THE MERCK VETERINARY MANUAL
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Overview of Meningitis, Encephalitis, and Encephalomyelitis

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Inflammation of the meninges (meningitis) and inflammation of the brain (encephalitis) often are seen concurrently (meningo-encephalitis) in the same animal, although either can be seen separately. Furthermore, many of the inflammatory diseases of the CNS of animals are diffuse and usually involve both the brain and spinal cord (encephalomyelitis and meningoencephalomyelitis). Because many inflammatory processes are disseminated throughout the CNS at the time of clinical observation, differentiation between meningeal-only inflammation vs extension of disease into the neuropil cannot be made without postmortem evaluation. Thus, from a clinical standpoint, any one of these conditions may be the case in an animal with inflammatory CNS disease.

In animals with meningoencephalitis, or meningoencephalomyelitis, the clinical signs of meningitis often precede the clinical signs of encephalitis and may remain the predominant feature of the illness. Causes of meningitis, encephalitis, and meningoencephalitis include bacteria, viruses, fungi, protozoa, rickettsia, parasite migrations, chemical agents, and idiopathic or immune-mediated diseases. In ruminants, generally bacterial infections are more common than other causes of meningitis or encephalitis. In species other than ruminants, especially adult animals, viruses, protozoa, rickettsia, and fungi are as frequent or more frequent causes of meningitis or encephalitis than are bacteria. Some causes of meningitis or encephalitis (eg, arboviruses, certain rickettsia, and bacteria) are seasonal.

The incidence of meningitis, encephalitis, and encephalomyelitis is fairly low compared with that of infections of other organs. However, with the recent global expansion of the flaviviruses, and tickborne Anaplasma phagocytophilum and other vectorborne diseases, the incidence and risk for infectious brain and spinal cord infections of animals has likely increased.

Bacterial Infections:

When bacterial infections occur, they are more likely to be sporadic than epidemic. The risk of hematogenously disseminated CNS infections is likely to be low in adult animals because of the blood-brain barrier. Many infections of the nervous system are the result of some injury to its protective barriers. In all species, direct extension of bacterial or mycotic infections into the CNS can develop from sinusitis, otitis media or interna, vertebral osteomyelitis, or diskospondylitis. Infections can also be secondary to migrating grass awns or other foreign bodies, deep bite wounds, or traumatic injuries adjacent to the head or spine. Iatrogenic infections are possible from diagnostic and surgical procedures.

Brain abscesses also can arise from direct infections or by septic embolism of cerebral vessels. Pituitary abscesses in ruminants are thought to originate from bacterial invasion of the rete mirabile surrounding the pituitary gland. In chronic brain abscesses, an adjacent or occasionally diffuse fibrinous leptomeningitis may develop. Streptococcus equi equi is one of the most common causes of brain abscessation in horses, and Rhodococcus equi abscesses have been described in foals.

Spontaneous bacterial meningitis or meningoencephalitis develop in dogs rarely, occur more commonly in food animals, and are most common in septic neonatal animals. Various aerobic bacteria (Pasteurella multocida, Staphylococcus spp, Escherichia coli, Streptococcus spp, Actinomyces spp, and Nocardia spp) and anaerobic bacteria (Bacteroides spp, Peptostreptococcus anaerobius, Fusobacterium spp, Eubacterium spp, and Propionibacterium spp) have been isolated from animal infections. Bacterial endocarditis with associated septicemia is important in the etiopathogenesis of CNS infection in adult dogs. In Lyme endemic areas, neurologic infection in dogs with Borrelia burgdorferi has been implicated. Other non-neonatal hematogenously derived infections are well-recognized disease entities, such as histophilosis or thromboembolic meningoencephalitis of cattle (Histophilus somni, see Histophilosis), Glässer's disease of pigs (Haemophilus parasuis, see Glässer's Disease), and Haemophilus agni septicemia in feeder lambs.

Bacterial meningoencephalitis often affects neonatal animals as a sequela of gram-negative septicemia. Members of the Enterobacteriaceae (E coli, Salmonella spp, and Klebsiella pneumoniae) are the most commonly isolated pathogens, as well as streptococci (commonly Enterococcus spp). Actinobacillus equuli infection is an important cause of meningoencephalitis in foals. Failure of passive transfer of immunoglobulins is the single most important factor predisposing neonates to omphalophlebitis or enteritis, with subsequent hematogenous spread of the infection to the CNS.

Listeriosis (see Listeriosis), which is caused by Listeria monocytogenes and is a common infection in cattle, sheep, and goats and less common in horses, is an example of a multifocal brain stem meningoencephalitis that ascends to the CNS via transaxonal migration in cranial nerves. Mannheimia haemolytica and Pasteurella multocida, although usually resulting in fibrinous pneumonia and hemorrhagic septicemia in ruminants, occasionally produce a localized fibrinopurulent leptomeningitis. Meningo-encephalitis due to M haemolytica has also been reported in horses, donkeys, and mules. Actinomyces, Klebsiella, and Streptococcus spp are sporadic causes of meningitis in adult horses.

