Movement Disorder 2

8/8/2019 Movement Disorder 2

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Extrapyramidal disorder

Incidence male: female- 3:2

Age of onset : above 50

Parkinsonism is a neurological syndrome characterised by

tremor, hypokinesia, rigidity and postural instability. Classified into

a) Idiopathic (Parkinson·s disease)

b) Secondary ² drug induced

- infectious ( post encephalitic, HIV)

- toxic ( CO & manganese poisoning)

- post traumatic

- Miscellaneous( hydrocephalus,paraneoplastic

syndrome)



Progressive neurodegenerative disorder a/wloss of dopaminergic nigrostriatal neurons.



A normally pigmented substantia nigra is seen grossly in the midbrain on the

right, but the midbrain on the left from the patient with Parkinson's diseaseshows a pale substantia nigra.

Pale substantia nigra Normal



Loss of

neuromelanin

containing

dopamine neurons

Lewy body



Dopamine- type of

neurotransmitter. chemical

messenger that affects the

brain processes that control

movement, emotional

response, and the capacityto feel pleasure and pain.

Dopamine is vital for

performing balanced and

controlled movements. A

shortage of dopamine can

cause a lack of controlled

movements such as thoseexperienced in Parkinson

disease.

.

GABAglut

GABA

GLUT GABA



Both the direct and indirect pathways lead to increased

inhibitory activity from GPi to the thalamus and brainstem.

Lesion to basal ganglia causes loss of inhibitory effect to

muscle tone leading to rigidity.



Two neurotransmitters that are involved in pre-synaptic modulation in the striatus

Dopamine

ACh

With the deficiency of dopamine, the effects of

ACh is exaggerated

The overactivity of the ACh system contributes tothe symptoms of Parkinson disease ² particularly

through the indirect pathway



Dopamine ² Facilitates the direct pathway

Inhibits the indirect pathway

1. Dopamine deficiency in striatum affects the cerebralcortex ²

Reduces direct pathway activity, resulting in akinesia (difficulty in initiating movements)

Increases indirect pathway activity, resulting in bradykinesia (decreased amplitude and velocity of

movement), by increasing antagonist muscle action tremors by increasing inappropriate movement

2. Dopamine deficiency affects the extrapyramidal nuclei ² Inhibit the brain stem nuclei, resulting in

rigidity



Aches and pain Tremor :- coarse , distal

- 4-7 Hz

-unilaterally in the upper limbs & eventuallyspread to all the limbs

-Occur at rest, improves with movement anddisappears drg sleep, pill rolling tremor.

Rigidity ² tone- increased resistance to passivemovement. The resistance is typically uniform throughoutthe ROM at a p·cular joint and affects agonist andantagonist muscles.

Cogwheel rigidity- superimposed rachetlike interruptions inthe passive movement.

flexors muscle of neck, trunk & limb- flexed posture



Bradykinesia- slowness or paucity of movement

- Reduced arm swing- Mask like facies- infrequent blinking and drooling

- Hypophonic, dysathria

- Dysphagia

- Reduced speed of movement

- Handwriting reduces in size- micrographia

Abnormal gait and posture

- Difficult to rise from a chair or bed

- Difficult to initiate movement (akinesia) as well as arrestthe movement & has to walk fast to prevent falling-

shuffling and festinating gait



y Eye movements affected- loss of upward gazey Excessive sweating and greasy skiny Depression, dementiay Postural hypotensiony Impaired postural reflex- last cardinal finding- Refers to ability of the patient to right himself and to keep

himself from losing his balance when sustaining minorpostural disturbances.

- EASILY««TRAPS

Tremor (resting)

Rigidity (cogwheel)

Akinesia/bradykinesia

Postural disturbances

Speech alteration DIAGNOSIS:BRADYKINESIA

REST TREMOR RIGIDITY

POSTURAL IMBALANCE



Hoehn & Yahr classification

Stage 1 : Unilateral disease

Stage 2 : Bilateral disease with no postural

disabilityStage 3 : Worsening bilateral disease withpostural disability

Stage 4 : Worsening of disease , patient's are

unable to live alone/independentlyStage 5 : Patients need wheel-chair assistance, bed bound .



