Morvan syndrome and related disorders associated with CASPR2 antibodies
Jan. 18, 2022
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Paradoxical insomnia (previously called sleep state misperception) is characterized by complaints of little or no sleep over long periods of time without the level of impairment expected with such a level of sleep deprivation. Patients often describe heightened awareness of their surroundings when lying down to sleep. Sleep study reveals normal sleep architecture with normal sleep onset latency and sleep efficiency, but with subjective patient reports indicating prolonged sleep onset latency and poor sleep efficiency. Treatment usually involves patient reassurance. Behavioral therapy and sedative-hypnotics have also been tried.
• Paradoxical insomnia should be considered in patients with insomnia who complain of severe insomnia, with little or no sleep but without objective evidence of consequences commensurate with the described level of sleep deprivation.
• Patients show evidence of overestimation of sleep onset latency and underestimation of sleep efficiency.
• Patients do not show other evidence of malingering or psychopathology.
• Polysomnographic recordings do not show evidence of sleep disorder, and sleep parameters such as sleep efficiency and sleep onset latency are within normal limits.
Sleep state misperception (paradoxical insomnia) is a diagnostic term adopted in the International Classification of Sleep Disorders (04) to replace 2 previously used diagnostic categories of sleep disorders: subjective insomnia complaint without objective findings and subjective sleepiness complaint without objective findings. In the ICSD-3 edition, the term sleep state misperception was replaced with “paradoxical insomnia” and will be used where appropriate herein (02). The American Academy of Sleep Medicine developed Research and Diagnostic Criteria (RDC) for insomnia (03). The RDC criteria also provided 3 subclassifications of primary insomnia: psychophysiologic insomnia, paradoxical insomnia, and idiopathic insomnia. Other terms used in the past to describe patients with this disorder include subjective insomnia, pseudo-insomnia, subjective sleepiness, and sleep hypochondriasis. Paradoxical insomnia implies a significant and persistent symptom, either insomnia or sleepiness, which is not documented on objective testing (nocturnal polysomnography and daytime multiple sleep latency test). Paradoxical insomnia is characterized by discrepancy between subjective and objective assessments of sleep measure and can be challenging to diagnose and to treat.
The ICSD-3 classifies paradoxical insomnia as a clinical and pathophysiological subtype of a chronic insomnia disorder, and symptoms must be present for at least 3 months.
A review of this concept of sleep state misperception addressed a different subset of individuals who seem to overestimate the amount of time spent in sleep compared to that captured on polysomnography. For extensive reviews, please see (32; 09).
The diagnosis of paradoxical insomnia requires that the patient complain of a sleep-related symptom, either insomnia or excessive daytime sleepiness, that is not documented by standard evaluation with nocturnal polysomnography and the multiple sleep latency test. Patients are otherwise psychiatrically and medically healthy. Additionally, the symptom must be present during the evaluation. In either case, the symptom must be long-standing and result in a disturbance of occupational or social function that the patient believes will improve with successful treatment of the symptom. The diagnosis does not apply to cases of malingering or to symptoms directly secondary to a diagnosed psychiatric disorder.
Patients typically describe many years of short sleep, no sleep, or nonrestorative sleep. Patients may also report constant or near constant awareness of environmental stimuli throughout most nights. They may also complain of constant thoughts or rumination through most of the night as they lay recumbent. Some patients report that pharmacological or behavioral treatment improved symptoms, in some cases for prolonged periods of time. In other cases, treatment was not effective, or was effective only briefly, and then the symptoms returned. After the sleep evaluation, no abnormality is found, leading to the diagnosis of paradoxical insomnia.
Patients may also present with a complaint of chronic disabling sleepiness; nonetheless, during polysomnographic evaluation no sleep disorder is found and the level of physiological sleepiness is not abnormal. Thus, as in the case of insomnia, the sleep state is misperceived.
The prognosis of this patient group is not clearly delineated. The condition appears to be chronic with persistent attempts to obtain relief of symptoms. A major complication is drug dependence, as the patients often receive hypnotics or stimulants from physicians. Chronic use of either type of drug can be associated with drug dependence.
A 42-year-old married Asian-American woman was referred to the sleep disorders center for the evaluation of difficulty initiating and maintaining sleep for the past 1.5 years. The sleep problem began when the patient and her husband had moved to New York City in connection with their business. The patient had gained 20 lb during the onset of the insomnia. She consulted an internist, who recommended weight loss, and the patient then began experiencing fainting spells and weakness that increased her distress. She then consulted a psychiatrist who prescribed fluoxetine, which worsened her sleep and other symptoms. The medication was discontinued and clonazepam was prescribed (0.25 mg), which improved her symptoms. Another move occurred about 1 year after the sleep complaint began. She consulted an internist in her new location; her cholesterol was mildly elevated but no other medical diagnoses were found, and the medication was continued.
