Pathology Flashcards
What are 3 clinical presentations associated with ↑ICP?
1) Nausea
2) Headache
3) Altered conscious level
4) Papilloedema
What is the clinical definition of raised ICP?
Increase in mean CSF pressure
- normal 7-15mmHg in supine adult
What are 3 causes of ↑ICP?
Diffuse conditions:
1) Cerebral oedema
- infection
- infarction
- trauma
2) Hydrocephalus
Localised conditions:
3) Space-occupying lesions
- tumours
- haemorrhage/infarct
- abscess
What is hydrocephalus?
Increase in CSF in CNS due to disturbance of formation, flow or absorption
- Normal 120-150ml
What are the 2 types of hydrocephalus and how are they different?
1) Communicating
- between ventricles and subarachnoid space
- causes:
(i) venous drainage insufficiency (eg. thrombosis)
(ii) defective absorption (eg. SAH)
(iii) Overproduction (eg. meningitis)
2) Non-communicating
- obstruction between ventricular and subarachnoid space
- causes (eg.)
(i) congenital (eg. Arnold Chiari malformation)
(ii) mass lesions (eg. tumour, cysts, haematoma)
(iii) meningitis (via scarring, ventricular outflow obstuction)
What are 3 complications of raised ICP?
1) Cerebral herniation
2) Loss of consciousness
3) Bradycardia
4) Hypertension
5) Neurogenic pulmonary oedema
What is cerebral herniation?
The displacement of parts of the brain past rigid dural folds or through and opening into another compartment due to raised ICP
What are 3 forms of cerebral herniation?
1) Subfalcine
2) Uncal(Transtentorial)
3) Tonsilar (“coning”)
What is the (i) location (ii) cause and (iii) sequelae of subfalcine herniation?
i) Cingulate gyrus below falx cerebri
ii) cerebral hemisphere lesion
iii) usually clinically silent BUT
- can cause infarct (compression of anterior cerebral artery)
What is the (i) location (ii) signs/sequelae of uncal (transtentorial) herniation
i) medial temporal love through tentorium cerebelli
ii)
a) Loss of consciousness
b) CNIII compression → ipsilateral fixed & dilated pupil
c) Posterior cerebral artery compression → cortical blindness
What is the (i) location (ii) cause and (iii) sequelae of tonsillar herniation “coning”?
i) Cerebellar tonsils through foramen magnum
ii) posterior fossa space occupy lesions
iii) neck stiffness, “coning”
- compression of cardiac and respiration centers in medulla and pons → cardiorespiratory arrest
What is “coning” in cerebral haemorrhage?
Tonsillar herniation → compression of cardiac and respiration centers in medulla and pons → cardiorespiratory arrestc
What are the 2 main pathogeneses of cerebrovascular disease?
1) Ischaemia and infarction
a) global hypoperfusion (eg. shock)
b) focal cerebral ischaemia (eg. thromboemboli)
2) Haemorrhage
a) Hypertension
b) Vascular malformations
c) Aneurysms
What is the clinical definition of a stroke?
Neurologic signs and symptoms that can be explained by a vascular mechanism, have an acute onset, and persist beyond 24hrs
What are 3 clinical manifestations of a stroke?
1) Localising signs (eg. hemiparesis)
2) Raised ICP (eg. haemorrhage, cerebral oedema)
3) Sudden severe headache (eg. ruptured vascular malformation)
What are 6 risk factors for cerebrovascular accidents?
1) HTN
2) DM
3) Atherosclerosis
4) Transient Ischaemic Attacks (TIA)
5) Afib
6) Vascular malformations/abnormalities
7) Coagulopathies
What is a transient ischaemic attack?
Temporary cerebrovascular insufficiency:
- transient episode of neurologic dysfunction caused by: focal brain, spinal cord or retinal ischemia
- NO acute infarction
Where do watershed infarcts of the brain most commonly occur?
Areas between those supplied by middle and anterior cerebral arteries
What does a watershed infarct result in?
Cortical pseudolaminar necrosis
What are 3 causes of global hypoperfusion?
1) Cardiac arrest
2) Shock
3) Severe hypotension
What is the pathogenesis of focal cerebral ischaemia?
Arterial occlusion due to thromboemboli resulting in reduced flow in a localised area of the brain
What are 3 underlying causes of thromboemboli in focal cerebral ischaemia?
1) Atherosclerosis
2) Arteriosclerosis
3) Vasculitis
What are 2 types of brain infarcts?
1) Pale/bland/non-haemorrhagic
2) Red/Haemorrhagic
What is the clinical significance of differentiating pale and red infarcts?
Pale can be treated with thrombolytics unlike red (contraindicated)
How do the pathogenesis of pale and red infarcts in focal cerebral ischaemia?
