Nervous System

Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy (BSE) is a progressive, fatal, infectious, neurologic disease of cattle that resembles scrapie of sheep and goats (see Scrapie). It was first diagnosed in the UK in 1986. Approximately 200,000 cases of BSE have been diagnosed in cattle, with 97% reported from the UK. In 1992, at the peak of the UK outbreak, 37,280 cases were reported in a single year. Lower incidences were found in cattle native to most European countries and to Israel, Japan, USA, Canada, and Brazil. The economic consequences of the BSE epidemic are important. Countries with BSE cases experienced a dramatic drop of consumer confidence in beef products and trade restrictions of cattle commodities. Since effective control measures have been implemented, BSE incidence has decreased to single cases in 2013.

Chronic Wasting Disease

Chronic wasting disease (CWD) is a contagious disease of captive and free-ranging deer, elk, and moose that causes progressive, fatal neurodegenerative disease in adult animals. It is a member of the transmissible spongiform encephalopathy (TSE) family of diseases, or prion diseases, that includes bovine spongiform encephalopathy; scrapie of sheep and goats; transmissible mink encephalopathy; and kuru, Creutzfeldt-Jakob disease (CJD), and variant CJD of people. CWD was first identified as a clinical syndrome in the late 1960s among captive mule deer in Colorado; a decade later, it was recognized to be a spongiform encephalopathy with characteristics similar to those of scrapie (see Scrapie). It is found in free-ranging populations of mule deer, white-tailed deer, and elk (wapiti) in 18 states (USA) and 2 Canadian provinces. Recently, the first cases of CWD in free-ranging moose were diagnosed in Colorado and in Alberta, Canada. CWD has also been found in farmed elk and white-tailed deer in a number of western states and Canadian provinces and a few midwestern states. CWD has been identified outside of North America only once; a few elk imported into Korea from Canada had CWD. Many states and provinces have developed regulations for control and management of CWD in farmed populations, and federal regulations are in place in Canada and the USA. It is a reportable disease in most jurisdictions.

CNS Diseases Caused by Helminths and Arthropods

A number of metazoan parasites (helminths and arthropods) are associated with pathology in the CNS and may be categorized as described below.

Congenital and Inherited Anomalies of the Nervous System

Congenital defects of the CNS are, by definition, present at birth. Some congenital defects may be inherited, others may be caused by environmental factors (eg, toxic plants, nutritional deficiencies, viral infections); for many, the cause is unknown. In those animals born with a well-developed nervous system (foals, calves, lambs, pigs), the clinical signs of a congenital neurologic disorder may be recognizable at birth. Kittens and puppies are born with a less well-developed nervous system, and in those species, neurologic signs may not be apparent until they begin to walk. In some inherited neurologic diseases, clinical signs of the disorder are not seen until the animal is an adult (eg, caudal fossa malformation syndrome/syringomyelia, neuronal ceroid lipofuscinosis), even though the defect has obviously been present since birth.

Demyelinating Disorders

Hypomyelination and dysmyelination are disorders of myelin development characterized by axons with thin myelin sheaths, or by axons that are nonmyelinated or have abnormal myelin. There are two possible pathologic classifications: 1) thinly myelinated axons with predominantly normal myelin and occasional nonmyelinated axons, or 2) thinly myelinated axons with predominantly abnormal myelin and mainly nonmyelinated axons. These categories have been called hypomyelinating and dysmyelinating disease, respectively, and are characteristic of the congenital myelin disorders seen in young animals. These pathologic changes should not be confused with demyelination, in which there is a breakdown and loss of previously normal myelin. In general, these types of demyelinating diseases do not present clinically as congenital problems.

Diseases of the Peripheral Nerves and Neuromuscular Junction

Diseases of the peripheral nerve and neuromuscular junction include degenerative diseases, inflammatory diseases, metabolic disorders, neoplasia, nutritional disorders, toxic disorders, trauma, and vascular diseases. For a discussion of congenital disorders, see Congenital and Inherited Anomalies of the Nervous System.

