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Dr Sadik AL-Ghazawi

MRCP FRCP UK

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Movement Disorder

The control of voluntary movement is affected by

the interaction of the pyramidal , cereballar &

extrapyramidal systems interconnecting with

each other as well as projecting to anterior

horn region or cranial nerve motor nuclei.

.

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The extrapyramidal system consists of

paired subcortical masses or nuclei of gray matter,

the basal ganglia which consist of, caudate,

butamen, globus pallidus , subthalamic nuclei, and

substantia nigra.

The caudate nucleus & butamen are collectively

referred to as the (striatum)

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Acetylcholine :

Synthesis by small striatal cells.

Greatest information in striatum.

Excitatory effect

Dopamine:

Synthesis by cell substantia nigra and nigral

projection in striatum .

Greatest concentration in substantia nigra

Inhibiting effects.

Note: these two transmitters normally are "in

balance" .

Imbalance –ACH depletion or dopamine excess

results in the movement disorder, chorea.

Dopamine depletion –results in the movement

disorder of Parkinsonism.

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Gamma aminobutyric acid ( GABA)

synthesis in the striatum & globus pallidus.

It has inhibitory action

Deficiency is associated with

Huntington's chorea.

.

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Negative features

1- Bradykinesia: a loss or slowness of voluntary

movement, this result in :

• reduced facial expression (mask- like).

• Reduced blinking

• Reduced adjustment of posture when seated

• When agitated , the patient will move swiftly- "

kineasia paradoxical".

.

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Postural disturbance: -2

Flexion of limbs and trunk is associated with Failure

" adjustment torighting to make quick postural or "

correct balance, patient falls whilst turning or if

pushed

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Positive features:

1- Involuntary movement

Tremor

Chorea ( irregular , repetitive, jerky

movement)

Athetosis (irregular , repetitive, writhing

movement).

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Dystonia ( slow, sustained abnormal movement).

Ballismus ( explosive, violent movement)

Choreaothetosis : chorea & athetosis may merge

into one another.

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2- Rigidity:

stiffness felt by the examiner when passively

moving a limb.

This "resistance is present with the same

degree through out the full range of

movement.

affecting flexor & extensor muscle groups

equally, & is described as lead pipe rigidity.

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when tremor is super imposed upon rigidity it

produces " cogwheel" rigidity.

Note: In Parkinson's Disease both positive

features e.g. tremor, & negative features e.g.

bradykinesia occur.

Note: In Huntington's chorea positive features

,e.g. chorea, predominate.

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Parkinson's disease:

Described by James Parkinson( 1817) in " An

assay on the shaking palsy".

Recognized as an extrapyramidal disorder by

Kenner Wilson 1912.

Annual incidence: 20/ 100000.

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Prevalence 190/100000

Sex incidence : M:F -3:2

Age of onset : 50 years upward.

Incidence peak in mid – 70s then decline.

Familial incidence occur in 5%.

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Risk Factors:

Family history of PD

Head trauma (Concussion)

Exposure to chemicals and pesticides

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Features of Parkinson's Disease occur in many

disorders ( Akinetic Rigid syndromes) :

Idiopathic Parkinson's Disease

Secondary Parkinsonism :

a-Drug induced ,e.g. haloperidol

b-Post encephalopathic

c- toxic e.g. CO

d- toxic (endogenous) e.g. Wilson's

Disease

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Multiple system atrophy (MSA).

Progressive supraneuclear palsy

Corticobasal degeneration

Diffuse Lewy’s bodies disease

Alzheimer's disease

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Pathology of idiopathic Parkinson's Disease:

The substantia nigra contains pigmented cells

( neuromelanin) which gives it a characteristics

black appearance.

These cells are lost in Parkinson's Disease& the

substantia nigra become pale.

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Remaining cells contain esonophilic inclusions in

the cytoplasm –Lewy’s bodies- although these are

not specific to Parkinson's Disease .

Lewy's bodies may be found in the cerebral cortex

especially when dementia is present (diffuse Lewy’s

body disease).

Minor changes are seen in other basal nuclei-

striatum & globus pallidus.

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Clinical features:

Initial symptoms are vague, the patient often\

complains of aches & pain .

1- coarse tremor:

Coarse at a rate 4/ second , usually develops

early in the disease.

It begins unilaterally in the upper limbs &

eventually spread to all 4 limbs.

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The tremor is often " pill-rolling”, the thumb

moving rhythmically back & forward on the

palm.

It occurs at rest , improve with movement &

disappears during sleep.

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2- Rigidity:

oPredominant in flexor muscles of the neck,

trunk, & limbs.

oResults in the typical " flexed posture".

