A 40-year-old male presents to the ED for headache and nausea following dialysis. He states that he normally has a headache at baseline at the back of his head but after this dialysis session, it became acutely worse and was associated with nausea, vomiting, and blurry vision. He has been compliant with his dialysis sessions and still produces some urine throughout the day. The patient states that he has been on dialysis for the past 5-6 weeks due to being in End-Stage Renal Disease status-post renal transplant 10 years ago. He has been compliant with his immunosuppression regimen of Tacrolimus, Mycophenolate, and Prednisone. The patient also endorses a history of hypertension that has been very difficult to control of late and has been running high. The rest of his review of symptoms is negative. 

The patient’s physical exam is significant for a blood pressure of 205/95 with remaining vitals within normal limits. Cardiac and Pulmonary exams show no abnormalities. On neurologic testing: cranial nerves, upper and lower strength, sensation testing, and finger to nose are intact and normal bilaterally. 

ECG was performed which showed no acute abnormalities. A CBC and CMP were also within normal limits with the exception of the patient’s creatinine being elevated to 6.8 which was near the patient’s baseline. While waiting for the patient to go to CT, he became acutely altered, was found to be febrile to 101.3F, and not following commands. Rectal tylenol was given and the patient’s mentation improved precipitously. A repeat set of vitals were obtained and was found to be tachycardic in the 110s and hypertensive with systolic in the 200s. 

At this time, the patient was taken to CT for a CT chest/abdomen/pelvis with IV contrast to rule out aortic dissection given hypertension and acute altered mental status. Unfortunately, due to agitation, only a CT head was able to be performed which showed post-surgical changes without acute abnormalities. Upon returning, blood cultures, lactic acid, coagulation studies, and a full septic workup was initiated as well with broad-spectrum antibiotic coverage given the patient’s clinical presentation and immunosuppressed status. 

Upon reevaluation to see if the remainder of the CT could be done, the patient is found to be seizing by nursing staff, aborticants were administered, and due to severely altered mental status, low GCS following the seizure, as well as making gurgling noises indicating airway protection compromise, the patient was intubated. The patient was admitted to the ICU for further care. An MRI of the brain without contrast the following day showed cortical and subcortical white matter FLAIR hyperintensities at the right occipital and parietal lobes with a differential of acute hypertensive encephalopathy/posterior reversible encephalopathy syndrome.

EPIDEMIOLOGY

While recently becoming more known with more identification, accurate statistics of its incidence are not yet known. Posterior Reversible Encephalopathy Syndrome (PRES), was first described relatively recently in 1996. PRES has been reported in all age groups but is most commonly seen in middle-aged individuals with females being more prevalent than males presenting with it. 

PRES has been associated with a variety of conditions, the most prominent of them being hypertension, renal disease, autoimmune disorders, and the use of immunosuppressants (specifically cyclosporine and tacrolimus). 

PATHOPHYSIOLOGY

While the condition has been established for a while now, the pathophysiology of it is still under study. The root cause of the condition is endothelial injury or dysfunction that leads to the breakdown of the blood-brain barrier causing brain edema. There are currently three main theories that are being studied that could potentially be the cause of this disease.

1. Hyperperfusion Theory
   1. Rapid blood pressure fluctuations, either increases or decreases, leads to vascular leakage and vasogenic edema. 
2. Long-Standing Hypertension
   1. Leads to increased pressure creating the vasogenic edema 
3. Toxic Theory
   1. Toxins disrupt the endothelium causing edema and vasospasm 

DIAGNOSTIC CRITERIA

There are no set criteria for the diagnosis of PRES, however, the following are the most common presenting factors:

• Acute onset of neurologic symptoms
• Vasogenic edema on neuroimaging 
• Reversibility of clinical/radiographic findings 

CLINICAL PRESENTATION

Symptoms of this condition usually revolve around hypertension, neurologic symptoms (seizures, altered mental status, visual changes), and neuroimaging findings. The following table lists symptoms and the percentage of patients with the symptoms. 

Encephalopathy	80%
Tonic Clonic Seizures	60-75%
Headache	50%
Hypertension	53-80%
Renal Disease	45-55%

RADIOGRAPHIC AND LABORATORY EVALUATION 

• MRI has been the diagnostic modality of choice. On MRI, vasogenic edema is usually found in the parieto-occipital lobes. An important note, however, radiographic findings do not correlate with the severity of the presentation. 

• CT can also be useful as it can show vasogenic edema. While much easier to access than MRI at most facilities, there is limited data in terms of diagnostic accuracy for PRES. It has been shown that CT is a great initial test of choice as PRES has been associated with intracranial hemorrhage (10-25% of cases). 

• Lumbar punctures should be performed when there is a suspicion of meningitis or encephalitis as the symptoms can commonly overlap. 
• Magnesium can be reduced in a large portion of PRES patients

TREATMENT 

The mainstay treatment for PRES is largely supportive. Efforts are made at treating any underlying causes that can be identified. Primarily, management of blood pressure is paramount in these patients. It is generally recommended to have strict hemodynamic monitoring. Blood pressure should be reduced by about 25% without overtreating and causing large drops in blood pressure, especially in patients who aren’t significantly hypertensive. Anticonvulsants are indicated when seizures are present or suspected. 

PROGNOSIS

Most patients will fully recover with radiologic improvement being seen in most cases. 75-90% of patients will be seen to recover fully. There is an increase in overall long-term morbidity and mortality due to the concurrent pathology associated with the condition. Intracranial hemorrhages and cerebral infarction have been known to happen in this patient population. Recurrence is seen in about 5-10% of patients and is usually due to uncontrolled hypertension.

Discussion

While mostly a straightforward case, this particular case does have a confounding variable of the fever. Ideally, looking back on this case, a lumbar puncture is an acceptable test to do to rule out meningitis. This case did not have CT evidence showing any acute pathology however the patient was empirically covered with antibiotics. Time permitting, the patient should have a lumbar puncture done. In our case, the patient was intubated and ready for transfer to the ICU with an MRI scheduled to be done right after which gave us the answer fairly quickly. In situations where this is not feasible, a lumbar puncture needs to be considered in the setting of a fever with similar presentations.

Parth H Patel, DO – PGY3 

Peer Reviewed: Stevely Koshy, DO

References:

Corependium, UpToDate, Tintinallis, Radiopaedia 

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