Outcome of Guillain-Barre syndrome patients with respiratory paralysis.

BACKGROUND AND AIMS: To evaluate the outcome of patients with Guillain -: Barre syndrome (GBS) having respiratory failure treated with modified intubation policy. DESIGN AND METHODS: Consecutive patients with GBS having single breath count below 12 and respiratory rate >30/min were included and their clinical details noted. The patients were intubated and mechanically ventilated (MV) if their PaO2 was <60 mmHg on venturi mask, PaCo2 > 50 mmHg or pH < 7.3. Their electrophysiological subtypes and complications were noted. The hospital mortality and 3 months outcome were compared in MV and those could be managed without MV even with respiratory compromise. RESULTS: Out of 369 patients, 102 (27.6%) patients had respiratory compromise who were included in this study. Of the patients with respiratory compromise, 44 (43.1%) were intubated and mechanically ventilated after a median of 4 days of hospitalization. The median duration of MV was 21 (range 1-88) days. The patients with autonomic dysfunction (56.8% vs. 19%), facial weakness (78% vs. 36.2%), bulbar weakness (81.8% vs. 31%), severe weakness (63.8% vs. 31%) and high transaminase level (47.7% vs. 25.9%) needed MV more frequently. In our study, 6.8% patients died and 26.6% had poor outcome which was similar between MV and non-MV patients. The MV patients had longer hospitalization and more complications compared with non-MV group. CONCLUSION: In GBS patients with respiratory compromise, conservative intubation does not increase mortality and disability.

A long-term evaluation of cryoballoon ablation in 205 atrial fibrillation patients: a single center experience.

BACKGROUND: Atrial fibrillation is the most prevalent cardiac arrhythmia with significant healthcare impact with regards to treatment costs, morbidity, and mortality. Many of the focal electrical activities that initiate and sustain atrial fibrillation have been found to reside within or near the pulmonary veins. Consequently, pulmonary vein isolation by catheter ablation has emerged as an effective method to eliminate the focal triggers associated with atrial fibrillation. METHODS: In this single-center study, 205 patients were ablated for atrial fibrillation using a cryoballoon catheter and followed-up long-term by retrospective chart examination to evaluate their post-procedural freedom from atrial fibrillation. RESULTS: Patients were followed for up to 6 years with a cohort median of 3 years of post-ablation evaluation. Overall, at 12, 24, and 36 months post-ablation, 71, 49, and 31% of evaluated patients were free of atrial fibrillation, respectively. We found the type of atrial fibrillation (paroxysmal vs. persistent) as an independent predictor for arrhythmia recurrence (HR 1.97; 95% CI: 1.24-3.13, P = 0.006). The cohort median atrial fibrillation-free survival time was 24 months (27 months for paroxysmal atrial fibrillation patients and 14 months for persistent atrial fibrillation patients). There were a total of 37 (18%) complications, 8 (3.9%) were categorized as major complications, all without permanent sequels. The most common complication was phrenic nerve palsy which occurred in 14 (6.8%) patients. CONCLUSION: Long-term outcomes in this study suggest that the pulmonary vein isolation using the cryoballoon technique is relatively an effective method especially in the treatment of paroxysmal atrial fibrillation.

Diaphragmatic nerve palsy after cardiac surgery in children in Egypt: outcome and debate in management.

INTRODUCTION: Diaphragmatic paralysis (DP) due to phrenic nerve injury is a complication which occurs in association with congenital cardiac surgery and may be a life-threatening event in infants and young children. Information about this complication is still scarce from the developing countries. METHODS: Retrospective study evaluated the incidence of DP among 414 patients who underwent congenital cardiac surgery in Abo Elriesh Children's Specialized Hospital, Cairo University, Egypt, in the duration from April 2009 to December 2011. RESULTS: Incidence of DP was 3.6% (15 of 414 cases). Median age of affected patients was 10 months (ranged from 1 month to 13 years). Diagnosis of DP was observed after ventricular septal defect repair (3.9%), Glenn anastomosis (8.6%), Tetralogy of Fallot repair (4.3%), Senning operation (10%), arterial switch operation (3.2%), Fontan procedure (33%), coarctation of the aorta repair (7%), and pulmonary artery banding (6.4%). Diaphragmatic plication was performed in 4 of 15 cases. Patients with DP had significantly prolonged mechanical ventilation duration as compared to unaffected patients (median 120, range 48-600 vs 4, range 0-48 hours, P < .000). They also had a higher incidence of nosocomial pneumonia in 8 of 15 (53%) cases, longer duration of intensive care unit stay (median 15, range 4-62 days, P < .006), and significant mortality in 7 of 15 (46%; P < .004). Mortality among patients who underwent diaphragm plication was 1 of 4 (25%). CONCLUSION: Diaphragmatic paralysis is a relatively rare complication of congenital cardiac surgery in children. Its occurrence is associated with increased morbidity and mortality. A high index of clinical suspicion, utilization of bedside diagnostic tools, and a policy of early plication for certain patients may lead to improved outcomes.

