Issam A. Awad, M.D.

Issam A. Awad, M.D.

Issam A. Awad, M.D.

Profile

Personal Bio

Treatment Philosophy

I practice multidiciplinary coordination of care with latest technology, evidence-based standards and individualized consideration of options. I strive to provide my patients with access to innovative interventions and clinical trials.

Conditions & Procedures

Conditions

Arterio-Venous Malformation (AVM), Brain Tumor, Cavernous Angioma, Cerebral Aneurysms, Skull Base Tumors, Stroke, Vascular Malformations

Procedures

Carotid Artery Stenting, Stereotactic Radiosurgery

General Information

Gender

Male

Affiliation

Independent Practitioner

Expertise

Neuro Critical Care, Neurovascular Surgery

Languages

Arabic, English, French

Board Certified

Neurological Surgery

Clinical Service

Education, Training & Fellowships

Medical School

Loma Linda University, 1980

Internship

Loma Linda University, 1981

Residency

Cleveland Clinic Foundation, 1985

Fellowship

Barrow Neurological Institute, 1986

Locations

A

5841 S. Maryland Ave.
MC3026/Room J341
Chicago, IL 60637
773.702.2123
773.702.3518 fax
Get Directions This location is wheelchair accessible.

Insurance

For information on the insurance plans this provider accepts:
  • Call: 773.702.2123

Publications

  • Micro-Computed Tomography in Murine Models of Cerebral Cavernous Malformations as a Paradigm for Brain Disease.

    Journal of neuroscience methods 2016 Jun 23

    Authors: Girard R, Zeineddine HA, Orsbon C, Tan H, Moore T, Hobson N, Shenkar R, Lightle R, Shi C, Fam MD, Cao Y, Shen L, Neander AI, Rorrer A, Gallione C, Tang AT, Kahn ML, Marchuk DA, Luo ZX, Awad IA
    Abstract
    Cerebral cavernous malformations (CCMs) are hemorrhagic brain lesions, where murine models allow major mechanistic discoveries, ushering genetic manipulations and preclinical assessment of therapies. Histology for lesion counting and morphometry is essential yet tedious and time consuming. We herein describe the application and validations of X-ray micro-computed tomography (micro-CT), a non-destructive technique allowing three-dimensional CCM lesion count and volumetric measurements, in transgenic murine brains.
    We hereby describe a new contrast soaking technique not previously applied to murine models of CCM disease. Volumetric segmentation and image processing paradigm allowed for histologic correlations and quantitative validations not previously reported with the micro-CT technique in brain vascular disease.
    Twenty-two hyper-dense areas on micro-CT images, identified as CCM lesions, were matched by histology. The inter-rater reliability analysis showed strong consistency in the CCM lesion identification and staging (K=0.89, p<0.0001) between the two techniques. Micro-CT revealed a 29% greater CCM lesion detection efficiency, and 80% improved time efficiency.
    Serial integrated lesional area by histology showed a strong positive correlation with micro-CT estimated volume (r(2)=0.84, p<0.0001).
    Micro-CT allows high throughput assessment of lesion count and volume in pre-clinical murine models of CCM. This approach complements histology with improved accuracy and efficiency, and can be applied for lesion burden assessment in other brain diseases.
    PMID: 27345427 [PubMed - as supplied by publisher]
  • Corrigendum: Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling.

    Nature 2016 May 25

    Authors: Shi C
    Abstract
    Cerebral cavernous malformations (CCMs) are relatively common vascular malformations, characterized by increased Rho kinase (ROCK) activity, vascular hyper-permeability and the presence of blood degradation products including non-heme iron. Previous studies revealed robust inflammatory cell infiltration, selective synthesis of IgG, in situ antigen driven B-cell clonal expansion, and deposition of immune complexes and complement proteins within CCM lesions. We aimed to evaluate the impact of suppressing the immune response on the formation and maturation of CCM lesions, as well as lesional iron deposition and ROCK activity. Two murine models of heterozygous Ccm3 (Pdcd10), which spontaneously develop CCM lesions with severe and milder phenotypes, were either untreated or received anti-mouse BR3 to deplete B cells. Brains from anti-mouse BR3-treated mice exhibited significantly fewer mature CCM lesions and smaller lesions compared to untreated mice. B cell depletion halted the progression of lesions into mature stage 2 lesions but did not prevent their genesis. Non-heme iron deposition and ROCK activity was decreased in lesions of B cell depleted mice. This represents the first report of the therapeutic benefit of B-cell depletion in the development and progression of CCMs, and provides a proof of principle that B cells play a critical role in CCM lesion genesis and maturation. These findings add biologics to the list of potential therapeutic agents for CCM disease. Future studies would characterize the putative antigenic trigger and further define the mechanism of immune response in the lesions.
    PMID: 27281211 [PubMed - as supplied by publisher]
  • Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling.

