Doppler Ultrasound Flow Reversal in the Superior Sagittal Sinus to Detect Cerebral Venous Congestion in Vein of Galen Malformation.

BACKGROUND AND PURPOSE: Vein of Galen malformation is a rare congenital cerebrovascular malformation. In affected patients, increased cerebral venous pressure constitutes an important etiologic factor for the development of brain parenchymal damage. The aim of this study was to investigate the potential of serial cerebral venous Doppler measurements to detect and monitor increased cerebral venous pressure. MATERIALS AND METHODS: This was a retrospective monocentric analysis of ultrasound examinations within the first 9 months of life in patients with vein of Galen malformation admitted at <28 days of life. Categorization of perfusion waveforms in the superficial cerebral sinus and veins into 6 patterns was based on antero- and retrograde flow components. We performed an analysis of flow profiles across time and correlation with disease severity, clinical interventions, and congestion damage on cerebral MR imaging. RESULTS: The study included 44 Doppler ultrasound examinations of the superior sagittal sinus and 36 examinations of the cortical veins from 7 patients. Doppler flow profiles before interventional therapy correlated with disease severity determined by the Bicêtre Neonatal Evaluation Score (Spearman ρ = -0.97, P = < .001). At this time, 4 of 7 patients (57.1%) showed a retrograde flow component in the superior sagittal sinus, whereas after embolization, none of the 6 treated patients presented with a retrograde flow component. Only patients with a high retrograde flow component (equal or more than one-third retrograde flow, n = 2) showed severe venous congestion damage on cerebral MR imaging. CONCLUSIONS: Flow profiles in the superficial cerebral sinus and veins appear to be a useful tool to noninvasively detect and monitor cerebral venous congestion in vein of Galen malformation.

Characteristic retinal atrophy pattern allows differentiation between pediatric MOGAD and MS after a single optic neuritis episode.

BACKGROUND: Optic neuritis (ON) is the most prevalent manifestation of pediatric multiple sclerosis (MSped) and myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGADped) in children > 6 years. In this study, we investigated retinal atrophy patterns and diagnostic accuracy of optical coherence tomography (OCT) in differentiating between both diseases after the first ON episode. METHODS: Patients were retrospectively identified in eight tertial referral centers. OCT, VEP and high/low-contrast visual acuity (HCVA/LCVA) have been investigated > 6 months after the first ON. Prevalence of pathological OCT findings was identified based on data of 144 age-matched healthy controls. RESULTS: Thirteen MOGADped (10.7 ± 4.2 years, F:M 8:5, 21 ON eyes) and 21 MSped (14.3 ± 2.4 years, F:M 19:2, 24 ON eyes) patients were recruited. We observed a significantly more profound atrophy of both peripapillary and macular retinal nerve fiber layer in MOGADped compared to MSped (pRNFL global: 68.2 ± 16.9 vs. 89.4 ± 12.3 µm, p < 0.001; mRNFL: 0.12 ± 0.01 vs. 0.14 ± 0.01 mm3, p < 0.001). Neither other macular layers nor P100 latency differed. MOGADped developed global atrophy affecting all peripapillary segments, while MSped displayed predominantly temporal thinning. Nasal pRNFL allowed differentiation between both diseases with the highest diagnostic accuracy (AUC = 0.902, cutoff < 62.5 µm, 90.5% sensitivity and 70.8% specificity for MOGADped). OCT was also substantially more sensitive compared to VEP in identification of ON eyes in MOGAD (pathological findings in 90% vs. 14%, p = 0.016). CONCLUSION: First MOGAD-ON results in a more severe global peripapillary atrophy compared to predominantly temporal thinning in MS-ON. Nasal pRNFL allows differentiation between both diseases with the highest accuracy, supporting the additional diagnostic value of OCT in children with ON.

