Factors associated with injury in REM sleep behavior disorder.

OBJECTIVE: As factors associated with injury in rapid eye movement (REM) sleep behavior disorder (RBD) remain largely unknown, we aimed to identify such factors. METHODS: We surveyed consecutive idiopathic (iRBD) or symptomatic RBD patients seen between 2008 and 2010 regarding RBD-related injuries. Associations between injuries and clinical variables were determined with odds ratios (OR) and multiple logistic regression analyses. The primary outcome variables were injury and injury severity. RESULTS: Fifty-three patients (40%) responded. Median age was 69 years, and 35 (73.5%) were men. Twenty-eight (55%) had iRBD. Twenty-nine (55%) reported injury, with 37.8% to self and 16.7% to the bed partner. 11.3% had marked injuries requiring medical intervention or hospitalization, including two (4%) subdural hematomas. iRBD diagnosis (OR = 6.8, p = 0.016) and dream recall (OR = 7.5, p = 0.03) were associated with injury; and iRBD diagnosis was independently associated with injury and injury severity adjusting for age, gender, DEB frequency, and duration. Falls (p = 0.03) were also associated with injury severity. DEB frequency was not associated with injury, injury severity, or falls. CONCLUSIONS: Injuries appear to be a frequent complication of RBD, although the relatively low response rate in our survey could have biased results. iRBD patients are more likely to suffer injury--and more severe injuries--than symptomatic RBD patients. In addition, recall of dreams was also associated with injury, and dream enactment behavior (DEB)-related falls were associated with more severe injuries. One in nine patients suffered injury requiring medical intervention. The frequency of DEB did not predict RBD-related injuries, highlighting the importance of timely initiation of treatment for RBD in patients having even rare DEB episodes. Future prospective studies will be necessary to define predictors of injury in RBD.

Total sleep time obtained from actigraphy versus sleep logs in an academic sleep center and impact on further sleep testing.

BACKGROUND: While actigraphy has been deemed ideal for the longitudinal assessment of total sleep time (TST) by select groups, endorsement has not been universal and reimbursement is lacking, preventing its widespread use in clinical practice. This study compares longitudinal TST data obtained by actigraphy and logs preceding a clinical evaluation, and secondarily ascertains whether longitudinal TST impacts clinicians' decisions to proceed with further sleep testing. METHODS: This was a retrospective, consecutive chart review spanning about 4 months in an academic sleep center. Eighty-four patients wore actigraphs in anticipation of clinical evaluations. Concomitant completion of sleep logs is routinely requested in this setting. Longitudinal TST data available in complete form was reviewed in a blinded fashion among a subset of these patients. A review of text from clinical notes of an expanded cohort with complete actigraphy data (regardless of the degree of completion of logs) enabled determination of the frequency and rationale for cancellation of prescheduled sleep testing. RESULTS: Of 84 actigraphy recordings, 90% produced complete data, and 30% produced fully completed logs. Among the subset with both available in complete form, significant mean TST differences were observed on weekends (7.06 ± 2.18 hours versus 8.30 ± 1.93 hours, P = 0.009), but not on weekdays (7.38 ± 1.97 hours versus 7.72 ± 1.62 hours, P = 0.450) for actigraphy and logs, respectively. Further analyses revealed poor agreement between the two measures, with predominantly increased TST estimation with logs. Among those with complete actigraphy data (±logs), testing was cancelled in 11 (15%), eight of whom (73%) presented with hypersomnia and three of whom (27%) presented with insomnia. Determination of insufficient sleep time was cited as the primary reason for cancellation (64%). CONCLUSION: Actigraphy and sleep logs provided discrepant mean TST data on weekends only, and the latter predominantly estimated increased TST. Actigraphy was completed more reliably than logs. Longitudinal TST information influenced clinicians' decisions to proceed with further testing, particularly among patients presenting with hypersomnia.

Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy type 2.

