Radiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cooney, M. J.
Right arrow Articles by Groncy, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cooney, M. J.
Right arrow Articles by Groncy, P. K.
(Radiology. 2000;214:711-716.)
© RSNA, 2000

Pediatric Imaging

Hypertensive Encephalopathy: Complication in Children Treated for Myeloproliferative Disorders-Report of Three Cases1

Michael J. Cooney, MD, William G. Bradley, MD, PhD, Sophia C. Symko, MD, Sangita T. Patel, MD and Paula K. Groncy, MD

1 From the Departments of Radiology (M.J.C., W.G.B., S.C.S., S.T.P.) and Pediatric Oncology (P.K.G.), Long Beach Memorial Medical Center, 403 E Columbia St, Long Beach, CA 90806. From the 1997 RSNA scientific assembly. Received November 9, 1998; revision requested December 29; revision received May 24, 1999; accepted June 29. Address reprint requests to W.G.B. (e-mail: wgbradley@pol.net).


   Abstract
TOP
 Abstract
Introduction
 Case Reports
 Discussion
 References
 
We routinely perform echo-planar diffusion-weighted sequences in all brain magnetic resonance (MR) imaging studies. When three children undergoing chemotherapy for acute leukemia presented with seizures, conventional MR images demonstrated what appeared to be acute, posterior, parasagittal infarcts. However, diffusion-weighted images were normal. These MR imaging findings were consistent with those of hypertensive encephalopathy. Early recognition and treatment of minimal hypertension in these patients allows reversal of encephalopathy.

Index terms: Brain, diseases, 10.64 • Brain, MR, 10.121411, 10.121413, 10.121416, 10.12143 • Chemotherapy, complications, 10.64 • Hypertension • Magnetic resonance (MR), in infants and children, 10.121411, 10.121413, 10.121416, 10.12143


   Introduction
TOP
 Abstract
 Introduction
Case Reports
 Discussion
 References
 
The importance of distinguishing the complications of combination chemotherapy and radiation therapy due to direct toxic reactions to drugs from the complications due to other causes is vital. A child with infectious encephalitis, altered coagulation, or correctable metabolic disorders requires therapy that is entirely different from that of a child with toxic reactions to drugs or radiation.

We identify hypertensive encephalopathy as a reversible cause of acute neurologic complications in pediatric patients who are being treated for myeloproliferative disorders. Several patients who developed acute neurologic changes had magnetic resonance (MR) imaging findings identical to those of hypertensive encephalopathy. MR imaging findings alone suggested the diagnosis. This led to a retrospective confirmation of coincident hypertension and clinical signs supportive of the diagnosis. We review the signs, symptoms, and MR imaging findings in this group of pediatric patients.


   Case Reports
TOP
 Abstract
 Introduction
 Case Reports
Discussion
 References
 
One of our pediatric oncologists (P.K.G.) suspected that L–asparaginase had caused a stroke in a pediatric patient who was being treated for acute lymphocytic leukemia and invited us to discuss the imaging findings at one of our multidisciplinary teaching conferences. The imaging findings, however, were consistent with hypertensive encephalopathy, not cerebral infarction. This case became our index case 1.

After we identified this case, we actively sought new cases with similar imaging findings in children who underwent imaging during the next 6 months. This prospectively yielded case 2. After we identified these two cases, we retrospectively reviewed all brain MR imaging studies performed in all pediatric patients who were being treated for myeloproliferative disorders during the preceding year. This retrospective review yielded case 3.

Of 50 patients who were treated during 18 months, 12 underwent brain MR imaging. We limited our evaluation to only those patients who developed acute neurologic symptoms and who had an abnormal brain MR image that was obtained within 12 hours of the onset of symptoms. Five such patients were identified.

One patient had an occipital lobe hematoma presumed to be secondary to profound thrombocytopenia (platelet count, 50 x 109/L). One patient had multiple bilateral cerebral infarctions that were proved at autopsy to be secondary to septic emboli caused by Aspergillus organisms. Both of these patients were normotensive at clinical examination.

