Depth and Distribution of Symptoms in Restless Legs Syndrome/ Willis-Ekbom Disease.

STUDY OBJECTIVES: To determine the depth and distribution of sensory discomfort in idiopathic restless legs syndrome/Willis-Ekbom disease (RLS) and RLS concurrent with other leg conditions, specifically peripheral neuropathy, sciatica, leg cramps, and arthritis. METHODS: RLS subjects (n = 122) were divided into 71 idiopathic RLS and 51 RLS-C, or Comorbid, groups. All subjects were examined by an RLS expert, answered standardized RLS questionnaires, and received a body diagram to draw the location and depth of their symptoms. RESULTS: Age was 63.04 ± 12.84 years, with 77 females and 45 males. All patients had lower limb involvement and 43/122 (35.25%) also had upper limb involvement. Of the 122 subjects, 42.62% felt that the RLS discomfort was only deep, 9.84% felt that the discomfort was only superficial, and 47.54% felt both superficial and deep discomfort. There were no defining characteristics in depth or distribution of RLS sensations that differentiated those patients with idiopathic RLS from those patients with RLS associated with other comorbid leg conditions. The sensation of arthritis was felt almost exclusively in the joints and not in the four quadrants of the leg, whereas the exact opposite was true of RLS sensations. CONCLUSIONS: Depth and distribution cannot be used as a discriminative mechanism to separate out idiopathic RLS from RLS comorbid with other leg conditions. Although seen in clinical practice, the total absence of patients with non-painful RLS only in the joints in the current study attests to the rarity of this presentation and raises the possibility of misdiagnosis under these circumstances. We recommend that such patients not be admitted to genetic or epidemiological studies.

Genetic variants associated with sleep disorders.

OBJECTIVE: The diagnostic boundaries of sleep disorders are under considerable debate. The main sleep disorders are partly heritable; therefore, defining heritable pathophysiologic mechanisms could delineate diagnoses and suggest treatment. We collected clinical data and DNA from consenting patients scheduled to undergo clinical polysomnograms, to expand our understanding of the polymorphisms associated with the phenotypes of particular sleep disorders. METHODS: Patients at least 21 years of age were recruited to contribute research questionnaires, and to provide access to their medical records, saliva for deoxyribonucleic acid (DNA), and polysomnographic data. From these complex data, 38 partly overlapping phenotypes were derived indicating complaints, subjective and objective sleep timing, and polysomnographic disturbances. A custom chip was used to genotype 768 single-nucleotide polymorphisms (SNPs). Additional assays derived ancestry-informative markers (eg, 751 participants of European ancestry). Linear regressions controlling for age, gender, and ancestry were used to assess the associations of each phenotype with each of the SNPs, highlighting those with Bonferroni-corrected significance. RESULTS: In peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), rs6888451 was associated with several markers of obstructive sleep apnea. In aryl hydrocarbon receptor nuclear translocator-like (ARNTL), rs10766071 was associated with decreased polysomnographic sleep duration. The association of rs3923809 in BTBD9 with periodic limb movements in sleep was confirmed. SNPs in casein kinase 1 delta (CSNK1D rs11552085), cryptochrome 1 (CRY1 rs4964515), and retinoic acid receptor-related orphan receptor A (RORA rs11071547) were less persuasively associated with sleep latency and time of falling asleep. CONCLUSIONS: SNPs associated with several sleep phenotypes were suggested, but due to risks of false discovery, independent replications are needed before the importance of these associations can be assessed, followed by investigation of molecular mechanisms.

Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep cycles.

