Diseases of the nervous system of equids in Brazil: a review

Abstract

In Brazil, CNS diseases in equids were little known until the 1980s. Since then, several diagnostic laboratories have been operating in different universities, initially in the South and Southeast regions and, later, in the Central-West, Northeast and North regions. However, the knowledge accumulated from the diagnoses of nervous system diseases of equids made at these institutions over the years has not been reviewed comprehensively, and many papers are published in Portuguese. Here, we review 18 diseases that occur in the nervous system of equids in Brazil, including some critical infectious diseases (rabies, equine encephalomyelitides, equine herpesviral myeloencephalopathy, protozoan myeloencephalitis), and diseases caused by toxic plants and mycotoxins. Our review provides reference data to assist pathologists and clinicians in diagnosing neurologic diseases in equids. We also hope it will serve as a reference for professionals in this field abroad, allowing them to compare data in the epidemiology and pathology of the nervous system diseases of equids in different regions of the world.

In Brazil, since the 1980s, public universities have been established in several states and regions. Many of these universities have developed diagnostic activities that have contributed to the knowledge of ruminant and equid diseases.^{41,91,115,118,127} To diagnose a variety of diseases (infectious, parasitic, toxic, nutritional, genetic, or neoplastic), it is necessary to understand their epidemiology, clinical signs, and clinical and anatomic pathology to establish appropriate control measures after diagnosis. Here we review the nervous system diseases of equids diagnosed in Brazil since ~1977.

We searched PubMed, CAB Direct, and SciELO using the search terms: “diseases,’ “horses”, “Equidae”, “Brazil”, and the name of the various diseases described herein. Because many cited articles cannot be found in those databases, we searched in Google using the aforementioned words in Portuguese and English.

Infectious diseases

Rabies

Rabies is an important zoonosis in South America and is caused by a neurotropic RNA virus (rabies virus, RABV; Rhabdoviridae, Lyssavirus rabies) that is transmitted mainly in the saliva of infected animals. In Brazil, rabies can be transmitted by dogs and cats (urban cycle), by vampire bats (rural cycle), and, rarely, by non-hematophagous bats (aerial sylvatic cycle) and several species of wild animals (terrestrial sylvatic cycle).^79,97 Five antigenic variants of RABV are recognized in Brazil: variant 2 from dogs, also isolated from humans and wild terrestrial animals; variant 3 from the common vampire bat (Desmodus rotundus), also isolated from other bat species, cattle, goats, sheep, horses, swine, dogs, cats, wild animals, and humans; variant 4 from the Brazilian free-tailed bat (Tadarida brasiliensis), also isolated from other non-hematophagous bat species and pets; a variant similar to variant 5 and also linked to the isolation from hematophagous bats in other countries, as well as from non-hematophagous bats and pets; and variant 6 from the hoary bat (Lasiurus cinereus), isolated from insectivorous bats, with a profile that shows positive reactions to all of the monoclonal antibodies used in samples of non-hematophagous bats, dogs, and humans. ⁹⁷ Rabies transmitted by the common vampire bat is an important disease in cattle and horses, but also affects buffalo, goats, sheep, swine, and humans.^7,52,81,147 Other hematophagous bats, the hairy-legged vampire bat (Diphylla ecaudata) and the white-winged vampire bat (Diaemus youngi), are not important for rabies transmission because they attack mainly birds. ²⁷

Rabies is endemic in all Brazilian regions; 12,167 foci of rabies were diagnosed in herbivores from 2002 to 2012 with a mean of 1,106 foci yearly. These diagnoses correspond to 27,218 bovine cases (cases with diagnosis plus cases with clinical signs in the same farm) and 2,257 cases in equids. ⁹⁶ From 1977 to 2021 in different Brazilian states, 4,149 (89.8%) outbreaks were reported in cattle and 469 (10.2%) in horses.^{7,8,22,52,81,113,136,147} In Brazil, cattle losses due to rabies are estimated at 30,000–40,000 deaths per year ¹³³ ; there are no estimates of horse losses.

The cattle population in Brazil is 240 million, and the equid population is ~5.6 million (5,580,000 horses; 40,000 mules and donkeys). Of the total number of rabies cases in these 2 species, 10.2% occurred in equids and 89.8% in cattle. Considering that the equid population is only 2.3% of the cattle population, the prevalence of rabies in equids is higher than in cattle, which may reflect the preference of D. rotundus to feed on equids. ¹² This observation was confirmed in the state of Rondônia, Brazil, where between 2001–2022 there were 16 cases per 100,000 animals in 22 y in cattle versus 127 cases per 100,000 horses. ¹⁴² Cattle and horses are usually found together, as most horses (72%) are used in rearing and management of cattle. ⁹⁷

In a study of the geographic and temporal spread of equine rabies, the incidence risk (IR = cases per 100,000 equids) from 2010 to 2019 varied from 2.8 in the state of Sergipe to 140 in Espírito Santo. The IR was 14.1 in the North region, 8.2 in the Northeast, 31.2 in the Midwest, 42.2 for the Southeast, and 16.5 in the South. ¹⁰⁴

Due to the role of vampire bats in the transmission of rabies, conditions favorable to their survival and multiplication, such as climate, natural shelters (caves, hills, hollows), or artificial shelters (tunnels, bridges, drains, coal ovens, abandoned buildings), increase the risk of the disease, in addition to the presence of species (cattle and horses) that act as a food source for bats in deforested areas. ¹³⁹ The construction of dams in areas previously occupied by cattle or the replacement of pastures with crops triggers the migration of bat colonies due to lack of food, consequently introducing the disease into areas where it had not occurred. Some of these environmental changes and the control of dog-borne rabies have likely led to increased human cases of vampire-borne rabies. ⁷⁹

There are few studies about rabies in equids, making clinical characterization difficult. In most cases, there are signs indicative of spinal cord lesions, including ataxia and paresis followed by paralysis of the thoracic and pelvic limbs, more marked in the pelvic limbs (Fig. 1A), reduction or absence of flexor, panniculus and anal reflexes, and flaccidity of the tail. These signs are followed by permanent decubitus, sometimes with paddling movements.^23,79,81 In a study of 5 horses, 3 predominantly had clinical signs related to lesions in the cerebrum, such as aggression, walking in circles, blindness, behavioral changes, pressing of the head against objects, bruxism, drowsiness (Fig. 1B), and involuntary movements. One of the horses also had loss of balance, a clinical sign that is related to lesions in the cerebellum. ⁸¹ Clinical signs related to brainstem damage can also be observed, including ataxia (Fig. 1C), absence of pupillary light reflex, difficulty in grasping or chewing, tongue paralysis, lip ptosis, and enophthalmos.^79,81,118 In most cases, the clinical course was 2–8 d. ⁸¹ However, in an adult horse with mainly cerebral signs and severe weight loss, the clinical course was 34 d (Fig. 1B). The incubation period after inoculation by infected bats was 179–190 d for horses and 92–99 d for donkeys. ⁹⁷

Figure 1.

Rabies. Horses with (A) weakness of the hindlimbs, (B) drowsiness with edema of the face due to continuous head-down posture, and (C) ataxia. D. Cerebellum with intracytoplasmic viral inclusions (Negri bodies; arrowhead) in Purkinje cells. H&E. Inset: rabies immunohistochemistry of a Purkinje cell with positive stain for viral antigen. Fig. 1A is courtesy of Ana Lucia Schild.

