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1. Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation.

Author

Weinsheimer, Shantel, Nelson, Jeffrey, Abla, Adib A, Ko, Nerissa U, Tsang, Cynthia, Okoye, Obiora, Zabramski, Joseph M, Akers, Amy, Zafar, Atif, Mabray, Marc C, Hart, Blaine L, Morrison, Leslie, McCulloch, Charles E, Kim, Helen, and Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group *

Subjects
Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group *, Humans, Hemangioma, Cavernous, Central Nervous System, Intracranial Hemorrhages, Cerebral Hemorrhage, Central Nervous System Vascular Malformations, Risk Factors, cerebral cavernous malformation, familial, hemorrhage, risk factor, Stroke, Clinical Research, Brain Disorders, Neurosciences, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Cardiorespiratory Medicine and Haematology
Abstract

Background Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in KRIT1, CCM2, or PDCD10. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (P=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], P=0.006). Conclusions Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.

Published
2023

2. Systemic and CNS manifestations of inherited cerebrovascular malformations

Author

Hart, Blaine L, Mabray, Marc C, Morrison, Leslie, Whitehead, Kevin J, and Kim, Helen

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Rare Diseases, Neurodegenerative, Neurosciences, Genetics, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Cerebral Arteries, Diagnostic Imaging, Hemangioma, Cavernous, Central Nervous System, Humans, Skin, Telangiectasia, Hereditary Hemorrhagic, Cerebrovascular malformations, Cerebral cavernous malformation, Arteriovenous malformation, Neurocutaneous syndrome, Capillary malformation-arteriovenous, malformation, Capillary malformation-arteriovenous malformation, Clinical Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized. Genetic and molecular mechanisms underlying the inherited disorders are becoming better understood, and treatments are likely to follow. An interaction between the intestinal microbiome and formation of cerebral cavernous malformations has emerged, with possible treatment implications. Two-hit mechanisms are involved in these disorders, and additional triggering mechanisms are part of the development of malformations. Hereditary hemorrhagic telangiectasia encompasses a variety of vascular malformations, with widely varying risks, and a more recently recognized association with cortical malformations. Somatic mutations are implicated in the genesis of some sporadic malformations, which means that discoveries related to inherited disorders may aid treatment of sporadic cases. This paper summarizes the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.

Published
2021

3. Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part II: Biomarkers and Trial Modeling

Author

Hage, Stephanie, Kinkade, Serena, Girard, Romuald, Flemming, Kelly D., Kim, Helen, Torbey, Michel T., Huang, Judy, Huston, John, III, Shu, Yunhong, Selwyn, Reed G., Hart, Blaine L., Mabray, Marc C., Feghali, James, Sair, Haris I., Narvid, Jared, Lupo, Janine M., Lee, Justine, Stadnik, Agnieszka, Alcazar-Felix, Roberto J., Shenkar, Robert, Hobson, Nicholas, DeBiasse, Dorothy, Lane, Karen, McBee, Nichole A., Treine, Kevin, Ostapkovich, Noeleen, Wang, Ying, Thompson, Richard E., Koenig, James I., Carroll, Timothy, Hanley, Daniel F., Jr, and Awad, Issam A.

Published
2024
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5. Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition

Author

Strickland, Corinne D, Eberhardt, Steven C, Bartlett, Mary R, Nelson, Jeffrey, Kim, Helen, Morrison, Leslie A, and Hart, Blaine L

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Pediatric, Rare Diseases, Neurosciences, Biomedical Imaging, Clinical Research, 2.1 Biological and endogenous factors, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Aetiology, Adolescent, Adrenal Gland Diseases, Adult, Biomarkers, Calcinosis, Case-Control Studies, Child, Contrast Media, Diagnosis, Differential, Female, Hemangioma, Cavernous, Central Nervous System, Humans, KRIT1 Protein, Magnetic Resonance Imaging, Male, Microtubule-Associated Proteins, Middle Aged, Proto-Oncogene Proteins, Tomography, X-Ray Computed, Medical and Health Sciences, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

