Parkinson’s DiseaseHarald Bjorndalen

Adapted from lecture by Dr Zoe Campbell(Medical SpR)

Understand difference between Parkinson’s Disease and Parkinsonism

Describe clinical features of Parkinson’s disease

Describe basic management of parkinson’s disease

Learning Outcomes

Case Pathophysiology Definition Clinical features Investigations Management Prognosis

Outline

Clinical scenario A 64 year old man attends his GP after his wife

persuaded him. For the last 6 months he has noticed that he is slowing down. It takes him a long time to do simple tasks like getting dressed. His hands are shaking all the time, more so on the right. His wife has noticed a change in his gait saying he shuffles when he walks. He has no past medical history of notes and is on no regular medication and has no known allergies. On examination he has a blank staring expression and marked rigidity of his limbs, more so on the right. He has resting pill rolling tremor. His gait is shuffling and festinant.

What are your differentials for this gentleman?

How would you investigate this man? How would you manage this gentleman? What are the stages of managing

Parkinson’s Disease? What are the Parkinson’s plus syndromes? What drugs can cause Parkinsonism?

Parkinson’s Disease

Loss of dopaminergic neurones in the substantia nigra and appearance of eosiniphilic inclusion bodies (Lewy bodies)

Parkinson’s - Pathophysiology

Classic TRIAD:

BRADYKINESIA / slowness RIGIDITY / stiffness / increased tone TREMOR / pill rolling / 4-6 Hz /resting

Postural instability

Parkinson’s - History

Neurodegenerative disease of the dopamine generating neurones in the substantia nigra, characterized by bradykinesia, rigidity, tremor, and postural instability

Definition

What is PARKINSONISM?

What are the causes?

Parkinson’s

Neurological syndrome characterised by tremor, bradykinesia and rigidity.

Causes DRUGS – Anti psychotics, metaclopramide,

TCA, MPTP Vascular disease Parkinson plus syndromes (multiple system

atrophy, progressive supranuclear palsy, corticobasal degeneration, Lewy-body dementia)

Trauma

Parkinsonism

Onset - gradual Tremor – at rest, usually first noticed in the

hands Stiffness and slowness of movement. Difficulty initiating movements (e.g. getting

out of chair, turning in bed) Falls – Not usually frequent early on Smaller hand writing

Parkinson's - History

Anxiety/depression Sleep disturbance Postural hypotension Sweating Constipation Drooling Incontinence Sexual dysfunction

Parkinson’s - History

Symmetry Lower body involvement Poor response to levodopa Early falls / postural instability Early autonomic disturbance (sexual,

bladder, postural hypotension) Early eye movement disorders Early dementia Early dysarthria

Parkinson's – Red Flags

Cranial nerves Upper limb Lower limb Gait Function

Parkinson's - Examination

Face – expressionless / mask like / reduced blinking

Parkinson's - Examination

Speech Monotonous Tremulous slurring dysarthria (due to

akinesia, tremor and rigidity of bulbar area) Dribbling and drooling

Parkinson’s - Examination

Tremor Worse at rest Asymmetrical

Parkinson’s - Examination

Increased tone / cogwheeling Power normal Reflexes normal Sensation normal Coordination normal (but might be slow)

Gait Stooped posture Gunslinger/Hands over hernias Shuffling Reduced arm swing Difficulty turning (axial rigidity)

Parkinson’s - Examination

Rapidly open and close hands Functional tasks Get the patient to write a sentence Draw a spiral AMT Lying / standing BP

Parkinson’s - Examination

Diagnosis is CLINICAL Bedside tests: Levodopa trial. Routine bloods CT and MRI usually normal but may exclude

other causes of parkinsonism PET / SPECT scans can be used to measure

dopaminergic function in basal ganglia.

Parkinson’s - Investigation

MDT: Physios OT Neurologist GP PD nurse Support societies Palliative care in the late stages

Parkinson’s - Management

Medical:◦ Dopamine agonists e.g. ropinirole, bromocriptine◦ MAO inhibitors e.g. rasagiline◦ Levodopa + decarboxylase inhibitor◦ COMT e.g. Entacapone◦ Continuous dopamine therapy – Apomorphine

(syringe driver) or Duodopa (Intrajejunal infusion of levodopa gel)

◦ Supportive medication e.g. Baclofen, antidepressants

Parkinson’s- Management

Depression, psychosis Dementia Sleep disorders

◦ Restless legs syndrome◦ Periodic limb movements of sleep◦ REM sleep behaviour disorder

Falls Autonomic disturbance

◦ urinary dysfunction◦ weight loss, dysphagia◦ constipation◦ erectile dysfunction◦ orthostatic hypotension◦ excessive sweating◦ sialorrhoea

Non-motor symptoms in PD

clonazepam

movicol

Citalopram Quetiapine, clozapine

Acetylcholinesterase inhibitors

Oxybutynin, tolterodine

Guidelines for drug management of PD

Significant functional disability Disease progressionDopamine agonist

Add levodopa (max 600mg/day)

Motor complications develop

Add DA or entacapone

MAO-B inhibitor

Add entacapone or DA

Levodopa (max 600mg/day)

Switch to tolcapone if entacapone fails

Add MAO-B inhibitor if not already given

Add amantadine for dyskinesia

Severe motor complications

Consider apomorphine, Duodopa, DBS

Parkinson’s - Management

• Surgical:• Deep brain stimulation• A lead is implanted into the target area (brainstem)• This lead connects to a implantable pulse generator• Which connects to a device in the subclavian area of

the chest• Device produces mono polar or bi polar electrical

stimulation to control symptoms

Parkinson’s - Management

74 year old Diagnosed with PD, right sided tremor,

bradykinesia/rigidity-all mild L-dopa started after 10 months as symptoms

worsened, problems with stairs Started on sinemet 62.5mg od then incresed

to tds over 1 week. No response after 2 weeks What next?

Case History 2

Dose incresed to 125mg tds with good response Stable over 2 years then mobility worsened and

patient getting slow and stiff before next drug dose

What next? Increase sinemet to qds (OR add entacapone) Over next 3 years, dose increased to sinemet

250, 125, 250, 125 plus sinemet CR nocte 3 years after increase- fluctuations in response-

drugs not always helping him switch on, extra movements an hour after taking his medications, switched off prior to his next dose

What next?

Sinemet decreased to 125 qds plus CR nocte

Entacapone added No improvement, slightly worse over 6

months What next? Ropinirole added Dose slowly increased over 8 months (79 yrs old), hallucinations, mild cognitive

decline Ropinirole decreased, symptoms worsened Quetiapine added Sinemet levels maintained

Surgical: Deep brain stimulation A lead is implanted into the target area

(brainstem) This lead connects to a implantable pulse

generator Which connects to a device in the

subclavian area of the chest Device produces mono-polar or bi-polar

electrical stimulation to control symptoms

Parkinson’s - Management

MDT: Physio OT Neurologist GP Support societies Palliative care in the late stages

Parkinson’s - Management

Progression variable Usually the course is over 10-15 years Death from pneumonia

Parkinson’s - Prognosis

- Sam AH, Teo JTH, Rapid Medicine, Wiley-Blackwell 2010

- BMJ learning module: Parkinson's disease - initial assessment and referral

- Lecture by Zoe Campell, Warwick Hospital, 2012

- SADH lecture by Naghme Adab, Management and treatment of Parkinson’s Disease, 2012

References/Further reading