People called night owls habitually have late bedtimes and late times of arising, sometimes suffering a heritable circadian disturbance called delayed sleep phase syndrome (DSPS). Those with DSPS, those with more severe progressively-late non-24-hour sleep-wake cycles, and those with bipolar disorder may share genetic tendencies for slowed or delayed circadian cycles. We searched for polymorphisms associated with DSPS in a case-control study of DSPS research participants and a separate study of Sleep Center patients undergoing polysomnography. In 45 participants, we resequenced portions of 15 circadian genes to identify unknown polymorphisms that might be associated with DSPS, non-24-hour rhythms, or bipolar comorbidities. We then genotyped single nucleotide polymorphisms (SNPs) in both larger samples, using Illumina Golden Gate assays. Associations of SNPs with the DSPS phenotype and with the morningness-eveningness parametric phenotype were computed for both samples, then combined for meta-analyses. Delayed sleep and "eveningness" were inversely associated with loci in circadian genes NFIL3 (rs2482705) and RORC (rs3828057). A group of haplotypes overlapping BHLHE40 was associated with non-24-hour sleep-wake cycles, and less robustly, with delayed sleep and bipolar disorder (e.g., rs34883305, rs34870629, rs74439275, and rs3750275 were associated with n=37, p=4.58E-09, Bonferroni p=2.95E-06). Bright light and melatonin can palliate circadian disorders, and genetics may clarify the underlying circadian photoperiodic mechanisms. After further replication and identification of the causal polymorphisms, these findings may point to future treatments for DSPS, non-24-hour rhythms, and possibly bipolar disorder or depression.

Sleep-related headaches.

Irrespective of diagnosis, chronic daily, morning, or "awakening" headache patterns are soft signs of a sleep disorder. Sleep apnea headache may emerge de novo or may present as an exacerbation of cluster, migraine, tension-type, or other headache. Insomnia is the most prevalent sleep disorder in chronic migraine and tension-type headache, and increases risk for depression and anxiety. Sleep disturbance (e.g., sleep loss, oversleeping, schedule shift) is an acute headache trigger for migraine and tension-type headache. Snoring and sleep disturbance are independent risk factors for progression from episodic to chronic headache.

Zolpidem ingestion, automatisms, and sleep driving: a clinical and legal case series.

STUDY OBJECTIVES: To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleep-related parasomnias. METHODS: A case series of eight clinical patients and six legal defendants is presented. Patients presented to the author after an episode of confusion, amnesia, or somnambulism. Legal defendants were being prosecuted for driving under the influence, and the author reviewed the cases as expert witness for the defense. Potential predisposing factors including comorbidities, social situation, physician instruction, concomitant medications, and patterns of medication management were considered. RESULTS: Patients and defendants exhibited abnormal behavior characterized by poor motor control and confusion. Although remaining apparently interactive with the environment, all reported amnesia for 3 to 5 hours. In some cases, the episodes began during daytime wakefulness because of accidental or purposeful ingestion of the zolpidem and are considered automatisms. Other cases began after ingestion of zolpidem at the time of going to bed and are considered parasomnias. Risk factors for both wake and sleep-related automatic complex behaviors include the concomitant ingestion of other sedating drugs, a higher dose of zolpidem, a history of parasomnia, ingestion at times other than bedtime or when sleep is unlikely, poor management of pill bottles, and living alone. In addition, similar size and shape of two medications contributed to accidental ingestion in at least one case. CONCLUSIONS: Sleep driving and other complex behaviors can occur after zolpidem ingestion. Physicians should assess patients for potential risk factors and inquire about parasomnias. Serious legal and medical complications can occur as a result of these forms of automatic complex behaviors.

A randomized, double-blind, placebo-controlled study to assess the efficacy and tolerability of gabapentin enacarbil in subjects with restless legs syndrome.

