A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays.

For decades, epineurial electrodes have been used in clinical therapies involving the stimulation of peripheral nerves. However, next generation peripheral nerve interfaces for applications such as neuroprosthetics would benefit from an increased ability to selectively stimulate and record from nerve tissue. This increased selectivity may require the use of more invasive devices, such as the Utah Slanted Electrode Array (USEA). Previous research with USEAs has described the histological response to the implantation of these devices in cats and rats; however, no such data has been presented in humans. Therefore, we describe here the degree of penetration and foreign body reaction to USEAs after a four-week implantation period in human median and ulnar nerves. We found that current array designs penetrate a relatively small percentage of the available endoneurial tissue in these large nerves. When electrode tips were located within the endoneurial tissue, labels for axons and myelin were found in close proximity to electrodes. Consistent with other reports, we found activated macrophages attached to explanted devices, as well as within the tissue surrounding the implantation site. Despite this inflammatory response, devices were able to successfully record single- or multi-unit action potentials and elicit sensory percepts. However, modifying device design to allow for greater nerve penetration, as well as mitigating the inflammatory response to such devices, would likely increase device performance and should be investigated in future research.

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.

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.

Parámetros biométricos y morfometría de la porción terminal del nervio mediano, ramo superficial del nervio ulnar y nervios digitales palmares comunes de la mano humana / Biometric and morphometric parameters of the terminal end of the median nerve, superficial branch of the ulnar nerve and common palmar digital nerves in the human hand

El conocimiento de la distribución de los nervios de la mano es necesario para realizar un adecuado diagnóstico de lesiones que le afectan y para realizar con efectividad la recuperación o reconstrucciones de la misma. Basados en esta premisa, se realizó un estudio biomorfométrico de la porción terminal del nervio mediano (NM), del ramo superficial del nervio ulnar (RSnU) y de los nervios digitales palmares comunes (NDPC). Se utilizó para ellos, 12 manos de cadáveres de individuos chilenos, adultos, pertenecientes a los Laboratorios de Anatomía, Facultad de Medicina, Universidad de La Frontera, Chile. Se realizó disección convencional y los registros morfométricos se efectuaron en 5 manos, de las cuales se extrajeron muestras y se trataron con técnicas histológicas adecuadas. Las distancias promedio entre el pliegue distal de la muñeca y el punto de división del NM, y, entre el mismo pliegue y la división del RSnU fueron de 35,5 y 26,1 mm, respectivamente; las distancias promedio entre el pliegue mencionado y el punto de división de los NDPC I, II, III y IV, fueron de 43,5; 68,1; 72,6 y 66,1 mm, respectivamente. Los diámetros externos promedios de estos últimos nervios fueron de 3,25; 1,92; 2,24 y 1,73, respectivamente. El número de fascículos del NM antes de su división fue en promedio de 30, del RSnU de 16,8; del NDPC I de 11,8; del NDPC II de 15,4; del NDPC III de 14,6 y del NDPC IV de 12,4. El número de fibras del NM antes de su división fue en promedio de 22.565, del RSnU de 8.835, del NDPC I de 4.859, del NDPC II de 5.767, del NDPC III de 5.233 y del NDPC IV de 3.606. Estos resultados aportan nuevos antecedentes para la clínica, cirugía y anatomistas, complementando el tema de la inervación de la mano.

It is necessary to know the distribution of the nerves in the hand in order to make a suitable diagnosis of the injuries that affect it and to effectively implement recovery or reconstructions. Based on this premise, a biomorphometric study was conducted on the terminal end of the median nerve (MN), the superficial branch of the ulnar nerve (SBUN) and the common digital palmar nerves (CDPN). 12 hands of adult cadavers Chileans housed in the Anatomy Laboratones in the Faculty of Medicine at the University de La Frontera, Chile were used for this purpose. 5 hands were dissected by conventional means and registered morphometricaily, from which samples were taken and treated using the appropriate histological techniques. The average distance between the distal wrist crease and the division of the MN, and between the same crease and the division for the SBUN was 35.5 and 26.1 mm, respectively; the average distances between the crease mentioned and the division of CDPN I, II, III and IV were 43.5, 68.1, 72.6 and 66.1 mm, respectively. The average external diameters of these latter nerves were 3.25, 1.92, 2.24 and 1.73, respectively. The average number fascicles prior to division was 30 from the MN, 16.8 from the SBUN, 11.8 from the CDPN I, 15.4 from CDPN II, 14.6 from CDPN III and 12.4 from CDPN IV. The average number of fibers prior to division was 22565 from the MN, 8835 from the SBUN; 4859 from the CDPN I, 5767 from the CDPN II, 5233 from the CDPN III and 3606 from the CDPN IV. These results will provide new support for clinicians, surgeons and anatomists, complementing the topic of innervation of the hand.

