Laryngeal paralysis-polyneuropathy complex in young related Pyrenean mountain dogs.

OBJECTIVES: To characterise clinical, electrophysiological and histopathological findings. To analyse pedigree information in six young related Pyrenean mountain dogs with laryngeal paralysis-polyneuropathy complex (LP-PNC). METHODS: A retrospective study of clinical records and pedigrees of six young related Pyrenean mountain dogs with LP-PNC was carried out. RESULTS: All dogs were presented with laryngeal paralysis and concurrent megaoesophagus. Electrodiagnostic testing was performed in three dogs and showed electrophysiological abnormalities in the distal appendicular muscles. Histopathological findings of peripheral nerve samples were dominated by distal axonal degeneration. Clinical, electrophysiological and histopathological findings were supportive of a diagnosis of degenerative, sensorimotor LP-PNC, similar to that reported in young dalmatians and rottweilers. All dogs died or were euthanased by two years of age. An autosomal recessive mode of inheritance was suspected based on pedigree analysis. CLINICAL SIGNIFICANCE: Congenital LP-PNC should be suspected in any young dog presenting with laryngeal dysfunction and other concurrent neurological abnormalities. The prognosis is usually poor.

Sensory neuropathy in two Border collie puppies.

A peripheral sensory neuropathy was diagnosed in two Border collie puppies. Neurological, electrophysiological and histopathological examinations suggested a purely sensory neuropathy with mainly distal involvement. Urinary incontinence was observed in one of the puppies and histological examination of the vagus nerve revealed degenerative changes. An inherited disorder was suspected.

Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis.

Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of nerves showed a significant increase in affected cats compared to normal cats. Magnetic resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats, consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging identified significant myelination abnormalities in both the PNS and CNS that have not been described previously in alpha-mannosidosis.

Neuromuscular effects of acute 2,4-dichlorophenoxyacetic acid (2,4-D) exposure in dogs.

2,4-Dichlorophenoxyacetic acid (2,4-D) was administered once orally to adult female mongrel dogs at 0, 25, 50, 75, 100 or 125 mg/kg of body weight (n = 4 per group). Clinical neurological examinations, electromyography (EMG) and motor nerve conduction velocity measurements were carried out before exposure, and on days 1, 3, 7, 14, 21 and 28 post-exposure. On day 7, two dogs per group were killed. Samples of the medial and lateral plantar nerves were removed for teased fiber and semi-thin section analysis; samples of appendicular muscles were removed for histology and histochemistry. Necropsy included histopathological examination of the brain and spinal cord at multiple levels. Remaining dogs were killed on day 28 and their tissues were processed similarly. Transient generalized myotonic discharges were found in skeletal muscles of dogs receiving 50 mg/kg or more of 2,4-D. A few dogs in the higher dosage groups also had mild muscle stiffness, myotonic dimpling and/or lethargy, lasting up to 3 days post-exposure. Other parameters remained within normal limits.

Concomitant brainstem axonal dystrophy and necrotizing myopathy in vitamin E-deficient rats.

The purpose of this study was to simultaneously evaluate in rats the effects of vitamin E depletion on tissue alpha-tocopherol (alpha-T) concentrations, electrophysiologic measurements and histopathology. Rats (21-day-old male Wistar) were fed either vitamin E-deficient or supplemented (control) diets (n = 6/group) for 10, 16, and 61 weeks. At these times, electrophysiologic tests (electromyography, spinal and somatosensory evoked potentials, and motor nerve conduction velocity) were performed, the rats were killed and alpha-T concentrations of adipose tissue, sciatic nerve, and cervical and lumbar spinal cord were measured along with histopathologic evaluation of skeletal muscles and the nervous system. By 61 weeks, depletion of alpha-T from adipose tissue and peripheral nerve was more severe (< 1% of controls) than from cervical and lumbar spinal cord (15 and 8% of controls, respectively). Electrophysiologic tests were normal at all times. Histopathologic evaluation at 61 weeks revealed normal peripheral nerve structure, but necrosis of type 1 muscle fibers and increased numbers of spheroids in the gracile and cuneate nuclei. Our results confirm that low alpha-T concentrations in tissues precede histologic changes in peripheral nerves and skeletal muscle. Furthermore, pathologic changes associated with vitamin E deficiency occur independently in muscle and nervous tissue of rats.

