CNS Pathology Flashcards
Hydrocephalus
- Non-communicating
- Communicating
- – reduced CSF resorption (eg. arachnoid fibrosis)
- – ?Normal Pressure Hydrocephalus (NPH)
- Elderly, brain atrophy, ataxia / incontinence / dementia: many respond to LP / shunt
- – ?Pseudotumour cerebri (‘Benign’ Intracranial Hypertension)
- Female, obese, headache / vision loss: many respond to LP(s), diuretics, corticosteroids, shunt
- Exvacuo: compensatory dilation of ventricles to brain atrophy
Etiopath:
- Congenital: aqueductal stenosis
- stretching of corona radiata due to increased CSF
Sx: headache, vomiting worse in morning & triad of nl hydrocephalus (urinary incontinence, gait instability, dementia)
Sx in children: bulging frontal bone, sunsetting eyes (downward deviation)
Epidural hemorrhage
- Associated with skull fracture, esp. temporal
- laceration of middle meningeal artery
- acute (arterial) accumulation
Subdural hemorrhage
- Rupture of veins bridging arachnoid and dura
- slower (venous) accumulation
- acute (hours)
- delayed (days to weeks)
- especially in elderly after trivial head injury
- risk of re-bleed
Diffuse Axonal Injury (DAI)
- Rotational acceleration
- shearing of axons as they are stretched beyond elastic point with rotational force
- No lucid interval - unplugged
Concussions
Transient and highly variable disturbance of neurological function following trauma
– Blow to the head is not required
– Predispositions (APO-E genotype, other)
– Repeated insults (boxing, football, hockey)
Theories: microscopic membrane injuries, dysruption of blood-brain-barrier, convulsive
Ischemic stroke
- red neurons are early findings (12 to 24 h)
- neutrophils, microglial cells, (1 d to 1 wk) and granulation tissue then ensue
- results in fluid-filled cystic space surrounded by gliosis
- leads to liquefactive necrosis
Cerebral Infarct
- loss of adequate blood supply, usually from thrombosis or embolization
- bland vs. hemorrhagic
- penumbra: central area of necrosis surrounding by less damaged brain tissue
- watershed areas most susceptible
- purkinje cells of cerebellum, layer 3 & 5 of neocortex (laminar necrosis), pyramidal cells of hipp
- Signs & sx: edema, TIA
Intraparenchymal/intracerebral hemorrhage
- Hypertensive (3 common sites: basal ganglia, brainstem, cerebellum)
- Other (often lobar)
- – Arterial
- – Venous (from cortical vein or dural sinus thrombosis)
- Coagulopathy
- Tumour hemorrhage
- Vascular malformation
- Amyloid angiopathy
- Cortical vein or dural sinus thrombosis due to extreme dehydration
- Arteriolosclerosis (bland “lacunes”)
- Charcot-Bouchard aneurysms (“slit” hemorrhages)
- Subarachnoid hemorrhage
- “Worst headache of my life”
- Berry aneurysms @ Branch points of Circle of Willis
- 1% incidence at autopsy (20% are multiple)
- 90% in ACA
- 10% in PCA
- Signs & Sx: meningial irritation (photophobia, papilledema, projectile vomitting
- Congenital: Marfan’s, ED, & PCKD
C&C:
- bleed stream cutting through brain parenchyma and leading to intracerebral bleeds
- Vasospasm -> manifesting as additional neuro deficits
- arrythmias
Vascular malformations
AVMs
– Greatest potential for hemorrhage
– High flow channels without arterial structure -> high calibre vessels in cortex where it should small calibre
– Rx: excision, endovascular occlusion, spray embolic agents
Also:
– venous angiomas, cavernous angiomas, capillary telangiectasias
Viral encephalitis / encephalomyelitis
- HIV Encephalitis (HIV) most common world-wide
- Many insect-borne viruses account for local outbreaks (Eastern equine, Western equine, St. Louis, West Nile, etc.)
