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Lower Motor Neurons (lower + motor_neuron)
Selected AbstractsSensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: A six-month longitudinal studyMUSCLE AND NERVE, Issue 2 2010Mamede de Carvalho MD Abstract By following a group of amyotrophic lateral sclerosis (ALS) patients longitudinally using lower motor neuron (LMN) and upper motor neuron (UMN) markers of dysfunction it may be possible to better understand the functional relationships between these motor systems in this disease. We used neurophysiological techniques to follow UMN and LMN dysfunction in a group of 28 patients with ALS, in comparison with the ALS functional rating scale (ALS-FRS) score and the forced vital capacity (FVC). We used motor unit number estimation (MUNE), compound muscle action potential (CMAP) amplitude, and the Neurophysiological Index (NI) to quantify the LMN disorder, and transcranial motor stimulation to study cortical motor threshold, motor-evoked response amplitude, central motor conduction time, and cortical silent period (CSP). The patients were studied shortly after diagnosis and then 6 months later, using both abductor digiti minimi muscles (ADM); ADM strength was initially >MRC 3 (Medical Research Council, UK). The NI and MUNE changed more than any other variable. CSP increased by about 30%, a change more marked than the slight increase observed in the cortical motor threshold (9%). The normal increase of CSP after acute muscle fatigue was preserved during disease progression. The CSP increase correlated with the MUNE rate of decay but not to the NI reduction, perhaps because NI includes F-wave frequency in itscalculation. There was no definite correlation between UMN and LMNdysfunction or progression, but there was a link between CSP and LMN changes in ALS. The CSP may be a useful variable in following UMN dysfunction in clinical practice and in clinical trials. Muscle Nerve, 2010 [source] Pick's disease with Pick bodies: An unusual autopsy case showing degeneration of the pontine nucleus, dentate nucleus, Clarke's column, and lower motor neuronNEUROPATHOLOGY, Issue 1 2007Tatsuro Oda We report a 51-year-old female with Pick's disease with Pick bodies (PDPB) showing a brainweight of 530 g. This case was considered to be a very rare case of PDPB, in which the lesion developed in the temporal and frontal lobes and later spread to the parietal lobe, occipital lobe, brainstem, cerebellum and spinal cord. This case showed very atypical clinicopathological findings. Clinically, bulging eyes and myoclonus were observed. Neuropathologically, Pick bodies were widely distributed beyond the usual distribution areas to the parietal cortices, occipital cortices, dentate nuclei, motor neuron nuclei in the brain stem, and spinal cord. The atypical clinical symptoms and the widespread neuropathological abnormalities observed in this case seem to represent an extremely extended form of PDPB. [source] Protocol for clinical neurophysiologic examination of the pelvic floorNEUROUROLOGY AND URODYNAMICS, Issue 6 2001Simon Podnar Abstract Clinical neurophysiologic examination of the pelvic floor is performed worldwide, but there is no consensus on the choice of tests, nor on technical details of individual methods. Standardized methods are, however, necessary to obtain their valid application in different laboratories for the purpose of collection of normative data, comparison of patient data and organization of multi-center studies. It is proposed that in patients with suspected "lower motor neuron" type lesions concentric needle electromyography (CNEMG) is the most informative test to detect pelvic floor denervation/reinnervation, and the external anal sphincter (EAS) muscle is the most appropriate muscle to be examined (either in isolation,when a selective lesion is suspected,or in addition to examination of other muscles). An algorithm consisting of standardized tests including a standardized approach to CNEMG examination of the EAS is presented. The proposed electrophysiologic assessment consists of a computer-assisted analysis of denervation and reinnervation features of the CNEMG signal, a qualitative assessment of reflex and voluntary activation of EAS motor units, and of electrical (or mechanical) elicitation of the bulbocavernosus reflex in those patients in whom manual anogenital stimulation failed to elicit a robust response in the EAS. The proposed protocol could serve as a basis for further studies on validity, sensitivity and specificity of electrophysiologic assessment in patients with different types of "lower motor neuron" involvement of pelvic floor muscles and sacral dysfunction. Neurourol. Urodynam. 