Week 2 - Seizures, Epilepsy, Meningitis, Tumours Flashcards
Outline the general features of CNS tumours.
• 10% of all tumours (10 to 17 per 100,000).
• Commonest solid cancers in children (2nd to leukaemia).
- Very common in children only second to leukaemia and lymphoma (~20% of childhood cancers).
• Age - double peak 1st and 6th decade.
- Childhood (1st decade) and adults (6th decade).
• Adults - 70% supratentorial
- Tumours above the tentorium cerebri (in cerebrum).
• Children - 70% infratentorial.
- Tumours typically in brainstem or cerebellum.
• Metastatic tumours - 50-70%.
- Common in adults.
• Commonest type is astrocytoma in both adults and children.
Special features:
• Glial origin, rarely neural (via germ cells).
- Commonly originate from glial cells (supporting cells) as neuron cells are non-dividing.
• Rarely spread outside CNS.
- Even high grade tumours usually remain in CNS.
• No capsule* no in-situ stage.
- No capsule as no collagen tissue. No in-situ or precancerous stage like in epithelial malignancies.
• Location of tumour determines clinical outcome (not type).
- E.g. malignant tumour lying outside vital areas may not kill patient however, benign tumour in brainstem can kill the patient.
Identify the clinical features of CNS tumours.
• Slow, progressive chronic morning headache, crescendo*
- Crescendo - neoplastic disease - continuously grows.
• Nerve damage - unilateral*, vision defects, anosmia, seizures etc.
- Nerve damage due to tumour is usually unilateral, motor/sensory abnormalities etc.
• Raised intracranial pressure - headache, vomiting, bradycardia, papilloedema.
- Raised ICP is a feature of rapidly growing tumour or late stage.
- Nausea or vomiting → ICP - medulla oblongata compression.
- Bradycardia → ICP - parasympathetic stimulation (vagus nerve).
- Seizures (convulsions) → irritation/injury/inflammation.
- Drowsiness, obtundation → brainstem compression.
- Personality or memory disturbances → frontal lobe injury.
- Changes in speech → temporal lobe injury.
- Limb weakness → motor area injury.
- Balance/ataxia → cerebellum injury.
- Eye movements → optic tract, occipital lobe injury.
*Some of the clinical signs help to determine the location.
Describe the classification of CNS tumours.
Metastasis - common
• ~50%* breast, lung, GIT, melanoma (commonest in adults).
Primary tumours (rarely from neurons - mainly from glia):
• Glial cells - Glioma* commonest.
- Astrocytoma (low grade) and glioblastoma (high grade astrocytoma) - most common. Oligodendroma, ependymoma - rare.
- Nerve sheath - Schwanoma (Schwann cells), Neurofibroma (perineural fibroblasts).
• Meninges - Meningioma* also common.
- Most common tumour but not included as CNS tumour as it is from the covering meninges.
- Germ cell - Medulloblastoma (commonest - in children), neuroblastoma, teratoma, neuroma, neuroganglioma.
- Other - Lymphoma, angioma, hemangioma, Pituitary and Pineal gland tumours. Epithelial - Craniopharyngioma.
- AV malformation - not true tumour*
What are the common CNS tumours in children and adults?
Children:
• Astrocytoma and medulloblastoma commonest in children (90%) - almost equal (~45%).
Adults:
• Metastasis and then astrocytoma. High grade astrocytoma (glioblastoma) is most common.
- Meningioma - from the meninges. Commonest intracranial tumour - most asymptomatic, adults.
- Glioma - most common CNS tumour. Commonest is astrocytoma - low grade and high grade (glioblastoma multiforme).
- Tumours occurring above tentorium cerebri are common in adults - majority astrocytomas.
- Children - brainstem and cerebellum (below tentorium cerebri). Commonest is astrocytoma and medulloblastoma.
Outline meningioma.
• Tumour of meningeal cells.
• Origin - arachnoid granulation fibroblasts within venous sinuses (attached to dura).
- Attached to the dura as it arises in the venous sinuses. Tumour of the meninges - usually only compresses but not infiltrate.
• Females (2:1), progesterone stimulates (cyclical/pregnancy - increase in size).
- Very common in females, increases in size with exposure to progesterone e.g. cyclical pain (menstruation), pregnancy.
• Multiple, asymptomatic* (slow growing benign tumour but can be symptomatic and rapidly growing - rare).
• Commonest - parasagittal tumour.