OBJECTIVES: Although sleep disturbances are common in myotonic dystrophy type 1 (DM1), sleep disturbances in myotonic dystrophy type 2 (DM2) have not been well-characterized. We aimed to determine the frequency of sleep disturbances in DM2. METHODS: We conducted a case-control study of 54 genetically confirmed DM2 subjects and 104 medical controls without DM1 or DM2, and surveyed common sleep disturbances, including symptoms of probable restless legs syndrome (RLS), excessive daytime sleepiness (EDS), sleep quality, fatigue, obstructive sleep apnea (OSA), probable REM sleep behavior disorder (pRBD), and pain. Thirty patients with DM2 and 43 controls responded to the survey. Group comparisons with parametric statistical tests and multiple linear and logistic regression analyses were conducted for the dependent variables of EDS and poor sleep quality. RESULTS: The mean ages of patients with DM2 and controls were 63.8 and 64.5 years, respectively. Significant sleep disturbances in patients with DM2 compared to controls included probable RLS (60.0% vs 14.0%, p < 0.0001), EDS (p < 0.001), sleep quality (p = 0.02), and fatigue (p < 0.0001). EDS and fatigue symptoms were independently associated with DM2 diagnosis (p < 0.01) after controlling for age, sex, RLS, and pain scores. There were no group differences in OSA (p = 0.87) or pRBD (p = 0.12) scores. CONCLUSIONS: RLS, EDS, and fatigue are frequent sleep disturbances in patients with DM2, while OSA and pRBD symptoms are not. EDS was independently associated with DM2 diagnosis, suggesting possible primary CNS hypersomnia mechanisms. Further studies utilizing objective sleep measures are needed to better characterize sleep comorbidities in DM2.

The role of nocturnal polysomnography in assessing children with Chiari type I malformation.

OBJECTIVE: To evaluate nocturnal polysomnogram findings in children with suspected symptomatic Chiari type I malformation, correlate them with clinical and magnetic resonance imaging data and to determine if this information has value in clinical decision making process. METHODS: A retrospective review identified 24 children with type I Chiari malformation, presumed symptomatic who had undergone neurological assessment, cranial magnetic resonance imaging and nocturnal polysomnography. Perimedullary subarachnoid space effacement on the magnetic resonance studies and the magnitude of cerebellar tonsillar descent in relation to the McRae line were correlated with frequency of obstructive or central sleep apnea, number of cortical arousals and evidence of impaired vocal mobility on laryngoscopy. The Wilcoxon rank sum test was applied for continuous variables and the Fisher exact test for categorical variables. RESULTS: The median age of the subjects was 6 years. The findings from 16/24 subjects with perimedullary subarachnoid space effacement (effaced group) were compared with those of 8/24 in the non-effaced group. The central apnea index [1.5 (IQR 1-3.5) versus 0.5 (IQR 0-1.5)] and cortical arousal index [12 (IQR 10-19) versus 8 (IQR 6.5-9)] were significantly higher in the effaced group than in the non-effaced group (p=0.0376 and 0.0036 respectively). Greater descent of tonsils as measured by distance from the McRae line to the tonsil tip was associated with significantly higher central apnea index, total arousal index and respiratory event related arousals. Measurements of clivus-canal angle, Klauss index and pB-C2 line did not correlate with abnormalities on polysomnography. CONCLUSION: The central apnea and arousal indices derived from the nocturnal polysomnogram correlate well with magnetic resonance imaging findings of subarachnoid space effacement and degree of tonsillar herniation. In children with Chiari type I malformation, the nocturnal polysomnogram findings provides important information that aids in the decision making process about proceeding with surgical decompression.

Treatment outcomes in REM sleep behavior disorder.

OBJECTIVE: REM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam. METHODS: We surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008-2010 to describe RBD-related injury frequency-severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency. RESULTS: Forty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p(m) = 0.0001, p(c) = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p(m) = 0.001, p(c) = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 ± 29.5 months, and for melatonin 27.4 ± 24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43). CONCLUSIONS: Melatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.

