Number Of Large Myelinated Fibers Research Articles

WS4.3. Overview of Axonal Excitability Studies

Nerve excitability testing is a non-invasive neurophysiological technique, which investigates nerve functions in vivo . While nerve conduction studies deliver supramaximal stimuli to measure conduction velocities and the number of large myelinated fibres, nerve excitability studies use weaker stimuli and measure strength of stimuli, which evoke target compound muscle action potential or sensory nerve action potential amplitudes. The combination of conditioning and test stimuli, with various strength and duration, can examine functions of various types of ion channels and ion pumps and exchangers, which are located in peripheral nerve axons, and membrane potential. Several paradigms, such as strength-duration properties, threshold electrotonus, current-threshold relationship and recovery cycle, are assessed in this testing, and alterations of parameters in these paradigms indicate changes in those functions. This technique has disclosed various pathophysiological alterations mainly in genetic and acquired channelopathies. A famous study, using this technique, disclosed an effect of puffer fish poisoning for nerve excitability. Tetrodotoxin is known to block sodium channels, and salient reductions of strength-duration time constant and refractoriness in recovery cycle, makers of persistent and transient sodium channel functions, respectively, were disclosed in patients with tetrodotoxin intoxation. This study firstly visualized an effect of tetrodotoxin for the human peripheral nerve. In another study, increased strength-duration time constant, i.e. increased excitability, was revealed in patients with neuropathic pain and muscle cramps. Mexiletine treatment, a sodium channel blocker, for these patients relieved those symptoms and decreased strength-duration time constant. As those studies, recent studies, using this testing, have disclosed an impact of altered ion channel functions for neurological diseases and utility of this technique as a treatment biomarker. In this session, I plan to introduce the principle of this testing and recent advances in clarification of pathophysiology in neurological diseases and treatment developments, using this testing.

White-matter microstructural properties of the corpus callosum: test-retest and repositioning effects in two parcellation schemes.

We investigated test-retest reliability of two MRI-derived indices of white-matter microstructural properties in the human corpus callosum (CC): myelin water fraction (MWF) and geometric mean T2 relaxation time of intra/extracellular water (geomT2IEW), using a 3D gradient and multispin-echo sequence in 20 healthy adults (aged 24-69years, 10 men). For each person, we acquired two back-to-back acquisitions in a single session, and the third after a break and repositioning the participant in the scanner. We assessed the contribution of session-related variance to reliability, using intra-class effect decomposition (ICED) while comparing two CC parcellation schemes that divided the CC into five and ten regions. We found high construct-level reliability of MWF and geomT2IEW in all regions of both schemes, except the posterior body-a slender region with a smaller number of large myelinated fibers. Only in that region, we observed significant session-specific variance in the MWF, interpreted as an effect of repositioning in the scanner. ThegeomT2IEW demonstrated higher reliability than MWF across both parcellation schemes and all CC regions. Thus, in both CC parcellation approaches, MWF and geomT2IEW have good test-retest reliability and are, therefore, suitable for longitudinal investigations in healthy adults. However, the five-region scheme appears more appropriate for MWF, whereas both schemes are suitable for geomT2IEW studies. Given the lower reliability in the posterior body, which may reflect sensitivity to the repositioning of the participant in the scanner, caution should be exercised in interpreting differential findings in that region.

Effect of alpha-tocopherol supplementation on the ultrastructural abnormalities of peripheral nerves in experimental diabetes.

Ultrastructural observations were made on myelinated fibers in the tibial nerves in order to investigate the beneficial effects of alpha-tocopherol administration in streptozotocin-diabetic rats. Male Wistar rats, aged 12 weeks and weighing between 250 g to 300 g were studied. Six onset control rats were used to obtain the baseline parameters for this strain and age. Further 3 groups--untreated diabetic animals, diabetic animals treated with alpha-tocopherol, and age-matched controls--were studied over a 3-month period. In the diabetic animal, administration of alpha-tocopherol resulted in a significant increase (p < 0.05) in total plasma vitamin E levels when compared with other groups. Myelinated fiber cross-sectional area (p < 0.05), axonal area (p < 0.01) and myelin sheath area (p < 0.05) were significantly less in the tibial nerve of diabetic animals than in age-matched controls, but not different from those of onset controls. In the alpha-tocopherol treated diabetic animals, the values for these parameters were intermediate without showing significant difference when compared with age-matched controls and untreated diabetics. The "g" ratio (axon to fiber area) did not differ between any experimental groups. The number of large myelinated fibers were less in the untreated diabetic animals, but in the alpha-tocopherol-treated diabetics, the values were significantly higher (p < 0.05) than with untreated diabetics and were similar to those of age-matched controls. In conclusion, this ultrastructural study reiterated the fact that structural abnormalities of myelinated fibers occur in experimental diabetes and that alpha-tocopherol administration may be useful in preventing the development of these abnormalities.

