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Chapter 7: Parkinson’s disease and other movement disorders 319

Geography Other features include facial masking, dribbling of
Common worldwide saliva, dysphagia, dysphonia and dysarthria – quiet
monotonous speech with a tendency to peter out with
continued effort. There is an increased incidence of
Aetiology
dementia in Parkinson’s disease.
There is little known about the aetiology
Nicotine: Some epidemiological evidence suggests a

Macroscopy/microscopy
decreased risk in smokers, but that may be due to
Loss of pigment from the substantia nigra due to the
younger death in this group.
death of melanin-containing dopaminergic neurones.
Therearesomefamilialforms,particularlyearly-onset

Surviving cells contain spherical inclusions called Lewy
Parkinson’s.
bodies – hyaline centres with a pale halo.
Pathophysiology
Investigations
The substantia nigra is one of the nuclei of the basal
Clinical diagnosis, but other parkinsonian syndromes
ganglia. In Parkinson’s disease there is progressive cell
should be considered.
loss and the appearance of eosinophilic inclusion bodies
(Lewy bodies) in the dopamine-rich part of the sub-
Management
stantia nigra (called the pars compacta). Biochemically
This includes a multidisciplinary approach for this
there is a loss of dopamine and melanin in the striatum
chronic disease, including education, support, physio-
which correlates with the degree of akinesia. Degener-
therapy and physical aids.
ation also occurs in other brain stem nuclei. The basal Levodopa, a dopamine precursor, is the most im-
ganglia project via a dopaminergic pathway to the thala-
portant agent used. It is given with an peripheral
mus and then to the cerebral cortex, where it integrates
dopa-decarboxylase inhibitor (such as carbidopa or
withthepyramidalpathwaytocontrolmovement.Hence
benserazide) to prevent the conversion of l-dopa to
it is sometimes called the extrapyramidal system.
dopamine peripherally, and so to reduce side-effects
of dopamine such as nausea and hypotension. Lev-
Clinical features odopa exerts most effect on bradykinesia and rigidity
The features are asymmetrical. (less on tremor).
The tremor is slow 4–6 Hz, typically pill-rolling and i After several years of treatment, patients develop

may involve the whole limb, legs and trunk. It is in- ‘on’ periods when they have a good response to the
creased by emotion and decreased on action. medication,lastingafewhours,thenan‘off’period,
Increased tone and tremor together cause a cog wheel- when they freeze. They may also have involuntary

ing rigidity. Increased tone alone may cause lead-pipe movements called dyskinesias, or painful dystonias
rigidity. (abnormal posturing – which may be an early fea-
The movement disorder consists of bradykinesia ture). These appear to be due to the progressive

(slowness of movement) and hypokinesia (reduced degeneration of the neuronal terminals, such that
size of movement). For example, tapping one hand on dopamine is not taken up properly. It is speculated
the other is slow, of reduced amplitude and frequency. that they may be prevented by using other drugs to
The gait is characteristic, with difficulty initiating treat mild symptoms, and using drugs which may

movement (hesitancy), then difficulty in stopping have a ‘neuroprotective’ action, e.g. by blocking free
(festination), slowness or freezing when asked to radicals, and preserve neuronal function.
turn. When walking there may be a reduced arm ii ‘On/off’ phenomenon may be treated by increas-
swing and increased pill-rolling tremor. The posture ing the frequency of doses, or using catechol-
is usually stooped, flexed and the person has diffi- O-methyl transferase (COMT) inhibitors such as
culty in keeping balance (postural instability), falling entacapone which inhibit the peripheral and cen-
whilst standing or walking. There is a loss of postural tral metabolism of l-dopa and dopamine, so giving
reflexes. amore stable level.