17-Oct-191

Dr Sadik AL-Ghazawi

MRCP FRCP UK

17-Oct-192

17-Oct-193

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.

.

17-Oct-194

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)

17-Oct-195

17-Oct-196

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.

17-Oct-197

Gamma aminobutyric acid ( GABA)

synthesis in the striatum & globus pallidus.

It has inhibitory action

Deficiency is associated with

Huntington's chorea.

.

17-Oct-198

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".

.

17-Oct-199

2- Postural disturbance:

Flexion of limbs and trunk is associated with Failure

to make quick postural or " righting" adjustment to

correct balance, patient falls whilst turning or if

pushed

17-Oct-1910

Positive features:

1- Involuntary movement

Tremor

Chorea ( irregular , repetitive, jerky

movement)

Athetosis (irregular , repetitive, writhing

movement).

17-Oct-1911

Dystonia ( slow, sustained abnormal movement).

Ballismus ( explosive, violent movement)

Choreaothetosis : chorea & athetosis may merge

into one another.

17-Oct-1912

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.

17-Oct-1913

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.

17-Oct-1914

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.

17-Oct-1915

❖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%.

17-Oct-1916

17-Oct-1917

17-Oct-1918

Risk Factors:

Family history of PD

Head trauma (Concussion)

Exposure to chemicals and pesticides

17-Oct-1919

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

17-Oct-1920

Multiple system atrophy (MSA).

Progressive supraneuclear palsy

Corticobasal degeneration

Diffuse Lewy’s bodies disease

Alzheimer's disease

17-Oct-1921

17-Oct-1922

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.

17-Oct-1923

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.

17-Oct-1924

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.

17-Oct-1925

➢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.

17-Oct-1926

2- Rigidity:

oPredominant in flexor muscles of the neck,

trunk, & limbs.

oResults in the typical " flexed posture".

17-Oct-1927

3- Bradykinesia :

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).

17-Oct-1928

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.

17-Oct-1929

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.

17-Oct-1930

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) .

17-Oct-1931

•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).

17-Oct-1932

Features of Parkinson disease

1-Bradykinesia2-Rigidity

3-Resting tremor

4-Postural Instability

17-Oct-1933

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.

.

17-Oct-1934

17-Oct-1935

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).

17-Oct-1936

17-Oct-1937

Levodopa or Dopamine Agonists shouldn’t be stopped

abruptly

Risk of Parkinsonism Hyperpyrexia Syndrome

17-Oct-1938

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.

17-Oct-1939

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.

17-Oct-1940

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.

17-Oct-1941

Dopamine Agonist:

When levodopa responsiveness is low , dopamine

agonist are used.

-Bromorciptine .

17-Oct-1942

-Apomorphine

given by continuous infusion or intermittent

injection & is affected in shortening periods of

prolong immobility (freezing).

Dopamine agonist may produce postural

hypotension & confusion.

17-Oct-1943

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.

17-Oct-1944

Amantidine,

an antiviral drug, may help rigidity, the mode of

action is not known.

17-Oct-1945

Surgical treatent of parkinson disease:

•1-Deep brain stimulation (STN, Gpi).

•2-Ablative surgery: (Thalamotomy, Pallidotomy &

Subthalamotomy).

17-Oct-1946

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).

17-Oct-1947

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.

17-Oct-1948

17-Oct-1949

17-Oct-1950

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.

17-Oct-1951

Chorea

17-Oct-1952

➢Rapid unpredictable nonrhythmic

involuntary contractions affecting mostly distal limbs, trunk,

neck and face which rapidly flip from region to region in an

irregular pattern.

➢DD ,Athetosis and ballism are sometimes confused with

chorea.

17-Oct-1953

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

17-Oct-1954

Pathophysiology Of Chorea

✓Loss of inhibition in the indirect pathway>> excessive

dopaminergic activity.

✓Putamen, Globus pallidus and subthalamic nuclei and

caudate in Huntington disease.

17-Oct-1955

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.

17-Oct-1956

17-Oct-1957

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 .

17-Oct-1958

Treatment

•Monoamine inhibitors: (depletes dopamine)Tetrabenazine, Reserpine

•Antipsychotics : (dopamine receptor antagonists)Haloperidol, risperidone

•Anticonvulsants:Clonazepam, valproic acid (chorea?)

