What % of all tumours are CNS tumours?
10%
-commonest SOLID tumour in children (2nd to leukemia)
What age are CNS tumours increasingly common?
- double peak
- 1st and 6th decade of life
Where are CNS tumours more likely to be located in adults vs. children?
adults –> 70% supratentorial (cerebral hemispheres)
children –> 70% infratentorial (brainstem/cerebellum)
N.B. tentorium = line separating cerebellum from occipital lobe
What % of CNS tumours are metastatic?
50-70% (common in adults)
Why are CNS tumours typically of glial cell origin rather than neurons?
neurons are NON-DIVIDING CELLS
What are the special features of CNS tumours?
- glial origin (rarely neural)
- rarely spread outside CNS
- NO capsule (no collagen tissue present)
- NO in-situ stage (like epithelial cell malignancies)
- location NOT type of tumour determines clinical outcome
What is the commonest CNS tumour in adults and children?
ASTROCYTOMA - glioma (glioblastoma = high grade)
- both adults + kids (kids also medulloblastoma - germ cell tumour - v. common)
- -> 90% in kids (+medulloblastomas); 70% in adults
N.B. in adults commonest cause of CNS tumour = metastasis (breast, lung, colon, melanoma)
What are the clinical features of CNS tumours?
- slow, progressive, chronic, morning headache, crescendo
- nerve damage –> unilateral* vision defects, anosmia, seizures
- raised ICP –> headache, vomiting, bradycardia, papilloedema
- nausea/vomiting –> ICP: medulla oblongata compression
- bradycardia –> ICP: parasympathetic (vagal) stimulation
- seizures (convulsions) –> irritation/injury/inflammation
- drowsiness/obtundation –> brainstem compression
- personality/memory –> frontal lobe injury
- changes in speech –> temporal lobe injury
- limb weakness –> motor area injury
- balance/ataxia –> cerebellar injury
- eye movements/vision –> optic tract/occipital lobe injury
What is a low grade vs. high grade glioma?
low grade = astrocytoma
high grade = glioblastoma (high grade astrocytoma)
What are the nerve sheath CNS tumours?
- schwanoma (schwann cells)
- neurofibroma
What tumour is common in meninges?
meningioma
-commonest CNS tumour but technically not included as a CNS tumour as it is of the meningeal layer covering the CNS
What is the commonest germ cell CNS tumours and what are the others?
- MEDULLOBLASTOMA (incr. in kids)
- neuroblastoma
- teratoma
- neuroma
- neuroganglioma
What is the commonest INTRACRANIAL tumour?
meningioma
- mostly asymptomatic
- usually in adults
What is the origin of meningiomas?
- meningeal cells
- arachnoid granulation fibroblasts within venous sinuses (attached to dura)
- compresses NOT infiltrates
- common in females (2:1)
What effect does progesterone have on meningiomas
- stimulates increase in size
- therefore F:M = 2:1
- cyclical (menstruation) and pregnancy –> stimulates meningiomas
What are the commonest types of meningiomas?
parasagittal meningiomas
What are the features of meningiomas?
- slow growth
- multiple; asymptomatic commonly*
- well differentiated and demarcated
- does not invade brain tissue (benign - rarely malig.)
- reactive hyperostosis of skull over tumour
What gene mutation is commonly seen in meningiomas?
NF2 gene mutation
-50% of meningiomas
What is the commonest histologic subtype of meningiomas?
- psammomatous
- rounded collection of epithelial-like looking cells (actually from fibroblasts)
- microcalcification = psammoma bodies
Compare low and high grade commonest glioma in adults?
commonest glioma = astrocytoma
low grade –> solid, diffuse astrocytoma
high grade –> glioblastoma multiforme* (necrotic, haemorrhagic + highly malignant)
What is pilocytic astrocytoma?
- commonest glioma in children
- ‘pilo’ = hairs (microscopically - cells have long, hairy processes)
What mutations can be found in adult + childhood astrocytomas?
Adults –> IDH1 mutation (immunostainng for IDH1 = important diagnostic tool)
Children –> BRAF mutation
What are grade IV astrocytomas AKA?
glioblastoma multiforme (GBM)
- v. necrotic/haemorrhagic and high graded tumours
- mean survival <1yr
- commonest astrocytoma in adults (>40yrs)
What mutation is commonly present in glioblastoma multiforme patients?
- mutation on chromosome 10
- 80% of cases
What are the 2 types of glioblastoma multiforme?
- primary (worst)
- starts as high grade tumour and rapidly kills pt. - secondary (more common - better prognosis)
- starts from low grade astrocytomas
- after many yrs –> high grade malignancy
What are the gross and microscopic features of glioblastoma multiforme?
