Neurology Flashcards
1
Q
What is dementia?
A
Not a disease, but a general term for the impaired ability to remember, think or make decisions that impacts everyday activities
An acquired, progressive cognitive impairment involving one or more cognitive functions
2
Q
What is Alzheimer’s disease?
A
A neurodegenerative disease that leads to the symptoms characteristic of dementia
3
Q
What does Amyloid Precursor Protein do?
A
Help the growth and repair of the neuron
4
Q
What is the pathophysiology of plaques in Alzheimer’s?
A
Amyloid Precursor Protein should be broken down by alpha and gamma secretase.
If it is broken down by beta and gamma secretase it creates insoluble amyloid beta. This is sticky and creates plaques just outside the neurons.
5
Q
How do plaques affect brain function?
A
- Plaques can get between neurons which can affect neuron signalling
- They can also trigger an immune response which can cause inflammation damage neurons
- They can also deposit on blood vessels (amyloid angiopathy) increased risk of rupture
6
Q
What is the pathophysiology of tangles in Alzheimer’s?
A
Tau protein in microtubules triggers kinase to attach phosphate to tau protein
Tau protein changes shape and stops supporting microtubules. Joins together to make neurofibrillary tangles.
Cells can’t signal as well and undergo apoptosis.
7
Q
What happens as neurons die in the brain?
A
Gyri get narrower and sulci widen
Ventricles get larger
8
Q
What percent of Alzheimer’s is sporadic?
A
90-95%
9
Q
What is sporadic Alzheimer’s?
A
Genetic and Environmental risk factors
Apolipoprotein E ^ risk
10
Q
What percent of Alzheimer’s is familial (early onset)?
A
5-10%
11
Q
What is familial / early onset Alzheimer’s?
A
Dominant gene speeds progression
PSEN-1 or PSEN-2 genes
12
Q
What is the effect of PSEN-1 or PSEN-2 mutation?
A
These genes affect gamma secretase, so APP is broken down in a way that encourages plaques
13
Q
What is a risk factor for early onset Alzheimer’s?
A
Trisomy 21 - the gene responsible for producing APP is located on chromosome 21
14
Q
How does Alzheimer’s progress?
A
Gradual progression as plaques and tangles build up
15
Q
What are the symptoms of Alzheimer’s?
A
Loss of short term memory
Loss of language and motor skills
Loss of long term memory
Disorientation
Bed-ridden
16
Q
How can Alzheimer’s be diagnosed?
A
Memory and cognitive assessments
History / changes in behaviour
Imaging
17
Q
What is the management of Alzheimer’s?
A
Rivastigmine - cholinesterase inhibitor
Supportive treatments and care
18
Q
What is vascular dementia?
A
Progressive loss of brain function caused by long term poor blood flow to the brain (typically because of a series of strokes)
19
Q
What is the pathophysiology of vascular dementia?
A
- Cerebral artery atherosclerosis
- Carotid artery / heart embolization
- Chronic hypertension -cerebral arterioles sclerosis
- Vasculitis
20
Q
What are some risk factors for vascular dementia?
A
Smoking
HTN
Diabetes
Hyperlipidaemia
Hyperhomocysteinaemia
21
Q
What are the features of vascular dementia?
A
Progressive, STEPWISE, cognitive function impairment (affected cortical area dependant)
22
Q
What symptoms might a person with vascular dementia of the frontal lobe experience?
A
Executive dysfunction
23
Q
What symptoms might a person with vascular dementia of the left parietal lobe experience?
A
Aphasia
Apraxia
Agnosia
24
Q
What is apraxia?
A
Inability to perform movements or tasks, even when they are understood
25
What is agnosia?
Unable to recognize and identify objects, persons, or sounds using one or more of their senses despite otherwise normally functioning senses
26
What symptoms might a person with vascular dementia of the right parietal lobe experience?
Hemineglect
Confusion
Agitation
Visuospatial difficulty
Constructional difficulty
27
What symptoms might a person with vascular dementia of the temporal lobe experience?
Anterograde amnesia (can't form new memories)
28
What deficits due to subcortical infarcts might be experienced in vascular dementia?
1. Focal motor signs
2. Gait disturbance
3. Urinary frequency / urgency
4. Personality / mood change
29
How can vascular dementia be diangosed?
1. Neuropsychological testing to detect cognitive impairment and domains involved
2. MRI/CT will show multiple cortical, subcortical infarcts
30
What is the management for vascular dementia?
No cure, so treatment is vascular risk factor control to try and prevent further infarcts
Cholinesterase inhibitors
31
Name some drugs that can be given as vascular risk factor conttrol
1. Antihypertensives
2. Anti diabetic agents
3. Statins
4. Antiplatelet agents
32
What is Lewy Body dementia?
A neurodegenerative disease characterised by the presence of Lewy bodies (abnormal deposits of a protein called alpha-synuclein)
33
What are some features of LBD?
