Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis

Shimizu, Toshio; Bokuda, Kota; Kimura, Hideki; Kamiyama, Tsutomu; Nakayama, Yuki; Kawata, Akihiro; Isozaki, Eiji; Ugawa, Yoshikazu

doi:10.1212/wnl.0000000000005424

Cited by 37 publications

(23 citation statements)

References 38 publications

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“…The average age at venipuncture (ALS, 63.5 [47.5-79.5] years; disease controls, 63.0 [47.75-78.25] years; healthy controls, 59.0 [45.0-74.0] years) and the sex ratio (male:female, ALS, 41:27; disease controls, 32:22; and healthy controls, 12:8) were not significantly different between the three groups. The average duration from onset to registration (months) in patients with ALS was 21.1 (5.12-37.1), the average ALSFRS-R at registration was 38.7 (32.5-44.9) and the average forced vital capacity (FVC) at registration was 84.9% (63.0%-106.8%), which are consistent with previous studies [2,[9][10][11]. At the end of this study, 33 patients had reached the primary end-point, and the average duration from registration to the primary end-point was 23.64 ± 14.33 months.…”

Section: Clinical Data Of the Als Patients Disease Control Patients A...supporting

confidence: 89%

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis

Ikenaka

Maeda

Hotta

et al. 2022

Euro J of Neurology

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Background and purpose:The aim was to investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.Methods: Serum ADMA levels of sporadic ALS patients (n = 68), disease control patients (n = 54) and healthy controls (n = 20) were measured using liquid chromatography tandem mass spectrometry. Correlations of the ADMA level and other markers (nitric oxide and neurofilament light chain levels) were analyzed. Changes in the ALS Functional Rating Scale Revised (ALSFRS-R) score from the onset of disease (ALSFRS-R pre-slope) was used to assess disease progression. Survival was evaluated using the Cox proportional hazards model and Kaplan-Meier analysis. Results:The serum ADMA level was substantially higher in patients with ALS than in healthy controls and disease controls. Serum ADMA level correlated with CSF ADMA level (r = 0.591, p < 0.0001) and was independently associated with the ALSFRS-R preslope (r = 0.505, p < 0.0001). Patients with higher serum ADMA levels had less favorable prognoses. CSF ADMA level significantly correlated with CSF neurofilament light chain level (r = 0.456, p = 0.0002) but not with nitric oxide level (r = 0.194, p = 0.219).

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Section: Clinical Data Of the Als Patients Disease Control Patients A...supporting

confidence: 89%

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis

Ikenaka

Maeda

Hotta

et al. 2022

Euro J of Neurology

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“…Intriguingly, median survival was significantly shorter in patients who had larger somatosensory cortical amplitudes in SEPs. Subsequent multivariate analyses identified a more pronounced N20p‐P25p amplitude as an independent prognostic factor (Shimizu et al, 2018). In line with this study, a marked disinhibition of somatosensory cortex in ALS patients from the second year of disease evolution has been recently reported (Nardone et al, 2020).…”

Section: Clinical Evidence Supporting the Coexistence Of Sensory Disomentioning

confidence: 99%

“…This is based on the hypothesis that at a particular point of the disease, somatosensorial cortex hyperexcitability might reflect a compensatory mechanism of the sensory cortex for motor disturbances (Hamada et al, 2007). To test this hypothesis, Shimizu et al (2018) studied a cohort of 145 sALS patients and 73 healthy controls and followed them until death or tracheotomy. Intriguingly, median survival was significantly shorter in patients who had larger somatosensory cortical amplitudes in SEPs.…”

Section: Clinical Evidence Supporting the Coexistence Of Sensory Disomentioning

confidence: 99%

Clinical and preclinical evidence of somatosensory involvement in amyotrophic lateral sclerosis

Riancho

Paz-Fajardo

Munáin

2020

British J Pharmacology

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Amyotrophic lateral sclerosis (ALS) is the most common motor neuron neurodegenerative disease. Although it has been classically considered as a disease limited to the motor system, there is increasing evidence for the involvement of other neural and non‐neuronal systems. In this review, we will discuss currently existing literature regarding the involvement of the sensory system in ALS. Human studies have reported intradermic small fibre loss, sensory axonal predominant neuropathy, as well as somatosensory cortex hyperexcitability. In line with this, ALS animal studies have demonstrated the involvement of several sensory components. Specifically, they have highlighted the impairment of sensory–motor networks as a potential mechanism for the disease. The elucidation of these “non‐motor” systems involvement, which might also be part of the degeneration process, should prompt the scientific community to re‐consider ALS as a pure motor neuron disease, which may in turn result in more holistic research approaches. LINKED ARTICLES This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc

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“…Few studies assessed the presence of SEPIA in neurodegenerative diseases: patients affected by ALS had a larger N20p-P25p, with respect to the healthy subjects; moreover, median survival time after examination was shorter in the group of ALS with N20p-P25p greater than 8 µV. [17] This large N20p-P25p was interpreted as a sign of cortical hyperexcitability in the sensorimotor cortical areas in the first stages of ALS, due to the early loss of cortical interneurons, preceding the loss of the upper motor neuron. SEPIA was found in PSP[15] and in MSA;[14] again, this finding probably reflected a mild form of cortical hyperexcitability.…”

Section: Discussionmentioning

confidence: 99%

Significance and clinical suggestions for the Somatosensory Evoked Potentials increased in amplitude revealed by a large sample of neurological patients

Sebastiano

Cazzato

Visani

et al. 2022

Preprint

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Background and purpose So far, giant Somatosensory Evoked Potentials (SEPs) in amplitude are usually related to the presence of cortical reflex myoclonus and epilepsy, even if growing evidences lead to rethink about their significance. To investigate the relationship between N20-P25 peak-to-peak amplitude (N20p-P25p) of SEPs and the occurrence of abnormalities of the sensory pathways and of myoclonus/epilepsy, in 308 patients with increased SEPs amplitude from upper limbs stimulation Methods We compared N20p-P25p in different groups of patients identified by demographic, clinical and neurophysiological factors and performed a cluster analysis for classifying the natural occurrence of subgroups of patients. Results No significant differences of N20p-P25p were found among different age-dependent groups, and in patients with or without PNS/CNS abnormalities of sensory pathways, while myoclonic/epileptic patients showed higher N20p-P25p than other groups. Cluster analysis identified four clusters including patients with myoclonus/epilepsy, patients with CNS abnormalities, patients with PNS abnormalities, patients with neither myoclonus nor CNS/PNS abnormalities. Conclusions Increased N20p-P25p correlated to different pathophysiological conditions: strong cortical hyperexcitability in patients with cortical myoclonus and/or epilepsy and enlarged N20p-P25p, while milder increase of N20p-P25p could be underpinned by plastic cortical changes following abnormalities of sensory pathways, or degenerative process involving the cortex. SEPs increased in amplitude cannot be considered a specific correlated for myoclonus/epilepsy, but it in several neurological disorders may represent a sign of adaptive, plastic and/or degenerative cortical changes

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Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis

Abstract: Sensory cortex hyperexcitability predicts short survival in patients with ALS.

Cited by 37 publications

References 38 publications

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis

Serum asymmetric dimethylarginine level correlates with the progression and prognosis of amyotrophic lateral sclerosis

Clinical and preclinical evidence of somatosensory involvement in amyotrophic lateral sclerosis

Significance and clinical suggestions for the Somatosensory Evoked Potentials increased in amplitude revealed by a large sample of neurological patients

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