Treatment Slides

PARKINSON'S DISEASE-

In 1817, James Parkinson, a British physician, reported on several patients with a condition now recognized as Parkinson's disease. In his monograph titled "An Essay On The Shaking Palsy" he gave an account of the major symptoms of the disease that would later bear his name. Over the next one hundred years, there was little advancement in the understanding of this disease, although the prominent French neurologist Jean Martin Charcot elaborated on Parkinson's clinical report and actually named the disease after James Parkinson. In the early 1900s, the pathology of the disease was identified, yet; it was not until the mid 1950s that a scientific breakthrough emerged with the suggestion by the Swedish neuroscientist, Arvid Carlsson that patients with Parkinson's disease suffered a deficiency of dopamine in a certain region of the brain called the striatum. This speculation was quickly confirmed by two Viennese neuroscientists leading to the first of several trials of the dopamine precursor levodopa, the active ingredient in Sinemet®, one of the most effective drugs used to treat the disease.

The Clinical Features of Parkinson's Disease?
Being Diagnosed with Early Symptoms

Prior to the diagnosis of Parkinson's disease, a person may begin to feel a drop in energy or a loss of coordination. Several symptoms such as impaired handwriting, reduced arm swing, a "limp" or tremor may begin to emerge on one side of the body. Other early symptoms may include internal shakiness, difficulty getting out of a chair, a soft voice and/or depression. These symptoms evolve gradually and may even be imperceptible to the patient or family members until a physically or emotionally stressful event occurs, triggering an exacerbation of these symptoms.
Disease Progression

Progression of Parkinson's disease is highly variable, although progression may be relatively slower in patients whose initial symptoms include tremor. Although the disease is invariably i progressive, the good news is that there are now a wide variety of very effective medications for the disease and surgical therapy, including "deep brain stimulation," has been shown to provide benefit in selected patients who have lost effi medications alone. When the disease is fully expressed, the major clinical features include bradykinesia (slow movement), tremor (typically at rest and extinguished with movement), rigidity (a clinical finding of resistance to movement, often associated with a jerky sensation called cogwheeling) and impaired postual reflexes (poor balance).

Treatments

1. Medication Lev-Dopa

Levodopa is a dopamine precursor, a substance that is transformed into dopamine by the brain. The prescription of high dosages of levodopa was the first dramatic brethrough in the treatment of PD. Unfortunately, patients experienced debilitating side effects, including severe nausea and vomiting.

Levodopa/carbidopa (Sinemet) represented a significant improvement. The addition of carbidopa prevents levodopa from being metabolized in the gut, liver and other tisues, and allows more of it to get to the brain. Therefore, a smaller dose of levodopa is needed to treat symptoms, and the unpleasant side effects are greatly reduced.

Symmetrel (amantadine hydrochloride), originally an anti-flu medication, is though to work in PD by either blocking the reuptake of dopamine or by increasing the release of dopamine by neurons, thereby increasing the supply of dopamine in the synapses. It is thus called an indirect-acting dopamine agonist, and is widely used as an early monotherapy, with the more powerful Sinemet added when needed. When its benefits seem to lessen, stopping the drug for a short period and then reintroducing it seems to again provide efficacy, according to some clinicians
Anticholinergics (trihexyphenidyl, benztropine mesylate, procyclidine, etc.) do not act directly on the dopaminergic system. Instead they act to decrease the activity of the balancing neurotransmitter, acetylcholine. Since it is known that PD relates primarily to decreased activity of dopamine, one avenue of treatment has been to decrease the cholinergic system to equal that of the dopaminergic system. Most effective in the control of tremor, these drugs may be contraindicated in certain older patients since they tend to cause confusion and hallucination.
Selegiline or deprenyl (Eldepryl) has been shown to delay the need for Sinemet when prescribed in the earliest stage of PD, and has also been approved for use in later stages to boost the effects of Sinemet.

Dopamine agonists are drugs that activate the dopamine receptor directly, and can be taken alone or in combination with Sinemet. Agonists available in the United States include bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex) andropinirole (Requip).

COMT inhibitors such as tolcapone (Tasmar) and entacapone (Comtan), represent a new class of Parkinson's medications. These drugs must be taken with levodopa. They prolong the duration of symptom relief by blocking the action of an enzyme which breaks down levodopa before it reaches the brain.

Side effects from medications

Like the symptoms of PD itself, the side effects caused by Parkinson's medications vary from patient to patient. They may include dry mouth, nausea, dizziness, confusion, hallucinations, drowsiness, insomnia, and other unwelcome symptoms. Some patients experience no side effects from a drug, while others have to discontinue its use because of them.

2. Surgical

i. Thalamotomy
ii. Pallidotomy
iii. Deep Brain Stimulation
iv. Gamma Knife Radiosurgery

Surgical interventions

Thanlamotomy & Pallidotomy: This procedure has a long history in the treatment of Parkinson's disease, but it fell out of favor with the advent of levodopa. In recent years it has gained new popularity, mainly because magnetic imaging now allows it to be performed with far greater precision. Thalamotomy is more effective in controlling tremor. Pallidotomy is indicated for patients who have developed dyskinetic movements in reaction to their medications. It targets the source of these unwanted movements, the globus pallidus, and uses an electrode to destroy the trouble-causing cells. As with any surgical procedure, there are risks involved. The most serious is the possibility of stroke; other risks include partial loss of vision, speech and swallowing difficulties, and confusion.

Brain tissue transplants: Although they have produced encouraging results, transplantation surgeries are still in the experimental stage. The experiments began with fetal tissue, but now scientists are also working with genetically engineered cells and a variety of animal cells that can be made to produce dopamine.

Deep brain stimulation: Like pallidotomy, this technique also seeks to stop uncontrollable movements. It is based on the technology of cardiac pacemakers. Electrodes are implanted in the thalamus or globus pallidus and connected to a pacemaker-like device, which the patient can switch on or off as symptoms dictate.

Gamma Knife Radiosurgery : This is equaly effective as any other surgical procedure. Indiactions remain same . Here a pallidotomyof thalamotoy is made using focussed gamma radioation without any physiological control. It need high resolution MRI for localization of target.

Comparison

Gamma knife is a safe treatmetn modality as comapred to other surgical treatments for Parkinson's disease, as it is totay non invasive. ther eis no stitichinf wound care or after care in hospital. There is no risk of intracranial bleed, infection and direct damage to surrounding structures. There are no implats which need repalcment of battereis in long run and also does not prevent pateitn from taking MRI imaging in future.