Cerebral Proton Magnetic Resonance Spectroscopy Research Articles

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease

BackgroundCongenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation. ObjectivesThe primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes. MethodsPregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel. ResultsWe acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04). ConclusionsCHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.

Feed-forward neural networks using cerebral MR spectroscopy and DTI might predict neurodevelopmental outcome in preterm neonates

ObjectivesWe aimed to evaluate the ability of feed-forward neural networks (fNNs) to predict the neurodevelopmental outcome (NDO) of very preterm neonates (VPIs) at 12 months corrected age by using biomarkers of cerebral MR proton spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) at term-equivalent age (TEA).MethodsIn this prospective study, 300 VPIs born before 32 gestational weeks received an MRI scan at TEA between September 2013 and December 2017. Due to missing or poor-quality spectroscopy data and missing neurodevelopmental tests, 173 VPIs were excluded. Data sets consisting of 103 and 115 VPIs were considered for prediction of motor and cognitive developmental delay, respectively. Five metabolite ratios and two DTI characteristics in six different areas of the brain were evaluated. A feature selection algorithm was developed for receiving a subset of characteristics prevalent for the VPIs with a developmental delay. Finally, the predictors were constructed employing multiple fNNs and fourfold cross-validation.ResultsBy employing the constructed fNN predictors, we were able to predict cognitive delays of VPIs with 85.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99.1% negative predictive value (NPV). For the prediction of motor delay, we achieved a sensitivity of 76.9%, a specificity of 98.9%, a PPV of 90.9% and an NPV of 96.7%.ConclusionFNNs might be able to predict motor and cognitive development of VPIs at 12 months corrected age when employing biomarkers of cerebral 1H-MRS and DTI quantified at TEA.Key Points• A feed-forward neuronal network is a promising tool for outcome prediction in premature infants.• Cerebral proton magnetic resonance spectroscopy and diffusion tensor imaging can be used for the construction of early prognostic biomarkers.• Premature infants that would most benefit from early intervention services can be spotted at the time of optimal neuroplasticity.

Differences in the variability of cerebral proton magnetic resonance spectroscopy (1H-MRS) measurements within three HIV-infected cohorts.

Cerebral functional impairment remains prevalent in effectively treated HIV-infected subjects. As the results of formal cognitive testing are highly variable, surrogate markers to accurately measure cerebral function parameters are needed. Such markers include measurement of cerebral metabolite ratios (CMR) using proton magnetic resonance spectroscopy (1H-MRS). However, data on the inter-subject variability of CMR are sparse. Our aim was to assess inter-subject variability in CMRs within three different HIV-infected cohorts. Cerebral 1H-MRS was performed using a Phillips Achieva™ 1.5 Tesla magnetic resonance scanner in HIV-infected subjects as follows: 12 subjects before (group 1) and after intensification of antiretroviral therapy with maraviroc (group 2) and 13 subjects with acute viral hepatitis C (HCV) co-infection (group 3). The coefficients of variation (CV) for CMRs in each group were determined and compared using non-parametric tests to determine whether the inter-subject variability differed significantly. All baseline characteristics between the groups were similar. Overall CVs for all CMRs in groups 1, 2 and 3 were 32.3%, 33.2% and 23.4%, respectively (group 1 vs. 2, p=0.863; group 1 vs. 3, p=0.076). On testing for differences in variability between individual CMRs, two metabolites in the right basal ganglia (RBG) had statistically significantly different CVs when comparing group 1 with group 3: N-acetyl aspartate/creatine (NAA/Cr), p=0.029 and myo-Inositol/creatine (mI/Cr), p=0.016. The variability of 1H MRS-measurable CMRs in HIV-infected individuals was lower in those with acute HCV co-infection (group 3).We can conclude that the use of these CMRs in 1H MRS imaging in patients with HIV/acute HCV co-infection is more reliable to assess cerebral function than in patients with HIV infection alone. This has implications for future sample size estimations.

PC.45 Quantification of N-Acetylaspartate Concentration in the Neonatal Brain: Initial Results from the Multi-Centre Marble Study

BackgroundEarly cerebral proton magnetic resonance spectroscopy (MRS) predicts medium-term outcomes in neonatal encephalopathy (NE). Metabolite peak-area ratios are most commonly used for prognosis, but conflate pathological information from different metabolites....

Acute HCV/HIV Coinfection Is Associated with Cognitive Dysfunction and Cerebral Metabolite Disturbance, but Not Increased Microglial Cell Activation

BackgroundMicroglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.MethodsA case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy (1H-MRS) and positron emission tomography (PET) using a 11C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling.ResultsTwenty-four aHCV cases completed NCT and 1H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent 1H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on 1H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in 11C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations.DiscussionPoorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher 11C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.

