Week 11

Question 1

CNS injuries- diverse group of disorders

Answer 1

Spinal cord injury SCI and traumatic brain injury TBI primarily affect young people 15-24
Stroke and brain cancer primarily affect older generation
Most common causes SCI- fall, road traffic accidents and sport

Question 2

Repair of tissues not in CNS

Answer 2

Proliferation of cells occurs- tissue repair
Cells can be replaced
Complexity at expense of individual immortality

Question 3

Repairing neuronal networks in CNS

Answer 3

In CNS in order for the final development and function of CNS there must be fast neuronal networks- hundreds of interconnected neurones
Taking one cell out makes entire systems fail
Can’t replace dead neurones, neurogenesis doesn’t happen- adult neurones dont proliferate so very difficult to repair
Complexity at the expense of reparability

Question 4

Topographical organisation of CNS

Answer 4

If you damage a specific region of the brain that function will be lost
In spinal cord- loss of movement, sensation and autonomic control below level of injured segment affects functions of that spinal region

Question 5

Functional consequences of injury

Answer 5

Depend on the site and size of the injury not the type of injury
Signs and symptoms tell you which part of the brain is injured but not the type of injury

Question 6

Energy supply to the brain

Answer 6

2% of the total body mass
Consumes 15% of the energy generated in the body, disproportionally high energy consumer
No energy stores of its own (small amount glycogen in astrocytes)
Energy is derived exclusively from glucose metabolism, constant supply of glucose and oxygen to the brain

Question 7

Skull fractures

Answer 7

Depression fracture- fracture of skull where fragment is depressed
Compound fracture- bone fracture that’s accompanied by breaks in skin, open wound
Temporal skull fracture- houses middle ear, inner ear, facial nerve, presence of bloody discharge from ear or ecchymosis (bruise) behind ear are signs

Question 8

Hypertensive cerebral haemorrhage

Answer 8

Subarachnoid- bleed between arachnoid and pia mater increasing pressure inside skull
Intracerebral- bleeding into tissues of brain or its ventricles

Question 9

Cerebral amyloid angiopathy and lobar haemorrhage

Answer 9

Amyloid- protein that’s deposited in liver, kidneys, spleen or other tissues in certain diseases
Angiopathy- disease of the blood vessels
Cerebral amyloid angiopathy- age related change in small vessels in brain, accumulation of amyloid, allow blood to leak out can lead to lobar haemorrhages
Lobar haemorrhage- bleeding into lobe of cerebrum, primary haemorrhage occur within either subcortical white matter or at junction of hemispheric grey-white matter

Question 10

Arterio-venous malformations

Answer 10

Proliferation of dilated blood vessels where blood stagnates and doesn’t flow properly leading to bleeding into tissue

Question 11

Aneurisms

Answer 11

Bulge that forms on thinning wall of an artery
Can have coagulated blood in it increasing pressure in CNS

Question 12

Lacunar infarcts and white matter damage

Answer 12

Lacunes are small areas in the brain where poor blood flow has starved a group of cells of oxygen causing them to die
Tiny parts of tissue that died away
Stroke
Affecting pathways in white matter leading to specific function deficits
Typical in patients who suffer from vascular dementia or multiinfarcts dementia

Question 13

Traumatic brain injury

Answer 13

Mechanical impact causes cerebral contusions (bruise brain tissue) and lacerations (Brain tissue is cut or torn)
Movement of the brain in the skull causes subdural hematoma (bleeding, collection of blood between inner layer of dura mater and arachnoid matter, tears in bridging veins) and diffuse axonal injury ( happens when brain rapidly shifts inside skull, axons sheared)
Consequences: hematomas (epidural and subdural) leads to compression of the brain, raised intracranial pressure.
Contusions and diffuse axonal injury- structural brain damage
Hypoxic injury, focal ischemic lesions
Multiple lesions and different types of lesions

Question 14

Hypoxic injury, focal ischemic lesions

Answer 14

Deficient blood supply
As a consequence of the oedema and raised intracranial pressure, compression of blood vessels- decrease in oxygen supply