Gross lesions include bladder distension, rectal ampulla distended and filled with dry feces, hyperemia of leptomeningeal vessels, and multifocal hemorrhage primarily in the gray matter of the spinal cord. Skin lesions due to trauma secondary to the nervous signs are also observed.^23,81,112 Histologic lesions consist of lymphoplasmacytic meningoencephalitis and meningomyelitis, focal or diffuse proliferation of glial cells, and neuronophagia that can affect both white and gray matter. The ganglia, mainly the trigeminal and paravertebral, are infiltrated by lymphocytes and plasma cells.^23,81,112 Intracytoplasmic inclusion bodies (Negri bodies; Fig. 1D), highly significant for the diagnosis of rabies, may be found in 28–64% of cases of rabies in horses.^23,81,112 Histologic lesions are observed primarily in the spinal cord and brainstem and with less frequency in the cerebellum and cerebrum. In some cases, there are only lesions in the spinal cord.^23,118

Laboratory diagnosis is made with the direct fluorescent antibody test (DFAT), which provides reliable results in 95–99% of cases when performed on fresh specimens. ⁹⁷ DFAT is usually performed simultaneously with isolation in murine neuroblastoma cells (NA-C1300) or mouse inoculation, which continues in use in some laboratories. ⁹⁷ A more modern technique is immunohistochemistry (IHC), which is more sensitive than DFAT and allows diagnosis in paraffin blocks but takes longer than DFAT.^1,112 Specimens should be sampled from different brain and spinal cord regions because the sensitivity of both techniques depends on the site of the CNS from which the samples are collected. ²³ IHC has allowed retrospective studies of autopsy material stored for long periods.^1,23,81,112

The control of rabies is based on the control of bats and mandatory vaccination of cattle and equids >3-mo-old in the endemic foci and in peripheral high-risk areas. In low-risk areas, vaccination is voluntary. Other measures include mandatory notification of suspect cases of rabies, detection of vampire bats in shelters, investigation of suspect cases, use of laboratory tests to confirm the diagnosis of the disease, and implementation of animal and human health education programs. ⁹⁷

The control of vampire bats is carried out through the use of anticoagulant poisons (mainly warfarin paste), which is fatal when ingested by bats. This poison may be applied by 2 methods. 1) The first method employs capturing D. rotundus in mist nets and applying the anticoagulant to their backs before releasing them. When returning to their natural or artificial roosting sites, these bats will be licked by other individuals, mainly females, who, in doing so, ingest the poison. For each D. rotundus treated with anticoagulant paste, ~20 other bats of the same species will die. The product causes hemorrhage that is fatal within 4–10 d. This method may only be conducted by properly trained and equipped personnel of the official services. 2) The second method does not involve the capture of vampire bats, consisting instead of the topical application of 2 g of vampiricide paste around recent bite wounds. Because the bats tend to return to the same wound on consecutive days to feed, they ingest the poison during feeding. The animal should remain where it had been bitten the previous night. This method may be done by the farmer guided by a veterinarian. Topical use of the paste may be repeated while the animal is being targeted by the bats. ⁹⁷

Encephalomyelitides

In Brazil, arboviral encephalomyelitides in horses are caused by infection by eastern equine encephalitis virus (EEEV; Togaviridae, Alphavirus eastern)^{3,35,45,106,140,144} and western equine encephalitis virus (WEEV; Togaviridae, Alphavirus western).^34,108 We did not find reports of the Venezuelan equine encephalomyelitis virus (VEEV; Togaviridae, Alphavirus venezuelan) causing disease in horses in Brazil.

EEEV and WEEV are transmitted by mosquitoes, mainly Culex, Aedes, Anopheles, and Culiseta. Horses and humans are accidental hosts, and the main reservoirs are birds of various species. ¹⁴⁰ Most reports on the identification of EEEV from different states^{3,45,76,100,106,144} reported the identification of the virus in the nervous system of horses but did not report the epidemiologic characteristics of the outbreaks. Many of these cases were found in rabies surveillance programs. In Brazil, only one case of EEE was reported in humans. ³

Epidemiologic, clinical, and pathologic characteristics of the disease have been described in detail in outbreaks reported from the states of the northeastern region ¹⁴⁰ and on Marajo Island. ³⁵ In Pernambuco, from April to August 2008, in 11 farms with 100 equids, morbidity was 61 of 100 (61%), and case fatality rate was 60 of 61 (98%). From March to July 2009, in 40 farms in the state of Ceará, and 42 in the state of Paraíba, in a population of 960 equids, mainly horses (165 horses, 1 pony, 1 donkey, 1 mule; 17.5%) were affected; 105 horses, the pony, and the donkey died (case fatality rate of 64.3%). Both female and male horses aged 6 mo to 16 y were affected. ¹⁴⁰ The frequency of the disease was not determined in the outbreak on Marajo Island where the disease affected horses from 6-mo-old to 11-y-old; 4 of 9 animals studied recovered. ³⁵

In the northeastern region, after DNA sequencing, all samples were identified as EEEV lineage III through BLASTn analysis; samples from the Ceará and Paraíba states were in the same cluster, whereas samples from the state of Pernambuco were in a different cluster. ¹⁴⁰ Because of the genetic divergence and significant differences in ecology and pathogenesis within American isolates, the South America isolates (lineages II–IV) had been classified as a distinct species, named Madariaga virus (MADV, EEEV-SA; EEEV South American; Togaviridae, Alphavirus madariaga). ¹⁴¹ This virus was isolated in 2023 from 2 horses in the state of Ceara. ⁶⁵ Numerous reports on antibodies against EEEV in horses from different states have been reviewed elsewhere.^65,122

Clinical signs or EEE infections are mainly cerebral, including circling (Fig. 2A), blindness, head pressing, lethargy, obtundation or hyperexcitability, and lip movements or other involuntary movements. Signs of brainstem disease may also be observed, such as tongue paralysis (Fig. 2B) and other signs of cranial nerve impairment and ataxia (Fig. 2B). Cerebellar and medullary signs, such as hypermetric gait, wide-base stance, paresis or paralysis, and stringhalt are less frequent but also occur. Drooling and nasal and eye discharge may be also observed. The clinical manifestation period is 3–15 d.^35,140 Hemorrhages may be observed in the CNS at autopsy, mainly in the cerebral cortex (Fig. 2C). Microscopic lesions are characterized by infiltration by lymphocytes, plasma cells, and neutrophils affecting mainly the gray matter of the cerebrum, with perivascular cuffing by lymphocytes, plasma cells, and macrophages (Fig. 2D), neuronal necrosis, neuronophagia, and sometimes hemorrhages. Less severe lesions may be observed in the brainstem and spinal cord.^35,140

Figure 2.

Arboviral encephalomyelitis. Horses with (A) circling, (B) tongue paralysis and ataxia. C. Cerebrocortical hemorrhages (arrow). D. Severe lymphoplasmacytic encephalomyelitis. H&E.

The presumptive diagnosis is based on the epidemiology (several foci in different farms during the rainy season, with variable morbidity and high lethality), clinical signs suggesting lesions of the cerebrum and brainstem and less frequently the spinal cord, and histology of the CNS. However, the definitive diagnosis should be confirmed by virus isolation or molecular techniques including semi-nested RT-PCR and DNA sequencing.^35,140

WEE is apparently much less frequent than EEE, and there is only one report of isolation and identification of the virus from a horse in Rio de Janeiro ³¹ ; seropositive animals have been reported.^31,110 However, from November 2023 to February 2024, a severe outbreak of WEE affected Uruguay and Argentina. In Argentina, the National Service of Agri-Food Health and Quality (SENASA) reported 1,419 cases of WEE (45 diagnosed by laboratory techniques and 1,374 diagnosed by clinical and epidemiologic criteria) in 20 provinces. In Uruguay, in the same period, the Ministry of Livestock, Agriculture and Fisheries (MGAP) reported 1,018 cases; 77 were confirmed by laboratory analysis in 16 of the 19 departments of the country. ¹⁰⁸ Up to April 2024, there were 103 confirmed human cases, 10 of them fatal. ¹⁰⁸ In the same period, in southern Brazil, in the same outbreak, WEEV was sequenced, and a novel lineage of the virus was identified in 3 fatal cases in horses on the border with Uruguay and/or Argentina. ³⁴

Inactivated vaccines effectively prevent EEE in horses. Vaccination is recommended for adults, with revaccination after 30 d and annually thereafter. Vaccines are usually combined with vaccines for eastern and western equine encephalomyelitis, influenza, rhinopneumonitis, and tetanus.

