CNS patho

Question 1

clinical presentations of patho of CNS

Answer 1

• raised ICP
• localising signs - sudden (hemorrhage), gradual (tumour)
• neurodegenerative stage: cognitive/motor impairment
• demyelinating diseases (problem w/ the myelin sheath)

Question 2

CNS diseases

Answer 2

V: cerebrovascular disease, intracranial hemorrhage
I: infections
T: raised ICP from trauma
A: demyelinating disease
M: alcoholic encephalopathy, storage diseases
I: idiopathic
N: neoplastic (tumour)

C: congenital malformations
D: neurodegeneration

Question 3

hydrocephalus

Answer 3

increase in CSF volume due to disturbances of formation/flow/absorption
- non-communicating: physical obstruction (tumour/mass, meningitis causing scarring)
- communicating: problem w/ venous drainage, defective absorption
subarachnoid hemorrhage -> block arachnoid villi in subarachnoid space
meningitis

Question 4

cerebral herniation

Answer 4

• subfalcine herniation: below falx cerebri
  can cause hemorrhage and necrosis -> compress cerebral artery -> infarction
  clinically silent
• uncal herniation: medial temporal lobe
  loss of consciousness
  compress CN3 -> pupil fixed and dilated
  can cause displacement of the brainstem -> stretch the vessels -> hemorrhage
• tonsillar herniation: through foramen magnum
  coning: compress pons and medulla -> affect respi and cardiac fn
  presents w/ neck stiffness

Question 5

causes of cerebrovascular accidents

Answer 5

• ischemia
• hemorrhage

increases risk:

• HTN -> lacunar infarcts; HT encephalopathy; HT intracerebral hemorrhage
• DM
• atherosclerosis
• TIA (transient ischemic attack) - temp cerebrovascular insufficiency
• atrial fibrillation
• vascular malformations
• coagulopathy

Question 6

ischemia

Answer 6

• thrombosis (pale infarct)
• embolism (red hemorrhagic infarct)
  hemorrhagic infarct CANNOT use thrombolytics

micro appearance - liquefactive necrosis

Question 7

hypertensive cerebrovascular disease (hemorrhagic)

Answer 7

effects:
- lacunar infarcts
multiple infarcts in basal ganglia/ white matter/ brainstem
- HT encephalopathy: diffuse cerebral dysfunction
can cause cerebral herniation (cause of the increased pressure)
- HT intracerebral hemorrhage: caused by atherosclerosis/ hyaline arteriolosclerosis/ aneurysms

Question 8

hemorrhage within brain tissue

Answer 8

• intraparenchymal - petechial hemorrhages (dislodged fat embolism, malaria, vasculitis, HT encephalopathy)
• intraventricular

causes:

• HTN
• amyloid angiopathy
• venous sinus thrombosis

Question 9

hemorrhage outside tissue

Answer 9

• subarachnoid: ruptured berry aneurysms (red) (high mortality)/ vascular malformations
• subdural: tearing of bridging veins, can be by trauma. acute has high mortality - need urgent decompression, chronic good prognosis
• epidural: caused by trauma: affects MMA
  lucid intervals, loss of consciousness, sudden deterioration
  immediate decompression surgery

Question 10

CNS tumours presentation

Answer 10

raised ICP -> compression/herniation
headaches
seizures
focal neurological deficits

Question 11

types of tumours

Answer 11

classification by age
children
- medulloblastoma
- ependymoma (ventricles/anywhere with CSF fluid)
- germ cell tumour (midline)
- pilocytic astrocytoma (arise from astrocytes)
adults: likely metastasis

site:

• meninges: meningioma
• parenchyma: neurons (neuroblastoma, medulloblastoma); glial cells (gliomas: astrocytoma/ oligodendroglioma/ ependomyoma)
• ventricles: choroid plexus tumour, ependymoma
• midline: pituitary tumour, germ cell tumour

Question 12

meningioma

Answer 12

uniform ovoid cells
psammoma bodies
nuclear inclusions

Question 13

astrocytoma (glial cells in parenchyma)

Answer 13

• pilocytic astrocytoma (low grade) = hairy cell
  IDH1 mutant better prognosis than wild type
  in children
• glioblastoma multiforme (high grade)
  aggressive
  ‘butterfly tumour’
  palisading necrosis (in a row)

Question 14

oligodendroglioma (glial cells in parenchyma)

Answer 14

affects cerebral cortex
mutation in the IDH1 gene and deletion of 1p and 19q
uniform round cells w/ fried egg appearance

