Parkinson's Disease

Question 1

Describe the pathophysiology of parkinson disease:

• where do changes occur?
• What process occurs?
• How does degeneration occur?
• progression?

Answer 1

-Pathology of the basal ganglia

-Degeneration of the dopamine producing neurones in substance nigra.
These neurones project to the corpus striatum via the nigrostratial pathway.
The consequence of the loss of these neurones is the dopamine deficiency in the corpus striatum.
noradrenaline and 5HT producing neurones are also affected- increased incidence of depression.

-lewy bodies form around neurones
Misfolded alpha-synuclein (Lewy neurites) of neurons. Lewy body pathology is not limited to the brain but also present in spinal cord and peripheral NS.

-differes widely between individuals, few years to decades
worsening motor features which initially respond well to symptomatic therapies
complications of these therapies then emerge (motor/ non-motor fluctuations, dyskinesia and psychosis)
in late stage get resistant motor symptoms

Question 2

What are the clinical features?

• motor (6)
• non-motor (7)

Answer 2

-Resting tremor (pill rolling)
Muscular rigidity (cog wheel & led pipe)
Bradykinesia (reduced blinking, lack of facial expression, reduced arm swing)
gait impairment (festinating gait, freeze in doorways)
postural impairment

-olfactory dysfunction
cognitive impairment 
psychiatric symptoms
sleep disorders
autonomic dysfunction
pain and fatigue 
often onset of these before other motor symptoms

Question 3

Rapid eye movement sleep behaviour disorder

• definition?
• how is it Dx?
• treatment?
• implications in PD?

Answer 3

• parasomnia characterised by abnormal or disruptive behaviours occurring during REM sleep
• overnight polysomnography to document REM sleep without atonia
• clonazepam/melatonin
• more severe autonomic dysfunction /gait impairment/dementia

Question 4

Risk factors for the development of PD? (3)

• genetic factors? (4)
• protective factors?

Answer 4

-age- over 60s
genetic predisposition
being male

-SNCA (encodes alpha synuclein)
LRRK2 (dominant)
parkin (recessive)
GBA mutations

-smoking, coffee, NSAIDs
CCB, alcohol

Question 5

Treatment of PD

• names and examples?
• effect?
• when initiated?
• for tremor?

Answer 5

-levadopa
(converted into dopamine by dopa-decarboxylase.)

dopamine agonists 
(cabergoline, pergolide)

monoamine oxydase type B inhibitors
(selegeline)

amantadine

• enhance intracerebral dopamine conc or stimulate dopamine receptors
• When symptoms cause disability or discomfort to improve QOL.
• anticholinergics, trhexyphenidyl or clozapine

Question 6

Treatment induced adverse reactions

• dopamine agonists & levodopa?
• just DAs?
• just levodopa?

Answer 6

-nausea, daytime somnolence and oedema
impulse control disorders

• hallucinations
• motor complications e.g. dyskinesia (involuntary chloroform or dystonic movement when levodopa at max) & motor fluctuations

Question 7

• How are the following complications of treatment managed:
• motor fluctuations & dyskinesias? (5)
• psychosis? (2)
• visual hallucinations? (1)
• Depression? (9)
• Late stage dementia? (1)
• surgical treatment?

Answer 7

-add dopamine agonist (Apomorphine, Cabergoline)
MAO B inhibitor (rasagiline)
Catechol-O-methyltransferase inhibitor (COMT inhibitor) (Entacapone)
amantadine and clozapine

• clozapine or quetiapine
• rivastigimine

-antidepressants
TCAs: desipramine and nortriptyline
SSRIs: Citalopram, escitalopram, fluoxetine, paroxetine, and sertraline
+ venlafaxine

• rivastigmine
• deep brain stimulation

Question 8

Bradykinesia

• definition?
• how is this assessed?
• clinical signs? (3)

Answer 8

• slowness of movement with progressive loss or amplitude/speed during attempted rapid alternating movement
• open/closing hand, foot tapping

-Hypomimia
Hypophonia
Micrographia

Question 9

Resting Tremor
-definition?
-features?
(4)

Answer 9

-rhythmic oscillatory involuntary movement if the affected body part at rest

-Vanishes with active movement
reappears after few sec when arms outstretched
low-mid range frequency
Pill rolling type

Question 10

Rigidity

• definition?
• features? (2)
• types?

