CNS Pathology Flashcards
1
Q
Provide an overview of PNS and CNS disorders
A
- PNS: Axonal injury and neuropathies
- CNS: Trauma, demyelinating disorders, neurodegenerative disorders, neoplasia, infectious disorders and CV related stress
2
Q
What is the PNS and structures involved
A
- Structures: Nerves, ganglia, neuronal cell bodies and nerve endings, ascending tracts (sensory information) and descending tracts (muscle action)
- Peripheral Nerves: Epineurium surrounds nerve, perineurium surrounds fascicles, endoneurium surrounds peripheral (myelinated) nerve fibre, myelin sheath formed by schwann cells surrounds axon
3
Q
List the different types of nerve injuries
A
- Neurapraxia
- Axonal degeneration
- Axonotmesis
- Neurotmesis
4
Q
What is neurapraxia
A
- Injury to a myelinated nerve by pressure that interrupts conduction
- Causes temporary paralysis and loss of function but not degeneration
- Followed by a complete and rapid recovery
- Relatively mild type of nerve injury, often result of trauma to the body
- Endoneurium intact, axon intact and no nerve degradation
5
Q
What is axonal degeneration
A
- Direct injury to axon leading to axon transection / crushing leads to Wallerian degeneration (axotomy, swelling, granulation)
- Controlled event leading to distal axon death
- Preventing neuronal death, promoting nerve regeneration
- Sensory / motor axons cannot effectively communicate between PNS and CNS
6
Q
What is axonotmesis
A
- Nerve injury where axons and myelin sheath are damaged
- Endoneurium, perineurium and epineurium remain intact
- Mainly follows a stretch injury
- Break down of axon at distal end causes Wallerian degeneration (axotomy, swelling, granulation)
- Optimal circumstances for regeneration and functional recovery possible
7
Q
What is neurotmesis
A
- Nerve injury involving complete severance or crushing of nerve
- Different degrees of severity
- Mostly spontaneous recovery not expected
- In all forms distal end will undergo Wallerian degeneration (axotomy, swelling, granulation)
8
Q
Differentiate between CNS and PNS nerve regeneration
A
- CNS: Most CNS fibres cannot regenerate
- PNS: If soma is damaged peripheral nerve cannot regenerate (cell body / nucleus) but if axon is damaged the cell can regenerate (axonal degeneration / demyelination)
9
Q
Describe the events following injury and mechanisms of repair
A
- Nerve injury and nerve will begin to degrade
- Axon surrounding myelin break down, myelin degenerates simultaneously
- Phagocytic macrophages interact with schwann cells to remove injured tissue debris
- Connection with target muscle lost, leading to muscle atrophy and fibrosis
- Axon sprouts with a fingerlike growth cone advance using schwann cells as guides (align in bungner bands and express surface molecules)
- Newly connect axon matures and the pre-injury cytoarchitecture and function are restored
10
Q
What are peripheral neuropathies and symptoms
A
- Heterogeneous group of diseases
- Result from inflammatory, toxic and metabolic conditions in addition to genetic defects
- Symptoms vary depending on the type of nerves affected
- Movement, sensory and autonomic nerve impairment (control of organs)
11
Q
What are the causes of peripheral neuropathies
A
- Altered metabolism, covalent modification
- Altered organelle function and reactive oxygen species formation
- Altered intracellular and inflammatory signalling
- Slowed axonal transport and altered ion channel dynamics and expression
12
Q
What are the types of peripheral neuropathies
A
- Trauma (car accidents, sports injuries)
- Diabetic neuropathy
- Chemotherapy induced peripheral neurotoxicity
- Viruses
- Autoimmune (Guillain-Barre Syndrome)
- Genetic (Charcot-Marie-Tooth disease)
13
Q
What is Guillain-Barre syndrome (acute peripheral)
A
- Acute peripheral neuropathy
- Demyelinating disorder
- Very rare (1:100,000)
- Can lead to death from failure of respiratory muscles within days of onset of symptoms
- Autoimmune disease (against myelin or axon)
- Antibodies and lymphocytes attack and damage peripheral nerves
- Symptoms appear suddenly, progress rapidly, and resolve slowly as damaged nerves heal
- Cause unknown, usually follows viral / bacterial infection
14
Q
What is Charcot-Marie-Tooth disease (chronic peripheral)
A
- Chronic peripheral neuropathy
- Symptoms begin subtly and progress slowly
- More common (1:2,500)
- Both motor and sensory abnormalities are common (muscle weakness & pain)
- Decreased reflexes, difficulty heel walking, calf atrophy
- Follows a chronic relapsing-remitting or progressive course
- Caused by duplication / mutation of PMP22 (peripheral myelin protein) or hereditary neuropathy
15
Q
What is trauma, a concussion and the types of trauma to the CNS
A
- Injury or damage to living CNS tissue caused by an extrinsic agent or force by either direct or indirect mechanisms
- Concussion: Traumatic brain injury that can lead to bruising, swelling, tearing of BV and injury to nerves
- Types: Diffuse and focal traumatic brain injury
16
Q
What is diffuse traumatic brain injury (DTBI)
A
- Generalised injury to all regions of the brain
