B06W12 Flashcards Preview

Block 6: Neuro > B06W12 > Flashcards

Flashcards in B06W12 Deck (376):
1

Compare and contrast the typical features suggestive of syncope vs seizure

Syncope: typically trigger (like vasovagal or postural hypertension), typical prodrome (weak, light headed, vision fading), crumple to ground and tend to break fall, brief or no convulsions or confusion; Seizure: no warning, no focal neurological disturbance, heavy fall, prolonge stiffening/convulsions over 1 minute, post-ictal confusion

2

What is the typical prodrome for syncope?

Weak, light-headedness, fading vision

3

Define seizure

Paroxysmal cerebral event resulting from abnormal, involuntary, rhythmis neuronal discharges (usually) causing altered behaviour, sensations or awareness

4

What are provoked seizures?

Seizure occuring in a previously normal brain because of an abnormal physiological stress (metabolic insult, drugs, acute neurological illness)

5

What are unprovokes seizures?

A seizure occuring in the absence of an identifiable acute insult

6

What is epilepsy?

A disorder predisposing to recurrent (more than 2) unprovoked seizures

7

Focal epilepsy is more common in _____, and generalised epilepsy is more common in _____

Adults; children

8

Give at least 3 examples of structures that might be altered in patient's with seizures

Developmental processes (age-related receptor/channel changes), ion channels and receptors, NTs, second messenger systems, synaptic number/morphology, synaptic plasticity (the same mechanisms that allow learning might reinforce epileptic pathways, neuronal size/shape/number and connectivity

9

What is the first step in classifying a seizure?

Descide whether there is a focal epilepsy (starting in one area and spreading) or generalised (whole brain affected at the same time)

10

Briefly discuss the pathophysiology of partial seizures

Focal/regional cortical abnormality causing a local imbalance between excitation and inhibition

11

What are the 2 main causes of partial seizures?

Structural lesions or regionally expressed genetic defects (i.e., channellopathy)

12

How are partial seizures defined?

By focal onset, regardless of eventual extent or severity

13

Describe how partial seizures can become generalised (secondary generalisation)

Because many neurons send excitatory inputs to neightbouring neurons, excessive firing at the focus may recruit normal brain into the seizure

14

Discuss the clinical features of partial seizures

Consciousness is usually preserved at the onset of partial seizures (because most of the brain is still unaffected), the intial symptoms depend on the part of the brain serving as the focus, spread by produce new symptoms or loss of consciousness and may be too rapid to allow identification of the focal phase.

15

List at least 2 common and potentially localising symptoms of a seizure of the temporal lobe

Altered awareness or memory-related phenomena (dŽjˆ vu), olfactory/visceral sensations

16

List a common and potentially localising symptoms of a seizure of the motor cortex

Motor activity/jerking

17

List a common and potentially localising symptoms of a seizure of the somatosensory cortex

Paraesthesia

18

List a common and potentially localising symptoms of a seizure of the occipital cortex

Visual hallucinations

19

When do localising symptoms of seizure provide the best value?

Early in the seizure

20

Compare positive vs negative symptoms in neurology

Positive = experience of something extra (unwanted movements, sensations, etc.) - implied part of CNS is overactive; Negative = lack of movement/sensation, e.g., numbness, blindness - implies CNS is underactive

21

Transient positive focal brain symptoms strongly imply what underlying pathology?

Seizures (and sometimes migraine)

22

Transient negative focal brain symptoms strongly imply what underlying pathology?

Ischaemia (TIA)

23

Define primary generalised seizures

Seizures that involve the entire cortex from the onset

24

What neurological changes occur in generalised seizures?

Neuronal firing excessively synchronised rather than excessive in terms of absolute number of action potentials - many neurons firing at the same time in synchrony over a broad area is abnormal

25

What is the main difference in imaging in patients who have had a focal vs generalised seizure?

Can sometime see focal lesion in focal/partial seizures, but often no causative lesions can be found on scanning for generalised seizures

26

Discuss what is currently understood about the aetiology of generalised seizures

Not certain, but may be due to a system-wide instability in cerebral rhythms, with a tendency to undergo abnormal corical synchronisation, probably involving genetic abnormalities in thalamocortical cricuits

27

Discuss the classical clinical features of generalised seizures

Consciousness is lost at the onset of a generalised seizure, so seizure onset is not remembered (unlike partical seizures, there is not unaffected cortex to observe the abnormality)

28

What are the major subtypes of generalised seizures?

Primary generalised tonic-clonic seizures, tonic seizures, clonic seizures, myoclonic s, absence s, atypical absence, atonic s, infantile spasms

29

What are absence seizures?

Brief (1-10s) bursts of synchronised activity, with transitory loss of awareness (often not noted by patient), no post-ictal drowsiness. Often a condition of childhood that subsequently resolves

30

What are primary generalised tonic-clonic seizures?

Excessive firing of entire cortex, causing sudden loss of consciousness, full body stiffness, jerking of limbs

31

What are myoclonic seizures?

Brief generalised cortical discharges causing lightening-like muscular jerks bilaterally

32

If there is a loss of consciousness at the onset of a siezure, what seizure classification is most likely?

Generalised seizures (e.g., absences and primary generalised tonic clonic seizures)

33

Suppose someone has a seizure that did not have loss of consciousness at onset, but did have alteration of consciousness at onset. What sort of seizure classification would be most likely?

Complex partial seizure

34

Suppose someone has a seizure that did not have loss or alteration of consciousness at onset. What sort of seizure classification would be most likely?

Simple partial seizure

35

What questions would you ask a patient presenting with a seziure to determine what sort of seizure they had?

Ask whether the patient lost consciousness at the beginning of the seizure (generalised) or if they have any awareness of the event at the beginning (focal)

36

Compare and contrast the characteristics of absence seizures vs complex partial seizures

Absence = childhood, seconds in duration, automatism rare, no post-ictal confusion, up to 100 episodes per day; Complex partial = all ages, 30-50s duration, automatism common, post-ictal confusion present and weekly-monthly in frequency

37

What are the 2 main axes of classification of epilepsy?

Generalised and partial

38

What seizure types are most common in culdhood absence epilepsy?

Absence and generalised tonic-clonic

39

What seizure types are most common in juvenille myoclonic epilepsy?

Myoclonic and generalised tonic-clonic

40

List at least 5 differential diagnoses of epilepsy

Syncope (simple or convulsive), peudoseizures (psychogenic), TIA, migraine with focal deficits, sleep disorder (sleep walking), movement disorder (dyskinesia), retrograde amnesia from head infury

41

What provoking factors of epilepsy should be asked about in history?

Alcohol, drugs, sleep-deprivation, hypoglycaemia, metabolic disturbance

42

What seizure types are most common in temporal lobe epilepsy?

Complex partial seizure and secondary generalised seizures

43

What investigations should be ordered for a patient who has had a first seizure?

CT to ensure there are no acute neurological emergencies, metabolic screen (glucose, electrolytes, FBC, EEG)

44

What is the gold standard for diagnosing seizures?

EEG (useful in about 50% of newly diagnosed epilepsy patients)

45

Briefly describe how EEG can be used to measure electrical activity inside the skull?

Needs amplification: 1. Major cortical neurons are aligned perpendicular to the cortical surface (allowing spatial summation - all voltage changes are aligned). 2. Neuronal activity is often synchronised (allowing temporal summation)

46

What are the main events events seen in EEG?

Synaptic potentials (excitatory/inhibitory post-synaptic potentials)

47

What information is given in an EEG 'spike'?

