Central Respiratory Dysfunction Research Articles

Neural correlate of reduced respiratory chemosensitivity during chronic epilepsy.

While central autonomic, cardiac, and/or respiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP), the specific neural mechanisms that lead to SUDEP remain to be determined. In this study, we took advantage of single-cell neuronal Ca2+ imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Weeks after induction of status epilepticus (SE), when mice were experiencing recurrent spontaneous seizures (chronic epilepsy), we observed that the adaptive ventilatory responses to hypercapnia were reduced for 5 weeks after SE induction with its partial recovery at week 7. These changes were paralleled by alterations in the chemosensory responses of neurons in the retrotrapezoid nucleus (RTN). Neurons that displayed adapting responses to hypercapnia were less prevalent and exhibited smaller responses over weeks 3-5, whereas neurons that displayed graded responses to hypercapnia became more prevalent by week 7. Over the same period, chemosensory responses of the presympathetic rostral ventrolateral medullary (RVLM) neurons showed no change. Mice with chronic epilepsy showed enhanced sensitivity to seizures, which invade the RTN and possibly put the chemosensory circuits at further risk of impairment. Our findings establish a dysfunctional breathing phenotype with its RTN neuronal correlate in mice with chronic epilepsy and suggest that the assessment of respiratory chemosensitivity may have the potential for identifying people at risk of SUDEP.

Novel role for non-invasive neuromodulation techniques in central respiratory dysfunction.

Respiration is a crucial steady-state function of human life. Central nervous system injury can damage the central respiratory pattern generator (CRPG) or interrupt its outflow, leading to central respiratory paralysis and dysfunction, which can endanger the patient's life. At present, there is no effective means to reverse this process. Commonly used non-invasive neuromodulation techniques include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and so forth, which have been widely applied in nervous system diseases and their various secondary symptoms, but rarely in respiratory function. Clinical and animal studies have confirmed that TMS is also suitable for investigating the excitability and plasticity of ascending corticospinal respiratory pathways. In addition, although rTMS and tDCS differ in their respective mechanisms, both can regulate respiratory networks in healthy individuals and in diseased states. In this review, we provide an overview of the physiology of respiration, the use of TMS to assess the excitability of corticophrenic pathways in healthy individuals and in central respiratory disorders, followed by an overview of the animal and clinical studies of rTMS, tDCS and so forth in regulating respiratory circuits and the possible mechanisms behind them. It was found that the supplementary motor area (SMA) and the phrenic motor neuron (PMN) may be key regulatory areas. Finally, the challenges and future research directions of neuroregulation in respiratory function are proposed. Through understanding how neuromodulation affects the respiratory neural circuit non-invasively, we can further explore the therapeutic potential of this neuromodulation strategy, so as to promote the recovery of respiratory function after central nervous system diseases or injury.

Respiratory arrest after posterior fossa decompression in patients with Chiari malformations: An overview.

Chiari malformation type 1 (CM1) is a structural abnormality in the skull and cerebellum, causing cerebellar tonsils to shift downward. Decompression of the posterior fossa is a common surgical method to relieve symptoms and prevent neurological deterioration. After posterior fossa decompression (PFD), individuals with CM1 were more likely to have respiratory arrest. Here, we present, for the first time, a comprehensive overview of the potential risk factors and causes of respiratory arrest following PFD. A review of the literature highlighting the risk factors for postoperative respiratory arrest in CM1 patients was conducted in the databases of PubMed, Medline, and Google Scholar. Patients with syringomyelia and CM1 are at increased risk for respiratory arrest due to a number of factors, including impaired respiratory mechanics, central respiratory center dysfunction from edema or ischemia, intraoperative brain stem ischemia, and delayed gastric emptying from autonomic dysfunction. Occipitalization of the first cervical vertebra, basilar impression, and fusion of C2-C3 are all risk factors for respiratory arrest. Implications for CM1 patient care and prospects for further investigation of postoperative respiratory arrest's causes and risk factors were discussed.

