Please enable JavaScript.
Coggle requires JavaScript to display documents.
CNS Pathology (Neoplasms (Familial Tumour Syndromes (Neurofibromatosis-1…
CNS Pathology
Neoplasms
Differentials:
- Children:
- Primary tumours > Secondary (3:1)
- Specific Tumour Types:
- Medulloblastoma
- Ependyoma
- Germ cell tumours
- Pilocytic astrocytoma
- Adults:
- Primary > Secondary (occurrence of secondary is higher)
- Immunosuppression:
- Consider CNS lymphoma or CNS infection mimicking tumour
- Syndromes:
Meninges
- 1. Meningioma
- Features:
- Originates from meningothelial cells (cerebral convexities, falx cerebri)
- Location: Adherent to meninges
- WHO grade I-III (type I most common)
- Common and slow-growing, may invade skull bone
- Females > males
- Molecular pathogenesis:
- Loss of 22q (NF-2 gene) - one of the more impt tumours in neurofibromatosis-2
- Morphology:
- Gross: Tumours stuck onto meninges
- Histology:
- Meningothelial whorls
- Uniformed ovoid cells
- +/- Psamomma bodies
- Nuclear inclusions
Ventricles
- 1. Ependyoma
- Features:
- Gliomas
- Periventricular, spinal cord
- Originates from ependymal cells lining ventricular system
- Can cause hydrocephalus
- Young patients
- Molecular Pathogenesis:
- Histology:
- Perivascular rosettes
- True rosettes (canals)
- 2. Choroid Plexus Tumours
- Papilloma (children)
- Carcinoma
- Can cause hydrocephalus
Brain Parenchyma
Gliomas
1. Astrocytomas
- Features:
- From astrocytes
- Location: Supra/Infra-tentorial
- WHO grade I-IV
- Grade I: Pilocytic astrocytoma (seen in children)
- May have cystic component
- Grade II: Diffuse astrocytoma
- Grade IV: Glioblastoma multiforme
- Seen in middle-aged and elderly
- Very bad prognosis (mean survival < 1 year)
- "Butterfly tumour"
- Very aggressive
- Crosses midline
- Palisading necrosis
- Nuclear pleomorphism
2. Oligodendrogliomas
- Features:
- From oligodendrocytes
- 5-25% of glial tumours
- Location: cerebral cortex
- WHO grade I-III
- Uniformed rounds cells with "fried egg" appearance
- Respond to chemotherapy - LOH 1p, 4q, 19q responds better
-
Neuronal Tumours
Mature
1. Central neurocytoma
- Originates from neurones
- Location: near 3rd ventricle
- Can cause raised ICP
- Relatively good prognosis
- Seen in adults
Immature
- Primitive/Poorly differentiated tumours
- Seen in children
- Aggressive
Supratentorial
1. Neuroblastoma/PNET (primitive neuroectodermal tumour)
- Supratentorial counterpart of medulloblastoma
- "Cerebral neuroblastoma"
- Rare
- Originates from neurons
- Poor prognosis
- Seen in children
- Different genetics from medulloblastoma
Infratentorial
2. Medulloblastoma
- Features:
- More common
- Better prognosis
- Location: Cerebellum, brainstem
- Aggressive, spreads via CSF
- Tx: surgery and radiotherapy
- Accounts for 20% of brain tumours in children
- Molecular pathogenesis:
- Loss of 17p
- Alterations in Sonic hedgehog/patched pathway
- Alterations in the Wnt signalling pathway
- Histology:
- Sheets of small cells, high N/C ratio, mitoses
- "Carrot-shaped" nuclei
- Rosettes (but look different from those in ependymomas)
Midline/Sellar Tumours
Pituitary Tumours
- Endocrine tumours
- Adenoma (most common)
- Features:
- Originate from pituitary gland
- Location: midline/sellar region
- May result in optic chiasma compression (bitemporal hemianopia) and endocrine effects (overproduction of pituitary hormones, pressure atrophy of normal pituitary tissue)
- Carcinoma
- Embryonal Remnant Tumours
- Craniopharyngioma
- Features:
- Originate from tooth-forming epithelium within the suprasellar region
- Location: midline/sellar region
- May cause similar clinical manifestations as pituitary adenoma
