Before the Exam Flashcards
(141 cards)
1
Q
what happens when there is damage to the premotor and supplementary motor cortex
A
- damage to areas 6 and 8 either medial or lateral lead to the clinical syndrome of motor apraxia
2
Q
what does damage to the posterior parietal cortex do
A
sensory apraxia
3
Q
what causes oculomotor apraxia
A
bilateral frontal field lesions
4
Q
what happens if you have a lesion in the dorosolateral prefrontal cortex
A
- apathy
- personality changes
- lack of ability to plan or to sequence actions of tasts
- poor working memory for verbal information (if the left hemisphere has a lesion ) or spatial information (if the right hemisphere has a lesion)
5
Q
What happens if you have damage to the orbitofrontal cortex
A
- Disinhibition of these drives after orbital damage leads to pseudopsychopathic behaviour
- This can be defined as impulsiveness, puerility, a jocular attitude, sexual disinhibition, and complete lack of concern for others.
- Patients with such acquired sociopathy, or pseudopsychopathic disorder, are said to have an orbital personality
6
Q
where do the lateral cotricospinal tract and anterior cotricospinal tract run
A
Lateral corticospinal tract runs in the dorsolateral cord
Anterior corticospinal tract in medial ventral cord (only present in the cervical cord)
7
Q
describe the lateral vestibulospinal tract
- origin
- where the nucleus projects
- what does it control
A
- Origins: vestibular nuclei in upper medulla/lower pons
- Nucleus projects ipsilaterally to antigravity muscles
- Tonically active during upright posture
- Controls posture and balance
8
Q
describe the reticulospinal tract
- origin
- where the nucleus projects
- what does it control
A
- Arises in reticular formation of pons and medulla
- Projects diffusely (bilaterally) down spinal cord
- Responsible for autonomic control (drives sympathetic preganglionic neurones) also drive to respiration (phrenic nerve)
- General ‘arousal’ of spinal cord
9
Q
describe the rubrospinal tract
- origin
- what does it do
A
- origin is the red nuclues in brainstem
- carries cerebellar commands to the spinal tract
- probably plays a role in control of movement velocity and transmitting motor commands from the cerebellum to the musculature
10
Q
describe what the tectospianl tract do and where does it originate
A
- a pathway that cooridnates voluntary head and eye movement, it activates reflex movements of the head in response to visual and auditory stimuli
- originates in the superior collicus and projects to the contralteral cervical spinal cord to terminate in lamine VI, VII, VIII
11
Q
describe upper motor neurones
- possible location
- common causes
- structures involved
- distribution
- voluntary movements
- muscle tone
- myotactic reflexes
- cutaneous relfexes
- muscle bulk
- classical description
A
- possible location - CNS only
- common causes - CVA, trauma, MS, ALS, infectious disease
- structures involved - Motor cortex or corticospinal tract
- distribution- never individual muscles, always group of muscles
- voluntary movements - paralysis or paresis especially of skilled movements
- muscle tone -increased, particularly in antigravity muscles
- myotactic reflexes - hyperactive or exaggerated
- cutaneous relfexes - some abnormalities e.g. positive babinski sign
- muscle bulk - may be slight atrophy
- classical description - spastic paralysis
12
Q
describe lower motor neurone lesion
- possible location
- common causes
- structures involved
- distribution
- voluntary movements
- muscle tone
- myotactic reflexes
- cutaneous reflexes
- muscle bulk
- classical description
A
- possible location - CNS or PNS
- common causes- CVA, polio, tumour, trauma, alcoholism, diabetes
- structures involved - spinal or brainstem - motor neurones or peripheral motor axons
- distribution - segmental - limited to muscles innervated by damaged motoneurons or their axons
- voluntary movements - paralysis
- muscle tone - decreased
- myotactic reflexes - decreased or absent
- cutaneous reflexes - decreased or absent
- muscle bulk - pronounced atrophy
- classical description - flaccid paralysis
13
Q
name the functional three zones in the cerebellum and what they comprise of
A
- Vestibulocerebellum comprises Flocculonodular lobe connected to lateral vestibular nucleus (in pons)
- Spinocerebellum comprises Anterior lobe and vermis connected to fastigial, globose & emboliform nuclei – connected to the spinal cord
- Cerebrocerebellum comprises Posterior lobe (cerebellar hemisphere) connected to dentate nucleus – connected to the cerebrum
14
Q
what does the vestibulocerebelum do
A
- coordinates head and eye movement to ensure the stability of gaze
- controls balance of the head on the body via the medial vestibulospinal tract
- control the balance of the body on the ground via the lateral vestibulospinal tract
15
Q
what does the spinocerebellum do
A
2) The Spinocerebellum (anterior lobe and vermis) controls locomotion and limb co-ordination:
- it sends motor commands down the reticulospinal tracts to co-ordinate postural and locomotor movement
16
Q
what does the cerebrocerebllum do
A
- Co-ordinates movement initiated by motor cortex.
