Movement disorders د.رشاد عبدالغني

8/3/2019 Movement disorders .

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MOVEMENT DISORDERS

Dr. Rashad Abdul ghani

Assistant Professor of Neurology


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Exrapyramidal system

This system includes

The non-

pyramidal motorareas in cerebral

cortexBasal ganglia

and their descending tracts


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The basal ganglia (BG) are a group of

nuclei situated in the deep part of the

cerebrum and upper part of the brain

stem

Thesenuclei are


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Functions

Premotor and somatosensory areas

control the axial and proximal limb

muscles and produce subconscious

associated automatic movements

The basal ganglia control the muscle tone

and are essential for performance of finevoluntary movements


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Basal ganglia circuit


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inhibitstimulate

Hyperkinetic disorderHypokinetic disorder


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Pathophysiology of basal ganglia disorders can be

classified into :

Hyperkinetic disorder

Chorea

Hemiballismus

Firing of VIN

Tremor


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Akinesia

RigidityParkinsonism

Dystonia is associated

with putamenal lesion

Hypokinetic disorder


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Movement disorders

A movement disorder impairs the regulation of

voluntary motor activity without directly affecting

strength, sensation or cerebellar function."

Movement disorders typically result from diseases

of the basal ganglia and can be classified intoAkinetic rigid syndromes (Hypokinesia) Parkinson

disease and other parkinsonism (Akinesia /

bradykinesiaand rigidity).Hyperkinesias (Hyperkinesia) (tremor, chorea,

athetosis, ballism, tics, dystonia and myoclonus).


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General concepts

Movement Disorder-Term for a physical sign

- Term to describe a specific syndrome/condition

Either excess of movement or paucity ofvoluntary and automatic movements, unrelatedto weakness or spasticity

Diagnosis of movement disorders requires:

- Identify the type and pattern of movement

- Isolated or accompanied with other neuro signs

- Determine probable etiology


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A systematic approach to diagnosis in patients presenting

with movement disorders

Abdo, W. F. et al. (2010) The clinical approach to movement disorders

Nat. Rev. Neurol. doi:10.1038/nrneurol.2009.196


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Characteristics to classify movements

Distribution Velocity

Amplitude

Stereotypy

Rythmicity

Suppressibility

Relationship to position, sleep, activity


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Parkinsonism -Akinesia / Bradykinesia

Impaired initiation of movement (Akinesia) Slowness of movement (Bradykinesia)

Reduced amplitude of voluntary movement

Slow initiating movement on command Loss automatic movements

Short shuffling steps

Loss spontaneous movement (gestures)

Hypomimina (decreased blink)

Hypophonia

Aprosody

Drool (decreased spontaneous swallow)


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Rigidity Increased muscle tone to passive motion

Present equally in all direction of the passive

movement throughout the range of motion

Distinguish from spasticity (velocity dependent)

Distinguish from paratonia (inability to relax)

Freezing Motor act halted transiently (several seconds)

Agonists and antagonist muscles are simultaneously andisometrically contracting

Start hesitation, turning hesitation, destination hesitation,freeze with obstacle


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Parkinson Disease (paralysis agitans)

Parkinson disease (PD) is a progressive

neurodegenerative disorder associated with a loss of

dopaminergic nigrostriatal neurons.

PD is recognized as one of the most common

neurological disorders, affecting approximately 1%

of individuals older than 60 years.

Cardinal features include aymmetrical sresting

tremor, rigidity, bradykinesia, and postural

instability.


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Pathophysiology

normal

Park dis


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Epidemiology

The incidence has been estimated to be 4.5-21cases per 100,000.

Prevalence range from 18-328 per 100,000population .

Most studies yielding a prevalence ofapproximately 120 per 100,000.

Male:female ratio 1.5: 1

Age:The incidence and prevalence of PD increasewith age. The average age of onset isapproximately 60 years


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Clinical features:

Onset of PD is typically asymmetric, with the mostcommon initial finding being an asymmetric resting

tremor in an upper extremity.


