Definition

Inflammation of the brain that may be accompanied by spinal cord and/or meningeal involvement.

Pathophysiology

• Inflammation-caused by an infectious agent or by the patient's own immune system.
• Immune-mediated-immune system derangement generally of unknown cause.

Systems Affected

• Nervous
• Multisystemic signs-may be noted in patients with infectious diseases

Incidence/Prevalence

Unknown

Geographic Distribution

Varies with the cause or agent implicated

Signalment

Signs

Causes

Risk Factors

• Immunosuppressive drugs and FIV or FeLV infection-infectious encephalitides.
• Tick-infected areas-rickettsial and Borrelia infections.

• Travel history-mycotic infections.

Differential Diagnosis

• Fungal encephalitides-frequently accompanied by systemic signs.
• Protozoal diseases-systemic; may have a chronic history.
• Rickettsial diseases-CBC abnormalities common.
• FIP-patients usually <3 years of age; protracted course; characteristic CSF results.
• Canine distemper virus-commonly seen as acute encephalitis with systemic signs in patients <1 year old; can be difficult to confirm antemortem.
• Primary CNS neoplasia-signs may be similar to encephalitis.
• Degenerative disorders-usually slow, insidiously progressive onset.
• Metabolic or toxic encephalopathy-bilateral, symmetrical neurologic abnormalities that relate to the cerebrum; confirm toxins by laboratory tests or serum assay.

CBC/Biochemistry/Urinalysis

• CBC-frequently normal; leukocytosis may be seen in diseases that produce systemic signs; may see lymphopenia in early stages of canine distemper virus and rickettsial infection; rickettsial encephalitis may be accompanied by thrombocytopenia and anemia.
• Biochemistry-frequently normal; hyperproteinemia with polyclonal gammopathy often with FIP and chronic systemic infections; creatine kinase may be moderately high with Neospora infection.

Other Laboratory Tests

• Serology-available for fungal, protozoal, rickettsial, and viral diseases; helpful but must be interpreted with caution because a positive titer does not always indicate active disease (e.g., toxoplasma in cats) and a negative titer does not always rule out active disease (e.g., FIP).
• Indirect fluorescent antibody-a single positive titer of 1:10 or greater confirms ehrlichiosis.
• ELISA-a four-fold rise between acute and convalescent IgG titers when the first titer is >1:128 confirms Rocky Mountain spotted fever; an IgM titer of >1:256 suggests infection within the previous 16 weeks by Toxoplasma gondii and may indicate exacerbation of chronic infection.
• Latex agglutination antigen-a single positive titer from serum or CSF confirms Cryptococcus.
• Agar-gel immunodiffusion-diagnose blastomycosis with a high degree of accuracy.
• Local production of canine distemper virus–specific antibody (IgG and IgM)-in CSF after virus infects the CNS.
• Positive Neospora caninum titer-correlates well with active disease.
• Positive FIP titer-indicates only infection with a coronavirus; may not be pathogenic.
• Positive Borrelia burgdorferi titer-indicates exposure to the organism, not necessarily active disease.

Imaging

• Thoracic radiographs-may confirm lung abnormalities.
• Skull radiographs-may confirm sinusitis/rhinitis in some cats with cryptococcosis.
• CT or MRI of the brain-may detect multifocal or single mass lesions.

Diagnostic Procedures

• CSF-perform on all animals with clinical signs that suggest encephalitis; results almost always abnormal; normal results do not rule out acute viral encephalitis that is limited to the parenchyma; with pleocytosis, culture for bacteria (aerobic and anaerobic).
• CSF-neutrophils indicate acute active inflammatory process; small lymphocytes indicate an antigenic response; eosinophils indicate an allergic response or a reaction to foreign material (tumor, parasite).

Pathologic Findings

The lesions are a function of the brain response to the infectious agent or other cause.

Appropriate Health Care

Inpatient-diagnosis and initial therapy

Nursing Care

• Symptomatic treatment-control brain edema and seizure activity as necessary.
• Cerebral edema-20% mannitol (2.2 g/kg IV over 30–45 minutes); may repeat within 1–2 hours to achieve maximum response; limit parenteral fluids to prevent rebound cerebral edema; short-term (72-hour) corticosteroid treatment can be added for further control (dexamethasone sodium phosphate at 0.5 mg/kg IV q12h for 24 hours; then reduce to 0.25 mg/kg q12h for 48 hours).
• Seizures-treat with antiepileptic drugs; with boluses or constant-rate infusion.

Activity

As tolerated

Diet

If severe depression or vomiting-nothing oral until condition improves to prevent aspiration.

Client Education

Inform client that relapse is possible with idiopathic or immune-mediated encephalitis when therapy is discontinued.

Surgical Considerations

Brain biopsy-may be needed in specific cases.

