Meningitis, Encephalitis, and Encephalomyelitis in Animals

Meningitis, encephalitis, and meningoencephalitis can be caused by bacteria, viruses, fungi, protozoa, rickettsia, parasitic migration, chemical agents, and idiopathic or immune-mediated diseases. In adult animals, viruses, protozoa, rickettsia, and fungi are more frequent causes than bacteria. However, in ruminants, bacterial infections are more common than other causes.

Pathogens enter the CNS through several routes:

• direct spread from infection at adjacent sites, such as sinuses or ears

• travel through the bloodstream through direct invasion (paracellular) or within red blood cells (Trojan horse)

• trafficking of viruses and certain bacteria along nerves

In the dog, the underlying causes of inflammatory disease of CNS have shifted over time from infectious agents to immune-mediated conditions (1, 2, 3). In general and depending on the study, immune mediated disease accounts for between 80 and 90% of inflammatory CNS disease, with 10–20% considered infectious (2, 3). Although the geographical and temporal distribution of infectious agents varies, canine distemper virus (CDV), Toxoplasma gondii, and Neospora caninum usually are the most frequently identified pathogens (1, 2, 3).

Infectious causes are believed to account for 30–45% of CNS infections in cats, with 40% having an unknown etiology (4).

In cattle, published studies indicate 32–50% of CNS diseases have been found to have infectious causes (5, 6).

In one retrospective study, 49% of cases of equine encephalomyelitis had an identified agent; however, over 60% of these cases were only confirmed on postmortem examination (7).

Bacterial Meningitis, Encephalitis, and Encephalomyelitis Infections

Bacteria gain access to the CNS either as a result of local trauma, such as puncture wounds from fighting (cats) or tail biting (pigs), or by direct extension, such as from sinusitis after dehorning (cattle), otitis media or interna (Mycoplasma bovis in calves), spinal column inflammation (salmonellosis in cattle), or migrating grass awns in hunting dogs.

Bacteria invade the CNS hematogenously as septic emboli from suppurative lesions in other locations of the body (endocarditis or arthritis in cattle or dogs, navel-ill in ruminants) or bacteremia that leads to CNS vascular damage (Histophilus somni infection, primarily in feedlot cattle) (8, 9, 10).

Whereas these latter lesions lead to blood-brain barrier damage, penetration of an intact blood-brain barrier can also occur by cells harboring intracellular bacteria, such as Mycobacterium spp and rickettsias leading to granulomatous inflammatory lesions.

Penetration of CNS by axonal transport, a prominent feature of viral infections, also occurs with infection by L monocytogenes (listeriosis).

Bacterial infections can vary from mild to severe and can be focal or widespread, presenting pathologically as brain abscesses, granulomas, foci of infarction, and/or hemorrhage (see bacterial meningitis image).

Bacterial meningitis, Atlantic gray seal

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Necropsy photograph of an Atlantic gray seal (Halichoerus grypus) with bacterial meningitis. The presence of substantial purulent exudate is typical of a bacterial etiology.

Courtesy of Brian Cloak.

Brain abscesses and granulomas occur in a number of disorders; however, they are particularly associated with peripheral chronic inflammatory conditions that deliver septic emboli to the brain (bacterial endocarditis in cattle and dogs, S equi equi infection in foals; see brain abscess image), deep puncture wounds from bites or migrating foreign bodies, or in association with intracellular pathogens such as Mycobacterium spp (in many species) or Rhodococcus equi infection in foals.

Brain abscess, foal, CT image

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CT image of a foal with a brain abscess from metastatic Streptococcus equi equi abscess formation. Arrows delineate a ring enhancement that outlines the lesion.

Courtesy of Dr. Rodney Belgrave.

Although abscesses are typically relatively random in location (eg, adjacent to sites of direct trauma, at the junction of gray and white matter in the brain for septic emboli), pituitary abscesses are more common in ruminants and are thought to originate from bacterial invasion of the rete mirabile (intracranial carotid mirabile) surrounding the pituitary gland.

In dogs, although uncommon, infections of the ear, sinuses, oral cavity, lungs, or bladder or from trauma can result in meningoencephalitis. Common aerobic bacteria include Staphylococcus spp, Streptococcus spp, Pasteurella spp, Escherichia coli, Klebsiella spp, Actinomyces spp, and Nocardia spp. Anaerobic bacterial infections can also occur in dogs, especially secondary to periodontal disease and procedures.

Septic meningitis in cats is relatively uncommon and results from hematogenous spread secondary to infections (similar to those in dogs) or trauma (see puncture wound images).

