Week 37- The Skull and an overview of Brain function Flashcards
1
Q
What are the brains primary sources of fuel?
A
Glucose and oxygen
2
Q
How does glucose and oxygen enter the brain?
A
Has to pass the blood brain barrier
3
Q
What is Glucose and oxygen used for in the brain?
A
To produce ATP –> to support normal brain function
4
Q
What is the potential pathologies associated with the brain not being able to utilise fuel?
A
- Supply reduction
- Altered BBB
- Decreased ATP production within cells
- Reduction in brain functionality
5
Q
What % body weight is the brain?
A
2%
6
Q
How much blood flow, glucose and O2 does the brain utilise?
A
15% blood flow output
20% of total O2 consumption
65% of blood glucose
7
Q
What are the fuel types apart from glucose used by the brain?
A
Glucose is main fuel
- Lactate –> supplementary fuel source
- Ketone bodies –> minor/supplementary source
- Phosphocreatine (Emergency supply under anaerobic conditions)
8
Q
What are the emergency fuels used by the brain?
A
Phosphocreatine (anaerobic)
Anaerobic metabolism of glucose to lactate for limited ATP
9
Q
What is ATP required for within the brain?
A
Maintaining resting potential ion gradients:
Na+/K ATPase –> using ATP to pump Na+ and K+ against their concentration gradients
10
Q
How is glucose transported across the BB and into neurons?
A
Facilitated diffusion
11
Q
What transporters are used in the brain for glucose transport and what are the differences between them?
A
- GLUT1 –> present on BBB endothelial cells and astrocytes
2. GLUT3 –> present on neurons –> 5x the transport capacity than GLUT1
12
Q
What happens in GLUT1 deficiency syndrome?
A
Defective glucose transport across BBB
- -> low glucose in CSF when glycaemia levels are “normal”
- -> leads to infantile seizures and developmental delay
- -> chronic epilepsy
13
Q
How can the affinity and capacity of glucose transport in the brain be described?
A
High affinity
High capacity
14
Q
How is lactate transported across the BBB?
A
Across BBB epithelium down its concentration gradient via MCT1 facilitated diffusion
15
Q
Where does the brain get its blood supply?
A
Four arteries:
Internal carotid arteries (80% of flow)
Vertebral arteries (20%)
16
Q
Where do the four brain supplying arteries meet before the brain?
A
Circle of Willis –> base of the brain
17
Q
How far are brain neurons from blood supply?
A
Within 20um of a capillary
18
Q
What is the blood-brain barriers role?
A
is a dynamic and highly selective permeable interface between central nervous system (CNS) and periphery that regulates the brain homeostasis.
19
Q
What exactly is the blood-brain barrier?
A
It is capillaries with many tight junctions that seal the endothelial cells along with a thick basement membrane around the capillaries.
20
Q
What is the roles of the pericyte?
A
- Regulates endothelium tight junctions
- Secrete basement membrane (basal lamina)
- Contractile properties of the pericyte give it the ability to regulate capillary blood flow
21
Q
What part of the astrocytes interacts with the capillaries of the blood-brain barrier?
A
The processes
22
Q
What do astrocytes do in relation to the BBB?
A
Press processes up against the capillaries
Secrete chemicals to maintain the endothelial cell tight junctions
Therefore –> reinforces the highly-selective permeability nature of the endothelium
23
Q
What does the BBB control the exchange of?
A
Ions
Molecules
Cells
24
Q
Why does the BBB control the entrance of things coming into the brain?
A
- Insulate the brain from toxins and invading pathogens
2. Maintaining its status as a immune-privileged organ
25
What types of transport is allowed by the BBB?
Paracellular transport
| Transcellular transport
26
What is paracellular transport and what regulates it within the brain?
1. refers to the transfer of substances across an epithelium by passing through the intercellular space BETWEEN the cells.
2. Within the brain this process is regulated by endothelium tight junctions
27
What is transcellular transport and what regulates it within the brain?
1. where the substances travel THROUGH the cell, passing through both the apical membrane and basolateral membrane
2. Within the brain this process is regulated by endothelium cell membrane transporters, pumps and receptors
28
What are some examples of channel mediated substance transport in the brain?
H2O, Na+, K+, Cl-
29
What are some examples of membrane transport in the brain?
```
Small lipophilic molecules
Anaesthetics
Ethanol
Nicotine
Caffeine
```
30
What are some examples of carrier-mediated transport in the brain?
Energy transport systems:
1. Glucose --> Glut 1
2. Lactate, monocarboxylates, pyruvate (MCT1)
3. Creatine (CrT)
Amino acid transport systems:
1. Large neutral AAs --> (LAT1)
31
What are some receptor mediated transporter examples for the brain?
```
Insulin
Transferrin
Leptin
IgG
TNF alpha
```
32
What are some examples of adsorption-mediated transcytosis systems in the brain?
Histone
| Albumin
33
What are some active efflux transporters in the brain?
