Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.

Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated patterns of brain alterations at the group level. Recently, a neuropathological staging system for amyotrophic lateral sclerosis has shown that amyotrophic lateral sclerosis may disseminate in a sequential regional pattern during four disease stages. The objective of the present study was to apply a new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130 diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis and 22 control subjects, were analysed by a tract of interest-based fibre tracking approach to analyse five tracts that become involved during the course of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the corticorubral and the corticopontine tracts (stage 2); the corticostriatal pathway (stage 3); the proximal portion of the perforant path (stage 4); and two reference pathways. The statistical analyses of tracts of interest showed differences between patients with amyotrophic lateral sclerosis and control subjects for all tracts. The significance level of the comparisons at the group level was lower, the higher the disease stage with corresponding involved fibre tracts. Both the clinical phenotype as assessed by the amyotrophic lateral sclerosis functional rating scale-revised and disease duration correlated significantly with the resulting staging scheme. In summary, the tract of interest-based technique allowed for individual analysis of predefined tract structures, thus making it possible to image in vivo the disease stages in amyotrophic lateral sclerosis. This approach can be used not only for individual clinical work-up purposes, but enlarges the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for amyotrophic lateral sclerosis studies within a clinical context.

ObjectiveNeuropathological studies in amyotrophic lateral sclerosis (ALS) have shown a dissemination in a regional sequence in four anatomically defined patterns. The aim of this retrospective study was to see whether longitudinal diffusion tensor imaging (DTI) data support the pathological findings.MethodsThe application of DTI analysis to fibre structures that are prone to be involved at each neuropathological pattern of ALS was performed in a monocentre sample of 67 patients with ALS and 31 controls that obtained at least one follow-up scan after a median of 6 months.ResultsAt the group level, longitudinal ALS data showed significant differences for the stage-related tract systems. At the individual level, 27% of the longitudinally scanned patients with ALS showed an increase in ALS stage, while the remaining were stable or were at the highest ALS stage. Longitudinal fractional anisotropy changes in the respective tract systems correlated significantly with the slope of the revised ALS functional rating scale.InterpretationThe DTI-based protocol was able to image the disease patterns of ALS in vivo cross-sectionally and longitudinally, in support of DTI as a technical marker to image ALS stages.

In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58+/-9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59+/-11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p = 0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p<0.01 in the right-hemispheric primary motor cortex (area of the highest Z-score) and in the left medial frontal gyrus. Furthermore, regional white matter alterations were observed along the corticospinal tracts bilaterally and in multiple smaller areas including corpus callosum, cerebellum, frontal and occipital subcortical regions. Besides considerable global atrophy in ALS, the topography of ALS-associated cerebral morphological changes could be mapped using VBM, in particular white matter signal changes along the bilateral corticospinal tracts, but also in extra-motor areas. VBM might be a potential tool to visualize disease progression in future longitudinal studies.

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