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At least 19 recordsLinked to original sources
PubMed1981

An etiology of narcolepsy-cataplexy and a proposed cataplexy neuromechanism.

Narcolepsy-cataplexy is an idiopathic sleep disorder that reflects a complex neuropathology. Surveys and physiological investigations indicate that genetic and stress factors are involved in its onset and that stress is associated with symptomatic fluctuations and exacerbations of its clinical course. This paper summarizes the literature regarding the evolution, characteristics and treatment of the disorder. A comprehensive etiology is advanced, integrating neurophysiological and psychological factors specific to narcolepsy-cataplexy with recent advances in blood pressure regulation. Moreover, a testable neuromechanism of cataplexy is proposed, based on longitudinal effects of chronic drowsiness, the strong hypnogenic effect obtained by carotid sinus stimulation, an experimental animal model of narcolepsy-cataplexy, the adaptive characteristics of baroreceptors and, finally, the interconnections between CNS sleep and blood pressure regulators of the brain stem. Through better understanding of the causes and mechanisms of narcolepsy-cataplexy, more effective treatments and preventive measures can be developed, high risk populations identified, and, perhaps, a cure found. Suggestions for future physiological and epidemiological research are made.

Cataplexy↗
PubMed1997

HLA DQB1*0602 is associated with cataplexy in 509 narcoleptic patients.

Narcolepsy is a sleep disorder associated with HLA DR15 (DR2) and DQB1*0602. We HLA typed 509 patients enrolled in a clinical trial for the drug modafinil and analyzed the results in relation to cataplexy, a symptom of narcolepsy characterized by muscle weakness triggered by emotions. The patients were either subjects with cataplexy who had a mean sleep latency (SL) of less than 8 minutes and two or more sleep onset rapid eye movement (REM) periods (SOREMPs) during a multiple sleep latency test, or narcoleptic patients without cataplexy but with a mean SL shorter than 5 minutes and two or more SOREMPs. The respective values of DRB1*15 (DR2) and DQB1*0602 as markers for narcolepsy were first compared in different ethnic groups and in patients with and without cataplexy. DQB1*0602 was found to be a more sensitive marker for narcolepsy than DRB1*15 across all ethnic groups. DQB1*0602 frequency was strikingly higher in patients with cataplexy versus patients without cataplexy (76.1% in 421 patients versus 40.9% in 88 patients). Positivity was highest in patients with severe cataplexy (94.8%) and progressively decreased to 54.2% in patients with the mildest cataplexy. A voluntary 50-item questionnaire focusing on cataplexy was also analyzed in 212 of the 509 HLA-typed patients. Subjects with definite cataplexy as observed by an experienced clinician were more frequently HLA DQB1*0602-positive than those with doubtful cataplexy, and the manifestations of cataplexy were clinically more typical in DQB1*0602-positive patients. These results show that the HLA association is as tight as previously reported (85-95%) when cataplexy is clinically typical or severe. We also found that patients with mild, atypical, or no cataplexy have a significantly increased DQB1*0602 frequency (40-60%) in comparison with ethnically matched controls (24%). These results could be explained by increased disease heterogeneity in the noncataplexy group or by a direct effect of the HLA DQB1*0602 genotype on the clinical expression of narcolepsy.

Adolescent↗
PubMed1994

Cholinergic mechanisms in canine narcolepsy--I. Modulation of cataplexy via local drug administration into the pontine reticular formation.

Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly into the pontine reticular formation on cataplexy, as defined by brief episodes of hypotonia induced by emotions, in narcoleptic canines. Carbachol and atropine were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of freely moving, narcoleptic and control Doberman pinschers. Cataplexy was quantified using the Food-Elicited Cataplexy Test, and analysed using recordings of electroencephalogram, electrooculogram and electromyogram. Cataplexy was characterized by a desynchronized electroencephalogram and a drop in electromyogram and electrooculogram activity. In narcoleptic canines, both unilateral and bilateral carbachol (10(-5) to 10(-3) M) produced a dose-dependent increase in cataplexy, which resulted in complete muscle tone suppression at the highest concentration. In control canines, neither bilateral nor unilateral carbachol (10(-5) to 10(-3) M) produced cataplexy, although bilateral carbachol, did produce muscle atonia at the highest dose (10(-3)). The increase in cataplexy after bilateral carbachol (10(-4) M) was rapidly reversed when the perfusion medium was switched to one containing atropine (10(-4) M). Bilateral atropine (10(-3) to 10(-2) M) alone did not produce any significant effects on cataplexy in narcoleptic canines; however, bilateral atropine (10(-2) M) did reduce the increase in cataplexy produced by systemic administration of physostigmine (0.05 mg/kg, i.v.). These findings demonstrate that cataplexy in narcoleptic canines can be stimulated by applying cholinergic agonists directly into the pontine reticular formation. The ability of atropine to inhibit locally and systemically stimulated cataplexy indicates that the pontine reticular formation is a critical component in cholinergic stimulation of cataplexy. Therefore, it is suggested that the pontine reticular formation plays a significant role in the cholinergic regulation of narcolepsy.

