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Letters Reply to “Central-Variant Posterior Reversible Encephalopathy Syndrome: More Than Meets the Eye” Gao and Lv [1] provide some helpful comments regarding the potential pathogenesis of central-variant posterior reversible encephalopathy syndrome (PRES). In particular, they raise the possibility that hypertension is intrinsically involved in central-variant PRES; this supposition is interesting and might be considered controversial because several prior studies have shown that hypertension is not a requirement in PRES because the insult is currently favored to arise from endothelial injury rather than pure “hyperperfusion” injury [2–5]. Although central-variant PRES is relatively rare, the authors’ theory that hypertension is usually involved in this central-variant of PRES may be plausible because there is histologic evidence that the brainstem and other structures located solely within the posterior circulation may have a lower concentration of protective sympathetic innervation relative to the anterior circulation [6]. Therefore, I went back and reviewed the medical records of the five central-variant PRES patients we described to obtain further information on the blood pressure values at the time of admission. In that article [7], we mentioned that hypertension was a cause in two of the patients; these were patients 3 and 4, who had blood pressures of ≈ 210/130 and ≈ 220/100 mmHg, respectively. The following is a summary of the blood pressure values at presentation in the other three patients with central-variant PRES from our series, which were not provided in that article. First, in patient 1 (the 27-year-old woman undergoing cyclosporine therapy for renal transplantation), the electronic medical record did not go back far enough but available reports noted that she had a long history of hypertension as well as at the time of developing central-variant PRES. Second, in patient 2 (the 59-year-old man who underwent cyclosporine and mycophenolate therapy for renal transplantation), the blood pressure was ≈ 187/110 mmHg at presentation. Finally, in patient 5 (the 35-year-old woman immediately after delivery), the blood pressure was also mildly elevated at presentation to
≈ 150/90 mmHg, and she also was thought to have hemolysis, elevated liver enzymes, and low platelet count syndrome. Therefore, the elevated blood pressure in at least four (and likely all five) of our central-variant PRES patients would seem to lend credence to the theory proffered by Gao and Lv [1] that hypertension is intrinsically involved in central-variant PRES patients although our number of centralvariant PRES patients was admittedly too small to reach a definite conclusion. I concur that, in patients 3 and 4, the underlying “patchy” supratentorial white matter and basal ganglia lesions that are not located within the parietooccipital cortexes (i.e., not typical of PRES) are likely related to underlying atherosclerosis because those lesions did not resolve over time. I also agree that the microhemorrhages noted on susceptibilityweighted imaging (SWI) within the pons and basal ganglia in patients 3 and 4 are likely related to underlying atherosclerosis from hypertension in PRES because the finding of chronic microhemorrhages in PRES due to hypertension has been recently described [8]. Meanwhile, in the two patients who underwent SWI who were not primarily hypertensive (patients 2 and 5; patient 1 never underwent SWI), there were no microhemorrhages within the brainstem or elsewhere. Because Gao and Lv [1] have proposed the theory that the residual lesions on FLAIR and the microhemorrhages on SWI may both be related to chronic underlying atherosclerosis from hypertension rather than PRES, the question arises whether such microhemorrhages, particularly in the brainstem, may be a factor that either portends or leads to centralvariant PRES. Hence, I then rereviewed the SWI examinations in the 31 patients from a prior study on SWI in PRES [8] in which 18 of 31 (58.1%) patients were found to have microhemorrhages on initial imaging (the vast majority of which were typically within the cortex or subcortical white matter) to evaluate for a difference in the number of brainstem pontine microhemorrhages in the 21 PRES patients in whom the primary cause was not hypertension versus those 10 patients who did present with solely hypertension. Interestingly, I subsequently found that only two of
10 patients who presented with hypertension as the primary cause (i.e., not on immunosuppressive therapy or pregnant) had microhemorrhages within the brainstem and had developed central-variant PRES (the same patients as patients 3 and 4 in the current study [7]), whereas none of the 21 PRES patients who underwent SWI who did not have primary hypertension had pontine microhemorrhages. Hence, a thorough discussion of all possible causes of central-variant PRES is speculative and beyond the scope of this response, but I thank the authors for raising a few interesting points that have made me rereview our PRES cases and may preliminarily provide insight into the pathophysiology of central-variant PRES. That rereview, albeit limited, seems to reveal that central-variant PRES only occurred in primarily hypertensive patients if there were microhemorrhages within the pons, and PRES patients in general lacking primary hypertension as the cause do not seem to experience brainstem microhemorrhages. Thus, pontine microhemorrhages may be implicated in or be a harbinger of central-variant PRES, but this needs to be studied prospectively or in a larger series of patients to discern what additional factors cause primarily hypertensive patients to develop central-variant PRES. I emphasize that this does not address why patients who are not primarily hypertensive, such as eclamptic patients or those on immunosuppressive medications, develop central-variant PRES; indeed, it is plausible that endothelial toxicity may act in concert with hypertension to cause centralvariant PRES in such patients. However, on the basis of the theory by Gao and Lv [1] and our preliminary data, hypertension certainly seems to play a major role in each case of central-variant PRES. Alexander M. McKinney Hennepin County Medical Center University of Minnesota Medical Center, Minneapolis, MN DOI:10.2214/AJR.14.12824 WEB—This is a web exclusive article.
