Parkinsons disease Flashcards
What are the different areas of the brain which can be affected by pathology which result in movement disorders ?
Corticspinal/pyramidal tract can be affected - this results in UMN features such as pyramidal weakness and spasticity
Basal ganglia can be affected, resulting in either hyperkinetic or hypokinetic signs:
Hyperkinetic disorders are also called dyskinesias. There are five forms of dyskinesias which include:
- Dystonia - Prolonged muscle spasms and abnormal postures
- Tics - a habitual spasmodic contraction of the muscles, most often in the face.
- Myoclonus - spasmodic jerky contraction of groups of muscles.
- Chorea - Fragments of movements flow irregularly from one body segment to another causing a dance-like appearance called Ballismus: if amplitude of these movements is large
- Tremor - unintentional, rhythmic muscle movement involving to-and-fro movements (oscillations)
Hypokinetic (rigidity and bradykinesia - slow movement) disorders:
- Parkinsonism
- Parkinson’s disease
Cerebellum - results in ataxia (incoordination)
What is the classic triad of parkinsonism ?
Note parkinsonism = a general term that refers to a group of neurological disorders that cause movement problems similar to those seen in Parkinson’s disease
- Bradykineasia/ hypokinesia
- Ridigity/ increased tone
- Rest Tremor
- Also postural and gait impairment
What are the different causes of parkinsonism ?
- Idiopathic PD (this is parkinsons disease)
- Drugs e.g. neuroleptics (antipsychotics), metoclopramide, prochlorperazine
- Rarely trauma/boxing
- Parkinsons plus syndromes
Define what parkinsons disease is
A common and complex neurodegenerative disease defined by the clinical motor features of parkinsonism
PD usually presents asymmetrically (I think e.g. the main tremor is usually in one arm etc)
What are the signs and symptoms of bradykinesia ?
- Slow to initiate and carry out movements - with progressive loss of amplitude or speed during attempted rapid alternating movement
- Hypomimesis - reduced facial expression
- Decreased eye blinking
- Monotonous Hypophonia - lacks variation in tone or pitch and is soft spoken
- Micographia (progressively smaller handwriting from initiating writing)
- Difficulty doing up buttons or cleaning teeth
Describe the rest temor in parkinsonism
- Defined as a rhythmic oscillatory involuntary movement of affected body part at rest that vanishes with active movement
- Tremor is unilateral
- Typically reappears after a few sec when arms held outstreched (‘reemerging tremor’)
- Tremor frequency in low to mid-range (4-6 Hz)
- Most distinguishing resting tremor is “Pill-rolling”-type or Finger flexion-extension or abducLon-adducLon
Describe rigidity in parkinonsim
- Increased muscle tone felt during examination by passive movement
- Resistance is felt throughout full range of movement
- “cog wheel” rigidity start-and stop movements through the range of motion of a joint
What are the postural and gait impairment problems suggestive of parkinsonism ?
- Stooped posture
- Parkinsonian gait is slow, occurs at narrow base with short, shuffling steps
- Decreased arm swing
- Slow turning with multiple small steps
- Freezing - can occur which is when they stop in places and are unable to move themselves because their muscle responses are now so slow
- Festination (very fast succession of steps and difficulLes stopping)
What are some of the non-motor features of parkinsons disease (idiopathic parkinsons disease)
Early non-motor features:
- Hyposmia - reduced smell
- REM
- Constipation
- Depression
- pain and fatigue
- cognitive impairment
Later non-motor features:
- Dementia - this occurs in >80% of patients after 20yrs
- Hallucinations
Describe the typical disease progression in someone with parkisons disease
- Non-motor symptoms can be present for upto a decade
- Motor symptoms present (this is when it gets diagnosed as parkinsons disease)
- Progression of PD is characterised by worsening motor features which initially respond well to symptomatic therapies
- Advanced stages of PD characterised by the emergence of complications related to long-term symptomatic treatment such as motor and non-motor fluctuations, dyskinesia, and psychosis
- In the late stage of PD treatment resistant motor and non-motor features are prominent and include axial motor symptoms such as postural instability, freezing of gait, falls, dysphagia, and speech dysfunction (note dementia also very very common)
What is the average age of onset of parkinsons disease ?
60
What is rapid eye movement (REM) sleep disorder ?
It is a parasomnia (disorder characterised by abnormal or unusual behaviour during sleep), characterised by abnormal or disruptive behaviours such as laughing, talking, shouting, gesturing, grabbing, punching, kicking, sitting up in bed. These behaviours occur during rapid eye movement (REM) sleep and are often related to dream enactment
How is REM sleep disorder diagnosed and treated ?