- This includes speech, voluntary movements of hands and arms, and hand-eye co-ordination.
17
Q
describe flocculonodular syndrome
A
- Little control of axial muscles
- Wide-based ‘ataxic’ gait, reeling and swaying
- Tendency to fall to side of lesion
- Nystagmus
- Severe cases cannot sit or stand without falling
18
Q
what are the symptoms of anterior lobe damage
A
Ataxia: ataxic gait (overlaps with flocculonodular syndrome) – widely spaced legs in order to keep balance
Hypotonia: generalised muscle weakness and fatigue,
Reflexes may be depressed or pendular (upper motor neurone lesions
19
Q
what symptoms are in neocerebellar syndrime
A
Loss of hand-eye co-ordination.
Dysmetria (inaccurate reaching with intention tremor
Dysdiadochokinesis is the irregular performance of rapid alternating movements of hands
Intention tremors occur on an attempt to touch an object. A kinetic tremor may be present in motion. The finger-to-nose and heel-to-knee tests are classic tests of anterior lobe cerebellar dysfunction. 0inability to flex and extend easily?
Loss of good speech articulation (slurred speech) due to loss of co-ordination of muscles involved in speech production.
There may be a loss of cognitive eye movement (active scanning) and other perceptual difficulties or motor difficulties involving skilled movements (eg playing a muscial instrument)
There may also be deficits in selective attention& perception due to failure of ‘eye movement programs”
20
Q
what gene defects can cause a life without pain
A
Loss of Tranduction/Transmission
Loss of NaV1.7
= (sodium channel subunit)
= Congenital indifference to pain
Loss of C fibres
= trkA - NGF receptor mutation
= Congenital insensitivity to pain with anhydrosis CIPA
21
Q
what are the two types of C fibres
A
- ‘peptidergic’ C fibres release peptides peripherally e.g., Substance P / CGRP
= this leas to Vasoactive, promote inflammatory responses (neurogenic inflammation) and healing; thermal nociception - ‘Peptide-poor’ C fibres have distinct receptors (e.g., P2X3 ATP receptors) and projections
= these leads to mechanical nocicpetion
22
Q
describe the pathway of the anterior spinothalamic (or neospinothalamic) tract
A
- Primary afferent: Aδ fibres as well as input from C (indirect via interneurons) and Aβ fibres innervate →
- Projection neurones in Lamina V – ‘wide dynamic range cells’. After decussating axons travel in the anterior spinothalamic tract
- innervate ventral posterior lateral (VPL) and ventral posterior medial (VPM) – somatosensory thalamus; and ventral posterior inferior (VPI) and central lateral (CL) nuclei of the thalamus (reticular and limbic associated areas).
- The main projection is to the primary somatosensory cortex (SI) from
VPL/ VPM →; localisation & physical intensity of noxious stimulus
- input to SII (secondary somatosensory cortex) via VPI
- and ACC (anterior cingulate cortex; emotion) and prefrontal cortex and striatum via CL (sites for cognitive function/ strategy)
23
Q
describe the pathway of the lateral spinothalamic (or paleospinothalamic) tract
A
- Primary afferent: C fibres but also some Aδ fibres innervate →
- Projection neurones in Lamina I –After decussating axons travel in the lateral spinothalamic tract
- innervate the more posterior/ medial parts of the thalamus
Mediodorsal nucleus (ventrocaudal) (MDvc)
‘Posterior thalamus’ – posterior nucleus (medial subnucleus) (POm) and ventral medial nucleus (posterior) (VMpo)
(also some projections to the VPL, VPM and CL) - Projections to Cortex MDvc → anterior cingulate cortex (ACC); (emotion/ motivation) Posterior thalamus (POm and VMpo) → anterior or rostral insula (emotion, quality i.e. ‘pain’, autonomic integration)
24
Q
describe the three other areas that the lateral spinothalamic tract project to
A
the limbic system
- subjective sensations of pain
- goes via the brainstem and posterior medial thalamus
Midbrain reticular formation
- pain - induced arousal and descending control of nociceptor input
Intralaminar(reticular) nuclei of thalamus
- alerting cerebral cortex and focus of attention of pain
25
How do prostaglandins lead to inflammatory pain
PGs sensitise C-fibres by increasing numbers of other receptors and increasing the number of open sodium channels. There are also central (i.e. spinal cord) sensitising effects
26
what causes the intensity of the pain
- superior parietal lobe and insula and amygdala pathway
27
What feeling causes the unpleasantness of pain
ACC - PFC - PAG path emotion/ placebo control-- unpleasantness
28
How does PAG and the nucleus raphe Magnus inhibit pain
Electrical stimulation of PAG or NRM inhibits spinal thalamic cells, (i.e. spinal neurons that project monosynaptically to the thalamus) in laminae I, II and V so that the noxious information from the nociceptors are modulated at the spinal cord level
Electrical stimulation of the PAG elicits release of endorphin while stimulation of the NRM causes release of serotonin (5-HT).
