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.     

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.     

Nonhypotensive autonomic agents in veterinary ophthalmology.

The parasympathetic and sympathetic divisions of the autonomic nervous system are involved in homeostatic control of a wide variety of ocular functions, including accommodation, pupillomotor control, lacrimation, eyelid position, and aqueous humor production. Familiarity with the functional anatomy of the autonomic nervous system is paramount to the understanding and application of the large number of autonomic drugs used in veterinary ophthalmology. The cholinergic and adrenergic agents discussed in this article are commonly employed to facilitate routine ophthalmic examination, in the diagnosis of autonomic dysfunction, and in the treatment of a variety of ocular diseases.     

Immunohistochemical characteristics of neurons supplying the porcine bulbourethral gland

In the male pig, the bulbourethral gland (BG) is a particulary well developed accessory genital gland (AGG) which produces complex secretion contributing to the fluid component of semen. The secretory and motor function of AGGs is thought to be under the autonomic nervous system control. Although relatively much is known about the innervation of the prostate gland and, to a lesser degree, of the seminal vesicle, the paucity of data dealing with the innervation of BG is striking. Therefore, combined retrograde tracing and double-labelling immunofluorescence have been used to investigate the distribution and immunohistochemical properties of autonomic and primary afferent neurons projecting to this gland in the pig. BG-projecting neurons were found in some ipsilateral (I) and contralateral (C) sympathetic chain ganglia (SChG), the caudal mesenteric ganglion (CaMG), pelvic ganglia (PG) and some dorsal root ganglia (DRG). Immunohistochemistry revealed that the vast majority of CaMG and SChG BG-projecting neurons contained tyrosine hydroxylase (TH) and dopaminebeta-hydroxylase (DbetaH), and some neuropeptides including neuropeptide Y (NPY), somatostatin (SOM) and galanin (GAL). Three subpopulations of PG neurons supplying BG could be distinguished: 1) cholinergic neurons [vesicular acetylcholine transporter (VAChT)-positive] which also contained vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), SOM and NPY, 2) adrenergic neurons (TH-positive) which also stained for NPY, GAL or leu5-enkephalin (LEU), and 3) non-adrenergic, non-cholinergic neurons (NANC). DRG BG-projecting neurons contained mostly substance P (SP) and/or calcitonin gene-related peptide (CGRP) which sometimes colocalized with GAL. The possible functional significance of the substances found within the neurons is discussed.     

From cell to cageside: autonomic influences on cardiac rhythms in the dog

The autonomic nervous system is pivotal in the characteristics of normal and abnormal cardiac rhythms. Some of the unique features (pronounced sinus arrhythmia and wandering pacemaker) of the canine electrocardiogram can be explained by the influence of parasympathetic tone. Perturbations that enhance the sympathetic nervous system can also potentiate arrhythmias, or counteract antiarrhythmic action. Moreover, disorders of the innervation to the heart may actually cause some life-threatening arrhythmias. This article reviews the interactions of the autonomic nervous system and cardiac rhythms as they pertain to the normal dog, as well as to specific arrhythmias in the boxer and German shepherd dog. Emphasis is placed on relating information from electrophysiological investigations to the clinical arena, thus demonstrating the value of linking the basic and clinical sciences as one medicine: knowledge from cell to cageside.     

Diarrhea associated with myenteric ganglionitis in a dog

Diarrhea in a Border Terrier was associated with inflammatory lesions of the myenteric plexus. This lesion has been documented rarely in dogs. It is speculated that the myenteric plexus lesions were responsible for an autonomic nervous system dysfunction, which resulted in extreme intestinal hypermotility and subsequent diarrhea. Suggested tests for dogs suspected to have autonomic dysfunction are given.     

Structure and ultrastructure of the celiac-mesenteric ganglion complex in the domestic dog (Canis familiaris)

A number of neurons of the autonomic nervous system are situated in the ganglia and can be systematically divided into pre-vertebrals, paravertebrals, intramural and para-viscerals. The celiac-mesenteric ganglion, an important pre-vertebral ganglion, is located together with the abdominal aorta and links the central nervous system to the peripheral system, participating in the coordination of peripheral reflexes and principally innervating the stomach, intestines, accessory glands (liver and pancreas). In addition, the celiac-mesenteric ganglion also contributes to the innervation of the spleen and has a role in gastrointestinal motility control. This study examined the structural and ultrastructural aspects of 40 celiac-mesenteric ganglia from domestic dogs. For light microscopy ganglia were included in paraplast and stained with haematoxylin-eosin, picrosirius, toluidine blue, Calleja's and Masson's trichrome. For examination by electron microscopy, the ganglia were submitted to cryofracture, enzyme digestion, hydrolysis and fixed in 5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4). The celiac-mesenteric ganglion was observed as a ganglionic complex composed of various ganglionic units separated by types I and III collagen fibres, predominantly unmyelinated nerve fibres and continuous capillaries. This complex is surrounded by a double-layer capsule (internal and external). The principal ganglion cells had eccentric nuclei with two nucleoli, the nucleolemma was double and presented nuclear pores. In the cytoplasm there were vesicles of the Golgi apparatus, electron-dense vacuoles, mitochondrias, smooth and granulated endoplasmic reticulum and free ribosomes. In conclusion, this ganglionic complex, in contrast to similar structures in the enteric nervous system, presents separate ganglionic units in a systematic arrangement related to the extrinsic and specific innervation of the target organs.     