There are no laboratory biomakers for PD. Investigations are done mainly to

exclude other causes that may mimic PD and for evaluation of atypical

parkinsonism patients. Evaluation of patient·s medical, surgical,drug and family

hx is vital followed by complete neurological examination.

investigation rationale

Thyroid function test Exclude hypothyroidism

Toxic screening Esp in younger onset PD &

exposure to manganese and

mercury

Copper metabolism studies:

-Serum ceruloplasmin

-Serum/ urinary copper

excretion-Kayser Fleischer rings

Wilson·s disease

Genetic studies Huntington·s disease

Brain CT scan Cerebral infarcts, tumor,

hydrocephalus, subdural

hematoma



MRI brain not considered helpful for dx of PD, MRI brain is

considered for patients with uncertainties eg: absence of tremor,

acute or stepwise progression in illness and young patients.

MRI in multiple system atrophy- putame abnormalities d/t loss of

neurons & gliosis with iron accumulation, pontine and cerebellar

atrophy may occur.

MRI in Progressive Supranuclear Palsy ² midbrain atrophy

Functional imaging with PET and SPECT is for clin. Research

though it can confirm loss of nigrostriatal dopamine neurons.



Aims to restore the dopamine

1. Levodopa + Dopa decarboxylase inhibitor

2. Dopamine agonist

3. Enzyme inhibitors ( MAO-B & COMT)

4. Amantadine

5. Anticholinergic



Dopami is ot s f l i tr atment of par insonism as itoes not ross lood- rain arrier

evodopa is a prodr of dopamine and it rosses t e lood- rain arrier.

est in relieving radykinesia. peak levels - rs aft oral dose, t : - rs

ombine it dopa decarboxylase inhibitor to reduce

peripheral metabolism to dopamine.

l p + car i pa = si t

l pa + benserazi e = madopar

SE :- Nausea, vomiting, hypotension

- dyskinesias (involuntary movements)- chorea,

dystonia

Dose : 300-400mg

to 600-800mg daily



- confusion, depression

- On and off phenomena : abrupt but transient fluctuations inthe severity of parkinsonism occur at frequent intervals drgday, apparently w/o any r/ship with last dose.

- Dopamine agonist

- In early symptomatic disease in younger patients- Add on therapy in more advanced therapy.

- Increase dopamine receptor activity

- Can delay onset of levodopa induce dyskinesia

- 2 types : a) ergot

- b) non- ergot



Ergot :-

- Bromocriptine- Pergolide

- Piribedil

- Cabergoline

Non-ergot :-

- Pramipexole

- Ropinirole

- SIDE EFFECTS : Nausea, vomiting, dyskinesias,hallucination, confusion, respi. depression



Monoamine oxidase type B inhibitors

MOA-B: metabolize dopamine

Seligiline 5-10mg daily

Prolongs the action of levodopa and reduce

dose required

SE : anxiety, insomnia



entacapone

Does not cross BBB

Reduces peripheral metabolism of L-Dopa (

similar to carbidopa)

Prolongs the effect of L-Dopa



Antiviral drug

Mechanism of action: increases the release &inhibit the reuptake of dopamine

Used as as initial therapy of mild PD - Lesseffective than levodopa & more effective thananticholinergics

Adverse Effects:CNS effects: restlessness, agitation, excitement,

hallucinations, confusion, irritability, depressionAnkle edema ² Local effect on blood vesselsHeadache, CHF, postural hypotension,

gastrointestinal disturbances, urinary retention



Trihexyphenidyl, benzatropine,

orphenadrine, procyclidine

Block central muscarinic receptors

Mostly to treat tremor, minimal effect onrigidity and bradykinesia

SE : dry mouth, constipation, urinary

retention, blurred vision, confusion

Dosage : begin with 1mg twice daily, increasing as

patient tolerates.



Indicated when medical therapy cannot

control the symptom or when side effect of

levodopa become significant.

CI : parkinsonism plus syndrome, secondary

parkinsonism, dementia, concomitant serious

medical condition, severe depression and

psychosis not caused by the drugs.



Globus pallidus internal-segment

pallidotomyThis procedure consists of microelectrode

destruction of a specific site in the basalganglia. It is used to relieve the dyskinesias

seen with levodopa therapy. If relief is

attained, the patient may be able to tolerate

a higher levodopa dosage and achieve

potentially better control of parkinsonian

symptoms



Deep brain stimulation

Rather than causing destruction in the brain,

this procedure uses an implantable electrode

that is placed in the brain and attached to anexternal pacemaker for control. It is most

effective for tremor and for relieving

dyskinesias, depending on where the

electrode is placed

Movement Disorder 2

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