Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight patients with myotonic dystrophy underwent comprehensive neuropsychological testing and overnight polysomnography to assess whether the waking cognitive impairment might be attributable to sleep structure abnormalities or to sleep-related respiratory problems. Patients showed substantial neuropsychological deficits, fragmented nocturnal sleep and, in half the patients, sleep apnea and/or hypopnea both mainly of central type. There was no statistically significant correlation between the degree of daytime cognitive deficit and the degree of sleep fragmentation or of respiratory problems at night. It was concluded that the neuropsychological deficit in mytonic dystrophy cannot be attributed to a secondary effect of nocturnal sleep apnea or sleep disruption but probably represents a direct effect of CNS lesions.
 ...
PMID:Neuropsychological deficits and sleep in myotonic dystrophy. 227 99

The magnitude, determinants and reversibility of cognitive deficits associated with the sleep apnea/hypopnea syndrome (SAHS) are of clinical and research interest. A quantitative overview of impairment effect sizes (ESs) from case-control studies of cognitive performance in SAHS suggests that deficits broadly worsen with disease severity, with large average values for attentional (ES approximately 1.0 SD units) and executive (ES approximately 0.9 SD units) cognitive scores, and moderate values for memory-related (ES approximately 0.6 SD units) performance scores. A study of determinants of cognitive outcomes conducted in 150 patients with SAHS (AHI 5+ and > or =2 symptoms) showed significant but weak associations between a cognitive 'intellectual ability' component score (CS) and both AHI (r=-0.14) and minimum oxygen saturation (r = 0.15), linking increasing disease severity with poorer performance. A somewhat stronger correlation between a cognitive 'response slowing' CS and a 'wakefulness' CS was observed (r=-0.34). That sleepiness as well as hypoxemia might contribute to cognitive deficit has also been suggested by experimental sleep fragmentation in normals, producing small to moderate impairments (average ES approximately 0.3 SD units) in attention-biased scores. The reversibility of attentional cognitive deficits has been investigated through a meta-analysis of randomized placebo-controlled crossover studies of CPAP treatment, involving 98 SAHS patients (AHI 5+ and > or =2 symptoms). While cognitive outcomes showed at least trends towards better performance on CPAP than on placebo (p< or =0.1), the ESs of cognitive enhancements following CPAP were small (average ES approximately 0.2 SD units). This may be due either to the relatively mild study population, suboptimal CPAP use or to an irreversible component in cognitive impairment in SAHS.
 ...
PMID:Cognitive function in the sleep apnea/hypopnea syndrome (SAHS). 1089 80

The sleep apnea syndrome (SAS), which is defined by more than 5 apneas or hypopneas per hour of sleep (9), is quite a frequent affection which concerns 1.4 to 10% of general population (1.7). The major daytime complaints of the SAS are daytime sleepiness, memory and attention disorders, headaches and asthenia especially in the morning, and sexual impotence (9). The nocturnal manifestations are dominated by sonorous and generally long standing snoring, increased by dorsal decubitus and intake of alcohol, with repeated interruptions by respiratory arrests. These manifestations are always noted but rarely spontaneously reported. The sleep, non refreshing, is agitated and perturbed by numerous awakenings. The findings of the clinical examination are poor: obesity is found in 2/3 of the cases and arterial hypertension in 1/2 of the cases (20). Polygraphic recording during sleep only permits an absolute diagnosis. This frequent affection is a real problem of public health because of its numerous complications (3, 10, 12, 13, 18, 21). Symptoms of depression are often found when a patient with a SAS is examined and conversely, symptoms which evoke a SAS can be found in the clinical examination of depressed patients. We decided so to study the thymic and anxious status of 24 patients investigated for a SAS and submitted to a polygraphic recording during sleep. Four clinical parameters were studied: DSM III-R diagnosis criteria, Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HARS) and thymasthenia rating scale of Lecrubier, Payan and Puech. We also reported Total Sleep Time (TST = 6.5 +/- 1.5), Apnea Hypopnea Index (AHI = 26.7 +/- 21.6), number (2.1 +/- 2.8/h) and duration (174.2 +/- 150.8 s/h) of hypoxic events. Results showed that among 24 patients, 8 were depressed according to DSM III-R diagnosis criteria and had MADRS > 25, 22 were anxious, 11 had a major anxiety (HARS > 15) and 15 presented thymasthenia (SET > 15). Significative correlations existed between anxiety and depression (r = 0.82; p < 0.0001), depression and thymasthenia (r = 0.77; p < 0.0001) and thymasthenia and anxiety (r = 0.75; p < 0.0001). Among the 8 depressed patients a correlation existed between AHI and depression (r = 0.72; p = 0.04), but no correlation was found between depression and hypoxic events. These results were comparable to those of Guilleminault (10), Reynolds (21), Kales (12), Bliwise (3), Klonoff (13) and Millman (18) who studied relations between SAS and depression. The evaluation of thymasthenia gave a more precise typology of the depressive state associated to SAS: the type of the mood disorder is more "blunted" and "anhedonic" than "sorrowful", particularly characterised by asthenia, lack of energy, reduction of interests (leisures, libido, work), loss of initiative, difficulties to organise tasks, fall of performances and reduction of pleasure usually felt in pleasant events (15). The physic symptomatology dominated the psychic one. The sleep disorganization, more than metabolic consequences of apneas, could be involved in this associated depressive state. Other neuropsychiatric troubles can be associated to the SAS. In fact, cognitive troubles (2, 8, 14, 16, 19, 22, 24) and personality disorders (12, 18) have been described. Our data confirm previous observations suggesting a frequent association between SAS, depression, fatigue and anxiety. Clinicians should consequently be aware that a depression with severe complaints of fatigue should deserve an investigation oriented towards SAS. Conversely, when a SAS is diagnosed, it is necessary to look for a possible depression in order to set up the most appropriate treatment. The frequency of SAS, like depression's one, increases with age. Prescription and consummation of sedative psychotropic drugs increase too with age. Since respiratory depressant effects of these drugs have been clearly demonstrated, it is important to evoke SAS when depressive and/or anxious states are diagnosed and not to aggravate it. An efficacious treatment of SAS can also cure the associated depressive state, but this one can persist. It is necessary, in this case, to select a non sedative antidepressant.
 ...
PMID:[Depressive symptomatology and sleep apnea syndrome]. 1240 78