[Ventilation in acute respiratory distress. Lung-protective strategies]. / Beatmung beim akuten Lungenversagen. Lungenprotektive Strategien.

Ventilation of patients suffering from acute respiratory distress syndrome (ARDS) with protective ventilator settings is the standard in patient care. Besides the reduction of tidal volumes, the adjustment of a case-related positive end-expiratory pressure and preservation of spontaneous breathing activity at least 48 h after onset is part of this strategy. Bedside techniques have been developed to adapt ventilatory settings to the individual patient and the different stages of ARDS. This article reviews the pathophysiology of ARDS and ventilator-induced lung injury and presents current evidence-based strategies for ventilator settings in ARDS.

Neurological causes of diaphragmatic paralysis in 11 alpacas (Vicugna pacos).

BACKGROUND: Diaphragmatic paralysis is a relatively uncommon medical condition in animals not reported in alpacas. OBJECTIVES: Describe the signalment, physical examination, diagnostic testing, clinical, and histopathologic findings related to diaphragmatic paralysis in alpacas. ANIMALS: Eleven alpacas with spontaneous diaphragmatic paralysis. METHODS: A retrospective study examined medical records from a 10-year period and identified 11 alpacas with confirmed diaphragmatic paralysis admitted to Washington State University and Colorado State University Veterinary Teaching Hospitals between September 2003 and October 2009. RESULTS: The 11 alpacas ranged in age from 2 to 12 months. Fluoroscopic imaging confirmed the presence of bilateral diaphragmatic paralysis in the 7 alpacas that were imaged. Arterial blood gas analyses showed hypercapnea, hypoxemia, and low oxygen saturation. Seven alpacas died or were euthanized between 2 and 60 days after onset of respiratory signs. Histopathologic examination of tissues found phrenic nerve degeneration in the 6 alpacas that were necropsied and additional long nerves examined demonstrated degeneration in 2 of these animals. Two animals had spinal cord lesions and 2 had diaphragm muscle abnormalities. No etiologic agent was identified in the alpacas. CONCLUSIONS AND CLINICAL IMPORTANCE: The etiology for diaphragmatic paralysis in these alpacas is unknown. A variety of medical treatments did not appear to alter the outcome.

Survival after short- or long-term ventilation after acute spinal cord injury: a single-centre 25-year retrospective study.

STUDY DESIGN: A retrospective review of acute spinal cord injury patients having assisted ventilation on or after admission between 1981 and 2005. OBJECTIVE: To assess survival after acute ventilatory support. SETTING: Northwest Regional Spinal Injuries Centre, Southport, England. METHODS: Causes of death were ascertained from the Office of National Statistics. Kaplan-Meier analysis of survival was calculated according to ventilator-wean status at discharge. Risk factors were obtained by Cox regression analysis. RESULTS: Over 50% of deaths in weaned and ventilated patients were respiratory in origin. The mean survival of weaned patients in the age group 31-45 was 19.3 compared with 10.5 years for ventilated patients (P=0.047). Those under 30 survived a further 22.1 and 18.4 years (P=0.31), while those over 45 lived for 11.0 and 8.3 years (P=0.50), values for weaned and ventilated patients, respectively. The survival advantage for weaned patients in the middle age group was less evident when the 1-year survivors were compared. The mean survival time of younger patients with diaphragm pacing was 1.8 years longer than those on mechanical ventilation (P=0.142). The variables with significant hazard ratios were any comorbidity (3.07); mechanical ventilation on discharge (2.26); and older age at injury, (3.1). CONCLUSIONS: The survival time for patients with high tetraplegia on long-term ventilation compares with other datasets and older patients have a proportionately greater loss in life expectancy. Self-ventilating patients with tetraplegia remain at considerable risk from respiratory death and consideration needs to be given to more effective preventative measures.

