Quantitative and qualitative study of sural nerve biopsies in Krabbe's disease

Summary Sural nerve biopsies from two infants with Krabbe's disease were examined morphologically, and quantitatively analyzed to obtain the density and size distribution of myelinated and unmyelinated nerve fibers as well as the variation in internodal lengths along the course of teased nerve fibers. When compared with age-matched control material, these sural nerves revealed a 50% reduction in density of myelinated fibers with a relative preponderance of small myelinated fibers. It was estimated that each nerve contained about 15% of the large (7–10) nerve fiber population found in control nerve. No reduction in the density of unmyelinated fibers was detected.Studies of teased preparations revealed an intermittent shortening of myelin internodes with resulting increased disparity of internodal lengths along individual fibers. These changes were indicative of widespread and severe demyelination and remyelination involving peripheral myelinated nerve fibers of all sizes in Krabbe's disease. No evidence of axonal or Wallerian degeneration was detected.Lipid accumulations were seen within endoneurial macrophage and within Schwann cells of myelinated fibers in both sural nerves and in the sympathetic chain removed at autopsy in case 2. The Schwann cell deposits were osmiophilic and appeared as focal collections of paranodal granules along myclinated fibers of teased preparations.Supported by U. S. P. H. S. Grants No. NB 08620 and NS 08054, and grants from the Allen P. and Josephine B. Green Foundation, Mexico, Missouri.     

Peripheral nerve pathological findings in familial amyloid polyneuropathy: a correlative study of proximal sciatic nerve and sural nerve lesions

To analyze the peripheral nerve pathological abnormalities in familial amyloid polyneuropathy, a correlative pathological study was carried out on the spinal nerve roots, proximal sciatic nerves, sural nerves, and brachial plexuses from 3 patients with the disease in Japan. The spinal nerve roots appeared to be unaffected except for amyloid deposition on the epineurium. In sciatic nerves and brachial plexuses the nerve lesions had a multifocal distribution, showing prominent interstitial edema in the endoneurium frequently adjacent to deposits of amyloid; in these regions the nerve fibers were severely depleted. A teased-fiber study revealed that segmental demyelination was the predominant type of nerve fiber abnormality. However, these findings were not seen in the sural nerves; instead a diffuse fiber loss with axonal degeneration was observed. It is suggested that multifocal lesions in the proximal portions of the long extremity nerves could summate distally to produce a symmetrical polyneuropathy in the disease. In addition to a space-occupying effect of amyloid deposits in the endoneurium, severe endoneurial edema associated with amyloid deposition in blood vessels and the endoneurial interstitium may induce ischemia in nerve fibers, thus causing the progressive polyneuropathy in this disorder.     

Peripheral nerve abnormalities of mutant (PMA) mouse--myelinated fiber counts of sciatic, peroneal, sural and tibial nerves

A mutant mouse characterized by peroneal muscular atrophy and congenital absence of the peroneal nerve has been described by Esaki et al. and investigated as a possible animal model of Charcot-Marie-Tooth disease or spinal muscular atrophy. However, the nature of the peripheral nerve abnormality of this mutant mouse has not been precisely defined yet. In this study, in addition to the qualitative evaluation of teased fiber and Epon-embedded preparations, the total transverse fascicular area and the total numbers of myelinated fibers per nerve in sciatic, peroneal (proximal and distal), sural (proximal and distal) and tibial (proximal and distal) nerves on both right and left sides were compared between six peroneal muscular atrophy (pma) mice with autosomal recessive gene manifesting mainly the peroneal muscular atrophy and their six control mice to understand and define the peripheral nerve abnormalities. The pma mice showed pes equinovarus bilaterally and their peroneal nerves were absent. No myelinated fibers showing axonal degeneration or segmental demyelination were found on teased fiber preparation. Onion bulb, demyelinated or remyelinated axons and myelin ovoids were not observed in Epon-embedded sections. The mean total transverse fascicular area and mean total number of myelinated fibers per nerve in the sciatic nerve in pma mice was significantly less (p less than 0.02) than that in control mice. On the other hand they were significantly greater (p less than 0.0001) in the sural nerve in pma mice than in control mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Axonal caliber and neurofilaments are proportionately decreased in galactose neuropathy

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.     

