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PubMed1964

THE ACTION OF SODIUM 4-HYDROXYBUTYRATE ON SPINAL REFLEXES.

The actions of sodium 4-hydroxybutyrate, gamma-aminobutyric acid and meprobamate have been studied in unanaesthetized animals, in local anaesthetic tests, on isolated organ preparations, on convulsions induced by picrotoxin and strychnine, and on monosynaptic (patellar) and polysynaptic (plantar) reflexes of the spinal cord. Sodium 4-hydroxybutyrate induced a sleep-like state with three unusual features: the righting reflex was remarkably persistent, respiration was good throughout and recovery was abrupt. gamma-Aminobutyric acid was inactive and meprobamate caused flaccid paralysis with loss of the righting reflex. None of the agents affected the responses of the rat diaphragm either to direct stimulation of the muscle or to indirect stimulation through the phrenic nerve. Only meprobamate reduced the responses of theguinea-pig isolated ileum preparation, showed local anaesthetic action and had an anticonvulsant action. All three compounds were capable, after intravenous or topical application, of blocking plantar reflexes in doses which did not affect the patellar reflex. The spinal animal responded in the same way, to the same dose of sodium 4-hydroxybutyrate, as the decerebrate preparation. Topical application to the motor cortex had no effect on spinal reflexes. We conclude that sodium 4-hydroxybutyrate acts preferentially on the internuncial neurones in the spinal cord but differs from meprobamate in its other actions. The similarity between the actions of sodium 4-hydroxybutyrate and of gamma-aminobutyric acid provides furtherevidence in support of the hypothesis that sodium 4-hydroxybutyrate is involved in the gamma-aminobutyric acid metabolic pathways.

Aminobutyrates↗
PubMed1991

Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children.

Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation.

Anesthesia↗
PubMed1991

Pathogenesis of sudden unexplained nocturnal death (lai tai) and endemic distal renal tubular acidosis.

Sudden unexplained nocturnal death (SUND), a disorder of unknown cause that occurs in otherwise healthy young adults, mostly male, during their sleep, is prevalent in the north-east region of Thailand, where it has been known for generations as lai tai. It occurs in the same population and area where hypokalaemic periodic paralysis (HPP), endemic distal renal tubular acidosis (EdRTA), and renal stones are also endemic. SUND has occurred in families of patients with EdRTA, and HPP can present as sudden onset of muscle parlysis with potentially lethal cardiac arrhythmias and respiratory failure from severe hypokalaemia occurring in the middle of the night. Surveys in which serum and urinary potassium have been measured indicate a deficiency of the electrolyte in the population. Potassium deficiency is probably the prime factor responsible for SUND and HPP. Low urinary citrate concentrations and the high prevalence of acidification defects in the population indicate that potassium deficiency is also responsible for the prevalence of EdRTA and for renal stones.

Acidosis, Renal Tubular↗
PubMed1992

Neurological impairment in congenital bilateral ptosis with ophthalmoplegia.

A case is described of congenital bilateral ptosis and ophthalmoplegia due to incomplete bilateral paralysis of the third cranial nerve associated with dysmorphisms, brain malformations and epileptiform EEG abnormalities. We hypothesize that in our case the ophthalmological disturbance is due to mesencephalic impairment. In literature there are few reports of congenital bilateral paralysis of the third cranial nerve and they lack detailed MRI findings. We stress in patients with congenital third cranial nerve palsy the importance of thorough neurological investigations including prolonged wake-sleep EEG monitoring as well as CT scan and MRI to establish the origin of the disorder.

Blepharoptosis↗
PubMed1997

Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects.

