Peripheral Nervous System Lesions Research Articles

Altered Expression of Microtubule-Associated Proteins in Cat Trochlear Motoneurons after Peripheral and Central Lesions of the Trochlear Nerve

Neurons lesioned in the peripheral nervous system (PNS) generally regenerate and survive, while neurons lesioned in the central nervous system (CNS) do not regenerate and often die. Investigators have traditionally compared the neuronal responses to PNS and CNS lesions in two separate populations of neurons. In this study, we compared the effects of PNS and CNS lesions on the expression of cytoskeletal proteins in a single neuronal population, the trochlear motoneurons of the cat. The trochlear nerve was lesioned either unilaterally in the PNS or bilaterally in the CNS (within the anterior medullary velum), and animals were allowed to survive 1, 2, or 4 weeks. Brain sections were reacted immunocytochemically using antibodies against microtubule-associated protein-2 (MAP-2) and a phosphorylated isoform of MAP1B, termed MAP1B-P. MAP-2 immunoreactivity (IR) was significantly decreased in the CNS-lesioned trochlear nucleus, compared to the lesioned and the unlesioned trochlear nucleus of PNS-lesioned animals. MAP1B-P IR was significantly increased in PNS- and CNS-lesioned trochlear axons, compared to axons in the unlesioned trochlear nerve of PNS-lesioned animals, and appeared in a small percentage of PNS- and CNS-lesioned cell bodies. These results support the growing body of evidence that MAP-2 can serve as a marker for cells that will eventually die following neuronal insult. The increased immunostaining of MAP1B-P in lesioned axons and its appearance in lesioned cell bodies are characteristic of the immature CNS and may reflect an initial recapitulation of early development, when the levels of this protein are high.

Peripheral neuromuscular manifestations in systemic sclerosis (scleroderma).

Systemic sclerosis (scleroderma) is thought to be the least likely of the collagen vascular disorders to cause nervous system damage. We evaluated the peripheral neuromuscular manifestations in 32 patients with scleroderma. A clinically defined peripheral nervous system (PNS) lesion was manifest in 5 of 32 patients (16%), including 2 patients with trigeminal neuropathy and single cases of polyneuropathy, brachial plexopathy, and lumbosacral radiculopathy. Neurophysiological studies suggested subclinical PNS involvement in 6 additional patients (3 with distal axonal polyneuropathy, 1 with probable myopathy and superimposed polyneuropathy, 1 with trigeminal neuropathy, and 1 with focal ulnar neuropathy). Even though subjective muscular complaints were numerous (16 patients, 50%), a defined primary muscular disease could be demonstrated only in 5 patients (16%). Our results indicate that peripheral neuropathy in scleroderma is not as uncommon as previously estimated.

The neuropathology of the acquired immune deficiency syndrome (AIDS). A review.

The nervous system has been involved in the majority (at least 75%), of cases of acquired immune deficiency syndrome (AIDS) examined postmortem, but the pathogenetic mechanisms involved are not well understood. The predominant pathological process is opportunistic infection secondary to the decrease of T-helper (T4) cells and includes toxoplasmosis, encephalitis due to cytomegalovirus and progressive multifocal leucoencephalopathy. On the other hand, mycoses (mainly cryptococcosis) are relatively uncommon. Primary lymphomas are three times more common than secondary lymphoma spreading from other sites. Cerebral involvement by Kaposi sarcoma is metastatic, probably from primary foci in the lungs. Lesions due to the direct involvement of the nervous system by the human immune deficiency virus (HIV) include subacute encephalitis and vacuolar myelopathy. The former is reported with increasing frequency and is localized predominantly to the white matter in which multinucleated giant cells can be found. These are considered typical of AIDS and have been shown to contain HIV particles in their cytoplasm. AIDS lesions due to infectious agents do not always conform to the typical pattern of the uncomplicated disease and not uncommonly there is evidence of more than one infectious agent in the same area. Peripheral nervous system lesions in HIV infections, responsible for a variety of clinical symptoms, usually appear, in biopsy material, as nonspecific inflammatory in type. CMV inclusions and lymphomatous infiltrations of peripheral nerve have been reported in autopsy cases.