P-glycoprotein
BRCP
MRP 1,2,4,5
34
What happens during Anaerobic glycolysis?
Pyruvate and NADH build up
Drives lactate production
Too much lactate --> lactic acidosis
Low yield ATP production compared to aerobic
35
What is the mechanism of Creatine production and utilisation in the brain?
1. Creatine synthesised --> two steps with AGAT and GMAT enzymes
2. Taken up into cells via SLC6A8 transporter
3. Allows ATP regeneration and high energy phosphate shuttling though the Cr/PCr/CK system
36
What is the main use of Creatine in the brain?
Alternative fuel --> used for ATP regeneration and high energy phosphate shuttling
37
When is Ketone bodies used as a fuel source in the brain?
1. During hypoglycaemia
| 2. During situations of intense neural activity
38
Where is lactate generated for use in the brain?
1. Astrocytes --> during glycogen breakdown (glycogenolysis)
2. Muscles --> from muscle pyruvate during anaerobic glycolysis (cori cycle) --> lactate enters the blood --> uptaken in the brain
39
How long can lactate extend neuronal function during hypoglycaemia?
More than 20mins
40
What is the mechanism suspected for the astrocyte to neuron lactate shuttle hypothesis?
1. Glucose into astrocytes via GLUT1
2. Glucose converted to glucose-6-phosphate (Glc-6-P)
3. Glucose-6-phosphate --> glycogen via glycogen synthase (GlyS)
4. During greater energy demand glycogenolysis reforms Glc-6-P
5. Synaptic transmission induces glycolysis and lactate production through glutamate uptake
6. Astrocyte lactate is transported into the extracellular space by MCT1
7. From extracellular space into neurons by MCT2
8. Neurons convert lactate to pyruvate for oxidative phosphorylation
41
Does the brain store glucose?
No --> it requires continuous supply of glucose and O2 to generate ATP via aerobic glycolysis
42
What are the effects of altered blood supply in the brain?
1. Sodium potassium (Na+/K+) exchanger maintains resting membrane potentials
2. Runs on ATP --> no ATP production pump no longer active
3. Sodium will begin to accumulate in the cells cause them to depolarise
4. Depolarisation leads to action potentials
5. Action potentials lead to neurotransmitter release:
- Impaired cognition
- Euphoria
- Convulsions
- Unconsciousness
- Continued inappropriate excitation --> seizures
43
What is an Excitatory Amino Acid (EAA) injury?
Neuronal death and injury caused by overstimulation of excitatory amino acid receptors by glutamate --> also termed excitotoxicity
44
What is the mechanism behind EAA injury?
1. Brain trauma --> ischaemia
2. Ischaemic cascade
3. Release of glutamate into extracellular space
4. Glutamate binds to NMDA receptors
5. Increase in intracellular calcium
6. Intracellular enzymes released
7. Cause neuronal injury and death
45
What are some effects of excessive glutamate?
1. Altered cell permeability
2. Release of toxic chemicals
3. Increase in nerve damage from electrolyte imbalance (cation influx)
4. Axon swells and bursts
5. Protease activated --> further damage to neurons
46
What is vasogenic oedema caused by?
Increased permeability of the capillary epithelium
47
What is cytotoxic oedema caused by?
Increase permeability of the parenchyma
48
What is interstitial oedema caused by?
Increased permeability of the ependymal cells
49
What is Oncosis?
A process of cellular death characterised by cellular swelling caused by a failure in ion pump function
50
Define cerebral ischemia?
Condition where there is insufficient blood flow to the brain to meet metabolic demands
51
What is the difference between Hypoxia and Anoxia?
Hypoxia is an oxygen deficiency reaching tissues
| Anoxia is an absence of oxygen reaching tissues (severe hypoxia)
52
What is the difference between hypoxic/anoxic ischaemia and anaemic ischaemia?
```
Hypoxic = lack of oxygen reaching tissues
Anaemic = lack of oxygen carrying capacity inducing hypoxic conditions at tissues
```
53
What is brain reperfusion?
Blood/oxygen is returned to the brain
54
What is a reperfusion injury mechanism?
Inflammatory response may occur
Phagocytic cells engulf damaged cells
BBB damaged by toxic chemicals
Cerebral oedema due to leakage of large molecules like proteins from blood vessels through BBB
55
What is a synapse?
Junction between two nerve cells consisting of a small gap in which impulses pass across via diffusion of neurotransmitters
56
What is pre-synaptic?
Relating to a nerve cell that releases a transmitter substance during transmission of an impulse
57
What is post-synaptic?
A neuron or cell body or dendrite of which the electrical impulse is transmitted across the synapse to from the presynaptic neuron
58
What is an example of an excitatory neurotransmitter?
Glutamate --> leads to opening of Na channels in the post synaptic neuron
--> Na in the post synaptic cell causes an action potential to continue the impulse transmission
59
What is an example of an inhibitory neurotransmitter?