West Nile virus (WNV; Flaviviridae, Orthoflavivirus nilense) has been identified in Brazil as a cause of encephalitis in equids^42,92,137 and humans. ¹⁵⁴ Antibodies against WNV were reported in horses for the first time in 2008 ¹¹⁰ ; studies on serology have been reviewed elsewhere.^24,122,137 The virus is maintained in birds (Passeriformes, Charadriiformes, Falconiformes) and is transmitted by mosquitoes, mainly Culex spp. Horses and other equids are highly susceptible, and human cases may occur simultaneously with outbreaks in horses.^24,137 WNV was detected by nested RT-PCR ¹³⁷ and isolated ⁹² for the first time in horses in 2018, in the state of Espirito Santo, from horses and donkeys in an outbreak that involved at least 12 cases of encephalomyelitis on at least 6 farms. ¹³⁷ Later, the virus was isolated in Minas Gerais, São Paulo, and Piauí states. ⁴² Frequency of the disease in Brazil is unknown, but in the United States, nearly 20% of infected horses may develop clinical signs, and lethality is 3–50%. ³² In one outbreak, 1 of 4 affected animals died within 72 h of onset of clinical signs, and the others were euthanized in extremis. ¹³⁷ WNV likely circulates endemically in Brazil within the mosquito–bird cycle. ⁴²

Clinical signs in the affected horses and donkeys included muscle tremors, ataxia, paresis or paralysis, deficits of cranial nerve function, loss of sensitivity over the spinal column, seizures, lateral recumbency, and paddling. Muscle fasciculations, hyperexcitability, and behavioral changes were also reported.^32,137

Microscopic lesions affect mainly the gray matter, but unlike EEE and WEE, they are localized mainly in the spinal cord and brainstem.^32,137 Polioencephalomyelitis is characterized by perivascular infiltration of lymphocytes, and fewer numbers of leukocytes and macrophages, microgliosis, and occasionally neuronophagia.^32,137

In Brazil, there are no approved vaccines to protect equids against WNV. The first human case of WNV, diagnosed by the detection of antibodies in CSF, was reported in 2014 in the state of Piauí. ¹⁵⁴ Three other cases of WNV infection causing neurologic signs in humans were reported in 2019, also in Piauí state. ²⁴

Equine herpesviral myeloencephalopathy

In Brazil, equid alphaherpesvirus 1 (EqAHV1; equine herpesvirus 1, equine abortion virus; Orthoherpesviridae, Varicellovirus equidalpha1) is described in horses, causing abortions, rhinopneumonitis, ¹⁰⁵ and sporadic cases of nervous system disease (equine herpesviral myeloencephalopathy [EHM]).^43,98,118

In 2006, a neurotropic mutant strain of EqAHV1 with a point mutation in the DNA polymerase gene (ORF 30) was reported in the United States, causing severe outbreaks of EHM.^103,120 The disease caused by this mutant strain, now considered an emerging disease, ⁹ was identified in Brazil in 2008. ⁷⁸ Despite the identification of neuropathogenic strains, more information is needed about EHM outbreaks in Brazil. In one farm, outbreaks occurred in the autumn of 2 consecutive years. The farm, a maternity ward for recipient mares, had an outbreak of EHM with concomitant respiratory disease and abortions. In a herd of 29 horses, 16 (55%) were affected and 13 of 16 (81%) died. The farmer moved all of the mares to another property (only 2 working horses remained) and replaced them with 42 young horses 1–2-y-old from different regions of the country. In the autumn of the following year, there was a new outbreak in which 8 of 42 (19%) horses became ill and 5 of 8 (62%) died. ¹⁰⁵ Another outbreak occurred in Pará on 10 farms, affecting 22 horses; 9 of these horses died and 13 recovered after treatment. ¹⁹

Despite the few reports of EHM in Brazil, numerous serosurveys, reviewed elsewhere,^88,105 with different techniques, reported antibody prevalence throughout the country of 4.5–95.7%. Like all herpesviruses, EqAHV1 remains latent in horses; intermittent release of the virus leads to disease outbreaks. ¹²⁰

Nervous signs may be preceded by fever, abortion, and respiratory signs. ¹²⁰ The main nervous signs are related to spinal cord disease, including ataxia and weakness or paralysis, most evident in the pelvic limbs. Difficulty standing, falling, bladder atony, urinary incontinence or retention, contact dermatitis with urine, sensory deficit in the perineal region and pelvic limbs, tail paralysis, loss of anal tone, and lethargy or drowsiness may also be observed.^19,105,120 Some horses have wear on the hoof wall of their pelvic limbs due to ataxia, which causes the hoof to drag on concrete floors. ¹⁹ The period from clinical manifestation to death is 1–11 d, but some animals may recover, especially if they are treated at the onset of clinical signs.^19,105,120

Grossly, the main lesions are observed in the spinal cord, mainly in the lumbosacral region, which may be seen as meningeal congestion and hemorrhages and, in some cases, on the cut surface, focal red areas of softening and hemorrhages in the gray and white matter. Less frequent, similar lesions can be seen in the brainstem and cerebellum. Additionally, in some cases, there is interstitial pneumonia with hyperinflated lungs that do not collapse and have variable amounts of interlobular edema and emphysema. Skin and muscle injuries associated with falls and decubitus may be present.^19,105

The main microscopic lesions in the spinal cord are vasculitis with perivascular infiltrates of lymphocytes, plasma cells, and macrophages; endothelial cell damage; and thrombosis. The lesions result in infarction and have a characteristic pattern that extends radially in the white matter, from the meninges to the gray matter. Lesions are less frequent in the brainstem, cerebellum, and cerebrum. Axonal degeneration and chromatolysis can be observed.^19,105

Isolation and identification of the virus, from nasal discharge, buffy coat, or samples from the nervous system, is definitive for the diagnosis of EqAHV1 infection, especially during EHM epidemics, and is also necessary to characterize the virus. PCR is used for rapid diagnosis of the disease, but it does not allow differentiation between replicating and non-replicating or latent viruses. However, this differentiation can be achieved by real-time PCR. ORF 30–based PCR assays have been developed and used to differentiate neuropathogenic from non-neuropathogenic EqAHV1 isolates.^105,120 IHC and in situ hybridization are also used for detection of EqAHV1in the CNS. Autopsies and microscopic lesions are also important to confirm the diagnosis. A 4-fold increase in antibody titers in acute patients 7–21 d later in the disease course is highly indicative of EHM. ¹²⁰

Disease control must be based on early diagnosis, isolation and treatment of affected animals, and other biosecurity measures to prevent the spread of disease between stalls and stables through nose-to-nose contact, contaminated equipment, and respiratory secretions or placental or fetal tissues. Biosecurity measures are especially important during or after horse shows, races, or other events. On farms, movements should be restricted, horses subdivided into small groups, and those groups maintained in isolation.^4,88,105,120 Vaccination does not prevent the neurologic disease but can reduce the severity of clinical signs, mainly when frequent revaccinations are carried out. ⁴ Treatment, which may be effective if started early, is reported elsewhere.^19,25,105

Tetanus

Tetanus, which occurs due to the action of exotoxins (tetanolysin, tetanospasmin, non-spasmogenic toxin) produced by Clostridium tetani, is one of the most common diseases in horses diagnosed in veterinary hospitals, accounting for 1–6% of cases in various hospitals.^{51,114,115,124,125} The higher frequencies are possibly associated with poor hygiene, especially in horses used for work in cities. In most cases, the disease occurs due to infections of perforating skin injuries, particularly involving the extremities of the hind- and forelimbs. However, wounds are often not observed at the time of admission. Surgical procedures, including castration, recent injection and shoeing, and umbilical infections are also routes of infection.^124,125 However, in many cases, the cause of infection is not determined. ¹²⁴ Some of these cases may be due to the consumption of fibrous or rough feed that causes lesions contaminated by C. tetani in the mouth or intestinal tract.^124,125

Lethality is generally high (48–80%).^{51,114,115,124,125} Survival for a longer period of time occurs in horses with intervals of >5 d between the onset of signs of disease and initial care or with >7 d of hospitalization. On the other hand, indicators of poor prognosis include dysphagia or aphagia at first examination, decubitus, and perforating injuries to the sole of the hoof caused by nails.^114,124,125 Lethality is higher in animals less than one year old. ¹²⁴

The incubation period is 7–28 d but may be longer in some cases.^124,125 Generally, a long incubation period is associated with less severe clinical signs and a good prognosis, and a short incubation is related to a short course of the disease and a poor prognosis. The first clinical signs are hyperesthesia, muscle spasticity with rigid limb movements, cervical stiffness, tetanic spasms, and restriction of jaw movements with difficulty in food prehension, mastication, and deglutition. The ears stand erect and immobile, the nostrils are dilated, the tail is held elevated, and nictitating membranes are prolapsed when the animal is disturbed. These signs are followed by a sawhorse posture, sweating, dysphagia or aphagia, severe dyspnea, and permanent lateral recumbency with severe spasticity of the limbs and neck. Death occurs due to restrictive and obstructive respiratory failure resulting from paralysis of the respiratory muscles. The clinical manifestation period is 5–10 d.^{51,114,115,124,125} There are no significant lesions on autopsy or microscopic evaluation. The diagnosis should be based on clinical signs and history of the disease, its probable association with injuries or surgical procedures, and the absence of proper tetanus vaccination.^{51,114,124,125}

Tetanus antitoxin at a dose of 1,500 IU is recommended to prevent tetanus in unvaccinated horses at risk of contracting tetanus due to wounds or surgical procedures. There are efficient vaccines (toxoids) for tetanus prophylaxis. Foals should be vaccinated when 5–8-wk-old, revaccinated in 3–4 wk, and given boosters annually thereafter. Mares must be vaccinated during the last 6 wk of pregnancy.^{51,114,124,125} Treatment of tetanus in equids is reported elsewhere.^51,124

