Bio

Clinical Focus


  • Stroke
  • Concussion
  • Cerebrovascular Circulation
  • Traumatic Brain Injury
  • Neurology

Academic Appointments


Professional Education


  • Fellowship:University of California San Francisco (2012) CA
  • Internship:Stanford University Hospital -Internal Medicine Residency Training Program (2007) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2010)
  • Residency:Johns Hopkins University (2010) MD
  • Medical Education:Stanford University (2012) CA

Research & Scholarship

Current Research and Scholarly Interests


Dr. Karen G. Hirsch cares for critically ill patients with neurologic disorders in the intensive care unit and for patients with cerebrovascular disease in the inpatient stroke unit. Dr. Hirsch's research focuses on novel imaging techniques such as functional brain imaging in patients with cardiac arrest and traumatic brain injury. She also studies methods of non-invasive measurement of cerebral blood flow, oxygenation, and cerebrovascular autoregulation and how these parameters might be targeted to improve outcome in patients with neurologic injury. In the outpatient clinic, she sees patients with head injury, stroke and other neurovascular diseases in addition to patients who have been discharged from the neurological intensive care unit.

Clinical Trials


  • Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4) Recruiting

    The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Recruiting

    The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part, the investigators propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. There will be no patient enrollment in part one of this project. During the second part, the investigators aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim the investigators will conduct a prospective cohort study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital, University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late follow-up MRI scan at day 5 to determine the final infarct.

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  • Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial Recruiting

    The Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial is a multicenter, randomized, controlled clinical trial of 1400 patients that will include approximately 60 enrolling sites. The study hypotheses are that treatment of hyperglycemic acute ischemic stroke patients with targeted glucose concentration (80mg/dL - 130 mg/dL) will be safe and result in improved 3 month outcome after stroke. Eligible subjects must be within 12 hours of stroke symptom onset and have diabetes and glucose concentrations of over 110 mg/dL on initial evaluation. The enrolling sites will include the Neurological Emergencies Treatment Trials (NETT) sites as well as non NETT sites from all over the United States. The study will evaluate the safety and efficacy of targeted glucose control (treatment group - IV insulin with target 80-130 mg/dl) verses control therapy of sub q insulin plus basal insulin with target glucose less than 180 mg/ dL. The primary outcome will be functional outcome at 3 months as measured by the modified Rankin Scale (mRS) Score. The primary safety outcome will be severe hypoglycemia defined as <40 mg/dL. Enrollment will occur over 3.5 - 4 years.

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Publications

Journal Articles


  • An Update on Neurocritical Care for the Patient With Kidney Disease ADVANCES IN CHRONIC KIDNEY DISEASE Hirsch, K. G., Josephson, S. A. 2013; 20 (1): 39-44

    Abstract

    Patients with kidney disease have increased rates of neurologic illness such as intracerebral hemorrhage and ischemic stroke. The acute care of patients with critical neurologic illness and concomitant kidney disease requires unique management considerations including attention to hyponatremia, renal replacement modalities in the setting of high intracranial pressure, reversal of coagulopathy, and seizure management to achieve good neurologic outcomes.

    View details for DOI 10.1053/j.ackd.2012.09.003

    View details for Web of Science ID 000313394500007

    View details for PubMedID 23265595

  • Treatment of Elevated Intracranial Pressure with Hyperosmolar Therapy in Patients with Renal Failure NEUROCRITICAL CARE Hirsch, K. G., Spock, T., Koenig, M. A., Geocadin, R. G. 2012; 17 (3): 388-394

    Abstract

    To evaluate the use of hyperosmolar therapy in the management of elevated intracranial pressure (ICP) and transtentorial herniation (TTH) in patients with renal failure and supratentorial lesions.Patients with renal failure undergoing renal replacement therapy treated with 23.4% saline (30-60 mL) and/or mannitol for high ICP or clinical evidence of TTH were analyzed in a retrospective cohort.The primary outcome measure was reversal of TTH or ICP crisis. Secondary outcome measures were modified Rankin scale on hospital discharge, survival to hospital discharge, and adverse effects. Of 254 subjects over 7 years, 6 patients with end-stage renal disease had 11 events. All patients received a 23.4% saline bolus, along with mannitol (91%), hypertonic saline (HS) maintenance fluids (82%), and surgical interventions (n = 2). Reversal occurred in 6/11 events (55%); 2 of 6 patients survived to discharge. ICP recording of 6 TTH events showed a reduction from ICP of 41 3.8 mmHg (mean SEM) with TTH to 20.8 3.9 mmHg (p = 0.05) 1 h after the 23.4% saline bolus. Serum sodium increased from 141.4 to 151.1 mmol/L 24 h after 23.4% saline bolus (p = 0.001). No patients were undergoing hemodialysis at the time of the event. There were no cases of pulmonary edema, clinical volume overload, or arrhythmia after HS.Treatment with hyperosmolar therapy, primarily 23.4% saline solution, was associated with clinical reversal of TTH and reduction in ICP and had few adverse effects in this cohort. Hyperosmolar therapy may be safe and effective in patients with renal failure and these initial findings should be validated in a prospective study.