Published
2017

6. Automated algorithm for counting microbleeds in patients with familial cerebral cavernous malformations

Author

Zou, Xiaowei, Hart, Blaine L, Mabray, Marc, Bartlett, Mary R, Bian, Wei, Nelson, Jeffrey, Morrison, Leslie A, McCulloch, Charles E, Hess, Christopher P, Lupo, Janine M, and Kim, Helen

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Neurosciences, Brain Disorders, Cerebrovascular, Algorithms, Cerebral Hemorrhage, Female, Hemangioma, Cavernous, Central Nervous System, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors, Automated lesion counting, Cerebral cavernous malformations, Microbleeds, Susceptibility-weighted imaging, Nuclear Medicine & Medical Imaging, Clinical sciences
Abstract

PurposeFamilial cerebral cavernous malformation (CCM) patients present with multiple lesions that can grow both in number and size over time and are reliably detected on susceptibility-weighted imaging (SWI). Manual counting of lesions is arduous and subject to high variability. We aimed to develop an automated algorithm for counting CCM microbleeds (lesions

Published
2017

9. Familial Cerebral Cavernous Malformations

Author

Zafar, Atif, Quadri, Syed A., Farooqui, Mudassir, Ikram, Asad, Robinson, Myranda, Hart, Blaine L., Mabray, Marc C., Vigil, Catherine, Tang, Alan T., Kahn, Mark L., Yonas, Howard, Lawton, Michael T., Kim, Helen, and Morrison, Leslie

Published
2019
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10. Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling

Author

Hage, Stephanie, Kinkade, Serena, Girard, Romuald, Flemming, Kelly D., Kim, Helen, Torbey, Michel T., Huang, Judy, Huston, John, Shu, Yunhong, Selwyn, Reed G., Hart, Blaine L., Mabray, Marc C., Feghali, James, Sair, Haris I., Narvid, Jared, Lupo, Janine M., Lee, Justine, Stadnik, Agnieszka, Alcazar, Roberto, Shenkar, Robert, Hobson, Nicholas, DeBiasse, Dorothy, Lane, Karen, McBee, Nichole, Treine, Kevin, Ostapkovich, Noeleen, Wang, Ying, Thompson, Richard E., Mendoza-Puccini, Carolina, Koenig, James, Carroll, Timothy, Hanley, Daniel F., and Awad, Issam A.

Subjects
Article
Abstract

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast enhanced quantitative perfusion (DCEQP) MRI sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cavernous angiomas. We assessed their prospective changes in cavernous angiomas with symptomatic hemorrhage (CASH) in a multisite trial readiness project ( clinicaltrials.gov NCT03652181 ). METHODS: Patients with CASH in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of CASH lesion were acquired at baseline, and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined lesional symptomatic hemorrhage (SH) or asymptomatic change (AC). Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (p= 0.019). Annual QSM increase by ≥ 6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with AC during the same epoch, and 3.82 times more frequently than clinical events. DCEQP change had lower sensitivity for SH and AC than QSM change, and greater variance. A trial with smallest sample size would detect a 30% difference in QSM annual change in 34 or 42 subjects (one and two-tailed, respectively), power 0.8, alpha 0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in CASH. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the U.S. F.D.A. of QSM as a biomarker of drug effect in CASH.

