Small intestine and small colon neuropathy in equine dysautonomia (grass sickness)

The number of neurons in the coeliacomesenteric ganglia and the myenteric and submucosal plexuses of the jejunum, ileum and small colon, and the pathological changes induced in them, were studied in various types of equine dysautonomia. In all forms of dysautonomia, severe and extensive neuron loss and damage occurred in the ileum. In acute and subacute dysautonomia, jejunal neuron loss and damage were severe, but in chronic cases significantly less loss or damage occurred. The damage followed the same pattern in the small colon but it was always less obvious than in the jejunum. The distribution of the damage was uniform within a segment of the intestine. In fatal cases of dysautonomia, the clinical severity and duration of illness seems, in most instances, to be related to the amount of neuronal disruption occurring in the jejunum. Severe disruption results in acute/subacute dysautonomia, while milder damage leads to the chronic form.No case of dysautonomia was encountered in which enteric neuron loss and damage occurred without significant neuronal disruption also occurring in the coeliacomesenteric ganglia.Ileal neuronal damage and loss are not invariably worse than that in the jejunum, and the possible reasons for this, together with the relationship between neuronal damage and possible causes of dysautonomia, are discussed.Abbreviations H&E haematoxylin and eosin Deceased. Formerly of the Moredun Research Institute, 408 Gilmerton Road, Edinburgh, EH17 7JH, UK     

Changes in nasal mucosal innervation in horses with grass sickness

REASONS FOR PERFORMING STUDY: Equine grass sickness is a dysautonomia characterised by widespread destruction of autonomic ganglia, resulting in the clinical signs of dysphagia, constipation, profuse sweating, tachycardia, rhinitis sicca and high mortality rate. Rhinitis sicca is a common finding in horses with the chronic form and we have postulated that alterations in autonomic innervation of the nasal mucosa might underlie this clinical presentation. OBJECTIVES: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal marker protein gene-product 9.5 (PGP 9.5; ubiquitin) and the intermediate neurofilaments (PAN-N; neurorfilaments L, M and H) in the nasal mucosa of normal horses (n = 10) and horses with EGS (n = 18; acute n = 8, subacute n = 3, chronic n = 7) was assessed. METHODS: Innervation density and distribution was investigated in the different groups using standard immunohistochemical techniques. RESULTS: Significant differences were noted when comparing the density and distribution of nerve fibres immunoreactive for PGP 95 and PAN-N, with PGP 95 consistently giving better staining in all groups and at all sites in the nasal mucosa. An apparent increase in the density of innervation was noted for acute vs. normal cases. A significant reduction in the density of innervation was noted only with PAN-N when comparing normal horses and acute cases with the chronic group (P < 0.05). CGRP and SP immunoreactive nerve fibres were typically most abundant in the epithelial and subepithelial layers, but the quality of staining and nerve fibre density was greater for SP, achieving significant difference in several comparisons. The density of innervation for SP was significantly reduced in the chronic group compared to the normal and acute groups (P < 0.01). A significant decrease was noted for CGRP only for the acute and chronic groups (P<0.05). CONCLUSIONS: These results demonstrate a reduction in the expression of the sensory neuropeptides in nasal mucosal innervation as a consequence of equine dysautonomia, and may underlie the clinical presentation of rhinitis sicca noted with this disease. POTENTIAL RELEVANCE: Nasal biopsy may be of use in antemortem diagnosis of grass sickness and identification of mucosal denervation; and might also be useful in the treatment of rhinitis in EGS cases.     

Equine grass sickness

Equine grass sickness (EGS; equine dysautonomia) is a polyneuronopathy affecting both the central and the peripheral nervous systems of horses. As the name implies, EGS almost exclusively affects grazing horses, resulting in the development of a characteristic array of clinical signs, most of which can be attributed to neuronal degeneration in the autonomic and enteric nervous systems. Varying disease severities occur, largely determined by the extent of neuronal degeneration in the myenteric and submucous plexuses of the enteric nervous system. Extensive neuronal degeneration, as seen in acute and subacute forms of EGS, results in intestinal dysmotility, the severity of which is incompatible with survival. In comparison, a proportion of chronic forms of EGS, characterised by less severe neuronal degeneration, will survive. Despite extensive research efforts since EGS was first reported over 100 years ago, the precise aetiology remains elusive. This article reviews much of the scientific literature on EGS, covering epidemiology, pathology, diagnosis, treatment and aetiological hypotheses.     