This physician referred her to the sleep disorders center. In the sleep consultation, she said her goal was 6 hours of undisturbed sleep each night without the use of medication. She used the medication every night over the past year and estimated about 3 to 4 hours of sleep. Further history revealed that her weight was stable over the past 1.5 years after the 20-lb gain (5 feet 2 inches and 135 lb). Her husband was concerned about her snoring and occasional pauses in her breathing while apparently asleep. She used no alcohol, caffeine, tobacco, or illicit drugs. Other than infertility, there was no history of other medical symptoms or disorders. The patient underwent 1 night of polysomnography at her usual bedtime with monitoring of respiration in addition to the usual polysomnographic parameters. Her medication had been discontinued for 10 days prior to the recording and the patient complained of very little sleep during that period. The morning after the sleep recording she stated that she had slept 5 or 10 minutes during the 8 hours in bed. The polysomnography found about 6 hours of sleep with normal sleep stages, and only 5 apnea episodes with mild intermittent snoring. The sleep disorders physician met with the patient as well as with the patient and her husband several times. The focus of these discussions was a description of the physiological normality of her sleep different than her perception. Sleep hygiene was emphasized as treatment. It was emphasized that physically her sleep was adequate and restorative. The patient agreed to stop the medication and adopt more regular sleep habits and decrease her work hours. This plan was successful in the short term, but the patient was lost to follow-up.
The etiology of paradoxical insomnia is not known, and the neurophysiological mechanisms of paradoxical insomnia still require further investigation (32). Some attribute the insomnia complaint to presleep cognition that imparts an impression of not sleeping. Others theorize that excessive mentation in sleep gives the patient the impression of not sleeping although, in fact, the mentation is in the sleep state. A report found that insomnia patients who were unable to identify the cause of their sleep disturbance were most likely to underestimate their sleep (12). Paradoxical insomnia and psychophysiological factors have overlapping symptoms as well as similarly elevated adrenocorticotropic hormone and cortisol levels as measured in a small study comparing the 2 groups (25).
In a similar vein, the disorder is seen as an extreme example of the tendency of most insomnia patients to exaggerate or misreport their sleep problem. Researchers have reported that patients with primary insomnia have attenuation in the mesograde amnesia that accompanies sleep and are more likely to recall information from sleep onset intervals than control subjects (30). It has been hypothesized that psychological distress influences perception of sleep, which is supported by the finding that elevated scores on the Psychasthenia scale of the Minnesota Multiphasic Personality Inventory correlate positively with sleep time underestimation. Others speculate that a physiological abnormality exists in these patients, but that it is too subtle to be detected by conventional polysomnography (18; 24). For instance, it has been shown that auditory stimuli sufficient to increase arterial blood pressure or heart rate without signs of arousal on the EEG can result in increased sleepiness. Actigraphy has shown increased movement in paradoxical insomnia patients, providing some support for this hypothesis.
In some patients with subjective sleepiness, misperception or mislabeling of another bodily state such as fatigue or depression probably accounts for the symptom. For instance, in 2 studies, both nefazodone and fluoxetine alleviated depression and resulted in improvements in subjective sleep quality, although patients given fluoxetine showed significant declines in objective sleep characteristics such as an increased number of awakenings and decreased sleep efficiency. No group difference in sleep diary measures of sleep quality was seen between patients given nefazodone or the antidepressant paroxetine, despite the declines in objective sleep measures observed in patients given paroxetine. Others may attribute such daytime dysfunction as trouble concentrating or memory problems to sleepiness when in fact sleepiness is not present. Alternatively, the usual changes in alertness that are related to the circadian rhythm can be perceived as abnormal somnolence by some patients when those are expected changes in the levels of sleepiness.
Patients with posttraumatic stress disorder underestimate total sleep time and sleep efficiency compared to objective sleep measured by actigraphy (15).
Sleep apnea patients are found to overestimate sleep-onset latency and underestimate total sleep time (10). In a large sample of patients with obstructive sleep apnea (n=405), perception of total sleep time improved when the patient underwent a CPAP titration study (10). These reports support the concept of paradoxical insomnia in somnolent patients. In the above cited reports, the authors conclude that marked discrepancies between patient reports and objective measures are not limited to insomnia patients. The subjective state of sleepiness is correlated with, but different than, physiological sleepiness or sleep propensity as measured by the multiple sleep latency test.