STUDY OBJECTIVE: To evaluate the efficacy and tolerability of gabapentin enacarbil (GEn) 1200 mg or 600 mg compared with placebo in subjects with moderate-to-severe primary restless legs syndrome (RLS). METHODS: This 12-week, multicenter, double-blind, placebo-controlled study randomized subjects (1:1:1) to GEn 1200 mg, 600 mg, or placebo. Co-primary endpoints: mean change from baseline in International Restless Legs Scale (IRLS) total score and proportion of responders (rated as "very much" or "much" improved) on the investigator-rated Clinical Global Impression-Improvement scale (CGI-I) at Week 12 LOCF for GEn 1200 mg compared with placebo. Secondary endpoints included GEn 600 mg compared with placebo on the IRLS and CGI-I at Week 12 LOCF and subjective measures for sleep. Safety and tolerability assessments included adverse events. RESULTS: 325 subjects were randomized (GEn 1200 mg = 113; 600 mg = 115; placebo = 97). GEn 1200 mg significantly improved mean [SD] IRLS total score at Week 12 LOCF (baseline: 23.2 [5.32]; Week 12: 10.2 [8.03]) compared with placebo (baseline: 23.8 [4.58]; Week 12: 14.0 [7.87]; adjusted mean treatment difference [AMTD]: -3.5; p = 0.0015), and significantly more GEn 1200 mg-treated (77.5%) than placebo-treated (44.8%) subjects were CGI-I responders (p < 0.0001). Similar significant results were observed with GEn 600 mg for IRLS (AMTD: -4.3; p < 0.0001) and CGI-I (72.8% compared with 44.8%; p < 0.0001). GEn also significantly improved sleep outcomes (Post-Sleep Questionnaire, Pittsburgh Sleep Diary and Medical Outcomes Sleep Scale) compared with placebo. The most commonly reported adverse events were somnolence (GEn 1200 mg = 18.0%; 600 mg = 21.7%; placebo = 2.1%) and dizziness (GEn 1200 mg = 24.3%; 600 mg = 10.4%; placebo = 5.2%). Dizziness increased with increased dose and led to discontinuation in 2 subjects (GEn 1200 mg, n = 1; GEn 600 mg, n = 1). Somnolence led to discontinuation in 3 subjects (GEn 600 mg). CONCLUSIONS: GEn 1200 mg and 600 mg significantly improve RLS symptoms and sleep disturbance compared with placebo and are generally well tolerated.

Sleep and headache.

OPINION STATEMENT: Headache has been linked to a wide range of sleep disorders that may impact headache management. There are no evidence-based guidelines, but the authors believe that literature supports the following clinical recommendations: 1. Diagnose headache according to standardized criteria. Specific diagnoses are associated with increased risk for specific sleep and psychiatric disorders. 2. Collect sleep history in relation to headache patterns. Screening questionnaires and prediction equations are cost-effective. 3. Rule out sleep apnea headache in patients with awakening headache or higher-risk headache diagnoses (cluster, hypnic, chronic migraine, and chronic tension-type headache); patients with signs and symptoms of obstructive sleep apnea warrant polysomnography and treatment according to sleep medicine practice guidelines. There is no evidence for suspending conventional headache treatment in suspected or confirmed cases of sleep apnea. Treatment of sleep apnea with CPAP may improve or resolve headache in a subset of patients. The impact on sleep apnea headache of other treatments for sleep apnea (eg, oral appliances, surgery, weight loss) is largely untested. At a minimum, sedative-hypnotic drugs should be avoided in suspected apneics until the sleep apnea is treated. 4. Among patients with migraine and tension-type headache, insomnia is the most common sleep complaint, reported by one half to two thirds of clinic patients. Patients who suffer from chronic migraine or tension-type headache may benefit from behavioral sleep modification. Pharmacologic treatment may be considered on a case-by-case basis, with hypnotics, anxiolytics, or sedating antidepressants used to manage insomnia, tailoring treatment to the symptom pattern. 5. Individuals with chronic headache are at increased risk for psychiatric disorders. Assessment for depression and anxiety may be warranted when either insomnia or hypersomnia is present. Psychiatric symptoms affect the choice of sedating versus alerting versus neutral pharmacologic agents for headache. 6. All headache patients, particularly those with episodic migraine and tension-type headaches, may benefit from inclusion of sleep variables in trigger management.

Wrist actigraphic scoring for sleep laboratory patients: algorithm development.

Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep-wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory. A convenience sample of 116 patients undergoing clinical sleep recordings volunteered to participate. Actiwatch-L recordings were obtained from 98 participants, along with 18 recordings using the newer Spectrum model (Philips Electronics), but some of the actigraphic recordings could not be adequately aligned with the simultaneous PSGs. Of satisfactory alignments, 40 Actiwatch recordings were used as a training set to empirically develop a new Scripps Clinic algorithm for sleep-wake scoring. The Scripps Clinic algorithm was then prospectively evaluated in 39 Actiwatch recordings and 16 Spectrum recordings, producing epoch-by-epoch sleep-wake agreements of 85-87% and kappa statistics averaging 0.52 (indicating moderate agreement). Wake was underestimated by the scoring algorithm. The correlations of PSG versus actigraphic wake percentage estimates were r = 0.6690 for the Actiwatch and r = 0.2197 for the Spectrum. In general, using a different weighting of activity counts from previous and subsequent epochs, the Scripps Clinic algorithm discriminated sleep-wake more successfully than the manufacturer's Actiware algorithms. Neither algorithm had fully satisfactory agreement with PSG. Further evaluations of algorithms for these actigraphs are needed, along with controlled comparisons of different actigraphic designs and software.

Circadian rhythm of CSF monoamines and hypocretin-1 in restless legs syndrome and Parkinson's disease.

The symptoms of restless legs syndrome (RLS) have a circadian pattern and central nervous system dopamine has been implicated in the pathogenesis of the condition. We sought to characterize circadian variation in dopamine and related compounds in human cerebro-spinal fluid (CSF). CSF was continuously withdrawn for 22 h from an implanted lumbar intradural catheter and sampled from three patients with RLS, three patients with Parkinson's disease (PD) and three healthy volunteers. Patients had moderate disease severity and took no medications. We assayed CSF dopamine (DA), homovanillic acid (HVA), dihydroxy-phenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5-HIAA) from samples every 30 min by reversed-phase HPLC coupled with electrochemical detection. We also measured CSF levels of hypocretin-1 every hour by RIA. The procedure was well-tolerated. One patient ended the study early due to lumbar radicular pain and was not included in the analysis. There were no changes in CSF cell counts or protein levels from the first to the last samples. There was no difference in any of the compounds between groups, so we fit 24-h cosines to examine if the entire group had significant phase consistency. There was a peak for dopamine at 10 a.m. (p<0.025) and for HVA at 2 p.m. (p<0.01), but no evidence of a significant 24-h rhythm for DOPAC, 5-HIAA, the HVA/5-HIAA ratio, or hypocretin-1. These results demonstrate a circadian rhythm for CSF dopamine and HVA concentrations in humans, with higher levels in the daytime than at nighttime. This circadian variation could underlie the symptoms of RLS and sleep-related variation in motor function in PD.

Evaluation of immobility time for sleep latency in actigraphy.

BACKGROUND: Actigraphy has become an important tool in sleep research, however, most actigraphic models have had little evaluation of their sleep scoring software. Some reports have described poor agreement of actigraph and polysomnogram (PSG) results. In this study, we examined the accuracy of the Actiwatch-L instrument with Actiware((R)) software version 5.0 (Minimitter-Respironics, Bend, Oregon). METHODS: We analyzed the sleep latencies and total sleep times in 33 actigraph recordings and compared performance to simultaneous polysomnography. For scoring sleep latency, the default criterion for scoring sleep onset (10min of immobility) was compared with criteria of 4, 5, 6, and 15min of immobility, and low, middle, and high activity thresholds were compared. RESULTS: Of 4, 5, 6, 10 and 15min of actigraphic immobility, the 5min criterion yielded the most accurate sleep latencies. The 5min criterion also yielded near-optimal estimates for total sleep time and wake after sleep onset. CONCLUSIONS: We found that a default 10-min immobility parameter for sleep onset was not as accurate as 5min for scoring sleep latency and total sleep time in this clinical sample. There is a need for expanded samples to further evaluate algorithm scoring parameters and the search for superior alternatives.

Sleep and headaches.

Sleep has long been recognized to both provoke and relieve headache. Epidemiologic research has associated sleep disorders with more frequent and severe headaches. Chronic daily, awakening, and morning headache patterns are particularly suggestive of sleep disorders, including sleep-related breathing disorders, insomnia, circadian rhythm disorders, and parasomnias. Snoring and other indicators of sleep-disordered breathing are the most commonly studied and are particularly salient because of the potential for headache to improve or resolve with treatment of sleep. In addition to sleep disorders, clinical research correlates specific headache diagnoses (eg, migraine, tension-type, and cluster) with chronobiologic patterns and sleep processes, implicating common anatomic structures and neurochemical processes involved in the regulation of sleep and headache. Evidence strongly supports screening for sleep disorders by headache practitioners. Headache management should identify and treat sleep disorders that may improve or resolve headache.