Comparison of Central and Peripheral Nervous System Lesions Caused by High-Dose Short-Term and Low-Dose Subchronic Acrylamide Treatment in Rats

The effects of high-dose subacute acrylamide treatment of up to 50 mg/kg/day for 4 or 10 d were compared to those of subchronic exposure, up to 12 mg/kg/day for 90 d. In the subacute study, Purkinje cells, long ascending tracts of the spinal cord, optic tract terminal or preterminal regions in superior colliculus, sensory ganglion cells, and distal large-caliber peripheral axons were severely affected. Purkinje cells and fasciculus gracilis changes were the earliest lesions. In the subchronic study, the dominant lesion was confined to the distal peripheral axon, with only minor changes occurring in spinal cord and medulla. Paranodal swellings with the characteristic appearance of neurofilament aggregations were not seen. This morphological study suggests a significant difference between high- and low-dose acrylamide-induced lesions. If there is a reduced tendency for long-term low-dose acrylamide exposure to produce CNS lesions, the risk of irreversible nervous system damage would be less than that predicted from subacute studies.

Peripheral and central nervous system lesions caused by triethyl- and trimethyltin salts in rats.

Both trimethyltin and triethyltin salts are known to produce toxic lesions in the central nervous system. Triethyltin intoxication has been associated with central intramyelin edema, while trimethyltin has been shown to produce neuronal necrosis in selected limbic and sensory regions of the brain. Only scant attention has been paid to peripheral nerves of animals treated with alkyltins. In this study, we have treated rats with 6 or 8 mg/kg trimethyltin, and 1, 2, 4, 6, or 8 mg/kg triethyltin (single or multiple exposure), and evaluated in detail at the light microscope level both central and peripheral nervous system lesions. In addition to the central neuron necrosis or myelin edema described previously, both compounds produced peripheral axon degeneration and chromatolysis of large spinal cord and brain stem neurons. Chromatolysis was seen in reticular neurons of the brain stem and ventral horn or spinal cord in rats receiving high doses (6 or 8 mg/kg) of triethyltin, and in these same areas plus mesencephalic trigeminal nucleus in animals treated with trimethyltin. Wallerian-like degeneration of peripheral axons was seen in sciatic and tibial nerve and ventral roots of animals receiving 3 injections of 4 mg/kg or single or multiple injections of 6 or 8 mg/kg triethyltin. Axon degeneration was also seen in sciatic and tibial nerves 21 days after a single exposure to 8 mg/kg trimethyltin. Since myelin edema is believed to be reversible, the axonal changes described here may be of greater clinical significance in relation to human exposure.

Peripheral nervous system lesions in experimental allergic encephalomyelitis. Ultrastructural distribution of T cells and Ia-antigen.

The distribution of T cells and Ia-antigen in peripheral nervous system (PNS) lesions of experimental allergic encephalomyelitis was studied by light- and electron-microscopic immunocytochemical techniques. Sprague Dawley rats, sensitized with guinea pig spinal cord tissue, developed a biphasic disease with acute inflammatory and chronic inflammatory demyelinating lesions in the PNS. In both the acute non-demyelinating and the chronic demyelinating disease inflammatory infiltrates were composed of T cells and Ia-positive monocytes/macrophages. Dependent upon the stage of the disease a variable percentage of T-lymphocytes carried the Ox 8 antigen (suppressor/cytotoxic cells). In demyelinating lesions no evidence for an interaction of T cells with myelin or Schwann cells was observed, thus arguing against a direct T-cell cytotoxicity in demyelination. The whole sequence of myelin destruction and digestion was performed by W3/13-, Ia+ mononuclear cells with ultrastructural features of monocytes/macrophages. In contrast to the acute inflammatory stage of the disease, high titers of anti-myelin antibodies were present in sera of affected animals sampled during the chronic inflammatory demyelinating stage. The sera from the latter animals also showed pronounced in vivo demyelinating activity when transferred into the cerebrospinal fluid (CSF) of normal recipient rats. It is thus suggested that demyelination in this model is induced by a co-operation of cell-mediated and humoral immune mechanisms. We did not find evidence for Ia-antigen expression on local elements of the PNS (Schwann cells, axons, or endothelial cells).

The lesion of peripheral nervous system in alcohol dependence syndrome

The lesion of peripheral nervous system in alcohol dependence syndrome

Wallerian degeneration demonstrated by magnetic resonance: spectroscopic measurements on peripheral nerve.

