Entrapment syndrome of multiple nerves in graft-versus-host disease.

INTRODUCTION: Peripheral nerve entrapment syndromes are associated with hereditary neuropathy with liability to pressure palsies and a variety of rheumatic and endocrinological diseases. METHODS: We report a patient with entrapment syndromes of multiple nerves associated with chronic graft-versus-host-disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Nerve ultrasound, histology, and ultrastructural changes were assessed. RESULTS: The 51-year-old man had developed severe deep dermal sclerosis due to chronic GVHD with a progressive polyneuropathy and entrapment syndromes of multiple nerves. Pre-stenotic enlargement was shown by nerve ultrasound. Histology demonstrated fibrosis of the epineurium with scarce infiltration of macrophages. Electron microscopy demonstrated alterations of the myelin sheaths and marked depletion of normal-sized myelinated nerve fibers. CONCLUSIONS: In addition to polyneuropathy, chronic GVHD can be associated with peripheral nerve entrapment syndromes and should be added to the differential diagnosis of compressive neuropathies.

High-resolution MRI demonstrates detailed anatomy of the axillary brachial plexus. A pilot study.

BACKGROUND: Axillary block is the most commonly performed brachial plexus block and may be guided by nerve stimulation or ultrasound. Magnetic resonance imaging (MRI) has proven to be beneficial in presenting anatomy of interest for regional anaesthesia and in demonstrating spread of local anaesthetic. The aim of this pilot study was to demonstrate the anatomy as shown by MRI of the brachial plexus in the axillary region. METHODS: Nine volunteers and nine patients were examined in a 3.0 Tesla MR. The patients had two different brachial plexus blocks. Subsequently, they were scanned by MRI and finally tested clinically for block efficacy before operation. Axial images, with and without local anaesthetics injected, were viewed in a sequence loop to identify the anatomy. RESULTS: With the high-resolution MRI, we obtained images of good quality, and cords and all terminal nerves could be identified. When local anaesthetics are injected, neurovascular structures are displaced, and the vein is compressed. Viewing the images in a sequence loop facilitates identification of the different nerves and has high instructive value (links S1-3 to these loops are enclosed). CONCLUSION: Clinical high-field 3.0 Tesla MRI scanner gives good visualization of brachial plexus in the axilla. The superior ability to detect local anaesthetics after it has been injected and the multiplanar imaging capability make MRI a useful tool in studies of the brachial plexus.

The digital venous drainage in the human embryonic hand.

The histogenesis and morphology of the digital venous drainage in human embryonic and fetal hands, aged from 6 to 12 weeks, were studied by light microscopy in 18 fingers. In the sixth week, capillaries could be identified around the cartilaginous models of the phalanges. By the ninth week, the neurovascular bundles were identifiable in the palmar part of the finger. In 12 week fetuses, all of the superficial and deep vascular venous system could be seen easily in the palmar aspect of the finger in positions similar to those in the adult hand. However, the arch systems, present on the dorsum of the finger in the adult hand, were not yet differentiated.

Activity-dependent regulation of myelin maintenance in the adult rat.

Hindlimb unloading (HU) is known to induce changes in the neuromuscular system. However, no data describing the effects of HU on morphological characteristics of peripheral nerve have been reported so far. Therefore, we used soleus and radial nerves obtained from control and rats submitted to 14 days of HU to study the consequences of a decrease (soleus) or an increase (radial) in neural activity on its morphology. The mean number of fibers was not changed after HU. The soleus nerve axon diameter was weakly affected after HU, whereas the myelin thickness was reduced. For the radial nerve, both axon and fiber diameter were increased, and the myelin thickness and internodal distance were higher in HU rats. These results suggest that regulation of myelin maintenance undergoes plastic mechanisms. Neural activity and/or neural pattern might be essential in the maintenance of myelin sheath in adults.

Regeneration of the radial nerve cord in a holothurian: a promising new model system for studying post-traumatic recovery in the adult nervous system.