GABA --> leads to flooding of the post synaptic end with negatively charged Cl- --> action potential is not generated to fire the post synaptic neuron
60
What is the other name for a neurons cell body?
Soma
61
What is the processes off cell bodies called?
Dendrites
62
What do neurons communicate with other neurons via?
Via the synapse using neurotransmitters
63
What is a synapse?
Chemical junction between neurons
64
What are the three types of synapses?
Axo-dendritic --> synapse joins to the dendrite of another neuron
Axo-somatic --> Synapse joins to the soma (cell body) of another neuron
Axo-axonic --> synapse joins to the axon of another neuron
65
What are the three major chemical groups that neurotransmitters are made from?
Amino acids --> GABA, glutamate, Glycine
Amines --> acetylcholine (ACh), Dopamine, Histamine, Serotonin, adrenalin, noradrenaline
Peptides --> cholecystokinin (CCK), Neuropeptide Y, substance P, Somatostatin
66
Where are small neurotransmitters synthesised?
Synaptic terminal
67
Where are neuropeptides synthesised?
Soma --> transported to the synaptic terminal
68
What is the mechanisms of neurotransmitter release?
1. Action potential arrival --> initiates Ca2+ entry into the cell
2. Ca+ entry --> stimulates exocytosis of neurotransmitter vesicles into the synaptic cleft
3. Vesicle membranes recovered by endocytosis
69
What does excitatory neurotransmitters do to the post synaptic membrane?
Transient depolarisation
70
What does inhibitory neurotransmitters do to the post synaptic membrane?
Transient hyperpolarisation
71
What happens to the neurotransmitters after they have their action?
1. Enzymatic degradation within the synapse
2. Presynaptic uptake followed by degradation or recycling
3. Uptake by glia
4. Uptake by the post synaptic neuron and desensitisation
72
What glial cells are present in the synapse and what is their role?
Astrocytes --> neurotransmitter metabolism
73
How do astrocytes interact with neuroactive substances in the synapse?
They have receptors and uptake systems to quickly terminate the post synaptic effect
74
What is the action of astrocytes on glutamate for example?
1. Glutamate is released to cause post synaptic effect
2. Glutamate is taken up by astrocytes to terminate post synaptic effect
3. Glutamate is inactivated by glutamine synthase with addition of ammonia to form glutamine
4. Glutamine is released from the astrocytes and taken up by neurons
5. Neurons reconvert glutamine to glutamate to future use
75
Can astrocytes themselves release neurotransmitters?
Yes
76
What is the effects of astrocytes secreting glutamate or d-serine?
Astrocytes secrete glutamate or d-serine in response to neural activity:
1. Binds to neuronal N-methyl-d-aspartate (NMDA) receptors
2. Modulates long term synaptic activity:
- long-term potentiation OR
- long term depression
77
What are some other neurotransmitters released by astrocytes and what are their effects?
1. GABA --> causes tonic inhibition of synapses in the surrounding area
2. ATP --> metabolised into the neurotransmitter adenosine
78
How does Astrocytes modulate the environment of the synapse?
1. Buffers ionic composition
2. and pH of the extracellular fluid
3. Propagate calcium waves --> to regulate secretory activity
79
How does Astrocytes modulate K+ levels in the extracellular fluid?
1. K+ release during AP firing
2. Astrocytes clear K+ with their plasma membrane ion channels
3. Astrocytes are interconnected by gap junctions allowing them to shunt K+ ions to perivascular spaces to restore local balance after heavy local activity
80
What are neurons specialised for?
Computing and communication
Chemical or physical stimuli
81
What is the resting transmembrane potential of a neuron?
-70mV
82
What enables the propagation of the electric signal from soma --> synaptic terminal?
Axon
83
What is the difference between ICF and ECF?
```
E = extracellular (outside)
I = intracellular (inside)
```
84
What is the relative proportion of common ions around neurons ECF vs ICF?
Sodium --> low inside, high outside
Potassium --> High inside, low outside
Calcium --> High inside, low outside
Chlorine --> low inside, high outside
85
What is Donnan's equilibrium potential?
When diffusion gradient (pushing K+ out) is equal to electrical gradient (pushing K+ in).
Consequence of positive charge outside and negative charge inside
86
What is Donnan's equilibrium determine?
The resting transmembrane potential (Vr)
87
What is some features of an action potential?
1. Transient reversal of membrane potential
2. Conducted at steady speed along the axon
3. All or none response
4. Has a refractory period
88
What is the steps in an Action potential generation?
1. Cell is at resting membrane potential
2. Stimulus causes depolarisation to threshold (small depolarisation)
3. Voltage gated Na+ channels open (makes sure its an all response)
4. Cell hits maximum depolarisation
5. Voltage gated K+ channels open, Voltage gated Na+ channels are inactivating
6. When membrane potential reaches back to threshold Voltage gated Na+ channels are in resting state and the open K+ channels return cell to resting potential (-70mV) after a small window of hyperpolarisation (small dip to more polarised than -70mV)
89
What is the difference between the Absolute refractory period and the relative refractory period for a neuron?
