Images: Facial cataplexy with demonstration of persistent eye movements

Abstract

A patient was transferred for management of “medication-refractory seizures” after failure of levetiracetam and valproate dual therapy. She had a life-long history of two types of events: periods in which she would rapidly and uncontrollably lapse into unconsciousness, and spells in which she would “pass out” but maintain consciousness, the latter happening with increasing frequency in association with laughing, as of late. She also reported hypnogogic/hypnopompic hallucinations, sleep paralysis, and disrupted nocturnal sleep. A clinical diagnosis of narcolepsy was made. The prevailing pathophysiological concept of narcolepsy details “partial intrusions of REM” sleep into wakefulness. Healthy REM sleep includes generalized atonia, but with preservation of eye movements, respiratory function, and sphincter tone. Cataplexy recapitulates this pattern, and is often induced by extreme emotions, laughter in this case. Despite generalized and severe weakness and areflexia during this patient's cataplectic events, she was able to volitionally move her eyes, which is consistent with the physiology of REM sleep. The diagnosis of cataplexy is often missed, due to clinicians being unfamiliar with the findings and the lack of ability to induce sufficient emotional responses to trigger an episode. This example of cataplexy is also quite characteristic of the “cataplectic facies.” The ability to observe the infrequently observed phenomenon of cataplexy serves as a reminder that consciousness is preserved, as are extra-ocular muscle movements.

Citation:

Schneider L, Ellenbogen J. Images: facial cataplexy with demonstration of persistent eye movements. J Clin Sleep Med. 2020;16(1):157–159.

INTRODUCTION

The prevailing pathophysiological concept of narcolepsy is one of sleep-wake instability, whereby elements of sleep physiology can impose themselves on wakefulness and vice versa. Cataplexy is felt to be one such example, a hallmark feature found in narcolepsy type 1¹ (formerly referred to as narcolepsy with cataplexy). Cataplexy is characterized by transient muscle atonia, focal or generalized, and is a reflection of partial intrusion of the normal muscle atonia seen in healthy rapid eye movement (REM) sleep.² Interestingly, in healthy REM sleep, even during generalized atonia, there is preservation of eye movements, as well as general autonomic functions (respiration, sphincter tone, etc.).³ Cataplexy is felt to recapitulate this overall pattern, with some speculating that, despite the absence of volitional activity of skeletal muscles caused by spinal inhibitory interneuronal suppression, there is preservation of eye movements.⁴ Knowing this information serves an important aid to the diagnostician who will attempt to distinguish cataplexy from events such as syncope and atonic seizures.⁴ While cataplexy bears distinctive features, such as reduced muscle tone and areflexia,⁵ being aware of the preservation of voluntary eye movements in cataplexy would be an important confirmation of the theories of narcolepsy physiology, and would be valuable in securing a diagnosis when circumstances are ambiguous. Here we present a case of a patient who presented with untreated, easily-inducible facial cataplexy that allowed for the demonstration of preserved consciousness and volitional eye movements.

REPORT OF CASE

A 76-year-old Caucasian woman with monotherapy-controlled hypertension was transferred from an outside hospital to the Neurology service’s epilepsy monitoring unit for “management of frequent, medication-refractory seizures” after failure of combination therapy with levetiracetam and valproate. The specific reason for transfer was for events that were described as “brief 30-to-60-second episodes of ‘passing out’ in which the patient reports that she is still awake and able to hear, despite 2 seizure medications.” Twenty-four-hour video electroencephalography (vEEG) captured multiple characteristic events triggered by laughter during morning rounds or interactions with epilepsy monitoring unit nursing staff. The vEEG during these prototypical events demonstrated a general decrement in muscle artifact in the EEG leads and persistence of a waking EEG throughout each episode, with no in-episode electrographic seizure activity, as well as no epileptiform discharges between episodes, confirming that these events did not represent seizures. A review of the outside MRI images demonstrated minor, global, age-associated atrophy and a minor degree of microvascular ischemic disease.

On further questioning the patient described a history since adolescence of two types of events: periods in which she would have an overwhelming drowsiness resulting in her lapsing into unconsciousness, only to wake up tens of minutes later; and spells in which she would “pass out,” but maintain consciousness despite either full-body paralysis or facial and neck laxity. The former events were reported to be less of a problem, rarely occurring if she was able to stay mentally and physically active in addition to taking brief naps once or twice a day. The latter event types were often triggered by laughter, and would spontaneously resolve after a minute or so. These spells were more frequent, and could happen with variable intensity multiple times a day if provoked by strong emotions. Despite her family and friends infrequently observing the patient’s episodes, the patient found them bothersome, causing the patient to attempt to restrain her emotions in social engagements. She rarely had full-body paralysis, but the recent increase in frequency of embarrassing facial episodes is what prompted the initial evaluation 1 year prior to the current presentation. Additionally, the patient reported hypnagogic/hypnopompic hallucinations and sleep paralysis.

