Delayed Diagnosis of Posterior Reversible Encephalopathy Syndrome: A Case Report

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Delayed Diagnosis of Posterior Reversible Encephalopathy Syndrome: A Case Report Roma Pegany, MD, Daniel J. Olson, MD, Khalid M. Aldaas, BS, Kevin R. Sitko, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdtwnfKZBYtws= on 05/04/2022 P osterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome of acute onset that includes symptoms of headache, hypertension, impaired visual acuity, and seizures (1). Imaging, especially MRI, plays an essential role in diagnosis (2). Features of diffuse symmetrical cerebral vasogenic edema usually affecting the posterior regions of the brain would indicate a diagnosis of PRES (2). We report a case of a patient with a delayed diagnosis of PRES due to an initially unremarkable MRI with later development of more classic findings on repeat imaging. A 17-year-old girl with a history of cystic fibrosis status after bilateral lung transplant 1 month prior and currently taking tacrolimus and cefiderocol presented to the emergency department (ED) with intractable frontal headaches. The headaches were associated with nausea, vomiting, photophobia, and phonophobia and were minimally responsive to conservative treatment before arrival. The patient denied pain with ocular movements and trauma. Physical examination was notable for physiologic anisocoria, with the right pupil slightly larger than the left. The remainder of the examination, including vitals, was unremarkable. At this time, MRI of the brain without contrast displayed no acute intracranial abnormality (Fig. 1). There were also no appreciable abnormalities in the MRI diffusion-weighted images or the apparent diffusion coefficient maps. A migraine cocktail including butalbital, acetaminophen, and caffeine was given in the ED and provided moderate pain relief. The patient was discharged only to return to the ED the following morning with a severe, pulsating headache. The patient was admitted for further workup with neurology consultation, which included a lumbar puncture that showed no evidence of acute inflammatory or infectious processes. Four days later, she began experiencing bilateral visual loss in the setting of worsening headaches, prompting urgent evaluation by Ophthalmology. The patient has a history of experiencing intermittent blurry vision and had been seen 3 weeks prior with visual acuities of 20/20 in the right eye and 20/25 in the left eye. However, ophthalmic examination was now significant for light perception vision in each eye, normal intraocular pressures, Department of Ophthalmology, UNC Kittner Eye Center, Chapel Hill, North Carolina The authors report no conflicts of interest. Address correspondence to Khalid M. Aldaas, BS, UNC Kittner Eye Center, 2226 Nelson Hwy #200, Chapel Hill, NC 27517; E-mail: [e-mail] e64 no afferent pupillary defects, and briskly reactive pupils. Extraocular movements remained full, and slit-lamp and fundus examinations showed no obvious signs of pathology. Because of the degree of reported vision loss, imaging was repeated. MRI of the brain with and without contrast now displayed evidence of symmetric T2/FLAIR (fluidattenuated inversion recovery) hyperintensities particularly involving bilateral posterior regions of the cerebrum and cerebellum consistent with a diagnosis of PRES (Fig. 2). With these new radiologic findings, tacrolimus, which was believed to be the trigger for PRES, was discontinued. Within 2 weeks, the patient reported near-complete resolution of vision loss with only mild, occasional headaches. She was discharged 2 weeks after admission, and follow-up examination in clinic showed persistent physiologic anisocoria and monocular diplopia due to refractive FIG 1. MRI of the brain, axial FLAIR image through the midbrain and parietal and occipital lobes showing no focal parenchymal signal abnormality and no midline shift, mass, intracranial hemorrhage, or acute infarct. Pegany et al: J Neuro-Ophthalmol 2021; 41: e64-e65 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence Hinchey et al (3) originally described 15 patients with clinical characteristics and imaging findings with PRES. In all 12 patients in whom the first imaging study performed was computed tomography, the radiologic evidence of PRES was apparent on the scan (3). In our patient, CT imaging was not obtained. Instead, MRI was obtained and even with its ability to yield a higher resolution image and shows small, focal abnormalities (4), the initial MRI scan in our patient was nondiagnostic, and she was discharged only to return the following morning with worsening symptoms. Unfortunately, it was not until she complained of bilateral vision loss 4 days later that imaging was repeated and now diagnostic of PRES. To the best of our knowledge, there is no study in the English-language literature examining the temporal relationship between the onset of clinical manifestations of PRES and the appearance of MRI findings. The lack of these initial imaging findings in this patient offers the suggestion that radiologic findings can lag behind clinical signs and symptoms of this rare central nervous system disorder. This patient case suggests that if initial neuroimaging is nondiagnostic in a patient with a high index of clinical suspicion for PRES, then repeat imaging may be helpful. FIG. 2. MRI of brain, axial FLAIR images through the midbrain and parietal and occipital lobes showing hyperintense signal involving posterior aspects of the cerebrum. error. However, best-corrected visual acuities were 20/20 in each eye, and Humphrey visual fields were full. The remainder of the ophthalmic examination was unremarkable, and the patient is being followed as needed. The immunosuppressed patient discussed here had an initial presentation of severe headaches and visual disturbances that are diagnostically suggestive of PRES. However, this clinical entity was not readily recognizable on this patient’s initial neuroimaging, thereby delaying diagnosis. A delay in prompt diagnosis of PRES can lead to lifethreatening neurological sequelae, including cerebral hemorrhage, cerebellar herniation, and refractory status epilepticus or long-term epilepsy (2). Timely diagnosis and treatment of PRES often results in a favorable prognosis with reversal of clinical symptoms and MRI abnormalities. However, the degree of reversibility depends on how promptly the diagnosis is made, with imaging playing a key role (2). Pegany et al: J Neuro-Ophthalmol 2021; 41: e64-e65 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: R. Pegany, D. J. Olson, and K. R. Sitko; b. Acquisition of data: R. Pegany, D. J. Olson, and K. R. Sitko; c. Analysis and interpretation of data: R. Pegany, D. J. Olson, and K. R. Sitko. Category 2: a. Drafting the manuscript: R. Pegany, D. J. Olson, and K. R. Sitko; b. Revising it for intellectual content: R. Pegany, D. J. Olson, and K. R. Sitko. Category 3: a. Final approval of the completed manuscript: R. Pegany, D. J. Olson, and K. R. Sitko. REFERENCES 1. Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. J Neurol. 2017;264:1608–1616. 2. Hugonnet E, Da Ines D, Boby H, Claise B, Petitcolin V, Lannareix V, Garcier JM. Posterior reversible encephalopathy syndrome (PRES): features on CT and MR imaging. Diagn Interv Imaging. 2013;94:45–52. 3. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334:494– 500. 4. Racchiusa S, Mormina E, Ax A, Musumeci O, Longo M, Granata F. Posterior reversible encephalopathy syndrome (PRES) and infection: a systematic review of the literature. Neurol Sci. 2019;40:915–922. e65 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.