Neurology: Parkinsonism

Question 1

What is Parkinson’s disease?

Answer 1

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.

Question 2

Distribution of symptoms in Parkinson’s disease?

Answer 2

Asymmetirical, with one side affected more than the other

Question 3

Classic triad of Parkinson’s Disease symptoms?

Answer 3

Resting tremor
Rigidity
Bradykinesia

Question 4

Basic pathophysiology of Parkinson’s Disease?

Answer 4

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

Question 5

What demographic of patient typically present with Parkinson’s Disease?

Answer 5

Male, older age (70s)

Question 6

What signs may suggest Parkinson’s Disease when a patient walks?

Answer 6

Stooped posture
Facial masking
Forward tilt
Reduced arm swing
Shuffling gait

Question 7

Characteristics of tremor in Parkinsons?

Answer 7

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

Question 8

What is ‘cogwheel’ rigidity?

Answer 8

Resistance to passive movement of a joint
Tension will be felt and joint moves in small incriments

Question 9

What is bradykinesia?

Answer 9

Slower and smaller movements

Question 10

How might bradykinesia present?

Answer 10

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)

Question 11

What is hypomimia?

Answer 11

Reduce facial movements and expressions

Question 12

Features of Parkinsons Disease?

Answer 12

Resting tremor
Bradykinesia
Cogwheel rigidity
Depression
Sleep distrubance and insomnia
Loss of the sense of smell (anosmia)
Postural instability
Cognitive impairment and memory problems

Question 13

Parkinson’s Tremor vs Benign Essential Tremor - symmetry

Answer 13

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

Question 14

What is benign essential termor?

Answer 14

(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.

Question 15

What can worsen a benign essentiel tremmor?

Answer 15

Voluntary movement
Tiredness
Stress
Caffeine

Question 16

When would a benign essentiel termor always be absent?

Answer 16

Sleep

Question 17

Differentials for patients presenting with a tremor?

Answer 17

Benign essential tremor?
Parkinson’s disease
Multiple sclerosis
Huntington’s Chorea
Hyperthyroidism
Fever
Medications (e.g. antipsychotics)

Question 18

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?

Answer 18

Propranolol
Primidone

Question 19

What are Parkinson-plus syndromes?

Answer 19

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).

Question 20

Types of Parkinson’s-plus Syndromes?

Answer 20

Multiple System Atrophy
Dementia with Lewy Bodies
Progressive Supranuclear Palsy
Corticobasal Degeneration

Question 21

What is multiple system atrophy?

Answer 21

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

Question 22

Notable consequences of autonomic dysfunction?

Answer 22

Postural hypotension
Constipation
Abnormal sweating
Sexual dysfunction

Question 23

Notable consequence of cerebellar dysfunction?

Answer 23

Ataxia

Question 24

What is Dementia with Lewy Bodies?

Answer 24

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.

Question 25

How is Parkinson's diagnosed?

Answer 25

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.

Question 26

What do patients with Parkinson's mean when they describe themselves as 'on' and 'off'?

Answer 26

On: Medications are acting and they are moving freely Off: Medications have worn out, they have significant symptoms and their next dose is due

Question 27

What medications are used to manage Parkinson's?

Answer 27

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

Question 28

What is the classic neuro pathological finding in IPD?

Answer 28

Lewybody formation in the affected neurones

Question 29

Diagnostic criteria for IPD?

Answer 29

1. 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 2. Exclusion of other causes of Parkinsonism 3. 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

Question 30

Non motor signs and symptoms of Parkinson’s disease?

Answer 30

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

Question 31

Non oral therapies in Parkinson’s disease

Answer 31

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.

Question 32

Stages of IPD (idiopathic Parkinson’s disease)

Answer 32

1. Early stage - Soon after diagnosis, symptoms are mild and normal life possible 2. Maintenance stage - Good response to treatment and no major disability 3. Advanced stage - Poor response to drugs with motor side effects 4. Palliative stage - Unable to live independently and in need of multidisciplinary support

Question 33

Complications in advanced IPD?