20:669,682, 2001. © 2001 Wiley-Liss, Inc. [source] Kennedy's disease: pathogenesis and clinical approachesINTERNAL MEDICINE JOURNAL, Issue 5 2004K. J. Greenland Abstract Kennedy's disease, also known as spinal and bulbar muscular atrophy, is a progressive degenerative condition affecting lower motor neurons. It is one of nine neurodegenerative disorders caused by a polyglutamine repeat expansion. Affecting only men, Kennedy's disease is the only one of these conditions that follows an X-linked mode of inheritance. The causative protein in Kennedy's disease, with a polyglutamine expansion residing in the first N-terminal domain, is the androgen receptor. Research in this field has made significant advances in recent years, and with the increased understanding of pathogenic mechanisms, feasible approaches to treatments are being investigated. In Kennedy's disease research, the most significant issue to emerge recently is the role of androgens in exacerbating the disease process. On the basis of animal experiments, a viable hypothesis is that higher circulating levels of androgens in men could trigger the degeneration of motor neurons causing this disease, and that lower levels in heterozygous and homozygous women are protective. This is a major issue, as treatment of individuals affected by Kennedy's disease with testosterone has been considered a reasonable therapy by some neurologists. The rationale behind this approach relates to the fact that Kennedy's disease is accompanied by mild androgen insensitivity. It was therefore believed that treatment with high doses of testosterone might compensate for this loss of androgen action, with the added benefit of preventing muscle wasting. The current review provides an overview of recent advances in the field of Kennedy's disease research, including approaches to treatment. (Intern Med J 2004; 34: 279,286) [source] Loss of translation elongation factor (eEF1A2) expression in vivo differentiates between Wallerian degeneration and dying-back neuronal pathologyJOURNAL OF ANATOMY, Issue 6 2008Lyndsay M. Murray Abstract Wallerian degeneration and dying-back pathology are two well-known cellular pathways capable of regulating the breakdown and loss of axonal and synaptic compartments of neurons in vivo. However, the underlying mechanisms and molecular triggers of these pathways remain elusive. Here, we show that loss of translation elongation factor eEF1A2 expression in lower motor neurons and skeletal muscle fibres in homozygous Wasted mice triggered a dying-back neuropathy. Synaptic loss at the neuromuscular junction occurred in advance of axonal pathology and by a mechanism morphologically distinct from Wallerian degeneration. Dying-back pathology in Wasted mice was accompanied by reduced expression levels of the zinc finger protein ZPR1, as found in other dying-back neuropathies such as spinal muscular atrophy. Surprisingly, experimental nerve lesion revealed that Wallerian degeneration was significantly delayed in homozygous Wasted mice; morphological assessment revealed that ~80% of neuromuscular junctions in deep lumbrical muscles at 24 h and ~50% at 48 h had retained motor nerve terminals following tibial nerve lesion. This was in contrast to wild-type and heterozygous Wasted mice where < 5% of neuromuscular junctions had retained motor nerve terminals at 24 h post-lesion. These data show that eEF1A2 expression is required to prevent the initiation of dying-back pathology at the neuromuscular junction in vivo. In contrast, loss of eEF1A2 expression significantly inhibited the initiation and progression of Wallerian degeneration in vivo. We conclude that loss of eEF1A2 expression distinguishes mechanisms underlying dying-back pathology from those responsible for Wallerian degeneration in vivo and suggest that eEF1A2 -dependent cascades may provide novel molecular targets to manipulate neurodegenerative pathways in lower motor neurons. [source] Amyotrophic lateral sclerosis: all roads lead to RomeJOURNAL OF NEUROCHEMISTRY, Issue 5 2007Jose-Luis Gonzalez de Aguilar Abstract Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons, generalized weakness and muscle atrophy. Most cases of ALS appear sporadically but some forms of the disease result from mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). Several other mutated genes have also been found to predispose to ALS including, among others, one that encodes the regulator of axonal retrograde transport dynactin. As all roads lead to the proverbial Rome, we discuss here how distinct molecular pathways may converge to the same final result that is motor neuron death. We critically review the basic research on SOD1-linked ALS to propose a pioneering model of a ,systemic' form of the disease, causally involving multiple cell types, either neuronal or non-neuronal. Contrasting this, we also postulate that other neuron-specific defects, as those triggered by dynactin dysfunction, may account for a primary motor neuron disease that would represent ,pure' neuronal forms of ALS. Identifying different disease subtypes is an unavoidable step toward the understanding of the physiopathology of ALS and will hopefully help to design specific treatments for each subset of patients. [source] Loss of synaptophysin-positive boutons on lumbar motor neurons innervating the medial gastrocnemius muscle of the SOD1G93A G1H transgenic mouse model of ALSJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2005Da Wei Zang Abstract Amyotrophic lateral sclerosis (ALS) is a common form of motor neuron disease (MND) that involves both upper and lower nervous systems. In the SOD1G93A G1H transgenic mouse, a widely used animal model of human ALS, a significant