Published
2023

11. Contributors

Author

Abbed, Khalid M., primary, Abdullah, Kalil G., additional, Ackerman, Paul D., additional, Alapan, Yunus, additional, Alentado, Vincent J., additional, Alvin, Matthew D., additional, Ames, Christopher P., additional, Anand, Neel, additional, Anderson, Paul A., additional, Angelov, Lilyana, additional, Anissipour, Alireza K., additional, Anson, John A., additional, Apfelbaum, Ronald I., additional, Archdeacon, Michael, additional, Arnold, Paul M., additional, Arun, Mike W.J., additional, Arzi, Harel, additional, Awad, Ahmed J., additional, Awad, Basem I., additional, Bahuleyan, Biji, additional, Bain, Mark D., additional, Baird, Lissa C., additional, Baisden, Jamie, additional, Baldwin, Nevan G., additional, Ball, Perry A., additional, Balsara, Karl E., additional, Baron, Eli M., additional, Batjer, H. Hunt, additional, Bauer, Andrew M., additional, Bauer, Thomas W., additional, Beckman, Joshua M., additional, Bell, Gordon R., additional, Bellabarba, Carlo, additional, Bennett, E. Emily, additional, Benzel, Edward C., additional, Bergey, Darren L., additional, Bhalla, Tarun, additional, Bierbrauer, Karin S., additional, Bilsky, Mark, additional, Birk, Harjus, additional, Bisson, Erica F., additional, Bono, Christopher, additional, Bransford, Richard J., additional, Brodke, Darrel S., additional, Brooks, Nathaniel, additional, Brotea, Cristian, additional, Brougham, Jared R., additional, Browd, Samuel R., additional, Buckley, Robert T., additional, Burch, Shane, additional, Butler, John, additional, Bydon, Mohamad, additional, Casha, Steven, additional, Ceuppens, Jeroen, additional, Chan, Andrew K., additional, Chen, Thomas C., additional, Cheng, Joseph, additional, Chou, Dean, additional, Choudhri, Tanvir, additional, Clark, Aaron J., additional, Conley, Adam M., additional, Cooper, Paul R., additional, Coric, Domagoj, additional, Corriveau, Mark, additional, Côté, Ian P., additional, Coumans, Jean-Valery C.E., additional, Crawford, Charles H., additional, Curry, William T., additional, Daffner, Scott D., additional, Dalbayrak, Sedat, additional, DeMicco, Russell C., additional, Deutsch, Harel, additional, Dhall, Sanjay S., additional, DiAngelo, Denis J., additional, Dickman, Curtis A., additional, Dodwad, Shah-Nawaz M., additional, Duarte, Siena M., additional, Ebrahim, Zeyd, additional, Eckardt, Gerald W., additional, Ehni, Bruce L., additional, Eichholz, Kurt M., additional, Eichler, Marc, additional, Elbabaa, Samer K., additional, Elder, Benjamin D., additional, Elder, James B., additional, Ellenbogen, Richard G., additional, Epstein, Nancy, additional, Errico, Thomas J., additional, Esquenazi, Yoshua, additional, Fahim, Daniel K., additional, Farag, Ehab, additional, Farley, Chad W., additional, Fehlings, Michael G., additional, Feigenbaum, Frank, additional, Fenton, Eoin, additional, Ferrara, Lisa A., additional, Fessler, R. David, additional, Fessler, Richard G., additional, Finn, Michael A., additional, Finnan, Ryan, additional, Fischgrund, Jeffrey S., additional, Foley, Kevin T., additional, Fontes, Ricardo B.V., additional, Francis, Todd B., additional, Freedman, Brett A., additional, Frost, Frederick, additional, George, John, additional, German, John W., additional, Gerszten, Peter C., additional, Ghobrial, George M., additional, Ghogawala, Zoher, additional, Gibson, Justin L., additional, Gillis, Christopher C., additional, Goel, Vijay K., additional, Goffin, Jan, additional, Gokaslan, Ziya L., additional, Gollogly, Sohrab, additional, Goodwin, C. Rory, additional, Goulart, Carlos R., additional, Goz, Vadim, additional, Gozal, Yair M., additional, Graham, Randall B., additional, Grant, Gerald A., additional, Guan, Jian, additional, Gulec, Ilker, additional, Gussous, Yazeed M., additional, Guyer, Richard D., additional, Gwinn, David, additional, Ha, Sung, additional, Hadar, Eldad, additional, Haldeman, Clayton L., additional, Halim, Alexander Y., additional, Hamilton, Kimberly M., additional, Hammer, Christine L., additional, Hanbali, Fadi, additional, Hann, Shannon W., additional, Harms, Jurgen, additional, Harrop, James