Understanding Parkinson's Disease: Neurological Underpinnings, Symptomatology, and Treatment Modalities

 

Parkinson’s Disease (PD) is the second most common neurological disease after Alzheimer’s because of the changing demographics. It is a neurodegenerative disease that affects humans in the later stages of their life. The formation of Lewy body, an abnormal proteinaceous spherical body and Lewy neurites, spindle-shaped in the initiation site of the affected neuron causes neuropathological changes. The PD has been categorized into 6 stages by Braak, pre-symptomatic stage (1-2), the affected cells are found in medulla oblongata and olfactory bulb, in stage 3-4, they progress to midbrain resulting in the onset of clinical symptoms, in stage 5-6, they further affect neocortex, damaging the dopaminergic neurons leading to motor and non-motor symptoms. 

 

There is no specific treatment for PD, but certain drugs can help with the symptoms of PD. Levodopa, monoamine oxidase type B inhibitors, catechol-O-methyltransferase inhibitors, the NMDA receptor antagonist amantadine and dopamine receptor agonists can be helpful with the characteristic symptoms and treatment of Parkinson’s Disease. When the drugs fail to treat the motor symptoms can be rectified by deep stimulation in the brain using surgical methods. 

80% of the dopamine neurons may have been lost before the initiation of motor symptoms in Parkinson’s disease. According to the criterias of UK PD Brain Bank the person should have a characteristic symptom, confirming unilateral symptom onset, asymmetry in symptoms, positive response to levodopa, and onset of dyskinesias with dopaminergic treatment. Bradykinesia in PG leads to stooped posture, stiffness in the body and limbs, reduced arm swing, and reduced facial expression, tremors in the limb on one-side and eventually the other side in the next few years resulting in gait.                         

PD also affects the postural stability of a person hence leading to abrupt falls. About 68% in 109 patients suffering from PD have experienced this symptom. Other symptoms include dementia, oral motor diseases like speech disturbances, swallowing issues. Dystonia, abnormal movement of muscles is a pre-diagnostic symptom, Parkinson’s disease may arise after 10 years of dystonia. It may also lead to postural deformities.

Lack of interest, depression, anxiety, sweating, fatigue, constipation, dream-enacting behaviors, frequent nightmares, daytime drowsiness and postprandial fullness are the pre non-motor symptoms. The non-motor symptoms are categorized into autonomic function, sleep disturbances, cognitive and psychiatric disturbances and sensory symptoms. The early symptoms can be urinary disturbances, dermatological problems like excess sweating, gastrointestinal issues, erectile dysfunction in male. 

Parkinson's disease is also known to affect the physiological sleep cycle. Polysomnographic indicates that the sleep cycle of a person with PD is disruptive than a normal person. Many sleep disorders like fractional sleep, excessive daytime sleep, REM behavior sleep disorder, restless leg syndrome, obstructive sleep apnoea, and sleep attacks are caused by Parkinson's disease. 

The neuropathological changes in the amygdala and hippocampus causes visual hallucinations and illusions, cognitive deterioration, visuospatial dysfunction, impaired speech fluency and memory impairment, depression and anxiety. Though it is known that anti-parkinsonian medications cause hallucinations, certain patients had reported hallucinations even before starting the drug therapy. The side effects of dopamine treatment may also induce dementia, euphoria, hypomania, hypersexuality, abnormal hoarding or punting, together known as dopamine dysregulation syndrome.

The progression of Parkinson's Disease varies in different patients. Only one side of the body is affected at the initial stage, as the disease advances both sides are affected, resulting in problems with walking, balance, speech, and swallowing. The treatments cannot be reliable as the disease advances. According to the study, a person lives only for 6.9 to 14.3 years after diagnosis, hence reducing the life expectancy of the person. They become untreatable and fatal in the advanced stages because of the difficulty to treat symptoms like dementia, cognitive decline, psychosis, and sleep disturbances. Though levodopa is a reliable drug for PD, it cannot cure non-motor symptoms. Hence new drug discovery for Parkinson’s disease is required in the contemporary world.

REFERENCE

Sveinbjornsdottir S. The clinical symptoms of Parkinson's disease. Journal of neurochemistry. 2016 Oct;139:318-24.

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