Neuropathology (2) Flashcards by Harriet Agnew

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What does a tare of the middle meningeal artery cause?

epidural aneurysm - most common cause

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

How are oligodendrogliomas classified?

regular branching capillary network on histological appearance
IDH mutation and 1p, 19q codeletion

How well did you know this?

Not at all

Perfectly

What are the common sites for meningiomas?

parafalcine, lateral sulcus, orbito-frontal cortex, cerebellopontine angle, thoracic spinal dura, sites at base of skull

How well did you know this?

Not at all

Perfectly

What are examples of peripheral nerve sheath tumours?

neurofibromatosis (type 1 and 2), neurofibroma (arise within nerve), schwannoma

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What are examples of intradural, intramedullary spinal tumours?

within substance of SC - Astrocytoma, ependymoma

How well did you know this?

Not at all

Perfectly

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