Patients with mild traumatic brain injury have been shown to estimate that they sleep a bit less than they actually do on PSG than perceived. A sample of 37 patients reported they slept 342 minutes in the lab when they actually slept 382 minutes on average (35).
The essential aspects of paradoxical insomnia are that physiological measurement of the sleep-wake system is intact, despite the complaint of sleep-related symptoms. The pathogenesis and pathophysiology for the perception of sleep and sleepiness remains unclear. An attempt has been made to correlate multiple EEG measures such as sleep stage, sleep onset latency, waking time and arousal frequency, total sleep time, EEG frequency, and sleep spindle density with the perception of sleep. It is clear that no single factor or combination of EEG factors completely explains the subjective perception of sleep. Likewise, the pathogenesis and pathophysiology for the misperception is unknown. However, some progress has been made in terms of the role of sleep spindles in paradoxical insomnia. Normand and colleagues suggest that a deficiency in sleep spindles might account, at least in part, for the sleep state misperception that occurs in paradoxical insomnia (27). Sleep spindle characteristics for 17 patients with paradoxical insomnia, 29 good sleepers, and 24 patients with psychophysiological insomnia were compared. Relative to the other groups, paradoxical insomniacs had the shortest sleep spindles on night 3 of 4 in the laboratory. The study highlights a need for additional studies on spindle length and its role in perception of sleep.
Perception of being asleep or awake in insomnia patients differs from the perception in normal sleepers (23; 22), and this is independent of age, sex, or laboratory versus ambulatory recording setting (34). In Trimmel and colleagues’ study, n = 303 patients with insomnia underestimated total sleep in the sleep laboratory by an average of 46 minutes. Paradoxical insomnia was not specifically studied in these reports, but these findings may point to a unique perceptual difference in insomnia patients. One paper investigated insomnia patients with paradoxical insomnia and reported differences in a physiological measure of arousal on comparing these patients to normal sleepers and objectively documented primary insomniacs (07). Another study compared REM sleep macrostructure and microstructure as well as clinical interviews between good sleepers, psychophysiological insomnia, and paradoxical insomnia. Participants underwent 4 consecutive PSGs in the laboratory. The paradoxical insomnia group was distinguished by higher number of wake intrusions in REM, and there was a relationship between REM duration and dream imagery activity (31).
Insomnia patients with less alpha EEG activity during recorded sleep have been reported to underestimate sleep time and overestimate intermittent awakening when compared to a group of insomnia patients with increased alpha activity (33). The aforementioned findings support an underlying neurophysiological mechanism in paradoxical insomnia.
Alpha-delta sleep (A-DS), which is an electroencephalographic (EEG) feature characterized by presence of alpha waves and low voltage fast activity representing relaxed wakefulness, superimposed on delta waves, characteristic of deep nonrapid eye movement (NREM) sleep, has long been associated with light sleep sensation. The literature regarding A-DS and sleep time misperception has been equivocal. However, in 1 study, investigators prospectively analyzed polysomnograms of about 5000 patients referred to a sleep laboratory and showed significant correlation between the discrepancy in subjective and objective sleep duration and perception of light sleep with degree of A-DS ranked from 1 to 4, especially in patients without obstructive sleep apnea and insomnia (21).
EEG spectral analyses of PSG recordings in insomnia patients have been explored in a number of studies. Some of the investigations showed greater relative amplitude of the high frequency (14 to 45 Hz) range as well as excessive high frequency activity amongst the subjective insomnia patients, suggesting a relationship to their sleep complaint (29; 20).
Cyclic alternating pattern (CAP) is an EEG pattern characterized by sequences of electrocortical events of non-REM sleep distinct from background activity and recurring with a periodicity of 20 to 40 seconds. This has been reported to correlate with poor sleep quality. Patients with paradoxical insomnia had significantly higher CAP rate overall, which increased before subjective sleep onset time compared to normal controls (28). These findings were supported in a study that compared CAPs in 10 individuals with paradoxical insomnia to 10 individuals with psychophysiological insomnia and to 10 normal controls. Differences mostly concerned increases in A3 and B3, and especially B3 in stage 2, in both psychophysiological insomnia and paradoxical insomnia. The authors attributed these findings to the level of hyperarousal. Moreover, although CAP rate was similar between the insomnia subtypes, the overall CAP time was increased in the paradoxical insomnia subgroup (11).