Parasitic diseases

Equine protozoal myeloencephalitis

Equine protozoal myeloencephalitis (EPM) was reported in Brazil for the first time in 1986. ²¹ It is a chronic debilitating neurologic disease of the CNS of horses caused by Sarcocystis neurona^55,66,67 or Neospora hughesi. ⁵⁴ The biology and definitive host of N. hughesi remain unknown, and infection by this agent has not been reported from Brazil. However, antibodies against this protozoon were detected in 24 of 961 (2.5%) horses examined. ⁷³

EPM occurs due to the presence of meronts and free merozoites of S. neurona within neurons. The life cycle is indirect and involves the opossum Didelphis albiventris in South America^56,66,67 and D. virginiana in North America as the definitive hosts, and a variety of mammals and probably cowbirds as intermediate hosts. ⁵⁵ Two other species of opossums present in South America, D. marsupialis and D. aurita, have not yet been identified as definitive hosts for S. neurona. ³⁸

True intermediate hosts [armadillos (Dasypus novemcinctus), raccoons (Procyon lotor), skunks (Mephitis mephitis), domestic cats (Felix catus), sea otters (Enhydra lutris)] are those whose skeletal muscles contain encysted infective bradyzoites that are consumed by opossums that in turn become infected and shed sporocysts and oocysts into the environment. ⁵⁵ Aberrant hosts are those in which the development of the parasite in the muscles or CNS tissues does not go beyond the meront stage, with no production in infective forms. ⁵⁵ Some aberrant hosts, including horses, zebras, and ponies, may develop clinical disease. ⁵⁵ The intermediate host(s) in South America has not been determined; however, in Brazil, there are 19 armadillo species, 2 skunk species (Conepatus semistriatus, C. chinga), and 1 raccoon species (Procyon cancrivorus). S. neurona was identified in microscopic slides in the muscles of domestic cats, ⁸⁷ and antibodies against S. neurona were found in 2.9% of feral and domestic cats. ⁹⁵ Horses were considered aberrant hosts because infective forms were not found in their muscles, but infective forms (schizonts and sarcocysts) were found in the muscle of a young foal. ⁹⁹

In most reports from different regions, the prevalence of S. neurona antibodies in horses was 26–70%.^{10,48,57,72,93,107,119,126} However, a low prevalence (2.8%) was found in one report. ¹⁵² In one report in which the prevalence of S. neurona antibodies in horses from different regions was 669 of 961 (70%), the prevalence of N. hughesi antibodies was 24 of 969 (2.5%). In donkeys, the prevalence of antibodies from the northeastern region was 69 of 333 (21%). ⁶³ These results, without clinical signs, suggest that donkeys are resistant to clinical EPM. ⁵⁴

EPM occurs sporadically in all regions.^{14,41,68,75,83,91,107} The disease frequency is difficult to estimate because veterinarians treat many horses instead of sending them to veterinary hospitals or samples to diagnostic laboratories. In Rio Grande do Sul, EPM cases autopsied at the Federal University of Rio Grande do Sul were 2.64% of the diagnoses in horses in 2010–2017. ⁶⁸ Also, in Rio Grande do Sul, in 61 horses with nervous signs studied by the Federal University of Pelotas in 1998–2006, 23 (37%) had clinical signs of EPM, and EPM was confirmed by Western blot (WB) in 18 (29.5%). ⁸³ The high frequency of seropositive animals and the relatively low number of cases of the disease confirm that the disease is subclinical in most animals infected with S. neurona.

In the first reports of EPM in Brazil, 3 horses (4.5- and 10-y-old) were affected.^21,93 In 2 reports, the age of the affected horses was 2.5–22-y-old (x̄ = 10.2 y),^68,83 with most horses >10-y-old. ⁸³ Horses of different breeds and of both sexes, both sport horses and horses used for work, mainly in metropolitan areas, were affected equally.^68,83

EPM, in general, is a chronic disease that begins insidiously; however, an acute course with severe signs may be also observed. Because S. neurona may cause focal or multifocal lesions in many areas of the CNS, any neurologic sign is possible. However, signs related to the spinal cord are more frequent, followed in frequency by signs of brainstem disease, which are also observed in many cases. Signs of cerebral and cerebellar disease are less frequent. Clinical signs are generally asymmetric. Ataxia and/or weakness affecting the hind- and/or forelimbs are observed (Fig. 3A), depending on the region of the spinal cord affected or whether it affects the gray or white matter. Tail paralysis and fecal and urinary incontinence may occur. Asymmetric muscle atrophy due to lesions of the gray matter is common. Areas of hypoalgesia or complete sensory loss may be observed. Asymmetric brainstem signs (Fig. 3B, 3C) include vestibular syndrome; facial, tongue, laryngeal, or ear paralysis; strabismus; corneal areflexia; poor jaw tone; and atrophy of the muscles of the face or tongue. Cerebral signs, such as obtundation, compulsive walking, or seizures, may be observed occasionally.^55,68,83

Figure 3.

Equine protozoal myeloencephalitis. Affected horses with (A) ataxia, (B) atrophy of the masseter muscle, (C) asymmetric paralysis of the upper lip and nasal orifice. D. Gross lesion in the spinal cord. There is a large asymmetric tan area of inflammation and malacia involving the gray matter of the ventral horn and extending into the white matter; this area is surrounded by hemorrhage. E. A perivascular cuff contains lymphocytes, plasma cells, macrophages, and eosinophils. F. A meront of Sarcocystis neurona with a distinct rosette of merozoites (arrow). H&E. Fig. 3D–F are courtesy of Brian Porter, Texas A&M University.

Gross lesions, not observed in all affected horses, are of variable intensity, dark-red to brown or tan, focal-to-multifocal areas in the brainstem or spinal cord (Fig. 3D), usually extending from the gray matter to the white matter. ⁶⁸

Microscopically, the perivascular inflammatory infiltrate is composed of lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils distributed in the white and gray matter. The perivasculitis is generally associated with necrosis and hemorrhage. Multinucleate giant cells and foamy macrophages occur associated with the affected area. S. neurona schizonts and meronts are observed occasionally (Fig. 3E, 3F). IHC or PCR may be used to identify schizonts and merozoites of S. neurona. ⁶⁸

Antibody detection can be performed using WB, indirect fluorescent antibody test (IFAT), direct agglutination test (SAT), or ELISAs, which must be performed on CSF. Antibodies in serum have no diagnostic value because many animals are infected subclinically. The CSF test has high sensitivity but low specificity, and can be contaminated with blood, giving a false-negative result. ⁵⁵

Various antiprotozoal drugs are efficient for EPM treatment, including sulfonamides and pyrimethamine, ponazuril, and diclazuril, which should be administered as quickly as possible after the first observation of clinical signs and may be efficient in 70–75% of affected horses. ⁵⁵

Trypanosoma evansi infection of horses

Trypanosomes are single-celled microorganisms of the family Trypanosomatidae, genus Trypanosoma. Trypanosoma spp. are divided into Salivaria (e.g., T. evansi), transmitted by the bite of biological vectors, and Stercoraria (e.g., T. cruzi), transmitted by contact with the host’s skin or mucous membranes with the contaminated feces of the vector. ¹⁴⁶

T. evansi is a monomorphic flagellate blood parasite. It is usually present in circulating blood as a trypomastigote shaped like an elongated and tapered spear. It is morphologically indistinguishable from T. equiperdum and intermediate forms of T. brucei. ³⁰ The parasite has a flagellum, a well-developed undulating membrane, and its posterior end can be rounded or tapered. ⁶⁴

T. evansi mainly affects horses, and the prevalence of infection varies according to the region. In the Pantanal, a sizeable floodable area in the midwestern region, antibodies are found in horses and several domestic and wild species, ⁶⁹ which suggests a situation of enzootic stability. Transmission of T. evansi is mechanical, and blood forms (trypomastigotes) are transferred directly from one horse to another in the saliva of hematophagous vectors, which include horseflies (Tabanidae) and stable flies (Stomoxydae). T. evansi does not develop in the vectors. Transmission can also occur artificially through needles contaminated with infected blood. In South America, T. evansi can also be transmitted by common vampire bats. ⁶⁴

