Synchronous ipsilateral cavernous malformations of the trochlear nerve

BackgroundCranial nerve cavernous malformations (CM) are rare benign congenital vascular anomalies, with approximately 44 preceding cases in the literature. We report the fifth case of trochlear CM, as well as the first instance of two discrete CM occurring simultaneously along the same cranial nerve.MethodsCase report.ResultsA fifty-seven year-old man presented with several years of diplopia; physical examination identified a complete left trochlear nerve paralysis. MRI revealed a 1 cm enhancing lesion within the left ambient cistern, and the patient underwent left pretemporal transcavernous resection. Intraoperatively, a second, discrete CM of the trochlear nerve was also discovered; wide excision of the intrinsic trochlear lesions was completed, allowing both tumors to be removed en bloc with negative margins. Pathologic analysis confirmed both to be CM of the trochlear nerve. The patient recovered with a persistent left trochlear paralysis only, and follow-up MRI was negative for residual or recurrent disease.ConclusionCranial nerve CM are rare but potentially morbid mass lesions, with the capacity to precipitate significant neuropathies. Differential diagnosis includes schwannoma and hemangioblastoma. Definitive diagnosis may not be possible preoperatively; however, resection is recommended in symptomatic patients, potentially accompanied by nerve repair.     

Aberrant regeneration in a case of syringobulbia: selective co-activation of abducens and facial nerves during saccades

Summary A patient suffering from syringobulbia and syringomyelia exhibited a phasic contraction of the ipsilateral facial muscles, mainly the levator labii, whenever he looked to the left or right. Facial muscle twitches occurred exclusively with saccades. The selective co-activation of abducens and facial nerves is interpreted as the result of bilateral misrouting of regenerating neurons from the parapontine reticular formation to the facial nerve in the tegmentum pontis.     

The numbers of unmyelinated and myelinated axons in normal and regenerated rat saphenous nerves

Counts have been made of the numbers of unmyelinated and myelinated axons in the proximal and distal stumps of regenerated rat saphenous nerves and from equivalent sites in normal nerves. In the proximal part of normal nerves there were averages of 1 045 myelinated axons and 4 160 unmyelinated ones. Regenerated nerves contained the same number of myelinated axons in their proximal stumps but there was a 40% reduction in the unmyelinated axon count. In the distal stumps of these nerves the myelinated axon count had increased by an average of 620; this comes about because some regenerated myelinated axons support more than one process in the distal stump. In contrast, the number of unmyelinated axons was reduced further, from a mean of 2 476 in the proximal stump to one of 2 219.

The sizes of Schwann cell units in the normal and regenerated nerves were also noted. Schwann cell units in the proximal and distal stumps of the regenerated nerves were smaller than those in the normal ones.

These changes associated with unmyelinated axons in regenerated nerves are likely to contribute to the sensory, vasomotor and sudomotor abnormalities that sometimes occur after peripheral nerve injury and regeneration.     

The effects of A- and C-fiber stimulation on patterns of neuropeptide immunostaining in the rat superficial dorsal horn

The present study determines the effects of sciatic nerve stimulation at intensities that activate A-fibers alone or both A- and C-fibers on immunostaining for substance P (SP), cholecystokinin-octapeptide (CCK-8), galanin (GAL), dynorphin (DYN) and vasoactive intestinal polypeptide (VIP) in the superficial dorsal horn of the rat spinal cord. The goal of this study is to provide a more precise spatial localization of the sites or release or accumulation of these compounds in relation to specific types of stimuli. Following A-fiber stimulation, there was no significant change in immunostaining for any of these compounds. However, A- and C-fiber stimulation resulted in major changes. For SP, CCK-8, GAL and DYN there was a large and significant loss of immunostaining in medial regions of the dorsal horn. This is the area where sciatic nerve primary afferent fibers terminate and the depletion is probably correlated with activity in these fibers. By contrast, VIP immunostaining is increased in the lateral part of the supeficial cord, which is outside of the central sciatic afferent fiber terminations. This indicates that the increase is not in the fine sciatic sensory axons that are directly stimulated. As a final point, the fact that C-fiber but not A-fiber stimulation causes marked changes in the immunocytochemical distribution of all these compounds is further evidence, albeit indirect, that they are involved in nociceptive information processing.     