Two patterns of cerebral metabolite abnormalities are detected on proton magnetic resonance spectroscopy in HIV-infected subjects commencing antiretroviral therapy

Cerebral function impairment remains problematic in subjects with chronic human immunodeficiency virus (HIV) infection despite effective combination antiretroviral therapy (cART). Using cerebral proton magnetic resonance spectroscopy ((1)H MRS), we aimed to determine if abnormalities could be detected in neurologically asymptomatic HIV-infected subjects electively commencing cART. Therapy-naive, HIV-infected individuals and HIV-uninfected controls underwent (1)H MRS in several anatomical voxels including the mid-frontal grey matter (FGM) and right basal ganglia (RBG). Differences in cerebral metabolite ratios between groups and correlations between immune and virological status were assessed. Forty-six subjects were recruited (26 HIV-infected and 20 control subjects). In the HIV-infected group, mean CD4+ count (SD, cells per microlitre) and plasma HIV RNA (SD, log10 copies per millilitre) were 192 (86) and 4.71 (0.64), respectively. Choline (Cho)/Creatine (Cr) and myoinositol (MI)/Cr ratios were significantly lower in the FGM in HIV-infected subjects compared to controls (0.67 (0.14) versus 0.88 (0.49), p = 0.036, and 0.94 (0.28) and 1.17 (0.26), p = 0.008, for Cho/Cr and MI/Cr, respectively) and Cho/Cr ratio associated with CD4+ lymphocyte count (p = 0.041). N-Acetyl-aspartate (NAA)/Cho ratio was significantly lower in the RBG in HIV-infected subjects compared to controls (2.27 (0.54) versus 2.63 (0.68), p = 0.002), and this was associated with greater plasma HIV RNA load (p = 0.014). Two patterns of cerebral metabolite abnormalities were observed in HIV-infected subjects electively commencing cART. Greater inflammatory metabolite ratios (Cho/Cr and MI/Cr) associated with lower markers of peripheral immune markers (CD4+ lymphocyte count) in the FGM and lower neuronal metabolite ratios (NAA/Cho) associated with greater HIV viraemia in the RBG were present in HIV-infected subjects.

Cerebral microglial activation in patients with hepatitis c: in vivo evidence of neuroinflammation

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.

Influence of hepatitis C virus on neurocognitive function in patients free from other risk factors: validation from therapeutic outcomes

Mild neurocognitive dysfunction and altered cerebral proton magnetic resonance spectroscopy ((1) H-MRS) have been demonstrated in patients with chronic hepatitis C (CHC). This longitudinal study aimed to quantify these abnormalities in a cohort of patients free from correlated risk factors and determine whether treatment-induced viral clearance abolished these abnormalities. Treatment-naïve, non-cirrhotic patients with CHC, rigorously screened and excluded for other causes of impaired neurocognition, underwent neurocognitive testing, (1) H-MRS and evaluation for quality of life (QOL), mood and fatigue, before and 6 months after the completion of antiviral therapy. A comparison group of healthy controls was similarly assessed at baseline and 1 year later. Post-treatment results in 40 patients with CHC [31 sustained virological responders, hepatitis C virus (HCV)-R and 9 non-responders, HCV-NR] were compared with their pretreatment results, and with the baseline and follow-up assessments of 39 healthy controls. Before receiving treatment, patients had impaired learning efficiency, poorer QOL and higher fatigue scores compared with the controls. Viral clearance was associated with a significant albeit small improvement in the QOL score that did not reach control levels. Cerebral (1) H-MRS demonstrated a lower N-acetyl aspartate/creatine (CRE) ratio in the globus pallidus (GP) of patients with hepatitis C, which was unchanged with viral clearance. The GP choline/CRE ratio increased in HCV-R following treatment, without a correlation with cognitive measures. The hepatitis C virus has a measurable effect on CNS integrity in patients screened for other medical and/or psychiatric comorbidities. Viral clearance has not been demonstrated to abolish these abnormalities.

Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.

Secondary creatine deficiency in ornithine delta-aminotransferase deficiency

Aims Ornithine delta-aminotransferase (OAT) deficiency causes gyrate atrophy (GA) of the retina, as a consequence of high plasma ornithine concentrations. Because creatine synthesis requires the conversion of arginine and glycine into ornithine and guanidinoacetate, high ornithine concentration inhibits this reaction thus causing secondary creatine deficiency. The aim of this study was to evaluate the neuropsychological features and creatine metabolism in patients with GA. Methods The study involved 7 GA patients, aged from 11 to 27 years who underwent neuropsychological evaluation and cerebral proton magnetic resonance spectroscopy (MRS). Results Neurocognitive impairment was found in 5/7 patients, including mental retardation (3/7), school failure (1/7), major visuospatial dyspraxia (1/7), aggressive behavior (3/7) and epilepsy (2/7). Two patients had normal neuropsychological evaluation. Cerebral proton magnetic resonance spectroscopy revealed a profound creatine deficiency in all patients. MRS data were confirmed by decreased levels of creatine and/or guanidinoacetate in plasma and urine in all patients. Conclusions In our group of patients with GA, we found a high prevalence of neurological impairment, not reported so far, and possibly related to secondary creatine deficiency and hyperornithinemia. We propose to treat mentally retarded GA patients with high doses of creatine, as it may normalize brain creatine levels and help to reduce ornithine levels.

