Neuropathology (2) Flashcards
What is the WHOs definition of cerebrovascular disease (stroke)?
3rd leading cause of death
Rapidly developing signs of focal disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin
What is global anoxia?
loss of neurons in areas of vulnerability to anoxia-pattern seen in total circulatory collapse - hypoxix ischaemic changes in the brain
- incl neurones in cortex, hippocampus and purkinje cells of cerebellum
What is a watershed/boundary zone infarction?
infarction in cerebral cortex located at the boundaries between different arterial territories
- form of ischaemia - found with severe reduction in oxygen delivery to the brain e.g. severe hypotension in surgical/septic shock
What can cause infarction?
occlusion of artery-atherosclerosis
- risk factors = hypertension, smoking
Embolism - more common than thrombotic inclusion
- 1) atheroma in extracranial arteries e.g. bifurcation of carotid arteries, origin of vertebral arteries, ascending aorta and the arch of aorta
- 2) cardiac e.g. atrial fibrilliation, endocardititis
What are the general RF, local RF and secondary factors for intracerebral haemorrhage?
General = hypertension Local = aneurysm, arterio-venous malformation Secondary = amyloid angiopathy, tumour, trauma
What are the key sites of aneurysms for subarachnoid haemorrhages?
1) anterior communicating artery - 90%
2) internal carotid artery and middle cerebral artery
3) basilar artery
4) cerebellar artery
What does a tare of the middle meningeal artery cause?
epidural aneurysm - most common cause
How is the relative brain tumour distribution different between adults and children?
In adults brain tumours/CNS tumours are 14th whereas in children they are 2nd
What is the most common type of cerebral tumour?
glioblastoma and anaplastic astrocytoma - 35%
- glioblastoma is one of the most aggressive tumours with a survival expectancy of about 9 months
What is different about the latest version of classifying cerebral tumours?
important to incorporate molecular parameters into the classification
- genotype trumps the histological phenotype
For sites that lack any access to molecular diagnostic testing, a diagnostic designation of NOS
What are the molecular patterns that need to be determined for glial tumours?
isocitrate dehydrogenase - part of the kreb’s cycle - mutation in glioma improves prognosis but increases rate of epilepsy
Loss of heterozygosity at 1p and 19q
06 methylguaninemethyltransferase (MGMT) - Promoter methylation status
What is the WHO grading system for astrocytic tumours?
Grade 1: pilocytic astrocytoma (childhood)
Grade 2: diffuse astrocytoma
Grade 3: anaplastic astrocytoma
Grade 4: Glioblastoma
What are the common characteristics of diffuse astrocytomas?
most are isocitrate dehydrogenase (IDH) (1 or 2) mutant
usually have a good prognosis
occur in 20-40s
eventually transform to anaplastic astrocytoma then to secondary glioblastoma mutliforme (GBM) (40-50s)
Secondary GBM = glioblastoma and IDH mutant
Primary GBM = IDH wild type, older age
How are oligodendrogliomas classified?
regular branching capillary network on histological appearance
IDH mutation and 1p, 19q codeletion
What are the common sites for meningiomas?
parafalcine, lateral sulcus, orbito-frontal cortex, cerebellopontine angle, thoracic spinal dura, sites at base of skull
What are examples of peripheral nerve sheath tumours?
neurofibromatosis (type 1 and 2), neurofibroma (arise within nerve), schwannoma
What are the different groups of medulloblastomas classified by the WHO?
Group 1: WNT activated
Group 2: Sonic hedgehog activated
Group 3&4: non-WNT and non-SHH activated
Nmyc is also an important prognostic factor
What are examples of intradural, intramedullary spinal tumours?
within substance of SC - Astrocytoma, ependymoma
What are examples of intradural, extramedullary spinal tumours?
outside of the spinal cord
- meningioma, schwannoma
What are examples of extradural spinal tumours?
metastatic carcinoma, lymphoma
What are primary forms of CNS lymphoma?
mostly large B cell lymphomas occurring in older patients
can also occur in severe immune deficiency and these cases are EBV associated
What does systemic disease of CNS lymphoma usually cause ?
lymphomatous meningitis, which is similar to carinomatous meningitis
What are the routes of infection for bacterial meningitis?
