Movement disorders

Applied Neuroanatomy Extra pyramidal term is applied to basal ganglion regulated motor system and is anatomically and functionally different from pyramidal (corticospinal system) and cerebellar. Basal ganglion consists of six pair of nuclei -caudate nucleus, putamen(together called Corpus striatum), globus pallidus, subthalamic nucleus, substantia nigra, nucleus accumbens. Basal ganglion and thalamus and cortex are interconnected via various pathways either inhibitor or stimulatory helping normal movements possible. Basal ganglion is primarily role is to scale movement amplitude and velocity and initiate movements. opamine is inhibitory neurotransmitter present esp. in sunstantia nigra and corpus striatum is rich in acetylcholine. !ovement disorders classification ") "#inetic-rigid syndromes or hypo#inesia$s -slowed movement with increased tone e.g.%diopathic &ar#inson's disease rug-induced par#insonism (e.g. phenothia(ines) &ar#insonism-plus B) )yper#inesias * uncontrollable movements. E.g. +remor, Chorea, )emiballismus, !yoclonus, ystonias Parkinsons disease (PD) &ar#inson$s disease (& ) is a common neurodegenerative disorder. %t predominately disease of elderly and incidence and prevalence both increase with age. Based on etiology &ar#inson$s disease can be classified as ") %diopathic &ar#inson$s disease , commonest cause B) Secondary parkinsonism (definable cause) rugs --- phenothia(ines, haloperidol, metoclopramide, reserpine. +oxins ---- !anganese- .-methyl /-phenyl tetrahydropyridine (!&+&) 0ascular ----atherosclerosis !etabolic --- 1ilson$s disease, hypoparathyroidism, )ead in2ury--- &unch-drun# syndrome. C. &ar#inson-plus syndromes &rogressive supranuclear palsy !ultiple system atrophy (olivopontocerebellar atrophy, 3hy- rager syndrome, striato-nigral degeneration)

Pathophysiology "ll forms of par#insonism result from reduction of dopaminergic transmission within the basal ganglia cause of this reduction in dopamine in %diopathic &ar#inson$s disease is not #nown. %n the pars compacta of the substantia nigra there is progressive cell degeneration and neuronal eosinophilic inclusion bodies (4ewy bodies) are seen. egeneration also occurs in other basal ganglia nuclei. 5educed dopaminergic output from the substantia nigra to the globus pallidus leads to reduced inhibitory effects on the subthalamic nucleus, neurons of which become more active than usual in inhibiting activation of the cortex. +his in turn results in brady#inesia. 6ormally e7uilibrium exists between acetylcholine and dopamine. 1ith dopamine deficiency, there is acetylcholine hyperactivity. linical features ") 3ymptoms +he classical symptoms &ar#inson$s disease of tremor, rigidity and brady#inesia and gait abnormalities. +he presentation is almost always unilateral and later becoming bilateral. +hese symptoms develop very slowly, over months or several years. &atients may present with non-specific symptoms of tiredness, aching limbs, mental slowness, depression and small handwriting (micrographia). B) 3igns 8eneral Expressionless face or mas# li#e face. 8reasy s#in 9lexed posture and %mpaired postural reflexes .)+remor 5esting /-: )( and ;sually first in fingers*thumb Coarse, complex movements, flexion*extension of fingers "bduction*adduction of thumb and 3upination*pronation of forearm !ay affect arms, legs, feet, 2aw, tongue %ntermittent, present at rest and when distracted and diminished on action 5igidity 3tiffness develops throughout the range of limb movement and is e7ual in opposing muscle groups (lead pipe). +his plastic rigidity is more easily felt when a 2oint is moved slowly and gently 3tiffness occurs with tremor, rigidity is bro#en up into a 2er#y resistance to passive movement - #nown as cogwheeling, or cogging. <)Brady#inesia 3lowness in initiating or repeating movements

%mpaired fine movements, especially of fingers.

=)8ait 3low to start wal#ing ,3hortened stride 5apid, small steps, tendency to run (festination) 5educed arm swing ,%mpaired balance on turning /)>ther features 3peech -- &ronunciation is initially a monotone but progresses to characteristic tremulous slurring dysarthria Cognitive, autonomic disturbances can also occur. 6ormal deep tendon reflexes but patient might have primitive reflexes li#e glabellar tap sign. ementia often develops in the late stages. "nxiety and depression are common. 6atural history &ar#inson's disease worsens over some years, beginning as a mild inconvenience but slowly progressing and remissions are un#nown. +he rate of progression is very variable, with a benign form running over several decades. ;sually the course is over .?-.@ years, with death resulting from bronchopneumonia. Diagnosis iagnosis if par#inson$s diseases is clinical and there is no diagnostic test for &ar#inson's disease. &atients presenting before the age of @? are usually tested for 1ilson's disease, %maging (C+ or !5%) of the head may be needed if there are odd features. Management 8oals of treatement !aintain function and 7uality of life "void drug-induced complications 6o treatment can alter the course of &ar#inson's disease ") rug therapy &harmacotherapy is the mainstay of management. %nitiate dopaminomimetic therapy when symptoms begin to interfere with 7uality of life. .) 4evodopa 4evodopa is combined with an aromatic amino acid decarboxylase inhibitor bensera(ide or carbidopa because if levodopa is administered orally, more than A?B is decarboxylated to dopamine peripherally in the gastrointestinal tract and blood vessels, and only a small proportion reaches the brain due decarboxylase. 4evodopa is particularly effective at improving brady#inesia and rigidity. !a2ority of patients with idiopathic & (but not other par#insonian syndromes) improves initially with levodopa