S., additional, Hart, Blaine L., additional, Hart, David J., additional, Harwell, Daniel, additional, Hayek, Reyaad A., additional, Heary, Robert F., additional, Henderson, Fraser C., additional, Hitchon, Patrick W., additional, Hoh, Daniel J., additional, Holman, Paul J., additional, Hosono, Noboru, additional, Houseman, Clifford, additional, Houten, John K., additional, Hsieh, Joseph C., additional, Hsu, Wellington K., additional, Huang, Meng, additional, Hurlbert, R. John, additional, Hwang, Lee, additional, Hwang, Steven, additional, İnceoğlu, Serkan, additional, Infinger, Libby Kosnik, additional, de Oliveira, Tatiana von Hertwig Fernandes, additional, Jalan, Devesh, additional, Jha, Neilank, additional, Johnson, J. Patrick, additional, Jones, Charles I., additional, Jones, G. Alexander, additional, Jones, Michael, additional, Juthani, Rupa G., additional, Kager, Christopher D., additional, Kalani, Maziyar A., additional, Kalani, M. Yashar S., additional, Kalfas, Iain H., additional, Kalra, Ricky R., additional, Karimi, Reza J., additional, Kashlan, Osama, additional, Kasliwal, Manish K., additional, Kaul, Vikas, additional, Kaushal, Mayank, additional, Kenning, Tyler J., additional, Khairi, Saad, additional, Khalaf, Tagreed, additional, Khalil, Jad G., additional, Khoo, Larry T., additional, Kiapour, Ali, additional, Kim, Daniel H., additional, Kim, David H., additional, Kimmell, Kristopher T., additional, Kirshblum, Steven, additional, Kitab, Sameer A., additional, Klimo, Paul, additional, Klineberg, Eric O., additional, Koski, Tyler R., additional, Kosztowski, Thomas A., additional, Kowalski, Robert J., additional, Krishnaney, Ajit A., additional, Krupa, Kelly, additional, Krupa, Kristin, additional, Kshettry, Varun R., additional, Kukreja, Sunil, additional, Kuntz, Charles, additional, Kurpad, Shekar N., additional, Kusuma, Srinivasu, additional, LaBagnara, Michael, additional, La Marca, Frank, additional, Laufer, Ilya, additional, Lavelle, Elizabeth Demers, additional, Lavelle, William F., additional, Lawrence, W. Thomas, additional, Lebl, Darren R., additional, Lee, Bryan S., additional, Lee, Sun-Ho, additional, Lenke, Lawrence G., additional, Leon, Steven P., additional, Li, Amy, additional, Li, Yiping, additional, Lieberman, Isador H., additional, Liu, James K.C., additional, Lo, Victor P., additional, Lollis, S. Scott, additional, Lopez-Gonzalez, Miguel, additional, Lubelski, Daniel, additional, Luciano, Mark G., additional, Machado, Andre G., additional, Maddela, Raghu, additional, Madineni, Ravichandra A., additional, Madura, Casey, additional, Maiman, Dennis J., additional, Malone, David G., additional, Mammis, Antonios, additional, Marawar, Satyajit, additional, Marcotte, Nicolas, additional, Maroon, Joseph C., additional, Martin, Michael D., additional, Martinez-del-Campo, Eduardo, additional, Massicotte, Eric M., additional, Mattei, Tobias A., additional, Maurer, Paul K., additional, Mayer, Eric A.K., additional, del Valle, Miguel Mayol, additional, Mazanec, Daniel J., additional, McCormick, Paul C., additional, McCormick, William, additional, Medress, Zachary A., additional, Mendel, Ehud, additional, Metkar, Umesh S., additional, Miele, Vincent J., additional, Mohyeldin, Ahmed, additional, Monsef, Jad Bou, additional, Moore, Timothy A., additional, Morisue, Hikaru, additional, Morone, Peter, additional, Mroz, Thomas E., additional, Mullin, Jeffrey P., additional, Murtagh, F. Reed, additional, Murtagh, Ryan D., additional, Naderi, Sait, additional, Nagaraj, Usha D., additional, Nalley, Charles C., additional, Nanda, Anil, additional, Nasca, Richard J., additional, Nater, Anick, additional, Neal, Matthew T., additional, Nockels, Russ P., additional, Norwig, John A., additional, Ondoma, Solomon M., additional, Oni-Orisan, Akinwunmi, additional, Oren, Jonathan H., additional, Orning, Jennifer, additional, Orr, R. Douglas, additional, Orrico, Katie, additional, Osorio, Joseph A., additional, Otero-Lopez, Ernesto, additional, O'Toole, John, additional, Park, Paul, additional, Parmar, Vikas, additional, Pashman, Robert S., additional, Patel, Rakesh