Effect and impact of mechanical ventilation in myotonic dystrophy type 1: a prospective cohort study.

Few studies have assessed the impact of home ventilation in patients with myotonic dystrophy type 1 (DM1) and no specific recommendations are available. We assessed the survival associated with category of home ventilation adherence of patients with DM1 followed up at a home ventilation unit using a Cox proportional hazards model. 218 patients were included; those who refused or delayed their acceptance of non-invasive ventilation were at higher risk for severe events (invasive ventilation or death) (P=0.03). Risk of death was associated with orthopnoea (HR 2.37; 95% CI 1.17 to 4.80; P<0.02) and adherence category (100 to 90% vs >75%: HR 3.26; 95% CI 1.32 to 8.04; P<0.03). Failure to use home ventilation as prescribed may be associated with increased mortality in patients with DM1.

Survival of patients with chronic respiratory failure on long-term oxygen therapy and or non-invasive ventilation at home.

BACKGROUND & AIMS: Chronic respiratory failure (CRF) is the common fate of respiratory diseases where systemic effects contribute to outcomes. In a prospective cohort of home-treated patients with CRF, we looked for predictors of long-term survival including respiratory, nutritional and inflammatory dimensions. METHODS: 637 stable outpatients with CRF, 397 men, 68 ± 11 years, on long-term oxygen therapy and/or non-invasive ventilation from 21 chest clinics were enrolled and followed over 53 ± 31 months. CRF resulted from Chronic Obstructive Pulmonary Disease (COPD) in 48.5%, restrictive disorders 32%, mixed (obstructive and restrictive patterns) respiratory failure 13.5%, bronchiectasis 6%. Demographic characteristics, smoking habits, underlying respiratory diseases, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), arterial blood gases, 6-min walking distance (6MWD), hemoglobin, body mass index (BMI), serum albumin, transthyretin, C-reactive protein (CRP), history of respiratory assistance, antibiotic and oral corticosteroid use during the previous year were recorded. RESULTS: 322 deaths occurred during the follow-up. One-, five- and 8-year actuarial survival was 89%, 56% and 47%. By Cox univariate analysis, age, respiratory disease, PaO2, PaCO2, FEV1/FVC, BMI, 6MWD, activity score, type and length of home respiratory assistance, smoking habits, oral corticosteroid and antibiotic uses, albumin, transthyretin, hemoglobin and CRP levels were associated with survival. Multivariate analysis identified eight independent markers of survival: age, FEV1/FVC, PaO2, PaCO2, 6MWD, BMI, serum transthyretin, CRP ≥ 5 mg/l. CONCLUSIONS: In CRF, whatever the underlying diseases, besides the levels of obstructive ventilatory defect and gas exchange failure, 6MWD, BMI, serum transthyretin and CRP ≥ 5 mg/l predicted long-term survival identifying potential targets for nutritional rehabilitation.

