Acute Encephalopathy With Unusual Brain Lesions

Case Resolution

JS presented with acute diffuse brain dysfunction, which is referred to as encephalopathy. Because this symptom is highly nonspecific, a medical investigation should consider both primary neurologic and systemic conditions. Therefore, the following underlying etiologies of acute encephalopathy were investigated:

Cerebrovascular diseases: global encephalopathy can occur because of strategically located ischemia (eg, bilateral thalamus, anterior cerebral artery territory, concomitant bilateral hemispheres because of diffuse emboli). Intracerebral hemorrhage is another possible diagnosis, owing to the extremely high blood pressure.

Nonconvulsive seizure or status epilepticus: these should be considered in people with sudden-onset encephalopathy.

Infections: central nervous system infection (eg, meningitis, encephalitis, abscess) or systemic infection (eg, sepsis, shock) are associated with acutely altered mental status.

Metabolic disturbances: electrolyte abnormalities (especially elevated sodium, calcium, or magnesium), hypoglycemia or hyperglycemia, hypothyroidism or hyperthyroidism, and hepatic or renal failure are major causes of acute encephalopathy.

Based on the exclusion of the main differential diagnoses by the initial workup, PRES was considered. Uncontrolled hypertension associated with retinal hemorrhage and renal failure reinforced this main hypothesis. However, MRI findings did not reveal the pattern typically observed and expected in PRES—that is, symmetric and bilateral white matter vasogenic edema in parieto-occipital regions. Nonetheless, this case resembles the less common, but well-established, central variant PRES, in which lesions predominantly are observed in the basal ganglia and brainstem, with typical sparing of subcortical and cortical regions.

Upon emergency department admission and based on the suspected diagnosis, intravenous antihypertensive treatment was initiated promptly. After 5 days, the blood pressure was well-controlled, and JS recovered without any neurologic deficits. A control MRI scan obtained after 3 months showed regression of the findings (Figure 2).

Overall, given the clinical context, MRI features, and evolution, the final diagnosis was atypical PRES.

Discussion

PRES typically has a fairly rapid onset, although clinical symptoms and severity can vary widely. Encephalopathy, seizure, headache, visual disturbances, and focal neurologic deficit are possible clinical manifestations.^1,2 Predisposing risk factors include severe hypertension or blood pressure fluctuations, impaired renal function, preeclampsia or eclampsia, autoimmune disorders, infection, and immunosuppressive or chemotherapeutic agents.^2,3

The proposed pathophysiologic mechanisms for PRES are hyperperfusion exceeding autoregulatory limits and toxin-mediated endothelial injury, both resulting in blood–brain barrier disruption.⁴

The classic brain MRI features are symmetric and bilateral hyperintense foci in the parieto-occipital subcortical regions on fluid-attenuated inversion recovery or T2-weighted images with the absence of diffusion restriction.⁵ Bartynski and Boardman⁶ described 3 primary patterns of PRES distribution: 1) dominant parieto-occipital, 2) holohemispheric watershed, and 3) superior frontal sulcus. Partial or asymmetric expressions of these patterns also were recognized. Unusual lesion locations include basal ganglia, thalamus, brainstem, and deep white matter, in particular the splenium. Terms such as central variant PRES and brainstem variant or isolated infratentorial PRES are being used to describe these variants.^5,6

Central variant PRES is recognized as vasogenic edema in the brainstem or basal ganglia, potentially in the thalamus, periventricular white matter, limb of internal capsule, or cerebellum, but sparing the typical subcortical and cortical regions.⁵ A typical PRES pattern is noted in more than 95% of cases, and the central variant incidence is not well described.^6,7 A study conducted by McKinney et al⁷ showed that only 4% (5 of 124) of cases of PRES were the central variant.

Diagnosis of atypical PRES can be challenging for several reasons. First, the condition could be mistaken easily for other pathologies, because symptoms are nonspecific and the radiologic findings are unusual. Neuroimaging abnormalities seen in the central variant can mimic rhombencephalitis, pontine myelinolysis, demyelinating disorders, brainstem glioma, or infarcts, potentially leading to different treatment strategies. Second, when PRES findings predominate in the brainstem, a clinical–radiologic dissociation is seen, characterized by extensive neuroimaging abnormalities with mild clinical symptoms.^4,5,8 However, both clinical and radiologic findings related to PRES usually are reversible, and improve once the triggering factor has been removed or treated. Therefore, the treatment is aimed at managing the underlying cause, with specific attention to blood pressure control.^5,6

Conclusion

PRES is a clinical-radiologic syndrome that can pose substantial diagnostic challenges, especially in the setting of atypical neuroimaging findings. Being aware of these less common patterns is essential to recognize and manage this condition promptly.