Absolute --> after the cell has depolarised and is returning to a potential a little above the threshold potential. After this point the cell can actually depolarise again without returning to the resting membrane potential
Relative --> the period after the absolute where the cell properly returns to the resting membrane potential
90
What is the simple key difference between the absolute and relative refractory periods?
Absolute --> cell cannot depolarise within
| Relative --> cell can depolarise within
91
What are the two main types of glia in the (PNS) Peripheral nervous system?
Schwann cells --> provide myelination to PNS axons --> cover axons
Satellite cells --> cover nerve cell bodies (soma) --> gives nutrients and protection to soma
92
What is saltatory conduction and where does it occur?
Conduction in leaps/hops --> occurs in myelinated neurons
93
What are the main types of glial cells in the CNS?
1. Microglia
2. Astrocytes
3. Oligodendrocytes
4. Ependymal cells
94
What are the role of microglia in the CNS?
1. Equivalent to macrophages --> phagocytosis when CNS damaged or infected)
2. Reuptake of neurotransmitters --> especially glutamate
3. Synaptic plasticity --> important for memory/adaption
4. Control of chemical environment --> release of inflammatory cytokines
95
What happens to the microglia in stressed rats?
Highly connected --> overgrowth --> potential neuroinflammatory theory of depression
96
What is the role of oligodendrocytes in the CNS?
Similar to Schwann cells --> myelinating glia
97
What are some examples of demyelinating diseases?
Guillain Barre Syndrome --> autoimmune disorder that causes demyelination in the PNS
Multiple Sclerosis (MS)--> autoimmune disorder which causes demyelination in the CNS
98
What is the role of Astrocytes in the CNS?
1. Fill spaces between neurons
2. Influence neurite growth --> guides neuronal migration during development
3. Regulate chemical content of extracellular space
4. Form blood-brain barrier --> astrocytes' perivascular feet
5. Most numerous glia in the brain
6. Responds to CNS injury --> damaged space filled by proliferating and hypertrophy of astrocytes --> results in the formation of an astrocytic scar
99
What are the two types of astrocyte in the CNS?
Fibrous astrocyte --> occur in white matter
Protoplasmic astrocyte --> occurs in grey matter
100
What is the role of Ependymal glial cells in the CNS?
Lining the CSF-filled ventricles, the ependymal cells play an important role in the production and regulation of CSF. Their apical surfaces are covered in a layer of cilia, which circulate CSF around the CNS.
101
What is the first line of defence for the CNS?
The skeletal system:
1. Brain --> located within the skull --> formed by interlocking cranial bones
2. Spinal cord --> enclosed within the vertebral column
102
What is the second line of protection for the CNS?
The meninges:
1. Brain --> cranial meninges
2. Spinal cord --> spinal meninges
103
What is the three layers of the meninges?
Dura mater --> outer --> strong --> dense irregular connective tissue
Arachnoid mater --> middle --> avascular --> Interstitial fluid between arachnoid and Dura mater
Pia mater --> inner --> adheres to brain and spinal cord --> CSF is between pia and arachnoid
104
What is the name of the spaces where ISF and CSF is?
ISF --> between dura and arachnoid --> subdural space
CSF --> between arachnoid and pia --> subarachnoid space
105
What is the role of cerebrospinal fluid (CSF)?
1. Mechanical protection --> shock absorbing medium --> allows brain to float and reduces impact of gravity on neural tissue
2. Chemical protection -->provides optimal chemical for neuronal function
3. Circulation --> provides medium for exchange of nutrients and wastes between the blood and the nervous tissues of the brain and spinal cord
106
Do all brain regions have a blood brain barrier?
No some regions don’t --> eg postrema
107
What is a Traumatic brain injury (TBI) normally characterised by?
An external mechanism of injury
| --> eg assault to the head
108
What is the difference between a primary and secondary brain injury?
Primary --> damage at the same time of injury --> tissue loss to trauma
Secondary --> post injury cause -->
--> extracranial causes --> hypoxia, hypotension or hypoglycaemia
--> intracranial causes --> eg haemorrhage, swelling, infection
109
What type of injuries are considered to have the potential to cause damage to the brain?
Anything that causes loss of consciousness
110
How do TBIs normally present?
1. Confusion
2. Altered level of conscious
3. Seizure
4. Coma
5. Autonomic deregulation
6. Neurological deficits
111
What is an acquired brain injury (ABI)?
Commonly associated with misuse/ abuse of drugs and/or alcohol or a causative agent
Examples --> strokes, tumours, etc
112
What are the three major physical mechanisms of traumatic brain injury (TBI)
1. Impact loading --> collision of the head with a solid object at tangible speed --> contact/inertial forces strain brain beyond tolerances --> brain tissue deformed by compression, stretching or sheering force.
2. Impulsive loading --> a sudden motion without significant physical contact
3. Static loading --> slow moving object traps the head --> gradually squeezing the skull and causing fractures which can cause deformity in the skull and brain
113
What are some common effects of primary traumatic brain injuries?
