Parkinson’s Disease

Content

• Introduction

• Cause and pathogenesis

• Case Study:

➢Symptoms

➢Diagnosis

➢Treatment

➢Conclusion

oIntroduction

• It is a progressive neurological condition

• Results from the degeneration of dopamine-producing neurons in the substantia nigra

• Various types of Parkinson’s disease

• Risk factors:

➢Middle aged and increased risk with age

➢Hereditary

➢Men (1.5 times more)

➢Environmental exposure to toxins

Symptoms

• 4 major symptoms:

➢Rigidity – muscles are tensed and contracted

➢ Resting tremor – trembling which is most obvious when the patient is at rest or when stressed

➢Bradykinesia – slowness in initiating movement

➢ Loss of postural reflexes or instability – poor balance and coordination

• Non-motor symptoms

➢Anxiety disorders, depression, sleep disturbances, orthostatic hypotension, olfaction dysfunction, dysphagia, sialorrhoea, dementia, psychosis and visual hallucinations

Diagnosis and Treatment

• Diagnosis:

➢ Neurological examination

➢ Autopsy of brain to find lewy bodies (trademark characteristic)

➢ Judgement of physicians

• Treatment:

➢ Medications

➢ Diet

➢ Exercise, physical and speech therapy

➢ Surgery

❖ Cryothalamotomy

❖ Pallidotomy

❖ Deep brain stimulation

oCauses and Pathogenesis

• Degradation of dopaminergic neuron.

• Free radicals.

• Neurotoxin - MPTP

• Genetic factors.

Degradation of Dopaminergic Neuron

• Substantia nigra pars compacta.

• Death of neuron.

• Symptoms of PD don’t appear until 50-80% of the neurons in the pars compacta have died.

• Cause of death of neuron is not known.

Free Radicals

• Unpaired electrons that can easily react with surrounding molecules and destroy them.

• Metabolism of dopamine by MAO produce hydrogen peroxide.

• Glutathione normally breaks down the hydrogen peroxide quickly.

• Reduced glutathione = loss of protection against free radicals → cell damage

Neurotoxin - MPTP

• 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) –neurotoxin.

• MPTP crosses the blood-brain barrier and oxidized to 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase B (MAO)-B

• MPP+ selectively enters dopamine neurons via the dopamine transporter.

• MPP+ inhibiting Complex I → leads to cell death via energy deficit.

Genetic Factors

• Mutation of SNCA genes in chromosome 4.• 2 types of alterations:

• Alanine is replaced with threonine.

• Cause alpha-synuclein to misfold.

• SNCA genes is inappropriately duplicated or triplicated.

• Extra copies of the gene lead to an excess of alpha-synuclein.

• Aggregate (Lewy bodies) and attract other protein.• Clog neuron and impair the function of neuron.

Symptoms

1. Nondisabling intermittent resting tremor of left hand

• Result of pallidal dysfunction

• Triggered by specific loss of dopa minergic projections from retrorubral area

2. Present of myerson

• Eyes blinking when tapped on glabella (glabellar reflex)

• Involuntary reflex disorder

3. Mild signs of asymmetrical cogwheel rigidity and bradykinesia (left > right)

• Cause to muscular aches and sensation of fatigue

• Face become masklike, opened mouth, drooling and reduced blinking

• Underscaling of movement commands in internally generated movements

• Reflect the role of the basal ganglia in selecting and reinforce appropriate patterns of cortical activity during movement preparation and performance

4. Normal gait and balance and postural reflexes

• Under activity in the left cerebellar hemisphere with contrast of over activity in vermis

• Associated with loss of lateral gravity shift in parkinsoniangait

• Loss of postural reflexes

• No tendency of falling forward

• No difficulty of walking, turning and stopping

Diagnostic Test

• No specific test.

• Usually based on present of symptoms.

• Referral time should not be more than 6 weeks and not exceed two weeks in severe case.

• No specific lab test used for diagnosis.

• Follow – up= every 6 to 12 months.

• Suggested method include:

➢Neurologic examination

➢Oculomotor examination

➢Electroencephalograms (EEG)

➢Single photon emission computed tomography (SPECT)

❑ Neurological examination

➢Patient’s medical and family history

➢Observe sign and symptoms present.

➢Suggested symptoms include:

❖Bradikinesia

❖Tremor

❖Hypokinesia

❖Rigidity

➢Patient had normal cognition and myerson sign is present.

➢Intermittent mild tremor was observed as well as cogwheel rigidity and bradykinesia.

❑ Oculomotor examination

➢To check abnormalities of eye movement, generation, and control.

➢Normal in patient.