Three patients with documented hypertension developed acute neurologic symptoms including seizures, disorientation, headache, focal weakness, and/or hemiparesis. Brain MR images in these patients demonstrated bilateral, nearly symmetric, paramedian supratentorial and cerebellar areas of reversible high signal intensity. Diffusion-weighted images were normal. These findings were identical to those previously described in hypertensive encephalopathy–induced cerebral edema (1–4). In two patients, resolution of hypertension led to resolution of clinical symptoms and brain MR imaging findings. In one patient, regions on T2-weighted images with mixed reversible and irreversible abnormal signal intensity suggested the presence of hypertensive encephalopathy–induced cerebral edema and hypertensive encephalopathy–induced cerebral infarction; these regions had normal and abnormal signal intensity, respectively, on diffusion-weighted images.

Brain MR imaging was performed at 1.5 T with either a 25 mT/m gradient and a 300-µsec rise time (Vision; Siemens, Iselin, NJ) or a 23 mT/m gradient and a 180-µsec rise time (Horizon EchoSpeed; GE Medical Systems, Milwaukee, Wis). Imaging sequences included conventional spin-echo intermediate-weighted sequences, T2-weighted sequences, fluid-attenuated inversion-recovery (FLAIR) sequences, pre- and postcontrast T1-weighted sequences, and echo-planar diffusion-weighted sequences applied along three axes (b = 1,000 sec/mm2).

Case 1
A 4-year-old boy undergoing delayed intensification chemotherapy (Children's Cancer Group protocol 1882 [5]) for acute lymphocytic leukemia presented with headache and a focal seizure involving the right leg, which became generalized. Symptoms progressed to right hemiparesis, and the patient became obtunded. The patient's blood pressure was 147/107 mm Hg at that time. FLAIR images of the brain (Fig 1a) showed bilateral parietal, occipital, and, to a lesser extent, frontal areas of high signal intensity. Diffusion-weighted images were normal (Fig 1b). Clinical symptoms resolved within 24 hours, and the patient's blood pressure returned to normal. FLAIR images obtained at 2-month follow-up (Fig 1c) showed complete resolution of the areas of abnormal signal intensity. Diffusion-weighted images remained normal. Findings of areas of reversible high signal intensity on FLAIR images with areas of normal signal intensity on diffusion-weighted images were consistent with those of hypertensive encephalopathy–induced edema.



View larger version (128K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1a. Case 1. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse FLAIR image (9,000/105/2,400 [repetition time msec/echo time msec/inversion time msec]) demonstrates bilateral, symmetric, paramedian, parietal, and occipital areas of high signal intensity (arrows) with sulcal effacement. (b) Initial transverse echo-planar diffusion-weighted image (4,200/118; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse FLAIR image (9,000/105/2,400) obtained at 2-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 


View larger version (132K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1b. Case 1. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse FLAIR image (9,000/105/2,400 [repetition time msec/echo time msec/inversion time msec]) demonstrates bilateral, symmetric, paramedian, parietal, and occipital areas of high signal intensity (arrows) with sulcal effacement. (b) Initial transverse echo-planar diffusion-weighted image (4,200/118; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse FLAIR image (9,000/105/2,400) obtained at 2-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 


View larger version (131K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 1c. Case 1. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse FLAIR image (9,000/105/2,400 [repetition time msec/echo time msec/inversion time msec]) demonstrates bilateral, symmetric, paramedian, parietal, and occipital areas of high signal intensity (arrows) with sulcal effacement. (b) Initial transverse echo-planar diffusion-weighted image (4,200/118; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse FLAIR image (9,000/105/2,400) obtained at 2-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 
Case 2
An 11-year-old girl presented with headache, seizures, and disorientation while undergoing intensification chemotherapy for a relapse of acute lymphocytic leukemia 6 years after bone marrow transplantation (Children's Cancer Group protocol 1941 [6]). Her blood pressure was 154/114 mm Hg. T2-weighted images of the brain (Fig 2a) showed bilateral parietal and occipital areas of high signal intensity. Diffusion-weighted images were normal (Fig 2b). Clinical symptoms completely resolved within 24 hours, and the patient's blood pressure returned to normal. T2-weighted images obtained at 4-month follow-up (Fig 2c) showed complete resolution of the areas of abnormal signal intensity. Diffusion-weighted images remained normal. Findings of areas of reversible high signal intensity on T2-weighted images with areas of normal signal intensity on diffusion-weighted images were consistent with those of hypertensive encephalopathy–induced edema.



