1. Parkinson’s disease Dartington 26 June 2003
What is Parkinson's disease? 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 (bradykinesia).

2. What causes Parkinson's disease?
It is caused by the progressive loss of neurones in the substantia nigra, which produces the chemical dopamine. As the cells die, less dopamine is produced and transported to the striatum (co-ordinates movement). Parkinson's sufferers may also lack other brain chemicals including serotonin (linked to mood), noradrenaline (linked to blood pressure control) and acetylcholine (linked to mental state).

3. Who is affected?
Parkinson's affects ,000 new people in the UK each year.
On average one person in every 500 is affected by Parkinson's disease.
Most patients are over 40 and it very rarely affects people below this age (only 5 per cent).
The risk rises so that by the age of 80 more than two people per 100 of the population have developed some signs of the condition.

4. The main symptoms of Parkinson's are:
What are the symptoms?
The main symptoms of Parkinson's are:
tremor, usually while resting. stiffness and muscle cramps (rigidity), particularly affecting the arm, leg and neck. slowness in initiating movement (bradykinesia) Poor balance and unstable walking (shuffling, difficulty in turning, falls).

5. Other symptoms include:
expressionless face reduced manual dexterity handwriting difficulties drooling sleep problems urination at night depression and anxiety constipation difficulty in turning in bed at night.

6. How does the disease progress?
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.

7. How is a diagnosis made?

8. Differential diagnoses
Multi-system atrophy (MSA), corticobasal degeneration (CBD), vascular pseudo-parkinsonism and progressive supranuclear palsy (PSP), diffuse Lewy Body disease, may all appear similar to Parkinson's disease. Where tremor is the main symptom, Parkinson's may be confused with essential tremor (ET). In this condition, tremors occur during activity rather than during rest.
Several medications may also cause symptoms similar to Parkinson's (antipsychotics and anti-emetics).

9. Treatment
Levodopa Levodopa remains the 'gold-standard' treatment for Parkinson's. Most patients notice an improvement almost immediately. Short-term side effects are uncommon but include nausea, hallucinations, tiredness and light-headedness. Virtually all patients suffer long-term complications, with about per cent on the drug for 5-10 years developing abnormal excessive and involuntary movements called dyskinesias.

10. Dopamine agonists
These drugs include bromocriptine, lisuride, pergolide, cabergoline, ropinirole, pramipexole and apomorphine. They are less effective at controlling symptoms than levodopa, particularly in advanced Parkinson's disease. Patients are advised to take an anti-sickness tablet (domperidone) for at least the first two weeks of treatment.
The side effects of dopamine agonists are similar to levodopa although nausea and mental problems such as hallucinations usually occur more often.

11. Apomorphine
Usually administered under the skin by injection or via an infusion pump over 12, 18 or 24 hours.
The main side effects are the formation of skin nodules, nausea, yawning and drowsiness. Apomorphine is usually reserved for patients in whom oral treatment is no longer effective.

12. COMT inhibitors
Catechol-O-methyl-transferase (COMT) prolongs the beneficial effect of levodopa. Two COMT inhibitors exist, tolcapone and entacapone. However, tolcapone is not in use in many countries including the UK as it may rarely cause severe liver toxicity. Entacapone is available in the UK and is usually used when the effect of levodopa starts wearing off.

13. Other drugs I Selegiline 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.

14. Other drugs II Amantadine Amantadine 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 livido reticularis.

15. Other drugs III Anticholinergics Common anticholinergics include benzhexol, procyclidine, benzatropine, orphenadrine and biperiden. Used with levodopa therapy, they can help control resting tremor and dystonia. 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 glaucoma.

16. Other non-drug treatment
Physiotherapy 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.

17. Surgery
Brain surgery, to the pallidum, the thalamus, and sub-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.

18. Pallidotomy
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.

19. Subthalamic deep brain stimulation
This operation involves putting an electrode into 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 nucleii, unlike pallidotomy.

20. The benefits of deep brain stimulation include the fact it is not necessary to make a lesion 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.

21. Diagnostic red flags for IPD?

22. Diagnostic red flags for IPD
Lack of tremor (PRRT)
Symmetry
Early balance problems
Early cognitive problems
Dopa unresponsiveness
Pyramidal or cerebellar signs
Supranuclear gaze palsies

23. Elderly Younger Intermediate When Specialist referral?
Treatment decisions
Elderly
Younger
Intermediate
When Specialist referral?

25. The confused PD patient on multiple medications

26. Parkinson’s specialist nurses Plymouth Cory Wroath Torbay Andrea Ford

27. Dementia
The development of multiple cognitive deficits that include memory impairment and at least one of the following:
Aphasia Apraxia Agnosia
Disturbance in executive functioning

28. Differential Diagnosis
Alzheimer’s Disease
Parkinson’s Plus Synd. - CLBD/PSPCBD
FTLD
Vascular Dementia
Prion disease
Others – MS/NPH/Whipple’s

29. Investigations for dementia
Bloods
Neuropsychometry incl MMTS
Neuroimaging
EEG
?LP
Longitudinal assessment