Parálisis diafragmática en el postoperatorio de cirugía cardiaca infantil / Diaphragmatic paralysis after pediatric cardiac surgery

Objetivo: Describir la frecuencia, morbimortalidad y tratamiento de la disfunción diafragmática (DD) en el postoperatorio de la cirugía cardiaca infantil. Pacientes y métodos: Serie de casos de DD identificados entre la población de niños intervenidos de cirugía cardiaca en el hospital «12 de Octubre» de Madrid, entre 1997 y 2006. Se obtuvieron retrospectivamente datos demográficos, de la cirugía y del postoperatorio, así como de la estancia hospitalaria yde la morbimortalidad. Resultados: Cirugía cardiaca en 1.063 niños, diagnosticándose 23 casos de DD. Se excluyó un caso secundario a neuropatía generalizada. La frecuencia global fue del 2,1%. La mediana de edad fue de 14 días (1 día-16 meses), siendo 20 de los casos menores de 1 año. Se realizó plicatura en 13 pacientes (62%). Las indicaciones de plicatura fueron: fracaso de extubación (n= 11) y dificultad respiratoria persistente (n= 2).Fue preciso realizar plicatura quirúrgica en 9 de los 13 neonatos. El tiempo de ventilación mecánica invasiva, estancia en unidad de cuidados intensivos pediátricos (UCIP) y estancia hospitalaria en los casos con paresia fue de 8, 12 y 20 días(mediana), respectivamente. Las parálisis precisaron mayor tiempo de ventilación invasiva y de ingreso (19, 34 y 47,5 días). Conclusiones: A todo neonato intervenido de una cardiopatía compleja debería realizársele una ecografía diafragmática en respiración espontánea previa a su extubación, para así establecer el diagnóstico de manera precoz, con el objetivo de reducir el tiempo de ventilación mecánica y la morbilidad asociada (AU)

The objective of this study is to describe the frequency, morbimortality and treatment of diaphragmatic dysfunction (DD) after pediatric cardiac surgery. Patients and methods: Series of DD cases identified among the population of children who underwent cardiac surgery at the hospital 12 de Octubre of Madrid from the years 1997-2006. Demographic, surgical and postsurgical data have been obtained retrospectively, as well as data on hospital stay and the morbimortality. Results: A total of 1,063 children underwent cardiac surgery, diagnosing 23 DD cases. A secondary case was excluded due to generalized neuropathy. The global frequency was of 2.1%,the mean age was 14 days (1 d-16 m), being 20 of the cases under 1 year of age. Reefing was performed in 13 patients (62%). The indications for reefing were due to extubation failure (n= 11) and persistent respiratory difficulties (n= 2).Surgical reefing had to be performed in 9 from the 13 newborns. In the cases of paresis the length of the invasive mechanical ventilation, stay at the PICU and hospital stay was 8,12 and 20 days (mean) respectively. The paralysis required alonger time of invasive ventilation and hospitalization (19, 34 and 47,5 days).Conclusions: A diaphragm echography in spontaneous breathing should be performed on any newborn that underwent a complex cardiopathy surgery previous to the extubation in order to determine an early diagnosis and to reduce the length of mechanical ventilation and associated morbidity (AU)

Natural history of Ullrich congenital muscular dystrophy.