Analysis of Variance↗
PubMed2005

Reevaluating spells initially identified as cataplexy.

BACKGROUND AND PURPOSE: Cataplexy, transient episodes of bilateral muscle weakness with areflexia provoked by emotions, is a state highly specific to narcolepsy. Cataplexy is diagnosed based on clinical interview. Two screening tools have been developed recently but their usefulness has been limited because of length or current lack of psychometric data. Used effectively even these screening tests require the interpreting physician to have an understanding of the typical features of cataplexy. Most physicians encounter patients with cataplexy fairly infrequently, making it difficult to gain proficiency in detecting cataplexy based on clinical interview alone. Relatively little attention has been given to the differential diagnosis of cataplexy, which increases the likelihood of unnecessary sleep testing or false positive diagnosis. PATIENTS AND METHODS: This case series describes six cases where cataplexy was initially diagnosed. In all cases the weakness spells were eventually not attributed to cataplexy. The presentation and characteristics of these cases will be presented as a means to discuss the differential diagnosis of cataplexy. RESULTS: These cases represent a diverse set of medical disorders including bradycardia, migraine, delayed sleep phase syndrome, conversion disorder, malingering and a chronic psychotic disorder. CONCLUSIONS: A more in-depth understanding of the classic features of cataplexy should improve recognition of this fascinating state. Improved cataplexy recognition will enhance the appropriate usage of sleep tests and eventually increase the timeliness and accuracy of the diagnosis of narcolepsy with cataplexy.

Adolescent↗
PubMed2002

Cataplexy-related neurons in the amygdala of the narcoleptic dog.

The amygdala plays an important role in the interpretation of emotionally significant stimuli and has strong projections to brainstem regions regulating muscle tone and sleep. Cataplexy, a symptom of narcolepsy, is a loss of muscle tone usually triggered by sudden, strong emotions. Extracellular single-unit recordings were carried out in the amygdala of narcoleptic dogs to test the hypothesis that abnormal activity of a subpopulation of amygdala neurons is linked to cataplexy. Of the 218 cells recorded, 31 were sleep active, 78 were active in both waking and rapid-eye-movement sleep, 88 were maximally active during waking, and 21 were state independent. Two populations of cells showed a significant change in activity with cataplexy. A population of sleep active cells localized to central and basal nucleus increased discharges prior to and during cataplexy. A population of wake active cells localized to the cortical nucleus decreased activity prior to and during cataplexy. We hypothesize that these cell populations have a role in mediation or modulation of cataplexy through interactions with meso-pontine regions controlling atonia. The anticholinesterase physostigmine, at doses which increased cataplexy, did not alter the activity of the cataplexy-related cells or of other amygdala cells, suggesting that its effect on cataplexy is mediated 'downstream' of the amygdala. The alpha-1 blocker prazosin, at doses which increased cataplexy, increased discharge in a subgroup of the cataplexy active cells and in a number of other amygdala cells, indicating that prazosin may modulate cataplexy by its action on amygdala cells or their afferents.

Action Potentials↗
PubMed1989

Heart rate and blood pressure changes during sleep-waking cycles and cataplexy in narcoleptic dogs.

Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed.

Animals↗
PubMed1994

Cholinergic regulation of cataplexy in canine narcolepsy in the pontine reticular formation is mediated by M2 muscarinic receptors.