Diseases of the Spinal Column and Cord

Diseases of the spinal column and cord include congenital disorders, degenerative diseases, inflammatory and infectious diseases, neoplasia, nutritional diseases, trauma, toxic disorders, and vascular diseases. Many of these diseases are discussed in full in other chapters and are only briefly described here. For a discussion of congenital disorders related to the spinal column and cord, see Congenital and Inherited Anomalies of the Nervous System.

Dysautonomia

Feline dysautonomia is characterized by widespread dysfunction of the autonomic nervous system. All breeds and age groups are susceptible, although the disease appears to be more common in younger cats. Feline dysautonomia was first reported in 1982 and initially became widespread in the UK (under the name Key-Gaskell syndrome). The incidence has declined considerably, but a few cases were recorded in Europe in the 1990s; sporadic cases have been seen in Dubai, New Zealand, and Venezuela; and a few cases have been reported in the USA, in eastern Kansas and western Missouri. The etiology is unknown. Dysautonomias in horses, dogs, rabbits, and hares share striking similarities to the condition in cats.

Equine Arboviral Encephalomyelitis

Equine encephalitides can be clinically similar, usually cause diffuse encephalomyelitis (see Meningitis, Encephalitis, and Encephalomyelitis) and meningoencephalomyelitis, and are characterized by signs of CNS dysfunction and moderate to high mortality. Arboviruses are the most common cause of equine encephalitis, but rabies virus, Sarcocystis neurona (see Equine Protozoal Myeloencephalitis), Neospora hughesii (see Neosporosis), equine herpesviruses, and several bacteria and nematodes may also cause encephalitis. Arboviruses are transmitted by mosquitoes or other hematophagous insects, infect a variety of vertebrate hosts (including people), and may cause serious disease. Most pathogenic arboviruses use a mosquito to bird or rodent cycle. Tickborne encephalitides are also a differential cause in the eastern hemisphere. Arboviral diseases are ever emerging, and there are arboviruses pathogenic to horses on virtually every continent.

Equine Protozoal Myeloencephalitis

Equine protozoal myeloencephalitis (EPM) is a common neurologic disease of horses in the Americas; it has been reported in most of the contiguous 48 states of the USA, southern Canada, Mexico, and several countries in Central and South America. In other countries, EPM is seen sporadically in horses that previously have spent time in the Americas.

Facial Paralysis

Asymmetry of facial expression is common with unilateral lesions of the facial nucleus or nerve in most species. Bilateral facial paralysis may be more difficult to recognize, but affected animals drool and have a dull facial expression. Complete facial paralysis is an inability to move the eyelids, ears, lips, or nostrils. Facial paresis is reduced movement of the muscles of facial expression and indicates milder nucleus or nerve involvement. The nucleus of the facial nerve is located in the rostral medulla oblongata of the brain stem. The facial nerve, cranial nerve VII, exits the brain stem near the vestibulocochlear nerve, passes through the petrous temporal bone, and then exits the skull through the stylomastoid foramen and splits into auricular, palpebral, and buccal branches.

Limb Paralysis

Paralysis of one limb is referred to as monoplegia and is most often associated with diseases of the peripheral spinal nerves. Paralysis of the thoracic limb is usually associated with a lesion of the C6 to T2 nerve roots, the brachial plexus, or musculocutaneous, radial, median, or ulnar nerves. Paralysis of the pelvic limb is usually associated with a lesion of the L4 to S2 nerve roots, the lumbosacral plexus, or femoral, sciatic, peroneal (fibular), or tibial nerves.

