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Neurology > Patho- Neurodegeneration > Flashcards

Patho- Neurodegeneration Flashcards

1
Q

Give some examples of neurodegenerative diseases?

A

Parkinson’s Disease
MND
Spinal muscular atrophy
Dementia

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2
Q

What are the four main forms of dementia?

A

Alzheimer’s Disease
Dementia with Lewy Bodies
Vascular dementia
Pick’s disease

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3
Q

What are some general symptoms of dementia?

A

Loss of memory
Lack of emotional control
Loss of motivation
Changes in social behavior

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4
Q

What are the two forms of AD?

A

Late Onset AD (LOAD)

Early Onset AD (EOAD)

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5
Q

What genetics are EOAD inked with?

A

Autosomal dominant

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6
Q

What is the patho of AD?

A

Neuron loss

ACh transmission deficiency

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7
Q

What causes neuron loss in AD?

A

Ab/senile plaques

Tau/neurofibrillary tangles

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8
Q

What are some symptoms of AD?

A 
Gradual onset
Loss of ability to take in info and form new memories
Decline in language
Failure to recognise objects 
Impaired ability to carry out skilled motor activities 
Behavioral changes
Loss of insight
Depression
Secondary hydrocephalus
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9
Q

What kind of behavioural changes are seen in AD?

A

Agitation
Aggression
Wandering
Persecution delusions

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10
Q

How do you diagnose AD?

A

No test as such
Clinical
Psychometric tests
Rule out vascular dementia etc- History of hypertension suggests VD

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11
Q

What are some symptoms of dementia with Lewy bodies?

A

Progressive dementia
Daily fluctuations in consciousness
Less memory loss in early stages
Prominent loss of attention and visuospacal skills
Parkinsonism- Falls
Delusions
Very sensitive to haloperidol- causes Parkinsonism

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12
Q

Give some symptoms of vascular dementia

A

Stepwise progression
History of hypertension of AF or diabetes etc
Brisk reflexes
Up going plantar

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13
Q

How can vascular dementia present on CT?

A

Can show areas of damage

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14
Q

Describe Pick’s disease

A

Progressive dementia in midlife

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15
Q

What is the patho of Pick’s disease

A

Neuron loss
Neuronal swelling- Pick’s bodies
Astrocyte proliferation

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16
Q

What are some symptoms of Pick’s disease?

A 
Slow progressive changes in character- Impaired memory, intellect and language
Personality and behavioural change
Speech and communication problems 
Changes in eating habits
Lower attention span
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17
Q

What are some differentials of dementia?

A

Pseudodementia
Delirium
Learning difficulties

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18
Q

How do you treat dementia?

A

Treat underlying cause if possible

Support

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19
Q

What are some symptoms of spinal muscular atrophy?

A

Slow progressive symmetrical muscle wasting

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20
Q

What are the three forms of spinal muscular atrophy?

A

Acute infantile
Chronic childhood
Adult

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21
Q

What is the differential for spinal muscular atrophy?

A

Muscular dystrophies

MND

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22
Q

What is MND?

A

Degenerative disease of upper and lower MN

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23
Q

What is the patho of MND?

A

Progressive deterioration of lower and upper motor neurons in the spinal cord, in cranial nerve motor nuclei and within the cortex

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24
Q

What is the cause of MND?

A

Generally unknown

Maybe genetic- Rare familial form

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25
Q

What are the four forms of MND?

A

Amyotrophic lateral sclerosis (ALS)
Progressive bulbar palsy
Progressive muscular atrophy
Primary lateral sclerosis

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26
Q

What is the most common form of MND?

A

ALS

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27
Q

Describe ALS

A

Disease of lateral corticospinal tracts causing muscle atrophy

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28
Q

What are some symptoms of ALS?

A

Evolve over weeks to months
Muscle weakness and spacticity
No sensory loss

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29
Q

How do you diagnose ALS?

A

Neurophysiology (EMG with evidence of fasciculations)
MRI brain and spine to exclude alternative causes
CK to exclude myopathy
If confirmed – overnight pulse oximetry and ABG

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30
Q

How do you treat ALS?

A

No cure
Palliative
Riluzole (NMDA blocker and sodium channel blocker)

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31
Q

Describe progressive bulbar palsy

A

Involves lower cranial nerve nuclei

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32
Q

What are some symptoms of progressive bulbar palsy?

A 
Dysarthria
Dysphagia
Chocking
Nasal regurgitation
Wasting of tongue
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33
Q

What is the patho of progressive muscular atrophy?

A

Spontaneous firing of abnormally large motor units due to loss of other nerve fibres resulting in one nerve fibre taking over many muscle fibres.

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34
Q

What are some symptoms of progressive muscular atrophy?

A

Muscle wasting- Wasting beginning in the small muscles of hand
Fasciculation
Late sphincter control loss

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35
Q

What are some symptoms of primary lateral sclerosis?

A

Progressive tetraplegia

36
Q

What are some general symptoms of MND?

A

Any sensory signs rule out the diagnosis of MND
Eye movement unaffected in all
Consciousness preserved
Sometimes develop dementia

37
Q

How do you diagnose MND?

A

Clinical

EMG

38
Q

How do you treat MND?

A

No cure- Death in 3 years
Riluzole slows progress
Symptomatic treatment

39
Q

What symptomatic treatment can used for MND?

A

Baclofen for spacticity
Amitriptyline for drooling
Ventilation and feeding etc

40
Q

What is the pathology of Parkinson’s?

