Neurology: Parkinsonism Flashcards
What is Parkinson’s disease?
Idiopathic Parkinson’s Disease (IPD) is a progressive degenerative disorder characterised by neuronal loss in the brainstem and basal ganglia. There is loss of dopaminergic neurones in the substantia nigra that leads to inadequate dopamine transmission. The characteristic neuropathological finding is Lewy Body formation in affected neurones. The condition is usually sporadic in nature, but some genetic variants do exist.
Distribution of symptoms in Parkinson’s disease?
Asymmetirical, with one side affected more than the other
Classic triad of Parkinson’s Disease symptoms?
Resting tremor
Rigidity
Bradykinesia
Basic pathophysiology of Parkinson’s Disease?
Gradual but progressive fall in production of dopamine by the substantia nigra (part of the basal gangila (group of structures situated in middle of brain responsible for coordinating habitual movements, controlling voluntary movements and learning specific movement patterns)
Loss of dopamenergic neurones leadys to loss of inhibitionin the neostriatum ,which allows increased production of Ach (excitatory)
Chain of abnormal signalling leads to impaired mobility
What demographic of patient typically present with Parkinson’s Disease?
Male, older age (70s)
What signs may suggest Parkinson’s Disease when a patient walks?
Stooped posture
Facial masking
Forward tilt
Reduced arm swing
Shuffling gait
Characteristics of tremor in Parkinsons?
4-6Hz
‘Pill rolling tremor’
More pronounced on resting, improving on voluntary movement
Tremor worsened as patient is distracted
When unilateral, tremor is exaggerated when pt asked to do a task with unaffected hand
What is ‘cogwheel’ rigidity?
Resistance to passive movement of a joint
Tension will be felt and joint moves in small incriments
What is bradykinesia?
Slower and smaller movements
How might bradykinesia present?
Their handwriting gets smaller and smaller (this is a classic presenting complaint in exams)
They can only take small steps when walking (“shuffling gait”)
They have difficulty initiating movement (e.g. from standing still to walking)
They have difficulty in turning around when standing, having to take lots of little steps
They have reduced facial movements and facial expressions (hypomimia)
What is hypomimia?
Reduce facial movements and expressions
Features of Parkinsons Disease?
Resting tremor
Bradykinesia
Cogwheel rigidity
Depression
Sleep distrubance and insomnia
Loss of the sense of smell (anosmia)
Postural instability
Cognitive impairment and memory problems
Parkinson’s Tremor vs Benign Essential Tremor - symmetry
Parkisons: Asymettrical, 4-6Hz, worse at rest, improves with intentional movement, other parkinsons features present, not affected by alcohol
Benign essential tremor; Symmetrical, 5-8Hz (Higher frequency), improves with rest but worse with intentional movement, no other parkinsons features present, IMPROVES WITH alcohol
What is benign essential termor?
(Differential in Parkinson’s presentation)
Common condition associated with old aged
Fine tremor affecting all the voluntary muscles, most notable in the hands but affects many other areas e.g. head tremor, jaw tremor, vocal tremor.
What can worsen a benign essentiel tremmor?
Voluntary movement
Tiredness
Stress
Caffeine
When would a benign essentiel termor always be absent?
Sleep
Differentials for patients presenting with a tremor?
Benign essential tremor?
Parkinson’s disease
Multiple sclerosis
Huntington’s Chorea
Hyperthyroidism
Fever
Medications (e.g. antipsychotics)
There is no definitive treatment for benign essential tremor as it is not harmful, but what medications can be trialed if it causes psychological or functional problems?
Propranolol
Primidone
What are Parkinson-plus syndromes?
Parkinson-plus syndromes ( PPS) are a group of neurodegenerative diseases featuring the classical features of Parkinson’s disease ( tremor, rigidity, akinesia / bradykinesia, and postural instability) with additional features that distinguish them from simple idiopathic Parkinson’s disease (PD).
Types of Parkinson’s-plus Syndromes?
Multiple System Atrophy
Dementia with Lewy Bodies
Progressive Supranuclear Palsy
Corticobasal Degeneration
What is multiple system atrophy?
A Parkinson’s plus Syndrome.
Rare condition.
Multiple systems in the brain degenerate, affecting the basal ganglia as well as multiple other areas.
The degenertation of the basal ganglia lead to a Parkinson’s presentation.
Degeneration in other areas lead to autonomic dysfunction and cerebellar dysfunction
Notable consequences of autonomic dysfunction?
Postural hypotension
Constipation
Abnormal sweating
Sexual dysfunction
Notable consequence of cerebellar dysfunction?