After a complete transection, the radial nerve cord (RNC) of the adult sea cucumber Eupentacta fraudatrix quickly regrows and reconnects. The description of the major cellular events that accompany this regeneration is derived from light and transmission electron microscopy. Shortly after lesioning, the extensive nerve fiber degeneration and neuronal apoptosis occur. The gap in the cord created by the transection is rapidly bridged, at first by connective tissue and subsequently by regenerating nerve tissue. On either side of the wound, the ectoneural and hyponeural components of the injured RNC form separate tubular rudiments, whose epithelial walls are composed mostly of dedifferentiated glial cells, capable of mitotic division, but also contain some nerve fibers and occasional neuronal perikarya. It is suggested that the glial cells play a crucial role in regeneration not only by providing the supporting guiding scaffold for regrowing nerve fibers, but also by producing new neurons. Other mechanisms of post-traumatic neurogenesis may involve proliferation and/or migration of existing perikarya. The anterior and posterior regenerates grow towards one another and eventually fuse to restore the anatomical continuity of the RNC. Re-differentiation of gliocytes and accumulation of nerve cells in the newly formed regions of the nervous tissue make histological organization of the fully regenerated RNC indistinguishable from that of the intact cord. The authors suggest that the holothurian RNC provides a valuable experimental model, which opens new possibilities for exploring the fundamental mechanisms underlying regeneration of the nervous system in deuterostomes.

Bridging small-gap peripheral nerve defects using acellular nerve allograft implanted with autologous bone marrow stromal cells in primates.

This study evaluated the effects of the transplantation of a tissue-engineered nerve derived from an acellular allogenic nerve graft, combined with autologous bone marrow stromal cells (MSCs), into peripheral nerve defects. In a rhesus monkey model, nerve regeneration was evaluated across a 1-cm lesion in the radial nerve by using an acellular allogenic nerve injected with autologous MSCs. Simple acellular nerve allografts served as control. Eight weeks after surgery, immunofluorescence staining, histologic morphometrical analysis and electrophysiologic evaluation were performed. Fluorescence microscopy revealed that some MSCs were immunopositive to S-100 protein, indicating a Schwann cell (SC) phenotype. The group treated with cultured MSCs showed a statistically higher number of nerve fibers, with well-shaped remyelinated axons. The motor conduction velocities and the peak amplitudes of compound muscle action potentials (CMAP) for the group treated with MSCs were higher than those of the controls. This outcome indicated that MSCs are able to differentiate into Schwann-like cells in vivo and to promote nerve regeneration in primates. Furthermore, the acellular nerves injected with MSCs provided a favorable environment for the growth and myelination of regenerating axons when compared to acellular nerves alone.

Unexpected motor axons in the distal superficial radial and posterior interosseous nerves: a cadaver study.

The prevalence of motor variations in the nerves supplying muscles of the first web space was evaluated by a visual dissection and immunohistochemical analysis from 56 cadaver hands. By microscopic visualization, 30% of the superficial radial nerves (SRNs) sent branches into muscles of the first web space. Since these unexpected penetrating branches were expected to be sensory or proprioceptive, markers of sensory and motor axons were used for confirmation. Positive identifications of motor axons (as identified by positive immunostaining for choline acetyltransferase) were made in 30% of SRNs and in 28.5% of posterior interosseous nerves. Classical teachings that the SRNs and PINs are exclusively sensory have been brought into question. Our data are in agreement with the rare clinical finding that motor function occasionally persists following devastating injury to both the ulnar and median nerves. Anatomic prevalence for this variation appears much higher than previous descriptions have indicated.

