Cataplectic Attack Research Articles

Rapid Eye Movement Sleep Is Initiated by Dopamine Signaling in the Basolateral Amygdala in Mice

The sleep cycle alternates between REM and NREM sleep, but the mechanisms by which this cycle is generated are totally unknown. We found that a periodic transient increase of the dopamine level in the amygdala during NREM sleep terminates NREM sleep and initiates REM sleep. This mechanism also plays a role in cataplectic attack, which is a pathological intrusion of REM sleep into wakefulness in narcoleptics.

The clinical characteristics of cataplectic attack in narcolepsy type 1

ObjectiveCataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). MethodsWe experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. ResultsWe observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. ConclusionFour-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

Fluctuation of primary motor cortex excitability during cataplexy in narcolepsy.

ObjectiveCataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages.MethodsThirty‐five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video‐polysomnogram monitoring. Transcranial magnetic stimulation motor‐evoked potential (TMS‐MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage.ResultsBased on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4.InterpretationThis study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack.

Ambulatory video-EEG-EMG monitoring and analysis during cataplexy in narcolepsy

Objective To comprehensively analyze the clinical and electroneurophysiological characteristics during the process of cataplexy by dynamic video?EEG?EMG monitoring. Methods Six narcolepsy type 1 patients with typical cataplexy were enrolled and 2 of them were diagnosed as status cataplecticus. All patients underwent polysomnography (PSG) and daytime Multiple Sleep Latency Test (MSLT) to clarify the diagnosis. Cataplexy was triggered by emotional stimulus and recorded under dynamic video-EEG-EMG monitoring. EEG characteristics during cataplexy were further compared and analyzed. Objective To comprehensively analyze the clinical and electroneurophysiological characteristics during the process of cataplexy by dynamic video-EEG-EMG monitoring. Methods Six narcolepsy type 1 patients with typical cataplexy were enrolled and 2 of them were diagnosed as status cataplecticus. All patients underwent polysomnography (PSG) and daytime Multiple Sleep Latency Test (MSLT) to clarify the diagnosis. Cataplexy was triggered by emotional stimulus and recorded under dynamic video-EEG-EMG monitoring. EEG characteristics during cataplexy were further compared and analyzed. Results Fourteen cataplectic attacks in 6 patients were recorded. According to the clinical and video- EMG characteristics, cataplectic attack was divided into 4 stages, including triggering phase (CA1), resisting phase (CA2), atonic phase (CA3) and recovering phase (CA4). EEG frequency and amplitude varied from one stage to another and hypersynchronous paroxysmal theta (HSPT) was observed in early resisting phase (CA2), which was supposed to be a distinctive EEG characteristic during the onset of cataplexy. Conclusions Generalized cataplectic ttack contain 4 stages, which indicate a complicated and dynamic process in clinical and electroneurophysiology. Moreover, it's highly possible that HSPT during resisting phase (CA2) is critical in the mechanism of cataplexy. DOI: 10.3969/j.issn.1672-6731.2017.09.006

A Case of Takotsubo Cardiomyopathy Complicated by Transient Cataplectic Attack of Upper Limb

A 60 year-old women realized chest pain during an argument. Next day, she visited a clinic, and was transferred to our hospital due to suspected acute coronary syndrome with ECG T-wave changes. Because coronary angiogram showed no significant stenosis, whereas left ventriculography demonstrated akinesis in the apical and mid-ventricular region and hyperkinesis in the basal area, we diagnosed as Takotsubo cardiomyopathy. Anticoagulation therapy was started as soon as possible because left ventricle (LV) apical wall motion was severely reduced. Nevertheless, she suffered a bout of cataplectic attack of upper limb at the day of admission. Head MRI demonstrated high intensity area located near right lateral cerebroventricle. At the same time, echocardiography also demonstrated improvement of LV apical and mid-ventricular wall motion. After that, intensification of anticoagulation therapy and start of rehabilitation were performed. She was discharged without paralysis after ten days of hospitalization. In this case, it took comparatively a long time for her to be diagnosed as Takotsubo cardiomyopathy from chest pain. Therefore, it seemed more likely that small thrombus was formed in LV apex. Because LV wall motion improved earlier than usual, free thrombus from LV wall caused cerebral embolism. This case suggested that intensification of anticoagulation therapy was needed when it took a long time to be diagnosed as Takotsubo cardiomyopathy from onset.