D., additional, Patel, Smruti K., additional, Perez-Cruet, Mick J., additional, Perin, Noel I., additional, Pettigrew, David B., additional, Phillips, H. Westley, additional, Placide, Rick, additional, Porensky, Paul, additional, Prager, Joshua P., additional, Prasad, Srinivas, additional, Prasarn, Mark L., additional, Ramakrishnan, Rakesh, additional, Ramayya, Ashwin G., additional, Rampersaud, Y. Raja, additional, Rasmussen, Peter A., additional, Ratliff, John K., additional, Rauschning, Wolfgang, additional, Rechtine, Glenn R., additional, Recinos, Pablo F., additional, Resnick, Daniel K., additional, Rhee, Jay, additional, Rhines, Laurence D., additional, Riccio, Alexander R., additional, Richardson, Marlin Dustin, additional, Richter, Bertram, additional, Riesenburger, Ron, additional, Riew, K. Daniel, additional, Rogers, Matthew, additional, Saavedra, Fanor M., additional, Safain, Mina G., additional, Saigal, Rajiv, additional, Sawin, Paul D., additional, Scheer, Justin K., additional, Scheidler, Joshua, additional, Schippert, David W., additional, Schlenk, Richard, additional, Schmidt, Bradley, additional, Schmidt, Meic H., additional, Sciubba, Daniel M., additional, Shaffrey, Christopher I., additional, Shaffrey, Mark E., additional, Shah, Anoli, additional, Sharan, Alok, additional, Sharan, Ashwini D., additional, Shedid, Daniel, additional, Shook, Steven, additional, Silverstein, Michael P., additional, Simpson, Venita M., additional, Sin, Anthony, additional, Singh, Harminder, additional, Smith, Donald A., additional, Smith, Gabriel A., additional, Smith, Justin S., additional, Smith, Kyle A., additional, Sonntag, Volker K.H., additional, Soriano-Baron, Hector, additional, Spetzler, Robert F., additional, Spiker, W. Ryan, additional, Staub, Blake, additional, Steinmetz, Michael P., additional, Stillerman, Charles B., additional, Strayer, Andrea, additional, Subramaniam, Gandhivarma, additional, Sukkarieh, Hamdi G., additional, Sumich, Andrew, additional, Sun, Derrick Y., additional, Sunna, Tarek P., additional, Sure, Durga R., additional, Tallarico, Richard A., additional, Tan, Lee A., additional, Tatsui, Claudio E., additional, Techy, Fernando, additional, Theodore, Nicholas, additional, Theologis, Alexander A., additional, Thomas, Nicholas W.M., additional, Thorp, Brian D., additional, Tintle, Scott, additional, Tjoumakaris, Stavropoula, additional, Tobler, William D., additional, Togawa, Daisuke, additional, Traul, David, additional, Traynelis, Vincent C., additional, Tritle, A. Sophia, additional, Trost, Gregory R., additional, Tsai, Eve C., additional, Ugokwe, Kene, additional, Uluc, Kutlauy, additional, Uribe, Juan S., additional, Vaccaro, Alexander R., additional, Valadka, Alex, additional, Vedantam, Aditya, additional, Veeravagu, Anand, additional, Verma, Kushagra, additional, Vitaz, Todd, additional, Voyadzis, Jean-Marc, additional, Wagner, Scott, additional, Wahlquist, Trevor C., additional, Waldrop, Robert, additional, Walsh, Kevin M., additional, Wang, Jeffrey C., additional, Wang, Michael Y., additional, Wang, Patrick T., additional, Ward, John D., additional, Wardak, Zabi, additional, Wathen, Connor, additional, Weinstein, Philip R., additional, Weisman, Michael, additional, Welch, William C., additional, Weller, Simcha J., additional, Westerlund, L. Erik, additional, White, Jonathan A., additional, Whitmore, Robert G., additional, Wilberger, Jack E., additional, Williams, Kim A., additional, Winkler, Ethan A., additional, Witiw, Christopher D., additional, Wolfla, Christopher E., additional, Wolinsky, Jean-Paul, additional, Wong, Cyrus, additional, Woodard, Eric J., additional, Yanamadala, Vijay, additional, Yanni, Daniel S., additional, Yazbak, Philip A., additional, Yen, Chun-Po, additional, Yilmaz, Mesut, additional, Yoganandan, Narayan, additional, Yonemura, Kenneth S., additional, Yonenobu, Kazuo, additional, Yuan, Hansen A., additional, Yue, John K., additional, Zanation, Adam M., additional, Zavarella, Salvatore M., additional, Zeidman, Seth M., additional, Zileli, Mehmet, additional, Zuckerman, Scott, additional, and Zywicke, Holly, additional