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:Bradykinesia -3

Slowness or paucity of movement affects

facial muscles of expression ( mask- like

appearance) as well as muscles of

mastication, speech, voluntary swallowing &

muscles of the trunk & limbs.

Dysartheria , dysphagia & slow deliprate gait

with little associated movement ( arm

swinging).

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Notes:

Tremor, rigidity & bradykinesia deteriorate

simultaneously, affecting every aspect of the

patient's life :

hand writing reduced in size (micrographia),

the gait become shuffling & festinant (small,

rapid steps to " keep up with" with the center of

gravity) and the posture more flexed.

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Rising from a chair becomes laborious with

progressive difficulty in initiating lower limb

movement from a stationary position .

Eye movement may be affected with loss of

ocular convergence & upward gaze.

Excessive sweating & greasy skin (seborrhea )

can be trouble some.

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Depression, drug- induced confusional state &

dementia occur in 30% of patients.

Occasionally autonomic features occur –

postural hypotension.

Note: Post-encephalictic Parkinson's disease

( encephalitis lethargica) now rarely encountered, is

characterize by an earlier age of onset & oculogyric

crisis ( acute ocular deviation) .

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•Cognitive dysfunction.

•Psychosis.

•Mood disorders (depression, anxiety, apathy/abulia).

•Sleep disturbances.

•Fatigue.

•Autonomic dysfunction (urinary urgency/frequency,

constipation, orthostasis, erectile dysfunction).

•Olfactory dysfunction.

•Pain and sensory disturbances.

•Dermatologic findings (seborrhea).

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Features of Parkinson disease

1-Bradykinesia 2-Rigidity

3-Resting tremor 4-Postural Instability

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Diagnosis:

When tremor, rigidity & bradykinesia

co-exist ,distinguish Parkinson's

disease from secondary Parkinsonism by the

absence of relevant drug history.

Tremor should be distinguished from :

senile tremor, essential tremor & metabolic

tremor; which are all absent at rest & more

pronounce on voluntary movement.

.

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Parkinson disease medical treatment (motor symptoms)

Levodopa

Dopamine Agonists

Monoamine Oxidase B inhibitors (e.g. Selegiline)

Anticholinergic Agents (e.g. Benztropine, Trihexyphenidyl).

Amantidine.

Catechol-O-Methyl transferase inhibitors (COMT) (e.g.

Entacapone).

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Levodopa or Dopamine Agonists shouldn’t be stopped

abruptly

Risk of Parkinsonism Hyperpyrexia Syndrome

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Exogenous dopa:

-Given as;

1-levodopa or

2- levodopa + decarboxylase inhibitor, which

prevents peripheral brake down of levadopa in

the liver allowing a higher concentration of dopa

to reach the blood-brain barrier; also the

peripheral side effects of levodopa ( nausea,

vomiting, hypotension) are diminished.

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Central side effects:

confusion, depression,

dyskinetic movements and following

long- treatment- " on /off" phenomenon.

Controlled –release or long acting preparations

produce constant plasma levels & a more even

clinical response.

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Exogenous dopa improve bradykinesia, rigidity,

& to a lesser extent, tremor, but in 20% the

response is poor.

The "good" responders often develop central side

effects later – especially the

" on/off " phenomenon.

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Dopamine Agonist:

When levodopa responsiveness is low , dopamine

agonist are used.

-Bromorciptine .

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-Apomorphine

given by continuous infusion or intermittent

injection & is affected in shortening periods of

prolong immobility (freezing).

Dopamine agonist may produce postural

hypotension & confusion.

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Selegililine:

The enzymes monoxidase (MAO) A & B play a key

role in the break down of Dopamine.

This drug is an MAO –B inhibitor, its usage

results in increased dopamine levels.

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Amantidine,

an antiviral drug, may help rigidity, the mode of

action is not known.

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Surgical treatent of parkinson disease:

•1-Deep brain stimulation (STN, Gpi).

•2-Ablative surgery: (Thalamotomy, Pallidotomy &

Subthalamotomy).

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Advances in drug treatment in recent years have

reduced the need for stereotactic surgery, but in

patients with intractable tremor this is still of

benefit, a steriostactic lesion is made in the

globus pallidus or ventrolateral nucleus of the

thalamus ( contralateral to the tremor).

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Essential tremor

•1-Worsens with age and may eventually significantly interfere with

normal activities.

•4-10 Hz

•2-50% AD, LINGO1 gene.

•3-Mild parkinsonian features (i.e., rest tremor, cog wheeling, and

breakdown in rapid alternating movements) may also be present.

•Improves with alcohol intake.

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Physiologic tremor

1-Normally present in healthy individuals.

8-12 Hz

2-Factors Enhanced physiological tremor:

Stress, fatigue, emotions, hypoglycemia, hypothermia, thyrotoxicosis,

pheochromocytoma, drug withdrawal, and alcohol intoxication and Beta

receptor agonists.

