Neuropathology 2 - vascular disease and tumours Flashcards
What type of herniation are a, b, c
what type of haemorrhage are small linear areas of bleeding in the midbrain and upper pons of the brainstem. They are caused by a traumatic downward displacement of the brainstem.
A - cingulate herniation(cingulate gyri of frontal lobe - can cause anterior cerebral artery branch to tear)
B- Transtentorial herniation - uncal herniation
C - cerebellar tonsillar herniation - fatal
Duret haemorrhages
1) What problems occur due to a transtentorial herniation?
2) compression of CN3 causes what clinical ?
3) What hernation do you get after cranioectomy?
1) Transtentorial herniation can compress cn3, crus cerebri(substancia niagra-descending coticospinal tracts)-posterior arterycircle of willis(you can get cortical blindness) - look for pupilary dilation
2) CN3 compression causes opthalmoplegia and pupil dilation - downwards and outward
3) Extracranial herniation
Cerobovascular disease is the 3rd leading cause of death
Define TIA
Define stroke
TIA: This is an ischaemic (usually embolic) neurological event with symptoms lasting <24h (often much shorter)
Stroke: Rapidly developing signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin
what cells tend to be affected in adults when there is global anoxia(Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury)
what changes do you see in adults to the neurones?
what part of the hippocampus are vulnerable to ischaemia?
what lamina are affected during ischaemia
Loss of neurons in areas of vunerability to anoxia-pattern seen with total circulatory collapse.
Includes neurons in the cerebral cortex, hippocampus and Purkinje cells of the cerebellum
Neurones undergo eosinophilic changes (pink in H +E)
In children you see apoptosis
Hippocampus: CA1, CA3, CA4 - hypoxia affects them but CA2 is resistant
Lamina 4,5,6 are affected by ischaemia whereas the 1,2 and 3 are resistant.
What is a watershed/boundary zone infarction?
Infarction in cerebral cortex located at the boundaries between different arterial territories.
What is infarction
what is pale infarct and red infarct?
What are the source of emboli?
What happens in the first 24 hour of the infarction?
Infarction - there is total loss of blood supply
Pale infarct - complete loss due to thromosis
Red infarct - emboli occludes vessel then the emboli fragments - causes bleeding.
Embolism can com in:
1)atheroma in extracranial arteries eg bifurcation of carotid arteries, origin of vertebral arteries, ascending aorta and the arch of the aorta
2) Cardiac eg atrial fibrillation, endocarditis, right to left shunt
In first 24 hours: there is oedema, then cystic changes due to the macrophages
The pictures - the blue shows infarct in descending branches.
You can see parasaggital infarction in hypercouagable state
What is the treatment for infarction?
What is the treatment for emboli?
Infarction - you use clot busters Alteplase under 4.5 hours
emoboli do a thrombectomy
Haemorrhage more common in developing world
what are the general risk factors, local risk factors and secondary risk factor?
If the bleed is in the basal ganglion it is usually due to?
If you see bleed in the lobes of the brain it is due to?
General risk factors eg Hypertension Local risk factors eg Aneurysm, Arterio-Venous Malformation Secondary eg Amyloid Angiopathy, Tumour, Trauma
Bleed in basal ganglion due to hypertension. Cerebellar and pons can also happen. Pons dorsolateral part - pedunlces - usually traumatic axonal,
Bleed in the lobes usually amyloid angiopathy - amyloid accumulate around vessels and can bleed
What does the person have?
What is the common reason for it?
Subarachnoid haemorhage
commonly by anterior cereberal artery aneurysm - media and intima absent
basilar artery - fusiform - whole vessel aneurysm
Can be caused by cough, intercourse
How common are brain tumours compared to others in adults compared to adults?
In adults it is 14th whereas children it is second
What are these pictures showing?
What classifcation is followed?
Grading of tumour
histology of the brain
WHO CNS 2016 - molecular groups are added too.
Grade 1 is excisable and well circumcised
Grade 4 - highly aggressive
Main group is diffuse astrocytic and oligodendroglial tumours
embryonal tumours - medullablastoma - good prognosis with treatment
Mengioma
What are common sites of metastatic CNS neoplasm?
Which rarely metastasise to the braim
Which tumour has the worst survival?
The 2016 World Health Organization Classification of Tumors of the Central Nervous System
How is it done
- practical advance over its 2007 predecessor
- uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era.
- The current update (2016 CNS WHO) thus breaks with the century-old principle of diagnosis based entirely on microscopy by incorporating molecular parameters into the classification of CNS tumor entities
the genotype trumps the histological phenotype
• For sites lacking any access to molecular diagnostic testing, a diagnostic designation of NOS(not otherwise specified)
Glial tumours
What do you look for this tumour?
what is the marker for therapeutic response?
Isocitrate DeHydrogenase (IDH) -part of 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. - important for treatment not diagnosis
Diffuse Astrocytomas and oligodendroglioma
What mutation is important to look for prognosis
what type of tumours are the following in the picture?
