Combined 3T diffusion tensor tractography and 1H-MR spectroscopy in motor neuron disease

BACKGROUND AND PURPOSE: Diagnostic confidence in motor neuron disease may be improved by the use of advanced MR imaging techniques. Our aim was to assess the accuracy (sensitivity/specificity) and agreement of combined ¹H-MR spectroscopy (proton MR spectroscopy) and diffusion tensor imaging (DTI) at 3T in patients with suspected motor neuron disease regarding detection of upper motor neuron (UMN) dysfunction.MATERIALS AND METHODS: Eighteen patients with suspected motor neuron disease were studied with MR spectroscopy/DTI and clinically rated according to the El-Escorial and ALSFRS-R scales. For MR spectroscopy, absolute N-acetylaspartate (NAA), choline (Cho), and phosphocreatine (PCr) concentrations and relative NAA/Cho and NAA/PCr ratios of corresponding volumes of interest within the primary motor cortex were calculated. For DTI, fractional anisotropy (FA) and mean diffusivity (MD) were measured bilaterally at the level of the precentral gyrus, corona radiata, internal capsule, cerebral peduncles, pons, and pyramid. FA and MD statistics were averaged on the corticospinal tracts (CSTs) as a whole to account for a region-independent analysis.RESULTS: MR spectroscopy indicated NAA reduction beyond the double SD of controls in 6 of 8 patients with clinical evidence for UMN involvement. Congruently, the mean FA of these patients was significantly lower in the upper 3 regions of measurements (P < .01). Overall, MR spectroscopy and DTI were concordant in all except 3 cases: 1 was correctly excluded from motor neuron disease by DTI (genetically proved Kennedy syndrome), whereas MR spectroscopy indicated CST involvement. MR spectroscopy and DTI each were false-positive for CST affection in 1 patient with lower motor neuron involvement only.CONCLUSION: Combined MR spectroscopy/DTI at 3T effectively adds to the detection of motor neuron disease with a high degree of accordance.

Amyotrophic lateral sclerosis (ALS), Lou Gehrig syndrome or Charcot disease, is the most common progressive motor neuron disease.¹ Classic ALS affects the upper (UMN) and lower motor neurons (LMN), but cases with predominant UMN or LMN involvement also occur. It is still debated whether primary lateral sclerosis (PLS) and ALS are distinct disorders or manifestations of a single disorder, and a classification into ALS, UMN–dominant ALS, and PLS has been proposed to systematize future trials,² hence the correctness of UMN assessment is crucial.In addition to traditional diagnostic steps, such as electromyography, transcranial magnetic stimulation,^3,4 and assessment according to established clinical rating scales (eg, El-Escorial [EE]⁵ or ALS Functional Rating Scale-Revised [ALSFRS-R⁶]), recent promising attempts to improve diagnostic confidence of UMN assessment used advanced MR imaging techniques: ¹H-MR spectroscopy (proton MR spectroscopy),^7–11 diffusion tensor imaging (DTI),^12–19 diffusion tensor tractography (DTT),²⁰ or combinations thereof.^21,22 However, systematic evaluation of their concordance in the same patients is still rare.^21,23To obtain a definite diagnosis early in the disease is important for therapeutic intervention,^21,24 quality of life,^17,25,26 and monitoring therapeutic trials.^16,22 Cervical myelopathy, Kennedy syndrome (spinobulbar muscle atrophy, [SBMA]), peripheral nerve lesions, and multifocal polyneuropathy are, among others, differential diagnoses that have to be excluded. The clinical diagnosis is especially difficult when UMN involvement remains unclear. The previously mentioned techniques not only hold the promise of a more specific and potentially objective MR imaging measure but may even lead to a biomarker of disease severity.In contrast, most characteristics observed on structural MR imaging, such as corticospinal tract (CST) hyperintensities in T2-weighted, proton density, and fluid-attenuated inversion recovery (FLAIR) imaging^27–32; hypointense precentral gyrus changes^33,34; or marked frontal or callosal atrophy,³⁵ are rather uncertain.^31,32 CST hyperintensities are frequently found in healthy individuals, whereas the hypointense precentral gyrus sign apparently is motor neuron disease–specific according to Ishikawa et al³³ but occurs only in a minority of patients with ALS. To our knowledge, none of these signs have yet been studied at 3T. The principal aim of the present study was to evaluate the diagnostic accuracy of combined MR spectroscopy and DTI at 3T as an additional diagnostic tool in patients with suggested motor neuron disease and to provide an estimate of their concordance when applied to the same patients.