Disorders of movement can be classified broadly into akinetic-rigid syndromes, where there is loss of move ment with increase in muscle tone, and dyskinesias, where there are added movements outside voluntary control. Both are due to disorders of neurotransmitters of the extrapyramidal system.
Parkinson’s disease is much the commonest of these conditions. A classification of movement disorders i
given in Table 18.37.
Idiopathic Parkinson’s disease In 1817, James Parkinson, a physician in Hoxton, London, described the clinical appearance of patients with the ‘shaking palsy’. The disease is common and worldwide,with prevalence increasing sharply with age to about 1 in200 in those over 70 years. The condition is clinically distinct from other ‘parkinsonian’ syndromes. There are few clues as to its cause:
NICOTINE. Some epidemiological studies suggest the disease is less prevalent in tobacco smokers than in lifelong abstainers.
MINUTE DOSES OF A PYRIDINE COMPOUND (MPTP)
(see p. 920) cause a severe parkinsonian syndrome. The significance of this to idiopathic Parkinson’s disease is not clear.
SURVIVORS OF ENCEPHALITIS LETHARGICA, which is presumed to be a viral disease, develop parkinsonism. However, it is not thought that the idiopathic disease is related to this or to another infective agent. The condition is not inherited.
In the pars compacta of the substantia nigra there is progressive cell degeneration and the appearance of eosinophilic inclusion bodies (Lewy bodies). Degeneration also occurs in other brain stem nuclei. Biochemically there is loss of dopamine (and melanin) in the striatum that correlates well with the areas of cell loss and also with the degree of akinesia. The underlying cause of these biochemical changes remains obscure. Akinetic-rigid syndromes
Idiopathic Parkinson’s disease
Drug-induced parkinsonism, e.g.
phenothiazines MPTP-induced parkinsonism
Postencephalitic parkinsonism ‘Parkinsonism plus’
Childhood akinetic-rigid syndromes
Tic or ‘habit spasm
There is a combination of tremor, rigidity and akinesia, together with important changes in posture. Symptoms
The commonest symptoms are tremor and slowness of movement. Patients also complain that the limbs feel stiff and ache and that fine movements are difficult. The slowness of movement causes the characteristic symptoms of difficulty in rising from a chair or getting into or out of bed. Writing becomes small (micrographia) and spidery, with a tendency to tail off at the end of a line. Other evidence of the disease often comes from relatives who have noted slowness and an impassive facial expression. Signs
TREMOR. This is a characteristic 4-7 Hz rest tremor that is usually decreased by action and increased by emotion. ‘Pill-rolling’ movements of the fingers and thumbs may be seen. The shaking is sometimes unilateral or more prominent on one side. .
RIGIDITY. Stiffnes s of the limbs develops that can be felt throughout the range of movement and is equal in opposing groups of muscles (in contrast to the selective increase in tone found in spasticity). This ‘lead-pipe’ rigidity is often more marked on one side and is present in the neck and axial muscles (where it is difficult to examine).
The rigidity is usually more easily felt when a joint is moved slowly and gently. Simultaneous active movement of the opposite limb increases the tone of the side under examination. When combined with tremor, the smooth plasticity of the increase in tone is broken up into a jerky resistance to passive movement, a phenomenon known as ‘cogwheeling’.
AKINESIA. The poverty and slowing of movement (bradykinesia) is an additional handicap, distinct from rigidity. There is difficulty in initiating movement. Rapid finger movements (such as piano-playing movements)
become indistinct, slow and tremulous. The immobility of the face gives a mask-like facies with the appearance of depression. The frequency of spontaneous blinking is reduced, causing a ‘serpentine stare’.
POSTURAL CHANGES. A stoop is characteristic and the gait is shuffling, festinant and with poor arm swinging. The posture is sometimes called ‘simian’ to describe the forward flexion, immobility of the arms and lack of facial expression. The patient sits with the trunk bent forward and motionless, without gesture or animation, but the limbs are tremulous. Balance is impaired, but despite this the gait remains on a narrow base. Falls are common as the usual corrective righting reflexes fail, the sufferer falling stiffly ‘like a telegraph pole’.
SPEECH. Speech is altered to a monotonous slurring dysarthria, due to the combination of akinesia, tremor and rigidity. Dribbling is frequent, and dysphagia occurs as the disease progresses.
GASTROINTESTINAL SYMPTOMS. These include heartburn, dysphagia, constipation and weight loss.
OTHER FIDINGS. Urinary difficulties are common, especially in men. The skin is greasy and sweating is excessive.
Power remains normal until advanced akinesia makes its assessment difficult. There is no sensory loss, although patients often complain of discomfort in the limbs. The reflexes are normal (though they may be asymmetrical, following an asymmetrical increase in tone). The plantar responses are flexor.
