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John Ravits - One of the best experts on this subject based on the ideXlab platform.

  • als Motor phenotype heterogeneity focality and spread deconstructing Motor Neuron degeneration
    Neurology, 2009
    Co-Authors: John Ravits, Albert R La Spada
    Abstract:

    Heterogeneity of Motor phenotypes is a clinically well-recognized fundamental aspect of amyotrophic lateral sclerosis (ALS) and is determined by variability of 3 independent primary attributes: body region of onset; relative mix of upper Motor Neuron (UMN) and lower Motor Neuron (LMN) deficits; and rate of progression. Motor phenotypes are determined by the anatomy of the underlying neuropathology and the common defining elements underlying their heterogeneity are that Motor Neuron degeneration is fundamentally a focal process and that it spreads contiguously through the 3-dimensional anatomy of the UMN and LMN levels, thus causing seemingly complex and varied clinical manifestations. This suggests Motor Neuron degeneration in ALS is in actuality a very orderly and actively propagating process and that fundamental molecular mechanisms may be uniform and their chief properties deduced. This also suggests opportunities for translational research to seek pathobiology directly in the less affected regions of the nervous system.

  • implications of als focality rostral caudal distribution of lower Motor Neuron loss postmortem
    Neurology, 2007
    Co-Authors: John Ravits, Patrick Laurie, Dan H Moore
    Abstract:

    Background: Because Motor manifestations of ALS begin focally and progress contiguously, the anatomic distribution of underlying lower Motor Neuron and upper Motor Neuron degeneration should correlate to onset. Objectives: To assess the rostral–caudal distribution of lower Motor Neuron loss in relation to the region of clinical onset. Methods: We evaluated 19 ALS postmortem nervous systems from patients whose Motor manifestations had begun in different body regions. In each, we looked at four neuraxis levels: hypoglossal nucleus and cervical, thoracic, and lumbar spinal cord. We used light microscopy and devised a technique of particle counting that indexed lower Motor Neuron loss. Results: The average overall loss of lower Motor Neurons in ALS nervous systems was 55%, and the range of loss had a normal distribution that ranged between 8% and 90%. The distribution of lower Motor Neuron loss was graded within the nervous system relative to onset ( p = 0.02 by analysis of variance). In 14 of the 19 nervous systems, the regional lower Motor Neuron loss within the nervous systems was graded radially away from the region of onset. In 1, radial degeneration seemed likely but did not meet significance. In 2, radial degeneration was apparent but loss was greatest in a region different than that identified as the region of onset. In the remaining 2, lower Motor Neuron loss was minimal and not graded (both from patients whose Motor manifestations had been predominantly upper Motor Neuron). Conclusion: Lower Motor Neuron degeneration in ALS is a focal process that advances contiguously, summates over time, and creates graded loss. Stage of degeneration in the nervous system is a function of anatomic location.

  • Implications of ALS focality Rostral–caudal distribution of lower Motor Neuron loss postmortem
    Neurology, 2007
    Co-Authors: John Ravits, Patrick Laurie, Dan H Moore
    Abstract:

    Background: Because Motor manifestations of ALS begin focally and progress contiguously, the anatomic distribution of underlying lower Motor Neuron and upper Motor Neuron degeneration should correlate to onset. Objectives: To assess the rostral–caudal distribution of lower Motor Neuron loss in relation to the region of clinical onset. Methods: We evaluated 19 ALS postmortem nervous systems from patients whose Motor manifestations had begun in different body regions. In each, we looked at four neuraxis levels: hypoglossal nucleus and cervical, thoracic, and lumbar spinal cord. We used light microscopy and devised a technique of particle counting that indexed lower Motor Neuron loss. Results: The average overall loss of lower Motor Neurons in ALS nervous systems was 55%, and the range of loss had a normal distribution that ranged between 8% and 90%. The distribution of lower Motor Neuron loss was graded within the nervous system relative to onset ( p = 0.02 by analysis of variance). In 14 of the 19 nervous systems, the regional lower Motor Neuron loss within the nervous systems was graded radially away from the region of onset. In 1, radial degeneration seemed likely but did not meet significance. In 2, radial degeneration was apparent but loss was greatest in a region different than that identified as the region of onset. In the remaining 2, lower Motor Neuron loss was minimal and not graded (both from patients whose Motor manifestations had been predominantly upper Motor Neuron). Conclusion: Lower Motor Neuron degeneration in ALS is a focal process that advances contiguously, summates over time, and creates graded loss. Stage of degeneration in the nervous system is a function of anatomic location.

Dan H Moore - One of the best experts on this subject based on the ideXlab platform.