Trypanosomes multiply at the site of the bite in the skin, causing edema, ¹³² and invade the bloodstream and lymphatic system, causing fever and inducing a systemic inflammatory response. ⁶⁴ Parasitemia increases and is accompanied by fever, followed by aparasitemic and afebrile periods, which occur due to antigenic variation on the parasite’s surface and evasion of the immune system. As the disease progresses, subcutaneous edema, anemia, petechiae in several organs, and, occasionally, invasion of the nervous system by trypanosomes may occur. ⁶⁴

Disease outbreaks have occurred in horses in southern Brazil.^{39,47,132,138,158} One of the outbreaks of trypanosomosis caused by T. evansi, in which >100 horses were affected by the disease, occurred on a property that annually received mares from other establishments for breeding. The outbreaks occurred during the breeding season when there were large numbers of mosquitoes and many capybaras (Hydrochoerus hydrochaeris), some of which, according to the owner, died after showing neurologic signs. As well, using the same needle to treat several sick horses was common practice on the farm. All of these features probably contributed to the onset and expansion of the outbreak.^131,132 Outbreaks reported from Marajó Island in the northern region were associated with a significant vector population at the end of the rainy season from January to June. In addition, there was a large number of leeches during the rainy season, which could increase the risk of T. evansi transmission because these worms could be vectors and reservoirs of this protozoan. ¹³⁸

The clinical manifestations in horses affected by T. evansi can be divided into cachectic and central neurologic forms. In the cachectic form, progressive emaciation occurs despite a voracious appetite, with incoordination and instability, atrophy of the large muscle masses of the pelvic limbs, anemia with paleness or jaundice of the mucous membranes, edema of the ventral subcutaneous tissue and limbs, lethargy, cough, hyperthermia, abortions, and enlargement of superficial lymph nodes, with a chronic clinical course that varies from weeks to several months. The central neurologic form is related to brain or spinal cord lesions. It can be observed in horses as a terminal phase of chronic wasting disease or in horses without previous chronic signs. Neurologic signs (Fig. 4A, 4B) include marked ataxia, blindness, circling, hyperexcitability, apathy, proprioceptive deficits, falls, head tilt, paddling movements, dog-sitting position, and head pressing. In this form, clinical signs evolve within 2–20 d.^132,138

Figure 4.

Trypanosomosis caused by Trypanosoma evansi infection. Horse with (A) head twist and fall, and (B) ataxia. C. Brain with edema and yellow discoloration of the thalamus and the internal and external capsule. D. Perivascular cuffing of lymphoplasmacytic cells including Mott cells (arrows). H&E. Inset: T. evansi in the blood. Diff-Quik stain.

The main hematologic alteration identified in animals with trypanosomosis is anemia, typically normocytic normochromic and occasionally microcytic normochromic anemia. ¹³² Leukocytosis due to lymphocytosis is one of the most critical findings in the leukogram of horses infected by T. evansi and is probably due to prolonged antigenic stimulation. When leukocytosis occurs, large lymphocytes with round, non-cleaved nuclei with loose chromatin and a moderate amount of basophilic cytoplasm (atypical lymphocytes) are frequently observed in the circulation. ¹³² Total plasma protein may be high due to hyperglobulinemia, mainly gamma globulins. The presence of flagellated protozoa is characteristic of the disease; however, the protozoa are morphologically indistinguishable from T. equiperdum, and molecular tests are necessary for definitive identification. ¹³²

Grossly, pale mucous membranes, emaciation, serous atrophy of fat, splenomegaly with hyperplasia of the white pulp, lymphadenomegaly, hepatomegaly, petechial hemorrhages in several organs, and atrophy of the large muscle masses of the pelvic limbs are observed. In horses with central neurologic signs, the convolutions of the cerebral hemispheres may be flattened and asymmetric. At cut surface, the brain and spinal cord may have yellow, gelatinous, and distended areas (edema and malacia; Fig. 4C).^131,132

Microscopic lesions in the brain include perivascular lymphoplasmacytic meningoencephalitis, edema, hemorrhage, and necrosis, mainly in the white matter. Many of the plasma cells have eosinophilic globules in the cytoplasm (clusters of immunoglobulins), which give the cell a morula-like aspect (Mott cells; Fig. 4D). Focal or diffuse gliosis and hemosiderosis are frequent. The yellow and gelatinous areas observed macroscopically in the brain correspond to focally extensive edema and necrosis with foamy macrophages. The intensity of the lesions is most pronounced in the parietal lobe of the cerebrum, followed by the basal nuclei, thalamus, and occipital lobe of the cerebrum. In the spinal cord, perivascular infiltrates and meningitis may occur occasionally. ¹³¹ Microscopic changes in lymphoid organs include lymphoid follicular hyperplasia, erythrophagocytosis, and hemosiderosis. Large numbers of plasmablasts are observed in the lymph nodes and spleen. In the liver, periportal lymphoplasmacytic infiltrate, Kupffer cell hyperplasia, hemosiderosis, and centrilobular degeneration and necrosis due to anemia are the most common findings. In some cases, floccular and hyaline necrosis of skeletal muscle alternating with myofiber regeneration, lymphoplasmacytic myositis, and hemosiderosis may be observed, in addition to lymphoplasmacytic neuritis and degeneration in peripheral nerves.^131,132

It is possible to diagnose trypanosomosis by observing trypanosomes in the blood (Fig. 4C, inset) using various parasitologic methods. However, these methods are not very sensitive, especially during low parasitemia. Frozen serum samples can be submitted for an indirect ELISA to detect circulating antibodies (Ab-ELISA) or circulating antigens (Ag-ELISA). Tissue or blood samples are used for molecular diagnosis through PCR testing. ⁶⁴ IHC to identify trypanosomes in the brain using antibodies specific to T. evansi is indicated; however, this technique is not widely available. In IHC, parasite specimens are immunostained in the perivascular spaces and brain parenchyma. ¹³¹

The use of prophylactic drugs is necessary when animals are at constant risk, and where the disease occurs with high morbidity throughout the year. ⁶⁴ One of several drugs can be chosen; diminazene aceturate is mainly used due to its availability in Brazil. ⁴⁷ This drug may also be used for the treatment of affected animals. ⁶⁴

Cerebral nematodosis by Halicephalobus gingivalis

Halicephalobus gingivalis (Rhabditida, Panagrolaimidae) is a soil-dwelling saprophytic nematode that primarily infects equids and, rarely, ruminants and humans.^59,143 Cases of H. gingivalis infection frequently involve the CNS of horses, but the parasite also causes lesions in other sites, such as gums, heart, lungs, eyes, and bones.^36,59

The life cycle, portals of entry, and disease pathogenesis need to be better understood. However, penetration of the oral mucosa or skin lesions is considered a possible entry point, followed by nematode migration via the hematogenous route.^36,59

Cerebral nematodosis by H. gingivalis occurs sporadically and affects adult horses from various regions of the country.^{44,134,143,153} Neurologic signs may be acute or last a few days. Clinical manifestations include blindness, eyelid ptosis, nystagmus, dysphagia, walking in circles, pressing the head against objects, incoordination followed by falls, paddling movements, ataxia, recumbency, and death.^{59,90,134,143,153}

In most cases, no relevant macroscopic changes are found in the CNS, but red foci are reported in the brain. Histopathology reveals granulomatous meningoencephalitis associated with intralesional rhabditiform nematodes, perivascular cuffs of lymphocytes, plasma cells, macrophages, multinucleate giant cells, and eosinophils; necrosis, hemorrhages, and axonal spheroids are also seen. The nematodes have a smooth cuticle, platymyarian–monomyarian musculature, rhabditiform esophagus (body, isthmus, bulb), a digestive tract lined by a single layer of cuboidal cells, and a reproductive tract with eggs.^36,143 Only parthenogenetic females and larvae are found in brain lesions, mainly in perivascular spaces. ³⁶

Because the disease does not cause macroscopic lesions, the diagnosis is established by histologic examination in which intralesional nematodes may be observed. The presence of a rhabditiform esophagus is characteristic of H. gingivalis and supports the diagnosis. The migration of larvae of other nematodes, such as Strongylus vulgaris and Setaria digitata, can induce traumatic lesions in the CNS. ³⁶ However, these conditions have not been described in horses in Brazil.

