Parkinson's Disease: Clinical Features, Management, and Differentials

Harald Bjorndalen Adapted from lecture by Dr Zoe Campbell (Medical SpR)

Understand difference between Parkinsons Disease and Parkinsonism Describe clinical features of Parkinson s disease Describe basic management of parkinson s disease

Case Pathophysiology Definition Clinical features Investigations Management Prognosis

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?

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

Classic TRIAD TRIAD: BRADYKINESIA / slowness RIGIDITY / stiffness / increased tone TREMOR / pill rolling / 4-6 Hz /resting Postural instability

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

What is PARKINSONISM? What are the causes?

Neurological syndrome characterised by tremor, Causes DRUGS Anti psychotics, metaclopramide, TCA, MPTP Vascular disease Parkinson plus syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, Lewy-body dementia) Trauma Neurological syndrome characterised by tremor, bradykinesia Causes bradykinesia and rigidity. and rigidity.

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

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

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

Cranial nerves Upper limb Lower limb Gait Function Gait Function

Face expressionless / mask like / reduced blinking ANd9GcS-tFkVF12AVh8PM5AKDpbAb0myIesV0856IM_QSsjTBiRmbmjdz_M3mg ANd9GcSYwnNU_zJaK0VNCHH0XBBKrQ8Rmfh375ZdZoi_MUnfhCVEoX7qDAIUQ3k

Speech Monotonous Tremulous slurring dysarthria (due to akinesia, tremor and rigidity of bulbar area) Dribbling and drooling

Tremor Worse at rest Asymmetrical

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)

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

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. parkinsonism

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

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

Citalopram Quetiapine, clozapine 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 Acetylcholinesterase inhibitors clonazepam Oxybutynin, tolterodine movicol

Dopamine agonist Disease progression Significant functional disability MAO-B inhibitor Levodopa (max 600mg/day) Add levodopa (max 600mg/day) Motor complications develop Guidelines for drug management of PD Add DA or entacapone Add entacapone or DA 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

Parkinsons - 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

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?

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

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

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

- 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