Neuromyotonia: an unusual presentation of intrathoracic malignancy.
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A 48 year old woman is described who presented with increasing muscular rigidity and who was found to have a mediastinal tumour. Electrophysiological studies revealed that the muscular stiffness resulted from very high frequency motor unit activity which outlasted voluntary effort, and which was abolished by nerve block. The abnormal activity may have arisen at the anterior horn cell level. Marked improvement followed the administration of diphenylhydantoin. (+info)
Rapid onset transverse myelitis in adolescence: implications for pathogenesis and prognosis.
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Five adolescents with transverse myelitis were reviewed. All presented with a rapid onset paralysis of the lower limbs and impairment of bladder control. The maximum disability developed between 10 minutes and six hours. There was no history of trauma, asthma, or prodromal illness. Investigations failed to demonstrate a vascular cause. Extensive spinal cord abnormalities were observed on magnetic resonance imaging. Electrophysiological investigations, performed in four cases, were all consistent with anterior horn cell damage. In all five adolescents there was poor recovery. The underlying pathogenesis of this rapid onset condition remains a subject of debate. Similarities with both transverse myelitis and fibrocartilaginous emboli are evident, widening the spectrum of conditions within the transverse myelitis umbrella. These observations suggest that in rapid onset "transverse myelitis" the combination of extensive hyperintensity on spinal cord neuroimaging with electrophysiological evidence of anterior horn cell involvement might have adverse prognostic significance. (+info)
Age-related atrophy of motor axons in mice deficient in the mid-sized neurofilament subunit.
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Neurofilaments are central determinants of the diameter of myelinated axons. It is less clear whether neurofilaments serve other functional roles such as maintaining the structural integrity of axons over time. Here we show that an age-dependent axonal atrophy develops in the lumbar ventral roots of mice with a null mutation in the mid-sized neurofilament subunit (NF-M) but not in animals with a null mutation in the heavy neurofilament subunit (NF-H). Mice with null mutations in both genes develop atrophy in ventral and dorsal roots as well as a hind limb paralysis with aging. The atrophic process is not accompanied by significant axonal loss or anterior horn cell pathology. In the NF-M-null mutant atrophic ventral root, axons show an age-related depletion of neurofilaments and an increased ratio of microtubules/neurofilaments. By contrast, the preserved dorsal root axons of NF-M-null mutant animals do not show a similar depletion of neurofilaments. Thus, the lack of an NF-M subunit renders some axons selectively vulnerable to an age-dependent atrophic process. These studies argue that neurofilaments are necessary for the structural maintenance of some populations of axons during aging and that the NF-M subunit is especially critical. (+info)
Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons.
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BACKGROUND: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." METHODS: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). CONCLUSION: The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine. (+info)
Long-term gene expression in the anterior horn motor neurons after intramuscular inoculation of a live herpes simplex virus vector.
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To clarify the feasibility of the herpes simplex virus (HSV) vector in expressing the foreign gene in the motor neuron, we inoculated a live attenuated HSV expressing beta-galactosidase (beta-gal) activity under a latency-associated transcript promoter in the right gastrocnemius muscle of rats. Expression of beta-gal activity was observed 5 days after inoculation in the bilateral anterior horn cells of the spinal cord that innervates the inoculation muscle. However, the spread of beta-gal activity was not observed in the inoculation muscle. Without significant pathological changes, the spread of beta-gal-expressing neurons was observed in the lumbosacral spinal cord until 14 days after inoculation with staining concentrated in the anterior horn cells. Ninety percent of the anterior horn motor neurons expressed beta-gal activity with expression continuing to at least 182 days after inoculation. Thus beta-gal activity was expressed in the bilateral anterior horn cells at the lumbosacral spinal cord that innervates the inoculated muscle for a long time, possibly a life-long period. This indicates that this recombinant HSV vector system to motor neurons may further improve the understanding and treatment of neurological diseases in motor neurons of the spinal cord. (+info)
Depression of group Ia monosynaptic EPSPs in cat hindlimb motoneurones during fictive locomotion.