Toxic diseases

Leukoencephalomalacia

Leukoencephalomalacia (LEM) is a disease caused by the consumption of corn contaminated by fumonisins produced by the fungi Fusarium verticillioides (F. moniliforme) and F. proliferatum. Multiple outbreaks of this disease have been reported in horses in all regions.^{2,20,29,33,58,60,70,71,94,121} Additionally, cases have been recorded in mules^{33,123,129,135} and donkeys. ²

Outbreaks have occurred in animals eating ground corn, green corn, corn on the cob, corn kernels, corn-containing feed, corn bran, and other corn by-products. The disease is seasonal in the South and Southeast regions, occurring mainly between June to September, but outbreaks have been reported from December to March.^20,94,118 There is little information on the occurrence of the disease in regions with tropical climates; in the northeast, there is no clear seasonal distribution, and the disease is probably related to the amount of feed supplied and the storage conditions of the corn. ⁹⁴ In corn samples from 21 LEM outbreaks, the moisture percentage was 13–21%; 5 samples had a moisture content within the required standard (<15%). ⁹⁴

Morbidity is 4–100%, and lethality is 100%, affecting males and females equally.^58,129,157 Clinical signs appear abruptly and include anorexia, dullness or hyperexcitability, difficulty prehending food and chewing, tremors, compulsive walking, head pressing, circling, unilateral or bilateral blindness, ataxia, decreased cranial nerve reflexes, diminution of the tone of the tongue and lips, diminution of the sensitivity of the face and palate, paralysis of the jaw, and, finally, recumbency. Clinical signs are associated mainly with lesions in the cerebrum, but signs caused by lesions in the brainstem are also present.^{2,20,29,121,128,129} In an outbreak in mules, the predominant signs resulted from brainstem lesions. ¹²⁹ The clinical manifestation period is 2–72 h, but most affected animals die within 6–24 h. Rarely, the clinical course may be 1–7 d. In the CSF, xanthochromia, hyperproteinorrachia, and pleocytosis may be observed. ²

In horses, gross lesions in the CNS include malacia of the white matter (Fig. 5A, 5B), with enlargement of one of the cerebral hemispheres and softening of the gyri. Edematous (yellow) and/or hemorrhagic areas are seen in the centrum semiovale and corona radiata of the cerebral hemispheres (Fig. 5A). Cavities containing fluid are often seen in these areas. The internal capsule and thalamus are usually affected. Yellow or hemorrhagic areas are often seen in the brainstem (Fig. 5B). Lesions are usually unilateral, but are occasionally bilateral, always more marked on one side. In mules, lesions are similar, but in one outbreak they were preferentially located in the basal ganglia, thalamus, and midbrain. Macroscopic lesions are best seen after fixation of the CNS in 10–25% formalin, but they are also easily seen in fresh brain.^{2,20,29,121,128,129}

Figure 5.

Leukoencephalomalacia. A. Transverse section of the brain with increased volume of the left hemisphere caused by yellow (edema) and hemorrhagic areas of the white matter. B. Transverse section of the formalin-fixed brainstem, with bilateral cavitations and hemorrhages. C. Histology of the white matter with perivascular edema and lymphoplasmacytic cells. H&E.

Microscopically, the brain parenchyma has areas of necrosis surrounded by edema and hemorrhage; around these areas, astrocytes have swollen nuclei and prominent cytoplasm. Axonal spheroids, degenerative and hypertrophic changes in the vascular endothelium, perivascular edema, hemorrhages, and eosinophilic globules are also seen. Some vessels have perivascular cuffs of eosinophils, a few neutrophils, or lymphoplasmacytic cells (Fig. 5C).^{20,29,33,121,127–129} In the liver of some animals, periportal hepatocytes are irregularly enlarged, with vacuoles of different sizes in the cytoplasm, and some contain yellow-brown pigment (bile). Necrotic hepatocytes are rarely observed. ³³

The mycotoxins responsible for the clinical picture are fumonisins (B1, B2, A1, A2), especially B1, produced by F. verticillioides and F. proliferatum. Fumonisins alter sphingolipid metabolism by inhibiting ceramide synthetase, an important enzyme in their biosynthesis. A second mechanism is a change in polyunsaturated fatty acids. Fumonisin B1 and B2 and F. proliferatum have been systematically found in samples collected during outbreaks.^{20,58,94,118,145}

The presumptive diagnosis of LEM is based on the occurrence of an acute nervous disease in equids that ingest corn or rations containing corn or its by-products, and by the presence of malacia in the white matter of the brain and/or brainstem. Determination of fumonisins in feed confirms the diagnosis. Trypanosomosis by T. evansi may have gross lesions similar to LEM, but in LEM the clinical course is more acute and the histologic lesions in the 2 diseases are different.

It is important to note that, to date, there is no treatment for LEM. This lack of treatment underscores the seriousness of the situation and the need for strict prevention measures. The only way to effectively prevent the disease is to avoid feeding corn or its by-products in amounts >20% of the dry matter ingested by equids. It is always recommended that corn is dried properly. ¹²⁷

Hepatic encephalopathy caused by pyrrolizidine alkaloid–containing plants

Nervous signs due to hepatic encephalopathy are the most common clinical presentation in horses intoxicated by the pyrrolizidine alkaloids (PAs) from Crotalaria spp. (Fig. 6A) and Senecio spp. (Fig. 6B). Intoxication by Senecio brasiliensis was reported from São Paulo^37,46 and Rio Grande do Sul,^49,109 and intoxication by S. brasiliensis and S. oxyphyllus was reported in the state of Santa Catarina. ⁶² Intoxication by C. retusa in grazing horses occurs in northeastern Brazil where it is the most important disease of the CNS in horses, corresponding to 31% of cases of nervous diseases in horses diagnosed in the semiarid region. ¹¹⁸ Also, there is a report in 5 farms in the central-western region of intoxication in horses caused by consuming oat seeds containing 10% C. spectabilis seeds. ⁷⁷ The morbidity of the intoxication is variable, but lethality is close to 100%.^{49,62,77,101,109}

Figure 6.

Hepatic encephalopathy caused by pyrrolizidine alkaloids–containing plants. A. Crotalaria retusa. B. Senecio brasiliensis. Inset: flower head closeup. C. Horse intoxicated by C. retusa with ataxia and dullness. D. Liver of a horse poisoned by C. retusa with irregular nodular surface due to fibrosis. Inset: group of Alzheimer type II astrocytes in the brain.

Main clinical signs include dullness or hyperexcitability, ataxia (Fig. 6C), weakness, compulsive walking or circling, occasionally violent and uncontrollable galloping, head pressing, faulty prehension of food, dysphagia, blindness, and depressed cranial nerve reflexes. Other signs are inappetence, weight loss, colic, subcutaneous edema, icterus, and photodermatitis. The clinical manifestation period is 3–60 d, but most horses have a history of weight loss.^{49,62,77,101,109} In blood biochemistry, elevated serum activities of gamma-glutamyl transferase, aspartate aminotransferase, and alkaline phosphatase can be found, as well as hypoalbuminemia.^77,101,109

Grossly, the livers are firm with an irregular surface, with white areas mixed with dark areas (Fig. 6D), and with accentuation of the lobular pattern. Edema of the mesentery, ascites, and hydropericardium are also observed. The main microscopic changes are periportal or diffuse fibrosis, hepatomegalocytosis, biliary hyperplasia, and cholestasis. Occasionally, in more acute cases, there is centrilobular necrosis. In the brain, there is morphologic evidence of hepatic encephalopathy with Alzheimer type II astrocytes (Fig. 6D, inset) mainly in the caudate nucleus and cerebral cortex.^{49,62,77,101,109}

PA intoxication is diagnosed based on microscopic lesions of the liver and evidence of the plant being consumed in the pastures. In the case of animals that consume grains or their by-products, it is necessary to look for seeds of Crotalaria spp. in the feed. The main differential diagnosis is other causes of hepatic encephalopathy, which may be determined by hepatic biopsies or by autopsy and histologic examination. ¹²⁷

There is no treatment for PA intoxication. Prophylaxis is based on the control of Senecio spp. and Crotalaria spp. using agronomic measures, application of herbicides, or biological control with sheep. In the case of biological control of Senecio spp. with sheep, 0.5–5 sheep per hectare should be used depending on whether the grazing with this species is continuous or alternating. In pastures with continuous grazing with 0.5 sheep per hectare, Senecio spp. is not found in the pastures. In the case of alternate grazing, higher stocking rates should be used, and it is advisable to place sheep before the plant sprouts, in early autumn in southern Brazil and at the beginning of the rainy season in other regions. It has also been shown that sheep control C. retusa, but that the seeds of this plant are poisonous; for this reason, sheep should be placed on the pastures before the plant goes to seed. Care should be taken to avoid contamination of crops with seeds of Crotalaria spp. during harvest. ¹²⁷

Trema micrantha intoxication

Trema micrantha (Cannabaceae; Fig. 7A, 7B) is a tree distributed throughout Brazil; its typical habitats are tropical and subtropical areas in South, Central, and North America. ¹⁵⁶ Spontaneous toxicosis induced by the ingestion of T. micrantha is reported in goats, ¹⁵¹ sheep, ¹⁵⁶ and equids,^16,85,111 and can be reproduced by feeding the plant to cattle, ¹⁵⁰ goats,^149,156 horses, ¹⁵ and rabbits. ¹⁴⁹

Figure 7.

