Parkinson s Disease Sirirak

8/4/2019 Parkinson s Disease Sirirak

1/33

Parkinsons Disease

Sirilak yimcharoen


2/33

EPIDEMIOLOGY

~1% of people over 55 years Age range 3585 years peak age of onset is in the early 60s ~5% of cases characterized by an earlier

age of onset (typically before age 45

years)


3/33

PATHOGENESIS

Microscopic presence of Lewy bodies in the remaining neurons

Genetic :earlier age onset


4/33

Etiology

Degradation of dopaminergic

neurons in the substantia

nigra


5/33


6/33

CLINICAL FEATURES

SymptomsMotor symptomsNon motor symptoms

cardinal signsrest tremorrigiditybradykinesia


7/33

Motor symptoms

Tremor, bradykinesia, rigidity, postural instability Hypominia, dysarthria, dysphagia, Decreased arm swing, difficult arising from chair micrographia Glabellar reflex, blebphalospasm, dystonia,

camptocormia, scoliosis


8/33

Bradykinesia

most characteristic clinical feature manifestations of bradykinesia

slowness of movementloss of spontaneous movements and gesturingdroolingmonotonic and hypophonicdysarthrialoss of facial expressionFreezing(motor blocks) is a form of akinesia


9/33

Bradykinesia

correlate best with degree of dopaminedeficiency

Assessment of bradykinesiarapid, repetitive, alternating movements of the

hand

observing not only slowness but alsodecrementing amplitude


10/33

Tremor

Rest tremor is the most common unilateral, frequency between 4 and 6 Hz Hand tremors are described as

supinationpronation (pill-rolling)

involve :lips, chin, jaw and legs rarely involve: the neck/head responsive to dopaminergic therapy


11/33

Rigidity

increased resistancecogwheel

Postural deformitiesCamptocormia


12/33

Non-motor symptoms

Mentalproblem : dementia, depression, apathy Autonomic disturbance : postural hypotension,

constipation, bladder dysfunction

Sensory symptom : anosmia, ageusia,paresthesia

Sleep disturbance


13/33

Diagnostic criteriaUK Parkinsons Disease Society Brain Banks clinical criteria for the diagnosis of

probable Parkinsons diseaseStep 1Bradykinesia

At least one of the following criteria:

Rigidity

46 Hz rest tremor

Postural instability not caused by primary visual, vestibular, cerebellar orproprioceptive dysfunction

Step 2

Exclude other causes of parkinsonism

Step 3

At least three of the following supportive (prospective) criteria:

Unilateral onset

Rest tremorProgressive disorderPersistent asymmetry primarily affecting side of onsetExcellent response (70100%) to levodopa

Severe levodopa induced chorea (dyskinesia)Levodopa response for 5 years or moreClinical course of 10 years or more


14/33

National Institute of Neurological Disorders and Stroke

(NINDS) diagnostic criteria for Parkinsons diseaseGroup A features (characteristic of PD)Resting tremor

Bradykinesia

RigidityAsymmetric onset

Group B features (suggestive of alternative diagnoses)

Features unusual early in the clinical courseProminent postural instability in the first 3 years after symptom onsetFreezing phenomenon in the first 3 yearsHallucinations unrelated to medications in the first 3 years

Dementia preceding motor symptoms or in the first year

Supranuclear gaze palsy (other than restriction of upward gaze) or slowing of verticalsaccades

Severe, symptomatic dysautonomia unrelated to medicationsDocumentation of condition known to produce parkinsonism and plausibly connected to

the patients symptoms (such as suitably located focal brain lesions or neurolepticuse within the past 6 months)


15/33

National Institute of Neurological Disorders and Stroke(NINDS) diagnostic criteria for Parkinsons disease

Criteria for definite PDAll criteria for probable Parkinsons are met and

Histopathological confirmation of the diagnosis is obtained at autopsy

Criteria for probable PDAt least three of the four features in group A are present and

None of the features in group B is present (note: symptom duration 3 years is

necessary to meet this requirement) andSubstantial and sustained response to levodopa or a dopamine agonist has beendocumented

Criteria for possible PDAt least two of the four features in group A are present; at least one of these is tremor

or bradykinesia and

Either none of the features in group B is present or symptoms have been present 3years and none of the features in group B is present

and

Either substantial and sustained response to levodopa or a dopamine agonist has beendocumented or the patient has not had an adequate trial of levodopa or a dopamineagonist


16/33

Disease staging and assessment

Hoehn and Yahr Staging UPDRS0 No signs of disease. There are 6 major parts;

1.Mentation, behavior andmood

2.Activities of daily living

3.Motor examination4.Complication of therapy5.Modified Hoehn and Yahrstaging

6.Schwab and Englandactivites of daily living scale

1 Unilateral disease.

2Bilateral disease, without impairment

of balance.

