Motor neuron disease: A primary disorder of corticomotoneurons?

Pamphlett, Roger; Kril, Jillian J.; Hng, Tien‐Ming

doi:10.1002/mus.880180308

Cited by 49 publications

(29 citation statements)

References 14 publications

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“…10 This leaves open the question of a specific contribution of the cortical site in the pathophysiology of ALS in primate species. 23,31,32,57 Previous anatomo-pathological studies 33,49,50 suggested that spinal and cortical motor neurons may degenerate independently. In contrast, on the basis of data obtained with transcranial magnetic stimulation (TMS) in ALS patients, it was suggested that an altered excitability of UMNs leading to glutamate excitotoxicity might be the primary event in the pathological process, 23,51,53 possibly promoted by an impairment of cortical inhibitory processes.…”

Section: Accepted 21 December 2005mentioning

confidence: 98%

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

et al. 2006

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Little is known about the possible link between cortical and spinal motor neuron dysfunction in amyotrophic lateral sclerosis (ALS). We correlated the characteristics of the responses to transcranial magnetic stimulation (TMS) with the electromechanical properties and firing pattern of single motor units (MUs) tested in nine ALS patients, three patients with Kennedy's disease, and 15 healthy subjects. In Kennedy's disease, 19 of 22 MUs were markedly enlarged with good electromechanical coupling and discharged with great variability. Their excitatory responses increased with MU size. In ALS, 17 of 34 MUs with excitatory responses behaved as in Kennedy's disease. By contrast, 28 MUs with nonsignificant responses showed poor electromechanical coupling and high firing rates, whereas 28 MUs with inhibitory responses showed moderate functional alterations. This result indicates that in ALS as in Kennedy's disease, sprouting of corticospinal axons may occur on surviving motoneurons. A clear relationship exists between the responsiveness of MUs to TMS and their functional state.

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Section: Accepted 21 December 2005mentioning

confidence: 98%

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

et al. 2006

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“…The reported degeneration of the dendritic arborizations, changes in synapses, and loss of Betz cells in amyotrophic lateral sclerosis and other degenerative illnesses involving the primary motor cortex suggest a participation of this neuronal subpopulation in the process of the disease (Hammer et al, 1979;Udaka et al, 1986;Kiernan and Hudson, 1991;Murayama et al, 1992;Nimchinsky et al, 1992;Nihei et al, 1993;Sasaki and Murayama, 1994;Pamphlett et al, 1995;Fujita et al, 1999;Sasaki and Iwata, 1999;Tsuchiya et al, 2000Tsuchiya et al, , 2002Hof and Perl, 2002). The hypothesis that spinal motoneuronal degeneration is secondary to cortical transynaptic degeneration (Eisen et al, 1992), even if widely criticized (Pamphlett et al, 1995), has refocused attention on the possible involvement of the primary motor cortex in lower motoneuron disease. Many authors have attempted to establish a relation between neuronal loss and shrinkage in the spinal cord and in large motoneurons in the primary motor cortex (Marie, 1928;Davison, 1941;Lawyer and Netsky, 1953;Kiernan and Hudson, 1991;Nihei et al, 1993;Pamphlett et al, 1995) by comparing neuronal size between pathologic and control cases and quantifying the total number of motoneurons in different cortical and spinal regions.…”

Section: Betz Cells Neurodegenerative Diseases and Normal Brain Agingmentioning

confidence: 99%

“…The hypothesis that spinal motoneuronal degeneration is secondary to cortical transynaptic degeneration (Eisen et al, 1992), even if widely criticized (Pamphlett et al, 1995), has refocused attention on the possible involvement of the primary motor cortex in lower motoneuron disease. Many authors have attempted to establish a relation between neuronal loss and shrinkage in the spinal cord and in large motoneurons in the primary motor cortex (Marie, 1928;Davison, 1941;Lawyer and Netsky, 1953;Kiernan and Hudson, 1991;Nihei et al, 1993;Pamphlett et al, 1995) by comparing neuronal size between pathologic and control cases and quantifying the total number of motoneurons in different cortical and spinal regions. These studies have limitations in that the neuronal distribution patterns in layer V of the primary motor cortex were considered random, and estimates of neuronal sizes were expressed as diameters (i.e., in a two-dimensional plane based on variable criteria).…”

Section: Betz Cells Neurodegenerative Diseases and Normal Brain Agingmentioning

confidence: 99%

Stereologic characterization and spatial distribution patterns of Betz cells in the human primary motor cortex

et al. 2003

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Betz cells are giant motoneurons located in layer Vb of the primate primary motor cortex. We conducted stereological analyses of Betz cells and neighboring pyramidal cells from the brains of six neurologically normal elderly humans to determine their volume, total number, and spatial distribution, and to relate these data to functional localization. The distribution of cellular volumes exhibits a bimodal pattern, delineating two different subpopulations. Betz cell volumes follow a mediolateral gradient, the largest Betz cells being located on the most medial part of the motor cortex. Additionally, the shape of Betz cells varies between the rostral and caudal parts of the primary motor cortex, supporting the notion that there are anatomically distinct zones in primary motor cortex. The total number of Betz cells per hemisphere accounts for about one-tenth of the total number of pyramidal cells in layer Vb. Analysis of spatial distribution using Voronoi tessellation revealed maximal clustering of Betz cells in a zone situated two-thirds from the midline along the mediolateral axis of the primary motor cortex. These data suggest that Betz cells have a discrete subregional distribution that may correspond to certain aspects of the functional parcellation of area 4. These results may offer a histological correlate of functional imaging studies and are relevant in the context of neurodegenerative diseases such as amyotrophic lateral sclerosis, progressive supranuclear palsy, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia, and in studies of normal brain aging. Anat Rec Part A 270A: 137-151, 2003. © 2003 Key words: amyotrophic lateral sclerosis; area 4; Betz cells; cytoarchitecture; human neocortex; motoneurons; stereologyThe human neocortex is characterized by regional and laminar specific distributions of a variety of neuronal subtypes and distinct afferent and efferent connections. The neocortex can be parcellated into a large number of more or less distinct fields according to microscopic architecture. Identification of the primary motor cortex and its boundaries, however, has been particularly contentious. Brodmann (1903Brodmann ( , 1909 originally described area 4 as an agranular zone, delineated by the presence of Betz cells, a subpopulation of giant infragranular pyramidal neurons in cortical layer V, located on its rostral border and buried in the depth of the anterior wall of the central sulcus. This definition has since been criticized (Zeki, 1979), and Brodmann's original delineation of the primary motor cortex has been revised by other investigators, who described an intermediate precentral area, an area precentralis A, area

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“…1,2 Whether the primary target of disease in ALS is the upper motor neuron, the lower motor neuron, or both simultaneously remains controversial. [3][4][5] Other diseases within the spectrum of MND include PMA and PLS. PMA is defined by progressive lower motor neuron signs and is diagnosed after exclusion of other lower motor neuron syndromes.…”

mentioning

confidence: 99%