Pale:
1) Thrombosis eg.
- atherosclerosis
- arteriolosclerosis
Red:
1) Venous Thrombosis
Emboli:
2) Carotid artery atheroma
3) Cardiac thrombi (post AMI, Afib, valvular disease)
4) Fat emboli (post bone trauma)
What form of necrosis is secondary to a cerebral infarction?
Liquefactive
How does the gross morphology of a pale infarct of the brain change over time?
48hrs:
- soft, swollen
- pale, indistinct grey-white matter junction
2-10D:
- gelatinous, friable
10D-3wks:
- liquid filled cavity
How does the gross morphology of a pale cerebral infarct change over time?
12hr:
- ischaemic neuronal change (red neurons, oedema)
<48hrs
- Neutrophils
2D:
- foamy macrophages
1-3wks:
- ↑↑macrophages
- reactive gliosis (astrocytes)
What are the 4 causes of intracerebral haemorrhage?
1) Hypertension (smaller vessels)
- hyaline arteriolosclerosis
- fibrinoid necrosis
- charcot bouchard microaneurysms → rupture
2) Cerebral amyloid angiopathy
- amyloid deposition → weakened wall (leptomeningeal, cortical arterioles)
3) Structural vascular abnormalities
- Arteriovenous malformation
- Berry/saccular aneurysms (in circle of willis
4) Coagulopathies
Which part of the brain do Charcot Bouchard microaneurysms most commonly occur?
Smaller vessels of the (i) Basal Ganglia and (ii) Thalamus
In which demographic are intracerebral haemorrhages due to structural vascular abnormalities seen?
Younger px
- sudden presentation
What are three effects of hypertension in the brain?
1) Lacunar infarcts
2) Hypertensive encephalopathy
3) Hypertensive intracerebral haemorrhage
What are lacunar infarcts and where do they most commonly occur?
Arteriolar sclerosis → occlusion → multiple small infarcts (lacunar infarcts <15mm)
Occur in:
deep penetrating vessels of basal ganglia, cerebral white matter, brainstem (eg. lenticular nucleus, thalamus, internal capsule, caudate nucleus, pons)
True or false: Lacunar infarcts are always a medical emergency.
False.
Site dependent
- may be clinically silent
What are the 2 main clinicopathologic entities in hypertensive encephalopathy?
1) Acute hypertensive encephalopathy (malignant hypertension)
2) Multi-infarct dementia
How are acute hypertensive encephalopathy/malignant hypertension and multi-infarct dementia different?
1) Clinical S/S:
MH: non-specific (headache, confusion, convulsion → coma)
MID: progressive dementia, gait abnormalities, focal neurological deficits
2) Pathogenesis:
MH: cerebral edema/herniation + petechial haemorrhages + fibrinoid necrosis of arterioles
MID: multifocal vascular disease (eg. thromboemboli)
Multi-infarct dementia is usually an (acute/progressive) condition affecting _______ age group.
Progressive
Middle aged to elderly (55-75y/o)
What is the most common cause of primary brain parenchymal haemorrhage?
Hypertensive intracerebral haemorrhage
What are the 3 forms of extra-axial intracranial haemorrhage?
1) Subarachnoid
- non-traumatic
- ruptured saccular aneurysms or arteriovenous malformations
2) Subdural
- traumatic
3) Epidural/extradural
- trauma
Which of the extra-axial intracranial haemorrhages are non-traumatic in aetiology?
Subarachnoid
What are 2 causes of subarachnoid haemorrhage?
1) Ruptured saccular (berry) aneurysms
2) Ruptured arteriovenous malformations
What is a “thunderclap headache” most commonly associated with?
Subarachnoid haemorrhage
What structure are berry aneurysms found on in an intracranial aneurysms?
Circle of Willis
- esp at junctions of communicating arteries
True or false: A “thunderclap” headache is a medical emergency.
True
a/w saccular “berry” aneurysm causing subarachnoid haemorrhage
- requires urgent surgical intervention (50% die w 1st bleed)
What genetic condition is associated with saccular aneurysms?
AD polycystic kidney disease
What are 4 forms of vascular malformations that increase a px risk of intracranial haemorrhage?
1) Arteriovenous malformation
2) Cavernous angioma
3) Capillary telangiectasis
4) Venous angioma
What are 2 intracranial complications of vascular malformations eg. arteriovenous malformations?
1) Intracerebral haemorrhage (CVA)
2) Subarachnoid haemorrhage
What does a laceration of the middle meningeal artery most likely lead to?
Epidural hematoma
What does a tear in the bridging veins in the subdural space most commonly lead to?
Subdural haemorrhage
What is the difference between the aetiology of a subdural and epidural haemorrhage?
