Lecture 8.2: Parkinson’s Disease (and some other motor disorders) Flashcards
What is Parkinson‘s Disease?
Chronic Progressive Neurodegenerative disorder that affects the dopaminergic neurons within the substantia nigra as a result, body movements are affected
Parkinson’s: TRAP
Tremor (usually starts on 1 side)
Rigidity (stiffness of limbs, neck or trunk)
Akinesia (loss/impairment in power of voluntary mvt)
Posture & Balance
Aetiology of Parkinson‘s Disease (7)
- Mostly Idiopathic (95%)
- Rarely Genetic (autosomal dominant & recessive)
- Medicine Related
- Toxins
- Vascular (multiple white matter infarcts)
- Traumatic
- Post-Infectious (post encephalitic parkinsonism)
What Medicines can contribute to Parkinsonism? (2)
- Antiemetics
- Antipsychotics
What Toxins can contribute to Parkinsonism? (3)
- Manganese
- Carbon Disulphide
- MPTP
What percentage of nigrostriatal dopaminergic neurones need to be lost before classical symptoms are noted?
> 50%
During a preclinical phase extending back for several years before the development of the motor deficit, what symptoms may be present? (5)
- Hyposmia
- Constipation
- Anxiety
- Depression
- Rapid Eye-Movement (REM) sleep behaviour
disorder (dream enactment)
Features of a Parkinson’s Tremor (4)
- 4-6Hz noticeable at rest
- ‘Pill-rolling’ – rhythmic flexion/extension of fingers,
supination-pronation of forearm - Increases during stress
- Reduces on movement
Clinical Features of Parkinson’s: Rigidity
- Increased tone = resistance to passive movement
- ‘cog-wheel’ = rachet like interruptions
- Due to tremor in muscles
- Creates a more flexed posture
Clinical Features of Parkinson’s: Akinesia (Bradykinesia)
- Slowness of voluntary movement
- Reduction in automatic movement (e.g arm swing
when walking) - Mask-like face, reduced blinking
- Power retained
Management of Parkinson’s (3)
- Precursors of Dopamine
- Inhibitors of Dopamine metabolism
- Dopamine receptor agonists
Levodopa (L-dopa)
- Precursor of dopamine converted both peripherally
and centrally by decarboxylation - Majority converted peripherally so need to block
peripheral decarboxylase - Dopamine stored in brain and one dose can last
several hours
Side-Effects of Levodopa (L-dopa) (4)
- Nausea
- Hypotension
- Hallucinations
- Nightmares
What are Selegiline & Rasagiline? What do they do?
- Selective MAO inhibitors
- Reduce metabolism of central dopamine
- Complement L-dopa
What are Entacapone & Tolcapone? What do they do?
- COMT inhibitors
- Increase dopamine availability
What are Pramipexole & Ropinirole? What do they do?
- Dopamine receptor agonists
What is Huntington’s Disease?
- Huntington‘s disease is a inherited Autosomal
Dominant neurodegenerative disease - It causes the progressive breakdown of nerve cells
in the brain and progressive movement disorder
with dementia
What chromosome is Huntington’s associated with?
- Chromosome 4
- CAG trinucleotide repeats
What parts of cerebrum atrophy in Huntington’s? (3)
- Cortex
- Caudate
- Putamen
Clinical Presentation of Huntington’s Disease (8)
- Changes in Mood
- Anxiety
- Irritability
- Memory Loss
- Quickly putting food in mouth (like chipmunks)
- Chorea
- Dystonia
- Slow or unusual eye movements
Treatment of Huntington’s Disease (5)
- No treatment only management of symptoms
- Psychological support
- Speech therapist
- Antipsychotics
- Tetrabenazine – FDA approved for managing Chorea
but can cause Parkinsonism as it depletes dopamine
and also may increase risk of depression
What is Wilson Disease?
An autosomal recessive genetic disorder of impaired copper transport and excretion caused due to the loss of function of the ATP7B copper-binding protein
Normal Cu Metabolism
- Loading of Cu onto protein ceruloplasmin for safe
transport in blood - Excretion of excess Cu via bile in faeces
Cu Metabolism in Wilson’s Disease
- No loading of Cu onto protein ceruloplasmin
- No excretion of excess Cu via bile in faeces
- Increased levels of toxic Cu in blood, liver, brain,
other organs
Clinical Features in Wilson’s Disease (10)
- Tremor
- Involuntary Movements
- Dysphagia
- Dysarthria
- Lack of Coordination
- Spasticity
- Dystonic Postures
- Muscle Rigidity
- Kayser-Fleischer Rings
- Liver Failure
What are Kayser-Fleischer Rings?
Dark rings that appear to encircle the iris of the eye
Investigations for Wilson’s Disease (3)
- Raised Urinary Copper (100 μg/24 hours)
- Reduced Caeruloplasmin (<20mg/dL)
- Serum Copper (25 μg/dL)
Treatment of Wilson’s Disease (4)
- Penicillamine (chelates copper and increases
excretion) - Trientine (Syprine)
- Zinc Acetate
- Liver Transplant
What is Wernicke Encephalopathy?
A degenerative brain disorder caused by the lack of vitamin B1
Triad of Wernicke Encephalopathy Symptoms
- Ataxia
- Ophthalmoplegia
- Confusion
What can cause Wernicke Encephalopathy?
- Alcohol Abuse
- Dietary Deficiencies
- Prolonged Vomiting
What is Vertebrobasilar Insufficiency?
- Inadequate blood flow through the posterior
circulation of the brain, supplied by the 2 vertebral
arteries that merge to form the basilar artery - The vertebrobasilar arteries supply the cerebellum,
medulla, midbrain, and occipital cortex.
Clinical Presentations of Cerebellar Infarct (3)
Ipsilateral Limb:
* Ataxia
* Lateropulsion
* Hypotonia
What is Multiple Sclerosis (MS)?
- MS is an autoimmune disease
- Caused by myelin-reactive T cells in the peripheral
circulation that become activated by a trigger - Invade the central nervous system and cause
destruction of myelin and axons directly and by
initiating the release of various inflammatory
mediators
Risk Factors for MS (6)
- Geography
- Vitamin D deficiency
- Obesity
- EBV exposure
- Smoking
- Gut Microbiome
When is typical disease onset of MS?
Between 20 to 40 year olds
Signs and Symptoms of MS (10)
- Fatigue
- Vision Problems (Optic Neuritis)
- Incontinence
- Muscle stiffness and spasms
- Relative Afferent Pupillary Defect (Marcus Gunn
Pupil) - Bilateral Internuclear Opthalmoplegia
- Pseudobalbar Palsy
- Memory loss, depression
- Ataxia
- Intention Tremor
What is Pseudobulbar Palsy is characterised by? (4)
- Dysarthria
- Dysphagia
- Facial and Tongue Weakness
- Emotional Lability
What are Clinical Signs of MS? (2)
- Lhermitte’s Sign
- Uhthoff’s Phenomenon
What is Lhermitte’s Sign?
An intense burst of pain like an electric shock that runs down your back into your arms and legs when you move your neck
What is Uhthoff’s Phenomenon?
Transient worsening of neurological symptoms when the body becomes overheated in hot weather, exercise, shower, saunas, or hot tubs
What is Charcot’s Neurological Triad for MS?
- Nystagmus
- Dysarthria
- Intention Tremor
Treatments of MS (6)
- High Dose Corticosteroids
- Plasmapheresis
- Interferon Beta
- Glatiramer Acetate
- Ocrelizumab
- Natalizumab