Just telling you that all the neurons in that area fired at the same time - which is abnormal - correspons with highly synchronised synaptic events and therefore follow volleys of action potentials

48

List the 4 main treatment aims in epilepsy

Reduce seizures, manage cause, harm minimisation and reduced side effcets

49

What sort of treatment options are availabe to reduce seizures in epilepsy?

Remove/minimise provoking factors, antiepileptic drugs, epilepsy surgery (useful for refractory cases when there is a definite lesion), ketogenic diet and vagal nerve stimulation

50

When are antiepileptic drugs indicated?

When there is good evidence that seizures will be an ongoing problem (i.e., in post patients with epilepsy - 2 or more seizures), rather than for anyone after the first isolated seizure

51

What sort of harm minimisation strategies should be advised for patients with epilepsy?

Avoid driving, swimming, bathing and other dangerous activities

52

Why do anti-epileptic drugs have so many side effects?

Because they affect normal neurons as well as epileptic ones

53

What are the 2 main modes of action of anti-epilepsy drugs?

1. Reduce excitation 2. Promote inhibition

54

What is the MOA of Valproate and phenytoin in epilepsy?

Blocks sodium channels to reduce excitation (also blocks low-threshold voltage-dependent calcium currents

55

What is the MOA of benzodiazapines in epilepsy?

Promote inhibition by actong on GABA receptors

56

What is the MOA of anti-absence drugs in epilepsy?

Block low-threshold voltage-dependent calcium currents (i.e., valproate)

57

Which anti-epileptic drug can be used for primary generalised seizures, absence seizures and partial seizures?

Valproate

58

Why is it important to start and stop anti-epileptic medications slowly?

Starting slowly avoids excessive sedation and may reduce side effects, stop slowly because rapid weaning can cause drug-withdrawal seizures

59

A 43 year old man with a recent diagnosis of lung cancer has prolonged jerking of right upper limb. What is the most likley cause?

Brain mets in motor cortex secondary to lung cancer

60

A 23 year old man has a single major convulsive seizure after heavy binge drinking for 5 days. What is the most likely cause?

Alcohol-induced seizure in a normal brain

61

A 10 year old girl has up to 100 brief starting spells each day. What is the most likley cause?

Absence seizures

62

A 33 year old woman has an episode of feeling light-headed, going pale, slumping to the ground, jerking several times, remaining unconscious for one minute and then waking up promtpy without confusion. What is the mostly likley cause?

Convulsive syncope

63

A 42 year old man has a 2 year Hx of going 'vague' for 3 minutes about once per month, often associated with olfactory hallucinations. What is the most likley cause?

Complex partial seizure arising from the temporal lobe

64

What is the largest lobe of the brain?

Frontal

65

What are the 5 components of normal behaviour?

1. Motivation 2. Inhibition 3. Appropriateness 4. Interpretation 5. Insight

66

List the 5 functions of the frontal lobe that are tested in the examination of higher cortical centres

1. Frontal reflexes 2. Proverb interpretation 3. Comparison/contrast 4. Expressive aphasia 5. Sequences

67

What tests are use to examine frontal lobe reflexes?

P-m, pout, snout and grasp

68

What test is used to examine frontal lobe sequences?

Luria's test (pantomime)

69

What are the 5 broad functions of the temporal lobe?

Memory, emotion, language (in the dominant hemisphere only), olfaction and hearing

70

List the 2 functions of the temportal lobe that are tested in the examination of higher cortical centres

1. Memory (immediate recall, short-term and long-term) 2. Language

71

Which 3 components of memory are tested in the temporal lobe examination of higher cortical function?

Immediate recall (3 objects), short-term memory (3 objects at 5 minutes) and long-term (names, dates of birth of children etc.)

72

List 4 abnormalities of the parietal lobe

1. Sensation 2. Sensory inattention 3. Visual inattention 4. Constructional aprexia

73

What is apraxia?

A neurological disorder characterised by loss of the ability to carry out learned (familiar) movements, despite having the desitre and physical ability to perform the movements

74

List at least 3 types of apraxias

Ideomotor (poor spatial orientation), limb kinetic, conduction, dressing

75

What is agnosia?

Loss of ability to recognise objects, persons, sounds, shapes or smells whilst the specific sense is not defective nor is there any significant memory loss

76

What is alexia?

Acquired inability to read

77

What is agraphia?

Acquired inability to write

78

What is nominal aphasia?

Inability to name

79

What is conductive aphasia?

Inability to repeat

80

What is the difference between alexia and dyslexia?

Alexia refers to an acquired reading diability where reading ability had previously been developed, while dyslexia refers to developmental reading disability

81

List the 7 functions of the parietal lobe that are tested in the examination of higher cortical centres

Sensation, neglect, construction, acalculia, L-R disorientation, finger agnosia and agraphia

82

What is alcalculia?

loss of the ability to perform simple calculations, typically resulting from disease or injury of the parietal lobe of the brain

83

What test is used to examine parietal lobe construction?

Intersecting pentagon

84

What test is used to examine parietal lobe acaculia?

Serial 7's

85

What are the 3 available tests for higher cortical function?

Montreal cognitive assessment, Addenbrook's cognitive examination (ACE-R) and mini mental state examination (MMSE)

86

Lst at least 5 of the functions tested in the MMSE

Orientation to time, place, attention, memory, naming, repeating, reception, written expression and visuo-spatial

87

List the corticl functions not tested by the MMSE

Lacks abstract resoning, calculations, long-term memory and does not test frontal lobes, is also education dependent

88

Which lobes are not tested via use of the MMSE? Why is this significant?

Frontal - MMSE will be normal in frontal lesions

89

Aside from level of education, list some of the other confounders of the MMSE

Age, language, crude testing, normal in right hemisphere and frontal lesions, does not distinguish between diffuse and focal lesions, is unhelpful in cases of acute confusion and cultural background may have an impact

90

List the advantages of the MMSE

Well standardised (English), easy to administer (if you have a cooperative patient), good inter-rater reliability, good for monitoring, ultility in global neurodegenerative conditions like Alzheimer's

91

Which standartised test of higher cortical function can differentiate between different forms of dementia?

Addenbrooke's Cognitive Examination (ACE-R)

92

What 5 functions are tested in the ACE-R?

Attention and orienta, memory, verbal fluency, language and visuospatial skills

93

Which 6 functions are tested in a bedside language examination?

1. Spontaneous speech (informal interview, structured talk and automatic sequences) 2. Naming 3. Auditory comprehension 4. Repetition 5. Reading (aloud and comprehension) 6. Writing (spontaneous, to dictation, copying)

94

List at least 4 of the bedside features of Broca's (expressive) aphasia

Spontaneous speech non-fluent/mute, naming imapired, comprehension in tact, repetition impaired, writing impaired with poor grammar and may have associated right hemiparesis and hemisensory loss

95

List at least 4 of the bedside features of Wernicke's aphasia

Spontanteous speech fluent but with paraphrasic errors, imapired naming and bizzaire mis-naming, impaired comprehension, impaired repetition, impaired reading, well-formed and paragraphic writing and may have associated hemianopia

96

What is the peripheral cortex?

Folded, multilayered sheet of grey matter on the surface of the brain that is thrown into folds forming gyri and sulci

97

List the three types of cerebral cortex (telencephalon)

1. Paleocortex 2. Archicortex 3. Neocortex

98

The hippocampus is part of which cerebral cortex type?

Archicortex

99

What structures make up the paleocortex?