29
What is the treatment for trigeminal neuralgia
Treatment = carbamazepine, baclofen, phenytoin, valproate, clonazepam, baclofen with carbamazepine
30
what are the other treatment options beyond drugs for epilepsy
Neuromodulation: vagal nerve stimulation, deep brain stimulation
Ketogenic diet (diet high in fat and low in carbohydrates, e.g. 4:1 ratio)
New anti-epileptic drugs: example of cannabidiol for treatment-resistant epilepsy
31
What are the three main areas in the brain that are important in chronic pain
- Sensory/discrimitive pain – localisation in time and space, assessment of intestine, lateral system, lateral thalamic nuclei S1, S2, SMA
- Affective/motivational – emotional/unpleasant aspects, reward in escape, medial system (HG medial thalamic nuclei, ACC, insula)
- Cogntivie/evaluative – interpretation of pain and its meaning, cogntivie system (ACC DLPC)
32
what can happen when MCA stroke occurs
– Dominant hemisphere(depends which hemisphere, tend to be the left hemisphere)
• Global aphasia (don’t understand and cant generate speech), can also have expressive and receptive aphasia if brocas or wernickes area is developed, – left hemisphere damage
• Sensorimotor loss on contralateral face, upper limb and trunk (for either left or right hemisphere)
– If it’s the Non-dominant hemisphere that is damaged
• Neglect syndrome
33
what happens in the anterior cerebral artery stroke
– Contralateral sensorimotor loss below waist – effects the medial wall, therefore effects below the waist
– Urinary incontinence
– Personality defects – if in the frontal lobe
– Split-brain syndrome
34
What are the effects of the posterior cerebral artery stroke
– Contralateral homonymous hemianopsia
– Reading and writing deficits
– Impaired memory (memory is in the temporal lobe which is largely supplied by PCA)
35
What are the symptoms of TIA in
- anterior circulation
- posterior circulation
– Anterior circulation
• Motor weakness
• Hemi-sensory loss
• Dysarthria - difficult or unclear articulation of speech
• Transient monocular blindness – if ophthalmic artery
```
– Posterior circulation
• Vertigo
• Diplopia
• Ataxia
• amnesia
```
36
describe the characteristic of an epidural (extradural) haematoma
– Traumatic
– Blood between dura mater and the skull
– Bleeding rapid (arterial*)
– 2.7-4% of Traumatic brain injury
– Mortality 10% if they are caught early – person seems fine and the next minute they have collapsed
37
describe the characteristics of a subdural haematoma
– Traumatic / Ageing(Chronic)
– Blood between dura mater and arachnoid mater – pushing onto the brain surface
– Rupture to bridging veins – therefore they tend to be venous drainage that has been affected
– These spread more
– Acute 12-29% of severe TBI
– Mortality 40-60%
38
describe the characteristics of a subarachnoid haematoma
```
– Spontaneous
– Between arachnoid and pia
– Ruptured aneurysm or head injury
– 1-7% of strokes
– Arterial
– Most frequent traumatic brain lesion
```
39
what are the symptoms of a subdural haematoma
```
– Irritability
– Seizures
– Headache
– Numbness
– Disorientation
```
40
What are the symptoms of extradural (epidural) haematoma
– As blood collects it compresses intracranial structures
– Compress cranial nerve III
– Weakness of extremities on opposite side of lesion (crossed pyramid pathways)
– Loss of visual field opposite to lesion (compress of PCA)
41
What are the symptoms of a subarachnoid haematoma
• Symptoms
- Severe headache (thunderclap) due to compression of the brainstem and confusion and fluctuations of consciousness
–
– Vomiting
– Confusion
– Lowered / fluctuating levels of consciousness
42
how do you administer gepants v monoclonal abs
Gepants - oral
| Monoclonal abs - IV/SC
43
describe how operant conditoning can lead to drug addiction
Behaviour leading to a central reward (one candidate is dopamine release in the core of nucleus accumbens) gets activated in circumstance in which the reward was attained with the same behaviour previously - example of operant conditioning as person gets a reward for their behaviour therefore they are more likely to do it again
44
name the positive reinforcement involved in drug use
Pleasurable sensation
Satisfaction of biological needs (e.g. cocaine and nicotine reduce hunger)
Social reinforcement, e.g. group membership
45
name the negative reinforcements involved in drug use
Reduction of habitual stress level
Reduction of acute distress
Increased pain threshold
Reduction of withdrawal symptoms
46
describe sensitivity to negative drug effects
Biological sensitivity to drug after-effects (hang-over)
Intensity of withdrawal discomfort
Reactions to withdrawal discomfort
47
describe Sensitivity to positive drug effects
Sensitivity to drugs (genetic/biological factors, but also expectancies)
High habitual stress levels
Absence of other sources of gratification
48
What is currently NICE approved for deep brain stimulation
- Parkinson’s disease (hypokinetic movement)
- essential tremor (hyperkinetic movement)
- dystonia (hyperkinetic movement)
49
describe and name the different types of tremor
there are two main categories these are resting tremor and action tremor
Resting Tremor
- this is when you have a tremor while resting
Action tremor
- either postural, kinetic and intention
- a postural tremor is a tremor when you life a limb such as an arm - holding something against gravity
- Kinetic - occurs with voluntary movement
- Intention - occurs with goal directed movement and worsens as approaching the target
50
Describe the neuronal connections in the limbic system
1. Information goesfrom the cingulate cortex to the parahippocampal gyrus
2. Information goes from the parahippocampal cortex to the hippocampus
3. Information goes from the hippocampus along the fornix to the mamillary bodies of the hypothalamus
4. Information goes from the hypothalamus to the anterior thalamus
5. Information goes from the anterior thalamus back to the cingulate cortex
51
what is kluver bucy syndrome and what are the symptoms
- this is when the subject loses all sense of fear
symptoms
- Psychic blindness (inability to process information).
