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Neurology

Parkinson's Disease

Parkinson’s disease is a progressive (chronic) nervous system disorder that occurs as a result of the loss of cells in the brain responsible for movement control. It is generally seen in middle and advanced ages.

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ℹWhat is Parkinson's Disease?

Cells in the region of our brain called the "substantia nigra" produce Dopamine, which ensures that our movements are fluid and coordinated. In Parkinson’s disease, these cells decrease, and since sufficient Dopamine cannot be produced, the body’s movement mechanism is disrupted.

By the time symptoms of the disease appear, approximately 70-80% of the Dopamine-producing cells in this region have already been lost. Additionally, nerve endings that produce the neurotransmitter Norepinephrine are also lost, which explains non-movement-related symptoms such as fatigue and changes in blood pressure.

Deposits of alpha-synuclein protein, known as Lewy bodies, are found in the brain cells of affected individuals.

Common Symptoms

Tremor
Often starts in the hand. A rhythmic, back-and-forth "pill-rolling" appearance. It becomes more pronounced at rest and under stress.
Rigidity
Resistance to movement and stiffness in muscles. It creates a feeling of pain and tightness.
Bradykinesia
The slowing of spontaneous movements. Facial expressions may decrease ("masked face").
Postural Instability
Balance problems, leaning forward, walking with small and fast steps (Festination). The risk of falling increases.
Depression and Anxiety
May appear in early stages, even before motor problems begin.
Swallowing and Speech Difficulty
In advanced stages, problems with swallowing and chewing, and changes in speech may develop.
Autonomic Dysfunction
Urinary problems, constipation, orthostatic hypotension, and sleep problems may occur.

Diagnosis Methods

Detailed Medical History and Neurological Examination
Many movement disorders specific to the disease and other symptoms are evaluated.
UPDRS Scale
Motor skills and activities of daily living are scored using the Unified Parkinson’s Disease Rating Scale.
Levodopa Test
Medication containing Dopamine is administered; improvement in motor symptoms strongly supports a Parkinson’s diagnosis.
Brain Imaging (SPECT, MRI)
Used to exclude other conditions that may lead to similar symptoms.
DaT Scan
The density of dopamine cells in the brain is measured with a Dopamine Active Transporter scan.
Alpha-Synuclein Amplification Assay (SAA)
Can detect abnormal alpha-synuclein in the cerebrospinal fluid, even in individuals who have not yet been diagnosed.

Causes

SNCA Gene
Encodes the alpha-synuclein protein; the first gene identified as associated with Parkinson's disease.
LRRK2 Gene
Encodes a complex protein called dardarin. Its activity may also be increased in sporadic Parkinson's disease.
PRKN (Parkin) Gene
Produces a protein that helps cells break down and recycle other proteins. Mutations can cause early-onset Parkinson's disease.
PINK1 Gene
Encodes a protein active in mitochondria. Linked to early-onset forms of the disease.
GBA (Glucocerebrosidase-beta) Gene
Mutations are associated with increased risk of developing Parkinson's disease and more rapid disease progression.

Treatments

Carbidopa-Levodopa
The cornerstone of Parkinson's treatment. Crosses the blood-brain barrier and is converted to dopamine. Reduces motor symptoms.
Dopamine Agonists
Mimic dopamine activity in the brain. Apomorphine, Pramipexole, Ropinirole, and Rotigotine.
MAO-B Inhibitors
Block the MAO-B enzyme that breaks down dopamine. Selegiline and Rasagiline.
COMT Inhibitors
Prolong the effect of Levodopa by preventing the breakdown of dopamine. Entacapone, Opicapone, and Tolcapone.
Deep Brain Stimulation (DBS)
Painlessly stimulates the brain via an electrode surgically placed in the subthalamic nucleus or the globus pallidus. It is considered for patients for whom medication is insufficient.
Lesion Surgery (Pallidotomy)
Tremor, rigidity, and bradykinesia are corrected by the selective destruction of the globus pallidus section of the brain.
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