GHB for cataplexy: Possible mode of action.

The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to 'heterologous denervation supersensitivity' resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors ('autoreceptors'). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the 'switching off' of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition.

Anomalous Hypothalamic Responses to Humor in Cataplexy

BackgroundCataplexy is observed in a subset of patients with narcolepsy and affects approximately 1 in 2,000 persons. Cataplexy is most often triggered by strong emotions such as laughter, which can result in transient, yet debilitating, muscle atonia. The objective of this study was to examine the neural systems underlying humor processing in individuals with cataplexy.Methodology/Principal FindingsWhile undergoing functional Magnetic Resonance Imaging (fMRI), we showed ten narcolepsy-cataplexy patients and ten healthy controls humorous cartoons. In addition, we examined the brain activity of one subject while in a full-blown cataplectic attack. Behavioral results showed that participants with cataplexy rated significantly fewer humorous cartoons as funny compared to controls. Concurrent fMRI showed that patients, when compared to controls and in the absence of overt cataplexy symptoms, showed pronounced activity in the emotional network including the ventral striatum and hypothalamus while viewing humorous versus non-humorous cartoons. Increased activity was also observed in the right inferior frontal gyri -a core component of the inhibitory circuitry. In comparison, the one subject who experienced a cataplectic attack showed dramatic reductions in hypothalamic activity.ConclusionsThese findings suggest an overdrive of the emotional circuitry and possible compensatory suppression by cortical inhibitory regions in cataplexy. Moreover, during cataplectic attacks, the hypothalamus is characterized by a marked decrease in activity similar to that observed during sleep. One possible explanation for these findings is an initial overdrive and compensatory shutdown of the hypothalamus resulting in full cataplectic symptoms.

Sodium oxybate: Efficacy, safety and tolerability in the treatment of narcolepsy with or without cataplexy

Sodium oxybate is the sodium salt of gamma- hydroxybutyrate, an endogenous cerebral inhibitory neurotransmitter. It is licensed in the United States for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy and in the European Union for the treatment of narcolepsy with cataplexy. Its mode of action is uncertain, but it increases 5-hydroxytryptamine turnover, interacts with opioid systems and may act as a gamma-aminobutyric acid B receptor agonist (GABA(B)). It is rapidly absorbed and eliminated, having a mean elimination half-life of 30-60 minutes. In controlled trials in narcolepsy without cataplexy, it decreased excessive daytime sleepiness and increased several quality of life domains. In combination with modafinil, it exerted an additive effect in diminishing daytime sleepiness. Both acute (four to eight weeks) and chronic (12 months) studies have demonstrated sodium oxybate's efficacy in decreasing cataplectic attack frequency. It is well tolerated with adverse event withdrawal rates of approximately 3-10% after acute and chronic administration. There is no clear evidence of a withdrawal syndrome after abrupt cessation of therapeutic doses. Sodium oxybate appears to be an effective and well-tolerated treatment for all the key symptoms of the two forms of narcolepsy.

Clinical, behavioural and polysomnographic correlates of cataplexy in patients with narcolepsy/cataplexy