View larger version (186K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2a. Case 2. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (2,500/90) demonstrates bilateral parietal and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (20,000/109; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 4-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 


View larger version (149K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2b. Case 2. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (2,500/90) demonstrates bilateral parietal and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (20,000/109; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 4-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 


View larger version (183K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 2c. Case 2. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (2,500/90) demonstrates bilateral parietal and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (20,000/109; b = 1,000 sec/mm2) is normal, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 4-month follow-up demonstrates complete resolution of the areas of high signal intensity.

 
Case 3
An 11-year-old girl undergoing induction chemotherapy for acute lymphocytic leukemia (Children's Cancer Group 1961 high-risk protocol [7]) presented with headache, seizures, and weakness in the right arm, which progressed to hemiparesis in the right arm. Her blood pressure was 150/98 mm Hg. T2-weighted images of the brain showed sulcal effacement in the occipital lobe with patchy areas of high signal intensity (Fig 3a), and diffusion-weighted images of the occipital lobes showed areas of normal signal intensity (Fig 3b). The patient had a slow but complete neurologic recovery. T2-weighted images of the occipital lobes obtained at 2-week follow-up showed resolution of the areas of high signal intensity (Fig 3c). Diffusion-weighted images remained normal. These findings were consistent with those of hypertensive encephalopathy–induced edema.



View larger version (174K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3a. Case 3. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) is normal in these regions, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 2-week follow-up demonstrates complete resolution of the occipital areas of high signal intensity.

 


View larger version (175K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3b. Case 3. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) is normal in these regions, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 2-week follow-up demonstrates complete resolution of the occipital areas of high signal intensity.

 


View larger version (174K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 3c. Case 3. Reversible hypertensive encephalopathy-induced cerebral edema. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, and occipital areas of high signal intensity (arrows). (b) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) is normal in these regions, without evidence of cytotoxic edema. (c) Transverse T2-weighted image (3,000/80) obtained at 2-week follow-up demonstrates complete resolution of the occipital areas of high signal intensity.

 
Additional patchy areas of high signal intensity on T2-weighted images (Fig 4a), gyriform swelling without hemorrhage (Fig 4b), and areas of abnormal increased signal intensity on diffusion-weighted images (Fig 4c) were noted in the posterior high frontal and parietal lobes near the cerebral convexities. MR images obtained at 2-week follow-up showed persistent areas of high signal intensity in these regions, with loss of white matter volume, gliosis, and gyriform petechial hemorrhage (Fig 4d, 4e). Diffusion-weighted images returned to normal. These findings were consistent with those of hypertensive encephalopathy–induced cerebral infarction. Findings of areas of high signal intensity on T2-weighted images and areas of abnormal signal intensity on diffusion-weighted images were consistent with those of cytotoxic edema.



View larger version (188K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4a. Case 3. Irreversible hypertensive encephalopathy-induced cerebral infarction. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, high frontal, and parietal areas of high signal intensity (arrows). (b) Initial transverse gadolinium-enhanced T1-weighted image (500/200) demonstrates gyriform edema (arrows) in these regions, without evidence of hemorrhage. (c) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) demonstrates areas of increased signal intensity (arrows) that suggest cytotoxic edema from acute infarction. (d) Follow-up transverse T2-weighted image (3,000/80) demonstrates persistent areas of high signal intensity (arrows) in the paramedian, posterior high frontal, and parietal lobes, with white matter volume loss and gliosis. (e) Follow-up transverse nonenhanced T1-weighted image (650/17) shows gyriform areas of increased signal intensity (arrows) that are consistent with subacute infarction.

 


View larger version (173K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4b. Case 3. Irreversible hypertensive encephalopathy-induced cerebral infarction. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, high frontal, and parietal areas of high signal intensity (arrows). (b) Initial transverse gadolinium-enhanced T1-weighted image (500/200) demonstrates gyriform edema (arrows) in these regions, without evidence of hemorrhage. (c) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) demonstrates areas of increased signal intensity (arrows) that suggest cytotoxic edema from acute infarction. (d) Follow-up transverse T2-weighted image (3,000/80) demonstrates persistent areas of high signal intensity (arrows) in the paramedian, posterior high frontal, and parietal lobes, with white matter volume loss and gliosis. (e) Follow-up transverse nonenhanced T1-weighted image (650/17) shows gyriform areas of increased signal intensity (arrows) that are consistent with subacute infarction.

