Changes in the Concentrations of Major Neurotransmitter within the Sensory and Motor Cortex of Adults with Acute Traumatic Brachial Plexus Injuries Measured Using Magnetic Resonance Spectroscopy
Ryckie George Wade, MBBS MSc MClinEd MRCS FHEA GradStat PhD1; Gráinne Bourke, MB BCh BAO FRCSI FRCS(Plast)2; Robert D Bains, MBChB BSc FRCS(Plast)2; Sven Plein, MD PhD FRCP FESC3; Alexandra M Olaru, BSc MSc PhD4; David Shelley, BSc PGCert MSc3; Steve R Williams, BA DPhil5; James Bedford, MSc FRCS(Plast) BrDipHandSurg6; Lucy Homer, MbChB(Hons) MRes MRCS6; Laura Parkes, MPhys(Hons) MSc PhD5; Caroline Lea-Carnall, BSc MSc PhD5
1Department of Plastic and Reconstructive Surgery, University of Leeds, Leeds, United Kingdom; 2Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom; 3University of Leeds, Leeds, United Kingdom; 4Siemens Healthcare Ltd, Surrey, United Kingdom; 5University of Manchester, Manchester, United Kingdom; 6Manchester University NHS Foundation Trust, Manchester, United Kingdom
Introduction: GABA (?-aminobutyric acid) is the major inhibitory neurotransmitter of the brain. In response to injury within the central nervous system, such as in stroke, levels of GABA in the sensory and motor cortices have been found to reduce which promotes cortical plasticity. This means GABA is a potential pharmacological target which may improve functional recovery. However, it is unclear how the concentrations of neurometabolites such as GABA, creatine (Cr) and N-acetylaspartate (NAA) change in the brain after major peripheral nerve injury. Magnetic resonance spectroscopy (MRS) is a technique used to measure metabolite concentrations in vivo. Here we used J-difference editing via the MEscher–GArwood Point RESolved Spectroscopy (MEGA-PRESS) to quantify GABA at 3 Tesla. This represents the rationale for using MEGA-PRESS MRS in the investigation of adults with acute traumatic brachial plexus injuries (BPI).
Methods: We have recruited 7 males (mean age 42 years [SD19] without head injury) who were scanned at baseline, 6 months and 1 year after traumatic BPI. T1-weighted images (MPRAGE, 1mm isotropic resolution) and J-edited spectra (MEGA-PRESS, TE 68ms, TR 2000ms, 2 cm isotropic voxel centred on the right and the left sensory and motor cortex, respectively) were acquired using a MAGNETOM Prisma 3T (Siemens Healthcare, Erlangen, Germany) equipped with a 64-channel head coil. Data were analysed in JMRUI blind to clinical information to quantify GABA, Cr, and NAA concentrations. Additionally, grey matter and white matter proportions were assessed using in-house software. Interhemispheric means were compared by bootstrapped linear methods. Confidence intervals (CI) were generated to the 95% level.
Results: Fourteen days after injury, the hemisphere representing the injured upper limb had a significantly lower GABA:NAA ratio (mean difference 0.23 [CI 0.06-0.40]; Figure 1) and GABA:Cr ratio (mean difference 0.75 [CI 0.25-1.24]; Figure 1) than the uninjured side. There were no interhemispheric differences in NAA:Cr (mean difference 0.49 [CI -0.025-1.00]; Figure 3). Over time, interhemispheric differences in metabolites concentrations equalised. There was no difference in the proportion of grey matter, white matter and CSF between the injured and uninjured hemispheres (Figure 4).
Conclusions: After acute traumatic brachial plexus injury, there are interhemispheric differences in the ratio of major neurotransmitters within the sensory and motor cortex. Pharmacological modulation of these metabolites may alter the potential for central plasticity, the available time for reconstructive surgery and ultimately, the function of the upper limb.
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