• Slow growth, well differentiated and demarcated. Does not invade brain (benign). Rare malignancy.
• Reactive skull hyperostosis occurs over the tumour (skull bone becomes thick over the tumour).
• 50% of meningiomas have NF2 gene mutation (neurofibromatosis type 2 gene).
• Multiple meningioma + 8th nerve schwanoma in Neurofibromatosis type 2 (NF2).
- Multiple meningiomas with auditory neuromas (8th nerve) - typical in NF2.
• Microscopy - many subtypes. Commonest is somatis - rounded collection of epithelium looking cells (actually fibroblasts).
Outline glioma.
- Tumours of glial cells, commonest both in adults and children.
- Benign to malignant.
- Astrocytoma (low and high grade) commonest.
- Adults - commonest 70%, cerebral (supratentorial).
- Low grade - solid, diffuse astrocytoma.
- High grade - glioblastoma multiforme*- necrotic, haemorrhagic areas and highly malignant - poor prognosis.
• Children - commonest 50% - known as pilocytic astrocytomas (pilo = hairs. Microscopically, cells have long hairy processes).
- Cystic, low grade*, pilocytic, infratentorial (cerebellum).
• Grossly, appears as a cystic lesion with a tumour attached to the wall of the cyst.
• Adult astrocytoma - immunostaining for mutated IDH1 - important diagnostic tool (BRAF in childhood astrocytoma).
- Adult astrocytomas usually have IDH1 mutation - important diagnostic tool. In children, some of the cases will show BRAF mutation.
- Adult astrocytoma is genetically and histologically different from childhood astrocytoma.
Outline glioblastoma multiforme.
• High grade astrocytoma - grade IV.
• Commonest and highly malignant brain tumour in adults >40y, mean survival <1y.
• Associated with mutation on chromosome 10 (80% of cases).
• Cerebral, supratentorial location.
• 2 types: primary (worst) or secondary from low grade astrocytomas (better prognosis).
- Primary - high grade, rapidly kills patient.
- Secondary - more common, starts as low grade astrocytoma and after many years, transforms to high grade malignancy (better prognosis).
• Gross: Pleomorphic (multiple morphology due to necrosis and haemorrhage), haemorrhagic, necrotic (multiforme).
• Microscopy:
1. Pleomorphic cells.
2. Central necrosis.
3. Palisading.
4. Haemorrhage.
Describe genetic abnormalities in glioma.
- Several abnormalities have been noted. Most important ones are Rb gene, EGF-R amplication and deletion of 10.
- Glioblastoma starts as a low grade astrocytoma → further mutations add to become a anaplastic astrocytoma → glioblastoma.
Glial cell → Astrocytoma → Anaplastic astrocytoma → Glioblastoma.
• Primary GBM can also occur without prior glioma.
Outline pilocytic astrocytoma.
• Children, slow growth, cerebellum.
- Low grade, usually in cerebellum (infratentorial).
• Abnormal gait.
- Affects cerebellum - abnormal gait as a clinical sign.
• BRAF mutations (not IDH as in adults).
• Gross: cystic with mural nodule.
• Micro: hair-like (pilocytic) astrocytes.
Outline pilocytic astrocytoma.
• Children, slow growth, cerebellum.
- Low grade, usually in cerebellum (infratentorial).
• Abnormal gait.
- Affects cerebellum - abnormal gait as a clinical sign.
• BRAF mutations (not IDH as in adults).
• Gross: cystic with mural nodule.
- cystic lesion in the centre of the cerebellum with a tumour attached to the wall.
• Micro: hair-like (pilocytic) astrocytes.
- long cytoplasmic processes.
Outline medulloblastoma.
• Tumour of embryonic cells.
• Common in children, cerebellum - vermis (upper portion of cerebellum).
• Primitive Neuro Ectodermal Tumour (PNET) embryonic cells.
• Highly malignant but radiosensitive (good response to radiation therapy).
• CSF seeding and meningeal infiltration is common.
- Tumour is known to seed the CSF and spread along the meninges → meningeal irritation - can present like meningitis.
• Microscopy: dark blue, small, blast cells scanty cytoplasm (similar appearance microscopically to retinoblastoma, neuroblastoma, nephroblastoma, lung SCC etc. - embryonic cancer of different tissues).
• Rosettes and neuronal differentiation (embryonic) may be seen.
Summary CNS tumours.
Adults: • Metastases common. • Primary - supratentorial. • Astrocytoma, GBM. • Meningioma * asymptomatic.