Both rapid eye movement sleep and cataplexy in the narcoleptic canine have been shown to increase after both systemic and local administration of cholinergic agonists in the pontine reticular formation. Furthermore, binding studies indicate an increase in the number of M2 muscarinic receptors in the pontine reticular formation of narcoleptic canines. In the present study we have investigated the receptor subtypes involved in mediating the cholinergic stimulation of cataplexy, as defined by brief periods of hypotonia induced by emotions, within the pontine reticular formation of narcoleptic canines. Specific cholinergic and monoaminergic agonists and antagonists, and excitatory or inhibitory amino-acid neurotransmitter receptor agonists, were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of narcoleptic canines, and cataplexy was monitored using the Food-Elicited Cataplexy Test and recordings of electroencephalogram, electrooculogram and electromyogram. In narcoleptic canines, bilateral perfusion with oxotremorine (M2 muscarinic) (10(-5)-10(-3) M) in the pontine reticular formation produced a dose-dependent increase in cataplexy, which reached complete muscle atonia (status cataplecticus) during the highest concentration. In control canines bilateral perfusion with oxotremorine (10(-5)-10(-3) M) did not produce any cataplectic attacks, but did produce muscle atonia after the highest concentration. Bilateral perfusion with either McN-A-343 (M1 muscarinic) or nicotine (both 10(-5)-10(-3) M) did not have any effect on cataplexy in either narcoleptic or control canines. The increase in cataplexy in narcoleptic canines produced by local perfusion with carbachol (10(-4) M) followed by equimolar perfusion with a muscarinic antagonist was rapidly reversed by atropine (muscarinic) and gallamine (M2 muscarinic), partially reversed by 4-DAMP (M3/M1 muscarinic) and completely unaffected by pirenzepine (M1 muscarinic). Bilateral perfusion with excitatory, glutamatergic receptor agonists N-methyl-D-aspartate, AMPA (both at 10(-4)-10(-3) M) and kainic acid (10(-5)-10(-4) M) did not have any effect on cataplexy, whereas bilateral perfusion with the inhibitory GABAergic receptor agonist muscimol (10(-4)-10(-3) M) produced a moderate increase in cataplexy in the narcoleptic canines. Bilateral perfusion with numerous monoaminergic compounds, BHT-920 (alpha-2 agonist), yohimbine (alpha-2 antagonist), propranolol (beta antagonist) and prazosin (alpha-1 antagonist), did not have any effect on cataplexy. These findings demonstrate that cholinergic regulation of cataplexy in the narcoleptic canine at the level of the pontine reticular formation is mediated by M2, and possibly M3, muscarinic receptors. The effects of muscimol indicate that the stimulation of cataplexy might be elicited by local neuronal inhibition.

Animals↗
PubMed1996

Local administration of dopaminergic drugs into the ventral tegmental area modulates cataplexy in the narcoleptic canine.

Cataplexy in the narcoleptic canine may be modulated by systemic administration of monoaminergic compounds. In the present study, we have investigated the effects of monoaminergic drugs on cataplexy in narcoleptic canines when perfused locally via microdialysis probes in the amygdala, globus pallidus/putamen, basal forebrain, pontine reticular formation and ventral tegmental area of narcoleptic and control Doberman pinchers. Cataplexy was quantified using the Food-Elicited Cataplexy Test and analyzed by electroencephalogram, electroculogram and electromyogram. Local perfusion with the monoaminergic agonist quinpirole, 7-OH-DPAT and BHT-920, into the ventral tegmental area produced a dose-dependent increase in cataplexy without significantly reducing basal muscle tone. Perfusion with the antagonist raclopride in the same structure produced a moderate reduction in cataplexy. Local perfusion with quinpirole, 7-OH-DPAT and BHT-920 into the globus pallidus/putamen also produced an increase, while raclopride produced a decrease, in cataplexy in narcoleptic canines. In control animals, none of the above drugs produced cataplexy or muscle atonia when perfused into either the ventral tegmental area or the globus pallidus/putamen. Other monoaminergic drugs tested in these two brain areas; prazosin, yohimbine, amphetamine, SKF 38393 and SCH 23390 had no effects on cataplexy. Local perfusion with each of the above listed drugs had no effect on cataplexy in any of the other brain regions examined. These findings show that cataplexy may be regulated by D2/D3 dopaminergic receptors in the ventral tegmental area and perhaps the globus pallidus/ putamen. It is suggested that neurons in the mesolimbic dopamine system of narcoleptics are hypersensitive to dopaminergic autoreceptor agonists.