Epidural
- laceration of artery (eg. middle meningeal)
Subdural
- venous bleed (eg. tear in subdural bridging veins)
What are 2 differences between acute and chronic subdural haematomas?
1) Cause
A: Acceleration-decelearion injuries → cerebral contusion (need rapid surgical decompression)
C: minor head trauma
2) Prognosis
A: high mortality rate
C: good prognosis
How would chronic subdural haemorrhage differ from an acute one on gross morphology?
Chronic: signs of organisation (fibrosis)
Which form of intracranial bleed is most likely in a temporal bone fracture?
Epidural haematoma (laceration of middle meningeal artery)
What is the classical clinical Hx of an epidural haematoma?
Head trauma
→ lucid interval
→ Sudden deterioration (eg. vomiting, restlessness, loss of consciousness)
What is a “lenticular (convex)” appearance on a head CT indicative of?
Epidural haemorrhage
What are 4 causes of intracerebral petechial haemorrhages?
1) Fat embolism (eg. after surgery)
2) Malaria
3) Vasculitis
4) Acute hypertensive encephalopathy
What are 2 conditions that are commonly associated with a ruptured berry aneurysm?
1) Polycystic kidney disease
2) Aortic coarctation
(Primary/secondary) tumours are more common in children.
Primary
What type of cells are arachnoid cells?
Meningothelial cells
What is the cellular origin of the meningiomas?
Menigothelial cells
What is the cellular origin of gliomas?
Glial tissue
What is the cellular origin of central neurocytoma?
Neurons
What is the cellular origin of medulloblastoma?
Embryonal
What are 2 cancers of the brain ventricles?
1) Choroid plexus tumours
2) Ependymomas (periventricular)
What are 3 cancers of brain parenchyma?
1) Medulloblastoma (embryonal)
2) Central neurocytoma
3) Gliomas
What are 3 brain tumours of midline structures?
1) Pituitary tumour
2) Germ cell tumours (children)
3) Pineal gland tumours
Meningiomas originate from _______________ cells usually occurring in the ________________ of the brain.
Arachnoid/Meningiothelial cells
Falx, cerebral convexities
Meningiomas are (common/rare), (fast/slow-growing) and may invade ___________.
Common and slow-growing
May invade skull bone
What syndrome is most common associated with meningiomas?
NF-2
Meningiomas are more common in (male/female) and the most common subtype is ___________________.
F > M
Commonest: Meningothelial type
What are 3 histological features of meningiomas?
1) Meningothelial whorls
2) Uniformed ovoid cells
3) Psammoma bodies
4) Nuclear inclusions
What are 3 forms of gliomas?
1) Astrocytoma
- WHO grade I-IV
2) Oligodendrogliomas
- WHO grade II-III
3) Ependymomas
- WHO grade II-III
What are the different types of astrocytomas?
1) Pilocytic (Grade I)
- children
- supra/infra-tentorial
2) Astrocytoma (Grade II-IV)
- IDH mutant
3) Glioblastoma (Grade IV)
- IDH wild-type
True or false:
IDH1 mutant gliomas are more favorable to wild type.
True.
Astrocytoma better prognosis than Glioblastoma
What is the histological appearance of pilocytic astrocytoma?
Astrocytes with long fibrillary cytoplasmic processes
Which demographic is most commonly afflicted with pilocytic astrocytoma?
Children
What are 2 histological characteristics of glioblastoma?
1) Palisading necrosis
2) Nuclear pleomorphism
What is the specific genetic profile of oligodendrogliomas?
IDH1 mutation and whole arm deletion of 1p and 19q
Which part of the brain is most commonly affected by oligodendrogliomas?
Cerebral cortex
True or false: Oligodendrogliomas are chemosensitive.
True
What is the histological appearance of oligodendrogliomas?
Uniformed round cells with “fried egg” appearance
Why does central neurocytoma cause raised ICP?
Near 3rd ventricle → compressive
Central neurocytomas usually affect ______ and have (good/poor) prognosis.
Adults
relative good prognosis
What is the difference between a CNS neuroblastoma and medulloblastoma?
Both aggressive embryonal brain parenchymal tumours in children
CNS neuroblastoma
- supratentorial
- poor prognosis
Medulloblastoma
- Medulloblastoma
- commoner
How are medulloblastomas classified?
According to molecular profile
- WNT and SHH activation status
- TP53 mutant/WT
What are the 2 treatment options for medulloblastoma?
Surgery and radiotherapy
Where do medulloblastomas commonly occur?
Cerebellum:
- Vermis (children)
- Hemispheres (adults)
Medulloblastomas are (aggressive/indolent) and spread via _______ causing ______________.
Aggressive
Spread via CSF → hydrocephalus
What are 3 histological features of medulloblastoma?