3

Mild to moderate bilateral disease;

some postural instability; physically

independent.

4Severe disability; still able to walk or

stand unassisted.

5Wheelchair bound or bedridden

unless aided.


17/33

Differential diagnosis of

parkinsonism

1. Primary parkinsonism parkinsons disease Juvenile parkinsonism

3.

Parkinson plus disorder Multiple system atrophy Cortico-basal ganglionic degeneration Progressive supranuclear palsy

5. Secondary parkinsonism Drug-induced Vascular parkinsonism


18/33

Differential diagnosis of

parkinsonism

3. Secondary parkinsonism

Normal pressure hydrocephalus Toxin-induced Infectious

4. Heredodegenerative parkinsonism

Dementia with Lewy Bodies Huntington disease Wilson disease


19/33

Treatment Algorithm


20/33

Treatment Algorithm

Dopaminereplacement

Dopamineagonists

Anticholinergics(Tremor)

Pharmacologic

Add COMT

inh., MAO-B

inh., or others

65

yrs

>65

yrs

Clinical pearls in

drug selection

AgeCognitivefunctionSeverity of motor

features

Response toprevious PD

treatment

P i h l


21/33

Alpha-synuclein NMDA

R

3OMD

COM

T3OMD

COMT

Peripheral organ

P i h l


22/33

Alpha-synuclein NMDA

R

3OMD

COM

T3OMD

COMT

Entacapone

Tolcapone

Benserazide

Carbidopa

Selegiline

Rasagiline

Amantadin

e

Dopamine

agonists

Peripheral organ


23/33

Dopamine Replacement

L-dopa/Benserazide (4:1), L-dopa/Carbidopa(10:1)

Start with low dose (prefer regular release)Select appropriate preparation

Beware of motor complications (later disease)


24/33

Complications from levodopa

Motor complicationsWearing off effectOn-off effectPeak-dose dyskinesia

Non-motor complicationsPsychosisHallucinationAutonomic symptoms e.g. constipation


25/33

Motor Complications from

Levodopa

Leveloflevo

dopa

int

he

bod

y

Dose Dose Dose Dose Dose

Wearingoff Peakdosedyskinesia

On3me

Off3me

http://www.mypdinfo.com/en/treatment_of_pd/treating_pd_with_medications/what_is_wearing_off/

Time


26/33

Management of Motor

ComplicationsWearing

off

Symptomdeterioration

Predictable

frequency,controlled

release

On-off

Randomdeterioration

Unpredictable

DT, add otherdrugs

Peak dose

Too muchmovement

dosefrequency,addan3dykine3cs

D i i


27/33

Dopamine agonists

e.g.Bromocriptine

Caution: Fibrosise.g. heart valve,lung (dose andtime of exposurerelated)

Fibrosis:stimulation of 5-HT2B that maypotentiateinflammation

Ergot e.g.pramiprexol, ropinirole

Caution: Sleepattack was firstreported in pttreated withropinirole andpramiprexol

Non-ergot

Benefit when use in early disease

(delays the use of levodopa)

Use in management of motor complications

e.g. dyskinesia esp. long acting

Start low, go slow(better tolerate with evening dose)

CNS Drugs 2010; 24 (11): 941-968


28/33

COMT Inhibitors

Entacaponeand Tolcapone (notavailable in Thailand) Benefit

Reduce dose of levodopa

Use to treat motor complications Cautions

Autonomic symptoms e.g. diarrhea levodopa

Hepatotoxic esp. tolcapone Monitor liver function closely in first 6 mons.

European Handbook of Neurological Management (2nd Ed), 2011


29/33

MAO-B Inhibitors

Selegiline and Rasagiline BenefitNeuroprotective

CautionsDrug interaction

CYP2B6, CYP2C19 SSRI, lithium, imipraminerisk of serotonin

syndrome

Selegiline metabolite is amphetaminederivatives

Minimal effects e.g. insomnia, hallucinationEuropean Handbook of Neurological Management (2nd Ed), 2011


30/33

Anticholinergics

Trihexylphenidyl, benztropine

BenefitTremor predominant

CautionsAnticholinergic side effects (start low, goslow)

Cognitive impairment (due to M1 mAChR)

BrainandCogni3on68(2008)41545,Pharmacology&Therapeu3cs117(2008)2224


31/33

NMDA-receptor antagonist


32/33

NMDA-receptor antagonist

Amantadine

BenefitInhibit excitatory pathway (glutamic

pathway)

Management of motor complication esp.dyskinesia

CautionDose adjustment in renal impairment

Euro ean Handbook of Neurolo ical Mana ement 2nd Ed 2011


33/33

The end

Parkinson s Disease Sirirak

Documents