- Oral tendencies.
- Hypermetamorphism; grabbing objects in view and appropriately using them-
but not at appropriate times.
- Altered sexual behaviour.
- Emotional changes.
52
Describe the pathway of the amygdala
- Septal nuclei is a sensory mechanism, which connects to the reticular formation.
- The RF forwards the signal to the ventral striatum (nucleus accumbens).
- The signal is sent to the amygdala where it can activate fight or flight.
- The commands are sent to the hypothalamus, which is then sent again to the RF.
- The reticulospinal tracts can then be activated and a response triggered.
53
What do plaques and tangles cause to happen
* neurotic dystrophy
* synaptic loss
* selective neuronal cell loss
54
what are the side effects of memantine
```
- less common and less severe than the cholinesterase inhibitors
side effects;
- dizziness
- headahces
- tiredness
- increased blood pressure
- constipation
```
55
What are the symptoms of addiction
Bingeing, having loss of control.
Withdrawal.
Cravings.
Intoxifiacation.
56
describe the mechanism of action underlying withdrawal symptoms
- the ventral tenemental area releases dopamine that will stimulate the dopamine receptors
- neurones receive that input and project back releasing GABA and dynorphin which stimulate Kappa receptors
- Dynorphin will have an inhibitor effect on the VTA neurone and will trigger an unpleasant feeling so in order to get more reward again you need to stimulate it with the drug again
57
What happens in acute MDMA toxicity
* Temperature elevation
* Disseminated intravascular coagulation
* Rhabdomyolysis (blocked by dantrolene) – muslces fall apart, release of protein from the muscles which effect the kidney
* Increased renal reabsorbtion of water
* Hyponatraemia
* Cerebral oedema
58
Where are CB1 receptors concentrated
in the CNS
| Distribution; neocortex, hippocampus, basal ganglia, brainstem
59
What is the typical resting potential
-65mv, this approximates to the potassium equilibrium potential
60
what is the equilibirum potential for sodium
this is the membrane potential at which there is no net flux of sodium across the membrane
+58mv
61
what is the resting potential of a neurone due to
potassium leaking out of the non gated potassium channels
62
what is an autoreceptor
- this is a receptor on the pre-synaptic membrane that is the same shape as the neurotransmitter and can either increase or decrease release of the neurotransmitter
63
describe how a G protein channel works
- single transmitter molecule binds to the G protein and it becomes activated by the displacement of GDP by GTP
- this causes the dissociation of alpha GTP, beta and gamma subunits
- Usually α GTP, but often β and gamma as well, stimulates the effector to bring about the response,
- Return of the G protein to its resting state occurs by α GTP hydrolysing its bound GTP to GDP, with subsequent reassociation with the β and gamma complex
64
Heterooligomeric protein is the typical structure of
ligand gated ion channel
65
what can membrane depolarisations also result from
I) Influx of Ca⁺⁺
II) Closing of K⁺ channels
III) Efflux of Cl
66
What does an action potential result from
(i) an unequal distribution of ions across the membrane due to the activity of the Na⁺/K⁺ pump and
(ii) the presence of a population of non gated K⁺ channels which allows K⁺ to leave the cell down its electrochemical gradient (outward K⁺ current).
67
what voltage is the depolarisation sufficient enough to open voltage gated sodium channels and trigger an action potential
At about -55mV (threshold), the depolarization is sufficient to open voltage gated Na⁺ channel, hence triggering an action potential.
