Abstract
Predominant brainstem or cerebellar edema is rare in hypertensive encephalopathy and usually affects patients with secondary hypertension. Despite the severity of the radiologic findings, clinical features of brainstem involvement are uncommon. The authors report the clinical and radiologic features of two patients.
Hypertensive encephalopathy (HE) is characterized by severe hypertension, confusion, visual complaints, headache, stupor, and seizures.1 Because CT scan and MRI frequently show edema in the occipital regions, the term “posterior reversible leukoencephalopathy” has been used.1-4⇓⇓⇓ Primary involvement of the brainstem or cerebellum has been reported, but little is known about precipitating factors, course, neuroimaging characteristics, or outcome.
Patients and methods.
We describe two patients seen at St. Louis University Hospital. We searched the MEDLINE databases from 1966 to date using the MeSH terms hypertensive encephalopathy, hypertension, encephalopathy, brainstem, imaging, CT, and MRI. We included articles published in English describing patients with enough clinical and imaging detail to ascertain age, gender, comorbidities, temporal profile, symptoms, physical findings, neuroimaging, and outcome. We regarded clinical and radiologic features as present if they were described and absent if they were either negative or not mentioned.
Case reports.
Case 1.
A 38-year-old man with sickle cell disease, hypertension, chronic renal insufficiency (CRI), and ethanol and marijuana abuse had nausea, vomiting, headache, “blurred vision,” and tremor. He had a generalized tonic-clonic seizure. His blood pressure was 280/160 mm Hg. He was drowsy, disoriented, and dysarthric. He had limited upward gaze, mild left facial weakness, and strength of 3/5 throughout. His deep tendon reflexes were brisk, and he had bilateral extensor responses.
Head CT showed his brainstem with a low attenuation consistent with edema. Brain MRI showed areas of increased signal from the medulla to the diencephalon and few areas in the left occipital lobe, bilateral basal ganglia, and cerebellum by fluid-attenuated inversion recovery (FLAIR) and T2-weighted images (figure 1, A and B). Diffusion-weighted imaging (DWI) was normal (figure 1C). There was no contrast enhancement. He improved after his blood pressure was controlled. A repeated MRI showed resolution of the abnormalities (figure 1D). He was discharged 14 days later with mild dysarthria and ataxia.
Figure 1. Initial MRI findings. (A) T1-weighted image. (B) Fluid-attenuated inversion recovery (FLAIR) image. (C) Diffusion-weighted image. (D) FLAIR image at follow-up evaluation.
Case 2.
A 30-year-old woman with systemic lupus erythematosus (SLE), antiphospholipid antibodies, hypertension, anemia, cardiomyopathy, and CRI had nausea and headache. Her initial blood pressure was 230/150 mm Hg. She had a generalized tonic-clonic seizure. Postictally she had blindness and became agitated. After a second seizure, she had a cardiac arrest and was successfully resuscitated.
A CT before cardiac arrest revealed hypodense areas in the cerebellum and less marked changes in the occipital lobes. Brain MRI revealed areas of high signal in the cerebellum and scattered areas in the occipital lobes (figure 2, A through C) by FLAIR but normal signal by DWI. Head CT 2 days later revealed cerebellar edema with compression of the fourth ventricle and resultant hydrocephalus (figure 3). A ventriculostomy was placed. She remained comatose. After the blood pressure was controlled, a repeated MRI showed resolution of the abnormalities (figure 2D). She died after sepsis.
Figure 2. Initial MRI (A) and fluid-attenuated inversion recovery (FLAIR; B) sequence. (C) Diffusion-weighted image. (D) FLAIR image at follow-up evaluation.
Figure 3. CT scan demonstrating compression of basal cisterns and hydrocephalus.
Results.
Literature review.
MEDLINE search yielded 190 articles; 174 were excluded because of lack of adequate clinical or imaging data. Only three of the excluded articles included patients with the brainstem variant. Fifteen reports of 21 patients met inclusion criteria (see Appendix E-1 on the Neurology Web site). Including our 2 patients, we had 23 patients for descriptive analysis.
Clinical presentation.