Background Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form of rapid eye movement (REM) sleep motor dyscontrol appearing during wakefulness and elicited by emotions. This study examined the relationship between the frequency of cataplectic attacks in patients with narcolepsy/cataplexy and (a) the clinical and behavioural characteristics of cataplectic attacks, including the emotional tone of trigger events, and (b) the polysomnographic characteristics of daytime sleepiness, nocturnal sleep structure and indices of motor disorders during sleep. Methods A consecutive series of 44 first-diagnosed drug-naive patients with narcolepsy/cataplexy, fulfilling the International Classification of Sleep Disorders, 2nd edition (ICSD-2) clinical and polysomnographic diagnostic criteria, were interviewed to estimate the frequency and clinical characteristics of cataplectic attacks and the occurrence of REM sleep behaviour disorder (RBD). All patients also underwent a video-polysomnographic recording to assess their sleep parameters and indices of altered motor control during sleep. Results Patients were divided into two groups on the basis of the frequency of cataplectic attacks, namely high-frequency ( n = 30) or low-frequency ( n = 14) depending on whether they estimated they had more or less than one attack per month. High-frequency patients (with a larger proportion of men) reported attacks more often affecting mainly the head, jaw and shoulder muscles and experienced more events among those listed as possible triggers of attacks. Sixty-one percent of patients reported RBD and 43% had an RBD episode at video-polysomnography regardless of the frequency of cataplectic attacks or gender. Lastly, the frequency of periodic leg movements (PLM) per hour was higher in men than women and increased with age. Conclusions Patients with more than one cataplectic attack per month had more frequent involvement of head, jaw and shoulder muscles and were mainly men. The proportions of patients with clinically assessed RBD and an RBD episode documented by video-polysomnography, as well as conspicuous values of PLM per hour, are fairly consistent with those reported in recent small-group studies. Therefore, it seems legitimate to argue that RBD and PLM are nocturnal manifestations intrinsic to narcolepsy/cataplexy and that the gender-related differences in the frequency of attacks and the value of PLM per hour may be indicative of a larger difference in the clinical and polysomnographic characteristics of narcolepsy/cataplexy than hitherto suspected.

Unusually prolonged rebound cataplexy after withdrawal of fluoxetine

We report an unusually prolonged cataplectic attack in a patient with narcolepsy who stopped fluoxetine to perform sleep investigations. A 57-year-old woman with a 24-year history of clinically definite narcolepsy with cataplexy was referred for reassessment of treatment because of increasing insomnia. The patient reported excessive daytime sleepiness (Epworth Sleepiness Scale score 20/24) and maintenance insomnia with creeping and itching sensations in the legs accompanied by an urge to move. She had daily episodes of cataplexy with sagging of the face, jaw, and eyelids, slurred speech, and rarely head drooping. The episodes were triggered by positive or negative emotions and lasted a few seconds up to 1 minute. She had also monthly episodes of sleep paralysis and auditory hypnagogic hallucinations. The Ullanlinna Narcolepsy Scale score was 30 of 44 (a score of >14 suggests narcolepsy), and the Swiss Narcolepsy Scale score was −66 (a score of <0 suggests narcolepsy). …

A video-polygraphic analysis of the cataplectic attack

Objectives and methods: To perform a video-polygraphic analysis of 11 cataplectic attacks in a 39-year-old narcoleptic patient, correlating clinical manifestations with polygraphic findings. Polygraphic recordings monitored EEG, EMG activity from several cranial, trunk, upper and lower limbs muscles, eye movements, EKG, thoracic respiration. Results: Eleven attacks were recorded, all of them lasting less than 1 min and ending with the fall of the patient to the ground. We identified, based on the video-polygraphic analysis of the episodes, 3 phases: initial phase, characterized essentially by arrest of eye movements and phasic, massive, inhibitory muscular events; falling phase, characterized by a rhythmic pattern of suppressions and enhancements of muscular activity, leading to the fall; atonic phase, characterized by complete muscle atonia. Six episodes out of 11 were associated with bradycardia, that was maximal during the atonic phase. Conclusions: Analysis of the muscular phenomena that characterize cataplectic attacks in a standing patient suggests that the cataplectic fall occurs with a pattern that might result from the interaction between neuronal networks mediating muscular atonia of REM sleep and neural structures subserving postural control.

Narcoleptic syndrome and paradoxical sleep.

