Brain-Heart-Lung Connection in SAH

How the brain, heart and lungs are connected in SAH.

Pathophysiology of cardiopulmonary complications in SAH. SAH leads to catecholamine surge, which activates alpha, alpha + beta, and beta receptors. This leads to pulmonary and myocardial dysfunction as well as platelet aggregation. Patients then develop neurogenic pulmonary edema, LV dysfunction and shock.


Muehlschlegel, S. (2018). Subarachnoid Hemorrhage. CONTINUUM: Lifelong Learning In Neurology24(6), 1623-1657. doi: 10.1212/con.0000000000000679

Pathophysiology of Delayed Cerebral Ischemia (DCI)

Historically, DCI thought to be caused by cerebral vasospasm. Recent studies now indicates DCI may be caused by several factors, including early brain injury, microthrombosis, cortical spreading depolarizations and related ischemia, in addition to cerebral vasospasm.

Cerebral vasospasm may be an epiphenomenon, and underlying biochemical and biophysical changes that lead to DCI occur as early as SAH onset.

Supporting evidence? Endothelin 1 is strongest vasoconstrictor mediator in SAH. Administration of clazosentan (potent endothelin 1 receptor inhibitor) resulted in less angiographic vasospasm but did not decrease DCI nor lead to improvement in 90-day outcomes.


Muehlschlegel, S. (2018). Subarachnoid Hemorrhage. CONTINUUM: Lifelong Learning In Neurology24(6), 1623-1657. doi: 10.1212/con.0000000000000679

Hypoglycorrhachia Differential Diagnosis

Common and Uncommon Etiologies of Hypoglycorrhachia in the LiteratureCapture


  • Bacterial meningitis (including atypical bacteria like nocardia and brucella)
  • Fungal meningitis
  • Mycobacterial (tuberculous meningitis)
  • Amebic meningoencephalitis
  • CMV-associated progressive polyradiculopathy or meningoencephalitis
  • Carcinomatous meningitis
  • GLUT 1-deficiency syndrome
  • Leukemia/lymphoma with CNS involvement
  • Subarachnoid hemorrhage



  • Syphilitic meningitis
  • Lyme meningitis
  • Viral meningitis
  • Neurocysticercosis5
  • CNS toxoplasmosis
  • Cholesterol-induced leptomeningitis secondary to Currarino syndrome
  • Neurosarcoidosis
  • Rheumatoid meningitis
  • Systemic lupus erythematosus with CNS involvement
  • Neuro-Behcet’s Disease
  • Dermoid cyst
  • Granulomatous angiitis of the central nervous system
  • Malignant atrophic papulosis


Etiologies reported to cause severe hypoglycorrhachia, (CSF glu ≤10 mg/dL)

  • Bacterial meningitis (including atypical bacteria like nocardia and brucella) *
  • Fungal meningitis*
  • Mycobacterial (tuberculous meningitis)*
  • Carcinomatous meningitis*
  • Leukemia/lymphoma with CNS involvement*
  • Subarachnoid hemorrhage*
  • Lyme meningitis*
  • Neurocysticercosis5*
  • Cholesterol-induced leptomeningitis secondary to Currarino syndrome*
  • Neurosarcoidosis*
  • Dermoid cyst*


Frequency of Different Known Diagnoses Seen in Patients with Hypoglycorrhachia

  1. All Patients


2. HIV-Infected Patients


3. Patients with History of Neurosurgery


4. Patients without HIV or Neurosurgical History




Chow, E., & Troy, S. (2014). The Differential Diagnosis of Hypoglycorrhachia in Adult Patients. The American Journal Of The Medical Sciences348(3), 186-190. doi: 10.1097/maj.0000000000000217


COVID-19 Acute Necrotizing Encephalopathy

Case report: COVID-19 associated acute necrotizine hemorrhagic encephalopathy – ANE – associated iwth other viral infections.  Female, late 50s, 3-day cough, fever, altered mental status.

Work-up NEG for influenza, nasopharyngeal swab (+) coronavirus, CSF limited – traumatic LP, CSF bacterial culture NG, HSV HSV 1 and 2, varicella, WNV NEG; unable to test CSF for SARSCoV-2.