Characteristics of REM sleep behavior disorder in childhood.

STUDY OBJECTIVE: To describe our experience regarding the clinical and polysomnographic features of REM sleep behavior disorder (RBD) in childhood. METHODS: This was a retrospective chart review of children and adolescents with RBD and REM sleep without atonia. Demographics, and clinical and polysomnographic information were tabulated. Our findings were compared with those in the existing literature. RESULTS: The 15 subjects identified (13 RBD and 2 having REM sleep without atonia) had a mean age at diagnosis of 9.5 years (range 3-17 years); 11/15 (73%) were male. Nightmares were reported in 13/15 and excessive daytime sleepiness in 6/15. Two children had caused bodily harm to bedmate siblings. Comorbidities, which were multiple in some subjects, included anxiety (8/15), attention deficit disorder (10/15), nonspecific developmental delay (6/15), Smith-Magenis syndrome (1/15), pervasive developmental disorder (1/15), narcolepsy (1/15), idiopathic hypersomnia (1/15), and Moebius Syndrome (1/15). Abnormal MRI scans were seen in 5/8 evaluated subjects. Treatments consisted of clonazepam (10/15), melatonin (2/15), and discontinuation of a tricyclic agent (1/15), with a favorable response in 11 of 13. Two of 15 patients with REM sleep without atonia did not require pharmacotherapy. CONCLUSIONS: RBD in children may be associated with neurodevelopmental disabilities, narcolepsy, or medication use. It seems to be modestly responsive to benzodiazepines or melatonin. The etiology is distinct from that of common childhood arousal parasomnias and RBD in adults; congenital and neurodevelopmental disorders, medication effect, and narcolepsy coexisted in some, but none had an extrapyramidal neurodegenerative disorder.

Maxillomandibular advancement in the management of obstructive sleep apnea.

Maxillomandibular advancement (MMA) is a surgical option for obstructive sleep apnea (OSA). MMA involves forward-fixing the maxilla and mandible approximately 10 mm via Le Fort I maxillary and sagittal split mandibular osteotomies. We retrospectively reviewed outcomes from 24 consecutive OSA patients who underwent MMA at our institution. MMA resulted in an 83% reduction in the group mean apnea-hypopnea index (AHI) per polysomnography an average of 6.7 months after surgery. Forty-two percent of patients achieved a post-MMA AHI of less than 5 events/hour sleep and 71% achieved an AHI less than or equal to 10 events/hour sleep. The Epworth Sleepiness Scale score decreased by an average of 5 post-surgery. No parameters predictive of cure for OSA by MMA were identified.

Nocturnal moaning and groaning-catathrenia or nocturnal vocalizations.

PURPOSE: Descriptions of nocturnal vocalizations, including catathrenia, are few. We undertook a study at our center on patients diagnosed with catathrenia, to evaluate the characteristic features of these events and their response to continuous positive airway pressure (CPAP) treatment. METHODS: Retrospective study of patients with a diagnosis of catathrenia who had an overnight polysomnogram (PSG) and available synchronized audio video recordings (to confirm the presence of moaning and groaning), at our center between January 2007 and May 2010. RESULT: Ten patients were included in the analysis. Three (30%) patients presented with the chief complaint of expiratory noises during sleep. The other moaning/groaning sounds were incidental findings noted by the sleep technologist and/or the sleep physician. The number of moaning/groaning events during PSG varied between 2 and 343 per patient with sound duration ranging from 0.4 to 21.4 s. Moaning/groaning events during exhalation (1,026 episodes) were separated into typical catathrenia events (as per the International Classification of Sleep Disorders, 2nd edition [ICSD-2] definition) and atypical/nocturnal vocalization events (moaning/groaning events that did not meet the ICSD-2 criteria). Typical catathrenia events (5% or 52/1,026) were experienced by five of the ten patients and had mean exhalation duration of 14.97 ± 5.13 s (range 5.8-24 s) with a mean sound duration of 8.47 ± 5.97 s (range 2-21.4 s). The typical and atypical events occurred predominantly in NREM sleep. Six of the ten patients had associated sleep-disordered breathing and four underwent CPAP titration. All four patients had significantly fewer events of moaning/groaning (mean reduction was 75.8 ± 26.2%) with CPAP. CONCLUSION: New and unique features were identified in our series of patients diagnosed with catathrenia. Though all events had the characteristic moaning and groaning sound during exhalation, only a small percentage (5%) met the catathrenia definition as outlined in ICSD-2. Do we label the atypical events as part of the spectrum of nocturnal vocalizations or consider them as catathrenia by redefining the criteria? CPAP appeared to be a reasonable treatment option.

