Our patient was a 30 year-old female, 5-weeks pregnant at presentation, with no history of epilepsy or neurological disease. She was brought to her local emergency department (ED) after she was found shaking and unresponsive by her partner. The seizure lasted for more than 1 h, and was aborted by 10 mg diazepam given by ambulance paramedics. Seizures recommenced in ED and were refractory to intravenous (IV) lorazepam (4 mg) and levetiracetam 1 g. She was subsequently intubated in ED and started on a propofol infusion (100 mg/h). CT head and lumbar puncture on admission were both unremarkable. Magnetic resonance imaging (MRI) and Magnetic resonance venogram (MRV) conducted on day two after onset were normal. The day after admission, the propofol infusion was held, which restarted seizure activity. The seizures started as distal limb myoclonic jerks in the upper and lower limbs, and then progressed to stimulus-sensitive (touch and sound), generalized myoclonus. Sedation was recommenced with propofol, fentanyl (200 micrograms/h) and midazolam (10 mg/h), and the levetiracetam dose was increased to 1.5 g BD. Clobazam 5 mg BD was also added. Generalized myoclonus/myoclonic jerks continued while she was on propofol, fentanyl, clobazam, levetiracetam, and midazolam. Obstetric input was sought, and phenytoin (100 mg TDS), lacosamide (100 mg BD), topiramate (100 mg BD) were added, in sequence. She was pulsed with methylprednisolone from day 5 of presentation.
Seven days after initial presentation, the patient was transferred to our center with ongoing right arm and left leg myoclonic jerks and head movements suggesting ongoing status epilepticus. Two hundred milligram biotin and pyridoxine 50 mg were commenced on arrival.
The patient's lumbar puncture was repeated on day 7 when she was admitted to our center and she was found to be HSV negative, and aciclovir was stopped. MRI head (Figure 1A) and spine were also repeated (day 11 after onset) and were unremarkable. On admission to our center metabolic, CSF virology, and autoimmune and paraneoplastic panels were all negative (detailed in Table 1), as were QuantiFERON-TB Gold, and blood, CSF and sputum cultures. Vitamin B12, folate and serum ferritin were normal. At this point, a diagnosis of NORSE was suspected, and the patient was managed as such.
The patient also underwent three EEGs: soon after admission to the local hospital CCU, a prolonged study after admission to our center, and after VNS implantation (Table 1; Figure 1B).
Propofol weaning was attempted again, 9 days after onset but this led to increased myoclonic jerks and it was reintroduced. Perampanel 6 mg was commenced via a nasogastric tube 11 days after onset. Five sessions of plasmapheresis (PLEX) were commenced 12 days after presentation. The patient was started on Anakinra (100 mg daily) after the last PLEX. Propofol was cross-tapered with ketamine (2.5 mg/kg/h) to reduce the risk of propofol infusion syndrome as the ketogenic diet as started. The ketogenic diet was commenced 22 days after onset, and Levetiracetam was switched to Brivaracetam (100 mg BD).
An CT chest abdomen and pelvis was performed and ruled out trophoblastic disease or ovarian teratoma.
Whilst there had been no collateral history or evidence of overdose, the toxicology panel conducted on admission to her local hospital, which was made available to us 20 days after onset, demonstrated grossly elevated levels of morphine, fentanyl, pregabalin, and cocaine. Two past admissions for ecstasy and pregabalin overdose also came to light. Based on these results, possible anoxic brain injury was considered although subsequent MRI Brain scans did not show any evidence of hypoxic injury.
Due to refractoriness of her myoclonus on weaning sedation, an unremarkable MRI brain study and difficulty in assessing her level of consciousness off sedation, the Epilepsy Surgery MDT agreed on VNS implantation. VNS was implanted 26 days after seizure onset.
The clinical outcomes post-VNS implantation have been outlined in Table 2. The VNS was switched on day 0 with immediate post-operative settings 0.25 mA, 30 Hz, 500 mus, 30 s on, 5 min off, Duty cycle 10%. VNS output was increased till day 7 post-op according to Figure 2. All other parameters stayed the same. No intraoperative or post-operative complications were noted. Two days post-operatively, myoclonic jerks were still occurring, but eye opening to voice and apparent purposeful movements (including reaching for the tube) were noted. On day 3 post-operatively slow ketamine weaning was started. The patient was extubated on day 5 post-op. Semi-purposeful movement in all four limbs was noted, and the stimulus-sensitive myoclonic jerks had diminished significantly. Midazolam was stopped. No myoclonus was noted 7 days post-op. The patient was discharged to a neurology ward in our center. Anakinra, the ketogenic diet, and prednisolone were weaned. Thirteen days after VNS implantation, the patient demonstrated full passive range of motion in all limbs. After 18 days, normal power was noted in all limbs (MRC 4+/5). Nineteen days later the GCS had improved to 15/15. The patient showed comprehensible speech, and was oriented to place and person. Twenty days after VNS implantation, no myoclonic jerks were noted, and the patient was transferred back to her local hospital for further rehabilitation. Four months after VNS implantation, occasional, inconsistent tremors in upper and lower limbs were noted thought to be either a functional overlay or enhanced physiological tremor: these movements were clinically distinctively different from myoclonic jerks, were distractable and could be voluntarily suppressed. A repeat EEG performed at about 5 months from hospital admission did not capture the tremor-like movements; it showed background slowing and occasional spikes with no clinical correlate (no motor manifestations). Five months after VNS implantation, no further seizures or focal neurology were reported. The patient continued to take clonazepam and perampanel and mobilized using a Sara Steady sit-to-stand aid. Fatigue and low mood were reported.
Except for a minor vaginal bleed lasting 2 days, pregnancy was uneventful: repeat fetal monitoring by ultrasound at day 17, 4 and 5 months after VNS implantation and a fetal anomaly scan were unremarkable and a spontaneous vaginal delivery was planned. The patient experienced preterm premature rupture of membranes (PPROM) at 33 + 2 weeks gestation, and went into preterm labor with transverse fetal lie and fetal bradycardia. The baby was delivered via emergency cesarean section under spinal anesthesia, and admitted to the neonatal ICU due to prematurity, but was discharged without neonatal concerns. Our patient made an unremarkable obstetric recovery.