 


View larger version (164K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4c. Case 3. Irreversible hypertensive encephalopathy-induced cerebral infarction. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, high frontal, and parietal areas of high signal intensity (arrows). (b) Initial transverse gadolinium-enhanced T1-weighted image (500/200) demonstrates gyriform edema (arrows) in these regions, without evidence of hemorrhage. (c) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) demonstrates areas of increased signal intensity (arrows) that suggest cytotoxic edema from acute infarction. (d) Follow-up transverse T2-weighted image (3,000/80) demonstrates persistent areas of high signal intensity (arrows) in the paramedian, posterior high frontal, and parietal lobes, with white matter volume loss and gliosis. (e) Follow-up transverse nonenhanced T1-weighted image (650/17) shows gyriform areas of increased signal intensity (arrows) that are consistent with subacute infarction.

 


View larger version (189K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4d. Case 3. Irreversible hypertensive encephalopathy-induced cerebral infarction. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, high frontal, and parietal areas of high signal intensity (arrows). (b) Initial transverse gadolinium-enhanced T1-weighted image (500/200) demonstrates gyriform edema (arrows) in these regions, without evidence of hemorrhage. (c) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) demonstrates areas of increased signal intensity (arrows) that suggest cytotoxic edema from acute infarction. (d) Follow-up transverse T2-weighted image (3,000/80) demonstrates persistent areas of high signal intensity (arrows) in the paramedian, posterior high frontal, and parietal lobes, with white matter volume loss and gliosis. (e) Follow-up transverse nonenhanced T1-weighted image (650/17) shows gyriform areas of increased signal intensity (arrows) that are consistent with subacute infarction.

 


View larger version (175K):
[in this window]
[in a new window]
[Download PPT slide]
  		Figure 4e. Case 3. Irreversible hypertensive encephalopathy-induced cerebral infarction. (a) Initial transverse T2-weighted image (3,000/90) demonstrates bilateral, symmetric, paramedian, high frontal, and parietal areas of high signal intensity (arrows). (b) Initial transverse gadolinium-enhanced T1-weighted image (500/200) demonstrates gyriform edema (arrows) in these regions, without evidence of hemorrhage. (c) Initial transverse echo-planar diffusion-weighted image (10,000/121; b = 1,000 sec/mm2) demonstrates areas of increased signal intensity (arrows) that suggest cytotoxic edema from acute infarction. (d) Follow-up transverse T2-weighted image (3,000/80) demonstrates persistent areas of high signal intensity (arrows) in the paramedian, posterior high frontal, and parietal lobes, with white matter volume loss and gliosis. (e) Follow-up transverse nonenhanced T1-weighted image (650/17) shows gyriform areas of increased signal intensity (arrows) that are consistent with subacute infarction.

 

   Discussion
TOP
 Abstract
 Introduction
 Case Reports
 Discussion
References
 
Hypertensive encephalopathy, described in 1928 by Oppenheimer and Fishberg (8), is a specific clinical syndrome characterized by acute neurologic change in the setting of sudden and/or prolonged hypertension that overcomes the autoregulatory capacity of the cerebral vasculature. It is a subset of the more generalized reversible posterior leukoencephalopathy syndrome (9,10). At clinical examination, the neurologic manifestations include headache, nausea, vomiting, seizures, convulsions, visual changes, confusion, and coma (11). Although myocardial, renal, hepatic, and hematologic manifestations exist, they are less easily identified. Treatment of hypertension often leads to complete neurologic recovery. Untreated hypertension can lead to progressive central nervous system failure with intracranial hemorrhage, irreversible cerebral infarction, coma, and death (12).

Hypertensive encephalopathy occurs most commonly in adult patients who have an abrupt elevation in systemic blood pressure. It often occurs in association with essential or severe chronic hypertension, renal disease, collagen-vascular disease, mixed connective-tissue disorders, endocrine abnormalities, preeclampsia-eclampsia syndrome, and/or use of immunosuppressive medications (most notably cyclosporine) (9,13–20).

