Session 8 Flashcards

1
Q

Describe the fine structure of the cerebral cortex

A

Arranged as 6 layers containing cell bodies and dendrites (i.e. cortex is grey mater) 

Most outputs from the cortex are the axons of pyramidal neurones (e.g. upper motor neurones in the primary motor cortex are pyramidal neurones) 

Outputs can be projection fibres going down to brainstem and cord (e.g. upper motor neurones) 

Outputs can be commissural fibres going between hemispheres (e.g. corpus callosum) 

Outputs can be association fibres connecting nearby regions of cortex in the same hemisphere (e.g. arcuate fasciculus) 

Most inputs are from thalamus and other cortical areas - An important population of inputs arise from the reticular formation, maintaining cortical activation (consciousness) 

Interneurones connect inputs and outputs in a complex way, giving rise to behaviour, emotion, memory etc.

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2
Q

What are the frontal lobe functions and how might these be affected with cortical damage?

A

 Frontal lobe functions, with effects of cortical damage

o Motor 

  • Primary motor cortex and associated areas are here 
  • Frontal lobe damage can result in contralateral weakness

o Expression of speech (usually left hemisphere) 

  • Broca’s area is here 
  • Damage to left frontal lobe can result in expressive dysphasia

o Behavioural regulation / judgement 

  • Prefrontal cortex etc. is here 
  • Damage to frontal lobes can lead to (usually) impulsive, disinhibited behaviours e.g. sexual inappropriateness, aggression

o Cognition 

  • Prefrontal cortex etc.

- Frontal lobe damage (particularly the right) can cause difficulty with tasks such as complex problem solving, including calculation

o Eye movements 

  • Contain the frontal eye fields 
  • Damage can cause problems with conjugate gaze and other eye movement disturbances (however, diplopia without other cortical features would suggest brainstem/cranial nerve problem)

o Continence 

  • Contain cortical areas responsible for maintenance of continence (e.g. paracentral lobules) 
  • Damage can cause urinary incontinence
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3
Q

What are the functions of the parietal lobe and the effects of cortical damage there?

A

o Sensory 

  • Contains primary sensory cortex and associated areas 
  • Damage might result in contralateral anaesthesia affecting all modalities (modalities converge at the cortex)

o Comprehension of speech 

  • Contains part of Wernicke’s area 
  • Damage to left parietal lobe can cause a receptive dysphasia

o Body image and awareness of external environment 

  • Seems to be involved with acknowledgement that things (including the body) exist 
  • Damage to right parietal lobe can lead to neglect.

o Calculation and writing 

  • Works with frontal lobe to perform these tasks 

Damage to left parietal lobe can affect calculation ability (but maybe also frontal lobe)

o Although not a cortical function, remember that the superior optic radiation projects through the parietal lobe 

  • Damage here can cause a contralateral inferior homonymous quadrantanopia
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4
Q

What are the functions of the temporal lobe and what would be the effects of cortical damage?

A

o Hearing 

Primary auditory cortex sits on superior surface of temporal lobe, near to Wernicke’s area

Damage can lead to a number of complex effects on hearing which are not the remit of

the unit. Auditory hallucinations may be a feature of temporal lobe lesions

o Olfaction 

Primary olfactory cortex sits on the inferomedial aspect of the temporal lobe 

Damage can lead to a number of complex effects on smell which are not the remit of the unit.

Olfactory hallucinations may be a feature of temporal lobe lesions

o Memory 

The hippocampus is a crucial structure for consolidating declarative memories 

Damage may lead to amnesia (but remember that there are two hippocampi, one in each temporal lobe). Also, some pathologies such as temporal lobe epilepsy can trigger memories, leading to a feeling of deja vu

o Emotion 

Temporal lobes contain a number of limbic system structures such as the hippocampus and amygdala 

Effects of lesions are complex, but may be related to pathogenesis of some psychiatric disorders

o Although not a cortical function, remember that the inferior optic radiation projects through the temporal lobe 

Damage here can cause a contralateral superior homonymous quadrantanopia

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5
Q

What is cerebral dominance?