Long‐term hypercapnia does not alter Galanin immunoreactivity in mouse brain respiratory and chemoreceptor regions

Long‐term hypercapnia has been implicated in respiratory disorders such as sleep apnea and chronic obstructive pulmonary disease (COPD). However, the mechanisms by which long‐term hypercapnia contributes to central respiratory dysfunction in these conditions are unclear. The brainstem respiratory circuit, including the ventral respiratory column (VRC), comprises distinct neuronal populations that govern expiratory and inspiratory drive. The neuropeptide galanin is extensively distributed in brainstem chemoreceptor regions and the VRC, and microinjection of galanin into the VRC inhibits breathing and attenuates ventilatory reflex responses to acute hypercapnia. Nevertheless, the normal pattern of regional expression of galanin in the mouse brain is not known and the impact of long‐term hypercapnia on galanin immunoreactivity (Gal‐ir) in the vicinity of brainstem respiratory and chemoreceptor regions has not yet been studied. Therefore, we aimed to determine Gal‐ir across the mouse brain and investigate the impact of prolonged hypercapnia exposure on Gal‐ir in brainstem respiratory and chemoreceptor regions (pons and medulla). Adult male Phox2b‐EGFP (MGI ID: 5776545) mice (31±2 g, n=5 mice/group) were exposed to hypercapnia (8% CO2; balance room air) or room air (control) for 10 or 14 days. To determine Gal‐ir, brain slices were collected and processed for immunohistochemistry. Quantitative measurement of Gal‐ir was performed using ImageJ 1.53a (a QuPath‐integrated version of ImageJ) where a positive area fraction, reflecting the proportion of positively labeled pixels, was calculated for each region of interest [locus coeruleus, the retrotrapezoid nucleus, caudal‐nucleus of the solitary tract (cNTS), rostral‐NTS (rNTS), VRC, lateral reticular nucleus, and caudoventrolateral reticular nucleus]. Under control conditions, we found that Gal‐ir was broadly present across the medulla oblongata, and abundant in the caudal aspects when compared with the rostral levels. The cNTS had a higher average percentage of Gal‐ir area (p = 0.043, p = 0.05, 2‐way ANOVA) compared to rNTS following 10‐ and 14‐days of room air exposure, respectively. A significant difference in Gal‐ir (p = 0.011, 2‐way ANOVA) was observed between the cNTS and rNTS following 14‐days of hypercapnia exposure. Overall, there was no significant difference of Gal‐ir in all regions assessed after long‐term hypercapnia compared to controls. Collectively, we found that long‐term hypercapnia does not induce changes in galanin neuropeptide levels within respiratory and chemoreceptor regions in the mouse brain. Under control and hypercapnia conditions, cNTS contains higher Gal‐ir compared to rNTS. Further investigation is required to elucidate the involvement of NTS‐galaninergic subsets in respiratory homeostasis.

Hypercapnia‐evoked Chronic Stress Alters IL‐1β Levels in Brain Respiratory Chemoreceptor Regions

Chronic stress often elicits neuronal, hormonal, and immune responses. Long term hypercapnia is a respiratory stressor linked with sleep apnea, sudden infant death syndrome (SIDS) and chronic obstructive pulmonary disease (COPD), however, mechanisms of central respiratory dysfunction in these conditions are unclear. We aimed to explore the neuroinflammatory responses to hypercapnia in key brain respiratory regions. We tested the hypothesis that long-term exposure to 8% CO2 activates the releaseof brain stress hormone corticosterone (CORT) in the circulation which may contribute to inflammation in brainstem circuits that regulate CO2-stimulated breathing. Age-matched adult male C57BL/6J mice (n=10 mice/group) were exposed to hypercapnia (8% CO2; balance room air) in the short-term (6 hours) or long-term (10 or 14 days), or room air (control) conditions.Following anesthesia, plasma samples were collected for corticosterone (CORT) assay and brain tissues including cerebellum, hypothalamus, the nucleus of the solitary tract (NTS), rostral and caudal retrotrapezoid nucleus (rRTN, cRTN) were micro-dissected and processed for cytokine assays. Plasma CORT levels were not different between hypercapnia and room air groups in the short-term, but a significantly higher CORT level (p < 0.01, 2 way ANOVA) was observed following 10 days of exposure to hypercapnia compared to control conditions. CORT level returned to baseline following 14 days of hypercapnia compared to control (14 days room air) conditions. In the brain, the pro-inflammatory cytokine interleukin-1β (IL-1β) was raised in the cerebellum (p < 0.01, 2 way ANOVA) following 6 hours but not 10 days of hypercapnia exposure, compared to control conditions. In the hypothalamus and cRTN, IL-1β was unaltered at the 6 hours time point, significantly upregulated (p < 0.05, p < 0.01, 2 way ANOVA) at 10 days of hypercapnia exposure, compared to controls. In these brain regions, IL-1β levels returned to baseline after 14 days hypercapnia exposure time point. There was no change in IL-1β in the rRTN and NTS following 6 hours, 10 days, and 14 days of hypercapnia, compared to controls. Taken together, the level of plasma CORT positively correlates to brain IL-1β during long-term hypercapnia. These results suggest that hypercapnia activates a physiological stress response, and the associated brain inflammation depends on the duration of hypercapnia exposure. We propose that the stress and inflammatory adaptive responses observed are part of compensatory mechanisms following long-term hypercapnia. The cellular source and underlying mechanisms of interactions between plasma CORT and brain IL-1β are under investigation.

