Hypoxic encephalopathy after near-drowning studied by quantitative 1H-magnetic resonance spectroscopy.

Abstract

Early prediction of outcome after global hypoxia of the brain requires accurate determination of the nature and extent of neurological injury and is cardinal for patient management. Cerebral metabolites of gray and white matter were determined sequentially after near-drowning using quantitative 1 H nuclear magnetic resonance spectroscopy (MRS) in 16 children. Significant metabolite abnormalities were demonstrated in all patients compared with their agematched normal controls. Severity of brain damage was quantified from metabolite concentrations and ratios. Loss of N -acetylaspartate, a putative neuronal marker, from gray matter preceded that observed in white matter and was more severe. Total creatine decreased, while lactate and glutamine/glutamate concentrations increased. Changes progressed with time after injury.A spectroscopic prognosis index distinguished between good outcome ( n ϭ 5) and poor outcome ( n ϭ 11) with one false negative (bad outcome after borderline MRS result) and no false positive results (100% specificity). The distinction was made with 90% sensitivity early (after 48 h) and became 100% later (by days 3 and 4). This compared with 50-75% specificity and 70-100% sensitivity based upon single clinical criteria.MRS performed sequentially in occipital gray matter provides useful objective information which can significantly enhance the ability to establish prognosis after near-drowning. ( J. Clin. Invest. 1996. 97:1142-1154.)

Clinical experience with 13C MRS in vivo

“…A novel (unpublished) finding in the same experiment, is that in hypoxic infant brain, glutamine rather than glutamate accumulates. This directly confirms the earlier and often controversial findings of short-TE 1 H MRS 23 and demands a re-thinking of the neuroscientists' dogma that it is toxic accumulation of glutamate which causes hypoxic neuronal injury. 24 Because NOE and proton decoupling in vivo and in vitro are similar, but not identical, a study of all the expected brain metabolites was undertaken using a series of phantoms.…”

“…2,3 It is the purpose of this Review to examine the hypothesis that dynamic analysis of metabolite flux rates in vivo is more powerful in clinical investigation than static analysis. In other words, that 13 C NMR after enrichment provides more useful diagnostic information than other steady-state concentration measurements using 1 H, 31 P, 23 Na etc., and thereby compensates for its poor sensitivity.…”

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

“…The Lac/Cr ratio during the subacute phase of stroke in humans ha been particularly useful in determining long term outcome, and is more predictive than diffusion weighted imaging of infarct size alone (Parsons et al, 2000;Walker et al, 2004). Kreis and colleagues provide evidence from studies after near-drowning that NAA levels in the human brain respond to hypoxia in a similar way to that described for animals (Kreis et al, 1996). In children examined repeatedly with quantitative MRS, T½ for NAA was estimated at about 48 hours after neardrowning.…”

“…In vivo MRS studies support the hypothesis of NAA as a surrogate for neuronal loss and dysfunction, and the clinically associated neurological deficits observed in patients after local or global hypoxia-ischemic incidents. Outcome predictions based upon residual NAA, and increased lactate levels in localized proton spectra have proved rather accurate in such varied ischemia settings as stroke (Barker and Gillard, 2005;Parsons et al, 2000;Wild et al, 2000), neonatal hypoxia (Barkovich et al, 1999;Cappellini et al, 2002), and near-drowning in children (Kreis et al, 1996). 1.1.2.…”

Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapeutic decision making

“…Here we know of only one report in which 1 H MRS actually influenced patient outcome. 42 With the approval of the local Hospital Ethics Committee, ventilator support was terminated if 1 H MRS findings, clinical neurology, and EEG all concurred in predicting vegetative outcome as the result of near-drowning. The complexity of researching efficacy in a disease when there is no treatment is well recognized.…”