Overview

• ~10–15% of all ischemic strokes occur in patients aged 18–50
• Etiologies differ significantly from older patients — atherosclerosis is less common; dissection, cardioembolism, and rare vasculopathies are more prevalent
• Cryptogenic stroke is more common in young adults (~30–40%) compared to the elderly (~25%)
• Higher proportion of women (OCPs, pregnancy, migraine with aura)

Etiologies by Mechanism

Expanded Workup for Young Stroke

• Standard stroke workup (CT/CTA, MRI/DWI, echo, telemetry, lipids, A1c) PLUS:
• Vessel wall imaging (MRI): Dissection, vasculitis, RCVS, intracranial atherosclerosis
• Hypercoagulable panel: APS antibodies (lupus anticoagulant, anticardiolipin, anti-β2GP1), protein C/S/AT III, Factor V Leiden, prothrombin mutation, homocysteine
• TEE with bubble study: PFO, atrial septal aneurysm, valvular vegetations
• Prolonged cardiac monitoring: 30-day event monitor or implantable loop recorder (CRYSTAL AF: 12.4% occult AF at 12 months)
• ESR/CRP, ANA, ANCA: Vasculitis screen
• HIV, RPR/VDRL, VZV IgG: Infectious causes
• Toxicology screen: Cocaine, amphetamines
• Genetic testing: NOTCH3 (CADASIL), alpha-galactosidase A (Fabry), hemoglobin electrophoresis (sickle cell) when clinically suspected
• CSF analysis: If vasculitis or infection suspected

Primary Angiitis of the CNS (PACNS)

Pathology & Epidemiology

• Rare granulomatous or lymphocytic vasculitis restricted to the CNS (no systemic involvement)
• Affects small and medium-sized leptomeningeal and cortical vessels
• Mean age of onset: 50s; slight male predominance

Presentation

• Insidious onset over weeks to months (NOT thunderclap headache — key distinction from RCVS)
• Headache (60–70%), cognitive decline (50–60%), focal neurological deficits (40–50%), strokes/TIAs
• Seizures, behavioral changes, progressive encephalopathy
• No systemic inflammation — ESR and CRP are typically NORMAL (unlike secondary vasculitis)

Diagnosis

• CSF: Abnormal in ~90% — lymphocytic pleocytosis, elevated protein; helps exclude infection
• MRI: Multifocal white matter and cortical lesions; may mimic MS, tumor, or infection; can show enhancement
• Angiography (DSA): “Beading” pattern (alternating stenosis and dilation) — but NOT specific (also seen in RCVS, atherosclerosis, infection); sensitivity only ~60–70% (misses small vessel disease)
• Brain biopsy = gold standard (leptomeningeal and cortical biopsy, non-dominant temporal tip); shows granulomatous/lymphocytic/necrotizing vasculitis; sensitivity ~75% (may miss focal disease)
• Calabrese criteria: Acquired neurological deficit + angiographic or histologic evidence of CNS vasculitis + exclusion of systemic vasculitis and mimics

Treatment

• Induction: High-dose corticosteroids + cyclophosphamide (3–6 months)
• Maintenance: Azathioprine or mycophenolate mofetil
• Treatment duration: typically 12–18 months minimum; relapses common
• Monitor with serial MRI and CSF

Secondary CNS Vasculitis

Causes

• Systemic vasculitides: PAN, GPA (Wegener), EGPA (Churg-Strauss), Takayasu, Behçet disease, giant cell arteritis
• Infections: VZV vasculopathy (most common infectious cause), HIV, syphilis, TB, fungal (Aspergillus, Mucor), bacterial meningitis
• Connective tissue diseases: SLE, Sjögren syndrome, sarcoidosis
• Drugs: Cocaine, amphetamines (can cause both direct vasoconstriction and true vasculitis)
• Malignancy: Intravascular lymphoma (mimics CNS vasculitis), lymphomatoid granulomatosis

Giant Cell Arteritis (GCA)