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study

SummaryBackgroundSudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS.MethodsWe did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system.FindingsFour (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057).InterpretationRare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths.FundingUK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.

Efficacy of naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy: study protocol for a double-blind, randomized, placebo-controlled trial.

BackgroundGeneralized tonic-clonic seizures (GTCSs) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Experimental and clinical data strongly suggest that the majority of SUDEP results from a postictal respiratory dysfunction progressing to terminal apnea. Postictal apnea could partly derive from a seizure-induced massive release of endogenous opioids. The main objective of this study is to evaluate the efficacy of an opioid antagonist, naloxone, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction.Methods/designThe Efficacy of Naloxone in Reducing Postictal Central Respiratory Dysfunction in Patients with Epilepsy (ENALEPSY) study is a multicenter, double-blind, randomized, placebo-controlled trial conducted in patients with drug-resistant focal epilepsy who are undergoing long-term video-electroencephalogram (EEG) monitoring (LTM) in an epilepsy monitoring unit (EMU). We plan to randomize 166 patients (1:1) to receive intravenous naloxone (0.4 mg) or placebo in the immediate aftermath of a GTCS. Because inclusion in the study needs to take place prior to the occurrence of the GTCS, and because such occurrence is observed in about one-fourth of patients undergoing LTM, we plan to include a maximum of 700 patients upon admission in the EMU. The primary endpoint will be the proportion of patients whose oxygen saturation is <90 % between 1 and 3 min after the end of a GTCS. Secondary outcomes will include the following: the proportion of patients who show postictal apnea, the occurrence and duration of postictal generalized EEG suppression, the total duration of the postictal coma, postictal pain, and the number of patients who have a second GTCS within 120 min after the intravenous injection.DiscussionThe demonstration of naloxone’s efficacy on the severity of postictal hypoxemia will have two primary consequences. First, naloxone would be the first and only therapeutic approach that could be delivered immediately to reverse postictal apnea. Second, demonstration that an opioid antagonist can effectively reduce postictal apnea would pave the way for an assessment of a preventive therapy for SUDEP targeting the same pathophysiological pathway using oral administration of naltrexone.Trial registrationClinicalTrials.gov identifier: NCT02332447. Registered on 5 January 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1653-1) contains supplementary material, which is available to authorized users.

Brainstem tethering syndrome: a report of 2 cases and literature review

Objective To investigate the etiology, clinical manifestation, imaging features, and treatment methods of brainstem tethering syndrome. Methods From January 2010 to March 2014, the clinical data of 2 patients with brainstem tethering syndrome admitted to the Department of Neurosurgery, the Second Affiliated Hospital of Zhengzhou University were analyzed retrospectively and the literature was reviewed. Results Two patients had meningocele and the history of simple meningoencephalocele resection. The clinical manifestations were central respiratory dysfunction (Ondin's curse), headache, and dizziness, respectively. The imaging results suggested that the brainstem tethering and ventricular dilatation. They were treated with the tethered cutting and ventriculo-peritoneal shunt respectively. Conclusions Brainstem tethering syndrome is a rare complication after meningocele surgery. Surgically releasing it and restoring the position of brainstem are the effective means of treatment. Brainstem tethering syndrome often complicates ventricular dilatation, if there is no intracranial hypertension or hydrocephalus signs of normal intracranial pressure, it does not need to be treated with shunt. Key words: Brainstem tethering syndrome; Sleep apnea, central; Respiration disorders; Meningocele

Evaluation of the hypothalamic-pituitary-adrenal axis and its relationship with central respiratory dysfunction in children with Prader-Willi syndrome.