Feline dysautonomia (the Key-Gaskell syndrome): a clinical and pathological study of forty cases

Feline dysautonomia is a dysfunction of the autonomic nervous system, the main features of which are dilated pupils, dry mucous membranes, mega-oesophagus and constipation. The clinical and pathological features, treatment and follow-up details of 40 cases seen at the University of Glasgow Veterinary School are described. The pathology was demonstrated to be mainly restricted to the autonomic ganglia and neurons in selected cranial nerve nuclei. Less marked changes were also found in neurons of the spinal cord and dorsal root ganglia. Nine cases recovered but this required up to one year and, in some, mild clinical signs persisted. Viral, toxicological and epidemiological studies were unrewarding and the aetiology is presently unknown. The similarities between this condition, grass sickness of horses and dysautonomia in the dog and man are discussed.     

Canine dysautonomia: two clinical cases

Two clinical cases of canine dysautonomia are described. Two young female neutered dogs were presented with clinical signs including vomiting, diarrhoea, faecal tenesmus, dysphagia and urinary retention. Decreased tear production, dry mucous membranes, bilateral Horner's syndrome, decreased anal sphincter tone and gastrointestinal hypomotility were also observed. Presumptive diagnoses of dysautonomia were made based on the clinical presentation and investigations. Postmortem histopathological examination in one of the cases demonstrated marked depletion of neuronal cell bodies in the intestinal myenteric plexuses and parasympathetic ganglia, confirming the diagnosis in this case. Criteria for aiding the antemortem diagnosis of this rare condition based on clinical observations and diagnostic testing are proposed.     

Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases

Dysautonomia of domestic animals is pathologically characterized by chromatolytic degeneration of the neurons in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. The exact cause is unknown. It has a poor prognosis among all species reported and no definitive treatment is available currently. To date, most reported feline cases have occurred in the United Kingdom and Scandinavia. The cases reported here highlight the clinical signs, physical examination findings, and results of autonomic nervous system function testing in nine cats with dysautonomia in the US. Feline dysautonomia is uncommon in the US, but may have a regional prevalence, as is seen in dogs with most cases reported in Missouri and Kansas.     

Serum lipids and lipoproteins in equine colic and grass sickness

Serum total lipids, lipoprotein fractions, triglycerides, cholesterol, phospholipids and free fatty acids were measured in horses with acute, subacute and chronic grass sickness (equine dysautonomia) and in colic cases. The values were compared with those of normal grazing and stabled horses. A marked individual variation occurred, but total lipids, triglycerides and free fatty acids were significantly higher than normal in grass sickness and colic cases with cholesterol was significantly higher than normal in grass sickness cases only. Pre-beta lipoprotein was significantly increased in colic and subacute grass sickness although all abnormal groups showed this fraction which was absent from normal horses. The percentage of alpha 2b lipoprotein was significantly higher in colic and grass sickness. The changes described are typical of those occurring in fat mobilisation in the horse and are considered to be due to a number of factors including decreased food intake, cortisol and catecholamine release and insulin resistance.     

Dysautonomia in dogs: 65 cases (1993-2000)

OBJECTIVE: To determine signalment, history, clinical findings, results of autonomic function testing and other antemortem diagnostic tests, and pathologic findings in dogs with dysautonomia. DESIGN: Retrospective study. ANIMALS: 65 dogs with dysautonomia. PROCEDURE: Case records of 68 dogs with a diagnosis of dysautonomia were reviewed; inclusion criteria included histologic confirmation of dysautonomia or clinical signs and results of pharmacologic testing consistent with dysautonomia. RESULTS: 65 dogs fulfilled all criteria for dysautonomia. Dogs from rural environments were overrepresented, and cases of dysautonomia were reported for every month, although the highest number of cases was reported in February and March. Vomiting was the most common clinical sign, followed by diarrhea, signs of anorexia and depression, weight loss, and dysuria. The most common physical examination finding was decreased or absent anal tone, followed by absent pupillary light reflexes and elevated nictitating membrane. Results of pharmacologic testing were consistent with dysautonomia, although no single test was 100% sensitive. Histologic lesions consistent with dysautonomia were found in the autonomic ganglia, brainstem nuclei, and ventral horns of the spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: Dysautonomia is an endemic disease in Kansas, and a high index of suspicion of the disease can be made by combining clinical signs, physical examination findings, and results of pharmacologic testing.     