Puncture wound, cerebral hemisphere, cat

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Necropsy photographs showing surface (top) and cross-sectional (bottom) views of the cerebral hemispheres of a cat. Note the suppurative process (arrows) induced by a puncture wound to the skull, speculated to be from a cat bite.

Courtesy of Brian Cloak.

Bacterial meningitis or meningoencephalitis develops more commonly in food animals than other species. These are most common in neonates, and the etiological agents are the same as those causing sepsis.

In equids, etiological agents of bacterial meningitis or meningoencephalitis include E coli, Enterobacter spp, Salmonella spp, Klebsiella spp, and Streptococcus spp. For ruminants, the most common etiological agents are H somni, Streptococcus spp, Mycoplasma spp, Salmonella spp, Pasteurella spp, Mannheimia haemolytica, Trueperella pyogenes, and Corynebacterium spp.

Failure of passive transfer and umbilical infections are two of the most common risk factors for meningoencephalitis in neonates.

Other than in neonates, sporadic meningoencephalitis in ruminants, horses, donkeys, and mules has been associated with alpha- and beta-hemolytic Streptococcus spp, Actinomyces spp, Fusobacterium spp, and Prevotella spp. Less commonly, anaerobic bacteria have been isolated from cases of meningoencephalitis, including Bacteroides spp, Peptostreptococcus anaerobius, Fusobacterium spp, Eubacterium spp, and Propionibacterium spp.

In geriatric horses, bacteremia secondary to periodontal disease, tooth root abscesses, and exodontia has been reported to result in translocation to the brain, causing meningitis (11).

In humans, Lyme disease (caused by Borrelia burgdorferi infection) is a cause of joint, cardiac, and CNS (meningoencephalitis) inflammation. In areas where Lyme disease is endemic, B burgdorferi exposure is common in dogs and horses. Numerous clinical syndromes have been attributed to Lyme borreliosis in domestic animals, including limb and joint disease and kidney, and cardiac abnormalities. While most seropositive dogs and horses do not have any clinical signs, neuroborreliosis does rarely occur.

Epidemics of meningoencephalitis with high mortality rates include thromboembolic meningoencephalitis of feedlot cattle (Histophilus somni), Chlamydophila pecorumin yearling cattle, Glässer disease of weaner pigs (Haemophilus parasuis), and Haemophilus agni septicemia in feeder lambs.

Encephalitis as a primary lesion with a predilection for the brainstem, accompanied by meningitis, is a common manifestation of listeriosis, which is caused by Listeria monocytogenes (12). Infection occurs in cattle, sheep, and goats and less commonly in horses (12). Incidentally, several species of Mycoplasma cause encephalitis in goats (M mycoides), poultry (M gallisepticum), cats (M felis), dogs (M edwardii), and rodents (M pulmonis) (13).

Several bacterial infections of animals are zoonoses and capable of causing CNS inflammation in humans:

• Bartonella henselae can cause meningoencephalitis in humans.

• Capnocytophaga canimorsus, a commensal, gram-negative bacterium from the mouth of dogs, can cause meningitis in elderly and immune-compromised patients.

• L monocytogenes, a foodborne illness obtained from contaminated food/animals, causes septicemia with CNS infection as a sequela.

• Coxiella burnetii, the causative agent of Q fever, can cause encephalitis in humans during acute infection.

• Although there is limited information on the pathogenesis of Elizabethkingia (formerly Chryseobacterium) meningoseptica, this bacterium causes meningitis in newborn and immunocompromised humans and animals (14).

• Others include Pasteurella multocida (infants), Leptospira interrogans, and rickettsial infections.

Viral Meningitis, Encephalitis, and Encephalomyelitis Infections

Many viruses cause meningitis, encephalitis, and meningoencephalitis. Viral infections typically cause nonsuppurative inflammation (ie, devoid of neutrophils or marked necrosis, other than that caused by death of individual infected cells). The extent of inflammation might not correlate well with the intensity of clinical signs.

Worldwide, many neurotropic viruses infect multiple species and are zoonotic, including rabies virus (RABV), West Nile virus (WNV), eastern equine encephalitis virus (EEEV), La Crosse virus, Powassan virus, lymphocytic choriomeningitis virus (LCMV), Japanese encephalitis virus (JEV), tickborne encephalitis virus (TBEV), louping ill virus (LIV), Nipah virus (NiV), bornavirus, and others.

Neurological signs are present with neurotropic virus infection in a variety of species (see eastern equine encephalitis horse video). Many viruses can cause disease in multiple species. Exotic birds are highly susceptible to infection with EEEV. Unlike horses, affected ratites frequently develop hemorrhagic enteritis that is laden with infectious virus (see eastern equine encephalitis emu image).

Eastern equine encephalitis, h...