Cross-chest median nerve transfer: a new model for the evaluation of nerve regeneration across a 40 mm gap in the rat.

A new animal model for the study of nerve regeneration in rats across a 40 mm gap between both median nerves is described. For autologous grafting, the ulnar nerves were dissected and sutured together. From the left median nerve, they were transplanted across the chest to the right median nerve. Animals having undergone this operation were observed for 12 months and periodically assessed using the grasping test and measurements of body-weight. For histological analysis rats were sacrificed after this period and axon counts were determined at the suture points of operated animals and in the median nerve of non-operated animals. Functional recovery could be seen, although partially, beginning as early as the fifth postoperative month, as demonstrated by the grasping test. Quantification of the number of axons demonstrated axonal regeneration across all three coaptation points. This model provides a new approach for analysis of long distance peripheral nerve regeneration without impairment of behaviour.

A neonatal diagnosis of congenital chronic inflammatory demyelinating polyneuropathy.

We report a female infant noticed by her mother to have reduced movements of her right wrist and left foot at birth. This female presented to the Accident and Emergency Department of Queen Elizabeth Hospital, London, UK, aged 6 weeks, with significant weakness of her right wrist and left foot. Her clinical history also revealed sudden diminution in fetal movements 2 weeks before delivery, consistent with neuropathology in utero and neuromuscular deficit in the immediate postnatal period. An initial examination revealed generalized hypotonia, areflexia, and paucity of movements. Electrophysiological studies suggested demyelinating polyneuropathy; sural nerve biopsy confirmed a diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). With the results and the pre- and postnatal clinical history, we believe this to be the first reported individual with congenital CIDP confirmed in the neonatal period. We describe the treatment and outcome up to the age of six years.

Tangier disease--a diagnostic challenge in countries endemic for leprosy.

A case of Tangier disease (TD) is reported from India. The patient had presented with indolent mononeuritis multiplex and trophic ulcers of 16 years duration mimicking Hansen's disease. He received antileprosy treatment for one and a half years. Nerve conduction studies revealed features of demyelinating neuropathy. Biopsies of the sural nerve and skin showed striking vacuolation of Schwann cells and myelin sheaths, and foamy vacuolated fibroblasts, respectively, and no evidence of Hansen's disease. Low levels of apolipoprotein A1 (ApoA1) and cholesterol in the serum and undetectable levels of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in the blood confirmed the diagnosis of TD. This is the first reported case of TD from a tropical country-India. An attempt to establish a correct diagnosis should be made by demonstrating the histopathological and lipoprotein abnormality to avoid long term medications that are chosen empirically and are unnecessary. The importance of recognising this disease in a country where Hansen's disease is highly endemic cannot be overemphasised.

[Acellular nerve allograft by chemical extraction in humans].

OBJECTIVE: To develop a procedure by which Schwann cells and myelin in the peripheral nerve could be removed while the basal lamina tubes remained intact, and to obtain a thick and long acellular nerve allograft in humans. METHODS: Four ulnar nerves 10.0 cm long and 4.0 - 5.0 mm in diameter were excised from a donated male body and cleaned from external debris. The nerves were treated with a solution of Triton X-100 and a solution of sodium deoxycholate at room temperature. After a final wash in water, the nerves were stored in phosphate-buffered saline (PBS, pH 7.2) at 4 degrees C. HE, luxol fast blue and fibrin staining were performed to visualize cells, myelin and basal membranes respectively and immunohistochemical staining was performed to visualize the presence of laminin, a Schwann cell lamina component, both in fresh and acellular nerve segments. To reveal overall structure better, methylene blue-fuchsin staining was performed in semithin section. The ultrastructure of acellular and fresh nerves were observed and photographed in a transmission electron microscope. RESULTS: The acellular human ulnar nerve was white long cylinder with well elasticity and ductility. HE, myelin and fibrin staining revealed that cells, axons and myelin sheath were removed and basal membrane was preserved after extraction procedure. Staining for the presence of laminin showed that the Schwann cell basal lamina component were present in the nerves after chemical treatment. Methylene blue-fuchsin staining and transmission electron microscopy showed that the myelin sheaths were absent in the extracted nerve segments and empty basal lamina tubes remained in the endoneurium. CONCLUSIONS: We developed an extracted procedure with the detergents of Triton X-100 and deoxycholate, by which cells, axons and myelin sheaths could be removed from a human ulnar nerve while the basal lamina tubes remain intact and a thick long acellular nerve allograft is obtained. The laminin, a Schwann cell basal lamina component, can be preserved in the acellular nerve.