A

o Some functions are represented more prominently in one hemisphere 

In 95% of people, the left hemisphere is dominant for language and mathematical/logical functions 

In 95% of people the right hemisphere is dominant for body image, visuospatial awareness, emotion and musical ability

o Knowledge of cerebral dominance allows us to predict the effects of lobe lesions (e.g. a dysphasia is likely to have arisen from left hemisphere damage)

o The corpus callosum allows the two hemispheres to communicate with one another, meaning we can be thought of as an ‘average’ of the two hemispheres 

Destruction of the corpus callosum can cause some interesting deficits such as alien hand syndrome and subtle effects on language processing

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6
Q

What is Broca’s area and what does it do?

A

In the infero-lateral frontal lobe 

Sits near to mouth/pharynx area of primary motor cortex 

Responsible for the production of speech 

Damage can cause staccato speech, where the patient still understands what is being said to them (Broca’s / expressive dysphasia)

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7
Q

What is Wernicke’s area and what does it do?

A

 At the parieto-temporal junction 

Sits near to primary auditory cortex in temporal lobe 

Responsible for the comprehension of speech 

Damage can cause fluent, nonsensical speech where the patient does not appear to understand what is being said to them (Broca’s / receptive dysphasia)

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8
Q

How can middle cerebral artery infarcts affect verbal language fucntion?

A

Large middle cerebral artery infarcts can cause am dense / global aphasia where both areas are destroyed leading to virtually no verbal language function

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9
Q

How are Broca’s and Wernicke’s areas connected?

A

Broca’s and Wernicke’s areas are connected by the arcuate fasciculus 

Damage to this white matter pathway can cause the inability to repeat heard words

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10
Q

What are the types of memory and how is memory stored in the brain?

A

o Memories are believed to be stored across wide areas of the brain

o Types of memory: 

Declarative / explicit 

Factual information 

Tends to be stored in cerebral cortex 

Nondeclarative / implicit 

Motor skills 

Emotion 

Tends to be stored in subcortical structures (e.g. basal ganglia) and cerebellum 

Short term memory 

Stored for seconds to minutes as a ‘reverberation’ or ‘echo’ in cortical circuits 

Long term memory 

Stored for very long periods in the cerebral cortex, cerebellum etc. (up to a lifetime) following consolidation

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11
Q

What is memory consolidation?

A

 Converting short term memories into long term memories 

Factors influencing consolidation:

o Emotional context (if an event has strong emotional content, then it tends to be remembered better)

o Rehearsal (you are all familiar with this idea)

o Association (if you can associate a piece of knowledge with something you already know it tends to be more easily remembered) 

The hippocampus helps to consolidate declarative memories

The hippocampus sits deep in the temporal lobe (in fact, it is the rolled medial edge of the temporal lobe) 

It has multimodal inputs from many brain systems (making it good at associating stimuli)  It has a role as an ‘oscillator’, facilitating consolidation of memories in the cortex via its output pathways (primarily the fornix⇒ mammillary bodies⇒ thalamus⇒cortex) 

Long term potentiation (LTP) is the key molecular mechanism of memory consolidation 

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12
Q

What is long term potentiation (LTP) of memories?

A

Long term potentiation (LTP) is the key molecular mechanism of memory consolidation 

Causes changes in glutamate receptors in synapses leading to synaptic strengthening 

New physical connections can also form between neurones to further strengthen connections (axonal sprouting)

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13
Q

What is consciousness?

A

o A very slippery concept

o Related to awareness of external environment and internal states

o Arousal is a related concept which is associated with goal-seeking behaviour and avoidance of noxious stimuli

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14
Q

What are the two neural components required for consciousness?

A

Consciousness requires two neural components to be functioning normally, and connected to each other

o Cerebral cortex – the site where conscious thoughts arise -Receives many inputs, including from the reticular formation

o Reticular formation (particularly the reticular activating system in the brainstem) – the circuitry that keeps the cortex ‘awake’ - Receives many inputs, including from the cortex and sensory systems

o Cortex and reticular formation are connected by reciprocal excitatory projections, forming a positive feedback loop - Positive feedback loops are seen when there is a binary outcome (e.g. sleep/awake, ovulating/not ovulating etc)

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15
Q

Describe outputs from the reticular formation to the cortex

A

o Occurs via three major relay nuclei

o Reticular formation sends cholinergic (excitatory) projections to these relays 

  • Basal forebrain nuclei send excitatory cholinergic fibres to cortex (think sedative side effects of anticholinergics) 
  • The hypothalamus sends excitatory histaminergic fibres to the cortex (think sedative side-effects of sedating antihistamines) 
  • The thalamus sends excitatory glutamatergic fibres to the cortex

o The reticular formation also sends projections down the cord, responsible for maintaining muscle tone

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16
Q

How is consciousness assessed clinically?