Multifocal fiber loss in proximal sciatic nerve in symmetric distal diabetic neuropathy

The lumbosacral spinal cord, lumber roots, L5 spinal ganglion, L5 segmental nerve and entire lengths of the sciatic, tibial, peroneal and sural nerves were taken at postmortem examination from 2 patients with insulin-dependent diabetes mellitus (IDDM) and a predominantly sensory symmetric distal polyneuropathy and compared with 2 non-diabetic control patients. Sections from proximal to middle levels of sciatic nerves of these patients showed a remarkable variability in myelinated fiber (MF) density within and between fascicles. Roots and segmental nerves appeared to be unaffected. Sections of peroneal, tibial and sural nerves showed only severe and diffuse fiber loss. The findings suggest that multifocal lesions at upper levels of sciatic nerve can summate distally to produce a symmetric diabetic neuropathy. The findings, if confirmed by using quantitative approaches in larger numbers of patients, suggest an underlying interstitial pathological process rather than a metabolic process.     

Peripheral nerve pathology in rats with streptozotocin-induced insulinoma

Peripheral nerve structure was systematically examined in rats with insulinoma induced by streptozotocin (STZ). Normal Wistar rats, aged 3 months (n = 10), were treated with intravenous injections of STZ (20 mg/ kg) and housed in plastic cages with free access to water and chow until 24 months of age. Three rats with insulinoma survived and were examined pathologically. Age-matched normal Wistar rats (n = 6) were used for comparison. The insulinoma-bearing rats showed a marked increase in body weight and decrease in blood glucose. In a teased nerve fiber study of the sciatic nerve, the percentage of abnormal fibers undergoing axonal degeneration and de- and remyelination in age-matched normal control rats was 3.9 ± 2.5% (means ± SD), whereas in the three insulinoma-bearing rats 49%, 50%, and 24%, respectively, of the fibers showed such changes. Regenerating fibers were also numerous in each insulinoma-bearing rat (36%, 42% and 27%, respectively). Morphometric analysis revealed smaller mean myelinated fiber and axonal areas in all the nerves examined (sciatic, tibial and sural) in insulinoma-bearing rats as compared to those in age-matched normal rats. Fiber area frequency histograms showed a decrease in large myelinated fibers and an increase in small regenerated fibers in insulinoma-bearing rats. Ultrastructurally, endoneurial microvessels exhibited a narrowed vascular lumen with swollen endothelial cells and vacuolar degeneration of pericytes, suggesting an involvement of vascular changes in the neuropathic development. The present study demonstrated marked structural changes in both motor and sensory peripheral nerves of rats bearing experimentally induced insulinoma. We consider that axonal degeneration, regeneration and demyelination constitute the main pathology in the peripheral nerves of insulinoma-bearing rats, although no particular difference in severity of the lesions between sensory and motor and between proximal and distal nerves was apparent. Received: 24 October 1995 / Revised, accepted: 27 December 1995     

Morphometric evaluation of degenerative and regenerative changes in isoniazid-induced neuropathy

Morphometric studies of the pathologic changes were carried out on the peripheral nerves, spinal roots, and different levels of the Goll's tract in rats given isoniazid and killed 1, 2, 3, 4, 5, 6, 7, 14, and 30 days after intoxication. In teased fiber preparations, axonal degeneration was the main change present, and this was seen as early as day 2 in the peroneal and distal sural nerves. The frequency of myelinated fibers showing axonal degeneration was higher in the distal than the proximal sural nerve, and in the ventral than the dorsal root. In the group of rats killed on 5, 6, 7, and 14 days, a significant decrease of the myelinated fiber density was observed in the distal and proximal sural nerves, ventral root, and at the third cervical level of the Goll's tract. The degree of fiber degeneration was more severe in the distal than in the proximal sural nerve and in the third cervical than the fifth thoracic level of the Goll's tract. Preferential decrease of large myelinated fibers was noted in all the affected nerves. No definite abnormalities, however, were seen in nerve cells of the 6th lumbar spinal ganglia and anterior horn cells of the lumbar spinal cord on light microscopy. On 30 days, regeneration at varying degrees was discerned in all the affected nerves with significant increase of small myelinated fibers, particularly in the ventral root. The findings indicate that both centrally and peripherally directed myelinated axons are more affected in the distal than in the proximal segments while the neuronal cell bodies are spared. The spatio-temporal evolution of this pattern of change is compatible with the concept of the "dying back" process or central-peripheral distal axonopathy.     