haematogenous
Nasopharynx
from local infection- middle ear, air sinuses etc
local defect - malformation, trauma
What are the different microorganisms that cause bacterial meningitis?
streptococci, staphylococci, meningococci
- diagnose by lumbar puncture
What are some of the key complications of CNS infection?
cerebral swelling
infective thrombophlebitis - venous infarction
subdural effusions
hydrocephalus
cranial nerve defects - especially deafness
What are the routes of infection for cerebral abscesses?
haematogenous - spread from purulent chronic infections elsewhere, especially lung abscess, bronchiectasis, SBE, congenital cyanotic heart disease
local - middle ear, air sinuses
local defect- malformation, trauma
What is the pathology of CNS infection?
cerebritis with cavitation and pus formation, encapsulated by gliosis and granulation tissue
What is death usually due to in terms of CNS infection?
cerebral swelling
ventriculitis (pus expelled in ventricle)
Meningitis
What happens in chronic meningitis and what is the time frame?
pus collects at the base of the brain- lead to cranial nerve defects
time frame: weeks rather than days, insidious onset
complications include hydrocephalus and venous thrombosis
What are some different causes of chronic meningitis?
1) tuberculosis - from tuberculoma
2) cryptococcal infection - usually in immunocompromised pt
3) inadequately treated bacterial meningitis
What viruses can cause viral meningitis?
benign illness caused by:
- enterovirus e.g. ECHO, coxsackie
- mumps
- varicella/zoster
- HSV 2 (neonates)
- adenovirus
What is the commonest infection causing viral encephalitis?
HSV 1 - commonest in europe, localised to temporal lobes and limbic system with some rarefaction (less dense)and necrosis
Where is herpes simplex encephalitis usually confined to?
temporal lobe - can cause haemorrhage, necrosis of limbic system
How can you contract rabies?
rhabdovirus from infected saliva via a bite, abrasion or mucosal membrane
- usually affects the brainstem and cerebellum
How long is the incubation period for rabies?
1-6 months, travels along axons - can be months before they get encephalitis
mortality is 100%
2 types: furious and paralytic types
What are the key viruses that cause encephalomyelitis and what are the key characteristics?
mostly poliovirus 1, 2 and 3 mostly asymptomatic, paralysis in 1-2% infection via GI tract Acute - general CNS involvement Loss of LMN
Where are neurons lost in poliomyelitis and what effect does this have?
loss in the anterior horn of the spinal cord leading to paralysis
What is subacute sclerosing panencephalitis (SSPE) and when does it occur?
slow viral infection - onset years after measles - especially if initial attack is before 2 years
incomplete form of virus in the brain
What is the prognosis for subacute sclerosing panencephalitis (SSPE) ?
50% die in 1 year
75% die in 2 years
M:F - 2.5:1
When does post infectious encephalomyelitis usually occur and what is the prognosis?
usually after viral infection - measles, varicella, rubella, mumps
post vaccination
10-15% mortality, generally good recovery in survivors
What are some example CNS infections caused by parasites?
malaria
trypanosomiasis
echinococcus granulosis - hydatid cyst
taenia solium- cysticercosis - caused by larval cysts of tape worms and can lead to seizures in adults
What are some CNS infections of immunosuppression?
1) fungal - cryptococcus, aspergillus, candida
2) viral- CMV, progressive multifocal leucoencephalopathy
3) parasites - toxoplasma gondii - have an antibody against this
4) AIDS
What are the treatments for autoimmune encephalitis?
paraneoplastic - often treated with antibodies that target intracytoplasmic antigens - dont respond to immunosuppression
others are treated with antibodies to membrane bound antigens and respond well to immunosuppression
Where is the main pathology in autoimmune encephalitis?
medial temporal lobe limbic encephalitis
What are the antibodies for autoimmune encephalitis?
anti-NMDA, anti-VGKC and anti-GABA
What is the clinical presentation of autoimmune encephalitis?
cerebellar syndrome
recent onset of intractable seizures
progressive memory problems, personality change, cognitive impairment
isolated psychiatric syndromes
brainstem syndrome
dysautonomia - failure of ANS = sympathetic and parasympathetic system disorder
