Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder of the motor neurons, characterized by focal onset of muscle weakness and incessant disease progression. While the presence of concomitant upper and lower motor neuron signs has been recognized as a pat...
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doaj-2c8e1330ed9d4eab8a290f6e704cbb3d2020-11-25T00:16:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-06-012011281810.3390/ijms20112818ijms20112818Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological TechniquesMehdi A. J. van den Bos0Nimeshan Geevasinga1Mana Higashihara2Parvathi Menon3Steve Vucic4Western Clinical School, University of Sydney, Sydney 2145, AustraliaWestern Clinical School, University of Sydney, Sydney 2145, AustraliaWestern Clinical School, University of Sydney, Sydney 2145, AustraliaWestern Clinical School, University of Sydney, Sydney 2145, AustraliaWestern Clinical School, University of Sydney, Sydney 2145, AustraliaAmyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder of the motor neurons, characterized by focal onset of muscle weakness and incessant disease progression. While the presence of concomitant upper and lower motor neuron signs has been recognized as a pathognomonic feature of ALS, the pathogenic importance of upper motor neuron dysfunction has only been recently described. Specifically, transcranial magnetic stimulation (TMS) techniques have established cortical hyperexcitability as an important pathogenic mechanism in ALS, correlating with neurodegeneration and disease spread. Separately, ALS exhibits a heterogeneous clinical phenotype that may lead to misdiagnosis, particularly in the early stages of the disease process. Cortical hyperexcitability was shown to be a robust diagnostic biomarker if ALS, reliably differentiating ALS from neuromuscular mimicking disorders. The present review will provide an overview of key advances in the understanding of ALS pathophysiology and diagnosis, focusing on the importance of cortical hyperexcitability and its relationship to advances in genetic and molecular processes implicated in ALS pathogenesis.https://www.mdpi.com/1422-0067/20/11/2818ALScortical hyperexcitabilityglutamate excitotoxicityTMS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mehdi A. J. van den Bos Nimeshan Geevasinga Mana Higashihara Parvathi Menon Steve Vucic |
spellingShingle |
Mehdi A. J. van den Bos Nimeshan Geevasinga Mana Higashihara Parvathi Menon Steve Vucic Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques International Journal of Molecular Sciences ALS cortical hyperexcitability glutamate excitotoxicity TMS |
author_facet |
Mehdi A. J. van den Bos Nimeshan Geevasinga Mana Higashihara Parvathi Menon Steve Vucic |
author_sort |
Mehdi A. J. van den Bos |
title |
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques |
title_short |
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques |
title_full |
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques |
title_fullStr |
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques |
title_full_unstemmed |
Pathophysiology and Diagnosis of ALS: Insights from Advances in Neurophysiological Techniques |
title_sort |
pathophysiology and diagnosis of als: insights from advances in neurophysiological techniques |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-06-01 |
description |
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disorder of the motor neurons, characterized by focal onset of muscle weakness and incessant disease progression. While the presence of concomitant upper and lower motor neuron signs has been recognized as a pathognomonic feature of ALS, the pathogenic importance of upper motor neuron dysfunction has only been recently described. Specifically, transcranial magnetic stimulation (TMS) techniques have established cortical hyperexcitability as an important pathogenic mechanism in ALS, correlating with neurodegeneration and disease spread. Separately, ALS exhibits a heterogeneous clinical phenotype that may lead to misdiagnosis, particularly in the early stages of the disease process. Cortical hyperexcitability was shown to be a robust diagnostic biomarker if ALS, reliably differentiating ALS from neuromuscular mimicking disorders. The present review will provide an overview of key advances in the understanding of ALS pathophysiology and diagnosis, focusing on the importance of cortical hyperexcitability and its relationship to advances in genetic and molecular processes implicated in ALS pathogenesis. |
topic |
ALS cortical hyperexcitability glutamate excitotoxicity TMS |
url |
https://www.mdpi.com/1422-0067/20/11/2818 |
work_keys_str_mv |
AT mehdiajvandenbos pathophysiologyanddiagnosisofalsinsightsfromadvancesinneurophysiologicaltechniques AT nimeshangeevasinga pathophysiologyanddiagnosisofalsinsightsfromadvancesinneurophysiologicaltechniques AT manahigashihara pathophysiologyanddiagnosisofalsinsightsfromadvancesinneurophysiologicaltechniques AT parvathimenon pathophysiologyanddiagnosisofalsinsightsfromadvancesinneurophysiologicaltechniques AT stevevucic pathophysiologyanddiagnosisofalsinsightsfromadvancesinneurophysiologicaltechniques |
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