Amygdala↗
PubMed2002

Hypocretin (orexin) levels in cerebrospinal fluid of patients with narcolepsy: relationship to cataplexy and HLA DQB1*0602 status.

STUDY OBJECTIVES: Hypocretin (orexin) deficiency (< 40 pg/ml) is highly associated with narcolepsy with cataplexy (89.5%) and more specifically with patients with cataplexy who are HLA DQB1*0602 positive (95.7%). The relationship between hypocretin-1 levels and narcolepsy without cataplexy or the DQB1*0602 allele is less clear. METHODS/DESIGN: This study compared cerebrospinal (CSF) hypocretin-1 in 13 patients with HLA DQB1*0602 allele and cataplexy to 4 HLA negative patients with cataplexy, 3 HLA positive patients without cataplexy, and 6 HLA negative patients without cataplexy, plus 15 neurologic controls. SETTING: Data were collected at a sleep disorders center. PATIENTS/PARTICIPANTS: Twenty-six patients with narcolepsy, with and without HLA DQB1*0602 and with and without cataplexy, as well as 15 neurologic controls. INTERVENTIONS: N/A. MEASUREMENT & RESULTS: Using analysis of variance techniques, statistically significant differences were found between the CSF hypocretin-1 levels in HLA positive patients and all other groups (P < 0.01). Although the sample size was small, subjects with the DQB1*0602 allele without cataplexy had lower hypocretin-1 levels than did other groups (other than the HLA and cataplexy positive group). Hypocretin-1 levels were not associated with age at diagnosis, age at lumbar puncture, body mass index at time of diagnosis, or body mass index at time of lumbar puncture. CONCLUSION: This data confirms the previous finding that undetectable hypocretin-1 levels are highly specific for HLA positive narcolepsy with cataplexy. The data suggests that the pathophysiology and, by extension, etiology of this disorder are distinctly different from the other conditions studied. The relationship of the DQB1*0602 allele and reduced hypocretin-1 levels needs further study.

Adolescent↗
PubMed2004

The clinical spectrum of narcolepsy with cataplexy: a reappraisal.

In the absence of a golden standard for the diagnosis of narcolepsy, the clinical spectrum of disorder remains controversial. The aims of this study were (1) to determine frequency and characteristics of sleep-wake symptoms in patients with narcolepsy with cataplexy, (2) to compare clinical characteristics with results of ancillary tests, and (3) to identify factors that discriminate narcolepsy from other conditions with excessive daytime sleepiness (EDS). We prospectively studied 57 narcoleptics with cataplexy, 56 patients with non-narcoleptic hypersomnia (H), and 40 normal controls (No). Based on suggested and published criteria, we differentiated between narcoleptics with definite cataplexy (N) and narcoleptics without definite cataplexy (possible cataplexy, NpC). Assessment consisted of questionnaires [all patients and controls, including the Ullanlinna Narcolepsy Score (UNS)], polysomnography (all patients), multiple sleep latency test (MSLT) and human leukocyte antigen typing (in most narcoleptics). A new narcolepsy score based on five questions was developed. Data were compared with those of 12 hypocretin-deficient narcoleptics (N-hd). There were significant differences between N and NpC (including mean sleep latency on MSLT), but none between N and N-hd. A score of sleep propensity during active situations (SPAS) and the frequency of sleep paralysis/hallucinations at sleep onset, dreams of flying, and history of sleep shouting discriminated N from H and No (P < 0.001). Cataplexy-like symptoms in H (18%) and No (8%) could be discriminated from 'true' cataplexy in N on the basis of topography of motor effects, triggering emotions and triggering situations (P < 0.001). Our narcolepsy score had a similar sensitivity (96% versus 98%) but a higher specificity (98% versus 56%) than the UNS. Analysis of co-occurring symptoms in narcolepsy revealed two symptom complexes: EDS, cataplexy, automatic behaviors; and sleep paralysis, hallucinations, parasomnias. Low/undetectable cerebrospinal fluid hypocretin-1 levels and a history of definite cataplexy identify similar subgroups of narcoleptics. Specific questions on severity of EDS (SPAS score) and characteristics of cataplexy allow the recognition of subgroups of narcoleptics and their differentiation from non-narcoleptic EDS patients, including those reporting cataplexy-like episodes. The existence of co-occurring symptoms supports the hypothesis of a distinct pathophysiology of single narcoleptic symptoms.

