Mostly the brain disorders are occur due to deficiency of neurons or neurotransmitters or may be due to the some neurons in the grain loss their activity. The diseases are called in the medical science as ‘Neurodegenerative Diseases’. Neurodegenerative diseases of the CNS (Central Nervous System) include Alzheimer’s disease. Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. The first three diseases are named on the names of the scientists discovered them or prepared their management and treatment. These devastating illnesses are characterized by the progressive loss of selective neurons in discrete areas of brain areas, resulting in characteristic disorders of movement, cognition, or both. But in this article I would like to discuss about the Parkinson’s disease.
Parkinson’s disease is characterized by the tremors at rest, muscle rigidity, bradykinesia, and slowness in the movements, gait abnormalities, and postural imbalance. Parkinson’s disease is usually associated with the loss or extreme deficiency of dopamine neurons in the very small area of the known as substantia nigra. This condition or phenomenon in the medical world is known as Parkinsonism. Most cases of Parkinsonism are seen in the old ages, usually of the people of age over 65 years. It is estimated that over 100% patients are present in the UK of Parkinson’s disease.
The real cause of the Parkinson’s disease is unknown for almost every patient. The disease is correlated with the destruction of the dopamine neurons in the substantia nigra which results in the consequent reduction of dopamine action in the nearly areas especially in the corpus striatum (parts of the brain’s basal ganglia system that are involved in the motor control. This deficiency of the important neurotransmitters can be visualized by the positron-emission tomography. When the question is asked by the patients or layman, the some doctors confuse but the answer of this question is very easy that is No, the Parkinson’s disease is not a genetic disease. Although some evidences are seen in some part of the world where this disease run in family, but most doctors and physicians say that is not the case with the Parkinson’s disease. It appears increasingly likely that an as yet un-identified environmental factor may play a role in the loss of dopaminergic neurons. The most important challenge in the Parkinson’s disease is the find the real cause of the disease. The symptoms of Parkinson’s disease started very slowly, so slowly that most of times the people cannot identify the exact time when the symptoms started. They come to know very late when the damage reaches on the extreme high stages. That is why the Parkinson’s disease is one of those diseases which are very difficult to cure, according to some of the scientists of UK (where this disease is more common than in any other part of the world) and of America that the Parkinson’s disease can only be controlled not cured or treated completely. Secondary symptoms of Parkinson’s disease are constipation, difficulty in swallowing, choking cough, excessive salvation (drooling), bladder and bowel control is diminished, anxiety, depression, soft whispered voice, slow response to question, small and crumbled hand writing (which started normally and goes on decreasing towards end).
STAGES OF PARKINSON’S DISEASE
There are five stages of Parkinson’s disease. These stages are very important for the diagnosis of the disease and for the treatment of the disease. By knowing these five stages a doctor can easy to prescribe the medicine and to advise the important guidelines during the treatment of disease. The five stages are following:
ZERO STAGE: In this stage no clinical sins and symptoms are evidenced.
STAGE І: At this stage unilateral involvement of the body is evidenced, including major features of tremors, rigidity or bradykinesia, and minimal functional impairment. But there is no postural imbalance evidenced.
STAGE ІІ: At this stage bilateral involvement of the body occurs but still no evidence of postural imbalance or abnormalities can be seen.
STAGE ІІІ: In this stage of disease along with the bilateral rigidity of the muscles of the body, there is little bit postural imbalance is also evidenced. But the patient has still the ability to function properly.
STAGE ІV: In this stage of Parkinson’s disease the patient lose most of his or her control over the muscle movement and postural instability is also increased.
STAGE V: This is the stage of the disease where the disease is at its severe condition. Patient is restricted to bed and he or she needed complete and 24 hour assistance.
PATHOPHYSIOLOGY OF THE PARKINSON’S DISEASE
Parts of the brain whose pathological conditions involved in the Parkinson’s disease are the following:
Substantia nigra: The substantia nigra, part of the extrapyrimidal system, is the source of dopaminergic neuron, is the source of dopaminergic neurons that terminate in the striatum. Each of dopaminergic neuron makes thousands of synaptic contacts within the neo-stratum and, therefore, modulates the activity of a large number of cells. These dopaminergic projections from the substantia nigra fire tonically rather than in response to specific muscular movements or sensory input. Thus, the dopaminergic system appears to sever as a tonic, sustaining influence on motor activity rather than participating in specific movements.
Neostriatum: Normally, the neostriatum is connected to the substantia nigra by neurons that secrete the inhibitory transmitter GABA at their termini in the substantia nigra. In turn, cells of the substantia nigra send neurons back to the neostriatum, secreting the inhibitory transmitter dopamine at their termini. This mutual inhibitory pathway normally maintains a degree of inhibition of two separate areas. In Parkinson’s disease, destruction of cells in the substantia nigra results in the degeneration of the nerve terminals responsible for secreting dopamine in the neostriatum. Thus, the normal modulating inhibitory influence of dopamine on cholinergic neurons in the neostriatum is significantly diminished, resulting in overproduction or a relative over activity of acetylcholine by the stimulatory neurons. This triggers a chain of abnormal signaling, resulting in loss of the control of muscle movements.
Parkinson’s disease symptoms infrequently follow viral encephalitis or multiple small vascular lesions. Drugs such as the phenothiazines and haloperidol, whose major pharmacologic action is the blockade of dopamine receptors in the brain, may also produce Parkinsonian symptoms. These drugs should not be used in Parkinsonian patients.
STRATEGY OF TREATMENT
In addition to an abundance of inhibitory dopaminergic neurons, the neostriatum is also rich in excitatory cholinergic neurons that oppose the action of dopamine. Many of the symptoms of Parkinsonism reflect an imbalance between the excitatory cholinergic neurons and the greatly diminished number of inhibitory dopaminergic neurons. Therapy is aimed at restoring dopamine in the basal ganglia and antagonizing the excitatory effect of cholinergic neurons, thus reestablishing the correct dopamine – acetylcholine balance. Because long term treatment with levodopa is limited by fluctuations in therapeutic responses, strategies to maintain CNS dopamine levels as constant as possible have been devised.
Ali Aun
BPD-01091006
Doctor of Pharmacy
Universty of Lahore