Ataxic neuropathy in the elderly--clinicopathological study of six cases

The combination of ataxia with peripheral neuropathy (ataxic neuropathy) is rare. Six elderly patients with peripheral neuropathy who developed ataxia were studied. Of the peripheral neuropathies, ataxic neuropathy was significantly more frequent in patients aged more than 65 years compared with younger patients. Ataxic neuropathy was associated with carcinoma (2 cases), Sjögren's syndrome (1 case), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, 1 case) and chronic idiopathic ataxic neuropathy (2 cases). The two cases of carcinomatous neuropathy initially showed ataxia, which preceded detection of the carcinomatous lesions in the lung by approximately 1 year. The study cases had many clinical features in common. In the nerve conduction study, sural nerve action potential could not be measured in five of the cases; sural nerve biopsy revealed a decreased density of myelinated fibers in all cases. In particular, the large myelinated fibers were markedly decreased. These findings were common, regardless of the underlying disease, except in the case of CIDP in which there was only a slight decrease in the number of large myelinated fibers. Differential diagnosis based on the clinicopathological features was difficult. Therefore, in cases of ataxic neuropathy, systemic evaluation is necessary to rule out the possibility of carcinoma or various systemic diseases, especially in elderly patients.

Chronic compression model of the cauda equina: Histological and electrophysiological study

Histological and electrophysiological changes of the cauda equina caused by chronic compression with silicone film were assessed in the lumbar spine of adult cats. Twenty cats underwent laminectomy of the sixth lumbar vertebra. The animals were divided into four groups (n = 5 each). In three groups, the dura was covered with silicone film. The fourth group (sham-operated) served as controls. Histological and electrophysiological studies, using spinal cord evoked potentials (SpEPs) with high frequency stimulation (HFS) were performed after periods of 4, 12, and 24weeks. Controls were examined at 12weeks. Dilatation of the endoneurial microvessels was noted in two of five cats in the 4-week group and in all animals in the 12- and 24-week groups. The nerve fibers of the control animals and the animals in the 4-week group were normal, in the 12-week group, a decrease in the number of large myelinated fibers and an increase in the number of small myelinated fibers was seen in the dorsal and ventral nerve roots. Electrophysiologically, there was no significant difference in SpEPs before and after the silicone film coverage. Recovery of the peak latency was significantly delayed after HFS in the 24-week group. This model is considered to be useful in studying the pathophysiology of chronically compressed cauda equina.

The effects of acetyl- l-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes

Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl- l-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 μm) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.

PREPUBERTAL HYPERGLYCEMIA CAUSES NERVE DAMAGE. † 538

It has been reported that prepubertal duration of diabetes has a minimal influence on the later risk of diabetic complications. Rats made hyperglycemic at 6 weeks of age (before puberty) manifest reduced nerve conduction velocity(NCV) by 10 weeks of age and show morphologic differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared to age matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers (> 6.5 um) were decreased. The number of small (< 6.5 um) developing myelinated fibers were increased. Rats made hyperglycemic at 26 weeks of age (post pubertal) had elevated glycosylated hemoglobin and sciatic nerve sorbitol but maintained normal NCVs and had little change in morphology after 7 months of hyperglycemia. Thus, animals with maturing peripheral nerve structure and function (characteristic of the prepubertal period) exposed to chronic hyperglycemia manifest greater pathologic alterations than occur when more mature nerves are exposed to similarly elevated glucose concentrations for an even greater duration. This suggests that growing maturing tissues of prepubertal children may be more sensitive to the toxic effects of hyperglycemia than mature adult tissues. In summary, the tissues of prepubertal animals are not immune to the toxic effects of hyperglycemia. Blood glucose control is likely to be important for the normal maturation of tissues in prepubertal children with diabetes mellitus.