Further characterization of the biology of Hammondia heydorni.

Hammondia heydorni oocysts, recovered from the diarrheic feces of a dog suffering from corticosteroid toxicosis, were sporulated and characterized morphometrically. Sporulated H. heydorni oocysts were administered to three dogs, five goats, a calf and three guinea pigs, and tissues from these inoculated animals fed to coccidia-free dogs to determine species susceptibility to H. heydorni. Morphometric characteristics of H. heydorni oocysts were similar to previous descriptions. Oocysts were not excreted in the feces of dogs inoculated with oocysts. Dogs fed tissues from goats killed 14, 28 or 42 days after inoculation (d.a.i.) with oocysts excreted H. heydorni oocysts in their feces after consuming goat tissues. Dogs fed tissues from a calf killed at 28 d.a.i., and from goats killed 21 and 56 d.a.i., did not excrete oocysts in their feces. Developmental stages of H. heydorni were not observed in histologic sections of tissues from any of the animals.

Potassium concentrations in muscle, plasma and erythrocytes and urinary fractional excretion in normal horses and those with chronic intermittent exercise-associated rhabdomyolysis.

Potassium concentrations were measured in semimembranosus muscle, plasma and erythrocytes, and the urinary fractional excretion determined in normal horses and those that had chronic intermittent exercise-associated rhabdomyolysis. Muscle from the rhabdomyolysis horses was also evaluated microscopically. The horses with rhabdomyolysis had a lower muscle potassium concentration on a dry weight basis. Although the wet weight potassium content was also lower, the difference was not significant. Urinary fractional excretion of potassium (and also sodium and chloride) did not differ significantly between the two groups although the rhabdomyolysis group had a lower percentage excretion of potassium. Erythrocyte potassium concentration was similar for both groups. Low grade to moderate degenerative myopathy or absence of lesions was seen on microscopic sections of muscle from horses with rhabdomyolysis; only one had a vacuolar myopathy and potassium content was not determined. These results suggest that altered muscle potassium content may be a factor in rhabdomyolysis.

Fibre type proportions of the buccinator muscle in clinically normal adult dogs.

In order to provide normal morphological data and reference values for fibre type proportions, against which changes due to facial nerve paralysis or primary facial muscle myopathies can be compared, a histological and histochemical study was carried out on the buccinator muscle of clinically normal adult dogs. Using myosin adenosine triphosphatase under acidic pre-incubation (pH 4.3) conditions, three histochemical fibre types--1, 2A and 2C were recognised. There was no significant difference in mean diameter between left- and right-sided buccinator muscle samples for type 1 versus 2. Mean diameters of fibre types were: type 1, 27.02 +/- 6.61 microns and type 2, 29.05 +/- 7.75 microns. The histographical distribution of fibre type diameters was unimodal. The buccinator muscle had a type 2 fibre predominance with a mean type 1 to type 2 ratio of 32:68. The number of fibres with internal nuclei was less than or equal to 1 per cent, atrophy-hypertrophy factors typically were less than or equal to 200, and variability coefficients approximated 250. Muscle spindles were not observed in any muscle sample.

Spinal mobility in the dog. A study in chondrodystrophoid and non--chondrodystrophoid animals.

Spinal mobility in chondrodystrophoid and nonchondrodystrophoid animal has been studied radiographically. Movement at the lumbo-sacral articulation is approximately three times greater than at other levels in the lumbar spine. The L7-L6 articulation is the second most mobile level. Movement at other lumbar segments is approximately equal. The range of motion is closely similar for both skeletal types which suggests that this factor alone is not of crucial importance in the aetiology of intervertebral disc disorder in chondrodystrophoid animals.

Morphological studies of the canine intervertebral disc. The assignment of the beagle to the achondroplastic classification.