First one has homogenous lesion
second one has heterogenous with areas of necrosis and haemorrhage. Can increase ICP
Check for IDH mutation.(Isocitrate DeHydrogenase (IDH) -part of Kreb’s cycle. Mutation in glioma improves prognosis ,but increases rate of epilepsy.) This mutation means they have a better prognosis than wild types
Most are IDH (1or 2) mutant Occur in 20s-40s Eventually transform to anaplastic astrocytoma then to secondary GBM (40-50s) Secondary GBM-glioblastoma, IDH mutant Primary GBM-IDH wild type, older age.
What is the histological and molecular findings needed to classify an olidodendroma?
Why is it important to classify these tumours
As well as showing the classical histology (a regular branching capillary network, with round, and often clear, cells) these also defined by IDH mutatation and 1p,19q codeletion
If it has only IDH mutation it is called astrocyotoma
Oligo have better prognosis(grade 2 or 3) and better action to chemotherapy - anaplastic ones are chemosensitive to treatments such as PCV(Procarbazine, lomustine and vincristine)
Perivascular pseudorosetts seen
What does the person have?
ependyoma
Myxopapillary ependymoma seen usually in conus medullaris of the spine
What are these?
Meningioma - they are usually grade 1 and benign. Grade 2 are atypical and grade 3 are metastatic meningioma
Peripheral nerve sheath tumour examples?
Neurofibromatosis , types 1 and 2
Type 1: cafe au lait spots seen
Type 2 (bilateral acoustic schwannoma)
Neurofibroma Schwannoma
Group 1 is activated by what?
Group 2 is activated by what?
Group 3 and 4 is activated by what?
Group 1: WNT activated
- Group 2: Sonic HedgeHog (SHH) activated
- Group 3 & 4: non-WNT, and non-SHH activated
- (Nmyc amplification is also an important prognostic factor)
What are routes of infections for bacterial meningitis?
how is it diagnosed
What complications can it cause?
what organism is common in children and which one in adults?
-haematogenous -nasopharynx -from local infection-middle ear, air sinuses, etc -local defect -malformation,trauma
get csf tap
a.Cerebral swelling b.Infective thrombophlebitis-venous infarction c.Subdural effusions d.Hydrocephalus e.Cranial nerve defects esp. deafness
What does this person have
What is the route?
what is the pathology
Routes of infection as above: 1)Haematogenous spread from purulent chronic infections elsewhere, esp lung abscess, bronchiectasis, SBE, congenital cyanotic heart disease 2) Local, as for meningitis
PATHOLOGY -cerebritis with cavitation and pus formation, encapsulated by gliosis and granulation tissue DEATH DUE TO 1) Cerebral swelling 2) Ventriculitis (pus expelled in ventricle) 3) Meningitis
CHRONIC MENINGITIS
What causes it
1)Pus collects at base of brain (cranial nerve defects) 2) Time course weeks rather than days 3) Insidious onset 4) hydrocephalus, venous thrombosis
CAUSES 1)Tuberculosis-from tuberculoma(shown in picture) 2)Cryptococcal infection-usually in immunocompromised 3) Inadequately treated bacterial meningitis
Viral meningitis caused by?
Viral encephalitis caused by
what three features do you look for in viral encephalitis
Benign illness caused by; -enteroviruses eg ECHO, Coxsackie -Mumps -Varicella/zoster -HSV II(neonates) - Adenoviruses
Encephalitis
1)HSV 1 - Commonest in Europe, localised to temporal lobes and limbic system with some rarefaction and necrosis 2) HSV 2 - neonates 3) Arboviruses eg West Nile 4) Others - adenoviruses, enteroviruses
Picture shows: haemorrhagic lesion in temporal
Viral encephalitis you look for three features: perivascular ,microglial nodules, macrophagia, viral inclusion - antibody stain.
What does this person have?
This person has gone rabid after being bitten
Rhabdovirus, infected saliva via bite, abrasion or mucosal membrane Incubation 1-6 months (travels along axons), mortality 100%, “furious”(hydrophobia, photophobia) and “paralytic”(later stage) types
Rabies negri bodies - eosonophilic inclusion in the large pyramdal cells - diagnostic of rabies
What causes ENCEPHALOMYELITIS
1) Mostly polioviruses 1, 2 and 3 occasionally others
2) Most asymptomatic, paralysis in 1-2%
3) Infection via GI tract
4) Acute; general CNS involvement
5) Loss of lower motor neurons
What parasites do these pictures show?
What are different types of parasite affecting the brain?
1)Malaria 2) Trypanosomiasis 3)Echinococcus granulosis-Hydatid cyst(rare) 4) Taenia solium- Cysticercosis(common worldwide) (contamination of the egg)- immune response when dead.
What do these people have?
What are some diseases caused in immunosuppressed?
1) Fungal-Cryptococcus, Aspergillus(branching filamentous fungi, emboli in lung go to brain), Candida
2) Viral-Cytomegalovirus (CMV), Progressive Multifocal Leucoencephalopathy (PML, due to JC virus)
3) Parasites-Toxoplasma gondii - seen commonly in cat hosts (it can also affect neonates, two forms, takizoids reproduce quickly
4) AIDS