Intoxications by plants. A, B. Trema micanthra. C. Transverse section of the brainstem and cerebellum of a horse intoxicated by T. micanthra with large red, yellow, and dark areas. D. Bambusa vulgaris. E. Horse intoxicated by B. vulgaris with tongue paralysis. Fig. 7C courtesy of David Driemeier and Saulo Pavarini. Fig. 7D, 7E courtesy of Diomedes Barbosa.

The leaves of T. micrantha are palatable to herbivores. Animals can access the toxic leaves only when branches are knocked down from the tree (pruning or wind), when owners, unaware of its toxicity, feed the plant to animals, or when livestock graze the lower parts of young trees. ¹¹¹ The plant induces acute liver failure in ruminants associated with marked centrilobular liver necrosis and neurologic clinical signs. ¹⁵¹ Although T. micrantha toxicosis in equids can cause acute hepatic lesions similar to those in ruminants, this is the exception and not the rule. Intoxicated equids develop severe primary brain lesions. ⁸⁵ Horses of any age and breed can be affected. Neurologic signs include ataxia, profuse drooling, compulsive walking, lateral recumbency, and sternal recumbency. The clinical course is 1–4 d.^85,111

The brain is usually diffusely yellow, mainly in the ventral portion of the brainstem. Multifocal-to-coalescent gray or dark-red areas of malacia are primarily observed on the cut surface (Fig. 7C). The most frequently affected sites are the brainstem (mainly pons, midbrain), diencephalon, and striatum. The most severe lesions are in the pons. Similar lesions occur in the spinal cord. ⁸⁵ However, the frequency and distribution of spinal lesions are challenging to estimate because examining the spinal cord is not always performed in large animals. The duration of clinical signs in horses with spinal cord lesions was longer (3–9 d) than in horses with only brain lesions. Liver changes, when observed, are slight hepatomegaly and accentuation of the lobular pattern, best demonstrated on cut surface.^85,111

Microscopically, CNS lesions consist of transmural fibrinoid necrosis of blood vessels, with faint eosinophilic material, blood, and hyaline globules in the perivascular space and sometimes extending into the adjacent brain parenchyma; occasionally, neutrophils, a few lymphocytes, and plasma cells are in the perivascular space. There is liquefaction necrosis of the white and gray matter of the brainstem, cerebellum, and spinal cord. These areas are associated with infiltration of foamy macrophages; axonal spheroids occur in the adjacent regions of the necrotic lesions, and Alzheimer type II astrocytes appear in the cortex. ¹⁵ These lesions suggest a vasogenic pathogenetic mechanism, like the one occurring in mycotoxic LEM, ¹⁵ although with a different distribution of lesions. ⁸⁵ The toxic principle has yet to be determined.

Diagnosing T. micanthra intoxication in equids should rely on the characteristic gross and microscopic brain lesions and the evidence of fallen tree branches having been consumed by the animals. ¹²⁷

Bambusa vulgaris intoxication

Bambusa vulgaris f. vulgaris (bamboo; Poaceae; Fig. 7D) is a plant in northern Brazil that is toxic to horses. The intoxication usually occurs in areas where the bamboo is planted to provide shade for animals. Horses ingest the plant when there is a lack of forage during the dry season or when they are on pastures of Urochloa brizantha or U. decumbens that are unpalatable to horses. It affects animals of various ages. ¹⁸

Clinical signs are somnolence, incoordination, ataxia, standing with abducted limbs, and difficulty turning around. Signs of impairment of cranial nerves are also observed, such as paresis of the tongue (Fig. 7E), difficulty in prehending, chewing, and swallowing food, and decreased palatal and labial reflexes. Cutaneous, anal, and flexor reflexes are depressed. Blindness and head pressing are occasionally observed. The clinical course is subacute or chronic, and most horses recover after being removed from the pastures. ¹⁸

There are no macroscopic lesions. Histology shows slight myelin edema and degenerative lesions of some axons, and digestion chambers with some macrophages observed in the medulla oblongata. ¹⁸

The toxic compound is unknown. The disease is reproduced experimentally by administering young or mature bamboo leaves in daily doses of 10–31 g/kg of body weight for 6–60 d. The first signs are observed 24–72 h after the start of ingestion, but in experimental cases, the signs are more discrete than in spontaneous cases. ¹⁸

The clinical signs, the presence of the plant, and the regression of signs after the end of ingestion allow for the diagnosis. ¹⁸ Horses should not be allowed in areas with bamboo, especially during periods of low forage availability or in areas where the primary forage is U. brizantha or U. decumbens, which is not palatable to horses. ¹⁸

Indigofera lespedezioides intoxication

Indigofera lespedezioides (Fabaceae; Fig. 8A) causes a neurologic illness in horses in the state of Roraima, where the intoxication has been recognized since at least the 1990s.^28,80 The plant is found mainly in native vegetation at the edges of forests. Most cases of intoxication occur at the end of the dry season (October–March), when I. lespedezioides is practically the only green vegetation available. Morbidity is usually >10%, and lethality can be 100%. Horses of all ages may be affected. ⁸⁰

Figure 8.

Intoxications by plants. A. Indigofera lespedezioides. B. Equisetum sp. C. Ipomoea fistulosa var. fistulosa. D. Horse intoxicated by I. fistulosa var. fistulosa with ataxia. E. Cerebellum of a horse poisoned by I. fistulosa var. fistulosa with severe vacuolation of a Purkinje cell (arrow) and an axonal spheroid (arrowhead) in the granular layer. H&E.

Clinical signs are anorexia, drowsiness, gait instability, severe ataxia, weakness, and falls. Gait disturbances are more marked in the hindlimbs, where hoof dragging causes excessive wear. If animals are disturbed or forced to move, nervous signs are exacerbated, and animals may fall. Blindness and tearing are also observed. Mares frequently abort. Death usually occurs 2–4 mo after the first clinical signs are observed. If consumption of the plant is stopped, some animals may recover.^28,80

There are no significant macroscopic lesions.^28,80 Microscopically, lipofuscin accumulates in neurons of the cerebrum, brainstem, spinal cord, and cerebellum. In the midbrain, in some axonal tracts, Wallerian degeneration with axonal debris and macrophages is observed. ⁸⁰

I. lespedezioides contains a toxic non-protein amino acid known as indospicin. ⁶¹ In one experiment, a horse had signs of intoxication after grazing for 44 d in a pasture where the plant was abundant. ⁸⁰ Diagnosis is made based on the presence of clinical signs and compatible lesions, as well as the presence of the plant in grazing areas.^28,80 The only effective way to control poisoning is to remove horses from pastures containing the plant. This measure is the most reliable way to ensure the safety and health of the horses. ⁸⁰

Equisetum spp. intoxication

Equisetum spp. (horsetails; Equisetaceae; Fig. 8B) contain the enzyme thiaminase, causing thiamine deficiency in horses. Plant ingestion occurs during the dry season when the plants are still green or when fed with contaminated hay.^5,148

Weight loss and nervous signs of drowsiness, staggers, unsteady gait, and ataxia are observed 3–6 wk after the start of ingestion. As the signs progress, animals become emaciated and recumbent and die soon thereafter. No macroscopic or microscopic lesions have been reported.^5,148 The diagnosis is based on knowledge of consumption of the plant by horses and the absence of lesions in the CNS.

