Issam A. Awad, M.D.

Issam A. Awad, M.D.

Issam A. Awad, M.D.


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


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


Carotid Artery Stenting, Stereotactic Radiosurgery

General Information




Independent Practitioner


Neuro Critical Care, Neurovascular Surgery


Arabic, English, French

Board Certified

Neurological Surgery

Clinical Service

Education, Training & Fellowships

Medical School

Loma Linda University, 1980


Loma Linda University, 1981


Cleveland Clinic Foundation, 1985


Barrow Neurological Institute, 1986



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


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


  • Peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease.

    Biomarkers in medicine 2016 Feb 9

    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
    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
    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: 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
    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
    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]
  • Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

    Genetics in medicine : official journal of the American College of Medical Genetics 2015 Mar

    Authors: Shenkar R, Shi C, Rebeiz T, Stockton RA, McDonald DA, Mikati AG, Zhang L, Austin C, Akers AL, Gallione CJ, Rorrer A, Gunel M, Min W, Marcondes de Souza J, Lee C, Marchuk DA, Awad IA
    The phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.
    We analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.
    We determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.
    These findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196.
    PMID: 25122144 [PubMed - as supplied by publisher]
  • Immune complex formation and in situ B-cell clonal expansion in human cerebral cavernous malformations.

    Journal of neuroimmunology 2014 Jul 15

    Authors: Shi C, Shenkar R, Kinloch A, Henderson SG, Shaaya M, Chong AS, Clark MR, Awad IA
    Cerebral cavernous malformations (CCMs) represent clusters of dilated vascular channels, predisposing to hemorrhagic stroke and seizures. They are associated with defective blood brain barrier, hemorrhages of different ages and a robust inflammatory cell infiltrate. We report for the first time evidence of co-localized IgG and complement membrane attack complexes in CCM lesions. CD4(+) and CD8(+) T-cells are aggregated with CD20(+) B-cells. And IgG repertoire analyses demonstrate in situ B-cell clonal expansion and antigen-driven affinity maturation in CCMs. These results suggest an organ-intrinsic adaptive immune response in CCMs that should be further characterized as a potential therapeutic target.
    PMID: 24864012 [PubMed - as supplied by publisher]
  • Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis.

    Human molecular genetics 2014 Aug 15

    Authors: McDonald DA, Shi C, Shenkar R, Gallione CJ, Akers AL, Li S, De Castro N, Berg MJ, Corcoran DL, Awad IA, Marchuk DA
    Cerebral cavernous malformations (CCMs) are vascular lesions affecting the central nervous system. CCM occurs either sporadically or in an inherited, autosomal dominant manner. Constitutional (germline) mutations in any of three genes, KRIT1, CCM2 and PDCD10, can cause the inherited form. Analysis of CCM lesions from inherited cases revealed biallelic somatic mutations, indicating that CCM follows a Knudsonian two-hit mutation mechanism. It is still unknown, however, if the sporadic cases of CCM also follow this genetic mechanism. We extracted DNA from 11 surgically excised lesions from sporadic CCM patients, and sequenced the three CCM genes in each specimen using a next-generation sequencing approach. Four sporadic CCM lesion samples (36%) were found to contain novel somatic mutations. Three of the lesions contained a single somatic mutation, and one lesion contained two biallelic somatic mutations. Herein, we also describe evidence of somatic mosaicism in a patient presenting with over 130 CCM lesions localized to one hemisphere of the brain. Finally, in a lesion regrowth sample, we found that the regrown CCM lesion contained the same somatic mutation as the original lesion. Together, these data bolster the idea that all forms of CCM have a genetic underpinning of the two-hit mutation mechanism in the known CCM genes. Recent studies have found aberrant Rho kinase activation in inherited CCM pathogenesis, and we present evidence that this pathway is activated in sporadic CCM patients. These results suggest that all CCM patients, including those with the more common sporadic form, are potentially amenable to the same therapy.
    PMID: 24698976 [PubMed - as supplied by publisher]
  • Evaluation of iron content in human cerebral cavernous malformation using quantitative susceptibility mapping.

    Investigative radiology 2014 Jul

    Authors: Tan H, Liu T, Wu Y, Thacker J, Shenkar R, Mikati AG, Shi C, Dykstra C, Wang Y, Prasad PV, Edelman RR, Awad IA
    The aims of this study were to investigate and validate quantitative susceptibility mapping (QSM) for lesional iron quantification in cerebral cavernous malformations (CCMs).
    Magnetic resonance imaging studies were performed in phantoms and 16 patients on a 3-T scanner. Susceptibility weighted imaging, QSM, and R2* maps were reconstructed from in vivo data acquired with a 3-dimensional, multi-echo, and T2*-weighted gradient echo sequence. Magnetic susceptibility measurements were correlated to susceptibility weighted imaging and R2* results. In addition, iron concentrations from surgically excised CCM lesion specimens were determined using inductively coupled plasma mass spectrometry and correlated with QSM measurements.
    The QSM images demonstrated excellent image quality for depicting CCM lesions in both sporadic and familial cases. Susceptibility measurements revealed a positive linear correlation with R2* values (R(2) = 0.99 for total, R(2) = 0.69 for mean; P < 0.01). Quantitative susceptibility mapping values of known iron-rich brain regions matched closely with those of previous studies and in interobserver consistency. A strong correlation was found between QSM and the concentration of iron phantoms (0.925; P < 0.01), as well as between QSM and mass spectroscopy estimation of iron deposition (0.999 for total iron, 0.86 for iron concentration; P < 0.01) in 18 fragments of 4 excised human CCM lesion specimens.
    The ability of QSM to evaluate iron deposition in CCM lesions was illustrated via phantom, in vivo, and ex vivo validation studies. Quantitative susceptibility mapping may be a potential biomarker for monitoring CCM disease activity and response to treatments.
    PMID: 24619210 [PubMed - as supplied by publisher]

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