Changes In Brain Metabolites Research Articles

Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection

To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations. Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent 1H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification. Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4+ T lymphocytes and a higher number of CD8+ T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8+ T cells, especially effector CD8+ T cells. These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8+ T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus-host interactions involved in CNS functional deficits.

The AT 1 Receptor Antagonist, L-158,809, Prevents or Ameliorates Fractionated Whole-Brain Irradiation–Induced Cognitive Impairment

We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of gamma rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.

Quantitative in vivo 1H spectroscopic imaging of metabolites in the early postnatal mouse brain at 17.6 T

Early postnatal brain maturation is closely connected to local changes of metabolite levels. Spatially resolved in vivo (1)H NMR spectroscopic imaging is applied to follow absolute changes of brain metabolites in early postnatal mouse brain. A short echo time semi LASER (localization by adiabatic selective refocusing) chemical shift imaging (CSI) sequence incorporating weighted k-space averaging was implemented at high magnetic field (17.6 T). In vivo measurements were carried out on postnatal days 5, 8, 12, 16, and 20. In vivo relaxation times T (1) and T (2) were measured using variable repetition times or a CPMG sequence, respectively, combined with LASER single voxel localization. Spectra were obtained with a spatial resolution of (1 x 1) mm(2) in a 1.5 mm slice as early as postnatal day 5. Maturational changes of absolute metabolite concentrations of major metabolites were calculated in four different brain regions. A significant increase of N-acetylaspartate (NAA), total creatine (tCr), and glutamate/glutamine (Glx) concentration was paralleled by a decrease of taurine (Tau) concentration with age (P < 0.05). Differences between brain regions were found for NAA, tCr, and Tau (P < 0.05). Furthermore, in vivo T (1) and T (2) of the four major brain metabolites in adult mice are reported. The implemented semi LASER CSI sequence allows following regional changes of metabolite levels. It is suitable for investigation of local differences in brain metabolism and development.

P.3.b.006 A proton magnetic resonance spectroscopy study of the brain metabolite changes after antipsychotic treatment

P.3.b.006 A proton magnetic resonance spectroscopy study of the brain metabolite changes after antipsychotic treatment

Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.

A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

Assessment of the metabolic profile in Type 2 diabetes mellitus and hypothyroidism through proton MR spectroscopy

The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ((1)H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.

Does Massage Therapy affect Brain Metabolites?

This performed study was to examine changes in brain metabolites following Light Touch (simulated massage) and Swedish massage (deep tissue massage) detected by MR Spectroscopy. The results showed no significant alteration in brain metabolites before and after Light Touch or Swedish massage.

Quantitative Magnetic Resonance Spectroscopy Reveals a Potential Relationship between Radiation-Induced Changes in Rat Brain Metabolites and Cognitive Impairment

To test the efficacy of magnetic resonance spectroscopy (MRS) in identifying radiation-induced brain injury, adult male Fischer 344 rats received fractionated whole-brain irradiation (40 or 45 Gy given in 5-Gy fractions twice a week for 4 or 4.5 weeks, respectively); control rats received sham irradiation. Twelve and 52 weeks after whole-brain irradiation, rats were subjected to high-resolution MRI and proton MRS. No apparent lesions or changes in T(1)- or T(2)-weighted images were noted at either time. This is in agreement with no gross changes being found in histological sections from rats 50 weeks postirradiation. Analysis of the MR spectra obtained 12 weeks after fractionated whole-brain irradiation also failed to show any significant differences (P > 0.1) in the concentration of brain metabolites between the whole-brain-irradiated and sham-irradiated rats. In contrast, analysis of the MR spectra obtained 52 weeks postirradiation revealed significant differences between the irradiated and sham-irradiated rats in the concentrations of several brain metabolites, including increases in the NAA/tCr (P < 0.005) and Glx/tCr (P < 0.001) ratios and a decrease in the mI/tCr ratio (P < 0.01). Although the cognitive function of these rats measured by the object recognition test was not significantly different (P > 0.1) between the irradiated and sham-irradiated rats at 14 weeks postirradiation, it was significantly different (P < 0.02) at 54 weeks postirradiation. These findings suggest that MRS may be a sensitive, noninvasive tool to detect changes in radiation-induced brain metabolites that may be associated with the radiation-induced cognitive impairments observed after prolonged fractionated whole-brain irradiation.