BackgroundChildren with Prader-Willi Syndrome (PWS) have been considered at risk for central adrenal insufficiency (CAI). Hypothalamic dysregulation has been proposed as a common mechanism underlying both stress-induced CAI and central respiratory dysfunction during sleep.ObjectiveTo evaluate CAI and sleep-related breathing disorders in PWS children.Patients and methodsRetrospective study of cortisol response following either insulin tolerance test (ITT) or glucagon test (GT) in 20 PWS children, and comparison with 33 non- Growth Hormone deficient (GHD) controls. Correlation between sleep related breathing disorders and cortisol response in 11 PWS children who received both investigations.ResultsIn PWS children, the cortisol peak value showed a significant, inverse correlation with age (Kendall’s τ = -0.411; p = 0.012). A similar though non-significant correlation was present between cortisol increase and age (τ = -0.232; p = 0.16). Similar correlations were found in controls. In only 1 of 20 PWS children (5 %), ITT was suggestive of CAI. Four patients had an elevated central apnea index but they all exhibited a normal cortisol response. No relationship was found between peak cortisol or cortisol increase and central apnea index (respectively p = 0.94 and p = 0.14) or the other studied polysomnography (PSG) parameters.ConclusionsCAI assessed by ITT/GT is rare in PWS children. Our data do not support a link between CAI and central respiratory dysregulation.

Brainstem Tegmental Necrosis and Olivary Hypoplasia: Raising Awareness of a Rare Neuropathologic Correlate of Congenital Apnea

This case study describes an instance of death in an early term female newborn with congenital apnea in the clinical setting of multiple congenital anomalies (retrognathia, posteriorly rotated ears, camptodactyly, and arthrogryposis) and prenatal history of polyhydramnios. Postmortem neuropathologic findings were significant for tegmental necrosis in the caudal pons and medulla characterized by a coalescence of microcalcifications accompanied by neuronal loss, axonal spheroids, gliosis, and a concomitant hypoplasia of the inferior olives. This report raises awareness of the rare lethal entity of brainstem tegmental necrosis and olivary hypoplasia and its nosological relationship to the Möbius syndrome in the context of differential diagnosis of congenital apnea owing to central respiratory dysfunction.

Ambiguous mechanisms of dysphagia in multiple system atrophy

Sir, we read with great interest the article by Schwarzacher et al. (2011) describing the neuroanatomical characteristics of the human pre-Botzinger complex and its involvement in multiple system atrophy and spinocerebellar ataxia 3 (SCA3). In this study, the authors provide a thorough analysis of the pre-Botzinger complex and demonstrate that somatostatin and neurokinin 1 receptor expressing neurons are severely reduced in a neurodegenerative disorder presenting with severe central respiratory dysfunction (multiple system atrophy), but spared in patients with no history of such respiratory deficits (SCA3). This study provides strong neuropathological evidence that degeneration of the pre-Botzinger complex occurs in multiple system atrophy and extends previous findings showing a drastic reduction of putative brainstem chemosensory neurons in this disease (Benarroch, 2007). Altogether, these findings strongly support the hypothesis that degeneration of these brainstem respiratory neurons underlies respiratory dysfunction in multiple system atrophy. In addition to the characterization of the pre-Botzinger complex, Schwarzacher et al. (2011) also provide a detailed analysis of the nucleus ambiguus in multiple system atrophy and SCA3. In both diseases, the ventral part of the nucleus ambiguus (containing pre-ganglionic cardiovagal neurons) display severe neuronal …

Percutaneous nocturnal oximetry in amyotrophic lateral sclerosis: Periodic desaturation

Percutaneous nocturnal oximetry (PNO) is useful to screen respiratory function in amyotrophic lateral sclerosis (ALS). PNO recordings of some patients disclose a periodical pattern of O(2) desaturation (PP), whose significance is unknown. We aimed to characterize PP pattern, and we used a prospective study enrolling 261 consecutive ALS patients. Clinical, pulmonary and neurophysiological tests performed included: ALS functional rating scale, forced vital capacity (FVC), maximal inspiratory pressure (PImax), mouth occlusion pressure (MOP), phrenic nerve motor response, needle electromyography of the diaphragm, PNO, and sleep study. A total of 837 PNO recordings were analysed (3.2 recordings/patient) and 45 patients showed typical PP (17.2%). Four were excluded, 13 had normal diaphragm (group 1, G1), and in 28 the diaphragm was abnormal (G2). The two groups were comparable, apart from respiratory score, FVC and PImax which were lower in G2. In G1, REM sleep was absent and hypoventilation occurred at slow-wave sleep. Five patients in G1 were very spastic, had low MOP/FVC and a short survival. This study identified a subgroup of ALS patients (G1) with marked signs of upper motor neuron lesion, strong respiratory muscles, PP, low MOP/FVC ratio and poor prognosis. We speculate that they have a central respiratory dysfunction and deserve special care.