A

Glasgow Coma Scale

 Four components, looking for best response in each

• Eye opening

o Spontaneous eye opening (4) suggests normal cortical and brainstem function

o Response to speech (3) suggests slightly diminished cortical function but still functioning brainstem

o Response to pain (2) suggests impaired cortical function but brainstem preserved so that reflex opening can occur

o No response (1) suggests severe damage to brainstem +/- cortex

• Motor response

o Obeys commands (6) suggests normal function with working connections from auditory system to brainstem/cord

o Localises to stimuli (5) suggests diminished higher cortical function but still connections working from sensory to motor cortex

o Withdraws to pain (4) suggests that there is still a ‘physiological’ reflex response to stimuli

o Flexor response to pain (3) suggests a lesion above the level of the red nuclei. This response is still ‘semiphysiological’

o Extensor response to pain (2) suggests a lesion below the red nuclei. This response is not physiological at all

o No response to pain (1) suggests severe damage to brainstem +/- cortex

• Verbal response

o Oriented in time/place (5) suggests normal cortical function

o Confused conversation (4) suggests diminished higher cortical function but language centres are still functioning adequately

o Inappropriate words (3) suggests language centres have been damaged

o Incomprehensible sounds (2) suggests cortical damage with brainstem mediated groans

o No response (1) suggests severe damage to brainstem +/- cortex

17
Q

What is an electroencephalogram

A

o Measures the combined activity of thousands of neurones in a particular region of cortex

o High temporal resolution, low spatial resolution

o Good for detecting neuronal synchrony (a phenomenon which occurs commonly in the brain during both physiological and pathological processes such as sleep and epilepsy), and evidence of normal cerebral function

18
Q

What are the functions of sleep?

A

 Generally unknown 

Energy conservation / repair? 

Memory consolidation? 

Clearance of extracellular debris? 

‘Resetting’ of the CNS?

19
Q

What are the stages of sleep?

A

 4 major stages + rapid eye movement (REM) sleep 

Typically pass through around 6 cycles of sleep per night 

Stages are characterised by typical EEG pattersn

• Awake with eyes open

o Beta waves – irregular, 50Hz

• Awake with eyes closed

o Alpha waves – regular, 10Hz

• Stage 1 sleep

o Background of alpha + interspersed theta waves (theta at around 5Hz, regular)

• Stages 2/3 sleep

o Background of theta + interspersed sleep spindles and k-complexes: 

  • Sleep spindles are high frequency bursts arising from the thalamus 
  • K-complexes represent the emergence of the ‘intrinsic rate’ of the cortex

• Stage 4 sleep

o Delta waves – regular, 1Hz 

  • Related to k-complexes seen in stages 2/3

• REM sleep

o EEG similar to beta waves

o Dreaming occurs in this stage, so similar to the EEG in a conscious patient

20
Q

Describe the neural mechanism of non-REM sleep?

A

 Complex 

Deactivation of the reticular activating system (and hence cortex) + inhibition of the thalamus 

This deactivation is facilitated by removal of sensory inputs (fewer positive influences on positive feedback loop)

21
Q

Describe the neural mechanism of REM sleep

A

 Initiated by neurones in the pons (i.e. initiation appears to be an active process) 

Similar EEG to when awake with eyes open (beta waves), but difficult to rouse due to strong thalamic inhibition
 Decreased muscle tone due to glycinergic inhibition of lower motor neurones 

Eye movements and some other cranial nerve functions can be preserved (e.g. teeth grinding) 

Autonomic effects are seen (e.g. penile erection, loss of thermoregulation) 

Essential for life – long term deprivation leads to death

22
Q

What is insomnia?

A

Habitual sleeplessness; inability to sleep.

Commonly caused by underlying psychiatric disorder as opposed to ‘primary’ insomnia

23
Q

What is narcolepsy?

