Harmen Reyngoudt

Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

OBJECTIVE To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). MATERIALS AND METHODS Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18-76 years, mean±SD, 48.4±16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. RESULTS Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P<0.05 and P≤0.001, respectively), and in the HC (P<0.01 for both). An increased tCr/H2O was only observed in the PCC (P<0.01). Following absolute quantification based on the internal water signal, significantly increased concentrations of Ins and tCr in the PCC confirmed the relative findings (P<0.01 for both). CONCLUSION Age-related increases of tCr and Ins are found in the PCC, whereas this holds only true for Ins in the HC, indicating possible gliosis in the ageing brain. No age-dependent NAA decreases were observed in the PCC nor the HC. The 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimers disease.

31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients

Background: Differences in brain energy metabolism have been found between migraine patients and controls in previous phosphorus magnetic resonance spectroscopy (31P-MRS) studies, most of them emphasizing migraine with aura (MwA). The aim of this study was to verify potential changes in resting-state brain energy metabolism in patients with migraine without aura (MwoA) compared to control subjects by 31P-MRS at 3 tesla. Methods: Quantification was performed using the phantom replacement technique. MRS measurements were performed interictally and in the medial occipital lobe of 19 MwoA patients and 26 age-matched controls. Results: A significantly decreased phosphocreatine concentration ([PCr]) was found as in previous studies. While adenosine triphosphate concentration ([ATP]) was considered to be constant in previously published work, this study found a significant decrease in the measured [ATP] in MwoA patients. The inorganic phosphate ([Pi]) and magnesium ([Mg2+]) concentrations were not significantly different between MwoA patients and controls. Conclusions: The altered metabolic concentrations indicate that the energy metabolism in MwoA patients is impaired, certainly in a subgroup of patients. The actual decrease in [ATP] adds further strength to the theory of the presence of a mitochondrial component in the pathophysiology of migraine.

Magnetic resonance spectroscopy in migraine: what have we learned so far?

Objective: To summarize and evaluate proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) findings in migraine. Methods: A thorough review of 1H and/or 31P-MRS studies in any form of migraine published up to September 2011. Results: Some findings were consistent in all studies, such as a lack of ictal/interictal brain pH change and a disturbed energy metabolism, the latter of which is reflected in a drop in phosphocreatine content, both in the resting brain and in muscle following exercise. In a recent interictal study ATP was found to be significantly decreased in the occipital lobe of migraine with aura patients, reinforcing the concept of a mitochondrial component to the migraine threshold, at least in a subgroup of patients. In several studies a correlation between the extent of the energy disturbance and the clinical phenotype severity was apparent. Less consistent but still congruent with a disturbed energy metabolism is an observed lactate increase in the occipital cortex of several migraine subtypes (MwA, migraine with prolonged aura). No increases in brain glutamate levels were found. Conclusion: The combined abnormalities found in MRS studies imply a mitochondrial component in migraine neurobiology. This could be due to a primary mitochondrial dysfunction or be secondary to, for example, alterations in brain excitability. The extent of variation in the data can be attributed to both the variable clinical inclusion criteria used and the variation in applied methodology. Therefore it is necessary to continue to optimize MRS methodology to gain further insights, especially concerning lactate and glutamate.

1H-MRS of brain metabolites in migraine without aura: absolute quantification using the phantom replacement technique

ObjectiveSeveral studies have demonstrated differences in migraine patients when performing 1H-MRS; however, no studies have performed 1H-MRS in migraine without aura (MwoA), the most common migraine subtype. The aim of this 1H-MRS study was to elucidate whether any differences could be found between MwoA patients and controls by performing absolute quantification.Materials and methods1H-MRS was performed in 22 MwoA patients and 25 control subjects. Absolute quantification was based on the phantom replacement technique. Corrections were made for T1 and T2 relaxation effects, CSF content, coil loading and temperature. The method was validated by phantom measurements and in vivo measurements in the occipital visual cortex.ResultsAfter calibration of the quantification procedure and the implementation of the required correction factors, measured absolute concentrations in the visual cortex of MwoA patients showed no significant differences compared to controls, in contrast to relative results obtained in earlier studies.ConclusionIn this study, we demonstrate the implementation of quantitative in vivo 1H-MRS spectroscopy in migraine patients. Despite rigorous quantification, no spectroscopic abnormalities could be found in patients with migraine without aura.

Absence of haemodynamic refractory effects in patients with migraine without aura – an interictal fMRI study

Background: In healthy controls, haemodynamic refractory effects are observed with blood-oxygenation-level dependent (BOLD) functional MRI (fMRI): the haemodynamic response function (HRF) to the second stimulus in a pair of stimuli with short interstimulus interval (ISI) shows a decreased amplitude and an increased time-to-peak. We hypothesize that there may be interictal haemodynamic abnormalities in migraineurs. Methods: An event-related fMRI design with paired face stimuli and varying ISIs was used to measure interictal HRFs in the face recognition area of patients with migraine without aura (MwoA) and controls. Net responses to the second stimulus in a pair were calculated and averaged per participant. Several characterizing parameters of the net responses were quantified and examined within each group. Results: Refractory effects were not observed in our patient group. There are no changes in the net responses compared with the reference situation in patients, irrespective of the ISI, whereas in controls all HRF parameters are decreased or delayed for an ISI of 1 second. Conclusion: This is the first fMRI study investigating the haemodynamic refractory effects in MwoA patients. Unlike in controls, these effects are not observed in migraineurs. Although currently unclear, it is tempting to speculate that this observation reflects the neurovascular correlate of lack of habituation measured with evoked potentials in migraineurs.

Quantifying hemodynamic refractory bold effects in normal subjects at the single‐subject level using an inverse logit fitting procedure

To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single‐subject level using a recently described hemodynamic response function (HRF) fitting algorithm.

Targeting phosphocreatine metabolism in relapsing–remitting multiple sclerosis: evaluation with brain MRI, 1 H and 31 P MRS, and clinical and cognitive testing

Background/objectivesFluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP–PKA pathway, an interesting target in the neurodegenerative mechanisms of MS.MethodsWe conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing–remitting MS patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n = 15), or prucalopride (n = 14) for 6 weeks. Proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6.ResultsNo significant changes were observed for both 31P and 1H MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores.ConclusionBoth fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on 31P and 1H MRS parameters, suggesting that these molecules do not influence the PCr metabolism.