Neurosteroid modulation of respiratory rhythm in rats during the perinatal period

Neurosteroids regulate neuronal excitability and are expressed at particularly high levels in the CNS during the perinatal period. Further, neurosteroid levels are increased by a variety of stressors including hypoxia, asphyxia, parturition, ethanol exposure and infection. One mechanism by which neurosteroids regulate neuronal activity is by negative or positive modulation of GABA(A) receptor function. Perinatal respiration is strongly modulated by GABAergic synaptic drive, and GABA release is increased during hypoxia to contribute to hypoxia-induced depression of neonatal ventilation. Here, we use in vitro and in vivo rat models to test the hypothesis that GABA(A) receptor-mediated modulation of perinatal respiration is markedly influenced by the presence of neurosteroids. The principal finding of this study was that the efficacy of GABA(A) receptor-mediated modulation of respiratory membrane potential and rhythmogenesis is markedly enhanced by allopregnanolone and depressed by dehydroepiandrosterone sulphate. These data demonstrate that the modulation of breathing via GABA(A) receptor activation will be determined by the overall balance of negative and positive neurosteroid modulators within respiratory nuclei. This adds a level of complexity that must be considered when examining the depression of breathing in mammals associated with various behavioural states and pathogenic conditions such as apnoea and sudden death suspected to be associated with central respiratory dysfunction.

Central respiratory dysfunction following vertebral artery dissection

Vertebral artery dissection (VAD) is a major cause of cerebral ischemia in young patients.1 Precipitating events associated with a hyperextension of the neck are common in cervical artery dissections2 and may damage the arterial vessel wall due to mechanical stretching. Typical initial symptoms are neck pain and headache, which is most often in the occipital area. The time interval between first symptoms and the onset of stroke varies from a few minutes to several weeks.3 The combination of medullary and cervical spinal cord ischemia due to VAD is uncommon4,5 and a central respiratory failure complicating VAD, even weeks after initial symptoms, is an unusual finding recently observed. A 42-year-old carpenter was admitted 2 hours after onset of nausea and unsteadiness of gait. He reported neck pain for 1 week after having painted …

NEURORADIOLOGIC CORRELATION IN MÖBIUS SYNDROME AND CENTRAL RESPIRATORY DISFUNCTION

Objectives: To describe neuroradiologic findings in six patients with Mobius syndrome and associated central respiratory dysfunction. Methods: Clinical, and neuroimaging (MRI) data were reviewed, including Brain CT, MRI 3 D. Results: We present six newborns, four premature neonates who suffered from bilateral VI and VII nerves paralysis, without respiratory effort from birth, who required prolonged mechanical ventilation until their death, and two term infants with the same symptoms, actually live with home care. Brain CT scans revealed bilateral brainstem calcifications in all the cases. Cerebral MRI showed typical findings; in the two term infants we perform a cerebral MRI with 3D reconstruction of the emergency of the VII cranial nerve, without finding the nerve. Conclusion: The anatomical studies show cranial nerves nuclei atrophy, secondary to periphery nerve lesion. Recent reports referred the clinical variability of this entity, a subgroup of patients showing risk of apnoea, and lack of respiratory impulse from birth in some of them. These central respiratory dysfunction patients had tegmental brainstem calcifications in brain CT scan. Brain MRI 3D of Mobius patients exhibit brainstem hypoplasia and absence of 7th cranial nerve. Diagnostic in the neonatal period may have relevance to take as soon as possible the appropriate decisions and interventions in the respiratory airway.

Síndrome de Möbius y episodio aparentemente letal

Möbius syndrome is characterized by congenital facial weakness with impairment of ocular abduction. A subgroup of these patients have associated apneas because of involvement of brainstem respiratory centers located slightly lateral to the abducens nuclei. We report a 7-month old infant admitted to the pediatric intensive care unit because of an episode of cyanosis, hypotonia and unresponsiveness. The patient then became respirator dependent afterwards. On examination, facial diplegia, impairment of ocular abduction and hypotonia were evident. Magnetic resonance imaging (MRI) revealed abnormal signal intensity in brainstem tegmentum. At the age of 11 months he was discharged but required a home ventilator. He died 5 months later due to an infection. Möbius syndrome is associated with central respiratory dysfunction. The finding of abnormal signal intensity in brainstem tegmentum on MRI is a possible predictor of apnea in these patients.