Olfactory cortex + entorhinal

100

What is the function of the paleocortex?

Incorporates representations of pain and emotional sensations (interoceptive self)

101

The principle input to entorhinal cortex is from which area?

All neocortx

102

The principle output from the enterohinal cortex is via which pathways?

Hippocampus and limbic pathways

103

What is the deep nucleus for the archistriatum? Which part of cortex is this strongly connected with?

Amygdala; archicortex = hippocampus

104

What is the deep nucleus for the paleostriatum? Which part of cortex is this strongly connected with?

Globus pallidus; pelocortex ; entorhinal cortex

105

What is the deep nucleus for the neostriatum? Which part of cortex is this strongly connected with?

Caudate/putamen; neocortex = everything other than hippocampus and entorhinal cortex

106

Where is the hippocampus located?

Medial part on interior durface of temporal lobe

107

List the 3 main parts of the hippocampus

Uncus, fornix, dentate gyrus

108

All cortical input to the dentate gyrus/hippocampus comes via which cortex?

Entorhinal; especially from multimodal association areas between neocortex and hippocampus

109

The entorhinal cortex receives direct projections from which structure?

Amygdala

110

Which cortex is known as the place where the 'interoceptive self' meets the 'exteroceptive self'?

Entorhinal

111

Which part of the human cortex is strongly affected in Alzheimer's disease?

Entorhinal

112

Which structures make up the limbic lobe?

Parahippocampal gyrus, septal area and cingulate gyrus

113

The entorhinal cortex and hippocampus are the mediators of what functions?

Declarative/conscious memory

114

The limbic lobe is comprosed of which types of cortex?

Archicortex and paleocortex

115

The limbic lobe is on the medial aspect of the brain and it's components encircle which structures?

Corpus callosum and diencephalon

116

The cingulate gyrus contains separate maps for which human experiences?

Pain and emotion

117

List at least 3 functions of the hippocampus

1. Formation and retrieval of sptial memory 2. Processing and categorisation of new information 3. Differentially modulates aggression and rage 4. Modulates endocrine functions of the hypothalamus

118

Hippocampal lobectomy results in what outcomes?

Inability to form new memories but long-term memories and intellectual skills not affected

119

Stimulation of the pole of the hippocampus closest to the amygdala promotes ______ behaviour; activation of he pole nearest the septal area suppresses ______ behaviour

Attack

120

List the 3 areas providing afferent information to the archicortex and paleocortex

1. Entorhinal cortex 2. Cortex (prefrontal, anterior cingulate gyrus) 3. Brainstem

121

Lateral and medial perforant pathways from the entorhinal cortex carry what sort of tertiary fibres to the hippocampus?

High order multisensory (olfactory, somatosensory, visual and auditory)

122

What are the 2 main efferent pathways from the hippocampus?

1. Via the fornix (projecting to septal area, diencephalon and contralateral hippocampus) 2. Cortex (entorhinal, cingulate and parts of the pre-frontal

123

What is the septal area of the limbic lobe?

A relay nucleus of the hippocampus to the hypothalamus

124

List the 3 afferents from the septal area of the limbic lobe

Hippocampus, brainstem monoaminergic systems, amygdala

125

List the 4 efferents from the septal area of the limbic lobe

Prefrontacl cortex, medial hypothalamus, medial thalamus and hippocapus (indirectly)

126

List at least 3 functions of the septal area of the limbic lobe

Control of aggression and rage, regulation of endocrine functions, reward/pleasure centre (self-stimulation; drinking behaviours), regulates the discharge of hippocampal neurons during learning of new tasks/goal-directed behaviour

127

Which brain strcuture is also known as the brain's alarm system?

Amygdala

128

What are the 3 subcortical afferents to the amygdala?

(from interoceptive self) Brainstem monoaminergic systems, thalamus, brainstem control centres including solitary nucleus and carioresp centres

129

What are the cortical afferents to the amygdala?

Olfactory areas (entorhinal) and visual, auditory and somatosensory areas

130

What are the 2 major functions of the amygdala?

1. Mediates adaptive responses 2. The most powerful regulator of the hypothalamus/endocrine functions

131

Which brain structure is the most powerful regulator of the hypothalamus/endocrine fucntions?

Amygdala

132

Unlike primary areas of the cortex, association areas project to which other cortex?

Entorhinal

133

Which type of human cortex is comprised of 6 layers?

Neocortex

134

What is primary neocortex?

Main input from a particular modality (i.e., vision, touch on skin, sound waves) = one function. All information must go through thalamus, and these two areas are reciprocally connected.

135

What is secondary neocortex?

Limited to particular modality but may be limited to a speicifc feature of that modality (i.e., specific area of visual cortex dealing with colour)

136

What is association neocortex?

Area that gets inputs from a number of different modalities (e.g., visual and auditory like Wernicke's).

137

The majority of cells in the neocortex are whay types of cells?

Large excitatory pyramidal cells with very long axons (and most non-puramidal cells are inhibitory GABAergic)

138

All sensory input enters which layer of the neocortex?

Layer 4

139

Why is layer 4 of the neocortex also known as the striatal layer?

So many axons come into this layer and synapse that a dark stripe can be seen on sectioning

140

Different cortical areas interact with each other through cells located in which layers of neocortex?

II and III

141

Primary sensory cortex has high density of inputs into which layer of the neocortex?

V

142

Primary motor cortex has high density of inputs into which layer of the neocortex?

Pyramidal cells in layers V and VI

143

What is the name of the structure comprised of alternating columns of striate cortex receiving inputs from one eye and then the other?

Ocular dominance columns

144

What process results in amblyopia?

Visual deprivation involving one eye results in the non-deprived eye taking over the territories of the deprived eye

145

Within each ocular dominance column, there are ____ columns

Orientation

146

____ sensicite regions are regulary spaces within each ocular dominance column

Colour

147

Projection (a) fibres originate in which layer of neocortex? What is their target?

V; striatum, brainstem, spinal cord

148

Projection (b) fibres originate in which layer of neocortex? What is their target?

VI; thalamus

149

Commisural fibres originate in which layer of neocortex? What is their target?

III; contralateral cortex

150

Association fibres originate in which layer of neocortex? What is their target?

III; ipsilateral cortex

151

List the 5 major association bundles of cortical white matter

1. Uncinate fasisculus 2. Superior occipitofrontal fasisculus 3. Superior longitudinal (arcute) fasisculus 4. Inferior occipitofrontal fasisiculus 5. Cingulum

152

What are the 2 most common categories of mental disorders?

Anxiety and mood disorders

153

List at least 4 types of anxiety disorders

Post traumatic stress disorder, social phobia, generalised anxiety disorder, panic disorder, obsessive-compulsive disorder

154

List at least 2 types of mood disorders

Major depressive disorder, unipolar depressive episodes, bipolar disorders

155

What is anhedonia in depression? What parts of the patient experience can this effect?

Patients have genuine inability to experience reward; impairs motivation and incentive based learning

156

MDD (major depressive disorder) is associated with polymorphisms in which genes? (name at least 2)

1. Glucocorticoid receptor gene 2. Monoamine oxidase A gene 3. Gene for glycogen synthase 4. Metabotropic glutamate receptor genes

157

Give one example of a poymorphism in depression that has been shown to improve liklihood of treatment

People with polymorphic variant to serotonin-transporter-linked-polymorphic region which affects the promotoer of the serotonin-transporter gene > show increased response to certain antidepressant treatment and reduced side effects

158

What are the characeristics of anxiety disorders?

