CNS Pathology Flashcards
What pathologies can affect the CNS?
Trauma, neurodegenerative disorders, cerebrovascular diseases, neoplasia, infectious disorders, demyelinating disorders
What is trauma (to CNS)?
Injury or damage to living CNS tissue caused by an extrinsic force or agent by either direct or indirect mechanisms
What can a concussion lead to?
Bruising, swelling, tearing of blood vessels, injury to nerves
What are two types of traumatic brain injury?
Diffuse and focal
What is a diffuse brain injury?
Generalised injury to all areas of brain
What are two examples of a diffuse traumatic brain injury?
Diffuse traumatic axonal injury, diffuse hypoxic injury
What is a focal traumatic brain injury?
Localised injury of the brain
What are two examples of focal traumatic brain injury?
Lobar cerebral contusion, subdural haemorrhage
What causes diffuse TBI?
Outside mechanical force applied to head, eg. fall, car crash, struck by/against object, assault, blasts (war)
What are primary brain injuries in diffuse TBI?
Mechanical damage, eg. laceration, cerebral contusion, diffuse axonal injury, haemorrhage
What are secondary injuries in diffuse TBI?
Indirect result of TBI, eg., intracranial hypertension, brain shift and herniation, biochemical processes, swelling, cerebral ischemia
What causes diffuse axonal injury?
Global disruption of axons due to severe shearing forces
What does diffuse axonal injury result in?
Immediate primary axotomy, delayed secondary axotomy due to ischemia
How does diffuse axonal injury present?
Immediate loss of consciousness, no lucid interval, sustained unconsciousness and vegetative state until death
Describe the histology of diffuse axonal injury
4-5 hours: focal accumulations of beta-amyloid precursor protein (APP)
12-24 hours: axonal varicosities, swelling
24 hours-2 months: axonal swellings
2 weeks-5 months: micro-gliosis
2 months-years: loss of myelinated fibres
What causes cerebral contusion in focal TBI?
Blunt trauma, ie. blow to the head, leading to rapid tissue displacement. Contact between brain and rough skull surfaces like orbital floor and petrous ridges
What does a cerebral contusion result in?
Rupture of vessels leads to haemorrhage, tissue injury and edema
What are the clinical symptoms of a cerebral contusion?
Drowsiness, confusion, agitation, hemiparesis, unequal pupil size
What is a brain hematoma?
Haemorrhaging from ruptured blood vessel caused by brain trauma
What is an epidural hematoma?
Hematoma between skull and dura mater caused by torn artery and branches
What does an epidural hematoma result in?
Increased intracranial pressure
What is the mortality rate for epidural hematomas?
30% when treated quickly
What is a subdural hematoma?
Hematoma between dura mater and arachnoid mater caused by torn subdural veins
What causes subdural hematoma?
Blunt trauma to frontal or occipital lobes
What causes Parkinson's disease?
Atrophy and loss of dopaminergic neurons in substantia nigra pars compacta (SNPc) in basal ganglia
What change can be seen in SNPc in PD?
Depigmentation
What symptoms does loss of dopamine in deep structures cause?
Resting tremor, bradykinesia, rigidity, postural imbalance
Describe the histology of PD.
Levy bodies visible. Result of accumulation of intracellular fibrillar aggregates, mutant alpha-synuclein forms fibrils together with ubiquitin and neurofilaments
What is the median age of PD onset?
60 years
What percentage of PD cases are sporadic and genetic?
95% sporadic, 5% genetic
What is an example of a cerebrovascular disease?
Stroke
What is a stroke?
Transient or permanent reduction to cerebral blood flow
What are two types of stroke?
Ischemic and haemorrhagic
What is a haemorrhagic stroke?
Rupture of weakened blood vessel in brain
What causes haemorrhagic stroke?
Weakened blood vessels, as a result of uncontrolled hypertension (mainly) and atherosclerosis
Where do most haemorrhagic strokes occur?
In cerebrum, bleed in to lateral ventricle
What symptoms precede a haemorrhagic stroke?
Intense headache and vomiting
What are the two types of haemorrhagic stroke?
Subarachnoid and intracerebral
What is an ischemic stroke?
Stroke in which a clot blocks an artery to the brain
What causes ischemic stroke?
Narrowed arteries in brain. Embolism, thrombosis of cerebral artery (thrombotic ischemic stroke), hypoperfusion
What is the result of ischemic stroke?
Decreased cerebral blood flow
What is and infarct in ischemic stroke?
Area of dead tissue at site of occlusion
What is penumbra in ischemic stroke?
Tissue surrounding ischemic event, which is also injured. Will succumb to death
What occurs immediately after ischemic event (stroke)?
Blood flow and oxygen reduced leading to hypoxia of local cells
Describe the ischemic cascade.
Energy depletion -> failure of Na and K pumps -> depolarisation of neuronal membrane -> glutamate released in synaptic cleft -> excitotoxin -> glutamate acts on channel receptors (NMDA, AMPA) -> calcium influx -> activation of catabolic enzymes or activation of NO synthase -> cellular injury (free radicals, destruction of structural proteins leads to necrosis; mitochondrial injured leads to apoptosis)
Describe the histology of ischemic stroke.
1 day- Injured neurons shrink and become eosinophilic (red anoxic neurons), nuclei condense, 1 week- damaged neurons disintegrate and removed by macrophages, >3 weeks- cortical atrophy and gliosis
How is ischemic stroke treated?
First line therapy: intravenous alteplase initiated within 4.5 hours of symptoms
Surgical thrombectomy in large blood vessels
What are gliomas?
Malignancy arising from glial cells in CNS
What are types of gliomas?
Astrocytoma, ependymoma, oligodendroglioma, glioblastoma
What are meningiomas?
Non-aggressive neoplasm arising from arachnoidal cells
What can result from a meningioma?
Hydrocephalus caused by interference with CSF circulation
What are two types of infectious disorders affecting the CNS?
Encephalitis and meningitis
What is encephalitis?
Infection causing inflammation of the brain, mostly caused by viruses
What is meningitis?
Inflammation of meninges of brain or spinal cord