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Eastern equine encephalitis, emu

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An emu with hemorrhagic enteritis resulting from eastern equine encephalitis virus infection.

Courtesy of Dr. Jim Wellehan.

Many viruses that affect the CNS are transmitted by ticks and mosquitoes and thus confined geographically by vector distribution as well as season.

Several viruses that specifically exhibit predilection for the CNS, using nerve axons to enter the CNS, also infect neurons and cause variable levels of inflammation. RABV infection (see rabies video) and pseudorabies virus (PRV, SuHV-1), transmitted by biting and eating infected meat, respectively, cause fulminant and rapidly fatal encephalitis.

Rabies, horse

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Other DNA (adenoviruses, herpesviruses, parvoviruses) and RNA (bunyavirus, lentiviruses, morbilliviruses, alphaviruses, flaviviruses) viruses are likely to enter the brain via the blood-brain barrier (within cells) and exhibit high neuropathogenesis once within the CNS.

Several viruses cause vascular damage in the CNS by inducing vasculitis in their viremic phase, resulting in loss of vascular integrity and subsequent hemorrhages and edema:

• Feline infectious peritonitis, caused by mutated feline coronavirus, uniquely induces a chronic granulomatous inflammation centered on and around blood vessels.

• Malignant catarrhal fever, caused by ovine herpesvirus 2, and canine herpesvirus encephalitis, caused by canine herpesvirus 1 represent typical examples of viral vasculitis in cattle and dogs, respectively.

• The neurotropic form of equine herpesvirus 1 replicates within the endothelial cells of the brain, resulting in vasculitis, localized hemorrhage, and necrosis of the brain and spinal cord (see herpesvirus vasculitis image).

Herpesvirus vasculitis, brain, horse, photomicrographs

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Photomicrographs showing vasculitis in the brain cells of two horses from infection by equine herpesvirus 1. (A) Vascular integrity is completely lost, with extravasation of RBCs into the neuropil itself (arrow). (B) Inflammatory cells are within the walls of the vessels, causing vasculitis (arrows). Magnification 400X.

(A) courtesy of Dr. Lisa Farina. (B) courtesy of Dr. Felipe Pierezan.

Viruses should be considered the prime causes of group outbreaks of meningitis, encephalitis, and meningoencephalitis, particularly in cattle, sheep, pigs, and horses. Full necropsies of recently dead animals with diagnostic testing performed directly on CNS tissues are important, because there are many histopathological hallmarks of viral infections (see inflammatory cells images).

Pearls & Pitfalls

Viruses should be considered the prime causes of group outbreaks of meningitis, encephalitis, and meningoencephalitis, particularly in cattle, sheep, pigs, and horses.

Inflammatory cells, brain, dog, photomicrographs

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Photomicrographs of brain tissue from a Greyhound with meningoencephalitis, showing perivascular cuffing of inflammatory cells (mainly lymphocytes and plasma cells; arrows), a hallmark of a viral or immune-mediated inflammatory process (original magnification 400X). Right: close-up view.

Courtesy of Brian Cloak.

Several encephalitic conditions in birds, mink, cattle, fish, and humans show histological features and clinical, epidemiological, and pathological signs that support a viral etiology, yet a viral agent has not yet been identified.

A number of reportable zoonotic conditions manifest as encephalitis or meningoencephalitis (rabies, West Nile virus infection, Nipah virus infection, Hendra virus infection, and Borna disease virus infection). Therefore, there is a constant need to be vigilant and accurately determine the cause of group outbreaks of encephalitis.

Parasitic Meningitis, Encephalitis, and Encephalomyelitis Infections

Many protozoal agents can cause meningoencephalitis in large and small animals:

• Neuropathogenic protozoa, including Toxoplasma gondii, Neospora caninum (see N caninum inflammation image), and Encephalitozoon cuniculi, are found in dogs and cats.

• E cuniculi can cause encephalomyelitis in rabbits.

• Sarcocystis neurona and Neospora hughesi are important agents in horses, with Trypanosoma spp important in equids outside of the US.

• A wide variety of protozoa can infect and cause severe CNS disease in adult cattle, including Babesia bovis, Theileria parva(theileriosis), and Trypanosoma spp, whereas N caninum and T gondii can cause congenital encephalitis in calves.

• Free-living amoebas, Naegleria fowleria, Acanthamoeba spp, and Balamuthia mandrillaris, are associated with amoebic meningoencephalitis in dogs.

Neospora caninum, brain inflammation, dog, photomicrograph

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Photomicrograph of brain cells from a dog, showing inflammation associated with protozoal cysts (Neospora caninum; small closed arrows). The open arrow points to perivascular inflammation. Magnification 400X.