Atrophy of optic nerve detected by transorbital sonography in patients with demyelinating diseases of the central nervous system.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) has emerged as promising imaging method for the diagnosis and follow-up of acute optic neuritis (ON). Available studies report an increase in the optic nerve diameter (OND) and the optic nerve sheath diameter (ONSD) in the case of a first episode of ON in the affected eye compared to either the contralateral unaffected eye or controls. However, the utility of TOS in the case of recurrent episodes of ON has never been assessed. METHODS: In our prospective cohort study, the diagnostic utility of TOS in patients with demyelinating diseases of the central nervous system was assessed, and the association between TOS, optical coherence tomography (OCT) and visual evoked potentials was examined further. RESULTS: Seventy-eight patients with a history of demyelinating disorders of the central nervous system (mean age 38.2 ± 14.2 years; 24% with acute ON) were included. No differences in the OND (3.2 ± 0.5 mm vs. 3.2 ± 0.4 mm) and ONSD (5.1 ± 0.8 mm vs. 5.1 ± 0.7 mm) measurements were found between patients with and without acute ON. Papillary swelling was more frequent in patients with acute ON (14.2% vs. 1.5%, P = 0.002). Patients with a history of previous ON were found to have lower OND (P < 0.001) and ONSD (P = 0.007) compared to patients without a history of previous ON. TOS measurements were inversely associated with disease duration and positively correlated with OCT findings. No association with visual evoked potential measurements was found. CONCLUSION: No evidence was found for TOS-sensitive differences in the OND and ONSD of patients with demyelinating diseases, according to the presence of acute ON. The association between TOS and OCT measurements deserves further investigation.

Septic shock in children in an urban area in Western Germany--outcome, risk factors for mortality and infection epidemiology.

BACKGROUND: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS: Children with septic shock aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

Early recognition of septic shock in children.

In the developed countries septic shock has a favorable outcome for the majority of previously healthy children but also in children with comorbidities if all available medical resources were used. However, septic shock remains a rare disease in children, and caregivers might not always recognize it at early stages. The resulting delay of appropriate treatment prevents lower mortality rates. The current review gives an overview of the pathophysiology of septic shock and the early clinical signs as well as new and future diagnostic approaches such as "point-of-care" laboratory tests for an early diagnosis.

Results and relevance of molecular detection of pathogens by SeptiFast--a retrospective analysis in 75 critically ill children.

BACKGROUND: Sepsis is a common cause of death in children. Early detection of bloodstream pathogens is crucial for the appropriate antibio­tic treatment. Blood cultures (BC) are the gold standard test used for detection. Recently, additional molecular detection methods of microbial DNA by multiplex PCR (SeptiFast, SF) have become available. AIM: Our retrospective study was aimed to compare results of BC to those of SF regarding results and therapeutic relevance. METHOD: We identified a total of 110 SF samples in 75 patients with suspected systemic infection by retrospective chart review. Each patient underwent SF and BC testing simultaneously. RESULTS: The initial analysis displayed no statistical significant difference in positive SF results compared to BC (p=0.19): in 26 of 110 samples (24%) microbial DNA was found. 19 BC (17%) showed microbial growth. 14 samples were positive in SF but negative in BC (13%). In patients who were pretreated with antibiotics (n=97) pathogens were identified in 24 samples by SF (25%) but only in 11 samples by BC (11%). Based on the clinical presentation and the spectrum of bacterial isolates 3 BC were considered contaminated. Considering this, SF yielded pathogens significantly more often than BC in the overall study population (p=0.04). SF results were available at least 31 h before BC results. Based on SF result antibiotic therapy was adjusted in 14 patients (13%). CONCLUSION: Molecular detection of pathogens by SF was faster and more frequently positive than BC. We have therefore demonstrated that SF might be superior to BC in testing for bloodstream pathogens. Prospective multicentric studies are required to determine whether this hypothesis can be maintained.

Use of linezolid in neonatal and pediatric inpatient facilities--results of a retrospective multicenter survey.

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

Primary HHV 6 infection after liver transplantation with acute graft rejection and multi-organ failure: successful treatment with a 2.5-fold dose of cidofovir and reduction of immunosuppression.

HHV type 6 has been reported with enhanced pathogenicity in immunocompromised patients. Herein, we report about a two-yr-old girl who experienced primary HHV 6 infection after liver transplantation. She clinically presented with graft rejection and necrotic hepatitis as well as high fever, pneumonitis with respiratory failure and a rash. Therapy with cidofovir of 5 mg/kg per wk did not show improvement, so that a full pharmacokinetic profile of cidofovir was performed. It demonstrated enhanced body weight normalized clearance of cidofovir and cidofovir dosage was augmented to 12 mg/kg per wk to reach adequate drug exposure. With additional reduction of immunosuppression, the patient dramatically improved and liver function stabilized.

When the heart kills the liver: acute liver failure in congestive heart failure.

Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases. Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach. As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST), bilirubin, and international normalized ratio (INR) did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI) was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m(2) vs. 1.6 L/min/m(2), p=0.04). Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock. In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.

Non-invasive ventilation reduces respiratory tract infections in children with neuromuscular disorders.

