The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Cantone, Mariagiovanna; Pino, Giovanni Di; Capone, Fioravante; Piombo, Marianna; Chiarello, Daniela; Cheeran, Binith; Pennisi, Giovanni; Lazzaro, Vincenzo Di

doi:10.1016/j.clinph.2014.04.010

Cited by 91 publications

(84 citation statements)

References 214 publications

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“…Importantly, SAI was restored by administration of anticholinesterase agents, which correlated with long-term clinical outcome [174], thereby suggesting that SAI may be a prognostic biomarker in AD. In contrast, no consistent changes in intracortical facilitation or cortical silent period duration have been reported in AD [6]. Consequently, the most robust TMS outcome measures in AD seem to be an increase in cortical excitability, as reflected by reduction of motor thresholds, accompanied by a reduction in SAI, which changes in other TMS outcome measures being less consistent, a finding that likely reflects the complexity of AD pathophysiology.…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 46%

“…One study reported a reduction of LICI in AD, which appeared to be correlated with cognitive deficits [179]. Separately, consistent reduction of SAI has been established in AD [6,43,180], in keeping with dysfunction of the cholinergic system. Importantly, SAI was restored by administration of anticholinesterase agents, which correlated with long-term clinical outcome [174], thereby suggesting that SAI may be a prognostic biomarker in AD.…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

“…TMS studies have reported abnormalities of motor thresholds, which appear to exhibit a bimodal trend [6]. Namely, the motor thresholds appear significantly reduced in early stages of the disease, with an initial threshold reduction paralleling disease progression, despite pharmacological treatment [167][168][169][170][171].…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

“…Motor disorders, including gait impairment, rigidity, and hypokinesia, develop in more advanced stages of the disease [6].…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

“…It should be highlighted, however, that most clinical studies no longer just use the Bdefinite^criteria for diagnosing ALS and this should be considered when discussing the TMS as an early diagnostic biomarker for ALS. Similarly, TMS outcome measures have yielded important pathophysiological insights into the mechanisms underlying neurodegenerative disorders characterized by dementias and movement disorders [6]. In this review, we provide an overview of the physiology of TMS outcome measures and cover the key advances in the understanding of pathophysiology and diagnosis in neurodegenerative diseases as heralded by these TMS outcome measures, focusing on the importance of cortical hyperexcitability as a pathogenic and diagnostic biomarker in ALS.…”

Section: Introductionmentioning

confidence: 99%

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Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Vucic

Kiernan

2017

Neurotherapeutics

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Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials. Abnormalities of TMS outcome measures heralding cortical hyperexcitability, as evidenced by a reduction of short-interval intracortical inhibition and increased in motorevoked potential amplitude, have been consistently identified as early and intrinsic features of amyotrophic lateral sclerosis (ALS), preceding and correlating with the ensuing neurodegeneration. Cortical hyperexcitability appears to form the pathogenic basis of ALS, mediated by trans-synaptic glutamate-mediated excitotoxic mechanisms. As a consequence of these research findings, TMS has been developed as a potential diagnostic biomarker, capable of identifying upper motor neuronal pathology, at earlier stages of the disease process, and thereby aiding in ALS diagnosis. Of further relevance, marked TMS abnormalities have been reported in other neurodegenerative diseases, which have varied from findings in ALS. With time and greater utilization by clinicians, TMS outcome measures may prove to be of utility in future therapeutic trial settings across the neurodegenerative disease spectrum, including the monitoring of neuroprotective, stem-cell, and genetic-based strategies, thereby enabling assessment of biological effectiveness at early stages of drug development.

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Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 46%

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

“…Motor disorders, including gait impairment, rigidity, and hypokinesia, develop in more advanced stages of the disease [6].…”

Section: Utility Of Tms In Alzheimer's Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Vucic

Kiernan

2017

Neurotherapeutics

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Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study

et al. 2016

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Several studies have shown that, in spite of the fact that motor symptoms manifest late in the course of Alzheimer's disease (AD), neuropathological progression in the motor cortex parallels that in other brain areas generally considered more specific targets of the neurodegenerative process. It has been suggested that motor cortex excitability is enhanced in AD from the early stages, and that this is related to disease's severity and progression. To investigate the neurophysiological hallmarks of motor cortex functionality in early AD we combined transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We demonstrated that in mild AD the sensorimotor system is hyperexcitable, despite the lack of clinically evident motor manifestations. This phenomenon causes a stronger response to stimulation in a specific time window, possibly due to locally acting reinforcing circuits, while network activity and connectivity is reduced. These changes could be interpreted as a compensatory mechanism allowing for the preservation of sensorimotor programming and execution over a long period of time, regardless of the disease's progression. Hum Brain Mapp 37:2083-2096, 2016. © 2016 Wiley Periodicals, Inc.

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Cortical hyperexcitability in patients withC9ORF72mutations: Relationship to phenotype

et al. 2016

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Introduction Patients with mutations in C9orf72 can have amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or ALS-FTD. The goals were to establish whether cortical hyperexcitability occurs in C9orf72 patients with different clinical presentations. Methods Cortical thresholds and silent periods were measured in thenar muscles in 19 participants with C9orf72 expansions and 21 healthy controls using transcranial magnetic stimulation (TMS). El Escorial and Rascovsky criteria were used to diagnose ALS and FTD. Fourteen participants with C9orf72 expansions were re-tested 6 months later. Correlations with finger-tapping speed, timed peg test, the ALS functional rating scale, and Dementia Rating Scale were examined. Results Most participants with C9orf72 expansions had normal or low cortical thresholds. Among them, ALS patients had the lowest thresholds and significantly shorter silent periods. Thresholds correlated with timed peg-test scores. TMS did not correlate with the Dementia Rating Scale. Conclusion TMS measures of cortical excitability may serve as non-invasive biomarkers of ALS disease activity.

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The contribution of transcranial magnetic stimulation in the diagnosis and in the management of dementia

Cited by 91 publications

References 214 publications

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

Sensorimotor cortex excitability and connectivity in Alzheimer's disease: A TMS-EEG Co-registration study

Cortical hyperexcitability in patients withC9ORF72mutations: Relationship to phenotype

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