Courtesy of Brian Cloak.

Aseptic suppurative or eosinophilic meningoencephalitis from aberrant migration of nematodes throughout the CNS can develop in a number of animal hosts. Neural larval migrans (NLM) can occur when parasites infect aberrant hosts:

• Angiostrongylus cantonensis causes a generally fatal meningoencephalitis in humans, primates, horses, dogs, and wildlife.

• Trichinella spp,Toxocara spp, and Gnathostoma spp, as zoonotic infections from ingestion of raw meat or fish and soil, cause fatal eosinophilic meningitis and myeloencephalitis in a variety of aberrant hosts.

• Baylisascaris procyonis, a roundworm of raccoons, causes NLM in small rodents, birds, foxes, humans, and primates.

• Larval stages of dipterans, includingCuterebra spp in dogs and cats and Setaria spp, Habronema spp, and Hypoderma spp in ruminants as well as horses, zebras, and llamas, can migrate to the CNS.

• The free-living nematode Halicephalobus gingivalis causes a severe granulomatous and eosinophilic meningoencephalitis in horses, humans, zebras, donkeys, and ruminants (cattle). 

NLM can also occur within definitive and intermediate hosts, often resulting in severe meningoencephalitis.

Dirofilaria immitis, Toxocara canis, Ancylostoma caninum, and Taenia spp. can cause CNS infections in dogs and cats.

Taenia multiceps (gidworm—coenurosis) can cause acute meningoencephalitis with heavy infection in sheep and goats (mainly) and less commonly in other intermediate hosts, such as cattle, horses, pigs, deer, and antelope.

Strongylus spp can migrate to the brain of horses, and Parelaphostrongylus tenia can migrate in goats and llamas.

Noninfectious Meningitis, Encephalitis, and Encephalomyelitis

Several noninfectious meningoencephalitides are recognized in dogs, likely driven by immune processes that can have genetic, infectious, or environmental triggers, or a combination thereof, at their core. These conditions fall into several subcategories: meningoencephalomyelitis of unknown origin (MUO), eosinophilic meningoencephalitis of unknown origin, idiopathic hypertrophic pachymeningitis, and idiopathic generalized tremor syndrome.

MUO includes several subtypes: granulomatous meningoencephalitis (GME), necrotizing meningoencephalitis (NME), and necrotizing leukoencephalitis (NLE).

MUO is definitively diagnosed on the basis of histopathological findings; however, a commonality of clinical findings exist such that a clinical diagnosis can be achieved, allowing for intervention. These findings include age (dogs greater than six months old), CSF pleocytosis with greater than 50% mononuclear cells, presence of infectious diseases unlikely on the basis of diagnostic testing, and MRI changes consisting of multiple, single, or diffuse hyperintensities.

GME is a relatively common subtype of MUO; however, it is a sporadic CNS disease that most often affects young to middle-aged dogs. Although small-breed females are more typically affected, there is not a clear familial or genetic basis as a driver for this immune-mediated encephalitis.

Pyogranulomatous meningoencephalomyelitis occurs in mature Pointer dogs; lesions are characterized by a mix of neutrophils and macrophages. Infectious causes, in particular Actinomyces spp and fungi, must be ruled out, and this syndrome is often classified as having an unknown origin.

NME is a severe, often fatal form of necrotizing encephalitis primarily affecting the gray matter of forebrain of Pug (Pug Dog Encephalitis), Maltese, Chihuahua, and Pekingese dogs.

NLE is nonsuppurative encephalitis that causes widespread and severe necrosis in young to middle-aged Yorkshire Terriers and French Bulldogs.

Steroid-responsive meningitis-arteritis (SRMA) is a necrotizing arteritis of leptomeninges (pia and arachnoid mater) affecting mainly young (less than 2 years old) large-breed dogs. It is usually observed in Beagles, Boxers, Bernese Mountain Dogs, German Short-haired Pointers, and Nova Scotia Duck Tolling Retrievers

Eosinophilic meningoencephalitis of unknown origin is diagnosed in animals with neurological signs and an eosinophilic pleocytosis that is not associated with an infectious cause. This syndrome generally affects young male large-breed dogs, including Golden Retrievers, Rottweilers, and South Africa Boerboels, and rarely cats.

Idiopathic hypertrophic pachymeningitis is a chronic, progressive, nonspecific inflammation causing thickening of the dura mater, mainly in Greyhound dogs (see idiopathic hypertrophic pachymeningitis image). The condition presents most commonly with cranial nerve deficits, vestibular ataxia, muscle atrophy, and pain. The trigeminal nerve is most affected, resulting in a "dropped jaw."