Ataxia
What is Dementia with Lewy Bodies?
This is a type of dementia associated with features of Parkinsonism. It causes a progressive cognitive decline.
There are associated symptoms of visual hallucinations, delusions, disorders of REM sleep and fluctuating consciousness.
How is Parkinson’s diagnosed?
Parkinson’s disease is diagnosed clinically based on symptoms and examination.
The diagnosis should be made by a specialist with experience in diagnosing Parkinson’s.
NICE recommend using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria.
What do patients with Parkinson’s mean when they describe themselves as ‘on’ and ‘off’?
On: Medications are acting and they are moving freely
Off: Medications have worn out, they have significant symptoms and their next dose is due
What medications are used to manage Parkinson’s?
Levodopa + peripheral decarvoxylase inhibitors: co-benyldopa (benserazide), co-careldopa (carbidopa)
COMT inhibitors: entacapone
Dopamine agonists: bromocryptine, pergolide, carbergoline
Monoamine Oxidase-B inhibitors: Selegiline, rasagiline
Anticholinergics (tremor) and Amantidine (bradykinesia) have a minor role also
What is the classic neuro pathological finding in IPD?
Lewybody formation in the affected neurones
Diagnostic criteria for IPD?
- Bradykinesia
And
At least one of the following:
o Muscular rigidity
o 4-6 Hz rest tremor
o postural instability not caused by primary visual, vestibular, cerebellar, or proprioceptive dysfunction
- Exclusion of other causes of Parkinsonism
- For definite diagnosis, Step one plus three or more of
Unilateral onset
Rest tremor present
Progressive disorder
Persistent asymmetry affecting side of onset most
Excellent response (70-100%) to levodopa
Severe levodopa-induced chorea
Levodopa response for 5 years or more
Clinical course of ten years or more
Non motor signs and symptoms of Parkinson’s disease?
Pain
Fatigue
Low blood pressure
Restless legs
Bladder and bowel problems
Skin and sweating
Sleep
Eating, swallowing and saliva control
Speech and communication issues
Eye problems
Anosmia
Restless legs
Mental health issues:
Mild memory and thinking problems
Anxiety
Dementia
Depression
Hallucinations and delusions
Non oral therapies in Parkinson’s disease
Apomorphine - injectable dopamine-injector pen or infusion pump
Deep brain stimulation -DBS: pulse generator placed under skin connected to fine wires in specific areas of the brain an a deliver high energy signals to this area of the brain (neurosurgical)
Duodopa - gel form of levodopa + carbidopa administered via PEG via a pump.
Stages of IPD (idiopathic Parkinson’s disease)
- Early stage - Soon after diagnosis, symptoms are mild and normal life possible
- Maintenance stage - Good response to treatment and no major disability
- Advanced stage - Poor response to drugs with motor side effects
- Palliative stage - Unable to live independently and in need of multidisciplinary support
Complications in advanced IPD?
Difficulty or swallowing
Dementia
Bladder and bowel incontinence
Difficulty walking, talking, eating, dressing
Falling
Reduced mobility
Hallucinations, dellusions
Clinical features vascular parkinsonism?
Acute or subactue onset with stepwise evolution of akinesia and rigidity
Presence of risk factors for CVD
Two or more basal ganglia infracts OR more widespread subcortical white matter lesions evident on neuroimaging
No rest tremor
Prominent postural instability and gait disorder
Unresponsive to levodopa treatment
What is vascular pseudo-parkinsonism
Vascular “pseudo-parkinsonism” refers to isolated gait disorders called “lower body parkinsonism”, “frontal-type gait disorders” or “gait ignition failure” that are reminiscent of, but distinct from, that found in IPD. The pathophysiology of VP is poorly understood.
Clinical features of lewy body dementia?
Characterised by alpha-synuclein cytoplasmic inclusions (Lewy bodies)
in the substantia nigra, paralimbic and neocortical areas.
Associated with Parkinson’s disease - patients are also highly sensitive to neuroleptics, which causes a deterioration in parkinsonism
Three core features: fluctuating cognition, parkinsonism and visual hallucinations
Progressive cognitive impairment seen
Diagnosis is usually clinical but dopamine uptake scanning may be used
What is drug induced parkinsonism and how does it present?
Bradykinesia, rigidity, mild termor, rabit syndrome
Caused by exposure to a dopamine-receptor blocking agent within 6 months of the onset of symptoms
Mild cases can remit after cessation of the offending drug
Usually unresponsive to dopaminergic therapy
Elderly patients are most susceptible
What drugs might cause drug induce parkinsonism?