Answer 10

• in muscle tone felt by examination by passive movement
• resistance felt through full ROM and no increase with higher mobilising speed
• Cog wheel and lead pipe

Question 11

Postural & gait impairment

• appearance?
• gait characteristics?
• asses?

Answer 11

-stooped posture (impaired postural reflexes)
Camptocormia

-slow, short, shuffling steps
decreased arm swing 
slow turning, small steps
freezing 
festination 

-observe walking and pull test

Question 12

Investigations in PD? (2)

Answer 12

rule out treatable conditions of asthenia (hypothyroid, anaemia)
Positive levodopa challenge

Question 13

Red flags that would make PD less likely as a diagnosis are? (12)

Answer 13

– Absence of asymmetry of symptoms
– Severe axial or lower limb involvement
– Frequent falls
– Fast disease progression
– Eye movement disorder (supranuclear palsy, dysmetric or slow saccades) – Other unexpected movement disorder, such as tics, myoclonus, chorea – Pyramidal or cerebellar dysfunction
– Bulbar or pseudobulbar features
– Parietal associative sensory disturbances
– Apraxia
– Severe cognitive deterioration or psychosis
– Marked autonomic dysfunction
– Negative levodopa challenge

Question 14

Vascular parkinsonism:

• what is it?
• features? (5)

Answer 14

-parkinsonian symptoms produced by one or more small strokes

-predominantly lower lomb involvement
Rest tremor is uncommon
Other signs of brian vascular lesions
poor levodopa response

Question 15

Drug induced parkinsonism:

• what is it?
• features? (5)

Answer 15

-parkinsonian symptoms due to effect of a drug, normally dopamine antagonists

-symmetrical parkinsonism
often coarse postural tremor
other drug induced disorders e.g. orolingual dyskinesias
resolution after drug withdrawal

Question 16

Tremor disorders

• what tremor is often confused with PD?
• how can it be distinguished?

Answer 16

-essential tremor

-symmetrical, postural or kinetic tremor with higher frequency
not often seen at rest
often autosomal dominant inheritance with mean onset of 15 yrs
Alcohol responsiveness
head tremor, will be mild

Question 17

Multi system atrophy

• what is it?
• age of onset?
• core triad?
• features? (4)
• MRI? (2)

Answer 17

• Multiple system atrophy (MSA) is a rare neurodegenerative disorder, caused by cell loss in certain areas of the brain and the spinal cord, leading to a variety of symptoms affecting especially the functions of the autonomic nervous system and the motor system. These are characterised by Parkinsonian features of varying severity, cerebellar ataxia and autonomic (particularly urogenital) dysfunction. There may also be some corticospinal features.
• 6th/7th decade
• Dysautonomia, cerebellar features, parkinsonism

-Jerky postural tremor 
pyramidal signs 
(hyperreflexia & + Babinski)
sub optimal levodopa response 
severe dysarthria, dysphonia etc

-cerebellar and pontine atrophy “hot cross bun sign”

Question 18

Progressive supra nuclear palsy

• what is it?
• features? (9)

Answer 18

-Symmetric akinetic rigid syndrome with predominantly axial involvement

-Gait and balance impairment 
tremor not normally seen
vertical gaze supra nuclear palsy 
pseudo bulbar symptoms 
Retrocollis
Continuous activity of the frontalis muscle 
cognitive deficits
no response to Levadopa

Question 19

Fragile X-tremor ataxia syndrome

• onset?
• what is it?
• symptoms? (6)
• features? (3)
• MRI?

Answer 19

• > 50 yrs
• neurodegenerative disorder in patients with abnormal no. of CGG repeats in the FMR1 gene

-ataxia
postural/intention tremor
parkinsonism 
dysautonomia 
cognitive decline
peripheral neuropathy 

-slwo progression
X linked inheritance
confirm by molecular testing

-MCP sign