1) Sheets of small cells, high N/C ratio, mitoses
2) “Carrot shaped” nuclei
3) Rosettes
What are 2 histological features of ependymomas?
1) Perivascular pseudorosettes
2) True rosettes (canals)
What are ependymomas and where are they most commonly located (3)?
Gliomas of the ventricles
1) Periventricular
2) Intraparenchymal (supertentorial or infratentorial esp posterior fossa)
3) Spinal cord
What are 3 demographics that are most commonly seen with ependymomas?
1) Children (esp posterior fossa)
2) Young adults
3) NF-2 px
True or false:
Unlike medulloblastomas and choroid plexus tumours, ependymomas cannot cause hydrocephalus.
False.
All 3 can lead to hydrocephalus
What are the 2 forms of choroid plexus tumours?
1) Papilloma
2) Carcinoma (greater N/C ratio, cellularity)
What are 2 forms of sellar tumours?
1) Pituitary adenomas
2) Craniopharyngiomas
What are 2 forms of pituitary tumours?
1) Endocrine
- adenoma (commonest)
- carcinoma
2) Embryonal remnant tumours
- Craniopharyngiomas
What are 2 clinical effects of pituitary tumours?
1) Visual field defects
- optic chiasma compression → bitemporal hemianopia
2) Endocrine effects
- functional hypersecretion
Where do craniopharyngiomas arise from?
Tooth-forming epithelium within suprasellar region
Which 2 demographics are most commonly affected by craniopharyngioma?
1) Children
2) Adults (50s-60s)
What are the 2 types of craniopharyngiomas?
1) Adamantinomatous
2) Papillary
What is the gross appearance of an adamantinomatous craniopharyngioma?
Cystic, containing yellow viscous fluid (“engine oil” appearance)
What is the histological appearance of adamantinomatous craniopharyngioma (3)?
1) Cysts lined by stratified squamous epithelium
2) “Wet keratin”
3) Calcifications
What are 2 germ cell tumours of the CNS?
1) Teratoma
2) Germinoma
Less common:
3) Embryonal carcinoma
4) Yolk sac tumour
5) Choriocarcinoma
CNS germ cell tumours EPC:
Children (</>) Adults
Males (</>) Females
Pineal gland (</>) Suprasellar region
Children > Adults
M > F
Pineal gland > Suprasellar region
What are 2 forms of pineal tumours?
1) Pineocytoma
2) Pineoblastoma
- high grade, primitive
Primary CNS lymphomas are mostly ________ in origin and are seen in ___________ px.
B cell, non-Hodgkin’s
Immunosuppressed px (eg. AIDS → EBV lymphomas)
What are 3 histological features of schwannomas?
1) Spindled cells
2) Nuclear palisading
3) Hyalinised vessels
What are 3 examples of peripheral nerve sheath tumours?
1) Malignant
Benign:
2) Schwannoma
3) Neurofibroma
How are schwannomas different from neurofibromas?
Schwannoma
- well circumscribed/encapsulated
- attached to nerve
Neurofibroma
- non-encapsulated
- cutaneous/deep nerves
What is the histological appearance of neurofibroma?
1) Spindle cells within loose stroma
2) Collagen fibres within stroma
What are 4 examples of neurocutaneous syndromes?
1) Neurofibromatosis 1
2) Neurofibromatosis 2
3) Tuberous sclerosis
4) Von Hippel-Lindau Disease
Neurocutaneous syndromes often show a __________ inheritance pattern and present in _______________.
AD
Present:
- tumours
- Skin hamartomas
- nervous system
In NF1, the ____________ gene, which functions as a ______________, is mutated.
NF-1 gene for neurofibromin (17q)
- TS gene for signal transduction
What is the inheritance pattern of NF-1?
AD
What are 4 manifestations of NF-1 syndrome?
Neural tumours:
1) Neurofibromas (skin, CNVIII, radiculopathy, plexiform)
2) Optic nerve glioma
3) Hamartomas (Lisch nodules)
Other abnormalities:
4) Cutaneous
5) MSK
6) Renal
How does NF- progress to malignancy?
Sarcomatous transformation of neurofibromas → malignant nerve sheath tumours
NF2 is a result of a mutation in the _________ gene.
NF2 (Merlin) gene
What is the inheritance pattern of NF-2?
AD
- or de-novo mutation
How is NF-2 diagnosed?
At least 1 of:
1) Bilateral vestibular schwannomas
2) 1° wNF2 and
i) Unilateral vestibular schwannoma OR
ii) Any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
3) Unilateral vestibular schwannoma and
i) Any two of: Meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
4) Multiple meningiomas and
i) Unilateral vestibular schwannoma OR
ii) Any two of: schwannoma, glioma, neurofibroma, cataract
In tuberous sclerosis, the __________ genes are mutated.