    View details for DOI 10.1007/s12028-012-9676-2

    View details for Web of Science ID 000312069400012

    View details for PubMedID 22328033

  • Boomerang Sign on MRI NEUROCRITICAL CARE Hirsch, K. G., Hoesch, R. E. 2012; 16 (3): 450-451

    Abstract

    Altered mental status and more subtle cognitive and personality changes after traumatic brain injury (TBI) are pervasive problems in patients who survive initial injury. MRI is not necessarily part of the diagnostic evaluation of these patients.Case report with relevant image and review of the literature.Injury to the corpus callosum is commonly described in traumatic brain injury; however, extensive lesions in the splenium are not well described. This image shows an important pattern of brain injury and demonstrates a common clinical syndrome seen in patients with corpus callosum pathology.Injury to the splenium of the corpus callosum due to trauma may be extensive and can cause significant neurologic deficits. MRI is important in the diagnostic evaluation of patients with cognitive changes after TBI.

    View details for DOI 10.1007/s12028-012-9699-8

    View details for Web of Science ID 000304619000016

    View details for PubMedID 22565630

  • Cerebral blood flow and cerebrovascular autoregulation in a swine model of pediatric cardiac arrest and hypothermia CRITICAL CARE MEDICINE Lee, J. K., Brady, K. M., Mytar, J. O., Kibler, K. K., Carter, E. L., Hirsch, K. G., Hogue, C. W., Easley, R. B., Jordan, L. C., Smielewski, P., Czosnyka, M., Shaffner, D. H., Koehler, R. C. 2011; 39 (10): 2337-2345

    Abstract

    Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during postresuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy.Prospective, balanced animal study.Basic physiology laboratory at an academic institution.Eighty-four neonatal swine.Piglets underwent hypoxic-asphyxic cardiac arrest or sham surgery and recovered for 2 hrs with normothermia followed by 4 hrs of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hrs postresuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared.Laser-Doppler flux was lower in postarrest animals compared to sham-operated controls during the 2-hr normothermic period after resuscitation. During the subsequent 4-hr recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and postarrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, postarrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to postarrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension.In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from noninvasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.

    View details for DOI 10.1097/CCM.0b013e318223b910

    View details for Web of Science ID 000294958500019

    View details for PubMedID 21705904

  • Clinical and Radiographic Natural History of Cervical Artery Dissections JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Schwartz, N. E., Vertinsky, A. T., Hirsch, K. G., Albers, G. W. 2009; 18 (6): 416-423

    Abstract

    Cervical artery dissection (CADsx) is a common cause of stroke in young patients, but long-term clinical and radiographic follow-up from a large population is lacking.Epidemiologic data, treatment, recurrence, and other features were extracted from the records of all patients seen at our stroke center with confirmed CAD during a 15-year period. A subset of cases was examined to provide detailed information about vessel status.In all, 177 patients (mean age 44.0 +/- 11.1 years) were identified, with the male patients being older than the female patients. Almost 60% of dissections were spontaneous, whereas the remainder involved some degree of head and/or neck trauma. More than 70% of patients were treated with anticoagulation. During follow-up (mean 18.2 months; 0-220 months) there were 15 cases (8.5%) of recurrent ischemic events, and two cases (1.1%) of a recurrent dissection. About half of recurrent stroke/transient ischemic attack events occurred within 2 weeks of presentation. There was no clear association between the choice of antithrombotic agent and recurrent ischemic events. Detailed analysis of imaging findings was performed in 51 cases. Some degree of recanalization was seen in 58.8% of patients overall, and was more frequent in women. The average time to total or near-total recanalization was 4.7 +/- 2.5 months. Patients with complete occlusions at presentation tended not to recanalize.This large series from a single institution highlights many of the features of CAD. A relatively benign course with low recurrence rate is supported, independent of the type and duration of antithrombotic therapy.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.11.016

    View details for Web of Science ID 000272114400002

    View details for PubMedID 19900642

  • Occurrence of Perimesencephalic Subarachnoid Hemorrhage During Pregnancy NEUROCRITICAL CARE Hirsch, K. G., Froehler, M. T., Huang, J., Ziai, W. C. 2009; 10 (3): 339-343

    Abstract

    Perimesencephalic subarachnoid hemorrhage (P-SAH) is a benign subset of subarachnoid hemorrhage with a favorable prognosis and low rate of re-bleeding. Risk factors may include hypertension and tobacco use, but it has not previously been reported during pregnancy.We report two cases of P-SAH in pregnant women, a 40-year-old female, 8-weeks pregnant and a 37-year-old female at 35 weeks gestational age.CT scan confirmed P-SAH in both cases. CT angiography in one case and cerebral angiogram in the other did not reveal aneurysm or other potential bleeding source. The patients underwent transcranial Doppler ultrasound monitoring without evidence of vasospasm.P-SAH hemorrhage may occur during early or late pregnancy. We do not propose an increased risk of P-SAH during pregnancy. The clinical course appears favorable and CT angiography alone may be considered the preferred diagnostic test to assess for aneurysm in first trimester pregnancy.