Idiopathic hypertrophic pachymeningitis, Greyhound

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A Greyhound displaying ventroflexion of the neck, a typical clinical sign of idiopathic hypertrophic pachymeningitis, which is a breed-specific neuroinflammatory condition.

Courtesy of Brian Cloak.

Idiopathic generalized tremor syndrome (white shakers, idiopathic cerebellitis) occurs in small-breed dogs less than 2 years old. Animals display mild tremors that are most prominent during excitement or exercise. On histological evaluation, the inflammation is mild and nonsuppurative.

High salt intake or water deprivation can lead to eosinophilic meningitis. In dogs and cats, this is usually associated with direct ingestion of seawater, table salt, or rock salt, or through ingestion of objects with a high salt content (paint balls, modeling compounds). In livestock, salt toxicosis can be caused by high levels of dietary salt or normal levels of salt in the face of water deprivation. Pigs are most susceptible to high salt concentrations; however, cattle, sheep, and poultry can also be affected.

Many etiological agents (arboviruses, certain rickettsias, and bacteria) for CNS inflammation are seasonal. Age can be a factor (bacterial meningitis associated with neonatal sepsis, rickettsia, and others).

Risk factors can vary within a species. Sporadic bovine encephalomyelitis, caused by Chlamydia pecorum, and thromboembolic meningoencephalitis, caused by Histophilus somni, primarily occur in feedlot cattle (6 months to 2 years old); however, they are also reported in cattle managed in dairies (20).

The case fatality rate is poor for neonatal large animals with bacterial meningitis has been reported to be up to 100% in both calves and foals (21, 22).

For viral infections, the case-fatality rate varies. The most lethal viral infections are rabies (100%) in all mammals (23), Eastern equine encephalomyelitis in horses (85–100%) (24), and distemper virus in dogs (50%) (25).

In the early stages of inflammatory diseases of the CNS, nonlocalizing clinical signs are frequent. In dogs, for example, meningitis can easily be mistaken for intervertebral disk extrusion, polyarthritis, pleuritis, pancreatitis, or pyelonephritis.

In horses, initial clinical signs of CNS inflammation can appear as lameness, myositis, vertebral instability, or even colic. In foals, extreme hyperexcitability and irritability are early indications of sepsis in the CNS.

Cattle can demonstrate anorexia, lethargy, lameness, diarrhea, and bizarre behavior, including strange vocalizations, because of peripheral nerve damage.

The usual clinical signs of meningitis are fever, hyperesthesia, neck rigidity, and painful paraspinal muscle spasms. Dogs and occasionally horses display this syndrome acutely and occasionally chronically, without clinical signs of brain or spinal cord involvement. However, in diffuse meningoencephalitis, a wide variety of clinical signs can occur, irrespective of the agent.

Neuroanatomical localization of clinical signs is the goal of a neurological examination, which can help differentiate disseminated inflammatory disease consistent with viruses, bacterial sepsis, and EMU versus a localized lesion more consistent with parasitic infection or bacterial embolus or abscess.

Acute forebrain signs of CNS inflammation include lethargy, blindness, seizures, circling, change in mentation (dementia, agitation, hyperexcitability), and depressed consciousness (including coma).

Brainstem and cerebellar lesions can manifest as progressive paresis, cerebellar or vestibular ataxia, opisthotonos (see opisthotonos image), and cranial nerve deficits. A combination of the above usually indicates more disseminated CNS disease.

Opisthotonos, calf

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A calf at 24 hours old that was recumbent with depressed mentation, showing clinical signs of opisthotonos. The calf also had hypopyon, and blood work was consistent with sepsis.

Courtesy of Dr. Marcelo Valdes Soto.

Lateralizing lesions to one side of the body (head or limbs) can be indicative of more focal disease; however, they can also reflect differences in regionally disseminated disease. Involvement of the spinal cord can also present as unilateral or bilateral ataxia and/or weakness, loss of proprioception, or gait abnormalities (dysmetria) that can progress to recumbency. In neonates with bacterial meningitis, opisthotonos is common.

In neonatal infections, omphalophlebitis, polyarthritis, and ophthalmitis with hypopyon can accompany CNS inflammation. Because of its unusual pathogenesis and development of asymmetrical brain lesions, listeriosis often causes asymmetrical vestibular dysfunction, with head tilt and circling in addition to other cranial nerve deficits, such as facial and pharyngeal paralysis.

In histophilosis of cattle, the CNS signs tend to be peracute, with sudden collapse and profound depression of consciousness (stupor or coma); fever and limb stiffness can be the only clinical signs detectable in the prodromal stages.

In sporadic bovine encephalomyelitis, calves demonstrate incoordination that can progress to recumbency and opisthotonos.