CT head:   symmetric hypoattenuation within the bilateral medial thalami with a normal CT angiogram and CT venogram

MRI: hemorrhagic rim enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular regions

Acute necrotizing encephalopathy

  • rare complication of influenza / viral infections
  • related to intracranial cytokine storms –> BBB breakdown
  • no direct viral invasion or parainfecitous demyelination
  • reported mostly in pediatric population but occurs in adults as well

Imaging Features

  • symmetric, multifocal lesions with invariable thalamic involvement
  • Other commonly involved locations include the brain stem, cerebral white matter, and cerebellum
  • hypoattenuating on CT
  • MRI shows T2 FLAIR hyperintense signal with internal hemorrhage
  • Postcontrast images may demonstrate a ring of contrast enhancement



Image from noncontrast head CT demonstrates symmetric hypoattenuation within the bilateral medial thalami (arrows). B, Axial CT venogram demonstrates patency of the cerebral venous vasculature, including the internal cerebral veins (arrows). C, Coronal reformat of aCT angiogram demonstrates normal appearance of the basilar artery and proximal posterior cerebral arteries.


MRI images demonstrate T2 FLAIR hyperintensity within the bilateral medial
temporal lobes and thalami (A, B, E, F) with evidence of hemorrhage indicated by hypointense signal intensity on susceptibility-weighted images (C, G) and rim enhancement on postcontrast
images (D, H).



Poyiadji, N., Shahin, G., Noujaim, D., Stone, M., Patel, S., & Griffith, B. (2020). COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology, 201187. doi: 10.1148/radiol.2020201187

Blood Pressure Augmentation in DCI

HIMALAIA Study – Netherlands. The only RCT looking at efficacy of BP augmentation in DCI in increasing cerebral blood flow (via CT perfusion).  Small n, negative study.

Tey article – XeCt to measure regional CBF, at onset of DCI suspicion, 5 days of induced HTN, hypervolemia, hemodilution. Compared XeCT before and after treatment and showed increase in regional CBF in worst vascular territories from 19 to 227ml/100g/min, significant reduction of regions with CBF <20ml/100g/min from 26 to 10%.


  1. decrease in GCS >=1
  2. new focal deficits
  3. other etiologies excluded:
    1. worsening HCP
    2. recurrent bleeding
    3. epilepsy
    4. infectious disease
    5. hypoglycemia
    6. hyponatremia
    7. metabolic enceph from renal or liver failure

Baseline echo:  cardiomyopathy is a contraindication

Drug of choice:  Induce HTN with norepinephrine? based on reference below (we usually use phenylephrine)

End points:

  1. improvement of neurologic deficits
  2. occurrence of complication
  3. MAP 130 mm Hg
  4. SBP 230 mm Hg

Risks of Induced HTN:

  1.  line placement risks
  2. vasopressor risks
  3. can induce PRES, neurologic deterioration

Literature does not support the use of induced HTN, but how can we ignore bedside observations of patients who clinically improve with induced HTN?


  1. Uses surrogate physiologic endpoints (CBF / cerebral o2 delivery). Are we looking at the right endpoint?  CBF correlates with cerebral O2 delivery assuming that other factors are constant (cerebral metabolism, arterial O2 content, partial pressure of O2 and CO2).
  2. Different patients have varied responses to induced HTN.  Induced HTN increases CBF only if cerebral autoregulation is distupted.

Dr. Diringer’s Advice: use induced HTN in a thoughtful and individualized manner.  Trial of induced HTN at onset of DCI.  If patient improves, continue.  If no change, back off and explore alternative treatments. If patient exam is poor (no followable exam), answer less clear but prolonged extreme elevations should be avoided.

Another way of doing it (Continuum article on SAH)

Onset of DCI / symptomatic vasospasm – induced hypertension indicated.  Standard treatment is now hypertensive and mild hpyervolemic therapy (HHT), and not Triple H therapy.

Initiate IV bolus, maintain fluids for euvolemia or mild hypervolemia.

Induce hypertension using Alpha 1 receptor agonists by infusion (norepinephrine or phenylephrine).  Vasopressors of choice as brain vessels lack alpha 1 receptors.  Stepwise progression of BP augmentation.  Neuro assessment at each step.

Follow MAP.  MAP about 20 mm Hg above baseline set as first goal, (often MAP>90).

