The patient is a 36-year-old man with a 2-year history of bizarre, hypermotor spells predominantly at nighttime admitted to the Neurobehavioral and traumatic brain injury (TBI) Unit of Walter Reed National Military Medical Center (WRNMMC). History of his illness was corroborated by his wife via telephone. The reported spells occurred at a rate range of 3-5 times while awake and up to 7-9 times from sleep. Sleep deprivation was perceived to increase rate of nighttime episodes. The subject described occasional "warming" aura before episodes and intense fatigue after episodes, which last 10-15 s, stopping and ending abruptly. When awake, episodes are described as a yell or grunting and jumping up or running. The subject used phrases such as "fight or flight sensation" and "panic." At night, episodes were described as a sudden sitting-up, yelling, and jumping out of bed in dramatic fashion, with uncomplicated return to sleep afterward. Episodes were anamnestic to the patient. He endorsed exceptionally rare associated loss of bladder control. He denied self-awareness and control at initiation of an episode but described reorientation and redirection of his actions toward the end, such as patting someone on the back when running past them or, offering a "high-five." He further denied temporally related oral injuries, changes in cognition, strength, sensation, and preceding olfactory hallucination. He had never injured others during episodes although had injured himself when leaping out of bed. He denied associated nightmares but does still dream, although more rarely due to sleep interruption.
He has no pertinent past medical or surgical history. Admission medications included venlafaxine 225 mg and propranolol 40 mg, prescribed by primary care and behavioral health providers to treat presumed behavioral disorder. Previous related medication trials included paroxetine, bupropion, sertraline, hydroxyzine, trazodone, and clonazepam. He completed behavioral health therapy for psychiatric and sleep-related diagnoses. No hypermotor episode frequency change was appreciated by the patient or spouse in that time. His family history is negative for movement disorders and parasomnias in his parents, but he has a sister with resolved juvenile myoclonic epilepsy. On review of systems, he endorsed changes in mood and energy, which he attributed to the impact his spells were having on his quality of life. He reported mild, recurrent traumatic brain injury history. He estimated one to two sports related concussions, several head impacts and a single temporary loss of consciousness. Later, during military training exercises and three deployments as an active duty military officer, he was exposed in close proximity to the regular discharge of weapons and ordnance, to include at least five high impact aerial landings, causing some degree of disorientation. He denied the persistence of somatic symptoms after these events. He suffered an indirect blast wave in 2007, causing disorientation, confusion, and epistaxis. He did not seek medical workup or require hospitalization after any of these events. He denied similar head injury for at least 2 years before onset of these symptoms. Lack of a posteriori knowledge of TBI significance likely contributed to difficulties in more precise description.
Workup before our evaluation was appropriate. Outside brain MRI was read as normal and revealed no intracranial findings. A sleep study with vEEG and polysomnography (PSG) was interpreted as periodic limb movements/REM behavior disorder and sleep apnea with insomnia. A 24-h ambulatory EEG with event recorder reported normal background during all episodes. As a result, overall, previous pharmacologic and non-pharmacologic treatment was directed toward behavioral health and sleep-related disorders.
Our admission physical exam and screening labs were within normal limits. Post-spell lactate was normal. He was tapered off of venlafaxine and propranolol without changes in episode rate or mood. He scored unremarkably on psychometric testing. Further review of parasomnia and psychiatric questioning was without significant positive findings. Sleep vEEG and PSG was repeated. The patient was observed to have five episodes with stereotyped behaviors arousing out of drowsiness, stage 2 and stage 3 of non-rapid eye movement (REM) sleep. Behaviors included bilateral flexing of his legs and kicking feet, flexing arms, moaning loudly, sitting up in bed, forcefully flinging back down and suddenly standing up out of bed (Figure 1; Video S1 in Supplementary Material). He was able to immediately answer the sleep technologist over the intercom. Duration of behaviors was about 15 s long without interpretable ictal EEG correlates, secondary to movement noise. There were a few right frontal epileptiform sharp transients that phase reversed on interictal EEG at probe F8 (right frontal). Ictal EEG waveforms were non-diagnostic due to severe movement artifact (Figure S1 in Supplementary Material). Moderate obstructive sleep apnea was also described.
Video EEG allowed for the semiologic diagnosis of SHE. He was initiated on and titrated to a therapeutic dose of oxcarbazepine, a functional relative of carbamazepine that lacks the complications of autoinduction. Seizures and related activity were completely resolved after 24 h at a dose of 1,800 mg/day. The patient was discharged and self-reports continued control of seizures 3 months later.
Etiology in this subject was unlikely to be genetic given the autosomal dominant pattern of SHE presenting earlier in life. He had a relatively benign developmental and family history, leaving an acquired etiology as a possible explanation. The patient was voluntarily enrolled in an existing approved study designed to use multishell diffusion-weighted imaging (DWI) MRI and tractography in brain injured patients to evaluate for diffuse axonal injury (DAI), not otherwise appreciated on traditional imaging techniques, such as computed tomography or outpatient MRI. Furthermore, tractography has been shown to detect significant white matter abnormalities in various non-lesional epilepsy syndromes, despite epilepsy being classically considered a disease of gray matter. This study was carried out in accordance with the recommendations of WRNMMC Institutional Review Board (20337) and Department of Defense, with written informed consent from the subject to participate and for his case and results, including supplementary videos and images, to be published in a scientific journal. The subject gave written informed consent in accordance with the Declaration of Helsinki. A multishell diffusion scheme was used, with b-values of 1,000, 2,000, and 3,000 s/mm2 and additional 19 volumes of non-DWI, and resolution of 1.7 mm x 1.7 mm x 1.7 mm. Each b-value was sampled in 90  directions. Two sets of DWI with opposite phase-encoding directions were acquired using simultaneous multislice sequence with a 3.0 T GE scanner accompanied by 32-channel head coil. The diffusion data were reconstructed using generalized q-sampling imaging (GQI) after preprocessing steps including denoising and correction of geometric distortion. As had previously been reported in this patient, no findings were appreciated on traditional structural MRI. However, using multishell GQI tractography, the right superior longitudinal fasciculus (SLF) was noted to be damaged, as evidence by a lesion in the image itself, as well as decreased generalized fractional anisotropy (gFA) compared with the contralateral SLF (Figures 2 and 3).