Cellular schwannoma of the abducens nerve: Case report and review of the literature

Schwannomas of the abducens nerve are extremely uncommon tumors. Here, we report the case of a 26-year-old woman who presented with a 6th nerve palsy and was found to have a large tumor at the right side of her pons. Neuropathologic exam revealed a cellular schwannoma with a high proliferation index. The case is presented in its clinical, neurosurgical and neuropathologic aspects and the literature on 6th nerve schwannomas is reviewed.     

The density of myelinated fibres is related to the fascicle diameter in human superficial peroneal nerve. Statistical study of 41 normal samples

The density of myelinated fibres in the superficial peroneal nerve was studied in 41 samples from 24 control human subjects. Photographic montages of the whole nerve fascicle were made from semithin and ultrathin transverse sections and used for a statistical analysis of sampling procedures, range of variations and relations between density and other variables. The results indicate that the spatial distribution of myelinated fibres within a nerve is often non-uniform. Therefore, it was not possible to define a statistically valid sampling system. The study of relations between variables shows the lack of any correlation between density and age and a considerable variation in the density. In contrast, there is a strong positive linear correlation between the surface area of the nerve fascicle and its content of myelinated fibres. That is, the fibre density of a given normal nerve is related to its diameter and can be predicted within a narrow range of error. We propose the term "derived density" for this value, and its application as a tool in the diagnosis of peripheral neuropathies is now being studied.     

Development of myelinated and unmyelinated fibers of human vagus nerve during the first year of life

As an important component of cardiorespiratory control, the vagus nerve and its maturation were evaluated in normal infants in order to provide standards of comparison with infants with dysfunctional neural control mechanisms. Myelinated and unmyelinated fibers in the cervical vagus nerve were examined in 27 term infants. Number of fibers, axon diameters, and myelin thickness were compared among four age groups. The histograms of axon size exhibited a skewed distribution that persisted during the age range examined for both myelinated and unmyelinated vagus fibers. Fiber size distributions of myelinated fibers, however, already showed an incipient multimodal distribution after 3 months. No major increase was observed in the average axon size of myelinated and unmyelinated fibers. A significant increase was observed, however, in the average content of myelin in myelinated fibers expressed as myelin thickness, number of lamellae or g ratio (internal/external diameter). These results suggest an active myelination during the first 9 months of life without a major change in the axonal characteristics of the fibers. A marginal increase in the density of myelinated fibers with age, both in terms of total number and the relation to unmyelinated fibers, suggests a slow transition from unmyelinated to myelinated fibers during the first year of life, particularly during the first 3 months. The present morphometric parameters indicate an active deposition of myelin before the maturation of cross-axonal dimensions. The distribution of g ratios also suggests that optimal conduction velocity is compromised only in a fraction of all vagal myelinated fibers.     

Morphometric aspects of peripheral nerves in adults and the elderly

There have been inconsistencies among reports of age-related differences in human peripheral nerves (PNs). For such studies, normal control values are necessary. Moreover, the diversity of methods employed makes it difficult to compare results. We used the same histological procedures and methods to measure 12 PNs: 8 in the cranial nerves, 2 motor nerves in the lower limb, and 2 nerves in the autonomic system. We performed a morphometric analysis of nerve fibers and estimated the change in the total number (TN) and average transverse area (ATA) of myelinated axons from adulthood to old age. The spinal nerves demonstrated notable age-related changes in TN and ATA. Most of the cranial nerves also demonstrated notable age-related changes in TN and ATA. However, some nerves demonstrated no such age-related changes and were affected more by other factors. With regards to the autonomic nerves, the lesser splanchnic nerve indicated age-related changes in TN, but the greater splanchnic nerve indicated no age-related changes in either TN or ATA. The autonomic nerves were affected not only by the aging process but also by the pathological changes to the peripheral tissues that they innervate.     

