Long-Term Cognitive Outcome and Brain Imaging in Adults After Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate the presence of cognitive dysfunction and brain lesions in long-term survivors after treatment with extracorporeal membrane oxygenation for severe respiratory failure, and to see whether patients with prolonged hypoxemia were at increased risk. DESIGN: A single-center retrospective cohort study. SETTING: Tertiary referral center for extracorporeal membrane oxygenation in Sweden. PATIENTS: Long-term survivors treated between 1995 and July 2009. Seven patients from a previously published study investigated with a similar protocol were included. INTERVENTIONS: Brain imaging, neurocognitive testing, interview. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients (i.e., n = 31 + 7) were enrolled and investigated in median 9.0 years after discharge. Only memory tests were performed in 10 patients, mainly due to a lack of formal education necessary for the test results to be reliable. Median full-scale intelligence quotient, memory index, and executive index were 97, 101, and 104, respectively (normal, 100 ± 15). Cognitive function was not reduced in the group with prolonged hypoxemia. Brain imaging showed cerebrovascular lesions in 14 of 38 patients (37%), most commonly in the group treated with venoarterial extracorporeal membrane oxygenation (7/11, 64%). In this group, memory function and executive function were significantly reduced. CONCLUSIONS: Patients treated with extracorporeal membrane oxygenation for respiratory failure may have normal cognitive function years after treatment, if not affected by cerebrovascular lesions. Permissive hypoxemia was not correlated with long-term cognitive dysfunction in the present study. Further prospective studies with minimal loss to follow-up are direly needed to confirm our findings.

Does permissive hypoxaemia during extracorporeal membrane oxygenation cause long-term neurological impairment?: A study in patients with H1N1-induced severe respiratory failure.

BACKGROUND: The Extracorporeal Life Support Organisation accepts permissive hypoxaemia in adult patients during extracorporeal membrane oxygenation (ECMO). The neurological long-term outcome of this approach has not yet been studied. OBJECTIVES: We investigated the prevalence of brain lesions and cognitive dysfunction in survivors from the Influenza A/H1N1 2009 pandemic treated with permissive hypoxaemia during ECMO for severe acute respiratory distress syndrome (ARDS). Our hypothesis was that this method is reasonable if tissue hypoxia is avoided. DESIGN: Long-term follow-up study after ECMO. SETTING: Karolinska University Hospital, Sweden, from October 2012 to July 2013. PATIENTS: Seven patients treated with ECMO for severe influenza A/H1N1-induced ARDS were studied 3.2 years after treatment. Blood lactate concentrations were used as a surrogate for tissue oxygenation. INTERVENTIONS: Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain. MAIN OUTCOME MEASURES: Cognitive functioning and hypoxic brain lesions after permissive hypoxaemia during ECMO. The observation period was the first 10 days of ECMO or the entire treatment period if shorter than 10 days. RESULTS: Eleven of 13 patients were still alive 3 years after ECMO. We were able to contact seven of these patients (mean age 31 years), who all agreed to participate in this study. Mean ±â€ŠSD peripherally measured arterial saturation during the observation period was 79 ±â€Š10%. Full-scale Intelligence Quotient was within one standard deviation or above from the mean of a healthy population in five patients, and was 1.5 SD below the mean in one patient. In one other patient, it could not be determined because of a lack of formal education. Memory functioning was normal in all patients. MRI showed no changes related to cerebral hypoxia. CONCLUSIONS: Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained. TRIAL REGISTRATION: at Clinicaltrials.gov NCT01763060.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants.

OBJECTIVE: To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN: This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION: This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study.

AIM: To investigate cerebral white matter (WM) abnormalities (J Pediatr 2003; 143: 171) and diffuse and excessive high signal intensities (DEHSI), (J Pediatr 1999; 135: 351) in a cohort of extremely preterm infants born in Stockholm during a 3-year period, using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: MRI at term-equivalent age was performed in 109 infants and DTI data were acquired in 54 infants. Survival rate in the entire cohort was 67%. Sixteen term-born healthy control infants were scanned for comparison. RESULTS: No or mild WM abnormalities were seen in 86% of infants and 14% had moderate or severe WM abnormalities. DEHSI were seen in infants with all grades of white matter abnormalities and were present in 56% of infants. In the WM at the level of centrum semiovale, infants with any WM abnormalities or DEHSI had lower Fractional Anisotropy and higher Apparent Diffusion Coefficient compared with control infants. No significant differences in diffusion were seen in infants without DEHSI compared with the controls in this region. Compared with controls, the preterm infants had significantly altered diffusion in the corpus callosum. CONCLUSION: Only 14% of the extremely preterm infants had moderate or severe WM abnormalities on MRI. However, the incidence of DEHSI was high. In the DEHSI regions, changes in diffusion parameters were detected, indicating altered WM organization.