Clinical Features

• Age >50 (mean onset ~70); female predominance (2:1)
• New-onset temporal headache, scalp tenderness
• Jaw claudication (most specific symptom — PPV ~95% for positive biopsy)
• Visual loss: Arteritic AION (pallid disc edema) — ophthalmologic emergency; without treatment, risk to fellow eye within days to weeks
• PMR (polymyalgia rheumatica) in ~50% of GCA patients
• Constitutional symptoms: fatigue, weight loss, fever
• Stroke: Predominantly vertebrobasilar territory (GCA preferentially affects extracranial vessels; rare intracranial involvement)

Diagnosis

• ESR markedly elevated (often >50–100 mm/hr); CRP elevated; thrombocytosis common
• Temporal artery biopsy: Gold standard; granulomatous inflammation with giant cells; skip lesions → obtain long specimen (≥2 cm); biopsy remains positive for 2–6 weeks after starting steroids
• Temporal artery ultrasound: “Halo sign” (dark hypoechoic wall thickening around the artery lumen); can be used as first-line in experienced centers
• PET-CT: Shows large vessel inflammation (aortitis pattern)
• Do NOT wait for biopsy to start treatment

Treatment

• Emergent high-dose corticosteroids:
  • Without visual symptoms: prednisone 1 mg/kg/day (max 60–80 mg)
  • With visual symptoms: IV methylprednisolone 1g/day ×3 days, then switch to oral
• Slow taper over 1–2 years guided by symptoms and ESR/CRP
• Tocilizumab (IL-6 receptor blocker): FDA-approved steroid-sparing agent for GCA (GiACTA trial); allows faster steroid taper
• Low-dose aspirin: Recommended to reduce ischemic events

Pathology & Epidemiology

• Progressive stenosis/occlusion of bilateral distal ICAs (supraclinoid segment) and proximal ACA/MCA
• Compensatory development of fragile collateral networks at the base of the brain → “puff of smoke” appearance on angiography (Japanese: moyamoya)
• Bimodal age distribution: peak in children (5–10 years) and adults (30–40 years)
• Higher prevalence in East Asian populations (Japan, Korea, China); associated with RNF213 gene (ring finger protein 213)

Disease vs. Syndrome

Clinical Presentation

• Children: Ischemic strokes and TIAs (most common); often precipitated by hyperventilation (crying, blowing) which causes hypocapnia → vasoconstriction → ischemia
• Adults: Hemorrhage is more common (fragile moyamoya collaterals rupture); also TIAs and ischemic strokes
• Headache (from collateral dilation), seizures, cognitive decline

Suzuki Staging (Angiographic)

Diagnosis

• MRA: Stenosis/occlusion of bilateral distal ICAs; flow voids at base of brain (moyamoya vessels)
• DSA (gold standard): Definitively shows stenosis pattern + “puff of smoke” collaterals + Suzuki staging
• MRI: Multiple infarcts in ICA territory; “ivy sign” on post-contrast FLAIR (leptomeningeal enhancement from cortical collaterals)
• Perfusion imaging (CTP, SPECT, PET) shows hemodynamic compromise

Treatment

• Surgical revascularization is the mainstay (medical therapy alone does NOT prevent progression)
• Direct bypass: STA-MCA (superficial temporal artery to MCA) anastomosis — immediate flow augmentation
• Indirect bypass (synangiosis): EDAS (encephaloduroarteriosynangiosis), EMS, multiple burr holes — place vascularized tissue on brain surface → angiogenesis over weeks-months; preferred in children (smaller vessels make direct anastomosis technically challenging)
• Aspirin for ischemic events; avoid anticoagulation (bleeding risk from fragile collaterals)
• Avoid dehydration and hyperventilation

Overview & Pathophysiology

• Transient, segmental narrowing of cerebral arteries that resolves spontaneously within 12 weeks
• Pathophysiology: dysregulation of cerebral vascular tone → multifocal vasoconstriction
• Female predominance (~2:1); mean age 40s

Triggers

• Postpartum (most common spontaneous trigger)
• Vasoactive drugs: Triptans, SSRIs/SNRIs, pseudoephedrine, cocaine, amphetamines, cannabis, ergot derivatives
• Exertion: Sexual activity, straining, exercise, Valsalva
• Blood products (transfusion, post-surgical), immunosuppressants (tacrolimus, cyclophosphamide)
• Catecholamine-secreting tumors (pheochromocytoma)
• Idiopathic in ~30–40%