1. Skull fractures
2. Linear fractures --> fractures that pass through entire skull thickness
3. Depression fractures --> bone fragmentation that cause depression in skull surface
4. Base of skull fractures --> base or cribriform plate
5. Concussion --> transient alteration in cerebral function
6. Contusion -->bruising to the brain
7. Haemorrhage
8. Diffuse axonal injury --> tearing/disruption of axonal fibres
114
What is concussion and how does it manifest?
Concussion is a transient alteration of cerebral function without structural defect
Manifests --> loss of consciousness with rapid recovery
115
What is the typical causes of concussion?
Acceleration/deceleration force
| Blunt forced trauma
116
What is contusion?
Bruising to the brain tissue --> resulting in alteration of neurological function that may alter consciousness levels
117
What is the two forms of contusion?
Coup --> the brain strikes the skull on the side of impact
| Countercoup --> the brain strikes the skull at the opposite side of impact
118
How long does it take for a secondary brain injury to occur (SBI)?
2-24 hours after the primary injury --> most prominent cause is impaired cerebral blood flow.
119
Does a brain injury promote an inflammatory response?
Yes --> release of cytokines, free radicals and excitatory amino acids
120
What happens during intracranial inflammation post brain injury?
1. Capillary permeability is altered (just like in any inflammatory response)
- BBB swelling
- Glial cell swelling
- The increase in BBB permeability may cause pharmaceutical agents to cross into the vertebral compartment and cause a further increase in intracranial pressure
121
What are the main factors that can vary the manifestations of a TBI?
1. The force of injury
2. Mechanism of injury
3. Developmental age of the skull
4. Friability and structures of the vasculature
122
What is Cerebral palsy?
A group of permanent disorders of the development of posture and movement, causing activity limitation associated with non-progressive disturbances in the developing foetus or infant brain.
123
What are some risk factors for cerebral palsy?
1. Low birth weight
2. Prenatal --> intra uterine infections
3. Perinatal --> instrument delivery, neonatal jaundice, asphyxia, neonatal convulsions, antepartum bleeding and neonatal infections
4. Postnatal --> Asphyxia, infections
124
What are the three main types of Cerebral Palsy?
1. Spastic (75%) --> cerebral cortex damaged --> some muscles tight and some weak --> jerky movements, limb deformities
2. Athetoid (24%) --> basal ganglia affected --> muscle change from floppy to tense --> involuntary flailing and contorted movements
3. Ataxic (1%) --> cerebellum damaged -->unsteady movement, poor balance, shaky hand and feet movement and jerky speech
125
What are the four affective type areas of cerebral palsy?
1. Monoplegia --> affects one limb
2. Hemiplegia --> affects one side of the body left/right
3. Diplegia --> affects symmetrical parts of both eg arms or legs
4. Quadriplegia --> affects all four limbs
126
What does intracranial haemorrhage lead to in pretty much all cases?
Increased intracranial pressure
127
What is some symptoms of intracranial haemorrhage and thus intracranial pressure increase?
1. Budging fontanelles --> in infants
2. Behavioural changes
3. Altered level on consciousness
4. Drowsiness
5. Seizures
6. Vomiting
7. Headache
8. BP changes
128
What is an extradural (epidural) haemorrhage?
Blood collects in the extradural space --> between the skull and the dura mater
129
What is the main cause of extradural (epidural) haemorrhage?
Impact loading to the skull with associated laceration of the Dural arteries or veins
130
How does an extradural (epidural) haemorrhage classically present?
1. Brief loss of consciousness --> followed by an increase in consciousness --> followed by a rapid decline into unconsciousness
2. When in consciousness period --> lethargic, nauseated, confused and headaches
3. Mortality rate of 20% if no surgical interventions available
131
What is a subdural haematoma/haemorrhage?
Bleeding between the dura and the arachnoid layers of the meninges
132
What is the main cause of subdural haematoma/haemorrhage?
Sudden acceleration then deceleration (severe blunt trauma) of the brain tissue with related tearing of the bridging veins
Generally venous in origin
133
How do the incidence and mortality rates of extradural vs subdural haemorrhage compare?
Extra --> 2% of TBI --> 20% mortality untreated
Subdural --> 30% of TBI --> 50% mortality (as slow to cause symptoms)
134
What is intracerebral bleeding?
Bleeding of the brain tissue itself
135
What are the most common regions for intracerebral bleeding?
Temporal and frontal lobes
136
What are intracerebral bleeds caused by?
Penetrating trauma or diffuse injury from blunt trauma
137
What is a subarachnoid haemorrhage?
Trauma leading to haematoma in the subarachnoid space (between arachnoid and pia)
138
What is an intraventricular haemorrhage?
Rupturing of the subependymal vessels --> mostly in premature babies
Blood fills the ventricles
139
What is contained in the ventricles normally?
