Neuro - Parkinson's Disease + Other Movement Disorders Flashcards
Parkinson’s Disease
Pathophysiology
Diagnosis
Non-Motor Features
Differentials for Idiopathic Parkinson’s Disease
1.) Pathophysiology - neuronal degeneration in the nigrostriatal pathway leads to dopamine deficiency in the substanstia nigra of the basal ganglia
- lose dopamine-driven facilitation of movement via the direct and indirect pathway
- can find the presence of Lewy bodies
2.) Diagnosis - clinically based on sx and examination
- motor/non-motor features, good response to L-DOPA
- clinical scales: Heohn and Yahr, UPDRS
- SPECT or MRI can be used as neuroimaging to help differentiate from benign essential tremor
3.) Non-Motor Features
- autonomic: postural hypotension, constipation, erectile dysfunction, urinary frequency
- depression/anxiety, dementia, cognitive impairment
- REM behaviour disorder, obstructive sleep apnoea
- anosmia (loss of smell)
4.) Differentials for Idiopathic Parkinson’s Disease
- Parkinson-plus syndromes: 4 types, all present as parkinsonism with additional clinical features
- benign essential tremor
- vascular pseudoparkinsonism
- drug-induced: anti-psychotics, metoclopramide, motor symptoms are generally rapid onset and bilateral, rigidity and rest tremor are uncommon
- antihistamines can worsen Parkinson’s
Motor Signs of Parkinson’s Disease
Resting Tremor
Cogwheel Rigidity
Bradykinesia
Postural Instability
Parkinsonian Gait
1.) Bradykinesia - slow initiation of voluntary movement w/ a progressive ↓ in speed during repetitive actions
- micrographia: handwriting gets smaller and smaller
- hypomimia: ↓facial movements and expressions
- hypophonia: quiet speech (affects larynx and tongue)
- dysdiadokinesia: can’t do rapid alternating actions
2.) Cogwheel Rigidity - arm tension that gives way to move in small increments (like little jerks)
- combination of tremor and lead pipe rigidity
3.) Resting Tremor - asymmetrical, 4-6Hz in amplitude
- pill-rolling tremor abolished by movement
- worsened if distracted (e.g. close eyes and count back from 20 or perform task w/another hand)
- others: postural and resting tremor
- can be absent in some patients
4.) Postural Instability - loss of postural reflexes leads to a stooped posture, this can lead to falls
- late feature of idiopathic PD, occurs earlier
5.) Parkinsonian Gait
- shuffling: only take small steps when walking
- festinant: stride length is shortened and steps become progressively more rapid
- difficulty initiating movement and turning around
- reduced arm swing, stooped posture
Benign Essential Tremor
What Is It?
Clinical Features
Differential Diagnoses
Management
1.) What is It? - fine tremor affecting voluntary muscles
- often hands but also head, jaw and vocal tremor
- relatively common, associated with older age
2.) Clinical Features
- symmetrical fine tremor, often in the head and neck
- better at rest, worse on voluntary movement
- worsens with stress, tiredness, caffeine
- improves with alcohol
3.) Differential Diagnoses
- Parkinson’s disease, MS, Huntington’s Chorea
- hyperthyroidism, fever, drugs (e.g. antipsychotics)
4.) Management - no definitive treatment
- no treatment if no functional or psych problems
- medication: propranolol, primidone (barbiturate AED)
Use of Levodopa (L-DOPA) in Parkinson’s Disease
Mechanism
Usage
Motor Complications
Other Side Effects
1.) Mechanism - synthetic dopamine ↑dopamine levels
- combined w/ peripheral decarboxylase inhibitors that prevent L-DOPA from being broken down in the body
- Co-careldopa: levodopa + carbidopa
- Co-beneldopa: levodopa + benserazide
2.) Usage
- first-line for patients w/ motor sx affecting their QoL
- most effective for sx but ↓effectiveness over time
- reserved for when others are not controlling sx
3.) Motor Complications - ↑↑↑dopamine –> dyskinesia which are movements due to excessive motor activity
- dystonia: excessive muscle contraction leads to abnormal postures or exaggerated movements.