References 1. Gao B, Lv C. Central-variant posterior reversible encephalopathy syndrome: more than meets the eye. (letter) AJR 2014; 203:[web]W454 2. McKinney AM, Short J, Truwit CL, et al. Poste-
AJR 2014; 203:W455 0361–803X/14/2034–W455 © American Roentgen Ray Society
AJR:203, October 2014 W455
Downloaded from www.ajronline.org by Iowa State University on 09/27/14 from IP address 129.186.1.55. Copyright ARRS. For personal use only; all rights reserved
Letters rior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR 2007; 189:904–912 3. Bartynski WS. Posterior reversible encephalopathy syndrome. Part 2. Controversies surrounding pathophysiology of vasogenic edema. AJNR 2008; 29:1043–1049 4. Horbinski C, Bartynski WS, Carson-Walter E, et al. Reversible encephalopathy after cardiac transplantation: histologic evidence of endothelial acti-
W456
vation, T-cell specific trafficking, and vascular endothelial growth factor expression. AJNR 2009; 30:588–590 5. Bartynski WS, Boardman JF. Distinct imaging patterns and lesion distribution in posterior reversible encephalopathy syndrome (PRES). AJNR 2007; 28:1320–1327 6. Edvinsson L, Owman C, Sjöberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels: a histochemical and pharmacologi-
cal study. Brain Res 1976; 115:377–393 7. McKinney AM, Jagadeesan BD, Truwit CL. Central-variant posterior reversible encephalopathy syndrome: brainstem or basal ganglia involvement lacking cortical or subcortical cerebral edema. AJR 2013; 201:631–638 8. McKinney AM, Sarikaya B, Gustafson C, Truwit CL. Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging. AJNR 2012; 33:896–903
AJR:203, October 2014
Letters Reply to “Central-Variant Posterior Reversible Encephalopathy Syndrome: More Than Meets the Eye” Gao and Lv [1] provide some helpful comments regarding the potential pathogenesis of central-variant posterior reversible encephalopathy syndrome (PRES). In particular, they raise the possibility that hypertension is intrinsically involved in central-variant PRES; this supposition is interesting and might be considered controversial because several prior studies have shown that hypertension is not a requirement in PRES because the insult is currently favored to arise from endothelial injury rather than pure “hyperperfusion” injury [2–5]. Although central-variant PRES is relatively rare, the authors’ theory that hypertension is usually involved in this central-variant of PRES may be plausible because there is histologic evidence that the brainstem and other structures located solely within the posterior circulation may have a lower concentration of protective sympathetic innervation relative to the anterior circulation [6]. Therefore, I went back and reviewed the medical records of the five central-variant PRES patients we described to obtain further information on the blood pressure values at the time of admission. In that article [7], we mentioned that hypertension was a cause in two of the patients; these were patients 3 and 4, who had blood pressures of ≈ 210/130 and ≈ 220/100 mmHg, respectively. The following is a summary of the blood pressure values at presentation in the other three patients with central-variant PRES from our series, which were not provided in that article. First, in patient 1 (the 27-year-old woman undergoing cyclosporine therapy for renal transplantation), the electronic medical record did not go back far enough but available reports noted that she had a long history of hypertension as well as at the time of developing central-variant PRES. Second, in patient 2 (the 59-year-old man who underwent cyclosporine and mycophenolate therapy for renal transplantation), the blood pressure was ≈ 187/110 mmHg at presentation. Finally, in patient 5 (the 35-year-old woman immediately after delivery), the blood pressure was also mildly elevated at presentation to
≈ 150/90 mmHg, and she also was thought to have hemolysis, elevated liver enzymes, and low platelet count syndrome. Therefore, the elevated blood pressure in at least four (and likely all five) of our central-variant PRES patients would seem to lend credence to the theory proffered by Gao and Lv [1] that hypertension is intrinsically involved in central-variant PRES patients although our number of centralvariant PRES patients was admittedly too small to reach a definite conclusion. I concur that, in patients 3 and 4, the underlying “patchy” supratentorial white matter and basal ganglia lesions that are not located within the parietooccipital cortexes (i.e., not typical of PRES) are likely related to underlying atherosclerosis because those lesions did not resolve over time. I also agree that the microhemorrhages noted on susceptibilityweighted imaging (SWI) within the pons and basal ganglia in patients 3 and 4 are likely related to underlying atherosclerosis from hypertension in PRES because