Cerebrospinal fluid (CSF)
140
What is Meningitis?
Is an inflammatory process of the leptomeninges (membrane surrounding the brain and spinal cord) and the CSF caused by bacteria, viruses, fungi or parasites.
141
What is Encephalitis?
Infection of the brain tissue or parenchyma
142
What is a Brain abscess?
Is a localised focus of necrosis of brain tissue with accompanying inflammation, usually caused by a bacterial infection
143
What is Brudzinski's sign and what does it indicate?
A test for meningeal irritation.
Supine patient has neck flexed by the doctor --> positive sign is if the patient flexes their hips and knees to help them relieve pain/irritation
144
What is Kernig's sign and what does it indicate?
A test for meningitis or subarachnoid haemorrhage
The thigh is flexed at the hip and knee at 90 degree angles, and subsequent extension in the knee is painful (leading to resistance).
Positive signs --> Generalised spinal pain, Resistance to the test, Involuntary hip flexion of the opposite hip
145
What is the outcomes for viral vs bacterial meningitis?
Viral --> full recover normal
Bacterial --> can have lasting damage --> CNS damage by bacterial toxins, compressions herniation from inflammatory oedema leading to ischemia
146
What are some symptoms of meningitis?
1. Fever
2. Nuchal rigidity (neck)
3. Altered mental state
(classic triad^^)
4. Headache
5. Photophobia
6. Lethargy
7. Vomiting
8. Purpural or petechial rash
9. Seizures
147
What is Encephalitis?
Inflammation of the brain
--> Reservoirs for virus --> wild animals and domestic animals --> biosecurity and public health protocols in place to prevent and contain these viruses
148
How does virus gain access to CNS to cause encephalitis?
- Bloodstream
- Direct from neighbouring structure --> nasal and middle ear
- Retroaxonally --> from peripheral nerve endings
149
What is the symptoms of Encephalitis?
1. Fever
2. Altered level of consciousness
3. Cerebral dysfunction
4. Seizures
5. Headache
6. Myalgia --> muscle pain/ache
7. Weakness
8. Paralysis
9. Mild respiratory infection
150
What is a brain abscess?
Collection of infected material at epidural or subdural locations
151
What commonly causes brain abscesses?
1. Bacterial cause is most common --> Commonly streptococcus infections but can also be staphylococci gram negative and Propionibacterium acnes
2. Parasites
3. Fungus
All of these are most likely to occur in immunocompromised patients
152
How do brain abscesses most commonly arise?
From infections elsewhere in the body --> endocarditis, pulmonary infections, IV drug use
OR
Nearby areas --> teeth, ear, paranasal sinuses or mastoid bone
153
What clinical information can a lumbar puncture assess?
```
Causative agent
Leucocytes
Protein
Increased pressure
Changes in glucose levels
```
154
What is some biographical information to attain first in the neurological history?
```
Age
Place of birth
Left/right handedness
Occupation
Level of education
```
155
What is an acute onset of neuro symptoms (seconds to minutes) suggestive of?
Vascular or Convulsive origins
156
What is a key sign of subarachnoid haemorrhage?
Explosive severe headache "thunderclap headache"
157
What may precede episodes of sudden neurological symptoms?
Precipitating events --> exercise or warning (aura)
158
What is the aura that precedes a seizure?
Partial (focal seizure)
159
What are the two kinds of auras preceding seizures and examples of their symptoms?
Localising --> auditory hallucinations, unusual smell/taste, loss of speech, motor changes
Non-localising --> feeling of apprehension
160
Aura followed by sudden unconsciousness is very suggestive of what?
Diagnosis of complex partial seizure
161
What is the normal time course for stroke symptom onset?
Seconds --> minutes before symptoms appear
| However symptoms may appear when the patient wakes from sleep
162
What is the hallmark of stroke?
Focal neurological dysfunction arising from a localised insult to the brain and symptomatic dysfunction reflects this area
163
What are examples of focal neurological dysfunction in stroke?
Patient unable to move one side of their body (hemiplegia)
Difficulty with speech or swallowing
164
What is it called when symptoms are resolved within completely post neurological dysfunction suspected from ischaemia
Transient ischaemic attack (TIA)
165
How long does symptoms need to persist to be associated with abnormal imaging results?
1-2 hours --> These cases are typically termed a stroke
166
What is the cause almost all cases of rapid focal neurological dysfunction without seizure?
Vascular causes --> infarction OR haemorrhage
167
In patients exhibiting symptoms of focal neurological dysfunction and can reply to questioning what is the crucial information to obtain?
Onset of symptoms
Risk factors for stroke
168
What is some examples of disease and time courses for subacute onset of neurological dysfunction?
Hours - days --> Infections (meningitis, encephalitis)
Days - weeks --> Inflammatory disorders (Guillian-Barre syndrome etc)
Weeks - months --> tumours
Months - Years --> degenerative processes
169
What time courses can Metabolic or toxic disorders be expected to take?
Any time course --> wide variation
170
What are some different types of headache and how can they present?