Characterised by chronic and persistent worry coupled with non-specific physical health compaints (major depression is a common coexisting condition)

159

What is needed for a diagnosis of MDD accodring to the DSM-V?

2 or more major depressive episodes - depressed mood and/or loss of interest or pleasure in life for over 2 weeks with 5 of the following: depressed mood for most of day, unintentional weight change, insomnia, sleeping too much, agitation, fatigue, feelings of worthlessness, diminished ability to think, thoughts of death

160

What is needed for a diagnosis of anxiety disorder according to the DSM-V?

Excessive anxiety and worry about events more days than not for a period of 6 months plus 3 of the following: restlessness, on edge, difficulty concentrating, easily fatigues, muscle tension and sleep disturbance. Anxiety must cause significant distress/impairement, not be due to substances or medical conditions and not better accounted for by another disorder

161

Discuss the normal HPA axis physiology in stress responses

Stress is perceived by the brain and transmitted to the hypothalamus (limbic system). Hypothalamus released CTRH onto pituitary, which results in secretion of corticotropin into the plasma and stimulation of receptros in adrenal cortex. This then releases cortisol into the blood. In homeostasis, hypothalamic cortisol receptors respons by reduced CTRH secrection (neg. feedback)

162

Discuss the changes in the HPA axis in mood disorders

In stress responses in depression, prefrtonal cortex and amygdala sense the stress and there is a significantly increased basal CTRH and cortisol level observed in these patients

163

Discuss some evidence supporting the HPA-axis theory of mood disorders

Increased levels of monoamines in the brain affect the HPA axis and can reverse some long-term effects of stress (ST, NA). Also, depressed patietns have elevated plasma cortisol levels and elevated PTRH levels in CSF

164

Discuss some evidence that refutes the HPA-axis theory of mood disorders

Stress = depression link not perfect - patients can be depressed with no signs of HPA-axis dysfunction

165

Which structures are considered in the 'default mode network'?

Anterior medial prefrontal cortex, cingulate cortex and angular gyrus

166

Describe the changes seen in the default mode network of a depressed patient in resting-state fMRI

Functional overactivation and hyperconnectivity

167

Which structures are included in the positive effect circuit (in relation to mood disorders)

Striatal nucleus accumbens and ventral tegmental areas with medial prefrontal cortices and anterior cingulate

168

What is the funciton of the 'default mode network' in regards to mental health?

Neural networks that modulate normal emotional behaviour implicated in mood disorders (medial and orbital prefrontal cortices, cingulate cortex and angular gyri are active in patients with depression, even whilst they are at rest)

169

Manifestations of increased default mode circuit activation are associated with what behaviours?

Maladaptive rumination about depressive thoughts

170

Describe the changes seen in the positive affect circuit of an rs-fMRI of a depressed patient

Distinct hypoactivation to ventral sitratal areas when viewing rewarding stimuli > may contribute to anhedonia

171

Anxiety disorders often focus on pathology of which brain structure in particular?

Amygdala

172

List some of the key regions identified in anxiety research

Limbic structures and areas linked to prefrontal cortex and anterior cingulate cortex

173

What is the fucntion of corticolimbic circuits in anxiety?

Mediate the interpretation of environmental stimuli producing an anxiety-like response (major determinant of whether environmental stimuli are interpreted as threatening happens at the amygdala - i.e., sensory stimuli imbued with emotional value). Hyperactivity of amygdala caused by white matter disruptions in inputs can lead to manifestations of anxiety where sensory information is inappropriately perceived as threatening and leads to emotion and behvaioural responses like panic diroders, phobias and GAD

174

What is the monoamine hypothesis?

Symptoms of mood and anxiety disorders can result from insufficiency levels of serotonin, noradreneline, dopamine and melatonin > agents that alter metabolism of these can relieve symptoms (monoamine oxidase inhibitors MAOIs and tricyclic antidepressants)

175

What are SSRIs?

Selective serotonin reuptake inhibitors

176

What are the advantages of SSRIs and SNRIs vs monoamine oxidase inhibitors and tricyclic antidepressants?

Specific, reducing symtoms and causing less side-effects

177

How are SSRIs believed to work?

By increasing extracellular level of serotonin > limits reasbsorption into the presynaptic cell > increase binding to the post-synaptic receptor

178

What is the aim of CBT?

Replace maladaptive interprettions of events with more helpful ones > thus angaging neural plasticity

179

Pharmacological therapy in anxiety disorders targets what?

Serotonergic and noradrenergic neurotransmission (SSRIs or SNRIs)

180

Give an example of a common SSRI or SNRI used in treatment of anxiety disorders

Benzodiazepines, alprazolam (xanax) and diazepam (valium) and medazepam

181

What are the main pharmacological treatments for depression?

Anti-depressants targeted at monoaminergic neurotransmission (serotenergic and noradrenergic): SRIs most sommonly prescribes as well tolerated and non-sedating; SNRIs often prescribed for more severe depression; Tricyclic antidepressants; MAOIs only under exceptional circumstances

182

Modifications to which neural circuits are hypothesised to cause rumination and anhedonia in depression?

Rumination: increased connectivity of default mode circuit - maladaptive self-referential rumination of depressive thoughts; Adhedonia: decreased activity of positive affect circuit - inability to feel pleasure

183

Describe the neural circuitry and changes hypothesised to contribute to anxiety?

Corticolimbic: symptoms may relate to loss of moderation fro mPFC and ACC over the amygdala > results in hyperactivity of the structure and a misinterpretation of ambiguous environmental stimuli as threatening - anxiogenic

184

Define the plaques and tangles seen in Alzheimer's disease

Plaque = extracellular deposit of beta-amyloid in centre and dystrophic nerve derminals filled with hyperphosphorylated tau around it; Tangle = intracellular deposit of hyperphosphorylated microtubule-association protein tau assembled into paired helical filaments

185

What is the typical 'incubation period' for Alzheimer's?

50 years

186

Which brain system is first affected in Alzheimer's? What specific structures are involved?

Limbic system (hippocampus, amygdala)

187

Which cortices are typically spared in Alzheimers?

Visual cortical areas, and somatosensory areas

188

What causes cognitive dysfunction in the late stages of Alzheimer's disease?

Neuromodulatory systems (NA, 5-HT) in brainstem affected later in disease

189

Describe the location and composition of plaques seen in Alzheimers

In nerve tissue as well as around blood vessels; consist of extracellular protein (beta-amyloid in precipitated/insoluble form) with high content of heavy metals like aluminium, zinc and copper

190

Beta-amyloid is assembled from which other protein?

A-beta oligomers

191

Discuss the pathophysiology of plaque emergence in Alzheimer's disease

Can emerge within days (i.e., fast), followed by microglial activation and recruitment (1-2 days) and progressive neuritic changes, leading to increasingly dysmorphic neurites/axons (days- weeks)

192

What is tau protein responsible for in the brain? What happens if it becomes hyperphosphorylated?

Stabilizing neurofilaments (cytoskeletal structures); if hyperphosphorylated, tau assembles into intracellular tangles, which causes neurofilaments to destabilise and break apart > axonal transport of mitochondria to and from synapse breaks, causes a mitochondrial energy and calcium homeostasis crisis at the synapse

193

Tangles in Alzheimer's are made from what protein? What is this protein notmally responsible for?

Made out of tau protein (crucial in making up normal microtubules in cytoskeleton)

194

What happens if tau protein is hyperphosphorylated?