Light exposure among adolescents with delayed sleep phase disorder: a prospective cohort study.

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n=16, 15.3±1.8 yrs) and unaffected controls (n=22, 13.7±2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00 h and 05:00 to 14:00 h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p< .02, 22:00-02:00 h) and less morning (p .05, 08:00-09:00 h and 10:00-12:00 h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p< .03, 5-7 h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p< .001 and p= .02, respectively) and morning (p= .01 and p< .001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p< .001). Increased total sleep time also correlated with increased exposure during the 9 h before sleep onset (p= .01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p< .001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD.

Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study.

STUDY OBJECTIVES: To determine the frequency of impulse control disorders (ICDs) with the use of dopaminergic agents in restless legs syndrome (RLS). DESIGN: Prospective case-control study using a screening questionnaire for ICDs, followed by phone interview to confirm diagnoses for those meeting preset scoring thresholds on the questionnaire. SETTING: Academic, comprehensive sleep medicine center. PATIENTS OR PARTICIPANTS: (1) One hundred patients with RLS treated with dopaminergic agents, (2) 275 patients with obstructive sleep apnea (OSA) without RLS or exposure to dopaminergic agents; and (3) 52 patients with RLS who were never treated with dopaminergic agents. Subjects with parkinsonism were excluded. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Based on the questionnaire, frequencies of ICDs for the RLS treatment group were 10% compulsive shopping, 7% pathologic gambling, 23% compulsive eating, 8% hypersexuality, and 10% punding. These values were statistically significant when compared with control subjects with OSA for compulsive shopping and pathologic gambling. With additional information from the phone interview, adjusted frequencies for the RLS treatment group were 9% compulsive shopping, 5% pathologic gambling, 11% compulsive eating, 3% hypersexuality, 7% punding, and 17% any ICD. These values were statistically significant when compared with those of control subjects with OSA for compulsive shopping, pathologic gambling, punding, and any ICD, as well as for compulsive shopping when compared with control subjects with RLS who were not treated with dopaminergic agents. In the RLS treatment group, a statistically significant dose effect was found for pramipexole in those subjects confirmed to have ICDs by both the questionnaire and phone interview. Mean duration of treatment at ICD onset was 9.5 months. CONCLUSIONS: ICDs are common with the use of dopaminergic agents for treatment of RLS. Given the potentially devastating psychosocial consequences of these behaviors, it is critical to actively screen for ICDs in this population.

Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset.