Headache and sleep disorders: review and clinical implications for headache management.

Review of epidemiological and clinical studies suggests that sleep disorders are disproportionately observed in specific headache diagnoses (eg, migraine, tension-type, cluster) and other nonspecific headache patterns (ie, chronic daily headache, "awakening" or morning headache). Interestingly, the sleep disorders associated with headache are of varied types, including obstructive sleep apnea (OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and hypersomnia. Headache, particularly morning headache and chronic headache, may be consequent to, or aggravated by, a sleep disorder, and management of the sleep disorder may improve or resolve the headache. Sleep-disordered breathing is the best example of this relationship. Insomnia is the sleep disorder most often cited by clinical headache populations. Depression and anxiety are comorbid with both headache and sleep disorders (especially insomnia) and consideration of the full headache-sleep-affective symptom constellation may yield opportunities to maximize treatment. This paper reviews the comorbidity of headache and sleep disorders (including coexisting psychiatric symptoms where available). Clinical implications for headache evaluation are presented. Sleep screening strategies conducive to headache practice are described. Consideration of the spectrum of sleep-disordered breathing is encouraged in the headache population, including awareness of potential upper airway resistance syndrome in headache patients lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep regulation strategies are offered that are also compatible with treatment of primary headache.

Sleep and headache disorders: clinical recommendations for headache management.

Clinical practice points were drawn from a review of sleep and headache disorders published in the regular issue of Headache (released in tandem with this supplement). The recommendations include: (1) Sleep as well as psychiatric disorders tend to become prevalent in more complex and severe headache patterns and regulation of sleep and mood may favorably impact headache threshold; (2) Specific headache patterns, irrespective of headache diagnosis, are suggestive of a potential sleep disorder (eg, "awakening" or morning headache, chronic daily headache); (3) Sleep disorders most implicated with headache include obstructive sleep apnea, primary insomnia, and circadian phase abnormalities, and treatment of such sleep disorders may improve or resolve headache; (4) Inexpensive screening tools (eg, sleep history interview, headache/sleep diary, validated questionnaires, prediction equations) aid identification of patients warranting polysomnography; and (5) Pharmacologic and behavioral therapies are effective in the regulation of sleep and are compatible with usual headache care.

Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262.

BACKGROUND: In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH). Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes. METHODS: Twenty postmenopausal women troubled by hot flashes underwent one week of baseline observation followed by 4 weeks of a randomized controlled trial of melatonin or matched placebo. The three randomized treatments were melatonin 0.5 mg 2.5-3 hours before bedtime, melatonin 0.5 mg upon morning awakening, or placebo capsules. Twelve of the women were admitted to the GCRC at baseline and at the end of randomized treatment for 24-hour sampling of blood for LH. Morning urine samples were collected twice weekly to measure LH excretion. Subjective responses measured throughout baseline and treatment included sleep and hot flash logs, the CESD and QIDS depression self-ratings, and the SAFTEE physical symptom inventory. RESULTS: Urinary LH tended to increase from baseline to the end of treatment. Contrasts among the 3 randomized groups were statistically marginal, but there was relative suppression combining the groups given melatonin as contrasted to the placebo group (p < 0.01 one-tailed, Mann-Whitney U = 14). Similar but not significant results were seen in blood LH. There were no significant contrasts among groups in hot flashes, sleep, depression, or side-effect measures and no significant adverse effects of any sort. CONCLUSION: The data are consistent with the hypothesis that melatonin suppresses LH in postmenopausal women. An effect related to the duration of nocturnal melatonin elevation is suggested. Effects of melatonin on reproductive endocrinology should be studied further in younger women and in men. Larger studies of melatonin effects on postmenopausal symptoms would be worthwhile.

Sleep-related headache syndromes.