Mean age at onset was 42 years; 12 were men. All patients had hypertension; 8 (34%) had hypertension alone; the rest had comorbidities, including renal failure (10), eclampsia (3), pheochromocytoma (2), SLE (2), hyperaldosteronism (1), sickle cell disease (1), and cocaine use (1). Time from onset of symptoms to diagnosis was 24 hours (range, 3 to 120 hours). Headache (73%), nausea or vomiting (43%), blurred vision (34%), abnormal gait (26%), coma (23%), seizures (17%), and paresis (9%) were the most frequently reported symptoms at onset. Mean systolic blood pressure was 230 mm Hg, whereas mean diastolic blood pressure was 140 mm Hg. Two-thirds of patients had symptoms of encephalopathy. Signs of brainstem dysfunction were noted in <25%. All but one patient survived. Cause of death was not related to HE.
Neuroimaging.
Sixteen patients underwent brain CT. Fifteen had low attenuation abnormalities in the brainstem or cerebellum. A lacunar infarct was found in one patient. Twenty patients had MRI. In all those patients, abnormalities were described as areas of high signal intensity in FLAIR (10) and T2-weighted (19) images. Five of seven patients had a normal DWI; two had mixed signal intensity. Two patients had an apparent diffusion coefficient (ADC) map that showed high signal in one and mixed signal in the other.
The regions affected were pons in 19 patients (82%), midbrain in 16 (70%), cerebellum in 10 (43%), deep white matter in 6 (26%), thalamus in 5 (22%), medulla in 3 (13%), occipital lobe in 2 (9%), and basal ganglia in 2 (9%). Eighteen patients (78%) had edema and mass effect, and 7 (30%) had hydrocephalus. In all patients, the abnormalities resolved after blood pressure was controlled. Imaging improvement was documented as early as 5 days after initial scan.
Discussion.
The prevalence of HE is not known. Hypertensive crises explain 27% of all medical emergencies. Hypertensive crises with evidence of acute end-organ injury, such as stroke, pulmonary edema, congestive heart failure, aortic dissection, acute myocardial infarction, unstable angina, acute renal failure and HE, accounted for 23% of them.4 From this group, HE occurred in 16%.5
Brainstem or cerebellar involvement in HE occurs in as many as 70% of CT or MRI scans; such changes are usually associated with hemispheric abnormalities in the occipital regions.1-3⇓⇓ The posterior predilection is thought to be related to dense sympathetic innervation of the anterior circulation that protects neural structures if blood pressure exceeds the limits of autoregulation.6
HE with only brainstem or cerebellar edema is reported uncommonly (see Appendix E-1 on the Neurology Web site). Although HE typically afflicts people in the fifth and sixth decades of life, brainstem HE affects people in the fourth decade.5,7⇓ One-third of patients had only hypertension as the precipitating factor, with most having comorbidities such as renal failure. Clinical manifestations of the brainstem variant are similar to those of the more common form of HE. Headache is the most frequent presenting symptom.7 Despite the presence of extensive lesions by imaging, there are few symptoms or signs of brainstem or cerebellar dysfunction, a typical “clinical radiologic dissociation” (see Appendix E-1 on the Neurology Web site).6
Two hypotheses may explain the abnormalities in HE. One proposes that infarction caused by fibrinoid necrosis and thrombosis of arterioles results in cytotoxic edema appearing as high signal in T2-weighted, FLAIR, and DWI images and as low signal in the ADC map.2,8,9⇓⇓ The other proposes that severe hypertension that exceeds autoregulation results in segmental vasodilatation and increased vascular permeability leading to vasogenic edema that appears as high signal in FLAIR images and the ADC map and as low or normal signal in the DWIs.3,9⇓ Reversibility of lesions supports the second hypothesis. Discrepancies between neuroimaging and pathologic findings of HE reflect the spectrum of disease with breakdown of the blood–brain barrier from failing autoregulation resulting in vasogenic edema at one end (reversible phase) and thrombosis, ischemia, and infarction at the other (irreversible phase).2,3,8,9⇓⇓⇓
Brainstem and cerebellar variants of HE are rare, affecting young people, many with secondary hypertension. Clinical-radiologic dissociation differentiates this disorder from infarction with the extensive abnormalities found on MRI to be reversible.
Footnotes
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 27 issue to find the title link for this article.
Presented in part at the 53rd Annual Meeting American Academy of Neurology, May 6–11, 2001, Philadelphia, PA.
- Received April 23, 2003.
- Accepted in final form December 15, 2003.
Disputes & Debates: Rapid online correspondence
- Brainstem involvement in hypertensive encephalopathy: Clinical and radiological findings
- Brainstem involvement in hypertensive encephalopathy: Clinical and radiological findings
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