Anatomic abnormalities of the pharynx are thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but their contribution has never been conclusively proven. The present study tested this anatomic hypothesis by comparing the mechanics of the paralyzed pharynx in OSA patients and in normal subjects. According to evaluation of sleep-disordered breathing (SDB) by nocturnal oximetry, subjects were divided into three groups: normal group (n = 17), SDB-1 (n = 18), and SDB-2 (n = 22). The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. Age and body mass index were matched among the three groups. The site of the primary closure was the velopharynx in 49 subjects and the oropharynx in only 8 subjects. Distribution of the location of the primary closure did not differ among the groups. Closing pressure (PC) of the velopharynx for SDB-1 and SDB-2 groups (0.90 +/- 1.34 and 2.78 +/- 2.78 cmH2O, respectively) was significantly higher than that for the normal group (-3.77 +/- 3.44 cmH2O; P < 0.01). Maximal velopharyngeal area for the normal group (2.10 +/- 0.85 cm2) was significantly greater than for SDB-1 and SDB-2 groups (1.15 +/- 0.46 and 1.06 +/- 0.75 cm2, respectively). The shape of the pressure-area curve for the velopharynx differed between normal subjects and patients with SDB, being steeper in slope near Pc in patients with SDB. Multivariate analysis of mechanical parameters and oxygen desaturation index (ODI) revealed that velopharyngeal Pc was the only variable highly correlated with ODI. Velopharyngeal Pc was associated with oropharyngeal Pc, suggesting mechanical interdependence of these segments. We conclude that the passive pharynx is more narrow and collapsible in sleep-apneic patients than in matched controls and that velopharyngeal Pc is the principal correlate of the frequency of nocturnal desaturations.

Adult↗
PubMed1978

[Focal EEG pathology in young children with infantile cerebral paralysis and an epileptiform syndrome].

A polygraphic study of 63 children of the 1st and 2nd year of age with child cerebral paralysis and a convulsive syndrome in 17 detected focal changes of the EEG, mainly in the central and parietal areas. The detection of the focus in many cases depended upon the phase and stage of sleep and could correspond to certain states (mainly--slow sleep, sometimes to rapid sleep, sometimes--intermediary stage). The mechanisms of these phenomena are discussed.

Brain↗
PubMed2002

Different mechanism of vocal cord paralysis between spinocerebellar ataxia (SCA 1 and SCA 3) and multiple system atrophy.

While multiple system atrophy (MSA) is frequently associated with vocal cord paralysis (VCP) causing severe respiratory failure, it is still unknown whether hereditary types of spinocerebellar degeneration develop similar laryngeal paralysis. We analyzed the laryngeal function from the viewpoints of fiberoptic laryngoscopy and laryngeal myopathology and then attempted to clarify the difference of the mechanism of VCP among the patients with spinocerebellar ataxia type 1 (SCA 1), type 3 (SCA 3), and MSA. Seven patients with SCA 1, nineteen with SCA 3, and eleven with MSA were studied. Vocal cord movement was analyzed by fiberoptic laryngoscopy during wakefulness and diazepam-induced sleep (sleep load test). Paraffin-embedded sections or cryosections of the intrinsic laryngeal muscles from five autopsied cases (one with SCA 1 and four with SCA 3) were histologically examined. VCP was found in two of the seven SCA 1 patients (29%), three of the nineteen SCA 3 patients (16%), and in nine of the eleven MSA patients (82%). VCP observed in SCA 1 and SCA 3 was various in the severity and showed no exacerbation on sleep load test in all of the eight patients but one SCA 3 patient. In this patient, the findings of fiberoptic laryngoscopy were quite similar to those found in MSA. All the intrinsic laryngeal muscles including cricothyroid (CT), interarytenoid (IA), and posterior cricoarytenoid (PCA) muscles showed neurogenic atrophy in one autopsied SCA 1 and four SCA 3 patients. Our conclusion is that VCP in SCA 1 and SCA 3 contrasts with that in MSA in its occurrence, response to the sleep load test, and the distribution of the neurogenic abnormalities among the intrinsic laryngeal muscles.

Adult↗
PubMed1999

The CHARGE association: the role of tracheotomy.