Answer 33

Difficulty or swallowing Dementia Bladder and bowel incontinence Difficulty walking, talking, eating, dressing Falling Reduced mobility Hallucinations, dellusions

Question 34

Clinical features vascular parkinsonism?

Answer 34

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

Question 35

What is vascular pseudo-parkinsonism

Answer 35

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.

Question 36

Clinical features of lewy body dementia?

Answer 36

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

Question 37

What is drug induced parkinsonism and how does it present?

Answer 37

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

Question 38

What drugs might cause drug induce parkinsonism?

Answer 38

Antipsychotics Anitemetics Metoclopramide

Question 39

Treatment for drug induce parkinsonism?

Answer 39

tetrabenazine, reserpine, vitamin E, bezodiazepines

Question 40

Limb tone in Parkinson’s?

Answer 40

Hypertonia

Question 41

Limb tone in parkinsons?

Answer 41

Hypertonia

Question 42

What causes vascular parkinsonism?

Answer 42

Cerebrovascular disease

Question 43

Which Parkinsons medications are most commonly responsible for impulse control disorders?

Answer 43

Dopamine agonists

Question 44

What is 'wearing off' in terms of anti-Parkinsons therapy?

Answer 44

Symptoms (either motor or non-motor) returning before the next dose and relieved by taking anti-Parkinsons therapy

Question 45

What is 'peak dose dyskinesia' in terms of anti-Parkinsons therapy?

Answer 45

Dyskinesia which occurs around 30 mins after taking medication

Question 46

What does a pill rolling tremor indicate?

Answer 46

Young patients: Drug induced Parkinsonism Older patients: IPD

Question 47

Anatomy of the basal ganglia?

Answer 47

****

Question 48

When do symptoms begin in IPD in terms of the pathophysiolgical course?

Answer 48

50% of dopaminergic neurones in SN lost (local adaptations, increased cell turnover, upregulation of receptors) SN will appear loss of pigment on post mortem

Question 49

Parkinsons gait?

Answer 49

Forward flexed shuffling gait with asymmetric arm swing Loss of fluidity in turns

Question 50

Rigidity in Parkinsons?

Answer 50

Lead pipe rigidity is Cogwheel rigidity if tremor superimposed on rigidity

Question 51

How can you assess bradykinesia?

Answer 51

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

Question 52

Poor prognostic factors in IPD?

Answer 52

More rapid progression in those with older age and more severe motor impairment at onset Dementia within 20 years of onset

Question 53

Why does levodopa become less effective as IPD progresses?

Answer 53

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

Question 54

What is Sinemet?

Answer 54

Co-careldopa

Question 55

IDP - management

Answer 55

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)

Question 56

Role of deep brain stimulation in IPD

Answer 56

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

Question 57

Tremor features to ellicit from history?

Answer 57

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

Question 58

Extrapyrmaidal symptoms?

Answer 58

Parkinsons gait Bradykinesia Lead pipe ridigity 3-5 hx rolling pill tremor

Question 59

What should be added on when patients develop dyskinesia due to long term levodopa use?

Answer 59

NICE suggest that, in this situation, an oral catechol-O-methyl transferase (COMT) inhibitor like entacapone is given in combination with levodopa and carbidopa.

Question 60

What drugs should be avoided in Parkinsons disease?

Answer 60

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)

Question 61

Diplopia is not common in Parkinson's disease and may suggest an alternative cause of parkinsonism such as what?

Answer 61

progressive supranuclear palsy

Question 62

Progressive supranuclear palsy presentation

Answer 62

Progressive supranuclear palsy: postural instability, impairment of vertical gaze, parkinsonism, frontal lobe dysfunction

Question 63

What Parkinsons drug is associated with pulmonary fibrosis?

Answer 63

Cabergoline

Question 64

What do the results of a DaTSCAN tell us?

Answer 64

An abnormal DaTSCAN indicates pathology which is either: 1. Neurodegenerative (e.g. Parkinson’s disease or multiple systems atrophy) 2. Neurogenetic (e.g. spinocerebellar ataxia) 3. 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).