Electrophysiological and spinal imaging evidences for sensory dysfunction in amyotrophic lateral sclerosis

Abstract

ObjectivesThe prevalence of sensory impairment at an early stage of amyotrophic lateral sclerosis (ALS) is still debated. The study aim was to investigate the anatomofunctional properties of sensory pathways in patients with ALS, combining spinal diffusion tensor imaging (DTI) and somatosensory evoked potentials (SEPs).DesignCase–control study.SettingsALS referral centre and laboratory of biomedical imaging (Paris, France).ParticipantsWell-characterised group of 21 patients with ALS with moderate disability (mean amyotrophic lateral sclerosis Functional Rating Scale (ALSFRS) score 39.3±1.0) and no clinical sensory signs and control group of 21 gender and age-matched healthy subjects.Outcome measuresFractional anisotropy and diffusivity of the dorsal columns at C5-T1 levels (DTI metrics) and SEPs after median and ulnar nerve stimulations (latency and amplitude of N9 and N20 components).ResultsAbnormal DTI metrics indicated anatomical damages of ascending sensory fibres in ∼60% of patients (p<0.05). Raw SEPs (μV) were smaller in ∼40% of patients but the difference with healthy subjects was not significant (p>0.16). Their normalisation to prestimulus activity strengthened the difference between groups (p<0.05) and allowed identification of ∼60% of patients with abnormal values. According to N9 latency, the peripheral conduction time was normal in patients (p>0.32) but based on N20 latency, the central conduction time (between spinal cord and parietal cortex) was found to be slower (p<0.05). Significant correlation was found between DTI metrics and N9 amplitude (p<0.05). Altered SEPs were also correlated with the disease duration (p<0.05). Taken together, spinal imaging and electrophysiology helped to identify ∼85% of patients with subclinical sensory defect while separated methods revealed abnormal values in ∼60%.ConclusionsSensory impairments have been underestimated at early stages of ALS. These results show for the first time the interest to combine electrophysiology and imaging to assess non-motor system involvement in ALS.Trial registration numberIDRCB2012-A00016-37.

In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

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A Novel Missense Mutation of the DDHD1 Gene Associated with Juvenile Amyotrophic Lateral Sclerosis

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Further development of biomarkers in amyotrophic lateral sclerosis

“…With the development of new methods such as cardiac and respiratory gating, DTI and magnetization transfer (MT) can detect changes in the spinal cord in ALS [142][143][144]. Detection of infraclinical abnormalities in the sensory tracts shows the sensitivity of this approach [145][146]. Local spinal cord atrophy correlated with muscle deficits and electrophysiolocal indices of lower motor neuron dysfunction, suggesting that regional atrophy is a sensitive biomarker of motor neuron loss in the anterior horns of the spinal cord [143].…”