17-Oct-1959

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.

17-Oct-1960

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

17-Oct-1961

Clinical features:

1-Chorea:

- may be the initial symptom.

gross involuntary movements which

interrupt involuntary movement & make feeding

& walking impossible.

2- Dementia

17-Oct-1962

17-Oct-1963

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.

17-Oct-1964

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.

17-Oct-1965

• 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.

17-Oct-1966

Treatment :

Phenothiazine, haloperidol, or tetrabenazine may

control the movements in the preliminary stages.

17-Oct-1967

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%)

17-Oct-1968

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.

17-Oct-1969

Treatment:

sedation, phenothiazines.

The condition may become recurrent – during

pregnancy, intercurrent infection.

17-Oct-1970

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.

17-Oct-1971

Benign chorea:

Dominant inheritance with incomplete

penetration.

Onset in childhood.

The movements are mild, occasionally

aggravated by physical exercise .

Rarely progressive.

17-Oct-1972

Dystonia

17-Oct-1973

DYSTONIA

Sustained contraction of agonist and antagonist muscles,

leading to abnormal postures with repetitive twisting

movements.

• Focal

Blephrospasm

Cervical dystonia

• Segmental

• Generalized

• Multifocal

17-Oct-1974

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

17-Oct-1975

✓Treatment ✓

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

17-Oct-1976

Spasmodic torticollis ( Wry neck):

Unilateral deviation of the head .

Etiology is unknown.

Dystonic contraction of the left

sternomastoid produces head turning to the

right.

17-Oct-1977

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.

17-Oct-1978

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.

17-Oct-1979

Treatment :

❖Benzodiazipine & anticholenrgic are of limited

value.

17-Oct-1980

Drug induced dystonia:

❖Acute adoption of abnormal dystonic posture

❖ – usually head & neck or oculogyric crisis

( upward deviation of eyes)- caused by

phenothiazine & metaclopramide.

❖Treatment

Anticholenergic, benztropine -24-48 hrs help

symptom settle.

17-Oct-1981

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.

17-Oct-1982

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.

17-Oct-1983

Treatment:

Levodopa & anticholenergics give disappointing

results.

The coarse is relentless with progression & death

in 2-5 yrs.

17-Oct-1984

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 .

17-Oct-1985

It usually results from vascular disease

( posterior cerebral artery).

Occasionally occur in MS.

Drug treatment is ineffective.

The condition often settled spontaneously.

17-Oct-1986

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.

17-Oct-1987

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-receptorantagonists or even years after the medication is

discontinued

17-Oct-1988

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

Treatment:

Discontinue neuroleptic. If not possible, continue on

lowest possible dose.

17-Oct-1989

Tics

17-Oct-1990

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

17-Oct-1991

17-Oct-1992

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.

17-Oct-1993

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.

17-Oct-1994

•Chronic ( young adult): marked proximal

tremor, dysartheria, dystonia,

•rigidity, choreoathetosis, psychosis,

•

behavioral disorders, dementia,

•

liver involvement less severe,

• untreated , death in 10 yrs.

17-Oct-1995

17-Oct-1996

Diagnosis:

Slitlamp (Kayser-Fleischer ring).

Low Ceruloplasmine < 20mg/dl.

Elevated unbound serum copper.

High urinary copper excretion.

Liver biopsy & copper metabolism test with

radioactive CU 64.

MRI

17-Oct-1997

In families, biochemical test identify low

ceruloplasmine in carriers and presymptomatic

patients.

17-Oct-1998

Treatment:

Low copper diet ,

pencillamine 1gm daily.

Treatment for the patient life, adequate treatment

is compatible with normal life.

17-Oct-1999

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

17-Oct-19100

Myoclonus

➢sudden, brief and shock-like involuntary

movements.

➢Types:

Physiologic: , Anxiety, Hiccups

Epileptic.

Symptomatic.

➢Treatment

Clonazepam, Sodium valproate, Levetricetam.

17-Oct-19101

Dr Sadik Sharief

MRCP, FRCP Edinburgh

Lecture