Morfologia microscópica do nervo radial do gato doméstico (Felis catus domesticus LINNAEUS, 1758) / Microscopic morphology of the radial nerve in domestic cat (Felis catus domesticus LINNAEUS, 1758)

No presente estudo investigou-se a estrutura histológica do nervo radial do gato doméstico. Foram utilizados cinco gatos, três fêmeas e dois machos, sem raça definida, provenientes do CCZ de Jaboticabal, SP. Dividiu-se o nervo em três regiões e foram coletados três segmentos: proximal, médio e distal. Após procedimentos de rotina histológica convencional, observou-se três tecidos de sustentação: o epineuro, o perineuro e o endoneuro. O epineuro é formado por tecido conjuntivo denso modelado e não modelado, e também por conjuntivo frouxo. Do epineuro partem septos, constituídos por conjuntivo denso não modelado e frouxo, rico em células adiposas. O perineuro, que reveste grupo de feixes nervosos, formando os fascículos, possui de duas a quinze camadas de células justapostas concêntricas com núcleo fusiforme, citoplasma delgado e alongado, diferenciando duas camadas, uma externa e outra interna. O espaço interlaminar da camada externa é preenchido por fibras colágenas e o da camada interna por fibras colágenas e reticulares. O endoneuro é constituído por tecido conjuntivo frouxo que circunda axônios predominantemente mielinizados, apresentando fibras colágenas e reticulares. Analisou-se, também, no presente estudo, o arranjo dos fascículos nervosos, notando-se no segmento proximal média de 11,50 + ou - 5,40 pequenos fascículos de diâmetros variados. O segmento médio apresentou média de 10,20 + ou - 2,94 fascículos com diâmetros maiores que os do segmento proximal. O segmento distal apresentou média de 15,30 + ou - 3,89 fascículos exibindo várias dimensões e menores que os observados no segmento médio. A análise estatística dos resultados demonstra diferença significativa (p<0,05) para as comparações das médias efetuadas entre as regiões estudadas. Os tecidos de revestimento do nervo radial do gato se apresentaram de modo semelhante aos descritos nos animais domésticos.

The aim of this study was to describe the histological structure of the domestic cat´s radial nerve, which has three conjunctive tissues for sustentation. The epineurium is formed by dense modeled and non modeled conjunctive tissue, and loose conjunctive tissue. Of epineurium they break septum for perineurium. They are rich in adipose cells and are formed by dense non-modeled conjunctive tissue and by loose conjunctive tissue. The perineurium revests a group of nervous bundles and has from two to fifteen juxtaposed cells. These cells are concentric and they have a fusiform nucleus, a thin and prolonged cytoplasm that is divided in two layers – one external and other internal. The external layer´s interlaminar space is filled by collagen fibers and the internal layer´s by collagen and reticular fibers. The endoneurium is formed by loose conjunctive tissue that embraces predominantly myelinated axons, and also has collagen and reticular fibers. It was also analyzed in the present study the arrangement of the nervous fascicles, noticing in the proximal segment the average from 11.5 to 5.4 small fascicles of varied diameters. The medium segment presented the average from 10.2 to 2.94 fascicles with bigger diameters than the proximal segment. The distal segment presented the average from 15.3 to 3.89 fascicles showing a lot of dimensions and smaller than the observed ones in the medium segment. The statistic analysis of the results demonstrated significant difference (p<0.05) to the comparisons of the averages effected between the studied regions. The revestiment tissues of the radial nerve had been presented in a similar way to the described ones in the domestic animals.

A hypothetical mathematical construct explaining the mechanism of biological amplification in an experimental model utilizing picoTesla (PT) electromagnetic fields.