F-waves and conduction velocities range.

A controversial aspect in F-wave studies is if these potentials are generated preferentially by large motoneuron or by motoneuron of all sizes. The purpose of this work is to compare the maximum and minimum conduction velocities of the fibers that generate the M-wave with the maximum and minimum conduction velocities of the F-waves elicited by ulnar nerve stimulation. There were no significant differences between maximum velocities. However, minimum F-wave velocity was significantly higher than minimum conduction velocity, suggesting that the F-waves registered were preferentially generated by the fastest conducting axons.

Transfer of flexor carpi ulnaris branch of the ulnar nerve to the pronator teres nerve: histomorphometric analysis.

Partial median-nerve injury high in the upper extremity, resulting from brachial plexus neuritis or trauma, can affect the pronator teres muscle and result in the inability to pronate the forearm. A nerve transfer from an ulnar nerve-innervated branch to the flexor carpi ulnaris (FCU) muscle to the branch to the pronator teres (PT) is an attractive option in this clinical scenario. This study, a histomorphometric analysis of nine cadaver specimens harvested at the proposed FCU branch to PT branch transfer site, demonstrates sufficient similarities between the two branches in total number of nerve fibers (371.6 with SEM 35.1, and 361.9 with SEM 47.1; p = 0.87) and nerve cross-sectional area (122,181 microm2 with SEM 14,546 microm2, and 142,492 microm2 with SEM 19,633 microm2; p = 0.42), to predict a functional transfer result. In addition, clinical application of this transfer resulted in functional pronation strength of M4+.

Focal upper limb demyelinating neuropathy.

Observations are presented on nine selected patients with chronic upper limb demyelinating neuropathy to illustrate the range of manifestations that may be observed. In three, the involvement was purely motor, in five, mixed motor and sensory and, in one, virtually purely sensory; in seven the symptoms were unilateral and in two bilateral. The presence of reduced nerve conduction velocity and conduction block and the response to treatment in seven of the cases indicate that they represented examples of chronic inflammatory demyelinating polyneuropathy (CIDP) with focal involvement. This was confirmed by nerve biopsy in two cases. The presentation in one patient was accompanied by forearm swelling initially suspected of being a tumour but shown to be due to muscle hypertrophy. This was probably the consequence of recurrent muscle cramps and fasciculation and possibly neuromyotonia. The patient with predominant sensory involvement restricted to the upper limbs demonstrates that sensory CIDP can present focally. In one patient with monomelic motor and sensory involvement, nerve biopsy showed multifocal areas of hypertrophic demyelinating neuropathy distally in the ulnar nerve without inflammatory infiltration. This patient failed to respond to therapy. Response in the others was satisfactory, although one patient with a monomelic motor neuropathy showed a severe deterioration after being given corticosteroids; he subsequently improved with intravenous human immunoglobulin therapy.

Structure, innervation, and age-associated changes of mouse forearm muscles.

In spite of a decline in muscle strength with age, the cause of the overall decrease in motor performance in aged mammals, including rodents, is incompletely understood. To add clarity, the gross organization, innervation, histochemical fiber types, and age-associated changes are described for mouse forearm muscles used in a variety of motor functions. The anterior (flexor) and posterior (extensor) forearm compartments have the same arrangement of muscles and gross pattern of innervation as the rat. Two primary histochemical fiber types, fast/oxidative/glycolytic (FOG) and fast/glycolytic (FG), with characteristic histochemical staining patterns were observed in all forearm muscles. Additionally, there was a small population of slow/oxidative (SO) fibers confined to the deep region of a single muscle, the flexor carpi ulnaris (FCU). Between 18 and 26 months the FCU muscle displayed fibers with morphological features distinct from earlier ages. Fibers displayed a greater variation in size, a loss of their uniform polygonal shape, and a dramatic increase in clumps of subsarcolemmal mitochondria, lysosomes, and lipofuscin granules. Many of the fibers had a distinctly atrophic, angular shape consistent with recent denervation. Morphometric analyses of the FCU's source of innervation, the ulnar nerve and one of its ventral roots (C8), were consistent with the denervation-like changes in the muscle fibers. Although, there was no net loss of myelinated axons between 4 and 26 months of age, there was a significant increase in the density of degenerating cells in both the ulnar nerve and ventral root C8.

