motor neuron disease

Summary

Summary: Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)

Top Publications

  1. Ayers J, Lelie H, Workman A, Prudencio M, Brown H, Fromholt S, et al. Distinctive features of the D101N and D101G variants of superoxide dismutase 1; two mutations that produce rapidly progressing motor neuron disease. J Neurochem. 2014;128:305-14 pubmed publisher
    ..We conclude that these mutants exhibit distinct properties despite producing similar disease phenotypes in patients...
  2. Johnson J, Gibbs J, Megarbane A, Urtizberea J, Hernandez D, Foley A, et al. Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease. Brain. 2012;135:2875-82 pubmed publisher
    ..Clearly, this makes an excellent candidate therapy for the SLC52A2 mutation-positive patients identified here. Initial riboflavin treatment of one of these patients shows promising results...
  3. Pamphlett R. Exposure to environmental toxins and the risk of sporadic motor neuron disease: an expanded Australian case-control study. Eur J Neurol. 2012;19:1343-8 pubmed publisher
    It remains unclear what role environmental toxins play in sporadic motor neuron disease (SMND) and its most common subtype, amyotrophic lateral sclerosis (SALS)...
  4. Yagi T, Ito D, Nihei Y, Ishihara T, Suzuki N. N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress. Hum Mol Genet. 2011;20:3831-40 pubmed publisher
  5. Ahmed Z, Doherty K, Silveira Moriyama L, Bandopadhyay R, Lashley T, Mamais A, et al. Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathies. Acta Neuropathol. 2011;122:415-28 pubmed publisher
    ..pathological features with progressive supranuclear palsy (PSP), but present with clinical features of motor neuron disease (MND) and/or frontotemporal dementia (FTD)...
  6. Kassa R, Kasensa N, Monterroso V, Kayton R, Klimek J, David L, et al. On the biomarkers and mechanisms of konzo, a distinct upper motor neuron disease associated with food (cassava) cyanogenic exposure. Food Chem Toxicol. 2011;49:571-8 pubmed publisher
    ..g. protein disulfide isomerase), and maintenance of the cytoskeleton integrity (e.g. ?-spectrin). Studies are needed to elucidate the role of the aformentioned modifications in the pathogenesis of cassava-associated motor-system disease...
  7. Bigini P, Veglianese P, Andriolo G, Cova L, Grignaschi G, Caron I, et al. Intracerebroventricular administration of human umbilical cord blood cells delays disease progression in two murine models of motor neuron degeneration. Rejuvenation Res. 2011;14:623-39 pubmed publisher
    ..In particular, we show that HuCB-MNCs release a series of cytokines and chemokines with antiinflammatory properties that could be responsible of the functional improvement of mouse models of motor neuron degenerative disorders...
  8. Goh K, Tian S, Shahrizaila N, Ng C, Tan C. Survival and prognostic factors of motor neuron disease in a multi-ethnic Asian population. Amyotroph Lateral Scler. 2011;12:124-9 pubmed publisher
    Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients...
  9. O Connor E, McCabe M. Predictors of quality of life in carers for people with a progressive neurological illness: a longitudinal study. Qual Life Res. 2011;20:703-11 pubmed publisher

More Information

Publications62

  1. van der Graaff M, Sage C, Caan M, Akkerman E, Lavini C, Majoie C, et al. Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study. Brain. 2011;134:1211-28 pubmed publisher
    ..Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time...
  2. Kanavouras K, Tzatzarakis M, Mastorodemos V, Plaitakis A, Tsatsakis A. A case report of motor neuron disease in a patient showing significant level of DDTs, HCHs and organophosphate metabolites in hair as well as levels of hexane and toluene in blood. Toxicol Appl Pharmacol. 2011;256:399-404 pubmed publisher
    b>Motor neuron disease is a devastating neurodegenerative condition, with the majority of sporadic, non-familial cases being of unknown etiology...
  3. Lim M, Selak M, Xiang Z, Krainc D, Neve R, Kraemer B, et al. Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease. J Neurosci. 2012;32:1123-41 pubmed publisher
    ..To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C...
  4. Østern R, Fagerheim T, Ørstavik K, Holmøy T, Heiberg A, Lund Petersen I, et al. Hereditary motor neuron disease in a large Norwegian family with a "H46R" substitution in the superoxide dismutase 1 gene. Neuromuscul Disord. 2012;22:511-21 pubmed publisher
    ..implications of the condition seen in this family have little in common with what is normally associated with sporadic amyotrophic lateral sclerosis and illustrates the complexity of the genetic etiology of lower motor neuron disease.