Non-invasive ventilation (NIV) has been shown to improve gas exchange and survival in patients with chronic neuromuscular disorders. Little is known about its influence on respiratory tract infections (RTIs). Twenty-four patients with regular use of NIV and 11 patients without NIV with neuromuscular disorders answered a questionnaire concerning the use of NIV and assisted coughing techniques, the status of influenza and pneumococcus vaccination, and the frequency and severity of RTIs. Additionally, we performed a retrospective chart review of twelve patients who were ventilated over a period of at least 5 years. In the first year of NIV consultations of a general practitioner due to RTI decreased from 9.2+/-20.8 to 3.2+/-5.3 per year (P<0.005), the number of antibiotic treatment due to RTI decreased from 4.1+/-3.4 to 1.9+/-2.2 per year (P<0.005) and the number of hospital admissions due to RTI decreased from 1.6+/-1.7 to 0.7+/-1.3 per year (P<0.005). Vaccinations against influenza and/or pneumococcus did not have a significant influence on the rate of infections. In 12 patients using NIV for more than 5 years the incidence of RTI requiring hospital admission decreased from 0.54+/-0.41/year in the pre-ventilation period to 0.12+/-0.09/year in the NIV period (P<0.005). NIV had a favorable impact on respiratory infectious complications in children with neuromuscular disorders.

Predictors of severe chest infections in pediatric neuromuscular disorders.

Chest infections are serious complications in neuromuscular disorders. The predictive values of lung and respiratory muscle function including peak cough flow still remain unclear. We performed retrospective analysis of 46 children and adolescents (12.7+/-3.7 years) in whom lung function, respiratory muscle function and peak cough flows had been obtained. Data were related to: (1). number of chest infections and days of antibiotic treatment the year prior to the study and (2). history of severe chest infection requiring hospital admission. The number of chest infections and the number of days treated with antibiotics correlated with Inspiratory Vital Capacity IVC, peak cough flow PCF and Peak Expiratory Pressure PEP. Twenty-two patients were hospitalized at least once due to severe chest infection. IVC (0.65 vs. 1.44 l; P<0.0001) and PCF (116 vs. 211 l/min; P<0.0005) in these patients were significantly lower than in the non-hospitalized group. IVC<1.1l and PCF<160 l/min were specific and sensitive thresholds to discriminate between patients who had already suffered severe chest infections and those who had not. Therefore, spirometry and peak cough flow are reliable tests to identify patients at high risk for severe chest infections. Patients with IVC below 1.1l and/or PCF below 160 l/min should be well monitored and introduced to assisted coughing techniques.

Disseminated adenovirus infection with respiratory failure in pediatric liver transplant recipients: impact of intravenous cidofovir and inhaled nitric oxide.

Adenoviruses (AdV) are opportunistic pathogens that can lead to severe infections and respiratory failure (acute respiratory distress syndrome, ARDS) with high mortality in immunosuppressed patients. Cidofovir (CDV) has been used in adenoviral disease in bone marrow transplant recipients. Two pediatric liver transplant recipients with disseminated adenoviral disease and ARDS were treated with reduction of immunosuppression, CDV, and inhaled nitric oxide (iNO). CDV 1 mg/kg was given three times per week intravenously with intravenous hydration and oral probenecid. Viral suppression and clinical improvement was achieved. AdV hepatitis did not occur, and graft function was preserved, although acute rejection occurred in both patients. Adverse effects were mild and transient not requiring dose modification. Severe hypoxemia was reversed with iNO 10-20 p.p.m. CDV treatment of AdV infections in organ transplant recipients and other immunocompromised patients should be further investigated in prospective studies.

[Diaphragmatic weakness and its impact on respiratory function in primary myopathies]. / Einfluss der Zwerchfellschwäche auf die respiratorische Funktion bei primären Myopathien.