Persistence of anti-NGF induced dorsal root axons: possible penetration into the mammalian spinal cord

Neonatal rats were given daily injections of antisera to nerve growth factor protein (anti-NGF) for a period of 1 month and then allowed to survive 17 more months. The number of neurons in dorsal root ganglia (DRG) and axons in the dorsal root (DR) were determined in the anti-NGF rats and compared to similar numbers from untreated littermates. We found a 32% decrease in DRG neuron number and 32 and 34% increases in myelinated and unmyelinated DR fibers, respectively, in the anti-NGF rats. The sensory cell bodies in the anti-NGF rats were on the average 23% larger than in the normal rats. We conclude that in an NGF deprived environment a population of DRG neurons dies, principally the small neurons, and in response the surviving neurons emit extra processes which persist for most of the life of the rat. This suggests that the anti-NGF induced axons enter the spinal cord and synapse.     

Prechiasmatic Reordering of Fibre Diameter Classes in the Retinofugal Pathway of Ferrets

This study examines the distribution of fibre diameter classes at various sites along the retinofugal pathway of adult ferrets. Light microscopic observations were made on semi-thin sections, and regional fibre diameter spectra were constructed from diameter measurements taken from electron micrographs of thin sections of the intraorbital optic nerve (2.5 mm from the optic disc), the intracranial optic nerve (1 mm rostral to the fusion of the nerves), and the optic tract (just caudal to the optic chiasm).
Whereas diameter types are relatively evenly distributed behind the eye in the postoptic nerve, they begin to segregate along its prechiasmatic course. Within this prechiasmatic region, coarse and fine calibre fibres are confined increasingly to more ventral locations in the nerve, leaving a dorsal band populated predominantly by intermediate calibre fibres. In conjunction with this redistribution of axon size classes, the fascicular arrangement of axons which is present distally, changes to a non-fascicular organization. The prechiasmatic organization of fibre types approximates that found in the optic tract where the coarse and fine calibre fibres lie further ventrally towards the pial surface.
The prechiasmatic region can be viewed as a region of transition where the order of fibres in the nerve (retinotopic) starts to change to that present in the optic tract (chronotopic), resulting in the first-born beta cell axons becoming segregated dorsally, and rostral to the coarse and fine calibre classes which segregate at further caudal locations. Further, since the sorting of fibres according to diameter appears before the fibres reach the optic chiasm, the segregation of diameter classes is not dependent on the chiasmatic sorting of fibres according to their crossed or uncrossed course.     

Compartmental and topographical distributions of axons in nerves to the amphibian (Bufo marinus) glutaeus muscle

The present work seeks to determine if axons to an amphibian muscle are segregated in nerve trunks between the spinal cord and muscle according to their primary nerve destination or their topographical projection in the muscle. The distribution of axons to different compartments and subcompartments of the amphibian (Bufo marinus) glutaeus muscle has been determined in transverse sections of spinal and limb nerves after retrogradely labelling the axons with horseradish peroxidase. Glutaeus axons were dispersed widely through spinal nerves 8 and 9 but loosely gathered together in one quadrant of the sciatic nerve after passing through the lumbar plexus. Glutaeus axons became tightly clustered to the exclusion of other axons along the length of the triceps femoris nerve after it divides from the sciatic nerve. Furthermore, axons destined for one of the two glutaeus primary nerve branches segregate from those of the other branch at the level of the triceps femoris nerve before the glutaeus nerve forms. On the other hand, motoneurones that subserve a primary branch are not segregated, but are found throughout the rostrocaudal extent of the glutaeus motoneurone pool. Injection of horseradish peroxidase under the epimysium of either the ventral or the dorsal surfaces of the glutaeus muscle labelled motoneurones preferentially in either the rostral or caudal part of the motoneurone pool, respectively. This confirms studies that have shown a topographical projection from the spinal motoneurone pool onto the glutaeus muscle. However, there was no segregation of dorsally projecting axons in the glutaeus and primary nerve branches. Thus, glutaeus axons segregate according to their muscle compartmental projections well before entering the muscle, but they show no organization in nerves with respect to their topographical projections within a compartment.     