Migraine with aura --> unilateral headache preceded by flashing lights or "zig-zag" lines and is associated with light hurting eyes (photophobia)
Common migraine --> unilateral headache, no aura
Cluster headache --> pain over one eye lasting minutes to hours associated with, Lacrimation, Rhinorrhoea, flushing of the forehead --> occurring in bouts that last several weeks a few times a year or less.
Coital headache --> during intercourse, middle aged men, severe for 15 minutes and persist in a mild form for a few hours
171
What is another name for cluster headache and why?
Alarm clock headache --> tend to wake patient from sleep at the same time each day during the cluster
172
What does coital headache need to be distinguished from that can also occur during sexual intercourse?
Subarachnoid haemorrhage
173
What is suggested by a generalised headache that is worse in the morning and is associated with drowsiness or vomiting?
Raised intracranial pressure
174
What are some symptoms of meningitis?
```
Generalised headache
Photophobia
Fever
Stiff neck
More gradual onset
```
175
What kind of headache occurs in acute sinusitis?
Headache with pain or fullness behind the eyes or over the cheeks or forehead
176
What may behind an instantaneous severe headache that is initially localised but then more general and associated with neck stiffness?
Subarachnoid haemorrhage
177
What is the most frequent type of headache?
Episodic or chronic tension-type headache
178
What is the presentation of a chronic tension-type headache?
Commonly bilateral
Occurs over frontal, occipital or temporal areas
Sensation of tightness that lasts for hours and reoccurs often
Not made worse by walking
No associated symptoms (nausea, weakness, tingling limbs)
Does not normally wake the patient from sleep
179
What is the mnemonic for differentiating between a migraine headache from a tension one?
```
P -->pulsatile headache
O --> hours duration (4-72hours)
U --> Unilateral, not bilateral
N --> Nausea and/or vomiting
D --> Disabling headache
```
180
What are the two major classes of seizure?
Focal
| Generalized
181
What are focal seizures?
Notable for symptoms localisable to a single part of the brain.
In "simple" forms --> no impaired consciousness
In "complex" forms --> consciousness is often lost from seizure activity spreading though the brain
182
What intracranial haemorrhage subtype encapsulates epidural, subdural and sub arachnoid haemorrhages?
Extra-axial haemorrhage --> within the skull but outside the brain tissue
183
What is the clinical pattern of presentation of epidural vs subdural haemorrhage?
```
Epidural:
Commonly triphasic --> altered consciousness --> lucid --> sharp neural decline
Altered consciousness
Headache
Vomiting
Confusion/seizures
Aphagia
```
Subdural:
Very similar to epidural haemorrhage symptoms
Coma in 50% of cases
LESS common Triphasic/lucid interval
184
What is difference in most common source of blood for epidural vs subdural haemorrhage?
Epidural --> arterial
| Subdural --> venous
185
What can be different about the presentation of epidural vs subdural haemorrhage?
Subdural can present in elderly with no obvious origin of trauma and be classed as chronic --> may present as a long term dementia before presentation
186
What is the most common cause/ source of blood for sub arachnoid haemorrhage?
Rupturing of an aneurism --> in particular the cerebral arteries
187
What is the clinical presentation of sub-arachnoid haemorrhage?
Similar to epi and subdural
Often occurs with a sudden "thunderclap headache"
Can cause symptoms of irritated meninges:
-nuchal rigidity etc
188
What are the symptoms of increased intracranial pressure?
```
Headache
Nausea
Vomiting
Increased BP
Altered cognition/ confusion
Double vision
Slow/ unresponsive pupils
Seizures
Coma
```
189
What are some ways intracranial pressure is measured?
- Intraventricular catheter --> hole drilled and catheter is inserted through the brain into the lateral ventricle
- Subdural screw (bolt) --> (fast way) hollow screw through hole in the skull and dura mater
- Epidural sensor --> epidural sensor is inserted through a drill hole in the skull
190
What are some features of the three intracranial pressure measurements?
- Intraventricular catheter --> most accurate, allows CSF sampling
- Subdural screw --> fastest method, no CSF sampling
- Epidural sensor --> least invasive, no CSF sampling
191
What are some ways meningeal irritation is assessed?
Kernig's sign --> hip and knee of patient flexed to 90 degrees --> Dr slowly extends the flexed knee --> will cause the patient to move their head up or be uncomfortable
Brudzinski's test --> flex the patients neck --> they will flex their knees and or hip in response to pain
192
What are some symptoms of meningitis?
```
Nausea/vomiting
Fever
Headache
Nuchal rigidity
Photosensitivity
Confusion
```
193
What is the effects of alcohol on the CNS?
Increases risk of ICH
| Affects consciousness
194
How is consciousness evaluated in a patient?
Glasgow coma scale (GCS)
195
What is the Glasgow coma scale?
```
is a neurological scale which aims to give a reliable and objective way of recording the state of a person's consciousness.
