EXTRAPYRAMIDAL DISORDERS

= Movement disorders = Degenerative disease

4 types of movements:
Voluntary movement Semivoluntary movement (=unvoluntary) Involuntary movement Automatic movement
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Movement disorders
= Extrapyramidal disorder Disorder of regulation of voluntary motoric activity without direct influence towards muscle strength, sensibility, or cerebellum.

Extrapyramidal disorder
Hyperkinetic disorder: abnormal involuntary movements Hypokinetic disorder: reduction of movements. = Movement disorders are caused by dysfunction of basal ganglia

Basal ganglia:
Caudate nucleus Putamen Globus pallidus Subthalamic nucleus Substantia nigra

Diseases & syndrome with abnormal movements:

Essential tremor (familial / benign) Parkinsonism Progressive supranuclear palsy Idiopathic torsion dystonia Chorea sydenham Sindroma Gilles de la Tourette Drug-induced movement disorders,

etc.
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Parkinsonism = Parkinson syndrome

1. Primary / Idiopathic = Paralysis agitans = Parkinson disease 2. Secondary/Symptomatic = Causes: - arteriosclerosis - anoxia /cerebral ischemia - drugs - toxic agent - encephalitis etc.

Parkinsonism (CONT)
3. Paraparkinson / Parkinson plus - Wilson disease - Huntington disease - Normotensive Hydrocephalus

Parkinson disease
= Parkinson idiopathic = Paralysis agitans

- Most commonly be found - Middle age to old age

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Etiology and pathogenesis

The certain Etiology is unknown PD is due to cells degeneration dopamine decreased in substantia nigra

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ACh --------------------------------- DA I DA ACh I ACh i DA

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Hypotesis:
Aging process: dopaminergic neuronal death !!! anti oxydative-protective mechanism decreased Environmental toxin: - heavy metal (Iron, Zinc, mercury etc) - MPTP Genetic sensitivity Oxydative stress: dopamine reaction free radicals
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Pathology
Cutting of mid-brain: degeneration & neuronal death which contain melanin in substansia-nigra. Microscopic: In compacta zone: - Most of neuron are loss - Residual : containings Lewy-bodies
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Lewy bodies in subst.nigra:

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Clinical findings.
Triad of symptoms: - rigidity - tremor - bradikinesis 1. tremor: - pill rolling tremor - during tension !!!, sleep disappear - resting tremor = Parkinsonian tremor
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Clinical findings (Cont)

2. 3. 4. 5. 6. 7. 8. Rigidity : cogwheel phenomenon. Bradikinese Weakness & fatique Dystonia Parkinsonian facies mask-like Micrographia Gait: Festinant gait = Parkinsonian gait
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Clinical findings (cont)

9. freezing: late stage, suddlenly stop walking 10. Slowly speaking and monotone 11. Eye movements: - lack of blinking - eye movement disturb. - Glabella reflex (+) 12. Pain: paresthesia of limbs

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Clinical findings (cont)

13. ANS disturbance: - salivary / excessive sweating -urinary incontinence etc. 14. Saliva !!! sialorrhea 15. Hypotension orthostatic hypotension 16. Depression 17. Dementia
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Gait:

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Tremor:

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Rising:

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Sitting:

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Hypomimia:

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Retropulsion:

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Freezing:

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Diagnostic procedure
Diagnosis is made clinically based on clinical symptoms found EEG examination : may show diffuse slow wave MRI & CT Scan : may show cortical atrophy.

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Treatment
It is considered: due to dopamine deficiency in CNS. 1. Levodopa 2. Anticholinergic drugs: trihexyphenidyl 3. Antihistamine: diphenhydramine 4. Bromocriptine 5. Amantadine 6. Selegiline
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TH DD L-tyrosine ----- l-dopa ----- DA TH: tyrosine hydroxylase DD: dopa-decarboxylase DA located outside vesicles will be catalyzed by enzymes : MAO(monoamine-oxydase) inside the neuron cell COMT(catechol-o-methyl-transferase) outside the neuron cell.
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In peripheral : 1. l-dopa dopamine I dopa-decarboxylase v ^ dopa-decarboxylase inhibitor = carbidopa sinemet = benserazide madopar

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2. l-dopa dopamine I catechol-O-methyltransferase (COMT) v ^ COMT inhibitor : - tolcapone - entacapone

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Prognosis:
The prognosis is still poor .

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Diseases & syndromes with abnormal movements :

Essential tremor (familial / benign) Parkinsonism Progressive supranuclear palsy Idiopathic torsion dystonia Chorea sydenham Sindroma Gilles de la Tourette Drug-induced movement disorders,

etc.
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Parkinsonism = Parkinson syndrome

1. Primary/ Idiopathic = Paralysis agitans = Parkinson disease 2. Secondary / Symptomatic = Well known causes : - arteriosclerosis - anoxia / cerebral ischemia - drugs - toxic agents - encephalitis, etc.

