Flavia B. Consens

Decreased striatal dopaminergic innervation in REM sleep behavior disorder.

Article abstract—REM sleep behavior disorder (RBD) is a possible herald of neurodegenerative disorders with parkinsonism. The authors determined the density of striatal dopaminergic terminals with [11C]dihydrotetrabenazine PET in six elderly subjects with chronic idiopathic RBD and 19 age-appropriate controls. In subjects with RBD, there were significant reductions in striatal [11C]dihydrotetrabenazine binding, particularly in the posterior putamen.

REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA

Objective: To explore the neurochemical basis of REM sleep behavior disorder (RBD) in multiple-system atrophy (MSA). Methods: In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of REM atonia loss by the percentage of REM sleep with tonically increased electromyographic (EMG) activity and the percentage of REM sleep with phasic EMG bursts. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was employed to measure the density of striatal monoaminergic terminals and SPECT with (−)-5-[123I]iodobenzovesamicol ([123I]IBVM) to measure the density of thalamic cholinergic terminals. Data in the patient group were compared with data from 15 normal control subjects scanned with [11C]DTBZ and 12 with [123I]IBVM. Results: Age and gender distributions were similar in patient and normal control groups. The MSA subjects showed decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) and decreased [123I]IBVM binding in the thalamus (p < 0.001). Moreover, in the MSA group, striatal [11C]DTBZ binding was inversely correlated with the severity of REM atonia loss (p = 0.003). Thalamic [123I]IBVM binding, however, was not correlated to the severity of REM atonia loss. Conclusion: Decreased nigrostriatal dopaminergic projections may contribute to RBD in MSA.

A Randomized Double-Blind Pilot Trial of Gabapentin Versus Placebo to Treat Alcohol Dependence and Comorbid Insomnia

BACKGROUND Insomnia and other sleep disturbances are common, persistent, and associated with relapse in alcohol-dependent patients. The purpose of this pilot study was to compare gabapentin versus placebo for the treatment of insomnia and prevention of relapse in alcohol-dependent patients. METHODS Twenty-one subjects, including 10 women who met study criteria for alcohol dependence and insomnia and expressed a desire to abstain from alcohol, were recruited to the study. During a 1 to 2 week placebo lead-in and screening phase, a complete medical history, physical exam, blood tests, urine drug test, and structured interviews were performed to determine eligibility and patterns of alcohol use and sleep. Insomnia due to intoxication or acute withdrawal, psychiatric or medical illness, medications, and other sleep disorders were ruled out. Subjects were then randomized to either placebo (n = 11) or gabapentin (n = 10) for 6 weeks and titrated over a 10-day period to 1,500 mg or 5 pills at bedtime. After a 4-day taper, subjects were reassessed 6 weeks after ending treatment. RESULTS Gabapentin significantly delayed the onset to heavy drinking, an effect which persisted for 6 weeks after treatment ended. Insomnia improved in both treatment groups during the medication phase, but gabapentin had no differential effects on sleep as measured by either subjective report or polysomnography. CONCLUSION Because gabapentin is a short-acting medication that was taken only at nighttime in this study, it may possibly exert a nocturnal effect that prevents relapse to heavy drinking by a physiological mechanism not measured in this pilot study.

Cerebral cortical and subcortical cholinergic deficits in parkinsonian syndromes

Objectives: Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects. Methods: We used PET with [11C]PMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP. Results: We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait. Conclusions: Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD.

Obstructive sleep apnea is related to a thalamic cholinergic deficit in MSA

Objective: To explore the neurochemical basis of obstructive sleep apnea (OSA) in multiple-system atrophy (MSA). Methods: In 13 patients with probable MSA, nocturnal, laboratory-based polysomnography was used to rate the severity of OSA using the apnea–hypopnea index during sleep. SPECT with (−)-5-[123I]iodobenzovesamicol ([123I]IBVM) was utilized to measure the density of thalamic cholinergic terminals, which project from the brainstem pedunculopontine and laterodorsal tegmental nuclei. PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) was also used to measure the density of striatal monoaminergic terminals, which project from the brainstem. Findings in the patient group were compared with data from 12 normal control subjects scanned utilizing [123I]IBVM and 15 normal control subjects utilizing [11C]DTBZ. Results: Age and gender distributions were similar in patient and control groups. The MSA subjects showed decreased [123I]IBVM binding in the thalamus (p < 0.001) and decreased mean [11C]DTBZ binding in the striatum (p < 0.0001) in comparison with the control subjects. In the MSA group, thalamic [123I]IBVM binding was inversely correlated with the severity of OSA (p = 0.011). Striatal [11C]DTBZ binding was not correlated with the severity of OSA (p = 0.19). Conclusion: Decreased pontine cholinergic projections may contribute to OSA in MSA.