BACKGROUND: Diaphragmatic weakness (DW) is a potential manifestation of primary myopathies. Prevalence and impact on respiratory function have not been defined. METHODS: Respiratory function (inspiratory vital capacity, IVC; maximal inspiratory muscle pressure, PImax; respiratory muscle effort, P (0.1)/PImax) and polysomnography/nocturnal capnometry (PtcCO(2)) was analysed in 49 patients with primary myopathies. DW was defined as > 25 % drop of IVC upon shift from upright to supine position. RESULTS: 19/54 (35 %) of patients, mostly AMD (68 %) and DMD (42 %) had DW. Restrictive ventilatory defect was moderate (IVC 37.2 +/- 26.2 %) in patients with and without DW (IVC 46 +/- 26 %, p = n. s.). DW caused a -33 %, respective - 25 %, supine drop of IVC and PImax, resulting in severe restriction in supine position (IVC (supine) 24.9 +/- 19.1 %, PImax (supine) 2.0 +/- 1.0 kPa, P (0.1)/PImax (supine) 19.9 +/- 12,8 %). All patients with DW and 75 % without had sleep-disordered breathing. This was significantly more severe in DW: 90 % (vs 17 % without DW) had continuous nocturnal hypoventilation (PtcCO(2) 62 +/- 2 mm Hg), 70 % (vs 18 % without DW) had combined nocturnal and diurnal hypercapnic respiratory failure (PaCO(2) 54,7 +/- 11.8 mm Hg). DW was an independent risk factor for sleep disordered breathing, for nocturnal and diurnal respiratory failure (r = 0.95, p < 0,05). Predictive thresholds thereof were accurate and identical to previously determined only for supine function data. CONCLUSION: DW is common in primary myopathies and predictive of nocturnal and diurnal respiratory failure. Supine respiratory function tests are necessary for clinical diagnosis and respiratory risk stratification.

Respiratory failure in Pompe disease: treatment with noninvasive ventilation.

In this study, noninvasive ventilation (NIV) was prospectively applied to eight patients (35.8 +/- 11.4 years) with late-onset Pompe disease and respiratory failure apparent from severe restrictive lung disease, nocturnal hypoxemia (83 +/- 8%), and daytime hypercapnia (66.7 +/- 17.9 mm Hg). The impact of NIV on respiratory function was followed for 34 +/- 17 months. Despite further decrease of vital capacity and inspiratory muscle strength, NIV normalized oxygen saturation during sleep (96 +/- 1%), daytime carbon dioxide tensions (44.1 +/- 3.6 mm Hg), and symptoms.

[Sleep-disordered breathing in neuromuscular diseases]. / Schlafbezogene Atmungsstörungen bei neuromuskulären Erkrankungen.

UNLABELLED: Sleep-disordered breathing is common in neuromuscular diseases but remains poorly defined in its relationship to daytime respiratory function. METHODS: We prospectively compared supine lung and respiratory muscle function with results of polysomnography/capnometry in 35 patients with progressive myopathies (age 32.5 +/- 15 years). RESULTS: 32/35 patients had restrictive ventilatory defect, 9/32 had hypercapnic respiratory failure by day (PaCO(2) 66.0 +/- 15.7 mm Hg). Supine inspiratory vital capacity (IVC(S)) correlated with maximal inspiratory muscle pressure (R = 0.75), respiratory muscle strain (P0.1/PImax, R = - 0.68), and daytime blood gases (p < 0.005 for all). SDB in the way of REM-sleep hypopneas, circumscribed hypoventilation episodes and sleep-stage independent continuous hypoventilation (PtcCO(2) > 50 mmHg > 50% of sleep time) was common at IVC(S)< 60% pred, and preceded daytime hypercapnia. IVC(S) correlated with nocturnal SaO(2) (R = 0.64), PtcCO(2) (R = - 0.87), percent light sleep (R = 0.67) and deep sleep (R = - 0.76). IVC(S) correlated only marginally with respiratory disturbance index (total sleep, R = - 0.45; REM-sleep, R = - 0.44). IVC(S) < 60% was 96% sensitive, 78% specific for presence of SDB. IVC(S) < 20 % was 89% sensitive, 96% specific for daytime hypercapnia. CONCLUSIONS: IVC(S) correlates with respiratory muscle function, daytime and nocturnal blood gases, and is highly predictive of SDB and daytime hypercapnia.

Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders.

The aim of the current study was to investigate the long-term impact of nocturnal noninvasive (positive-pressure) ventilation (NIV) on sleep, sleep-disordered breathing (SDB) and respiratory function in children and adolescents with progressive neuromuscular disorders (NMD). Thirty patients (12.3 +/- 4.1 yrs) with various inherited NMD were treated with NIV for ventilatory insufficiency (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep studies, spirometry and peak inspiratory muscle pressure. Ten patients were studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal gas exchange in all patients and diurnal gas exchange in patients with ventilatory insufficiency. The effects persisted over 25.3 +/- 12.7 months. Nocturnal transcutaneous partial pressure of carbon dioxide improved from (baseline versus latest control) 7.1 +/- 1.3 to 5.5 +/- 0.6 kPa (53.7 +/- 9.9 to 41.6 +/- 4.8 mmHg), diurnal carbon dioxide arterial tension from 6.3 +/- 1.6 to 5.4 +/- 0.5 kPa (47.5 +/- 11.9 to 40.6 +/- 3.6 mmHg). NIV improved respiratory disturbance index, arousals from sleep, nocturnal heart rate and sleep architecture. Vital capacity decreased in five adolescents with Duchenne muscular dystrophy -183 +/- 111 mL x yr(-1) but remained stable in 25 children with other conditions (8 +/- 78 mL x yr(-1)). Three nights withdrawal of NIV in 10 previously stable patients resulted in prompt deterioration of SDB and gas exchange back to baseline but could be instantly normalised by resumption of NIV. Noninvasive (positive-pressure) ventilation has favourable long-term impact on nocturnal and diurnal gas exchange and sleep and in patients with non-Duchenne neuromuscular disorders on vital capacity as well. It is indicated in children and adolescents with symptomatic sleep-disordered breathing or ventilatory insufficiency due to neuromuscular disorders.

