Vasculitis: Due to autoimmune dz, arteritis (temporal, Takayasu), infectious (Tb, syphilis, VZV), or primary CNS vasculitis.

Dissections: Strokes typically in younger pts (35-50 yr).

Fibromuscular dysplasia: Uncommon, affects women (30-50 yr). Imaging: String of beads (segmental narrowing & dilations of arteries), usu B/L. Arteries affected: Renal, ICA > vert > intracranial a. Stenosis causes thrombosis or dissection. Rx: Antiplatelet therapy.

Moyamoya: Best studied in Asians but occurs worldwide. Occlusion of large arteries (usu distal ICA or main stem MCA/ACA) → lenticulostriate develops collaterals. Angio: Collaterals = “puff of smoke” = moyamoya in Japanese. Stroke 2/2 large artery occl, ICH 2/2 breakdown/fragility of collaterals. Rx: Surgical (↓ ischemic stroke). Bypass (first line) or EDAS (if bypass not feasible, involves laying branch of STA onto affected brain hoping it’ll grow into brain).

Drugs: Amphetamines & cocaine, cause either acute HTN or drug-induced vasculopathy.

Subcortical vascular dementia: Elderly w/long-standing HTN; multiple subcortical infarctions → dementia. MR: Extensive white matter changes. Rx: Alzheimer meds not found to be helpful (Lancet Neurol 2008;7:310).

CADASIL (cerebral autosomal dominant arteriopathy w/subcortical infarcts & leukoencephalopathy): 30-50 yr, inherited (incomplete penetrance), Notch 3 mutation. P/w: Lacunar strokes, progressive dementia, h/o migraine w/aura. MR: Extensive WM Δs. Hypercoagulable states: see below.

Unknown causes: “Paradoxical embolism”: technically “cryptogenic” (not lacunar, no clear cardioembolic (e.g., afib)/large artery source). 2/2 PFO. See below for Rx.

CBC, BMP, PT, PTT, cardiac enzymes q8h × 3. Noncontrast head CT: r/o ICH (only required imaging for IV rt-PA).

Labs: Fasting lipid panel, including lipoprotein (a); hemoglobin A1c (looking for underlying DM; glucose may be elevated s/p stroke); homocysteine; TSH looking for hyperthyroidism (increases risk of afib); ESR & CRP if suspecting vasculitis or endocarditis; hypercoagulable panel → before starting heparin for pts <50 yr (antiphospholipid antibodies, lupus anticoagulant, prothrombin G20210A gene mutation, factor V Leiden, protein C/protein S/antithrombin III deficiencies, β-2 glycoprotein).

Imaging: CTA: For endovascular intervention/medical therapy (e.g., dissection, atherosclerosis, vasculitis), comparable to U/S for ICA stenosis. MRI/MRA: Measure infarct volume on DWI to assist w/pt selection for intra-arterial thrombectomy in pts w/large-vessel occlusions; Se 95% w/in first few hours of stroke. Final infarct volume predictor of outcome. Carotid U/S: If CTA or MRA not done.

Other tests: Holter: 24-h Holter, looking for atrial fibrillation, in pts w/high suspicion of afib can do extended cardiac monitoring for 7-14 days (or longer) as outpt. Echocardiogram: Ruling out PFO or atrial septal aneurysm (ASA) (in cryptogenic stroke), CHF, thrombus, left atrial dilatation (↑ risk for afib), LV hypokinesis, valvular abnormality. Consider TEE: For younger pts w/o clear cause, better for looking at valves. May be less sensitive for PFO detection than TTE if pt unable to Valsalva due to sedation. CT venogram of lower extremities: For + PFO & cryptogenic stoke, to rule out DVTs; LE U/S do not evaluate for DVT in iliac veins. MRV or CTV of pelvis may be necessary.

Thrombolysis: IV rt-PA if <3 h from last seen well (dose: 0.9 mg/kg, 10% as bolus). NNT for improvement: 3; number needed to harm: 30. 3-4.5 h rt-PA window in select pts, ECASS-3 showed benefit. Favorable outcome 52.4% w/rt-PA vs. 45% w/placebo (NEJM 2008;359:1317). Not used in minor/mild sxs, rapidly resolving symptoms, other contraindications (hemorrhage, AVM, endocarditis, abscess). Sooner Rx → better outcome (˜2 million neurons lost every minute) (Stroke 2006;37:263). BP prior to & during rt-PA: BP ≤ 185/110 (if BP ↑, give labetalol IV; if BP remains stable at target, then can give rt-PA). Post rt-PA precautions for 24 h: No NG tube, NPO. No arterial sticks in noncompressible sites. No antiplatelets or anticoagulation (including DVT dosing of heparin & LMWH). Use TEDs/pneumoboots for DVT ppx. CT scan at 24 h to determine if hemorrhage present, earlier w/any clinical worsening. Hemorrhagic transformation: Important complication of rt-PA: symptomatic ICH 6% rt-PA vs. 0.6% placebo. ↑ risk w/↑ NIHSS: score ≥ 20 → 17% risk <10 → 3% risk (Stroke 1997;28:2109). Sxs: ↑ somnolence, HA, neurologic deterioration. If suspected: stop rt-PA, STAT noncontrast CT, coagulation panel, type & cross-match 6-8 units platelets & cryoprecipitate. Negative CT: Resume rt-PA (if still w/in 3 h window). Positive CT: Transfuse; neurosurgery consult. Angioedema (orolingual) in 5% receiving rt-PA, usu mild (Rx: steroids & antihistamine)

Heparin: Guidelines do not recommend heparin; some centers consider it for large artery etiology (including actively embolizing carotid; some evidence) or for afib (little evidence). Others: LV thrombus, mechanical heart valve, dissection, cerebral venous thrombosis. Do not give heparin if large infarction, mass effect or ICH on CT, MAP >130, NIHSS >15.