Cognitive function is preserved, at least in the early stages. Dementia sometimes occurs in the late stages.
Parkinson’s disease progresses over a period of years, beginning as a mild inconvenience but slowly overtaking the patient. Remissions are unknown except for rare and emarkable short-lived periods of release. These tend to occur at times of great emotion, fear or excitement, when the sufferer is released for seconds or minutes and ableto move quickly.
The rate of progression is very variable, with a benign form running over several decades. Usually the course is over 10-15 years, with death resulting from bronchopneumonia.
There is no laboratory test for the disease. The diagnosisis made on clinical grounds alone. The condition must be distinguished from other akinetic-rigid syndromes. Hypothyroidism and depression also cause slowing of movement.
Certain diffuse or multi focal brain diseases cause some features of ‘parkinsonism’ (i.e. the slowing, rigidity and tremor). Alzheimer’s disease, multi-infarct dementia, and the sequelae of repeated head injury or hypo ia are the commoner examples.
Older treatments with anticholinergic drugs altered the disease little, and frequently caused mental confusion. Benzhexol is still used in mild cases and as an adjunct to other therapy. Amantadine, originally introduced as an antiviral agent, is also sometimes helpful.
The introduction of levodopa in the late 1960s was a revolutionary therapeutic approach, apparently replacing thelost neurotran mitter dopamine. Today levodopa is usually combined with a peripheral decarboxylase inhibitor- benserazide (co-beneldopa, as Madopar) or carbidopa (co-careldopa, as Sinemet). This combined therapy reduces the periperal side-effects, principally nausea, oflevodopa and its metabolites. Tratment is commenced gradually (co-beneldopa 125 mg or co-careldopa ‘1l0’ one tablet three times daily) and increased until either an adequate improvement has taken place or side-effects limit further increase in dose. The great majority of patients with idiopathic Parkinson’s disease (but not other parkinsonian syndromes)
improve initially with levodopa. The response in severe, previously untreated disease may be dramatic.
UNWANTED EFFECTS OF LEVODOPA THERAPY. Nausea and vomiting within an hour of treatment are the commonest symptoms of the dose being too large. Confusion and visual hallucinations also occur. Chorea occurs in acute overdose.
As there are considerable problems with long-term treatment, levodopa therapy should not be started until necessary. Sometimes the drug appears to become ineffective, even with increasing doses. The disease progresses and the patient suffers from severe episodes of ‘freezing’and falls. Fluctuation in the response to levodopa may also occur. The duration of action of the drug contracts, and the patient begins to suffer from a ‘chronic levodopa syndrome’, fluctuating between dopa-induced dyskinesias (chorea and dystonic movements) and severe and sometimes
sudden immobility (on-off syndrome).
These are major and often insoluble problems in management. Approaches to treatment of the complications
include the following:
THE INTERVAL BETWEEN LEVODOPA DOSES can be shortened and the individual doses reduced. SELEGILINE-a type B monoamine oxidase inhibitorinhibits the catabolism of dopamine in the brain. This sometimes has the effect of smoothing out the response to levodopa.
BROMOCRIPTINE, a directly acting dopaminergic agonist, is sometimes used.
‘DRUG HOLIDAYS’ -periods of drug withdrawal-are sometimes helpful. They require close supervision since severe rigidity and akinesia follow the withdrawal of levodopa.
Depression is common in Parkinson’s disease as the symptoms become worse and unresponsive to treatment. It is particularly difficult to treat, since type A monoamine oxidase inhibitor antidepressants (e.g. phenelzine) are absolutely contraindicated with levodopa, and tricyclic antidepressants (e.g. amitriptyline) have extrapyramidal side-effects.
All antiparkinsonian drugs, particularly in high doses, may cause confusion with visual hallucinations, which may exacerbate an associated dementia. Neurosurgery
Stereotactic placement of small lesions in the ventrolateral nucleus of the thalamus was commonly used in the two decades preceding the development of levodopa. The procedure was effective in reducing tremor but poor for relieving akinesia; it is now rarely performed.
Attempts to transplant fetal or autologous dopaminecontaining tissue (adrenal medulla) to the cerebral ventricles or basal ganglia, though technically feasible, have not produced any major clinical improvement in patients with Parkinson’s disease despite some early claims.
Physiotherapy and physical aidsSkilled and determined physiotherapy can improve he gait and help the patient to overcome particular problems. Sensible guidance should be given about:
CLOTHING-avoiding zips, fiddly buttons and lace-up shoes.
CUTLERy-using built-up handles.
CHAIRS-high, upright chairs are easier to rise fromthan deep, comfortable armchairs. RAI LS-should be fitted near the lavatory and bath. SHOES- should be easy to put on and have smooth soles.FLOORING-patients’ feet sometimes ‘stick’ to carpets and rugs and they prefer to walk on vinyl or linoleum. ALKING AIDS are often a hindrance in the early stages but later a frame or a tripod may be helpful.
Drug-induced parkinsonism Reserpine, phenothiazines and butyrophenones induce a parkinsonian syndrome, with slowness and rigidity but usually little tremor. Methyldopa and tricyclic ntidepressants also cause some slowing of movement. These syndromes tend not to progress. They respond poorly to levodopa. They disappear when the drug is stopped. Other movement disorders due to neuroleptic drugs Neuroleptic drugs (i.e. phenothiazines and butyrophenones) also produce other varieties of movement disorder.Three are described here.
AKATHIS IA. This is a restless, repetitive and irresistible need to move.
ACUTE DYSTONIC REACTIONS. These sometimes follow, unpredictably, single doses of these drugs, even those used as antiemetics or vestibular sedatives (such as prochlorperazine and metoclopramide). Spasmodic torticollis, trismus and oculogyric crises (i.e. episodes of sustained upward gaze) may occur. These acute dystonias respond promptly to the intravenous injection of an anticholinergic drug (e.g. benztropine 1-2 mg).
CHONIC TARDIVE DYSKINESIAS. These disabling disorders consist of mouthing and smacking of the lips, rimaces and contortion of the face and neck. They tend to occur some 6 months after commencing neuroleptic therapy and may be made temporarily worse when the offending drug is stopped. Only about half of the cases eventually recover.
An epidemic of an encephalitic illness (encephalitis lethargica) occurred in 1918-1930 that left in its wake a severe extrapyramidal syndrome of parkinsonism with added dystonic movement disorders. Many of the survivors were permanently disabled. Occasionally, sporadic cases of the disease have been recorded recently in the UK; a recent epidemic may have occurred in Bulgaria. MPTP-induced parkinsonism MPTP (l-methyl-4-phenyl-,2,3,6-tetrahydropyridine) is an impurity roduced inadvertently when opiate analgesics are synthesized illicitly. A few cases of a severe and largely irreversible parkinsonian syndrome have followed
ingestion of minute quantities of M PTP. The relevance of this to idiopathic Parkinson’s disease is not clear. ‘Parkinsonism plus’
This describes rare disorders in which there is parkinsonism and evidence of a separate pathology. Progressive supranuclear palsy is the commonest disorder and consists of axial rigidity, dementia and signs of
parkinsonism together with a striking inability to move the eyes vertically or laterally.Other examples of ‘Parkinsonism plus’ are the rare
multiple system atrophies, e.g. olivopontocerebellar degeneration and primary autonomic failure (Shy- Drager syndrome).
Akinetic-rigid syndromes in children
A group of extremely rare disorders cause an akineticrigid syndrome in those under 20 years of age. The most important are Wilson’s disease and athetoid cerebral palsy.
This is a rare and treatable disorder of copper metabolism that is inherited as an autosomal recessive disease. There is deposition of copper in the brain (particularly in the basal ganglia), in the cornea and in the liver (see p. 270). It is most important that all young patients with cirrhosis are screened for this condition, as the neurological damage is irreversible unless early treatment is instituted. Children with the disease have an akinetic-rigid syndrome and/or dyskinesias followed by progressive intellectual impairment.
DIAGNOSIS AND TREATMENT
Athetoid cerebral palsy Writhing movements of the limbs, sometimes with an increase in tone, are seen in cerebral palsy following kernicterus. This is now much less common following the prophylactic treatment of rhesus haemolytic disease. DYSKINESIAS Benign essential tremor This common condition, often inherited as an autosomal dominant trait, causes tremor at 5-8 Hz that is usually worse in the pper limbs. The head is often tremulous (titubation) and also the trunk. Pathologically there is patchy neuronal loss in the cerebellum and cerebellar connections. Tremor is seen when the hands adopt a posture, such as holding a glass or a spoon. Oscillations are not usually present at rest nor do they worsen on movement. Essential remor may be seen at any age but occurs most frequently in the elderly. It is slowly progressive but rarely produces a severe disability. Writing is shaky and
untidy but there is no micrographia. Anxiety exacerbatesthe tremor, sometimes dramatically. Treatment is often unnecessary. Many of those affected are reassured to find they do not have Parkinson’s disease, with which the condition is often confused. Small doses of alcohol and f3-adrenergic blockers such as propranolol often reduce the tremor. The anticonvulsant primidone also helps some patients. Sympathomimetics (e.g. salbutamol) make the tremor worse.Though usually postural, in some cases the tremor may occur at rest (i.e. like Parkinson’s disease) or be cerebellar (i.e. with past pointing).