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Over time, patients notice symptoms related to

progressive bradykinesia, rigidity, and gait

difficulty. Symptoms of autonomic dysfunctionare common.


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Postural instability refers to imbalance and loss of

righting reflexes. Its emergence is an importantmilestone, because it is poorly amenable to

treatment and a common source of disability in late

disease.

Patients may experience freezing when starting to

walk (start-hesitation). Dementia generally occurs

late in PD and affects 15-30% of patients. Short-

term memory and visuospatial function may be

impaired


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Parkinson disease


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Causes and classification of parkinsonian

syndromes:

Primary parkinsonism: (77.7%)Parkinson disease:Sporadic and familial.

Secondary parkinsonism: (8.2%)

Drug-induced: dopamine antagonists and depletors

Toxins: Mn, CO, MPTP, cyanide

Trauma,Tumour,Vascular: multiinfarct state.

Infectious; postencephalitis

Metabolic; parathyroid dysfunction, hypoxia

Hydrocephalus; normal pressure hydrocephalus


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Parkinson plus syndrome: (8.2%)Cortical basal ganglionic degeneration (parkinsonism, apraxia,myoclonus)

Dementia syndromes:Alzeheimer disease, Diffuse lewy body disease ,Frontotemporal dementia

Multiple system atrophy syndromes:

Striatonigral degeneration (pure parkinsonism)

Shy-Drager syndrome (parkinsonism, dysautonomia)

Sporadic olivopontocerebellar degeneration(atypical tremor, ataxia, pseudobulbar palsy)

Amyotrophy-parkinsonism

Progressive supranuclear palsy (parkinsonism, supranuclear

palsy, pseudobulbar palsy, dementia)


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Heredodegenerative diseases:(0.6%)

Willson disease

Huntington disease

Neuroacanthocytosis

Hallervorden-spatz disease


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Lab Studies:No laboratory biomarkers exist for PD.

Serum ceruloplasmin concentration is obtained as

a screening test for Wilson diseasein in young

patients who present with parkinsonian

(MRI) and (CT) scan are unremarkable in PD.MRI is useful to exclude multi-infarct state,

hydrocephalus, and the lesions of Wilson disease.

PET) and (SPECT) may differentiate parkinsonsdisease from other parkinsonism.


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Treatment:

The goal of medical management of PD is to

provide control of signs and symptoms for as

long as possible while minimizing adverse

effects. Medications usually provide goodsymptomatic control for 4-6 years. After this,

many patients develop long-term motor

complications including fluctuations anddyskinesia.


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Neuroprotective therapy:

To date, no drug has been shown to influence theprogression of the disease. A clinical study

demonstrated that selegiline delays the need for

levodopa therapy in early PD by about 9 months


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Symptomatic therapy:

When should symptomatic treatment be started in

the treatment of PD?

A rational strategy is to start treatment when the

symptoms begin to impair activities of daily

living or to interfere with social and occupational

functioning.


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Levodopa, coupled with a peripheral

decarboxylase inhibitor (PDI), provides the

greatest antiparkinsonian. Dopamine agonists

provide symptomatic benefit but lack sufficient

efficacy to control signs and symptoms by

themselves in later disease.


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Early disease treatment strategies

Young patients have a longer life expectancy andare more likely to develop motor fluctuations and

dyskinesia, so other antiparkinsonian drugs should

be used first to delay the introduction of levodopa.This approach is known as dopa sparing strategy.

M di i


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Medication

L-dopaPDI-

Dopamine

agonists

COMT inhibitors

-MAO-B

inhibitors -

Amantadine

DA releaser

Anticholinergic


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Surgery

Stereotactic surgery has made a resurgence in the

treatment of PD. This is mainly because many

patients with advanced PD experience significant

disability or adverse effects despite optimal medical

management.
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Thalamotomy and chronic thalamic stimulation

are effective in reducing medically refractory

tremor.

