Parkinson's Disease Lecture 2025 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Parkinson's Disease Prof Alan Moore Department of Geriatric and Stroke Medicine, Beaumont Hospital Dublin LEARNING OUTCOMES 1. Define Parkinson's Disease 2. Explain the pathophysiology of Parkinson's Disease 3. List t...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Parkinson's Disease Prof Alan Moore Department of Geriatric and Stroke Medicine, Beaumont Hospital Dublin LEARNING OUTCOMES 1. Define Parkinson's Disease 2. Explain the pathophysiology of Parkinson's Disease 3. List the cardinal symptoms and signs of Parkinson's Disease 4. Explain how each symptom and sign is caused in Parkinson's Disease 5. Develop a differential diagnosis for Parkinson's Disease 6. Outline the overarching principles of investigation and management of Parkinson's Disease LEARNING OUTCOME 1 Define Parkinson's Disease PARKINSON'S DISEASE A neurodegenerative, progressive movement disorder of the central nervous system First described in 1817 by Dr James Parkinson “An Essay on the Shaking Palsy” Majority of cases are idiopathic Symptoms begin 55-60 years 1% of over 60-year-olds Males: Females 1.5:1 EPIDEMIOLOGY Chronic, progressive, degenerative disease of CNS Disturbance of muscle control – affects movement 2nd most common neurological disorder Prevalence varies – most studies 120 per 100,000 1 million affected in US – greatest prevalence LEARNING OUTCOME 2 Explain the pathophysiology of Parkinson's Disease PATHOPHYSIOLOGY ▪ Loss of pigmented dopaminergic neurones in substantia nigra. ▪ Presence of Lewy bodies within pigmented neurons is characteristic. ▪ 60-80% of neurones are lost before the motor signs emerge. ▪ As the disease progresses, components of the autonomic, limbic, and somatomotor systems become particularly badly damaged. ▪ Braak staging 1-6 correlates with clinical manifestation of the disease. BASAL GANGLIA – WHAT IS IT? 'basal ganglia' means: the caudate nucleus, putamen & globus pallidus. They are functionally important for controlling voluntary movements and establishing postures. When they are altered - like in Parkinson’s disease - the person has unwanted movements.  SUBSTANTIA NIGRA ▪ The substantia nigra (in the midbrain) is an important motor centre. ▪ It projects to the caudate & putamen (2 nuclei of the basal ganglia that together comprise what is called the Striatum). ▪ These Nigrostriatal cells use the neurotransmitter Dopamine & cells within the nigra produce dopamine normally. ▪ The substantia nigra is the lesion site in PD - degeneration of the melanin- containing cells. ▪ Absence of this transmitter produces the crippling features of PD. Nigrostriatal pathway MOTOR CIRCUIT CORE ▪ This circuit modulates output from the motor cortex ▪ Loss of Substantia nigra results in dysfunctional stimuli to basal ganglia. ▪ Imbalance of excitatory and inhibitory pathways regulating movement. symptoms seen in PD. Nigrostriatal pathway AETIOLOGY CORE ▪ Idiopathic (most common) ▪ Toxins (Manganese, iron, MPTP, pesticides/herbicides) ▪ Head trauma ▪ Drug induced (antipsychotics, antiemetics, antihistamine) ▪ Genetic (Park-1, Park-3 & Park-12) accounts for < 5% ▪ Abnormal proteosome system ▪ Oxygen free radicals LEARNING OUTCOME 3+4 List the cardinal symptoms and signs of Parkinson's Disease Explain how each symptom and sign is caused in Parkinson's Disease CARDINAL MOTOR SYMPTOMS CORE ▪ Tremor ▪ Bradykinesia ▪ Rigidity ▪ Postural instability TREMOR CORE ▪ pill rolling ▪ unilateral ▪ rapid at rest ▪ increased with stress ▪ frequency of 4- 5 Hertz BRADYKINESIA CORE ▪ slowness of movement ▪ difficulty initiating voluntary movement ▪ difficulty with sequential complex movements ▪ decreased amplitude of movement (writing) ▪ rapid fatigability of repetitive movements RIGIDITY CORE ▪ Increased resistance of relaxed muscles to passive stretch ▪ commonly asymmetrical 1. cogwheel (tremor and rigidity) 2. lead pipe POSTURAL INSTABILITY CORE Balance well preserved until later stages Shuffling gait & poor arm swing contribute to high falls risk CLINICAL FEATURES: NON-MOTOR SYMPTOMS CORE Depression Sleep disturbance prevalence varies (>30%) insomnia ? reactive process daytime somnolence/fatigue ? dopamine effect vivid dreams hallucinations Cognitive decline executive dysfunction dementia (~30%) ?DLB always o/r other causes CLINICAL FEATURES: MOTOR SYMPTOMS/ SIGNS CORE Gait: Function Shuffling Poor bed mobility Flexed axial posture Difficulty with transfers Festination Poor dexterity/coordination Decreased arm swing Micrographia Turning ‘en bloc’ Painful dystonia Freezing Face Falls Hypophonia Dysphagia/Drooling Hypomimia On reviewing patients always assess for Motor and Non-motor symptoms and signs CLINICAL FEATURES: NON-MOTOR SYMPTOMS CORE Sensation Autonomic orthostatic hypotension seborrhoeic dermatitis (?meds) urinary incontinence anosmia constipation pain weight loss impaired proprioception sexual dysfunction sweating abnormalities CLINICAL ASSESSMENT History with collateral if available Neurological examination looking for the key features of – Tremor – Bradykinesia Assess rapid repetitive movements – Rigidity Lead pipe and cog-wheel rigidity – Postural instability Look for signs of Parkinsons plus syndromes: – Cerebellar signs – Autonomic dysfunction – Cognitive impairment – Eye movements LEARNING OUTCOME 5 Develop a differential diagnosis for Parkinson's Disease DIFFERENTIAL DIAGNOSIS CORE essential tremor vascular parkinsonism drug – Induced parkinsonism parkinsonism in parkinson plus syndromes Thyrotoxicosis PARKINSON PLUS SYNDROMES ▪ Early postural instability & dementia ▪ These progress more quickly than IPD (worsening in first 3-5 yr) ▪ Anti-Parkinsons medications are less effective and patients are very sensitive to neuroleptic medications/ levodopa ▪ Autonomic features are common. ▪ Axial > limb involvement MULTISYSTEM ATROPHY CORE ▪ Postural Instability with falls ▪ Postural Hypotension ▪ Bladder dysfunction ▪ Pyramidal Signs ▪ Cerebellar Signs PROGRESSIVE SUPRANUCLEAR PALSY CORE ▪ Parkinsonism (Symmetrical) ▪ Paralysis of upward gaze ▪ Dementia ▪ Personality change ▪ Speech difficulties LEARNING OUTCOME 6 Outline the overarching principles of investigation and management of Parkinson's Disease  DIAGNOSIS It is a CLINICAL diagnosis using the Movement Disorder Society clinical diagnostic criteria for Parkinson Disease Based on Medical History & Clinical examination NO laboratory tests CT and MRI brain - Generally normal MRI can outrule Multi-infarcts, Hydrocephalus & Wilsons (so used to exclude other diseases which may mimic PD) DaTscan DAT SCAN A nuclear medicine scan that assesses the dopamine uptake in the brain. It can be used to can reliably distinguish patients with IPD and parkinsons plus syndromes from patients with essential tremor (ET), but it cannot differentiate IPD and the other parkinsonian syndromes from one another. The available evidence suggests that the accuracy of DaTscan for parkinsonian syndromes is equal to but not better than the accuracy of a carefully obtained clinical diagnosis It can be used for patients where diagnosis is unclear, such as suspected essential tremor, drug induced Parkinson's or patients that don't respond to treatment Image: American Parkinsons Disease Assocation website MANAGEMENT – AIMS CORE 1. educate & support 2. preserve function 3. maintain general health and fitness 4. treat other medical problems MANAGEMENT – NONPHARMACOLOGICAL CORE PD Support Group Physiotherapy & Occupational Therapy SALT & Dietician & MSW Communication with GP MANAGEMENT- PHARMACOLOGICAL Replace dopamine deficiency Prevent dopamine breakdown Dopamine – levodopa Dopamine decarboxylase inhibitors Dopamine