Viral Infections:

Viruses commonly cause nonsuppurative meningitis, encephalitis, and encephalomyelitis. Several viruses are specifically neurotropic or exhibit predilection for the CNS, causing a fulminate or fatal encephalitis, the most notorious being rabies virus infection (see Rabies). While rabies viruses primarily spread to the CNS transaxonally, several other DNA (adenoviruses, herpesviruses, parvovirus) and RNA (bunyavirus, flaviviruses, lentiviruses, morbilliviruses, togaviruses) viruses are likely spread via the bloodstream but exhibit high neuropathogenesis once within the CNS. Most animals have viral species-specific infections that exhibit predilection for the CNS. Rarely, a post-vaccinal encephalomyelitis in dogs is associated with immunizations against canine distemper virus, rabies, and canine coronavirus-parvovirus vaccines.

Infections Caused by Parasites:

Many parasitic agents can cause meningoencephalitis in both large and small animals. Possible neuropathogenic protozoa include Toxoplasma gondii, Neospora caninum, and Encephalitozoon cuniculi in dogs and cats. Sarcocystis neurona and N hughesii are important causes in horses, with Trypanosoma spp important in equids outside of the USA. A wide variety of protozoa can infect and cause severe CNS disease in adult cattle, including Babesia bovis, Theileria parva, and Trypanosoma spp, while N caninum and T gondii can cause congenital encephalitis in calves.

Aseptic suppurative or eosinophilic meningoencephalitis associated with aberrant migration of parasites throughout the CNS can develop in a number of animal hosts. In dogs and cats, CNS infections have been reported with Dirofilaria immitis, Toxocara canis, Ancylostoma caninum, Cuterebra spp larva, and Taenia spp. A wide variety of nematodes have been reported to cause severe meningoencephalitis in horses, including Setaria spp, Habronema spp, Strongylus spp, and Halicephalobus gingivalis. In cattle, migrating Setaria and Hypoderma larva are commonly implicated. Parelaphostrongylus tenuis is especially important in goats and llamas.

Fungal Infections:

Pathogenic fungi, including Coccidioides immitis, Blastomyces dermatitidis, and Histoplasma capsulatum, can cause meningoencephalitis. Opportunistic invasion with Cryptococcus neoformans and Aspergillus spp has also been described in several mammalian species. Rarely, other fungi, such as Candida spp, Cladosporium trichoides, Paecilomyces variotii, Chryseobacterium meningosepticum, and Geotrichum candidum, cause meningoencephalitis. Unicellular plants, Prototheca wickerhamii and P zopfii, can also produce an eosinophilic meningoencephalomyelitis in dogs, cattle, and horses.

Idiopathic/Immune Mediated:

Several idiopathic meningoencephalitides are recognized in dogs. Granulomatous meningo-encephalomyelitis (see Idiopathic Inflammatory Diseases) is a relatively common CNS disease of dogs that most often affects young to middle-aged, small-breed females. A pyogranulomatous meningoencephalomyelitis is seen in mature Pointer dogs. This acute, rapidly progressive disorder is characterized by extensive mononuclear cells and neutrophils infiltrating the leptomeninges and parenchyma, especially in the cervical spinal cord and brain stem. A necrotizing meningoencephalitis of unknown etiology has been reported in young, adult Pug dogs (Pug encephalitis), as well as in Yorkshire Terriers and Maltese dogs. A steroid-responsive suppurative meningitis affecting mainly young (<2 yr), large-breed dogs and a severe necrotizing vasculitis and meningitis syndrome in Beagles, Bernese Mountain Dogs, and German Shorthaired Pointers have both been identified as possible immunologic disorders with a hereditary predisposition. (Also see Congenital and Inherited Anomalies of the Nervous System.) An eosinophilic meningoencephalitis that has been described in adult dogs is believed to have an immunologic basis.

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 can appear as lameness, myositis, vertebral instability, or even colic. In foals, extreme hyperexcitability and irritability can be an early indication of sepsis in the CNS. Cattle can demonstrate anorexia, depression, and bizarre behavior.

The usual si gns of meningitis are fever, hyperesthesia, neck rigidity, and painful paraspinal muscle spasms. Dogs and occasionally horses display this syndrome acutely and sometimes chronically without clinical signs of brain or spinal cord involvement. However, in diffuse meningoencephalitis due to any agent, depression, blindness, progressive paresis, cerebellar or vestibular ataxia, opisthotonos, cranial nerve deficits, seizures, dementia, agitation, and depressed consciousness (including coma) can develop, depending on the rapidity of onset, pathology, and location of the lesions. Visual deficits, neck pain, seizures, behavioral disturbances, ataxia, weakness, cranial nerve deficits, and depression may be seen in either focal or disseminated CNS disease.

In neonatal infections, omphalophlebitis, polyarthritis, and ophthalmitis with hypopyon can accompany the CNS inflammation. Because of its unusual pathogenesis, listeriosis often causes asymmetric 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 nervous signs tend to be peracute, with sudden collapse and profound depression of consciousness (stupor or coma); fever and limb stiffness may be the only signs detectable in the prodromal stages.