  • implications of als focality rostral caudal distribution of lower Motor Neuron loss postmortem
    Neurology, 2007
    Co-Authors: John Ravits, Patrick Laurie, Dan H Moore
    Abstract:

    Background: Because Motor manifestations of ALS begin focally and progress contiguously, the anatomic distribution of underlying lower Motor Neuron and upper Motor Neuron degeneration should correlate to onset. Objectives: To assess the rostral–caudal distribution of lower Motor Neuron loss in relation to the region of clinical onset. Methods: We evaluated 19 ALS postmortem nervous systems from patients whose Motor manifestations had begun in different body regions. In each, we looked at four neuraxis levels: hypoglossal nucleus and cervical, thoracic, and lumbar spinal cord. We used light microscopy and devised a technique of particle counting that indexed lower Motor Neuron loss. Results: The average overall loss of lower Motor Neurons in ALS nervous systems was 55%, and the range of loss had a normal distribution that ranged between 8% and 90%. The distribution of lower Motor Neuron loss was graded within the nervous system relative to onset ( p = 0.02 by analysis of variance). In 14 of the 19 nervous systems, the regional lower Motor Neuron loss within the nervous systems was graded radially away from the region of onset. In 1, radial degeneration seemed likely but did not meet significance. In 2, radial degeneration was apparent but loss was greatest in a region different than that identified as the region of onset. In the remaining 2, lower Motor Neuron loss was minimal and not graded (both from patients whose Motor manifestations had been predominantly upper Motor Neuron). Conclusion: Lower Motor Neuron degeneration in ALS is a focal process that advances contiguously, summates over time, and creates graded loss. Stage of degeneration in the nervous system is a function of anatomic location.

  • Implications of ALS focality Rostral–caudal distribution of lower Motor Neuron loss postmortem
    Neurology, 2007
    Co-Authors: John Ravits, Patrick Laurie, Dan H Moore
    Abstract:

    Background: Because Motor manifestations of ALS begin focally and progress contiguously, the anatomic distribution of underlying lower Motor Neuron and upper Motor Neuron degeneration should correlate to onset. Objectives: To assess the rostral–caudal distribution of lower Motor Neuron loss in relation to the region of clinical onset. Methods: We evaluated 19 ALS postmortem nervous systems from patients whose Motor manifestations had begun in different body regions. In each, we looked at four neuraxis levels: hypoglossal nucleus and cervical, thoracic, and lumbar spinal cord. We used light microscopy and devised a technique of particle counting that indexed lower Motor Neuron loss. Results: The average overall loss of lower Motor Neurons in ALS nervous systems was 55%, and the range of loss had a normal distribution that ranged between 8% and 90%. The distribution of lower Motor Neuron loss was graded within the nervous system relative to onset ( p = 0.02 by analysis of variance). In 14 of the 19 nervous systems, the regional lower Motor Neuron loss within the nervous systems was graded radially away from the region of onset. In 1, radial degeneration seemed likely but did not meet significance. In 2, radial degeneration was apparent but loss was greatest in a region different than that identified as the region of onset. In the remaining 2, lower Motor Neuron loss was minimal and not graded (both from patients whose Motor manifestations had been predominantly upper Motor Neuron). Conclusion: Lower Motor Neuron degeneration in ALS is a focal process that advances contiguously, summates over time, and creates graded loss. Stage of degeneration in the nervous system is a function of anatomic location.

John H. J. Wokke - One of the best experts on this subject based on the ideXlab platform.

  • the spectrum of lower Motor Neuron syndromes
    Journal of Neurology, 2003
    Co-Authors: Renske M Van Den Bergvos, L H Van Den Berg, Hessel Franssen, M De Visser, J. Visser, John H. J. Wokke
    Abstract:

    This review discusses the most important lower Motor Neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom Motor Neurons (lower Motor Neuron disease (LMND)) are primarily affected or Motor axons and their surrounding myelin (multifocal Motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation. MMN is a lower Motor Neuron syndrome with presumed immunemediated pathogenesis. Evidence of Motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower Motor Neuron syndromes. For the individual patient, dist inction between the various lower Motor Neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.

  • The spectrum of lower Motor Neuron syndromes
    Journal of Neurology, 2003
    Co-Authors: R. M. Berg-vos, L H Van Den Berg, Hessel Franssen, M De Visser, J. Visser, John H. J. Wokke
    Abstract:

    This review discusses the most important lower Motor Neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom Motor Neurons (lower Motor Neuron disease (LMND)) are primarily affected or Motor axons and their surrounding myelin (multifocal Motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation. MMN is a lower Motor Neuron syndrome with presumed immunemediated pathogenesis. Evidence of Motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower Motor Neuron syndromes. For the individual patient, dist inction between the various lower Motor Neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.

  • New hope for patients with pure lower Motor Neuron syndromes
    Journal of Neurology Neurosurgery and Psychiatry, 1999
    Co-Authors: John H. J. Wokke, L H Van Den Berg
    Abstract:

    Motor Neuron disease is still one of the most dramatic neurological conditions; it reflects a range of which one end encompasses patients with the bulbar form of amyotrophic lateral sclerosis who have dysarthria and dysphagia and have a dramatically shortened life expectancy. For patients with probable or definite Motor Neuron disease according to established criteria, the recent introduction of the antiglutamate drug riluzole gives a mean prolongation of life after diagnosis of some 3 months.1 The other end of the range of Motor Neuron disease is formed by patients with so called multifocal Motor neuropathy. This is characterised by lower Motor Neuron dysfunction in the areas of selected Motor nerves. Neurophysiological demonstration of conduction block over these nerves is pivotal for the diagnosis.2 Before the discovery of multifocal Motor neuropathy as a separate and treatable condition, patients with …

L H Van Den Berg - One of the best experts on this subject based on the ideXlab platform.