OBJECTIVES: To evaluate the need for a tracheotomy and its timing during the evolution of an association of malformations, including coloboma, heart defects, choanal atresia, developmental and growth retardation, genitourinary malformation, and ear anomalies (CHARGE association). DESIGN: Retrospective study from January 1988 through December 1997. SETTING: Four academic tertiary care centers. PATIENTS AND METHODS: Forty-five patients with CHARGE association having at least 3 cardinal malformations (growth retardation excluded) and review of the malformations and respiratory manifestations encountered. All the patients underwent endoscopic exploration on several occasions. We reviewed the nature and the timing of therapeutic interventions performed on the airway. RESULTS: Two patients died (one patient of septicemia, the other of unknown causes). Abnormalities of blood gas levels and/or sleep were found in 30 patients (67%), were responsible for cardiorespiratory arrest in 9 (20%), and required admission to the intensive care unit in 21 (47%). Pharyngolaryngeal anomalies leading to dyspnea (discoordinate pharyngolaryngomalacia, glossoptosis, retrognathia, laryngeal paralysis, cleft, stenosis, and difficult intubation) were found in 26 patients (58%). Tracheobronchial anomalies (esophagotracheal fistula, esophageal atresia, and tracheomalacia) were present in 18 patients (40%). Resection of the aryepiglottic folds was attempted 3 times, but without success. Tracheotomy was necessary in 13 patients (29%) at a median age of 2.4 months (mean duration, 25 months). Among these infants, the posterior nasal choanae were patent in 10 patients at the time of tracheotomy. Gastroesophageal reflux was encountered in 36 patients (80%). Prolonged enteral feeding was necessary in 21 patients (47%), with gastrostomy in 16 (of whom 9 needed a tracheotomy). These feeding difficulties and airway problems were highly correlated. CONCLUSIONS: We encountered multiple, complicated airway abnormalities. Resection of aryepiglottic folds was inadequate. Often, a tracheotomy could not be avoided in these patients, regardless of choanal patency. Tracheotomy needs to be performed early to avoid hypoxic events. In some selected patients, ventilation using bilevel positive airway pressure may be an alternative.

Abnormalities, Multiple↗
PubMed1977

Acute supine respiratory failure due to bilateral diaphragmatic paralysis.

This report documents the first known case of bilateral diaphragmatic paralysis following blunt trauma to the chest. The important role of diaphragmatic function in maintaining ventilation, particularly with the patient in the supine position, is illustrated by the reduced total lung capacity, functional residual capacity, and vital capacity. Severe hypoxemia with the patient in the supine position, was markedly improved by elevation of the patient to 30 degree and was further improved by sitting the patient upright. Following an initial period of acute respiratory failure, the patient was managed acceptably by maintaining an elevated position for sleeping until diaphragmatic function returned, about nine months after the injury.

Accidents, Traffic↗
PubMed1998

Comparison of static mechanical properties of the passive pharynx between normal children and children with sleep-disordered breathing.

Collapsibility of the active pharynx, where active contraction of the upper airway muscles is evident, was previously reported to be higher in children with obstructive sleep apnea (OSA) than in those with primary snoring during sleep. Contribution of neuromuscular and anatomic factors to the increased collapsibility, however, was not estimated. We therefore evaluated collapsibility of the passive pharynx, in which upper airway muscle activities were eliminated. Our aim in the present study was to test the hypothesis that children with sleep-disordered breathing (SDB) have a structurally narrowed and a more collapsible pharynx compared with normal children. The static pressure/area relationship of the passive pharynx was endoscopically quantified in 14 children with SDB and in 13 normal children under general anesthesia with complete paralysis. The majority of children with SDB primarily closed their airways at levels of enlarged adenoids and tonsils with positive closing pressure (Pclose) (3.5+/-4.3 cm H2O), whereas half of the normal children closed their airways at the soft palate edges and the other half at the tongue bases with subatmospheric Pclose (-7.4+/-4.9 cm H2O). Cross-sectional area of the narrowest segment was significantly smaller in SDB children than in normal children. Interestingly, collapsibility of the retropalatal and retroglossal segments significantly increased in SDB children, compared with the normal subjects. We conclude that anatomic factors play a significant role in the pathogenesis of pediatric OSA and that predisposing structural abnormalities of the entire pharynx are likely to contribute to manifestation of OSA in addition to enlarged adenoids and tonsils.

Adenoids↗
PubMed2006

Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation.