68
what is dopamine broken down into
COMT - HVA
| MAO - DOPAC
69
what does COMT do
- catalyses the transfer of a methyl group S- adenosylmethionine to a donor phenolic hydroxyl group on dopamine
70
what receptors are post synaptic or presynaptic out of D1 and D2
- D1 - these are just postsynaptic and they activate adenyl cyclase
- D2 - these are pre and post synaptic and they inhibit adenyl cyclase
71
Where do you find D1 and D5 receptors
D1 receptors are found mainly in the caudate-putamen, nucleus accumbens and olfactory tubercle, with lesser amounts in the cerebral cortex, limbic system and hypothalamus.
D5 receptors are in the hippocampus and hypothalamus
72
What do D2 receptors do
They exert the following effects:
1. Inhibit adenylate cyclase
2. Activate K+ channels
3. Decrease Ca2+ conductance
4. Potentiate ATP-mediated arachidonic acid release
73
where are D2, D3, D4 receptors found
D2 - Caudate, putamen, nucleus accumbens, olfactory tubercle
D3 - limbic areas (mostly nucleus acumbens and olfactory tubercle)
D5 - fontal cortex, midbrain, amygdala and medulla
74
name the affinity for dopamine receptors for
Raclopride:
Spiperone:
Clozapine:
Raclopride: D2=D3>D4
Spiperone: D2=D4>D3
Clozapine: D4>D2=D3
75
What is 5HT
5-HT (5-hydroxytryptamine, serotonin) is an indolealkylamine neurotransmitter with an uneven distribution in the CNS.
76
where do 5HT fibres primarily project to
medulla
| dorsal horn of the spinal cord
77
what 5HT receptor is ligand gated
5HT-3
| - all the others are G protein coupled receptors
78
```
Where is
5HT1A
5HT1B
5HT1D
5HT1E
5HT1F
```
found
5HT1A
- limbic areas and spinal cord
5HT1B
- striatum, hippocampus, cerebellum, layer IV of the cortex
5HT1D
- olfactory, striatum, cerebellum, limbic system
5HT1E
- in the hippocampus and cortex.
5HT1F
- in the hippocampus and cortex. and uterus
79
what are the auto receptors
5HT1A
5HT1b
5HT1D
80
what are the 5HT2 subtypes coupled to and what do they do
- All three subtypes are coupled to inositol phosphate turnover to increase formation of diacylglycerol and inositol-1,4,5-triphosphate.
81
where is
5HT2A
5HT2B
5HT2C found
5HT2A
- frontal cortex
5HT2B
- limbic and some peripheral tissues such as the gut, heart kidney and lung
5HT2C
- choroid plexus, spinal and supraspinal distribution
82
where is 5HT3 found
- High densities of post-synaptic receptors in the hippocampus, amygdala, area postrema, and some primary afferent terminals in the dorsal horn of the spinal cord.
- Peripheral location in the gastrointestinal tract.
83
where is 5HT4 found and what does it do
High levels in limbic structures and the striatum, but role in the CNS unknown.
Mediate excitation in the CNS by reducing K+ and increasing Ca²+ conductances.
In the periphery, they open voltage gated Ca²+ channels, directly relax oesophageal smooth muscle, indirectly contract other GIT smooth muscle (by releasing acetylcholine) and increase cardiac rate and force of contraction.
84
where is 5ht5A and 5ht5B
5-ht5A receptors are found in the cortex, hippocampus and cerebellum.
5-ht5B receptors have a more limited distribution.
Not expressed in the periphery
85
what drugs bind to 5HT6 and 5HT7
Several antidepressants bind with high affinity to the 5-HT6 receptor.
Several neuroleptics bind with high affinity to the 5-HT7 receptor.
86
What are the withdrawal effects of physical dependence in
- opiates
- barbiturates
- benzodiazepines
- alcohol
Opiates
- Nausea/vomiting
- Hypertension
- Anxiety/agitation/apprehension
Barbiturates
- Sweating
- Tremors
- Delirium tremens (delirium/vivid hallucinations)
- Anxiety/agitation
Benzodiazepines
- Convulsions
- Panic Attacks
- Anxiety/agitation
Alcohol
- Sweating Tremors
- Delirium tremens (delirium/vivid hallucinations)
- Anxiety/agitation
87
What are the two types of chronic tolerance
2a. Cellular tolerance
2b. Pharmacokinetic tolerance- increase in liver enzymes causing metabolism so in order to overcome this you have to take more of the drug
88
How does nicotine act
- Nicotine stimulates nicotinic acetylcholine receptors in the brain to produce its rewarding effects.
89
Where does nicotine act
Nucleus accumbens
- stimulates nicotonic receptors on dopamine neurones leading to the release of dopamine
- helps develop dependence on nicotine
Hippocampus
- stimulation in this area increases attention and may underlie the improvement seen in nicotine
ventral tegmental area
- stimulates nicotonic receptors on dopamine
- this causes the release of dopamine from the nucleus accumbens and ventral tegemental area
- develops dependence
reticular formation
- increases alertness
90
Where do benzodiazepines act
Raphe nuclei
- stimulation of GABA receptors in the dorsal raphe nuclei attenuates the firing of 5HT neurones in this region, this mediates the anxiolytic effect
Reticular formation
- inhibit neurones in the reticular formation to cause sedation
91
What is delirium tremens
```
- withdrawal effect of barbiturates
Delirium tremens – this is a major withdrawal reaction which is very characteristic of sedative hypnotic dependence i.e. not only barbiturates but also alcohol.