- Good prognosis, but may recur
- Seen in children and adults (50-60 yo)
- Gross: Cystic, containing yellow viscous engine-oil like fluid
- Histology:
- Cysts lined by stratified squamous epithelium
- Wet keratin
- Calcification
Germ Cell Tumours
- 1. Teratomas
- Can be cystic
- Benign (mature) or malignant
- 2. Germinomas
- Less common
- Embryonal carcinomas, endodermal sinus tumours and choriocarcinomas
- Children > Adults
- Males > Females
- Sites: Pineal gland > Suprasellar region
Pineal Gland Tumours
- Pineocytoma
- Pineoblastoma (resembles neuroblastoma)
Others:
- Metastases
- Primary CNS Lymphomas:
- Mostly non-Hodgkin B-cell lymphomas
- Location: supratentorial (multiple lesions)
- Associations: Immunosuppression (HIV), EBV
Peripheral Nerve Sheath Tumours (Non-CNS)
- Benign
- Schwannoma (eg. vestibular schwannoma)
- Well-circumscribed
- Encapsulated
- Attached to nerve
- Histology:
- Spindled cells
- Nuclear palisading
- Hyalinised vessels
- Neurofibroma
- Non-encapsulated
- Cutaneous or deeper
- Malignant
- Malignant peripheral nerve sheath tumours
- May be seen in neurofibromatosis
-
CNS Infections
Routes of Infections
- Direct implantation
- Local extension
- Sinusitis
- Otitis media
- Dental caries
- Haematogenous spread
- Septicaemia
- Infective emboli
- Facial interactions (retrograde venous spread)
- Transport along peripheral nervous system
- Rabies virus
- Herpes simplex virus
Clinical Presentations
- Meningitis
- Headache, fever, malaise
- Photophobia
- Neck stiffness
- Kernig's sign
- Cerebral abscess
- Swinging fever
- Signs of raised ICP
- Localising signs of CNS disease
- Encephalitis
1. Meningitis
- Inflammation of the meninges and CSF within the subarachnoid space
- Causes:
- Acute bacterial
- Neonates: E.coli, Listeria Monocytogenes, Grp B Streptococci.
- Empirical Tx: Ampicillin + Gentamicin
- Infants: Haemophilus influenzae
- Empirical Tx: Ceftriaxone
- Adolescents: Meningococcus
- Empirical Tx: Ceftriaxone
- Adults: Meningococcus, S. pneumoniae
- Empirical Tx: Ceftriaxone
- Elderly and IC: S. pneumoniae, H. influenzae, Meningococcus, Listeria monocytogenes
- Empirical Tx: Ceftriaxone + Ampicillin
- Tuberculous
- Gelatinous exudate in subarachnoid space, often at base of brain
- White granules (tubercles) scattered all over meninges
- Also causes TB meningoencephalitis
- Complications:
- Obliterative endarteritis of arteries in subarachnoid space (leading to cerebral ischemia and infarct)
- Fibrous adhesive arachnoiditis (leading to cranial nerve palsies and hydrocephalus)
- Tuberculoma (producing space-occupying symptoms)
- Aseptic
- Viral usually: Enteroviruses - echovirus, coxsackie
- Often self limiting
- Meningoencephalitis
- Investigations:
- CSF Examination (spinal tap)
- Cloudy
- Cytology: neutrophils++ (bacteria), lymphocytes++ (viral), either (TB)
- Protein content: ++ (bacteria), + (viral)
- Glucose content: - (bacteria), normal (viral)
- Gram stain, culture
- Complications
- Brain infarction
- Meningeal fibrosis and hydrocephalus
- Damage to cranial nerves (esp in TB)
- Raised ICP
- Mental retardation (children)
- Waterhouse-Friderichsen Syndrome (resulting from meningitis-related septicaemia - most often with meningococcal or pneumococcal meningitis)
2. Cerebral Abscess
- Routes of Spread
- Single abscess: direct implantation, local extension (otitis media, sinusitis, facial infections, skull trauma, surgery etc)
- Multiple abscesses: hematogenous spread. Predisposing factors:
- Infective endocarditis
- Congenital R to L shunts
- Chronic pulmonary sepsis
- Causes (usu bacteria)
- Streptococci
- S. aureus
- Bacteroides spp.