    View details for DOI 10.1007/s12028-009-9189-9

    View details for Web of Science ID 000266328900013

    View details for PubMedID 19184552

  • Inhibition of PI-3 kinase sensitizes human leukemic cells to histone deacetylase inhibitor-mediated apoptosis through p44/42 MAP kinase inactivation and abrogation of p21(CIP1/WAF1) induction rather than AKT inhibition ONCOGENE Rahmani, M., Yu, C. R., Reese, E., Ahmed, W., Hirsch, K., Dent, P., Grant, S. 2003; 22 (40): 6231-6242

    Abstract

    Effects of the PI-3 kinase inhibitor LY294002 (LY) have been examined in relation to responses of human leukemia cells to histone deacetylase inhibitors (HDIs). Coexposure of U937 cells for 24 h to marginally toxic concentrations of LY294002 (e.g., 30 microM) and sodium butyrate (SB; 1 mM) resulted in a marked increase in mitochondrial damage (e.g., cytochrome c and Smac/DIABLO release, loss of DeltaPsi(m)), caspase activation, and apoptosis. Similar results were observed in Jurkat, HL-60, and K562 leukemic cells and with other HDIs (e.g., SAHA, MS-275). Exposure of cells to SB/LY was associated with Bcl-2 and Bid cleavage, XIAP and Mcl-1 downregulation, and diminished CD11b expression. While LY blocked SB-mediated Akt activation, enforced expression of a constitutively active (myristolated) Akt failed to attenuate SB/LY-mediated lethality. Unexpectedly, treatment of cells with SB+/-LY resulted in a marked reduction in phosphorylation (activation) of p44/42 mitogen-activated protein (MAP) kinase. Moreover, enforced expression of a constitutively active MEK1 construct partially but significantly attenuated SB/LY-induced apoptosis. Lastly, cotreatment with LY blocked SB-mediated induction of p21(CIP1/WAF1); moreover, enforced expression of p21(CIP1/WAF1) significantly reduced SB/LY-mediated apoptosis. Together, these findings indicate that LY promotes SB-mediated apoptosis through an AKT-independent process that involves MEK/MAP kinase inactivation and interference with p21(CIP1/WAF1) induction.

    View details for DOI 10.1038/sj.onc.1206646

    View details for Web of Science ID 000185506200013

    View details for PubMedID 13679862

  • The cyclin-dependent kinase inhibitor (CDKI) flavopiridol disrupts phorbol 12-myristate 13-acetate-induced differentiation and CDKI expression while enhancing apoptosis in human myeloid leukemia cells CANCER RESEARCH Cartee, L., Wang, Z. L., Decker, R. H., Chellappan, S. P., Fusaro, G., Hirsch, K. G., Sankala, H. M., Dent, P., Grant, S. 2001; 61 (6): 2583-2591

    Abstract

    Interactions between the cyclin-dependent kinase inhibitor (CDKI) flavopiridol (FP) and phorbol 12-myristate 13-acetate (PMA) were examined in U937 human leukemia cells in relation to differentiation and apoptosis. Simultaneous, but not sequential, exposure of U937 cells to 100 nM FP and 10 nM PMA significantly increased apoptosis manifested by characteristic morphological features, mitochondrial dysfunction, caspase activation, and poly(ADP-ribose) polymerase cleavage while markedly inhibiting cellular differentiation, as reflected by diminished plastic adherence and CD11b expression. Enhanced apoptosis in U937 cells was associated with an early caspase-independent increase in cytochrome c release and accompanied by a substantial decline in leukemic cell clonogenicity. Moreover, PMA/FP cotreatment significantly increased apoptosis in HL-60 promyelocytic leukemia cells and in U937 cells ectopically expressing the Bcl-2 protein. In U937 cells, coadministration of FP blocked PMA-induced expression and reporter activity of the CDKI p21WAF/CIP1 and triggered caspase-mediated cleavage of the CDKI p27KIP1. Coexposure to FP also resulted in a more pronounced and sustained activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase cascade after PMA treatment, although disruption of this pathway by the mitogen-activated protein kinase kinase 1 inhibitor U0126 did not prevent potentiation of apoptosis. FP accelerated PMA-mediated dephosphorylation of the retinoblastoma protein (pRb), an event followed by pRb cleavage culminating in the complete loss of underphosphorylated pRb (approximately Mr 110,000) by 24 h. Finally, gel shift analysis revealed that coadministration of FP with PMA for 8 h led to diminished E2F/pRb binding compared to the effects of PMA alone. Collectively, these findings indicate that FP modulates the expression/activity of multiple signaling and cell cycle regulatory proteins in PMA-treated leukemia cells and that such alterations are associated with mitochondrial damage and apoptosis rather than maturation. These observations also raise the possibility that combining CDKIs and differentiation-inducing agents may represent a novel antileukemic strategy.

    View details for Web of Science ID 000167697500042

    View details for PubMedID 11289135

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