TSC1 and 2
- participate in cell proliferation
What are 4 manifestations of tuberous sclerosis?
1) Brain: cortical tubers, hamartomas
2) Skin: adenoma sebaceum, shagreen patch, ungual fibroma
3) Lung lesions
4) Renal angiomyolipomas
What is the inheritance pattern of tuberous sclerosis?
AD
What is the inheritance pattern of Von-Hippel Lindau syndrome?
AD
- variable penetrance
In Von-Hippel Lindau syndrome the __________ gene is affected.
VHL TS gene (3p25-26)
- angiogenesis + cell cycle
What are 5 manifestations of Von-Hippel Lindau Syndrome?
1) Hemangioblastomas
- retinal, cerebellar, supratentorial
2) Cysts
- renal, pancreatic, adrenal
3) RCC
4) Paraganglioma
5) Phaeochromocytomas
6) Endolymphatic sac tumour (inner ear)
What are 2 examples of paraneoplastic syndromes of the CNS?
1) Paraneoplastic cerebellar degeneration
2) Limbic encephalitis
What are 4 components of the Brain’s natural barrier against infection?
Physical:
1) Skull
2) Dura mater
3) BBB
Cell:
4) Microglia
5) WBCs
What are 3 routes of CNS infection?
1) Local
- disruption of coverings (eg. trauma, spina bifida)
2) Regional
- sinusitis, otitis media, dental carries, facial infections
3) Blood borne
- septicemia
- septic emboli
4) Peripheral nerves
- rabies, HSV
What are 4 patterns of CNS infection involvement?
1) Meningitis
2) Subdural empyema, extradural abscess
3) Localised infection
4) Encephalitis
What are 3 clinical presentations of meningitis?
1) Headache
2) Fever
3) Neck Stiffness
4) Photophobia
What is the most common clinical presentation of encephalitis?
Altered mental state
What are 3 clinical presentation of an intracranial abscess?
1) Swinging fever
2) Localising signs of CNS disease
3) Raised ICP
- vomiting, LOC
What are 3 investigations for a CNS infection?
1) Imaging
- localise
Sterile samples:
2) CSF microscopy/culture/labs
3) Blood culture
What are 5 infective causes of meningitis?
Bacterial:
1) E. coli
2) Listeria cytomonogenes
3) H. influenzae
4) Neisseria meningitides
5) Strep pneumo
6) TB
Aseptic:
7) Echovirus
8) Coxsackie
Fungal:
9) Cryptococcus neoformans
10) Candida albicans
What are 2 bacterial causes of meningitis in neonates?
1) E. coli
2) Listeria monocytogenes
What is the main bacterial cause of meningitis in infants?
Haemophilus influenzae
What is the main cause of meningitis in adolescents?
Neisseria meningitides
What are 2 bacterial causes of meningitis?
1) Neisseria meningitides
2) Strep pneumoniae
Which part of the brain does TB usual infect?
Base of brain
What are 2 aseptic causes of meningitis?
1) Echovirus
2) Coxsackie
What are 2 fungal causes of meningitis?
1) Cryptococcus neoformans
2) Candida albicans
Which Ix is most important in the management of meningitis?
CSF exam (spinal tap)
What would the CSF of a px with meningitis show?
1) Cloudy
2) Cytology
- bacterial: ++polymorphs
- viral: lymphocytes++
- TB: either
What are 4 complications of meningitis?
1) Brain infarct
2) Meningeal fibrosis → hydrocephalus
3) Damage to cranial nerves
4) Raised ICP
5) Mental retardation (in children)
What are 2 gross features of tuberculous meningitis?
1) Gelatinous exudate on base of brain
2) White granules on tubercles (granulomas)
What are 3 complications of tuberculous meningitis?
1) Obliterative endarteritis
- cerebral ischemia, infarct
2) Fibrous adhesions in arachnoid mater
- cranial nerve deficits
- hydrocephalus
3) Tuberculoma of brain
Where do subdural empyemas usually originate from?
1) Skull infection
2) Paranasal sinus infection
What are 2 clinical manifestations of subdural empyema?
1) Local symptoms
- thrombophlebitis of bridging veins → localised infarct
2) Meningitis symptoms
- Headache, Fever, Neck Stiffness, Photophobia
How are subdural empyemas treated?
Surgical drainage
Where do extradural abscesses originate from?
1) Sinusitis
2) Iatrogenic
What is a condition that is commonly a/w extradural abscesses and what is the main concern with this condition?
Osteomyelitis
→ spinal cord epidural infection → cord compression
How do the aetiologies of single vs multiple cerebral abscesses differ?