The trochlear nucleus of the frog Rana ridibunda: Localization, morphology and ultrastructure of identified motoneurons

The organization of the trochlear nucleus (N IV) was investigated in the frog Rana ridibunda. Retrograde tracing with horseradish peroxidase and biotinylated dextran amines resulted in labeling on the contralateral N IV of motoneurons with diverse morphologies and in direct caudal continuation with the oculomotor nucleus. Their dendritic arborizations extend profusely in the ipsilateral tegmentum and reach the oculomotor nucleus, the fasciculus longitudinalis medialis and also small processes branch towards the ventricle. Occasionally, one to three cells are labeled in the ipsilateral N IV, whereas mesencephalic trigeminal cells that would send their peripheral branch in the IVth nerve are never observed. The course of the labeled trochlear axons varies depending on the localization within the N IV of their cells of origin and different points of decussation are present above the midbrain ventricle. The ultrastructural analysis of identified trochlear motoneurons shows numerous axo-somatic synaptic contacts and six types of terminals with variable morphologies have been observed. Among them, a peculiar type of axon terminal forms mixed junctions with synaptic specializations and gap junctions together in the membrane interfaces that could represent the simultaneous presence of a chemical as well as an electrical component. The present data give more insights into the organization of the N IV and demonstrate that, although the organization of the trochlear nucleus is highly conservative in gnathostome vertebrates, it shows specific features for each species studied, as demonstrated for amphibians.     

The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves

The atrophy of cutaneous (sural) and muscle (medial gastrocnemius) nerves proximal to a ligation were studied in cats for periods up to 9 months, using light and electron microscopy, conduction velocity measurements and computer simulations. As atrophy proceeds, nerve fibres become increasingly non-circular. Cross-sectional areas of axons and fibres (axon + myelin) were measured. The diameters of equivalent circles (having the same axon and fibre cross-sectional area) were then calculated. A linear relation was found between axon diameter and fibre diameter, but the slope decreased as atrophy continued. This indicates that the axon cross-sectional area decreases relatively more than the total fibre area. Reduction in conduction velocity correlates more closely with reduction in axon diameter than fibre (axon + myelin) diameter.The ratio of the inner (axon) perimeter to the outer (myelin) perimeter remains constant at or near the optimal value of 0.6 for conduction in all groups of fibres at all periods of atrophy. Futhermore, the thickness of the myelin remains constant for a given perimeter over the entire period of atrophy studied. This suggests that the number of turns of myelin and the length of each turn remain unchanged during peripheral nerve atrophy. A simple geometric model explains how this can occur without gaps developing between the axon and myelin or between the turns of myelin. The Frankenhaeuser-Huxley equations for conduction in myelinated nerve fibres predict changes in conduction velocity similar to those observed, if the axons atrophy without changes in myelin. The advantages of this mode of atrophy are discussed.     

Nerve compound action current (NCAC) measurements and morphometric analysis in the proximal segment after nerve transection and repair in a rabbit model

In the evaluation of nerve regeneration using magneto-neurography (MNG), the proximal segment showed a reproducible decrease in peak-peak amplitude of the nerve compound action current's (NCAC) of 60%. To explain these changes, morphometry of myelinated axons in the proximal segment is compared to the MNG signals. A standardised nerve transection and reconstruction was performed in rabbits. NCACs were measured approximately 5 cm proximal to the lesion from operated and control nerves after 12 weeks. Histological samples were taken from the same area of the nerve where the NCACs were obtained. Results showed a decrease of the peak-peak amplitude of the NCAC of 57% compared to the control. Conduction velocity decreased 15% (not significant). Morphometry elicited a decrease in larger (10-15 microm) axons (284 +/- 134 vs 82 +/- 55) and an increase in smaller (2-5 microm) axons (1445 +/- 360 vs 1921 +/- 393). A strong correlation existed between the decrease in amplitude and the decrease in larger axons (0.85). Peak-peak amplitude varies approximately with the square of the diameter axon. Therefore, because peak-peak amplitude is mainly dependent on the larger-diameter axons, the decrease in peak-peak amplitude of the NCACs may be explained by a decrease in numbers of 10-15-microm axons.     

