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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.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.Long-term follow-up study after ECMO.Karolinska University Hospital, Sweden, from October 2012 to July 2013.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.Neurocognitive outcome was studied with standardised cognitive tests and MRI of the brain.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.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 ± SD peripherally measured arterial saturation during the observation period was 79 ± 10%. 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.Permissive hypoxaemia during ECMO might not negatively affect long-term cognitive outcome if adequate organ perfusion is maintained.at Clinicaltrials.gov NCT01763060.

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.

Aim: Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. Methods: Twenty-six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. Results: CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. Conclusion: In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2–0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.

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.

Objectives Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. Methods In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. Results Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. Conclusions All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.

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 11) 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.

Purpose: To describe a child with Muscle-Eye-Brain disease (MEB), one of three types of congenital muscular dystrophy associated with ocular abnormalities. Methods: Case report. Results: The child showed severe visual impairment due to progressive myopia and retinal degeneration, a pachygyria-type of migration disorder of the brain with a nodular cortical surface, i.e. cobblestone cortex, as well as muscular weakness and severe mental retardation. Conclusion: Ophthalmological assessments are important to help to diagnose and follow children with congenital muscular dystrophy.

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).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.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.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.

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.

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 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.All infants with gestational age27 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.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.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.

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.

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.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.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.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.

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.

Primary brain tumors with prominent desmoplasia include the gliofibroma, desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA), and desmoplastic cerebral astrocytoma. In the present report, we describe unusual pathological appearances in two successive resections of a left temporal tumor in a patient with complex partial seizures. Both tumors showed focal astroglial and very prominent neuronal differentiation. In the first resection at age 11 years, the tumor showed only focal desmoplastic areas and prominent neuronal differentiation with bizarre atypical giant cells. In the second resection at age 14 years, the morphology was dramatically different. Now the tumor showed marked desmoplasia with tumor cells coexpressing neuronal and glial markers. Electron microscopy showed prominent neuronal differentiation in both resections and presence of basal lamina around tumor cells. Our case represents a unique example of an extraordinary degree of neuronal differentiation in a desmoplastic cerebral tumor. While cellular pleomorphism in a desmoplastic tumor traditionally suggests the diagnosis of PXA, we wish to underscore that many cells exhibiting marked cytologic atypia may in fact be of neuronal rather than of glial origin as in our case.

This paper illustrates the cases of two infants with an identical appearance of a periventricular band (PVB) of increased echogenicity on cranial sonography, shown on CT to be due to edema in one and calcification in the other. Such a PVB due to edema has not been reported previously, and its similarity to calcification on sonography is emphasized.

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

106 Neonatal Magnetic Resonance Imaging in Extremely Low Gestational Age Infants and Outcome at 30 Months

Top of pageAbstract Aim/ subject: Magnetic resonance imaging (MRI) has contributed to the understanding of brain damage in infants with extremely low gestational age (ELGA

MR COMPATIBLE INCUBATOR AND QUIET IMAGING SEQUENCES FOR THE EXAMINATION OF NEWBORN INFANTS 29

Ten patients with findings at computed tomography (CT) suggesting intracranial supratentorial glioma were investigated to compare the diagnostic efficacy of this technique with that of positron emission tomography (PET) using11C-methionine and exminations with magnetic resonance (MR). The findings were related to histopathologic examination of serial stereotactic biopsies, which were guided by the appearance of the lesions on PET examination. To obtain corresponding slice orientation with the different examination techniques, an individually shaped helmet fixation was used. However, in 3 cases this fixation device could not be used for MR. Histopathologic diagnosis, obtained in all cases from multiple target stereotactic biopsies, included glioma in 9 patients and reactive gliosis in one case. A detailed comparison of the three imaging techniques and the findings at stereotactic biopsies was possible in 7 patients, while in 3 patients comparison with MR was less exact due to the patient's refusal to wear the helmet during this examination. MR was the most accurate method for outlining the total extent of a lesion, i.e. the tumor and the edema surrounding it. Four lesions had homogeneous signal characteristics and in 6 lesions two (or more) compartments could be distinguished with MR. In 5 cases the MR findings were in complete agreement with the histopathologic findings. However, a thorough correlation between signal characteristics and histology was not possible. Using PET the occurrence and the extent of tumor tissue was correctly predicted in 7 patients. The PET was normal in one case. Findings at CT were in agreement with the histopathologic diagnosis in 5 patients. MR was the most sensitive method for the detection of lesions. PET using methionine appeared to have a somewhat higher capacity to outline correctly the true extent of a tumor. The combination of CT and PET was superior to MR for determining the type and grade of the tumors.

Five patients with glioma were examined with positron emission tomography using ([11C]methyl)-L-methionine. The study was repeated while the patient was being infused with branched chain amino acids (BCAA), 250 μmol/min. The accumulation rates of methionine in tumor tissue and in normal brain tissue were compared without and with the infusion of amino acids. Both tumor tissue and normal brain tissue showed a reduction in the methionine accumulation by 35% while the patient received the infusion. In one patient with a severe blood-tissue barrier disruption the tumor accumulation rate was unaffected. It is concluded that in gliomas without severe blood-tissue barrier disruption, the accumulation of methionine is governed by processes exhibiting similar properties regarding competition with BCAA as in normal brain tissue.

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.

Disruption of the blood brain barrier or rather blood tumour barrier in cerebral tumours was studied with CT after intravenous injection of contrast medium and with PET after intravenous administration of 68-Ga-EDTA. Histology from stereotactic biopsies or open surgery is compared with the radiologic findings and advantages of the respective methods are discussed. The material consisted of 47 patients mainly with supratentorial gliomas and a few miscellaneous tumours. Astrocytomas (Kernohan grade II) were found to have no disruption of blood tumour barrier while anaplastic astrocytomas and glioblastomas (Kernohan grade III and IV) had. PET is somewhat superior to CT in detection of disruption of the blood tumour barrier. It is concluded that the combination of CT and PET is of value in the assessment of intracranial tumours.

Patients with clinically suspected intracranial tumours are as a rule examined with computed tomography before and after intravenous injection of contrast medium. This is often sufficient to establish an accurate diagnosis especially in tumours which enhance after contrast injection. Expanding lesions which only lower the attenuation diffusely are much more difficult to delineate.

Four cases with lesions suspected to be low-grade intracerebral tumours but later proved to be cavernous haemangiomas are described. The patients were examined with contrast enhanced CT and with positron emission tomography (PET). The lesions were partly calcified with a mild or no mass effect and a slight contrast enhancement at CT. There were signs of disrupture of the blood-lesion barrier also on radionuclide studies. PET with11C-methionine and11C-glucose showed a normal or decreased accumulation of the tracers. This combination of findings has not been encountered in intracranial tumours. As a comparison, one case of glioblastoma is described. In this patient, the CT findings suggested a cavernous haemangioma. However, PET showed a markedly increased accumulation of11C-methionine, which is compatible with brain tumour but not with haemangioma.

Carbon-11-labelled glycine has been prepared by a Bucherer-Strecker synthesis using [11C]cyanide, formaldehyde and ammonium carbonate. Total synthesis time, including chromatographic purification, was 30-35 min from end-of-bombardment. Radiochemical yield was 35%, based on [11C]cyanide and radiochemical purity was shown to be greater than 98% by analytical HPLC. The 11C-labelled glycine thus prepared was used along with [68Ga]EDTA and L-[methyl-11C]methionine in the visualization of an anaplastic astrocytoma by positron emission tomography.