Single:
- local source (otitis media, sinusitis, skull trauma, iatrogenic, facial infections, etc.)
Multiple:
- septicaemia, septic emboli (eg. infective endocarditis)
What are 4 common infective causes of cerebral abscesses?
Usually bacterial:
1) Strep
2) Staph aureus
3) Bacteroides
4) E. coli
What is the causative organism of neurosyphilis?
Treponema pallidum
What are 7 causes of localised infections in the CNS?
Bacterial:
1) Strep
2) Staph aureus
3) Bacteroides
4) E. coli
Spirochaetes:
5) Treponema pallidum
Fungal:
6) Candida spp.
7) Cryptococcus
8) Aspergillosis
Parasitic:
9) Toxoplasma gondii
10) Taenia solium
11) Amoeba (eg. Naegleria, acanthamoeba)
What is the typical imaging presentation of CNS toxoplasmosis?
Multiple ring-enhancing lesions on CT/MRI
In which demographic does CNS toxoplasmosis most commonly occur?
HIV+ px
Encephalitides are usually (bacterial/viral/parasitic/fungal/idiopathic)
Viral
How do the causes of encephalitides differ?
Acute: Acute meningoencephalitis
i) HSV, measles, CMV, HIV
ii) Fetal nervous system: rubella, CMV
Delayed / subacute:
a) Subacute sclerosing panencephalitis → Measles
b) Reactivation → VZV
Prion disease
Which virus(es) tend to target neurons and glial tissue?
1) HSV (esp temporal lobe)
2) Rabies
Which virus(es) tend to target motor neurons?
1) Poliovirus
2) Enteroviruses
Which virus(es) tend to target microglia?
HIV
Which virus(es) tend to target dorsal root ganglia?
VZV
What are 3 histological features of HSV1 encephalitis?
1) Cowdry type A nuclear inclusion
2) Tissue necrosis and haemorrhage
3) Perivascular lymphocytic infiltrates
Which demographics are most commonly afflicted with HSV1 encephalitis?
1) Children
2) Young adults (10% Hx of labial HSV)
What is common clinical presentation of HSV1 encephalitis?
Alteration in mood, memory, behaviour
Describe the pathogenesis of rabies.
Virus ascends from wound site → spinal ganglion → CNS → severe encephalitis (1-3mths depending on site)
How does rabies typically present?
Early: nonspecific
- malaise, fever, headache
- focal paraesthesia around wounds
Advanced:
i) marked CNS excitability
- painful touch, violent motor responses, convulsions
ii) pharyngeal muscle contraction when swallowing
- foaming, hydrophobia
iii) mania and stupor → coma and death
What is the characteristic histological finding in rabies?
Negri bodies
- cytoplasmic round/oval eosinophilic inclusions i
- in (i) pyramidal/hippocampal neurons (ii) purkinje cells (cerebellum)
Describe the pathogenesis of poliomyelitis.
Fecal-oral route → multiplies in lymphoid tissues (tonsils, peyer’s patches, lymph nodes, etc.)
→ Viraemia
→ invade CNS
True or false: poliomyelitis is rarely self-limiting as it frequently penetrates CNS in viraemia.
False.
Most self-limiting inflammation of meninges, rarely penetrate CNS
What is the main complication/sequelae from poliomyelitis penetrating the CNS?
Damage motor neurons → flaccid paralysis + hyporeflexia
What are 2 types of CNS infections by HIV?
1) Aseptic meningitis
2) Encephalitis
How does HIV present in the spinal cord?
Vacuolar myelopathy
- holes in myelin sheath
- posterior columns
- corticospinal tract
How does CNS involvement of HIV present?
1) Imbalance
2) Sensory loss
3) Slowly progessive painless leg weakness, stiffness
What are 2 pathologies a/w HIV encephalitis?
1) Opportunistic infections in CNS (eg. toxoplasmosis, CMV, fungi, PML)
2) CNS lymphomas
What are 3 histological features of HIV encephalitis?
1) Multinucleated giant cells
2) Microglial nodules
3) Perivascular lymphocyte cuffing
What are 4 pathologies of neurosyphilis?
1) Tertiary syphillis
2) Meningovascular syphilis
3) Brain: general paresis of the insane
4) Spinal cord: tabes dorsalis
What are 2 histological features of meningovascular syphilis?
1) Granulomatous meningitis
2) Subintimal vessel thickening
How does neurosyphilis of the brain usually present?
Dementia
- neuronal loss
How does neurosyphilis of the spinal cord present?
Tabes dorsalis
- posterior column demyelination → charcot joints, skin damage
What are 3 CNS pathologies caused by fungi?
