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Parkinsonism Flashcards

1
Q

What is the definition of motor parkinsonism?

A

Motor Parkinsonism is a clinical syndrome characterized by Resting Tremor, Rigidity, Akinesia/Bradykinesia, Postural Instability.

Clinical Diagnosis is made when there is Bradykinesia + 1 of T/R/P

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2
Q

What are the causes of primary parkinsonism?

A

Neurogenerative causes

1) (Idiopathic) Parkinson’s Disease: Amenable to DA therapy as underlying patho is due to degeneration of substantia niagra causing DA deficiency in N-S pathway

2) Atypical Parkinsonian disorders
- Multiple System Atrophy (MSA): alpha-synuclein (in Lewy body) pathology affecting oligodendroglia
- Dementia with Lewy Bodies (DLB): alpha-synuclein (in Lewy body) pathology, concomitant onset of dementia and PD
- Progressive Supranuclear Palsy (PSP): Tau disorder
- Corticobasal Degeneration (CBD): Tau disorder

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3
Q

What is a rest tremor?

A

Occurs when body part is completely supported against gravity

e.g. hand resting on one’s lap or dangling freely without working

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4
Q

What is a postural tremor?

A

occurs when voluntarily maintained against gravity

e.g. hand extended out in from of the body

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5
Q

What is a kinetic tremor?

A

occurs when voluntary movement is made e.g. while drinking from a cup

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6
Q

What is an intention tremor?

A

tremor has increased amplitude at the end of a goal directed movement e.g. when performing finger to nose testing

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7
Q

What is a task specific tremor?

A

Occurs only during specific activities or postures

e.g. while writing (at primary writing tremor)

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8
Q

What is an isometric tremor?

A

Results when muscle contraction occurs a rigid object e.g. while making a fist.

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9
Q

Motor symptoms of parkinsonism: Resting, Pill Rolling Tremor (4-6Hz)

  • Typically, most pronounced in hands, ____________, worse at rest; pill rolling
  • Exacerbated by _________________
  • Cog-wheeling 🡪 when times tremor freq correlates w cogwheeling

DDX: ________________– not associated with hypokinesia or rigidity; improves with alcohol, kinetic tremor 🡪 hence worsens with movement or postural change. Usually affects hands

A

unilateral;

mild stress e.g. mental calculations, counting backwards;

Essential tremor

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10
Q

Motor symptoms of parkinsonism: Rigidity

  • Felt as muscle tension or spasm.
  • Described as ____________
  • Velocity Independent
  • Throughout _______________
  • Bidirectional
A

lead-pipe rigidity;

range of movement

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11
Q

Motor symptoms of parkinsonism: Akinesia/ Bradykinesia

  • Difficulty __________ or maintaining repetitive movements?
  • Progression or improvement (if on treatment)

This in turn causes:

  • Changes in _________: Difficulty terminating and turning
  • ____________: Mask like facies
  • ____________: speaking softer
  • : ______________ Monotony in pitch
  • _______________: changes in handwriting
  • hoarse
  • difficulty swallowings
  • In early PD we have ________________ instead of BRADYkinesia 🡪 patient will have smaller rather than slower movements 🡪 important to ask patient to exaggerate movements during the tests!
A

initiating

gait (shuffling);

Hypomimia;

Hypophonia

Dysarthrophonia

Micrographia

HYPOkinesia

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12
Q

Motor symptoms of parkinsonism: Postural Instability

What do you ask in the history?

A

Any falls? (what happened during the fall)

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13
Q

What are the non motor symptoms of parkinsonism?

*Non motor symptoms such as olfactory dysfunction, autonomic dysfunction tend to occur way before onset of TRAP 🡪 hence impt to assess in Hx

A

Hyposmia (reduce ability to smell/detect odours)

Autonomic disturbance (constipation, diarrhoea, weight loss, bladder dysfunction, erectile dysfunction, orthostatic HypoTN)

Neuropsychiatric symptoms (hallucinations, agitation, apathy, anxiety, delusions, irritability, disinhibition)

Memory deficits

  • PD is a/w development of dementia
  • This is b/c of the spread of α-synuclein in Lewy bodies to the rest of the brain
  • To differentiate from LBD

Depression / low mood

Seborrheic dermatitis

Sleep disorder – REM sleep disorders such as acting up or shouting during sleep

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14
Q

What is the drug history to ask for in a patients with parkinsonism?