The morphological development of the epiphyseal growth plate and intervertebral discs of newborn and nine-month-old beagles, greyhounds and dachshunds have been studied. On the basis of the cellular and matrix development of these canine tissues together with the known characteristics associated with achondroplasia it is concluded that the beagle should be assigned to the chondrodystroid breed classification.

Elemental composition, water, and total lipid content in peripheral nerves, spinal cord and brain of healthy adult dogs.

Peripheral nerves, spinal cord, and brain of healthy adult dogs were analysed biochemically for sodium, potassium, calcium, magnesium, copper, zinc, iron, aluminium, silicon, total chloride, total tissue water and total lipid content. Flame atomic absorption spectrophotometry was used for elemental quantitation of the hydrochloric acid tissue extracts. Cerebrum and spinal cord had similar values for all parameters measured. Total sodium values were higher in nerves compared to central nervous system (CNS) (brain and spinal cord), while respective values for potassium were lower. Tissue levels of calcium, iron and silicon were comparable in brain, spinal cord and nerves. However, magnesium concentrations were two to three times higher in CNS than in nerves; and the reverse was true for aluminium levels. Tissue concentrations of zinc and copper were marginally higher in CNS than in nerves.

The qualitative assessment of glycosaminoglycans in the canine intervertebral disc using a critical electrolyte concentration staining technique.

Through the use of a critical electrolyte concentration staining technique, the glycosaminoglycans (GAGs) in the nucleus pulposus region of the canine intervertebral disc were arbitrarily identified as "hyaluronic acid", chondroitin sulphate and keratan sulphate. Approximate estimates of GAG concentration could be qualitatively deduced by determining the appropriate GAG "ALCIANOPHILIC INDEX". This index was considered to be an effective qualitative adjunct to chemical quantitation of GAGs in the intervertebral disc.

Intracellular electrolytes and water analysis in dystrophic canine muscles.

Skeletal muscles from normal dogs and labrador retrievers with a hereditary muscular dystrophy were examined morphologically and histochemically and were analysed for sodium (Na+), potassium (K+) and chloride (Cl-) ions and total muscle water. The partition of total muscle water and electrolytes between intracellular and extracellular phases was calculated on the basis of the chloride space method as the estimate of extracellular fluid volume. Muscle samples from dystrophic dogs contained significantly increased concentrations of Na+, Cl-, total muscle water, and a significant reduction in the level of K+ compared with normal values. There was a significant increase in the intracellular water and Na+ levels with a concomitant reduction of intracellular K+ content. Most dystrophic muscle samples had a pronounced type 2 fibre deficiency and a marked increase in numbers of fibres with internalised nuclei.

Genetic aspects of Labrador Retriever myopathy.

Labrador Retriever myopathy (LRM) has become a relatively common muscular disease. The objective of our prospective study was to determine by segregation analyses a plausible mode of inheritance within a Labrador Retriever population. Therefore we performed neurological examinations, as well as electromyographic and histopathological evaluations of 58 closely related dogs. Seven dogs with an average age of 27.8 months had clinical signs consistent with LRM including exercise intolerance or fatigue. The diagnosis was based on neurological deficits and confirmed by histopathological results of muscle biopsy. We found in all cases obvious differences in fiber calibre size associated with texture disturbances. In addition, we found 41 clinically normal dogs with histological findings consistent with LRM. Three genetic models, the major gene, the mixed inheritance as well as the environmental model, were evaluated by segregation analyses. They were applied to an extended pedigree including 164 non-randomly ascertained related Labradors. According to phenotype the clinically examined dogs were divided into two different data sets. One data set distinguished between clinically normal and abnormal dogs, the second data set between histopathologically normal and abnormal dogs. We concluded that the clinical form of LRM is transmitted by a major gene and controlled by an autosomal recessive mode of inheritance. Furthermore, for expression of the subclinical form an additional gene or an environmental factor is responsible. Our findings suggest that LRM is similar to limb-girdle muscular dystrophy in man and therefore, may be used in the future as an animal model.

Laryngeal paralysis-polyneuropathy complex in young Rottweilers.