An association between headache and sleep is long recognized in the medical literature and deemed highly clinically relevant for at least a portion of headache sufferers. Sleep-related headaches are not well understood, but recent advances in the neurophysiology of sleep and headache shed light on common biological processes potentiating their association. Respective diagnostic nosologies for headache and sleep disorders offer limited guidance but are evolving to better represent the known associations. A rational approach based on the available empiricism can assist the clinician in the assessment and treatment of headache. Each headache evaluation should include at least a brief sleep history. Headaches that occur during or after sleep, so called morning headache, may be secondary to a sleep disorder and call for a specific treatment. This case is best established for sleep-related breathing disorders, and treatment of apnea often leads to resolution of the headache. Although pure sleep-related headaches, such as hypoxemia-related headache and hypnic headache, are less prevalent and more easily recognized, primary headaches are often impacted to some degree by sleep. Additionally, common headache medications and comorbid conditions alter sleep architecture. Management of primary headache may be facilitated by attention to sleep complaints.

Zolpidem for postanoxic spasticity.

A 28-year-old male sustained anoxic brain damage following aborted cardiac arrest, and subsequently developed severe muscular rigidity and spasticity involving all extremities. The spasticity was refractory to the standard regimens used for spastic hypertonia. Zolpidem dramatically inhibited muscular rigidity, spasticity, and dystonic posturing in a dose-dependent manner, resulting in a sustained improvement of his global performance over four years. The authors postulate a central mechanism of action by selective inhibition of GABAergic inhibitory neurons, and suggest a controlled clinical study to investigate the potential efficacy of zolpidem in relieving spasticity related to postanoxic brain injury.

Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome.

STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS). DESIGN: Double-blinded, placebo-controlled, parallel-group study. SETTING: 15 tertiary referral centers in the USA. PARTICIPANTS: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group. CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.

Sleep-related headache syndromes.

The relationship between sleep and sleep disorders and headache remains unclear. Clinical experience and numerous studies document some sort of relationship, but the exact nature remains understudied and complex. Changes in sleep duration and sleep quality appear to be capable of affecting headaches of different types. Obstructive sleep apnea can cause or exacerbate headaches in a susceptible person. Obstructive sleep apnea also may cause a specific headache when awakening, which is different from migraine or tension headache and disappears after treatment of the sleep and breathing disturbance. Hypnic headache is another type of sleep-exclusive headache that has been proposed. Hypnic headaches are brief, moderately severe, and affect the elderly primarily.

Sleep-related Headache.

The relationship between sleep and headache has great individual variation. Headaches that arise primarily out of sleep have a broader differential diagnosis than random headaches, and a specific cause should be identified, if possible. Sleep apnea can trigger or cause sleep-related headaches. Hypnic headache is one of a few specific, uncommon, idiopathic sleep-related headache syndromes. Treatment of sleep-related headache includes treating the underlying cause, such as sleep apnea, and prescribing medications usually used for headache as well as medications for sleep disorders.

Mortality in Obstructive Sleep Apnea: Association with Impaired Wakefulness.

Sleep fragmentation from obstructive sleep apnea (OSA) is correlated with a shortened sleep latency on the Maintenance of Wakefulness Test (MWT) and the Multiple Sleep Latency Test. Whether impairment of wakefulness is associated with increased mortality in OSA patients is unknown. We evaluated survival over an average timespan of 7.5 years from the date of diagnosis in a consecutive series of 322 OSA patients who had undergone nocturnal polysomnograpy and the MWT. Evaluable survival data were obtained in 142 patients. Twenty two had died. Deaths were predominantly due to cardiovascular disease. A comparison of the demographic and sleep study data between the alive and dead groups was significant for differences in MWT sleep latency and in age at time of diagnosis. The MWT mean sleep latency, when adjusted for age, was significantly shortened in the dead patients (28 +/- 11 min vs. 21 +/- 10 min, p < 0.005). Also, there was a significant decrease in survival in the patients whose MWT mean sleep latency was less than 20 min. These findings demonstrate an association between impairment of wakefulness and long-term mortality in OSA patients. This association was not evident for the other measures used to assess OSA severity.