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Parkinsonism (Cont)
3. Paraparkinson / Parkinson plus - Wilson disease - Huntington disease - Normotensive Hydrocephalus

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ESSENTIAL TREMOR
Familial tremor Benign tremor Autosomal dominant Begin at teen-agers or young adults

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 Tremor usually affect one or both hands, head and voices, whereas foot is not affected. Neurological assessments show no other abnormality. Despite the longer the tremor the clearer the symptoms, usually it does not disturb ,but the patient feels ashamed.

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 Sometimes it disturbs fine and difficult movements, writing and speaking when laryngeal muscle is involved .

Consuming small amount of alcohol temporary improvement is reported, but the mechanism has not been known yet.

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Treatment - Diazepam 6 15 mg per day - Propranolol 40 - 120 mg per day - Primidone - Alprazolam - Not responsive: # thalamotomy # thalamic stimulation

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CHOREA SYDENHAM
Affecting children and young adults resulting from complication of streptococcus hemolytic A infection and the possible basic pathological features is arteritis. Approximately 30% of cases occur 2 or 3 months following rheumatoid fever or polyarthritis, the rest without such historys.

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 Onset can be acute or gradually within 4-6 months, can also occur during pregnancy or oral contraceptive users. Symptoms including abnormal chorea movements, sometimes unilaterally in mild cases. Changes of behavior In children may reveal easily to anger and doughty Labile of emotions

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 In 30% of cases involves the heart Treatment: bed rest, sedatives, prophylaxis antibiotics even though without acute rheumatoid fever . Penicillin injection to be continued orally until 20 years of age to prevent staphylococcal infection. The prognosis basically lies on the complication of the heart.

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Drug-induced movement disorders

1. 2. 3. 4. 5. 6. Parkinsonism Acute dystonia or dyskinesis Akathisia Tardive dyskinesis Neuroleptic malignant syndrome Others.

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Parkinsonism.
Complication of dopamine receptor inhibitor drugs: - phenothiazine - butyrophenone - thioxanthene - metoclopramide

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Parkinsonism (Cont)
Symptoms : - rigidity - mask-like face - bradykinesis - tremor (seldom) Treatment : - Discontinue the drug - anti-cholinergic drugs (trihexyphenidyl)
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Acute dystonia / dyskinesia

blepharospasm torticollis facial grimacing following phenothiazine administration. Treatment: Intravenous anti-cholinergicdrug (benztropine 2 mg or diphenhydramine 50 mg).
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Blepharospasm

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Akathisia
Motoric restlessness, compulsion to move or inability to sit still for more than a short period of time, keep standing or walking. Receiving phenothiazine Treatment: - Lowering the dose if possible - propranolol 40-120 mg/hari - anticholinergic drugs / benzodiazepines
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Tardive dyskinesia
Repetitive involuntary movements of the mouth, tongue and lips, occasionally accompanied by dystonic posturing or choreoathetotic movements of trunk and limbs. Mostly following administration of neurolep tic, metoclopramide, antihistamines, tri-cyclic antidepressant and chronic alcohol abuse.

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Tardive dyskinesia (Cont)

Treatment: - Dopamine antagonists : haloperidol - Catecholamine-depleting agents: reserpine, tetrabenazine. - Baclofen - Calcium channel blocking agents - Vitamin E, etc.
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Neuroleptic malignant syndrome

An acute idiosyncratic reaction to neuroleptic medication due to central dopamine receptor blockade. May also originate from non-neurololeptic drugs: metoclopramide, domperidone, amphetamines, reserpine, tetrabenazine, tricyclic antidepressants with lithium or with MAO inhibitor and withdrawal of antiparkinsonian medication.
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Neuroleptic malignant syndrome(Cont)

The use of cocaine and 3.4 methy- lene dioxymethamphetamine (MDMA) = Ecstasy Symptoms are usually abrupt in onset, fever, encephalopathy with fluctuating confusion and agitation progressing to coma, labile BP, tachycardia, diaphoresis in association with dystonia and tremor. The couse is often rapid in untreated cases wit deterioration leading to cardiac failure , pulmonary congestion, pneumonia, renal failure and death.

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Neuroleptic malignant syndrome (Cont)

Treatment: - Discontinue the neuroleptic drugs - Control of body temperature - Monitor the BP, urine, electrolytes, temperature change - Administer bromocriptine 75 -100 mg/day by NGT - Dantrolene sodium i.v and convert to oral as improvement occurs.

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Others:
Levodopa various abnormal movement is related to dosage. Bromocriptine, anticholinergic drugs, phenytoin, carbamazepine, amphetamine, lithium and oral contraceptive may also result in chorea ect.

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