Meningitis and Encephalitis: Introduction - The Merck Veterinary Manual

Meningitis and Encephalitis: Introduction

Inflammation of the meninges (meningitis) and inflammation of the brain (encephalitis) often are seen simultaneously (meningoencephalitis) in the same animal, although either can be seen separately. In animals with meningoencephalitis, 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, certain rickettsia and bacteria, are seasonal.

Etiology and Pathogenesis:

The incidence of meningitis and encephalitis is fairly low compared with that of infections of other organs. This appears to result from the better protection offered to the nervous system by its barriers, rather than to a scarcity of infectious agents that can attack the nervous system. Infections of the nervous system often are the result of some injury to its protective barriers. In all species, direct extension of bacterial or mycotic infections to the CNS can develop from sinusitis, otitis media or interna, vertebral osteomyelitis, or diskospondylitis; these 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 contaminated spinal needles or surgical instruments. Infections may develop if CSF taps are performed in animals with bacteremia. 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. A spontaneous bacterial meningitis or meningoencephalitis can develop in dogs (although less commonly than in farm animals) from which 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. Bacterial endocarditis and septicemia are important sources of CNS infection in dogs. When bacterial infections do occur, they are more likely to be sporadic than epidemic.

Bacterial meningoencephalitis often affects neonatal farm animals as a sequela of septicemia caused by E coli ( Colisepticemia: Introduction) or streptococci; 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. In older or adult animals, well-recognized disease entities, such as histophilosis of cattle ( Histophilus somni , Histophilosis : Introduction), Glässer’s disease of pigs ( Haemophilus parasuis , Glässer’s Disease: Introduction), and Haemophilus agni septicemia in feeder lambs, also cause meningoencephalitis by the hematogenous route. Listeriosis ( Listeriosis: Introduction), which is caused by Listeria monocytogenes and is a common infection in cattle, sheep, and goats, 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. Meningoencephalitis 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.

Other agents that can cause meningoencephalitis, especially in dogs and occasionally cats and other species, include protozoa such as Toxoplasma gondii , Neospora caninum , Sarcocystis neurona , Encephalitozoon cuniculi , and Trypanosoma spp ; fungi such as Cryptococcus neoformans , Blastomyces dermatitidis , Histoplasma capsulatum , Aspergillus spp , and Coccidioides immitis ; the rickettsial organisms that cause Rocky Mountain spotted fever, salmon poisoning, and ehrlichiosis; and Acanthamoeba spp . Rarely, other fungi, such as Candida spp , Cladosporium trichoides , Paecilomyces variotii , Chryseobacterium (Flavobacterium) meningosepticum , and Geotrichum candidum , cause meningoencephalitis. Aseptic suppurative or eosinophilic meningoencephalitis associated with aberrant migration of parasites into the CNS can develop in number of species, especially Parelaphostrongylus tenuis in goats and llamas. Viruses such as those of canine distemper, canine parvovirus, feline infectious peritonitis, malignant catarrhal fever in ruminants, and sporadic bovine encephalomyelitis also produce meningitis in addition to encephalitis. Eosinophilic meningoencephalitis is an unusual inflammatory response to salt poisoning in pigs. Unicellular plants, Prototheca wickerhamii and P zopfii , can also produce an eosinophilic meningoencephalomyelitis in dogs.

Several idiopathic meningoencephalitides are recognized in dogs. A pyogranulomatous meningoencephalomyelitis is seen in mature Pointer dogs. It has been reported as an acute, rapidly progressive disorder. The lesions consist of extensive mononuclear cells and neutrophils infiltrating the leptomeninges and parenchyma, especially in the cervical spinal cord and brain stem. An etiologic agent has not been identified. Granulomatous meningoencephalomyelitis (GME, Idiopathic Inflammatory Diseases) is a more common CNS disease of dogs that most often affects young to middle-aged small-breed females. 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. (See also congenital and inherited anomalies of the nervous system, Congenital and Inherited Anomalies of the Nervous System: Introduction.) An eosinophilic meningoencephalitis that has been described in adult dogs is believed to have an immunologic basis.

Clinical Findings:

Encephalitis, head turn, calf

Meningitis, head-pressing

The usual signs 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.

Ophthalmitis with meningitis

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. Clinical signs of pyogranulomatous meningoencephalomyelitis include neck rigidity, kyphosis, inability to raise the head, reluctance to move (eggshell gait), and limb incoordination (ataxia). Sometimes, bradycardia, vomiting, and in chronic cases, atrophy of cervical muscles may be seen. Cranial nerve signs may include Horner’s syndrome and paralysis of any cranial nerve but most commonly the trigeminal and facial nerves. The signs of GME in dogs vary with the distribution of the lesions. The ocular form of GME is characterized by acute loss of vision with dilated, unresponsive pupils. Visual deficits, neck pain, seizures, behavioral disturbances, ataxia, weakness, cranial nerve deficits, and depression may be seen in either the focal or disseminated form of the CNS disease. The focal form of GME typically progresses insidiously over many months to years. The disseminated form of GME has a shorter, more fulminating course, with death typically occurring within weeks to months. The necrotizing encephalitis of Pugs and Maltese dogs causes forebrain signs, such as seizures, behavioral changes, visual deficits, and circling, while the condition in Yorkshire Terriers may manifest with either forebrain or brain-stem dysfunction. The latter is characterized by depression of consciousness, limb weakness, and cranial nerve deficits.

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.

Diagnosis:

The analysis of CSF is the most reliable and accurate means of identifying meningitis or meningoencephalitis. CSF should be collected whenever history or 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 and perhaps a mild fever may be misdiagnosed. In the early stages, meningitis can easily be mistaken for intervertebral disk extrusion, polyarthritis, pleuritis, pancreatitis, or pyelonephritis. Dogs with bacterial meningitis and encephalitis, steroid-responsive suppurative meningitis, and vasculitis and 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. 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 for isolation of the causative organism. Viral infections and listeriosis typically produce a mild to moderate mononuclear pleocytosis in CSF, with an associated increase in protein levels. Feline infectious peritonitis is an exception to this, and classically results in a neutrophilic pleocytosis with a protein concentration >200 mg/dL. Rickettsial infections most often cause a mild to moderate mononuclear pleocytosis, although Rocky Mountain spotted fever can cause neutrophilic inflammation secondary to vasculitis. 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 GME is often difficult. Eosinophilic inflammation can be seen with some fungal (especially Cryptococcus ) and protozoal infections. Cryptococci and occasionally protozoa have been identified in CSF, but usually serology is necessary to confirm mycotic and protozoal infections in vivo. The necrotizing encephalitides typically cause a mild increase in CSF mononuclear cells and protein concentration.

Treatment:

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 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, trimethoprim-sulfas, 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 promising. 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 sulfa/pyrimethamine combination or to clindamycin therapy. However, relapse may occur due to the inability to clear encysted organisms from the CNS. 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 GME. Supportive care should be specific for the needs of the individual animal and may include analgesics, anticonvulsants, fluids, nutritional supplementation, and physical therapy.