agonists- bromocriptine, pramipexole, ropinirole, cabergoline, apomorphine MAOB inhibitors – Selegiline, Rasagiline COMT inhibitor – Entacopone Anticholinergics (for tremor/drooling) Procyclidine, Biperidin MANAGEMENT - PHARMACOLOGICAL Aims to control signs/symptoms for as long as possible while minimising adverse effects. Usually provide good symptomatic control for 4-6 years. After this disability progresses. Motor fluctuations and dyskinesias may become troublesome. No proven neuroprotective therapies exist for PD. ?MAOB Inhibitors No standard algorithm – treat when function is a problem MANAGEMENT – PHARMACOLOGICAL CORE ▪ Levodopa therapy is the mainstay of treatment but has side effects ▪ Its use is therefore often deferred initially due to long term side effects ▪ Lower potency drugs are reasonable in patients with mild symptoms ▪ Levodopa & Dopa decarboxylase inhibitor (DCI) (benserazide or carbidopa) ▪ Levodopa is the most potent and effective for initial therapy >70y ▪ Gives greatest benefit with fewest S/E in short term ▪ Aim to restore normal function using minimum dose of levodopa ▪ Pre meals on empty stomach gives better absorption ▪ Domperidone for transient nausea when start treatment ▪ Long term S/E as receptor stimulation becomes less effective motor fluctuations (on-off phenomenon) dyskinesias (chorea or dystonia) 1 2 3 4 5 6 7 8 A74-year-old male has recently been diagnosed with Parkinson's disease after experiencing a gradual onset of worsening slowness of movement and Tremors. He visited a neurologist specializing in movement disorders for further evaluation and treatment. Who decided to start him on levodopa. What is the most appropriate piece of information to communicate to the patient regarding Levodopa? A. Take the tablet with a heavy meal B. It is best to take the tablet with a glass of milk C. Take the tablet immediately after a meal D. Take the tablet pre meals on an empty stomach E. Split the tablet into smaller portions and take throughout the day. D Correct Answer: Pre meals on empty stomach gives better absorption MOTOR FLUCTUATIONS “Wearing off phenomenon” due to decreased response to levodopa 1. at night - use CR nocte 2. frequent “wearing off” between doses – add COMT inhibitor 3. freezing episodes - increase dose or frequency of levodopa - add COMT inhibitor, MAO-B inhibitor or dopamine agonist - use liquid levodopa ( fast onset ) MANAGEMENT - SURGERY Since 1960s – Thalamotomy & Pallidotomy were common practice Destruction of brain tissue to control the symptoms Thalamotomy (thalamus) – reduces tremor Pallidotomy (globus pallidus) – reduces tremor, rigidity, bradykinesia & dyskinesias. Levodopa subsequently took over but surgery has since re-emerged as long term complications of levodopa have become apparent. Has a role where drug therapy is no longer sufficient.  DEEP BRAIN STIMULATION ▪ Intracerebral electrode connected to a pulse generator. ▪ Hand held device activates the pulse generator ▪ Leads to electrical stimulation of thalamus/globus pallidus ▪ Resets abnormal firing patterns ▪ Can be reversed & adjusted DEEP BRAIN STIMULATION HONOURS It improves symptoms that formerly responded to levodopa. Extends ‘on’ time. Subthalamic stimulation is commonest surgical procedure which reduces dyskinesias and medication use. Improvements maintained for up to 5 years post op Need: a clear diagnosis of PD levodopa responsive patients with motor fluctuations or dyskinesias no psychiatric problems good insight into risks/benefit of this treatment PARKINSON’S DISEASE - STAGES Ho ne ymo o n Mo to r c o mplic a tion pe rio d pe rio d Late stage SUMMARY Common but treatable disease where diagnosis is clinical. Monitoring is important ? Improvement ? Side effects ? fluctuations Aim to improve function & QOL Levodopa is mainstay of pharmacological treatment. Continuous MDT involvement central to care.