Development of a clinical prediction score for detection of suspected cases of equine grass sickness (dysautonomia) in France

Equine grass sickness (EGS) (equine dysautonomia) is a neurodegenerative condition of grazing equines. Pre-mortem diagnosis of EGS is a challenge for practitioners as definitive diagnosis requires ileal/myenteric lymph node biopsies. This study aimed to develop a clinical score that could be used by practitioners to improve the detection of acute or subacute EGS cases in the field. Suspected EGS cases were declared by veterinary practitioners. A case was classified as confirmed positive if ileal or rectal biopsy samples showed neuronal degeneration typical of EGS. A semi-quantitative scoring system, including epidemiological and clinical data, was created to attempt to classify suspected EGS horses into confirmed positive or negative cases. Each variable was weighted based on a boosted regression trees model, while taking into account its clinical relevance. Twenty-eight EGS cases were confirmed by biopsy during the entire study period. The best cut-off value for the score to have a high sensitivity while maximizing specificity was 8, with a sensitivity of 100% and a specificity of 53%. In our dataset, 77% of animals would be correctly classified with this cut-off value of 8. Highest sensitivity was chosen in order to detect the highest number of potential cases. Our score represents an inexpensive and useful tool to aid in the identification of suspected EGS cases in the field and selection for further diagnostics procedures to confirm or rule out the disease. Application of the score to larger populations of animals would be required to further adapt and refine the score.     

Spongy transformation of the brain in sheep with lupinosis.

Spongy transformation in the brain of sheep affected with chronic lupinosis in the field is described. Identical lesions were reproduced in sheep with experimental acute and chronic lupinosis. The primary brain lesion was vacuolation of the white matter of the brain stem with no malacia, neuronal damage or gliosis being present. The extent and severity of the vacuolation was related to the severity of the liver lesion.     

Equine dysautonomia (grass sickness) is associated with altered plasma amino acid levels and depletion of plasma sulphur amino acids

To determine whether equine dysautonomia (ED) is associated with alterations in plasma amino acid metabolism, plasma amino acid profiles were determined for horses with acute (n = 10), subacute (n = 6) and chronic (n = 7) ED and for healthy cograzing horses (n = 6) and control horses (n = 10). Horses with acute ED had perturbations in plasma amino acid profiles resembling those of severe protein malnutrition. In addition, horses with ED and cograzing healthy horses had depletion of the plasma sulphur amino acids cyst(e)ine and methionine. As similar plasma amino acid perturbations occur in subacute/chronic cyanide toxicity, the role of cyanogenic glycosides in the aetiology of ED warrants further study. Unfortunately, amino acid analysis cannot be used as a definitive premortem diagnostic test for ED, since there was overlap in the individual amino acid levels of control, cograzing and ED horses.     

Acute phase proteins in grass sickness (equine dysautonomia)

Four acute phase proteins were assayed in the serum of normal horses and those with acute, subacute and chronic grass sickness, colic and inflammatory conditions, in order to investigate their diagnostic value in grass sickness. The grass sickness and inflammation group had a significantly increased haptoglobin concentration (P less than 0.01-P less than 0.001). Orosomucoid was elevated in acute, subacute and chronic grass sickness and inflammation (P less than 0.001, P less than 0.001, P less than 0.05 and P less than 0.05, respectively). Highest concentrations of haptoglobin and orosomucoid were recorded in subacute grass sickness. Ceruloplasmin was significantly higher in acute grass sickness cases than all other groups except the colic group (P less than 0.05-P less than 0.01). alpha 2-macroglobulin was significantly higher in acute grass sickness than normal, colic and chronic grass sickness cases (P less than 0.01, P less than 0.05 and P less than 0.05). The time scale of changes suggests that the stimulus to haptoglobin and orosomucoid synthesis occurs at the onset of clinical signs whereas the increase in ceruloplasmin and alpha 2-macroglobulin is more likely to reflect haemoconcentration.     

