Parkinson Disease Pathophysiology

Parkinson Disease: Pathophysiology

• Basal ganglia control movement by regulating inhibitory and excitatory stimuli
• Basal ganglia include functionally associated structures like the striatum (caudate nucleus and putamen), globus pallidus interna, subthalamic nucleus, and substantia nigra.
• Substantia nigra is a midbrain structure.
• Substantia nigra cells appear dark due to melanin pigment.
• Substantia nigra cells secrete dopamine.
• Neurons in the substantia nigra and locus ceruleus are heavily pigmented with neuromelanin.
• Dopamine deficiency is a key feature of Parkinson's disease.

Parkinson Disease: Pathophysiology (Continued)

• The nigrostriatal pathway is critical for movement control.
• The pathway degenerates in Parkinson's disease, resulting in decreased dopamine levels.
• Dysfunction in this pathway leads to dopamine deficiency, which causes the motor symptoms associated with Parkinson's disease.
• Lewy body formation is seen in neurons not receiving enough dopamine.
• Lewy bodies are abnormal protein clumps associated with Parkinson's and related diseases.
• These Lewy bodies form from misfolded proteins, including alpha-synuclein.
• Genetic predisposition accounts for approximately 15% of Parkinson's disease cases.
• The condition may be influenced by oxidative stress, mitochondrial dysfunction, loss of nerve growth factors, and apoptosis (cell death).

Parkinson Disease: Clinical Manifestations

• Early neural degeneration occurs before the onset of visible symptoms, called the preclinical period.
• The four primary symptoms are tremor, rigidity, akinesia/bradykinesia, and postural instability.
• Tremor involves involuntary shaking, often in one limb first and sometimes in the head.
• Rigidity is muscle stiffness that makes movement difficult.
• Akinesia or bradykinesia is slow movement or difficulty initiating movement.
• Postural instability results in balance issues and a shuffling gait.
• Parkinson's disease also affects posture to the point where the person bends forward.
• Additional symptoms include impaired speech, decreased mobility in facial features, difficulties chewing and swallowing leading to pneumonia as a possible cause of death.

Parkinson Disease: Clinical Manifestations (Continued)

• Common indirect manifestations stem from basal ganglia influence on autonomic functions.
• Examples include increased sebaceous, sweat, and saliva secretions; altered blood pressure; impaired thermal regulation; constipation; incontinence; impotence; cognitive changes (including dementia).

Parkinson Disease: Diagnosis

• Diagnosis relies on clinical evaluation, including a neurological exam and assessing psychological aspects.
• The Hoehn and Yahr rating scale is used to stage progression and severity of the disorder.
• The scale is a series of stages with symptoms increasing in severity.
• Parkinson's disease has no single definitive diagnostic test.

Parkinson Disease: Treatment

• The initial approach to Parkinson's disease treatment involves medication that aims to increase dopamine levels in the brain.
• Dopamine precursors (like L-dopa), dopamine agonists (that stimulate dopamine receptors), and other therapies are considered.
• In later stages, if medication isn't effective enough, surgery like pallidotomy (destruction of globus pallidus to decrease nerve firing) or deep brain stimulation (to alter abnormal brain function) might be considered.
• Deep brain stimulation involves inserting a neurostimulator and delivering electrical signals to specific targeted brain areas.
• Location for deep brain stimulation is identified by methods such as MRI and CT scans.