Pallidotomy: This procedure is effective in

reducing contralateral dyskinesia.

Thalamic deep brain

stimulation (DBS) had

demonstrated benefit for

contralateral bradykinesiaand dyskinesia.
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Transplantation

Neural transplantation is a potential treatment forPD. Multiple sources of dopamine-producing

cells, including fetal nigral cells, sympathetic

ganglia, carotid body glomus cells have beenstudied. In animal PD models, fetal nigral

dopaminergic cells have been shown to form

synaptic connections that exhibit relatively

normal electrical firing patterns, and improve

motor function.


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Tremor

Non-purposeful, rhythmic, patterned to and fro oscillation

produced by regular and sequential contraction ofagonistic and antagonistic muscles.

Clinical classification:

Physiologic tremor

Rest tremor Action tremorduring voluntary contraction muscles

a-Postural tremorvoluntarily maintained against gravity

b-Kinetic tremorduring any voluntary movement

-Simple kinetic tremorduring non target directed voluntarymovement

-Intention tremorwith increasing amplitude at end ofmovement

c- Taskspecific tremorduring specific activity


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Eatiological classification of tremor

Metabolic: (B-12 deficiency,

Hyperthyroidism,

HyperparathyroidismHypocalcemia, Hyponatremia,

Kidney disease, Liver disease).

Toxic:Alcohol, Arsenic, Caffeine,

Lead, Nicotine, Withdrawal of

alcohol , cocaine.

Psychogenic tremor

Essential tremor

Parkinsonian tremor

Dystonic tremors

Cerebellar tremor

Drug-induced tremors

(antidepressants, especially

tricyclics, beta-agonists,

dopamine, lithium,metoclopramide, Na valproate,

neuroleptics, thyroid hormones).

Enhanced physiologic tremor, such as

medications, substances such as caffeine, fever,and anxiety.


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Essential tremor

Essential tremor (ET) is the most common

movement disorder. It is a syndrome

characterized by a slowly progressive postural

and/or kinetic tremor, usually affecting both

upper extremities.

The pathophysiology of ET is not known.


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Epidemiology:

The prevalence: 0.3-5.6% of the generalpopulation.

The prevalence of ET increases with age.

Age at onset has bimodal peaks- one in late

adolescence to early adulthood and a second in

older adulthood.


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Clinical features:

Tremor usually begins in one upper extremity andsoon affects the other. In about 30% of cases,

tremor involves the cranial musculature. The

tremor is characteristically postural and kinetic.Fifty to sixty percent have a family history of ET.


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Treatment:

Primidone and propranolol are the cornerstones

of maintenance medical therapy for ET.

Ch A h i B lli


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Chorea, Athetosis, Ballism

Chorea: rapid, jerky, non-rhythmic, non-patterned

aimless proximal and distal involuntarymovements (dancing-like).

Flow from one part body to another

Unpredictable in timing, direction, distribution

(random)

Athetosis: mixture of slow, twisting and writhinginvoluntary movements (snake-like)which

mainly distal. Often blends with chorea(choreoathetosis)

Ballism: Violent, flinging limb movements, which

are mainly proximal.


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Choreiform and ballistic movement

disorders

Causes and classification of chorea

Idiopathic

Hereditary - Huntington disease,

neuroacanthocytosis,

Dentatorubropallidoluysian atrophy(DRPLA), ataxia-telangiectasia,

familial calcification of basal

ganglia, Hallevorden-Spatz

disease, Mitochondrial cytopathies.

Hereditary (metabolic) - Wilson

disease, Lesch-Nyhan disease,

phenylketonuria, acute intermittent

porphyria

Other metabolic and endocrine disorders - Kernicterus, hyperthyroidism

hypoparathyroidism, hypoglycemia, nonketotic hyperglycemia, chorea

gravidarum, hypomagnesemia, chronic nonfamilial hepatic encephalopathy,

anoxic encephalopathy.