Sarcocystis neurona infection can manifest as asymmetrical muscle wasting consistent with lower motor neuron infection.

Early in the course of a West Nile virus infection, horses display involuntary muscle tremors in over 80% of confirmed cases (see fasciculations/hyperesthesia and depression/tongue paralysis videos) (26).

West Nile virus infection, fas...

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West Nile virus infection, dep...

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Lesions of Meningitis, Encephalitis, and Encephalomyelitis

Gross CNS lesions are extremely variable, depending on cause and location and whether the disease is diffuse or multifocal.

Pathological changes characteristic of meningitis include diffuse infiltration of leukocytes into the leptomeninges. This can be mild in flaviviral infections, visible to the eye as an increased opacity with thickened meninges in suppurative bacterial meningitis, or a series of multifocal hemorrhages if the organisms damage vascular endothelium.

Depending on the insult and the agent, varying levels of necrosis can be present, in addition to inflammation. This can take the form of individual cell death, microabscesses, or extensive necrosis with cavitations or large abscesses. There can also be regions of demyelination, hemorrhage, and edema. Grossly, this can translate to observing swollen and/or hemorrhagic brain tissue and/or herniation of brain tissue (see herniation image).

Regions of cavitation or abscesses can often be observed grossly. The identification of causative agents cannot be confirmed from gross examination, however, apart from focal cryptococcal lesions and the cysts formed by the cestode Coenurus cerebralis, the larval stage of Taenia multiceps.

Herniation, cerebellum, dog

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Necropsy of a dog, showing herniation of the caudal part of the cerebellum (coning of the cerebellum) at the foramen magnum (arrow), suggestive of intracranial pressure from brain edema or space-occupying lesions.

Courtesy of Brian Cloak.

Histological evaluation enables the identification of characteristics that separate viral, bacterial, parasitic, and fungal infections, often allowing for the visualization of agents. The presence of inclusion bodies in the cytoplasm of cells in the hippocampus and cerebellum of the brain (see inclusion bodies image) is a hallmark of rabies virus infection.

Pearls & Pitfalls

The presence of inclusion bodies in the cytoplasm of cells in the hippocampus and cerebellum of the brain is a hallmark of rabies virus infection.

Rabies, inclusion bodies, brain, horse, photomicrographs

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Photomicrographs of cerebellar tissue from a horse with rabies, showing inclusion bodies within the cytoplasm of Purkinje cells (arrows). Scale bars in the lower right corners represent 50 mcm.

Courtesy of Dr. Ian K. Hawkins.

• History and clinical evaluation

• CBC and serum biochemical analysis

• CSF analysis

• Imaging (typically MRI in cats and dogs)

• Necropsy

• PCR assay, immunohistochemistry, serological testing

Diagnosis of meningitis, encephalitis, and encephalomyelitis in animals is difficult. Physical examination, extensive laboratory workup, neurological examinations, and CSF analysis are important starting points in the evaluation of meningoencephalitic conditions in animals.

Lack of successful identification of a causative agent or immunopathogenesis hampers understanding of inflammatory CNS disease, often preventing successful intervention.

Vaccine history is an essential factor in consideration of differential diagnosesin animals with clinical signs of inflammation of the CNS, especially those caused by viruses. Rabies and arboviruses can be ruled out in appropriately vaccinated animals. (See vaccination guidelines for dogs, cats, cattle, and horses).

Results of CBCs and serum biochemical profiles often are unremarkable in CNS infections; however, they are necessary to rule out or identify noninfectious encephalopathies, such as hepatoencephalopathy.

The most reliable and accurate means to identify an encephalitis, meningitis, or meningoencephalitis is CSF analysis. CSF should be collected whenever history, species, or breed predisposition suggests meningitis or encephalitis or whenever clinical signs indicate a disseminated or multifocal CNS disorder. Without CSF analysis, an animal exhibiting back or neck pain with an increase in rectal temperature can be misdiagnosed.

Adult large animals and dogs with bacterial meningitis and encephalitis or with steroid-responsive meningitis-arteritis (SRMA) typically have a marked neutrophilic pleocytosis (40% to > 90%) in the CSF (27, 28). The neutrophils are often degenerate and can contain intracellular bacteria with bacterial meningoencephalitis. However, in cases with SRMA, they are nondegenerate. The protein content of the CSF is usually also considerably increased (> 100 mg/dL), with an increase in the globulin component of CSF (see SRMA CSF image) (27, 28).

Steroid-responsive meningitis-arteritis, cytocentrifugation preparat...