Plasma exchange for Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome is an acute paralysing disease caused by peripheral nerve inflammation. This is an update of a review first published in 2001 and last updated in 2008. OBJECTIVES: To assess the effects of plasma exchange for treating Guillain-Barré syndrome. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 June 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (January 1966 to June 2011) and EMBASE (January 1980 to June 2011). SELECTION CRITERIA: Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. DATA COLLECTION AND ANALYSIS: Two review authors agreed the selection of eligible studies and independently assessed the risk of bias in included studies. Data were extracted by one review author and checked by a second review author. Likewise data for adverse events were extracted by one review author and checked by a second review author. MAIN RESULTS: In the first version of this review there were six eligible trials concerning 649 participants comparing plasma exchange with supportive treatment. No new eligible trials have been identified in subsequent updates. Overall the included trials had a low risk of bias.Primary outcomes In one trial with 220 severely affected participants, the median time to recover walking with aid was significantly faster; with plasma exchange (30 days) than without (44 days). In another trial with 91 mildly affected participants, the median time to onset of motor recovery was significantly shorter with plasma exchange (six days) than without (10 days). After four weeks, combined data from three trials accounting for a total of 349 patients showed that plasma exchanged significantly increased the proportion of patients who recovered the ability to walk with assistance (risk ratio (RR) 1.60, 95% confidence interval (CI) 1.19 to 2.15).Secondary outcomes In five trials with 623 participants in total, the RR of being improved by one or more grades after four weeks was 1.64 (95% CI 1.37 to 1.96) in favour of plasma exchange. Participants treated with plasma exchange also fared significantly better in time to recover walking without aid (three trials with 349 participants, RR 1.72 (95% CI 1.06 to 2.79)) and requirement for artificial ventilation (five trials with 623 participants, RR 0.53 (95% CI 0.39 to 0.74)). There were significantly more participants with relapses by the end of follow-up in the plasma exchange than the control group (6 trials with 649 participants, RR 2.89 (95% CI 1.05 to 7.93)). Despite this, at one year the likelihood of full muscle strength recovery was significantly greater with plasma exchange than without (five trials with 404 participants, RR 1.24 (95% CI 1.07 to 1.45)) and the likelihood of severe motor sequelae was significantly less (six trials with 649 patients, RR 0.65 (95% CI 0.44 to 0.96)). There was no significant difference in deaths (six trials with 649 participants, RR 0.86 (95% CI 0.45 to 1.65)) or participants with adverse events (three trials with 556 participants), except fewer arrhythmias in plasma exchange treated participants (RR 0.75 (95% CI 0.56 to 1.00)). AUTHORS' CONCLUSIONS: Moderate-quality evidence shows significantly more improvement with plasma exchange than supportive care alone in adults with Guillain-Barré syndrome without a significant increase in serious adverse events. There was a small but significant increase in the risk of relapse during the first six to 12 months after onset in people treated with plasma exchange compared with those that were not treated. Despite this, after one year, full recovery was significantly more likely and severe residual weakness less likely with plasma exchange.

Preceding infections and anti-ganglioside antibody profiles assessed by a dot immunoassay in 306 French Guillain-Barré syndrome patients.

We describe by an in-house dot immunoassay, specific anti-ganglioside and sulfatide antibodies, by comparing the results from a large group of 134 infected French GBS patients and those from 172 noninfected French GBS and 142 control groups. A recent infection was identified in 134/306 (43.8%) GBS patients: Campylobacter jejuni (24.6%) was the most common agent, followed by cytomegalovirus (12.4%), Mycoplasma pneumoniae (3.2%) and Epstein-Barr virus (1.3%). Anti-ganglioside antibodies were detected in 97/306 (31.7%) of total GBS patients, 82/134 (61.2%) of GBS patients with a recent identified infection and 15/172 (8.7%) of the patients without identified infection. According to the specificities and antibody classes, four specific IgG antibody profiles were individualised against the two major GM1 and GD1a gangliosides in motor axonal C. jejuni-associated GBS variants, against GQ1b and disialylated gangliosides in Miller Fisher syndrome and its variants. One specific IgM profile against GM2 was found in 16/38 (42%) of severe sensory demyelinating CMV-associated GBS and in 8/17 (47%) of subjects with recent CMV infection with no neurological disease. IgG or IgM antibodies to GM1 were found in 5/10 M. pneumoniae-infected patients. IgM antibodies to GM1 were observed in the control groups, 15% of the 74 patients with amyotrophic lateral sclerosis, 19% of the 51 patients with chronic inflammatory demyelinating polyneuropathy, and 9% of the 21 healthy control subjects. The fine specificity of the four IgG antibody profiles and the IgM anti-GM2 profile is closely related to the nature of the preceding infections and the pattern of clinical features.

Guillain-Barré syndrome following primary cytomegalovirus infection: a prospective cohort study.