We seek to answer the conundrum: What is the fundamental mechanism by which very weak, low frequency Electromagnetic fields influence biosystems? In considering the hydrophobicity of intramembranous protein (IMP) H-bonds which cross the phospholipid bilayer of plasma membranes, and the necessity for photonic recycling in cell surface interactions after dissipation of energetic states, present models lack structure and thermodynamic properties to maintain (DeltaE) sufficient energy sources necessary for amplifications by factors of 10(12). Even though one accepts that the ligand-receptor association alters the conformation of extracellular, extruding portions of IMP's at the cell surface, and that this change can be transmitted to the cytoplasm by the transmembranous helical segments by nonlinear vibrations of proteins with generation of soliton waves, one is still unable to account for repair and balanced function. Indeed, responses of critical molecules to certain magnetic field signals may include enhanced vibrational amplitudes, increased quanta of thermal energies and order inducing interactions. We may accept that microtrabecular reticulum-receptor is associated with actin filaments and ATP molecules which contribute to the activation of the cyclase enzyme system through piezoelectricity. Magnetic fields will pass through the membrane which sharply attenuates the electric field component of an EM field, due to its high impedance. Furthermore, EM oscillations are converted to mechanical vibrations; i.e., photon-phonon transduction, to induce molecular vibrations of frequencies specifically responsible for bioamplifications of weak triggers at the membrane surface, as well as GAP junctions. The hydrogen bonds of considerable importance are those in proteins (10(12)Hz) and DNA (10(11)Hz) and may be viewed as centers of EM radiation emission in the range from the mm microwaves to the far IR. However, classical electrodynamical theory does not yield a model for biomolecular resonant responses which are integrated over time and account for the connection between the phonon field and photons. Jacobson Resonance does supply an initial physical mechanism, as equivalencies in energy to that of Zeeman Resonance (i.e., zero-order magnetic resonance) and cyclotron resonance may be derived from the DeBroglie wave particle equation. For the first time, we view the introduction of Relativity Theory to biology in the expression, mc(2)=BvLq, where m is the mass of a particle in the 'box' or 'string' (molecule in a biosystem), c is the velocity of electromagnetic field in space, independent of its inertial frame of reference, B is the magnetic flux density,v is the velocity of the carrier or 'string' (a one or two dimensional 'box') in which the particle exists, L is its dimension (length) and q represents a unit charge q=1C, by defining electromotive force as energy per unit charge. Equivalencies suggest that qvBL is one of the fundamental expressions of energy of a charged wave-particle in magnetic fields, just as Zeeman and cyclotron resonance energy expressions, gbetaB and qhB/2pim, and is applicable to all charged particles (molecules in biological systems). There may exist spontaneous, independent and incessant interactions of magnetic vector B and particles in biosystems which exert Lorentz forces. Lorentz forces may be transmitted from EM field to gravitational field as a gravity wave which return to the phonon field as microgravitational fluctuations to therein produce quantum vibrational states that increase quanta of thermal energies integrated over time. This may account for the differential of 10(12) between photonic energy of ELF waves and the Boltzman energy kT. Recent data from in vivo controlled studies are included as empirical support for the various hypotheses presented.

The role of glycation in the pathogenesis of diabetic polyneuropathy.

The most common neuropathy associated with diabetes mellitus is a distal sensory polyneuropathy. The relative importance of the direct effects of prolonged glycaemia on nervous tissue compared with indirect damage resulting from changes in blood vessels is not known. Although the importance of glycaemia is confirmed by a study showing that the incidence of neuropathy is greatly reduced by strict glycaemic control, many of the details of the deleterious effects of glycaemia on the peripheral nervous system (PNS) are not understood. These may be the result of direct damage to any of the cells in the PNS or the disruption of neuronal metabolism, axonal transport mechanisms, or repair capabilities; in addition, they may result from the effects of glycation on PNS connective tissue or a combination of some or all of the above mentioned mechanisms. The relative importance of these various mechanisms by which diabetes damages the PNS is a matter of conjecture. Therapeutic approaches targeting a specific mechanism such as those utilising aldose reductase inhibitors, or advanced glycation endproduct inhibitors have met with limited success. Clearly, it is difficult to design a treatment for diabetic neuropathy while its pathogenesis is still poorly understood.

Brain phagocytes may empty tissue debris into capillaries.