- chorea: involuntary jerking/ dance-like movements
- athetosis: involuntary twisting/writhing movements
- motor complications are worst w/ levodopa
4.) Other Side Effects - all worse w/ dopamine agonists and MAO-Bi
- excessive sleepiness, hallucinations and psychosis
- ‘on-off’ effect: due to ‘wearing off’ of dopamine
- GI: reduced appetite, dry mouth, N+V (domperidone used as it blocks D2 and doesn’t cross the BBB)
- others: postural hypotension, cardiac arrhythmias, reddish discolouration of urine upon standing, neuroleptic malignant syndrome (when abruptly stopping levodopa)
- impulse control disorders: pathological gambling, hypersexuality, compulsive shopping, punding, desire to increase dosage of medications
Other Medication used in Parkinson’s Disease
Dopamine Agonists
Monoamine Oxidase-B Inhibitors (MAO-Bi)
Catechol-O-MethylTransferase Inhibitors (COMTi)
Anticholinergics
Amantidine
Non-Oral Continuous Drug Delivery (CDD)
1.) Dopamine Agonists - mimics dopamine
- first-line if motor sx aren’t affecting the patient’s QoL
- can add L-DOPA if not working (↓dose of L-DOPA)
- ergot-derived: bromocriptine, cabergoline
- non-ergot agonists now used due to ↓side effects, e.g. ropinirole (PO), rotigotine (TD, very useful in those with Parkinson’s and NBM), apomorphine (SC), pramipexole
- apomorphine is a rescue drug for severe motor sx+
- most likely to cause impulse control disorders
2.) MAO-B Inhibitors - blocks MAO-B (breaks down dopamine) which helps to ↑ circulating dopamine
- first-line if motor sx aren’t affecting the patient’s QoL
- can add L-DOPA if not working (↓dose of L-DOPA)
- examples: selegiline, rasagiline
3.) COMT Inhibitors - entacapone
- inhibits COMT (metabolises L-DOPA in brain+body) which leads to slowing the breakdown of L-DOPA
- only used w/ L-DOPA to extend it’s effective duration
4.) Anticholinergics - orphenadrine, procyclidine
- ↓antagonistic effects of ACh on dopamine
- useful for tremors but no effect on bradykinesia
- adjunct to help with side effects
- mainly for drug-induced parkinsonism
5.) Amantadine - mechanism uncertain
- an adjunct to help with side effects
6.) Non-Oral Continuous Drug Delivery (CDD)
- for advanced disease w/ severe drug side effects
- continuous subcutaneous apomorphine infusion
- levodopa-carbidopa intestinal gel infusion
- transdermal rotigotine therapy
Parkinson-Plus Syndromes
Multple System Atrophy (MSA)
Dementia with Lewy Bodies (DLB)
Progressive Supranuclear Palsy (PSP)
Corticobasal Degeneration (CBD)
1.) Multiple System Atrophy (MSA) - degeneration of neurones in multiple brain systems inc basal ganglia
- early autonomic sx: e.g. tachycardia, incontinence, ED, etc
- can also lead to cerebellar dysfunction (DANISH)
- has poor response to levodopa
2.) Dementia with Lewy Bodies (DLB)
- fluctuations in cognitive impairment and visual hallucinations, often occur before Parkinsonism
3.) Progressive Supranuclear Palsy (PSP)
- early postural instability –> falls
- early dementia and cognitive impairment
- vertical gaze palsy (impairment of vertical gaze), axial rigidity
- has poor response to levodopa
- suspect in patients with a fall after a recent diagnosis of Parkinson’s disease
4.) Corticobasal Degeneration (CBD)
- involves spontaneous activity by an affected limb, or akinetic rigidity of that limb
Huntington’s Chorea
What is it?
Clinical Features
Management
Prognosis
1.) What is it? - AD genetic condition that causes a progressive deterioration in the nervous system
- often presents around age 30-50
- genetic mutation in HTT gene on chromosome 4
- trinucleotide repeat disorder, shows ‘anticipation’:
- successive generations have more repeats in the gene –> earlier age of onset and ↑disease severity
2.) Clinical Features - insidious, progressive worsening of sx often starting w/ cognitive, psychiatric or mood problems followed by the movement disorders:
- chorea: involuntary, abnormal muscle movements
- eye movement disorders, dysarthria, dysphagia
- diagnosed in a specialist genetic centre
3.) Management - no treatment options, can only provide support for the person and their family:
- MDT: OT/PT, SALT, psychology
- genetic counselling for relatives
- patients wishes and end of life care planning
- some medications can suppress the movements:
- antipsychotics (e.g. olanzapine), benzos (diazepam),
dopamine-depleting agents (e.g. tetrabenazine)
- depression can be treated with antidepressants
4.) Prognosis
- progressive condition with no cure
- life expectance is around 15-20 years after sx onset
- death is often due to respiratory disease (e.g. pneumonia) and suicide rates are also much higher
