A Pressing Headache

Abstract

Case: A 58-year-old woman presented to the emergency department with the complaint of headaches for one day. She was brought to the ED by her son after she told him about her severe headaches. She was not answering all questions appropriately so the son provided most of the history. She was able to state that the headaches began the day before she came to the ED and that they were intermittent, 10 of 10 on the pain scale, and sharp to the back of her head. The son stated she was acting strangely and complained of worsening headaches while in the car on the way to the ED and then developed blurry vision. The son stated she has had headaches in the past, but never anything that required her to come to the ED. She denied vomiting, diarrhea, recent colds, runny nose, cough, chest pain, shortness of breath, or weakness. The patient had no allergies to medications, but she did have a history of hypertension and anemia. The son stated she had been taking medication for her blood pressure, but neither he nor the patient could recall the names. She had no surgical history, was a former smoker of 1 pack of cigarettes a day for 20 years, but quit 20 years before. Both denied any drug or alcohol use. The son did not recall any family history of serious headaches, CVA, or brain cancers. On physical exam, this patient was well nourished and in no apparent distress, but she was unable to concentrate for long periods of time. She would stare off into the distance, and had difficulty cooperating with the staff. Her vital signs were: 97.6°F, pulse 94 bpm, blood pressure 150/90 mm Hg (sitting), and respiratory rate 20 bpm with an oxygen saturation of 98% on room air. The head was atraumatic and normocephalic. Examination of the eyes, however, was difficult to assess because she could not track a finger, perform a finger-to-nose test, or cooperate with a visual acuity examination. The patient was oriented to person only. Cranial nerves did appear to be intact grossly, but she did not fully cooperate with the neurologic examination. There was no nuchal rigidity. Cardiac, respiratory, and abdominal examinations were within normal limits. She did not have a gait disturbance and extremity strength was 5/5x4, with full range of motion. Given the patient's inability to cooperate fully with her examination, her change in mental status, and her blurry vision, intravenous access was established immediately and blood was sent for CBC, complete metabolic panel, PTT/PT/INR, CK, troponin I, and serum alcohol level. The patient was sent for a stat brain CT without contrast. The patient arrived back from CT scan, and repeated vital signs showed a rectal temp 99.2°F, pulse 116 bpm, respiratory rate 22 bpm, and blood pressure 220/118 mm Hg (supine). Shortly after her return, the patient began to have a tonic-clonic seizure. Lorazepam 2 mg IVP was administered, and the seizure abated. The brain CT showed no evidence of CVA, hemorrhage, or mass. (Fig. 1.) The chest x-ray revealed clear lungs with no focal infiltrate (Fig. 2), and labs were reviewed. (Fig. 3.) Given these findings, a stat lumbar puncture was performed, and fluid was sent for analysis. (Fig. 4.)Figure 1: CT of the brain without contrast.Figure 2: Chest x-ray.The patient had another tonic-clonic seizure 30 minutes after the lumbar puncture, Lorazepam 2 mg IVP was again administered, and the patient was given a loading dose of phenytoin 1 gram IVPB. Repeat vital signs showed pulse 114 bpm, respiratory rate 20 bpm, and blood pressure 180/100 mm Hg. The patient had a fever of 102.4°F rectally three hours later. Urinalysis showed no evidence of infection, and urine toxicology screen was negative. She was admitted, and neurology consultation was obtained. Given the cluster of symptoms and most notably the headache, altered tmental status, elevated blood pressure, and seizures, the diagnosis of possible posterior reversible encephalopathy syndrome (PRES) was entertained. MRI of the brain was completed, and showed evidence of posterior cerebral edema consistent with PRES. (Fig. 5.)Figure 3: Laboratory values.The patient was restarted on her blood pressure medications, resulting in the return of her blood pressure to a normal level. Blood cultures were negative for bacteremia, and the patient had no other episodes of fever. The patient's neurological status and overall condition improved after two days. She was discharged home on day five. In discussion with the patient after her mental status returned to baseline, she stated she was often not compliant with her blood pressure medications. She was advised of the extreme importance to be strict with her blood pressure medication regimen to avoid future episodes of the syndrome. The patient had subsequent follow-up