BACKGROUND: Little is known about the epidemiology and the prognostic factors of Guillain-Barré syndrome (GBS) following primary infection with cytomegalovirus (CMV-GBS). METHODS: We prospectively followed up 506 patients with cases of GBS who were admitted to our center from 1996 through 2006. We diagnosed 63 (12.4%) CMV-GBS cases by immunoglobulin (Ig) M detection and IgG avidity. Plasma CMV DNA was detected at hospital admission. Patient subgroups were compared using Fisher's exact test and the Wilcoxon rank-sum test. Temporal variations were analyzed with time series methods. RESULTS: Patients with CMV-GBS were mostly young (median age, 32 years; sex ratio, 0.85), but we also identified a subpopulation of patients consisting of women aged >50 years. Sensory defects (in 72% of cases) and facial palsy (49%) were frequent, and test results positive for CMV DNA in plasma at hospital admission (found in 62% of cases) tended to be associated with objective sensory defect (P=.052). The main factors associated with long-term neurological sequelae (21%) were older age (P<.001) and assisted ventilation during hospitalization (P=.005). The number of CMV-GBS cases decreased between 1996 and 2006 (P=.019) and displayed an annual periodicity between the months of July and October. The incidence of CMV-GBS was estimated to be between 0.6 and 2.2 cases per 1000 cases of primary CMV infection (versus 0.25 to 0.65 cases per 1000 cases of Campylobacter jejuni infection). CONCLUSIONS: This study provides new insights about the epidemiology of CMV-GBS and shows that the risk of developing GBS is similar following primary CMV infection or C. jejuni infection. Our results also suggest a direct or indirect involvement of viral replication in the neuropathological processes of CMV-GBS.

Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials.

INTRODUCTION: Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial. OBJECTIVES: To assess HBO in patients poisoned with CO. DESIGN: Two prospective randomized trial on two parallel groups. SETTING: Critical Care Unit, Raymond Poincaré Hospital, Garches, France. SUBJECTS: Three hundred eighty-five patients with acute domestic CO poisoning. INTERVENTION: Patients with transient loss of consciousness (trial A, n = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n = 86) or 4 h of NBO plus one HBO session (arm A1, n = 93). Patients with initial coma (trial B, n = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n = 105). PRIMARY ENDPOINT: Proportion of patients with complete recovery at 1 month. RESULTS: In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47-1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23-0.79)]. CONCLUSION: In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.

Detection of Campylobacter jejuni by culture and real-time PCR in a French cohort of patients with Guillain-Barre syndrome.

Bacteriological culture and real-time PCR (RT-PCR) were used to detect Campylobacter jejuni in fecal samples from a French cohort of 237 patients with Guillain-Barré syndrome (GBS). We provide evidence that diverse serotypes and genotypes of C. jejuni are a major trigger of GBS in France.

Automatic air-leak compensation in neuromuscular patients: a feasibility study.

Air leaks often result in alveolar hypoventilation in mechanically ventilated patients with neuromuscular disease. The primary objective of this study was to assess the feasibility, efficacy and tolerance of a ventilator equipped with an automated air-leak compensation system in a clinical situation. Fourteen neuromuscular patients with nocturnal air leaks during home ventilation were included in a prospective randomised crossover study. A modified VS Ultra ventilator was studied during two consecutive nights and patients were randomly ventilated with and without a leak-compensation system, respectively. Tolerance, minute ventilation, blood gas values, sleep parameters, and nocturnal oxygen saturation were assessed. Leak compensation significantly increased the mean inspiratory and expiratory tidal volumes (731+/-312 vs. 1094+/-432 ml [p=0.002] and 329+/-130 vs. 496+/-388 ml [p=0.006], respectively) and inspiratory and expiratory flows (51.7+/-8.2 vs. 61.8+/-12.4 l/min [p=0.016] and 63.3+/-26.2 vs. 83.3+/-37.8 l/min [p=0.013], respectively). The system acted by increasing both inspiratory time (from 1355+/-230 to 1527+/-159 ms, p=0.038) and inspiratory pressure (from 14.0+/-2.8 to 18.3+/-3.4 cm H(2)O, p=0.002). Leak compensation improved arterial PCO(2) (6.18+/-0.9 vs. 5.21+/-1.0 kPa, p=0.004), slow-wave-sleep latency (119+/-69 vs. 87+/-35 min, p=0.04), and tolerance. Air-leak compensation is feasible and may produce beneficial effects in neuromuscular patients. The automatic air-leak compensation system tested here should be evaluated in long-term efficacy and tolerance studies and compared to other ventilation modes capable of compensating for leaks, such as pressure support.