Distribution of lesions in ovine salmonellosis

SUMMARY Four forms of salmonellosis were recognised in feedlots and during transport by sea: septicaemic, and acute, subacute and chronic enteric. The severity and distribution of lesions in the enteric forms varied according to the progression of the pathological process. The acute disease involved the abomasum and small intestine whereas the subacute disease centred on the lower small intestine and upper large intestine. Chronic disease involved considerable mucosal repair in the ileum, caecum and proximal colon. Septicaemic salmoneiiosis was often accompanied by acute enteritis and occasionally by cholecystitis. S typhimurium was the most frequently encountered serotype.     

Key-Gaskell syndrome in a cat in Switzerland

As far as the authors know this is the first case of Key-Gaskell-syndrome being described in Switzerland. The clinical signs of megaoesophagus, anorexia, constipation, dryness of all mucous membranes, reduced tear production, protrusion of the membrana nictitans, mydriasis, regurgitation and bradycardia are pathognomonic and can't be mistaken by any other disease. The subject of the Key-Gaskell-syndrome is a dysfunction of the autonomic nervous system. Histopathological changes are exclusively related to the autonomic nervous system and to neurons of some nuclei in the cranial nerves. Less severe changes can be found in the neurons of the spinal cord or in the dorsal root ganglia. The etiology remains still unclear. There is a relationship to the grass sickness syndrome in horses and to dysautonomia of man and dog.     

Light Microscopy of the Enteric Nervous System of Horses with or without Equine Dysautonomia (Grass Sickness): its Correlation with the Motor Effects of Physostigmine

Light microscopy was undertaken on sections from the caudal flexure of the duodenum and the terminal ileum proximal to the ileocaecal fold in 5 control horses, 5 horses with acute grass sickness (AGS), and 5 horses with chronic grass sickness (CGS). With the exception of the ileal submucous plexus of the CGS group, the AGS group had the lowest number of neurons as measured using a subjective scoring scheme. The proportion of abnormal neurons in the AGS group was similar in both plexuses and both regions, whereas the values for the CGS group were much higher in the duodenal region than in the ileal region. The motility of tissue adjacent to that used for histology was measured isometrically in vitro. The increase in the rate of contractions following exposure to physostigmine was greatest for the AGS group, both from the duodenal and from the ileal region. The latency was longest for the AGS group, suggesting that the material from this group had the least number of active cholinergic neurons. The studies with physostigmine thus indicated that the most severe functional damage occurred in cases of AGS. These findings confirm that extensive damage occurs in the enteric neurons in equine grass sickness. There was good correlation between the functional cholinergic responses and the extent of neuronal degeneration.     

Diabetes mellitus-related morphoquantitative changes in the celiac ganglion neurons of the dog

Diabetes mellitus is the most common endocrine disturbance of domestic carnivores and can cause autonomic neurological disorders, although these are still poorly understood in veterinary medicine. There is little information available on the quantitative adaptation mechanisms of the sympathetic ganglia during diabetes mellitus in domestic mammals. By combining morphometric methods and NADPH-diaphorase staining (as a possible marker for nitric oxide producing neurons), type I diabetes mellitus-related morphoquantitative changes were investigated in the celiac ganglion neurons in dogs. Twelve left celiac ganglia from adult female German shepherd dogs were examined: six ganglia were from non-diabetic and six from diabetic subjects. Consistent hypertrophy of the ganglia was noted in diabetic animals with increase of 55% in length, 53% in width, and 61.5% in thickness. The ordinary microstructure of the ganglia was modified leading to an uneven distribution of the ganglionic units and a more evident distribution of axon fascicles. In contrast to non-diabetic dogs, there was a lack of NADPH-diaphorase perikarial labelling in the celiac ganglion neurons of diabetic animals. The morphometric study showed that both the neuronal and nuclear sizes were significantly larger in diabetic dogs (1.3 and 1.39 times, respectively). The profile density and area fraction of NADPH-diaphorase-reactive celiac ganglion neurons were significantly larger (1.35 and 1.48 times, respectively) in non-diabetic dogs compared to NADPH-diaphorase-non-reactive celiac ganglion neurons in diabetic dogs. Although this study suggests that diabetic neuropathy is associated with neuronal hypertrophy, controversy remains over the possibility of ongoing neuronal loss and the functional interrelationship between them. It is unclear whether neuronal hypertrophy could be a compensation mechanism for a putative neuronal loss during the diabetes mellitus.     

