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
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Parkinson’s disease (PD) is the most common neurodegenerative cause of parkinsonism, a clinical syndrome characterized by lesions in the basal ganglia, predominantly in the substantia nigra. PD makes up approximately 80% of cases of parkinsonism.
As a rule, PD begins between the ages of 40 and 70 years, with peak age onset in the seventh decade. The prevalence of PD is approximately 160 cases per 100,000 population, and the incidence is about 20 cases per 100,000 population. The pathological changes of PD may appear as early as three decades before the appearance of clinical signs. The cause of PD is probably multifactorial, with contributions from hereditary predisposition, environmental toxins, and aging.
Several studies have indicated that PD is more common among relatives of index cases. When all studies are analyzed, first degree relatives of probands are two to three times more likely to develop PD.
The primary lesion of PD is degeneration of the neuromelanin-containing neurons in the brainstem, particularly those in the pars compacta of the substantia nigra. The cardinal motor signs and symptoms of PD, include the characteristic clinical picture of resting tremor, rigidity, akinesia, and impairment of postural reflexes. It evolves slowly. Although preclinical detection of PD have been investigated, a practical, inexpensive, sensitive and specific screening test has yet to be made available.
Furthermore, in the absence of a disease-specific biologic marker, a definitive diagnosis of PD can be made only at autopsy by the presence of specific neuropathological findings including Lewy bodies. The pharmacologic /surgical treatment of PD can be divided into three major conceptual categories: symptomatic, protective, restorative. Although the goal of therapy is to reverse the functional disability, abolition of all symptoms and signs is not currently possible even with high doses of medication.
Before the introduction of levodopa, PD caused severe disability in 16% of patients within five years of onset, in 37% during the next five years, and in 42% of those surviving for 15 years. The introduction of levodopa has been considered one of the success stories of modern medicine. It remains the most effecacious drug available for the relief of symptoms in PD since its first introduction in the 1960s.
The drug has produced dramatic results even in severely affected patients. However, complications of chronic therapy soon became apparent. Superimposed upon the disease-related problems are the additional burden of motor fluctuations (the “on-off” reaction), dyskinesias, and visual hallucinations. Other different pharmacologic advances during the last three decades have significantly augmented the antiparkinson armamentarium: dopamine agonist, inhibitors of catechol-0-menthyltransferase (COMT), monoamine oxidase type B (MAO-B) inhibitors
The dementia associated with PD has been estimated to affect at least 20% of patients, with prevalence higher among older patients, less common among those with young-onset disease. An estimated 40% to 60% of PD patients suffer from depression, which appears to be related to duration of disease. Psychiatric adverse effects are much more likely to occur in patients with predisposing characteristics such as: dementia, advanced age, premorbid psychiatric illness and exposure to high daily doses of levodopa.
A wide variety of neurosurgical operations have been proposed over the years for the treatment of PD. Currently the most popular techniques are: pallidotomy, chronic deep-brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (Gpi) using an implantable pulse generator (IPG).
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.