CAA and others Flashcards
What is the typical presentation of CAA?
- Lobar intracranial hemorrhages (vessels rupture)
- Transient focal neurologic episodes (stereotypy spells of weakness, numbness, paresthesia, cortical symptoms)
50% of patients >80 report no clinical manifestations
What is the underlying pathology of CAA?
- Deposits of beta amyloid within cerebral vasculature
- Vascular rupture and bleeding
Inc BP can inc risk of hemorrhage
Pathophysiology is distinct from AD
Relationship between CAA and AD
Both have AB40 and 42
CAA = inc risk of AD dementia
CAA can occur independently of AD
How does CAA cause cognitive decline?
- New ICH
- Alzheimer’s disease pathology
- CAA related neurodegeneration (hypoperfusion, micro infarcts, inflammation, atrophy, white matter disconnect)
What genetic factors are involved in CAA?
- APOE2 and APOE4 - associated with sporadic CAA and lobar ICH
- ABPP or presenilin genes - hereditary cases
- CR1
Modified Boston Diagnostic Criteria for CAA = definite
Definite
Full brain post mortem
1. Sev CAA with vasculopathy
2. Absence of other diagnostic lesion
3. Presentation with spontaneous ICH, TFNE, cSAH, CI/dementia
Modified Boston CAA = Probable CAA with supporting pathology
Clinical data and pathologic tissue
1. Some degree of CAA in specimen
2. Absence of other diagnostic lesion
3. Presentation with spontaneous ICH, TFNE, cSAH, CI/dementia
Modified Boston = Probable CAA
Clinical data and MRI showing:
1. Age 50+
2. Presentation with spont ICH, TFNE or CI/dementia
3. 2+ of strictly lobar hemorrhagic lesions on T2 MRI (ICH, CMB, CSS/CSAH foci)
OR
- 1 lobar hemorrhagic and 1 white matter feature
- Absence of deep hemorrhagic on T2MRI
- Absence of other cause of hemorrhagic lesion
- Hemorrhagic lesion in cerebellum not counted as lobar or deep
Modified Boston Possible CAA
Clinical data and MRI showing:
1. Age 50+
2. Presentation with spont ICH, TFNE or CI/dementia
3. 1 strictly lobar hemorrhagic lesion on T2 MRI (ICH, CMB, CSS/CSAH foci)
or
- 1 white matter feature
- Absence of deep hemorrhagic on T2MRI
- Absence of other cause of hemorrhagic lesion
- Hemorrhagic lesion in cerebellum not counted as lobar or deep
Target BP for CAA and agent
<120/80
Preferred perindopril and indapamide
Target lipids in CAA
LDL <1.8 = inc risk ICH
Give statins if CAA but need clear indication per AHA guidelines
Antiplatelets in CAA
Avoid unless clear indication for use for secondary prevention
Anticoagulants in CAA
Non valvular AF
- Start 4-8 wks post lobar ICH
- Prefer DOAC over warfarin
- If very sev CAA may consider LAAC
Mechanical valve
- Must use warfarin
- If very high risk could consider bio prosthetic
PE/DVT
- short term benefit > risk
CAARI - related inflammation criteria
- Age >40
- Present with at least one of: acute/subacute HA, dec LOC, behavioural change, focal neurology deficits, seizure, (HA/dec LOC could occur over longer time frames)
- MRI patchy or confluent T2/FLAIR lesions (asymmetric white matter hyper intensity)
- At least one of cerebral macrobleed, microbleed, cortical superficial siderosis
- No neoplastic or infectious cause
CAARI definition
Autoimmune reaction to cerebral beta amyloid deposits
CAARI Treatment
Immunosuppression increases likelihood of clinical and radiologic improvement and less recurrence
Steroids alone = pulse methylprednisolone followed by 6 months oral taper
What drug has ARIA been found as a side effect for?
Adacanumab
Higher in APOE4 positive
Most common in first 8 doses or when dose increasing
What are the two types of ARIA?
E = focal vasogenic oedema with FLAIR hyper intensity, usually no sx but sometimes HA, fatigue, confusion, dizzy, falls, vision change, nausea
H = microhemorrhage or superficial siderosis, often occurs with E
Management of ARIA
Asymptomatic - if no sx and mild MRI changes, continue on drug with close monitoring and monthly MRI, don’t inc dose until edema resolves
Symptomatic or mod-sev - hold drug
Monthly F/U MRI to see if can restart after edema resolves
Monitoring for ARIA
MRI prior to therapy, prior to 5th, 7th and 12th doses
Additionally if any symptoms
Include FLAIR, T2, GRE, SWI and DWI
What is CADASIL?
Cerebral autosomal dominant arteriopathy and subcortical infarcts with leukoencephalopathy
Non-atherosclerotic arteriopathy affecting small vessels in brain
Develop a subcortical VaD
Caused by NOTCH3 gene mutation
Suspect when cognitive changes with early exec dysfunction, migraines, neuropsychological sx, famhx and absence of traditional stroke risk factors
Signs usually appear in mid 30s
What is CARASIL?
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy
Damage to small vessels of the brain
Caused by HTRA1 gene mutations
Abnormalities in 20s-30s, spasticity in legs
Stroke before age 40
Develop mood/personality, dementia, worsening movement
Premature hair loss and attacks of LBP
What are two associated pathologic features of chronic traumatic encephalopathy?
- Beta amyloid plaques (not consistent, no in early stages)
- P-tau - tangles
- TDP-43
List Gauss criteria for limbic encephalitis
All 4 must be met
1. Subacute onset (<3 mos) of working memory deficits, seizures or psych symptoms
2. Bilateral Brian abnormalities on T2 MRI, restricted to medial temporal lobes
3. At least one of: CSF pleocytosis, EEG with epileptic or slow waves (involving temporal lobes)
4. Reasonable exclusion of alternatives
What differentiates HSV and limbic encephalitis on MRI?
Bilateral medial temporal lobe changes on MRI T2 FLAIR
In HIV it’s unilateral
What is the best way of assessing acuity of ALE?
Collateral history from reliable informant