Children with acute hypoxic-ischaemic events (e.g. stroke) and chronic neurological conditions associated with hypoxia frequently present to paediatric neurologists. Failure to adapt to hypoxia may be a common pathophysiological pathway linking a number of other conditions of childhood with cognitive deficit. There is evidence that congenital cardiac disease, asthma and sleep disordered breathing, for example, are associated with cognitive deficit, but little is known about the mechanism and whether there is any structural change. This review describes what is known about how the brain reacts and adapts to hypoxia, focusing on epilepsy and sickle cell disease (SCD). We prospectively recorded overnight oxyhaemoglobin saturation (SpO2) in 18 children with intractable epilepsy, six of whom were currently or recently in minor status (MS). Children with MS were more likely to have an abnormal sleep study defined as either mean baseline SpO2 <94% or >4 dips of >4% in SpO2/hour (p = .04). In our series of prospectively followed patients with SCD who subsequently developed acute neurological symptoms and signs, mean overnight SpO2 was lower in those with cerebrovascular disease on magnetic resonance angiography (Mann-Whitney, p = .01). Acute, intermittent and chronic hypoxia may have detrimental effects on the brain, the clinical manifestations perhaps depending on rapidity of presentation and prior exposure.
 ...
PMID:Hypoxic adaptation during development: relation to pattern of neurological presentation and cognitive disability. 1676 14

Anesthesia for patients with Steinert's syndrome (myotonic dystrophy, MD) is a challenge for the anaesthetist. MD is a multisystemic disease and the neuromuscular symptoms can be associated with sleep apnea, endocrine disorders (diabetes, hypogonadism, hypothyroidism), cardiac, gastroenteric or cognitive disorders (mental deficiency, attention disorders). The diagnosis is facilitated when one or more of these symptoms are associated with the neuromuscular symptoms; however, the latter are not always present at the onset, which makes the diagnosis of MD a difficult and often late one. The choice of drugs and the choice of anesthesia in these patients can be very challenging for many reasons. A myotonic crisis can be triggered by several factors including hypothermia, shivering and mechanical or electrical stimulation. These patients are very sensitive to the usual anesthetics such as hypnotics and paralyzing agents (both depolarizing and nondepolarizing). The following case report describes pathophysiological considerations and a technique for anaesthesia during thoracic surgery that has been able to assure hemodynamic peroperative stability, early extubation and prolonged respiratory autonomy in a patient affected by this genetic disorder.
 ...
PMID:Anesthesia and myotonic dystrophy (Steinert's syndrome). The role of total intravenous anesthesia with propofol, cisatracurium and remifentanyl. Case report. 1766 Jul 41

Sleep apnea causes cognitive deficits and is associated with several neurologic diseases. Intermittent hypoxia (IH) is recognized as a principal mediator of pathophysiology associated with sleep apnea, yet the basis by which IH contributes to impaired cognition remains poorly defined. Using a mouse model exposed to IH, this study examines how the transcription factor, hypoxia inducible factor 1a (HIF1a), contributes to disrupted synaptic physiology and spatial memory. In wild-type mice, impaired performance in the Barnes maze caused by IH coincided with a loss of NMDA receptor (NMDAr)-dependent long-term potentiation (LTP) in area CA1 and increased nuclear HIF1a within the hippocampus. IH-dependent HIF1a signaling caused a two-fold increase in expression of the reactive oxygen species (ROS) generating enzyme NADPH oxidase 4 (NOX4). These changes promoted a pro-oxidant state and the downregulation of GluN1 within the hippocampus. The IH-dependent effects were not present in either mice heterozygous for Hif1a (HIF1a+/-) or wild-type mice treated with the antioxidant manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP). Our findings indicate that HIF1a-dependent changes in redox state are central to the mechanism by which IH disrupts hippocampal synaptic plasticity and impairs spatial memory. This mechanism may enhance the vulnerability for cognitive deficit and lower the threshold for neurologic diseases associated untreated sleep apnea.
 ...
PMID:A HIF1a-Dependent Pro-Oxidant State Disrupts Synaptic Plasticity and Impairs Spatial Memory in Response to Intermittent Hypoxia. 3249 57