  • the spectrum of lower Motor Neuron syndromes
    Journal of Neurology, 2003
    Co-Authors: Renske M Van Den Bergvos, L H Van Den Berg, Hessel Franssen, M De Visser, J. Visser, John H. J. Wokke
    Abstract:

    This review discusses the most important lower Motor Neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom Motor Neurons (lower Motor Neuron disease (LMND)) are primarily affected or Motor axons and their surrounding myelin (multifocal Motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation. MMN is a lower Motor Neuron syndrome with presumed immunemediated pathogenesis. Evidence of Motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower Motor Neuron syndromes. For the individual patient, dist inction between the various lower Motor Neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.

  • The spectrum of lower Motor Neuron syndromes
    Journal of Neurology, 2003
    Co-Authors: R. M. Berg-vos, L H Van Den Berg, Hessel Franssen, M De Visser, J. Visser, John H. J. Wokke
    Abstract:

    This review discusses the most important lower Motor Neuron syndromes. This relatively rare group of syndromes has not been well described clinically. Two subgroups can be distinguished: patients in whom Motor Neurons (lower Motor Neuron disease (LMND)) are primarily affected or Motor axons and their surrounding myelin (multifocal Motor neuropathy (MMN)), both leading to muscle atrophy and weakness. Both hereditary and sporadic forms of LMND have been described. The discussion of recent advances in the genetic knowledge of several hereditary forms of LMND may lead to a better understanding of the pathophysiology and the development of therapeutic strategies. By contrast, the pathogenesis of sporadic LMND is largely unknown. It is, therefore, difficult to consider the various sporadic forms of LMND, discussed in this review, as separate diseases. Because the diagnostic and therapeutic options may differ, it would seem rational to consider sporadic LMND as a spectrum of syndromes which can be distinguished from each other on the basis of clinical presentation. MMN is a lower Motor Neuron syndrome with presumed immunemediated pathogenesis. Evidence of Motor conduction block on nerve conduction studies and a positive response to treatment with intravenous immunoglobulins (IVIg) are considered the most relevant criteria for the diagnosis of MMN. As it is treatable, it is important to distinguish MMN from LMND. Careful electrophysiological analysis in the search for conduction block is, therefore, required in all adult patients with pure lower Motor Neuron syndromes. For the individual patient, dist inction between the various lower Motor Neuron syndromes is important as it enables the physician to provide adequate information over the disease course in LMND and to facilitate early treatment in MMN.

  • New hope for patients with pure lower Motor Neuron syndromes
    Journal of Neurology Neurosurgery and Psychiatry, 1999
    Co-Authors: John H. J. Wokke, L H Van Den Berg
    Abstract:

    Motor Neuron disease is still one of the most dramatic neurological conditions; it reflects a range of which one end encompasses patients with the bulbar form of amyotrophic lateral sclerosis who have dysarthria and dysphagia and have a dramatically shortened life expectancy. For patients with probable or definite Motor Neuron disease according to established criteria, the recent introduction of the antiglutamate drug riluzole gives a mean prolongation of life after diagnosis of some 3 months.1 The other end of the range of Motor Neuron disease is formed by patients with so called multifocal Motor neuropathy. This is characterised by lower Motor Neuron dysfunction in the areas of selected Motor nerves. Neurophysiological demonstration of conduction block over these nerves is pivotal for the diagnosis.2 Before the discovery of multifocal Motor neuropathy as a separate and treatable condition, patients with …

Dame Pamela Shaw - One of the best experts on this subject based on the ideXlab platform.

  • 1736 diagnostic classification of lower Motor Neuron disorders
    Journal of Neurology Neurosurgery and Psychiatry, 2017
    Co-Authors: Jennifer Hosty, Amogh Patil, Dame Pamela Shaw, Tom Jenkins
    Abstract:

    Background There is a lack of clear classification systems for non-progressive, benign lower Motor Neuron syndromes of the upper limb, resulting in misdiagnosis of Motor Neuron disease (MND) at first presentation. Appropriate investigation and identification of distinguishing features is required to reduce this risk. Methods A retrospective analysis of 91 patients with an atypical presentation of a pure lower Motor Neuron weakness and/or wasting of the upper limb was performed. These were divided into final diagnostic categories and disease onset, progression and investigations were compared to identify features more indicative of benign disease. In addition, we assessed whether flexion-extension MRI was performed appropriately to investigate for Hirayama disease, a benign cervical flexion myelopathy Discussion 24.2% of the cohort had benign disease, 45.1% developed MND. Features more predictive of a diagnosis of MND at initial presentation were bilateral arm involvement (OR 15.6, p=0.002), upper limb fasciculations (OR 29.07, p