Question 15

neuronal tumour

Answer 15

neuroblastoma
supratentorial (above tentorial cerebelli)
rare, poor prognosis
affects children

medulloblastoma - better prognosis w/ treatment, more common
infratentorial
aggressive, spread via CSF
micro: sheets of small cells, high n/c, mitosis, “carrot shaped nuclei”, rosettes (canals)
treatment: surgery and radiotherapy
- loss of 17p

Question 16

ependymoma (ventricle and tumour of glial cells in parenchyma)

Answer 16

young patients
can cause hydrocephalus -> raised ICP
micro: perivascular pseudorosettes and true rosettes (canals)

Question 17

choroid plexus tumour

Answer 17

• papilloma
• carcinoma
  can cause hydrocephalus -> raised ICP

Question 18

midline tumour

Answer 18

pituitary tumour: can compress optic chiasma -> visual field defects (bitemporal hemianopia)
- endocrine: adenoma (more common), carcinoma
- embryonal remnant: craniopharyngioma (benign)
—> micro: cysts lined by sse, calcification
good prognosis but possible recurrence

germ cell tumour ** (when there is a midline tumour, think GC tumour 1st)
affects children & males more
- teratoma: benign/malignant
- germinoma

pineal gland tumour

• pineocytoma
• pineoblastoma (high grade)

Question 19

lymphoma

Answer 19

B cell non-hodgkin lymphoma

affects immunosuppressed pts, esp AIDS pts

Question 20

peripheral nerve sheath tumours

Answer 20

benign:
- schwannoma: attached to nerve, well circumscribed & encapsulated
micro: spindled cells, nuclear palisading (arises from neural cells), hyalinised vessels
- neurofibroma: cutaneous (skin/nervous system), non-encapsulated
autosomal dominant
-> NF1 (neurofibromatosis)
can affect skin, CN8, spinal cord nerve roots. optic nerve lioma, hermartomas nodules
renal/musculoskeletal abnormalities
potential malignant transformation of neurofibromas
-> NF2
clinical diagnosis:
- bilateral vestibular schwannoma/
- 1st deg relative w/ NF2 + unilateral
- multiple meningiomas + unilateral
-> tuberous sclerosis
TSC1 and 2 gene alterations
presentation:
(brain) cortical tubers, hermartoma
(skin) lesions: thickened, elevated, pebbly skin on the lower back - contains a lot of fibrous tissue + lumps of fibrous tissue growth on nail bed
(lung) lesions
(renal) angiomyolipoma
-> von hippel-lindau disease (tumour in many organs)
hemangioblastoma (retinal, cerebellar)
cysts (renal, pancreatic, adrenal)
RCC
pheochromocytoma

malignant:
- neurofibromatosis

Question 21

CNS infections possible routes

Answer 21

• trauma
• blood borne: septicemia, infective emboli
• peripheral nerves: rabies, HSV
• sinusitis, otitis media, dental caries, facial infection (affecting venous sinuses)

Question 22

bacterial infection

Answer 22

can cause:

• extradural abscess
• meningitis
• brain parenchyma abscess formation (localised)

Question 23

fungal infection

Answer 23

can cause:

• meningitis
• brain parenchyma abscess formation (localised)

Question 24

viral infection

Answer 24

can cause:

• meningitis
• encephalitis
• meningoencephalitis

Question 25

prion disease (misfolded proteins)

Answer 25

can cause: | - encephalitis

Question 26

meningitis

Answer 26

clinical presentation: - headache - fever - neck stiffness, kernig's sign (stiffness of leg doesnt allow extension of knee) - photophobia bacterial: - neonates: e.coli, listeria - infants: h.influenza - adolescent: n.menigitidis - adults: s.pneumonia

Question 27

encephalitis

Answer 27

clinical presentation: altered mental state usually caused by viral infection: - acute: HSV, measles, HIV, CMV, rubella - delayed: VZV, measles - prion disease HSV, rabies -> affect neuron/glial cells polio, enterovirus -> motor neurons VZV -> DRG HIV -> microglia

Question 28

parenchyma abscess

Answer 28

clinical presentation: - swinging fever - raised ICP -> vomitting/ fluctuating conscious level - localising signs causes: - single abscess: local source (otitis media/ sinusitis/ trauma) - multiple: from septic emboli of infective endocarditis - organisms (bacteria): strep, s.aureus, e.coli

Question 29

subdural empyema (pus)

Answer 29

from skull/air infection | cause: thrombophlebitis (clotting of blood) of bridging veins -> infarction