The effect of hyperglycemia on nerve conduction and structure is age dependent.

The nerve conduction velocity (NCV) of nondiabetic male Wistar rats continues to increase until approximately 26 weeks of age. Rats made hyperglycemic at 6 weeks of age manifest reduced NCV by 10 weeks of age and show morphological differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared with age-matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers were decreased in the tibial nerves of the hyperglycemic animals. Rats made hyperglycemic at 26 weeks of age had elevated glycosylated hemoglobin and sciatic nerve sorbitol levels but maintained normal NCVs and had little change in morphology after 7 months of hyperglycemia. Thus, animals with maturing peripheral nerve structure and function exposed to chronic hyperglycemia manifest greater pathological alterations than those that occur when more matured nerves are exposed to similarly elevated glucose concentrations for an even greater duration. We suggest that immature animal models commonly used to study diabetic peripheral neuropathy may not be appropriate for understanding a process that commonly develops in humans who become hyperglycemic after maturation of the peripheral nerves.

Flutamide-Induced Testicular Undescent in the Rat is Associated with Alterations in Genitofemoral Nerve Morphology

Androgen regulation of testicular descent is an established fact. However, the mechanisms by which androgens assert their influence is unknown. One of the leading hypotheses regarding androgenic control of testicular descent is based upon the assumption that testosterone regulates the development of the sexually dimorphic genitofemoral nucleus and nerve (GFN). To investigate whether or not alterations in the genitofemoral nerve are indeed androgen dependent and associated with testicular undescent, we administered flutamide in a time-specific manner to pregnant Sprague-Dawley rats. The GFN of ten animals with unilateral intra-abdominal testicular undescent was compared with the contralateral GFN associated with the descended testicle. Digital microscopic evaluations found that the GFN associated with testicular undescent did express altered morphologic abnormalities. Specifically, the GFN associated with the cryptorchid testicle had significant reductions in the neural diameter (.0169 ± .0024mm.2 versus .0275 ± .0079mm.2; p <.01), the number of large myelinated fibers per mm.2 (8.4 ± 3.3 versus 18.8 ± 5; p <.001) and the number of small myelinated nerve fibers per mm.2 (632 ± 87.4 versus 1090.7 ± 104.3; p <.001). These data suggest that testicular undescent in the rat is associated with morphologic alterations in the ipsilateral genitofemoral nerve. The exact mechanism of how these alterations are related to cryptorchidism remains to be elucidated.

Smaller number of large myelinated fibers and focal myelin thickening in mutant quails deficient in neurofilaments.

The peripheral nervous system of a mutant of a Japanese quail deficient in neurofilaments (mutant) and of a normal Japanese quail (control) was morphometrically evaluated to characterize the morphological findings, especially those of the myelinated fibers of the mutant. In the proximal peroneal nerves, the frequency of the teased myelinated fibers showing the focal myelin thickening was higher in mutant than in control (P < 0.001) without obvious ongoing axonal degeneration and segmental demyelination. The total numbers of the myelinated fibers in the proximal and distal peroneal nerve, and in the tibial nerve branch to gastrocnemius muscle (pars medialis) were similar between control and mutant, although the number of the large myelinated fibers was less (P < 0.01) and the number of the small myelinated fibers was greater (P < 0.01) in mutant compared with control. The median diameters of neuronal cell bodies of the sacral dorsal root ganglia were similar in control and mutant. The percentages of light, dark and unclassified cells evaluated based on the histologic cytoplasmic features were also similar in control and mutant. Therefore, morphometric alterations were more pronounced in the peripheral myelinated nerve fibers compared with those in the cell bodies of the spinal dorsal root ganglia. We concluded that a smaller number of large myelinated fibers with a greater number of small myelinated fibers and the presence of focal myelin thickening are the main morphologic findings in this mutant, probably due to the arrest of radial growth or maturation of the axons of the myelinated fibers in the absence of ongoing myelinated fiber degeneration.