Lesions:

Pathologic changes characteristic of meningitis include diffuse infiltration of leukocytes into the leptomeninges. Frequently, the entire subarachnoid space of the brain and spinal cord is inflamed. Vasculitis of meningeal vessels and CNS arterioles may also be apparent. In meningoencephalitis, the inflammation extends into the CNS parenchyma, resulting in leukocyte infiltration with large areas of perivascular cuffing. Necrosis and malacia of the CNS may be seen, with infiltrations of macrophages, neutrophils, and plasma cells. Listeriosis uniquely causes microabscesses deep within the CNS parenchyma, which consist of accumulations of neutrophils and microglial cell reaction with central liquefactive necrosis.

Often, there are no related changes in a CBC or serum biochemical profile to indicate CNS infection. The analysis of CSF is the most reliable and accurate means of identifying meningitis or meningoencephalitis. 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 may be misdiagnosed.

Adult large animals and dogs with bacterial meningitis and encephalitis, or steroid-responsive suppurative meningitis typically have a marked neutrophilic pleocytosis in the CSF, with cell counts in the hundreds to thousands. The protein content of the CSF is usually also significantly increased (>100 mg/dL), with an increase in the globulin component of CSF.

Rickettsial infections most often cause a mild to moderate mononuclear pleocytosis, although Rocky Mountain spotted fever can cause neutrophilic inflammation secondary to vasculitis.

Foals with meningitis have an increased protein content, and even slight increases in WBC in the CSF are significant (>10 WBC/µL). Any neutrophils observed on cytology in CSF from a foal warrant treatment with antimicrobials that can obtain high therapeutic levels in the CNS. Viral infections and listeriosis typically produce a mild to moderate mononuclear pleocytosis in CSF, with an associated increase in protein levels. Herpesvirus infections cause markedly increased proteins and xanthochromia (yellow to reddish discoloration). Feline infectious peritonitis (FIP) in cats and Eastern equine encephalitis in horses are exceptions and can cause markedly high neutrophil counts. In FIP, a markedly high protein concentration (>200 mg/dL) can also occur.

Parasitic and fungal meningoencephalitides cause eosinophilic or occasionally a highly degenerate neutrophilic pleocytosis. Granulomatous inflammations usually induce moderate to high cell numbers and increased protein in the CSF. The cell population is predominately mononuclear or a mixed population of neutrophils and mononuclear cells. Distinguishing a granulomatous infection due to 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 seen on cytologic examination of the CSF and identified with Gram's stain. Successful culture of bacteria from CSF is more likely in large animals than in dogs. In some cases, serial blood cultures are more successful, especially in foals. Cryptococci and occasionally protozoa have been identified in CSF, but serology is usually necessary to confirm mycotic and protozoal infections in vivo. Many of these diseases are fatal, and final identification is made at postmortem with in situ identification of the organism.

Other than for animals with the probable immune-mediated, steroid-responsive inflammatory CNS diseases and animals with meningoencephalitis caused by rickettsia and certain bacteria, the prognosis is guarded and treatment is often of little benefit. The case fatality rate in calves with bacterial meningitis has been reported to be 100%.

Appropriate use of antibiotics, according to culture or serology results, is basic to successful therapy. Relapses are common, and prolonged therapy is often necessary. Correction of any immunodeficiency is critical in neonatal large animals. Broad-spectrum antibacterials that can penetrate the blood-brain barrier should be selected, and bactericidal drugs are preferred over those that are bacteriostatic. Recommended drugs include ampicillin, metronidazole, tetracyclines, potentiated sulfonamides, fluoroquinolones, and third-generation cephalosporins; higher than normal dosages may be necessary to achieve and maintain adequate concentrations in the CNS. In farm animals, selection of drugs must be based not only on drug efficacy but also on whether the available drug is appropriate for use in a food animal.

Mycotic infections of the CNS have been treated successfully in humans, but results in veterinary medicine are less rewarding. Treatment with itraconazole or fluconazole may be of benefit, but longterm therapy is required and relapses are frequent. Protozoal infections (eg, toxoplasmosis, neosporosis, sarcocystosis) may respond to a potentiated sulfonamide (trimethoprim, pyrimethamine and sulfonamides). These are commonly used in combination with clindamycin in small animals. However, relapse may occur due to the inability to clear encysted organisms from the CNS. Over the last decade, new antiprotozoal medications have been licensed for use in the horse, including ponazuril and nitozoxanide.

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 may control life-threatening complications such as acute cerebral edema and impending brain herniation. Immunosuppressive doses of corticosteroids are required for successful therapy of the idiopathic CNS inflammations seen in dogs.

Radiation therapy and immunomodulatory drugs have been used in the treatment of granulomatous meningoencephalitis.

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

Last full review/revision July 2011 by Maureen T. Long, DVM, PhD, DACVIM

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