Dysmaturation neuromyopathy: correlation with minimal neuropathy in sural nerve biopsies

Dysmaturation (neuro)myopathy without specific histochemical or cytoarchitectural characteristics accounts for many cases of hypotonia in infancy. We obtained a maturation profile for type I and type II fibers from birth to 6 years of age, from which a classification of fiber dysmaturation based on fiber-type hypotrophy and coefficient of fiber variation is presented. We analyzed the morphometric, ultrastructural, and single fiber teasing findings in the sural nerve of ten infants with hypotonia and dysmaturation myopathy based on the above classification. Data on endoneurial area, myelinated fiber density, proportion of large (greater than 6 micron) myelinated fibers, unmyelinated fiber density, regression analyses of myelin area:axon area, and mean myelin thickness were developed. Abnormalities in large myelinated fiber density (3 cases), disturbances in myelination index (5), and single fiber teasing abnormalities in internode length (1) were found. Ultrastructural abnormalities were observed and classified as group 0 changes similar to the five control nerves; group 1, in which rare fibers showed degeneration or basement membrane duplication; and group 2, which was characterized by multiple abnormalities including degenerate nuclei, amyelinate fibers, degeneration/regeneration, excessive basal lamina reduplication, and hypomyelination. This study provides evidence that minimal neuropathic abnormalities are present in the sural nerve of infants carrying a diagnosis of dysmaturation neuromyopathy.     

Selective neuronal destruction by Ricinus communis agglutinin I and its use for the quantitative determination of sciatic nerve dorsal root ganglion cell numbers

The selectivity of the neurotoxic lesion of Ricinus communis agglutinin I (RCAI) in rat dorsal root ganglia was examined. RCAI was injected in the sural nerve on one side. Two weeks later, the injected nerve, as well as the ipsilateral peroneal nerve, were examined in 1-micron-thick plastic embedded sections in the light microscope. The injected nerves showed a complete or almost complete Wallerian-like degeneration of myelinated fibers, but there were no signs of fiber damage in the uninjected nerves, which to a large extent originate in the same ganglia as the injected ones. We conclude that RCAI does not diffuse into and destroy ganglion cells adjacent to those that have transported the substance. We then used this selectivity in the effect of RCAI to determine indirectly the relative number of neurons in dorsal root ganglia L4-L6 which contribute to the sciatic nerve. Three weeks after unilateral injections of RCAI in the sciatic nerve, the L4-L6 dorsal root ganglion cells were counted bilaterally. On average, relative neuronal numbers between injected and uninjected sides were 0.36, 0.15 and 0.64 for L4, L5 and L6 respectively. From these data we conclude that the sciatic nerve receives on average of 64%, 85% and 36%, respectively of its sensory contribution from these ganglia.     

Prior Collateral Sprouting of Sensory Axons Delays Recovery of Pain Sensitivity after Subsequent Nerve Crush