A

Condition characterized by an extreme tendency to fall asleep whenever in relaxing surroundings.

  • Rare disorder
  • Some cases are caused by mutations in the orexin gene. Orexin is a peptide transmitter involved in sleep
24
Q

What is sleep apnoea ?

A

Potentially serious sleep disorder in which breathing repeatedly stops and starts.

  • Common condition, often caused by excess neck fat leading to compression of airways during sleep and frequent waking
  • Causes excessive daytime sleepiness
25
Q

How can microorganisms gain access to the CNS?

A

o CNS normally sterile

o Microorganisms can gain entry via: 

Direct spread (from middle ear, basal skull fracture, even through ethmoid bone) 

Blood-borne in sepsis or infective endocarditis 

Iatrogenic (post neurosurgery, ventriculoperitoneal shunt, lumbar puncture

26
Q

What is Meningitis?

A

 Potentially life threatening condition 

Inflammation of leptomeninges (pi-arachnoid)

• +/- septicaemia (remember that non-blanching rash is a sign of meningococcal septicaemia, not meningitis per se) 

Causative organisms:

  • Neonates – E. coli, L. monocytogenes
  • 2-5 years old – H. influenza
  • 5-30 years – N. meningitidis (‘meningococcus’)
  • Immunocompromised patients – a variety of organisms e.g. fungi 

‘Chronic’ meningitis

  • Caused by M. tuberculosis
  • Granulomas
  • Meningeal fibrosis
  • Cranial nerve entrapment
  • Bilateral adrenal haemorrhage (Waterhouse-Friederichsen syndrome) can occur as a complication 

Complications of meningitis

• Local

o Death due raised intracranial pressure

o Cerebral infarction (stroke)

o Cerebral abscess

o Subdural empyema

o Epilepsy (due to direct irritation of brain)

• Systemic

o Resulting from septicaemia

27
Q

What is Encephalitis?

A

Usually viral 

Inflammation of brain parenchyma not meninges (but can occur as a complication of meningitis) 

Virus kills neurones causing inflammation and presence of intracellular viral inclusions. Lymphocytic infiltrate typical

  • Temporal lobe affected by Herpesviruses (most common)
  • Spinal cord affected by polio (now eradicated)
  • Brainstem affected by rabies (very rare)
28
Q

What are Prion diseases?

A

Prion protein (PrP) is a normal protein found in synapses (unknown function) 

PrP can transform into PrPsc (abnormal form) following sporadic mutation, familial inheritance of mutated gene or following ingestion of PrPsc itself

  • PrPsc can convert PrP into itself (i.e. induce a conformational change) by protein-protein interactions alone
  • PrPsc is extremely stable (resistant to disinfectants, irradiation) and not susceptible to immune attack as it is essentially a ‘self’ sprotein 

PrPsc causes damage by forming aggregates which destroy neruones and cause the brain to take on a sponge-like (spongiform) appearance

Spongiform encephalopathies:

  • o Scrapie in sheep
  • o BSE in cows (‘mad cow’ disease)
  • o Kuru in New Guinean tribes (due to cannibalism and ingestion of PrPsc)
  • o Creutzfeld Jacob disease (CJD) 
    • Variant CJD (vCJD)
      • First described in 1996
      • Different from ‘classical’ CJD
      • Strongly linked to BSE through ingestion of prions
      • Essential difference compared to classical CJD is that there seems to be a much higher prion load associated with earlier age at death and more prominent psychiatric symptoms

Unclear as to whether this is an infection as does not completely fulfil all of Koch’s postulates

29
Q

What is Dementia?

A

Acquired global impairment of intellect, reason and personality without impairment of consciousness 

Alzheimer’s disease (50% of cases)

  • Loss of cortical neurones
    • Leading to cortical atrophy and decreased brain weight
    • Damage caused by neurofibrillary tangles and amyloid plaques 
      • Tangles
        • Intracellular twisted filaments of Tau protein
        • Tau normally binds to microtubules
        • Hyperphosphorylation of tau is thought to lead to tangle formation 
      • Plaques
        • Foci of enlarged axons, synaptic terminals and dendrites
        • Amyloid deposition in centre of plaque associated with vessels
        • Trisomy 21 associated with Alzheimer’s disease (amyloid precursor protein (APP) found on this chromosome hence extra ‘dose’ of gene in patients with Down’s syndrome
  • Associated gene mutations
    • APP
    • Presenelin genes
30
Q

What is normal intraccranial pressure and what can cause it to rise?