Wallerian degeneration of rat sciatic nerves was induced by nerve section. Fifteen days later the degenerated nerves were compared with the intact contralateral nerves from the same animal. Histological sections showed the changes typical of wallerian degeneration: axonal degeneration and secondary demyelination. The freshly dissected nerves were analyzed by magnetic resonance (MR) spectroscopy at 10 MHz, and the water content was determined by dehydration. In the degenerated nerves there was a marked prolongation of both T1 and T2 relaxation times, accompanied by an increase of water content. The results demonstrate the sensitivity of MR for detection of secondary demyelination and disintegration of nerve structures. These results suggest that it should be possible to detect wallerian degeneration in MR images; this will have an important impact on neuropathological diagnosis of central and peripheral nervous system lesions.

LOCALIZE: Computer-assisted localization of peripheral nervous system lesions

A computer program, LOCALIZE, has been developed to assist physicians with localization of lesions in the peripheral nervous system. It uses a knowledge base which embodies the connective relationships of peripheral nerves in the human nervous system. It accepts as input clinical and electromyographic evidence of specific muscle weaknesses, and then suggests sites where single or multiple lesions could account for the abnormalities. Heuristic guidelines are employed to detect incomplete or inaccurate data. In addition, an explanatory capability exists to justify the assertions of the program and to make LOCALIZE potentially useful as a teaching aid. LOCALIZE is the first localization program to use a symbolic representation of neuroanatomy as its source of expertise. This allows the program to localize lesions that have not been previously described, and gives the program the capability to generate explanations based on the neuroanatomy. Although not fully evaluated in clinical trials, LOCALIZE has performed successfully using sample patient cases of varying complexity.

Nitroimidazole neurotoxicity: Are mouse studies predictive?

The purpose of this investigation was: (i) to determine if data on the relative neurotoxicity of nitroimidazole sensitizers in mice using different quantitative functional endpoints were similar, (ii) to compare misonidazole (MISO) with desmethylmisonidazole (DMM) in relation to central nervous system (CNS) versus peripheral nervous system (PNS) effects; neural tissue exposure dose and peak level; route of administration and mouse strain; and, (iii) to determine if inhibition of glycolysis was a potential mechanism of neurotoxicity. The data indicate good agreement between the functional endpoints used to determine relative neurotoxicity and the incidence of CNS and PNS pathology in mice. MISO is 2 times more toxic per administered dose and equitoxic per brain exposure dose compared with DMM in BALB/cka mice. C3H mice are approximately 2 times more sensitive than BALB/cka to both MISO and DMM. DMM (i.p., oral or i.v.) is slightly more toxic than MISO to the CNS of C3H mice. DMM given i.v. resulted in more severe PNS lesions than either i.p. or oral DMM or i.p. or oral MISO. In general, CNS and PNS lesion development coincided suggesting these effects are separate. Significant decreases in the lactate/ pyruvate ratio of the brain-stem of MISO treated mice indicates that inhibition of glycolysis is a potential mechanism of neurotoxicity. Results are discussed in relation to the predictive significance of mouse studies to the clinical testing of sensitizers.

Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys.

A consistent group of progressive central and peripheral nervous system lesions developed in seven rhesus monkeys maintained on a vitamin E-deficient diet for 30 to 33 months. These lesions were absent from vitamin E-supplemented monkeys. The principal neuropathologic alteration was loss of sensory axons in the posterior columns, sensory roots, and peripheral nerves. Morphologic and morphometric studies indicated that the distal segments of the axons were affected most severely and large-caliber myelinated fibers are selectively involved. Swollen, dystrophic axons (spheroids) occurred infrequently. Degeneration and phagocytosis of small numbers of neuronal perikarya were observed in the dorsal root ganglia and the anterior horns. The number of affected neurons was not proportional to the number of affected axons. Accumulation of lipopigment was evident in neuronal perikarya and CNS endothelial cells. The nervous system lesion were usually accompanied by a chronic necrotizing myopathy. The neuropathologic lesions in vitamin E-deficient monkeys are compared with those in vitamin E-deficient rats and in humans with low serum vitamin E concentrations. A similar type of sensory axonopathy is associated with chronic deficiency of vitamin E in these three species.