appointments with her neurologist, and a repeat MRI was completed two months later. (Fig. 6.) This MRI showed no further evidence of posterior cerebral edema, indicating this was indeed a case of PRES. Discussion: Posterior reversible encephalopathy syndrome (PRES) is also known as posterior leukoencephalopathy syndrome, reversible posterior cerebral edema syndrome, hyperperfusion encephalopathy, and brain capillary leak syndrome. PRES is described as a clinical syndrome of abrupt onset of headache, confusion or decreased level of consciousness, visual changes, and seizures. It is necessary to have all four criteria to diagnose PRES clinically. Typically, these symptoms are associated with some characteristic neuroimaging findings consistent with posterior cerebral white matter edema on MRI. PRES has been described in several conditions including hypertensive encephalopathy, eclampsia, and the use of cytotoxic drugs and immunosuppressant drugs. PRES is being increasingly recognized throughout the world, and the exact incidence is still unknown. It has been described in patients from ages 2 to 90, and women are affected more than men even when eclamptic women are removed from the statistics. (J Child Neurol 2007;22[4]:406; Intern Med J 2005;35[2]:83.) Risk factors for PRES include hypertensive disorders, renal disease, and immunosuppressive therapies. PRES is a relatively new diagnosis, but it has been described in various case reports for many years, and was defined as a single syndrome in 1996. (N Engl J Med 1996;334[8]:494.) The pathogenesis of the syndrome is still not understood. There are data to suggest that endothelial dysfunction may play a major role. In several disorders, there is disruption of the endothelial lining of blood capillaries and seems to be more common in eclampsia and cytotoxic drug administration. (J Child Neurol 2007;22[4]:406.) In eclampsia, a release of fibronectin, tissue plasminogen activator, thrombomodulin, endothelin-1, and von Willebrand factor may damage the endothelial lining of blood vessels. (Am J Obstet Gynecol 1988;159[4]:908.) Cytotoxic drugs are believed to have direct toxicity on the vascular endothelium, which leads to capillary leakage, blood-brain barrier disruption, and axonal swelling. (J Child Neurol 2007;22[4]:406.) Acute hypertension and endothelial damage when combined will result in hydrostatic edema. This is characterized by the forced leakage of serum through capillary walls into the brain interstitium, and is a form of vasogenic edema. If enough fluid accumulates, it will become radiographically evident. If vascular injury to the blood-brain barrier endothelium is unregulated, it will lead to edema, protein extravasation, and fibrinoid necrosis. (J Neurol Sci 1970;10[3]:215.) Because the cortex is more tightly packed than the white matter, it resists accumulation of edema, which is why edema is seen in the white matter. (Med Biol 1986;64[2-3]:133.)In episodes of hypertensive encephalopathy, blood pressure rises beyond the upper limits of cerebral autoregulation, which also leads to vasogenic edema. The primary involvement of the posterior regions of the brain is still not understood.Figure 4: CSF results.As noted in the name, the condition is reversible if treated early and damage to the brain from additional seizures can be avoided. Control of blood pressure is imperative in patients with hypertensive encephalopathy and eclampsia. Discontinuation of the cytotoxic drugs for those on such therapy can reverse the syndrome in these cases as well.Figure 5: MRI of brain on day of admission showing posterior cerebral white matter edema.Figure 6: MRI of brain two months later. No cerebral edema noted.This current case highlights the symptoms necessary to make the clinical diagnosis of posterior reversible encephalopathy syndrome. The patient had all of the signs and symptoms, and after ruling out an infectious etiology, it was considered in the differential diagnosis. Knowing this cluster of symptoms is particularly useful in the emergency setting because early treatment of elevated blood pressure can help reduce the chance of additional seizures. A patient presenting with onset of headache, confusion or decreased level of consciousness, visual changes, and seizures should prompt the emergency physician to consider treating blood pressure aggressively. Neurology consultation should be obtained, and an MRI of the brain should be done as soon as possible after CT scan fails to diagnose the cause.Figure: Dr. Bozek, left, a second-year emergency medicine resident; Dr. Zimmerman, second from left, an emergency physician; Dr. Rogove, second from right, a neurologist; and Dr. Eisenberger, far right, a radiologist, all practice at Good Samaritan Hospital in West Islip, NY.