Quantitative in vivo proton MR spectroscopic evaluation of the irradiated rat brain

To investigate if in vivo localized proton magnetic resonance spectroscopy (MRS) can detect putative metabolic changes in the irradiated rat brain and quantitatively measure brain metabolite changes in this model. A total of 20 adult male Fischer 344 rats were exposed to a fractionated regimen of whole brain irradiation (WBI) (total 45 Gy, given as five Gy fractions, twice per week for 4.5 weeks); 10 control rats received sham irradiation. A total of 52 weeks after WBI, all animals were subjected to high-resolution MRI and in vivo proton MRS to determine structural and brain metabolite changes. Brain metabolites were measured by using single-voxel MRS. Quantitative analysis of detectable metabolites was performed by using the spectral analysis method, LCModel. Significant differences in brain metabolite concentrations were detected in rat brains irradiated with a clinically relevant fractionated radiotherapy regimen in 52 weeks, in comparison to age-matched sham-irradiated rats. These findings indicate that quantitative in vivo MRS may serve as a sensitive imaging tool to noninvasively detect neurochemical changes in the irradiated brain.

The relationship between white matter brain metabolites and cognition in normal aging: The GENIE study

Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50–90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age ( r = 0.495, p < 0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.

Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice

Translational biomarkers in Alzheimer's disease based on non-invasive in vivo methods are highly warranted. 1H magnetic resonance spectroscopy (MRS) is non-invasive and applicable in vivo in both humans and experimental animals. In vivo1H MRS and 3D MRI were performed on brains of double transgenic (tg) mice expressing a double mutant human β-amyloid precursor protein APP(K670N,M671L) and human mutated presenilin gene PS1M146L, and wild-type (wt) littermates at 2.5, 6.5 and 9 months of age using a 9.4T magnet. For quantification, LCModel™ was used, and the data were analyzed using multivariate data analysis (MVDA). MVDA evidenced a significant separation, which became more pronounced with age, between tg and wt mice at all time points. While myo-inositol and guanidoacetate were important for group separation in young mice, N-acetylaspartate, glutamate and macrolipids were important for separation of aged tg and wt mice. Volume segmentation revealed that brain and hippocampus were readily smaller in tg as compared to wt mice at the age of 2.5 months. Amyloid plaques were seen in 6.5 and 9 months, but not in 2.5 months old animals.In conclusion, differences in brain metabolites could be accurately depicted in tg and wt mice in vivo by combining MRS with MVDA. First differences in metabolite content were readily seen at 2.5 months, when volume defects in tg mice were present, but no amyloid plaques.

Structural and metabolic brain changes in the striatum associated with methamphetamine abuse

To review structural, chemical and metabolic brain changes, particularly those in the basal ganglia, in individuals who used methamphetamine, as well as in children with prenatal methamphetamine exposure. Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies that evaluated brain structural, chemical and metabolite changes in methamphetamine subjects, or children with prenatal methamphetamine exposure, were reviewed and summarized. Relevant pre-clinical studies that provided insights to the interpretations of these imaging studies were also reviewed. In adults who used methamphetamine, MRI demonstrates enlarged striatal volumes, while MR spectroscopy shows reduced concentrations of the neuronal marker N-acetylasparate and total creatine in the basal ganglia. In contrast, children with prenatal methamphetamine exposure show smaller striatal structures and elevated total creatine. Furthermore, PET studies consistently showed reduced dopamine transporter (DAT) density and reduced dopamine D(2) receptors in the striatum of methamphetamine subjects. PET studies also found lower levels of serotonergic transporter density and vesicular monoamine transporter (VMAT2) across striatal subregions, as well as altered brain glucose metabolism that correlated with severity of psychiatric symptoms in the limbic and orbitofrontal regions. Neuroimaging studies demonstrate abnormalities in brain structure and chemistry convincingly in individuals who used methamphetamine and in children with prenatal methamphetamine exposure, especially in the striatum. However, many important questions remain and larger sample sizes are needed to validate these preliminary observations. Furthermore, longitudinal studies are needed to evaluate the effects of treatment and abstinence on these brain changes and to determine whether imaging, and possibly genetic, markers can be used to predict treatment outcome or relapse.

Manifestations of early brain recovery associated with abstinence from alcoholism

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample suggest that early brain recovery through abstinence does not simply reflect rehydration. Instead, even the adult human brain and particularly its white matter seems to possess genuine capabilities for regrowth. Our findings emphasize metabolic as well as regionally distinct morphological capacities for partial brain recovery from toxic insults of chronic alcoholism and substantiate early measurable benefits of therapeutic sobriety. Further understanding of the precise mechanisms of this recovery may become a valuable model of brain regeneration with relevance for other disorders.