- E. coli
- Clinical Features:
- Spinal tap: Increased white cell count + protein, normal glucose
- Signs of raised ICP
- Focal deficits
- Complications:
- Cerebral herniation
- Abscess rupture leading to venous thrombosis and meningitis
3. Subdural Empyema & Extradural Abscess
- Subdural Empyema:
- Local source: skull, air sinus infection
- Clinical features:
- Spinal tap: similar to cerebral abscess
- Local symptoms, meningitis symptoms
- Complications:
- Thrombophlebitis of bridging veins leading to cerebral infarction
- Treatment: Surgical drainage
- Extradural Abscess:
- Local source: sinusitis, iatrogenic
- Asc with osteomyelitis
- Complications:
- In the case of a spinal cord epidural infection --> spinal compression (emergency)
4. Encephalitis
- Causes:
- Usually viral
- Acute Encephalitis:
- Often involves meninges concomitantly: acute meningoencephalitis
- Causative viruses: HSV, measles, CMV, HIV
- Fetal nervous system: CMV, rubella
- Delayed/Subacute Encephalitis:
- Subacute sclerosing pan encephalitis: measles
- Progressive multifocal leukoencephalopathy: JC virus
- Reactivation disease: VZV
- Prion disease
CNS Targets of specific viruses:
- Neurons and glia
- HSV (temporal lobe)
- Rabies
- Motor neurons
- Poliovirus (poliomyelitis - flaccid paralysis, hyporeflexia)
- Enteroviruses
- Dorsal Root Ganglion
- Microglia
HSV
- HSV1 encephalitis
- Children, young adults (10% previous labial HSV)
- Alteration in mood, behaviour
- Necrotising enc, perivascular lymphocytic infiltrates, Cowry nuclear inc
Rabies
- Virus ascends from wound site --> severe encephalitis
- 1-3 months (depends on site)
- Early symptoms:
- Non-specific: Malaise, fever, headache + focal paraesthesia around wound
- Advanced symptoms:
- Marked CNS excitability: Touch is painful, violent motor responses, convulsions, pharyngeal muscle contraction when swallowing
- Foaming, hydrophobia
- Mania and stupor --> coma and death
- Morphology:
- Gross: Oedema, congestion
- Micro: Basal ganglia, midbrain, floor IV ventricle; medulla, spinal cord, dorsal root ganglia
- Negri body: Intracellular eosinophilic bodies found in pyramidal neurons of hippocampus or Purkinje cells of cerebellum
Progressive Widespread Viral Diseases
- 1. Progressive Multifocal Leukoencephalopathy (PML)
- Cause: Papovavirus (JC virus) infection of oligodendrocytes resulting in demyelination
- Mainly in IC patients eg. HIV, ChT
- Presents with progressive neurologic deficits
- Histology:
- Areas of pallor in white matter (cerebrum, cerebellum, brainstem)
- Atypical oligodendrocytes with viral inclusions, bizarre astrocytes
- 2. Subacute Sclerosis Panencephalitis (SSPE)
- Caused by altered measles virus
- Persistent but non-productive infection
- Occurs in children or young adults months to years after acute meals infection
- Presents with cognitive decline, spasticity and seizures
- Histology:
- Widespread gliosis, myelin degeneration, intranuclear viral inclusions within oligodendrocytes and neurons
- 3. HIV Infection
- Direct effects of HIV on CNS: Aseptic meningoencephalitis. Histology: Multinucleated giant cells, microglial nodules, perivascular lymphocyte cuffing
- Effects on spinal cord: Vacuolar myelopathy of posterior columns and corticospinal tracts ("holes" in myelin sheath and macrophage infiltration)
- Vacuolar myelopathy typically presents as a slow progression of painless leg weakness, stiffness, sensory loss, imbalance and sphincter dysfunction
- Relapsing-remitting courses have also been described
- Associated pathological conditions:
- Opportunistic CNS infections (toxoplasmosis, CMV, aspergillosis, cryptococcosis, PML)
- Lymphomas
-
Cerebrovascular Diseases
1. Cerebral Ischemia
- Causes:
- Global cerebral ischemia
- Due to generalised reduction of cerebral perfusion (cardiac arrest, shock, severe HTN)
- Focal cerebral ischemia
- Due to reduction of blood flow to a localised area of the brain (thrombosis, embolism, vasculitis)
- Pathological Effects:
- Cortical laminar necrosis