  5. Green P, Wiseman M, Crow Y, Houlden H, Riphagen S, Lin J, et al. Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54. Am J Hum Genet. 2010;86:485-9 pubmed publisher
    ..We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families...
  6. Di Fonzo A, Ronchi D, Gallia F, Cribiù F, Trezzi I, Vetro A, et al. Lower motor neuron disease with respiratory failure caused by a novel MAPT mutation. Neurology. 2014;82:1990-8 pubmed publisher
    ..To investigate the molecular defect underlying a large Italian kindred with progressive adult-onset respiratory failure, proximal weakness of the upper limbs, and evidence of lower motor neuron degeneration...
  7. Gowing G, Svendsen C. Stem cell transplantation for motor neuron disease: current approaches and future perspectives. Neurotherapeutics. 2011;8:591-606 pubmed publisher
    ..and questions remain, the beneficial effects observed following transplantation therapy in animal models of motor neuron disease has sparked hope and a number of clinical trials...
  8. Chanson J, Echaniz Laguna A, Vogel T, Mohr M, Benoilid A, Kaltenbach G, et al. TDP43-positive intraneuronal inclusions in a patient with motor neuron disease and Parkinson's disease. Neurodegener Dis. 2010;7:260-4 pubmed publisher
    ..The role of the 43-kDa transactivation-responsive DNA-binding protein (TDP43) in neurodegenerative diseases is not yet clearly established...
  9. Kosaka T, Fu Y, Shiga A, Ishidaira H, Tan C, Tani T, et al. Primary lateral sclerosis: upper-motor-predominant amyotrophic lateral sclerosis with frontotemporal lobar degeneration--immunohistochemical and biochemical analyses of TDP-43. Neuropathology. 2012;32:373-84 pubmed publisher
    ..PLS, with 43-kDa TAR DNA-binding protein (TDP-43) abnormality, we examined two adult patients with motor neuron disease, which clinically was limited almost entirely to the UMN system, and was followed by progressive ..
  10. Xu L, Shen P, Hazel T, Johe K, Koliatsos V. Dual transplantation of human neural stem cells into cervical and lumbar cord ameliorates motor neuron disease in SOD1 transgenic rats. Neurosci Lett. 2011;494:222-6 pubmed publisher
    Stem cells provide novel sources of cell therapies for motor neuron disease that have recently entered clinical trials...
  11. Almeida V, Mestre T, de Carvalho M. Pseudobulbar syndrome in two patients with human immunodeficiency virus infection. Amyotroph Lateral Scler. 2010;11:220-2 pubmed publisher
    Different forms of motor neuron disease occurring in association with HIV infection have been described...
  12. Murray L, Talbot K, Gillingwater T. Review: neuromuscular synaptic vulnerability in motor neurone disease: amyotrophic lateral sclerosis and spinal muscular atrophy. Neuropathol Appl Neurobiol. 2010;36:133-56 pubmed publisher
    ..We conclude that future experiments developing therapeutic approaches specifically targeting neuromuscular synaptic vulnerability are likely to be required to prevent or delay disease onset and progression in human MND patients...
  13. Kanning K, Kaplan A, Henderson C. Motor neuron diversity in development and disease. Annu Rev Neurosci. 2010;33:409-40 pubmed publisher
    ..Extrinsic and intrinsic mechanisms that confer resistance represent promising therapeutic targets in these currently incurable diseases...
  14. El Kadi A, Bros Facer V, Deng W, Philpott A, Stoddart E, Banks G, et al. The legs at odd angles (Loa) mutation in cytoplasmic dynein ameliorates mitochondrial function in SOD1G93A mouse model for motor neuron disease. J Biol Chem. 2010;285:18627-39 pubmed publisher
    ..These data suggest that the Loa mutation reduces the vulnerability of mitochondria to the toxic effects of mutant SOD1, leading to improved mitochondrial function in SOD1(G93A) motor neurons...
  15. Finsterer J, Kallab V, Auer H. Neurotoxocariasis associated with lower motor neuron disease. Report of one case. Rev Med Chil. 2010;138:483-6 pubmed publisher
    ..Whether lower motor neuron disease was causally related to neurotoxocariasis or due to a general metabolic defect, remains speculative.