Cerebral immune activation in chronic hepatitis C infection: A magnetic resonance spectroscopy study

Abnormal cerebral metabolism and cognitive impairments have been reported in patients with chronic hepatitis C (HCV) but studies have failed to demonstrate a relationship between these findings. Twenty-five HCV-positive patients with histologically-mild liver disease were studied with cerebral proton magnetic resonance spectroscopy (MRS), using acquisition parameters to quantify myo-inositol (mI) and other metabolites in frontal white matter (FWM). Patients underwent automated attention and working memory tests (Cognitive Drug Research test system). The mean mI/ creatine ratio in the HCV+ve patients (0.64, SD 0.21) was significantly higher (p=0.02) than in healthy controls (0.52, SD 0.10). On cognitive testing, the HCV+ve patients showed impairments in 2/4 composite scores, reflecting working memory and attention, compared to normative data from healthy volunteers (p<0.005) and HCV-ve controls (p=0.03). There was a significant association between elevated FWM mI/creatine and prolonged working memory reaction times (R=0.72, p=0.002). Elevated FWM mI/ creatine is a feature of HIV-related minor cognitive-motor disorder. It is associated with infection and immune activation of microglial cells. The similar findings in this study suggest that cerebral immune activation may also occur in HCV infection. This may underlie the mild neurocognitive impairment and neuropsychological symptoms observed in a proportion of patients.

Usefulness of Magnetic Resonance Spectroscopy in Urea Cycle Disorders

Late-onset urea cycle disorders are characterized by chronic encephalopathy and a risk of hyperammonemic crises triggered by environmental stressors. Reported here is the case of a 30-year-old woman with chronic encephalopathy due to argininosuccinate lyase deficiency. Cerebral proton magnetic resonance spectroscopy showed brain creatine deficiency and its normalization during treatment. These findings are in keeping with recent reports suggesting that creatine deficiency is involved in the neurological dysfunction of urea cycle disorders and demonstrate the usefulness of magnetic resonance spectroscopy in the diagnosis and follow-up of urea cycle disorders.

Phenotypic Variability Among Adult Siblings With Sjögren-Larsson Syndrome

Sjögren-Larsson syndrome (SLS) is an early childhood-onset disorder with ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy caused by the deficiency of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene (the gene that encodes microsomal fatty aldehyde dehydrogenase). Cerebral proton magnetic resonance spectroscopy in those with SLS demonstrates an abnormal white matter peak at 1.3 ppm, consistent with long-chain fatty alcohol accumulation. To define the clinical course and proton magnetic resonance spectroscopic findings of SLS in adults. Case series in a tertiary care center. Six siblings of a consanguineous Arab family with early childhood-onset SLS who carry the 682C-->T mutation in the ALDH3A2 gene were reinvestigated in adulthood. The 6 affected siblings ranged in age from 16 to 36 years. All exhibited the typical clinical and imaging manifestations of SLS, but their severity markedly varied. Neurological involvement was apparently nonprogressive, and its severity showed no correlation with age. Cerebral proton magnetic resonance spectroscopy showed a lipid peak at 1.3 ppm, with decreasing intensity in the older siblings. These observations document significant clinical variability and the nonprogressive neurological course of SLS in adult siblings with the same ALDH3A2 genotype, and demonstrate possible correlation of proton magnetic resonance spectroscopic changes with age, suggesting unknown pathogenic mechanisms to compensate for the responsible biochemical defect in this disease.

Hepatitis C virus infection affects the brain—evidence from psychometric studies and magnetic resonance spectroscopy

Up to 50% of patients infected with the hepatitis C virus (HCV) complain of chronic fatigue and difficulties in concentration and memory. The aim of the present study was to seek evidence for the presence of central nervous system involvement in HCV infected patients with only mild liver disease. Thirty HCV infected patients with normal liver function, 15 of whom were identified as having mild and 15 moderate to severe fatigue using the fatigue impact scale, underwent neurological and neuropsychological examination, electroencephalography (EEG) and cerebral proton magnetic resonance imaging (MRI) and spectroscopy (MRS). Fifteen healthy volunteers, matched for age and educational attainment, served as controls. In comparison to the healthy controls the patients with HCV infection showed evidence of cognitive impairment, primarily attention and higher executive functions, higher levels of anxiety and depression and impairment of quality of life. In addition they showed a significant decrease of the N-acetyl-aspartate/creatine ratio in the cerebral cortex on 1H MRS while the EEG was slowed in 25%. In general the deficits were more marked in the patients with moderate rather than mild fatigue. The data provide evidence of central nervous system involvement in patients with HCV infection.