Guillain-Barré syndrome and influenza virus infection.

BACKGROUND: In Western countries, the cause of 60% of all Guillain-Barré syndrome (GBS) cases remains unidentified. The number of cases of unidentified cause peaks in winter, and these cases are commonly preceded by respiratory tract infection or influenza-like illness. We investigated the triggering role of influenza virus infection. METHODS: Of 405 patients with GBS who were admitted to a French reference center during 1996-2004, 234 had cases caused by an unidentified agent. We used time-series methods to study the correlation between the monthly incidence of such cases and influenza-like illnesses reported by the Sentinelles surveillance network. We analyzed anti-influenza antibodies using complement fixation testing and hemagglutination-inhibition assays. We studied etiological subgroups using Wilcoxon and Fisher's exact tests. RESULTS: We found a positive association between the monthly incidence of GBS caused by an unidentified agent and reported influenza-like illnesses. Of 73 patients whose cases occurred during periods in which there was a possible link to influenza, 10 (13.7%) had serological evidence of recent influenza A, and 4 (5.5%) had serological evidence of influenza B. Eight of 10 influenza A-related cases occurred during "major" influenza seasons, and antibodies specific to the current epidemic strain were found in 9 cases. Most patients with influenza A-related cases were aged < 65 years, and none had antiganglioside antibodies. Influenza-related cases differed both from Campylobacter jejuni-related cases, with regard to the lack of need for mechanical ventilation (P = .014), and from the cases caused by an unidentified agent, with regard to the presence of preceding influenza-like illness or respiratory tract infection (P = .015) and longer time from the infectious event to GBS onset (P = .04). CONCLUSIONS: Influenza viruses are infrequent triggering agents of GBS but may play a significant role during major influenza outbreaks. Influenza-related GBS displays specific features and is not associated with antiganglioside antibody response, which suggests the presence of underlying immune mechanisms.

[Acute carbon monoxide poisoning]. / Intoxication aiguë par le monoxyde de carbone.

Carbon monoxide (CO) poisoning is still complicated by a high mortality and morbidity rate. Diagnosis can be obvious but is most of time difficult and sometimes remained unknown. It is usually based on clinical signs and must be confirmed by assessment of CO level in room air or in patient's expired breathing or blood and detection of a source. Mild neurological sequelae are very common. Normobaric oxygen is the first line treatment. Comatose and pregnant patients must undergo hyperbaric oxygen. All CO poisoning has to be declared to sanitary authority, which will in turn conduct a technical inspection to remove the source. The patient must be informed that he is at risk of new poisoning and of neurological complications. Progress in prevention and research in therapeutics are needed in order to reduce CO related morbidity.

Noninvasive ventilation as an alternative to endotracheal intubation during tracheotomy in advanced neuromuscular disease.

OBJECTIVE: To compare conventional tracheotomy with endotracheal intubation to tracheotomy with noninvasive positive-pressure ventilation (NPPV) in advanced neuromuscular disease. METHODS: This was a retrospective study of a historical cohort of patients tracheotomized while sedated and intubated versus patients tracheotomized under NPPV and local anesthesia. We recorded previous intubation difficulties, complications (eg, aspiration pneumonia), and hospital stay. RESULTS: Conventional tracheotomy was performed in 7 patients. We performed tracheotomy during NPPV with local anesthesia in 13 patients. All but 3 patients had risk factors for difficult intubation. Hospital stay was 23.3 +/- 10.3 d in the conventional group and 25.3 +/- 12.9 d in the NPPV group (p = 0.87). The number of pneumonias was higher in the conventional-tracheotomy group (4 vs 1, p = 0.03). CONCLUSION: In neuromuscular patients, performing tracheotomy with NPPV and local anesthesia may help avoid endotracheal intubation and reduce morbidity.

Hand versus mouth for call-bell activation by DMD and Becker patients.