Cecal impaction due to dysautonomia in a llama (Lama glama).

A llama (Lama glama) died after 1 wk of obstipation, lethargy, and rolling. Necropsy showed that the stomach and small intestine were distended with gas and fluid. The cecum was impacted with dry contents and the colon was empty. No gross lesions were found in the wall of the gastrointestinal tract or other organs. Histologic changes consisted of chromatolysis of neurons of autonomic ganglia, enteric plexi, and the accessory cuneate nucleus, consistent with lesions associated with dysautonomia in other domestic animals.     

The course of experimental Trypanosoma vivax infection in Uda sheep

The course of experimental Trypanosoma vivax infection in eight Uda rams was studied. All the infected animals became parasitaemic 2 days post-inoculation and remained so throughout the study period. A three-phase disease pattern was recognized, i.e. acute, subacute and chronic stages lasting 17-85 days. The disease was characterized by fever and a terminal decrease in rectal temperature despite an increase in parasitaemia with time for rams with acute and subacute infections. Mean weight loss was most marked in subacute followed by chronic cases. Gross pathological changes observed in some infected rams with subacute and chronic trypanosomosis were oedema of the face and lower jaw, hydropericardium and atrophy of the pericardial fat. Petechial haemorrhages were observed on the surfaces of the heart and kidney of rams with acute infection. Anaemia was most severe in infected rams with acute disease, followed by those with subacute infections. Also, hypoproteinaemia was observed in all infected rams. Severe clinical findings associated with the death of all the infected rams during this study might indicate that the Uda breed of sheep in very susceptible to trypanosomosis. It is, therefore, recommended that this breed of sheep, which is strictly bred and reared in tsetse-free Sahel savannah, should not be introduced into endemic areas devoid of therapeutic cover and strict tsetse fly control.     

猪丹毒

猪丹毒又称“红热病” “打火印”或“钻石皮肤病”,是一种急性的、热性的传染病,引起该病的病原为红斑丹毒丝菌,可以通过伤口感染人,也是一种人兽共患病。患病猪的临床表现形式大致可分为3种类型,即急性、亚急性和慢性型。急性型病例主要的表现为出现明显的败血症症状。亚急性型病例则是在四肢、胸腹部、背部等皮肤处出现红色菱形、方形或圆形疹块。慢性型则多以出现关节炎和心内膜炎引起的关节肿胀、运动障碍和心跳加速、呼吸急促为主的临床表现;有时还可见皮肤坏死。红斑丹毒丝菌的最易感动物是猪,没有品种和年龄差异。使用疫苗是最佳的预防手段,治疗方面除使用抗生素外还可以选择中药方剂进行治疗。     

Temporary inhibition of neuronal apoptosis in Aujeszky's disease virus-infected swine

Previous studies have shown that during acute infection of the porcine trigeminal ganglia (TG), Aujeszky's disease virus (ADV)-infected neurons are protected from apoptosis induced by the virus itself and by cells of the immune system. However, TG neurons productively infected by ADV finally die and are phagocytosed by adjacent cells, a fact that leads us to speculate that the inhibition of neuronal apoptosis by ADV may be temporary rather than absolute. To address this issue we used TG and brain stem from pigs during acute infection by ADV. Infected cells were detected by immunohistochemical staining of viral antigens, whereas apoptotic cells were identified with an anti-active caspase-3 antibody, the TUNEL assay and by transmission electron microscopy. The results obtained in this study support the contention that the inhibition of neuronal apoptosis by ADV is temporary, since activation of caspase-3 could be detected in infected neurons at late stages in infection and because foci of advanced neuronophagia contained neurons exhibiting typical ultrastructural features of apoptosis.