Regeneration of motor axons is enhanced if they have sprouted prior to nerve injury. We examined whether sensory axon regeneration and recovery of pain response was affected by previous collateral sprouting. In the experimental group of rats, the right saphenous, tibial, and sural nerves were transected and ligated. The peroneal nerve was left to sprout into the adjacent denervated skin. Two months later, the axons of the peroneal nerve were crushed in the sciatic nerve. In the control group, the right sciatic nerve was crushed at the same time that the saphenous, tibial, and sural nerves were transected. Recovery of pain response in the foot was determined by the skin pinch test. Sensory axon elongation rate was measured by the nerve pinch test. The number of myelinated axons was determined in nerve cross sections stained by Azur blue. Recovery of pain sensitivity in the animals of the experimental group was delayed for 2–3 weeks in comparison to the control group. Moreover, the spatial pattern of pain response in the experimental group was irregular, displaying residual regions of insensitive skin which were not present in controls. The elongation rate of regenerating sensory axons in the experimental group was not decreased, and the number of myelinated axons in the peroneal nerves was even about 10% higher than in the control group. Therefore, we assume that the terminal arborization of the neurilemmal tubes pertaining to the former axon sprouts delayed regrowth of sensory axon terminals in the skin.     

Mild ischemia causes severe pathological changes in experimental diabetic nerve.

Nerve ischemia is considered one of etiological factors in the development of structural changes in peripheral nerves associated with diabetes mellitus. To assess the effect of mild ischemia on diabetic nerve, a subthreshold dose of polystyrene microspheres was injected intraarterially to occlude microvessels of the sciatic nerve and its branches in 20-week streptozotocin-induced diabetic and control rats. Diabetic sciatic and tibial nerves showed severe pathological change of myelinated fibers, whereas nondiabetic nerves were normal or had minor structural abnormalities. Morphometrical evaluation confirmed a greater frequency of abnormal myelinated fibers in diabetic nerves especially in central fascicular regions. The results indicate that diabetic nerve has an increased morphological susceptibility to nerve ischemia. Endoneurial hypoxia, which may result from hemorheological and vascular abnormalities, is likely to cause a lowered threshold to ischemic tolerance in diabetic nerve. This increased vulnerability to ischemia may render diabetic nerve unduly susceptible to hyperglycemia-induced systemic tissue abnormalities.     

Morphometric analysis of the peripheral neuropathy of AIDS

A morphometric study of the peripheral nervous system at autopsy was undertaken in 11 AIDS patients and 10 controls. The left L4, L5, and S1 dorsal root ganglia (DRG) and samples of the sciatic nerve at the buttock, tibial nerve at the knee, and sural nerve at the ankle were collected. Indices of neuronal/axonal degeneration and of segmental demyelination/remyelination were measured at each level. The small number of cases and evidence of neuropathy in a number of the control cases resulted in statistical significance for only a limited number of comparisons. Nodules of Nageotte in the DRG were increased fivefold in AIDS cases compared with controls, and axonal degeneration in single-teased nerve fibers was increased 9-fold in the sciatic nerve, 28-fold in the tibial nerve, and 12-fold in the sural nerve. The ratios of AIDS to controls for the density of remaining DRG neurons and large myelinated axons were reduced to 0.71 in the DRG, 0.84 in the sciatic nerve, 0.84 in the tibial nerve, and 0.66 in the sural nerve. Axonal regeneration in single-teased nerve fibers was increased threefold at the sciatic nerve level in AIDS, but was markedly reduced at distal levels. Acute segmental demyelination in single-teased nerve fibers was present to a greater extent than in controls at all levels of the peripheral nerves in the AIDS cases. Remyelinating fibers were increased compared with controls only in the proximal sciatic nerve. No case showed the changes of cytomegalovirus infection. In a parallel immunohistochemical study of these AIDS peripheral nerves, T-cell and macrophage infiltration, with cytokine expression, was demonstrated. The pathological process in the neuropathy of terminal AIDS appears to be a multifocal immunologically mediated inflammatory disease, with increased density of macrophages and T cells at all levels of the peripheral nervous system, producing segmental demyelination and axonal degeneration. Reparative processes (axonal regeneration and remyelination) occurred only at the most proximal levels of the nerves. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:1188–1195, 1998.     

Characterization of nerve and microvessel damage and recovery in type 1 diabetic mice after permanent femoral artery ligation

Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc.     