Severe hand dysfunction is common in patients with Duchenne muscular dystrophy (DMD) and may preclude the use of conventional call-bells. We prospectively evaluated a call-bell with two hand-controlled interfaces (push-button and key-pinch) and two mouth-controlled interfaces (sip-or-puff) in 32 consecutive DMD and Becker patients. Patients called intentionally 348 times, using the sip-or-puff device 237 times and the hand-controlled interfaces 147 times. Use of the hand-controlled interfaces correlated with key-pinch strength (R=0.366; P=0.04). Six patients reported being unable to call with the hand interfaces and five patients reported temporary call failure due to inaccessibility of the sip-or-puff interface. Ease-of-use scores on a visual analogue scale were best for puff, followed by sip then key-pinch interrupter and push-button (8.7+/-2.1, 7.5+/-2.7, 6.2+/-3.9, and 0.5+/-2.0 respectively; ANOVA: P<0.00001). In conclusion sip-or-puff devices should be considered more often to provide neuromuscular patients with greater independence.

Immunotherapy for Guillain-Barré syndrome: a systematic review.

Guillain-Barré syndrome (GBS) is an acute inflammatory disorder of the peripheral nervous system thought to be due to autoimmunity for which immunotherapy is usually prescribed. To provide the best evidence on which to base clinical practice, we systematically reviewed the results of randomized trials of immunotherapy for GBS. We searched the Cochrane Library, MEDLINE and EMBASE in July 2006 and used the methods of the Cochrane Neuromuscular Disease Group to extract and synthesize data. Almost all trials used a 7-point disability grade scale. In four trials with altogether 585 severely affected adult participants, those treated with plasma exchange (PE) improved significantly more on this scale 4 weeks after randomization than those who did not, weighted mean difference (WMD) -0.89 (95% confidence interval (CI) -1.14 to -0.63). In five trials with altogether 582 participants, the improvement on the disability grade scale with intravenous immunoglobulin (IVIg) was very similar to that with PE, WMD -0.02 (95% CI -0.25 to 0.20). There was also no significant difference between IVIg and PE for any of the other outcome measures. In one trial with 148 participants, following PE with IVIg did not produce significant extra benefit. Limited evidence from three open trials in children suggested that IVIg hastens recovery compared with supportive care alone. Corticosteroids were compared with placebo or supportive treatment in six trials with altogether 587 participants. There was significant heterogeneity in the analysis of these trials which could be accounted for by analysing separately four small trials of oral corticosteroids with altogether 120 participants, in which there was significantly less improvement after 4 weeks with corticosteroids than without, WMD -0.82 (95% CI -0.17 to -1.47), and two large trials of intravenous methylprednisolone with altogether 467 participants, in which there was no significant difference between corticosteroids and placebo WMD -0.17 (95% CI 0.06 to -0.39). None of the treatments significantly reduced mortality. Since approximately 20% of patients die or have persistent disability despite immunotherapy, more research is needed to identify better treatment regimens and new therapeutic strategies.

Breathing-swallowing interaction in neuromuscular patients: a physiological evaluation.

RATIONALE: Malnutrition and aspiration are major problems in patients with neuromuscular disease. Because impaired swallowing contributes to malnutrition, means of improving swallowing are needed. OBJECTIVES: To investigate interactions between breathing and swallowing in neuromuscular disorders and to evaluate the impact of mechanical ventilation (MV) on swallowing in tracheostomized patients. METHODS: We studied 10 healthy individuals and 29 patients with neuromuscular disease and chronic respiratory failure (including 19 with tracheostomy). The tracheostomized patients who could breathe spontaneously were recorded during spontaneous breathing (SB) and with MV, in random order. MEASUREMENTS AND MAIN RESULTS: Breathing-swallowing interactions were investigated by chin electromyography and inductive respiratory plethysmography, using three water-bolus sizes (5, 10, and 15 ml) in random order. In contrast to healthy individuals, neuromuscular patients showed piecemeal deglutition with several swallows over several breathing cycles for each bolus. The percentage of swallows followed by expiration was about 50% in the patients compared with nearly 100% in the control subjects. The number of swallows and total swallowing time per bolus correlated significantly to maximal inspiratory pressure. In the 10 tracheostomized patients who were recorded both in SB and MV, the number of swallows and total swallowing time per bolus were significantly reduced during MV compared with SB. CONCLUSION: Neuromuscular patients showed abnormal breathing-swallowing interactions, which correlated to maximal inspiratory pressure. Moreover, MV improved the swallowing parameters in tracheostomized patients who were able to breathe spontaneously.