Progressive, fluctuating cognitive function impairment
Attention, executive, visuospatial functions. Memory affected later
Visual hallucination
34
What can happen in the later stage of LBD?
Motor symptoms mimic Parkinson's disease
35
What are some other clinical features of LBD?
1. REM sleep behaviour disorder and other sleep disturbances
2. Autonomic dysfunction (syncope, urinary incontinence, postural drop)
3. Falls (Parkinsonism)
4. Neuroleptic sensitivity
36
How can LBD be diagnosed?
Exclude other dementia causes
Neuropsychological testing
DaTSCAN to show dopamine perfusion
37
What is the treatment for LBD?
No cure, medications to alleviate symptoms
38
How can Acetylcholinesterase inhibitors help in the treatment of LBD?
Reduce cognitive symptoms
39
How can dopamine analogues help motor symptoms in LBD?
Reduce motor symptoms
40
How can atypical neuroleptic agents help in the treatment of LBD?
Reduce psychotic features and persistent disabling hallucinations
41
Name three cholinesterase inhibitors
Donepezil
Rivastigmine Galantamine
42
Name two atypical antipsychotics that can be used in LBD treatment
Quetiapine
Clozapine
43
What is frontotemporal dementia?
Neurodegenerative condition of the frontal and temporal lobes of the brain
44
What is Pick disease?
A subset of FTD, characterised by the presence of Pick bodies (tangles of tau protein)
45
What is the pathophysiology of FTD?
Tau protein hyperphosphorylation causes tangles of Tau proteins
Intracellular inclusions of Tau proteins causes loss of function or apoptosis
Brain atrophy
46
What is the difference between Pick bodies and neurofibrillary tangles?
Pick bodies - 3R Tau isoforms only
Neurofibrillary tangles - 3R and 4R Tau isoforms
47
What is the behavioural variant of FTD?
Frontal lobe atrophy - personality and behaviour changes
48
What is semantic variant primary progressive aphasia in FTD?
Difficulty finding the right words
49
What is nonfluent variant primary progressive aphasia?
Difficulty speaking while knowing the meanings of individual words
50
How can FTD be diagnosed?
Brain imaging - frontal/temporal atrophy and brain enlargement
Mental status scale assessments
51
How can FTD be treated?
No cure, symptom management
Antidepressants for severe behavioural symptoms
Antipsychotics can have significant side effects and no convincing evidence of benefit from cholinesterase inhibitors
52
Features of PICK disease
Progressive degeneration of neurons
Intracytoplasmic Pick bodies
Cortical atrophy
Knife edge gyri
53
What is the biggest risk factor for all forms of dementia?
Increasing age
54
Causes of dementia
Diabetes
Ethanol
Medication
Environmental (CO poisoning)
Nutritional
Trauma
Infection
Alzheimer's
55
What isthe prevalence of different causes of dementia?
Alzheimer's 60%
Vascular 15%
Mixed 10%
Lewy Body 10%
FTD 2%
PD 2%
Other 1%
56
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57
What is Parkinson's disease?
A neurodegenerative disorder of the dopaminergic neurons in the substantia nigra
58
What is the basal ganglia?
A collection of brain regions that help to initiate and control movement through their connection to the motor cortex
59
What are the two parts of the substantia nigra?
Pars reticulata and Pars compacta
60
What does the Pars reticulata do?
Receive signals from the striatum (caudate nucleus and putamen)
Relay messages to the thalamus via neurons rich in the neurotransmitter GABA
61
What is the function of the Pars compacta?
Relays messages to the striatum via neurons rich in the neurotransmitter dopamine
Helps to stimulate the cerebral cortex and initiate and fine tune movement
62
What part of the substantia nigra is affected in Parkinson's?
The pars compacta
63
What are the hallmarks of Parkinson's?
1. Resting tremor (70%)
2. Bradykinesia, Hypokinesia or Akinesia
3. Rigidity
4. Postural Instability
64
What sort of tremor occurs in Parkinson's?
Resting tremor that diminishes with intentional movement
"Pill-rolling tremor"
65
What rigidity occurs in Parkinson's?
Stiffness that can appear as cogwheel rigidity that has catches or stalls as a persons arms and legs are moved passively
66
What are some other physical symptoms of Parkinson's?
Hypomimia
Reduced arm swing
Micrographia
Dystonic cramp
Gait distrubance
67
What are some non-motor symptoms of Parkinson's?
1. Depression / Low mood
2. Dementia
3. Sleep problems
4. Anosmia
5. Impulse control behaviours
6. Daytime sleepiness
7. Autonomic symptoms (constipation, postural drop, urinary incontinence)
68
What are some pre-symptomatic warning signs of Parkinson's?