Perineurium contributes to axonal damage in acute inflammatory demyelinating polyneuropathy

OBJECTIVE: To assess if axonal damage in severe acute inflammatory demyelinating polyneuropathy (AIDP) correlates with the appearance of epiperineurium in nerve trunks. BACKGROUND: Increase of endoneurial fluid pressure in nerve trunks possessing epiperineurium may be an important mechanism of axonal damage in AIDP. METHODS: A 79-year-old man had a 2-day history of acroparesthesias and ascending paralysis culminating in quadriplegia, bilateral facial palsy, and mechanical ventilation. Five intravenous immunoglobulin cycles were given without response. He died on day 60. Electrophysiologic studies (days 4, 17, and 50) initially showed normal nerve conduction velocities with further slowing, progressive attenuation of compound muscle action potentials, and profuse denervation. The authors studied the preforaminal anterior and posterior L3 and L5 spinal roots, third and fifth lumbar nerves and their branches, and femoral and sural nerves. RESULTS: Density of myelinated fibers was preserved in L5 ventral and dorsal roots and reduced in sural nerve. Mild de-remyelination was observed in lumbar roots. In both lumbar nerves and their branches, there were extensive de-remyelination and centrofascicular or wedge-shaped areas with marked loss of large myelinated fibers. Axonal degeneration was the predominant lesion in sural nerve. CONCLUSION: The presence of epiperineurium correlates with a drastic change of pathology with superimposed ischemic lesions and distally accentuated axonal loss, suggesting that endoneurial fluid pressure increase could cause axonal damage in AIDP.     

Hereditary peroneal muscular atrophy in the mouse: An experimental model for congenital contractures (arthrogryposis)

A new mutant, peroneal muscular atrophy (pma) mouse in CF#1 strain has an autosomal recessively inherited equinovarus (club foot deformity) of the hind legs because of the absence of the common peroneal nerve branch of the sciatic nerve. We found the peroneal muscles were hypoplastic with histochemical and electron microscopic characteristics of fetal muscle. The anterior horn cells in the spinal cord were not reduced in number and they appeared to be normal. The density and size of the myelinated fibers in the anterior spinal roots of L3, L4, and L5 and the sciatic nerve in the affected side were not different from those in the unaffected. Therefore, the absence of the common peroneal nerve in the pma mouse is thought to result from the misdirection of these nerve bundles into other peripheral nerves. As the anomalous condition was present at birth with no progression, the pma mouse may be an experimental model for the study of arthrogryposis multiplex congenita or club foot deformity, and may lead to the understanding of the muscle and nerve interaction during development.     

Aggravated reperfusion injury in STZ-diabetic nerve

The streptozocin (STZ)-diabetic nerve manifests increased morphological susceptibility to a superimposed acute ischemic injury, and reperfusion injury exaggerates ischemic nerve pathology. To determine whether STZ-diabetic nerves are susceptible to reperfusion, we evaluated the pathological consequences after 2.5 hours of ischemia followed by 3 and 24 hours of reperfusion in a 20-week STZ-diabetic rat sciatic nerve. After 3 hours of reperfusion, endoneurial edema developed in diabetic nerves, whereas non-diabetic controls showed mild or no edema. Morphometric analysis of endoneurial edema, quantified by the total transverse fascicular area and the point-count score of endoneurial structureless space, confirmed significantly more reperfusion-induced edema at thigh and knee levels in diabetic nerves than in controls. Reperfusion caused a significant increase in the number of endoneurial mast cells at the thigh level in diabetic nerves. After 24 hours of reperfusion, there were striking morphological anomalies of myelinated nerve fibers in diabetic nerves, without any observable changes in control nerves. In conclusion, we have demonstrated that STZ-diabetes exacerbates the morphological change to reperfusion. Diabetes therefore renders the microvasculature more vulnerable to the deleterious effects of ischemia/reperfusion.     