Gross:
- pleomorphic
- necrotic (multiforme)
- haemorrhagic
Micro:
- pleomorphic cells
- central necrosis
- pallisading
- haemorrhage
How can you differentiate between low grade and high grade (GBM) astrocytomas on MRI?
low grade = diffuse margins
high grade = well demarcated (due to rapidly growing tumour); also RING ENHANCEMENT
What is ring enhancement?
- feature of very high grade astrocytoma (GBM)
- peritumoral edema
Where are pilocytic astrocytomas located and what clinical feature do they cause?
- cerebellum
- abnormal gait
- *children, slow growth, low grade, BRAF mutation (not IDH1 - adults)
What are the gross and microscopic features of pilocytic astrocytomas?
Gross:
-cystic mass with mural nodule
Micro:
-hair-like (pilocytic) astrocytes
What cells are affected in medulloblastomas? and where in the brain do they occur?
- embryonic cells
- Primitive Neuro Ectodermal Tumour (PNET)
- located in cerebellum (upper portion –> vermis)
N.B. highly malignant but v radiosensitive
True or False?
CSF seeding and meningeal irritation is common in medulloblastomas
True
-can present like meningitis
What is the microscopy of medulloblastoma?
- dark blue, small, blast cells with scanty cytoplasm
- similar to retinoblastoma, neuroblastoma, nephroblastoma, lung SCC, etc
- rosettes and neuronal differentiation (embryonic) may be seen
What is infection of the dura known as?
pachymeningitis
- rare
- following sinusitis, fracture, etc
What is leptomeningitis?
infection/inflammation of the arachnoid only
What are the 2 types of meningitis?
Acute:
- septic –> bacterial
- aseptic –> viral
Chronic:
-fungal, TB, parasitic, etc
What is bacterial meningitis AKA?
acute pyogenic meningitis
What is the term used when meningitis is combined with infection of the brain?
meningoencephalitis
What are the causative pathogens for bacterial meningitis in infants, young adults and adults?
etiology = breakthrough the blood brain barrier
- infants –> E. coli
- young adults –> Neisseria meningitides; S. pneumoniae
- adults –> S. pneumoniae
What is the pathogenesis of neck stiffness in meningitis?
-inflammation of meninges is so severe that any movement of the head causes pain due to sensory nerves in the meninges
What are the clinical features of meningitis?
-acute
-fever
Meningeal irritation:
-headache
-photophobia –> irritation to optic nerves
-clouding of consciousness –> raised ICP
-irritability
-neck stiffness –> severe meningeal inflammation
(-seizures)
*MENINGISM
How is meningitis diagnosed?
Lumbar puncture (CSF)
- increased pressure
- increased WBCs/neutrophils
- increased proteins
- decreased glucose –> in bacterial as bacteria use up the glucose!
What type of bacteria is Neisseria meningitides and how is it transmitted?
- gram negative, aerobic, encapsulated diplococci
- transmitted via contact, schools, congregations, etc
What % of people are healthy carriers for Neisseria meningitides?
10%
What are the features of meningococcal meningitis and what is the characteristic feature?
- begins as throat infection
- headache
- RASH* –> petichial/ecchymosis, non-blanching rash
- drowsiness
- confusion
- convulsions/seizures
Which meningococcal serotype is the most common?
serotype B
-vaccine now available for students :)
What type of bacteria is responsible for streptococcus meningitis? and what % of the population have it as a commensal?
gram positive, aerobic, diplococci
–> 40% population = commensal
True or false?
clinical features of streptococcal meningitis include meningism plus rash
False
-NO rash in strep meningitis, rash IS present in meningococcal meningitis
Which age group is most affected by acute viral meningitis and what is the commonest causative virus?
- more common in young (<5yrs)
- enterovirus –> coxsackie B virus
What is the peculiarity of viral meningitis with regards to clinical features?
- can be asymptomatic
- v. mild –> v. severe
Describe the CSF features in viral meningitis?
- clear (aseptic)
- increased proteins
- increased lymphocytes
- NORMAL glucose –> virus does NOT use glucose (c.f. bacterial meningitis)
What is the only microscopic finding supportive of viral meningitis?
perivascular lymphocyte cuffing
What is the commonest cause of fungal meningitis?
Cryptococcus neoformans
-increased in immunosuppressed (AIDS) pts.
What are the features of fungal meningitis?
- thick, fibrotic exudate over meninges
- mucoid exudate in ventricles –> hydrocephalus
- small cysts in parenchyma (soap bubble lesions)
- specifically in basal ganglia
What % of AIDS pts have CNS involvement and how do they typically present?
- 80%
- present as progressive dementia
What cells in the CNS does HIV infect?
microglial cells –> glial nodules + multinucleate giant cells
Which herpes virus is the most common in herpes encephalitis and what are the clinical features?
HSV-1
- children/young adults
- marked necrosis/destruction of inferior frontal/anterior temporal lobes due to virus –> memory, mood, and behavioural abnormalities result
If CSF from a lumbar puncture appeared opalescent with ‘cobweb-like’ structures what is suspected?