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Infectious - Sydenham chorea,

encephalitides, subacute sclerosing

panencephalitis, syphilis, HIV

infection, cerebral toxoplasmosis,Creutzfeldt-Jakob disease, subacute

bacterial endocarditis.

Drug induced - Neuroleptics,

levodopa, anticholinergics, oral

contraceptives, antihistamines,

amphetamines, cocaine, phenytoin,

tricyclics.

Toxins - Alcohol intoxication and

withdrawal, carbon monoxide,manganese, mercury.

Vascular - Cerebrovascular

disease (ischemic or

hemorrhagic), vasculitidis.

Immunologic - Systemic lupus

erythematosus, primary

antiphospholipid antibody

syndrome, multiple sclerosis,

postcardiac transplantation,

postvaccination

Tumors - Primary, metastaticc


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Sydenhams (rheumatic) chorea:

Sydenham chorea is a major manifestation ofacute rheumatic fever, seen in up to 10 per cent of

patients after streptococcal infection in endemic

areas. It arises some months after the acute illnessand is largely confined to children 5-15 years of

age. The condition is considered to be the result of

auto-antibodies reacting with the caudate nucleus.

Cli i l f t


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Clinical features

Rheumatic chorea is characterized by muscle

weakness and the presence of chorea. The patients

have the milkman grip sign, clumsy gait, and

dysarthric speech. Psychological symptoms are

equally prominent and typically precede theappearance of even the most subtle choreiform

movements.


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Lab studies: Antistreptococcal antibody titers

may no longer be elevated at presentation.

Neuroimaging: Most cases of Sydenham chorea

show no abnormalities.


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Huntingtons disease

Huntingtons disease is inherited as an autosomal

dominant. The relevant gene has been mapped tothe short arm of chromosome 4.

Neuropathology


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Neuropathology

The most striking neuropathology in HD occurs

within the neostriatum (medium spiny

neurones), in which gross atrophy of the caudate

nucleus and putamen is accompanied by

astrogliosis.


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The genetic basis of HD is the expansion of a

cysteine-adenosine-guanine (CAG) repeatencoding a polyglutamine. The increase in

polyglutamine seems to prevent the normal

turnover of the protein, resulting in aggregation ofthe protein with accumulation in the cytoplasm

and nucleus.

The prevalence of HD: 4.1-8.4 per 100,000

people.


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Clinical features:

In most, onset is in the third or fourth decade but

about 10 per cent of cases present before the ageof 20 years. Juvenile onset cases are more likely

to show paternal transmission, a fulminant

course, and a predominantly rigid picturecompared to late-onset cases.


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The clinical features of HD include a movement

disorder, a cognitive disorder, and a behavioral

disorder. Patients may present with one or alldisorders in varying degrees. Chorea is the most

common movement disorder seen in HD. As the

disease progresses, chorea coexists with andgradually is replaced by dystonia and parkinsonian

features, such as bradykinesia, rigidity, and postural

instability. Other late features are spasticity, clonus,

and extensor plantar responses.

T


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Cognitive decline is characteristic of HD.TThe

dementia syndrome associated with HD includes

early onset behavioral changes. Slowing ofcognition, impairment of intellectual function, and

memory disturbances are seen later. Other features

include ataxia, a general motor clumsiness, an

inability to sustain muscle contraction and

personality change. Saccadic eye movements are

slowed.

.


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Juvenile HD (Westphal variant), defined as

having an age of onset of younger than 20 years,

is characterized by parkinsonian features,dystonia, long-tract signs, dementia, epilepsy,

and mild or even absent chorea.

Investigations


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Investigations

Investigative findings, while often suggestive, do

not provide specific confirmation of thediagnosis.

Genetic testing

CT SCAN

MRI

SPECT


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Treatment

No specific treatment.Symptomatic treatment may improve the quality of

life and prevent complications. The choreic

movements can be controlled by the use ofneuroleptic agents.