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Chorea

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c nonrhythmie unpredictablid Rap

, trunk, distal limbsinvoluntary contractions affecting mostly

in an rapidly flip from region to regionneck and face which

.irregular pattern

DD ,Athetosis and ballism are sometimes confused with chorea.

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Ballismus:

Movement of the proximal limb muscles with

a larger amplitudes and more rotatory or flinging quality than chorea.

Hemiballismus

Athetosis:

Slow flowing writhing involuntary movement

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Pathophysiology Of Chorea

Loss of inhibition in the indirect pathway>> excessive dopaminergic

activity.

Putamen, Globus pallidus and subthalamic nuclei and caudate in

Huntington disease.

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Chorea:

Uninvoluntary, irregular, jerking movement

affecting limb & axial muscle groups.

These movements are suppressed with

difficulty and are incorporated into voluntary

gestures resulting in a "semi purposeful“

appearance e.g. crossing & uncrossing of legs.

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Causes :

Hereditary)(Huntington's disease), benign chorea.

Drugs: Antiparkinsonian drugs, oral

contraceptive.

Toxins: alcohol, CO poisoning.

Infections: Sydenham's chorea, encephalitis.

Metabolic: hyperthyroidism, hypocalcemia.

Immunological: SLE, PAN

Miscellaneous: Chorea gravidarum, polycythemia

rubra vera .

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Treatment

•Monoamine inhibitors: (depletes dopamine) Tetrabenazine, Reserpine •Antipsychotics : (dopamine receptor antagonists) Haloperidol, risperidone

•Anticonvulsants: Clonazepam, valproic acid (chorea?)

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Huntington's disease :

Autosomal disorder

Onset in middle life & progression to death within

10-12 yrs .

It may occur in young person (juvenile) ; here

chorea less apparent & negative symptoms

( rigidity) predominate.

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Pathology:

Neuronal loss in the striatum is associated with

reduction in projections to other basal ganglia

structure.

.

The neurochemical basis of this disorder

involves deficiency off GABA & Ach

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Clinical features:

1-Chorea:

- may be the initial symptom.

gross involuntary movements which

interrupt involuntary movement & make feeding

& walking impossible.

2- Dementia

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3- Behavioral disturbance:

1- Personality change.

2- Affective disorder & psychosis occurs.

4- Hypotonicity often accompanies choreiform

movement.

5- Primitive reflexes : grasp,

6- Eye movements are disturbed with impersistence

of gaze.

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Diagnosis:

On clinical ground

• Family history ( although true

• parents may be unknown or

•knowledge of illness suppressed.

• Distinguish from benign hereditary chorea in

which intellect is preserved.

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• Exclude senile chorea by older age of onset &

absence of dementia .

• CT scan may demonstrate atrophy of the

caudate nucleus.

MRI shows an increased in the T2 signal in the

caudate nucleus.

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Treatment :

Phenothiazine, haloperidol, or tetrabenazine may

control the movements in the preliminary stages.

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Sydenham's chorea

•Group A beta hemolytic streptococcus

•Age (5-15 years)

•Rheumatic fever

•Few weeks after onset.

•Associated with psychiatric symptoms.

•Self limited.

•Recurrence (20%)

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Sydenham's chorea:

Acute onset.

Associated with streptococcal infection.

Remits in weeks.

Necrotizing arteritis in thalamus, caudate

nucleus & potamin.

Diagnosis is confirmed by elevated ESR &

antistreptolycine ( ASL) titer.

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Treatment:

sedation, phenothiazines.

The condition may become recurrent – during

pregnancy, intercurrent infection.

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Chorea Gravidarum:

Acute onset in pregnancy, usually the first

trimester.

Restricted to face or generalized.

Perhaps caused by reactivation of

Sydenham's chorea.

Pathology unknown.

Treatment: Haloperidol.

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Benign chorea:

Dominant inheritance with incomplete

penetration.

Onset in childhood.

The movements are mild, occasionally

aggravated by physical exercise .

Rarely progressive.

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Dystonia

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Sustained contraction of agonist and antagonist muscles,

leading to abnormal postures with repetitive twisting

movements.

• Focal

Blephrospasm

Cervical dystonia

• Segmental

• Generalized

• Multifocal

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Cervical dystonia • The most common focal dystonia. • Manifests with involuntary head posture, neck pain and a tremor Task-specific dystonia • Only with specific activities • The most common task-specific dystonia is writer’s cramp

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Botulinum injection (focal) Anticholinergics Dopamine-depleting ( Tetrabenazine) Muscle relaxants (GABA agonists) Levodopa Surgical (DBS of the Gpi)

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Spasmodic torticollis ( Wry neck):

Unilateral deviation of the head .

