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Motor Neuron Dysfunction (motor + neuron_dysfunction)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin

JOURNAL OF NEUROCHEMISTRY, Issue 3 2006
Stéphanie Millecamps
Abstract Peripherin is a type III neuronal intermediate filament detected in motor neuron inclusions of amyotrophic lateral sclerosis (ALS) patients. We previously reported that overexpression of peripherin provokes late-onset motor neuron dysfunction in transgenic mice. Here, we show that peripherin overexpression slows down axonal transport of neurofilament (NF) proteins, and that the transport defect precedes by several months the appearance of axonal spheroids in adult mice. Defective NF transport by peripherin up-regulation was further confirmed with dorsal root ganglia (DRG) neurons cultured from peripherin transgenic embryos. Immunofluorescence microscopy and western blotting revealed that excess peripherin provokes reduction in levels of hyperphosphorylated NF-H species in DRG neurites. Similarly the transport of a green fluorescent protein (GFP)-tagged NF-M, delivered by means of a lentiviral construct, was impaired in DRG neurites overexpressing peripherin. These results demonstrate that peripherin overexpression can cause defective transport of type IV NF proteins, a phenomenon that may account for the progressive formation of ALS-like spheroids in axons. [source]

Sensitivity of electrophysiological tests for upper and lower motor neuron dysfunction in ALS: A six-month longitudinal study

MUSCLE AND NERVE, Issue 2 2010
Mamede 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]

Cortical versus spinal dysfunction in amyotrophic lateral sclerosis

MUSCLE AND NERVE, Issue 5 2006
Shahram Attarian MD
Abstract 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. Muscle Nerve, 2006 [source]

Clinical Practice of Functional Electrical Stimulation: From "Yesterday" to "Today"

ARTIFICIAL ORGANS, Issue 8 2008
Milan R. DimitrijevicArticle first published online: 18 AUG 200
Abstract:, Functional electrical stimulation (FES) is an accepted treatment method for paresis or paralysis after spinal cord and head injury as well as stroke and other neurological upper motor neuron disorders. At the beginning, FES worked like an electrophysiological brace for the correction of drop foot of patients after a stroke. When analyzing early accomplishments, it becomes evident that FES was influenced rather by technological and biomedical engineering development than by contemporary knowledge on neurocontrol of movement in individuals with upper motor neuron paralysis. Nevertheless, with better understanding of pathophysiology of spasticity and neurocontrol of impaired movement, FES advanced from an electrophysiological brace to a treatment modality for the improvement of muscle control, neuroaugmentation of residual movements, and supportive procedure for "spontaneous recovery" of motor control. In the present article we shall illustrate barriers which delayed FES to be applied in clinical practice of neuron rehabilitation from "Yesterday" to "Today." We shall discuss the importance to apply FES early after the onset of neurological conditions to prevent disuse of noninjured portions of the CNS. Moreover, FES can play a significant role in the supporting processes of neuroplasticity in the subacute phase of upper motor neuron dysfunction. Therefore, the electrophysiological brace of "Yesterday" provides "Today" a correction of missing neuromuscular function. At the same time, it is an active external device for the correction of motor deficits interacting with the somatosensory-motor integration. Thus, "Yesterday" and "Today" of the same technological approach can be very different, thanks to a different understanding and assessment of "external" and "internal" components of human motor control. [source]

Optimized Synthesis of AMPA Receptor Antagonist ZK,187638 and Neurobehavioral Activity in a Mouse Model of Neuronal Ceroid Lipofuscinosis

CHEMMEDCHEM, Issue 10 2006
Bernd Elger Dr.
Abstract Previous structure,activity relationship studies in the search for a potent, noncompetitive , -amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist led to 2,3-dimethyl-6-phenyl-12H -[1,3]dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine (ZK,187638). However, the first synthesis had some drawbacks regarding reagents, processes, and overall yield, which furthermore decreased when the synthesis was scaled up. Therefore, we now report a new synthetic route for this compound which requires fewer steps and is suited for large-scale production. This compound significantly relieved the symptoms of neuromuscular deficit in mnd mice, a model of neuronal ceroid lipofuscinosis with motor neuron dysfunction. After oral administration, the concentrations of the compound in the brain and spinal cord were about threefold higher than those in the plasma. In summary, this novel AMPA antagonist is accessible through an optimized synthetic route, has good neurobehavioral activity, oral bioavailability, and favorable brain penetration. This opens new possibilities for the treatment of devastating neurological diseases that are mediated by the AMPA receptor. [source]