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Whether compression nerve injury is due to ischemia, direct mechanical injury, or both remains unsettled. To assess structural changes of nerve during compression, peroneal nerves of rats were compressed at various pressures for different times, and the structural alterations were stopped by simultaneous in situ and perfusion fixation. The structural changes observed during a few minutes of compression cannot be explained by ischemic injury because the pathologic alterations characteristic of ischemia take many hours to develop and in any case are different from the ones found here. The pressure- and time-related structural changes observed in the present study under the cuff were (i) decrease in fascicular area and increase in fiber density due to expression of endoneurial fluid; (ii) compression and expression of axoplasm, sometimes to the point of fiber transection; (iii) lengthening of internodes; and (iv) obscuration of nodes of Ranvier due to cleavage and displacement of myelin and overlapping of nodes by displaced loops of myelin. At the edges of the cuff the changes were (i) increase of fascicular area probably from expressed endoneurial fluid; (ii) widening of nodal gaps, perhaps mainly from translocated axonal fluid; and (iii) disordered structure of axoplasm. We suggest that the process of paranodal demyelination and axonal transection are linked, occur during the act of compression, and are due to shear forces. The initial event is expression of endoneurial fluid, followed by compression and expression of axoplasm and cleavage and displacement of layers of myelin. Conceivably, with prolonged cuff compression ischemic injury might be found to be superimposed on mechanical injury.

The peripheral axons of lower motor and spinal ganglion neurons were permanently transected and not allowed to regrow to target tissue in adult cats by amputation of the hind limb at the hip. The number and sizes of L-7 lower motor neurons at two levels (cell bodies of lateral group motor neurons and myelinated fibers [MFs] of ventral root) and of L-7 spinal ganglion neurons at two levels (cell bodies of L-7 spinal ganglion and MFs of dorsal root) were morphometrically evaluated in groups of cats at 3 months, 9 months, and 18 months after amputation and compared with the number and sizes of neurons in controls or with those on the opposite side. The number of neurons decreased only minimally after amputation. The diameter of neuron cell bodies was only equivocally reduced. By contrast, the median diameter and the peak diameter of both large and small MFs of dorsal and ventral nerve roots were significantly (approximately 30%) less than those of controls. This reduction in diameter of MFs is judged to be related to chronic axonal atrophy rather than to selective loss of large fibers. Permanent transection of distal axons should therefore prove to be a good model of chronic axonal atrophy.

A new synthetic pyrethroid, permethrin, has recently been granted a registration by the United States Environmental Protection Agency. Permethrin and a large number of other chemicals of its type are expected to receive widespread use in the environment in the near future. Since the mechanism by which these compounds exert their toxic effect in insects (and at higher doses in mammals) is by disruption of the normal function of nervous tissue, a detailed morphologic evaluation of the nervous system was performed on rats from two long-term feeding studies conducted on permethrin. In this evaluation, examination of central and peripheral nervous plus examination of extensive morphometric data and teased myelinated fibers of distal sural and tibial nerves and of the maxillary division of cranial nerve V did not reveal any changes which could be attributed to the feeding of the pesticide.

Alterations of primary afferent axons in the nucleus gracilis were studied at three weeks and four, 12, and 24 months after peripheral nerve axotomy by hindlimb amputation at the hip joint in 19 female cats. The contralateral side and two cats not subjected to amputation were controls. We observed two major types of fiber alterations. One, fibers showed changes of axonal atrophy, myelin remodelling, and degeneration. Adaxonal invagination occurred more frequently (p less than 0.005) at three weeks postamputation, in territories known to contain centrally directed axons of primary afferent neurons of the lower limb, than in controls. Perhaps adaxonal sequestration contributed to axonal attenuation. Two, there were filamentous, granular, central core, and other types of axonal swellings found in territories containing central axons of primary afferent neuron terminals of the lower limb. These changes occurred most frequently at 12 and 24 months and were significantly more frequent than in control tissue. These reactive/dystrophic axons therefore were associated with permanent axotomy, but we have not established that they occur in central axons of primary afferent neurons, or whether they are degenerative or abortive regenerative changes.

Morphometric characterization of fiber regeneration in a distal nerve after focal proximal nerve injury may provide useful clinical information and insights about underlying neurobiologic mechanisms. The myelinated (MF) and unmyelinated (UF) fibers of peroneal nerve of groups of mice were assessed 9 months after crush, graft, and multiple crush injury of the proximal sciatic nerve: number and size distribution of axon areas, myelin areas, and fiber diameters. After crush, number of regenerated MF and UF was almost identical to that of controls. Their size distribution had almost returned to normal. After graft and multiple crush, fiber number had returned to normal or was significantly increased beyond normal but there were only a few large fibers present. This may be explained by: (a) disproportionate regeneration of small-diameter compared to large-diameter classes of fibers; (b) misdirected regrowth of fibers, so that functional reinnervation was not established, resulting in failure of development or retrograde atrophy and degeneration; or (c) cellular alterations at the site of injury or in the distal nerve which inhibited neural outgrowth or elongation or did not inhibit outgrowth but retarded or prevented maturation. We conclude that explanation (b) is involved, and that there is some evidence favoring the roles of (a) and (c).