The possibility that brain phagocytes may empty remnants of degenerated neurons into capillaries has been studied in frogs. Degeneration of nerve fibers was brought about by transectioning the optic tract, the tectothalamic and tectoisthmic tracts, the postoptic commissure or the radial nerve. To help identification of phagocytozed degenerated neuronal elements, the transected fibers were filled either with horseradish peroxidase (HRP) or cobaltous-lysine complex. The survival times were 3, 4, 7, 27, 47 and 70 days after the application of the markers. The HRP-labeled structures were identified in 60 microm thick sections using diaminobenzidine as chromogen, while cobalt was precipitated in the form of cobaltous sulfide. Small pieces of these sections were further processed for electron microscopy. In each area of the brain and spinal cord investigated, microglial cells and astrocytic processes containing fragments of degenerated neuronal elements could be seen close to capillaries. In some cases a microglial or astrocytic process pierced the capillary basal lamina and seemingly delivered inclusion bodies into the cytoplasm of capillary endothelial cells and pericytes. In the inclusion bodies, which were usually large vesicles, fragments of HRP or cobalt-labeled or unlabeled membranes with a foamy appearance, or condensed myelin lamellae could be observed. These vesicles protruded the luminal membrane of the endothelial cell that was disrupted in some cases suggesting that the content of the inclusion body was discharged into the lumen of the capillary. These results give support to Penfield's hypothesis (1925) that glial cells may empty phagocytozed materials into capillaries.

Myelin widenings and MGUS-IgA: an immunoelectron microscopic study.

A few studies have reported a variety of nonspecific histological lesions in patients with IgA monoclonal gammopathies and polyneuropathy. In our case, using electron microscopy, we observed widenings of the myelin lamellae identical to those commonly described in IgM neuropathies with anti-myelin-associated glycoprotein activity. Using immunoelectron microscopy, we demonstrated a direct involvement of IgA in myelin lesions. The search for a direct link between monoclonal dysglobulinemia, regardless of type, and polyneuropathy is important and may influence treatment.

Light and electron microscopic study of peripheral nerve damage in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL).

Cutaneous branches of radial nerves in patients with lepromatous leprosy (LL) and borderline lepromatous (BL) were studied by light and electron microscopy. Foamy macrophages were found more or less in the nerve fibers of all leprosy patients and distributed in the epineurial, perineurial and endoneurial areas. In the endoneurium, the foamy macrophages were mainly located in the subperineurial and perivascular spaces. Vacuolated Schwann cells were also found in the nerve fasciculus. In electron microscopy, these foamy macrophages and vacuolated Schwann cells contained numerous small dense materials, irregular in size and shape, considered to be degenerated and fragmented mycobacterium leprae. These dense materials were found also in the cytoplasm of vascular endothelial cells. These findings suggest that mycobacteria enter into the endoneurium via the blood vessels. In our present study, on the other hand, it was very difficult to find the intact mycobacteria in the cytoplasm of the foamy macrophages, Schwann cells or endothelial cells, as well as in the Ziehl-Neelsen staining of paraffin sections. The disappearance of intact bacilli in our present study might have been caused by multi drug therapy. The myelinated nerve fibers were degenerated and disappeared in variable degrees. Degenerative changes of the myelin sheath developed from the outer layer to the inner layer with disarrangement of the lamellar structure. These findings were different from myelin destruction of peripheral nerves in Wallerian degeneration. The degenerative changes of the myelin sheath are caused by degeneration and destruction of Schwann cells in leprosy patients. Fibrosis surrounding myelinated and unmyelinated nerve fibers, i.e., periaxonal fibrosis, was found to a greater or lesser extent in the endoneurium. In the present study, it is still unclear whether the periaxonal fibrosis was due to necrosis of the Schwann cells by infection of mycobacteria or to an autoimmune mechanism such as antiperipheral nerve antibody. However, lamellated concentric fibrosis surrounding regenerative myelinated and unmyelinated nerve fibers with the disappearance of mycobacteria suggests that degenerations and regenerations of nerve axons were repeated during clinical cause. These findings indicated that autoimmune mechanisms play an important role in the pathogenesis of periaxonal fibrosis.