Distribution of orexin B and its relationship with GnRH in the pig hypothalamus

Increasing evidence suggests that orexins--hypothalamic neuropeptides--act as neurotransmitters or neuromediators in the brain, regulating autonomic and neuroendocrine functions. Orexins are closely associated with gonadotropin-releasing hormone (GnRH) neurons in the preoptic area and alter luteinizing hormone (LH) release, suggesting that they regulate reproduction. Here, we investigated the distribution of orexin B (immunohistochemical technique) and the relationship between orexin B and GnRH containing fibres and neurons in the pig hypothalamus using double immunofluorescence and laser-scanning confocal microscopy. Orexin B immunoreactive neurons were mainly localized in the perifornical area (PeF), dorsomedial hypothalamic nucleus (DMH), zona incerta (ZI) and the posterior hypothalamic area (PH), with a sparser distribution in the preoptic and anterior hypothalamic area. Immunoreactive fibres were distributed throughout the central nervous system. Approximately 30% GnRH neurons were in close contact with orexin B immunoreactive fibres, among these approximately 6% of GnRH neurons co-localized with orexin B perikarya in the region between the caudal preoptic area and the anterior hypothalamic area. Orexin B may regulate reproduction by altering LH release in the hypothalamus.     

"Shaker" calf syndrome: a newly recognized inherited neurodegenerative disorder of horned Hereford calves

The clinical and pathological features of a newly recognized, inherited neurodegenerative disorder in horned Hereford calves are described. The disorder is expressed in newborns by tremulous shaking of the head, body and tail, difficulty in rising, a wobbly spastic gait, and aphonia. Transient improvement is followed by deterioration and progressive spastic paraplegia. Generalized tremors can be induced easily by a variety of stimuli, and spinal reflexes may be exaggerated or depressed. The major pathological finding is an excessive accumulation of neurofilaments within neurons of the central, peripheral, and autonomic nervous systems. The involvement of multiple systems of neurons and the similarity with some forms of human motor neuron disease and spinocerebellar degeneration suggest that this unique bovine disease may serve as a suitable animal model for these human neurodegenerative disorders.     

Cholinergic manipulation of digestive function in ruminants and other domestic livestock: a review

Exocrine secretions in the digestive tract of domestic livestock are controlled by a combination of neural and endocrine inputs. The parasympathetic domain of the autonomic nervous system is responsible for efferent signals that regulate most exocrine secretory processes. Exocrine tissues possess cholinergic muscarinic receptor subtypes that are different from those found in brain, heart and muscle tissues. Cholinergic stimulation of specific muscarinic receptor subtypes has enhanced secretions of the salivary glands and pancreas. These changes in output of exocrine glands can alter digestive function that may benefit production of cattle and swine.     

Vasoactive intestinal peptide (VIP), a putative neurotransmitter of nonadrenergic, noncholinergic (NANC) inhibitory innervation and its relevance to therapy

Nonadrenergic, noncholinergic (NANC) innervation, the third division of the autonomic nervous system, has both inhibitory and excitatory parts. The excitatory part received only limited attention. Substance P has been suggested to be the neurotransmitter of the excitatory part. The NANC-inhibitory innervation has recently been studied in detail. Although the neurotransmitter has not been conclusively identified, a substantial body of evidence exists to support vasoactive intestinal peptide (VIP) as the neurotransmitter. VIP is widely distributed in the body. Reports show that this innervation in animals and man plays a significant role in both health and disease. Pathological conditions could result from either an increase or decrease in VIP production. An absence of VIP-producing neurons has been identified to be responsible for Hirschsprung's disease in the alimentary system and hyperactive airways in the respiratory system. An increase in VIP production is associated with chronic water diarrhea syndrome in humans. Taking these factors into consideration, various therapeutic measures are suggested with the use of VIP or its antagonists.     

