Congenital hypomyelinating polyneuropathy in two golden retriever littermates

Serial peripheral nerve biopsies from two golden retriever littermates with chronic neurologic disease were taken for morphologic and morphometric evaluation. Teased nerve preparations were difficult to interpret due to the lightness of myelin staining. Light and electron microscopic findings were characterized by the following: reduced number of myelinated axons, presence of myelinated sheaths inappropriately thin for the caliber of the fiber, poor myelin compaction, increased numbers of Schwann cell nuclei, increased concentration of neurofilaments in myelinated axons, many Schwann cells with voluminous cytoplasm, and increased perineurial collagen. Onion bulb formation was not seen. In contrast to control data, a poor correlation was seen between numbers of myelin lamellae (ML) and axonal circumference (AC). The frequency distribution of ML ranged from 5 to 55 lamellae in affected animals (mean, 28 lamellae) compared to 20 to 140 lamellae in controls (mean, 66 lamellae). The ML/AC ratio was significantly reduced (P less than 0.001) in nerves of affected dogs. Morphometric results indicated that fibers of all calibers were hypomyelinated.     

Idiopathic Polyneuropathy in Alaskan Malamutes

Clinical and morphologic features of a progressive polyneuropathy in young mature Alaskan Malamutes are described. Clinical signs included progressive paraparesis, synchronous pelvic limb gait, exercise intolerance, hyperesthesia, hypore-flexia, muscle atrophy, and tetraplegia. Electromyographic testing revealed diffuse fibrillation potentials and positive sharp waves in limb muscles, especially in muscles below the elbow and stifle. Pathologic findings in skeletal muscles and peripheral nerves included neurogenic muscle atrophy, focal or diffuse loss of myelinated nerve fibers, myelinoaxonal necrosis, and variable demyelination or remyelination.
Ultrastructural changes included axonal degeneration, presence of numerous Büngner bands, and denervated Schwann cell subunits. The nature and distribution of abnormal electrophysiologic and pathologic findings were suggestive of a distal sensorimotor polyneuropathy, which we have termed idiopathic polyneuropathy of Alaskan Malamutes to distinguish this condition from hereditary polyneuropathy of Norwegian Alaskan Malamutes, last described in 1982.     

Tumor-specific diagnostic marker for transmissible facial tumors of Tasmanian devils: immunohistochemistry studies

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.     

Age-related immunohistochemical and ultrastructural changes in rat oculomotor nerve

During ageing process, multiple changes occur on nervous tissue composed of cells and extracellular matrix. Changes on nervous tissues are usually known as degenerative changes on axon structure and connective tissue covering the nerve such as a decrease in the number of fibre or general structural changes. For this purpose, we have studied age-dependent ultrastructural changes in the rat oculomotor nerve with electron microscopy and also demonstrated collagen structure of the neural sheaths with immunohistochemical techniques. This study was conducted in Gazi University Faculty of Medicine, Department of Anatomy with a total of nine Wistar albino rats. We observed strong collagen type I immunoreactivity in endoneurium and slight to moderate reactivity in fibroblast cytoplasm in 3-month- and 12-month-old groups and mild reactivity in 24-month-old group. Collagen type IV immunoreactivity was stronger in endoneurium and perineurium in the 3-month- and 12-month-old groups compared with collagen type I and fibroblast cytoplasm showed a very strong reactivity. On the other hand, in the 24-month-old group, there was slight reactivity in endoneurium and a strong reactivity in perineurium. NGF staining showed moderate to strong reactivity on Schwann cells of the 3-month-old group. The immunoreactivity decreased in the 12-month- and 24-month-old groups. In the 3-month-old rat group, Schwann cell cytoplasm, mitochondrial structure and neurofilaments were normal. In the 12-month-old group, there were no changes in organelle distribution, mitochondrial structure and neurofilaments, but there was an increase in the connective tissue. An inconsiderable number of degenerated myelinated nerves were observed. We detected an important decrease in the collagen type I immunoreactivity, which could suggest that the endoneurium, perineurium and epineurium are less resistant to the age-related collagen loss and that the peripheral nerve is protected by a weaker barrier in the old group. The collagen type IV immunoreactivity was significantly decreased with age. NGF synthesis decreases with age because of Schwann cell structural degeneration or for different reasons. Thus, this could explain the diminished capacity of regeneration and damage of the myelination of the peripheral nerve.     