Prognostic Role of Proton Magnetic Resonance Spectroscopy in Acute Traumatic Brain Injury

Proton magnetic resonance spectroscopy (MRS) is being used to evaluate individuals after acute traumatic brain injury. These studies have shown that changes in certain brain metabolites are associated with poor neurologic outcomes. The majority of MRS studies have been obtained relatively late after injury, but there have been a few reports of use early after injury to assist with outcome prediction. Altered brain metabolites may be sensitive indicators of injury and thus provide additional prognostic information when spectroscopy is done early after injury. This technology may provide a noninvasive means to evaluate early excitotoxic injury, and show changes associated with both neuronal injury and membrane disruption secondary to diffuse axonal injury. This article will review the technology of MRS, discuss its role in patient assessment after traumatic brain injury, and present a summary of our published and ongoing research.

Preliminary findings of proton magnetic resonance spectroscopy in occipital cortex during sleep deprivation

Proton magnetic resonance spectroscopy ( 1H MRS) has revealed biochemical alterations in various psychiatric disorders. Changes in brain metabolites may be caused not only by the disease's progression or response to treatment, but also by physiological variability. The aim of this study was to use 1H MRS to assess the effects of specific short-term physiological states on major metabolites. Eight healthy women underwent 1H MRS at the beginning and end of a 40-h period of sleep deprivation. The ratios of N-acetyl-aspartate (NAA), total creatine ( tCr), and choline-containing compounds (Cho) to water (H 2O) were determined from the occipital cortex during both baseline and photic stimulation conditions. During sleep deprivation, NAA/H 2O decreased by 7% and Cho/H 2O by 12%. Photic stimulation had no effect on the measured metabolites in the alert state, but in the sleep-deprived state the level of Cho/H 2O increased during neuronal activation. The results suggest that NAA/H 2O and Cho/H 2O may depend on the state of alertness.

Brain Metabolite Concentrations and Neurocognition During Short‐term Recovery from Alcohol Dependence: Preliminary Evidence of the Effects of Concurrent Chronic Cigarette Smoking

Longitudinal studies of brain tissue metabolite recovery in short-term abstinent alcoholics have primarily investigated the frontal lobes and cerebellum with variable results. Preliminary proton magnetic resonance spectroscopic imaging (1H MRSI) suggested that chronic cigarette smoking exacerbates alcohol-induced brain injury in 1-week abstinent alcoholics. However, the potential effects of chronic cigarette smoking on the recovery of alcohol-induced brain injury have not been studied. Multislice short-echo time 1H MRSI was used to measure longitudinal changes in common brain metabolites in 25 recovering alcohol-dependent individuals (RA), retrospectively assigned to smoking (n = 14) and nonsmoking (n = 11) subgroups. Recovering alcohol-dependent individuals in longitudinal analyses were studied after approximately 7 and 34 days of abstinence from alcohol. In cross-sectional analyses, 36 RA (19 smokers, 17 nonsmokers) with approximately 34 days of sobriety were compared with 29 light drinkers (LD). Relationships between neurocognition and metabolite concentrations in abstinent RA were also examined. Over 1 month of abstinence from alcohol, RA, as a group, showed significant increases of regional N-acetylaspartate (NAA; marker of neuronal viability) and choline-containing compounds (Cho; marker of cell membrane synthesis/turnover) primarily in frontal and parietal lobes. These increases appeared to be driven by nonsmoking RA. Cross-sectional results indicate that metabolite levels in RA at 35 days of sobriety are not significantly different from those in LD in most regions, except for lower NAA and Cho in parietal WM and subcortical structures. However, metabolite levels at that time appear to be strongly modulated by smoking status. The patterns of metabolite-neurocognition relationships were different for nonsmoking and smoking RA. Within the first weeks of sobriety, regional brain NAA and Cho levels increased, but metabolite levels did not normalize in all brain regions after 35 days of sobriety. Neurobiologic recovery in RA appeared to be adversely affected by chronic smoking. Greater consideration of the effects of continued cigarette smoking on the neurobiologic and neurocognitive recovery of alcohol-dependent individuals is warranted.