Patterns and predictors of sleep disordered breathing in primary myopathies.

BACKGROUND: Sleep disordered breathing (SDB) is common in neuromuscular diseases but its relationship to respiratory function is poorly defined. A study was undertaken to identify distinct patterns of SDB, to clarify the relationships between SDB and lung and respiratory muscle function, and to identify daytime predictors for SDB at its onset, for SDB with continuous hypercapnic hypoventilation, and for diurnal respiratory failure. METHODS: Upright and supine inspiratory vital capacity (IVC, % predicted), maximal inspiratory muscle pressure (PImax), respiratory drive (P(0.1)), respiratory muscle effort (P(0.1)/PImax), and arterial blood gas tensions were prospectively compared with polysomnography and capnometry (PtcCO(2)) in 42 patients with primary myopathies. RESULTS: IVC correlated with respiratory muscle function and gas exchange by day and night. SDB evolved in three distinct patterns from REM hypopnoeas, to REM hypopnoeas with REM hypoventilation, to REM/non-REM (continuous) hypoventilation, and preceded diurnal respiratory failure. SDB correlated with IVC and PImax which yielded highly predictive thresholds for SDB onset (IVC <60%, PImax <4.5 kPa), SDB with continuous hypoventilation (IVC <40%, PImax <4.0 kPa), and SDB with diurnal respiratory failure (IVC <25%, PImax <3.5 kPa). CONCLUSION: Progressive ventilatory restriction in neuromuscular diseases correlates with respiratory muscle weakness and results in progressive SDB which, by pattern and severity, can be predicted from daytime lung and respiratory muscle function.

Sleep-disordered breathing and respiratory failure in acid maltase deficiency.

BACKGROUND: Sleep-disordered breathing (SDB) and respiratory failure (RF) are complications of acid maltase deficiency (AMD), a rare hereditary myopathy. OBJECTIVE: To define the relationship between lung and respiratory muscle function, to establish incidence and patterns of SDB, and to determine daytime predictors of SDB. METHODS: Sitting and supine lung and respiratory muscle function tests were obtained in 27 subjects with juvenile and adult AMD (aged 39 +/- 19 years) and compared with outcomes of polysomnography. RESULTS: Ventilatory restriction was present in 17/27 subjects. Inspiratory vital capacity (IVC) correlated (p < 0.005) with peak inspiratory muscle pressure (PIP, R = 0.61), respiratory muscle strain (P(0.1)/P(0.1max), R = -0.68), and gas exchange by day (PaO(2): R = 0.71; PaCO(2): R = -0.64) and night (SaO(2): R = 0.73; P(tc)CO(2): R = -0.75). Diaphragm weakness (DW) was present in 13 subjects, 10 of whom had hypercapnic RF (PaCO(2) 65 +/- 7 mm Hg), and was associated with longer disease course. SDB was found in 13 subjects, 12 with DW. It was characterized by REM-sleep hypopneas that, as ventilatory restriction worsened, were complemented by hypoventilation (P(tc)CO(2) > 50 mm Hg) first in REM sleep, then in non-REM sleep (p < 0.005). SDB was predicted by DW (sensitivity 80%, specificity 86%) and nocturnal hypoventilation by IVC < 40% (sensitivity 80%, specificity 93%). Noninvasive ventilation, instituted for daytime respiratory failure or nocturnal hypoventilation, normalized daytime and nocturnal gas exchange (p < 0.005). CONCLUSION: Vital capacity correlates with respiratory muscle function in AMD. Diaphragm weakness is the major cause of SDB and RF. SDB and nocturnal hypoventilation are predictable from daytime function tests.