This is manifest as:
- Tremors
- Delusions
- Agitation
- Disorientation
- These symptoms usually take some days to develop and last approximately two weeks.
```
92
Where do barbiturates work
Raphe nuclei
- stimulation of GABA nuclei in the dorsal raphe nuclei increases 5HT neurones in this region, they mediate an anxiolytic effect
reticular formation
- inhibit neurones in the reticular formation and cause sedation
93
Where does alcohol work
reticular formation
- Depress the firing of ascending inhibitory neurones at low intake this causes the initial disinhibitory behaviour
Frontal cortex
- higher doses of alcohol inhibit the cortical neurones resulting in hypnotic effects and loss of consciousness
94
describe how cannabis works
- 9-THC binding to CB1 receptors activates G-proteins, that can ultimately activate or inhibit a number of signal transduction pathways.
- The G-proteins directly inhibit N and P/Q-type voltage dependent calcium channels and sodium channels, and indirectly inhibit other calcium channels via inhibition of adenylate cyclase.
- 9-THC binding and G-protein activation also can ultimately activate inwardly rectifying potassium channels and the MAP kinase signalling pathway.
95
where do opiates act
nucleus accumbens
- contains mu-opiate receptors
- stimulation mediates the eurphoric and dependence effects
periaquaductal grey
- stimulation of Mu opiates receptors in this region leads to analegic effects
- opiates also acts directly as anaselgic effects on the kappa opaite receptor stimulating by inhibiting pain transmission in the dorsal root of the spinal cord
ventral tegmental area
- stimulation of Mu opiates, this increases the firing of dopamine neurones
- thus this increases the release of dopamine in the nucleus accumbens
- this contributes to the euphoria and development of dependence
reticular formation
- stimulation of this area causes sedation and can lead to respiratory depression
area postrema
- contains the chemoreceptor trigger zone and this causes nausea and vomiting
96
Where does cocaine act
nucleus accumbens
- causes euphoria
- development of dependence
reticular formation
- increases alertness
hypothalamus
- increases temperature
- decreases food consumption
97
where does caffeine work in the brain
nucleus accumbens
- increases the amount of dopamine that is released
- mediates the pleasurable and dependence part of caffeine
reticular formation
- increases alertness
98
How do Amphetamines work
Amphetamines are indirectly acting sympathomimetics which act to potentiate the effects of catecholamines in three ways:
1. Stimulate release of catecholamines
2. Inhibit their recapture by the uptake system
3. Inhibit monoamine oxidase (MAO) activity
99
In what part of the brain do amphetamines act
Nucleus accumbens
- euphoria
- development of dependence
hypothalalmus
- increases temperature
- decreases food consumption
reticular formation
- increases alertness
100
Name some psychomotor stimulants
- cocaine
- caffiene
- nicotine
- amphetamines
101
Name some CNS depressants
- Barbiturates
- alcohol
- opiates
- benzodiazopines
102
How do you diagnose schizophrenia
• At least two of the following (per DSM-5):
o Delusions.
o Hallucinations.
o Disorganized Speech.
o Disorganized/catatonic behavior.
Catatonic = a variety of abnormal motor postures.
o Negative symptoms (flat effect = inappropriate response, avolition = decreased motivation).
• At least one must be delusions, hallucinations or disorganized speech.
- Continuous signs of disturbance must persist for 6 months, where the patients must experience at least 1 months of active symptoms with deterioration problems occurring over a significant time.
- must be without substance misuse or mood disorder
103
describe the structural changes that occur in schizophrenia
- increased rate of grey matter loss this leads to larger ventricles and smaller medial temporal lobes
- hypofrotnality - decreased frontal lobe activation during cognitive task
- overal brain volume loss
- when measuring event related potentials in schizophrenic patients the reaction to stimulation is increased
104
Name and describe some explanations for the psychotic symptoms of schizophrenia
Corticolimbic Circuits and Dopaminergic Systems
• Hypofrontality leads to excessive striatal dopamine release.
Altered brain Connectivity
• Mainly of the default brain network.
o Increased synchrony of DBN when subjects rest/allow mind to wander in SD.
Possible explanation for psychotic symptoms.
105
Define and describe the symptoms of extrapyramidal side effects
* Dystonia: continuous spasms and muscle contractions
* Akathisia (restlessness)
* Parkinsonism (rigidity)
* Bradykinesia
106
what is neuroleptic malignant syndrome
```
• Rare but potentially lethal complication.