Clinical Presentation

• Thunderclap headache = hallmark — severe, peaks within seconds, recurrent (multiple episodes over 1–3 weeks); can mimic SAH
• Headaches may be triggered by exertion, sexual activity, bathing, Valsalva, emotional stress
• Focal deficits if complicated by stroke or hemorrhage
• Seizures (~3–5%)

Complications

• Convexal SAH (early, days 1–5; from cortical arteriolar constriction)
• Intracerebral hemorrhage (early)
• Ischemic stroke (later, ~days 7–14; from sustained vasoconstriction)
• PRES overlap: ~10–40% of RCVS patients have concurrent PRES; both share endothelial dysfunction and blood-brain barrier breakdown

Imaging

• CTA/MRA/DSA: Multifocal segmental stenosis (“string of beads”) affecting multiple vascular territories; resolves on follow-up imaging at 12 weeks
• CT/MRI: May show convexal SAH, ICH, ischemic infarcts, or PRES-pattern edema
• Normal initial CTA/MRA is possible (vasoconstriction may progress centripetally from distal to proximal arteries over days → repeat imaging if initial is negative and clinical suspicion high)

RCVS vs. PACNS — Critical Board Distinction

Treatment

• Remove trigger (stop vasoactive drugs, avoid exertion triggers)
• Calcium channel blockers: Verapamil (preferred) or nimodipine — reduce headache frequency and may reduce vasoconstriction
• Analgesics for headache (avoid triptans and ergots)
• AVOID glucocorticoids — associated with worse outcomes in RCVS (paradoxically may worsen vasoconstriction)
• Intra-arterial vasodilators (milrinone, verapamil) and balloon angioplasty for severe refractory cases with progressive ischemia

Genetics & Pathology

• Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
• NOTCH3 gene mutation (chromosome 19p13); autosomal dominant; >260 pathogenic mutations identified
• Pathology: Non-atherosclerotic, non-amyloid small vessel vasculopathy; degeneration of vascular smooth muscle cells; thickened arteriolar walls
• GOM (granular osmiophilic material) deposited in the media of small arteries — seen on electron microscopy of skin biopsy (pathognomonic)

Clinical Progression

• 20s–30s: Migraine with aura (onset symptom in ~30–40%; auras may be atypical or prolonged)
• 30s–40s: Recurrent subcortical ischemic strokes (lacunar type) and TIAs
• 40s–50s: Progressive cognitive decline → subcortical vascular dementia
• 50s–60s: Psychiatric symptoms (depression, apathy, ~30%), pseudobulbar palsy, gait disturbance
• Mean age of death: ~65 years

MRI Findings

• Extensive white matter hyperintensities (T2/FLAIR) disproportionate to age and vascular risk factors
• Pathognomonic involvement of anterior temporal poles and external capsules — this distribution is highly specific for CADASIL
• Subcortical lacunar infarcts (basal ganglia, thalamus, pons, centrum semiovale)
• Microbleeds (common, predominantly subcortical)
• Progressive cerebral atrophy

Diagnosis

• NOTCH3 genetic testing: Definitive diagnosis; sensitivity ~90–95%
• Skin biopsy: GOM on electron microscopy or NOTCH3 immunostaining of dermal arterioles; sensitivity ~85–90%
• Screen family members when diagnosis is confirmed

Management

• No specific treatment — supportive and risk factor management
• Antiplatelet therapy (aspirin) for stroke prevention; avoid anticoagulation (hemorrhage risk from microbleeds)
• Avoid thrombolytics: Theoretical concern for hemorrhage (microangiopathy + microbleeds), though case reports exist of safe use
• Treat migraine (avoid triptans in some guidelines due to vasculopathy; prefer preventive agents)
• Manage vascular risk factors (hypertension, diabetes, smoking)
• Genetic counseling for affected families

CARASIL

• Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
• HTRA1 gene mutation; autosomal recessive
• Similar to CADASIL but with alopecia (premature baldness) and spondylosis deformans (lumbar disc disease) in young adults
• No GOM deposits; skin biopsy NOT helpful

Overview & Pathophysiology

• Autoimmune thrombophilia with arterial AND venous thrombosis + pregnancy morbidity
• Antibodies: Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β₂ glycoprotein I (anti-β2GP1)
• Primary APS: isolated; Secondary APS: associated with SLE (most common), other autoimmune diseases, infections, malignancy
• Paradox: “Lupus anticoagulant” causes thrombosis, NOT bleeding (prolongs aPTT in vitro but is prothrombotic in vivo)

