Parkinson’s Diseases

The Department of Neurology

 Extrapyramidal conditions cause disorders of
movement which can be broadly divided into two
categories:

※ Those where there is diminished movement with an

increase in ton----akinetic-rigid sydrome.

※ Those in which there are added movements outside

voluntary control----dyskinesias.
 These conditions involve lesions of the
basal ganglia and their connections.
Parkinson’s Diseases
 Parkinson’s disease was first described by
James Parkinson in 1817, who named it the “shaking
palsy”. It is the commonest of all the movement
disorders. The disease is seen worldwide, with
increasing incidence with age. The prevalence is 1 in
200 in those over 70 years. It is more common in men
than in women.
Pathology

There is progressive degeneration of cells

within the pars compacta of the substantia nigra in
the midbrain, with the appearance of eosinophilic
inclusions (Lewy bodies). Minor changes may also be
seen in other brainstem nuclei. As a result, there is a
reduction in dopamine in the striatum, disrupting
the normal dopamine: acetylcholine ratio.
Etiology
The cause of Parkinson’s disease is unknown.
Discordance in identical twins suggests that genetic
factors are not paramount. However, a consistent
environmental factor has not been elucidated.
Increased interest in exogenous toxins as a cause arose
with the finding that drug addicts taking heroin
contaminated with MPTP developed a similar
condition, with selective destruction of the nigral cells
and their striatal connections.
 A distinction must be made between
“idiopathic Parkinson’s disease” and “Parkinsonism”.
Parkinsonism denotes a syndrome that appears
clinically similar to idiopathic Parkinson’s disease but
has a different pathological or etiological basis.
Cause of parkinsonism include:

►Drugs ----especially dopamine antagonists

►Trauma ----especially repetitive head injury

►Cerebrovascular disease----especially lacunar

infarcts of the basal ganglia

►Toxins such as MPTP

Clinical features

Clinical features of Parkinson’s disease comprise

the classical triad of tremor, rigidity, and bradykinesia,
in association with important changes in posture and a
mask-like, expressionless face.
 There is usually striking asymmetry in tremor
and rigidity, such that a symmetrical onset should
make one doubt a diagnosis of idiopatic Parkinson’s
disease.
Tremor

This is a characteristic coarse resting tremor(4-

7HZ), which is usually decreased by action,
increased with emotion, and disappears during sleep.
The tremor is often “pill-rolling”, the thumb moving
rhythmically backwards and forwards on the
palmar surface of the fingers.
 Rigidity

There is stiffness of the limbs which can be fell throughout the

range of movement and equally in the flexors and extensors. This is
termed “lead-pipe” rigidity. When combined with the tremor, there
is a jerky element ,which is termed “cog-wheel” rigidity. The
increase in tone can be fell most easily when the joint is moved
slowly and steadily, and can be made more apparent when the
patient is asked to voluntarily move the opposite limb.

The rigidity is often asymmetrical and may be very markde in

the trunk.
Bradykinesia

Slowing and paucity of movement also occurs.

In addition to the limbs, this affects the muscles of
facial expression (mask-like facies),the muscles of
mastication, speech, and voluntary swallowing, and
the axial muscles. There is difficulty in initiating
movements and alternating movement.
Postural changes

The posture is characteristically stooped, with a

shuffling, festinant gait with poor arm swing. Falls
are common, as the normal righting reflexes are
affected. The patient falls stiffly, “like a telegraph
pole”.
Other features
Speech is altered, producing a monotonous, hypophonic
dysarthria, due to a combination of bradykinesia, rigidity, and
tremor. Power is normal, however in advanced disease, the
slowness and rigidity makes testing power difficult. Sensory
examination is also normal, although patients describe
discomfort in legs. Handwriting reduces in size and becomes
spidery. Constipation is usual and urinary difficulties are
common, especially in men. Depression is common. Cognitive
function is preserved in the early stages, although dementia may
occur late.
Differential diagnosis

The diagnosis of Parkinson’s disease is a clinical one.

It must be differentiated from the other akinetic-rigid
syndromes, secondary cause of parkinsonism, and diffuse
multifocal brain diseases that may have some of the
features of parkinsonism.
Treatment

Drug treatment is aimed at restoring the

dopamine acetylcholine balance caused by the
dopamine deficiency and therefore either involves
restoring dopamine or reducing acetylcholine.
Levodopa

Levodopa forms the mainstay for the treatment of most

patients with Parkinson’s disease. It is given in a combined form
with a peripheral decarboxylase inhibitor to provent peripheral
breakdown of the drug and to reduce the perpheral side effects.

Treatment is commenced gradually and increased slowly until

either an adequate effect is achieved or side effect limit further
increases. Levodopa improves bradykinesia and rigidity, but has a
lesser effect on tremor.
 The majority of patients with Parkinson’s disease initially
improve with levodoap. However , with time the effect becomes
diminished, the duration of action of the drug contracts, there
are marked fluctuations in symptoms, and patients experience
the on-off syndrome. In the latter, there are marked swings
between dopa-induced dysdinesias and sever and often suden
periods of immobility, which may bear no relationship to the
timing of the levodopa dose. Consequently , levodopa therapy
should not be started until necessary.
Dopamine agonists

Dopamine agonists are analogues of dopamine and

directly stimulate the dopamine receptors. The most
effective antiparkinsonian dopamine agonists stimulate D2
receptors predominantly.

These can be used alone, especially in younger

patients(aged less than 60 years) or to delay levodopa use,
or as an adjunct to levodopa.
Anticholinergic drugs

Anticholinergic drugs include benzhexol and

bentropine, which are antimuscarinic agents that
penetrate the central nervous system. They are most
effective in reducing tremor, though not so effective
for rigidity and bradykinesia. Side effects often
prevent their use, especially in the elderly.
Selegiline

Selegiline is an inhibitor of monoamine oxidase B,

so blocking the metabolism of central dopamine. Early
use can delay the need for levodopa, but there may be
an increased risk of cardiovascular morbidity in
advanced cases.
Surgery

Surgery is not extensively carried out but dose

have a place in sever cases and young patients. The
techniques used include stereotactic thalamotomy for
sever tremor, pallidotomy, transplantation of fetal
substantia nigra, and subthalamic neurostimulators.