Question 15

Anoxia

Answer 15

No oxygen

Question 16

Difference between thrombosis and embolism

Answer 16

Thrombosis is the formation and presence of blood clot in any blood vessels
Embolism is the obstruction of a artery by a blood clot

Question 17

Energy crisis- demand outruns the supply

Answer 17

Drop in cerebral perfusion (blood flow in the brain) Global ischemia- cardiac arrest or severe hypotension (shock)
Hypoxia- CO poisoning
Hypoglycaemia
Severe anaemia can trigger energy crisis in brain
Generalised seizures

Question 18

Anoxic neurons

Answer 18

Differential sensitivity of different neuronal populations
-ischaemia lasting 4-5 minutes-irreversible damage:
Hippocampal and neocortical pyramidal cells
Striatal neurones
Purkinje cells- inhibitory neurons in cerebellum
-more protracted ischaemia- irreversible damage:
thalamic and brainstem neurones- need longer periods of ischaemia , less sensitive
In hypoxic patients there’s few pyramidal cells, loss shape

Question 19

Pseudolaminar and laminar necrosis

Answer 19

Death of cells in cortex of brain, layer 3 neocortex, clear band pattern
Affected by hypoxic events
Selective vulnerability of different neuronal populations

Question 20

The progressive changes following a cerebral infarct

Answer 20

1-2 days: tissue swelling, anoxic neurones, pyramidal cells lose shape
2 weeks: no neurones, tissue necrosis (cell death), lots of glial cells. Neovascularisation- proliferation of new blood vessels
2 months: glial scar, replaces dead neuronal tissue, large glial cells, no neurones

Question 21

Series of events in TBI

Answer 21

Neuronal death and tissue loss (partially due to direct impact and also the movement of brain in skull)
Blood brain barrier BBB breakdown and oedema- consequence of primary and secondary injuries, makes oedema worse perpetuating neuronal loss
Upregulation of inflammatory mediators- cytokines, as response to repair, inflammatory response.
Gliosis and cell infiltration- local proliferation of glial cells
However can make tissue damage worse in CNS: cytokines can be neurotoxic, substances released by glial cells prohibit regenerative attempts in CNS

Question 22

Consequence of CNS injury

Answer 22

Loss of cells and connections:
-functional deficit
- BBB breach
Response to injury:
-inflammatory response
-oedema
-gliosis
Reactive change of glial cells mainly astrocytes in response to damage of CNS. Proliferation or hypertrophy glial cells
Long term consequences:
-sequelae: pathological condition following injury
-repair: depends on how big original damage was and how much repair will happen in brain, regions affected

Question 23

Long term consequences of severe TBI

Answer 23

Seizures
Focal neurological deficits
Dementia
Persistent vegetative state
Increased risk of Alzheimer’s disease

Question 24

PNS: axonal regeneration present

Answer 24

Axonal injury— macrophage clear debris— no inhibitory molecules present, extending growth cone

Question 25

CNS: no axonal regeneration

Answer 25

Axonal injury— no macrophage to clear debris— myelin associated inhibitory molecules (Nogo, MAG, OGmp) and reactive astrocytes upregulate inhibitory extracellular matrix ECM molecules that inhibit regeneration

Question 26

Features of CNS injury

Answer 26

CNS axons intrinsic capacity for regeneration Inhibitory environment: -lack of neurotrophic stimulation - neuronal death -demyelination -glial scar -inhibitory molecules: associated with glial scar proteoglycans (CSPG), associated with damaged myelin (Nogo, MAG, OMgp). Prevent regenerative attempt Neurotrophins are a family of proteins that induce development, function of neurones

Question 27

Treatment options for CNS injury

Answer 27

Surgery: -remove hematoma -repair skull fractures -decompression: to decrease raised intracranial pressure, prevent hypoxia, prevent extension damage Medication: -anti seizure medication-reduce risk of seizures -reduce oedema- diuretics (increase urine production in kidney, promoting removal salt and fluid in body) -induced coma- reduce oxygen and nutrient requirements, prevent further damage due to high demand without appropriate supply Rehabilitation