OBJECTIVE: To describe the course, complications, and prognosis of Ullrich congenital muscular dystrophy (UCMD), with special reference to life-changing events, including loss of ambulation, respiratory insufficiency, and death. METHODS: Review of the case notes of 13 patients with UCMD, aged 15 years or older at last visit, followed up at a tertiary neuromuscular centre, London, UK, from 1977 to 2007. Data collected were age at onset of symptoms, presenting symptoms, mobility, contractures, scoliosis, skin abnormalities, respiratory function, and feeding difficulties. RESULTS: The mean age at onset of symptoms was 12 months (SD 14 months). Eight patients (61.5%) acquired independent ambulation at a mean age of 1.7 years (SD 0.8 years). Nine patients (69.2%) became constant wheelchair users at a mean age of 11.1 years (SD 4.8 years). Three patients continued to ambulate indoors with assistance. Forced vital capacity (FVC) values were abnormal in all patients from age 6 years. The mean FVC (% predicted) declined at a mean rate of 2.6% (SD 4.1%) yearly. Nine patients (69.2%) started noninvasive ventilation at a mean age of 14.3 years (SD 5.0 years). Two patients died of respiratory insufficiency. CONCLUSION: In Ullrich congenital muscular dystrophy (UCMD), the decline in motor and respiratory functions is more rapid in the first decade of life. The deterioration is invariable, but not always correlated with age or severity at presentation. This information should be of help to better anticipate the difficulties encountered by patients with UCMD and in planning future therapeutic trials in this condition.

Defining survival as an outcome measure in amyotrophic lateral sclerosis.

OBJECTIVES: To examine how respiratory interventions affect survival as an outcome measure and to define survival rate for trials in amyotrophic lateral sclerosis. DESIGN AND SETTING: We reviewed the data of 3 phase 3 clinical trials and examined differences in times to death, tracheostomy, and permanent assisted ventilation. We assessed the outcomes with chi(2) and Fisher exact tests for categorical variables and unpaired, 2-tailed t tests for continuous variables. We used Kaplan-Meier methods to estimate the differences in survival times between interventions. A power analysis generated sample size estimates for different end points. PATIENTS: In all, 2077 patients in 2 phase 3 trials of xaliproden and 400 patients in a phase 3 trial of pentoxifylline. MAIN OUTCOME MEASURES: Death or combined death, tracheostomy, or permanent assisted ventilation. RESULTS: Of 745 deaths, 611 (82.0%) were owing to respiratory failure and 134 (18.0%) to other causes. The use of respiratory interventions across centers ranged from 0% to 6.6% (P = .001) of patients for tracheostomy and 11.1% to 23.1% (P = .05) of patients for noninvasive ventilation. Twelve of 55 patients (21.8%) undergoing tracheostomy had a vital capacity of 50% or more. Mean (SD) survival time was 457.9 (3.1) days using a combined end point and 467.2 (2.9) days with death alone as the outcome (P = .02). An estimated sample size to detect a 10% difference at 18 months between groups was 490 patients per arm for the combined end point and 410 patients for death alone. CONCLUSIONS: Tracheostomy and permanent assisted ventilation are not equivalent to death in amyotrophic lateral sclerosis. The use of respiratory interventions differs between centers, leading to variability in combined outcome assessments. The time to the end point can differ significantly depending on its definition, and combining outcomes does not reduce the estimated sample size of a trial. The death rate alone is the least variable and most easily identifiable measure of survival rate in amyotrophic lateral sclerosis.

Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study.

BACKGROUND AND PURPOSE: To prospectively investigate causes of death and the circumstances surrounding death in 302 patients with amyotrophic lateral sclerosis (ALS). The functional status of patients immediately before death was also determined. METHODS: Information was obtained from neurologists at ALS centres, patients' files, and, when deaths occurred outside a medical facility, attending physicians. RESULTS: Most patients (63%) died in a medical facility. The most frequently reported cause of death was respiratory failure (77%), including terminal respiratory insufficiency (58%), pneumonia (14%), asphyxia due to a foreign body (3%) and pulmonary embolism (2%). Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%). The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside). At the time of death, only 55% of patients were receiving riluzole, 33% were undergoing non-invasive ventilation, 3% had a tracheotomy and 37% a gastrostomy. CONCLUSION: The information provided by this study helps to improve our understanding of the natural history of the disease and may help optimize the quality of care we can offer patients at the end of life.

Evidence supporting a role of serotonin in modulation of sudden death induced by seizures in DBA/2 mice.