Clinical and electrophysiological predictors of respiratory failure in Guillain-Barré syndrome: a prospective study.

BACKGROUND: Respiratory failure is the most serious short-term complication of Guillain-Barré syndrome and can require invasive mechanical ventilation in 20-30% of patients. We sought to identify clinical and electrophysiological predictors of respiratory failure in the disease. METHODS: We prospectively assessed electrophysiological data and clinical factors, including identified predictors of delay between disease onset and admission, inability to lift head, and vital capacity, in patients admitted with Guillain-Barré syndrome. We related these factors to subsequent need for ventilatory support. Neurophysiological findings were classified as demyelinating, axonal, equivocal, unexcitable, or normal. Predictive values of clinical and electrophysiological data were tested using classification trees to build up a predictive model. This model was initially built up in a two-third (fitting set) then validated in a one-third (validation set) of the total sample. The fitting and validation sets were randomly selected. We also assessed the predictive value of this model for disability at 6 months. FINDINGS: From 1998, to 2006, 154 patients with Guillain-Barré syndrome were included in the study and 34 (22%) were subsequently ventilated. Demyelinating Guillain-Barré syndrome was more common in patients who went on to be ventilated than in those who were not (85%vs 51%, p=0.0003). Vital capacity and the proximal/distal compound muscular amplitude potential (p/dCMAP) ratio of the common peroneal nerve were retained in the tree model, with a probability of needing ventilation of less than 2.5% in patients with a ratio of greater than 55.6% and a vital capacity more than 81% of predicted. A p/dCMAP ratio of the peroneal nerve less than 55.6% and age older than 40 years were retained as independent predictors of disability at 6 months. INTERPRETATION: Neurophysiological testing is helpful for assessing risk of respiratory failure, which is highest in patients with evidence of demyelination and very low in those without both 55.6% conduction block of the common peroneal nerve and a 20% reduction in vital capacity.

Prognosis and risk factors of early onset pneumonia in ventilated patients with Guillain-Barré syndrome.

OBJECTIVE: Invasive mechanical ventilation is required in 30% of patients with Guillain-Barré syndrome (GBS) and is associated with pneumonia and increased mortality. Our objective was to determine the incidence, characteristics, outcomes, and risk factors of pneumonia in GBS patients receiving mechanical ventilation. DESIGN AND SETTING: Study of a prospective database in an intensive care unit of a university hospital. PATIENTS: The study included 81 patients who required intubation for GBS. Neurological findings, vital capacity, and signs of respiratory distress were recorded at admission and at intubation. A score predicting the risk of intubation (0-4) was calculated for each patient. Pneumonia was diagnosed based on predefined criteria and retrospectively confirmed by two observers. Early-onset pneumonia was defined as pneumonia diagnosed within 5 days after intubation. MEASUREMENTS AND RESULTS: Mean vital capacity was 57 +/- 22% of predicted at admission and 33 +/- 11% at intubation. Pneumonia developed in 63 patients (78%), including 48 with early-onset pneumonia. Bacteria were consistent with aspiration. Of the 63 patients with pneumonia 11 (18%) had septic shock, 6 (10%) had acute respiratory distress syndrome, and 9 (14%) died. In the univariate analysis milder weakness, a lower risk of intubation (score < 2), and time from admission to intubation longer than 2 days were associated with early-onset pneumonia. Time from admission to intubation was the only independent predictor in the multivariate logistic regression model. CONCLUSIONS: Early-onset pneumonia is a common and severe complication that is related to aspiration in patients with GBS. Delaying intubation may increase the risk of early-onset pneumonia.