OBJECTIVE: To determine sleep characteristics in patients receiving mechanical ventilation who require a neuromuscular blocking agent (NMBA). DESIGN: Observational study. SETTING: Adult medical ICU at a university hospital. PARTICIPANTS: Eighteen patients with respiratory failure requiring mechanical ventilation were classified into three groups based on medication regimen determined a priori: intermittent sedation (IS), continuous sedation (CS), or CS and an NMBA. MEASUREMENTS: Twenty-four-hour polysomnography was performed to determine sleep architecture and fragmentation. Measurement of severity of illness, laboratory indexes, patient-care interventions, and drug dosage were compared between groups, and the effects on sleep staging and fragmentation were analyzed. Sleep stages were scored manually using criteria of Rechtschaffen and Kales, as well as by a modified 50-muV voltage criteria for scoring delta activity. RESULTS: All patients demonstrated abnormal sleep architecture. In each group of patients, the total sleep time (TST) was > 10 h. There was no statistical difference in the delta activity between the two scoring methods; delta activity was increased in all groups: 32.9%, 49.6%, and 43.7% in the IS, CS, and CS/NMBA groups, respectively. Patients receiving NMBAs spent 22% of the sleep period awake. Rapid eye movement sleep could not be detected in the patients receiving NMBAs and was reduced in the other two groups (3.5%). TST, sleep stage, or arousal/awakening index were not statistically correlated with either severity of illness, clinical laboratory indexes, drug dosage, patient-care interventions, or mode of mechanical ventilation. CONCLUSION: TST during a 24-h period is not reduced in patients requiring mechanical ventilation. Delta activity is increased and may reflect age, drug, or a contributing metabolic process. The effect of wakefulness in patients receiving chemical paralysis on recovery and weaning from mechanical ventilation, and overall clinical outcome is unknown.

Adult↗
PubMed1996

Laryngeal dyskinesia as a cause of stridor in infants.

OBJECTIVE: To describe 9 cases of stridor attributed to the failure of the vocal cord to abduct during inspiration. DESIGN: Case series. SETTING: Pediatric otolaryngology referral center. PATIENTS: Nine hospitalized infants, aged 1 to 13 months, presented over a 3-year period for exploration of inspiratory stridor that was attributed to a condition that we have termed laryngeal dyskinesia. RESULTS: A consistent clinical presentation was noted in all cases. The laryngeal dyskinesia occurred during calm breathing, crying, or sleep and was associated with gastroesophageal reflux in 8 cases (diagnosed clinically and/or with pH monitoring). In addition, 3 infants suffered from fainting spells associated with vagal hypertonia that was confirmed by 24-hour Holter monitoring. True paralysis of the abductor muscles was ruled out in all infants because of the presence of normal glottic motion during calm breathing or induction of anesthesia. The stridor resolved between the ages of 4 and 13 months in 7 of the patients. Improvement was progressive and had no clear relationship to treatment for gastroesophageal reflux. CONCLUSION: Laryngeal dyskinesia in infants seems to be a distinct clinical entity, frequently associated with gastroesophageal reflux.

Age Factors↗
PubMed2001

[Diagnosis of facial and craniofacial asymmetry].

Craniofacial asymmetry is caused by various aetiologies but clinical examination remains the most important criteria since minor asymmetry is always present. The diagnosis can be confirmed by anthropometric measurements and radiological examinations but only severe asymmetries or asymmetries with an associated functional impairment should be treated. The treatment depends on the cause, and on the time of appearance. Congenital asymmetries might be treated early, during the first year of life if a craniosynostosis is present. Hemifacial microsomia are treated later if there is no breathing impairment. Since the pediatricians have recommended the dorsal position for infant sleeping, an increasing number of posterior flattening of the skull has been appearing, and could be prevented by adequate nursing. Other causes of craniofacial asymmetries are rare and should be adapted to the cause (tumors, atrophies, neurological paralysis, hypertrophies) by a specialized multidisciplinar team.

Craniofacial Dysostosis↗
PubMed1993

Diaphragmatic dysfunction in neuralgic amyotrophy: an electrophysiologic evaluation of 16 patients presenting with dyspnea.

We report 16 adult men (age, 41 to 75 yr) with neuralgic amyotrophy (NA) who presented with dyspnea due to involvement of the diaphragm. All patients developed breathlessness after a prodrome of acute severe neck and shoulder pain. Bilateral diaphragm paralysis (BDP) was confirmed in 12 patients and unilateral diaphragm paralysis (UDP) in four by the absence of electrical and mechanical responses to percutaneous phrenic nerve stimulation. Global expiratory muscle strength was well preserved in all patients, but inspiratory muscle strength was reduced in proportion to the extent of diaphragmatic involvement. Lung function showed low lung volumes with preservation of carbon monoxide transfer coefficient in all patients. Two BDP patients were hypoxic (PaO2 = 67 and 54 mm Hg, respectively) on daytime arterial blood gas analysis; the latter patient with pre-existing chronic obstructive pulmonary disease and marked obesity also had borderline hypercapnia (PaO2 = 49 mm Hg). Overnight sleep studies in three BDP and two UDP patients showed frequent intermittent arterial oxygen desaturations apparently caused by obstructive sleep apneas, but there was no evidence of alveolar hypoventilation. Follow-up muscle studies in five BDP and four UDP patients between 2 and 4 yr after initial referral showed complete recovery of diaphragmatic function in only two UDP patients, one of whom relapsed a year later. We postulate that NA may be an important but underrecognized cause of diaphragmatic paralysis in otherwise normal patients. Diaphragmatic strength returns very slowly, if at all.