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The effects of fictive locomotion on monosynaptic EPSPs recorded in motoneurones and extracellular field potentials recorded in the ventral horn were examined during brainstem-evoked fictive locomotion in decerebrate cats. Composite homonymous and heteronymous EPSPs and field potentials were evoked by group I intensity (<= 2T) stimulation of ipsilateral hindlimb muscle nerves. Ninety-one of the 98 monosynaptic EPSPs were reduced in amplitude during locomotion (mean depression of the 91 was to 66 % of control values); seven increased in amplitude (to a mean of 121 % of control). Twenty-one of the 22 field potentials were depressed during locomotion (mean depression to 72 % of control). All but 14 Ia EPSPs were smaller during both the flexion and extension phases of locomotion than during control. In 35 % of the cases there was < 5 % difference between the amplitudes of the EPSPs evoked during the flexion and extension phases. In 27 % of the cases EPSPs evoked during flexion were larger than those evoked during extension. The remaining 38 % of EPSPs were larger during extension. There was no relation between either the magnitude of EPSP depression or the locomotor phase in which maximum EPSP depression occurred and whether an EPSP was recorded in a flexor or extensor motoneurone. The mean recovery time of both EPSP and field potential amplitudes following the end of a bout of locomotion was approximately 2 min (range, < 10 to > 300 s). Motoneurone membrane resistance decreased during fictive locomotion (to a mean of 61 % of control, n = 22). Because these decreases were only weakly correlated to EPSP depression (r 2 = 0.31) they are unlikely to fully account for this depression. The depression of monosynaptic EPSPs and group I field potentials during locomotion is consistent with the hypothesis that during fictive locomotion there is a tonic presynaptic regulation of synaptic transmission from group Ia afferents to motoneurones and interneurones. Such a reduction in neurotransmitter release would decrease group Ia monosynaptic reflex excitation during locomotion. This reduction may contribute to the tonic depression of stretch reflexes occurring in the decerebrate cat during locomotion. (+info)
White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate receptor antagonism.
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BACKGROUND AND PURPOSE: Spinal cord ischemia is a serious complication of surgery of the aorta. NMDA receptor activation secondary to ischemia-induced release of glutamate is a major mechanism of neuronal death in gray matter. White matter injury after ischemia results in long-tract dysfunction and disability. The AMPA/kainate receptor mechanism has recently been implicated in white matter injury. METHODS: We studied the effects of AMPA/kainate receptor blockade on ischemic white matter injury in a rat model of spinal cord ischemia. RESULTS: Intrathecal administration of an AMPA/kainate antagonist, 6-nitro-7-sulfamoyl-(f)-quinoxaline-2, 3-dione (NBQX), 1 hour before ischemia reduced locomotor deficit, based on the Basso-Beattie-Bresnahan scale (0=total paralysis; 21=normal) (sham: 21+/-0, n=3; saline: 3.7+/-4.5, n=7; NBQX: 12. 7+/-7.0, n=7, P<0.05) 6 weeks after ischemia. Gray matter damage and neuronal loss in the ventral horn were evident after ischemia, but no difference was noted between the saline and NBQX groups. The extent of white matter injury was quantitatively assessed, based on axonal counts, and was significantly less in the NBQX as compared with the saline group in the ventral (sham: 1063+/-44/200x200 microm, n=3; saline: 556+/-104, n=7; NBQX: 883+/-103, n=7), ventrolateral (sham: 1060+/-135, n=3; saline: 411+/-66, n=7; NBQX: 676+/-122, n=7), and corticospinal tract (sham: 3391+/-219, n=3; saline: 318+/-23, n=7; NBQX: 588+/-103, n=7) in the white matter on day 42. CONCLUSIONS: Results indicate severe white matter injury in the spinal cord after transient ischemia. NBQX, an AMPA/kainate receptor antagonist, reduced ischemia-induced white matter injury and improved locomotor function. (+info)
Delaying caspase activation by Bcl-2: A clue to disease retardation in a transgenic mouse model of amyotrophic lateral sclerosis.
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Molecular mechanisms of apoptosis may participate in motor neuron degeneration produced by mutant copper/zinc superoxide dismutase (mSOD1), the only proven cause of amyotrophic lateral sclerosis (ALS). Consistent with this, herein we show that the spinal cord of transgenic mSOD1 mice is the site of the sequential activation of caspase-1 and caspase-3. Activated caspase-3 and its produced beta-actin cleavage fragments are found in apoptotic neurons in the anterior horn of the spinal cord of affected transgenic mSOD1 mice; although such neurons are few, their scarcity should not undermine the potential importance of apoptosis in the overall mSOD1-related neurodegeneration. Overexpression of the anti-apoptotic protein Bcl-2 attenuates neurodegeneration and delays activation of the caspases and fragmentation of beta-actin. These data demonstrate that caspase activation occurs in this mouse model of ALS during neurodegeneration. Our study also suggests that modulation of caspase activity may provide protective benefit in the treatment of ALS, a view that is consistent with our recent demonstration of caspase inhibition extending the survival of transgenic mSOD1 mice. (+info)