A canine peripheral nerve sheath tumor including peripheral nerve fibers

Peripheral nerve sheath tumor was found in a 7-year-old male mongrel dog. The tumors were located in the right cheek subcutis and oral submucosa. Histologically, neoplastic cells were arranged in streaming bundles, occasionally interlacing bundles or whorls of elongated and spindle cells. Cellular atypia was poor and mitotic figures were rarely observed. Ultrastructurally, neoplastic cells had basement membrane, typical of Schwann cells. One bundle of normal peripheral nerve fibers and some myelinated axons were seen within the tumor tissues. Immunohistochemically, neoplastic cells reacted to vimentin, glial fibrillary acidic protein, S-100 protein and neuron specific enolase. In addition to the above immunoreactions, the included nerve fibers were positive for myelin basic protein and neurofilament protein. This paper also discusses immunohistochemical findings on differential diagnosis in comparison with those of canine hemangiopericytomas reported hitherto.     

Pathological aspects of Australian Stringhalt.

Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown.     

Recurrent demyelination and remyelination in 37 young Bengal cats with polyneuropathy

Background: With the exception of diabetic neuropathy, polyneuropathy associated with hyperchylomicronemia, and a few inherited polyneuropathies, peripheral neuropathies are poorly characterized in cats. A chronic polyneuropathy is described in a cohort of young Bengal cats. Objective: To characterize the clinical and histopathological features of a chronic‐relapsing peripheral neuropathy in young Bengal cats. Animals: Thirty‐seven young Bengal cats with clinical weakness consistent with peripheral neuropathy. Methods: Bengal cats were included in this study after a diagnosis of polyneuropathy was confirmed by muscle and peripheral nerve biopsy specimens. Pathological changes were characterized at the light and electron microscopic level and by morphometry. Clinical information and long‐term outcome from case records of Bengal cats with histologically confirmed peripheral neuropathy were then assessed. Results: Nerve fiber loss within distal intramuscular nerve branches was a consistent finding in young Bengal cats with polyneuropathy. The most common abnormalities in peripheral nerve biopsies included inappropriately thin myelin sheaths and thinly myelinated fibers surrounded by supernumerary Schwann cell processes, indicative of repeated cycles of demyelination and remyelination. Recovery was common. Response to treatment could not be determined. Conclusions and Clinical Importance: A chronic‐relapsing form of polyneuropathy associated primarily with episodes of demyelination and remyelination was identified in young Bengal cats. The prognosis for recovery is good, although relapses are possible and there can be residual motor deficits.     

Peripheral neuropathy associated with dietary riboflavin deficiency in the chicken. I. Light microscopic study

Chickens fed a riboflavin-deficient diet from hatching had leg weakness and paralysis as early as 12 days of age. Signs worsened through day 16; after 35 days, recovery was evident. Sciatic nerves from affected chickens were enlarged. Significant microscopic lesions were confined to peripheral nerves and included tissue separation (suggesting interstitial edema), Schwann cell swelling, perivascular leukocytic infiltration, and segmental demyelination accompanied by accumulation of osmiophilic debris in Schwann cell cytoplasm. Axon degeneration was present, but was not a primary lesion. Acid phosphatase enzyme activity of Schwann cells was increased in affected nerves. These results demonstrate that dietary riboflavin deficiency causes a demyelinating peripheral neuropathy in young, rapidly growing chickens.     

Myelinated axons in peripheral nerves of adult beagle dogs: morphometric and electrophysiological measurements

The myelinated fibre composition and conduction velocities were measured for the ulnar, saphenous and caudal cutaneous sural nerves of 10 healthy beagle dogs. A systematic random sampling technique was used to estimate the fibre diameter frequency distributions and densities. Conduction velocities were measured from evoked compound nerve action potentials. All nerves showed bimodal diameter frequency distributions with modes being approximately the same for each nerve (2 to 4 microns and 8 to 10 microns or 10 to 12 microns). The variation in the average densities and in the shapes of histograms of the different nerves was slight; however, there was a wide variation for the same nerve in different individuals. The conduction velocities for the fastest conducting axons in the nerves ranged from 63 to 79 m s-1. These normal quantitative processes affecting peripheral nerves in the dog.     

Mobilization and activation of nonspecific cytotoxic cells (NCC) in the channel catfish (Ictalurus punctatus) infected with Ichthyophthirius multifiliis

Channel catfish demonstrate a shift in the tissue distribution of nonspecific cytotoxic cells (NCC) when infected with the protozoan parasite, Ichthyophthirius multifiliis. NCC, isolated from head kidney (HK) tissues (hemopoietic organ) or peripheral blood leukocytes, were assessed for cytotoxic activity against NC-37 (a transformed mammalian cell line). NCC activity from HK tissue of moribund I. multifiliis-infected fish was depressed compared to HK-NCC activity in uninfected or I. multifillis-immune fish. The activity of NCC, isolated from the peripheral blood of moribund I. multifiliis-infected fish was significantly greater than the NCC activity in peripheral blood from either immune or uninfected fish. Chromium-51 release assays were combined with effector and target conjugate assays to determine killing capacity (Vmax) and affinity (Km) for target cells of peripheral blood NCC from moribund I. multifiliis-infected and uninfected fish. These experiments indicated that the peripheral blood from the moribund infected fish contained an increased percentage of active NCC with increased killing capacity and target cell affinity compared to peripheral blood NCC activity of uninfected fish.     

