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The Onset of Parkinson's Disease & its Treatment

Dr Brian Sweeney, Consultant Neurologist, Cork University Hospital.

Parkinson's Disease (PD) was described by the London physician James Parkinson in 1817 in his monograph 'On The Shaking Palsy'. It is characterised by increasing tremor, slowness of movement (bradykinesia), rigidity and impaired balance. It affects up to 1% of the population over the age of 50. PD is associated with degeneration of the substantia nigra cells of the brain which reduces Dopamine levels in the brain. This degeneration/deficiency leads to the impairment of movement which is characteristic of the disease. Other diseases can mimic Parkinson's disease, for example in patients with exposure to anti-psychotic drugs or with other neurodegenerative diseases such as Multiple Systems Atrophy. These diseases can be considered when there is no response to appropriate medication or when the patient's course follows an atypical pattern. In this article I will deal predominantly with straightforward PD with the initial 'honeymoon' period where the patient is relatively well for the first few years then evolving into the more complex and difficult-to-manage later stages of the disease.

Drug treatments are effective at relieving the symptoms but do not prevent the progression of the disease. Ultimately many patients will experience major disabling symptoms which can prevent them from living independently. In this article I will deal briefly with the initial stages of PD when independence can be maintained and then concentrate on the problems that patients can experience in the later stages of the disease. It must be emphasised at the outset that physiotherapy, occupational therapy, speech and language therapy, urology and psychiatry have a major input into managing the later stages of PD. Newer options for PD treatment include surgical insertion of deep brain stimulators and ongoing work on nerve regeneration and transplantation. Unfortunately not all patients are suitable for these new treatments, particularly if cognitive impairment has developed.

The initial stages are characterised by a variety of well known phenomena including reduced facial expression ('mask-like' face), small handwriting (micrographia), flexed posture, reduced arm swing when walking, a coarse 'pill-rolling' tremor which is usually asymmetric and most evident when the limb is at rest or when the patient is concentrating on another task or when anxious, and rigidity on passively moving the limbs which is called 'cogwheel rigidity'.

Drugs used for the disease include L-DOPA containing drugs (Sinemet, Madopar, Stalevo); Dopamine agonists including Bromocriptine, Pergolide, Pramipexole, Ropinirole,Cabergoline, Apomorphine; Anti-cholinergics such as Artane; Amantidine; and the COMT-inhibitor Entacapone.

L-DOPA is a precursor of Dopamine which can cross from the circulation into the brain and is metabolised into Dopamine in the substantia nigra. The drugs which contain L-DOPA, Sinemet, Madopar and the newer drug Stalevo, are still the most effective drugs available but after time (usually around 5 years) side-effects become more common, including motor fluctuations ('on-off' phenomena), involuntary movements (dyskinesia) and other problems including confusion/hallucinations. The management of patients at this stage of the disease involves adjusting medication doses and timing and considering trials of new drugs.

Despite the physician's best efforts, the onset of these problems often marks the onset of difficulties which can prove difficult to manage and a point where patients become more dependent. Typically these problems occur in the areas of motor function, autonomic function and cognition.

Motor problems include gait and balance problems, speech and swallowing difficulties. Gait problems include increasing difficulty initiating movement, festination and 'freezing' when the patient suddenly get rooted to the spot. Balance problems include retropulsion when the patient may tend to fall backwards. The patient will tend to become more flexed and even scoliotic with time. Drugs such as L-DOPA often have little impact on these symptoms and sometime can contribute to imbalance for example.

Other late-stage motor manifestations include dysarthria and dysphagia. The speech problems include low volume to the voice, rapid speech, palilalia and dysarthria. Speech problems again may not respond in any significant way to drug therapy but speech therapy may help. Dysphagia is also common in later stages of the disease and this will also be best managed with the help of the speech and language therapy department.

Significant autonomic problems in late PD include urinary urgency, sexual dysfunction, constipation, and postural hypotension (which can be exacerbated by medication).. These can be investigated and defined better by urodynamic studies and urology referral.

Cognitive impairment and mood changes also occur frequently in the latter stages of PD. Patients exhibit memory problems, slowing of thought and often develop hallucinations and psychosis. These cognitive problems may be compounded by the anti-Parkinsonian drugs. However if the drugs are reduced the patient may develop more rigidity and impaired movement. In addition well known tranquillisers such as Haloperidol or Chlorpromazine can exacerbate PD. Drugs such as Seroquel (Quietapine) can be used but can still have a negative effect on the PD symptoms. Depression and anxiety occur in up to 50% of patients with adverse effects on the patient's quality of life. Depressive symptoms should be sought from patients and treated appropriately.

Other issues for patients include painful dystonic cramping of the limbs which may respond to muscle relaxants such as Baclofen. Drooling of saliva can be treated by interventions such as Hyoscine cutaneous patches or radiotherapy to the parotid glands. Weight loss is a major problem for PD patients.

Ultimately pneumonia, urinary tract infection and falls leading to hip fractures and other injuries are often the cause of major acute morbidity and mortality in PD. These problems will continue to be experienced by a large number of patients until better treatments evolve in the future.