Parkinson's Disease & Parkinsonism

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.

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
 

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.

Contributed by David John Burn, MD, FRCP, Professor, Clinical Ageing Reserach Unit, Campus for Ageing and Vitality, Newcastle University, Newcastle Upon Tyne, UK
 

According to predominance of parkinsonian or cerebellar symptoms patients are classified into subtype MSA-P or MSA-C, respectively. Mean age at motor symptom onset is 56.2 ± 8.4 years with no difference in sex distribution, and median survival is 6 to 10 years (9.8 years). Prior to motor symptom onset 20-75% of patients experience a prodromal phase which lasts from several months to years and is characterized by autonomic failure affecting cardiovascular, respiratory, urogenital, gastrointestinal, and sudomotor functions. In addition, rapid eye movement sleep behavior disorder (RBD) is frequently observed in the premotor stage of α-synucleinopathies with more than half of patients reporting RBD prior to motor onset and is present in up to 88% of patients diagnosed with probable MSA. To date, the etiology of MSA is still elusive, yet a complex interaction incorporating genetic predisposition and environmental factors is suggested to drive disease initiation and progression, as familial aggregation following an autosomal dominant or recessive inheritance pattern has been reported in several European and Japanese families. Nevertheless, MSA is largely considered to occur sporadically.

Currently, treatment options focus on specific signs and symptoms, and include medications to raise blood pressure or to reduce signs of Parkinsonism (transient response rate for 1-3 years in 38%), impotence drugs, bladder care, physiotherapy and speech therapy.

Authored by Gregor Wenning, MD, PhD, Professor of Clinical Neurbiology, Medical University of Innsbruck, Austria (July 2019)

There are numerous causes of CBS. The most common cause is corticobasal degeneration (CBD), a 4-repeat (4R) tauopathy. The differential diagnosis includes progressive supranuclear palsy (PSP), Alzheimer's disease and frontotemporal lobar degeneration (FTD) with TDP-43 inclusions, which may clinically also present as CBS. Most CBS cases occur sporadically, but familial CBS has been observed. In the latter, progranulin gene (GRN) mutations are the most common cause of familial CBS. Globally, progranulin mutations are exceedingly rare. Treatment for CBS remains symptomatic with a growing number of clinical trials focusing on this condition.

Authored by Giorgia Sciacca, MD, PhD, University of Catania, Catania, Italy (May 2026)