It assesses:
Eye movements/responses
Verbal ability
Motor ability
```
196
What is pain sensitive in the brain?
Meningeal layers
197
What does the epidural haemorrhage CT shape look like?
Biconvex --> near skull
198
What does a subdural haemorrhage CT shape look like?
Crescent shaped
199
What does a subarachnoid haemorrhage CT shape look like?
Amorphous substance that fills the normally dark, CSF-filled subarachnoid spaces around the brain --> can spread further than epi or subdural haemorrhage
200
Why does a epidural haemorrhage shoe up as biconvex on CT?
Cannot cross the sutures lines as the dura matter is tightly adhered there
201
Why does a subdural haemorrhage present as crescent shaped on CT?
can expand along the inside of the skull, creating a concave shape that follows the curve of the brain, stopping only at Dural reflections like the tentorium cerebelli and falx cerebri.
202
How is raised intracranial pressure treated?
Fluid draining through shunt in a small hole in skull or spine
Medications mannitol and hypertonic saline solution
Intubation and hyperventilation
203
How does Hyperventilation assist raised ICP?
Cerebral blood flow is largely dependent on PaCO2. Hyperventilation causes decreased PaCO2 which subsequently leads to arterial vasoconstriction thus lowering cerebral blood flow (CBF), cerebral blood volume, and ICP.
204
What are the three essential findings for brain death?
Coma
Absence of brainstem reflexes
Apnoea --> not breathing
205
What is encephalopathy?
a disease in which the functioning of the brain is affected by some agent or condition (such as viral infection or toxins in the blood).
206
Why does encephalopathy cause confusion?
Impaired brain function --> altered mental state --> confusion
207
What is the difference between depression, delirium and dementia?
Delirium --> reversible
Depression --> reversible
Dementia --> not reversible
208
How does vit b12 deficiency cause confusion?
- -> leads to pernicious anaemia
- -> anaemia reduces rates of oxygen delivery
- -> less oxygen to the brain
209
What are some resp causes of confusion?
Hypoxia
Acidosis
Alkalosis
210
What are symptoms of alcohol/drug withdrawal?
```
Headaches
Nausea
Anxiety
Tremor
Vomiting
Insomnia
Sweating
```
211
What is ketotic breathe and what is it a sign of?
describes the characteristic fruity smell of breath laden with ketones. It can occur in any condition associated with ketosis
212
What is ketosis and when does it occur?
Ketosis --> fat provides most of the fuel for the body
| Happens in situations with limited glucose --> starvation or diet induced
213
What direction are CT scans?
Its in the inferior --> superior direction
214
What colour is blood on a CT?
White
215
What is leads affect on RBC?
Haem production interference --> leads to anaemic
216
What is the purpose of a randomized control trials/clinical trials?
is a type of scientific (often medical) experiment that aims to reduce certain sources of bias when testing the effectiveness of new treatments; this is accomplished by randomly allocating subjects to two or more groups, treating them differently, and then comparing them with respect to a measured response.
217
What are key design features of RCTs?
The only expected difference between the control and experiment group should be the outcome variable being tested if the randomization is good enough
218
What are some other types of RCTs apart from clinical trials?
Superiority trials
Noninferiority trials
Equivalence trials
219
What is the difference between an Randomized controlled trial and an observational study?
Observational studies --> no randomization --> difference in outcomes observed after a therapy has been selected
RCTs --> randomization --> patients are assigned a treatment/group
220
What are some strengths of RCTs?
* Good randomization will "wash out" any population bias
* Easier to blind/mask than observational studies
* Results can be analyzed with well known statistical tools
* Populations of participating individuals are clearly identified
221
What are some weaknesses of RCTs?
* Expensive in terms of time and money
* Volunteer biases: the population that participates may not be representative of the whole
* Loss to follow-up attributed to treatment
222
What is single blinding?
The subjects do not know if they are receiving treatment or placebo
223
What is double blinding?
Subjects and experimenters do not know who is receiving treatment or placebo
224
What is triple blinding?
Subjects, people administering treatment and experiment evaluators do not know who received treatment or placebo
225
What is randomization in study design?
Process of assigning trial subjects to treatment or control using an element of chance --> to reduce bias
226
What is loss to follow up?
Patients who are lost-to-follow-up lead to incomplete study results, which in turn can put a bias on the result of the study as well as a bias on the investigational study medication
227
What is intention to treat?
means all patients who were enrolled and randomly allocated to treatment are included in the analysis and are analysed in the groups to which they were randomized
228
What is the method used to minimise confounding in RCTs?
Randomization
229
What proportion of strokes are ischaemic vs haemorrhagic?
Ischaemic --> 80%
| Haemorrhagic --> 20%
230
5 Major causes of strokes?
Atherosclerosis
Embolic (plugs of clotted material which have mobilised)
Small vessels or lacunar
Cryptogenic (unknown cause) (20%)
Rare but known causes
231
Atherothrombosis is?
Thrombus superimposed on atherosclerosis