Stabillity of cytoskeleton and microtubules decay > axonal transport severely impaired > form intracellular deposits (Alzheimer's)

195

Which type of Alzheimer's has early onset and a mutated gene?

Familial autosomal dominant

196

Sporadic Alzheimer's disease has similar risk factors to which other significant disease?

Atherosclerotic (i.e., in BP, lipids etc)

197

List the 3 main theories of disease generation in Alzheimer's disease

1. Amyloid hypothesis 2. Vascular hypothesis 3. MAM (mitochondria associated membrane) hypothesis

198

Briefly outline the amyloid hypothesis for Alzheimer's disease

Abnormal Amyloid precursor protein cleavage causes Amyloid-beta deposition > formation of senile plaques > neurodegeneration > disease

199

Briefly outline the vascular hypothesis for Alzheimer's disease

Advanced ageing and vascular risk factors lead to brain hypoperfusion > produces neuroglial energy crisis >mild cognitive impairement > neurodegeneration > disease

200

Briefly outline the MAM hypothesis for Alzheimer's disease

Altered lipid raft formation causes altered calcium homeostasis > altered Amyloid precursor protein/tau processing > plaques/tangles/lipid droplets form > neurodegeneration > disease

201

If Amyloid Precursor Protein proteolysis is done via alpha-secretase, what is produced?

NO Amyloid-beta

202

Which particular Amyloid-beta is cytotoxic? What events does it promote?

Amyloid-beta42; aggregtion (oligomers), excitotoxicity, oxidation, inflammation and tau hyperphosphorylation

203

Amyloid-beta is produced in the ____ of a cell, and stored in ____

ER; vesicles

204

Vesiscular secretion of Amyloid-beta is controlled by what chemical at what time?

Orexin; under circadian control (decreased in sleep and increased when awake)

205

What are the protperies of Amyloid-beta?

Monomers may be neurotrophic, oligomers are toxic (escp A-beta42), produced in ER and stored in vesicles which are secreted via orexin and circadian control - secretion goes down during sleep and increases throughout the day)

206

What is the physiological role of the head of Amyloid Precursor Protein (N-terminus)?

Development - axonal pruning via DR6 that activates capsase 6 > apoptosis

207

What is the physiological role of Amyloid Precursor Protein's Amyloid-beta?

Secreted as a monomer and maintains synapses, also form amyloid sheets as oligomers in vesicles for storage

208

What is the physiological role of the tail of Amyloid Precursor Protein (AICD)?

Calcium homeostasis, ATP availability (mitochondria) and transcriptional modulation

209

The gamma-secretase complex comsists of which components?

Presenilin (PS1 PS2) as catalytic core and 3 accessory proteins (nicastrin, Alph1-1 and Pen-2)

210

List some of the ways that presenilin plays a central role in calcium homeostasis

Modulate SERCA pump, IP3 receptor and ryanodine receptor (in SER membrane), interact with calcium binding proteins like calpain, form calcium channels in expression system (SER calcium leak channels) and are essential for regulating transmitter release (presynaptic calcium stores)

211

Release of which ion from storage actives beta-secretase?

Calcium

212

What happens to the number of synapses and number of cells in Alzheimers?

Both decreased

213

What changes in synaptic efficacy are seen in Alzheimer's disease?

AMPA-type fEPSPs are reduced, NMDA-dependent LTP may be affected

214

Spines are the sites of _____ synapses in the hippocampus

Excitatory

215

When exposed to control and Amyloid-beta42 monomers, spine density is _______. When exposed to Amyloid-beta42 oligomers, spine density _____

Normal; drops

216

Alzheimer's plaques are made from ______

Amyloid-beta oligomers

217

List the 3 drug classes approved for use in Alzheimers in Australia? Give an example of a drug within each class.

1. Anticholinesterases (donezepil) 2. Cholinomimetics (galantamine) 3. Glutamate (NMDA) receptor antagonists (memantine)

218

List at least 4 synaptic-related changes seen in Alzheimer's disease

Fewer synapses and cells, synapses with smaller efficacy, larger NMDA receptor currents at synapses, larger NMDA receptor-dependent spine loss, activity-dependent synaptic Amyloid-beta secretion

219

Why is the length of amino acid chain important? i.e., beta-amyloid in Alzheimer plaques

Because amino acid chains longer than 42 are toxic (but reason is unknown)

220

The amyloid see in Alzheimer's plaques is realted to which other amyloid deposit in human disease?

Pancreatic amyloid in diabetes

221

What is the result of exposing mitochondria in an axons to amyloid beta?

Axonal transport stops

222

Why is the incidence of Alzheimer's disease higher in people with Down's syndrome?

Because chromosome 21 abnormality is known to be implicated, and down's syndrome is a tripling of this chromosome

223

Familial Alzheimer's shares which 3 genes? What is clinically significant about this?

Amyloid precursor protein, PS1 and PS2 - if any one of these is mutated, the person WILL get the disease - there is no prevention

224

How does the cognittive decline of Alzheimer's relate to number of plaques?

No link

225

Why is gamma-secretase difficult to use as a drug target for Alzheimer's disease?

Involved in a number of different signalling cascades (not just neuronally in Alzheimers), therefore if blocking this with drug - also block other cascades, such as the Notch pathway in enteric cells - don't re-generate as per normal and causes diarrhoea

226

What is the Aboriginal definition of health?

Aboriginal health means not just the physical well-being of an individual but refers to the social, emotional and cultural well-being of the whole community in which each individual is able to achieve their full potential as a human being thereby bringing about the total well-being of their community

227

List some of the associations of low birth weight in Indigenous populations

Lack of antenatal care, poor meternal nutrition, maternal smoking, alcool or drug use, extremes of maternal age, limited birth spacing and socioeconomic disadvantage

228

List 4 roles of a doctor in improving ATSI health

Be aware of the inequalities in healthcare, cultural awareness, knowledge of preventative activities unique to ATSI people, knowledge of the programs available to ATSI people

229

What are some of the secondary complications of scabies in indigenous populations?

Secondary bacterial infection (MRSA or GAS), post-strep glomerulonephritis, acute rheumatic fever

230

Low birth weight can lead to what complications?

Increased risk of diabetes, chronic renal disease, ischaemic heart disease etc.

231

How can low birth weight be prevented in Indigenous communitites?

Support women to present early and often, support women's diet during pregnancy, limit supply of alcohol in community, offer effective contraception to teenagers and following delivery

232

What immunisations are provided for preventative health in ATSI populations?

BCG (tuberculosis), Hep A, booster of pneumococcal vaccine at 2 years old, influenza (everyone over 18 for free and 6months-5years for free), pneumococcal (everyone over 50 or over 18 wth risk factors gets it for free

233

List some preventative screening practices used in ATSI populations

Anaemia in childhood, hearing loss in childhood, sexual health (gonorrhoea and pyphilis higher prevalence - recommended up to 35 years old), diabetes, chronic kidney disease and CVD (begins at younger age)

234

How does Closing the Gap progam impact GP practice?

ATSI populations encouraged to have yearly health check, better access to allied health care, cheaper medications, access to care coordinators and transport, access to funds to pay for private specialises and expensive imaging and GPs encouraged to see patients regularly

235

List some specific PBS for ATSI people

Antifungal creams, terbinafine, ciprofloxacin ear drops, nicotine patches, folic acid, magnesium and thiamine, paracetamol and aspirin

236

Which cells line the ventricles of the brain?

Ependymal cells

237

Astrocytes I the brain connect which structures?

Neurons with blood vessels

238

What are neurodegenerative diseases?