Action Potentials↗
PubMed1997

[A particular type of epilepsy in patients with congenital hemiparesis associated with polymicrogyria or unilateral pachygyria].

INTRODUCTION: Magnetic resonance has permitted the recognition of cortical dysplasias in patients with congenital hemiparesia and epilepsy. OBJECTIVE: To study the clinic-EEG characteristics and course of epilepsy in patients with congenital hemiparesia and unilateral polymicrogyria. METHODS AND RESULTS: We analyzed the clinical histories of 11 patients seen between 1990 and 1996. We studied 6 girls and 5 boys aged between 5 and 13 years, with a follow-up period of from 1 to 6 years. The epilepsy began at between 1 and 6 years old with partial motor seizures. On EEG there were frontotemporal spikes in 9 cases, temporooccipital in 1 and parieto-occipital in another. All 11 patients had hemiparesia, with slight mental retardation in 9 patients and moderate mental retardation in 2. The CT/MR brain scan showed unilateral polymicrogyria. At between 2 and 8 years of age, all 11 patients developed subintrant atonic crises with a pseudo-ataxic gait, absences in 7 patients and myoclonia in 3. Awake EEG showed bilateral asymmetrical spikes. During sleep 7 patients had continuous spikewave discharges and 4 had frequent asymmetrical bilateral spikes. Four patients relapsed. Five patients are free of crises, five have sporadic crises and one continues to have daily crises. CONCLUSIONS: These patients had hemiparetic cerebral paralysis, slight mental retardation and epilepsy. At about the age of 6 a peculiar electro-clinical condition developed. Response to treatment was satisfactory, although the follow-up period is still not long.

Brain↗
PubMed1988

Bilateral abductor paresis masquerading as asthma.

Rare upper airway lesions may be mistaken for asthma. A 16-year-old Hispanic male athlete presented to our allergy clinic with a 4-month history of wheezing and snoring with hoarseness and progressive fatigue on exertion or during sleep. His mother taped periods of harsh stridor and sleep apnea. There was no family history of vocal cord abnormalities. A year before the onset of symptoms, he suffered injury to his oral cavity with a loss of consciousness during a wrestling match. He denied dysphagia or dysphonia. He failed to respond to bronchodilators, cromolyn, or prednisone therapy during 4 weeks. On referral to our clinic, his physical examination and tape recording were characterized by harsh inspiratory stridor. His pulmonary function tests were significant for peak flow depressed out of proportion to FEV1 with reduced FVC, no response to bronchodilator, and flattened inspiratory loop unresponsive to cough or panting. Fluoroscopy and endoscopy of the upper airway was consistent with "marked bilateral limitation of vocal cord abduction." Sleep study demonstrated desaturation with CO2s in the 60s during sleep. He was started on continuous positive airway pressure, 10 cm at night, with no desaturation or sleep disturbance on follow-up.

Adolescent↗
PubMed1984

Perinatal development of laryngeal function.

The resistance of the upper airway is strongly influenced by the action of opposing sets of laryngeal muscles. Expiratory airflow may be retarded by active adduction of the arytenoid cartilages or by a reduction in the activity of abductor muscles. In developing sheep the adductor muscles appear to represent the principal means by which lung recoil is opposed. This mechanism, which is most pronounced during non-rapid-eye-movement sleep, is regulated by afferent traffic from the lungs. In fetal sheep the laryngeal muscles are also influenced by breathing movements and sleep states. The adductor muscles are normally tonically active during non-rapid-eye-movement sleep when rhythmical breathing movements are absent. It is possible that this activity is at least partially responsible for elevated tracheal pressures and depressed flow of tracheal fluid during fetal apnea. This hypothesis has been tested by observing the effects of fetal paralysis and recurrent laryngeal nerve section. These experiments suggest that in the fetus near term the larynx makes a major contribution to upper airway resistance and hence to the maintenance of pulmonary expansion which has been shown to influence lung development.

Airway Resistance↗