Neuropathology 2 Flashcards
What are the types of focal lesions in trauma?
=scalp lacerations =skull fractures =contusions (bruises on the brain) =intracranial haemorrhages =lesions secondary to raised intracranial pressure
What are the types of diffuse lesions in trauma?
=Global ischaemia
=Brain swelling
=Traumatic axonal injury
What are the causes of head injury?
=Road traffic accidents
=Falls
=Assault
What are the mechanisms of head injury?
-Direct contact =object striking head/ being struck by head -acceleration/deceleration =unrestricted movement of the head -Penetrating -Blast
Where are acute contusions usually seen?
Frontal and temporal regions
What are the types of intracranial haemorrhages?
-Extradural
=usually associated with squamous temporal bone fractures damaging the underlying middle meningeal artery
=concave deformation of brain (haematoma space occupying)
-Subdural
=extensive, associated with cortical contusions and torn bridging veins
-Subarachnoid
=rarely extensive, usually associated with contusions
-Intracerebral
=superficial associated with contusions
deeply seated often within the basal ganglia
What are the consequences in the brain from an extradural haemorrhage?
- Subfalcine herniation
- Tentorial herniation
- Axial displacement
- Tonsillar herniation
Describe diffuse traumatic axonal injury
- Rotational injury
- Corpus callosum and internal capsule involved, brainstem
- T2 star MRI (black dot in corpus callosum)
- Susceptibility Weighted Image (black dots are haemorrhage)
- DAI
What is Penetrating Head Injury?
- Brain parenchyma damaged by missile
- In ballistic parenchymal damage there is a “blast wave” which can cause damage distant from the tract
- Strength of wave determined by velocity of bullet
Describe the aetiology of brain tumours
-X-irradiation; meningiomas / sarcomas / gliomas associated with previous therapeutic irradiation (20-30 year delay).
-Occupational exposure to herbicides?
-Electrical and magnetic fields?
-Oncogenic virus SV40 (introduced via polio)?
-Hereditary tumour syndromes
=NF; meningiomas, schwannomas, gliomas
=VHL; haemangioblastomas
=Tuberous sclerosis; SEGA
=Li Fraumeni; gliomas, medulloblastomas
What are the general principles of CNS tumours?
- Anatomical location
- Local invasion
- Angiogenesis
Why is it difficult to get complete resection of even low grade tumours?
- Frontal lobectomy
- Follow tumour into normal white matter (macroscopic resection)
- Glioma cells diffusely infiltrate beyond macroscopic resection
What are the common brain tumour types?
- Metastatic tumours
- Gliomas (astrocytomas including glioblastoma, oligodendrogliomas etc)
- Meningiomas (usually low grade)
- In children, medulloblastoma (posterior fossa/ cerebellum)
What are the main categories of neurodegenerative disorders?
- Tauopathies
- Synucleinopathy
- Trinucleotide repeat disorders (Huntington’s)
- TDP43 proteinopathy (motor neurone disease)
- Prion disorders
- Motor neurone disorders
- Others
How are these abnormal proteins formed?
- Abnormal cleavage in Alzheimer’s
- Misfolding in prion disease (CJD)
What happens when disposal systems cannot cope?
In disease states where large amounts of abnormal protein may aggregate, these mechanisms are overwhelmed and ubiquitinated proteinaceous inclusions are formed
- Ubiquitin Proteasome System= manage abnormal proteins
- Ubiquitinated proteins when abnormal, taken off to proteasome to digest
What is Dementia?
- Defined as a loss of cognitive and other higher functions without loss of consciousness
- Prevalence: 5%> 65 years, 15%>80 years F > M
- The “silent epidemic”
What are the causes of Dementia?
=Alzheimer’s disease =(AD) 75% -AD and vascular disease =5-10% -Lewy body disease (+/- AD) =5-10% -Vascular disease =5-10% -Others: =1-3% =Huntingdon’s disease =Prion diseases =Metabolic diseases
What is the pathology of Alzheimer’s?
- Cortical beta amyloid pathology in frontal cortex
- Tauopathy
- Deposits in parenchyma and blood vessels
- Cerebral amyloid angiopathy
- Spreads from Hippocampus to temporal/ frontal lobes then occipital/ parietal lobes
Describe vascular dementia
- Generally due to multiple infarcts (multi-infarct dementia)
- Lacunar type infarcts= caused by blockage of striate arteries
- Binswanger’s disease (probably end-stage of chronic hypertension)
What are the movement disorders?
- Parkinson’s disease
- Other causes of parkinsonism
- Ataxias
- Disorders of the motor neuron
Describe Parkinson’s
- Commonest of the movement disorders
- Due to loss of dopaminergic neurones in substantia nigra
- Characterised by Lewy bodies (alpha synuclein protein)
What are other causes of parkinsonism?
- Multiple system atrophy
- progressive supranuclear palsy (tauopathy)
- Iatrogenic (anti-psychotics)
- vascular
- drug induced
What are the types of motor neuron disorders?
- Motor neuron disease (adults)
- Spinal muscular atrophies (children)= degeneration of LMN, accumulation of TDP-43
- Hereditary spastic paraparesis
Describe demyelination
-Commonest cause is multiple sclerosis (MS).
-Other causes include;
=Infective
(Progressive multifocal leucoencephalopathy
Acute haemorrhagic leukoencephalitis)
=Developmental (dysmyelination)
=Post-vaccination
Describe MS
- Commonest cause of demyelination
- Auto-immune condition with the response being directed against a protein found in only central nervous system myelin.
- Common sites for plaques include periventricular region and optic tracts.
What are the pathologies of the cornea?
-Inflammatory (keratitis)
=infective/non-infective
-Degenerations
=corneal dystrophies (epithelium, stroma, endothelium)
-Neoplasms
=very rare; epithelial/ melanocytic, squamous cell carcinoma
What are the pathologies of the iris, ciliary body and choroid?
-Inflammatory (uveitis) =often non-infective (RA, Behcet's) -Neoplasms =melanocytic =soft tissue
What are the pathologies of the retina?
-Inflammatory =CMV, HSV, toxoplasma -Degenerative =retinitis pigmentosa =macular etc. -Neoplastic =retinoblastoma (childhood) =lymphoid =glial
What are orbital lesions?
-Inflammatory
-Neoplastic
=soft tissue; rhabdomyosarcoma, osteosarcoma
=lymphoid