Question 30

extradural abscess

Answer 30

cause: local - sinusitis | if it infects the spinal cord -> cord compression (emergency)

Question 31

diagnostic method for infections

Answer 31

- imaging: localise the infection - sterile samples: CSF/blood - EEG: detect prion disease

Question 32

HSV infection

Answer 32

affect neuron/glial cells - temporal lobe abscess think HSV clinical: alteration in mood/memory/behavior micro: necrotising, perivascular lymphocytic infiltrates, intranuclear inclusions

Question 33

rabies

Answer 33

affect neuron/glial cells edema, congestion location: basal ganglia, midbrain, 4th ventricle, spinal cord, DRG micro: (hippocampus) cytoplasmic oval eosinophilic inclusion (cerebellum) purkinje cells symptoms: early - (nonspecific) malaise, fever, headache advanced - CNS excitability: painful touch, violent motor response, spasms, convulsions

Question 34

HIV infection

Answer 34

cause menigitis, encephalitis micro: multinucleated giant cell, microglial nodules (elongated nuclei), perivascular cuffing if it infects spinal cord: vacuolar myelopathy (holes in myelin sheath) of posterior column presentation: progressive painless leg weakness/stiffness; sensory loss; imbalance

Question 35

neurosyphilis

Answer 35

affects (brain) neuronal loss -> dementia (meninges) granulomatous meningitis, subintimal vessel thickening (spinal cord) demyelination of post cord -> damage skin and joints

Question 36

fungal infection

Answer 36

affects immunocompromised pts - candida - Cryptococcus neoformans cause vasculitis and thrombosis -> infarction, hemorrhage meningitis (crypt) parenchymal invasion

Question 37

parasitic infection

Answer 37

protozoa: - malaria - toxoplasma - amoeba - trypanosoma helminths - echinococcus - taenia solium

Question 38

prion disease pathogenesis

Answer 38

usually genetic cause, affects males more can also be transmissible - contaminated transplant tissue/ food spread of misfolded proteins -> causes spongiform encephalopathy -> neuronal death CJD: rapidly progressive dementia; abnormal muscular coordination (jerks, myoclonus); personality changes (impaired memory, depression) variant CJD affects young adults slower progress; prominent behavioral changes micro: spongiform transformation (cerebral cortex, deep grey matter) amyloid deposits and plaques

Question 39

CNS malformations

Answer 39

causes - prenatal insult: folate def/ radiation/ infections/ drugs - genetic types: - neural tube defects: neural tube fail to close folate def -> spina bifida (spine) (causes LL weakness/paralysis; bladder and bowel dysfunction, UTIs; clubbed feet, hip dilocation) (brain) anencephaly (born w/o parts of brain/skull cause forebrain development got disrupted); encephalocele (outpouching of membrane into skin) - forebrain anomalies polymicrogyria: seizures, mental retardation, hemi/quad paresis (paralysis) microencephaly: difficulty swallowing, seizures, psychomotor retardation - post fossa anomalies 1. Arnold chiari (chirai type 2) malformation*: displacement of cerebellar tonsils through foramen magnum -> headaches, muscle weakness, fatigue severe: brainstem damage 2. dandy walker syndrome: enlarged post fossa -> enlargement of skull raised ICP - vomitting, irritability poor coordination of eye and facial muscles affects females & infants (slow motor development) more

Question 40

Alzheimer's disease

Answer 40

pathology: mutation of chromosome 21 (amyloid precursor protein) -> production and deposition of beta amyloid peptides (in hippocampus, amygdala, neocortex) -> neuronal damage frontal and parietal lobes affected + brain atrophy micro: amyloid deposits; intracellular tau protein

Question 41

parkinson disease

Answer 41

``` pathology: loss of nerve cells from midbrain -> reduced dopamine lewy bodies (contain a-synuclein gene) ``` gross: substantia nigra (basal ganglia) becomes pale

Question 42

metabolic/toxic diseases

Answer 42

``` vit B1 (thiamine) def = wernicke encephalopathy: thiamine def -> damage medial thalamus and mammillary bodies -> cerebral atrophy vit B12 def = degeneration of spinal cord ``` storage diseases: niemann pick, tay-sachs disease hepatic encephalopathy CO poisoning: diffuse cortical necrosis

Question 43

alcohol affecting CNS

Answer 43

- fetal alcohol syndrome: growth retardation, cerebral malformation of baby - acute intoxication -> respiratory depression - chronic: cerebral cortical atrophy cerebellar atrophy wernicke encephalopathy (cause of b1 def) -> korsakoff psychosis