Louping Ill

Louping ill is an acute, tick-transmitted viral disease of the CNS that primarily affects sheep, but cattle, goats, horses, dogs, pigs, South American camelids, red grouse, and people also can be affected; people can be infected by tick bites or exposure to tissues or instruments contaminated with virus. The disease is seen throughout the rough hill grazings of the British Isles wherever the vector tick, Ixodes ricinus, is prevalent. Diseases of sheep indistinguishable from louping ill and caused by similar viruses have been reported in Norway, Spain, Turkey, and Bulgaria, which suggests that the condition may not be restricted to the British Isles.

Meningitis, Encephalitis, and Encephalomyelitis

Inflammation of the meninges (meningitis) and inflammation of the brain (encephalitis) are seen in animals and often manifest concurrently (meningoencephalitis). Many of the inflammatory diseases of the CNS of animals are diffuse, involving both the brain and spinal cord (encephalomyelitis and meningoencephalomyelitis). Because many inflammatory processes are disseminated throughout the CNS at the time of clinical observation, differentiation between meningeal-only inflammation vs extension of disease into the neuropil is often difficult to make antemortem. Thus, from a clinical standpoint, any one of these conditions may be the case in an animal with an inflammatory condition of the CNS.

Motion Sickness

Motion sickness is characterized by signs referable to stimulation of the autonomic nervous system, including excessive salivation and vomiting. Affected animals may also yawn, whine, or show signs of uneasiness and apprehension; severely affected animals may also develop diarrhea. Motion sickness is seen during travel by land, sea, or air, and signs usually disappear when vehicular motion ceases. The principal causative mechanism involves stimulation of the vestibular apparatus in the inner ear, which has connections to the emetic center in the brain stem. The chemoreceptor trigger zone (CRTZ) and H₁-histaminergic receptors are involved in this pathway in dogs but apparently are less important in cats. Recent evidence has revealed that the neurokinin 1 substance P receptors (NK1) in the emetic center play a major role in motion sickness in both dogs and cats and are more important than the receptors in the CRTZ. Fear of the vehicle may also become a contributory factor in dogs and cats that develop a conditioned response to the event; signs may be seen even in a stationary vehicle. In this situtation, behavioral modification may be needed to eliminate this fear, or the use of drugs that provide a sedative effect may be needed.

Neoplasia of the Nervous System

Neoplasia of the nervous system has been reported in all domestic animal species. Nervous system tumors have been detected in 1%–3% of necropsies in dogs. In cats, nervous system tumors are less common and are mainly meningiomas and lymphomas. Primary nervous system tumors originate from neuroectodermal, ectodermal, and/or mesodermal cells normally present in (or associated with) the brain, spinal cord, or peripheral nerves. Secondary tumors affecting the nervous system may originate from surrounding structures such as bone and muscle or from hematogenous metastasis of a primary tumor in another organ. Tumor emboli can lodge and grow anywhere in the brain, meninges, choroid plexus, or spinal cord. Dissemination or metastasis of CNS tumors is rare but may occur via the CSF pathways, especially if the tumors are located close to the subarachnoid space or ventricular cavities (eg, choroid plexus papilloma, ependymoma, medulloblastoma, neuroblastoma, pinealoblastoma), or via a hematogenous route such as the dural sinus, with later development of remote metastasis, most often in the lung. Tumors may also spread by direct extension to surrounding tissues, especially bone. The osseous tentorium may be used as a reference point to localize different areas of the brain within the cranial vault. Thus, tumors in the cerebral hemispheres are often referred to as supratentorial or anterior fossa tumors, while those in the brain stem or cerebellum are called infratentorial or posterior fossa tumors.

Nervous System Introduction

The nervous system is composed of billions of neurons with long, interconnecting processes that form complex integrated electrochemical circuits. It is through these neuronal circuits that animals experience sensations and respond appropriately.