Degeneration of neurons and their synapses that affect brain function

239

List some of the basic principles/characteristics of neurodegenerative disorders

Progressive loss of neurons causing grey matter changes; pattern of neuronal loss is selective (in certain areas of the CNS); occur in previously healthy patients; development of abnormal interneuronal protein aggregates (can cause cofnromational changes in normal proteins surrounding - works similarly to a prion); protein aggregates are resistant to cellular mechanisms of degradation; protein aggregates are cytotoxis to neurons

240

Where do abnormal interneuronal protein aggregates originate from in Huntingtons, Alzheimers and Parkinsons?

Huntingtons = genetic mutation (abnormal protin aggregatces in the nucleus and kills the cell); Alzheimer's = peptide derived from large amyloid precursor protein; Parkinson's = unexplained alteration in a normal cellular protein

241

What is Alzheimer's disease?

Cortical degenerative disease with progressive loss of cognitive function (causing dementia)

242

List some of the characteristics of Alzheimer's disease

Insidious onset, disorders of thought content/perception/affect, behavioural disturbances, personality changes, can cause amnesia, aphasia and immobility

243

Genes on which chromosomes are thought to be implicated in familial forms of Alzheimer's disease?

21 (amyloid precursor protein is on this chromosome), 14, 1

244

Amyloid precursor protein is located on which chromosome?

21

245

What combination of techniques allow correct diagnosis of Alzheimer's disease?

Clinical assessment and radiology (definitive diagnosis autopsy)

246

List at least 4 macroscopic features of Alzheimer's disease seen in autopsy specimens?

Cortical atrophy, widened sulci, narroweed gyri, ventricular dilatation, thinned cortical ribbon

247

What are the 3 main hitological findings in Alzheimer's disease?

Neuritic plaques, neurofibrillary tangles and amyloid angiopathy (extracellularly)

248

Where are neuritic plaques best seen in Alzheimer's disease?

Seen in hippocampus, amygdala, neocortex

249

What are neuritic plaques of Alzheimer's comprised of?

Central amyloid core, surrounded by dilated tortuous dystrophic neurites > all surrounded by reactive astrocytes (macrophages of the CNS - causing scarring) and microglia are present at the periphery

250

Where are neurofibrillary tangles of Alzheimer's best seen?

Hippocampus and amygdala (intracellularly)

251

What are neurofibrillary tangles in Alzheimer's disease?

Intracellular bundles of filament in the cytoplasm encircling or displacing the nucleus - appearing as elongated flame-shaped or basket weave patterns.

252

Neurofibrillary tangles may persist as ______ after the death of neurons

Ghosts

253

What are neurofibrillary tangles in Alzheimer's composed of?

Paired helical filaments, hyperphosphorylated protein tau and mictotubule associated protein

254

What histo stain may be used to view neurofibrillary plaques as well as background axons in Alzheimers?

Silver Bielschowsky

255

What is cerebral amyloid angiopathy? What disease may this be associated with?

Intramural deposits of amyloid in small arterieal vessels - may be sporadic or associated with Alzheimer's disease

256

What histo stain may be used to highlight amyloid as brick-red colour within the wall of a small artery?

Congo red stain (can then also apply polarised light to make briefringement of amyloid appear green)

257

What histo stain may be used to highlight amyloid as brown colour within the wall of a small artery?

Beta amyloid immunohistochemical

258

What are Hirano bodies, and in which disease state can they be seen?

Elongated glassy eosinophilic beaded bodies; Alzheimer's

259

In what disease may granulovacuolar degeneration of neurons (GVD) be seen?

Alzheimers

260

List 5 main changes seen in an aging brain

1. Atrophy (decrease in brain weight, shrinkage of gyri/expansion of sulci, enlargement of ventricles) 2. Vascular changes 3. Accumulation of pigment (lipofuchsin) 4. Loss of pigment (substantial nigra) 5. Senile plaques (neuritic in deep cortex and non-neuritic in superficial cortex)

261

What mnemonic can be used to remember the clinical features of Parkinsons

TRAP - tremor, rigidity, akinesia and postural instability

262

There is a minor proportion of Parkinsons disease that have a familial form. Which 2 inheritance patterns do these follow?

Autosomal dominant, autosomal recessive

263

What change is seen in the histology of the substantia nigra in Parkinson's disease?

Loss of pigmented neurons in the substantia nigra

264

What macroscopic change can be seen in a cross section of the pons vs midbrain in Parkinsons disease?

Pons = Loss of pigmentation of locus ceruleus; Midbrain = Loss of melanin pigmentation of substantia nigra

265

List the histopathological changes seen on a H&E stain of the substantia nigra in Parkinson's disease

Loss of pigmented catecholaminergic neurons, lewy bodies in the remaining neurons (round to elongated cytoplasmis eosinophilic inclusions)

266

What are lewy bodies composed of?

Tightly packed fine filaments of alpha-synuclein, parkin and ubiquitin

267

Which chromosome(and protein) is thought to be implicated in Huntington's disease, and how?

Chromosome 4: protein Huntingtin; triplet nucleotide repeat expansion > exhibits anticipation

268

Huntington's disease results from a degeneration of what type of neurons?

Striatal

269

List at least 4 clinical features of Huntingtons

Insidious onset (35-45 years), chorea, dementia, emotional symptoms, occassionally present with parkinsonian dynsrome, depression

270

What is chorea?

Arrythmix involuntary movements that are typically sudden and brief and that seem to flow from one part of the body to another

271

Dicuss the macroscopic changes that can be seen in the brain specimen of a patient with Huntington's disease

Atrophy of the caudate and putamen, widespread cerebral atrophy of the striatum and cerebral cortex

272

What is needed for the diagnosis of Huntingtons?

Distinguish from other causes of chorea, demetia and psychosis; genetic testing; MRI and PET scans

273

What pathological processes occur in amyotrophic lateral sclerosis?

Destruction and loss of upper and lower motor neurones and denervation and atrophy of the corresponding muscle fibres

274

In the few cases of hereditary amyotrophic lateral sclerosis, which 4 genes have been implicated?

SOD1, ALS2, NEFH, VAPB

275

What is the SOD1 gene (implicated in amyotrophic lateral sclerosis) responsible for?

Coding for superoxide dismutase hence it is proposed that the neuronal cell death in ALS may be related to excess of free radicals

276

Which functions are spared in amyotrophic lateral sclerosis?

Mental functions and physical sensation

277

List at least 3 clinical features of amyotrophic lateral sclerosis

Progressive loss of voluntary muscle contraction; progressive wasting and atrophy of affected muscles; spontaneous twitching of motor units (fasisculations); difficulty with chewing, swallowing and movements of the face and tongue; progressive phsyical disability

278

List the 2 macroscopic features of amyotrophic lateral sclerosis that can be seen on a cauda equina and filum terminae specimen

Withered nerve roots and thinned spinal chord

279

What sort of histo stain can be used to stain myelin blue?

Luxol fast blue

280

What changes are seen on a luxol fast blue histo stain of the spinal cord in amyotrophic lateral sclerosis?

Degeneration of lateral columns of spinal cord (pale due to loss of anterior horn)

281

Discuss the pathophysiology of the CNS seen in amyotrophic lateral sclerosis

Motor neurons undergo shrinkage with accululation fo lipofuscin pigment > presence of spheroids (focal accumulations of neurofilaments) > thinning of corticospinal tracts due to loss of cortical motor neurons > loss of fibres in the lateral columns of the spinal cord and replacement by filbrillary gliosis imparting some firmness (lateral sclerosis) > gliosis (the term for scarring of the CNS: astrocytes + their processes proliferate instead of fibroblasts. Collagen is not laid down as in a normal scar)

282

What is gliosis?