Children: • 2nd common (leukaemia/lymphoma). • Infratentorial. • Pilocytic astrocytoma (cystic, cerebellar). • Medullablastoma (PNET).
Outline CNS infections/inflammation - meningitis.
• Infections of Dura - Pachymeningitis - rare, following sinusitis, fracture etc.
- Infection of dura mater - pachymeningitis - occurs following sinusitis, fracture etc. - rare.
• Common Meningitis - Arachnoid/Leptomeningitis.
- Inflammation/infection of the arachnoid only - known as leptomeningitis. 2 major types - acute and chronic.
• Acute - Septic/Bacterial, Aseptic/Viral, Chronic - fungal, TB, parasitic etc.
- Acute meningitis - septic (bacterial) and aseptic (viral).
- Chronic meningitis - fungal, TB, parasitic.
• Others: Chemical, drugs, cancer.
- Also rarely, chemicals/toxins, drugs and cancer can cause meningitis.
• Common: Bacterial/Acute Pyogenic Meningitis*
- Bacterial meningitis common. AKA acute pyogenic meningitis.
• When combined with infection of brain → Meningoencephalitis.
Outline acute pyogenic meningitis - bacterial.
Aetiology: breakthrough blood brain barrier.
• Infants - Escherichia coli (E. coli).
• Young adults - Neisseria meningitides (meningococci), Strep. pneumoniae.
• Adults - Strep. pneumoniae (pneumococci).
• Acute, fever, meningeal irritation - headache, photophobia (irritation to optic nerve), irritability, clouding of consciousness (increased ICP) and neck stiffness.
- Fever plus additional meningeal irritation characterised by headache, photophobia, neck stiffness (meninges so inflamed that any movement of the head causes pain - sensory nerves) etc. (signs of meningism).
Diagnosis:
• Lumbar puncture - increased pressure (in CSF), increased WBC, neutrophils, increased protein, decreased glucose (bacteria use up glucose).
- Blood vessels in brain have a specialised wall - endothelium, basement membrane and astrocytes - very thin → hypertension causes haemorrhage.
- Astrocytes provide defence mechanism (filter) so not all pathogens can enter the brain. Only some pathogens can → meningitis and encephalitis.
Outline meningococcal meningitis.
- Neisseria meningitides.
- Gram negative, aerobic, cocci, capsule.
- 10% healthy carriers.
- Person to person spread - congregations, contacts, schools etc.
- Begins as throat infection, leads to headache, rash* (important feature - skin petechiae, ecchymosis), drowsy, confusion, convulsions.
- Serotype B most common. Vaccine for students.
Outline streptococcal meningitis.
• GAS: group A adults, GBS - new born.
• Commonest in adults
• Gram positive, aerobic, diplococci.
• Common in extremes of age (vaccination given), health problems (e.g. diabetes), pneumonia etc.
• Commensal ~40% population.
- Any decline in health status makes the bacteria overgrow.
• Typically presents with fever, chills, nausea, vomiting.
• Meningism - headache, stiff neck, photophobia.
• No rash*
• Microscopy - dark blue (gram positive) diplococci arranged in pairs.
Outline acute viral meningitis.
• More common. Young, children <5 years.
- More common in young children.
• Enterovirus - Coxsackie B (enteroviral meningitis).
- Many viruses can cause meningitis but Coxsackie B is commonest.
• Arbovirus - Murray valley, tickborne etc.
• Influenza, Herpes simplex, HIV.
• Mumps, Measles.
• Incubation - 3-6 days. Asymptomatic*
• Fever - 7-10 days. Fever, headache, seizures, lethargy. Asymptomatic.
- Coxsackie incubation 3-6 days followed by 7-10 days of fever, headache, seizures and lethargy. However, can be asymptomatic (ranges from mild to severe).
• CSF - clear, increased protein, increased lymphocytes, glucose normal.
• Microscopy - only finding supportive of viral infection is perivascular lymphocyte cuffing. Plenty of lymphocytes surround the blood vessels - common in all types of viral infection.
Outline fungal meningitis.
Cryptococcus neoformans (common).
• Causes chronic basal leptomeningitis (in AIDS patients).
- In chronic meningitis/TB, the pus accumulates in the base of the brain.
- More common in immunosuppressed patients (but can occur in normal patients).
• Thick, fibrotic, exudate over meninges (in the basal areas).
• Mucoid exudate in ventricles, Hydrocephalus*
- Thick mucous can block and cause hydrocephalus.