Spontaneous brain activity in the newborn brain during natural sleep--an fMRI study in infants born at full term.

Recent progress in functional neuroimaging research has provided the opportunity to probe at the brain's intrinsic functional architecture. Synchronized spontaneous neuronal activity is present in the form of resting-state networks in the brain even in the absence of external stimuli. The objective of this study was to investigate the presence of resting-state networks in the unsedated infant brain born at full term. Using functional MRI, we investigated spontaneous low-frequency signal fluctuations in 19 healthy full-term infants. Resting-state functional MRI data acquired during natural sleep was analyzed using independent component analysis. We found five resting-state networks in the unsedated infant brain born at full term, encompassing sensory cortices, parietal and temporal areas, and the prefrontal cortex. In addition, we found evidence for a resting-state network that enclosed the bilateral basal ganglia.

Neuropsychologic outcomes in children with neonatal herpes encephalitis.

Neonatal herpes simplex virus infection with involvement of the central nervous system is a serious disease with high morbidity, even with acyclovir therapy. The disability includes cerebral palsy and different aspects of cognitive dysfunction which are of utmost importance for the child's future habilitation. We conducted a descriptive cohort study to define neuropsychologic outcomes and determine the relationship between neonatal neuroimaging and neuropsychologic outcomes. Among 267,690 children born in the Stockholm area over 12 years (1989-2000), 14 were diagnosed with neonatal herpes including central nervous system involvement. Nine children were neuropsychologically evaluated. Neonatal herpes virus infection had an even greater impact on cognitive function, speech ability, and attention deficit than anticipated. Relapse leading to deterioration was demonstrated in one child. Social skills were influenced to a lesser degree. Neurodevelopmental outcomes of the children were not well-correlated with extent of cerebral damage as visualized by computed tomography at 7-28 days after onset of signs. Neuropsychologic assessment is essential in the habilitation of the child, and a prerequisite for the evaluation of new treatments and for the assessment of deterioration of cerebral function related to relapses.

Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI study.

AIMS: Brain abnormalities are common in preterm infants and can be reliably detected by magnetic resonance (MR) imaging at term equivalent age. The aim of the present study was to acquire population based data on brain abnormalities in extremely low gestational age (ELGA) infants from the Stockholm region and to correlate the MR findings to perinatal data, in order to identify risk factors. METHODS: All infants with gestational age <27 weeks, born in the Stockholm region between January 2004 and August 2005, were scanned on a 1.5 T MR system at term equivalent age. Images were analysed using a previously established scoring system for grey and white matter abnormalities. RESULTS: No or only mild white matter abnormalities were observed in 82% and moderate to severe white matter abnormalities in 18% of infants. The Clinical Risk Index for Babies (CRIB II) score, use of inotropes, the presence of high-grade intraventricular haemorrhages and posthaemorrhagic ventricular dilatation were associated with white matter abnormalities. CONCLUSION: The incidence of moderate to severe white matter abnormalities in a population-based cohort of ELGA infants from the Stockholm region was 18%. To examine the clinical relevance of these promising results, neurodevelopmental follow up at 30 month corrected age, is ongoing.

Cranial CT for diagnosis of intracranial complications in adult and pediatric patients during ECMO: Clinical benefits in diagnosis and treatment.