It is important to keep in mind that even in normal healthy volunteers, misperceptions of sleep can occur. In a sample of 44 participants, all were asked to sleep at their normal nighttime schedule on their first night in the laboratory. Then they had a 12-hour nighttime sleep opportunity as well as a 4-hour daytime nap opportunity without access to time cues. The extended night sleep opportunities and long daytime naps were designed to induce an “insomnia” with substantial time awake during scheduled sleep. Results showed that sleep estimations were accurate when participants sleep according to their normal night’s schedule. Participants underestimated sleep time in the 12-hour sleep opportunity, and this was inversely correlated with stage 2 sleep. Participants overestimated sleep in the 4-hour daytime nap opportunity, and this was correlated with REM and stage 3 sleep. The study suggests that sleep misperceptions may be related in part to the presence or absence of time cues and time of day (06).
Further studies are needed for better understanding of the underlying pathophysiology of paradoxical insomnia, which should include, but not be limited to, quantitative EEG analysis, neurophysiological, and objective psychological variables. Evaluating the impact of various stimuli on cortical measures such as examining event-related potentials (ERPs) to study hyperarousal is also recommended (05). By the same token, more patients evaluated for subjective complaints of excessive sleepiness or perceived insomnia should be evaluated with polysomnogram studies and multiple sleep latency tests, in order to correctly identify paradoxical insomnia.
Paradoxical insomnia can present as insomnia or daytime sleepiness. A serious insomnia problem is found on surveys in 15% to 20% of the general adult population. A complaint of sleepiness is found in 2% to 5% of the adult population. Nine percent of patients complaining of insomnia and 5% of patients complaining of sleepiness were classified as paradoxical insomnia among a large number of patients evaluated in sleep disorders clinics. Thus, a small percentage (less than 10%) of insomnia and sleepiness patients would be classified in this diagnostic category. A multicenter field trial of diagnostic systems found that 6.6% of cases were assigned paradoxical insomnia as a primary or secondary diagnosis.
Paradoxical insomnia is poorly understood. There is no information about prevention or about the risk factors associated with its development. Education about the range of normal sleep-wake patterns may alleviate concern in some patients.
Whether paradoxical insomnia should be considered a distinct subtype of insomnia or lumped under primary insomnia has been an area of considerable debate and review. Paradoxical insomnia typically includes a complaint of either insomnia or daytime sleepiness. Insomnia can be associated with difficulty initiating sleep, maintaining sleep, or with a sensation of nonrestorative sleep. With paradoxical insomnia, daytime symptoms associated with the sensation of lack of restoration are endorsed more frequently than the nighttime complaints. The critical difference between paradoxical insomnia and other insomnia categories (psychophysiologic, idiopathic) is that these patients have physiologically normal sleep on polysomnographic evaluation. Criteria for other diagnostic entities related to insomnia require the presence of disturbed sleep that is related to the cause of the insomnia. In most cases of insomnia, there is a degree of misperception of the sleep problem; however, in paradoxical insomnia this is the major finding, and the diagnosis is utilized only after completion of the sleep disorder evaluation. Over-reliance on polysomnographic data may increase the number of patients classified as having paradoxical insomnia through misinterpretation of night to night variability of the sleep of insomnia patients, or because differences in sleep needs of individuals are not considered.
Perception of sleep may also be influenced by psychiatric comorbidities. When 211 patients completed both the Pittsburgh Sleep Quality Index (PSQI) and sleep diary–derived sleep quality measures, the patients who endorsed more psychiatric comorbidities had a weaker correlation between these 2 measures (P = .047) (16).
In sleep state misperception of sleepiness, the essential difference from other diagnostic categories is the lack of corroboration of the sleepiness by the multiple sleep latency test (MSLT), a series of nap opportunities across the daytime following a nocturnal polysomnography. However, misperception of whether sleep has occurred on the MSLT has been documented in older adults (> 60 years old) with cognitive impairment. With a criterion of misperceiving at least 2 nap opportunities, patients who scored lower on the mini mental status examination and lower on the Epworth Sleepiness scale tended to “underperceive” naps (26). Other factors often associated with daytime sleepiness, such as sleep apnea syndrome or disturbed nocturnal sleep, are not present.
To establish the diagnosis of paradoxical insomnia requires that the patient's complaint of persistent insomnia is not verified by polysomnography, even though the patient feels that the evaluation night was representative of usual sleep.
Polysomnography should include routine sleep stage monitoring, a requirement not sustained in the International Classification of Sleep Disorders, third edition, as well as monitoring of respiration (airflow, effort, oximetry), ECG, leg movements, and continuous video observation (02). The RDC criteria for paradoxical insomnia suggest sleep efficiencies greater than 85% to 90% and a total sleep time (TST) greater than 6.5 hours on recorded nocturnal polysomnography. The MSLT is necessary in patients with a complaint of sleepiness. The assessment should also include a psychiatric evaluation to determine if depression or malingering accounts for the patient's sleep complaint.