• Small cysts within parenchyma (soap bubble).
- Soap bubble lesions - small cysts with the parenchyma of the brain.
• Specially in basal ganglia.
Other fungi - Candida, Histoplasma, aspergillus, Mucor mycosis etc. (different features).
Describe CNS infections in AIDS.
• >80% of AIDS patients have CNS involvement.
• Progressive dementia*
- Unlike other meningitis or infections, it presents with progressive dementia.
• HIV infects microglial cells, forming glial nodules and multinucleate giant cells.
• + Opportunistic infections - Toxoplasma, Cryptococcus, CMV, Candida etc.
- In addition, there will be opportunistic infections - additional clinical features.
• Primary cerebral lymphoma - late.
- Late complication in AIDS patients.
Outline herpes encephalitis.
• HSV-1 common.
• Children, young adults.
• Necrosis and inflammation.
- Characterised by extensive necrosis at the base of the brain (both lower portions of the frontal and temporal lobes).
• Affects memory, mood, behaviour abnormality (involves frontal lobe).
• Destruction of inferior frontal and anterior temporal lobes.
• HSV-2 in adults especially with AIDS.
Microscopy:
• Extensive necrosis - necrotic pink cells.
• Microglial cells show large round inclusions within the nucleus.
Outline CSF examination for pyogenic, viral and TB.
Pyogenic: • Appearance - often turbid. • Predominant cell - polymorphs. • Pressure - normal/increased. • Glucose - decreased. • Protein (g/L) - increased. • Microbiology - organisms on Gram stain and/or culture.
Viral: • Appearance - usually clear. • Predominant cell - mononuclear* • Pressure - normal. • Glucose - normal • Protein (g/L) - normal/increased. • Microbiology - sterile/virus detected.
*May also be lymphocytes in TB, listerial and cryptococcal meningitis.
TB:
• Appearance - often fibrin web (cobweb).
• Predominant cell - mononuclear.
• Pressure - normal/increased.
• Glucose - decreased.
• Protein (g/L) - increased.
• Microbiology - Ziehl-Nielson/auramine stain or TB culture positive.
Outline brain abscess.
- Infection spreading usually in immunocompromised, IV drug users where skin infections transmit to brain - staph and strep infections can cause these abscesses.
- Acute abscesses will usually show cerebral oedema. Multiple abscesses or may appear like it is budding and forming more abscesses (spreading).
- Abscess is necrotic. Surrounding the abscess, there is intense inflammation → ring enhancement (typical of abscesses and rapidly growing tumours).
Cerebral abscess:
• Ring enhancement.
• Budding daughter lesions.
• Hypodensity of adjacent area (oedema).
Summary meningitis.
• Leptomeningitis (infection of only arachnoid mater), Pachymeningitis* (dura mater) rare, sinusitis, fracture etc. (secondary to).
• Meningism (features of meningitis) - headache, neck stiffness, photophobia etc.* seizures, cloudy consciousness.
• Infective (most common) - Acute (Septic/Bacterial, Aseptic/Viral), Chronic Fungal, TB, parasitic.
• CSF findings - bacterial, viral and TB*
• Bacterial (common organisms) - Strep, Meningo, E. coli (infants).
• Complications - acute/chronic
- Acute - oedema, increased ICP, herniation, ischaemia and infarction (death).
- Chronic - epilepsy, abscess (formation), hydrocephalus (obstruction).
Outline epilepsy.
• Abnormal, recurrent, spontaneous, neuronal firing manifest clinically by changes in motor, sensory, behaviour and/or autonomic function.
- Activation of neuron.
- Sudden activation of motor, sensory, behaviour and/or autonomic function.
- 1-2% in Australia. Ictus - period of seizure.
- A key feature is its stereotypic nature. Preceded by aura (subjective sensation) and followed by postictal state (drowsy, confusion etc.).
- Key feature of epilepsy unlike other seizures is its stereotypic nature - occurs recurrently and always presents in a similar pattern in a patient.
- Particular damage in the brain, which is producing repeated activation of the same area.
- Many times it is preceded by an aura (subjective sensation from the patient that they can tell they are going to have a seizure) followed by a postictal state (recovery period - drowsy, confusion etc.).
- Functional disorder.
- Epilepsy is the result of neuronal hyperexcitability and neuronal hypersynchrony. Prolonged calcium dependent depolarisation (has been identified in these patients).
- Temporal lobe and hippocampus - most seizure-prone areas.