Derivation and validation of a simple perioperative sleep apnea prediction score

BACKGROUND:Obstructive sleep apnea (OSA) is a largely underdiagnosed, common condition, which is important to diagnose preoperatively because it has implications for perioperative management. Our purpose in this study was to identify independent clinical predictors of a diagnosis of OSA in a general surgical population, develop a perioperative sleep apnea prediction (P-SAP) score based on these variables, and validate the P-SAP score against standard overnight polysomnography. METHODS:A retrospective, observational study was designed to identify patients with a known diagnosis of OSA. Independent predictors of a diagnosis of OSA were derived by logistic regression, based on which prediction tool (P-SAP score) was developed. The P-SAP score was then validated in patients undergoing overnight polysomnography. RESULTS:The P-SAP score was derived from 43,576 adult cases undergoing anesthesia. Of these, 3884 patients (7.17%) had a documented diagnosis of OSA. Three demographic variables: age >43 years, male gender, and obesity; 3 history variables: history of snoring, diabetes mellitus Type 2, and hypertension; and 3 airway measures: thick neck, modified Mallampati class 3 or 4, and reduced thyromental distance were identified as independent predictors of a diagnosis of OSA. A diagnostic threshold P-SAP score ≥2 showed excellent sensitivity (0.939) but poor specificity (0.323), whereas for a P-SAP score ≥6, sensitivity was poor (0.239) with excellent specificity (0.911). Validation of this P-SAP score was performed in 512 patients with similar accuracy. CONCLUSION:The P-SAP score predicts diagnosis of OSA with dependable accuracy across mild to severe disease. The elements of the P-SAP score are derived from a typical university hospital surgical population.

Predictors of Habitual Snoring and Obstructive Sleep Apnea Risk in Patients With Asthma

BACKGROUND A high prevalence of obstructive sleep apnea (OSA) symptoms was reported in patients with asthma. Our goal was to evaluate factors associated with habitual snoring and OSA risk in these patients. METHODS Patients with asthma were surveyed at specialty clinics with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ) and questions about the frequency of asthma symptoms (National Asthma Education and Prevention Program guidelines), followed by medical record review. SA-SDQ scores >or= 36 for men and >or= 32 for women defined high OSA risk. Logistic regression was used to model associations with habitual snoring and high OSA risk. RESULTS Among 244 patients, 37% snored habitually and 40% demonstrated high OSA risk. Independent predictors of habitual snoring included gastroesophageal reflux disease (GERD) [odds ratio (OR), 2.19; 95% confidence interval (CI), 1.19 to 4.02] and use of an inhaled corticosteroid (ICS) [OR, 2.66; 95% CI, 1.05 to 6.72]. High OSA risk was predicted by asthma severity step (OR, 1.59; 95% CI, 1.23 to 2.06), GERD (OR, 2.70; 95% CI, 1.51 to 4.83), and ICS use (OR, 4.05; 95% CI, 1.56 to 10.53). Linear, dose-dependent relationships of ICS with habitual snoring and high OSA risk were seen (p = 0.004 and p = 0.0006, respectively). Women demonstrated a 2.11 times greater odds for high OSA risk (95% CI, 1.10 to 4.09) when controlling for the above covariates. CONCLUSIONS Symptoms of OSA in patients with asthma are predicted by asthma severity, coexistent GERD, and use of an ICS in a dose-dependent fashion. The well-recognized male gender predominance for OSA symptoms is not apparent in these patients. Further exploration of these relationships may help to explain the increased prevalence of OSA in asthma and provide new insights into the reported female predominance of asthma morbidity.

Alternating leg muscle activation during sleep and arousals: A new sleep-related motor phenomenon?