Presence of unmyelinated axons in the spinal root of the feline accessory nerve

The spinal root of the accessory nerve was studied electron microscopically at different levels in 3 adult cats. It was found that this nerve contains several unmyelinated axons. In the main nerve trunk the proportion of unmyelinated axon profiles was 27% at the level of the foramen magnum. In juxtamedullary root fascicles near the PNS/CNS transition the proportion of unmyelinated axons was lower and these axons tended to occupy superficial positions in the fascicles. No intrafascicular unmyelinated axons were found in the immediate vicinity of the PNS/CNS transition but bundles of unmyelinated axons occurred in the surrounding pia mater. The findings suggest that unmyelinated axons in the spinal accessory nerve contribute to the pial vasomotor and/or sensory innervation.     

The permeability of the extracellular spaces at the Schmidt-Lanterman clefts and paranodes in peripheral myelin sheaths

Summary Electron dense material was observed in the extracellular spaces between adjacent components of the Schmidt-Lanterman clefts and between lateral loops at the paranodes in some of the heavily myelinated fibers of the anterior roots and peripheral nerves of a patient with amyotrophic lateral sclerosis. Similar deposits were seen in tissue derived from patients who died with no neurological disease. These deposits were also present in the extracellular spaces of the endoneurium and beneath the outer cytoplasmic collar of the sheath, but did not penetrate the intraperiod line of the compact myelin or the periaxonal space and the lateral loops tended to remain in contact with the axon. The findings suggest that a pathway exists between the extracellular spaces outside the sheath to the innermost portion of the sheath but that the periaxonal space is resistant to the penetration of the extraneous material.Supported in part by the Amyotrophic Lateral Sclerosis Society of America     

Quantitative studies of the abnormal axon-Schwann cell relationship in the peripheral motor and sensory nerves of the dystrophic mouse

The nature and extent of abnormal axon-Schwann cell relationships in peripheral portions of dystrophic motor and sensory nerves were quantitatively evaluated between 1 and 9 months of age using teased fibres and electron micrographs.The results show that in the dystrophic (dy/dy) common peroneal (CPN) and tibial nerves (TN), and less in the dy/dy sural nerve (SN): (1) the number of Schwann cell nuclei associated with myelinated axons is increased with respect to normal; (2) the average internodal length is correspondingly reduced; (3) the average dystrophic internode elongates roughly in parallel with the average normal internode, and with the dystrophic limb; the longitudinal growth of the dystrophic limb is normal; (4) the variation of internodal length is greater than normal; it does not increase with age; (5) the incidence of the nodes of Ranvier which are wider than the normal 3 μm limit does not increase with age; and (6) the number of myelinated axons is reduced in the dy/dy CPN and TN but not in the dy/dy SN; it shows no change with age.These data indicate that: (1) in the dy/dy peripheral nerves (PNS) the abnormal axon-Schwann cell relationships and the reduced number of myelinated axons have been established prior to 1 month of age, thereafter progressive degenerative processes do not appear to take place, and (2) the dy/dy sensory nerve are less affected than the motor ones.     

Use of collision tests to identify physiological differences between the median and ulnar nerves

Introduction: Median and ulnar nerves are used in comparative electrophysiological studies. We analyzed the conduction values in these hand nerves in healthy volunteers to find any physiological differences between them. Methods: We performed standard conduction studies and conduction velocity distribution (CVD) tests with estimation of 3 quartiles in 31 healthy right-handed volunteers (17 women, 14 men) with a mean age of 44.8 ± 15.5 years. Results: The conduction velocities in all quartiles of CVD tests were statistically faster in the ulnar nerve (P < 0.00001), with no differences in the spread of conduction values and no differences between sides. In the ulnar nerve, CVD velocities in all quartiles were faster in the female group (P < 0.05). Discussion: The ulnar nerve has more fibers conducting with high velocities than does the median nerve. Electrophysiological comparisons between hand nerves must be performed carefully. Muscle Nerve 59:470–474, 2019