Near nerve local insulin prevents conduction slowing in experimental diabetes

Insulin may have direct effects on axons through its actions on insulin receptors or through cross occupancy of insulin-like growth factor-1 receptors. We tested the hypothesis that insulin itself influences conduction of myelinated fibers independent of hyperglycemia in experimental diabetes. Low dose intermittent (0.2 units thrice weekly) Toronto (regular) insulin was injected at the sciatic notch and knee near the left sciatic nerve of rats rendered diabetic with citrate buffered streptozotocin or nondiabetic rats given citrate only. Identical volumes of normal saline were injected near the contralateral right sciatic nerve. The diabetic rats developed hyperglycemia, elevated glycosylated hemoglobin levels and had slowing of right (saline treated) sciatic tibial motor and caudal sensory conduction velocity. In contrast, local insulin treatment on the left side prevented conduction slowing, unilaterally increasing conduction velocity. In nondiabetic rats, conduction velocities were slightly higher on the insulin treated side, but the influence of insulin was less robust than in diabetics. The insulin treated sural branches of the sciatic nerves in diabetics had a higher percentage of small (≤9.0 μm diameter) myelinated fibers than the saline treated nerves. Local insulin has a trophic influence on myelinated fibers that is prominent in diabetic nerves and is independent of hyperglycemia.     

Chronic constriction model of rat sciatic nerve: nerve blood flow,morphologic and biochemical alterations

We evaluated the nerve blood flow (NBF), light and electron microscopy, and adrenergic innervation of rat sciatic nerve at 2–45 days after the application of four loose ligatures. Ischemia developed at the lesion edge, creating an endoneurial dam. Calcitonin gene-related peptide, norepinephrine and NBF were increased within the lesion. Morphologic alterations consisted of early endoneurial edema, followed by myelinated fiber degeneration, with relative sparing of small myelinated and unmyelinated nerve fibers, and leukocyte adhesion to microvessels. Axonal degeneration predominated over demyelination. At 45 days, profuse regeneration of small myelinated fibers was seen. The mechanism of lesional sensitization is discussed. Received: 30 May 1996 / Revised, accepted: 13 August 1996     

Peripheral nervous system and central nervous system pathology in rapidly progressive lower motor neuron syndrome with immunoglobulin M anti-GM1 ganglioside antibody

Pathological studies, including novel teased peripheral nerve fiber studies, were performed in a patient who presented with a rapidly progressive, lower motor neuron syndrome and high titer of immunoglobulin M anti-GM1 ganglioside antibody. In the central nervous system, there was a severe loss of motor neurons and central chromatolysis with ubiquitin immunopositive cytoplasmic inclusions in residual motor neurons. In the peripheral nervous system, axonal degeneration of myelinated fibers in the anterior nerve roots was evident. Pathologic evidence of sensory nerve involvement was also found despite the absence of clinical or electrophysiological sensory abnormalities. Sectional studies of single myelinated nerve fibers from an antemortem sural nerve biopsy showed remyelination and globular paranodal swellings due to focal complex myelin folding and degeneration in 13% of fibers. Postmortem studies of the sural nerves 4 weeks later showed paranodal demyelination (90% of fibers), but no paranodal swellings and similar findings were present in samples of the ulnar, radial, median, tibial, and common peroneal nerves. Paranodal abnormalities of enlargement of the adaxonal space, myelin degeneration, and axonal compaction were found on cross-sectional studies of individual teased fibers, which on conventional light microscopic assessment appeared normal. These changes suggest a disturbance of paranodal axonal-myelin adhesion due to binding of the anti-GM1 ganglioside antibody to the common epitope known to be present on the myelin sheath and nodal axolemma in the paranodal region of both motor and sensory nerves.     

Progression of regeneration after nerve infarction

We performed morphologic studies on the progression of regeneration in cat hind limb nerves after acute ischemic injury. None of the damaged nerve trunks showed a major increase in endoneurial connective tissue. Despite this fact, regeneration of nerve with transfascicular infarct was far from complete even 16 months after injury as manifested by a striking increase in the small myelinated fibers (MF) number and decrease in large MF number. Restoration of infarcted nerves was less complete than that previously reported after a nerve crush. Changes in the necrotic nerve segment and difficulty in making target contact with muscle and other tissues damaged by ischemia may be limiting factors in the regeneration of infarcted nerves.