Adult↗
PubMed2004

Sodium oxybate demonstrates long-term efficacy for the treatment of cataplexy in patients with narcolepsy.

BACKGROUND AND PURPOSE: This study was conducted to demonstrate the long-term efficacy of sodium oxybate for the long-term treatment of cataplexy in patients with narcolepsy. PATIENTS AND METHODS: Fifty-five (55) narcoleptic patients with cataplexy who had received continuous treatment with sodium oxybate for 7-44 months (mean 21 months) were enrolled in a double-blind treatment withdrawal paradigm. A 2-week single-blind sodium oxybate treatment phase established a baseline for the weekly occurrence of cataplexy. This was followed by a 2-week double-blind phase in which patients were randomized to receive unchanged drug therapy or placebo. Patients recorded the incidence of cataplexy attacks and adverse events in daily diaries. RESULTS: During the 2-week double-blind phase, the abrupt cessation of sodium oxybate therapy in the placebo patients resulted in a significant increase in the number of cataplexy attacks (median=21; P<0.001 ) compared to patients who remained on sodium oxybate (median=0). Cataplexy attacks returned gradually with placebo patients reporting a median of 4.2 and 11.7 cataplexy attacks during the first and second weeks, respectively. There were no symptoms of frank withdrawal. CONCLUSIONS: This controlled trial provides evidence supporting the long-term efficacy of sodium oxybate for the treatment of cataplexy. In contrast with antidepressant drug therapy, there is no evidence of rebound cataplexy upon abrupt discontinuation of treatment.

Anesthetics, Intravenous↗
PubMed2006

Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.

BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs. CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.

Adolescent↗
PubMed2006

Sodium oxybate for cataplexy.

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling of sodium oxybate for the treatment of cataplexy in patients with narcolepsy. DATA SOURCES: OVID and PubMed databases were searched (1966-January 2006) using the key words sodium oxybate, gamma-hydroxybutyrate, narcolepsy, and cataplexy. Only English-language articles were selected. STUDY SELECTION AND DATA EXTRACTION: All information on sodium oxybate related to narcolepsy and cataplexy was considered. Study selection included human trials evaluating safety and efficacy of sodium oxybate for the treatment of cataplexy. DATA SYNTHESIS: Sodium oxybate is approved by the Food and Drug Administration for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. In placebo-controlled trials, sodium oxybate demonstrated efficacy in reducing the number of cataplexy attacks. The dosing regimen includes a split dose given at bedtime and 2.5-4 hours later due to its short elimination half-life. The drug is generally well tolerated, with headache, nausea, dizziness, pain, and somnolence being the most common adverse events. CONCLUSIONS: Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.

Cataplexy↗
PubMed1992

Activity of medial mesopontine units during cataplexy and sleep-waking states in the narcoleptic dog.

Narcolepsy has been hypothesized to be a disease of rapid eye movement (REM) sleep. According to this hypothesis, cataplexy is a result of the triggering during waking of the mechanism that normally serves to suppress muscle tone in REM sleep. REM sleep control mechanisms have been localized to the pons. Narcoleptic dogs have increased numbers of cholinergic receptors in the medial pons. These findings suggest that neurons mediating the triggering of cataplexy might be located in medial pontine regions. In the present study, this hypothesis has been investigated by recording the discharge of units in the medial mesopontine region of the narcoleptic dog. Unit activity was examined in the nucleus reticularis pontis oralis, caudalis, and central gray, with each cell being recorded during both cataplexy and sleep states. Maximal discharge rates were observed, in all of these regions, during active waking states (mean rate, 45.3/sec) and REM sleep (16.0/sec), with minimal discharge rates in non-REM sleep (8.3/sec). Unit discharge was reduced in cataplexy relative to precataplexy periods. Cataplexy discharge rates were 8.3/sec, 52% of the mean REM sleep rate. Cataplexy discharge rates were also significantly lower than those at REM sleep onset. Cataplexy discharge rates were comparable to rates in quiet waking and non-REM sleep. While medial mesopontine neurons discharge at high rates in REM sleep, they have little or no activity in cataplexy. We interpret the lack of activation of medial mesopontine units in cataplexy as indicating that the characteristic phasic motor activation of REM sleep does not occur in this state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Off-label treatment of severe childhood narcolepsy-cataplexy with sodium oxybate.