The term for scarring of the CNS - astrocytes and their processes proliferate instead of fibroblasts, so collagen Is not laid down as in a normal scar (as there is no fibroblasts in the brain)

283

What are the clinical manifestations of amyotropic lateral sclerosis in peripheral muscles?

Denervation and atrophy of corresponding muscle fibres - clinically recognised muscle wasting (amyotrophy)

284

List some of the differential diagnoses of amyotropic lateral sclerosis

Mass lesions, infections, toxins and drugs (lead poisoning), motor neuropathy with conduction block, paraneoplastic syndromes and hyperthyroidism

285

Which neurodegenerative disease is inherited as an autosomal dominant condition?

Huntington's disease

286

In an STPase stain at a pH of 9.4, how do type 1 vs type 2 muscle fibres appear?

Type 1 = light; Type 2 = dark

287

List at least 4 symptoms of muscle/NMJ disease

Muscle pain, weaknes, cramp, fatigue, wasting, family history, (note important of absence of sensory symptoms)

288

A 26 yo presents with proximal lower limb weakness for 6 months (avoiding stairs), fatigue worse later in day, also affects proximal upper limb muscles. She was previously good at sports, has no medial or family history and appears skinny with small muscle bulk, lower limb weakness and mild ptosis. What is the differential diagnosis?

Myasthenia gravis

289

List some investigations used for muscle/NMJ diseases

Bloods (CK, antibodies, TFTs), genetic studies, neurophysiology, muscle biopsy and imaging

290

What changes would be expected on a nerve conduction study of a patient with myasthenia gravis?

Electrical fatigue - successive decreases in muscle repsonse to stimuli over time

291

List at least 3 neuromuscular disorders

Myasthenia gravis (most common), Labert-Eaton (associated with lung cancer), botulism, congenital myasthenic syndromes, drugs/toxins (poisonous animals)

292

Discuss the pathogenesis of myasthenia gravis

Autoimmune disease of the NMJ caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. The pathogenesis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin IgG1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients.

293

Myasthenia gravis is mediated by ___ cells and

B cells

294

How do AChR antibodies contribute to disease in myasthenia gravis?

Block ACh binding site, cross linking of AChR on postsynaptic receptor, complement activation with destruction of postsynaptic receptor

295

What is MUSK, what does it do and in which disease is it implicated?

Muscle-specific tyrosine kinase; reduced AChR clustering; myasthenia gravis

296

What are the clinical features of myasthenia gravis

Ocular or generalised forms (ocular weakness in diplopia or ptosis), limb weakness or generalised weakness of proximal muscles (can include bulbar muscles); fluctuating weakness exacerbated by exercise and improved with rest (fatigue)

297

What are the exacerbating factors for myasthenia gravis?

Intercurrena illness, especially infection and drugs (like anaesthetics)

298

List 4 investigations for myasthenia gravis

1. Antibodies 2. Neurophysiology (repetivie stimulation or single fibre study) 3. Pharmacology testing (administering adrophonium which reverses weakness) 4. Imaging (chest CT for thymoma or hyperplasia)

299

List some of the treatment options for myasthenia gravis

Cholinesterase inhibitors, corticosteroids, azathioprine, plasmaphareses in myasthenic crisis, IVIG (acute setting), thymectomy if thymic hyperplasia present and a number of other immunosuppresants

300

What is the MOA of cholinesterase inhibitors?

Reduce breakdown of acetylcholine at NMJ

301

Why are cholinesterase inhibitors not the ideal treatment for myasthenia gravis?

Do not modify disease - progressive loss of AChR antibodies over time

302

What type of drug is pyridostigime? Which disease may it be used for?

Cholinesterase inhibitor (myasthenia gravis)

303

What side effects are elicited by increasing dose of cholinesterase drugs?

GIT motibility, salivation/lacrimation and hyperhidrosis - can also promote cholinergic crisis

304

Lambert Eaton myasthenic syndrome is characterised by antibodies against what channels?

Presynaptic volatge gated channels at the NMJ

305

List at least 3 types of botulism

Food borne, wound, overdose for treatment, infantile

306

List the 3 most common clinical features of botulism

Pupillary involvement, autonomic involvement, reflexes may be depressed

307

List 3 ways that botulism may be diagnosed

Wound culture, serum antibodies and toxin in food

308

Describe how Duchene's muscular dystrophy typically presents over time

X-linked: Normal at birth, clumsy in first year, arise using Gower's procedure, child does not run or jump, by 6-7 years child starts to fall, wheelchair usually needed by age 12, scoliosis and cardiac involvement common and death usually occurs in early adulthood or late teens

309

State the inheritance pattern for Duchene's and Becker's muscular dystrophies

X-linked

310

List at least 3 treatments for Duchene's muscular dystrophy

Physiotherapy, bracing, predisolone (slows progression) and reconstructive surgery

311

Describe how Becker's muscular dystrophy typically presents over time

Weakness usually appears in first decade but may not present until 30s. Calf hypertrophy and contractures are common, as are leg muscle cramps. Cardiac disease can present later

312

What is facioscapulohumeral dystrophy (FSHD)? What are the clinical features

Autosomal dominant disease that is characterised by facial weakness, scapula weakness, biceps and triceps affected but deltoid spared, ankle dorsiflexors and abdo msucles may be affected. Asymmetry is common

313

What are the 2 types of myotonic dystrophy?

Distal and proximal

314

Discuss the inheritance pattern and genetics of myotonic dystrophy

Autosomal dominant; chromosome 19 affected and causes trinucleotide repeat of CTG

315

What are the clinical features of myotonic dystrophy?

Hand weakness, foot drop, ptosis and facial weakness, neck weakness and myotonia (may also include frontal balding, cardiac, daytime sleepiness, diabetes, cataracts and other endocrine involvement)

316

List some of the clinical features of polymyositis and dermatomyositis

Painles weakness, eyes spared and face rarely involved, proximal weakness of gradual onset, may have systemic features

317

List at least 3 drugs than can cause drug-induced myopathies

Corticosteroids, statins, gemfibrozil and chemo agents

318

List the common clinical positive symptoms of schizophrenia

Hallucinations, delusions, thought disorder

319

List the common clinical negative symptoms of schizophrenia

Decreased motivation, altered expressions of emotions, decreased amount or content of speech, anhedonia

320

List the common clinical cognitive deficit symptoms of schizophrenia

Impairements in attention, verbal learning, verbal fluency, executive function and working memory

321

What are the diagnostic criteria for schizophrenia in the DSM V?

1. 2 or more characteristic symptoms present for 1 month of delusions, hallucinations, disorganised speech (formal thought disorder), grossly disorganised or catatonic behaviour, negative symptoms; 2. Reduced functioning (occupational/social/self-care); 3. Duration: continuous signs of the disturbance for at least 6 months

322

On average, people with schizophrenia die ____ years earlier than the general population

12-15 years

323

List the 8 steps in normal neurodevelopment

1. Induction of neural plate (3 weeks post-conception) 2. Neuronal proliferation 3. Neuronal migration and aggregation 4. Axon and dendrite growth 5. Synaptogenesis 6. Myelination 7. Pruning 8. Apoptosis/synapse rearrangement

324

List at least 5 neuropathological findings in schizophrenia

1. Reduced brain weight 2. Enlarged lateral/third ventricles 3. Decreased markers of synapses and dendrites 4. Absence of neurodegenerative changes 5. Absence of gliosis (suggests prenatal brain insult) 6. Cytoarchitectural abnormalities (pyramidal cell disaray)

325

Describe the changes in white matter in a diffusion tensor MRI of a patient with schizophrenia

Thinning in corpus callosum, long intrahemispheric fibre tracts and subcortical projection systems. Abnormal functional lateralisation, impaired interhemipheric transfer, intrahemispheric processing and corticosubcortical information processing loops are affected

326

What is the main neurochemical finding in schizophrenia?