- Herpes family members (HSV, CMV, VZV) noteworthy causes of an aggressive encephalitis, esp. in immunocompromised hosts
C&C:
- Progressive multifocal encephalopathy:
- caused by papova virus or JC virus (polyoma virus)
- cytoplasmic inclusions in oligodendrocytes
HIV-1 Associated Neuropathology
HIV
Morphology:
lymphocyte, histiocyte, giant cells
– encephalitis and leukoencephalopathy
– Vacuolar myelopathy
– Neuropathy, inflammatory myopathy
Opportunistic infections
– CMV, VZV, candida, papova virus (PML)
– Mycobacteria, fungi, ameoba
- “Opportunistic neoplasms”,esp. **primary CNS lymphoma **
Prion Diseases
2 forms: CJD and vCJD
CJD
Morphology: intracell vacuoles w abnormal protein aggregates
– Sporadic & degenerative
– 1 per million annual incidence
– Rapidly progressive dementia
– Myoclonus
Variant CJD (vCJD)
– Associated with BSE meat consumption
– Almost all cases from UK origin, new cases waning
– Slower onset, progressive personality changes
- sporadic
Brian abscess
Etiology:
- liquefactive necrosis surrounded by fibrous capsule
- causative agents: mixed infection
- risk factors: post-surgical, mastoiditis, sinustis, otitis media, infective endocarditis, R-L shuts, brochiectasis
- Parasites can also cause brain abscess
- AIDS Pt need prophylatic rx T. gondii causing brain abscess
- T. soli (neurocysterocosis)
- E. histolytica
Sx: ICP: Cushing triad (lower heart rate, mental changes, irregular breathing), papilledema, projectile vomitting, headache, fever
Dx:
- ring enchancing lesions
- CSF showing PMN and low glucose
Alzheimer’s disease
Gross
– atrophy, esp. frontal, temporal, parietal (apraxia)
Micro
– neuronal loss in cerebral cortex
– gliosis (astrocyte proliferation and hypertrophy)
– neurofibrillary tangles (Tau hyperphosphorylated intracell) and neuritic plaques (extracell)
- Carenal bodies in HIPP
Etiopath
- 80% are sporadic: Late onset (no identified risk factor): age & incr risk w Apo E4 and decr risk w Apo E2
- 20% are hereditary: Early onset AD: APP (Chr 21 assoc w Down syndrome), Presenilin (Chr 1 and 14), Clusterin (Chr 8), Complement receptor-1 (Chr 1) …
- Abeta amyloid depostions -> brain deficits
- *C&C:**
- ex vacuo hydrocephalus
- cerebral amyloid angiopathy -> lobar hemorrhage
Parkinson’s
Sx: tremor, rigidity, akinesia, postural instability & shuffling gait (TRAP)
usually no family history
Gross
– pallor and atrophy of substantia nigra (nucleus of dopaminergic neurons in the midbrain)
Micro
– neuronal dropout, gliosis
– Lewy bodies (in substantia nigra neurons)
Etiopath
- Cause unknown
- most cases are sporadic
- small percentage due to mutation in the synuclein gene (alpha-synuclein is a component of Lewy bodies)
- leads to degeneration of DA neurons of SNpc
Huntington’s Disease
Clinical:
choreiform movements, motor difficulties, athetosis, dementia
Pathology:
– Gross
- Marked atrophy of Caudate and Putamen
- Lesser atrophy of globus pallidus and cerebral cortex
– Micro
- Neuronal loss
- Gliosis
Etiopath:
- AD Triplet repeat (CAG) in huntingtin gene
- Anticipation due to CAG repeat expansion during spematogenesis
- loss of GABA neurons in striatum
Amyotrophic Lateral Sclerosis (ALS)
- Synonyms: Lou Gehrig’s disease, Motor Neuron Disease
- affects middle-aged
- muscle weakness, muscle atrophy
- intellect, sensation, sphincter control and eye movements spared
- life expectancy ∼2-5 years after onset
- ∼10% of cases are hereditary
Pathology
Neuronal loss
– spinal cord anterior horns, motor cortex
Cytoplasmic inclusions
– Ubiquitin (a protein deposited in response to cell injury)
– TDP-43, FUS (DNA/RNA binding/stabilizing proteins)
Pathogenesis