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Photomicrograph of a cytocentrifugation smear of CSF from a 1-year-old Keeshond treated for steroid-responsive meningitis-arteritis on the basis of CSF testing. Cells present consist mostly of nondegenerate neutrophils with moderate macrophages (arrows). Macrophages are not vacuolated or phagocytic (nonreactive). Modified Wright stain; scale bar = 50 mcm.

Courtesy of Dr. Tracy Stokol.

CSF changes from rickettsial infections often have a mild to moderate pleocytosis. However, the CSF in Rocky Mountain spotted fever infections can be predominately neutrophilic (29). Mild to moderate increased CSF protein concentration is also common.

In foals with suspected bacterial meningitis, protein concentrations are high, and the cells counts can be highly variable; in one study, the mean total nucleated cell count was 1216 cells/mcL, ranging from 13 to 5810 cells/mcL (30). However, even slight increases in WBCs in the CSF are important (> 10 WBC/mcL). Observation of neutrophils on cytological evaluation of CSF from a foal warrants treatment with antimicrobials that can obtain high therapeutic concentrations in the CNS. When fulminant, bacteria can be observed, and neutrophils are often degenerate.

Viral infections and listeriosis typically produce a mild to moderate mononuclear (usually lymphocytic) pleocytosis in CSF with an associated increase in protein concentrations. However, the CSF is normal in rabies virus infections. Herpesviral infections cause markedly increased proteins and xanthochromia (yellow to reddish discoloration) without dramatic increase in cell count.

Feline infectious peritonitis in cats and Eastern equine encephalitis in horses are exceptions and can cause markedly high neutrophil counts, and with EEEV, the neutrophils are nondegenerate (see CSF image) (24, 31).In feline infectious peritonitis, a markedly high protein concentration (> 200 mg/dL) can also be present (31).

Eastern equine encephalitis, CSF, horse, photomicrograph

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Photomicrograph of CSF from a horse with eastern equine encephalitis virus. Nondegenerate neutrophils are the predominant cell type. Magnification 400X.

Courtesy of Dr. Heather Wamsley.

Parasitic and fungal meningoencephalitides cause eosinophilic or occasionally a highly degenerate neutrophilic pleocytosis, the latter of which is most often present in fungal infection. CSF protein concentrations can be extremely elevated.

In Halicephalobus gingivalis infections in the horse, besides an eosinophilic pleocytosis, systemic globulins are usually elevated, and peripheral eosinophilia is evident on CBC.

Granulomatous inflammations usually induce moderate to high cell numbers and increased protein in the CSF. The cell population is predominantly mononuclear or a mixed population of neutrophils and mononuclear cells.

Distinguishing a granulomatous infection by a fungal or protozoal organism from granulomatous meningoencephalitis is often difficult.

The necrotizing encephalitides typically cause a mild increase in CSF mononuclear cells and protein concentration.

Occasionally, bacteria are present on cytological evaluation of the CSF and identified by Gram stain. Successful culture of bacteria from CSF is more likely in large animals than in dogs (32). In some cases, serial blood cultures are more successful, especially in foals.

Fungi and occasionally protozoa can be identified in CSF; however, serological testing is usually necessary to confirm mycotic and protozoal infections in vivo. Many of these diseases are fatal, and final identification is made on postmortem examination with in situ identification of the organism (see cryptococcus image).

Cryptococcus, cat, photomicrograph

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Photomicrograph of a cytocentrifuged preparation of CSF from a cat. The arrow indicates pseudohyphae formation by a rare cryptococcal organism. Wright stain; original magnification 50X.

Courtesy of Dr. Tracy Stokol.

For antemortem etiological identification, agent-specific testing is recommended; however, most agents, once in the CNS, are not detectable by direct testing through culture or nucleic acid–based testing of body fluids. Although CSF analysis is generally rewarding, detection of a pathogen within the CSF can also be unreliable, depending on the location and pathogen load within the CNS.

Culture of the CSF will often yield growth of the organism in bacterial meningitis. Culture of CSF for viruses is generally not pursued. PCR assays composed of panels of pathogens are now offered by many diagnostic laboratories.

Serological testing is available for most viral encephalitides. Paired serum is required for IgG-based tests, especially those confounded by vaccination. For arboviruses, the most reliable test examines IgM in a single sample.

For several diseases, intrathecal antibody production is an important marker for identification of organisms that have invaded the CNS. Detection of intrathecal antibody is useful in distinguishing active infection with canine distemper virus from vaccination (33). Comparison of serum and CSF antibody titers is considered the most reliable method for antemortem detection of infections with Sarcocystis neurona in the horse (34). Detection of IgG within the CNS can be nonspecific if there is leakage through the blood-brain barrier or contamination while sampling. In the horse, the detection of IgM in the CSF is a reliable indication of WNV infection and can also be used to differentiate recent vaccination for infection (35).

