Parkinson's Disease & Parkinsonism
Contributed by Marcelo Merello, MD
Director, Neuroscience Department
Head Movement Disorders Section
Institute for Neurological Research Raul Carrea (FLENI)
Buenos Aires, Argentina
2019 Updates contributed by Angelo Antonini, MD, PhD
Professor, Department of Neuroscience
University of Padua, Italy
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Parkinson’s disease (PD) is a neurodegenerative disorder characterized primarily by loss of dopamine neurons in the substantia nigra. Symptoms generally develop on one body side slowly over years but the progression may differ from one person to another due to the diversity of the disease. People with PD may experience tremor, mainly at rest (described as pill rolling tremor in hands), bradykinesia, limb rigidity, gait and balance problems. Prevalence is approximately 200 cases per 100,000 population, and the incidence is about 25 cases per 100,000 population, but these figures might show differences from one region of the world to another.
When motor manifestations appear, people with PD have lost more than 50% of nigral dopamine cells suggesting that pathological changes may begin many decades before the appearance of clinical signs. The premotor phase is characterized in many cases by non-motor manifestations such as REM-sleep behavior disorder, apathy, mood changes, anxiety, constipation and loss of olfaction.
The cause of PD is probably multifactorial, with contributions from hereditary predisposition, environmental toxins, and aging. In recent years it has become evident that there is also a genetic contribution to PD and several mutations have been identified (GBA, LRRK2, PRKN, SNCA), although in most world regions only a minority cases are explained by genetics.
Diagnosis remains clinical and is based on motor manifestations. Brain MRI or CT and molecular imaging (ie of the dopamine transporter in the striatum) of the striatum may be performed to support clinical evaluation. The clinical features of PD include both the motor symptoms (described above), as well as non-motor issues. These non-motor symptoms include neuropsychiatric symptoms including mood disturbances and cognitive changes; autonomic dysfunction, pain and sleep issues.
Levodopa has remained the cornerstone of PD treatment for more than 50 years. However, after a few years of treatment and mainly due to the progression of the disease, the benefit of levodopa shortens and motor complications appear in many patients. This had led to the introduction of many other medications including inhibitors of catechol-O-methyltransferase (COMT), monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists. Enzyme blockers act by either extending levodopa or dopamine half-life while dopamine agonists mimic the action of dopamine on brain dopamine receptors.
More recently, surgical and infusion therapies have become available to improve management in selective patients with motor complications. Surgery includes the use of deep brain stimulation of the subthalamic nucleus and globus pallidus internus. The use of drug infusions is based on the possibility to deliver continuously either levodopa or apomorphine (a dopamine agonist with high affinity to dopamine receptors), mimicking the natural tonic receptor stimulation in the basal ganglia.
Parkinsonism
Contributed by David John Burn, MD, FRCP
Professor, Clinical Ageing Reserach Unit
Campus for Ageing and Vitality, Newcastle University
Newcastle Upon Tyne, UK
The defining feature of parkinsonism is bradykinesia, or slowness with decrement and degradation of repetitive movements (“fatigue”). Subtle “bradykinesia” has been reported to occur in the “normal elderly” population, but this may reflect a non-specific slowness rather than bradykinesia as defined above. Parkinson’s disease is the most common neurodegenerative cause of parkinsonism. Other causes include multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration.
These other neurodegenerative conditions are sometimes grouped together under term of “atypical parkinsonism” or “parkinson-plus syndromes”. They do not respond as well to dopaminergic treatments and generally have a worse prognosis compared to typical Parkinson’s disease. Degenerative causes of parkinsonism may be difficult to diagnose in the earliest stages and ancillary investigations may be of limited value in this instance.
Parkinsonism can also be symptomatic, as a result of various vascular, drug-related, infectious, toxic, structural and other known secondary causes. Of these, drug-induced parkinsonism is probably the most common and includes agents that block post-synaptic dopamine D2 receptors with high affinity (such as antipsychotic and anti-emetic medications) and sodium valproate. Vascular parkinsonism (“arteriosclerotic pseudoparkinsonism”) tends to have a lower body emphasis with gait disturbance and concomitant cognitive impairment.