A

Normal intracranial pressure (ICP)

  • 0-10mmHg
  • Coughing/straining can increase it to 20mmHg
  • Compensatory mechanisms in place to compensate for increased pressure
    • Reduced blood and CSF volume
    • Brain atrophy if chronically elevated
  • Cerebral blood flow can be maintained as long as ICP <60mmHg 

Space occupying lesions (e.g. tumour)

  • Deforms or destroys surrounding brain
  • Displaces midline structures – loss of symmetry, midline shift
  • Can cause brain herniation where part of the brain protrudes through a wall that normally contains it
    • Subfalcine herniation 
      • Cingulate gyrus is pushed under the free edge of the falx cerebri 
      • Herniated brain can become ischaemic due to compression of anterior cerebral artery (which normally loops up around corpus callosum and can get pinched)
    • Tentorial herniation 
      • Medial temporal lobe (classically the uncus) pushed down through the tentorial notch (free edge of tentorium cerebelli) 
      • Can compress ipisilateral oculomotor nerve and ipsilateral cerebral peduncle causing ipsilateral third nerve palsy but contralateral UMN signs in limbs 
      • Can be complicated by secondary brainstem haemorrhage (Duret haemorrhage) – often fatal 
      • Usual mode of death for those with large brain tumours or severe intracranial haemorrhage

Brain tumours

  • o Generally rare 
    • Benign
      • • Meningioma (from meninges) 
    • Malignant
      • • Astrocytoma
        • Low grade slow growing but difficult to remove
        • High grade aka glioblastoma multiforme
        • Direct spread along white matter pathways
        • Can also spread to distant parts of CNS via CSF
    • Others
      • Neurofibroma (from Schwann cells of peripheral or cranial nerve)
      • Ependymoma (from ependymal cells lining ventricular system)
      • Neuronal tumours (from neurones, extremely rare)
      • From non-CNS tissues:
        • o Lymphomas
        • o Metastases (most common of all brain tumours)
31
Q

What is stroke, what is the prevalence of stroke, risk factors, pathogenesis, types and symptoms?

A

A sudden event producing a disturbance of CNS function due to vascular disease 

2 per 1000 of general population per year but more frequent in elderly 

A variety of described syndromes depending on which parts of brain affected 

Risk factors include hyperlipidaemia, hypertension, smoking, diabetes 

Pathogenesis

  • Embolism (most common)
    • Various sources: 
      • Heart (due to AF, mural thrombus) 
      • Atheromatous debris (carotids) 
      • Thrombus over ruptured plaque 
      • Aneurysms
  • Thrombosis
    • Over atheromatous plaque 

Cerebral infarction (85% of all strokes)

  • Regional
    • In the territory of a named cerebral artery
  • Lacunar
    • o Small (less than 1cm area affected)
    • o Associated with hypertension
    • o Commonly affect basal ganglia and internal capsule 

Cerebral haemorrhage (15% of all strokes)

  • Usually spontaneous (i.e. non-traumatic)
    • Intracerebral haemorrhage (10% of all strokes) 
      • Associated with increased age, hypertensive vessel damage and amyloid deposition in vessels
      • Charcot-Bouchard aneurysms are seen (aneurysms of the brain vasculature which occur in small blood vessels. Charcot–Bouchard aneurysms are most often located in the lenticulostriate vessels of the basal ganglia)
      • May be inherited 
      • Produces a space occupying lesion
    • Subarachnoid haemorrhage (5% of all strokes) 
      • Rupture of berry aneurysms, usually found at branch points in circle of Willis
      • Blood in subarachnoid space can cause secondary spasm of cerebral arteries 
      • Associations
        • Male
        • Hypertension
        • Atherosclerosis
        • Linked to other diseases (e.g. connective tissue disorders, congenital weakness in vessel walls?) 
      • Symptoms
        • Thunderclap headache
        • May be preceded by a ‘sentinel’ headache
        • Loss of consciousness
        • Often instantly fatal