Diagnosis = overnight polysomnography
Treatment = clonazepam or melatonin at bedtime.
How is parkinsons disease diagnosed ?
It is a clinical diagnosis:
Bradykinesia + one or more of the following:
- Muscular rigidity
- 4-6Hz resting tremor
- Postural instability not caused by primary visual, vestibular, cerebellar or proprioceptive dysfunction
Describe the pathological process of parkinsons disease
Pathological hallmark - consists of prominent dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) with α-synuclein-containing Lewy bodies and Lewy neurites
Loss of dark pigment in the substantia nigra correlates to loss of dopaminergic cell loss
Note that neuronal loss in PD does affect other areas of the brain including locus ceruleus, nucleus basalis Meynert etc etc
What genetic mutations are associated with an increased risk of PD and which genetic mutation in particular is associated with the greatest risk for PD ?
- LRRK2 and parkin are the most common causes of dominantly and recessive PD,
- SNCA also increases risk
- The greatest genetic risk factor for PD is mutations in GBA
Do drugs in the treatment of PD slow disease progression ?
No - they are symptomatic treatments and do not slow the disease progression
Symptomatic treatments enhance intracerebral dopamine concentrations or stimulate dopamine receptors
What is the treatment of parkinsons disease ?
Offer levodopa to people in the early stages of Parkinson’s disease whose motor symptoms impact on their quality of life. - usually people are started on the levodopa (note its always given with a COMT e.g. carbidopa, entacapone, tolcapone
Consider a choice of dopamine agonists, levodopa or monoamine oxidase B (MAO‑B) inhibitors for people in the early stages of Parkinson’s disease whose motor symptoms do not impact on their quality of life. (go more for MAO-B or dopamine agonist here, as want to hold off giving levodopa if possible, dopamine agonist I think preferred out of the 2)
If a person with Parkinson’s disease has developed dyskinesia and/or motor fluctuations, including medicines ‘wearing off’ Offer a choice of dopamine agonists, MAO‑B inhibitors or catechol‑O‑methyl transferase (COMT) as an ajunct to carbidopa/levodopa
- Examples of dopamine agnosits = apomorphine, pramipexole, ropinirole and rotigotine.
- Other options of dopamine agnoists ‘ergot’ types ergot’ types include bromocriptine,pergolide and cabergoline
- monoamine oxidase B (MAO‑B) inhibitors = rasagiline or selegiline)
What is the purpose of giving levodopa with carbidopa ( a dopa-deoxycarbxylase inhibitor)?
The deoxycarboxylase inhibitor blocks enzymes from breaking down drug (levodopa)
What drug may be useful in the treatment of mild parkinsons with a prominent tremor (as dopamine replacement therapy is not great for treating tremor esp in treatment of mild disease as lower doses used)? (not used often as plenty of side effects in elderly)
Anti-cholinergics - trihexyphenidyl, or clozapine
What side effects are both dopamine agonists and levodopa both associated with ?
nausea, daytime somnolence (sleepiness), and oedema
What patients should dopamine agonists be avoided in and why ?
- should be avoided in patients with a history of addiction, obsessive-compulsive disorders and impulsive personality
- Impulse control disorders, including pathological gambling, hypersexuality, binge eating, compulsive spending can occur in patients on dopamine agonists
- Also more commonly associated with hallucinations
What are the long-term complications of dopaminergic therapies for PD?
Motor fluctuations & Non-motor fluctuations::
- Alterations between periods of good motor symptom control and periods of reduced motor symptom control
- Alterations between periods of good non-motor symptom control and periods of reduced nonmotor symptom control
Dyskinesias:
- Most frequently when levodopa concentraLons are at their maximum (peak-dose)
Drug induced psychosis:
- Hallucinations may be minor but also well-formed visual and less-commonly non-visual (tactile, auditory, olfactory) hallucinations. Other psychotic features might include illusions and delusions (often with paranoia)
Also dry mouth, anorexia, palpitations, postural hypotension
What is motor fluctuations and dyskinesias in PD thought to signify and what does the presence of this mean for treatment ?
Thought to result from the pulsatile stimulation of striatal dopamine receptors in later disease stages
When this is present this is when you would add either of the following to the current treatment with levodopa/carbidopa):
- A dopamine agonist - ropinirole or pramipexole
- Monoamine oaxidase type B inhibitor (MAO B inhibitor) - rasagiline, selegiline
- Catechol-O-methyltransferase inhibitor (COMT inhibitor) - carbidopa, entacapone, tolcapone