- Axonal or hypoxic injury
- Negatively impacts brain functioning
- Brain can become injured whether or not the skull is fractured
- Primary (mechanical damage) and secondary (indirect result)
17
Q
What is axonal injury (DTBI)
A
- Caused by global disruption of axons due to severe shearing forces
- Immediate primary axotomy, delayed secondary axotomy principally due to ischaemia
Pathology - Focal accumulations of β-amyloid precursor protein (4-5h)
- Axonal varicosities / swelling (12-24h)
- Axonal swellings (24h-2m)
- Microgliosis (2w-5m)
- Loss of myelinated fibres (>2m)
18
Q
What is focal traumatic brain injury (FTBI) and cerebral contusion
A
- Localised injury of the brain
- Blunt forced trauma, rapid tissue displacement, bruising of brain parenchyma, brain contacts rough skull surfaces (orbital floor / petrous ridges)
19
Q
What is a hematoma (FTBI)
A
- Brain haemorrhaging from a ruptured vein or artery
- Increasing pressure forces brain towards foramen magnum
- Symptoms: Headaches, agitation and drowsiness, can result in death if not treated quickly
20
Q
What are the two types of hematoma’s (FTBI)
A
Epidural:
- Between skull and dura mater
- 30% mortality rate
- Torn artery increases intracranial pressure
- Rapidly expanding with arterial blood, skull fracture, torn middle meningeal artery
- Dura pushed away by hematoma
Subdural:
- Between dura matter and arachnoid meningeal layers
- Occur more slowly (venous)
- Pushes brain away from skull across midline (including ventricles)
- Dura is attached to skull, hematoma cannot cross falx cerebri, tentorium may form
21
Q
What are neurodegenerative disorders
A
- Characterised by the progressive loss of neurons, typically affecting groups of neurons with functional interconnections
- Parkinsons
- Alzheimers
- Huntingtons
22
Q
What is Parkinson disease and Lewy bodies
A
- Atrophy and loss of dopaminergic neurons in substantia nigra pars compacta (SNPc) in basal ganglia
- Depigmentation of substantia nigra
- 99% sporadic and 5% genetic causes
- Loss of dopamine
- Resting tremor, bradykinesia, rigidity, postural imbalance)
- Lewy Body: Accumulation of intracellular fibrillar aggregates
23
Q
What are cerebrovascular diseases and strokes
A
- Cerebrovascular Disease: Brain disorders caused by pathologic processes involving blood vessels
- Stroke: Acute-onset neurologic deficits resulting from hemorrhagic or obstructive vascular lesion
24
Q
What is an ischaemic stroke
A
- A clot blocks BF to an area of the brain due to occlusion
- Cause: Embolism, thrombosis of cerebral artery, hypo-perfusion
- Result: Decrease in cerebral blood flow / oxygen supply (hypoxia), widespread neuronal cell death (infarct grows and spreads), penumbra (injury of surrounding tissue)
- Histology: Eosinophilic neurons and cytoplasm, pyknosis, cortical atrophy and gliosis develop
25
Q
What is a haermorrhagic stroke
A
- Bleeding occurs inside or around the brain tissue due to rupture of blood vessels
- Types: Subarachnoid and intracerebral
- Cause: Rupture of a weakened blood vessel (atherosclerosis from hypertension), uncontrolled hypertension
- Location: Cerebrum and bleed into the lateral ventricle
- Result: Sudden and often lethal, poor prognosis
26
Q
What is the ischaemic cascade
A
- Series of biochemical reactions that are started in the brain after ischaemia takes place
- Within seconds or minutes of inadequate blood supply
27
Q
List the steps involved in the ischaemic cascade
A
- Vascular occlusion decreases BF (ischaemia) leading to energy depletion
- Failure of NaK pumps, depolarisation of neuronal membrane (loss of function) and AnO2 glycolysis (acidosis)
- Neurons release glutamate into synaptic cleft leading to excitotoxin
- Glutamate acts on channel receptors and opens NMDA and AMPA receptors leading to Ca influx
- Ca influx causes activation of catabolic enzymes and NO synthase (formation of free radicals)
- Free radicals and catabolic enzymes destroy structural proteins and DNA
- Neuronal necrosis edema / lysis, lipid peroxidation and membrane disruption (all induce apoptosis)
- Free radicals also injure mitochondria and lead to apoptosis through pro-apoptotic molecules
28
Q
What is neoplasm and neoplasia
A
- Neoplasm: Abnormal mass of tissue, growth exceeds and is uncoordinated with that of normal tissues and persists in excessive manner after cessation of stimuli
- Neoplasia: Cancer, new growths of cells in the body
29
Q
What are the two types of neoplasms
A
- Glioma: Tumours that arise from the glial group of cells (supporting cells), 50% of all brain tumours, highly malignant
- Meningioma: Non-glial tumours, slow growing, form from meninges, non-aggressive, interfere with circulation of CSF (hydrocephalus), 80% surgically removed
30
Q
What are infectious disorders
A
- Infections of the brain can be caused by viruses, bacteria, fungi, or, occasionally, protozoa or parasites
31
Q
What are two examples of infectious disorders
A
- Encephalitis: Infection causing inflammation of the brain, viruses are most common cause
- Meningitis: Inflammation of meninges, bacterial and viral meningitis can develop into encephalitis