In vivo MR spectroscopy in diagnosis and research of neuropsychiatric disorders

Magnetic resonance spectroscopy is one of the most important tools for quantitative analysis of chemical composition and structure, and this non-invasive technique is now being applied in vivo to study biochemical processes in those neuropsychiatric disorders that are part of the phospholipid spectrum. Interpretation of a clinical magnetic resonance spectrum can provide information about membrane phospholipid turnover, cellular energetics, neuronal function, selected neurotransmitter activity and intracellular pH. Cerebral proton and phosphorus magnetic resonance spectroscopy findings are summarized in relation to schizophrenia, dyslexia and chronic fatigue syndrome.

Cerebral proton magnetic resonance spectroscopy of a patient with giant axonal neuropathy

Magnetic resonance imaging of a girl with giant axonal neuropathy revealed a progressive white matter disease. In close agreement with histopathological features reported previously, localized proton magnetic resonance spectroscopy at 9 and 12 years of age indicated a specific damage or loss of axons (reduced N-acetylaspartate and N-acetylaspartylglutamate) accompanied by acute demyelination (elevated choline-containing compounds, myo-inositol, and lactate) in white matter as well as a generalized proliferation of glial cells (elevated choline-containing compounds and myo-inositol) in both gray and white matter.

Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease

Patients with chronic hepatitis C virus (HCV) infection frequently report fatigue, lassitude, depression, and a perceived inability to function effectively. Several studies have shown that patients exhibit low quality-of-life scores that are independent of disease severity. We therefore considered whether HCV infection has a direct effect on the central nervous system, resulting in cognitive and cerebral metabolite abnormalities. Twenty-seven viremic patients with biopsy-proven mild hepatitis due to HCV and 16 patients with cleared HCV were tested with a computer-based cognitive assessment battery and also completed depression, fatigue, and quality-of-life questionnaires. The HCV-infected patients were impaired on more cognitive tasks than the HCV-cleared group (mean [SD]: HCV-infected, 2.15 [1.56]; HCV-cleared, 1.06 [1.24]; P = .02). A factor analysis showed impairments in power of concentration and speed of working memory, independent of a history of intravenous drug usage (IVDU), depression, fatigue, or symptom severity. A subgroup of 17 HCV-infected patients also underwent cerebral proton magnetic resonance spectroscopy (1H MRS). The choline/creatine ratio was elevated in the basal ganglia and white matter in this group. Patients who were impaired on 2 or more tasks in the battery had a higher mean choline/creatine ratio compared with the unimpaired patients. In conclusion, these preliminary results demonstrate cognitive impairment that is unaccounted for by depression, fatigue, or a history of IVDU in patients with histologically mild HCV infection. The findings on MRS suggest that a biological cause underlies this abnormality. (HEPATOLOGY .)

Correlation between neuropsychometric scores and cerebral proton magnetic resonance spectroscopy (1H-MRS) in chronic hepatitis C infection

Correlation between neuropsychometric scores and cerebral proton magnetic resonance spectroscopy (1H-MRS) in chronic hepatitis C infection

Correlation between neuropsychometric scores and cerebral proton magnetic resonance spectroscopy (1H-MRS) in chronic hepatitis C infection

Correlation between neuropsychometric scores and cerebral proton magnetic resonance spectroscopy (1H-MRS) in chronic hepatitis C infection

Early brain proton magnetic resonance spectroscopy and neonatal neurology related to neurodevelopmental outcome at 1 year in term infants after presumed hypoxic–ischaemic brain injury

This study investigated the accuracy of prediction of neurodevelopmental outcome at 1 year using cerebral proton magnetic resonance spectroscopy (MRS) and structured neonatal neurological assessment in term infants after presumed hypoxic-ischaemic brain injury. Eighteen control infants and 28 infants with presumed hypoxic-ischaemic brain injury underwent proton MRS investigation. Studies were carried out as soon as possible after the cerebral insult, most within 48 hours. Infants had an early structured neurological assessment at a median of 19 hours (range 0 hours to 9 days) from the presumed hypoxic-ischaemic insult and a late assessment at a median of 7 days (range 3 to 25 days) during recovery. The maximum cerebral peak-area ratio lactate:N-acetylaspartate measured by proton MRS accurately predicted adverse outcome at 1 year with a specificity of 93% and positive predictive value of 92%. Neurological assessment had a tendency for false-positive predictions. However, both early and late neurological examination can be used as a reliable indicator for a favourable outcome at 1 year having negative predictive values of 100% and 91% respectively.