  16. Luty A, Kwok J, Dobson Stone C, Loy C, Coupland K, Karlstrom H, et al. Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease. Ann Neurol. 2010;68:639-49 pubmed publisher
    ..Pathological ubiquitinated inclusion bodies observed in FTLD and motor neuron disease (MND) comprise trans-activating response element (TAR) DNA binding protein (TDP-43) and/or fused in sarcoma ..
  17. Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343:506-511 pubmed publisher
    ..Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease...
  18. Dal Bello Haas V, Florence J. Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database Syst Rev. 2013;:CD005229 pubmed publisher
    Despite the high incidence of muscle weakness in individuals with amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND), the effects of exercise in this population are not well understood...
  19. Raaphorst J, Beeldman E, de Visser M, de Haan R, Schmand B. A systematic review of behavioural changes in motor neuron disease. Amyotroph Lateral Scler. 2012;13:493-501 pubmed publisher
    b>Motor neuron disease (MND) and the behavioural variant of frontotemporal dementia (bvFTD) are thought to be part of a disease spectrum...
  20. Müller H, Unrath A, Huppertz H, Ludolph A, Kassubek J. Neuroanatomical patterns of cerebral white matter involvement in different motor neuron diseases as studied by diffusion tensor imaging analysis. Amyotroph Lateral Scler. 2012;13:254-64 pubmed publisher
    ..For potential future developments in MRI diagnostics in MND, a (perhaps multiparametric) ROI-based approach should include CST and the CC motor segment...
  21. Vlam L, van der Pol W, Cats E, Straver D, Piepers S, Franssen H, et al. Multifocal motor neuropathy: diagnosis, pathogenesis and treatment strategies. Nat Rev Neurol. 2011;8:48-58 pubmed publisher
    ..The clinical presentation of MMN may mimic amyotrophic lateral sclerosis, other variants of motor neuron disease, or chronic inflammatory demyelinating polyneuropathy with asymmetric onset...
  22. Bak T, Chandran S. What wires together dies together: verbs, actions and neurodegeneration in motor neuron disease. Cortex. 2012;48:936-44 pubmed publisher
    For more than a century the research on Motor Neuron Disease (MND) has been dominated by a tension between the concept of a selective, purely motor degeneration and a growing realisation of the high frequency and importance of cognitive ..
  23. Hein N, Rainier S, Richardson R, Fink J. Motor neuron disease due to neuropathy target esterase mutation: enzyme analysis of fibroblasts from human subjects yields insights into pathogenesis. Toxicol Lett. 2010;199:1-5 pubmed publisher
    Recently, we identified neuropathy target esterase (NTE) mutation as the cause of an autosomal recessive motor neuron disease (NTE-MND)...
  24. Kim J, Lee S, Choi Y, Kang S, Lee J, Choi J, et al. Association between survivor motor neuron 2 (SMN2) gene homozygous deletion and sporadic lower motor neuron disease in a Korean population. Ann Clin Lab Sci. 2010;40:368-74 pubmed
    ..such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) suggest that sporadic lower motor neuron disease (LMND) may be related to SMN gene deletion...
  25. Rainier S, Albers J, Dyck P, Eldevik O, Wilcock S, Richardson R, et al. Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families. Muscle Nerve. 2011;43:19-25 pubmed publisher
    Recently, we reported that mutations in the neuropathy target esterase (NTE) gene cause autosomal recessive motor neuron disease (NTE-MND)...
  26. Lunn J, Sakowski S, Federici T, Glass J, Boulis N, Feldman E. Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011;6:201-13 pubmed publisher
  27. Chio A, Calvo A, Moglia C, Mazzini L, Mora G. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry. 2011;82:740-6 pubmed publisher
    ..However, the differential characteristics of these phenotypes are still largely unknown...
  28. Rusina R, Kovacs G, Fiala J, Hort J, Ridzon P, Holmerová I, et al. FTLD-TDP with motor neuron disease, visuospatial impairment and a progressive supranuclear palsy-like syndrome: broadening the clinical phenotype of TDP-43 proteinopathies. A report of three cases. BMC Neurol. 2011;11:50 pubmed publisher
    ..degeneration with ubiquitin and TDP-43 positive neuronal inclusions represents a novel entity (FTLD-TDP) that may be associated with motor neuron disease (FTLD-MND); involvement of extrapyramidal and other systems has also been reported.
