Proton Spectroscopy Detected Myoinositol in Children with Traumatic Brain Injury

Abstract

Previous studies have shown that proton magnetic resonance spectroscopy (MRS) is useful in predicting neurologic prognosis in children with traumatic brain injury (TBI). Reductions in N-acetyl derived metabolites and presence of lactate have been predictive of poor outcomes. We examined another spectroscopy metabolite, myoinositol (mI), to determine whether it is altered after TBI. Found primarily in astrocytes, mI functions as an osmolyte and is involved in hormone response pathways and protein-kinase C activation. Myoinositol is elevated in the newborn brain and is increased in a variety of diseases. We studied 38 children (mean age 11 y; range 1.6 -17 y) with TBI using quantitative short echo time occipital gray and parietal white matter proton MRS at a mean of 7 d (range 1-17 d) after injury. We found that occipital gray matter mI levels were increased in children with TBI (4.30 Ϯ 0.73) compared with controls (3.53 Ϯ 0.48; p ϭ 0.003). We also found that patients with poor outcomes 6 -12 mo after injury had higher mI levels (4.78 Ϯ 0.68) than patients with good outcomes (4.15 Ϯ 0.69; p Ͻ 0.05). Myoinositol is elevated after pediatric TBI and is associated with a poor neurologic outcome. The reasons for its elevation remain unclear but may be due to astrogliosis or to a disturbance in osmotic function. Over the past decade, proton magnetic resonance spectroscopy (MRS) has been proven helpful in evaluating adults and children with traumatic brain injury (TBI) (1,2). Reductions in the neuronal marker N-acetyl aspartate (NAA) and in creatine (Cre), a marker of cell energy metabolism, as well as increases in choline (Cho), an indicator of membrane disruption, occur within the first several days. In adults, the magnitude of these metabolite changes correlate with the severity of injury and also with neurologic and neuropsychological outcomes (3,4). Our previous studies in children have also confirmed these findings (5,6).Myoinositol (mI) is another metabolite that can be detected using short echo time spectroscopy. Myoinositol is found primarily in astrocytes and functions as a marker of astrocytic activity. It serves as an osmolyte, and is involved in phosphoinositide-mediated signal transduction. Myoinositol as detected by MRS has been shown to be elevated in the newborn brain and is increased in Alzheimer's disease, renal failure, diabetes mellitus, bipolar disease, use of lithium, hypoxia, hyperosmolar states, in some patients with Canavan disease and after severe neonatal encephalopathy (7,8). It may be decreased in chronic hepatic encephalopathies, stroke, tumor, infection and low-grade malignancies.Within the first hours after TBI, the complex process referred to as reactive astrocytosis, astrogliosis, or glial scarring begins (9). After the initial injury, which is accompanied by ABSTRACT630

Correlation of MR Imaging and MR Spectroscopy Findings with Cognitive Impairment in Mucopolysaccharidosis II

“…24 Studies from primate models showed significant correlation between markers of astrogliosis and mIns/Cr ratios. [25][26][27][28][29][30] For these reasons, mIns is considered to be a glial marker, and an increase in its content is believed to represent glial proliferation or an increase in glial cell size. Because intraneuronal deposition of GAG and microglial activation in MPS models have been reported in the literature, 22,31 it is possible that cerebral GAG deposition is responsible for inducing the changes in glial cells that can be measured by MR spectroscopy as an elevation of mIns/Cr ratio.…”

MR spectroscopy: Predicting long‐term neuropsychological outcome following pediatric TBI

“…The correlations imply poor cognitive outcome with increases in metabolite levels. Elevations in mI post pediatric head injury have been linked with poor neurologic outcome, possibly due to the role of mI in astrogliosis or brain osmotic function (8). Elevations in Glx have been demonstrated in all pediatric TBI patients compared to controls regardless of injury severity (7) and have been linked to secondary apoptosis associated with head injury (40).…”

Imaging Evidence and Recommendations for Traumatic Brain Injury: Advanced Neuro- and Neurovascular Imaging Techniques

“…67 In chronic brain injury, the mechanism for increased Cho is more likely diffuse glial proliferation, corroborated by elevated myoinositol that persists for months after injury. 82 More recent studies have shown changes in the energy marker Cr 58,83 ; if Cr is affected by mild TBI, metabolite ratio measurements would not be accurate because it would be difficult to assess if changes were due to the metabolite of interest or in Cr itself.…”

“…In children, myo-inositol has been shown to increase as a result of glial proliferation and has also been correlated with poor outcomes after TBI. 82,96 Currently, there remains insufficient evidence at the time of writing to conclude that MR spectroscopy is sufficiently sensitive and specific for routine clinical use at the individual patient level (class IIb recommendation).…”