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Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.

ABSTRACT: Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes in water distribution of the brain tissue that may relate to the pathogenesis of hepatic encephalopathy (HE). We designed a study to investigate the disturbances in brain water and metabolites during episodic HE using a 3-T MR scanner. Cirrhotic patients with different grades of HE underwent MR during hospitalization (n=18). The MR was repeated at 6 weeks' follow-up (n=14). The results were compared with those of a group of healthy volunteers (n=8). During episodic HE, brain diffusion-weighted imaging showed a high apparent diffusion coefficient (ADC) (12% to 14%) that decreased during follow-up (-1% to -4%). These disturbances were accompanied by high glutamine (581%), low choline (-31%), and low myo-inositol (-86%) peaks on MR spectroscopy. In overt HE, patients showed high glutamine that decreased during follow-up (-22%). In addition, these patients exhibited a rise in plasma S100 beta and enlargement of brain white-matter lesions. In conclusion, several disturbances detected by MR support the presence of impaired brain water homeostasis during episodic HE. Although astrocytes have a major role in this condition, brain edema during episodic HE may be extracellular and does not appear to be directly responsible for the development of neurologic manifestations.

SUBMITTER: Chavarria L

PROVIDER: S-EPMC3564202 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.

Chavarria Laia L Alonso Juli J García-Martínez Rita R Simón-Talero Macarena M Ventura-Cots Meritxell M Ramírez Clara C Torrens Maria M Vargas Víctor V Rovira Alex A Córdoba Juan J

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20121121 2

Brain magnetic resonance (MR) study has shown metabolic abnormalities and changes in water distribution of the brain tissue that may relate to the pathogenesis of hepatic encephalopathy (HE). We designed a study to investigate the disturbances in brain water and metabolites during episodic HE using a 3-T MR scanner. Cirrhotic patients with different grades of HE underwent MR during hospitalization (n=18). The MR was repeated at 6 weeks' follow-up (n=14). The results were compared with those of a ...[more]

PMID: 23168529

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Project description:BackgroundIn neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy.MethodsWe did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711.FindingsBetween Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97).InterpretationThalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration.FundingNational Institute for Health Research UK.

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Project description:Background: Hypoxic-ischemic encephalopathy (HIE) is a major contributor to child mortality and morbidity. Reliable prognostication for HIE is of key importance. Proton magnetic resonance spectroscopy (1H-MRS) is a quantitative, non-invasive method that has been demonstrated to be a suitable complementary tool for prediction. The aim of this study was to investigate the prognostic capability of 1H-MRS in the era of therapeutic hypothermia (TH). Methods: Databases, namely MEDLINE, Embase, Web of Science, and the Cochrane library (Cochrane Center Register of Controlled Trials), were searched for studies published before July 17, 2017. Study selection and data extraction were performed by two independent reviewers. The mean difference (MD) or standardized MD (SMD) and 95% confidence interval (CI) were calculated using random-effects models. Subgroup analyses were conducted based on the use of TH. Results: Among the 1,150 relevant studies, seven were included for meta-analysis, but only two small studies were conducted under TH. For 1H-MRS measurement, three peak area ratios revealed predictive values for adverse outcomes in TH subgroup and the combined results (with and without TH): N-acetylaspartate (NAA)/creatine in basal ganglia/thalamus (BG/T) in TH (MD -0.31, 95%CI -0.55 to -0.07) and combined results (MD -0.37, 95% CI -0.49 to -0.25); NAA/choline in BG/T in TH (MD -0.89, 95%CI -1.43 to -0.35) and combined results (MD -0.25, 95%CI -0.42 to -0.07); and myo-inositol/choline in cerebral cortex in TH (MD -1.94, 95%CI -3.69 to -0.19) and combined results (MD -1.64, 95%CI -2.64 to -0.64). Moreover, NAA relative concentration is associated with adverse outcomes: in TH (MD -0.04, 95%CI -0.06 to -0.02) and combined results (MD -0.06, 95%CI -0.11 to -0.01) in white matter; in TH (MD -0.04, 95%CI -0.07 to -0.01) and combined results (MD -0.05, 95%CI -0.07 to -0.02) in gray matter. Conclusions: NAA may be a potential marker in outcome prediction for all HIE subjects. It seems that MDs for the ratios including NAA are larger than for its relative concentration, and therefore are more likely to be measurable in a clinical context. Larger prospective multicenter studies with a standardized protocol for both measurement protocols and analysis methods are required in future studies.

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Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.

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Brain magnetic resonance spectroscopy in episodic hepatic encephalopathy.

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