Experimental investigation of cross-nerve transfers relating to repair of brachial plexus avulsion injuries.

There is a lack of agreement regarding the potential for peripheral nerve cells with short axons to regenerate and innervate the terminal end organs of nerve cells with long axons. We designed a study to evaluate experimentally the possibility of neurons to reconstitute much longer axonal segments. Twenty Wistar rats were used. The brachial plexus was isolated and the radial nerve transected immediately after its origin. The proximal end of the axillary nerve (previously cut) then was coapted tot he distal stump of the radial nerve. In 10 other rats, the cut radial nerve was simply recoapted to itself without involvement of the axillary nerve; these animals served as controls. Finally, in 10 rats, nerves were cut without repair to evaluate the degenerative changes. After 90 days, the distal part of the radial nerve was examined by light microscopy, calculating the number and area of regenerated axons. We also checked the motor end-plates of reinnervated muscles. In the nerve-transferred group, good axonal regeneration with good reinnervation of the muscles was seen. In this way, we have experimentally demonstrated a plasticity of regeneration in peripheral nerves. This suggests that the surgeon may use nerves connected to proximal muscles to neurotize avulsed nerves of distal muscles.

Myelin changes in leprous neuropathy.

Myelin changes were observed in fibres of nerves from cases of leprosy. The myelin had a 'loosened' appearance caused by increased and irregular separation of the intraperiod line. 'Loosening' might affect all, or only some, of the lamellae forming a myelin sheath. There was a patchy distribution of fibres with abnormal myelin, and they were seen only in nerves showing other marked pathological changes including the presence of oedema. The appearances are suggestive of intramyelinic oedema which may be related to the presence of endoneurial oedema.

The pathobiology of human neuromas: an electron microscopic and biochemical study.

The formation of neuroma scar after trauma or neurorrhaphy is believed to be mediated by the response of collagen forming fibroblasts. In this study of twenty human neuromas, myofibroblasts were identified as a component of the scar. These cells occurred singly or as aggregates. There was a qualitative increase of myofibroblasts during the period from two to six months post-injury. From six months to one and one-half years post-injury, numbers and aggregations of myofibroblasts diminished, concurrent with collagen proliferation. Ultrastructural alcian blue staining and biochemical analyses revealed a glucosamine--glycosaminoglycan matrix within neuromas when compared to control nerves. Myofibroblasts appear to play a part in the pathobiology of human neuromas.

Ultrastructural study on nervous system of fetus with GM1-gangliosidosis type 1.

The nervous system of a 22-year-old fetus with GM1-gangliosidosis type 1 was studied by electron microscopy. The tissues thus examined were the cerebral cortex at the parietal region, the cerebellum, the thoracic spinal cord, the Auerbach's myenteric plexus in the large intestine and the radial nerve fibers. In the cerebral cortex, membrane-bound vacuoles, which occasionally contained stacks of fine fibrils, were observed in the large young neurons in the deeper part of the cortical plate. The neurons in the other part of the cerebral cortex carried no storage materials. In the cerebellum, the membrane-bound vacuoles with stacks of fine fibrils were seen only in the Purkinje cells. The neurons in the spinal cord also contained several zebra-like bodies and the above membrane-bound vacuoles. As for the peripheral nervous system (PNS), neurons in the Auerbach's myenteric plexus carried membranous cytoplasmic bodies and zebra-like bodies. Some of the axons in the radial nerve fibers also contained a lot of pleomorphic electron-dense bodies and a few membranous cytoplasmic ones. These results show that the accumulation of storage materials is started in the large neurons which are produced in the early stage of neurogenesis in the central nervous system (CNS). Additionally, the observed membrane-bound vacuoles are considered to be structures which occur before the membranous cytoplasmic bodies and/or the zebra-like bodies. It is also elucidated that the PNS is affected earlier than the cerebral and cerebellar cortices and thoracic spinal cord.