Actigraphy is another useful tool in documenting the discrepancy between subjective and objective sleep duration and latency. These evaluations can also be used to reassure the patient regarding good sleep efficiency noted on multiple nights in the usual sleep environment. According to the AASM (American Academy of Sleep Medicine) practice parameters, no specific recommendations were made with regards to use of actigraphy for paradoxical insomnia. Its use for insomnia in general is regarded as “guideline” (this is a patient care strategy that reflects a moderate degree of clinical certainty).
There is no standard treatment for paradoxical insomnia. Management of paradoxical insomnia requires an adequate evaluation leading to accurate diagnosis and appropriate medical care.
Nonpharmacological treatments of paradoxical insomnia may include psychoeducation and behavioral experiments to test misperceptions of sleep. The clinician can use other objective methods available, such as comparing evidence of sleep on the polysomnogram or inactivity on actigraphy to sleep diaries with the patient. In 1 method developed by Geyer and colleagues, patients receive sleep education specifically for paradoxical insomnia (13). They are shown their polysomnogram waveforms and a video of themselves sleeping in the sleep lab. The patient is asked to indicate when on the video sleep onset occurred. Follow-up sessions include discussions about the discrepancy between objective sleep onset latency and subjective sleep onset latency. This method plus behavioral treatments (sleep education, sleep hygiene, progressive muscle relaxation, and stimulus control) was tested in 4 individuals with paradoxical insomnia. Post-treatment sessions were conducted 4 and 5 months after baseline. Two of the 4 patients who received sleep education for paradoxical insomnia had self-reported improvements in insomnia severity, sleep latency, and total sleep time. The other 2 patients who did not improve had elevated N1% sleep (14).
Other strategies include having the patient use a counter during the night to count the number of awakenings they experience. Patients often report that they press the counter fewer times than they thought they might have. Cognitive therapy is also used to address the patient’s difficulty in perceiving sleep reliably. Patients are reminded that time influences our perception of sleep and that sleep is essentially defined by the absence of memories (17).
In other cases, symptomatic treatment with sedative hypnotics is beneficial. Some propose the perception of sleep in insomnia patients is affected by sedative-hypnotic medications differently than in normal sleepers (23; 22). This finding may partially explain the benefit of these medications in patients with paradoxical insomnia. However, there is one case report of a man who developed paradoxical insomnia as a result of taking zolpidem (01).
The authors in a case report describe a patient with paradoxical insomnia and severe depression who responded to electroconvulsive therapy (ECT) treatments (08). The patient had severe insomnia that was causing major depression with suicidal ideation. She reported sleeping for only 35 hours in a month and had no response to multiple sedatives including zolpidem, zaleplon, temazepam, trazodone, chloral hydrate, and oxazepam. She was also started on antidepressants, including mirtazapine and venlafaxine. Actigraphy recordings showed consolidated periods of apparent sleep. Patient underwent ECT treatments 3 times a week, and following the very first treatment, she reported sleeping 7 hours. The improvement persisted for up to 24 months postdischarge.
Another study examined 29 Iranian patients with paradoxical insomnia who were randomized to receive either olanzapine or risperidone daily for 8 weeks. A Pittsburgh Sleep Quality Index (PSQI) was completed before and after therapy. Patients on olanzapine showed significantly greater improvements in sleep compared to those who received risperidone (19).
In paradoxical insomnia with a complaint of sleepiness, CNS stimulants temporarily improve the symptom, especially if fatigue or a latent mood disorder underlies the complaint. The physician must be concerned about an increased risk of drug dependence when prescribing sedatives or stimulants to this patient population as there is little reason to expect a physiological benefit despite symptomatic improvement.
No information is available about the relationship of paradoxical insomnia to pregnancy. The medications used for symptomatic relief are often contraindicated in pregnancy and should be avoided in women who are or who might become pregnant.
There is no evidence that paradoxical insomnia alters anesthetic risk. Any medication used for symptom relief should be stopped prior to the use of elective anesthetics.
Deirdre A Conroy PhD
Dr. Conroy of the University of Michigan has no relevant financial relationships to disclose.See Profile
Antonio Culebras MD FAAN FAHA FAASM
Dr. Culebras of SUNY Upstate Medical University at Syracuse received an honorarium from Jazz Pharmaceuticals for a speaking engagement.See Profile
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