• It is a medical emergency
• Characterized by:
o Hyperpyrexia (high fever)
o Tremor
```
107
what side effect can come with clozapine
- There is a risk of agranulocytosis – therefore blood monitoring is essential
108
describe the different sections of the mental state examination
Appearance (age, sex, ethnicity, appropriateness of dress and self care, anything unusual, signs of emotion, affect - external expression of emotion, mood on face)
Behaviour (appropriateness of interaction, rapport, friendliness/hostility, eye contact, movements, postures)
Speech and the form of thought (rate, rhythm, volume, spontaneity)
Mood (Subjective & Objective, ability to enjoy things, sleep, appetite, libido, energy, negative/positive thoughts, self esteem,) + RISK (hopes and future plans, suicidal thoughts or thoughts of harming others).
Thought content (delusions - paranoid, religious, worries/anxieties, preoccupations/obsessions, signs of thought interference, or passivity
Cognition (orientation in time/ place/ person, attention/concentration, comment on intellectual ability (IQ testing), memory (MMSE, frontal lobe test)
Insight (patients ideas about their condition and illness, health beliefs, attitudes to treatment/medication/talking therapy)
Other psychotic symptoms (thought interference - like in schizophrenia
Perceptions (illusions - false perception of real external stimulus e.g. seeing person in curtains, Hallucinations - false perception in the absence of any real stimulus (can be in any sensory modality).
109
name 4 types of psychoses
Schizophrenia - thought echo, insertion, withdrawal or broadcast, delusions of control of the body (thoughts, actions or sensations), delusional perception, hallucinatory voices commenting or discussing, persistent delusional beliefs, negative thoughts
Drug induced psychosis
Puerperal psychosis - postpartum psychosis, woman with onset of symptoms following childbirth
Delusional disorder - patients present with delusions, but with no accompanying prominent hallucinations, thought disorder, mood disorder, or significant flattening of affect.
110
What is neurosis
lass of functional mental disorders involving distress but neither delusions nor hallucinations
- OCD
- Obsessive compulsive personality
- impulse control
- anxiety disorder
- hysteria
- phobias
111
name the symptoms of neurosis
* Avoidance
* Irritability
* Low mood
* Interferes with life
* Physical symptoms
* Preoccupation and concentration problems
112
what are the mechanisms by which an intracerebral haemorrhage occurs
- Charcot-Bouchard microaneurysms
- Microbleed
- Haemorrhagic transformation of infarcts
- Vasculitis
113
name some complications that can occur with intracerberal haemorrhage
- Local damage
- Local mass effect/herniation – if the haematoma is large enough, can cause subfalcine herniation or tentorial or tonsillar herniation
- Raised ICP – causes brain perfusion to fall (CPP) and leads to ischemia and hypoxia
- Hydrocephalus – if there is an outflow obstruction caused by the stroke, this causes the ventricles to expand and the brain matter to be squashed
114
What are the risk factors for stroke
* Demographic: age, male, race, socioeconomic status
* Lifestyle: smoking, weight, inactivity, alcohol.
```
• Medical:
o Hypertension
o Hypercholesterolaemia
o Diabetes
o Vascular disease
o Cardiac
o Rare Associations.
```
115
describe the Oxford Bamford classification for
- anterior circulation
- posterior cinrcualtion
- lacunar circulation
Anterior circulation – TACI/PACI (15/35%)
- Unilateral motor deficit
- Homonymous hemianopia
- Higher cerebral function (dysphasia, neglect)
Posterior circulation – POCI (25%)
- Pure hemianopia
- Cerebellar sgins
- Diplopia and CN palsy
- Bilateral/crossed sensory motor signs
Lacunar – LACI (25%)
- Pure motor (50%)
- Pure sensory (5%)
- Ataxic hemiparesis (10%)
- Sensorimotor stroke(35%)
116
what is the ABCD2 score
- Age
- Blood pressure
- Clinical features
- Duration
- Diabetes
117
describe what happens in TIA management
CT
- Doppler/CTA
- ECG
- Start Antiplatelets
```
Admit if
Atrial Fibrillation(unless FRT)
Carotid stenosis(for surgery)
>2 in 1 week(forIx)
ABCD2 >4 and no clinic in 24hrs
```
IfABCD2 <4 &none of above
Can refer to local TIA clinic
118
define consciousness, wakefulness and awareness
Consciousness
- full awareness of the self and environment
Wakefulness
- ability to have basic reflexes such as open eyes, cough, swallow and suck
Awareness
- ability to carry out complex thought processes
119
describe the Glasgow coma scale
```
Eye opening response
score
4 = spontaneously
3 = to speech
2 = to pain
1 = no response
```
```
Best verbal response
5 = orientated to time, place and person
4 = confused
3 = inappropriate words
2 = incomprehensible sounds
1 = no response
```
```
best motor response
6 = obeys commands
5 = moves to localised pain
4= flexion withdraws from pain
3 = decorticate
2 = decerebrate
1 = no response
```
Best response = 15
Coma 8 or less
totally unresponsive 3
120
what are the three main categories for the level of consciousness
1, comatose state
2, vegetative state
3, minimally conciseness state
121