Follow SBP:  some institutions use SBP goals.  No evidence exists which parameter is better to follow.  Goal should be ~20-40mm Hg above baseline SBP.  Commonly SBP goal >180 or >200 mm Hg.

If clinical exam returns to baseline – no further BP elevations.  If exam deteriorates at this BP goal, attempt further increases.  No optimal max BP goal known, but adverse effects (cardiopulmo, brain autoregulation, PRES) should be considered.

Inotropic agents (milrinone, dobutamine) reserved for patients with poor CO from acute or chronic CMP.

If neuro deficits persist despite induced HTN, perform CT/CTA ffd by DSA with endovascular therapy if VSP confirmed.  NCCT prior to DSA to rule out HCP / determine pre-existing stroke prior to endovascular treatment.


Gathier, C., Dankbaar, J., van der Jagt, M., Verweij, B., Oldenbeuving, A., Rinkel, G., van den Bergh, W. and Slooter, A. (2015). Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage. Stroke, 46(11), pp.3277-3281.

Diringer, M.  Editorial. Hemodynamic Therapy for Delayed Cerebral Ischemia in SAH.  Neurocritical Care Journal.  Pre-print.

Muehlschlegel, S. (2018). Subarachnoid Hemorrhage. CONTINUUM: Lifelong Learning In Neurology24(6), 1623-1657. doi: 10.1212/con.0000000000000679

TIA Management

Low-risk TIA

  • ABCD scores 0-3
  • out patient work-up in the next 1-2 days
  • alternative is to admit
  • begin ASA 81mg or plavix 75 or ASA 25/ER dipyridamole 200mg BID
  • perform carotid imaging: US, CTA, MRA
  • consider TTE (if bilateral infarcts on CT, high suspicion of cardioembolic source and TTE normal – obtain TEE)
  • consider 30d ambulatory cardiac monitor to document cryptogenic Afib
  • smoking cessation
  • Statins:
    • start high-dose statin (atorvastatin 40-80; rosuvastatin 20-40)
    • consider mod intensity statin if >75 y/o (atorvastatin 10-20, rosuvastatin 5-10, simvastatin 20-40, pravastatin 40-80)
  • consider anticoagulation if ECG (+) Afib, calculate CHADS or CHADSVASC and HAS-BLED scores
  • ? Referral to vascular neurologist or cardiologist


High-Risk TIA:

  • admit
  • permissive HTN
  • gradually lower BP limits over 24-48h




Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.

Criteria for Thrombectomy / Endovascular Treatment of Stroke

Patients eligible for intravenous alteplase should receive intravenous alteplase even if endovascular treatments are being considered

Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria:

  1. prestroke mRS score 0–1,
  2. acute ischemic stroke receiving intravenous alteplase within 4.5 h of onset
  3. causative occlusion of the internal carotid artery or proximal MCA (M1),
  4. age >18 years, (note: there is no upper age limit),
  5. NIHSS score of C6,
  6. ASPECTS of C6
  7. treatment can be initiated (groin puncture) within 6 h of symptom onset

As with intravenous alteplase, reduced time from symptom onset to reperfusion with endovascular therapies is highly associated with better clinical outcomes

When treatment is initiated beyond 6 h from symptom onset, the effectiveness of endovascular therapy is uncertain for patients with acute ischemic stroke who havecausative occlusion of the internal carotid artery or proximal MCA (M1)

In carefully selected patients with anterior circulation occlusion who have contraindications to intravenous alteplase, endovascular therapy with stent retrievers completed within 6 h of stroke onset is reasonable

Although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for carefully selected patients with acute ischemic stroke in whom treatment can be initiated (groin puncture) within 6 h of symptom onset and who have causative occlusion of the M2 or M3 portion of the MCAs, anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries

Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 h of symptom onset, but the benefits are not established in this age group

Observing patients after intravenous alteplase to assess for clinical response before pursuing endovascular therapy is not required to achieve beneficial outcomes and is not recommended

Endovascular therapy with stent retrievers is recommended over intra-arterial fibrinolysis as first-line therapy

It might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke. However, the ultimate selection of anesthetic technique during endovascular therapy for acute ischemic stroke should be individualized based on patient risk factors, tolerance of the procedure, and other clinical characteristics


Gross, H. and Grose, N. (2017). Emergency Neurological Life Support: Acute Ischemic Stroke. Neurocritical Care, 27(S1), pp.102-115.