1) Vasculitis and thrombosis → infarction, hemorrhage
2) Meningitis (Cryptococcus)
3) Parenchymal invasion → abscess granulomas (Candia, Cryptococcus)
What are the modes of prion transmission?
1) Genetic
2) Sporadic
3) Transmissible
- contaminated transplantation tissue, food ingestion
What is the pathogenesis of prion diseases?
“Spreading”/accumulation of misfolded prion protein (PrP)
→ “Spongiform encephalopathy”
→ neuronal death
What are 2 histological features of prion disease?
1) Spongiform transformation
- cerebral cortex, deep grey matter
2) Amyloid deposits and plaques
What are 2 aetiologies for CNS malformations?
1) Prenatal/perinatal insult
a) Nutritional deficiency
- folate → neural tube defects
b) radiation → neural tube defects, anencephaly
c) infections, drugs, toxins, etc.
2) Genetics
What are neural tube defects and why are they pathogenic?
Failure of part of tube to close/re-opening of tube
→ abnormalities of neural tissue and overlying bone/soft tissue
Neural tube defects occur during ____________ of embryogenesis and can be detected in utero via ________.
3-4 week
Detected via:
- amniotic fluid and maternal blood
What is the main cause of spina bifida?
Folate deficiency
How can spina bifida be treated?
Folic acid (0.4mg) in periconceptional period
What are 3 neural tube defects?
Brain:
- anencephaly
- encephalocele
Spinal cord:
- spina bifida/spinal dysraphism
Anencephaly occurs in a ______ neural tube defect, (F </> M) and results in disrupted _________________________, sparing the ______________.
Anterior neural tube defect (F>M)
- disrupted forebrain development → absent brain and calvarium in the cerebrovasculosa
- spares posterior fossa
How does spina bifida present?
Occulta → hairy patch
Myelomeningocele/meningocele
- LL weakness/paralysis
- Skeletal abnormalities (club feet, hip dislocation)
- Bladder and bowels dysfunction, UTIs
- Pressure ulcers
What are 3 examples of forebrain abnormalities?
1) Polymicrogyria
2) Lissencephaly
3) Holoprosencephaly
How does polymicrogyria present?
1) Seizures
2) Mental retardation
3) Hemi/Quadriparesis
How does Lissencephaly present?
1) Dysphagia, aspiration
2) Seizures
3) Severe psychomotor retardation
How does holoprosencephaly present?
1) Facial midline abnormalities (eg. cyclopia)
2) Early mortality
3) Movement disorders
4) Feeding problems
What is the pathogenesis of holoprosencephaly?
Trisomy 13, maternal DM
→ incomplete separation of the cerebral hemispheres across midline
What are 2 examples of posterior fossa anomalies?
1) Arnold Chiari Malformation
2) Dandy Walker Syndrome
What is a Arnold Chiari Malformation?
Chiari type II malformation
- small posterior fossa
- cerebellar tonsils displaced through foramen magnum
What are 2 associations of Arnold Chiari Malformation?
1) Hydrocephalus
2) Spina bifida myelomeningocele
What are 3 clinical features of Arnold Chiari Malformation?
1) Headache especially on Valsalva maneouvre
2) Muscle weakness, fatigue
3) Brainstem damage/death
What is Dandy Walker Syndrome?
Enlarged posterior fossa
- cerebellar vermis absent/shrunken
- central open cyst
What are 4 clinical presentations of Dandy Walker Syndrome?
1) Slow motor development (infants)
2) Gradual skull enlargement
3) Raised ICP → vomiting, irritability, convulsion
4) Poor coordination, eye and face muscles
What are 4 neurodegenerative diseases?
1) Dementia
- eg. Alzheimer disease
2) Movement disorder
- eg. Parkinson disease (substantia nigra)
- Huntington Chorea (basal ganglia)
3) Motor weakness
- eg. Motor neurone disease
4) Others
- eg. spinocerebellar degenerations, Friedreich’s ataxia, etc.
Describe 2 genetic predispositions in early onset Alzheimer disease?
1) Chromosome 21
- Amyloid Precursor Protein → Aß (ß amyloid peptides) deposition
2) Chromosome 19
- ApoE4 subtype → tau hyperphosphorylation
What are 3 clinical features of Alzheimer disease?
1) Progressive cognitive decline
2) Immobility
3) Pneumonia
What are 2 demographics that are most commonly afflicted by Alzheimer disease?
1) >80y/o (20%)
2) younger with Chromosome 21 APP or Chromosome 19 Apo E4 mutation
What is the the pathogenesis of Alzheimer’s disease?
Abnormal protein deposition
i) amyloid (neuritic/senile) plaque
ii) Neurofibrillary tangles
→ neuronal damage and loss
What is the main gross feature of Alzheimer’s disease?