Question 28

Difference between hematoma and haemorrhage

Answer 28

Hematoma- accumulation of leaked blood inside body within tissue planes, localised bleeding Haemorrhage- leaking of blood from blood vessels due to lack of integrity in the vessel wall

Question 29

Neurorehab

Answer 29

A process whereby patients who suffer from impairment following neurologic diseases regain their former abilities or, if full recovery is not possible, achieve their optimum physical, mental, social and vocational capacity

Question 30

Neurological and functional recovery

Answer 30

Neurological recovery: -early recovery (local processes), due to rapid intervention of surgery or medication -late recovery (Neuroplasticity) modification in structural and functional organisation. Ability of brain to form and reorganise synaptic connections, growing and evolving Functional recovery: -recovery in everyday function with adaptation to absence of certain functions and training in presence/absence of natural neurological recovery -dependent on quality, intensity of therapy and patients motivation

Question 31

Neuronal plasticity signalling mechanisms involved

Answer 31

Neuronal activity increases neurotrophin synthesis, secretion and signalling Increases postsynaptic responsiveness, synaptic morphology, presynaptic transmitter release, membrane excitability Leading to modification of synaptic transmission and connectivity Plasticity much quicker in development than in adult- remodelling of connections, rapid neuronal network over a long period of time ~90 days

Question 32

Neuroplasticity principles

Answer 32

Use it or lose it Use it and improve Specificity Repetition matters Intensity matters Time matters Salience matters- earlier process starts the better outcome for patient Age matters- Neuroplasticity slows down as we age Interference - plasticity on response to one training experience can impede acquisition of similar behaviours

Question 33

Experimental strategies for treatment of CNS injury

Answer 33

Trophic support: neurotrophic factors to neuronal cell bodies, that would support neuronal regeneration and survival Inhibiting the inhibitors, changing environment: NOGO antibodies, digestion of GSPG-chondroitinase, Rho inhibitors (siRNA) Endogenous stem cells: neurogenesis- subventricular zone, subgranular zone. Cells with neurogenic potential found in these zones. Get depleted over time with age Cell therapy especially if local damage: replace dead cells, create favourable environment, bridge cyst cavities, autologous stem cells (Same individual)

Question 34

Multiple sclerosis MS

Answer 34

Affects CNS Immune system attacks the myelin causes inflammation and lesions. Oligodendrocytes affected Affect conduction of action potentials Episodes, comes and goes. Affect different anatomical locations Motor and sensory Double vision and vertigo (loss of balance) Ataxic- lack of coordinated movement Brisk reflexes and planar reflexes were up going Reduction in pinprick sensation, tingling and numbness on one side of body

Question 35

Guillian Barre syndrome

Answer 35

Rapid onset muscle weakness cause by immune system destroys myelin sheath of nerves in PNS Has a preceding infection, immune response to infection starts generating antibodies that attack myelin Motor and sensory Numbness and tingling in limbs LMN signs- muscle weakness, reduced tone and absent reflexes in all limbs Plantar reflexes down going Reduction in pinprick sensation over lower limbs Symptoms often start in feet and hands before spreading to arms and legs

Question 36

Sensory peripheral neuropathy due to diabetes mellitus

Answer 36

Numbness and tingling Sensory Reduction in pinprick sensation in distal, extreme peripheries (stocking distribution) Ankle jerks absent Impairment of vibration and joint position sense- Proprioception Sensory neurones affects first, smaller diameter

Question 37

Brown- Sequard syndrome

Answer 37

Caused by damage to one half of spinal cord Numbness and tingling on one side right - sensory Dragging leg on other side left - motor Increased tone, brisk reflexes, up going plantar on left leg Position and vibration sense are lost in left leg- sensory Impairment of pin prick sensation and temperature over right leg up to level of umbilicus, sensory loss different to left CNS reflexes- spinal cord T10 level of umbilicus UMN sign (cortiospinal) left leg, posterior column lost Pain and temp (spinothalamic) right leg Left sided T10 spinal cord Ipsilateral weakness with loss of position and vibration sense Contralateral loss of pain and temp

Question 38

What is the major reason why CNS neuronal axons do not regenerate after axonal transection

Answer 38

Inhibitory molecules are expressed and up-regulated on glial cells