- Preservation of some layers of the cortex and involvement of others
- Border zone/watershed infarct
- Occurs at area of supply by anterior and middle cerebral arteries
- Produces a sickle-shaped band of necrosis over the cerebral convexity a few centimetres lateral to the inter hemispheric fissures
2. Cerebrovascular Accidents (Cerebral Infarction)
- "Strokes" - sudden focal brain necrosis (cerebral infarction) due to complete and prolonged cerebral ischemia, clinically categorised as ischemic or hemorrhagic infarction
- Etiology:
- HTN
- DM
- Atherosclerosis
- Cardiac arrhythmias (eg. atrial fibrillation)
- Transient Ischemic Attack (TIA)
- Brief episodes of non-traumatic neurological defect due to focal brain or retinal ischemia (usually < 1hr)
- Vascular malformations
- Berry aneurysms
- Arteriovenous malformations
- 2 types of CVS/Cerebral infarction:
- Ischemic Infarction
- Thromboembolic
- HTN, DM --> arteriolosclerosis
- Atherosclerosis and thrombosis
- Embolic - Myocardial infarcts, arrhythmias, valvular disease, fat emboli etc
- Vasculitis
- Venous thrombosis
- Systemic hypoperfusion
- Hemorrhagic Infarction
- HTN --> Charcot Bouchard aneurysms
- Vascular malformations (AVM, saccular/berry aneurysms)
- Cerebral amyloid angiopathy
- Leptomeningeal, cortical arterioles
- Coagulopathy
- Gross Morphology:
- 48hrs: Soft, pale, swollen, indistinct corticomedullary junction
- 2-10 days: gelatinous, friable
- 10 days - 3/52: Liquid filled cavity
- Liquefactive necrosis
- Microscopic:
- 12hrs: Ischaemic neuronal change - red neurones, oedema
- < 48hrs: Neutrophils
- 2D: Macrophages (foamy macrophages)
- 1-3/52: Macrophages++, reactive gliosis
- Effects of HTN in the brain:
1. Lacunar infarcts
- Where: At arteries and arterioles in basal ganglia, cerebral white matter, brainstem
- What:
- Arteriolar sclerosis --> Occlusion --> Multiple small infarcts (lacunar infarcts/lacunae)
- Lacunae: <15mm wide (lenticular nucleus, thalamus, internal capsule, caudate nucleus, pons)
- Clinical: Silent or severe neurologic impairment (site dependent)
2. Hypertensive encephalopathyTwo main clfinicopathologic entities:1. Acute hypertensive encephalopathy
- Malignant HTN
- Clinical:
- Diffuse cerebral headaches
- Headaches, confusion, convulsion --> coma
- Increased ICP --> IMMEDIATE intervention
- Pathology:
- Cerebral oedema, cerebral herniation
- Petechial haemorrhages
- Fibrinoid necrosis of arterioles
2. Multi-infarct dementia
- Months/years; 55-75 yrs
- Clinical:
- Progressive dementia, gait abnormalities
- Focal neurological deficits
- Pathology:
- Multifocal vascular disease:
- Cerebral atherosclerosis
- Thromboemboli
- Grey matter (cortex, thalamus, basal ganglia) or white matter
3. Hypertensive intracerebral haemorrhage
- Commonest cause of primary brain parenchymal haemorrhage
- 15% of deaths in chronic hypertensives
- Etiology:
- Arteries: accelerated atherosclerosis
- Arterioles: Hyaline arteriosclerosis; fibrinoid necrosis
- Site:
- Putamen (50-60%), thalamus, pons > cerebellar hemispheres
-
4. Vascular Malformations1. Arteriovenous Malformation (AVM)
- Tangled network of dilated vessels with prominent pulsatile arteriovenous shunting with high blood flow
- Involves vessels in the subarachnoid space and/or parenchymal vessels
- Complications:
- Intracerebral haemorrhage and hemorrhagic stroke
- Subarachnoid haemorrhage
2. Cavernous Malformation3. Capillary Telangiectasias4. Venous Angiomas
Neurodegenerative Disease
- Progressive loss of specific groups of neurones or brain areas
- Above 65yo higher incidence
Alzheimer Disease
- 20% in > 80 years age group
- Early onset group
- Mutations in chromosome 21
- Codes for amyloid precursor protein
- Production of abnormal beta amyloid
- Mutations in chromosome 19
- Presence of Apolipoprotein E4 subtype on chromosome 19 --> tau hyperphosphorylation --> increases risk of Alzheimer's and earlier onset
- Clinical features:
- Progressive cognitive decline
- Immobility
- Pneumonia
- Pathology:
- Abnormal protein deposition (Hippocampus, neocortex)