Etiology is unknown.

Dystonic contraction of the left

sternomastoid produces head turning to the

right.

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Treatment:

Anticholenergic & phenothiazines produce

some benefit in 50% of patients.

Injection off botulinum toxin into the

sternomastoid muscle gives variable

systematic relieve so requires regular

repetition.

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Writer's Cramp:

Variable age of onset.

Muscles of the hand & forearm tighten on

attempting to right and pain may occur in the

forearm muscles.

Previously regarded as an " occupational

neurosis" but now is classified as a partial

dystonia.

May be precursor of Parkinson's Disease.

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Treatment :

Benzodiazipine & anticholenrgic are of limited

value.

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Drug induced dystonia:

Acute adoption of abnormal dystonic posture

– usually head & neck or oculogyric crisis

( upward deviation of eyes)- caused by

phenothiazine & metaclopramide.

Anticholenergic, benztropine -24-48 hrs help

symptom settle.

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Progressive supranuclear palsy:

A condition characterize by gaze palsy,

extrapyramidal features, axial dystonia (

truncal) .

Progressive psudobulbar palsy.

Onset in the 5th – 6th decade.

Etiology unknown.

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Down eye movement is initially impaired

followed by all other voluntary eye movement,

lid retraction is common.

Psudobulbar signs develop.

The head then hyperextend & rigidity ensues in

the limbs.

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Treatment:

Levodopa & anticholenergics give disappointing

results.

The coarse is relentless with progression & death

in 2-5 yrs.

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Hemiballismus:

Unilateral, violent, flinging of the limbs.

Occusionally severe enough to throw the patient

of balance or even from his bed.

Lesion of subthalamic nuclei .

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It usually results from vascular disease

( posterior cerebral artery).

Occasionally occur in MS.

Drug treatment is ineffective.

The condition often settled spontaneously.

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Athetosis:

Present in childhood

Slow writhing movement, the rate of movement

between chorea or dystonia.

Involve the digits , hands & face on each side.

Associated with hypoxic neonatal brain

damage, kirnicterus, lipid storage disease.

Response to anticholenergic is variable &

occasionally dramatic.

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Tradive Dyskinesia(TDs) are involuntary movements of the tongue, lips, face, trunk, and extremities that occur in patients treated with long-term dopaminergic antagonist medications • May occur during therapy with dopamine-receptor antagonists or even years after the medication is discontinued

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• Oro-bucco-lingual movements , restlessness), dystonia , tremor, parkinsonism, or combination of these

Treatment:

Discontinue neuroleptic. If not possible, continue on

lowest possible dose.

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Tics

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Sudden, relatively quick, stereotyped movements (motor tics) or sounds (phonic tics) which are repeated at irregular intervals.

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Wilson's Disease:

Autosomal recessive disorder of copper metabolism.

Neuronal loss within potamine & globus pallidus .

Copper accumulate in descemet membrane in the

eyes, nail bed, liver & kidney.

Deficiency of alpha 2 globuline – ceruloplasim – which

normally binds 98% of copper in the plasma.

Increased in loosely bound copper- albumine &

deposition occur in all organs.

Urinary copper is increased.

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Clinical features:

Two clinical forms:

•Acute (Children): characterized by ,

•bradykinesia, behavioral changes,

•

involuntary movement, liver involvement is

common,

•untreated , death in 2 yrs from hepatic & renal

failure.

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•Chronic ( young adult): marked proximal

tremor, dysartheria, dystonia,

•rigidity, choreoathetosis, psychosis,

•

behavioral disorders, dementia,

•

liver involvement less severe,

• untreated , death in 10 yrs.

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Diagnosis:

Slitlamp (Kayser-Fleischer ring).

Low seruloplasmine < 20mg/dl.

Elevated unbound serum copper.

High urinary copper excretion.

Liver biopsy & copper metabolism test with

radioactive CU 64.

MRI

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In families, biochemical test identify low

ceruloplasmine in carriers and presymptomatic

patients.

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Treatment:

Low copper diet ,

pencillamine 1gm daily.

Treatment for the patient life, adequate treatment

is compatible with normal life.

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Clinical presentation:

- Childhood.

- Motor before vocal tics.

- (85%) experience reduction in tics during and after adolescence.

- Psychiatric manifestations:

Depression and mood disorders.

Tourette’s syndrome

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Myoclonus

sudden, brief and shock-like involuntary

movements.

Types:

Physiologic: , Anxiety, Hiccups

Epileptic.

Symptomatic.

Treatment

Clonazepam, Sodium valproate, Levetricetam.

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Dr Sadik Sharief

MRCP, FRCP Edinburgh

Lecture