Nerve Fibre Degeneration in the Brain in Amyotrophic Lateral Sclerosis

Abstract

The purpose of this paper is to report briefly some findings concerning the distribution of degenerating myelinated nerve fibres in the brains of patients who had amyotrophic lateral sclerosis. It is not intended to report in detail the distribution of degenerating fibres throughout the central nervous system in this condition, nor to review the lengthy literature concerning it. In order to establish that the patients did in fact suffer from amyotrophic lateral sclerosis a few sections from the spinal cord and brain-stem showing the classical picture of the condition are included. Further, these sections are used to validate the staining methods used in the brain sections.The customary concept of amyotrophic lateral sclerosis is of a degenerative process affecting mainly the motor neurones of the central nervous system. The lower motor neurones in the spinal cord are usually affected and, to a variable extent, those of the cranial nerves. The upper motor neurones in the hemispheres may also be affected. In the spinal cord the typical fibre picture is of degeneration of cortico-spinal fibres; there is sometimes also degeneration of spino-cerebellar and other anterior and lateral column fibres.Cases have been described in which degeneration was found to extend throughout the entire corticospinal system, from the motor cortex through the cerebral peduncle, pons, medulla, and cord. But it is more frequently stated that the degeneration in the cortico-spinal tract is, in most cases, limited to the distal part of the fibres, and that it often cannot be traced further rostrally than the medulla or pons. This was the experience of Davison, who reported in 1941 (a and b) that in the 37 cases which he had studied he could not find any degeneration above the medulla in 16 cases, nor above the peduncle in 25 cases. On the other hand, Holmes had found degeneration throughout the cortico-spinal system, from cortex to cord inclusively, in all 10 of the 10 cases he reported in 1909. Later workers have tended to neglect both his work and the methods he used.Apart from the degeneration in the cortex, a little degeneration has been occasionally noted in other parts of the brain. Holmes found a few fibres passing between the main mass of degenerating cortico-spinal fibres in the internal capsule and the lateral nucleus of the thalamus. These degenerating fibres were observed in three of the 10 cases he studied. Other workers do not seem to have confirmed this finding. A very few degenerating fibres have also been occasionally seen in the brain-stem. These observations have never been adequately illustrated nor confirmed; nor have they been generally accepted. Material and MethodsThe material consists of the central nervous system from seven patients who were diagnosed as suffering from amyotrophic lateral sclerosis.In the first three cases representative blocks from different regions of the brain and cord were examined. In the last four cases a large series of blocks was taken from the hemispheres. As the first three cases had reve...

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study

“…This correlation was strongest within the left CST at the level of the diencephalon ( r = 0.77, p < 0.05). For CC and CST, the white matter regions involved were largely congruent with ALS-related WM changes reported in previous imaging and post-mortem studies ( Filippini et al, 2010 , Smith, 1960 ). Involvement of the forceps minor is less well-established but has been reported ( Lillo et al, 2012 ).…”

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study

“…This correlation was strongest within the left CST at the level of the diencephalon ( r = 0.77, p < 0.05). For CC and CST, the white matter regions involved were largely congruent with ALS-related WM changes reported in previous imaging and post-mortem studies ( Filippini et al, 2010 , Smith, 1960 ). Involvement of the forceps minor is less well-established but has been reported ( Lillo et al, 2012 ).…”

Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS

“…In relation to the WM changes, the area of reduced NDI extends from the posterior limb of the internal capsule and continues rostrally into the subcortical WM of the PCG. This supports the notion that loss of motor neuron axon density within the cerebral WM is a core feature of the neurodegenerative process associated with ALS, consistent with many pathological studies 28 29. It is possible that alterations in glial cells and myelin may also contribute to these changes in NDI.…”

Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

“…Involvement of the CST could be demonstrated below the motor cortex, in the posterior limb of the internal capsule and brainstem. This is in line with the hallmark degeneration observed in neuropathological studies of ALS brains [ 6 ]. In agreement with the description of asymmetry in ALS pathology [ 18 ], we found a correlation with disease severity mainly at the right CST.…”

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study

“…This correlation was strongest within the left CST at the level of the diencephalon ( r = 0.77, p < 0.05). For CC and CST, the white matter regions involved were largely congruent with ALS-related WM changes reported in previous imaging and post-mortem studies ( Filippini et al, 2010 , Smith, 1960 ). Involvement of the forceps minor is less well-established but has been reported ( Lillo et al, 2012 ).…”

Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS

“…In relation to the WM changes, the area of reduced NDI extends from the posterior limb of the internal capsule and continues rostrally into the subcortical WM of the PCG. This supports the notion that loss of motor neuron axon density within the cerebral WM is a core feature of the neurodegenerative process associated with ALS, consistent with many pathological studies 28 29. It is possible that alterations in glial cells and myelin may also contribute to these changes in NDI.…”

Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

“…Involvement of the CST could be demonstrated below the motor cortex, in the posterior limb of the internal capsule and brainstem. This is in line with the hallmark degeneration observed in neuropathological studies of ALS brains [ 6 ]. In agreement with the description of asymmetry in ALS pathology [ 18 ], we found a correlation with disease severity mainly at the right CST.…”

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study

“…This correlation was strongest within the left CST at the level of the diencephalon ( r = 0.77, p < 0.05). For CC and CST, the white matter regions involved were largely congruent with ALS-related WM changes reported in previous imaging and post-mortem studies ( Filippini et al, 2010 , Smith, 1960 ). Involvement of the forceps minor is less well-established but has been reported ( Lillo et al, 2012 ).…”

Neurite orientation and dispersion density imaging (NODDI) detects cortical and corticospinal tract degeneration in ALS

“…In relation to the WM changes, the area of reduced NDI extends from the posterior limb of the internal capsule and continues rostrally into the subcortical WM of the PCG. This supports the notion that loss of motor neuron axon density within the cerebral WM is a core feature of the neurodegenerative process associated with ALS, consistent with many pathological studies 28 29. It is possible that alterations in glial cells and myelin may also contribute to these changes in NDI.…”

Susceptibility-Weighted Imaging Provides Insight into White Matter Damage in Amyotrophic Lateral Sclerosis

“…Involvement of the CST could be demonstrated below the motor cortex, in the posterior limb of the internal capsule and brainstem. This is in line with the hallmark degeneration observed in neuropathological studies of ALS brains [ 6 ]. In agreement with the description of asymmetry in ALS pathology [ 18 ], we found a correlation with disease severity mainly at the right CST.…”