Antipsychotics
Anitemetics
Metoclopramide
Treatment for drug induce parkinsonism?
tetrabenazine, reserpine, vitamin E, bezodiazepines
Limb tone in Parkinson’s?
Hypertonia
Limb tone in parkinsons?
Hypertonia
What causes vascular parkinsonism?
Cerebrovascular disease
Which Parkinsons medications are most commonly responsible for impulse control disorders?
Dopamine agonists
What is ‘wearing off’ in terms of anti-Parkinsons therapy?
Symptoms (either motor or non-motor) returning before the next dose and relieved by taking anti-Parkinsons therapy
What is ‘peak dose dyskinesia’ in terms of anti-Parkinsons therapy?
Dyskinesia which occurs around 30 mins after taking medication
What does a pill rolling tremor indicate?
Young patients: Drug induced Parkinsonism
Older patients: IPD
Anatomy of the basal ganglia?
When do symptoms begin in IPD in terms of the pathophysiolgical course?
50% of dopaminergic neurones in SN lost (local adaptations, increased cell turnover, upregulation of receptors)
SN will appear loss of pigment on post mortem
Parkinsons gait?
Forward flexed shuffling gait with asymmetric arm swing
Loss of fluidity in turns
Rigidity in Parkinsons?
Lead pipe rigidity is
Cogwheel rigidity if tremor superimposed on rigidity
How can you assess bradykinesia?
Ask patient to do small repetitive motor movements:
Finger tapping
Foot tapping
Glabellar Tap
Look out for:
reduce amplitude of movements
an inability to maintain good rhythm
Slowness of movement
Poor prognostic factors in IPD?
More rapid progression in those with older age and more severe motor impairment at onset
Dementia within 20 years of onset
Why does levodopa become less effective as IPD progresses?
Must be taken up by dopamenergic cells in the substantia nigra to be converted to dopamine
Disease progression - degenreation of cells - fewer remaining cells - less reliable effect of levodopa- motor fluctations seen
What is Sinemet?
Co-careldopa
IDP - management
Pharmacology: L-DOPA + decarboxylase inhibitor, dopamine receptor agonists, MAOI type B inhibitors + COMT inhibitors, (anitcholenergics, amantidine)
Physio
OT
SALT
Surgery (DBS, PEG insertion for duodopa)
Role of deep brain stimulation in IPD
Carried out sterotactively
DBS of subthalamic nucleus
Of value in highly selected cases of patients who:
Are dopamine responsive
Experience significant side effects with L-DOPA and are
Free of psychiatric illness
Tremor features to ellicit from history?
Amplitude - fine/course
Frequency - fast/slow
Distribution - symettry/body part
Occurence - intermittent/persistent/resting/action/postural
Other factors - relieving/provoking factors, fhx, generic clinical state
Extrapyrmaidal symptoms?
Parkinsons gait
Bradykinesia
Lead pipe ridigity
3-5 hx rolling pill tremor
What should be added on when patients develop dyskinesia due to long term levodopa use?
NICE suggest that, in this situation, an oral catechol-O-methyl transferase (COMT) inhibitor like entacapone is given in combination with levodopa and carbidopa.
What drugs should be avoided in Parkinsons disease?
chlorpromazine (Largactil) - antipsychotic/antiemetic
fluphenazine (Modecate) - antipsychotic
perphenazine (Fentazin/Triptafen) -antipsychotic
trifluoperazine (Stelazine) - antipsychotic
flupentixol (Fluanxol/Depixol) - antipsychotic
haloperidol (Serenace/Haldol) - antipsychtoic
metoclopramide (Maxalon) -antiemetic
prochlorperazine (Stemetil)
Diplopia is not common in Parkinson’s disease and may suggest an alternative cause of parkinsonism such as what?
progressive supranuclear palsy
Progressive supranuclear palsy presentation
Progressive supranuclear palsy: postural instability, impairment of vertical gaze, parkinsonism, frontal lobe dysfunction
What Parkinsons drug is associated with pulmonary fibrosis?
Cabergoline
What do the results of a DaTSCAN tell us?
An abnormal DaTSCAN indicates pathology which is either:
- Neurodegenerative (e.g. Parkinson’s disease or multiple systems atrophy)
- Neurogenetic (e.g. spinocerebellar ataxia)
- The result of cerebrovascular disease
A normal scan means the pathological process producing symptoms does not affect dopamine transports (e.g. essential tremor, drug-induced parkinsonism, or functional parkinsonism).