A

Antipsychotics (esp 1st gen, high potency eg: Haloperidol), antidepressant, anti-emetics (DA Antagonists) use

Treatment of PD

  • Which drugs? Compliance?
  • Are they effective?
  • Adverse effects?
  • Motor fluctuations / dyskinesias?
  • Neuropsychiatric effects?
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15
Q

What is the Hehn and Yahr staging of Parkinson’s disease?

A

1) Symptoms on one side of body
2) Bilateral symptoms, no balance impairment
3) Impaired postural reflexes, physically independent
4) Severe disability, yet able to walk or stand unassisted
5) Wheelchair bound or bedridden

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16
Q

What are features suggestive of Parkinson Plus syndromes (features appearing too early)?

A

Bilateral involvement early on!

Early cognitive impairment (eg: early dementia) < 1 year 🡪 think Lewy Body Dementia, normal pressure hydrocephalus

Early hallucinations <3 years 🡪 DLB

Early significant postural instability causing multiple falls 🡪 think PSP, CBD, NPH, MSA

Early freezing/ gait disorder 🡪 MSA, PSP

Early autonomic dysfunction 🡪 MSA

Early dysphagia 🡪 MSA

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17
Q

What are features suggestive of Parkinson Plus syndromes (features that are absent)?

A
  • No resting tremor
  • No asymmetry
  • No response to levodopa
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18
Q

What are features suggestive of Parkinson Plus syndromes (features that are typical of other Parkinsonian disorders )?

A

Saccadic slowing 🡪 PSP, CBD

Limb apraxia 🡪 CBD

Cerebellar/ pyramidal signs 🡪 MSA, PSP

Myoclonus 🡪 MSA, CBD

Stridor 🡪 MSA

Rapid progression (wheelchair sign) 🡪 MSA, PSP

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19
Q

Progressive & supranuclear palsy

  • Progressive sporadic disease
  • Neuropathology: accumulation of ____________________
  • HTR: Postural instability & Supranuclear (gaze) Palsy 🡪 PSP

Looks like a PISSED OFF BUGGER looking at you, and just LOOK OFF!

  • Classically described as a _________________
  • When looking at you, the whole body turns because of rigidity!
  • And they classically __________ a lot
  • They are more ___________, as though wearing a neck brace
  • Also some _______________!

Very prone to falls because

  • Axial rigidity
  • ______________: not super scared of falling like PD patient. After all PD is a/w FTLD

_________________ – hummingbird sign, mickey mouse sign, morning glory

A

hyper-phosphorylated tau protein;

STARING facies with minimal movement of eyes;

FROWN;

AXIALLY RIGID

FRONTAL lobe disinhibition;

Motor impulsiveness and disinhibition;

Midbrain atrophy

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20
Q

What are the features of supranuclear gaze palsy?

A

Postural instability & Supranuclear (gaze) Palsy 🡪 PSP

Supranuclear gaze palsy (but VOR intact), specifically Vertical gaze palsy, first affecting vertical SACCADES

  • Slowing before limitation
  • Saccades before pursuit
  • Vertical before horizontal
  • Down before up

Postural instability with frequent falls – can have cerebellar dysfunction

Parkinsonism: symmetrical; rigidity predominantly axial (poor response to L-DOPA)

Behavioural changes from frontal cognitive abnormalities

Pseudobulbar palsy (dysarthria, dysphagia, uncontrollable laughing and crying)

21
Q

Multi-System Atrophy

  • Progressive, sporadic neurodegenerative disease
  • ________________ + parkinsonism (MSA-P) or ________________ (MSA-C)
  • Onset usually in 6th decade
  • Neuropathology: ______________ inclusions
  • How To Remember: Mimics PD but with, Spinocerebellar, Autonomic 🡪 MSA

MSA-P = when parkinsonism is predominant

  • ____________involvement, rather than pontocerebellar tract (like in MSA-C)
  • Also severe autonomic dysfunction
  • Predominant parkinsonism signs because of ____________ mainly

MSA-C = when cerebellar signs are predominant

  • ____________________ over the Pons on an axial projection
  • The lesion (where the hot cross bun sign is) lies very near ____________________ 🡪 hence SEVERE cerebellar dysfunction, Some autonomic dysfunction, and MILD Parkinsonism
  • Due to degeneration of mainly pontocerebellar tract
A

Autonomic dysfunction (bladder, bowel, orthostatic hypotension, syncope);

cerebellar symptoms

cytoplasmic alpha-synuclein positive

Putamen (in BG) ;

basal ganglia involvement;

Hot Cross Buns / Cruciform shaped T2 hyperintensity;

pontocerebellar tract and the midline raphe nuclei w/ autonomic tract

22
Q

What is the features of Multi System Atrophy?

