The patient is a 70-year-old female with a medical history of diabetes mellitus type 2, hypertension, hyperlipidemia, and herpes zoster of right face who presented with subacute left chest pain, shortness of breath and a diffuse painful rash for 7 days with progressive worsening despite the treatment with oral prednisone and antibiotics. Vital signs upon presentation were normal except for mild tachypnea. Diagnostic tests for pulmonary embolism and acute coronary syndrome were unrevealing. On day 2 of admission a progressive mental status change was noted. Initial head CT was normal. An extended EEG was remarkable for diffuse slowing of background to 5–7 Hz which was thought to be related to cefepime neurotoxicity. Cefepime was subsequently transitioned to ceftriaxone. In the following days, she continued to have a fluctuating level of awareness, but was in stable condition with an EEG background 7–8 Hz during a routine EEG study. Brain MRI (3 T) with and without contrast was unremarkable except for two punctate subcortical infarcts.
On day 9 of hospitalization, she had an acute episode of altered mental status, desaturation (SpO2 80%) with atrial fibrillation (HR 160/min) and bowel incontinence. After vital signs were stabilized by a rapid response team, an EEG was ordered due to suspicion of a seizure. During the hook-up, the patient was noted to have right gaze deviation with left arm and leg clonic jerking. Since the electrodes had not yet been fully applied, EEG was not interpretable during this period. She underwent immediate endotracheal intubation and mechanical ventilation and she was treated with fosphenytoin. Overnight continuous video-EEG captured another generalized tonic clonic seizure that lasted for 3 min while receiving nursing care, which was followed by postictal generalized EEG suppression (PGES) that lasted for approximately 2 min (Fig. 1).
After this point, EEG suppression was persisted with rare (1–2 s) bursts of diffuse delta activity. Four subclinical nonconvulsive seizures (NCS) were observed over the right hemisphere lasting 30–75 s, and the last NCS was approximately 8 h after the GTCS. Portable chest X-ray showed possible aspiration pneumonia or mild neurogenic pulmonary edema (Fig. 2a to d). A repeat head CT scans 9 h after the GTCS did not show acute changes (Fig. 2e and f). After the GTCS, heart rate ranged between 70 and 100 bpm and O2Sat was > 96%. There was a significant fluctuation of systolic blood pressure between 50 and 180 mmHg with several bouts of hypotension < 60 mmHg (Fig. 3). Twelve hours later, the EEG became electrically silent and the patient developed dilated, unreactive pupils and absent brainstem reflexes, consistent with brain death. A repeat head CT showed diffuse cerebral edema and loss of gray-white differentiation (Fig. 2g). The patient subsequently died on the same day.
There was no significant hypoxemia, electrolyte imbalance and sepsis prior to the onset of last GTCS. Basic metabolic panel showed sodium 139 and potassium 5.0, chloride 107, anion gap 14, BUN 33, creatinine 1.5 and GFR 34. Complete blood count (WBC) was within normal range except for mild thrombocytopenia (WBC 10.9, RBC 4.6, HB 12.2 and platelet 125). Blood and urine cultures were negative for bacteria. Lactic acid was 2.1. Arterial blood gas showed PH 7.43, PCO2 32, SO2 99.4%. After the onset of last GTCS, the patient developed significant metabolic acidosis with PH 7.1, lactic acid 7.9 and worsening renal insufficiency.
Gross examination of the brain during the autopsy demonstrated a somewhat dusky cerebral surface and moderate symmetrical edema. The cerebellar tonsils showed some notching, raising the possibility of tonsillar herniation through the foramen magnum. Microscopic examination revealed shrunken neurons and mottling of the cerebral cortex, suggestive of hypoxic ischemic injury. The meninges contained small foci of acute inflammation. These could be secondary to hypoxic ischemic injury or could represent incipient meningitis. Overall though, the inflammation is interpreted as too subtle and potentially too early to explain the clinically observed cerebral edema. There are no other changes that would explain cerebral edema, and no other inflammatory changes or neoplastic infiltrates are seen. With that, the possibility of hypoxic ischemic brain injury leading to cerebral edema should be considered.