ビタミンB&lt;sub&gt;6&lt;/sub&gt;（ピリドキシン）大量投与ラットの腰部第一次感覚ニューロンの変性過程

The morphologic effects of the toxicity of high doses of pyridoxine hydrochloride (vitamin B6) on the lumbar primary sensory neurons in rats were studied. The test rats were treated with 1,200 mg/kg of pyridoxine hydrochloride by intraperitoneal injection once a day, and were sacrificed by perfusion at periods ranging from one to seven days after the injection, together with the control rats. Initial lesions consisted of eccentricity and crenation of the nucleus and vacuole formation in the cytoplasm of large dorsal root ganglion neurons, 2 days after the injection. These lesions were followed by segregation of the nucleolus, axon reaction-like changes in the cytoplasm and axonal degeneration of both peripheral axons in the sural nerve and central axons in the fasciculus gracilis. The frequency of teased myelinated fibers showing axonal degeneration during tests was significantly greater than in control 3 to 7 days after the injection. No significant difference of such frequency was found between the proximal and distal sural nerve during tests. The number of large myelinated fibers per nerve in the sural nerve, when compared with control, was preferentially decreased during tests. In the fasciculus gracilis, the decrease of the density of myelinated fibers was more pronounced in the third cervical segment than in the fifth thoracic segment. Because both peripheral and central axons were similarly affected and the initial lesions were found in the neuronal cell body, the mode of degeneration of axons in this study was regarded as "neuronopathy". By both light and electron microscopy, accumulation of mitochondria, vesicles, multilamellar and dense bodies were found in the nodal and distal paranodal axons of myelinated fibers in the sixth dorsal root ganglion on the 2nd day after the injection, which preceded the degeneration of both peripheral and central axons. Such accumulation, revealed for the first time in this study, may reflect the presence of a blockade of the axoplasmic transport in the proximal axon and cell body of the lumbar primary sensory neuron and subsequently give rise to the degeneration of both peripheral and central axons of the lumbar primary sensory neuron. The pathologic alterations at the different sites of the lumbar primary sensory neuron revealed in this study should be taken into consideration for the better understanding not only of the pathogenesis of human pyridoxine-induced sensory neuropathy, but also of other human and experimental neuropathies.

Rett syndrome: findings suggesting axonopathy and mitochondrial abnormalities

We report the histopathologic findings of 3 sural nerve biopsies and 1 muscle biopsy from 3 patients with Rett syndrome. The 3 sural nerve biopsies demonstrated a few ultrastructural abnormalities, including the presence of many Pi-granules and mitochondrial changes in the cytoplasm of Schwann cells, occasional bands of Büngner and onion-bulb formations, and mitochondrial alterations in myelinated axons. Morphometric analysis disclosed reduction in the number of large myelinated fibers with normal densities in comparison to those of an age-matched normal control. Light microscopic examination of the biopsied muscle from a 6-year-old patient with Rett syndrome revealed the existence of many small, dark, angulated fibers with NADH-TR staining. Ultrastructural investigation of the muscle confirmed the presence of the dumbbellshaped mitochondria. Peripheral nerve involvement and the possibility of mitochondrial abnormalities in Rett syndrome were suggested by the results.

Quantitative and qualitative morphological properties of the soleus motor nerve and the L5 ventral root in young and old rats: Relation to the number of soleus muscle fibres

The motor nerve to the soleus muscle and the L5 ventral root from young adult (3–6 months) and old (20–25 months) male Wistar rats were studied with regard to total number of myelinated nerve fibres, calibre spectra of myelinated fibres and morphological properties. The soleus muscle was examined with respect to total number of muscle fibres. A significant decrease in the number of myelinated nerve fibres was found in the old soleus nerves, and was mainly confined to the large-diameter fibres. Similarly, there was a significant decrease in the number of large myelinated fibres in the L5 ventral roots of old animals. Morphological changes in old nerves and spinal roots consisted of axonal degeneration with areas devoid of myelinated nerve fibres, and also myelin sheath irregularities, including myelin splitting with myelin balloon formation, infolded myelin loops and myelin reduplication. The axonal degeneration was more pronounced in the peripheral nerves than in spinal roots. In conformity with other studies, the soleus muscle showed an age-related decrease in the number of muscle fibres. These findings indicate that the decrease in fibre number in old soleus muscle is associated with degenerative neuronal changes and loss of α-motoneurons.