Revised Sapporo/Sydney Criteria (2006)

• Requires ≥1 clinical criterion + ≥1 laboratory criterion:
• Clinical:
  • Vascular thrombosis (arterial, venous, or small vessel) confirmed by imaging or histopathology
  • Pregnancy morbidity: ≥1 unexplained fetal death at ≥10 weeks, OR ≥1 premature birth before 34 weeks due to preeclampsia/eclampsia/placental insufficiency, OR ≥3 unexplained consecutive early miscarriages before 10 weeks
• Laboratory (must be positive on ≥2 occasions ≥12 weeks apart):
  • Lupus anticoagulant (most specific for thrombosis)
  • Anticardiolipin IgG or IgM (medium-high titer)
  • Anti-β₂ glycoprotein I IgG or IgM
• “Triple positive” (all 3 antibodies) = highest thrombotic risk

Neurological Manifestations

• Ischemic stroke (most common CNS manifestation; can affect any territory)
• TIA, CVT
• Livedo reticularis (lace-like purple skin discoloration, especially on extremities)
• Sneddon syndrome: Livedo reticularis + recurrent stroke — ~50% are APS-related
• Cognitive dysfunction, headache/migraine, seizures, chorea, myelopathy
• Valvular disease: Libman-Sacks endocarditis (nonbacterial thrombotic vegetations)

Catastrophic APS (CAPS)

• Rare, life-threatening: Widespread multi-organ thrombosis (≥3 organs) developing simultaneously or within 1 week
• Mortality ~30–50%
• Treatment: Anticoagulation + corticosteroids + plasma exchange or IVIG; consider rituximab or eculizumab in refractory cases

Treatment

• Warfarin is the standard (target INR 2–3); INR 3–4 for recurrent events on therapeutic INR
• DOACs are INFERIOR to warfarin in APS: TRAPS trial (rivaroxaban vs. warfarin in triple-positive APS) was stopped early for excess thrombotic events in the rivaroxaban group
• Anticoagulation is lifelong in most patients with APS-related stroke
• Low-dose aspirin as adjunctive therapy in some patients
• Hydroxychloroquine: Antithrombotic properties; used in APS (especially with SLE)

Epidemiology & Risk

• Stroke risk is 3–9 times higher during pregnancy and postpartum compared to age-matched non-pregnant women
• Highest risk in the third trimester and first 6 weeks postpartum
• Hypercoagulable state of pregnancy: Increased fibrinogen, factors VII, VIII, X, von Willebrand; decreased protein S; resistance to activated protein C

Unique Etiologies

• Preeclampsia/eclampsia: Hypertension + proteinuria ± seizures; can cause PRES, ICH, ischemic stroke
• Cerebral venous thrombosis: Particularly in postpartum period; hypercoagulable state + dehydration
• RCVS: Postpartum is a common trigger; thunderclap headaches days after delivery
• Arterial dissection: Labor-related Valsalva; connective tissue changes during pregnancy
• Peripartum cardiomyopathy: Dilated cardiomyopathy in last month of pregnancy or first 5 months postpartum; source of cardioembolism
• Amniotic fluid embolism: Rare, catastrophic; DIC + cardiopulmonary collapse; can cause ischemic stroke
• HELLP syndrome: Hemolysis + Elevated Liver enzymes + Low Platelets; associated with preeclampsia; can cause ICH or ischemic stroke
• Choriocarcinoma: Hemorrhagic brain metastases

Diagnostic Considerations

• MRI without gadolinium: Preferred imaging modality (no radiation); DWI for ischemic stroke, MRV for CVT
• CT/CTA: Acceptable in emergencies; radiation risk to fetus is minimal with abdominal shielding
• Gadolinium: Crosses placenta; avoid in pregnancy (FDA Category C; theoretical risk of nephrogenic systemic fibrosis in fetus)
• Iodinated contrast (for CTA): Can be used in emergencies; risk of neonatal hypothyroidism is low