TB –> meningitis
What characteristic imaging finding is present in brain abscess?
- ring enhancement (same as glioblastoma multiforme)
- peritumoral oedema
What are the acute and chronic complications of meningitis?
acute: -oedema, raised ICP, herniation, ischaemia/infarction –> death
chronic: -epilepsy, hydrocephalus, abscess
What is epilepsy?
- abnormal, recurrent, spontaneous neuronal firing
- manifests clinically by changes in motor, sensory, behavioural +/or autonomic function
What is ictus?
period of seizure
What is a key feature of epilepsy that differentiates it from other causes of seizures?
stereotypic nature:
- preceded by aura (subjective sensation –> pt can tell they are about to have a seizure)
- postictal state (drowsiness, confusion, etc)
Where are the most seizure-prone areas of the brain?
temporal lobe + hippocampus
What is the commonest etiology of epilepsy?
idiopathic
What is the pathogenesis of epilepsy?
-decreased inhibition of neurotransmission due to defective GABA neurons (gamma aminobutyric acid = major inhibitor of neurotransmission)
How is epilepsy diagnosed?
- MRI
- CT
- interictal EEG** –> abnormal spikes of neuronal activity in between seizure activity
What is the commonest subtype of epilepsy?
complex partial epilepsy
- partial = localised to one area of brain (INCR. TEMPORAL)
- complex = altered LOC/behaviour
**SECOND COMMON = GRAND MAL (TONIC CLONIC)
Outline subtypes of epilepsy
Partial: -seizure activity starts on one brain area
- simple –> retains awareness
- complex –> altered awareness/behaviour
Generalised: -seizure involves whole brain with ALOC
- tonic clonic –> grand mal/convulsion
- absence –> petit mal/staring fit
- atonic/tonic –> drop attack
- myotonic –> sudden muscle jerksq
What is status epilepticus?
- > 30 mins seizure OR from which a person does NOT regain consciousness
- convulsive or non-convulsive
What is the normal ICP and what is it comprised of?
5-10mmHg
-blood, brain, CSF
What is the Monro-Kellie doctrine?
“the sum of the intracranial volumes is constant and therefore an increase in any one of these compartments must be offset by an equivalent decrease in the other two”
What is the clinical definition of increased ICP?
> 20mmHg for >5mins
What is cerebral perfusion pressure (CPP) and what is the normal level?
CPP = mean arterial pressure - intracranial pressure
CPP = MAP - ICP
-normal >50mL/100g/min
What level of CPP is clinically defined as ischaemia?
<20mL
What are the common causes of increased ICP?
- cerebral oedema
- congestion (inflammation, infection - meningitis)
- hydrocephalus (block in CSF flow)
- mass (tumour)
What are the common clinical features of increased ICP?
- headache, vomiting + visual disturbances
- depressed consciousness
What is Cushing’s triad?
- increased BP (hypertension)
- decreased pulse (bradycardia)
- irregular breathing
*v. severe injury involving the BRAINSTEM
What are the 4 common types of herniation?
- Subfalcine/Cingulate
- common; headache + contralateral leg weakness - Transtentorial: central
- thalamus and midbrain push towards 4th ventricle
- small but reactive pupil; drowsiness; ALOC; agitation - Transtentorial: temporal/uncal
- CN III injury; ipsilateral dilated pupil; decreased LOC - Tonsillar
- obtundation; decerebrate posture; cardiorespiratory arrest (brainstem affected) **MOST SEVERE!
What is the commonest type of herniation and what is the most severe type?
commonest = subfalcine/cingulate herniation
most severe = tonsillar
What is the pathogenesis of contralateral leg weakness in subfalcine/cingulate herniation?
- subfalcine herniation of cingulate gyrus causes block of ACA –> more infarction, oedema and further raised ICP
- clinically (due to ACA block) –> contralateral leg weakness (hemipariesis)
What is the typical Tx for central herniation?
craniectomy to relieve pressure (remove portion of skull)
True or False?
dilated pupil with normal LOC is not herniation
True
What are duret haemorrhages?
- small areas of bleeding in midbrain/upper pons
- caused by compression of central veins due to cerebellar/tonsillar herniation
What is the definition of hydrocephalus?
excess CSF in brain
Where is CSF produced?
choroid plexus within ventricles of brain
Through what does the CSF travel through to reach the subarachnoid space?
Foramen luschke and magendie
-absorbed back in arachnoid villi in venous sinuses
What are the 3 major types of hydrocephalus?
- obstructive/non-communicating
- obstruction to CSF flow –> dilatation of part of CSF space - non-obstructive/communicating
- excess CSF due to lack of absorption, infections/inflammations - compensatory
- secondary dilatation due to brain atrophy
Cyclical pain is typically seen in which CNS tumour?
meningioma
What are brain abscesses typically surrounded by?
scar tissue