Hypertensive encephalopathy is rare in the pediatric population. When present, it is usually related to renal diseases such as acute glomerulonephritis, renal vascular hypertension, or chronic renal failure from any cause (21–23). As in the adult population, hypertensive encephalopathy may also occur with an acute abrupt elevation in blood pressure. Since there are age-dependent normal ranges of blood pressure in pediatric patients, the requirement for blood pressure to exceed a particular value is inappropriate as the sole criterion for the diagnosis of hypertension. The diagnosis of hypertensive encephalopathy should be made in children who demonstrate a change in neurologic function that is coincident with an elevation in blood pressure above the age-dependent normal range and in whom other causes of acute encephalopathy have been excluded (21).

Physiologic autoregulatory modulation of precapillary arteriolar vasomotor tone maintains a constant cerebral perfusion pressure despite fluctuations in systemic blood pressure (24,25). Perivascular sympathetic tone is increased in the setting of hypertension and serves to protect the brain from increased intravascular pressure. Initial investigators (26–28) postulated that hypertensive encephalopathy was the result of uncontrolled autoregulatory vasoconstriction that led to hypoperfusion, with focal areas of ischemia and infarction. Although some controversy still persists about the exact mechanism that leads to hypertensive encephalopathy, it is now generally believed that cerebral vascular vasodilatation caused by high-pressure autoregulatory failure is the pathophysiologic mechanism (1,4,13,20,24,29,30). Increased vascular permeability results in cerebral edema due to extravasation and transudation of protein and fluid into the brain parenchyma. The relative paucity of sympathetic innervation to the posterior circulation compared with that of the anterior circulation likely accounts for the resultant distribution of changes with a preponderance of posterior circulatory changes (25,26,31).

Neurologic MR imaging and computed tomographic findings consistent with those of hypertensive encephalopathy have been described previously; these include reversible and predominantly posterior temporal, parietal, and occipital edema that is preferentially located in the paramedian subcortical white matter. In cases of mild hypertension, the findings are usually supratentorial; in cases of more severe hypertension, similar changes are noted in the basal ganglia, cerebellar hemispheres, and brainstem (1–4).

Neurologic findings at follow-up imaging reflect the clinical outcome. With control of hypertension and reversal of symptoms, the imaging findings normalize. If left untreated, hypertension leads to progressive neurologic deterioration, and images demonstrate progressive areas of abnormal signal intensity that reflect hypertensive encephalopathy–induced ischemia, infarction, and/or hemorrhage.

Given that hypertension is uncommon in the pediatric population and that the findings of hypertensive encephalopathy are nonspecific and reversible, it has been suggested that the diagnosis is often unrecognized, and its true prevalence may be underestimated (22). It should be noted that, in all of our cases, the clinical diagnosis was made only because we suggested it by recognizing the imaging findings that supported the diagnosis. The syndrome would otherwise likely have gone undiagnosed.

In both of the patients in whom the diagnosis of hypertensive encephalopathy was made retrospectively (cases 1 and 3), the presence of hypertension at the time of initial presentation was confirmed. In case 1, the hypertension was empirically treated with a single dose of nifedipine. In case 3, no treatment was instituted, and the hypertension resolved on its own. The acute neurologic changes and initial imaging findings, however, were initially attributed to a direct neurotoxic complication due to L–asparaginase, one of the chemotherapeutic agents used in the patients' treatment regimens. L–Asparaginase has been implicated as the causative agent in a number of cerebrovascular complications in children who are being treated for acute lymphocytic leukemia (32–34).

Both of the patients' treatment protocols were revised, and L-asparaginase was withheld on the presumption that it was the offending agent. Although both patients improved clinically, with eventual near-complete resolution of neurologic abnormalities, an association between the patients' hypertension and clinical symptoms was not made at the time.

Both patients had normal blood pressure and no clinical symptoms at follow-up. The patient in case 1 had initial and follow-up imaging findings that were consistent with those of reversible hypertensive encephalopathy–induced cerebral edema (Fig 1). The patient in case 3 had initial and follow-up imaging findings that were consistent with a combination of reversible hypertensive encephalopathy–induced cerebral edema and irreversible hypertensive encephalopathy–induced cerebral infarction (Fig 3). We suggested that both patients' symptoms and imaging findings were consistent with those of hypertensive encephalopathy. After several multidisciplinary conferences, the diagnoses were revised, and both patients received additional doses of L-asparaginase without incident.