what can cause locked in syndrome
- trauma and ishcemia to the ventral pons causing interruption to the corticospinal and corticobulbar tracts causing quadriplegia
- severe cases of guillian barre syndrome
122
what is akinetic mutism associated with
- Associated with Alzheimer’s disease, picks diseases, Creutzfeldt disease
123
What are the areas that are affected by akinetic mutism
Frontal lobe (supplementary motor area, cingulate gyrus),
Basal ganglia (caudate, putamen/globus pallidus)
Mesencephalothalamic regions (midbrain-thalamus)
124
What is the difference between a persistent vegetative state and a permanent vegetative state
Persistent vegetative state
- Vegetative state persisting for at least 1 month after TBI or non-TBI
Permanent vegetative state
- Persists for at least 12 months after traumatic injury
- Vegetative state persisting for at least 3 months after non traumatic causes such as anoxic hypoxia or others
125
what are the characteristics of minimally conscious state
- Recognise verbeal or gestural yes or no responses
- Provide simple verbal
- Follow simple commands
- Provide purposeful movements
- Often after passing through coma and vegetative state
126
what are the characterises of the confusional state
- Interactive communication
- Amnesia/confusion
- Hypokinetic or agitated
- Labile behaviour
127
describe the characteristics of the post confusional state
- Resolution in amnesia/confusion (months to years)
- Cognitive impairments in higher levels, attention, memory retrieval and executive functioning
- Deficits in self-awareness, social awareness, behavioural and emotional regulation
- Achieve functional independence in daily self care
128
what is the diagnostic criteria of the PVS
Cycles of eye opening and closing (appearance of sleep/wake cycle)
Complete lack of self or environment
Complete/partial preservation of hypothalamic and brainstem autonomic functions.
129
Describe how an auditory event related potential works
* Aim to identify a mismatch negativity (MMN, a negative component appearing in the primary auditory and prefrontal cortices around 100-250 ms after an auditory change in a monotonous sequence of sounds
* Aim to identify a P300 (a positive component appearing in the primary auditory and prefrontal cortices around 300 ms after an auditory change in a monotonous sequence of sounds
* The P300 appearance corresponds to activation of a frontoparietal network
130
what waves are used in normal wakefulness
beta waves (13-30hz)
131
what waves are used when you are awake and relaxed
alpha waves (8-12hz)
132
what receptors does orexin bind to
• orexin OX1 and OX2 receptors
133
what does suvroextant result in
o Morning sedation
o Sleep paralysis
o Decreased amnesia
o Decreased confusion
134
what are complications of benzodiazepine use in the elderly
- Psychomotor impairment
- Risk of falls
- Daytime drowsiness
- Intoxication
- Amnesia
- Depression
- Respiratory problems
- Abuse and dependence
135
Where does the control of sleep and wakefulness happen
- controls happens in the reticular formation of the pons
| - this is modulated by the hypothalamus which decides when we need to sleep
136
what do orexin stimulate the release of
* Acetylcholine
* Noradrenaline
* Serotonin.
* Dopamine
137
describe how the locus coeruleus activates the alertness and attention system
. The locus coeruleus is a “control centre ’for the sympathetic nervous system, but it also projects rostrally to the cerebral cortex and activates a form of ‘central sympathetic system’
- This central noradrenaline system activates our brain’s ALERTNESS AND ATTENTION systems. With it switched off we are inattentive to the outside world.
138
What are the most common symptoms of multiple sclerosis
- sensory and motor problems - can experience numbness or tingling down arms and legs, or an electric current sensation down he back of the legs or useless hand syndrome
- vision problems; vision blurriness or loss or diplopia
- slow progressive or subacute motor defeicts
What symptoms of MS occur in less than 5% of patients
- Bladder dysfunction
- Heart intolerance
- Paroxysmal symptoms
- Pain
- Movement disorders
- Dementia
139
what are the types of MS that can occur
relapsing remitting
- this is when an attack will occur but then go back to baseline - this is the most common type and affects 75-90% of patients
primary progressive
- patient never relapses and progressively gets worse
secondary progressive
- between relapses the disease gets worse
140
what are other differential illnesses in comparison to MS
- Cerebrovascular disease
- Syphilis
- Lyme borreliosis
- SLE
- Vitamin B12 deficiency
- Rare hereditary diseases
141
```
what isa
- proactive lesion
- chronic active lesion
- chronic inactive lesion
in MS
```
Proactive
- activated microglia and loss of myelin
- lymphocyte infiltration around the blood vessel
chronic active lesion
- lymphocyte spread out around the lesions
- macrophages engulf myelin and sit on the lesions edge
chronic inactive lesion
- attempt at demyelination
- however there is already significant demyelination and axonal loss
- forms an astrocytic scar
