Sleep hypermotor epilepsy (SHE) and non-rapid eye movement (NREM) sleep disorders of arousal (DOAs) have many features in common and can be difficult to distinguish. But doing so is essential, as the correct diagnosis has important implications for a patient’s future.
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Insights into the diagnosis of these two disorders were presented in a keynote talk at SLEEP 2021, a joint meeting of the American Academy of Sleep Medicine and the Sleep Research Society, by Nancy Foldvary-Schaefer, DO, MS, Director of Cleveland Clinic’s Sleep Disorders Center and a staff neurologist in its Charles Shor Epilepsy Center.
“Knowledge in the areas of sleep-related seizures and arousal disorders has burgeoned recently, thanks to international experts who are bridging the fields of sleep medicine, epilepsy medicine and clinical neurophysiology,” says Dr. Foldvary-Schaefer.
Her presentation, “The Devil Is in the Details: Using Semiology and Electro-clinical Correlation to Differentiate Sleep-Related Seizures and NREM Arousal Disorders,” included a case vignette recapped here to help compare and contrast the respective conditions.
Case: A 10-year-old girl with “sleep terrors”
Several times a month, the patient arouses with wailing about one hour after falling asleep. She hyperventilates, draws her knees to her chest and looks around in a frenzy for two to three minutes. Immediately afterwards, she can follow commands but cannot recall what happened.
Initial evaluations with EEG and MRI are negative, and she is diagnosed with sleep terrors, a DOA.
SHE and DOAs overlap
Both SHE and DOAs are associated with sleep and share a broad range of semiology, including seemingly purposeful, goal-directed complex behaviors outside consciousness, as well as autonomic nervous system changes (heart and respiratory rate elevations) and skeletal muscle activation. Both conditions can have ill-defined EEG manifestations and be activated by sleep deprivation and stress. They are genetically related, suggesting a shared pathophysiological mechanism.
Sleep-related epilepsies occur exclusively or predominantly in sleep and include:
Benign focal epilepsy of childhood with centro-temporal spikes
SHE (formerly known as nocturnal frontal lobe epilepsy)
SHE, the type most often confused with DOAs, has an estimated prevalence of 1.8/100,000, which is likely an underestimate. Scalp EEG abnormalities are uncommon. Seizure frequency tends to be high, leading to fragmented sleep with diurnal consequences. Etiology is unknown in many cases, but genetic associations and structural abnormalities can be found in others.
The following major semiology patterns are characteristic:
Unilateral or asymmetric tonic activity
Unnatural hypermotor movements (atypical proximal repetitive large movements, such as thrashing and dystonic posturing, sometimes with grimacing)
Integrated hypermotor movements (movements possible in normal activity, e.g., kicking, rocking or pedaling)
Gestural behaviors with high emotional content (e.g., fear or rage)
Dr. Foldvary-Schaefer emphasizes that seizures are not a random phenomenon but are the result of neuronal synchronization, engaging locally and distally connected networks involving the cortex and subcortex. They tend to evolve or originate in the ventromedial prefrontal region, although they can arise from almost any lobe.
“Identifying the onset zone of electrical activity and area of early spread are most important, underscoring the need for careful semiology analysis,” she adds.
DOAs differ from SHE in subtle ways
DOAs, which involve recurrent episodes of incomplete awakening from sleep, are common. They are often accompanied by daytime impairment, mood disorders, injuries, social isolation and embarrassment.
Limited or no associated cognition or dream imagery
Partial or complete amnesia for episode
Frequent involvement of crying or sobbing
Waxing and waning quality
Potential ability to interact with the environment (observers may be able to modify the interaction)
In some cases, coherent speech and normal arousal behaviors such as rubbing the face
Traditional DOA categories are as follows:
Confusional arousal (lifetime prevalence of 18.5%), characterized by mental confusion or confused behavior while patient remains in bed
Sleep terror (10.4%), characterized by episodes of abrupt terror, typically beginning with a frightening scream, and accompanied by autonomic arousal (mydriasis, tachycardia, tachypnea, diaphoresis)
Sleepwalking (22.4%), characterized by ambulation or other complex behaviors out of bed
Like SHE, DOAs are marked by increasingly complex behavior, but unlike SHEs, DOA motor events are not stereotyped, clustered or associated with extrapyramidal features. In addition, events may halt temporarily, which is not seen in seizures. Timing during sleep also differs: DOAs are more common in the first half of sleep, and at least one major event occurring outside deep sleep (stage N3) is highly supportive of a SHE diagnosis.
(For more on NREM parasomnias, see Handbook of Clinical Neurology [2019;161:397-410].)
Optimizing clinical evaluation
Differentiating SHE and DOAs requires obtaining a detailed history including semiology sequence, tempo, timing, duration and stereotypy. Polysomnography requires 18-channel EEG, expanded electromyography and high-quality video, possibly using a protocol for sleep deprivation to increase the likelihood of recording an event.
Assessment by skilled technologists who are trained in recognizing events and interacting with patients safely and effectively is of critical importance. Dr. Foldvary-Schaefer notes that her team teaches technologists to follow three steps when an event occurs:
Establish responsiveness. Commands and questions should require verbal and nonverbal responses (e.g., “What’s your name?” “Point to the door,” “Stick out your tongue,” “What are you feeling?”).
Describe behavior. Often the technologist detects behavior that cannot be seen on video, such as eye movements.
Test recollection after return to baseline. This provides a unique opportunity to determine whether a patient is aware of what happened. Ask what happened, whether there was a warning and if the episode was typical.
The case patient from earlier underwent further testing, including overnight polysomnography. During an event, EEG showed an ictal pattern in the left temporal lobe, evolving into a rhythmic beta temporal pattern classic for temporal lobe epilepsy (see images below). Repeat MRI was abnormal for a subtle malformation of cortical development in the temporal pole. Subsequent resection left the patient seizure-free.
“Normal EEG and MRI findings never exclude the diagnosis of epilepsy,” concludes Dr. Foldvary-Schaefer. “In this case, further evaluation was prompted, in part, by the high stakes of an incorrect diagnosis, ultimately leading to an excellent outcome.”