Published
2017
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12. Imaging

Author

Hart, Blaine L., primary and Hayek, Reyaad A., additional

Published
2017
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15. Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation

Author

Choksi, Foram, primary, Weinsheimer, Shantel, additional, Nelson, Jeffrey, additional, Pawlikowska, Ludmila, additional, Fox, Christine K., additional, Zafar, Atif, additional, Mabray, Marc C., additional, Zabramski, Joseph, additional, Akers, Amy, additional, Hart, Blaine L., additional, Morrison, Leslie, additional, McCulloch, Charles E., additional, and Kim, Helen, additional

Published
2021
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17. Transverse Myelitis in a Child With COVID-19

Author

Kaur, Harsheen, primary, Mason, John Alan, additional, Bajracharya, Manish, additional, McGee, John, additional, Gunderson, Matthew D., additional, Hart, Blaine L., additional, Dehority, Walter, additional, Link, Nathaniel, additional, Moore, Brian, additional, Phillips, John P., additional, and Rogers, Danny, additional

Published
2020
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41. Radon: is it a problem?

Author

Hart, Blaine L., Mettler, Fred A., Jr., and Harley, Naomi H.

Subjects
Carcinogens -- Environmental aspects, Radioactive pollution -- Physiological aspects, Indoor air quality -- Research, Lung cancer -- Risk factors, Radon -- Health aspects, Health
Abstract

Radon-222, a naturally-occurring radioactive by-product of uranium-238, is present in all soils. It enters buildings in varying degrees of concentration as an odorless and colorless gas. As this substance breaks down it emits products called 'radon daughters' that can be deposited in the lungs and may result in the development of lung cancer. In some homes, (e.g., in the area around Reading Prong, PA.) very high levels of radon have been recorded, noticeably in basements and poorly ventilated areas. Radon exposure, particularly in the home, is now considered a significant radiation hazard. The degree of risk from exposure to low levels of radon over a long period of time is not known. Occupational exposure to radon daughters occurs in such work settings as mines. Radon may be responsible for a large portion of the 'spontaneous' lung cancer mortality figures (i.e., lung cancer deaths not attributed to known carcinogens). This hypothesis is supported by studies of Navajo uranium miners who have otherwise had a low incidence of lung cancer. However, the interplay of cigarette smoking and radon remains an unsettled question with some reports suggesting an increased risk of lung cancer in smokers who are exposed to radon (in mining occupations) and others suggesting that smoking may provide a protective effect against such radon exposure. Radon may account for 55 percent of the ionizing radiation that persons are exposed to; other common sources are medical X-rays and nuclear medicine procedures. Clearly further studies are necessary to determine the health risk of radon exposure in members of the general population, specific occupational groups and in smokers.

Published
1989

42. Pathology Case Study: Temporal Bone Mass

Author

Becher, Mark W., Hart, Blaine L., Havlik, Dean M., Becher, Mark W., Hart, Blaine L., and Havlik, Dean M.