BACKGROUND: A retrospective, case-control chart review was performed to examine the relationship between the age of onset of idiopathic RBD and secondary associations. METHODS: Forty-eight idiopathic RBD patients were divided into early-onset and late-onset groups, compared to each other, and to their respective non-RBD controls. RESULTS: There were more females in the early-onset group as compared to their older counterparts (45% vs. 11%, p=0.007). Early-onset patients also had significantly more past and present psychiatric diagnoses [85% (both categories) vs. 46% and 36%, respectively, p<0.01 for both comparisons] and antidepressant use (80% vs. 46%, p=0.02) than the late-onset group. In comparison to non-RBD controls, early-onset patients again exhibited more psychiatric diagnoses (odds ratio=17.0 [3.5-83.4], equivalent for past and present diagnoses) and antidepressant use (odds ratio=12.0 [2.7-53.3]). Late-onset patients also had a higher frequency of past (odds ratio=7.2 [1.8-29.6]) and present (odds ratio=4.6 [1.1-19.3]) psychiatric diagnoses as compared to their non-RBD controls, but did not demonstrate a statistically significant difference in antidepressant use. There were otherwise no significant intergroup or intragroup differences with respect to the other assessed variables. CONCLUSIONS: Although causality cannot be inferred, numerous implications can be entertained, particularly in the early-onset group, including direct or indirect correlations with medication use and/or psychopathology and the development of RBD. The relatively high number of females in the early-onset group suggests a unique clinical profile for a condition typically characterized as male-predominant.

Idiopathic hypersomnia: clinical features and response to treatment.

OBJECTIVE: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. METHODS: A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. RESULTS: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). CONCLUSIONS: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

Cataplexy Emotional Trigger Questionnaire (CETQ)--a brief patient screen to identify cataplexy in patients with narcolepsy.

STUDY OBJECTIVES: This pilot study explored the sensitivity and specificity of a brief survey to determine the presence of cataplexy. We hypothesized that the brief questionnaire could provide a quick, sensitive, and specific screening tool to identify those patients with cataplexy, which would result in more timely referrals for further diagnostic testing. DESIGN: The pilot study utilized a brief questionnaire that was developed by including 5 questions that were found to be strong positive predictors of cataplexy from a previous 51-item cataplexy questionnaire. SETTING: Participants with a laboratory-confirmed diagnosis completed the questionnaire via mail correspondence or at the time of scheduled appointments in the Mayo Clinic Sleep Disorder Center, Rochester, Minn. PARTICIPANTS: Seventy-eight patients with narcolepsy and cataplexy and 78 patients with obstructive sleep apnea completed the questionnaire. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: The sensitivity, specificity, area under the curve, positive predictive value, and negative predictive value/were computed for each question individually, along with appropriate 95% confidence intervals. CONCLUSIONS: The first item of the cataplexy emotional trigger questionnaire (CETQ) discriminates patients with cataplexy from controls with excellent sensitivity and specificity. The addition of the other 4 questions, in the context of question 1, did not improve specificity, area under the curve, positive predictive value, or negative predictive value but did provide useful confirmatory data. Thus, a single question provides a brief practical tool that could improve the recognition of cataplexy in the clinical setting. Depending on the circumstance, users may be interested in utilizing 1 or all 5 questions.

Analysis of hypocretin (orexin) antibodies in patients with narcolepsy.

STUDY OBJECTIVES: We tested the hypothesis that patients with narcolepsy have serum antibodies specific for preprohypocretin and its derivatives. DESIGN: We tested sera from strictly diagnosed HLA DQB1*0602-positive narcoleptic patients with cataplexy for evidence of autoantibodies against human preprohypocretin, hypocretin 1 and 2, N-terminal leader and C-terminal peptides of preprohypocretin using enzyme-linked immunosorbent assays (ELISA). These results were compared to samples from nonnarcoleptic psychiatric and sleep apnea controls. Laboratory personnel were blinded to subject status. SETTING: Narcoleptic patients and nonnarcoleptic controls were recruited from the Mayo Clinic facilities in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. Laboratory testing was conducted in the Mayo Psychogenomic Laboratory at the Rochester Mayo Clinic. PARTICIPANTS: A sample of 34 narcoleptic patients and 49 nonnarcoleptic controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: ELISA measurements were in optical density. Primary analyses were of the entire narcoleptic and control groups for each potential antigen, and none of the differences reached P values required for significance after Bonferroni adjustment. Secondary analyses by age and sex yielded P values that were significant after Bonferroni adjustment in only 2 cases, but further statistical analyses cast doubt on the veracity of these differences. In all cases where a significant difference was recorded, the hypothesis was not supported because the control optical density reading was higher than the narcoleptic values. CONCLUSIONS: These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.

Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy.

BACKGROUND: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. METHODS: Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. RESULTS: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. CONCLUSIONS: The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Characterizing the emotions that trigger cataplexy.

Cataplexy is an intriguing example of how emotions can trigger muscle weakness by activating neural pathways. When associated with excessive daytime sleepiness, cataplexy is considered pathognomonic of narcolepsy. A questionnaire was administered to 55 patients with narcolepsy-cataplexy and 47 comparison subjects with obstructive sleep apnea. The area under the receiver-operating curve was 0.94 for the combination of muscle weakness with laughter and ability to hear during the episode. A 51-item questionnaire succeeds in identifying cataplexy in narcolepsy-cataplexy patients measured up against a comparison group. In the future, an abbreviated survey with these two questions should identify cataplexy with high sensitivity and specificity. These selected questions could subsequently be included into screening tools for use with different patient populations.

Risks of high-dose stimulants in the treatment of disorders of excessive somnolence: a case-control study.

STUDY OBJECTIVES: To ascertain complications associated with high-dose stimulant therapy in patients with narcolepsy or idiopathic hypersomnia. DESIGN: Case-control, retrospective chart review. SETTING: Sleep center in an academic hospital. PATIENTS: 116 patients with narcolepsy or idiopathic hypersomnia were individually matched by sex, diagnosis, age of onset, and duration of follow-up from both onset and diagnosis. Members of the high-dose group (n = 58) had received at least 1 stimulant at a dosage > or = 120% of the maximum recommended by the American Academy of Sleep Medicine Standards of Practice Committee. The standard-dose control group (n = 58) had received stimulants at a dosage < or = 100% of the American Academy of Sleep Medicine guidelines. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The prevalence of psychosis (odds ratio = 12.0 [1.6-92.0]), alcohol or polysubstance misuse (odds ratio = 4.3 [1.2-15.2]), and psychiatric hospitalization (odds ratio = 3.2 [1.1-10.0]) was significantly increased in the high-dose group. More high-dose patients also experienced tachyarrhythmias (odds ratio = 3.3 [0.92-12.1] and anorexia or weight loss (odds ratio = 11.0 [1.4-85.2]). The frequency of physician-diagnosed depression, drug-seeking and suicide-related behaviors, hypertension, and cardiovascular disease did not differ significantly between the groups. CONCLUSIONS: This study demonstrated a significantly higher occurrence of psychosis, substance misuse, and psychiatric hospitalizations in patients using high-dose stimulants compared to those using standard doses. Tachyarrhythmias and anorexia or weight loss were also more common in this group as compared with controls. Clinicians should be very cautious in prescribing dosages that exceed maximum guidelines.

A putative link between childhood narcolepsy and obesity.

BACKGROUND AND PURPOSE: While there have been anecdotal observations of binge eating in childhood-onset narcolepsy, the possible relationship between increased weight gain and childhood-onset narcolepsy has not been evaluated. PATIENTS AND METHODS: A retrospective, case-control design was used to compare the body mass index (BMI) of 31 narcolepsy children at the time of diagnosis with that of healthy, age- and gender-matched controls. RESULTS: The median BMI in the narcolepsy subjects was 22.93 as compared to that in controls of 20.36 (P=0.001). BMI did not differ significantly between narcolepsy subjects who had received prior psychotropic medications and those who had not. The mean BMI of 22 of 31 narcolepsy subjects who had not received psychotropic medications prior to diagnosis was also significantly higher than that of controls (25.1, SEM 1.53 versus 21.1, SEM 0.56; P=0.008 ). CONCLUSION: The tendency for increased weight gain is intrinsic to childhood narcolepsy and is manifested relatively early in the course of the disorder. Correlation of this finding with hypocretin and leptin metabolism may further understanding of the pathogenesis of narcolepsy.