Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Day time video records of 14 girls with the Rett syndrome (RS) (6-17, mean 7 years) were analysed to correlate episodic abnormalities in respiration, movement and electroencephalograms (EEG). Records were compared with those of 12 healthy girls (6-18, median 14 years) who hyperventilated voluntarily. Three RS girls (6-7 years) had minimal respiratory dysrhythmia and showed no correlation between EEG respiration and movement. The other 11 RS girls (6-17 years) had severe awake respiratory dysrhythmia; 10 showing hyperventilation (with hypocapnia) which alternated with active expiratory apnoeic pauses and one with the latter only. All had periods of awake regular breathing with normal respiratory gases. In these girls EEG showed non-epileptic generalised slow activity some of which was paroxysmal. In the six youngest (6-10 years) of these 11 RS girls, non-epileptic paroxysms of EEG slow activity at 1 1/2-4 Hz occurred and were associated with periods of normal breathing and normal pCO2 levels whether girls were alert, drowsy or asleep, but were uncommon during episodes of hyperventilation (and hypocapnia). In four of these girls the EEG paroxysms occupied less than or equal to 1-3% of the time during periods of respiratory dysrhythmia (81 minutes) and 8-100% of the time during alert periods with normal breathing (29 minutes), p less than or equal to 0.001 for this difference. Short bursts of EEG slowing occasionally followed prolonged apnoeic pauses. In two cases brief partial complex seizures occurred. In five of these girls stereotypic movements exacerbated during episodes of respiratory dysrhythmia and reduced during normal breathing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation of electroencephalogram, respiration and movement in the Rett syndrome. 234 29

Hyperventilation, which occurs in some patients with severe mental handicap, is a prominent feature in the histories of most girls with Rett syndrome but its mechanism and effects have not been established. Respiratory function was therefore studied in 18 patients with Rett syndrome and 23 healthy controls. Ten of the patients (56%), but none of the controls, hyperventilated only when awake, and began doing so after a period of normal breathing without hypoxaemia. After hyperventilation was established it was interspersed with prolonged periods of apnoea (over 19 seconds) accompanied by Valsalva manoeuvres. Hypoxaemia (less than 90%) occurred in 47% of these periods of apnoea and five (50%) of the patients had oxygen saturation values of under 50%. During hyperventilation severe hypocapnia developed in every patient, and recorded arterial pH measurements ranged from 7.47 to 7.60. A further four patients (22%) did not hyperventilate, but had clear histories of hyperventilation when younger. All had frequent apnoeic pauses accompanied by Valsalva manoeuvres. The remaining four girls (22%) neither hyperventilated nor gave a clear history of doing so. Three had occasional apnoeic pauses associated with the Valsalva manoeuvres. All but one of the 18 patients had increased quantities of periodic apnoea compared with the control subjects. The hypocapnic alkalaemia and hypoxaemia resulting from hyperventilation may contribute to the cerebral impairment in Rett syndrome. Since the hyperventilation is 'primary', and not secondary to preceding apnoea, it is potentially treatable. Further studies will determine if treatment is practical and of benefit.
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PMID:Hyperventilation in the awake state: potentially treatable component of Rett syndrome. 277 26

We report values for CSF and blood lactate and acid-base balance in 8 girls with the Rett syndrome and correlate the findings with respiratory dysfunction. Three patients had elevated CSF lactate values; their hyperventilation (HV) was so intensive that the acid-base balance showed respiratory alkalosis with an abnormally low base excess. One of these three patients had normal CSF lactate and acid-base balance before she developed HV. Two patients were so young that they had not yet developed HV and their CSF lactate values were normal. One patient had elevated CSF lactate when she was younger and her HV was more intensive, but now her CSF and blood lactate were normal; her acid-base balance showed mild hypocapnia but was otherwise normal. Thus, in the Rett syndrome, CSF lactate elevation seems to be a secondary phenomenon connected with the intensive HV and alkalosis rather than a sign of any mitochondrial disorder.
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PMID:Elevated CSF lactate in the Rett syndrome: cause or consequence? 789 61