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is a serious concern for epilepsy patients. DBA/2 mice are proposed as a SUDEP model, because these mice exhibit respiratory arrest (RA) after audiogenic seizures (AGSs), and RA is also implicated in human SUDEP. Respiratory mechanisms are modulated, in part, by serotonin. Therefore we evaluated the effects of serotoninergic agents on RA incidence in DBA/2 mice. METHODS: DBA/2 mice (75%) exhibited AGS and RA, and approximately 99% of animals could be resuscitated. The mice exhibiting RA were given a selective serotonin reuptake inhibitor, fluoxetine, 24 h after the initial AGS, and RA susceptibility was evaluated 30 min later. Ten percent of DBA/2 mice exhibited tonic hindlimb extension (TE) without RA, and a serotonin antagonist (cyproheptadine) was administered to these mice. RESULTS: Fluoxetine (15-25 mg/kg, i.p.) significantly reduced the incidence of RA in DBA/2 mice after AGSs, and this effect was reversible by 72 h. Only the 25-mg/kg dose reduced AGS severity. In mice exhibiting TE without RA, the incidence of RA was significantly increased 30 min after cyproheptadine (1-2 mg/kg i.p.). Most of these mice exhibited AGSs without RA again by 72 h. CONCLUSIONS: These findings indicate that fluoxetine reduced RA in DBA/2 mice at doses that did not reduce seizure severity. Because DBA/2 mice are a proposed model for human SUDEP, these data support evaluation of fluoxetine for SUDEP prevention in the patient population most susceptible to SUDEP. The data raise concern about the use of serotonin antagonists in this patient population.

Characterization of Clostridium sp. RKD producing botulinum-like neurotoxin.

A Gram positive, motile, rod-shaped, strictly anaerobic bacterium isolated from intestine of decaying fish was identified as Clostridium sp. RKD and produced a botulinum type B-like neurotoxin as suggested by mouse bioassay and protection with anti botulinum antibodies. The neurotoxicity was functionally characterized by the phrenic nerve hemi-diaphragm assay. Phylogenetic analysis based on 16S rDNA sequence, placed it at a different position from the reported strains of Clostridium botulinum. The strain exhibited differences from both Clostridium botulinum and Clostridium tetani with respect to morphological, biochemical and chemotaxonomic characteristics. Botulinum group specific and serotype specific primers amplified the DNA fragments of 260 and 727 bp, respectively, indicating presence of botulinum type 'B' toxin gene. Sequence of nearly 700 bp amplified using primers specific for botulinum neurotoxin type B gene, did not show any significant match in the database when subjected to BLAST search.

Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), the progressive loss of upper and lower motor neurons leads to respiratory failure, often with predominant diaphragm dysfunction, and death. Because the diaphragm is the only active inspiratory muscle during rapid eye movement (REM) sleep, there is a high theoretical risk of respiratory disorders during REM sleep in patients with ALS. To assess this hypothesis, we studied sleep characteristics (polysomnography) in 21 patients with ALS, stratified according to the presence or absence of diaphragmatic dysfunction. Diaphragmatic dysfunction was defined as an absent or delayed diaphragm response to cervical or cortical magnetic stimulation, abdominal paradox, or respiratory pulse (Group 1, 13 patients). These patients did not differ in age, clinical course, or form (bulbar or spinal) from the eight others, who did not have diaphragmatic dysfunction (Group 2). REM sleep was reduced in Group 1 (7 +/- 7% of total sleep time; mean +/- SD) and normal in Group 2 (18 +/- 6%, p = 0.004). Apneas or hypopneas were rare in both groups. In Group 1, REM sleep was absent or minimal (less than 3 min) in five patients. An unusual and remarkable preservation of phasic inspiratory sternomastoid activation during REM was associated with longer REM sleep duration in six of the other patients with diaphragmatic dysfunction. Median survival time was dramatically shorter (217 d) in Group 1 than in Group 2 (619 d, p = 0.015).

Respiratory function deterioration is not time-linked with upper-limb onset in amyotrophic lateral sclerosis.

INTRODUCTION: In amyotrophic lateral sclerosis (ALS), symptoms apparently spread following regional rules, and depending on the site of onset. We examined if respiratory function deterioration appears earlier or is more severe in patients with upper-limb onset. MATERIAL & METHODS: We compared the results of various pulmonary function tests (PFT) obtained at diagnosis depending on the site of onset in 49 ALS patients. In a longitudinal study, we compared the deterioration of forced vital capacity (FVC) in relation to the site of onset, and analyzed the time elapsed to reach values below 80% of predicted according to site of onset, and we compared the survival depending on the site of onset. RESULTS: No significant differences in PFT were found in the upper-limb onset group in any of the analysis performed. No differences in survival were detected in any disease onset group. CONCLUSION: Pulmonary function deterioration does not appear to be time-linked to arm onset in ALS.