Feeding galactose to rats induces nerve conduction abnormalities, increased levels of nerve galactitol, endoneurial edema, elevated pressure and hypoxia of endoneurial fluid, and pathological abnormalities of nerve fibers. To investigate the cellular mechanisms of the fiber lesions and their possible relationship to alterations in the nerve microenvironment, rat peroneal nerves were morphometrically evaluated eight months after the commencement of galactose feeding. Whereas the density of neurofilaments (NF/micron2) in the transverse axonal area of myelinated fibers was not significantly different between the nerves of galactose-fed and control rats, axonal areas and the number of NF/axon, when related to myelin spiral length, were significantly less in nerves of galactose-fed rats. Myelin alterations, characteristic of axonal atrophy, were also significantly increased. The present data provide evidence of a proportionate decrease in axonal caliber and the number of NF/axon in myelinated fibers in experimental galactose neuropathy, suggesting that galactose induces fibers in experimental galactose neuropathy, suggesting that galactose induces either decreased NF synthesis, assembly or transport. The possible role of microenvironmental alterations, including endoneurial hypoxia and hyperosmolarity, in the production of this axonal atrophy is discussed.

To determine the effect of diabetes on the development of axonal degeneration after acute nerve compression, the mobilized peroneal nerves of rats with streptozotocin-induced diabetes and of control rats were compressed at 150 mmHg (1 mmHg = 133 Pa) for 30 min by using specially devised cuffs. At three intervals after compression--3 days, rats diabetic for 31 wk; 14 days, diabetic for 6 wk; and 24 days, diabetic for 31 wk--groups of nerves were studied to assess numbers and sizes of fibers above, at, and below the cuff and to assess frequency of fiber degeneration in teased fibers from nerve distal to the cuff. Teased fibers with pathologic abnormalities were more frequent in nerves from controls than in nerves from diabetic rats in all three groups but the difference was statistically significant only at 3 and 14 days after compression. The lack of significant difference at 24 days may be explained by higher rates of disappearance of degenerating products and of fiber regeneration at 24 than at 3 and 14 days. This study provides evidence that in addition to delaying the reported functional deficit of vibratory detection threshold and conduction block during nerve compression, diabetes also may partially prevent axonal injury. Low nerve myo-inositol concentration did not predispose diabetic nerve to acute compression injury. If these results also apply to human diabetes and if repeated acute compression is involved in the genesis of fiber degeneration in entrapment, then a higher frequency of entrapment neuropathy among diabetics might be due to mechanisms other than increased susceptibility of fibers to acute compression--e.g., possibly to greater constriction of nerve due to pathologic alterations of the carpal ligament.

The diagnostic criteria, natural history, nerve conduction characteristics, pathology, laboratory features, and efficacy of corticosteroid treatment have been evaluated personally in 53 patients with chronic inflammatory polyradiculoneuropathy (CIP) who were followed up for an average of about 7.5 years. These were patients whose monophasic neurologic deficit had not crested by 6 months, patients with recurrences, and patients with a steady or stepwise progression. The typical features of CIP include absence of an associated disease, frequent history of preceding infection or receipt of foreign protein, and tendency to involve cranial, truncal, and proximal as well as distal limb structures and to have diffusely slow conduction velocity of peripheral nerves. The most marked slowing is often very proximal. The pathologic features include serous edema, mononuclear cell infiltrates (especially in perivascular areas, but without evidence of vasculitis), macrophage-induced segmental demyelination, and hypertrophic neuritis. If our patients are representative, complete recovery occurs only infrequently; about 60% of patients are able to be ambulatory and work, 25% become confined to a wheelchair or become bedridden, and approximately 10% die from their disease. Although the bulk of the pathologic changes affect spinal roots and proximal nerves, the brain and spinal cord may be involved also. Degeneration into linear rows of myelin ovoids is the predominant type of myelinated fiber degeneration of the sural nerve at the ankle.

Some patients with radiologic findings of neurogenic arthropathy or multiple fractures do not exhibit overt neurologic signs. Results of nerve conduction velocity, computer-assisted sensory examination, periosteal nociception, and morphometric and graded teased-fiber evaluation of cutaneous nerves allowed us to recognize a mild neuropathic abnormality. Neurogenic arthropathy and subclinical neuropathy were also found in relatives. In three kinships, the underlying disorder was probably hereditary sensory neuropathy type 1 and in several others, it was recessively inherited sensory neuropathy. These arthropathies were often painful, and overt loss of superficial and deep pain sensation was not a prominent or necessary condition. An interplay of multiple factors including insensitivity, trauma, obesity, activity, abuse, personality, mental subnormality, and metabolic joint and bone disease are probably involved in the development of the bony lesions and thus provide further evidence that environmental factors affect expression of human mutant genes for inherited neuropathy.