Flashcards in Parkinson's disease and parkinsonism Deck (33):
Movement disorders - where is the problem in 'pyramidal' or 'upper motor neurone' disorder? what does this result in?
Problems with corticospinal/pyramidal tract
Movement disorders - where is the problem in hyperkinetic movement disorder?
problem in the basal ganglia
movement disorders - where is the problem in hypokinetic movement disorder?
-lack of dopamine in the basal ganglia
ataxia - where is the problem?
What is the aetiology of parkinson's disease?
sections through brainstem reveals loss of the normally dark pigment in the substantia nigra and locus coeruleus
pigment loss correlates with dopaminergic cell loss
neurohistological landmark of PD are Lewy bodies
usually an asymmetric disorder
Describe the tremor in parkinson's disease
-what is it like?
-what does it affect?
-when is it present?
Involuntary, repetitive, rhythmic sinusoidal movement usually affecting one or more limbs
Primarily affects hands, may involve upper/lower limbs, less frequently jaw and lips, never head or neck
Pill-rolling in the hands, or finger flexion-extension or abduction/adduction
Present at rest, exacerbated by anxiety or stress
Improves/disappears on action
Typically reappears after few sec when arms held outstretched
Tremor frequency in low to mid range (3-6hz) with varying amplitude
Can observe tremor while patient is focused on a particular mental task e.g. counting backward
Describe the rigidity in parkinson's disease
-what is it like?
-what is cogwheel rigidity?
-how can rigidity be accentuated?
Increase in muscle tone in parkinson’s disease is relatively constant throughout the range of movement: lead pipe rigidity
No increase with higher mobilising speed (distinguishing it from spasticity)
Cogwheel rigidity is a consequence of the tremor of parkinsons disease being superimposed on background of lead-pipe rigidity
Rigidity in one arm can be accentuated by asking the patient to lift and lower the contralateral arm repeatedly at the same time
Positive froments manouvre
Describe the bradykinesia found in parkinson's disease
-what is it like?
-what is micrographia
-how can lack of spontaneous movement manifest?
Slowness of movement with progressive loss of amplitude or speed during attempted rapid alternating movement of body segments
Assessed by foot tapping/opening and closing hand, quickly and widely as poss.
Particular difficulty with complex motor tasks (micrographia)
Smaller hand writing
Lack of spontaneous movement nay manifest:
Poverty facial expression/mask-like face and eye-blinking - hypomimia
Difficulty changing position
Quiet/monotonous speech - hypophonia
Abnormal gait and stance
Describe the gait seen in parkinson's disease
-what is particularly difficult?
-what are steps like?
Flexed or stooped posture
In some cases extreme anterior truncal flexion - camptocormia
Unable to maintain a normal stance in response to pressure
Initiation of walking may be difficult – freezing
Turning may be difficult
Patients may use trick such as deliberately stepping over a walking stick to change direction
Steps are small and shuffling
Normal arm swing on walking is lost
Festination – very fast succession of steps and difficulty stoppping
Other motor symptoms in parkinsons disease:
-what kind of gaze is difficult?
-what is difficult to do in the GI system?
-is there any MSK manifestations?
-is muscle power/reflexes/sensations/plantar response affected?
Mild impairment of upgaze, eyelid tremor
Difficulty swallowing, including saliva
Many patients have a frozen shoulder
Muscle power/reflexes/sensations/plantar response is normal
What are the non-motor symptoms found in parkinson's disease? 7
Depression – chemical depression
Visual hallucinations – esp. at night
Psychosis – worsening hallucinations and delusions may escalate
Dementia – common feature of advanced parkinsons, >80% of pt.s after 20years
Autonomic symptoms – greasy skin, constipation, bladder disturbance, erectile dysfunction
Parkinson's disease epidemiology:
-is it common?
-male to female?
-what increases the probability of a genetic cause?
Second most common neurodegenerative disorder after AD
!- 2% over 60- 65’s affected
male to female 3:2
annual incidence rates 8.6-19 per 1000
due to ageing population, prevalence and socioeconomic burder expected to rise exponentially
early onset (below 40years) increases probability of genetic cause
What are the risk factors for parkinson's disease?
old age = strongest risk factor
28 distinct chromosomal regions have been linked to PD
6 of these contain genes that conclusively cause monogenetic PD
monogenetic PD accounts for 30% familial and 3-5% sporadic cases
pesticide exposure and +ve FH are other risk factors
possible protective role of NSAIDs and high uric acid levels
smoking has a protective affect
therefore etiology is genetically heterogeneous and multifactorial – genes, modifying effects by susceptible alleles and environmental factors
Should you see sensory/pyramidal/cerebellar signs in parkinson's disease?
What are the investigations for parkinsons disease?