 >ral tablets of carbidopa*levodopa is available as .?*.?? mg, <@*.?? mg, and <@*<@? mg strengths. %t is available in immediate release and controlled release (C5) formulations. 9re7uency ,+% and gradually increased.

3ide-effects a)Common immediate side effects - )ypotension, nausea and vomiting. "nd dose related involuntary movements, particularly orofacial dys#inesias, limb and axial ystonias. b) 4ong-term therapy side effects 9luctuation in response causeing Con and off phenomenonD i.e. free(ing(severe rigidity) alternating with dopa-induced dys#inesias, chorea and dystonic movements. C>n and off phenomenonD can be managed by dividing the levodopa into smaller but more fre7uent doses or by converting to a slow-release preparation. <) opamine receptor agonists e.g. Bromocriptine, pergolide, cabergoline pramipexole and ropinirole are oral directly acting dopamine receptor agonists, acting principally on . and < receptors. +hese are used as an alternative or an addition to levodopa therapy 3ide effects -6ausea, postural hypotension, psychiatric symptoms, daytime sedation "pomorphine, given by subcutaneous metered infusion is an effective method of smoothing out fluctuations in response to levodopa. =)C>!+ (catechol->-methyl-transferase) inhibitors E.g. Entacapone and tolcapone. +hese drugs are very are very useful for Con and off phenomenonD /) "nticholinergic agents +hese have a useful effect on tremor and rigidity, but do not help brady#inesia. Example, trihexyphenidyl and orphenadrine. 3ide-effects - dry mouth, blurred vision, difficulty with micturition and constipation. confusion and hallucinations @) "mantadine "mantadine enhances dopamine release at the nerve terminal, ;sed early in the disease. "mantadine can be particularly useful in controlling the dys#inesias produced by dopaminergic treatment later in the disease 3ide effects-livedo reticularis, edema, erythema. :) 3elegiline %t is !">-B inhibitor so bloc#s dopamine brea#down.

 3elegiline has a mild therapeutic effect. 3ide effect - %nsomnia E) >thers 9or depression in par#insonism patients, 3elective serotonin reupta#e inhibitors (335%s) are the drugs of choice. B) 3urgery 3tereotactic thalamotomy can be used to treat tremor in resistant cases. %mplantation of fetal mid-brain cells into the basal ganglia to enhance dopaminergic activity remains experimental. C) &hysiotherapy and physical aids &atients at all stages of &ar#inson's disease benefit from physiotherapy, which helps reduce rigidity and corrects abnormal posture !"#M$"S %t is abnormal rhythmical hyper#inetic movement disorder. +remors are divided into three typesF rest, postural, and intention tremor. ") 5est tremor is maximal at rest and becomes less prominent with activity. E.g. &ar#insonism B) &ostural tremor is maximal while limb posture is actively maintained against gravity- it is lessened by rest and is not mar#edly enhanced during voluntary movement toward a target. E.g. hyperthyroidism or stress and benign or familial essential tremor. C) %ntention tremor is most prominent during voluntary movement toward a target and is not present during postural maintenance or at rest. %t is a sign of cerebellar disease. "sterixis- which may superficially resemble a tremor is an intermittent inhibition of muscle contraction that occurs with metabolic encephalopathy. %enign #ssential (&amilial) !remor +he cause of benign essential tremor is uncertain, but it is sometimes inherited in an autosomal dominant manner. 3ymptoms and signs +remor may begin at any age and is enhanced by emotional stress +he tremor usually involves one or both hands, the head and legs tend to be spared. Examination reveals no other abnormalities. %t generally leads to little disability +reatment +reatment is most often not re7uired. rugs that are useful- propranolol, alpra(olam, clo(apine. rugs are started at low dose and gradually increased.

isabling tremor unresponsive to medical treatment may be helped by contralateral thalamotomy or thalamic stimulation 3low irregular involuntary movements "thetosis is a slow, writhing' sinuous movement that occurs nearly continuously in distal muscles ystonia is a slowly varying but nearly continuous deviation of posture about one or more 2oints 5apid irregular movements )emiballismus manifests as a sudden and often violent flinging movement of a proximal limb, usually an arm. Chorea is a rapid, 2er#y, irregular movement that tends to occur in the distal limbs or face but may also occur in proximal limbs and trun#. E.g. excess levodopa or dopamine-agonist therapy, control pills, pregnancy (chorea gravidarum), hyperthyroidism, or the antiphospholipid syndrome. !yoclonus is a rapid, brief, irregular movement that is usually multifocal.