In our prospectively identified case 2, the diagnosis of hypertensive encephalopathy was suggested at the time of initial imaging. Hypertension (blood pressure, 154/114 mm Hg) was documented and treated. Clinical symptoms resolved, and imaging findings returned to normal. Because we appropriately identified and promptly treated the syndrome, the symptoms resolved, and the patient's chemotherapeutic treatment protocol was not altered.

In our review, we did not identify any normotensive patient with imaging findings that were similar to those seen in the patients with hypertensive encephalopathy. We did not identify any patient with the clinical symptoms of hypertensive encephalopathy who did not have the typical MR imaging findings of hypertensive encephalopathy.

Whether the hypertensive encephalopathy seen in these patients is a complication of the use of a particular drug (ie, a direct neurotoxic effect on the vascular endothelium), combination of drugs, or treatment regimen is unclear. Any number of additional unknown or complicating factors may have come into play. It is interesting to note, however, that the large body of literature on central nervous system complications associated with L-asparaginase (32–34) focuses on thromboembolic and/or hemorrhagic events, both of which can be seen as the result of untreated hypertensive encephalopathy. Further investigation of the potential role of hypertensive encephalopathy in the development of neurologic complications associated with L-asparaginase may be indicated.

Whatever the cause of hypertensive encephalopathy in this patient population, recognition of the syndrome allows appropriate clinical management with targeted treatment of hypertension.

In conclusion, hypertensive encephalopathy is an often unrecognized reversible complication that occurs in children who are being treated with multidrug chemotherapy and radiation therapy for myeloproliferative disorders. It is a specific subtype of the more generalized reversible posterior leukoencephalopathy syndrome. It has unique clinical and neuroimaging findings that allow its distinction from other causes of acute neurologic change or encephalopathy that can occur in these patients.

Early recognition of hypertensive encephalopathy as posterior parietal parasagittal areas of high signal intensity on T2-weighted images and normal signal intensity on diffusion-weighted images allows the institution of appropriate antihypertensive treatment when the potential for complete neurologic recovery still exists. Failure to recognize this syndrome may lead to progressive, irreversible neurologic deterioration with cerebral ischemia and infarction. In this patient population, it can also lead to alterations in treatment regimens, with the potential to discontinue the use of chemotherapeutic agents that have been proved to be highly efficacious in the treatment of such disorders.


   Footnotes
 
Abbreviation: FLAIR = fluid-attenuated inversion recovery

Author contributions: Guarantors of integrity of entire study, M.J.C., W.G.B.; study concepts and design, M.J.C., W.G.B.; definition of intellectual content, M.J.C., W.G.B.; literature research, M.J.C., S.C.S.; clinical studies, P.K.G.; data acquisition, M.J.C., S.C.S., S.T.P.; data analysis, M.J.C., S.C.S.; manuscript preparation, M.J.C., S.C.S., W.G.B.; manuscript editing, M.J.C., W.G.B.; manuscript review, W.G.B., S.T.P., P.K.G.