Distal denervating disease: a degenerative neuropathy of the distal motor axon in dogs

A group of ten dogs affected by an apparently identical denervating disease, is described. There was no breed or age predisposition but females were preferentially affected (70%). The rate of onset of signs was variable from a week to greater than 1 month. Quadriparesis was present to varying severities and in two dogs the head and neck could not be supported. Mastication, swallowing, respiration and bladder function were unimpaired. Pain sensation was normal, tone was usually decreased and the local limb reflexes depressed or absent. Muscle atrophy was often prominent. All cases bar one recovered but another dog was also destroyed. Electrophysiology revealed diffuse spontaneous activity in the muscles and the motor nerve conduction velocities were at the lower end of or just below the normal range. The evoked muscle potentials were reduced in amplitude. Sensory nerve potentials were normal. The pathology showed a degeneration of the distal intramuscular axons with collateral axonal sprouting. The muscle changes were typical of neurogenic atrophy. The disease has been called distal denervating disease (DDD) until the precise aetiology can be determined.     

雏鸡核黄素缺乏症的外周神经酶细胞化学

为进一步探讨核黄素缺乏时外周神经变化的发生机理,对琥珀酸脱氢酶、酸性磷酸酶、腺苷三磷酸酶、碱性磷酸酶进行了酶细胞化学研究。结果表明,核黄素不足的鸡,雪旺氏细胞和轴突中琥珀酸脱氢酶活性下降,酸性磷酸酶活性明显升高,定位于雪旺氏细胞膜上的腺苷三磷酸酶和碱性磷酸酶活性均下降。通过对琥珀酸脱氢酶、腺苷三磷酸酶、碱性磷酸酶活性变化的动态观察,证明轻症鸡自愈的现象以及雪旺氏细胞中琥珀酸脱氢酶活性下降可能是形成脱髓鞘、外周神经水肿、导致雪旺氏细胞膜上的腺苷三磷酸酶和碱性磷酸酶活性下降的原因之一,而增生的雪旺氏细胞中琥珀酸脱氢酶活性增强则可能是修复损伤的一种代偿。腺苷三磷酸酶活性下降与神经水肿密切相关。     

Normal ultrastructure and histochemical characteristics of canine lacrimal glands

Lacrimal glands of 12 dogs free of ocular disease were examined to determine the normal structure of these glands. The glands consisted of tubuloacinar cells that ultrastructurally and histochemically were of a single type of secretory cell in the tubules and possibly 3 types of secretory cells in the acini. The tubular epithelium contained homogenous electron-dense granules that stained as neutral glycoconjugates (periodic acid-Schiff positive and Alcian blue and high iron diamine negative). The predominant acinar cells contained granules of lesser electron density than those of the tubules, and stained as sialomucin (Alcian blue [pH 2.5] and periodic acid-Schiff-positive, and high iron diamine-negative). A second type of acinar cell was in peripheral lobules that ultrastructurally and histochemically appeared like lipid granules (positive with oil red O and osmium tetroxide). Ultrastructurally, a third type of acinar granule was finely granular, electron-lucent, and frequently coalesced. It was not readily apparent whether the latter was an artifact, a stage in the maturation of the sialomucin granules, or a third type of acinar granule. Individual acinar cells usually had a predominance of 1 granule type, but greater than 1 granule type could be found in some cells. The basal surfaces of the acinar, tubular, and ductal cells were incompletely ensheathed by myoepithelial cells. Plasma cells, lymphocytes, mast cells, endothelial cells, fat cells, and Schwann cells composed the cellular elements of the interstitium. Lymphocytes, mast cells, and nerve endings also were found in the parenchyma.     