Abstract

This is a case study presented by the University of Pittsburgh Department of Pathology in which a man experienced episodes of vertigo and dizziness, possibly related to suffering a rubella viral infection as a child. Visitors can view both microscopic and neuroimaging descriptions, and have the opportunity to diagnose the patient. This is an excellent resource for students in the health sciences to familiarize themselves with using patient history and laboratory results to diagnose disease. It is also a helpful site for educators to introduce or test students of neuropathology.

Published
2001

45. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1)

Author

Yamada, Koki, primary, Andrews, Caroline, additional, Chan, Wai-Man, additional, McKeown, Craig A, additional, Magli, Adriano, additional, de Berardinis, Teresa, additional, Loewenstein, Anat, additional, Lazar, Moshe, additional, O'Keefe, Michael, additional, Letson, Robert, additional, London, Arnold, additional, Ruttum, Mark, additional, Matsumoto, Naomichi, additional, Saito, Nakamichi, additional, Morris, Lisa, additional, Monte, Monte Del, additional, Johnson, Roger H, additional, Uyama, Eiichiro, additional, Houtman, Willem A, additional, de Vries, Berendina, additional, Carlow, Thomas J, additional, Hart, Blaine L, additional, Krawiecki, Nicolas, additional, Shoffner, John, additional, Vogel, Marlene C, additional, Katowitz, James, additional, Goldstein, Scott M, additional, Levin, Alex V, additional, Sener, Emin C, additional, Ozturk, Banu T, additional, Akarsu, A Nurten, additional, Brodsky, Michael C, additional, Hanisch, Frank, additional, Cruse, Robert P, additional, Zubcov, Alina A, additional, Robb, Richard M, additional, Roggenkäemper, Peter, additional, Gottlob, Irene, additional, Kowal, Lionel, additional, Battu, Ravi, additional, Traboulsi, Elias I, additional, Franceschini, Piergiorgio, additional, Newlin, Anna, additional, Demer, Joseph L, additional, and Engle, Elizabeth C, additional

Published
2003
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49. Effect of lordosis on the position of the nucleus pulposus in supine subjects: A study using magnetic resonance imaging

Author

Beattie, Paul F., Brooks, William M., Rothstein, Jules M., Sibbitt, Wilmer L. Jr, Robergs, Robert A., Maclean, Thomas, Hart, Blaine L., Beattie, Paul F., Brooks, William M., Rothstein, Jules M., Sibbitt, Wilmer L. Jr, Robergs, Robert A., Maclean, Thomas, and Hart, Blaine L.

Abstract

Study Design - Healthy young women (N = 20) underwent magnetic resonance imaging while supine with their hips and knees flexed (flexed position) and supine with a lumbar roll under the low back (extended position). The posterior end anterior margins of the nucleus pulposus (MP) relative to posterior and anterior margins of the adjacent vertebral bodies were calculated from mid-sagittal T 2-weighted images to determine the position change of the NP as a function of two supine postures.Objectives - This study describes the effect of two commonly used supine postures on the position of the NP. Summary of Background Data - Management of patients with low back pain is often based on theorized positional changes of the NP during spinal extension and flexion, Date describing NP positional changes have not been reported for noninvesive measurements. Results - The distance of the posterior margin of the NP to the posterior margins of the adjacent vertebral bodies was greater in the extended compared with the flexed position. There was no difference in the anterior distance. Eight of the 20 subjects had at least one degenerative disc in the lower lumbar spine. The NFs of the degenerative discs did not move the same as normal discs. Conclusions - The use of a lumbar roll under the low back when supine causes an increase in the distance from the posterior margin of the NP to the posterior portions of the vertebral bodies in normal discs of healthy young females. Degenerative discs deform differently from non degenerative discs.

Published
1994

50. Biochemical markers of cognition

Author

Jung, Rex E., primary, Yeo, Ronald A., additional, Chiulli, Stephen J., additional, Sibbitt, Wilmer L., additional, Weers, David C., additional, Hart, Blaine L., additional, and Brooks, William M., additional

Published
1999
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