- Mar 30, 2007
Parkinson's disease is a degenerative disease of the nervous system associated with trembling of the arms and legs, stiffness and rigidity of the muscles and slowness of movement
It is caused by the progressive loss neurones in a part of the brain called the substantia nigra, which produces the chemical dopamine.
As the cells die, less dopamine is produced and transported to the striatum, the area of the brain that co-ordinates movement.
Parkinson's patients may also lack other brain chemicals including serotonin (linked to mood), noradrenaline (linked to blood pressure control) and acetylcholine (linked to mental state).
tremor, usually while resting.
- stiffness and muscle cramps known as rigidity, particularly affecting the arm, leg and neck.
- slowness in initiating movement known as bradykinesia.
- poor balance and unstable walking (shuffling, difficulty in turning, falls).
- expressionless face
- reduced manual dexterity
- handwriting difficulties
- sleep problems
- urination at night
The onset of symptoms is slow and may go unnoticed for several years. Early signs include stiffness of fingers or a stiff shoulder accompanied by stiffness of muscles. Pain may be a feature.
Symptoms usually only affect one side of the body for one to two years and then spread to the other. Tremor is often noticed first and usually provokes a visit to the doctor. However, up to 30 per cent of sufferers may not have tremor, which can lead to misdiagnosis.
Parkinson's is incurable but the symptoms can be controlled for many years. Treatment is primarily based on dopamine replacement using dopamine-enhancing drugs such as levodopa. This improves disability in most patients and reduces the risk of fatal complications.
Levodopa) probably remains the 'gold-standard' treatment for Parkinson's although recent evidence suggests that levodopa is responsible for many long-term side effects seen in Parkinson's. Most patients notice an improvement almost immediately although some may not for months or years.
Short-term side effects are uncommon but include nausea, hallucinations, tiredness and light-headedness. Virtually all patients suffer long-term complications, with about 50 to 75 per cent on the drug for 5 to 10 years developing abnormal excessive and involuntary movements called dyskinesias. The short half-life of levodopa (1.5 hrs) is implicated in the development of disabling dyskinesias.
Dopamine agonists work by directly stimulating the dopamine receptors to bypass the degenerating brain cells. The side effects of dopamine agonists are similar to levodopa although nausea and mental problems such as hallucinations usually occur more often.
Recently, clinical studies have shown that in early untreated Parkinson's, initiation of treatment with a dopamine agonists such as ropinirole, canergoline, pramipexole or pergolide reduces the chance of dyskinesias (normally caused by levodopa therapy) by about 50 per cent.
These observations suggest that there may be strong consideration for starting treatment with a dopamine agonist in younger parkinson's patients till levodopa is required. The long half-life of drugs such as cabergoline suggest that this may be an useful treatment for night-time problems faced by many patients with Parkinson's.
Catechol-O-methyl-transferase (COMT) prolongs the beneficial effect of levodopa. However, tolcapone is not in use in many countries as it may rarely cause severe liver toxicity. Entacapone is usually used in the early stages of Parkinson's when the effect of levodopa starts wearing off.
A report by the Parkinson's Disease Research Group of the UK suggested a 60 per cent increase in mortality among patients treated over a long period of time with selegiline. This has not been found in other studies and a recent study from Scotland has suggested that selegiline therapy does not increase mortality in Parkinson's.
Side effects include hallucinations, sleep disorder, agitation, postural hypotension (a drop in blood pressure on standing) and problems associated with the withdrawal of the medicine.
is a mild antiviral agent and used in young patients to delay the need to use levodopa. In high doses, amantadine can act as an anti-dyskinetic drug. Amantadine can cause visual hallucinations, confusion and agitation. It should be given as a single dose in the morning to prevent sleep problems. It can cause a specific discolouration of the legs (livido reticularis).
Common anticholinergics used with levodopa therapy, they can help control resting tremor and abnormalities of posture.
In older patients they may cause confusion and aggravate dementia. Other side effects include difficulty in passing urine, constipation, blurred vision, dry mouth and the onset of narrow angle glucoma
Anticholinergics are rarely used in Parkinson's treatment.
Other drugs in development
Many drugs are being developed for treatment of Parkinson's disease. Some of these drugs spare dopamine and work on different brain chemicals. Examples are riluzole, adenosine antagonists, canabinoids and neuroimmunophilins. Some drugs are being developed so that they can be adminstered in the form of a skin patch.
Other non-drug treatment
Counselling, physiotherapy (aerobic exercise) and speech therapy can also help patients to manage their symptoms and enjoy a better quality of life. A dietitian can also advise on better nutrition to avoid constipation. Depression, sleep problems and urinary difficulties are common in Parkinson's and may need specific treatment.
Brain surgery, to structures deep within the brain known as the pallidum and the thalamus, has been shown to reduce symptoms in some patients. Operations may involve lesioning (destroying cells in a target area by burning a hole), stimulation (electrically stimulating cells using a pacemaker) or transplantation.
In this operation a group of nerve cells in the pallidum are destroyed. It is particularly effective for treating involuntary movements (dyskinesias) and is relatively widely available. However, operations on both pallidum may cause severe side effects such inability to speak properly and memory difficulties.
Subthalamic nucleus deep brain stimulation
This operation involves putting an electrode into a specific cluster of nerve cells in an area known as the subthalamic nucleus. The stimulation can be controlled by the patient using a switch that can turn the stimulator 'on' or 'off'. This operation is effective at controlling all the features of Parkinson's but the procedure is complex. Operation can be safely performed on both subthlamic nucleus unlike pallidotomy.
Pallidal deep brain stimulation
Like subthalamic nucleus deep brain stimulation, this operation involves putting an electrode into a specific (but different) cluster of nerve cells. However, its effects are closer to that of pallidotomy in that it is particularly effective for dyskinesias.
The benefits of deep brain stimulation include the fact it is not necessary to make a lesion (burn a hole) in the target and stimulation can be adjusted if necessary. However, the pacemaker battery has to be replaced under anaesthetic and the procedure is extremely expensive and is only available at some regional centres in the UK.
Researchers have found that tissue from a foetus can survive being transplanted into adult brain cells that have died as a result of Parkinson's disease. However, this procedure remains experimental and controversial. A recent study form the US suggested that transplanted Parkinson's patients may sometimes develop a disabling 'runaway' dyskinesias possibly due to overgrowth of grafts. However, the Swedish experience is more positive and they have shown that properly harvested and implanted grafts can survive within the brain and establish connections with surviving cells.
Transplantation therefore, holds hope for the future. Furthermore, in future transplantation may be attempted using neural stem cell or growth factors which enhance nerve cell growth. The experience from the US, however, highlights the dangers of performing clinical trails before extensive experimental studies are undertaken.