The patient was a 13 year old spayed female Pembroke Welsh Corgi with lethargy, intermittent poor appetite and mentation changes, and slowly progressive weakness and inability to walk. Her systemic systolic blood pressure was consistently over 200 mmHg upon presentation.
There is diffuse, bilateral T2 and FLAIR hyperintensity in the cerebral white matter, appearing most prominent and symmetric in the occipital and parietal lobes, and asymmetric in the frontal lobes (L>R). It is associated with a mild mass effect, as the ventricles and corpus callosum are slightly ventrally displaced and there is mild coning of the cerebellum. The lesions are isointense to mildly hyperintense on DWI and mildly hyperintense on ADC compatible with elevated diffusion. T2 shine through likely accounts for the DWI hyperintensity. No contrast enhancement is noted.
There are numerous small T2* signal voids, mostly within the cerebrum. The largest is 4mm in the right hippocampus. They are less conspicuous on the T2W spin echo images, not visible on the T1W images, and do not exhibit contrast enhancement.
1. Bilateral, slightly asymmetric T2 hyperintensity of the cerebral white matter, most prominent in occipital and parietal lobes.
DDX: metabolic, toxic, or inherited neurodegenerative encephalopathy. In light of the sustained systemic hypertension, suspect vasogenic edema associated with hypertensive encephalopathy, one of the leading causes of posterior reversible encephalopathy syndrome (PRES) in people.
2. Multiple ≤ 4mm T2* signal voids (cerebral microbleeds)
Bilaterally symmetric lesions within the brain often point to neurodegenerative disorders including toxic, metabolic, or inherited encephalopathies. In this patient, diffuse T2 and FLAIR hyperintensity was limited to the cerebral white matter, and was symmetric within the occipital and parietal lobes. Asymmetric involvement of the frontal lobes was also noted.
Based on the patient’s advanced age, lack of reported exposure to intoxicants, and sustained systemic blood pressure, hypertensive encephalopathy was considered more likely than genetically determined or toxic leukoencephalopathies.
In people, systemic hypertension is one of the leading causes of posterior reversible encephalopathy syndrome (PRES), a condition classically associated with reversible vasogenic edema predominantly distributed within the white matter of the posterior (occipital and parietal) lobes of the cerebrum. A vast array of causes underlie PRES in people, including preeclampsia/eclampsia, bone marrow and organ transplantation, autoimmune disease, immune suppression, and high dose chemotherapy (Bartynski 2008).
Hypertensive encephalopathy has been reported in animals and the MR features of two dogs with protein-losing nephropathy, one cat with chronic renal failure, and a cat with no known underlying cause were recently documented (O’Neill). Non-contrast enhancing, ill-defined T2 hyperintensities were observed within the white matter of frontal, parietal, temporal and occipital lobes, and also within the caudate nucleus and thalamus. Intracranial hemorrhage was noted in one animal.
The MR features in our patient were consistent with vasogenic edema within the cerebral white matter. Although the caudal lobes had bilaterally symmetric involvement, asymmetric frontal lobe lesions were also evident. In people, in fact, involvement of the frontal and temporal lobes and cerebellar hemispheres is common, along with the occasional presence of lesions in the brainstem, basal ganglia, deep white matter and splenium (Bartynski 2007), as well as atypical unilateral distributions (McKinney 2007, Stevens).
Hemorrhage and ischemia/infarction are complicating factors associated with PRES in people. Parenchymal hematomas, subarachnoid hemorrhage and micro-hemorrhages (<5mm diameter) have been identified using T2*GRE, FLAIR and CT (Hefzy) and susceptibility-weighted MR (McKinney 2012). Our patient had numerous small round to ovoid (≤4mm) T2* signal voids on GRE images, compatible with micro-hemorrhages or micro-bleeds. These are tiny deposits of blood degradation products (mainly hemosiderin) contained within macrophages occurring from past hemorrhage, presumably due to leakage from structurally abnormal vessels (Greenberg). Although sometimes seen in healthy elderly individuals, micro-bleeds appear to have value as markers of small vessel disease and underlying vasculopathies such as cerebral amyloid angiopathy and hypertensive vasculopathy (Greenberg). A recent report of micro-bleeds in dogs described T2* signal voids appearing analogous to those in people (Fulkerson). They were typically less conspicuous on T2W spin echo images and absent on T1W images. Although the precise relationship is unknown, hypertension was presumed to play a role in the development of PRES and cerebral microbleeds in our patient.
The elevated diffusion on ADC images in our patient supported the presence of vasogenic edema. Unlike routine MRI, diffusion imaging reliably differentiates between vasogenic edema and cytotoxic edema, and thus can afford clear differentiation between hypertensive encephalopathy and infarction (Schaefer). Although the exact mechanism is under debate, breakdown of cerebral autoregulation is believed to be responsible for vasogenic edema in PRES; with prompt management this is usually reversible (Covarrubias). The progression to cytotoxic edema due to ischemia and infarction is signified by high DWI signal intensity and pseudo-normalized ADC values, and may represent the earliest signs of non-reversibility and adverse outcomes (Covarrubias). Nevertheless, foci of restricted diffusion have been seen to resolve on follow-up imaging and should not preclude the diagnosis of PRES in the appropriate clinical context (Stevens).
No contrast enhancement was evident on T1WC+ images in our patient. Although inconsistently described, the presence or absence of contrast enhancement correlates poorly with edema severity in PRES (McKinney2007, Ugurel).
Despite anti-hypertensive therapy, follow-up blood pressures remained elevated (171/88 and 175/90 mmHg) and the patient died without identification of an underlying cause. The reason for a lack of response to therapy was uncertain, as diffusion imaging did not support a definitive progression to infarction.
Acknowledgement: Dr. Jay McDonnell for neurologic workup of this patient
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