Histological differences between rootlets sectioned during selective posterior rhizotomy by two surgical techniques

During selective posterior rhizotomy, for the treatment of spasticity in infantile cerebral palsy, the rootlets to be divided are chosen by the type of electromyographic response elicited by intraoperative electrical stimulation. Two different surgical techniques were used for exposing the lumbar roots. The first approach was to expose the conus medullaris through a T 12-L 1 laminectomy, while the other approach to the dorsal roots was distally in the cauda equina through a L 2-L 3 to S1 laminectomy. Although the clinical results obtained with either of them are not very different, there is anatomical evidence that suggests that the histological structure of the divided rootlets may be different in the two techniques. We designed our study to determine of a significant difference in the number of large myelinated fibers was found between rootlets divided close to the conus medullaris and those divided distally in the cauda equina. Two groups of five children with spasticity secondary to cerebral palsy where randomly designed to be operated upon by one of the techniques. The divided rootlets were processed with standard histological techniques and the large myelinated fibers were counted on enlarged (40 x) photomicrograph of the rootlet. A significantly (p less than 0.001) larger number of large myelinated axons was found in the rootlets dissected and divided close to the conus medullaris.

Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man.

Reduction in the number of large myelinated nerve fibers in spinal nerve roots has been described previously. We observed a reduction in myelinated nerve fiber diameters which at least in part explains the apparent marked reduction in the number of large myelinated fibers with age.

Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management.

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of the motor system in adults that occurs in sporadic, familial, and Western Pacific forms. Involvement of non-motor pathways has been increasingly recognized, both clinically and pathologically. Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end-plates reveal small or absent nerve terminals. Subclinical non-motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non-motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.

Morphometric and biochemical studies of peripheral nerves in amyotrophic lateral sclerosis.

Phrenic nerves of 11 patients with amyotrophic lateral sclerosis studied postmortem contained only 33% of the normal number of large myelinated fibers (9 controls; p less than 0.001). In the phrenic nerves of these patients, there were 18% fewer large myelinated fibers in the distal segment than in the proximal segment (p less than 0.025). The ratio of axonal circumference to myelin lamellae in large myelinated fibers in the distal segment was 34% greater than that in control fibers (p less than 0.002). The proportion of acute axonal degeneration was the same at all levels (48.0 +/- 13.7%). Sural nerves of 21 patients with amyotrophic lateral sclerosis had more acute axonal degeneration and 30% fewer myelinated fibers (p less than 0.05) than controls; evidence of degeneration also extended to unmyelinated fibers. The amount of axonal transport of acetylcholinesterase in 9 sural nerves determined in vitro was reduced by 24% (p less than 0.05) and the apparent transport rate was reduced by 44% (p less than 0.01) compared with 4 controls. These findings show that in amyotrophic lateral sclerosis a small degree of dying-back change and of distal axonal atrophy is superimposed on the degeneration of motor neuron cell bodies, and that the disease effects spread beyond the motor neurons.

Amyotrophic lateral sclerosis. Lack of central chromatolytic response of motor neurocytons corresponding to active axonal degeneration.

Ventral spinal roots and anterior horn cells in the lateral nuclear group of the fourth lumbar segment from 21 patients with amyotrophic lateral sclerosis (ALS) and 23 control patients were morphometrically analyzed. The number of large myelinated fibers was remarkably decreased, while small myelinated fibers were well preserved. The population of large myelinated fibers significantly correlated with the population of anterior horn cells. Numerous axonal degenerations were observed in the ventral spinal roots of patients with ALS, even in patients with severe loss of neurons and axons. In spite of this high frequency of active axonal degeneration, the incidence of central chromatolysis of anterior horn cells remained at the control level.

SENSORY ACTION POTENTIALS AND BIOPSY OF THE SURAL NERVE IN NEUROPATHY

In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy ("proportionate slowing"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres ("disproportionate slowing"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver.

Ultrastructure of the onion bulb-like lamellated structure observed in the sural nerve in a case of von Recklinghausen's disease.

Examination of photo and electron microscopical preparations of a biopsied sural nerve from a patient with von Recklinghausen's disease is reported. In the toluidine blue stained Epon-sections the number of myelinated fibers per square millimeter was moderately decreased and the number of large myelinated fibers was severely reduced. Large, circular, lamellated structures which resemble the onion bulb were observed. These structures are different from the previously reported onion bulb in their size and core structure which contains usually a degenerated nerve fiber. Some consideration was given to the origin of these onion bulb-like lamellated structures.