Small, atrophied brain
- temporal lobe most affected
What are 2 histological features of Alzheimer’s disease?
1) Amyloid/Neuritic/Senile plaques
- collections of dilated, tortuous neuritic process surrounding a core of ß amyloid
2) Neurofibrillary tangles
- hyperphosphorylated tau protein within neurons
What are 3 clinical features of Parkinson disease?
1) Rigidity
2) Slowing of voluntary movements
3) Rest tremor
Describe the genetic pathogenesis of Parkinson disease.
Disorder of α-synuclein gene → accumulation of α-synuclein protein → lewy bodies
What are 2 pathologies of Parkinson disease?
1) Loss of nerve cells from substantia nigra (midbrain)
- ↓ dopamine to basal ganglia
- pallor in substantia nigra
2) Lewy bodies in neuron
What is the gross appearance of Parkinson’s disease?
Pallor in substantia nigra
What is the histological feature of parkinson’s disease?
Lewy bodies in neurons
What are 4 clinical presentations of Huntington’s Chorea?
1) Personality alterations
2) Cognitive decline
3) Abnormal movements
4) Death from aspiration, heart disease
What are 3 gross features of Huntington’s Chorea?
1) Small brain with atrophy of caudate nucleus and frontal lobe
2) Atrophied putamen and globus pallidus (later)
3) Dilated ventricles
What is the inheritance pattern of Huntington Chorea?
AD
Describe the pathogenesis of Huntington’s disease?
Mutattion in Huntingtin gene
→ ↑TNR → accumulation of Huntingtin protein in neurons of stratium (caudate nucleus, putamen) & cortex
→ atrophy + neuronal inclusions →
i) loss of striatal neurons → motor dysfunction
ii) loss of cortical neurons → cognitive decline
Why is Huntington’s chorea associated with anticipation?
↑TNR → earlier age of onset
- Spermatogenesis → ↑TNR → paternal transmission a/w anticipation (early onset in next generation)
What are 7 metabolic/toxic causes of CNS disease?
Deficiencies
1) Vit. B1 (Thiamine)
2) Vit. B12
Storage Diseases:
3) Niemann Pick disease
4) Tay-Sachs disease
Hepatic encephalopathy (5)
CO poisoning (6)
Alcohol-related (7)
What CNS disease is caused by Vit. B1 defiency?
Wernicke encephalopathy
What disease is caused by Vit. B12 deficiency?
Subacute combined degeneration spinal cord
What are 2 CNS pathologies caused by CO poisoning?
1) Necrosis of globus pallidus
2) Diffuse cortical necrosis
What are 3 CNS pathologies caused by alcohol?
1) Fetal alcohol syndrome
- growth retardation, cerebral malformations
2) Acute intoxication
- respiratory depression → death
3) Chronic alcoholism
- cerebral cortical atrophy
- cerebellar atrophy
- Wernicke encephalopathy
- Korsakoff’s psychosis
What is the pathogenesis of Thiamine deficiency CNS pathology?
Thiamine deficiency → damage to medial thalamus and mammillary bodies + generalised atrophy
What is Wernicke encephalopathy?
Acute development of psychotic symptoms of ophthalmoplegia
What is the gross appearance of Wernicke encephalopathy?
Hemorrhage and necrosis in mamillary bodies, walls of 3rd adn 4th ventricles
What is Korsakoff’s syndrome?
Chronic alcohol abuse characterised by:
1) Anterograde amnesia
2) Retrograde amnesia
3) Confabulation
4) Meager content in conversation
5) Lack of insight
6) Apathy
What is the gross appearance of Korsakoff’s syndrome?
Cystic spaces with haemosiderin-laden macrophages
What are 3 presentations of Horner’s syndrome?
Sympathetic system failure:
1) Ptosis
2) Miosis
3) ±Ptosis
What is Harlequin’s syndrome?
Unilateral blockade of the T2-T3 fibers carrying sudomotor and vasomotor supply
- asymmetric sweating and flushing on the upper thoracic region of the chest, neck and face
What are the neurological effects of a Pancoast tumour?
Apical lung tumour:
1) T1/lower brachial plexus lesions
2) Sympathetic outflow → anhydrosis
3) Phrenic nerve → hemidiaphragm paralysis
4) Recurrent laryngeal nerve → dysphonia
What are 3 conditions in which dorsal column involvement is seen?
1) B12 deficiency
2) Syphilis
3) Copper deficiency
What are 2 ways that Guillian-Barre may be life-threatening?
1) Type 2 Respi failure
2) Cardiac arrythmias
How is Guillain-Barre syndrome treated?
1) IVIG
2) Supportive
Why does Guillain Barre syndrome not cause wasting despite being a LMN disease?
Wasting takes too long, GBS is a one-off attack
