Functional magnetic resonance imaging responses to expiratory loading in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by diminished upper airway muscle phasic and tonic activation during sleep, but enhanced activity during waking. We evaluated neural mechanisms underlying these patterns with functional magnetic resonance imaging procedures during baseline and expiratory loading conditions in nine medication-free OSA and 16 control subjects. Both groups developed similar expiratory loading pressures, but appropriate autonomic responses did not emerge in OSA cases. Reduced neural signals emerged in OSA cases within the frontal cortex, anterior cingulate, cerebellar dentate nucleus, dorsal pons, anterior insula and lentiform nuclei. Signal increases in OSA over control subjects developed in the dorsal midbrain, hippocampus, quadrangular cerebellar lobule, ventral midbrain and ventral pons. Fastigial nuclei and the amygdala showed substantially increased variability in OSA subjects. No group differences were found in the thalamus. OSA patients show aberrant responses in multiple brain areas and inappropriate cardiovascular responses to expiratory loading, perhaps as a consequence of previously-demonstrated limbic, cerebellar and motor area gray matter loss.

Effect of amitriptyline on symptoms, sleep, and visceral perception in patients with functional dyspepsia.

OBJECTIVE: Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders, yet the mechanism(s) of action of these drugs in these disorders is not known. In the current study, we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms, perceptual responses to gastric distension, and subjective and objective measures of sleep. METHODS: Patients were randomized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo. There was a 3-wk washout phase, followed by a cross-over to the alternate treatment. Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period. Diaries of symptoms were maintained throughout. RESULTS: Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo. Five of seven patients had evidence for altered perception of gastric balloon distension during placebo. However, the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension. Baseline sleep dysfunction in the form of reduced sleep efficiency, increased arousal, or abnormal amounts of REM sleep was found in all seven patients. Amitryptiline significantly reduced absolute and relative amounts of REM sleep, but had no effect on sleep parameters related to nonregenerative sleep. CONCLUSION: The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension, or to measures of arousal from sleep. An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect.

The incidence of parasomnias in child bruxers versus nonbruxers.

Bruxism in children has been reported to occur in association with certain parasomnias (i.e., sleep talking, bed wetting). Various dental, medical, neurological, and psychological risk factors also have been correlated with bruxism. A case-control study was therefore conducted to test the null hypothesis that there is no difference between bruxers and nonbruxers in the occurrence rate of other parasomnias and these reported risk factors. A 54-item survey questionnaire was developed and mailed to 342 pediatric patients, half of whom were avowed to be bruxers by their parents. These patients were selected randomly from a private pediatric practice in Northern California. One-hundred fifty-two subjects (77 bruxers and 75 controls) returned the questionnaire, and stepwise logistic regression analysis revealed that five of the 54 factors (nocturnal muscle cramps, bed wetting, colic, drooling while sleeping, and sleep talking) showed significant differences between bruxers and controls (odds ratios ranged from 3.11 to 1.95). These findings strongly suggest the possibility of a common sleep disturbance underlying these nonsleep-stage specific parasomnias.

Effect of jaw position and posture on forced inspiratory airflow in normal subjects and patients with obstructive sleep apnea.

OBJECTIVE: This study evaluated whether substantial airflow changes occur by changing both body posture and jaw position in normal subjects and patients with obstructive sleep apnea (OSA). DESIGN: A case-control design was utilized to assess group differences (OSA vs control) and each subject served as his/her own control subject to assess condition differences (jaw position and body posture changes). Subjects included 16 male patients with OSA (aged 33 to 71 years) whose conditions were diagnosed at the UCLA Sleep Disorders Laboratory with a polysomnographic recording, and 9 male non-OSA subjects (aged 22 to 52 years). The experimental intervention in the study involved alterations in body posture and jaw positioning. Airflow changes were determined using a spirometer that assessed the velocity of airflow during a forced inspiration. Subjects in this study all had the middle portion (25 to 75%) of their maximum forced inspiratory flow (FIF25-75) curve measured in three positions; (1) normal jaw position-upright body posture (N-U); (2) normal jaw position-supine body posture (N-S); and (3) protrusive jaw position-supine body posture (P-S). SETTING: The study was conducted at the UCLA Dental Clinical Research Center. RESULTS: Both groups had a significant decrease in their FIF25-75 upon reclining, and there were no significant group differences regarding the magnitude of this change. Both groups also had a nearly full recovery of their FIF25-75 airflow when their jaws were positioned forward while reclining. CONCLUSIONS: These data document that when a patient is in a supine position, a 100% protrusive jaw position allows significantly more inspiratory airflow to occur.

Self-reported automobile accidents involving patients with obstructive sleep apnea.

We developed a routine survey instrument, which included data on self-reported motor vehicle accidents (MVA), among 253 patients who attended the UCLA Sleep Disorders Center to evaluate whether patients with diagnosed sleep apnea syndrome (SAS) have a higher ratio of MVAs. We used unconditional multiple logistic regression to determine the odds ratio between MVA and SAS, adjusted for the following covariates: age, sex, work shift, daytime nap, alcohol and coffee intake, and history of neurologic diseases. Thirty-one percent of patients with SAS compared with 15% of patients without SAS reported at least one MVA (p < 0.01). The adjusted odds ratio found through logistic multiple regression analysis was 2.99 (p < 0.01). The results demonstrate that patients with SAS had a higher ratio of self-reported MVA than did those without SAS and that the characteristics of falling asleep at inappropriate times and driving past destinations were two good indicators of probability of having an MVA. Nevertheless, sleep apnea is a very treatable condition; once treated the risk factors diminish considerably.

Chronic lymphocytic leukemia presenting as a pituitary mass lesion.

We describe a unique case of chronic lymphocytic leukemia (CLL) in a patient who presented with bitemporal hemianopsia, adrenal insufficiency, and gonadotrophin deficiency. Studies revealed an enhancing intrasellar mass with suprasellar extension and displacement of the optic chiasm. Peripheral blood and cerebrospinal fluid (CSF) studies disclosed a monoclonal IgM kappa expressing B-cell CLL. Biopsy of the pituitary mass revealed dense infiltration of the pituitary gland by leukemic cells. This is, to our knowledge, the first reported case of CLL presenting as a pituitary mass lesion.

A progressive neurologic disorder with supranuclear vertical gaze paresis and distinctive bone marrow cells.

Nine patients with a progressive neurologic disorder that was characterized by mental deterioration, supranuclear vertical gaze paresis, and foam cells or sea-blue histiocytes in the bone marrow are described and compared with patients who were previously described as having " neurovisceral storage disease with vertical supranuclear ophthalmoplegia" and "dystonic lipidosis." The clinical manifestations of our patients and those described by others and the pathologic findings and profiles of lipid analysis reported by others are similar to those in patients with Niemann-Pick disease, type C. Sphingomyelinase activities in leukocytes and skin fibroblasts were normal in our patients and in more than half of the reported cases; these findings are also compatible with those in patients with Niemann-Pick disease, type C. Until the biochemical and genetic abnormalities of Niemann-Pick disease, type C are clearly defined, it is justifiable to classify the disorder under discussion as a subgroup of Niemann-Pick disease, type C because it seems to be a heterogeneous group. From the clinical point of view, the diagnosis is difficult to establish in the absence of abnormalities in the bone marrow in patients who are older than 20 years; repeat examinations of the bone marrow are necessary in such patients. Clinicians should be aware of this disorder not only in patients in the first and second decades of life, when this disorder usually becomes symptomatic, but also in patients in the fourth and fifth decades.