Ti


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Tics

Tics: rapid lightening-like brief semi-purposeful,

repetitive and stereotyped movements.

Abnormal movement (motor tics) or abnormal

sounds (phonic tics) or both (tourette syndrome)

Precede by urge , can be suppressed for various

periods of time, inner tension, relieved by

increased burst of tics

P i ti di d S d ti di d


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Primary tic disorder Secondary tic disorders

Transient

Motor or vocal15% children (male>female)

Mild usually single movement

Chronic single tic disorder

Motor or vocal > 1 year

Adult onset (recurrent) tic

Tourettesyndrome

Motor and vocal > 1 year

Onset < 21 year old

Drugs

- CNS stimulants: amphetamines,methylphenidate, pemoline, cocaine

-Neuroleptics: tardive tics

Levodopa

Anticonvulsants: carbamazepine,

lamotrigine, phenytoin, phenobarbital

Hereditary:HD, Wilsons, others

Neurodevelopmental disordersPerinatal injury, chromosomal Disorders

Brain injuryStroke, encephalitis, trauma, CO poison

InfectionsSydenhams chorea, PANDAS

Postviral encephalitis, lyme, HIV


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Isolated tics are quite common in childhood,

usually remitting within a year or so of onset.

Multiple tics are classified as motor and vocal

tics. Where they are accompanied byvocalization, the diagnosis of Gilles de la

Tourettes syndrome is made .

Gilles de la Tourettes syndrome


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Clinical features

This condition usually begins in the first decade of

life, and is more common in girls. Associated

problems include echolalia, echopraxia and

various behavioural disturbances. Haloperidol has

proved the most effective drug for the treatment ofthis condition.

Dystonia


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Dystonia

Dystonia: involuntary, sustained muscle

contractions, causing twisting and repetitivemovements and abnormal postures.

Progress to prolonged abnormal postures

Repeatedly involve the same group of muscles

(unlike chorea)

Relatively long duration (compared to myoclonus

and chorea)

Agonists and antagonists contract simultaneously


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D t i


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Dystonia

Eatiological classification

Idiopathic or primary (Familial or sporadic)

Dystonis plus syndrome

Secondary as a consequence of focal brain damage

Neurodegenerative dystonia

Anatomic Distribution of Primary


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Anatomic Distribution of Primary

Torsion Dystonia

Focal Single Body Site

Segmental Contiguous body regions

Multifocal Multiple, noncontiguous body sites

Generalized Leg involvement with other body sites

Hemidystonia Unilateral

Causes of dystonias:


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Causes of dystonias:

Idiopathic or primary torsion dystonia

Vascular

Cerebrovascular,

AVMPerinatal cerebral injury

Secondary etiologies of dystonia

Infectious

Viral encephalitisSSPE

AIDS

Creutzfeldt-Jakob disease

Trauma

Head trauma

Peripheral trauma

Tumor

Brain tumor

ToxinsManganese, carbon

monoxide, carbon disulfide,

methanol

DrugsMetabolic

Kernicterus


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ugs

Levodopa, dopamine agonists,

antipsychotics, metoclopramide,

fenfluramine, flecainide, ergot

agents, anticonvulsant agents,

certain calcium channel blockers

Kernicterus

Wilson disease

Homocystinuria

Metachromatic leukodystrophyNeuronal ceroid lipofuscinosis

Niemann-Pick disease, type C

Primary antiphospholipid

antibody syndrome

Mitochondrial encephalopathies

Lesch-Nyhan syndrome

Structural

Atlanto-axial subluxationSyringomyelia

Arnold-Chiari malformation

Congenital Klippel-Feil syndrome

D t i l d


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NeurodegenerativeProgressive supranuclear palsy

Multiple systems atrophy

Corticobasal-ganglionic degeneration

Hallervorden-Spatz disease

Neuroacanthocytosis

Spinocerebellar ataxia (SCA), types 1, 2, 3Ataxia telangiectasia

Huntington disease

Dentatorubropalidoluysian atrophy

Dystonia plus syndromesMyoclonus dystonia

Rapid-onset dystonia parkinsonism

Xlinked dystonia parkinsonism (Lubag)

Wilson disease


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Wilson disease

Wilson disease, or hepatolenticular degeneration, is

a neurodegenerative disease of copper metabolism.Wilson disease is an autosomal recessive inherited

condition caused by mutations of a gene being

located on the long arm of chromosome 13.