Endovascular Rx: See Interventional Neurology chapter.

ASA: ASA 81 mg qd (full dose not proven more effective). No other antiplt tested acutely (e.g., clopidogrel, ticlopidine, dipyridamole). Two large trials showed (nonsignificant) ↓ in death or disability w/ASA w/in 48 h (CAST & IST; Lancet 1997;349:1641; Lancet 1997;349:1569). Meta-analysis of both trials → modest/significant benefit: 7 strokes prevented/1,000 pts treated, 4 deaths/1,000; likely no effect on severity of current stroke but ↓ recurrent ones.

Statins: For 2° prevention. Some rec high-dose statin (as in ACS) acutely (for atherosclerotic stroke—see AHA/ASA Guidelines 2008). SPARCL trial (NEJM 2006;355:549) 2.2% absolute risk reduction recurrent stroke w/atorvastatin 80 mg. Statin withdrawal study (Neurology 2009;69:904): Stopping outpt statin → worse outcome (˜5× ↑ in death/dependence) & worse infarct volume; statin withdrawal perhaps triggers prothrombotic/inflammatory response.

Induced HTN: Small clinical trials; useful in select group of pts; use w/caution. Possibly ↑ BP restores perfusion to penumbra. How to do trial of HTN: Consider in pts w/fluctuating exam w/BP changes (i.e., worse when ↓ BP) or known stenoses. Exclude pts w/h/o CAD, PVD, CHF, ischemic, ICH/midline shift, rt-PA, SBP >200, heparin drip. ↑ admission SBP by 20% (max SBP 200) w/phenylephrine drip, titrate to neurologic improvement. If NIHSS ↓ by 2 points after 30 min, continue drip. Daily attempt to titrate drip off, only if neurologic sx do not worsen during titration. Should be seen as bridge to more definitive therapy (e.g., stent, CEA, bypass).

Hemicraniectomy: potentially useful for malignant MCA infarcts. STATE criteria (Score GCS <8, Time <48 h since LSW, Age <60 yo, Territory infarct >150 cm³ or >50% MCA territory infarct, Expectations life expectancy) to guide OR decision. Age <60 hemicraniectomy vs. medical management mRS ≤3 43% vs. 21% & survival 78% vs. 29% (Lancet Neurol 2007;6:215). Less benefit if age >60 (NEJM 2014;370:12), no pts w/mRS 0-2, hemicraniectomy vs. medical management mRS 3 7% vs. 3%, mRS 4-5 60% vs. 28%.

SSRI: FLAME Trial (Lancet 2011;10:123) fluoxetine 20 mg daily vs. placebo for motor recovery at 90 days. Fluoxetine ↑’d Fugl-Meyer motor scale; fluoxetine 34 vs. placebo 24.3 points.

Hypertension: >60% of stroke pts have SBP > 160. Rx BP > 220/120 in pts not receiving t-PA, or if end-organ damage (kidney, heart, eye). Rx BP > 185/110 in pts receiving rt-PA. Don’t ↓ BP by >15%. Can initiate HTN meds w/in 24 h of stroke.

Hypotension: Worse outcomes, esp < 100/70. Rx underlying cause of hypotension (volume depletion, arrhythmia, blood loss, sepsis). Rx: Fluids, pressors.

Glucose: Hyperglycemia: Goal BG 80-140, Rx w/ISS or insulin drip. 1/3 stroke pts affected, a/w poor outcomes, hemorrhagic conversion, & infarct progression. SHINE Trial in progress: IV insulin w/BG 80-130 vs. insulin sliding scale w/BG <180. Hypoglycemia: Promptly correct hypoglycemia (may mimic strokes).

Temperature: Fever: ↑ mortality, seek cause of fever, & Rx w/antipyretic. Hypothermia: ↓ mortality, insufficient data for use of cooling in stroke.

Oxygenation: Keep O₂ sats ≥92%. Pts needing intubation have 50% mortality at 30 days. Aspiration PNA important complication & leading cause of death.

NINDS rt-PA (NEJM 1995;333:1581): 624 pts, placebo vs. rt-PA w/in 3 h. Two parts: Part 1: No diff in neuro improvement at 24 h vs. placebo. Part 2: Favorable outcome vs. placebo at 3 mo (OR for favorable outcome 1.7). ↑ benefit for pts treated w/in 90 min. No difference in mortality.

ECASS (JAMA 1995;274:1017): European trial, multicenter, 620 pts, placebo vs. rt-PA w/in 6 h, sl. larger rt-PA dose. Overall no difference at 3 mo in rt-PA vs. placebo, ↑ mortality w/rt-PA. Post hoc analysis: (nonsignificant) trend → better outcome w/pts Rx’d w/in 3 h.

ECASS II (Lancet 1998;352:1245): 800 pts, same dose as NINDS (0.9 mg/kg), w/in 6 h. No benefit w/rt-PA; not enough pt to see if Rx w/in 3 h makes a difference.

ATLANTIS (JAMA 1999;282:2019): Rt-PA 3-5 h, 613 pts. No difference in functional outcome & mortality, extending window >3 h not beneficial.