SummaryIn order to elucidate the mechanism of the narcoleptic syndrome, the course of all‐night sleep was investigated by means of poly graphic methods or by using inducing stimuli. Further study on each symptom was performed in relation to the sleep mechanism using similar methods. Thirty‐three cases of typical narcolepsy were examined. The results from these studies are summarized as follows.1. The paradoxical phase of sleep occurs immediately after sleep onset in the natural nocturnal sleep of narcoleptics. The proportion of sleep time spent in the paradoxical phase (30%) in narcoleptics is higher than in normals, whereas that of the deep sleep stage is lower.2. In narcolepsy, hypnagogic hallucination and sleep paralysis appear mostly during the paradoxical phase. During these episodes the level of cerebral vigilance ascends temporarily but slight differences are found between these two episodes. The responses to the stimuli (auditory evoked response, the H reflex and the knee jerk) are similar to those in normals in each stage of sleep.3. Chlorpromazine, being effective against hypnagogic hallucination and sleep disturbance, stabilizes a night's sleep and prolongs the duration of deep sleep and the paradoxical phase. Imipramine with a suppressing action on cataplectic attack, inhibits the occurrence of the paradoxical phase at sleep onset and diminishes the following paradoxical phases, accompanied by a decrease of hypnagogic hallucination.4. The level of wakefulness tends to descend easily in narcoleptics. In sleep attacks, the subjects fall rapidly into the paradoxical phase from alert or drowsy state. Both sleep attacks and a tendency to fall asleep are apt to occur periodically in the daytime with lucid intervals.5. A cataplectic attack closely relates to the paradoxical phase. During the episode, a great discrepancy is found between hypofunction of the arousal system and function of the motor and autonomic systems. Cataplectic occur frequently concomitant with the sleeping‐waking rhythm.6. Fundamental disorders of narcolepsy are considered as follows: the abnormal occurrence of the paradoxical phase of sleep, the tendency to fall asleep easily, the sleep cycle through night and day and the remarkable dissociation of the arousal system from the motor or autonomic systems. Accordingly, disorders in the sleep‐wakefulness regulating mechanisms are found. Dysfunction of the brain stem reticular formation, especially in the pons, and disturbances of the interrelationship among them are discussed.

Electroencephalographic study on narcolepsy

A total of 124 EEG examinations were performed in 75 narcoleptic patients. The routine EEGs were normal (abnormal slow waves being observed in less than 10%). The majority of the patients fell in drowsy state and sleep in the early part of the examination and about a half of them did so even during overbreathing. Polygraphic recording of the EEG, EKG, eye movements and respiratory movements were obtained in 34 examinations performed in 21 narcoleptics. An EEG pattern resembling that of drowsy state was found in 18 records in association with rapid eye movements (REM) at the sleep onset or several minutes after the onset. The patients often experienced sleep paralysis and/or hallucinations exclusively in the sleep onset REM period. During a cataplectic attack lasting for a brief period of about 30 sec, low voltage alpha rhythm was observed. Two other recordings obtained soon after the onset of and during cataplectic attacks which lasted several minutes indicated that the patients fell in the REM period soon after the onset of the attacks. The patients experienced hallucinations and/or dreams in the later parts of the attacks, which corresponded to the REM period. It would thus seem that cataplectic attacks are experienced in the transitional state from wakefulness to the REM period. The patients were in a similar or slightly higher level of consciousness in the early part of the sleep onset REM period than in drowsy state. In the REM period occurring several minutes after the sleep onset, they were in sleep, the depth of which corresponded to the sleep stages with spindles and high voltage slow waves. When the EEG pattern of the other sleep stages were observed, they were really in sleep, the depth of which was comparable to that of normal persons in the corresponding sleep stages. The EEG response to arousing stimuli were much decreased in the REM period as compared with those observed in the other sleep stages. In the early part of the sleep onset REM period as well as in the other part of the REM period the flash stimuli induced little or no EEG responses, although in the former period the patients were conscious of the stimuli and later recollected the correct number of them. In other sleep stages than the REM period the patients responded to and remembered only those but not all stimuli that induced marked arousal response in their EEGs. In conclusion, the basic disturbances characterizing narcoleptics are a persistent and intense inclination to fall in sleep and to fall into the REM period of sleep directly from wakefulness and at the sleep onset. Both, but predominantly the former, characterize sleep attacks, and the latter is manifested as cataplectic attacks, sleep paralysis and hypnagogic hallucinations. Narcolepsy is considered to be a disease not related to epilepsy.