  29. Gibbons C, Mills R, Thornton E, Ealing J, Mitchell J, Shaw P, et al. Development of a patient reported outcome measure for fatigue in motor neurone disease: the Neurological Fatigue Index (NFI-MND). Health Qual Life Outcomes. 2011;9:101 pubmed publisher
    ..Fatigue was defined as reversible motor weakness and whole-body tiredness that was predominantly brought on by muscular exertion and was partially relieved by rest...
  30. Kuzma Kozakiewicz M, Usarek E, Ludolph A, Baranczyk Kuzma A. Mice with mutation in dynein heavy chain 1 do not share the same tau expression pattern with mice with SOD1-related motor neuron disease. Neurochem Res. 2011;36:978-85 pubmed publisher
    Due to controversy about the involvement of Dync1h1 mutation in pathogenesis of motor neuron disease, we investigated expression of tau protein in transgenic hybrid mice with Dync1h1 (so-called Cra1/+), SOD1G93A (SOD1/+), double (Cra1/..
  31. Mitchell J, McGoldrick P, Vance C, Hortobagyi T, Sreedharan J, Rogelj B, et al. Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion. Acta Neuropathol. 2013;125:273-88 pubmed publisher
    ..Furthermore, these mice will provide a new model to study disease mechanism, and test therapies. ..
  32. Ramesh T, Lyon A, Pineda R, Wang C, Janssen P, Canan B, et al. A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Dis Model Mech. 2010;3:652-62 pubmed publisher
    ..These phenotypes were more severe in lines expressing higher levels of mutant Sod1 and were absent in lines overexpressing wild-type Sod1. Thus, we have generated a vertebrate model of ALS to complement existing mammal models...
  33. Unrath A, Müller H, Riecker A, Ludolph A, Sperfeld A, Kassubek J. Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging. Hum Brain Mapp. 2010;31:1727-40 pubmed publisher
    ..Future advanced MRI-based investigations might help to provide a fingerprint-identification of MNDs...
  34. Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011;10:253-63 pubmed publisher
    ..An improved understanding of the biological processes that cause neuroinflammation will help to define its medical importance and to identify the therapeutic potential of interfering with this reaction...
  35. Peters M, Fitzpatrick R, Doll H, Playford E, Jenkinson C. Patients' experiences of health and social care in long-term neurological conditions in England: a cross-sectional survey. J Health Serv Res Policy. 2013;18:28-33 pubmed publisher
    ..To investigate patients' experiences of health and social care services in long-term neurological conditions in England...
  36. Nunn P, Lyddiard J, Christopher Perera K. Brain glutathione as a target for aetiological factors in neurolathyrism and konzo. Food Chem Toxicol. 2011;49:662-7 pubmed publisher
  37. Nandedkar S, Barkhaus P, Stalberg E. Motor unit number index (MUNIX): principle, method, and findings in healthy subjects and in patients with motor neuron disease. Muscle Nerve. 2010;42:798-807 pubmed publisher
    ..When the CMAP changed significantly (>30%) in 1 year, the CMAP and MUNIX decreased in parallel. MUNIX would be useful to study MU loss in degenerative diseases of motor neurons. Muscle Nerve 42: 798-807, 2010...
  38. Fujita Y, Fujita S, Takatama M, Ikeda M, Okamoto K. Numerous FUS-positive inclusions in an elderly woman with motor neuron disease. Neuropathology. 2011;31:170-6 pubmed publisher
    We report an autopsy case of a 75-year-old Japanese woman with motor neuron disease (MND) showing numerous neuronal and glial inclusions immunostained with anti-fused in sarcoma (FUS) antibody...
  39. Thomson S, Wishart T, Patani R, Chandran S, Gillingwater T. Using induced pluripotent stem cells (iPSC) to model human neuromuscular connectivity: promise or reality?. J Anat. 2012;220:122-30 pubmed publisher
  40. Katsuno M, Adachi H, Banno H, Suzuki K, Tanaka F, Sobue G. Transforming growth factor-? signaling in motor neuron diseases. Curr Mol Med. 2011;11:48-56 pubmed
  41. Bucher T, Colle M, Wakeling E, Dubreil L, FYFE J, Briot Nivard D, et al. scAAV9 intracisternal delivery results in efficient gene transfer to the central nervous system of a feline model of motor neuron disease. Hum Gene Ther. 2013;24:670-82 pubmed publisher
    ..vegf) were administered in a limb-expression 1 (LIX1)-deficient cat-a large animal model of lower motor neuron disease-using three different delivery routes to the central nervous system. AAV...
