CAA and others

Question 1

What is the typical presentation of CAA?

Answer 1

1. Lobar intracranial hemorrhages (vessels rupture)
2. Transient focal neurologic episodes (stereotypy spells of weakness, numbness, paresthesia, cortical symptoms)

50% of patients >80 report no clinical manifestations

Question 2

What is the underlying pathology of CAA?

Answer 2

1. Deposits of beta amyloid within cerebral vasculature
2. Vascular rupture and bleeding

Inc BP can inc risk of hemorrhage
Pathophysiology is distinct from AD

Question 3

Relationship between CAA and AD

Answer 3

Both have AB40 and 42
CAA = inc risk of AD dementia
CAA can occur independently of AD

Question 4

How does CAA cause cognitive decline?

Answer 4

1. New ICH
2. Alzheimer’s disease pathology
3. CAA related neurodegeneration (hypoperfusion, micro infarcts, inflammation, atrophy, white matter disconnect)

Question 5

What genetic factors are involved in CAA?

Answer 5

1. APOE2 and APOE4 - associated with sporadic CAA and lobar ICH
2. ABPP or presenilin genes - hereditary cases
3. CR1

Question 6

Modified Boston Diagnostic Criteria for CAA = definite

Answer 6

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

Question 7

Modified Boston CAA = Probable CAA with supporting pathology

Answer 7

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

Question 8

Modified Boston = Probable CAA

Answer 8

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. 1 lobar hemorrhagic and 1 white matter feature
2. Absence of deep hemorrhagic on T2MRI
3. Absence of other cause of hemorrhagic lesion
4. Hemorrhagic lesion in cerebellum not counted as lobar or deep

Question 9

Modified Boston Possible CAA

Answer 9

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. 1 white matter feature
2. Absence of deep hemorrhagic on T2MRI
3. Absence of other cause of hemorrhagic lesion
4. Hemorrhagic lesion in cerebellum not counted as lobar or deep

Question 10

Target BP for CAA and agent

Answer 10

<120/80
Preferred perindopril and indapamide

Question 11

Target lipids in CAA

Answer 11

LDL <1.8 = inc risk ICH
Give statins if CAA but need clear indication per AHA guidelines

Question 12

Antiplatelets in CAA

Answer 12

Avoid unless clear indication for use for secondary prevention

Question 13

Anticoagulants in CAA

Answer 13

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

Question 14

CAARI - related inflammation criteria

Answer 14

1. Age >40
2. 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)
3. MRI patchy or confluent T2/FLAIR lesions (asymmetric white matter hyper intensity)
4. At least one of cerebral macrobleed, microbleed, cortical superficial siderosis
5. No neoplastic or infectious cause

Question 15

CAARI definition

Answer 15

Autoimmune reaction to cerebral beta amyloid deposits

Question 16

CAARI Treatment

Answer 16

Immunosuppression increases likelihood of clinical and radiologic improvement and less recurrence
Steroids alone = pulse methylprednisolone followed by 6 months oral taper

Question 17

What drug has ARIA been found as a side effect for?

Answer 17

Adacanumab
Higher in APOE4 positive
Most common in first 8 doses or when dose increasing

Question 18

What are the two types of ARIA?

Answer 18

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

Question 19

Management of ARIA

Answer 19

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

Question 20

Monitoring for ARIA

Answer 20

MRI prior to therapy, prior to 5th, 7th and 12th doses
Additionally if any symptoms
Include FLAIR, T2, GRE, SWI and DWI

Question 21

What is CADASIL?

Answer 21

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

Question 22

What is CARASIL?

Answer 22

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

Question 23

What are two associated pathologic features of chronic traumatic encephalopathy?

Answer 23

1. Beta amyloid plaques (not consistent, no in early stages)
2. P-tau - tangles
3. TDP-43

Question 24

List Gauss criteria for limbic encephalitis

Answer 24

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

Question 25

What differentiates HSV and limbic encephalitis on MRI?

Answer 25

Bilateral medial temporal lobe changes on MRI T2 FLAIR
In HIV it’s unilateral

Question 26

What is the best way of assessing acuity of ALE?

Answer 26

Collateral history from reliable informant