Clinical aspects of Parkinson's disease
Definition
A slowly
progressive loss of dopamine cells in the substantia nigra causing bradykinesia
(slowness of movement with progressive reduction of speed and amplitude of
repetitive voluntary movement) or rest tremor or both. Muscular rigidity and a
degree of postural imbalance are common features A diagnosis of possible Parkinson's disease can be made if
bradyinesia or rest tremor are present, and if the following features are
absent (history of repeated stroke head injury or encephalitis, toxin exposure
(manganese, MPTP) neuroleptic therapy oculogyric crises, supranuclear gaze palsy, pyramidal or cerebellar signs,
early severe autonomic involvement or dementia CT scan showing tumour,
hydrocephalus or basal ganglia calification, spontaineous remission, failure of
akinesia to respond to large doses of 1-dopa). Probable Parkinson's disease
also requires an asymmetrical, wide-amplitude rest tremor for 6 months or two
of the following: excellent response (70-100%) to l-dopa, swings in motor
function related to l-dopa doses, severe I-dopa induced chorea, l-dopa response
for 5 years, clinical course of 10 years.
Parkinson's
disease has a sporadic worldwide occurrence with no classical Mendelian
inheritance of the usual form. A family history is obtained in 15% of patients,
occasionally 2 or more family members can be found to have the disease, and
there are rare large kindreds with autosomal dominant disease imitating the
sporadic form apart from an earlier age of onset, a more rapid disease
progression, and in some kindreds a predominance of associated dementia. The
prevalence of sporadic Parkinson's disease in the UK and USA is approximately
1601100,000, but in China, Japan and Nigeria prevalence may be lower at 45-80
/100,000. The disease may begin after the age of 20 but is rare before 30
years, and is rare beforev30 years and
is increasingly common with age affecting up to 2% of the population aged ove
80 years. Men and women are equally affected. Patients are less likely to have
smoked before disease onset than the general population Patients are also said
to have been more introspective than unaffected twins or siblings, but there is
some, controversy as to how robust this observation is.
In addition to
the substantia nigra, the distribution of neuronal loss in the nervous system
affects other specific populations in a highly selective fashion. These are the
locus coeruleus, nucleus basalis of Mynert, thalamus, raphe nuclei, limbic
cortex and neocortex, and the entire autonomic nervous system. Neural
degeneration is also associated, invariably with the formation of
intracytoplasmic neuronal inclusions called Lewy bodies, in some of the
neurones. In addition to Parkinson's disease, it can therefore be predicted
that disease in these other regions may produce symptoms. In particular, loss
of the cholinergic innervation of the cerebral cortex from the nucleus basalis of Meynert, and pathology in the
cerebral cortex itself, may Predispose to dementia.
The condition
usually presents insidiously with development of rest tremor of one arm,
alternatively stiffness in an arm with slowness and difficulty with moving such
as turning over in bed dressing, eating and swallowing Sometimes the onset is associated with acute
physical or emotional stress, and a period of weeks or months of remission may
then occur after stress has been alleviated, only tor the presenting symptoms
to return again. The presentation may be complicated by prodromal features of
anxiety, and possibly depression and lethargy. The classic clinical criteria
are said to be rest tremor, bradykinesia, muscular rigidity and postural
instability. Bradykinesia affects many bodily functions, producing a masked
face, slowness in eating, micrographia, a short step and shuffling gait, and
loss of associated movements. Muscular rigidity often causes stiffness,
classically a frozen shoulder, and together with akinesia this symptom may
cause pain. Early postural instability responds to therapy, and is mild Late in disease, particularly in the
elderly, postural instability is intractable and profound.
Dementia is rare
before age 60 years, but thereafter becomes increasingly common. In the 80s the
risk of dementia over 5 years is 50 % compared with a figure of approximately
20% in the population for demential/Alzheimer's disease.
No abnormalities
are found on routine investigation of Parkinson's disease. It may be
appropriate to measure thyroid function, serum calcium, syphilis serology, and
have a CT scan.
Anxiety,
essential tremor, other parkinsonian disorders such as drug induced,
striatiatonigral degeneration and Steele-Richardson~Olszewski disease. Uncommon
toxic causes are MPTP, carbon monoxide, cyanide, carbon disulphide, manganese.
Other causes are chronic trauma (pugilistic encephalopathy) and brain tumours.
The mainstay of
treatment remains I-dopa therapy, combined with a dopa-decarboxylase inhibitor.
However, it can be argued that approximately 60-70 years divides patients into
younger and older onset in relation to therapy. In view of the fact that patients
maintained on l-dopa therapy will invariably develop profoundly troublesome
motor fluctuations after 10-15 years can be treated initially with levodopa
sparing agents such as amantadine, direct acting dopamine agonists
(bromocriptine/pergolide) or possibly an anti-cholinergic drug. One or more of
these ca n be used. Where additional treatment is required madopar or sinemet,
preferably in a slow release formulation can be added. For older onset patients
treatment should be initiated with madopar or sinemet, increasing quickly to a
modest twice daily dose. In this older age group other therapies, which are more
likely to produce side effects, should be avoided.