- – uncertain,?abnormal RNA and/or protein processing
- Identified mutations: Chromosome 9 hexanucleotide repeat (C9ORF72) & SOD-1
Multiple Sclerosis
– common, young adults, F:M = 3:1, latitude
– Other associations: smoking, low vitamin D, maternal history
MRI: demyelination plaques
Pathology
– perivascular lymphocytic inflammation
– demyelination (patchy loss of myelin): grey & white matter *
– symptoms related to area involved & gray matter injury may correlate best with disability*
Risks:
– Smoking, low vitamin D, race (white), EBV, HLA , maternal family history, move to endemic area before puberty
Pathogenesis
- poorly understood; perivascular inflammation
- multifactorial?: genetic, immune, infection
- Genetic: 15x inc risk w affected 1st degree relative; assoc w HLA-DR2; IL-2 and IL-7 polymorphism
- autoimmune: CD4+, Th17, and Th1 thought to be critical
- infection:
Sx
- Optic n. demyelination (oligodendroctyes): blurred vision
- Cerebellum: ataxia and motor deficits
- Brain stem: vertigo and scanning speech
- internuclear ophthalmoplegia
- ascending and descending fiber tracts -> hemiparesis or unilateral loss of sensation
- spinal cord -> lower extremity loss of sensation or weakness (spinal cord)
- Bowel bladder, and sex dysfunction (autonomic nervous system)
Investigations: MRI, CSF showing oligoclonal bands of IgG, lymphocytes, and MBP
C&C: relapse and remission type: 80%
Rx: high dose cort during acute attaack & interferon therapy to slow progression
Myelinolysis
- Central pontine myelinolysis
- Extra-pontine myelinolysis
- – Pathogenesis: unknown
- – Associated with rapid correction of hyponatremia
- Common settings for hyponatremia:
- – renal or hepatic disease
- – severe vomiting or diarrhea
- – congestive heart failure
- – SIADH
Wernicke’s Encephalopathy
Thiamine deficiency
- Encephalopathy, confusion
- Ocular palsies
- Ataxia
- Korsakoff’s pychosis: no new memories
- Key targets: Mamillary bodies, thalamus, periaqueductal gray matter
Hypoglycemia
- Most often in poorly controlled IDDM
- Occasionally in insulin overdose
- Rarely, insulinoma
- – Hippocampal pyramidal neurons are exquisitely sensitive to hypoglycemia
- – Cerebellar Purkinje neurons also at risk
Tumour types
Primary
– intrinsic: gliomas (astrocytic, oligodendroglial, mixed)
- grade of anaplasia determines prognosis
– extrinsic: meningiomas, schwannomas, pituitary adenomas
Adults: Astrocytomas, oligoendrogliomas, mixed (>90% supratentorial)
Children: Astrocytomas pilocytic, ependymomas, medulloblastomas (>90% infratentorial)
Secondary
- metastases (lung, breast, melanoma)
- lymphoma (esp. in immunocompromised)
Glioblastoma multiforme
Morphology
- pseudo-pallisade: necrosis surrounded by pallisading tumour cells
- astrocytes seen on microscopy
- butterfly lesion crossing CC
- Supratentorial in adults
- Infratentorial in Children (cerebellar & pons)
Etiopath:
- Malignant tumor of astrocytes. Most common primary CNS tumor in adults.
- can cross midline
- prognosis: 3 to 4 years
- overtime will lead to GBM(prognosis 1 to 2 years)
- Primary intrinsic tumors of CNS: Abnormal proliferation of cells due to gene mutations such as EGFR, IDH-1, p53,
- MGMT methylation: MGMT normally takes demethylates
- Isocitrate Dehydrogenase (IDH-1): backup of alpha-KG will promote methylation
- *Sx:**
- headaches and seizures worse in morning
- mass-related effects
Dx:
- EGFR: bad prognosis
- everything else is better prognosis
- GFAP from biopsy
Better prognosis if: younger, - EGFR, + IDH-1, + P53, + MGMT methylation
Side note: Anaplastic Astryocytoma dx requirments -> pleiomorphic, mitotic figures, dysplasia