STUDY OBJECTIVES: To evaluate the efficacy and side-effect profile of off-label sodium oxybate (gamma hydroxy butyrate) therapy in severe childhood narcolepsy-cataplexy. DESIGN: Retrospective; chart review. SETTING: A multidisciplinary tertiary sleep center. PATIENTS: A group of eight children with severe narcolepsy-cataplexy diagnosed on the basis of clinical history, nocturnal polysomnography and the multiple sleep latency test were studied. A modified Epworth Sleepiness Scale and an arbitrary cataplexy severity scale (1 = minimal weakness, 2 = voluntarily preventable falls, 3 = falls to the ground) were utilized. INTERVENTIONS: Sodium oxybate therapy; concurrent medications were maintained. MEASUREMENTS AND RESULTS: Before sodium oxybate therapy, all subjects had suboptimally controlled sleepiness and cataplexy. Following treatment with sodium oxybate, 7/8 subjects (88%) improved. Cataplexy frequency decreased from a median of 38.5 to 4.5/ week (p = 0.0078). Cataplexy severity decreased from 2.75 to 1.75 (p = 0.06). The Epworth Sleepiness Scores improved from a median of 19 to 12.5 (p = 0.02). Suicidal ideation, dissociative episodes, tremor and constipation occurred in one subject each and terminal insomnia in two. Three of the 8 (38%) discontinued therapy. Two stopped the drug owing to side effects and one due to problems with postal delivery of the medication. CONCLUSIONS: This is the first report on sodium oxybate therapy in childhood narcolepsy-cataplexy. Our finding of improvement in cataplexy and sleepiness suggests that this medication is effective in treating severe childhood narcolepsy-cataplexy.

Adolescent↗
PubMed1981

Monoaminergic mechanisms and experimental cataplexy.

The effects of pharmacological alteration of the monoamine systems were investigated in a canine model of narcolepsy. Cataplexy was quantified in eight severely affected dogs by means of the food-elicited cataplexy test. The specific norepinephrine (NE) uptake blocker nisoxetine, and (to a much lesser extent) the specific serotonin (5-HT) uptake blocker fluoxetine, significantly suppressed cataplexy, as did the tricyclic antidepressants protriptyline, amitriptyline, and chlorimipramine. Thus, experimental cataplexy is suppressed more by inhibition of the uptake of NE than of 5-HT. Methylphenidate, the alpha-adrenoreceptor blocker clonidine, and the dopamine receptor blocker pimozide also suppressed cataplexy in dogs. The beta-adrenergic blocker propranolol, the fatty acid gamma-hydroxybutyrate, and the monoamine oxidase inhibitors clorgyline and pargyline had little or no effect. With one exception (pimozide), all the drugs that suppressed cataplexy are known to be potent suppressors of REM sleep. The suppression of cataplexy induced by nisoxetine or protriptyline was reversed by the anticholinesterase physostigmine, further supporting a postulated aminergic-cholinergic interaction in the mechanisms for cataplexy.

Animals↗
PubMed1999

Validation of a cataplexy questionnaire in 983 sleep-disorders patients.

Our goal was to validate a self-administered narcolepsy questionnaire focusing on cataplexy. Nine hundred and eight three consecutive subjects entering the Stanford Sleep Disorder Clinic completed the questionnaire. Clinic physicians reported on the presence or absence of "clear-cut" cataplexy. Responses to 51 cataplexy-related questionnaire items were compared between subjects with clear-cut cataplexy (n = 63) and all other patients (n = 920). As previously reported, a large portion of the non-narcoleptic population was found to experience muscle weakness with various intense emotions (1.8% to 18.0%) or athletic activities (26.2% to 28.8%). Factor analysis and Receiver Operating Characteristic Curve (ROC) analysis were used to determine the most predictive items for clear-cut cataplexy. Most strikingly, cataplexy was best differentiated from other types of muscle weakness when triggered by only three typical situations: "when hearing and telling a joke," "while laughing," or "when angry." Face or neck, rather than limbs, were also more specifically involved in clear-cut cataplexy. Other items, such as length of attacks, bilaterality, and alteration in consciousness, were poorly predictive. A simple decision tree was constructed to isolate high-(91.7%) and low-(0.6%) risk groups for cataplexy. This questionnaire will be used to increase diagnostic consistency across clinical centers, thus providing more homogenous subject pools for clinical and basic research studies.

Adolescent↗