REM sleep behaviour disturbance can be a PC 20 years before motor symptoms
69
How can you differentiate between Parkinson's and cerebellar disease?
Cerebellar disease gives an intention tremor
70
How can you differentiate between Parkinson's and diseases of the motor cortex or corticospinal pathway?
Parkinson's does not cause weakness!!! Normal power, reflex, sensation
71
What is the management for Parkinson's?
Medication to help with symptoms (but none stop neurodegeneration)
72
What is the first line treatment for Parkinson's?
Levodopa, which is usually given with a dopa decarboxylase inhibitor
Co-beneldopa or Co-careldopa
73
Why do we give the precursor Levodopa and not just dopamine?
Dopamine can't cross the blood brain barrier
74
What is the purpose of a dopa decarboxylase inhbitor?
Dopa decarboxylase converts levodopa to dopamine. It is found centrally and peripherally. The dopa decarboxylase inhibitor stops peripheral conversion and cannot cross the blood brain barrier
75
What is Stavelo?
Co-careldopa and entacapone (COMT inhibitor, prevents breakdown of levodopa in the brain and periphery)
76
What is Amantidine?
An antiviral medication that increases dopamine production. Helps with dyskinesia
77
What are dopamine agonists?
Drugs that stimulate dopamine receptors to trick the brain into thinking there is more dopamine than there really is
78
Name an ergot derivative dopamine agonist
Bromocriptine
79
Name three non-ergot derivative dopamine agonists?
Ropinirole
Pramipexole
Rotigotine
80
What are the advantages of dopamine agonists over levodopa?
1. Less dyskinesia
2. Longer acting
81
What are the disadvantages of dopamine agonists over levodopa?
1.More risk of hallucinations and compulsive behaviour
2. Postural hypotension
3. Daytime sleepiness
82
How do COMT inhibitors work?
Inhibit catecholamine O-methyltransferase to stop it from degrading dopamine and levodopa
83
Name three COMT inhibitors
Entacapone
Tolcapone
Opicapone
84
How do MAO-B inhibitors work?
Inhibit monoamine oxidase B to stop it from degrading dopamine and levodopa
85
Name two MAO-B inhibitors
Selegiline
Rasagiline
86
What is safinamide?
Used in combination with co-careldopa to treat adults with Parkinson's who are having "off" episodes
87
What is the mechanism of safinamide?
It has multiple mechanisms of action including as a MAO-B inhibitor
88
What is apomorphine?
A strong type of dopamine agonist
89
How can apomorphine be given?
Rescue treatment in pen form
Continuous daytime infusion (constant blood levels help smooth motor fluctuations)
90
How often should Parkinson's patients be reviewed?
Every 6- 12 months
91
Who should Parkinson's patients have access to?
1. Physiotherapy
2. Occupational therapy
3. Speech and Language therapy
4. Dietician
92
What should Parkinson's patients take?
Vitamin D
93
What drug can be given to patients experiencing Parkinson psychosis?
Clozapine
94
How should depression and anxiety be managed in Parkinson's disease?
Current guidelines are same as rest of population
95
What drugs can be given to patients experiencing mild to moderate Parkinson dementia?
Cholinesterase inhibitors
96
What is deep brain stimulation?
Implantable device that sends signals directly to basal ganglia.
Used in late Parkinson's when fluctuations become an issue and is no longer controlled by best medical therapy
97
What problems can people experience with Parkinson medication?
"Wearing off phenomena"
People get "off" periods and need more frequent medications
98
What is Parkinsonism?
Symptoms of Parkinson's seen in other diseases or side effects from medication
99
What are some causes of Parkinsonism?
1. Lewy Body dementia
2. WIlson disease
3. Pick disease (FTD)
4. Normal pressure hydrocephalus
5. Vascular
6. Iatrogenic (anti-psychotics and anti-emetics) Haloperidol and Metoclopramide
100
What is an essential tremor?
A condition that affects the nervous system, causing involuntary and rhythmic shaking or trembling
101
What part of the body is usually affected with essential tremor?
Hands, fingers, sometimes head, vocal cords
102
What are the causes of essential tremor?
The exact cause is unknown, but it may be familial with an autosomal dominant inheritance pattern
103
What sort of tremor is an essential tremor?
Rhythmic, symmetrical tremor
104
What is the treatment for essential tremor?
1. Beta blockers
2. Anti-epileptics
3. Benzodiazepines
4. Botulinum toxin (Botox) (head tremors not responsive to medication
105
What are some other interventions for essential tremor>
1. Avoid nicotine and caffeine
2. Get enough sleep
106
How can alcohol affect essential tremor?
It can cause a short term benefit and reduce the tremor
107
How does an essential tremor differ from a Parkinson tremor?
1. Essential tremor is symmetrical
2. Essential tremor is on movement / posture
3. Essential tremor is higher frequency
4. Parkinson's tremor affects hands, legs, chin
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