Five Rottweiler puppies from 3 unrelated litters developed inspiratory stridor at 11-13 weeks of age. Physical examination disclosed tetraparesis in all dogs, and bilateral lenticular cataracts in 4 dogs. Laryngeal examination under light anesthesia showed laryngeal paralysis in all dogs. Electrodiagnostic testing revealed denervation potentials in the distal appendicular muscles of 4 dogs tested and in the intrinsic laryngeal muscles of 2 dogs tested. Motor nerve conduction velocity was slightly low in 1 dog. Neurogenic muscular atrophy was found in distal appendicular muscles (n = 3) and intrinsic laryngeal muscles (n = 2), and degenerative changes were found in peripheral nerves (n = 3) and recurrent laryngeal nerves (n = 2). No abnormalities were detected in the spinal cord, spinal nerve roots, or ganglia of 3 dogs autopsied. The clinical, electrophysiologic, and histopathologic findings support a diagnosis of polyneuropathy and resemble the finding reported in young Dalmatians. Young dogs with laryngeal paralysis should be evaluated neurologically to rule out a more generalized polyneuropathy. The condition is suspected to be hereditary in nature and the prognosis is poor.

Insulinoma and subclinical peripheral neuropathy in two dogs.

Two dogs with diffuse, subclinical polyneuropathy associated with insulinoma are reported. Seizures were the dominant sign of central nervous system disease. One dog had clinical signs of facial nerve paralysis. Lesions in selected appendicular and cranial nerves included a mixture of demyelination, remyelination, and axonal degeneration. The incidence (range: 18-47%) of these changes far exceeded that of comparable nerves from six control dogs (range 0-11%). Myopathic and electrodiagnostic findings were compatible with the nerve changes.

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, hyporeflexia, 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.

Histochemical differentiation of fiber types in neonatal canine skeletal muscle.

Differentiation of fiber types in developing canine skeletal muscle was studied, using morphologic, morphometric, and histochemical techniques. Sample collections were made from 6 muscles from the pectoral and pelvic limbs of 16 healthy pups between 1 day and 12 weeks of age. In newborn pups, 90% to 95% of the fibers in the 6 muscles were classified as undifferentiated or type IIC; the remaining fibers were classified either normal or large-size type I. Large-size type I fibers usually accounted for 2% to 4% of the total population and were considered analogous with the B fiber of Wohlfart. These fibers were larger than all other fiber types and disappeared after pups reached 4 to 5 weeks of age. After 2 to 4 weeks, the number of undifferentiated fibers decreased with the appearance of, and the concomitant numerical increases of, normal size type I and type IIA fibers. The percentages of type I and IIA fibers approached proportions of the adult dog by 12 weeks, at which time a type IIA fiber predominance was present in biceps femoris, lateral head of the gastrocnemius, cranial tibial, and long head of the triceps. Type I fibers predominated in medial head of the triceps and superficial digital flexor after 4 to 5 weeks. The mean fiber diameters of type I and IIA fibers were similar to any given muscle throughout the postnatal development. All fiber types stained uniformly with the oxidative stain nicotinamide adeninedinucleotide-tetrazolium reductase during the first 12 weeks of life, whereas a distinction between type I and II fibers was evident after 3 to 4 weeks with the periodic acid-Schiff stain reaction.

German Shepherd dog myelopathy--a morphologic and morphometric study.

The concept that a degenerative neurologic disease in German Shepherd Dogs (designated "German Shepherd Dog myelopathy") represents a dying-back disease process was not substantiated by morphologic and morphometric data derived from central and peripheral nervous system evaluation in 23 dogs. The occurrence of this identifiable disease complex in German Shepherd Dogs suggested a role by genetic determinants.

Fascicular nerve biopsy in the dog.

A nerve fascicular biopsy technique that preserves the functional integrity of the parent nerve is reported in the dog. Fascicular biopsies from ulnar and peroneal nerves did not produce clinical sensory or motor deficits. Electrodiagnostic testing for the modalities of latency, duration, amplitude, and conduction velocities were not markedly altered after fascicular biopsies. Morphometric analysis of muscle fiber types, delineated by histochemic techniques, revealed no statistical (P greater than 0.05) difference between muscles from biopsied or control limbs. Fascicular biopsies resulted in small neuromas in all dogs.