   References
TOP
 Abstract
 Introduction
 Case Reports
 Discussion
 References
 

  1. Schwartz RB, Jones KM, Kalina P, et al. Hypertensive encephalopathy: findings on CT, MR imaging and SPECT imaging in 14 cases. AJR Am J Roentgenol 1992; 159:379-383.[Abstract/Free Full Text]
  2. Weingarten K, Barbut D, Filippi C, Zimmerman RD. Acute hypertensive encephalopathy: findings on spin-echo and gradient-echo MR imaging. AJR Am J Roentgenol 1994; 162:665-670.[Abstract/Free Full Text]
  3. Schaeffer PW, Buonanno FS, Gonzalez RG, Schwamm LH. Diffusion-weighted imaging discriminates between cytotoxic and vasogenic edema in a patient with eclampsia. Stroke 1997; 28:1082-1085.[Abstract/Free Full Text]
  4. Schwartz RB, Mulkern RV, Gudbjartsson H, Jolesz F. Diffusion-weighted MR imaging in hypertensive encephalopathy: clues to pathogenesis. AJNR Am J Neuroradiol 1998; 19:859-862.[Abstract]
  5. Nachman JB, Sather HN, Sensel MG, et al. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 1998; 338:1663-1671.[Abstract/Free Full Text]
  6. Zipf TF, Johnston DA, Ouspenskaia MV, et al. Levels of residual childhood acute lymphoblastic leukemia at the end of 6-drug intensive reinduction after marrow relapse are similar to those from newly diagnosed patients at the end of 3- or 4-drug induction (abstr). Blood 1997; 90(suppl 1):182-183.[Abstract/Free Full Text]
  7. Sun L, Goodman PA, Wood CM, et al. Expression of aberrantly spliced oncogenic Ikaros isoforms in childhood acute lymphoblastic leukemia. J Clin Oncol 1999; 17:3753-3766.[Abstract/Free Full Text]
  8. Oppenheimer BS, Fishberg AM. Hypertensive encephalopathy. Arch Intern Med 1928; 41:264-278.[Abstract/Free Full Text]
  9. Hinchy J, Chaves C, Appignani B, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334:494-500.[Abstract/Free Full Text]
  10. Bakshi R, Bates VE, Mechtler LL, Kinkel WR. Occipital lobe seizures as the major manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings. Epilepsia 1998; 39:295-299.[Medline]
  11. Dinsdale HB. Hypertensive encephalopathy. Neurol Clin 1983; 1:3-16.[Medline]
  12. Calhoun DA, Oparil S. Treatment of hypertensive crisis. N Engl J Med 1990; 323:1177-1183.[Medline]
  13. Port JD, Beauchamp NJ, Jr. Reversible intracerebral pathologic entities mediated by vascular autoregulatory dysfunction. RadioGraphics 1998; 18:353-367.[Abstract]
  14. Sanders TG, Clayman DA, Sanchez-Ramos L, Vines FS, Russo L. Brain in eclampsia: MR imaging with clinical correlation. Radiology 1991; 180:475-478.[Abstract/Free Full Text]
  15. Merimsky O, Chaitchik S. Neurotoxicity of interferon-alpha. Anticancer Drugs 1992; 3:567-570.[Medline]
  16. Vaughn DJ, Jarvik JG, Hackney D, Peters S, Stadtmauer EA. High-dose cytarabine neurotoxicity: MR findings during the acute phase. AJNR Am J Neuroradiol 1993; 14:1014-1016.[Abstract]
  17. Cohen RB, Abdallah JM, Gray JR, Foss F. Reversible neurologic toxicity in patients treated with standard-dose fludarabine phosphate for mycosis fungoides and chronic lymphocytic leukemia. Ann Intern Med 1993; 118:114-116.[Abstract/Free Full Text]
  18. Ito Y, Arahata Y, Goto Y, et al. Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy syndrome. AJNR Am J Neuroradiol 1998; 19:415-417.[Abstract]
  19. Truwit CL, Denarco CP, Lake JR, DeMarco T. MR imaging of reversible cyclosporin A–induced neurotoxicity. AJNR Am J Neuroradiol 1991; 12:651-659.[Abstract]
  20. Schwartz RB, Bravo SM, Klufas RA, et al. Cyclosporine neurotoxicity and its relationship to hypertensive encephalopathy: CT and MR findings in 16 cases. AJR Am J Roentgenol 1995; 165:627-631.[Abstract/Free Full Text]
  21. Wright RR, Mathews KD. Hypertensive encephalopathy in childhood. J Child Neurol 1996; 11:193-196.[Abstract/Free Full Text]
  22. Jones BV, Egelhoff JC, Petterson J. Hypertensive encephalopathy in children. AJNR Am J Neuroradiol 1997; 18:101-106.[Abstract]
  23. Kandt RS, Caoili AQ, Lorentz WB, Elster AD. Hypertensive encephalopathy in children: neuroimaging and treatment. J Child Neurol 1995; 10:236-239.[Free Full Text]
  24. Strandgaard S, Paulson OB. Cerebral autoregulation. Stroke 1984; 15:413-416.[Free Full Text]
  25. Beausang-Linder M, Bill A. Cerebral circulation in acute arterial hypertension: protective effects of sympathetic nervous activity. Acta Physiol Scand 1981; 111:193-199.[Medline]
  26. MacKenzie ET, Strandgaard S, Graham DI, Jones JV, Harper AM, Farrar JK. Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Circ Res 1976; 39:33-41.[Abstract/Free Full Text]
  27. Byrom FB. The pathogenesis of hypertensive encephalopathy and its relation to the malignant phase of hypertension. Lancet 1954; 2:201-211.
  28. Trommer BL, Homer D, Mikhael MA. Cerebral vasospasm and eclampsia. Stroke 1988; 19:326-329.[Abstract/Free Full Text]
  29. Nag S, Robertson DM, Dinsdale HB. Cerebral cortical changes in acute hypertension: an ultrastructural study. Lab Invest 1977; 39:150-161.
  30. Skinhoj E, Strandgaard S. Pathogenesis of hypertensive encephalopathy. Lancet 1973; 1:461-462.[Medline]
  31. Edvinsson L, Owman C, Sjoberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels: histochemical and pharmacologic study. Brain Res 1976; 115:377-393.[Medline]
  32. Feinberg WM, Swenson MR. Cerebrovascular complications of L-asparaginase therapy. Neurology 1988; 38:127-133.[Abstract/Free Full Text]
  33. Gugliotta L, Mazzucconi MG, Leone G, et al. Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L-asparaginase during induction therapy: a retrospective study. Eur J Haematol 1992; 49:63-66.[Medline]
  34. Kingma A, Tamminga RY, Kamps WA, Le Coultre R, Saan RJ. Cerebrovascular complications of L-asparaginase therapy in children with leukemia: aphasia and other neuropsychological deficits. Pediatr Hematol Oncol 1993; 10:303-309.[Medline]



