Atypical form of amyotrophic lateral sclerosis.
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OBJECTIVE: To investigate patients with an unusual type of muscular atrophy confined to the upper limbs (proximally dominant) and the shoulder girdle, while sparing the face and the legs until the terminal stage. METHODS: Eight patients (six men and two women) were clinically examined. The age at onset ranged from 42 to 73 years, and the clinical course varied from 28 to 81 months. There was no family history of motor neuron disease in any of these patients. Necropsy was performed in two of them. RESULTS: All eight patients basically showed a similar distribution of muscular weakness and atrophy. Subluxation of the shoulder joints was found in all patients. Reflexes were absent in the upper limbs in all patients, but were almost normal in the face and legs in most patients. Pathological reflexes could be elicited in only one patient. Electromyography showed typical neurogenic changes in the limbs of all patients. Cervical MRI disclosed moderate spondylotic changes in seven patients. Antiganglioside antibodies were negative in six patients tested. Abnormal trinucleotide (CAG) repeat expansion of androgen receptor gene was not recognised in five patients examined. Bulbar involvement developed in three patients during the course of the disease. At necropsy, one patient showed degeneration of the pyramidal tracts and motor cortex including Betz cells as well as loss of spinal anterior horn cells and brainstem motor neurons, which is consistent with ALS; in another patient there was neuronal loss of anterior horn cells at the spinal cord accompanied by astrogliosis, whereas the motor cortex and brainstem motor nuclei were relatively well preserved. Intracytoplasmic inclusions such as Bunina bodies, skein-like inclusions, and Lewy body-like inclusions were found in both patients. CONCLUSION: These patients with their peculiar pattern of muscular atrophy seem to have ALS or a subtype of ALS. (+info)
Vasculitic polyradiculopathy in systemic lupus erythematosus.
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A 22 year old woman with recently diagnosed systemic lupus erythematosus presented with subacute progressive areflexic paraparesis, electrophysiologically identified as a pure axonal polyradiculopathy. Sural nerve biopsy disclosed necrotising vasculitis. A striking radiological feature was marked enhancement of the cauda equina with gadolinium. (+info)
Neurological complications of anterior spinal surgery for kyphosis with normal somatosensory evoked potentials (SEPs).
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We report a case of neurological complications of anterior release for correction of kyphosis. After the operation, the patient had pyramidal weakness and decreased pain sensation below T5, whereas light touch, proprioception and vibration sensation were intact. Clinical and neurophysiological findings in this patient suggested a partial lesion of the spinal cord probably due to ischaemia in the territory of the anterior spinal artery. Intraoperative and postoperative tibial nerve SEPs remained normal, which stresses the need for recording from the motor pathways. (+info)
Insertion of a retrotransposon in Mbp disrupts mRNA splicing and myelination in a new mutant rat.
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Our understanding of myelination has been greatly enhanced via the study of spontaneous mutants that harbor a defect in a gene encoding one of the major myelin proteins (myelin mutants). In this study, we describe a unique genetic defect in a new myelin mutant called the Long Evans shaker (les) rat that causes severe dysmyelination of the CNS. Myelin deficits result from disruption of the myelin basic protein (Mbp) gene caused by the insertion of an endogenous retrotransposon [early transposons (ETn) element] into a noncoding region (intron 3) of the gene. The ETn element alters the normal splicing dynamics of MBP mRNA, leading to a dramatic reduction in the levels of full-length isoforms (<5% of normal) and the appearance of improperly spliced, chimeric transcripts. Although these aberrant transcripts contain proximal coding regions of the MBP gene (exons 1-3), they are unable to encode functional proteins required to maintain the structural integrity of the myelin sheath. These chimeric transcripts seem capable, however, of producing the necessary signal to initiate and coordinate myelin gene expression because normal numbers of mature oligodendrocytes synthesizing abundant levels of other myelin proteins are present in the mutant CNS. The les rat is thus an excellent model to study alternative functions of MBP beyond its well characterized role in myelin compaction. (+info)
Activity patterns and synaptic organization of ventrally located interneurons in the embryonic chick spinal cord.
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To investigate the origin of spontaneous activity in developing spinal networks, we examined the activity patterns and synaptic organization of ventrally located lumbosacral interneurons, including those whose axons project into the ventrolateral funiculus (VLF), in embryonic day 9 (E9)-E12 chick embryos. During spontaneous episodes, rhythmic synaptic potentials were recorded from the VLF and from spinal interneurons that were synchronized, cycle by cycle, with rhythmic ventral root potentials. At the beginning of an episode, ventral root potentials started before the VLF discharge and the firing of individual interneurons. However, pharmacological blockade of recurrent motoneuron collaterals did not prevent or substantially delay interneuron recruitment during spontaneous episodes. The synaptic connections of interneurons were examined by stimulating the VLF and recording the potentials evoked in the ventral roots, in the VLF, or in individual interneurons. Low-intensity stimulation of the VLF evoked a short-latency depolarizing potential in the ventral roots, or in interneurons, that was probably mediated mono- or disynaptically. At higher intensities, long-latency responses were recruited in a highly nonlinear manner, eventually culminating in the activation of an episode. VLF-evoked potentials were reversibly blocked by extracellular Co2+, indicating that they were mediated by chemical synaptic transmission. Collectively, these findings indicate that ventral interneurons are rhythmically active, project to motoneurons, and are likely to be interconnected by recurrent excitatory synaptic connections. This pattern of organization may explain the synchronous activation of spinal neurons and the regenerative activation of spinal networks when provided with a suprathreshold stimulus. (+info)
NK-1 receptor immunoreactivity in distinct morphological types of lamina I neurons of the primate spinal cord.