椎骨動脈りゅうに対する直達術・血管内手術における術後中枢性呼吸機能不全についての検討

Vertebral aneurysm surgery and endovascular procedures carry a potential risk of postoperative respiratory disorders. This is because the respiratory centers, which are located in the reticular formation of the ponto-medullary junction, are supplied by perforators originating from the basilar artery (BA), the vertebral artery (VA) close to the VA union, the proximal posterior inferior cerebellar artery (PICA), and the proximal anterior inferior cerebellar artery (AICA). A retrospective study of 13 patients (7 men and 6 women, mean age 54.5 years, range 21-72 years) surgically treated for vertebral aneurysms during the past 4 years in our hospital was done to determine the relationship between treatment modality and postoperative central respiratory dysfunction. Among our patients, there were 4 saccular aneurysms, 8 dissecting aneurysms and 1 giant fusiform aneurysm; 8 aneurysms were located in the VA between the origin of the PICA and the VA union (including 2 cases whose PICAs were not confirmed by angiography); 4 aneurysms were in the VA-PICA junction; and 1 aneurysm was located in the PICA. Six aneurysms were treated by direct surgery: neck clipping was performed in 3 cases; proximal clipping of the VA at the site distal to the PICA was done in 1 case; trapping was done in 1 case; and trapping with an occipital artery-PICA anastomosis was done in 1 case. Seven aneurysms were treated by endovascular procedure with intra-aneurysmal coil embolization. Respiratory arrest occurred in 3 cases whose postoperative course was uneventful. Rerupture and medullary infarction were not confirmed by CT/MRI obtained immediately and a few days after the respiratory arrests. However, more than half of the intra-dural VA was occluded proximally from the VA union after the direct surgical/endovascular procedure, which included proximal clipping for a giant fusiform aneurysm in 1 case and coil embolization for dissecting aneurysms in 2 cases. The periods between surgery and respiratory arrest were 10 hours, 4 days, and 32 days, respectively, for the 3 patients. Voluntary respiration eventually resumed in 2 patients. In the surgical treatment of vertebral aneurysms, the possibility of respiratory complications should be kept in mind even though the early postoperative course may be uneventful. Postoperative respiratory failure can be reversed. Thus prompt diagnosis and treatment under close observation are mandatory, especially in cases with a high risk for postoperative central respiratory dysfunction.

Moebius syndrome and central respiratory dysfunction

Two infants, 18 months and 4 months of age, who were born with bilateral VI and VII nerve palsy (Moebius syndrome) experienced central respiratory failure requiring persistent ventilation. The computed tomography scan showed small brainstem tegmental calcifications. These findings suggest intrauterine brainstem necrosis including the respiratory center and poor prognosis for independent respiration.

Fatigue in multiple sclerosis is not due to sleep apnoea

Fatigue is a frequent and disabling phenomenon among patients with multiple sclerosis (MS). Daytime sleepiness is a typical symptom of the sleep apnoea/hypopnoea syndrome due to nocturnal hypoxia and recurrent arousals causing sleep fragmentation. Since MS plaques are often found in the midbrain, brain stem and upper cervical cord on magnetic resonance imaging (MRI) we hypothesized that fatigue in MS patients might be caused by a central respiratory dysfunction. We investigated 10 patients with definite MS by oligography, two questionnaires assessing fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS), MRI and pulmonary function tests. A total of six patients had either an elevated FSS and/or an elevated ESS. None of the six patients with an elevated FSS and/or ESS has an apnoea index > 5/hour. CT90 was normal in nine patients. We conclude that fatigue and daytime sleepiness in MS cannot be explained by nocturnal apnoeas or oxygen desaturations. The Fatigue Severity Scale should be integrated to the extended Barthel index, which is a new instrument for disability assessment in MS patients.

Carbon monoxide — does fetal exposure cause sudden infant death syndrome?

The epidemiological features of sudden infant death syndrome (cot death) include a peak incidence between 8 and 13 weeks of age, a time of death or conception occurring during the winter months and an excess of deaths in infants born to young multiparous women of low socioeconomic status who smoke. We suggest that, through hypoxia, carbon monoxide in tobacco smoke and in the home exerts a noxious effect on the developing central respiratory control mechanism of the fetal brain which then remains particularly susceptible to further insults in the early postnatal period from infection and hyperthermia, resulting in death from central respiratory dysfunction.