the finding of chronic microhemorrhages in PRES due to hypertension has been recently described [8]. Meanwhile, in the two patients who underwent SWI who were not primarily hypertensive (patients 2 and 5; patient 1 never underwent SWI), there were no microhemorrhages within the brainstem or elsewhere. Because Gao and Lv [1] have proposed the theory that the residual lesions on FLAIR and the microhemorrhages on SWI may both be related to chronic underlying atherosclerosis from hypertension rather than PRES, the question arises whether such microhemorrhages, particularly in the brainstem, may be a factor that either portends or leads to centralvariant PRES. Hence, I then rereviewed the SWI examinations in the 31 patients from a prior study on SWI in PRES [8] in which 18 of 31 (58.1%) patients were found to have microhemorrhages on initial imaging (the vast majority of which were typically within the cortex or subcortical white matter) to evaluate for a difference in the number of brainstem pontine microhemorrhages in the 21 PRES patients in whom the primary cause was not hypertension versus those 10 patients who did present with solely hypertension. Interestingly, I subsequently found that only two of
10 patients who presented with hypertension as the primary cause (i.e., not on immunosuppressive therapy or pregnant) had microhemorrhages within the brainstem and had developed central-variant PRES (the same patients as patients 3 and 4 in the current study [7]), whereas none of the 21 PRES patients who underwent SWI who did not have primary hypertension had pontine microhemorrhages. Hence, a thorough discussion of all possible causes of central-variant PRES is speculative and beyond the scope of this response, but I thank the authors for raising a few interesting points that have made me rereview our PRES cases and may preliminarily provide insight into the pathophysiology of central-variant PRES. That rereview, albeit limited, seems to reveal that central-variant PRES only occurred in primarily hypertensive patients if there were microhemorrhages within the pons, and PRES patients in general lacking primary hypertension as the cause do not seem to experience brainstem microhemorrhages. Thus, pontine microhemorrhages may be implicated in or be a harbinger of central-variant PRES, but this needs to be studied prospectively or in a larger series of patients to discern what additional factors cause primarily hypertensive patients to develop central-variant PRES. I emphasize that this does not address why patients who are not primarily hypertensive, such as eclamptic patients or those on immunosuppressive medications, develop central-variant PRES; indeed, it is plausible that endothelial toxicity may act in concert with hypertension to cause centralvariant PRES in such patients. However, on the basis of the theory by Gao and Lv [1] and our preliminary data, hypertension certainly seems to play a major role in each case of central-variant PRES. Alexander M. McKinney Hennepin County Medical Center University of Minnesota Medical Center, Minneapolis, MN DOI:10.2214/AJR.14.12824 WEB—This is a web exclusive article.
References 1. Gao B, Lv C. Central-variant posterior reversible encephalopathy syndrome: more than meets the eye. (letter) AJR 2014; 203:[web]W454 2. McKinney AM, Short J, Truwit CL, et al. Poste-
AJR 2014; 203:W455 0361–803X/14/2034–W455 © American Roentgen Ray Society
AJR:203, October 2014 W455
Downloaded from www.ajronline.org by Iowa State University on 09/27/14 from IP address 129.186.1.55. Copyright ARRS. For personal use only; all rights reserved
Letters rior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR 2007; 189:904–912 3. Bartynski WS. Posterior reversible encephalopathy syndrome. Part 2. Controversies surrounding pathophysiology of vasogenic edema. AJNR 2008; 29:1043–1049 4. Horbinski C, Bartynski WS, Carson-Walter E, et al. Reversible encephalopathy after cardiac transplantation: histologic evidence of endothelial acti-
W456
vation, T-cell specific trafficking, and vascular endothelial growth factor expression. AJNR 2009; 30:588–590 5. Bartynski WS, Boardman JF. Distinct imaging patterns and lesion distribution in posterior reversible encephalopathy syndrome (PRES). AJNR 2007; 28:1320–1327 6. Edvinsson L, Owman C, Sjöberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels: a histochemical and pharmacologi-
cal study. Brain Res 1976; 115:377–393 7. McKinney AM, Jagadeesan BD, Truwit CL. Central-variant posterior reversible encephalopathy syndrome: brainstem or basal ganglia involvement lacking cortical or subcortical cerebral edema. AJR 2013; 201:631–638 8. McKinney AM, Sarikaya B, Gustafson C, Truwit CL. Detection of microhemorrhage in posterior reversible encephalopathy syndrome using susceptibility-weighted imaging. AJNR 2012; 33:896–903
AJR:203, October 2014