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In cat and monkey, lamina I cells can be classified into three basic morphological types (fusiform, pyramidal, and multipolar), and recent intracellular labeling evidence in the cat indicates that fusiform and multipolar lamina I cells are two different types of nociceptive cells, whereas pyramidal cells are innocuous thermoreceptive-specific. Because earlier observations indicated that only nociceptive dorsal horn neurons respond to substance P (SP), we examined which morphological types of lamina I neurons express receptors for SP (NK-1r). We categorized NK-1r-immunoreactive (IR) lamina I neurons in serial horizontal sections from the cervical and lumbar enlargements of four monkeys. Consistent results were obtained by two independent teams of observers. Nearly all NK-1r-IR cells were fusiform (42%) or multipolar (43%), but only 6% were pyramidal (with 9% unclassified). We obtained similar findings in three monkeys in which we used double-labeling immunocytochemistry to identify NK-1r-IR and spinothalamic lamina I neurons retrogradely labeled with cholera toxin subunit b from the thalamus; most NK-1r-IR lamina I spinothalamic neurons were fusiform (48%) or multipolar (33%), and only 10% were pyramidal. In contrast, most (approximately 75%) pyramidal and some (approximately 25%) fusiform and multipolar lamina I spinothalamic neurons did not display NK-1r immunoreactivity. These data indicate that most fusiform and multipolar lamina I neurons in the monkey can express NK-1r, consistent with the idea that both types are nociceptive, whereas only a small proportion of lamina I pyramidal cells express this receptor, consistent with the previous finding that they are non-nociceptive. However, these findings also indicate that not all nociceptive lamina I neurons express receptors for SP. (+info)
Leukemia inhibitory factor augments neurotrophin expression and corticospinal axon growth after adult CNS injury.
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The cytokine leukemia inhibitory factor (LIF) modulates glial and neuronal function in development and after peripheral nerve injury, but little is known regarding its role in the injured adult CNS. To further understand the biological role of LIF and its potential mechanisms of action after CNS injury, effects of cellularly delivered LIF on axonal growth, glial activation, and expression of trophic factors were examined after adult mammalian spinal cord injury. Fibroblasts genetically modified to produce high amounts of LIF were grafted to the injured spinal cords of adult Fischer 344 rats. Two weeks after injury, animals with LIF-secreting cells showed a specific and significant increase in corticospinal axon growth compared with control animals. Furthermore, expression of neurotrophin-3, but not nerve growth factor, brain-derived neurotrophic factor, glia cell line-derived neurotrophic factor, or ciliary neurotrophic factor, was increased at the lesion site in LIF-grafted but not in control subjects. No differences in astroglial and microglial/macrophage activation were observed. Thus, LIF can directly or indirectly modulate molecular and cellular responses of the adult CNS to injury. These findings also demonstrate that neurotrophic molecules can augment expression of other trophic factors in vivo after traumatic injury in the adult CNS. (+info)
Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats.
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Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief of pain. The literature on the clinical application of TENS is extensive. However, surprisingly few reports have addressed the neurophysiological basis for the actions of TENS. The gate control theory of pain is typically used to explain the actions of high-frequency TENS, whereas, low-frequency TENS is typically explained by release of endogenous opioids. The current study investigated the role of mu, delta, and kappa opioid receptors in antihyperalgesia produced by low- and high-frequency TENS by using an animal model of inflammation. Antagonists to mu (naloxone), delta (naltrinodole), or kappa (nor-binaltorphimine) opioid receptors were delivered to the spinal cord by microdialysis. Joint inflammation was induced by injection of kaolin and carrageenan into the knee-joint cavity. Withdrawal latency to heat was assessed before inflammation, during inflammation, after drug (or artificial cerebral spinal fluid as a control) administration, and after drug (or artificial cerebral spinal fluid) administration + TENS. Either high- (100 Hz) or low- frequency (4 Hz) TENS produced approximately 100% inhibition of hyperalgesia. Low doses of naloxone, selective for mu opioid receptors, blocked the antihyperalgesia produced by low-frequency TENS. High doses of naloxone, which also block delta and kappa opioid receptors, prevented the antihyperalgesia produced by high-frequency TENS. Spinal blockade of delta opioid receptors dose-dependently prevented the antihyperalgesia produced by high-frequency TENS. In contrast, blockade of kappa opioid receptors had no effect on the antihyperalgesia produced by either low- or high-frequency TENS. Thus, low-frequency TENS produces antihyperalgesia through mu opioid receptors and high-frequency TENS produces antihyperalgesia through delta opioid receptors in the spinal cord. (+info)