Drug(s) Of Choice

• Apply specific therapy once diagnosis is reached or highly suspected.
• Idiopathic and immune-mediated-2 mg/kg prednisone q12h initially; tapered over 6 months.
• Rickettsial and borreliosis-doxycycline.
• Protozoal-clindamycin.
• Mycotic-requires treatment for 1–2 years; itraconazole (5 mg/kg PO q12h with food) or fluconazole (6.25–12.5 mg/kg PO or IV q12h); corticosteroids often needed during the first 4–6 weeks to control cerebral edema.
• Viral and post-vaccinal-none definitive; treat symptomatically.
• Bacterial-broad-spectrum antibiotics that penetrate the blood-brain barrier; if agent is unknown, try a combination of enrofloxacin (5–10 mg/kg PO or IV q12h) and ticarcillin-clavulanate (50 mg/kg IV q8h) or amoxicillin-clavulanate (13.75 mg/kg PO q8h).

Contraindications

• Bacterial and Rocky Mountain spotted fever-corticosteroids contraindicated.
• Puppies <6 months of age with a rickettsial disease-use chloramphenicol (doxycycline-induced tooth discoloration).
• Puppies <8 months of age-enrofloxacin contraindicated (cartilage damage); use amoxicillin-clavulanate or ticarcillin-clavulanate alone.
• CNS infections-do not use aminoglycosides and first-generation cephalosporins because CNS penetration is poor.

Precautions

• Administer mannitol intravenously 10 minutes prior to anesthesia for CSF collection to decrease intracranial pressure.
• Corticosteroids-observe closely for worsening signs that suggest an infectious cause.

Possible Interactions

• Chloramphenicol and cimetidine-do not use concurrently with phenobarbital to avoid toxic serum phenobarbital levels due to interference with liver metabolism.
• Corticosteroids alter CSF results if used for 12 hours or more.

Alternative Drug(s)

• Leflunomide 1.5–4 mg/kg PO q24h individualized based on its active metabolite, teriflunomide, blood level done 24h post-medication 7 days after therapy initiated due to long half-life. Safe therapeutic range is 20–40 µg/mL. Often effective for immune-mediated encephalitis unresponsive to conventional therapy. Leukopenia, thrombocytopenia, and hemorrhagic colitis are possible adverse effects. CBCs done monthly; treatment is for 1.5 years.
• Mycophenolate mofetil 10–16 mg/kg PO or IV q12h can be used in addition to leflunomide and prednisone in dogs with immune-mediated encephalitis to achieve further immune suppression. Adverse effects are similar to leflunomide. A CBC should be done 2 weeks after onset of therapy and then monthly.

Patient Monitoring

• Frequent neurologic evaluations in the first 48–72 hours to monitor progress.
• Relapse as medication is withdrawn-repeat CSF analysis.
• Measure serum titer of cryptococcus capsular antigen every 3 months until negative.

Prevention/Avoidance

• A method of effective tick control should be used on animals that live in endemic areas.
• Avoid vaccination of dogs that have had GME.

Possible Complications

• Long-term corticosteroid therapy-signs of iatrogenic hyperadrenocorticism.
• CSF collection or natural course of the disease-tentorial herniation and death.

Expected Course and Prognosis

• Resolution of signs-generally gradual (2–8 weeks).
• Protothecal-almost always progresses to death.
• Immune-mediated-fair to good prognosis for complete remission with aggressive immunosuppression.
• Rickettsial, mycotic, bacterial, protozoal, and spirochete infections-fair chance of survival.
• Parasite migration, migrating foreign bodies, PME, YNE, and polioencephalomyelitis-usually fatal.
• Pug and Maltese encephalitis-may be fatal; course varies greatly; some patients respond to steroid treatment for long periods.
• Post-vaccinal encephalomyelitis-may resolve on its own; often permanent damage and death.

Age-Related Factors

• Young (<2 years) and old (>8 years) animals-more risk for infectious diseases.
• Dogs <6 years of age-immune-mediated and idiopathic encephalitides.

Zoonotic Potential

• Rabies-consider in endemic areas if the patient is an outdoor animal that has rapidly progressive encephalitis.
• Humans may be infected by the same vector tick that affected the patient.
• Exudates from animals with mycosis can revert to the spore-forming, infectious mycelial stage.
• Cultures are highly contagious and should be handled with great care.

See Also

• Under “Causes”
• Seizures (Convulsions, Status Epilepticus-Cat)
• Seizures (Convulsions, Status Epilepticus-Dog)
• Stupor and Coma

Abbreviations

• CNS = central nervous system
• CSF = cerebrospinal fluid
• CT = computed tomography
• ELISA = enzyme-linked immunosorbent assay
• EME = eosinophilic meningoencephalitis
• FeLV = feline leukemia virus
• FIP = feline infectious peritonitis
• FIV = feline immunodeficiency virus
• GME = granulomatous meningoencephalitis
• MRI = magnetic resonance imaging
• PME = pyogranulomatous meningoencephalitis
• YNE = Yorkshire terrier necrotizing encephalitis.

Internet Resources

http://www.ivis.org/advances/Vite/toc.asp.

Author Allen Franklin Sisson

Consulting Editor Joane M. Parent

Client Education Handout Available Online