Paraneoplastic Disorders of the Nervous System

Paraneoplastic syndromes are nonmetastatic complications of cancer with effects distant from the primary tumor. They are unrelated to neurologic complications secondary to metabolic or nutritional disorders, infection, cerebrovascular incidents, or adverse effects of treatments. They can affect all parts of the nervous system, including the brain, cranial nerves, spinal cord, dorsal root ganglia, peripheral nerves, and the neuromuscular junction. Some are thought to be immunologically mediated through cross-reactivity by immune cells against antigens expressed by tumors and neural tissues (molecular mimicry), whereas others are related to the production of circulating hormones, peptides, or other substances that exert systemic effects.

Polioencephalomalacia

Polioencephalomalacia (PEM) is an important neurologic disease of ruminants that is seen worldwide. Cattle, sheep, goats, deer, and camelids are affected. PEM is a pathologic diagnosis and a common end point of several conditions. Historically, PEM has been associated with altered thiamine status, but more recently an association with high sulfur intake has been seen. Other toxic or metabolic diseases (eg, acute lead poisoning, sodium toxicosis/water deprivation) can result in PEM as well.

Pseudorabies

Pseudorabies is an acute, frequently fatal disease with a worldwide distribution that affects swine primarily and other domestic and wild animals incidentally. The pseudorabies virus has emerged as a significant pathogen in the USA since the 1960s, probably because of the increase in confinement swine housing or perhaps because of the emergence of more virulent strains. Clinical signs in nonporcine animals are similar to those of rabies, hence the name “mad itch” (pigs do not display this sign). Pseudorabies is a reportable disease and has been successfully eradicated from the vast majority of the USA.

Rabies

Rabies is an acute, progressive viral encephalomyelitis that principally affects carnivores and bats, although any mammal can be affected. The disease is fatal once clinical signs appear. Rabies is found throughout the world, but a few countries claim to be free of the disease because of either successful elimination programs or their island status and enforcement of rigorous quarantine regulations. Globally, the dog is the most important reservoir, particularly in developing countries. Integrated veterinary management of local animal populations, by mass vaccination of dogs and community promotion of responsible pet ownership, is the most cost-effective, humane, long-term solution toward eliminating regional canine rabies in a One Health context.

Scrapie

Classic scrapie, a natural disease of sheep and goats, is seen worldwide except in Australia and New Zealand. It is one of the transmissible spongiform encephalopathies (TSE), related to bovine spongiform encephalopathy and chronic wasting disease of deer and elk, all of which are thought to result from the accumulation of an abnormal form of a cellular protein in the brain. Natural transmission of scrapie to other species has not been shown. In the USA, scrapie primarily affects black-faced sheep breeds (eg, Suffolk, Hampshire, and their crosses), accounting for ~96% of cases. In other countries, the disease is commonly seen in other breeds, including those with white faces.

Sporadic Bovine Encephalomyelitis

Sporadic bovine encephalomyelitis (SBE) is reported in various parts of the world. The disease affects cattle and buffalo, resulting in neurologic signs and polyserositis.

Teschovirus Encephalomyelitis

Teschovirus encephalomyelitis (formerly known as porcine enteroviral encephalomyelitis) is analogous to human poliomyelitis. Severe disease is now rare; it is seen in eastern Europe and Madagascar but was last reported in western Europe from Austria in 1980. In other countries, sporadic mild disease is reported, or the disease is unrecognized.

Tick Paralysis

Tick paralysis (toxicity) is an acute, progressive, symmetrical, ascending motor paralysis caused by salivary neurotoxin(s) produced by certain species of ticks. With some species, other signs of systemic "single organ" toxicity (eg, cardiac, airway, bladder, lung, esophagus, etc) may be seen separate to or within the classic paretic-paralysis presentation. People (usually children) and a wide variety of other mammals, birds, and reptiles may be affected. Human cases of tick paralysis caused by the genera Ixodes, Dermacentor, and Amblyomma have been reported from Australia, North America, Europe, and South Africa; these three plus Rhipicephalus, Haemaphysalis, Otobius, and Argas have been associated with paralysis to varying degrees in animals.