Treatment Considerations

• IV tPA: Relative contraindication in pregnancy (not absolute); consider case-by-case for severe LVO when benefit clearly outweighs risk; tPA does NOT cross placenta (large molecule)
• Mechanical thrombectomy: Preferred for LVO in pregnancy (avoids systemic thrombolysis risks; use lead shielding for fluoroscopy)
• Anticoagulation: LMWH (does not cross placenta; safe throughout pregnancy); warfarin is teratogenic (chondrodysplasia punctata in first trimester; fetal CNS hemorrhage in third trimester); DOACs are contraindicated (cross placenta, insufficient safety data)
• Antihypertensives: Labetalol and nifedipine are first-line in pregnancy; avoid ACE inhibitors/ARBs (teratogenic); avoid nitroprusside (cyanide toxicity to fetus)
• Magnesium sulfate: For eclamptic seizures (standard of care); NOT for other seizure etiologies

Epidemiology & Pathophysiology

• 11% of children with SCD (HbSS) will have a clinically apparent stroke by age 20
• Silent cerebral infarcts are even more common (~35% by age 14)
• Children: Large vessel ischemic stroke from intimal hyperplasia of ICA/proximal MCA/ACA (moyamoya pattern)
• Adults: Small vessel disease and hemorrhagic stroke become more common; large vessel disease persists
• Mechanisms: Sickled RBCs → endothelial damage → intimal hyperplasia + thrombosis; chronic hemolysis → nitric oxide depletion → vasculopathy

TCD Screening (STOP Trial)

• STOP trial (1998): TCD screening in children (2–16 years) with HbSS or HbSβ⁰-thalassemia
• Time-averaged mean velocity (TAMV) in MCA or distal ICA:
  • <170 cm/s: Normal (low risk) — repeat TCD annually
  • 170–199 cm/s: Conditional — repeat in 3–6 months
  • ≥200 cm/s: Abnormal (high risk) — start chronic transfusion therapy
• Chronic transfusions reduced stroke risk by 92% (from 10% to <1% per year)
• STOP II: Discontinuing transfusions after TCD normalizes → reversion to high-risk velocities and stroke; transfusions must continue indefinitely

Acute Stroke Management in SCD

• Exchange transfusion (automated erythrocytapheresis) is the treatment of choice — rapidly reduces HbS to <30% while avoiding hyperviscosity
• Simple transfusion if exchange is not immediately available; target Hb ~10 g/dL (do NOT exceed — increases viscosity)
• IV tPA: Not well studied in SCD; case-by-case decision; exchange transfusion is preferred
• Thrombectomy for LVO: May be considered
• Hydroxyurea: Long-term stroke prevention; increases HbF; reduces sickling

SWiTCH Trial

• Compared chronic transfusion + chelation vs. hydroxyurea + phlebotomy for secondary stroke prevention
• Stopped early: Hydroxyurea arm had more strokes; chronic transfusions remain standard for secondary prevention

Genetics & Pathophysiology

• Alpha-galactosidase A (GLA) deficiency → accumulation of globotriaosylceramide (Gb3/GL-3) in vascular endothelium, neurons, renal podocytes, cardiomyocytes
• X-linked recessive (GLA gene, Xq22); classic form in hemizygous males; heterozygous females can be symptomatic (variable X-inactivation)
• Vascular Gb3 deposition → endothelial dysfunction, intimal proliferation, prothrombotic state

Clinical Features

• Small fiber neuropathy: Burning pain in hands and feet (acroparesthesias), onset in childhood/adolescence; “Fabry crises” triggered by heat, fever, exercise
• Angiokeratomas: Clusters of dark red papules in “bathing trunk” distribution (umbilicus, buttocks, groin)
• Corneal verticillata (whorl-like corneal deposits; also seen with amiodarone)
• Renal disease: Progressive proteinuria → renal failure (major cause of morbidity)
• Cardiac disease: LVH, arrhythmias, cardiomyopathy
• Stroke: Young stroke (posterior circulation predilection); dolichoectasia of vertebrobasilar arteries; white matter lesions
• Hypohidrosis: Decreased sweating, heat intolerance
• “Pulvinar sign” on T1 MRI: bilateral hyperintensity of the pulvinar nuclei of the thalamus (calcification from Gb3 deposition)