Spectral analysis of circadian rhythms in heart rate variability of dogs

OBJECTIVE: To determine characteristics of power spectral analysis of heart rate variability (HRV) during a 24-hour period in dogs and to evaluate the effects of vagal and sympathetic tone on HRV ANIMALS: 16 healthy adult Beagles. PROCEDURE: Power spectral analysis of HRV was conducted, using 24-hour ambulatory ECG recordings. Circadian rhythms were evaluated in terms of absolute units of low-frequency (LF) and high-frequency (HF) powers, their ratio (LF:HF), and their adjusted (normalized) units (LF[norm] and HF[norm]). Three or 4 dogs were used for simultaneous measurement of heart rate and respiratory waveform as well as to evaluate treatment (propranolol, atropine, or both) administered to cause blockade of the autonomic nervous system. RESULTS: Values for LF and HF powers, LF:HF, LF(norm), and HF(norm) had obvious rhythmicity in clinically normal dogs. The HF power of HRV in dogs was extremely high, compared with that of other species, and HF peaks corresponded to peaks obtained from respiratory waveforms. Blockade of the autonomic nervous system documented that HRV in dogs was mostly attributable to vagal activity. CONCLUSION AND CLINICAL RELEVANCE: We determined characteristics of power spectral analysis of HRV in dogs, including circadian rhythm of the autonomic nervous system. Power spectral analysis of HRV may provide a useful noninvasive technique for assessing the effect of drugs on activity of the autonomic nervous system in dogs.     

Dysautonomia and autonomic neuropathies.

The autonomic nervous system can be affected as part of a more diffuse peripheral nerve disease such as inflammatory polyneuropathy or diabetes, or as a primary disease, such as dysautonomia. Dysautonomia is being diagnosed with increasing frequency in dogs and other species in the Midwest. Affected animals present with absence of parasympathetic and autonomic ganglia and brainstem nuclei degenerate with minimal inflammation. The cause is unknown and treatment symptomatic.     

A syndrome resembling feline dysautonomia (Key-Gaskell syndrome) in a dog.

Dysautonomia, or autonomic nervous system dysfunction, was diagnosed in a 1-year-old dog. Clinical signs of disease included diarrhea, vomiting, prolapse of nictitating membranes, and urinary incontinence. Bilateral keratoconjunctivitis sicca, xerostomia, and decreased anal sphincter tone were also observed. On the basis of response to atropine, results of intradermal histamine testing and gastric motility studies, and ocular response to parasympathomimetics and sympathomimetics (direct and indirect acting), autonomic nervous system function was determined to be abnormal. Treatment with metoclopramide hydrochloride and bethanechol chloride resulted in improved attitude, appetite, Schirmer tear test response, and decrease in frequency of vomiting within 24 hours. Bladder function and anal tone improved within 3 weeks.     

Experimental study on the location of neurons associated with the first sacral sympathetic trunk ganglion of the pig

The neurons associated with the left first sacral sympathetic trunk ganglion (STG S1), an autonomic ganglion particularly concerned in the innervation of the smooth and striated musculature associated with pelvic organs, were identified in the pig, using the non-trans-synaptic fluorescent retrograde neuronal tracer Fast Blue. The labelled neurons were located mostly ipsilaterally, in the intermediolateral nucleus of the spinal cord segments T10-L5, in the sympathetic trunk ganglia L3-Co1, in the caudal mesenteric ganglia, in the pelvic ganglia, and in the spinal ganglia T13-S4. Our results could indicate the existence of visceral neuronal circuits concerning the ganglia of the sympathetic trunk and the caudal mesenteric, pelvic and spinal ganglia with or without the intervention of the central nervous system, whose identification and preservation during surgical treatments could be helpful in reducing the risk of subsequent urinary and sexual disfunctions.     

The anatomy of the visceral and autonomic nervous systems

The visceral nervous system has several levels of anatomical organization. Individual viscera, including the heart and the intestines, have neural tissue embedded in their walls that is capable, under some circumstances, of a truly autonomic self-regulation of that organ's activity. This self-regulation will not respond to all the varying needs of the organ control, particularly when external or internal changes affect the whole animal. The parasympathetic, sympathetic, and visceral afferent systems and their CNS connections are the next level of reflex neural organization. A greater degree of central regulation is managed at this level. The third level of visceral control is located in the brainstem and includes the hypothalamus, parts of the reticular formation, and cardiorespiratory centers in the medulla. These visceral upper neuron centers exert a high degree of control over the parasympathetic and sympathetic LMN centers of the brainstem and spinal cord. The reticulobulbar and reticulospinal pathways are the means by which the visceral upper motor neurons communicate with the LMN systems. The hypothalamus-hypophyseal system exerts control by releasing hormones to act on distant target organs. The highest level of organization of visceral function takes place in the limbic system. The limbic system is in a position to integrate sensory information originating from both within (interoceptive) and outside (exteroceptive) the animal. Associations are made at this level and with the help of cortical association areas, memory is integrated with these sensations. The limbic system is then able to influence the hypothalamic and medullary centers as well as the somatic motor centers to develop the appropriate responses for the preservation of the animal.     

