Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis

Menke, Ricarda; Körner, Sonja; Filippini, Nicola; Douaud, Gwenaëlle; Knight, Steven; Talbot, Kevin; Turner, Martin R

doi:10.1093/brain/awu162

Cited by 166 publications

(205 citation statements)

References 68 publications

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“…Rate of disability progression (ΔALSFRS‐R) was calculated as the decrease in ALSFRS‐R from a presumed baseline score of 48, divided by the disease duration in months from reported symptom onset. A measure of the burden of clinical UMN signs was based upon a pathological reflex sum score [Menke et al, 2014; Turner et al, 2004]…”

Section: Methodsmentioning

confidence: 99%

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Proudfoot

Rohenkohl

Quinn

et al. 2016

Human Brain Mapping

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Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Proudfoot

Rohenkohl

Quinn

et al. 2016

Human Brain Mapping

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“…After initial assessment of 248 relevant documents with the search strategy, a total of 32 VBM studies on GM investigations in ALS patients versus healthy controls were identified, among which 9 did not report the whole brain stereotactic coordinates (Bede, et al, 2013,Cosottini, et al, 2012,Douaud, et al, 2011,Kassubek, et al, 2005,Lillo, et al, 2012,Menke, et al, 2014,Mioshi, et al, 2013,Tsujimoto, et al, 2011,Turner, et al, 2007 and 3 had overlapping data sets (Agosta, et al, 2014,Rajagopalan, et al, 2014,Tedeschi, et al, 2012. Finally, 22 case-control whole-brain data sets from 20 VBM studies (Agosta, et al, 2007,Canu, et al, 2011,Cerami, et al, 2014,Chang, et al, 2005,Cosottini, et al, 2013,Devine, et al, 2015,Ellis, et al, 2001,Grosskreutz, et al, 2006,Luo, et al, 2012,Meoded, et al, 2013,Mezzapesa, et al, 2007,Minnerop, et al, 2009,Rajagopalan and Pioro, 2014,Sage, et al, 2007,Senda, et al, 2011,Stoppel, et al, 2014,Tavazzi, et al, 2014,Thivard, et al, 2007,Trojsi, et al, 2014,Zhang, et al, 2014) that were composed of 454 ALS patients (mean age 56.5, 42.3% females) and 426 healthy controls (mean age 54.6, 48.3% females), met the inclusion criteria for the meta-analysis mentioned above ( Figure 1).…”

Section: Included Studies and Sample Characteristicsmentioning

confidence: 99%

Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies

Sheng

Zhong

et al. 2015

Neurobiology of Aging

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“…Contemporary research provides indications for a possible biological substrate of the suggested relationship between cognitive/behavioral decline and prognosis. For example, progressive grey matter abnormalities have been shown to be related to language deficits [38]. Moreover, recent research reports a possible link between specific genetic abnormalities, cognitive and behavioral impairment, and reduced survival [39] .…”

Section: Discussionmentioning

confidence: 99%

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis

et al. 2015

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Background: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. Objective: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. Methods: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). Results: Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. Conclusions: We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed.

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Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis

Cited by 166 publications

References 68 publications

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Motor and extra-motor gray matter atrophy in amyotrophic lateral sclerosis: quantitative meta-analyses of voxel-based morphometry studies

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis

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