  42. Ostberg P, Bogdanovic N. Semantic dementia with lower motor neuron disease showing FTLD-TDP type 3 pathology (sensu Mackenzie). Neuropathology. 2011;31:271-9 pubmed publisher
    We describe a case of frontotemporal lobar degeneration with semantic dementia and lower motor neuron disease. A 63-year-old man presented with the full clinical picture of semantic dementia, including semantic anomia, surface alexia, ..
  43. Ganesalingam J, Bowser R. The application of biomarkers in clinical trials for motor neuron disease. Biomark Med. 2010;4:281-97 pubmed publisher
    ..The application of biomarkers into the clinical arena of motor neuron disease should both determine if a drug hits its proposed target and whether the drug alters the course of disease...
  44. Parlett L, Bowman J, van Wijngaarden E. Evaluation of occupational exposure to magnetic fields and motor neuron disease mortality in a population-based cohort. J Occup Environ Med. 2011;53:1447-51 pubmed publisher
    ..the association between electromagnetic fields and amyotrophic lateral sclerosis, the most common form of motor neuron disease (MND), has been inconclusive...
  45. Douglass C, Kandler R, Shaw P, McDermott C. An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease. J Neurol Neurosurg Psychiatry. 2010;81:646-9 pubmed publisher
    New criteria for the neurophysiological diagnosis of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) were recently proposed at an international symposium in Awaji-shima, Japan...
  46. Raaphorst J, de Visser M, van Tol M, Linssen W, van der Kooi A, de Haan R, et al. Cognitive dysfunction in lower motor neuron disease: executive and memory deficits in progressive muscular atrophy. J Neurol Neurosurg Psychiatry. 2011;82:170-5 pubmed publisher
    ..sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA)...
  47. Alonso V, Villaverde Hueso A, Hens M, Morales Piga A, Abaitua I, de la Paz M. Increase in motor neuron disease mortality in Spain: temporal and geographical analysis (1990-2005). Amyotroph Lateral Scler. 2011;12:192-8 pubmed publisher
    The aim of this study was to assess the trend of motor neuron disease mortality in Spain from 1990 to 2005, and to ascertain the existence of geographical differences in mortality rates...
  48. Hein N, Stuckey J, Rainier S, Fink J, Richardson R. Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties. Toxicol Lett. 2010;196:67-73 pubmed publisher
    ..esterase domain of NTE were identified in patients with a novel type of HSP (SPG39) designated NTE-related motor neuron disease (NTE-MND)...
  49. Snowden J, Rollinson S, Thompson J, Harris J, Stopford C, Richardson A, et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain. 2012;135:693-708 pubmed publisher
    ..repeat expansion in the C9ORF72 gene as the cause of chromosome 9-linked frontotemporal dementia and motor neuron disease offers the opportunity for greater understanding of the relationship between these disorders and other ..
  50. Geser F, Stein B, Partain M, Elman L, McCluskey L, Xie S, et al. Motor neuron disease clinically limited to the lower motor neuron is a diffuse TDP-43 proteinopathy. Acta Neuropathol. 2011;121:509-17 pubmed publisher
    b>Motor neuron disease (MND) may present as an isolated lower motor neuron (LMN) disorder...
  51. Grace G, Orange J, Rowe A, Findlater K, Freedman M, Strong M. Neuropsychological functioning in PLS: a comparison with ALS. Can J Neurol Sci. 2011;38:88-97 pubmed
  52. Iwata N, Kwan J, Danielian L, Butman J, Tovar Moll F, Bayat E, et al. White matter alterations differ in primary lateral sclerosis and amyotrophic lateral sclerosis. Brain. 2011;134:2642-55 pubmed publisher
    ..These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders...
  53. Palmisano R, Golfi P, Heimann P, Shaw C, Troakes C, Schmitt John T, et al. Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: implications for human motor neuron disease. BMC Neurosci. 2011;12:24 pubmed publisher
    ..VPS54 protein as a component of a protein complex is involved in vesicular Golgi trafficking; impaired vesicle trafficking might also be mechanistic in the pathogenesis of human ALS...