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Pathophysiology: Wilson disease involves loss

of ability to export copper from the liver into bile

and to incorporate copper into hepatic

ceruloplasmin. Consequently, copper accumulates

in the liver, brain, kidney, and cornea.

Pathological changes include cirrhosis of the liverand atrophy of the putamen where cavitation may

appear.


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Microscopically there is neuronal cell loss

together with astrocytic proliferation.

i i


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Epidemiology

Incidence is 1 in 35,000-100,000 live births.

Age:The onset of liver disease is usually at age 8-

16 years.

Neurological symptoms are rare before age 12

years.

Clinical features


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Clinical features

About 40-50% of patients present with liver

disease and 35-50% with neurological orpsychiatric symptoms.

Kayser-Fleischer rings are almost always present

when the patient has neurological symptoms.


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Neurological Wilson disease may develop very

gradually, sometimes with acute deterioration.

There are three main types:

Dystonic type

Akinetic-rigid form

Cerebellar pseudosclerotic type


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A dystonic type presents with dysarthria,

dysphagia and drooling of saliva due to dystoniaof the face and bulbar musculature. Dystonia of

the limbs lead to rigidity, abnormal posture and a

dystonic gait.


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An akinetic-rigid form presents with prominent

resting or postural tremor and variable

bradykinesia and rigidity. The tremor of the armsmay be very severe (wing beating tremor).

A cerebellar pseudosclerotic type presents with

gait ataxia, dysarthria, limb ataxia and titubationof head.


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Psychiatric manifestation include hyperkinetic

behavior, irritability or emotional lability,

psychosis, abnormal behavior, personalitychanges and depression.


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Lab Studies:

No one test is completely reliable; diagnosis

depends upon a high index of suspicion and

supporting laboratory abnormalities.

Low serum copper level.

Low serum ceruloplasmin level.

Increased urinary copper level.

Liver biopsy Reveals evidence of liver cirrosis

with increased hepatic copper.


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Treatment


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Treatment

Treatment is based on the use of D-penicillamine,

trientine or zinc. The former two are chelatingagents; zinc acts by blocking uptake of copper from

the intestine.

Myoclonus


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y

Myoclonus: Sudden brief shock like involuntarypurposeless movement from muscle contraction(positive myoclonus) or inhibition (negative myoclonus)

Rhythmic or arrhythmic

Generalized, focal or multifocal

Stimulus sensitive or action sensitive

Symmetric or asymmetrical

Involuntary movementno preceding urge as seen in Tic.

Arise from any point in neuroaxis

Cortexcan be associated with seizures

Subcortical

Brainstem

Spinal cord

Peripheral nerve


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Differential diagnosis of MyoclonusPh i l i h i j k hi b i i f til


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Physiologichypnic jerk, hiccup, benign infantilemyoclonus

Epilepticepilepsia partialis continua, infantile spasms,juvenile myoclonic epilepsy

Progressive myoclonic epilepsyinborn errors metabolism,lysosomal storage diseases, mitochondrial disorders, etc.

Heterogeneous group of disorders characterized by epilepsy, myoclonus, progressive

neurological deterioration Symptomatic Post hypoxic

Post traumatic

Myoclonic dementiasCJD, AD, LBD

Toxic

Metabolic

Drug induced

Post infectious

Inflammatory

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Movement disorders د.رشاد عبدالغني