Rare Case of Atypical, Unilateral Methotrexate-induced PRES mimicking Stroke Symptoms: Case Report

Posterior reversible encephalopathy syndrome (PRES) is a reversible neurotoxic state which illustrates typical symmetric features on brain MRI scans. However, the uncommon atypical radiological presentations of PRES may lead to misdiagnosis as the clinical and radiological findings are similar to other neurological conditions. Although the pathophysiology of this syndrome is not fully understood, PRES represents a radiographic feature of vasogenic edema in areas of the brain supplied by the posterior circulation. Methotrexate-induced neurotoxicity is a common therapeutic complication in the pediatric population but has been uncommon in adults. A 76-year-old female presented with symptoms similar to stroke, but on further investigation was diagnosed with atypical, unilateral methotrexate-induced PRES. Both clinical condition and radiological abnormalities were resolved after cessation of methotrexate. This case report demonstrates an atypical presentation of unilateral vasogenic edema from an underlying cause of methotrexate which suggests clinicians to consider the prognosis of PRES.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurological disorder primarily represented with vasogenic edema affecting the parieto-occipital regions [1]. The incidence rate of unilateral involvement in PRES cases is 2.6% [2]. The T2-weighted and fluid attenuated inversion recovery (FLAIR) sequences of magnetic resonance imaging (MRI) aid in visualizing the vasogenic edema to confirm the diagnosis of PRES. Arterial spin labelling (ASL) allows in differential diagnosis of PRES from ischemic stroke. ASL assesses the perfusion by visualizing the cerebral blood flow to detect PRES. MRI diffusion-weighted imaging (DWI) confirms vasogenic edema and at times shows restriction in certain cases [3].

Case Report

History of Presentation

A 76-year-old woman presented in the emergency department with chief complaints of right-sided weakness and slurring of speech, along with staring gaze to the right which was followed by disorientation. She was vitally stable, with her blood pressure measuring 130/70 mmHg, SpO2 98% on room air and pulse rate of 90/min. On CNS examination, GCS score was 13/15, E4V3M6, power in right upper and lower limb was 2/5, plantars bilateral withdrawal and disorientation. No other abnormality was detected in the systemic examination.  Upon her examination, code white was activated, and an MRI examination of the brain was performed; findings of which are explained in detail further.

Footnote

CNS: Central Nervous System; GCS: Glasgow Coma Scale; E: Eye opening; V: Verbal response; M: Motor response.

Past Medical History

The patient has a medical history of rheumatoid arthritis for which she received treatment, chronic venous insufficiency of both lower limbs and hypothyroidism.

Investigations

An MRI (3 Tesla) scan of the brain was performed using T1 and T2-weighted sequences in multiple planes, using a multiple array head coil. The scan revealed large area of mild diffusion restriction involving the left parieto-occipitotemporal cortex and subcortical white matter (Figure 1), with subtle FLAIR hyperintensity (Figure 2). On 3D ASL, there is relative hyper perfusion in the same region (Figure 3).

The methotrexate medication was discontinued, and the patient was conservatively managed. Anti-epileptic medicines were administered. 

To evaluate the treatment response and clinical changes in the brain, another MRI scan was performed before discharge. The DWI scan (Figure 4) showed resolution of diffusion restriction in the left parieto-occipito-temporal cortex and subcortical white matter.  On 3D ASL images, there was symmetrical perfusion seen in bilateral cerebral parenchyma (Figure 5) which confirmed improvement in patient’s condition.

Follow-Up

At discharge, the patient was hemodynamically and vitally stable. 

Differential Diagnosis

PRES may be misdiagnosed for progressive multifocal leukoencephalopathy (PML), posterior circulation infarct, inflammatory cerebral amyloid angiopathy or reversible cerebral vasoconstriction syndrome (RCVS) since they illustrate resemblance in radiological findings coupled with similar clinical representation. [4] PML is a viral disease affecting the brain’s white matter characterized by destruction of myelin. [5] Posterior circulation infarct is a neurological deficit caused by infarction within the vertebrobasilar arterial system affecting the posterior circulation of the brain. [6] Cerebral amyloid angiopathy is a rare encephalopathy characterized by inflammatory response from amyloid-b deposition in the small and medium-sized arteries of the leptomeninges and cerebral cortex. [7] RCVS is a group of disorders characterized by vasogenic edema, watershed infarcts and reversible vasoconstriction of the cerebral arteries. [8] Table 1 represents the clinical representations and MRI findings of PRES and its differentials.

Table 1: Clinical profile and MRI findings of PRES and its differentials

There are many underlying causes, medical treatments or medical conditions that may result in PRES. The pathophysiological mechanism underlying the development of PRES is not well understood. PRES is a neurological entity characterized by reversible vasogenic edema affecting the occipital and parietal lobes.[3] The typical MRI findings of PRES show symmetric hyperintensity with bilateral vasogenic edema in parieto-occipital cortical and subcortical locations in the white matter on FLAIR images whereas <5>Table 2 represents the conditions associated with the development of PRES [3].

Table 2: Conditions associated with the development of PRES

MRI is the gold standard for diagnosing PRES as it assists with confirming the syndrome and shows its extent. The symmetric vasogenic edema affecting the subcortical and cortical location is best seen on MRI with FLAIR sequence while DWI allows in confirming vasogenic edema with absence of restricted diffusion. [3] ASL, a non-contrast, noninvasive MR perfusion technique is commonly used to accurately detect stroke mimics like PRES. Often, there is symmetric regional hyper perfusion in the bilateral occipital lobes seen on the ASL for the PRES condition, which is the result from breakdown of cerebral autoregulation, caused due to severe hypertension resulting in excessive blood flow, increased capillary pressure and subsequent vasogenic edema. But in this case, there was relative hyper perfusion on the left parieto-occipitotemporal cortex and subcortical white matter which seemed atypical. [10]

Etiological findings revealed methotrexate (as the cause). After discontinuing medication, the patient’s clinical condition significantly improved. This along with the findings of MRI solidified the diagnosis of methotrexate-induced unilateral PRES. This case report suggests that clinicians should consider prognosis of PRES in radiological representation of unilateral vasogenic edema.