellence (UK); 2017 Jul. (NICE Guideline, No. 71.) Appendix B, National Institute for Health and Care Excellence. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535852/
• Talati R, Reinhart K, Baker W, et al. Pharmacologic treatment of advanced Parkinson’s disease: a meta-analysis of COMT inhibitors and MAO-B inhibitors. Parkinsonism Relat Disord. 2009 Aug;15(7):500-5