[Diaphragmatic paralysis and respiratory insufficiency]. / Zwerchfellparese und respiratorische Insuffizienz.

BACKGROUND: Phrenic nerve palsy leads to disfunction of the main respiratory muscle. With bilateral palsy dyspnoea in the supine body position will typically occur. With one-sided lesion symptoms will only appear when a second pulmonary disease is present. PATIENTS: We refer of 6 patients with bilateral and 5 with unilateral diaphragmatic paresis. In 3 patients neuralgic shoulder-arm-amyotrophy was diagnosed, in further 4 there was suspicion of it. Amyotrophic lateral sclerosis developed in 2 after 4 respectively 8 months. In 1 case a cervical operation led to palsy, mediastinitis in 1 case. Lung function tests showed a restrictive pattern, especially in bilateral palsy. RESULTS: Vital capacity was reduced by almost 50% respectively 25% in the supine body position. Mouth occlusion pressure reduction was apparent. Near normal to marked hyperkapnia developed in bilateral paresis. In 5 cases non-invasive intermittent ventilation is instituted (2 volume controlled, 3 pressure supported). Two patients died (1 patient with amyotrophic lateral sclerosis after 13 months, 1 with malignant pleurisy after 4 months). Three patients continued non-invasive intermittent ventilation since 14 to 64 months.

Phrenic nerve injury complicating closed cardiovascular surgical procedures for congenital heart disease.

Phrenic nerve injury (PNI) with resulting hemidiaphragmatic paralysis occurred in 19 (2.1 +/- 0.5%) of 891 closed cardiac surgical procedures during a twenty-three-year period. Diagnosis was confirmed by standard radiographic criteria. Phrenic nerve injury was most commonly noted following systemic-pulmonary artery anastomosis, ligation of persistent ductus arteriosus plus pulmonary artery banding, and atrial septectomy. Most patients were managed conservatively (nasotracheal or orotracheal intubation and positive end-expiratory pressure). Although no deaths were a direct result of PNI, major complications occurred in 15 of the 19 instances of PNI (79% +/- 10%). The serious morbidity and the hospital costs associated with this complication, however, underscore the cardinal importance of prevention. If injury does occur, early surgical intervention (diaphragmatic plication) in very young infants may reduce the attendant morbidity, but the complete role of diaphragmatic plication remains to be defined.

Intestinal infection and toxin production by Clostridium botulinum as one cause of sudden infant death syndrome.

The spontaneous production of botulinum toxin in the infant gut by ingested Clostridium botulinum organisms is the underlying cause of infant botulism, recognised as an infectious disease only in late 1976. Because of the recognition of the pathophysiology of this disease and because the known potency and action of botulinum toxin can lead to rapid respiratory arrest, it appeared possible that the in-vivo production of botulinum toxin could cause the sudden death of some infants. To test this hypothesis, serum, selected tissues, and bowel contents from 280 dead infants were examined for the presence of C. botulinum toxin and/or organsisms. We found C. botulinum organisms in 10 infants, all of whom died suddenly and unexpectedly. 9 of these deaths were classified by the forensic pathologist as sudden infant death syndrome (S.I.D.S. or crib death). In 2 of these 10 sudden deaths both C. botulinum organisms and botulinum toxin were identified, and from the spleen of 1, C. botulinum organisms were isolated. Faecal specimens from 160 age-matched healthy infants who served as controls in studies of inpatient infant botulism cases were negative for both C. botulinum organisms and toxin, except for one specimen that contained only C. botulinum type A organisms. The 9 S.I.D.S. cases with evidence of C. botulinum infection comprised 4.3% of the 211 S.I.D.S. cases examined over 12 months. These findings suggest that intestinal production of botulinum toxin by C. botulinum is one cause of S.I.D.S. The strikingly similar age-distribution of 62 inpatient infant botulism cases and the 211 S.I.D.S. cases is also consistent with this concept. The possibility that in-vivo production of botulinum toxin may account for a larger proportion of S.I.D.S. cases is discussed.