Parkinson disease – Doctor Guidelines

Parkinson disease is a disorder characterized by dopamine depletion on the basal ganglia (striatum, pallidum, substancia nigra, subthalamic nucleus), which leads to dysfunction of the thalamus and motor cortex. As one could expect, Parkinson disease is the most common cause of parkinsonism (rest tremors, rigidity, bradykinesia, and postural instability). The prevalence is around 100-200/100.000 (0.3%) in the population over 40 years.

SIGNS & SYMPTOMS:

The cardinal feature of Parkinson disease is parkinsonism, which consists in:

Tremors: Rest tremor (coin-counting or pill-rolling) that is usually intermittent and initially starts in one side before becoming bilateral. It may affect other areas of the body (e.g. legs) and is exacerbated by stressful situations.
Bradykinesia: A state of generalized slowness of movement.
Rigidity: Usually starts in one side and it is characterized by increased resistance to passive movements.
Postural instability: It only appears later in the course of the disease. It is characterized by lack of balance and unsteadiness that creates a tendency to fall.

Other motor features may include hypomimia = masked facial expression, speech impairment, dysphagia, visual issues, micrographia, dystonia, and gait abnormalities (short-stepped gait, festination = quickening and shortening of normal strides, freezing).

In addition to the motor symptoms, patients may also have neuropsychiatric symptoms (cognitive dysfunction, mood disorders, sleep disorders, hallucinations) and other nonmotor manifestations (fatigue, GI dysfunction, autonomic dysfunction) later in the course of the disease.

DIAGNOSIS:

Parkinson disease is mostly a clinical diagnosis. A detailed history and physical examination should show the cardinal features of parkinsonism. The symptomatic improvement with dopamine agonists is also an important feature of the disease.

MRI of the brain may be useful to exclude another causes of parkinsonism. Striatal dopamine transporter imaging (DaTscan) may also be useful in patients with an unclear diagnosis.

The gold standard would be neurophatologic examination, although this is not routinely performed.

The diagnosis of clinically established PD requires all of the following:

The presence of parkinsonism (at least bradykinesia + rest tremor AND/OR rigidity).
No absolute exclusion criteria (cerebellar abnormalities, downward vertical supranuclear gaze palsy, frontotemporal dementia, parkinsonism restricted to lower limbs, parkinsonism caused by medications, no response to levodopa, normal functional neuroimaging of the dopaminergic system, other condition that can cause parkinsonism).
At least two supportive criteria (clear response to dopaminergic therapy, rest tremor of a limb, presence of olfatory loss or cardiac sympathetic denervation, presence of levodopa-induced dyskinesia).
No red flags (rapid progression of gait impairment, absence of progression of motor symptoms over 5 years or more, early bulbar dysfunction = speech impairment, dysphagia, inspiratory dysfunction, recurrent falls, absence of nonmotor features, pyramidal tract signs, bilateral and symmetric parkinsonism).

Differential diagnosis include: Lewy bodies dementia, essential tremors, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, frontotemporal dementia, secondary parkinsonism, among others.

TREATMENT:

The treatment is usually symptomatic and the disease progresses regardless of treatment.

Levodopa-carbidopa or dopamine agonists (bromocriptine, pramipexole, ropinirole, rotigotine or apomorphine) can be used initially and may reduce parkinsonism and improve quality of life. Dopamine agonists are preferred for patients <65 years and levodopa for patients > 65 years.

COMT inhibitors (tolcapone, entacapone) may be used together with levodopa.

Alternatives include MAO B inhibitors (selegiline, rasagiline) that may be taken alone early in the disease or together (with levodopa-carbidopa and/or dopamine agonists), anticholinergics (in patients without significant bradykinesia or gait disturbance), amantadine and estrogen.

Doses:

Carbidopa-levodopa (SINEMET) 12.5/50mg, 25/100mg or 50/200mg PO TID.
Bromocriptine (CYCLOSET, PARLODEL) 1.25mg-2.5mg PO BID.
Pramipexole (MIRAPEX) 0.125mg PO TID.
Apomorphine 2mg SC.
Selegiline (ELDEPRYL) 5mg PO BID.
Rasagiline (AZILECT) 1mg PO daily.
Trihexyphenidyl 0.5-1mg BID.
Benztropine (COGENTIN) 0.5-2mg BID.
Amantadine 200-300mg daily.
Tolcapone (TASMAR) 100mg PO TID.
Entacapone (COMTAM) 200mg PO with every dose of levodopa

SOURCES & FURTHER READING: