Medicine 5th year, 4th lecture (Dr. Hassan Al-Jumaily)
PARKINSONISM<br />It is a clinical syndrome consisting of 4 cardinal signs: tremor at rest, rigidity, bradykinesia and loss of postural reflexes. And it is the commonest extrapyramidal disorder.<br />Classification:-<br />Classification of parkinsonism is according to the causes:<br /><ul><li>Primary: idiopathic parkinsonism (Parkinson’s disease)
Huntington’s disease</li></ul> In all these types generally there is dopamine depletion as pathology but the mechanism differs in each type.<br />Idiopathic parkinsonism (Parkinson’s disease): or called ‘paralysis agitans’. It occurs at the age of 40 years and its incidence increases with age and maximally at 75 years.<br /> Both sexes are affected, males are more than females affected by a ratio of 3:2 and it could occur before the age of 40, as in Wilson’s disease, Huntington’s disease, drug-induced parkinsonism and in post-encephalitic parkinsonism.<br />Pathology:-<br />In idiopathic parkinsonism there is loss of pigmented cells in the substantia nigra and other brainstem centers, with presence of eosinophilic intraneural inclusion granules called ‘Lewy bodies’.<br />Pathogenesis:-<br />Both dopamine and acetylcholine are present in the corpus striatum (caudate and putamen), where they act as neurotransmitters. In idiopathic parkinsonism, the normal balance between them is disturbed due to dopamine depletion in the nigrostriatal system.<br />Clinical Picture:-<br />The disease begins insidiously, most commonly in one limb then involves the other limb in the same side and remains unilateral for several years before spreading to the opposite side. Patients describe motor slowness, stiffness, or easy fatigability in a single limb or in hemiparetic distribution. <br /> The disease has 4 cardinal signs which are characteristic for it, they are: tremor, hypokinesia, rigidity and abnormal gait and posture.<br /><ul><li>Tremor: it is most conspicuous at rest called ‘resting tremor’ and increases at times of emotional stress and often improves during voluntary activity. It commonly begins in the hand or foot where it takes the form of rhythmic flexion-extension of the fingers or the hand or the foot, or rhythmic pronation-supination of the forearm and it is sometimes called ‘pill-rolling tremor’.
Rigidity: it is increase in tone (that’s increased resistance to passive movement), it is a characteristic feature of parkinsonism. The resistance is typically uniform throughout the range of movement which sometimes interrupted by tremor and called ‘cog-wheel rigidity’. In contrast to spasticity, where the increase in tone is of ten greatest at the beginning ‘clasp-knife’.
Hypokinesia (bradykinesia): it is the most disabling feature of the disease. It means slowness of voluntary movements and a reduction in automatic movements such as swinging the arms while walking. The patient’s face is relatively immobile called ‘masked face’, with widened palpebral fissures and infrequent blinking. The voice is slow and monotonous (poorly modulated), power is not diminished. The handwriting is small and tremulous ‘micrographia’.
Abnormal gait and posture: the patient generally finds it difficult to get up from bed or an easy chair and tends to adopt a flexed posture on standing. It is often difficult to start walking and the gait itself is characterized by small, shuffling steps with absence of the arm swing and there may be difficulty in stopping. In advanced cases, the patient tends to walk with increasing speed to prevent a fall, called ‘festinating gait’.
Blepharoclonus: fluttering of the closed eyelids
Blepharospasm: involuntary closure of the eyelids
Drooling of saliva may be due to impairment of swallowing</li></ul>There is no alteration in tendon reflexes and plantar responses are flexor (negative).<br />Diagnosis:-<br />The disease is diagnosed clinically and the investigations are of no value.<br />Treatment:-<br />Treatment, when indicated, is directed towards restoring the dopaminergic-cholinergic balance in the striatum by blocking the effect of acetylcholine with anticholinergic drugs or by enhancing of dopaminergic effect. Early and mild parkinsonism need no medical treatment.<br /><ul><li>Anticholinergic drugs: these drugs are more helpful in tremor and rigidity, among the most common of them are:
Orphenadrine (Disipal)</li></ul>We must watch their side effects especially in elderly.<br /><ul><li>Amantadine: it may potentiate the release of dopamine it could be given in a dose of (100 mg) orally twice daily.
Levodopa: it is unlike the anticholinergic drugs, it is often partically helpful against (hypokinesia), its side effects are nausea, vomiting, hypotension, abnormal movements and most common late complication is on-off phenomenon. Most of levodopa is broken down to its active metabolite (dopamine) outside the central nervous system by the enzyme (dopa decarboxylase) but does not cross the blood-brain barrier, so carbidopa is given with L-dopa in a combination known as (Sinemet) to limit the breakdown of L-dopa outside the central nervous system by inhibiting the effects of dopa decarboxylase enzyme. The carbidopa is generally combined with L-dopa in a fixed preparation (1:10 or 1:4) as Sinemet. Either Sinemet (10:100 mg) or (25:100 mg) orally three times daily.
Bromocriptine: it is an ergot derivative that directly stimulates dopamine receptors. The starting dose is 1.25 mg and the maintenance doses are usually between 2.5 to 10 mg orally, three times daily.
Pergolide: it is like bromocriptine an ergot derivative and dopamine receptor stimulator.
Selegiline: is mono amine oxidase inhibitor type B (MAOI-B), therefore; it inhibits the metabolic breakdown of dopamine, and enhances the antiparkinson effect. Some studies suggest that it can delay the progression of the disease.