Post confirmatory testing is performed on a postmortem basis if the animal dies.

To aid in the diagnosis of meningoencephalitis of unknown origin, several animal health state and commercial diagnostic laboratories offer testing for combinations of biomarkers for inflammation (interferon-gamma, interleukin-2 [IL-2], IL-6, IL-8, IL-17, and tumor necrosis factor) and neuronal damage (neurofilament light chain, glial fibrillary acidic protein, and nonspecific enolase) in the CSF and serum.

• Antimicrobials or other specific therapy

• Supportive care

Depending on clinical signs, supportive therapy is likely required, in addition to specific therapies focused on the etiological agent or the mechanism driving the CNS inflammation.

Other than for animals with probable immune-mediated, steroid-responsive, inflammatory CNS diseases and animals with meningoencephalitis caused by rickettsia, protozoa, and certain bacteria, the prognosis is guarded. Anti-inflammatory therapy can decrease the immune drive observed in the immune-mediated and breed-associated meningoencephalitic disorders; however, in many instances, fatalities ultimately occur.

Appropriate use of antimicrobials, according to culture or serological testing results, is key to successful therapy. Relapses are common, and prolonged therapy is often necessary. Correction of failure of passive transfer is critical in neonatal large animals. High-dose broad-spectrum antimicrobials that can penetrate the blood-brain barrier should be selected, and bactericidal drugs are preferred over bacteriostatic agents (36).

For dogs and cats, recommended drugs include ampicillin, doxycycline, enrofloxacin, ceftriaxone and cefoxitin; higher-than-normal dosages can be necessary to achieve and maintain adequate concentrations in the CNS. However, use of high dosages of some antibiotics can result in adverse events (36). In farm animals, selection of drugs must be based not only on drug efficacy but also on whether the available drug is legal and appropriate for use in a food animal.

Availability of antivirals is limited, and cost can be prohibitive.

Famciclovir is used to treat the ocular and respiratory forms of feline herpesvirus 1 in cats with varying degrees of success. Acyclovir and ganciclovir are used to treat the neurotropic form of equine herpesvirus 1; however, the cost is prohibitive in most cases, and the prognosis is guarded in recumbent horses, even with treatment. Zidovudine is used to treat neurological signs of feline immunodeficiency virus in cats. For information on antiviral medications, see Antiviral Agents.

Mycotic infections of the CNS have been treated successfully in humans; however, results in veterinary medicine are less rewarding. Treatment with itraconazole or fluconazole can be of benefit; however, long-term therapy is required, and relapses are frequent (37, 38).

Protozoal infections (eg, toxoplasmosis, neosporosis, sarcocystosis) can respond to a potentiated sulfonamide (trimethoprim, pyrimethamine, and sulfonamides). These are commonly used in combination with clindamycin in small animals. However, relapse can occur, because of the inability to clear encysted organisms from the CNS. Antiprotozoal medications have been approved for use in horses, such as the triazine analogues, including diclazuril and ponazuril (see Equine Protozoal Myeloencephalitis).

In balantidiasis, a zoonotic disease in working donkeys, secnidozole has been shown to decrease fecal cyst counts, which should theoretically decrease the risk of development of CNS disease (39).

Glucocorticoids are usually contraindicated in animals with meningitis or meningoencephalitis with an infectious etiology; however, a high-dose, short-term course of dexamethasone or methylprednisolone can control life-threatening complications such as acute cerebral edema and impending brain herniation. Immunosuppressive doses of corticosteroids are required for successful therapy of immune-mediated syndromes in dogs (40).

Immunosuppressive therapy is the cornerstone of treatment for meningoencephalitis of unknown origin. Glucocorticoids are typically initiated at immunosuppressive doses and gradually tapered according to clinical response. Additional immunosuppressive agents — eg, cyclosporine, cytarabine (cytosine arabinoside), procarbazine, azathioprine, leflunomide, mycophenolate mofetil, cyclophosphamide, and vincristine — are commonly administered concurrently or sequentially to improve efficacy and reduce adverse effects of steroids. Radiation therapy has been used in selected dogs with focal intracranial lesions (41, 42, 43, 44, 45).

Supportive care should be specific for the needs of the individual animal and can include analgesics, anticonvulsants, fluids, nutritional supplementation, and physical therapy.

• Coates JR. Emerging treatments for granulomatous meningoencephalomyelitis (Proceedings). dvm360. August 1, 2009. Accessed March 9, 2026.

• CAPC Guidelines. Companion Animal Parasite Council. (For expert articles on parasitological diseases and management of veterinary parasites.)

• Also see pet owner content regarding meningitis and encephalitis in dogs, cats, and horses.

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