Brain metabolism and cognitive impairment in HIV infection: a 3-T magnetic resonance spectroscopy study

Background and Purpose

Human immunodeficiency virus (HIV)-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 T. Higher magnetic field strengths (such as 3 T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3-T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln).

Methods

Eighty-six HIV+ subjects were evaluated at 3 T using quantitative short echo time single-voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into three groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia (clinical MSK stage=0.5), and 34 had dementia (HAD) (MSK≥1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed and motor and psychomotor speed. Between-group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive results.

Results

FWM Glx was lower in HAD (8.1±2.1 mM) compared to both the MCI (9.17±2.1 mM) and NC groups (10.0±1.6 mM) (P=.006). FWM myo-inositol (mI) was higher in HAD (4.15±0.75 mM) compared to both MCI (3.86±0.85 mM) and NC status (3.4±0.67 mM) (P=.006). FWM Glx/creatine (Cr) was lower and FWM mI/Cr was significantly higher in the HAD compared to the MCI and NC groups (P=.01 and P=.004, respectively). BG N-acetyl aspartate (NAA) was lower in the HAD group (6.79±1.53 mM), compared to the MCI (7.5±1.06 mM) and NC (7.6±1.01 mM) groups (P=.036). Significant negative correlations were observed between Glu, Glx and NAA concentrations with Trail-Making Test B (P=.006, P=.0001 and P=.007, respectively), and significant positive correlation was found with the Digit symbol test (P=.02, P=.002 and P=.008, respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved Pegboard nondominant hand (P=.02 and P=.04, respectively).

Conclusion

Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. Three-Tesla MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection.     

Effect of creatine monohydrate in improving cellular energetics and muscle strength in ambulatory Duchenne muscular dystrophy patients: a randomized,placebo-controlled P MRS study

Randomized, placebo-controlled single blinded study was carried out to evaluate the effect of oral creatine supplementation on cellular energetics, manual muscle test (MMT) score and functional status in steroid-naive, ambulatory boys suffering with Duchenne muscular dystrophy (DMD; n=33). Eighteen patients received creatine monohydrate (Cr; 5 g/day for 8 weeks), while 15 received placebo (500 mg of vitamin C). Phosphorus metabolite ratios were determined from the right calf muscle of patients using phosphorus magnetic resonance spectroscopy (³¹P MRS) both prior to (baseline) and after supplementation of Cr or placebo. In addition, metabolite ratios were determined in normal calf muscle of age and sex matched controls (n=8). Significant differences in several metabolite ratios were observed between controls and DMD patients indicating a lower energy state in these patients. Analysis using analysis of covariance adjusted for age and stature showed that the mean phosphocreatine (PCr)/inorganic phosphate (Pi) ratio in patients treated with Cr (4.7; 95% CI; 3.9–5.6) was significantly higher (P=.03) compared to the placebo group (3.3; 95% CI; 2.5–4.2). The mean percentage increase in PCr/Pi ratio was also more in patients <7 years of age compared to older patients after Cr supplementation indicating variation in therapeutic effect with the age. In the placebo group, significant reduction in PCr/Pi (P=.0009), PCr/t-ATP (P=.05) and an increase in phosphodiester (PDE)/PCr ratios was observed after supplementation. Further, in the placebo group, patients <7 years showed reduction of PCr/t-ATP and Pi/t-ATP compared to older patients (>7 years), after supplementation. These results imply that the significant difference observed in PCr/Pi ratio between the Cr and the placebo groups after supplementation may be attributed to a decrease of PCr in the placebo group and an increase in PCr in the Cr group. Changes in MMT score between the two groups was significant (P=.04); however, no change in functional scale (P=.19) was observed. Parents reported subjective improvement on Cr supplementation versus worsening in placebo (P=.02). Our results indicated that Cr was well tolerated and oral Cr significantly improved the muscle PCr/Pi ratio and preserved the muscle strength in short term. However, this study provides no evidence that creatine will prove beneficial after long-term treatment, or have any positive effect on patient lifespan.     

Monitoring the brain metabolites of children with acute encephalopathy caused by the H1N1 virus responsible for the 2009 influenza pandemic: a quantitative in vivo H MR spectroscopy study

Background and Purpose

Influenza viral infection, which results in central nervous system dysfunction, is a major cause of acute encephalopathy (AE). The purpose of this study was to investigate the changes in the concentrations of brain metabolites in children with AE using single-voxel magnetic resonance spectroscopy (MRS) and to provide diagnostic information about the relationship between the symptoms of AE and metabolite concentrations.

Materials and Methods

The subjects were 10 children (mean age: 6.2 years; range: 1–13) with AE caused by the novel influenza A virus responsible for the 2009 influenza pandemic. The serial MRS data (TE/TR=30/5000 ms, 3 T) acquired from the basal ganglia (BG) and centrum semiovale (CS) of each patient were categorized into three periods: (1) initial neurological symptom presentation and the start of treatment (n= 10), (2) short-term follow-up (n= 9) and (3) long-term follow-up (n= 3). As controls, the magnetic resonance (MR) spectra of eight age-matched children were also investigated.

Results

In both regions, the concentrations of the major metabolites (N-acetylaspartate, creatine, choline, myo-inositol, glutamate/glutamine complex and glutamate) only showed minor fluctuations between the three periods. On the other hand, higher levels of taurine (Tau) were observed in the BG during the second period (P=.005), and increased levels of glucose were observed in the CS during the first (P=.005) and second (P=.036) periods.

Conclusions

Serial monitoring of brain metabolite changes was carried out with a clinical MR system. The concentrations of major metabolites only displayed very minor fluctuations in response to mild H1N1-related AE. However, a higher Tau concentration was found to be associated with neurological symptoms. Further studies are required to improve our understanding of the detailed activity of Tau in AE.