A
  • Autonomic dysfunction: orthostatic hypotension, hypohydrosis, constipation, urge incontinence, urinary retention, erectile dysfunction
  • Motor symptoms: akinesia, rigidity, postural instability (poorly responsive to L-DOPA); rigidity > tremor
  • Cerebellar signs: ataxia, dysarthria, dysmetria, nystagmus, dysdiadochokinesia
  • Corticospinal dysfunction: Positive Babinski’s, hyperreflexia
23
Q

What are the features of Lewy Body Dementia?

A

Triad of: Fluctuating cognition, visual hallucinations, parkinsonism

May also exhibit REM sleep disorder

Spontaneous motor features of parkinsonism concomitant w/ onset of dementia

Dementia is EARLY and PREDOMINANT

24
Q

Corticobasal Degeneration

  • Sporadic progressive neurodegenerative disease of slow onset
  • ____________ atrophy + ___________ degeneration
  • Age > 60
  • How to remember: __________, ______, __________due to Basal Ganglia Involvement 🡪 CBD
A

Frontoparietal cortical;

extrapyramidal;

Chorea, Bradykinesia, Discrete jerks (myoclonus)

25
Q

What are the features of Corticobasal Degeneration?

A

Limb Apraxia: Alien limb phenomenon

  • Causing little or no control, appears to move on its own; may manifest as chorea / discrete jerks
  • If mild, some may describe difficulty using the limb / hand
  • If severe, pt does not recognise the limb as theirs

Sensory Neglect – perform line bisection test

Ideo-motor apraxia: ask patient to button shirt, mimic combing hair — important to just give verbal command and not give visual cues (test one hand at a time)

Parkinsonism: Asymmetric or focal akinetic rigidity, bradykinesia, tremor, dystonia

Cortical sensory loss (astereognosis, graphanesthesia)

Executive dysfunction, apraxia

26
Q

Vascular Parkinsonism
- Due to lacunar infarcts of basal ganglia or multiple lacunar infarcts in white matter

Features:

  • ________________ patient: risk factors for Lacunar Infarcts
  • Pyramidal signs (mainly ________)
  • Gait problems with no ________ typical of PD
A

Diabetic or hypertensive;

lower limb;

festination

27
Q

What are the causes of secondary parkinsonism?

A

Drugs

  • Antipsychotics (Chlorpromazine, haloperidol, Trifluoperazine, prochlorperazine),
  • metoclopramide

Toxins (carbon disulphide, carbon monoxide, cyanide, MPTP, manganese, organic solvents)

Post-traumatic injury

Infection (Post-encephalitis, Creutzfeld-Jakob Disease)

Structural brain lesions affecting striato-nigral circuits (eg. Normal Pressure Hydrocephalus)

Metabolic (Wilson’s disease, hypoparathyroidism, pseudohypoprathyroidism)

Cerebrovascular disease

28
Q

What are the features of normal pressure hydrocephalus (NPH)?

A

NPH: has a triad of Apraxia/ magnetic gait (difficulty initiating), urinary incontinence and dementia/ cognitive dysfunction

29
Q

What are examples of L- DOPA + peripheral decarboxylase inhibitor?

A

Madopar (Levodopa + Benserazide)

Sinemet (Levodopa + Carbidopa)

30
Q

What are the indications of L- DOPA + peripheral decarboxylase inhibitor?

A

All stages of disease - most effective symptomatic therapy

However, highest risk of dyskinesia hence generally reserved for older patients (>65yo) unless akinetic symptoms severely threatening QOL

31
Q

What are the side effects of L- DOPA + peripheral decarboxylase inhibitor?

A

N&V (Mx w/ Domperidone a Peripheral D2R antagonist): ↑ DA on peripheral DA-R🡪 triggers chemotactic trigger zone 🡪 N&V

Orthostatic hypotension

Dyskinesia (dose dep) (>6Y): On-off phenomenon due to dopaminergic modulation; usually after >6Y of therapy: rapid fluctuations in clinical state, ‘off period’ where symptoms = resurface may last from minutes to hours; patient is immobilised and feels “locked in”

Psychosis, visual hallucinations, impulsive
- After all, antipsychotics causes parkinsonism whereas PD Mx can cause psychosis

Do NOT stop abruptly 🡪 HypoDa state 🡪 ppt NMS

32
Q

What are the examples of dopamine agonists?