A 
Eosinophilic inclusion bodies (Lewy bodies) develop
Substantia nigra (in basal ganglia) undergoes progressive neuronal degeneration- Loss of dopamine
41
Q

What are some symptoms of Parkinson’s?

A 
Resting tremor- Pill rolling tremor
Rigidity
Bradykinesia- Delayed initiation of movement
Restlessness
Shuffling gait
Constipation
Loss of facial expression
Flexed back
Monotone then slurring
Cognitive changes- Depression
Brisk reflexes
42
Q

What symptom is not seen in Parkinson’s?

A

No power or sensory loss

43
Q

How do you treat Parkinson’s?

A

Clinical: Must have bradykinesis + tremor/disorder of posture balance or gait
Dopamine brain imaging
Symptoms improve with levodopa
Rule out Parkinsonism

44
Q

How do you rule out Parkinsonism?

A

Bloods for: TSH, Copper, U+E

CT for vascular

45
Q

What is the differential for Parkinson’s?

A

Parkinsonism

46
Q

What is Parkinsonism?

A

Symptoms of Parkinson’s without Lewy Bodies

47
Q

What can cause Parkinsonism?

A

Drug induced

Vascular

48
Q

What are some symptoms of drug induced Parkinsonism?

A

Symmetrical

Coarse postural tremor

49
Q

What are the symptoms of Parkinsonism?

A

Tremor, bradykinesia, rigidity, and postural instability

50
Q

What drugs can cause Parkinsonism?

A

Haloperidol

TCAs

51
Q

How do you treat drug induced Parkinsonism?

A

Stop offending drug

52
Q

What are some of the symptoms of vascular induced Parkinsonism?

A

Affects lower limb
No tremour
Poor levodopa response
Brain vascular lesions

53
Q

How do you treat Parkinson’s?

A

Dopamine agonists
Levodopa
MAO-B inhibitors
Symptom treatment

54
Q

Give an example of a dopamine agonist used in Parkinson’s?

A

Ropinerol

55
Q

What are some side effects of Ropinerol?

A

N+V
Postural hypotension
Confusion
Psychosis

56
Q

Why are dopamine agonists used before levodopa?

A

Less effective but less side effects

57
Q

What are some side effects of levodopa?

A

N+V
Postural hypotension
Confusion
Movement disorders- Freezing

58
Q

What should you always give with levodopa?

A

Aromatic amino acid decarboxylase inhibitor

59
Q

What does MOA-B do?

A

Break down dopamine

60
Q

WHen should you prescribe MOA-B inhibitor?

A

With levodopa

61
Q

Give an example of a MOA-B inhibitor?

A

Selegiline

62
Q

What are some side effects of MOA-B inhibitors?

A

Hypertension
AF
Sudden uncontrolled movements
Hallucinations

63
Q

What symptoms do you treat in Parkinson’s?

A

Tremour

64
Q

What treatment do you give for tremor in Parkinson’s?

A

Antimuscarinics and anticholinergics

65
Q

What protein is LOAD associated with?

A

ApoE

66
Q

What genes is EOAD associated with?

A

APP, PSEN1/2

67
Q

Physiologically what does ApoE do?

A

Forms a major part of VLDLP

68
Q

What are the three major forms of ApoE?

A

ApoE2
ApoE3
ApoE4

69
Q

Which form of ApoE is associated with AD?

A

ApoE4

70
Q

What is the benefit of ApoE2?

A

Protective from AD

71
Q

What is ApoE4 associated with in AD?

A 
More extensive plaques and tangles
Higher CSF concentrations of soluble Aβ
Impaired synaptic plasticity
Increased hypocampal atrophy
Reduced cerebral metabolism
More brain inflammation
72
Q

What is the relationship between ApoE and Abeta?

A

ApoE in VLDLP can uptake and remove Abeta

73
Q

What does ApoE4 in VLDLP cause?

A

Abeta uptake into neurons (toxic) instead of glial cells (protective)

74
Q

What does the APP gene code for?

A

Amyloid Precursor Protein

75
Q

What does APP do?

A

Cell adhesion and signalling

76
Q

What are the three main forms of APP?

A

APP695, APP751 and APP770

77
Q

What enzymes can first cleave APP extracellularly?

A

α-secretase (ADAM10/17) or β- secretases (BACE1/2)

78
Q

What happens to ADAM cleaved APP?

A

Non-amyloidogenic sAPPα and an 83 amino acid C-terminal domain (C83) are produced,

79
Q

What happens to BACE cleaved APP?

A

Amyloidogenic sAPPβ and a 99 amino acid C-terminal (C99) are produced

80
Q

What do the PSEN genes code for?

A

Presenilin

81
Q

What does presenilin do?

A

Forms part of y-secretase which cleaves the C-terminal end of APP

82
Q

What happens to C83 when cleaved by y-secretase?

A

Splits into P3 and APP intracellular domain (AICD).

83
Q

What happens to C99 when cleaved by y-secretase?

A

Splits into Abeta and APP intracellular domain (AICD).

84
Q

How does Abeta plaques and Tau tangles cause AD patho?

A

Increased inflammation
Decreased antioxidants
Calcium toxicity

85
Q

WHich drugs can help treat ACh loss in AD?

A

Donepezil- AChE blocker
Galantamine- AChE blocker
Rivastigmine- AChE- blocker

86
Q

What drug can be used to help treat Ca toxicity in AD?

A

Memantine- Blocks NMDAR

Neurology (30 decks)

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