This article has been cited by other articles:


Home page
 RadiologyHome page
C. L. Hollingsworth, D. P. Frush, J. Kurtzburg, and V. K. Prasad
Pediatric Hematopoietic Stem Cell Transplantation and the Role of Imaging
Radiology, August 1, 2008; 248(2): 348 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Neuroradiol.Home page
W.S. Bartynski
Posterior Reversible Encephalopathy Syndrome, Part 1: Fundamental Imaging and Clinical Features
AJNR Am. J. Neuroradiol., June 1, 2008; 29(6): 1036 - 1042.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. M. Pinedo, F. Shah-Khan, and P. C. Shah
Reversible Posterior Leukoencephalopathy Syndrome Associated With Oxaliplatin
J. Clin. Oncol., November 20, 2007; 25(33): 5320 - 5321.
[Full Text] [PDF]

Home page
 Br. J. Radiol.Home page
N Prasad, S Gulati, R K Gupta, K Sharma, K Gulati, R K Sharma, and A Gupta
Spectrum of radiological changes in hypertensive children with reversible posterior leucoencephalopathy
Br. J. Radiol., June 1, 2007; 80(954): 422 - 429.
[Abstract] [Full Text] [PDF]

Home page
 J Child NeurolHome page
H. Ozyurek, G. Oguz, S. Ozen, C. Akyuz, K. K. Oguz, B. Anlar, and S. Aysun
Reversible Posterior Leukoencephalopathy Syndrome: Report of Three Cases
J Child Neurol, December 1, 2005; 20(12): 990 - 993.
[Abstract] [PDF]

Home page
 RadioGraphicsHome page
E. Vazquez, J. Lucaya, A. Castellote, J. Piqueras, P. Sainz, T. Olive, J. Sanchez-Toledo, and J. J. Ortega
Neuroimaging in Pediatric Leukemia and Lymphoma: Differential Diagnosis
RadioGraphics, November 1, 2002; 22(6): 1411 - 1428.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Neuroradiol.Home page
D. J. Covarrubias, P. H. Luetmer, and N. G. Campeau
Posterior Reversible Encephalopathy Syndrome: Prognostic Utility of Quantitative Diffusion-Weighted MR Images
AJNR Am. J. Neuroradiol., June 1, 2002; 23(6): 1038 - 1048.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Neuroradiol.Home page
J. M. Provenzale, J. R. Petrella, L. C. H. Cruz Jr, J. C. Wong, S. Engelter, and D. P. Barboriak
Quantitative Assessment of Diffusion Abnormalities in Posterior Reversible Encephalopathy Syndrome
AJNR Am. J. Neuroradiol., September 1, 2001; 22(8): 1455 - 1461.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cooney, M. J.
Right arrow Articles by Groncy, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cooney, M. J.
Right arrow Articles by Groncy, P. K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
RADIOLOGY RADIOGRAPHICS RSNA JOURNALS ONLINE