To rule out treatable conditions of asthenia: hypothyroid, anaemia
Structural brain imaging
Possibly dopamine functional imaging
PET with fluoro-dopa (limited avail. And high cost)
These are unable to distinguish PD from other causes of parkinsonism, but should be normal in essential tremor, dystonic tremor, psychogenic parkinsonism
Positive levodopa challenge (or s.c. apomorphine)
Genetic testing if appropriate
What are common causes of parkinsonism? 6
-drug-induced/iatrogenic parkinsonism (prochloperazine, metoclopramide, antipsychotics, severe calcium channel blockers, amiodarone, chloroquine)
-progressive supranuclear palsy
-multi system atrophy – parkinsonism
-dementia with lewy bodies
-diffuse white matter ischaemia/vascular parkinsonism
-lower half parkinsonism with marked gait apraxia
Describe drug induced parkinsonism
Any drug that bocks action of dopamine esp. neuroleptic drugs
coarse postural tremor
presence of other drug induced disorders
orolingual dyskinesias, tardive dystonia, akathisia
series of events important: emergence of symptoms after drug exposure
improvement/resolutions within a few mths of complete withdrawal of drug
what is progressive supranuclear palsy?
Symmetric akinetic-rigid syndrome with predominantly axial involvement
Gait and balance impairment (early falls)
Tremor is infrequently seen in these patients
Vertical gaze supranuclear palsy
Continuous activity of the frontalis muscle with eyes wide open (staring)
Frontal-subcortical cognitive deficits
No response to levo-dopa
Some patients may also present with parkinsonism (PSP-parkinsonism)
what is multi system atrophy?
Common cause of degenerative parkinsonism
Age of onset 6th/7th decade
Core triad: dysautonomia (atonic bladder/postural hypotension), cerebellar features and parkinsonism
Jerky postural tremor, pyramidal signs (generalised hyperreflexia and extensor plantar responses)
Sub-optimal and short-lived levodopa response in 1/3 pts.
Other suggestive features:
Severe dysarthria or dysphonia
MRI may show cerebellar and pontine atrophy (hot cross bun sign or hypertense rim surrounding theputamen in T2-weighted sequences
What is dementia with lewy bodies?
Dementia is predominant feature
Daily fluctuations in alertness and cognition
Visual hallucinations (colourful, often involving human figures)
Extreme sensitivity to neuroleptic medication
Controversial as to whether this is a separate disease entity
What is vascular parkinsonism?
affects predominantly lower limbs
rest tremor uncommon
other signs of brain vascular lesions might be present – spasticity/hemiparesis/pseudobulbar palsy
poor levodopa response
structural brain imaging guides diagnosis
Describe an essential tremor:
-what does it respond to?
symmetrical, postural or kinetic tremor with higher frequency (up to 12Hz)
infrequently observed at rest
often autosomal dominant inheritance with mean onset 15yrs
head tremor – if present – mild
What is SWEDDs?
(scans without evidence of dopaminergic deficit)
Often rest and asymmetrical tremor but no true bradykinesia
Clinical and electrophysiological characteristics of dystonia
Describe the principles of treatment of parkinson's disease?
Delay treatment until onset of disabling features and then initiate treatment.
Initial maintenance dose of levodopa should start with 50mg TDS and not exceed 600mg/day
All other agents for the treatment of motor symptoms can be combined with levodopa to reduce end of dose deterioration and the on-off syndrome
Why is levodopa used with a decarboxylase inhibitor?
-side effects of levodopa?
usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine
reduced effectiveness with time (usually by 2 years)
unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness
no use in neuroleptic induced parkinsonism
What are dyskinesias/'wearing off' and on-off effects in relation to levodopa?
Dyskinesia are involuntary movements occurring in association with drug treatment, e.g. twisting/turning movements when dopamine levels are high (peak-dose dyskinesia)
Wearing off is when individual doses only produce short lived affects
On-off is where the patient switches from symptomatic benefit of medication (on) to an akinetic-rigid state often without any predictable relationship to the timing of drug doses
What other drugs exist for the treatment of motor symptoms in parkinson's disease?
-Ergot derivatives: bromocriptine, pergolide, di-hydroergocryptine
-Non-ergot derivatives: ropinirole, pramipexole, rotigotine, apomorphine
Catechol-O-methyltransferase inhibitor (entacapone, tolcapone)
What are ergot derivative dopamine agonists assoc. with? what does this mean for initiation of this treatment?
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
What side effects are assoc. with all dopamine agonists?
patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence
more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patient
What is the role of COMT inhibitors in parkinson's disease?
e.g. Entacapone, tolcapone
COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy
used in conjunction with levodopa in patients with established PD
What is the role of amantadine in parkinsons disease?
mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses
side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis
How do MAOB inhibitors help treat parkinson's disease?
inhibits the breakdown of dopamine secreted by the dopaminergic neurons