RATIONALE AND OBJECTIVES: To evaluate the clinical utility of cranial computed tomography (CT) in pediatric and adult patients during ongoing extracorporeal membrane oxygenation (ECMO) treatment from acute respiratory failure and to assess the frequency of intracranial hemorrhage (ICH) and infarction during the treatment. MATERIALS AND METHODS: The medical records of 123 consecutive patients, 54 children (ages 3 months-17 years) and 69 adults (ages 18-62 years), treated with ECMO over a 10-year period were searched for cranial CT performed during ECMO. Indications for CT, CT findings, impact on clinical management, and patient outcome were noted. In addition, all CT scans were reviewed for the frequency of ICH or infarction. RESULTS: Seventy-eight patients had cranial CT while on ECMO. ICH or cerebral infarction were detected in 45 (37%) of the 123 patients. Eighteen patients (15%) had focal hemorrhage, 11 (9%) focal infarction, and 16 (13%) general brain edema. In 16 of the 45 patients, the CT findings were decisive to withdraw the ECMO treatment. Five patients were weaned from ECMO, and in four patients the findings motivated cranial surgery during ECMO. In the remaining 20 patients with less extended intracranial pathology, the ECMO treatment was continued with high survival. CONCLUSION: Cranial CT has an important role during ECMO treatment to reveal or exclude severe intracranial complications where ECMO treatment should be discontinued. Less severe complications have a favorable prognosis with continued treatment. Our study suggests an underreporting of intracranial complications in adults and pediatric patients on ECMO because of low utilization of neuroimaging.

MRI of the brain and thorax during extracorporeal membrane oxygenation: preliminary report from a pig model.

Early diagnosis of cerebral hypoxic ischemic complications during extracorporeal membrane oxygenation (ECMO) is important to guide further treatment. However, diagnostic methods available during ECMO are limited, especially in adults and older children. Magnetic resonance imaging (MRI) is a sensitive and noninvasive method for assessment of vessel patency and brain parenchymal changes, and for measurement of brain perfusion. The use of MRI during ECMO has, to our knowledge, never been reported. We report the first animal experiment with MRI examination during ECMO. After a preliminary test with the mobile ECMO system in the MRI environment, a healthy pig was put on venoarterial ECMO, transported to the MRI department, and examined with sequences for anatomy and function of the brain and thorax. The results showed that the ECMO system was not adversely affected by the magnetic field at a distance from the camera where positioning and examination of the animal was possible. High-quality anatomical and functional images of the brain, heart, and thoracic vessels were acquired. The results suggest that MRI may be used for early diagnosis of cranial complications in patients on ECMO. MRI may also provide a useful tool for further research on flow dynamics and brain perfusion during ECMO.

Five-year follow-up of two siblings with aspartylglucosaminuria undergoing allogeneic stem-cell transplantation from unrelated donors.

BACKGROUND: Aspartylglucosaminuria is a rare, inherited lysosomal disease characterized by a slowly progressive mental retardation and coarse facial and body features. With the intent to provide the deficient enzyme aspartylglucosaminidase, allogeneic stem-cell transplantation (ASCT) has been attempted. Only a few cases of transplants have been reported. METHODS: Two siblings with aspartylglucosaminuria underwent allogeneic bone marrow transplants using unrelated human leukocyte antigen-A, -B, and DR identical donors at ages 10 years 5 months and 5 years 10 months, respectively. They were followed during 5 years with biochemical, neuroradiologic, neuropsychologic, and clinical investigations. RESULTS: During 5 years follow-up, no neuropsychologic or clinical deterioration was noted in the children. A stable expression of aspartylglucosaminidase was found during the whole follow-up period. The spinal fluid concentration of Tau-protein, a marker of neuronal and axonal degeneration and damage, peaked at approximately 12 months after bone-marrow transplantation and then declined to almost normal levels after 5 years. By magnetic resonance imaging (MRI), an improvement of myelination in the youngest sibling and an arrest of demyelination in the older one were observed. CONCLUSION: The importance of long-term follow-up of children after ASCT in this rare, very slowly progressive lysosomal disease must be emphasized. We report that none of the children had lost any capabilities since the transplantation; moreover, an improvement is shown in biochemical markers and MRI white-matter signals, suggesting a beneficial effect.

Brain 18-FDG PET scan in central nervous system langerhans cell histiocytosis.

We used positron emission tomography (PET) to characterize cerebral metabolism in 7 patients (serial examinations in 2 patients) with central nervous system disease in Langerhans cell histiocytosis (CNS-LCH) who had neuroendocrine abnormalities (n = 7), neuropsychiatric disabilities (n = 3), and CNS degenerative disease (n = 1). The PET scan alterations occurred at localizations with known CNS-LCH disease. The PET scans revealed areas where the metabolism and function were altered in 6 of the 7 patients studied, with either an increased or a decreased metabolism (uptake of glucose). Serial examinations may indicate alterations in the degree of ongoing disease activity, but further studies on functional imaging are desired. The additional information of PET compared with MRI is the ability to detect alterations in CNS metabolic activity in certain patients with CNS-LCH. PET may also provide a tool for longitudinal follow-up of therapeutic measures in selected patients.