Morphological changes in the peripheral nervous system in the case of congenital malformations of the spinal cord.

A 21-year-old oligophrenic man developed after upper respiratory tract infection, quadriplegia with sphincter and respiratory disturbances. Lumbar punction revealed subarachnoid bleeding and elevated cerebrospinal protein level. Guillain-Barré syndrome and subarachnoid hemorrhage were diagnosed. At autopsy intraspinal angioma (C2-D6) and diastematomyelia (D11-lumbar segments) were found. Beside, intraspinal hemorrhage was present. Morphological examination of posterior and anterior spinal roots as well as peripheral nerves was done. Spheroids, axonal degeneration and prominent loss of myelinated fibers were observed in the proximal parts of the spinal roots. Axonal degeneration of myelinated fibers and regenerated fibers were noted in the distal parts of spinal roots and in peripheral nerves. Abnormal, fetal-like vessels were present in the spinal roots. Two mechanisms of acute and chronic changes (transneuronal and Wallerian degeneration) are discussed.

Morphological and biochemical changes in peripheral nerves with aging.

The ulnar nerve taken at autopsy from 30 subjects aged 24-98 who died without features of clinical involvement of peripheral nerves was examined morphologically. Density of myelinated fibers (m.f) per 0.1 mm2, frequency distribution of the external diameter of m.f., and teased fiber were estimated. Besides, in 8 nerves some lipids were assessed biochemically. The study showed that the percentage of fibers with morphological changes increases with aging (7-10% in adults and even up to 35% in aged subjects). In older subjects loss of m.f. may be marked. Morphological changes in the nerves of subjects in all groups of age are unspecific (axonal degeneration, and segmental demyelination). Striking feature for the nerve is the preserved ability to repair damage of the fiber independently of the subjects' age. Accidental factors play some role as a cause of morphological changes in the nerve in all groups of age but in the elderly, aging of the neuron seems to be an important factor. Biochemical changes in the nerves with age are not prominent, and much less expressed than morphological changes.

Light and electron microscopy studies of the ulnar, saphenous, and caudal cutaneous sural nerves of the dog.

Transverse sections of the ulnar, saphenous, and sural nerves taken at specific levels in normal, young-adult beagle dogs were examined qualitatively and quantitatively at both the light and electron microscopic levels. The aim of this investigation was to provide baseline information for future studies of peripheral nerve disease in this species. A systematic sampling technique was used for the determination of nerve components (i.e., unmyelinated axons and Schwann cell and fibroblast nuclei). In all nerves sampled, the average size distribution for unmyelinated axons was unimodal, and most of the axons were 0.4-1.1 micron in diameter. Within this range, there were slight individual and nerve-to-nerve variations in the location of the largest diameter peak. The mean densities of Schwann cell nuclei (numbers/mm2) ranged from 841/mm2 in the palmar branch of the ulnar nerve, to 1,223/mm2 in the caudal cutaneous sural nerve, being nearly four times the average density or fibroblast nuclei. In every animal and in almost every nerve, a few abnormalities were found; and these should be kept in mind when assessing peripheral nerves in the dog.

The immunohistochemical demonstration of early perineurial change in the development of localized hypertrophic neuropathy.

A case of localized hypertrophic mononeuropathy was studied by electron microscopy and immunohistochemistry for S100 protein, epitopes recognized by the Leu-7 monoclonal antibody, 200 kD neurofilament polypeptide, and the epithelial membrane antigen (EMA). The primary role of perineurial cell proliferation without the participation of Schwann cells in this process was directly demonstrated by EMA immunohistochemistry. Focal delamination of the EMA-positive perineurium, increased fibrosis between its layers, and compartmentalization of the fascicles by EMA-positive septae were the first recognizable changes. In practice, recognition of these early changes by EMA immunocytochemistry may be important for the clear definition of functionally unimpaired segmental margins for excision and graft implantation, and also for the future study of the process responsible for aberrant perineurial proliferation.

Structural and regenerative changes in deafferented and deefferented ulnar nerves.

Both brachial plexuses of Wistar rats were deafferented or deefferented by disrupting their dorsal or ventral roots. At the same time, the ulnar nerves were transected and sutured. A sham group and another group in which the upper (C-5) and lower (T-1) spinal nerves were transected on both sides were included as control groups. Clear differences in the ulnar nerve regeneration rate were found between the deafferented and the deefferented animals. Ultrastructural studies disclosed signs of transient axonopathy in the nontransected fibers of the proximal segment of the ulnar nerve. The possible role of bioelectricity in the genesis of these changes is discussed.