A 46 years old female was admitted to the emergency department in comatose state accompanied by sustained convulsive generalized tonic-clonic seizures. She had a history of alcoholic liver cirrhosis and depression with heavy chronic alcoholism and took AEDs, including levetiracetam and clobazam twice daily and lorazepam once daily owing to alcohol-related seizures a year ago. In the emergency room, intravenous lorazepam 4 mg was administered immediately. Although the tonic-clonic seizures terminated, focal seizures with jerking movements of the left arm and legs were not controlled, and there was no recovery in consciousness. Intra-cerebral hemorrhage on the initial brain computed tomography (CT) scan was absent. The body temperature was 39.8°C. Initial laboratory findings showed mild leukocytosis (16,200/μL) with elevated C-reactive protein (CRP, 2.59 mg/dL), and elevation of the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Serum glucose and electrolytes with ionized calcium were within the normal range. Arterial blood gas analysis revealed severe acidosis with carbon dioxide retention. An endotracheal tube was inserted and mechanical ventilation was performed because of compromised respiratory dysfunction with an abrupt decrease in oxygen saturation. Thereafter, intravenous fosphenytoin (20 mg/kg) and levetiracetam (3,000 mg) were administered. Brain magnetic resonance imaging (MRI) revealed high signal intensities in the right hemisphere in T2 fluid attenuated inversion recovery (FLAIR), which suggested seizure-related changes. After shifting to the intensive care unit, continuous video EEG monitoring was performed, which showed a nearly continuous 1-Hz rhythmic sharp waves in the right temporo-occipital areas (Fig. 1A). The patient did not respond to first-and second-line treatment regimens for SE and presented with autonomic dysfunctions, including tachycardia (160–230 beats/min) and fluctuating blood pressure due to alcohol withdrawal syndrome. Third line treatment for SE as low-dose combination therapy with ketamine and midazolam was initiated. Continuous intravenous ketamine 1.5 mg/kg/h up to 2 mg/kg/h infusion with intravenous midazolam 0.03 mg/kg/h up to 0.07 mg/kg/h were administered for the management of unstable hemodynamic status (Fig. 2).

Rhythmic sharp and waves on EEG disappeared within 24 hours of combination continuous midazolam and ketamine infusion, and autonomic dysfunctions were controlled. After continuous combination infusion for 48 hours, both regimens were tapered out with concomitant intravenous phenobarbital 20 mg/kg loading and a maintenance dose of 30 mg three times a day. Upon improvement of the EEG findings with recovered consciousness, the patient was treated with levetiracetam 750 mg, phenytoin 150 mg, lacosamide 150 mg, and phenobarbital 30 mg twice daily. The patient was successfully weaned off the ventilator on hospital day 8 and continued with physical therapy to return to her baseline (modified Rankin score improved from 5 to 1).

A 77-year-old man was admitted to the emergency room with acute stuporous mental change preceding generalized tonic-clonic seizures of at least 20 minutes. He had a history of angina and atrial fibrillation. He was a chronic alcoholic and had no history of seizures or other major neurological illnesses. He was promptly administered intravenous lorazepam (total 8 mg), followed by 3,000 mg levetiracetam and 20 mg/kg fosphenytoin sodium. Convulsive seizures ceased; however, the mental status was still stupor. The body temperature was 39°C. Initial laboratory tests showed leukocytosis (10,610/μL) with elevated CRP (3.32 mg/dL) and mildly elevated AST and ALT levels. Other laboratory tests, including glucose, electrolytes, and ammonia, were within the normal range. Arterial blood gas analysis showed mild metabolic acidosis. Cerebrospinal fluid analysis showed no white blood cells (WBCs), with normal glucose and protein concentrations. Blood gram staining and bacterial culture showed positive results for Staphylococcus aureus. No intra-cerebral hemorrhage was observed on the initial brain CT scan: however, liver cirrhosis and basal pneumonia were reported. Pancytopenia and markedly increasing CRP levels were detected (CRP, 14.94 mg/dL; WBC, 950/μL; absolute neutrophil count, 853.6/μL; hemoglobin, 11.6 g/dL; and platelet, 103,000/μL) in the blood laboratory follow up results. Brain MRI revealed high signal intensities in the right hemisphere of T2 FLAIR, implying seizure-related changes. No meningeal enhancement or basal exudate was observed. An endotracheal tube with mechanical ventilation was placed for respiratory failure, and the patient was admitted to the intensive care unit. Vasopressor (norepinephrine 2 mL/h.kg) was infused for hemodynamic instability, which originated due to the provisional septic condition. Continuous EEG monitoring and continuous 1-Hz peridodic lateralized epileptiform discharges were detected (Fig. 1B). To prevent hemodynamic instability and RSE, ketamine was administered at a dose of up to 3 mg/kg/h. Continuous EEG monitoring revealed epileptiform discharges in spite of ketamine infusion. Epileptic discharges terminated immediately on starting low-dose midazolam at 0.08 mg/kg/h while on ketamine infusion. During continuous combination infusion, the mean arterial pressure was stable, and norepinephrine was tapered out (Fig. 2). Concomitant AEDs (lacosamide, phenobarbital, perampanel, and clobazam) were added by tapering out the continuous anesthetic drug infusion. Overlapping of these drugs was ensured for approximately 3 days with successful seizure control. The patient’s mental status gradually improved, and he was discharged from the hospital after 6 weeks of treatment with antibiotics for pneumonia. At the time of discharge, he was administered two AEDs including lacosamide and phenobarbital.