A

Ergot (1st gen): Bromocriptine, pergolide (now withdrawn)

Non-ergot (2nd gen): Ropinerol, Pramipexole, Rotigotine (patch)

33
Q

What are the indications for dopamine agonists?

A

Monotherapy in early PD in young pt (to delay need to start L-DOPA) or combined treatment in all stages

  • Weaker than L-DOPA
  • ↓ motor fluctuations (on-off) & Dyskinesia

Effectiveness of Dopa-Agonist is INDEPENDENT on DA neurons -> effect does NOT dec w time

Preferred in younger pt <65YO

34
Q

What are the side effects of dopamine agonists?

A

N&V

Somnelence

Psychosis, visual hallucinations, impulsive

Fibrosis (a/w ergot DA – pleuro-pulmonary, retroperitoneal, heart valves)

Impulse control disorders (a/w 2nd gen DA) -> addictive behaviours: gambling, sex, compulsive disorders

Do NOT stop abruptly 🡪 HypoDa state 🡪 ppt NMS

35
Q

What are examples of COMT inhibitors?

A

Entacapone
Tolcapone

*Tolcapone is no longer used in clinics. Only one we have now is peripheral: Entacapone

36
Q

What are the indications for COMT inhibitors?

A

Ineffective alone (hence no MonoTx), used as adjunct

Used to ↓ L-DOPA dose 🡪 ↓ S/E (esp motor fluctuations & on-off symptoms)

37
Q

What are the S/Es of COMT inhibitors?

A

N&V (Mx w/ Domperidone – Peripheral D2R antagonist): ↑ DA on peripheral DA-R🡪 triggers chemotactic trigger zone 🡪 N&V

Dyskinesia (dose dep); >6Y

Psychosis, visual hallucinations, impulsive

Less On-Off Oscillations

Dark urine

Diarrhoea

Hepatotoxic (Tolcapone)

C/I in pt with CV problems

38
Q

What are examples of MAOB inhibitors?

A

Rasagiline (neuroprotective)

Selegiline

39
Q

What are the indications for MAOB inhibitors?

A

Monotherapy in early disease to preserve natural DA being produced
- Mild symptomatic benefit

Can be used to ↓ L-DOPA dose 🡪 ↓ S/E (esp on-off symptoms)

40
Q

What are the S/Es of MAOB inhibitors?

A
  • Postural hypotension
  • Atrial fibrillation
  • Selegiline causes confusion in elderly (avoid in late onset PD)
  • Sertonin syndrome
41
Q

What are the indications for the use of Amantadine?

A

Monotherapy in early disease

Effective against L-DOPA dyskinesia

LAST LINE – because tolerance develops

42
Q

What are the complications of Amantadine?

A

Cognitive impairment (avoid in elderly)

Livedo reticularis

43
Q

What are examples of anticholinergics?

A

Benztropine, trihexyphenidyl, procyclidine, biperiden

44
Q

What are the indications for anticholinergics?

A

For young patients (<60) in whom tremor is the main problem

45
Q

What are the side effects of anticholinergics?

A

Cognitive impairment (avoid in elderly)

Constipation

Glaucoma

Urinary dysfunction

Dry mouth

46
Q

What is the indication for deep brain stimulation (targets subthalamic nucleus)

A

Medically untreatable or drug resistant symptoms or complications e.g. Marked dyskinesia, on-off periods, marked tremor

47
Q

!! Parkinsonism-Hyperpyrexia syndrome

  • Certain PD patients may develop neuroleptic malignant syndrome upon sudden withdrawal or dose reductions of Levodopa or DA, or switching from one drug to another.
  • Management involves _________________________
A

replacing the anti-PD drug at the dose that was used prior to the onset of the syndrome + admission for intensive care as well as monitoring for potential dysautonomia and other complications

48
Q

Parkinson Treatment PEARLS

For Total Effective Treatment

  • Younger patients: start ____________🡪 less on-off symptoms and dyskinesia
  • Older Patients: start _________ (stronger but more S/E)

For Mild Symptoms / no need for full functional return: ________________

For pt on L-DOPA with worsening symptoms: ____________________

For pt on L-DOPA with S/E of dyskinesia or on-off oscillation
- _____________________, add on MAOB-I or COMT
If S/E against MAOB-I or COMT-I
- Consider other drugs such as ____________________

A

Dopamine Agonist ;

L-DOPA;

Monotherapy with MAOB-I;

Increase L-DOPA dose OR Add on MAOB-I or COMT-I

Reduce L-DOPA dose;

Amantadine, Anticholinergics (mainly used for tremors)

Neuro (13 decks)

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