Article Text

Research paper
Memory in multiple sclerosis is linked to glutamate concentration in grey matter regions
  1. Nils Muhlert1,2,
  2. Matteo Atzori3,4,
  3. Enrico De Vita5,6,
  4. David L Thomas6,
  5. Rebecca S Samson1,
  6. Claudia A M Wheeler-Kingshott1,
  7. Jeroen J G Geurts7,
  8. David H Miller1,8,
  9. Alan J Thompson3,8,
  10. Olga Ciccarelli3,8
  1. 1Department of Neuroinflammation, NMR Research Unit, UCL Institute of Neurology, London, UK
  2. 2Cognitive Neuroscience, Department of Psychology, Cardiff University, Cardiff, UK
  3. 3Department of Brain Repair and Rehabilitation, NMR Research Unit, UCL Institute of Neurology, London, UK
  4. 4Department of Neurology, University of Padova, Padova, Italy
  5. 5Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK
  6. 6Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, London, UK
  7. 7Department of Anatomy and Neuroscience, Section of Clinical Neuroscience, VU University Medical Center, VUmc MS Center Amsterdam, Amsterdam, The Netherlands
  8. 8National Institute for Health and Research (NIHR) University College London Hospital (UCLH) Biomedical Research Centre, London, UK
  1. Correspondence to Dr Nils Muhlert, Cognitive Neuroscience, Cardiff University, Tower Building, Cardiff CF10 3AT, UK; MuhlertN{at}


Objective Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance.

Methods Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent 1H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. Regression models investigated the association between glutamate concentration and memory performance independently of magnetisation transfer ratio values and grey matter lesions withint he same regions, and whole-brain grey matter volume.

Results Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls.

Conclusions The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS.

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