Unmasking the silent motor neuron loss in amyotrophic lateral sclerosis

2018 ◽  
Vol 58 (2) ◽  
pp. 184-185
Author(s):  
Christoph Neuwirth ◽  
Markus Weber
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

scholarly journals Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Junmei Wang ◽  
Lydia Tierney ◽  
Ranjeet Mann ◽  
Thomas Lonsway ◽  
Chandler L. Walker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Lumbar Spinal Cord ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Neuron Loss ◽  
Neuroprotective Therapy ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.

Longitudinal study of functional spinal alpha motor neuron loss in amyotrophic lateral sclerosis

2002 ◽  
Vol 25 (4) ◽  
pp. 520-526 ◽  
Author(s):  
K. Arasaki ◽  
Y. Kato ◽  
A. Hyodo ◽  
R. Ushijima ◽  
M. Tamaki
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Longitudinal Study ◽  
Motor Neuron ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Alpha Motor Neuron ◽  
Lateral Sclerosis

Motor Unit Number Index (MUNIX) detects motor neuron loss in pre-symptomatic muscles in Amyotrophic Lateral Sclerosis

2017 ◽  
Vol 128 (3) ◽  
pp. 495-500 ◽  
Author(s):  
Christoph Neuwirth ◽  
Paul E. Barkhaus ◽  
Christian Burkhardt ◽  
José Castro ◽  
David Czell ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Unit ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

Motor unit number index and neurophysiological index as candidate biomarkers of presymptomatic motor neuron loss in amyotrophic lateral sclerosis

2018 ◽  
Vol 58 (2) ◽  
pp. 204-212 ◽  
Author(s):  
Marcio Luiz Escorcio‐Bezerra ◽  
Agessandro Abrahao ◽  
Karlo Faria Nunes ◽  
Nadia Iandoli De Oliveira Braga ◽  
Acary Souza Bulle Oliveira ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Unit ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

Presymptomatic motor neuron loss and reactive astrocytosis in the SOD1 mouse model of amyotrophic lateral sclerosis

2001 ◽  
Vol 24 (11) ◽  
pp. 1510-1519 ◽  
Author(s):  
Sandra J. Feeney ◽  
Penelope A. McKelvie ◽  
Lawrence Austin ◽  
M.J. Bernadette Jean-Francois ◽  
Robert Kapsa ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Sod1 Mouse ◽  
Lateral Sclerosis ◽  
Reactive Astrocytosis

Tracking motor neuron loss in a set of six muscles in amyotrophic lateral sclerosis using the Motor Unit Number Index (MUNIX): a 15-month longitudinal multicentre trial

2015 ◽  
Vol 86 (11) ◽  
pp. 1172-1179 ◽  
Author(s):  
Christoph Neuwirth ◽  
Paul E Barkhaus ◽  
Christian Burkhardt ◽  
José Castro ◽  
David Czell ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Unit ◽  
Biceps Brachii ◽  
Intraclass Correlation ◽  
Abductor Hallucis ◽  
Rater Reliability ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

BackgroundMotor Unit Number Index (MUNIX) is a novel neurophysiological measure that provides an index of the number of functional lower motor neurons in a given muscle. So far its performance across centres in patients with amyotrophic lateral sclerosis (ALS) has not been investigated.ObjectiveTo perform longitudinal MUNIX recordings in a set of muscles in a multicentre setting in order to evaluate its value as a marker of disease progression.MethodsThree centres applied MUNIX in 51 ALS patients over 15 months. Six different muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor dig. brevis, abductor hallucis) were measured every 3 months on the less affected side. The decline between MUNIX and ALSFRS-R was compared.Results31 participants reached month 12. For all participants, ALSFRS-R declined at a rate of 2.3%/month. Using the total score of all muscles, MUNIX declined significantly faster by 3.2%/month (p≤0.02). MUNIX in individual muscles declined between 2.4% and 4.2%, which differed from ASLFRS-R decline starting from month 3 (p≤0.05 to 0.002). Subgroups with bulbar, lower and upper limb onset showed different decline rates of ALSFRS-R between 1.9% and 2.8%/month, while MUNIX total scores showed similar decline rates over all subgroups. Mean intraclass correlation coefficient for MUNIX intra-rater reliability was 0.89 and for inter-rater reliability 0.80.ConclusionMUNIX is a reliable electrophysiological biomarker to track lower motor neuron loss in ALS.

Multiple Orofacial Indices in Amyotrophic Lateral Sclerosis

1993 ◽  
Vol 36 (6) ◽  
pp. 1158-1167 ◽  
Author(s):  
Roxanne DePaul ◽  
Benjamin R. Brooks
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Muscle Strength ◽  
Motor Neuron ◽  
Speech Intelligibility ◽  
Lower Lip ◽  
Neuron Loss ◽  
Initial Symptoms ◽  
Swallowing Problems ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by significant speech and swallowing problems resulting from upper and lower motor neuron loss. Weakness is the primary ALS disease-related sign, and measures of muscle strength have revealed nonuniform patterns of muscle weakness in orofacial muscles. To a large extent, muscle strength measures in these studies have not been evaluated in terms of functional significance, and few researchers have addressed the relation between weakness and motor neuron loss. This study addressed whether multiple measures, including static isometric maximum voluntary contraction (MVC), a dynamic measure of the peak rate of change of force (PRCF), an upper motor neuron (UMN) index, and a functional disability score (FDS) might enhance understanding of speech dysfunction in ALS. Ten males diagnosed with sporadic ALS showing mild speech impairment and an equal number of matched controls were studied. Tongue MVC and PRCF were more impaired than those of the lip and jaw, irrespective of the time post onset and site of initial symptoms. Results also suggested that disproportionate tongue impairment may be related to UMN deficits. However, impairments in the rate of contraction did not appear to be related to UMN deficits. Tongue weakness and tongue and lower lip PRCF were related to the degree of speech severity, but none of the measures was related to speech intelligibility. The value of a functional outcome measure like speech intelligibility and its role in characterizing orofacial involvement in the early stages of ALS bulbar impairment are discussed.

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