Psychiatric Morbidity and Its Prognosis in Posterior Reversible Encephalopathy Syndrome

In a retrospective case series conducted in the liaison neuropsychiatry service of a large South London teaching hospital serving four boroughs, we identified patients with PRES presenting between April 2010 and April 2019. The study was authorized by the South London and Maudsley National Health Service Foundation Trust Clinical Audit and Effectiveness Team on June 16, 2016. We retrieved records from the hospital’s clinical radiology information system using the search term “reversible encephalopathy” to address disambiguation problems with “PRES.” For each patient for whom a scan report mentioned reversible encephalopathy, we reviewed clinical and radiological records to determine whether PRES was ultimately the confirmed diagnosis. We audited the clinical records of these patients using a piloted data collection form and entered pseudonymized data into a spreadsheet stored in password-protected hard drives.

In this study, we found that psychiatric symptoms were not reported in all cases of PRES, although confusion and agitation were common. However, psychiatric symptoms often occurred before, during, or following PRES onset, which is consistent with evidence of psychiatric comorbidities in neurological disorders, including epilepsy, migraine, stroke, and traumatic brain injury (16). The subgroup of patients who received psychiatric consultation was a median of 5 years older than the total sample, with a higher proportion of females and a higher mortality rate (33% versus 28%).

Physicians treating PRES and liaison psychiatrists should be alert to psychiatric comorbidities. In addition, multidisciplinary staff should consider PRES as a rare, organic differential diagnosis for acute mental state changes, especially when PRES coincides with neurological symptoms, hypertension, or medical comorbidities. Physicians treating PRES should assess for post-PRES psychiatric symptoms, to consider whether consultation-liaison psychiatry, specialist substance use, or community psychiatric follow-up may enhance recovery.

Given these rates of psychiatric comorbidity, it is striking that mental health comorbidity is near-absent from literature on PRES, which focuses on neuroimaging, neurological sequelae, treatment, and prognosis. This is surprising, given the association between neuropsychiatric symptoms and temporo-limbic network lesions, which are not uncommon in PRES. Despite the term reversible, residual infarcts and subsequent leukomalacia are recognized sequelae of PRES (17), supporting the likelihood of longer-term psychiatric symptoms in a proportion of patients, which is well recognized in acute neurological disorders such as encephalitis (11, 12).

As expected, our study sample had high rates of underlying medical comorbidity. Worldwide, depression prevalence is higher among people with chronic conditions (18), including neurological (19) disorders. The most common reasons for psychiatric services referral in our sample were alcohol and intravenous drug addictions, acute psychosis, depression, suicidality, and refusal of medical treatment due to delirium or agitation. There were few or no referrals for severe anxiety, long-standing psychotic illnesses, bipolar illness, intellectual disability, and personality or eating disorders. Perhaps during critical illness treatment and follow-up, only markedly acute psychiatric symptoms were detected by physicians and referred for assessment. It is not possible to definitively quantify the extent to which some psychiatric morbidity predating PRES onset may have gone undetected. Such morbidity would be expected to be increased over the population baseline in the context of chronic medical illness. The United Kingdom National Health Service provides open access to family health practitioners, and therefore most moderate to severe mental disorders are recorded. Substance use disorders, however, may not always be identified, treated, and recorded by health care services.

To our knowledge, this is the first study to provide preliminary support for our clinically informed hypothesis of elevated psychiatric morbidity among individuals following PRES onset, which requires more widespread, prospective investigation. One strength of our study is its relatively large sample size, drawn from a broad, diverse, densely populated region of South London in a teaching hospital with expertise in a range of relevant medical disorders. One limitation is its pragmatic, retrospective audit design, dependent on routinely documented free-text clinical records. Future research and PRES case series should investigate psychiatric comorbidity and sequelae systematically, including the premorbid period, to elaborate on these findings. Perspectives of patients and their care givers on pre- and post-PRES mental states, as well as longitudinal follow-up of neuropsychiatric outcomes, would be particularly informative.