Nervous System

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.

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.

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 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 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.

The dysautonomias are a group of diseases with strikingly similar clinical and pathologic signs reported in a number of unrelated species, including horses, dogs, cats, rabbits, and hares. The disease is characterized by the degeneration of neurons in autonomic ganglia and clinical signs of autonomic nervous system dysfunction. The etiology is unknown in all species, and there is no effective treatment.

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.

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.

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 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.

Primary neoplasia of the nervous system includes tumors originating from the brain, spinal cord, and peripheral nerves. Clinical signs are related to location: causing seizures, affecting mentation, altering sensation, or producing dysfunction of enervated muscles. Most tumors are presumptively diagnosed with advanced imaging (ie, MRI or CT) and definitively diagnosed with biopsy. Therapy can include surgery, radiation therapy, chemotherapy, or a combination.

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 is a common neurologic disease of ruminants. The main clinical signs reflect dysfunction of the cerebrum and include wandering, circling, cortical blindness, incoordination, head pressing, recumbency, nystagmus, and seizure activity. Some animals are found dead. Clinical diagnosis is often difficult and suspected based on the combination of neurologic signs, elimination of other diagnoses, and response to thiamine administration. Antemortem diagnostic tests include blood thiamine levels, erythrocyte transketolase activity, thiamine pyrophosphate, and, in cases of suspected sulfur-induced polioencephalomalacia, by determination of sulfur content in feed and water.

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 is a transmissible spongiform encephalopathy that affects deer and other cervids, primarily in North America. It is a fatal, progressive neurodegenerative disorder and affects both wild and farmed animals. The primary signs are significant weight loss, ataxia, and hypersalivation. Diagnosis is made by ELISA and Western blot, with confirmation by immunohistochemistry. There are no treatments or vaccines, so control in farmed animals relies on depopulation of affected herds.

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.

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.

Louping ill, caused by louping ill virus and transmitted by ticks, causes a frequently fatal encephalitis that results in highly variable neurologic signs and has no specific treatment or available vaccine. Antemortem diagnosis is usually by serology using hemagglutination inhibition, which can also identify acute infections by differentiating IgM from IgG predominance. Postmortem, diagnosis is by histologic and immunohistochemical examination of the brain and also by PCR.

Pseudorabies is an acute, often fatal, viral disease with a worldwide distribution. Swine are the primary host, but other species are also occasionally infected. Clinical signs include reproductive failure and CNS and respiratory signs in growing pigs. The diagnosis is suspected based on clinical signs and confirmed by serology, PCR, or viral isolation. There is no specific treatment, but highly effective vaccines are available. The disease is reportable and has been successfully eradicated from commercial swine in the USA.

Rabies is an acute, progressive encephalomyelitis caused by lyssaviruses. It occurs worldwide in mammals, with dogs, bats, and wild carnivores the principle reservoirs. Typical signs include acute behavioral change and progressive paralysis. The disease is fatal once clinical signs appear, but treatment with local wound care, immune globulin, and vaccination can prevent disease in humans following exposure. Vaccines are available for domestic animals, wildlife, and people to prevent rabies and help control spread in reservoir populations.

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.

Sporadic bovine encephalomyelitis is caused by infection of cattle and buffalo with Chlamydia pecorum. Infection occurs mainly in calves <6 months old. Nonspecific early signs (eg, fever, depression, anorexia, diarrhea) may be followed by peritonitis, decreased tail tone, incontinence, staggering, circling, and other neurologic signs. Diagnosis is based on clinical signs, bacterial culture, and PCR. Supportive care and antibiotics are the primary treatments.

Equine protozoal myeloencephalitis (EPM) is caused by CNS infection of equids with either of the apicomplexan protozoa Sarcocystis neurona or Neospora hughesi. Common clinical signs are asymmetric ataxia and weakness of limbs and regional neurogenic muscle atrophy. Less common signs are obtundation, seizures, facial paralysis, head tilt, and other signs of cranial nerve dysfunction. Serologic support for the diagnosis is obtained using serum:CSF titer ratios for ELISA or indirect fluorescent antibody tests. EPM is treated with antiprotozoal drugs and immunomodulators.

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

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.