Due to the patient’s pleasant disposition and frequent laughter, a facially-limited episode of cataplexy was able to be observed, in which the progressive onset of muscle atonia was noted following laughter (Figure 1 and Video 1 in supplementary material). The patient’s effort to resist the paralytic ptosis is notable through activation of the frontalis muscles (note the furrowing of the brow), in a manner similar to neuromuscular disorders.⁶ Moreover, the patient had prominent dysarthria as the paralysis affected voluntary muscles of the mouth. Also, demonstration of the maintenance of eye movements despite cataplexy-associated atonia was possible. During episodes, reflexes were absent (returning to 2+ between episodes) and diminished tone was consistent with the level of clinically apparent atonia. Based on the presentation and findings a clinical diagnosis of narcolepsy type 1 was suspected. The diagnosis was later confirmed with diagnostic polysomnography demonstrating sleep-state dysregulation and a sleep-onset REM period (SOREMP; REM sleep latency of 4.5 minutes) arising from stage N1 sleep, followed by a positive Multiple Sleep Latency Test (mean sleep latency 3.2 minutes; SOREMPs on naps 1, 4, and 5).

Figure 1. Persistence of volitional eye movements during facial cataplexy.

Still images from the video of facial cataplexy demonstration volitional leftward (A) and rightward (B) gaze despite facial muscle paralysis. The patient’s cataplectic episode is brought on by a period of intense emotion, her typical trigger being laughter. Note the progressive onset of muscle atonia in the facial muscles, as cataplexy is often likened to a melting. During the video (supplementary material), the patient is activating the frontalis muscles, causing furrowing of the brow, as she attempts to resist the progressive facial paralysis and ptosis. Craniofacial muscle weakness is more common in pediatric-onset narcolepsy. Her consciousness remains intact throughout the episode, but her speech becomes dysarthric as her muscles grow weaker, leaving her with only her diaphragm for breathing control. Finally, her volitional eye movements persist, as is characteristic of REM sleep.

DISCUSSION

Cataplexy is a central feature of hypocretin deficiency, yet is seldom observed by clinicians, resulting in under-recognition and frequent misdiagnosis, particularly given the relative frequency of cataplexy mimics such as syncope, epilepsy, hyperekplexia, drop attacks, and pseudocataplexy.⁷ Nonetheless, it is important to obtain video documentation of or, preferably, elicit a cataplectic event, because demonstration of clear-cut cataplexy (characteristic muscle atonia elicited by telling/hearing a joke or laughing) results in a high pretest probability of narcolepsy type 1.^8,9

The mechanisms underlying REM sleep are still being elucidated, yet the basis for preservation of eye movement activity has not been clearly identified.^10,11 It may be that the main generators of REM sleep atonia—the pontine sublaterodorsal nucleus and the more caudal ventral medulla—reside below the main eye-movement brainstem nuclei in the midbrain and upper pons.¹² Nonetheless, cataplexy, serves as a marker of the sleep-wake state instability that results from hypocretin deficiency, as the spells clearly recapitulate the atonia of REM sleep without necessarily inducing sleep or dream-like mentation. This potentially suggests that strong emotions very selectively activate the sublaterodorsal nucleus-ventral medullary atonia circuitry, rather than other parts of the REM sleep flip-flop switch.¹² As such, despite generalized and severe weakness during this patient's cataplectic events, she was able to volitionally move her eyes, which has not been previously demonstrated during a cataplectic attack, even though it is apparent that this should be the case.

DISCLOSURE STATEMENT

All authors have seen and approved this manuscript. Work for this study was performed at Adult and Pediatric Neurology Residency Programs, Johns Hopkins University, 600 N. Wolfe Street, Carnegie 490, Baltimore, MD 21287. Dr. Schneider reports no financial support related to this manuscript; Dr. Schneider reports personal fees from Medibio, personal fees from Hatch Baby, other from Knit, personal fees from Alphabet, personal fees from Jazz Pharmaceuticals, outside the submitted work. Dr. Ellenbogen reports no financial support or conflicts of interest related to this manuscript. Writing of this manuscript was supported by the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.

ABBREVIATIONS

EEG

electroencephalography

REM

rapid eye movement

SOREMP

sleep-onset REM period