Abnormal dopaminergic neurotransmission

327

List the arguments for the dopamine hypothesis of schizophrenia

Illicit drugs which increase sopamine release (e.g., amphetamines and cocaine) may lead to psychosis; mediation which blocks dopamine receptors reduce schizophreniz symptoms; cannabis increases dopamine release can cause or exacerbate schizophrenia

328

List the arguments against the dopamine hypothesis of schizophrenia

Amphetamines don't act only on dopaminergic neuron; antipsychotics targeting dopamine neurons don't have an immediate effect; antipsychotics have little effect on negative symptoms; hyperdopaminergic state can be a consequence of NMDA hypofunction

329

What changes in GABA are seen in schizophrenia?

GAD (glutamic acid decarboxylase) is the enzyme responsible for the synthesis of GABA, and this enzyme is decreased in the cerebral cortex of patients with schizophrenia

330

Genes involving which 5 chromosomes have been identified in schizophrenia?

1, 2, 8, 13 and 22

331

Which 2 neurotransmitter systems are implicated in schizophrenia?

dopaminergic and glutamatergic

332

Compare positive vs negtive symptoms in neurological disorders

Positive symptoms are experiences that should not be there in a healthy state, whereas negative symptoms tend to be an absence of norma things (i.e., decrease in motivation which would be normal in a healthy person)

333

List some reasons why there is such an excess of death rates in patients with schiozphrenia when compared to the normal population

Diet high in saturated fats and high in fibre, more likey to be smokers etc., poorer access to health care (paranoid, lack of motivation, lack of services etc), life style factors, psychotropic medications

334

Compare the cause of death for men vs women with schizophrenia

Men tend to die more from unnatural

335

What is the chance of developing schizophrenia if you have an identical twin with the disease?

Almost exactly 50%

336

What are the two largest contributors to development of schizophrenia?

Genetics and evironment

337

Screening is a form of what sort of prevention?

Secondary

338

What is screening?

Process of using tests on large scale to identify the presence of disease in apparently healthy people

339

List 4 different types of screening tests?

1. Mass screening 2. Multiple of multiphasic screenin 3. Targeted screening 4. Case-finding or opportunistic screening

340

What is mass screening?

Aims to screen the whole population or subset of

341

What is multiple or multiphasic screening?

Using several different screening tests

342

What is targeted screening?

Screening of groups with specific exposures, e.g., workers in lead bettery factories, is often used in environmental and occupational health

343

What is case-finding or opportunistic screening?

Aimed at patients who consult a health practicitioner for some other purpose

344

List at least 3 reasons to screen patients

1. Reduce morbidity, mortality and disability (heelprick test for CF) 2. Protection of other members of the public (screening of immagrants for HIV and Hep B) 3. Prevention of severe diseases in individuals

345

Screening in prevention is effective if what precention types are not available?

Primordial or primary prevention

346

Discuss the level of prevention provided by HPV vaccination

May prove effective as primary prevention for cervical cancer, but currently secondary prevention of pap smear testing continues

347

What are the 4 requirements for a screening program?

1. Characteristics of disease 2. Quality and acceptability of screening test 3. Disease treatable 4. Net benefit to community from program

348

What are the disease characteristics needed for effective screening?

Disease should be serve and perceived as a problem; High prevalence of pre-clinical disease (not essential if disease severe and test simple); Early intervention must improve outcome (understanding of natural hisotry important); Long lead time (slow progression of disease)

349

At what point during the natrual history of diease is screening ideal?

Critical point 2 - this is the point between the early diagnosis possible and the time that the usual clinical diagnosis would have been make (i.e., screening before the earliest diagnosis or after the clinical diagnosis is not helpful)

350

What are the screening test factors for effective screening?

Safety, acceptable and impose minimal discomfort, easy to administer, inexpensive, accurate and reliable

351

What treatment charactersists are needed for effective screening?

Diagnostic confirmatory testing must be available, treatment must be safe and effective and acceptable, and there must be resources available for screening and follow-up

352

Which measures determine the accuracy of a screening test?

Sensitivity and specificity

353

Is sensitivy or specificity more important in a screening test?

Specificity - don't want to miss anyone

354

When is a test considered to be reliable?

If it provides consistent results

355

When is a test considered to be valid? What measures are used to determine this?

If it correctly cateorises people into groups with and without disease (as measured by its sensitivity and specificity)

356

What is sensitivity?

The proportaion of people with the disease in a screened population who are identified as having the disease by the test (i.e., when the disease is present, how often does the test detect it)

357

What is specificity?

The proportion of disease-free people who are identified as not having disease by a test (when the disease is absent, how often does the test provide a negative result?)

358

If an entire population was screening, prevalence would euqal what other measure?

Pre-test probability

359

The pre-test probablity of the test about to be used =

post-test probability (post predictive value) of the tests just done

360

What is pre-test probability?

The probability that the patient had the condition on the basis of information available before the test was undertaken.

361

How do pre-test probability and PPV relate?

Higher pre-test probability gives higher PPV

362

PPV and NPV change with ____ probability

Pre-test

363

The accuracy of a screening test is defined by what measures?

Positive and negative predictive values

364

What is a high positive predictive value?

The probability of a person having a disease when the test is positive (true positives)

365

What is a high negative predictive value?

The probability of a person not having a disease when the test is negative (true negatives)

366

What factors determine predictive values?

The sensitivy and specificity of the test

367

When the prevalence of a disease in a population is applied to an individual, what is it called?

Pre-test probability

368

When is test with high sensitivity most important?

When a disease is serious and definitive treatment exists, when the disease can be spread, when there is minimal cost and risk of subsequent diagnostic evaluations

369

When is a test with high specificity most important?

When costs or risks of subsequent disagnostic evaluations are substantial, when false positives could harm the patient

370

Discuss the usual situation of PPV in general population screening

Probability that a positive test reflects the true disease (PPV) is very low

371

Discuss the positives and negatives of screening tests used in the general population

Most negatives are true negatives, but most positives are false positives

372

List at least 6 things that make a good screening test

Sensitive and specific, not harmful, acceptable, minimal discomfort, cheap, easy to perform, repeatable (reliable) and appropriate in a given situation regarding predictability

373

Which 3 questions should be considered when determining whether screening is worthwhile?

1. What is the evidence of effectiveness? 2. Does the benefit outweigh the harm? 3. Does the burden of the illness justify the effort?

374

What is the ideal study design for the evaluation with a screening program? How would it be carried out?

RCT; use current screening as control, plus the new screening as the experimental group. If no current program, randomise people to screening vs not screening at the individual level and follow up over time until outcomes are seen (i.e., death or diagnoses). Use intention-to-treat analysis to retain the benefits of randomisation

375

What 3 cancer screening programs exist in Australia?

Colorectal, breast cancer, cervical

376

Screening for prostate cancer is not recommended except in which 2 situations?

1. The man specifically asks for it 2. The man is fully councelled on the pros and cons