Diagnosis & Treatment

• Males: Alpha-galactosidase A enzyme activity (reduced or absent); confirm with GLA gene sequencing
• Females: Enzyme activity may be normal; genetic testing is required
• Elevated plasma/urine Gb3 and lyso-Gb3
• Enzyme replacement therapy (ERT): Agalsidase beta (Fabrazyme) or agalsidase alfa (Replagal) — slows progression of renal and cardiac disease
• Oral chaperone: Migalastat (for amenable GLA mutations) — stabilizes mutant enzyme
• Stroke prevention: Antiplatelets, statins, BP control

Cocaine

• #1 drug-related cause of stroke in young adults
• Mechanisms: Sympathomimetic vasoconstriction, accelerated atherosclerosis, enhanced platelet aggregation, direct endothelial toxicity
• Can cause both ischemic stroke (vasoconstriction/thrombosis) and hemorrhagic stroke (hypertensive ICH, rupture of pre-existing aneurysm/AVM)
• Crack cocaine: Higher risk due to rapid absorption and peak levels
• May also cause RCVS or true vasculitis with chronic use
• Management: Benzodiazepines first-line for sympathomimetic crisis; avoid pure beta-blockers (unopposed alpha stimulation); phentolamine for refractory hypertension

Amphetamines & Methamphetamine

• Similar mechanism to cocaine: sympathomimetic vasoconstriction + direct vascular toxicity
• Hemorrhagic stroke more common than ischemic; chronic use → necrotizing vasculitis
• Methamphetamine has longer duration of action than cocaine → more sustained hypertension

Cannabis

• Emerging evidence for stroke risk, especially in young males with heavy use
• Mechanisms: Vasoconstriction (CB1 receptor activation), RCVS, multifocal intracranial stenosis, cardioembolism (cannabis-related AF)
• Typically presents as posterior circulation stroke or multifocal ischemia

Other Drug-Related Causes

• Heroin: Endocarditis → septic emboli; hypotension → watershed infarcts; contaminants → vasculitis
• Anabolic steroids: Polycythemia, cardiomyopathy, prothrombotic state
• Oral contraceptives: 2–3 fold increased stroke risk (higher with smoking + age >35 + migraine with aura)
• Ergot derivatives: Vasospasm; contraindicated in patients with vascular disease

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes)

• m.3243A>G mutation in mitochondrial DNA (most common); maternal inheritance
• Stroke-like episodes that do NOT follow vascular territories (metabolic, not vascular)
• Cortical/subcortical lesions, often posterior (occipital/parietal); DWI shows mixed restricted/facilitated diffusion
• Short stature, sensorineural hearing loss, diabetes, myopathy, seizures
• Elevated serum/CSF lactate
• Muscle biopsy: Ragged red fibers (Gomori trichrome), SDH-positive/COX-negative fibers
• Treatment: L-arginine (improves endothelial NO production), CoQ10, avoid valproic acid and metformin

Susac Syndrome

• Triad: Branch retinal artery occlusions + sensorineural hearing loss (low/mid-frequency) + encephalopathy
• Autoimmune endotheliopathy affecting small vessels in brain, retina, and cochlea
• MRI: “Snowball” lesions in corpus callosum (central callosal involvement = highly characteristic; differs from MS which affects callosal-septal interface)
• Fluorescein angiography shows branch retinal artery occlusions
• Treatment: Immunosuppression (steroids, IVIG, plasma exchange); often relapsing

Fibromuscular Dysplasia (FMD)

• Non-atherosclerotic, non-inflammatory vascular disease; predominantly affects young to middle-aged women
• “String of beads” appearance on CTA/MRA (medial fibroplasia type, most common)
• Most commonly affects renal arteries (renovascular hypertension) and cervical ICA/vertebral arteries
• Associated with dissection (up to 20% of FMD patients), intracranial aneurysms (7–15%)
• Screen for intracranial aneurysms in all FMD patients; screen for renal FMD in those with cervical FMD (and vice versa)

Radiation Vasculopathy

• Cranial radiation → accelerated atherosclerosis of large vessels (ICA, MCA) and small vessel occlusive disease
• Typically presents years to decades after radiation
• Children are especially susceptible → may develop moyamoya pattern
• Higher risk with radiation dose >50 Gy, younger age at treatment
• Can also cause cavernous malformations (de novo formation post-radiation)