❑ Single photon emission computed tomography (SPECT)

➢Show dramatic (50%) loss of striatal uptake in patient compared to normal individual.

❑Electroencephalograms

➢Record patient’s brain electrical activity.

Single photon emission computed tomography (SPECT)

Treatment

According to the case study the patient was on initiation of treatment:In early-stage disease, the pharmacological options

for the treatment of PD are multiple.

• Levodopa:➢ is a medicine that the brain converts to dopamine.

➢ is a medicine used to control symptoms of Parkinson's disease and used at all stages of the disease.

➢ Levodopa does not slow the disease process, but it improves muscle movement and delays severe disability.

➢ long-term levodopa therapy within 5 to 10 years can cause complication to occur such as Dyskinesia.

• Dopamine agonist:

➢Example of drugs:pramipexole,ropinirole

➢directly stimulate the receptors in nerves in the brain that normally would be stimulated by dopamine.

➢used in the early stages of Parkinson’s disease to reduce symptoms.

➢effective in people who have been newly diagnosed with the disease (especially those younger than 60).

➢Not effective as levodopa in reducing symptom but can prevent long term effect caused by levodopa.

• Monoamine oxidase type B inhibitor

➢MAO-B is an enzyme in our brain that naturally breaks down several chemicals in our brain including dopamine.

➢Prevent the breakdown dopamine.

➢they prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells.

➢Example of drug: Rasagiline and selegiline.

➢used in the early stages, to treat very mild symptoms (such as resting tremor) and delay the need for levodopa.

➢rasagiline or selegiline may be added to levodopa treatment to reduce motor fluctuations , increase the time of effect of the levodopa.

• Amantadine

➢ treat people who are in the early stages of Parkinson's disease.

➢ It is best used in people who have mild to moderate symptoms.

➢cause greater amounts of dopamine to be released in the brain.

➢can be used with levodopa in the later stages of Parkinson's disease to reduce dyskinesias.

• Anticholinergic

➢Example of drugs: benztropine,biperiden

➢Anticholinergic medicines decrease levels of acetylcholine to achieve a closer balance with dopamine levels.

➢In order to reduce the symptom.

Treatment In MalaysiaDecision pathway for the initiation of

medication

• Selegiline ( Jumex and Selegos)

➢usual dose is 10 mg in the morning.

➢has a mild antiparkinsonian effect.

• Dopamine agonist

➢Next most potent class of drug after L-dopa.

Dopamine agonist

Usual Starting Dose

Maximum recommended Dose

Piribedil (TrivastalRetard *)

25-50mg 300mg/d

Ropiniroleimmidiate release ( Requip *)

0.25mg 24mg/d

RopiniroleProlong Release (Requip PD*)

2mg 24mg/d

• Anticholinergic agents

• These include trihexyphenidyl or benzhexol (Apo-Trihex® and Benzhexol®)(1 or 2 mg 2-3x daily) and orphenadrine (Norflex®) (50 mg 2-3x daily).

• Non-Pharmocologic Management

➢physiotherapy: stretching and strengthening exercises and balance training.

➢occupational therapy: lifestyle adaptations and assessment of safety in the home environment.

➢speech therapy: rehabilitation techniques to strengthen speech for improved communication.

➢Dietitian: advice from them.

Physiotherapy management

The aim of physiotherapy in Parkinson’s-

--Maximise independence and functional potential.-- Minimise secondary complications.

Main areas of Difficulty---

-Posture-Balance-Gait-Fine movements – handwriting, buttons-Automatic movements – blinking, swallowing, coughing, swinging arms.

Posture—Excessive flexion (bending) of neck, trunk, hips, knees;Contractures (muscle shortening)Reduced rotation – difficulty turning, to sit in chair, tight cornersReduced arm swingSlumping in chair

Balance---

Reduced rotationIncreased flexion (stooping) leading to decreased balance and falls..

Gait—

-Difficulty initiating walk-Petit pas (small steps)-Festination-Freezing-Difficulty turning-Heel-toe gait

Home exercise programme—

-Lying supine/prone-Standing back to wall-General exercises – promoting extension/rotation-Postural advice – in sitting position-Breathing exercises-Relaxation

As time goes on---

-Advise family/carer re cues, handling, positioning-Avail of community physiotherapy in own home-Avoid the problem of hypomobility-Encourage independence for as long as possible.

Conclusion

• Patient has idiopathic Parkinson’s disease

• There is no cure but therapies are available

• Treatments aim to:

➢Prevent clinical progression

➢Improvement of parkinsonism

➢Delay of motor complications

• Complications: choking, falls and side effects of drugs

• Prognosis: normal life expectancy for treated patients