pathology is linked to the degeneration of lower motor neurons in the lumbar spinal cord and brainstem. In the current study, the number of presynaptic boutons immunoreactive for synaptophysin was estimated on retrogradely labeled soma and proximal dendrites of , and , motor neurons innervating the medial gastrocnemius muscle. No changes were detected on both soma and proximal dendrites at postnatal day 60 (P60) of , and , motor neurons. By P90 and P120, however, , motor neuron soma had a reduction of 14 and 33% and a dendritic reduction of 19 and 36%, respectively. By P90 and P120, , motor neuron soma had a reduction of 17 and 41% and a dendritic reduction of 19 and 35%, respectively. This study shows that levels of afferent innervation significantly decreased on surviving , and , motor neurons that innervate the medial gastrocnemius muscle. This finding suggests that the loss of motor neurons and the decrease of synaptophysin in the remaining motor neurons could lead to functional motor deficits, which may contribute significantly to the progression of ALS/MND. © 2005 Wiley-Liss, Inc. [source] Spinal muscular atrophy: Recent advances and future prospectsMUSCLE AND NERVE, Issue 1 2002Sophie Nicole PhD Abstract Spinal muscular atrophies (SMA) are characterized by degeneration of lower motor neurons associated with muscle paralysis and atrophy. Childhood SMA is a frequent recessive autosomal disorder and represents one of the most common genetic causes of death in childhood. Mutations of the SMN1 gene are responsible for SMA. The knowledge of the genetic basis of SMA, a better understanding of SMN function, and the recent generation of SMA mouse models represent major advances in the field of SMA. These are starting points towards understanding the pathophysiology of SMA and developing therapeutic strategies for this devastating neurodegenerative disease, for which no curative treatment is known so far. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 4,13, 2002 [source] Bunina bodies in amyotrophic lateral sclerosisNEUROPATHOLOGY, Issue 2 2008Koichi Okamoto Bunina bodies, which are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons, are generally considered to be a specific pathologic hallmark of amyotrophic lateral sclerosis (ALS). One year before a publication by Bunina, van Reeth et al. described similar intracytoplasmic inclusions in the anterior horn cells in a patient with Pick's dementia with atypical ALS. At present, only two proteins have been shown to be present in Bunina bodies, one is cystatin C and the other is transferrin. Bunina bodies consist of amorphous electron-dense material surrounded by tubular and vesicular structures on electron microscopy. Although the nature and significance of Bunina bodies in ALS are not yet clear, the bodies may be abnormal accumulations of unknown proteinous materials. [source] Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis,ANNALS OF NEUROLOGY, Issue 3 2009Johannes Vogt MD Objective Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Methods We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology. Results Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor,related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes. Interpretation Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310,332 [source] Neuropathology with Clinical Correlations of Sporadic Amyotrophic Lateral Sclerosis: 102 Autopsy Cases Examined Between 1962 and 2000BRAIN PATHOLOGY, Issue 1 2003Yue-Shan Piao MD Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder affecting adults. We studied the neuropathology and clinical correlations in 102 autopsy cases of ALS. The age at onset of the disease was significantly higher for the bulbar-onset form (30 cases) than for the limb-onset form (72 cases). Dementia was confirmed in 7 cases. These 102 cases were divided into 4 pathological subgroups: typical ALS (59 cases), lower-motor-predominant ALS (23 cases), ALS with temporal lesions (18 cases), and ALS with pallido-nigro-luysian degeneration (2 cases). The age at onset was significantly higher for lower-motor-predominant ALS and ALS with temporal lesions than for typical ALS. In the lower motor neurons, Bunina bodies were detected in 88 cases, whereas ubiquitin-immunoreactive skein and/or spherical inclusions were detected in all 102 cases. Of the 100 available cases, 50 and 16 also showed ubiquitin-immunoreactive inclusions in the neostriatal and temporal small neurons, respectively. Ubiquitin-immunoreactive dystrophic neurites were also observed in the neostriatum in 3 of the 50 cases with neostriatal inclusions, and in the temporal cortex in 4 of the 16 cases with temporal inclusions. There was a significant association between the bulbar-onset form, temporal lesions, neostriatal inclusions and temporal inclusions, and between dementia, temporal lesions and temporal inclusions. Neostriatal and temporal dystrophic neurites were associated with dementia and bulbar-onset form through temporal lesions and temporal inclusions. The present findings may be helpful for designing further studies on the mechanisms underlying the development of ALS. 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