Early detection of clinical signs is key. Horses recover if treated with daily administration of 100 mg of thiamine, but when they are emaciated and recumbent, treatment might be ineffective. ¹⁴⁸

Intoxication by swainsonine-containing plants

In Brazil, there are several species of plants [Ipomoea spp. and Sida carpinifolia (syn. S. acuta)] that contain swainsonine and poison mainly goats. However, S. carpinifolia in the southern region ⁸⁶ and I. sericosepala (syn. Turbina cordata; Fig. 8C) in the northeastern region ¹²⁷ have also been reported in equids. Affected horses and ponies have difficulties in standing, ataxia, hypermetria, wide-based stance, intention tremors, spastic paresis mainly in the hind legs, nystagmus, abnormal postural reactions, head tilting, and falling.^86,127 In one outbreak, 3 of 11 ponies died 15–20 d after grazing in a paddock heavily infested by S. carpinifolia. ⁸⁶ Gross lesions are nonspecific, and microscopic lesions are vacuolation of the perikaryon of neurons in different areas of the CNS, trigeminal and celiac ganglia, and submucosal and myenteric plexus of the intestines. Vacuolation of the epithelial cells of the proximal convoluted tubules is also observed. ⁸⁶

The diagnosis is made by observing the typical chronic nervous signs, the microscopic lesions, and one of the swainsonine-containing plants. ¹²⁷

Hypochaeris radicata intoxication

Hypochaeris radicata (false dandelion; Asteraceae; Fig. 9A) causes Australian stringhalt (involuntary hyperflexion of the hindlimbs) in horses in Rio Grande do Sul and Paraná.^11,130 The disease occurs during dry periods (July–August in Paraná; January–March in Rio Grande do Sul) in pastures invaded by the plant. Young and adult animals are affected. The number of affected animals varies between properties, probably due to the variation in plant toxicity. ¹¹ However, morbidity of 17% and lethality close to zero have been recorded. ¹³⁰ The toxic principle and pathogenesis of intoxication are unknown.

Figure 9.

Intoxication by Hypochaeris radicata. A. H. radicata. B. Horse with stringhalt. C. Demyelination of nerve fibers (arrow) in the lateral digital nerve. H&E. D. Axonal spheroids (arrowheads) in the lumbar spinal cord. H&E.

Clinically, there is unilateral or bilateral, abnormal pelvic limb gait with hyperflexion (Fig. 9B) and difficulty in backing up or walking in circles. In cases of marked hyperflexion, the pelvic limb reaches the abdomen during walking. Laryngeal hemiplegia and muscle atrophy of the hindlimbs can also be observed in animals affected by this intoxication.^11,130

Grossly, marked atrophy of the muscles of the pelvic limbs is observed. Histologic findings consist of axonal degeneration of peripheral nerves (Fig. 9C) and spinal cord (Fig. 9D), as well as muscle atrophy.^89,130 Demyelination, regeneration, and remyelination of peripheral nerves are the main ultrastructural findings. ¹³⁰ Most horses recover spontaneously after being removed from areas invaded by the plant, but this process can last several months. It is recommended that horses be removed as soon as the first clinical signs appear. The use of phenytoin and myotenectomy of the lateral digital extensor in treatment has shown variable results.^89,130

Amitraz intoxication

Amitraz (N,N′-[methylimino)dimethylidyne]di-2,4-xylidine) is an acaricide used in the form of spray or immersion baths for various species to control ectoparasites. Amitraz intoxication has been described in horses treated by spray. The amitraz molecule is hydrolyzed in aqueous solutions with acidic pH, forming the toxic compound N-3,5-dimethylphenyl N-methylformamidine. Intoxication can occur with solutions in concentrations >0.025% or with repeated applications. Digestive signs of impaction of the large intestine and nervous signs may be observed, generally 2–3 d after the bath.^50,53

Nervous signs include obtundation, ataxia with dragging of the hoof on the ground, weakness, ptosis, difficulty in grasping, chewing, and swallowing food, reduced or absent skin sensitivity, instability in standing, reduced reflexes of the upper lip and palate, yawning, flaccid lips, and exposure of the tongue and penis. Some horses recover spontaneously or within 7 d after empiric treatment, but others die. Grossly, the large colon contents are compacted. There is no description of histologic lesions in the nervous system. Diagnosis is made by clinical signs and history of treatment with amitraz. Amitraz is not recommended for treating ectoparasites in horses.^50,53

Other diseases

Equine motor neuron disease

Equine motor neuron disease (EMND) is a chronic disease of horses associated with increased oxidative stress caused by vitamin E deficiency, which leads to progressive loss of motor neurons and muscle atrophy. The disease was reported in horses kept by the Sao Paulo Police Cavalry in the state of São Paulo^6,17 and on a farm in northeastern Brazil (unpublished data). Horses of different breeds, ages, and sexes kept in stables, fed low-quality hay, and without access to green pastures are affected.^6,17,26 In the horse population study, mixed and Brazilian breeds had a significantly higher risk of EMND in comparison to Standardbred horses. ¹⁷

Clinical signs are progressive and include generalized weakness and weight loss, symmetric muscle atrophy, muscle fasciculations and tremors, narrow-based posture keeping the feet well under the body, frequent shifting of the limbs, short-stride gait, lowered head and neck, and excessive time in recumbence. Death occurs after a clinical manifestation period of 1–8 mo, sometimes longer. Serum activities of creatine kinase and aspartate aminotransferase are increased.^6,17

Grossly, there is poor nutritional status, and the skeletal muscles of the neck, trunk, and limbs appear atrophic, with edema and clear focal areas. Microscopically, there is muscle atrophy with angular fibers. In the spinal cord, there is chromatolysis, degeneration, and loss of neurons, mainly in the ventral horns of the spinal cord and also in the brainstem in the nuclei of some cranial nerves. Wallerian degeneration with axonal spheroids is also observed.^6,26

The diagnosis of EMND is based on the clinical signs associated with a history of feeding low-quality hay, microscopic lesions, and low vitamin E plasma concentrations.^6,26 Horses with clinical signs should be treated with vitamin E (D-α-tocopherol 5,000–7000 IU/d). However, less than half of cases are stabilized or have slight improvement in clinical signs, so the prognosis is guarded. ²⁶ Supplementation with vitamin E and a change in diet using green pasture, high-quality hay, or concentrates with sufficient vitamin E prevent the appearance of new cases. ²⁶

Cervical stenotic myelopathy (equine wobbler syndrome)

Cervical stenotic myelopathy (CSM) is a neurologic disease affecting horses worldwide. The disease occurs in 2 different presentations: cervical vertebral instability and static cervical stenosis. In the former, the lesion is located between cervical vertebrae C3 and C5, causing dynamic spinal cord compression. It occurs when the neck is flexed and mainly affects 4–18-mo-old horses. In static cervical stenosis, the narrowing of the cervical canal occurs between vertebrae C5 and C7, causing compression, which happens regardless of the position of the neck and usually affects 1–4-y-old horses. Both forms of CSM mainly affect horses with long necks, and male horses are more represented than females. It is believed that there is a genetic predisposition to CSM; however, feeding energy-dense diets and other nutrients, rapid growth, trauma, and excessive exercise may be involved. ¹¹⁷ In Brazil, there are descriptions of MCE affecting Quarter Horses, Campolina, Thoroughbreds, and Mangalarga Marchador horses.^{13,40,82,84,102,116,117,155}

Clinical signs usually appear insidiously but may appear suddenly after exercise or trauma. Spinal cord compression leads to neurologic deficits, including spastic paresis and ataxia. There is a lack of balance and stumbling with an abnormal gait in the fore- or hindlimbs, or both, often accompanied by various degrees of incoordination and weakness. Ataxia is usually more marked in the hindquarters. Signs may progress for several weeks and then remain static. ¹¹⁷

In static cervical stenosis, malformations of one or more cervical vertebrae cause stenosis of the spinal canal and, consequently, compression and degenerative changes in the spinal cord. ⁷⁴ Neurologic examination, radiography, and myelography of the cervical region can diagnose static cervical stenosis. The absence of changes in the CSF can rule out inflammatory diseases with similar clinical signs. ¹¹⁷

Concluding remarks

Our review will allow veterinarians in Brazil and other countries to become familiar with the diseases that affect the equid CNS. We described the epidemiology, clinical signs, pathology, diagnosis, and prevention of most of the diseases affecting the CNS of horses and other equids. This information will be helpful to veterinarians working in the field in making a presumptive diagnosis and collecting the proper samples for laboratory work, consequently facilitating an accurate final diagnosis and subsequent treatment and control measures. The knowledge generated and the development of diagnostic techniques will allow for a disease surveillance system in the country that is essential for detecting diseases that affect animals, some of which may also affect humans. The surveillance of zoonotic diseases such as rabies, equine encephalomyelitis, and West Nile encephalitis must be continuous. Also, emerging diseases such as EHM require permanent surveillance, which can also detect other emerging or exotic diseases. We also described here several diseases caused by previously unknown toxic plants.

Such information is essential in controlling diseases, as happened in Brazil with LEM, a common disease in the country during the 1980s and 1990s. After the information on its cause, epidemiology, and diagnosis became widespread, veterinarians and horse owners implemented prevention measures, and the frequency of LEM plummeted. However, Brazil still has few operating veterinary diagnostic laboratories, and some states lack them. Therefore, developing new diagnostic laboratories in all Brazilian states will undoubtedly contribute to increasing knowledge about diseases of horses and other livestock species.