We describe a quickly alternating pattern of anterior tibialis activation, recorded during nocturnal polysomnography in 16 patients. Polysomnography, usually for sleep‐disordered breathing, included surface electromyograms over the anterior tibialis of each leg. Cases were identified from approximately 1,500 studies reviewed in the course of standard clinical care. Patients were 12 men and 4 women (mean age, 41 ± 15 years; range, 12–70 years). Brief activation of the anterior tibialis in one leg alternated with similar activation in the other leg. Activations occurred at a frequency of approximately 1 to 2 Hz, each lasted between 0.1 and 0.5 seconds, and sequences of alternating activations usually lasted between several and 20 seconds. The phenomenon occurred in all sleep stages but particularly during arousals. Ten of the 16 patients had periodic leg movements during sleep at a rate ≥ 5.0 per hour, and 12 of the 16 patients were taking antidepressant medication. Alternating leg muscle activation (ALMA) during sleep, at this relatively high frequency, may be a newly described phenomenon. We speculate that ALMA could represent transient facilitation of a spinal central pattern generator for locomotion, perhaps due to serotonergic effects of antidepressant medication.

Sleep Disorders and Medical Conditions in Women

Sleep disorders affect women differently than they affect men and may have different manifestations and prevalences. With regard to obstructive sleep apnea (OSA), variations in symptoms may cause misdiagnoses and delay of appropriate treatment. The prevalence of OSA appears to increase markedly after the time of menopause. Although OSA as defined by the numbers of apneas/hypopneas may be less severe in women, its consequences are similar and perhaps worse. Therapeutic issues related to gender should be factored into the management of OSA. The prevalence of insomnia is significantly greater in women than in men throughout most of the life span. The ratio of insomnia in women to men is approximately 1.4:1.0, but the difference is minimal before puberty and increases steadily with age. Although much of the higher prevalence of insomnia in women may be attributable to the hormonal or psychological changes associated with major life transitions, some of the gender differences may result from the higher prevalence of depression and pain in women. Insomnias negative impact on quality of life is important to address in women, given the high relative prevalence of insomnia as well as the comorbid disorders in this population. Gender differences in etiology and symptom manifestation in narcolepsy remain understudied in humans. There is little available scientific information to evaluate the clinical significance and specific consequences of the diagnosis of narcolepsy in women. Restless legs syndrome (RLS) is characterized by an urge to move the legs or other limbs during periods of rest or inactivity and may affect as much as 10% of the population. This condition is more likely to afflict women than men, and its risk is increased by pregnancy. Although RLS is associated with impaired quality of life, highly effective treatment is available.

Association of Obstructive Sleep Apnea Risk or Diagnosis with Daytime Asthma in Adults

Objective. Obstructive sleep apnea (OSA) worsens nocturnal asthma, but its potential impact on daytime asthma remains largely unassessed. We investigated whether the sleep disorder is associated with daytime, in addition to nighttime, asthma symptoms. Methods. Asthma patients at tertiary-care centers completed the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and an asthma control questionnaire. SA-SDQ scores ≥36 for males and ≥32 for females defined high OSA risk. Medical records were reviewed for established diagnosis of OSA and continuous positive airway pressure (CPAP) use. Results. Among 752 asthma patients, high OSA risk was associated similarly with persistent daytime and nighttime asthma symptoms (p < .0001 for each). A diagnosis of OSA was robustly associated with persistent daytime (p < .0001) in addition to nighttime (p = .0008) asthma symptoms. In regression models that included obesity and other known asthma aggravators, high OSA risk retained associations with persistent daytime (odds ratio [OR] = 1.96 [95% confidence interval [CI] = 1.31–2.94]) and nighttime (1.97 [1.32–2.94]) asthma symptoms. Diagnosed OSA retained an association with persistent daytime (2.08 [1.13–3.82]) but not with nighttime (1.48 [0.82–2.69]) asthma symptoms. CPAP use was associated with lower likelihood of persistent daytime symptoms (0.46 [0.23–0.94]). Conclusions. Questionnaire-defined OSA risk and historical diagnosis were each associated with persistent daytime asthma symptoms, to an extent that matched or exceeded associations with nighttime asthma symptoms. Unrecognized OSA may be a reason for persistent asthma symptoms during the day as well as the night.