    Nature 2016 Apr 7

    Authors: Zhou Z, Tang AT, Wong WY, Bamezai S, Goddard LM, Shenkar R, Zhou S, Yang J, Wright AC, Foley M, Arthur JS, Whitehead KJ, Awad IA, Li DY
    Abstract
    Cerebral cavernous malformations (CCMs) are common inherited and sporadic vascular malformations that cause strokes and seizures in younger individuals. CCMs arise from endothelial cell loss of KRIT1, CCM2 or PDCD10, non-homologous proteins that form an adaptor complex. How disruption of the CCM complex results in disease remains controversial, with numerous signalling pathways (including Rho, SMAD and Wnt/β-catenin) and processes such as endothelial-mesenchymal transition (EndMT) proposed to have causal roles. CCM2 binds to MEKK3 (refs 7, 8, 9, 10, 11), and we have recently shown that CCM complex regulation of MEKK3 is essential during vertebrate heart development. Here we investigate this mechanism in CCM disease pathogenesis. Using a neonatal mouse model of CCM disease, we show that expression of the MEKK3 target genes Klf2 and Klf4, as well as Rho and ADAMTS protease activity, are increased in the endothelial cells of early CCM lesions. By contrast, we find no evidence of EndMT or increased SMAD or Wnt signalling during early CCM formation. Endothelial-specific loss of Map3k3 (also known as Mekk3), Klf2 or Klf4 markedly prevents lesion formation, reverses the increase in Rho activity, and rescues lethality. Consistent with these findings in mice, we show that endothelial expression of KLF2 and KLF4 is increased in human familial and sporadic CCM lesions, and that a disease-causing human CCM2 mutation abrogates the MEKK3 interaction without affecting CCM complex formation. These studies identify gain of MEKK3 signalling and KLF2/4 function as causal mechanisms for CCM pathogenesis that may be targeted to develop new CCM therapeutics.
    PMID: 27027284 [PubMed - as supplied by publisher]
  • Peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease.

    Biomarkers in medicine 2016 Mar

    Authors: Girard R, Khanna O, Shenkar R, Zhang L, Wu M, Jesselson M, Zeineddine HA, Gangal A, Fam MD, Gibson CC, Whitehead KJ, Li DY, Liao JK, Shi C, Awad IA
    Abstract
    To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically.
    A prospective case-control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains.
    Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features.
    Validation of these biomarkers and their potential treatment modulation may influence the clinical care of patients with CCM disease.
    PMID: 26861901 [PubMed - as supplied by publisher]
  • Obituary: John F. Mullan, MD, 1925-2015: neurosurgery's modern statesman.

    Journal of neurosurgery 2016 Jan 29

    Authors: Webb AJ, Ullman NL, Morgan TC, Muschelli J, Kornbluth J, Awad IA, Mayo S, Rosenblum M, Ziai W, Zuccarrello M, Aldrich F, John S, Harnof S, Lopez G, Broaddus WC, Wijman C, Vespa P, Bullock R, Haines SJ, Cruz-Flores S, Tuhrim S, Hill MD, Narayan R, Hanley DF, MISTIE and CLEAR Investigators
    Abstract
    The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography-based planimetry (CTP).
    In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression.
    In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC (r(2)=0.93) than with site-ABC (r(2)=0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm(3); CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P<0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots.
    ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots.
    URL: http://www.clinicaltrials.gov. Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.
    PMID: 26824372 [PubMed - as supplied by publisher]
  • Vascular permeability in cerebral cavernous malformations.

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 2015 Oct

    Authors: Mikati AG, Khanna O, Zhang L, Girard R, Shenkar R, Guo X, Shah A, Larsson HB
    Abstract
    Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.
    PMID: 25966944 [PubMed - as supplied by publisher]
  • Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial.

    Neurosurgery 2015 Mar

    Authors: Dey M, Stadnik A, Riad F, Zhang L, McBee N, Kase C, Carhuapoma JR, Ram M, Lane K, Ostapkovich N, Aldrich F, Aldrich C, Jallo J, Butcher K, Snider R, Hanley D, Ziai W, Awad IA, CLEAR III Trial Investigators
    Abstract
    Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication.
    To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature.
    Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software.
    Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis.
    Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.
    PMID: 25635887 [PubMed - as supplied by publisher]

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