- Leads to neuronal damage and loss
- Gross:
- Smaller, atrophied brain
- Temporal lobe most affected, also fronted and parietal regions
- Histology:
- Neuritic (senile) plaques - extracellular amyloid deposits
- Neurofibrillary tangles (tau protein) - intracellular within neurons
Parkinson Disease
- Above 45 years old
- Pathology:
- Loss of nerve cells from substantial nigra (midbrain)
- Nerve cells contain neuromelanin --> Loss of pigment
- Reduced dopamine to basal ganglia
- Lewy bodies in neurons
- Genetics:
- Disorder of alpha-synuclein gene --> accumulation of abnormal protein: Lewy bodies
- Clincal features:
- Rigidity
- Slowing of voluntary movements
- Rest tremor
Huntington Disease (Chorea)
- AD
- Mutation in Huntingtin gene --> increased trinucleotide repeats --> Huntingtin protein accumulates in neurons of striatum (caudate nucleus, putamen), cortex --> Atrophy, neuronal inclusions
- Clinical features:
- Personality alterations, cognitive decline
- Abnormal movements
- 15-20 years average duration
- Death from aspiration pneumonia, heart disease
Metabolic and Toxic Diseases
- Deficiencies
- Vit B1 (thiamine) --> Wernicke encephalopathy
- Vit B12 --> Subacute combined degeneration of spinal cord
- Storage diseases:
- Riemann Pick disease
- Tay-Sachs disease
- Hepatic encephalopathy
- Carbon monoxide poisoning
- Necrosis of globes pallidus
- Diffuse cortical necrosis
- Alcohol-related diseases
- 1. Fetal alcohol syndrome
- 2. Acute intoxication
- Respiratory depression and death
- 3. Chronic alcoholism
- Cerebral cortical atrophy
- Cerebellar atrophy
- Wernicke encephalopathy (thiamine deficiency)
- Korsakoff's psychosis
- Caused by a deficiency of thiamine
- Damage to the medial thalamus and possibly to the mammillary bodies
- Generalised cerebral atrophy
- Neuronal loss and haemorrhage in mammillary bodies
- Wernicke-Korsakoff syndrome (accompanying Wernicke's encephalopathy)
CNS Malformations
1. Neural Tube Defects
- Failure of part of tube to close/Re-opening of tube
- Abnormalities of neural tissue and overlying bone/soft tissue
- During 3-4 weeks of embryogenesis
- Multifactorial - genetic, environmental
- Folate deficiency during initial weeks of gestation --> spina bifida
- Folic acid 0.4mg, periconceptional period
- Detection in utero (test amniotic fluid and maternal blood)
- alpha-fetoprotein elevation
- Acetylcholinesterase
Brain1. Anencephaly
- Absence of brain and calvarium due to disrupted forebrain development
- In its place lies area cerebrovasculosa (a flattened remnant of disorganised brain tissue with admixed ependyma, choroid plexus and meningothelial cells)
- Sparing of posterior fossa structures
- Females > males
2. Encephalocele/cranium bifida
- Outpouching of the brain and its membranes that cover it
- Due to failure of closure of rostral portions of neural tube
Spinal Cord1. Spina bifida/Spinal dysraphism
- Failure of closure of caudal portions of neural tube
- LL weakness and paralysis
- Skeletal/orthopaedic abnormalities - Club feet, hip dislocation
- Bladder and bowel dysfunction, UTIs
- Pressure ulcers
- Spina bifida occulta
- Asymptomatic bony defect with hairy patch on overlying skin
- Meningocele
- Isolated meningeal extrusion
- Myelomeningocele
- Extrusion of meninges and CNS tissue (most commonly lumbosacral region)
2. Forebrain anomalies
1. Microencephaly
- Small brain
- Etiology:
- Chromosomal abnormalities
- Fetal alcohol syndrome
- HIV infection acquired in utero
- Presentation can range from a noticeable decrease in gyri to total absence
- Lissencephaly (agyria): complete absence of gyri - brain has smooth surface
2. Polymicrogyria
- Small, unusually numerous and irregularly formed cerebral convolutions
- Entrapment of meningeal tissue at points of fusion that would otherwise be at the cortical surface
3. Holoprosencephaly
- Spectrum of malformations characterised by incomplete separation of the cerebral hemispheres across the midline
- Etiology:
- Trisomy 13
- Maternal diabetes
- Facial midline abnormalities:
-
-