鸡马立克氏病外周神经的病理组织学研究

用光镜、电镜及特殊染色法对兰州某鸡场２０例自然发生的马立克氏病鸡进行了外周神经的病理组织学研究。结果表明,外周神经主要表现增生性和渗出性病变,前者以瘤细胞增生为主,伴以脱髓鞘和雪旺氏细胞增生;后者以浆液渗出为特征,并发生神经纤维轴索肿胀和髓鞘变化,瘤细胞浸润很少。本文首次报告了马立克氏病的内脏－皮肤－神经混合型病变,还探讨了瘤细胞增生与脱髓鞘、神经水肿之间的关系。     

Preferential denervation of the adductor muscles of the equine larynx. II: Nerve pathology

The terminal branches of the recurrent laryngeal nerve (RLN) of three normal ponies and six horses with sub-clinical laryngeal disease were examined qualitatively and quantitatively in an attempt to explain the preferential denervation of the laryngeal adductor muscles in the neuropathy of idiopathic laryngeal hemiplegia (ILH). The myelinated fibre spectra of all the motor nerve fibres in the left and right abductor and adductor branches of the RLN in three normal ponies were measured. The density of myelinated fibres was also calculated. There was no significant difference between the larger group of myelinated fibres in the adductor or abductor branches. In the six horses with laryngeal hemiparesis, however, there was a marked preferential loss of the medium/large size myelinated fibres in the left adductor branch, although nerve fibre densities were not significantly different. While no simple morphometrical feature was found to explain the selective muscle denervation, the greater loss of large diameter myelinated fibres in the adductor branches confirms the earlier observation of adductor muscle susceptibility in the neuropathy of ILH.     

Experimental Alkylmercurial Poisoning in Swine. Lesions in the Peripheral and Central Nervous Systems

The effects of alkylmercurial poisoning were studied in 16 pigs poisoned with daily oral doses of a fungicide containing methylmercury 2, 3-dihydroxy propyl mercaptide and methylmercury acetate. Clinical signs included weakness, wobbling gait, blindness, recumbency and death. Microscopic studies of the peripheral nervous system revealed Wallerian degeneration in sensory fibers and neuronal degeneration in dorsal root ganglia. In the central nervous system, there were neuronal degeneration of ischemic type, glial degeneration, gliosis and necrosis of the media of meningeal arterioles. The last mentioned lesion was not extensive.

The sequential development o lesions and the absence of segmental demyelination suggest that the primary lesion in the peripheral nervous system was neuronal-axonal degeneration rather than degeneration of the Schwann cell and myelin sheath.

     

MALIGNANT PERIPHERAL NERVE SHEATH TUMOR IN A CAT

A report of a cat with a cranial tumor of nerve sheath origin is presented. The cranial mass, with a cyst-like character on presentation to the referring veterinarian suggested a benign lesion, but the clinical course was rapid and indicative of central nervous system involvement. The tumor was poorly differentiated by histologic examination, but immunohistochemistry was consistent with Schwann cell origin. Features of peripheral nerve sheath tumors in cats and other species are briefly discussed.     

Induction of telomerase activity in avian lymphoblastoid cell line transformed by Marek's disease virus, MDCC-MSB1

Telomerase has been studied extensively in human and murine tumors, but little is known about the role of telomerase in the tumor biology of other vertebrate species such as the chicken. We studied the telomerase activity of the lymphoblastoid cell line derived from lymphomas induced by Marek's disease virus (MDCC-MSB1) compared with another avian cell line (PA5) and peripheral blood lymphocytes (PBL) using the telomeric repeat amplification protocol (TRAP) Assay. Telomerase activity in MDCC-MSB1 was 4.5 times greater than in the PA5 cell line and normal avian lymphocytes. These results demonstrate for the first time that telomerase is more intense in one transformed cell line than in normal cells, suggesting a potential role for telomerase in carcinogenesis induced by an avian virus.     

Lymphocyte subpopulations in spontaneous disease of rhesus macaques.

The immunologic status of rhesus macaques (Macaca mulatta) with naturally occurring disease was evaluated by determining the percentages of B and T lymphocytes and mitogen responsiveness of lymphocytes in peripheral blood and lymph nodes. The B lymphocytes were identified by the presence of cell surface immunoglobulin and receptors for complement. The T lymphocytes were identified by their ability to form spontaneous rosettes with sheep red blood cells. Rhesus macaques with idiopathic or primary amyloidosis had normal lymphocyte characteristics. Peripheral blood lymphocytes from rhesus macaques with atypical tuberculosis had decreased percentages of spontaneous rosette-forming cells and depressed responses to concanavalin A, and those with chronic diarrhea or chronic arthritis were also found to have abnormal peripheral blood lymphocyte characteristics. The percentage of B and T lymphocytes in normal lymph nodes was variable, making simultaneous histologic examination necessary for evaluation of diseased animals.     

An improved method for the isolation of enriched canine peripheral blood mononuclear cell and peripheral blood lymphocyte preparations

A two-step purification method was developed for obtaining (1) peripheral blood mononuclear cell preparations of greater than 97% purity and (2) peripheral blood lymphocyte preparations of greater than 95% purity from canine whole blood with yields similar to or greater than those obtained by conventional techniques.