CNS patho Flashcards
clinical presentations of patho of CNS
- raised ICP
- localising signs - sudden (hemorrhage), gradual (tumour)
- neurodegenerative stage: cognitive/motor impairment
- demyelinating diseases (problem w/ the myelin sheath)
CNS diseases
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
hydrocephalus
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
cerebral herniation
- 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
causes of cerebrovascular accidents
- 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
ischemia
- thrombosis (pale infarct)
- embolism (red hemorrhagic infarct)
hemorrhagic infarct CANNOT use thrombolytics
micro appearance - liquefactive necrosis
hypertensive cerebrovascular disease (hemorrhagic)
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
hemorrhage within brain tissue
- intraparenchymal - petechial hemorrhages (dislodged fat embolism, malaria, vasculitis, HT encephalopathy)
- intraventricular
causes:
- HTN
- amyloid angiopathy
- venous sinus thrombosis
hemorrhage outside tissue
- 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
CNS tumours presentation
raised ICP -> compression/herniation
headaches
seizures
focal neurological deficits
types of tumours
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
meningioma
uniform ovoid cells
psammoma bodies
nuclear inclusions
astrocytoma (glial cells in parenchyma)
- 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)
oligodendroglioma (glial cells in parenchyma)
affects cerebral cortex
mutation in the IDH1 gene and deletion of 1p and 19q
uniform round cells w/ fried egg appearance
neuronal tumour
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
ependymoma (ventricle and tumour of glial cells in parenchyma)
young patients
can cause hydrocephalus -> raised ICP
micro: perivascular pseudorosettes and true rosettes (canals)
choroid plexus tumour
- papilloma
- carcinoma
can cause hydrocephalus -> raised ICP
midline tumour
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)
lymphoma
B cell non-hodgkin lymphoma
affects immunosuppressed pts, esp AIDS pts
peripheral nerve sheath tumours
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
CNS infections possible routes
- trauma
- blood borne: septicemia, infective emboli
- peripheral nerves: rabies, HSV
- sinusitis, otitis media, dental caries, facial infection (affecting venous sinuses)
bacterial infection
can cause:
- extradural abscess
- meningitis
- brain parenchyma abscess formation (localised)
fungal infection
can cause:
- meningitis
- brain parenchyma abscess formation (localised)
viral infection
can cause:
- meningitis
- encephalitis
- meningoencephalitis
prion disease (misfolded proteins)
can cause:
- encephalitis
meningitis
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
encephalitis
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
parenchyma abscess
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
subdural empyema (pus)
from skull/air infection
cause: thrombophlebitis (clotting of blood) of bridging veins -> infarction
extradural abscess
cause: local - sinusitis
if it infects the spinal cord -> cord compression (emergency)
diagnostic method for infections
- imaging: localise the infection
- sterile samples: CSF/blood
- EEG: detect prion disease
HSV infection
affect neuron/glial cells
- temporal lobe abscess think HSV
clinical: alteration in mood/memory/behavior
micro: necrotising, perivascular lymphocytic infiltrates, intranuclear inclusions
rabies
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
HIV infection
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
neurosyphilis
affects
(brain) neuronal loss -> dementia
(meninges) granulomatous meningitis, subintimal vessel thickening
(spinal cord) demyelination of post cord -> damage skin and joints
fungal infection
affects immunocompromised pts
- candida
- Cryptococcus neoformans
cause
vasculitis and thrombosis -> infarction, hemorrhage
meningitis (crypt)
parenchymal invasion
parasitic infection
protozoa:
- malaria
- toxoplasma
- amoeba
- trypanosoma
helminths
- echinococcus
- taenia solium
prion disease pathogenesis
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
CNS malformations
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
Alzheimer’s disease
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
parkinson disease
pathology: loss of nerve cells from midbrain -> reduced dopamine lewy bodies (contain a-synuclein gene)
gross: substantia nigra (basal ganglia) becomes pale
metabolic/toxic diseases
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
alcohol affecting CNS
- 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