The evaluation of autonomic nervous system activation during learning in rhesus macaques with the analysis of the heart rate variability

The aims of this study were to measure the activity of the autonomic nervous system using heart rate variability (HRV) during learning tasks and to clarify the relationship between learning to overcome a difficult situation and the autonomic nervous system in monkeys. Two young male monkeys (Macaca mulatta) were given simple discrimination learning tasks (DL) and delayed matching to samples tasks (DMTS); Holter-type electrocardiography was done, and HRV was measured. We defined the frequency bands of HRV in rhesus macaques; the low frequency (LF) was 0.01-0.15 Hz, and the high frequency (HF) was 0.15-0.50 Hz. Based on these frequency bands, the LF/HF ratios during learning tasks were analyzed, and a significant increase in the ratio was found during the tasks. The variances in the HF differed between the DL and DMTS tasks; during DMTS tasks, HF variances had a tendency to increase. Our results indicate that increased sympathetic activity accompanied learning and suggest that the parasympathetic nervous system plays a key role during learning, particularly when difficult tasks are being learned.     

Equine Performance and Autonomic Nervous System Improvement After Joint Manipulation: A Case Study

A nine-year-old gelding quarter horse, whose discipline is barrel racing, was experiencing difficulty performing tight turns around the barrels for 8 months prior to treatment. He demonstrated tail swishing as if aggravated when under the saddle, which would escalate to bucking for 3 weeks prior to treatment. This gelding had no previous history of bucking under the saddle. Static and motion palpation findings indicated multiple segmental joint fixations located throughout the spine and extremities. High-velocity low-amplitude adjustments were performed to address the joint fixations found during examination. A comparison of pre and post-treatment thermographic images showed a temperature change indicative of autonomic nervous system improvement caused by joint manipulation. A follow-up at two weeks revealed subjective long term improvements. Subjective, objective, and thermographic evidence indicated that segmental joint dysfunction was causing increased nociception and autonomic dysregulation, most notably over the sacroiliac joints, lateral front left cannon bone and right carpus. Previous research has indicated causative effects of joint manipulation on the autonomic nervous system and nociceptive processes. This case shows the positive thermographic effects post-adjustment on the nervous system, and a two week follow-up indicated that the gelding no longer showed signs or symptoms of pain. This case demonstrates how joint manipulation can affect the autonomic and nociceptive nervous systems in the equine patient.     

Endocrinal responses in exercising horses

The intensity and duration of exercise exert a major influence on energy expenditure and physiological changes in the horse. Stressful environmental conditions, acclimation, and training status may further modify these responses. To maintain functional homeostasis during exercise, changes in autonomic nervous activity and hormone secretion are coupled to both the feedforward and the feedback mechanisms that control substrate mobilisation and utilisation.During exercise, both the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis are activated, which increases the circulating levels of adrenocorticotropin (ACTH), cortisol, adrenaline and noradrenaline. Furthermore, adrenaline inhibits the release of insulin from the pancreas. Catecholamines, adrenaline, and noradrenaline increase glycogen breakdown in the muscles. In the liver, catecholamines, together with cortisol, increase blood glucose by activating glycogen breakdown and gluconeogenesis. Cortisol and catecholamines also enhance the mobilisation of free fatty acids from fat stores.In addition to efficient energy metabolism, the ability to exercise is highly dependent on the well-coordinated neuroendocrine control of cardiovascular function. Catecholamines increase oxygen delivery during exercise by enhancing cardiac output, splenic erythrocyte release, and skeletal muscle flow. Furthermore, cardiovascular homeostasis is maintained by changes in plasma renin activity and in plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin, and aldosterone.     

Diagnosis of dysautonomia in a cat by autonomic nervous system function testing

Clinical signs of dysautonomia, including dilated pupils, dry mucous membranes, and megaesophagus, were observed in a cat. The diagnosis was confirmed by use of autonomic nervous system function testing including 0.1% pilocarpine and physostigmine ocular response tests, plasma catecholamine assays, and cardiovascular responses to various perturbations intended to elicit autonomic responses. The cause of the autonomic dysfunction was not ascertained, and the cat was euthanatized after 5 weeks of unsuccessful treatment with pilocarpine, metoclopramide, prochlorperazine, and parenteral nutrition.