An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model

The effects of traumatic brain injury (TBI) on brain chemistry and metabolism were examined in three groups of rats using high-resolution (1)H NMR metabolomics of brain tissue extracts and plasma. Brain injury in the TBI group (n = 6) was produced by lateral fluid percussion and regional changes in brain metabolites were analyzed at 1 h after injury in hippocampus, cortex and plasma and compared with changes in both a sham-surgery control group (n = 6) and an untreated control group (n = 6). Evidence was found of oxidative stress (e.g. decreases in ascorbate of 16.4% (p<0.01) and 29.7% (p<0.05) in cortex and hippocampus, respectively) in TBI rats versus the untreated control group, as well as excitotoxic damage (e.g. decreases in glutamate of 14.7% (p<0.05) and 12.3% (p<0.01) in the cortex and hippocampus, respectively), membrane disruption (e.g. decreases in the total level of phosphocholine and glycerophosphocholine of 23.0% (p<0.01) and 19.0% (p<0.01) in the cortex and hippocampus, respectively) and neuronal injury (e.g. decreases in N-acetylaspartate of 15.3% (p<0.01) and 9.7% (p>0.05) in the cortex and hippocampus, respectively). Significant changes in the overall pattern of NMR-observable metabolites using principal components analysis were also observed in TBI animals. Although TBI clearly had an effect on the metabolic profile found in brain tissue, no clear effects could be discerned in plasma samples. This was at least partly due to large variability in dominant glucose and lactate peaks in plasma. However, disruption of the blood-brain barrier and the subsequent movement of metabolites from brain into blood may have been relatively small and below the detection limits of our analytical procedures. Overall, these data indicate that TBI results in several significant changes in brain metabolism early after trauma and that a metabolomic approach based on (1)H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes within specific brain regions. The results also provide support for further development and application of metabolomic technologies for studying TBI and for the utilization of multivariate models for classifying the extent of trauma within an individual.

Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus

The metabolite changes in the brains of children with poorly controlled type 1 diabetes mellitus (DM) were investigated by proton magnetic resonance spectroscopy (MRS). A total of 30 subjects and 14 age-matched healthy volunteers underwent single-voxel MRS (TE: 136). The duration of disease, medication, presence of hypoglycaemia episodes and the level of haemoglobin A1C (HbA1C) in the patients were noted. Voxels were placed in the pons, left basal ganglion (LBG) and left posterior parietal white matter (PPWM). N-acetylaspartate (NAA)/creatinine (Cr) and choline (Cho)/Cr ratios were calculated. The average HbA1c level was 11.9 +/- 3.4 (8.2-19.4). The average number of keto-acidosis episodes was 1.9 +/- 2.2 (0-9) and the average number of daily insulin injections was 2.8 +/- 0.97 (2-4). MRS revealed lower NAA/Cr and Cho/Cr ratios in the pons and lower NAA/Cr ratio in the PPWM of patients with DM than in control subjects. No significant correlation was observed between the number of hypoglycaemia episodes and metabolite ratios. Metabolic abnormalities have been observed by MRS in the brain of poorly controlled type 1 DM children. These metabolic changes, in particular in the pons region, include a decrease in NAA, indicating neuronal loss or functional impairment, and likely explanations for a decrease in Cho may be dynamic changes in membrane lipids and/or decreased membrane turnover.

Functional 1H-MRS findings in migraine patients with and without aura assessed interictally

The present study was aimed at investigating changes in brain metabolites due to visual cortex activation in migraineurs and normal subjects by 1H-magnetic resonance spectroscopy (MRS). Twenty-two migraine patients with aura, 22 migraine patients without aura, and 10 control subjects were assessed. The volume of interest (about 8 cm 3) was placed on the visual cortex area and the visual stimulus was applied using MR-compatible goggles with a flashing red light at a frequency of 8 Hz and an intensity of 14 lx. Data were acquired over 36′40ʺ. The experimental time course was: baseline phase, from 0 to 3′40ʺ (1 spectrum); on phase (flashing light condition), from 3′40ʺ to 29′20ʺ (1540ʺ) (7 spectra), and off phase, from 29′20ʺ to the end of the experiment at 36′40ʺ (2 spectra). The main result of photic stimulation in patients with migraine with aura is the more consistent decrease (−14.61%) of the N-acetylaspartate (NAA) signal, which is significantly greater than that found in migraine patients without aura and control subjects. A parallel slight increase in the lactate peak was also detected. The above findings support little differences in brain metabolites between the two patient groups assessed in interictal periods, which suggests a less efficient mitochondrial functioning in migraine with aura patients.