Polygraphic recordings in the awake state and during sleep were performed in two girls with Rett syndrome, aged 9 y and 17 y, in order to characterize the clinically manifest breathing disorder of these patients. Primary hyperventilation was detected, leading to hypocapnia and compensatory apnoea. Hypoxaemia occurred as the consequence of prolonged apnoea. In the younger patient these disturbances were observed only in the awake state, whereas in the older patient they were found in the awake state and during sleep.
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PMID:Polysomnographic recordings of respiratory disturbances in Rett syndrome. 1060 3

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) that encodes a DNA binding protein involved in gene silencing. Selective deletion of Mecp2 in post-mitotic neurons in mice results in a Rett-like phenotype characterized by disturbances in motor activity and body weight, suggesting that these symptoms are exclusively caused by neuronal deficiency. Included in the RTT phenotype are episodes of respiratory depression that follow hyperventilation. Here we show that the respiratory phenotype depends on the organ distribution of Mecp2 deficiency. Both female mice heterozygous for a null mutation in Mecp2 (Mecp2+/-) and those with selective deletion of the protein in neurons (Mecp2+/nestin-Cre lox), showed an initial response to hypoxia that exceeded that in wild type (WT). However, marked respiratory depression following hypoxic hyperventilation was only seen in Mecp2+/- animals. Addition of carbon dioxide to the hypoxic exposure eliminated the respiratory depression. Tidal volume and lung volume were larger in Mecp2+/- and respiratory depression was directly related to tidal volume. Taken together these results indicate that the depression is due to hypocapnia. Respiratory depression in this mouse model of Rett Syndrome is seen in with ubiquitous deficiency in Mecp2 but not when it is confined to neurons.
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PMID:Separate respiratory phenotypes in methyl-CpG-binding protein 2 (Mecp2) deficient mice. 1654 21

Hyperventilation is a known feature of Rett syndrome (RTT). However, how hyperventilation is related to other RTT symptoms such as hyperexcitability is unknown. Intense breathing during hyperventilation induces hypocapnia and culminates in respiratory alkalosis. Alkalinization of extracellular milieu can trigger epilepsy in patients who already have neuronal hyperexcitability. By combining patch-clamp electrophysiology and quantitative glutamate imaging, we compared excitability of CA1 neurons of WT and Mecp2 (-/y) mice, and analyzed the biophysical properties of subthreshold membrane channels. The results show that Mecp2 (-/y) CA1 neurons are hyperexcitable in normal pH (7.4) and are increasingly vulnerable to alkaline extracellular pH (8.4), during which their excitability increased further. Under normal pH conditions, an abnormal negative shift in the voltage-dependencies of HCN (hyperpolarization-activated cyclic nucleotide-gated) and calcium channels in the CA1 neurons of Mecp2 (-/y) mice was observed. Alkaline pH also enhanced excitability in wild-type (WT) CA1 neurons through modulation of the voltage dependencies of HCN- and calcium channels. Additionally alkaline pH augmented spontaneous glutamate release and burst firing in WT CA1 neurons. Conversely, acidic pH (6.4) and 8 mM Mg2+ exerted the opposite effect, and diminished hyperexcitability in Mecp2 (-/y) CA1 neurons. We propose that the observed effects of pH and Mg2+ are mediated by changes in the neuronal membrane surface potential, which consecutively modulates the gating of HCN and calcium channels. The results provide insight to pivotal cellular mechanisms that can regulate neuronal excitability and help to devise treatment strategies for hyperexcitability induced symptoms of Rett syndrome.
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PMID:Rescue of hyperexcitability in hippocampal CA1 neurons from Mecp2 (-/y) mouse through surface potential neutralization. 2962 Dec 62