Profile
Definition
Inflammatory central nervous system (CNS) diseases are a group of sporadic inflammatory diseases that affect the brain and/or spinal cord in the absence of an infectious cause (ie, pathogen-free).
- Based on histopathologic findings, 3 distinct forms of inflammatory CNS disease have been identified in dogs:
♦Granulomatous meningoencephalomyelitis (GME): Canine GME is the current term for an idiopathic CNS disease (most likely first described in 1936). GME still attracts a confusing and lengthy number of synonyms reflecting changes only in immunologic terminology (eg, inflammatory reticulosis, lymphoreticulosis, neoplastic reticulosis).
♦Necrotizing meningoencephalitis (NME): Canine NME was originally recognized in dogs in the U.S. in the 1970’s as a breed-specific disease of pug dogs (colloquially known as “pug dog encephalitis”). Since 1989, based on morphologically defined lesion patterns and histology, NME has been recognized in other small-breed dogs, including Maltese, Chihuahua, Pekinese, Boston terrier, Shih Tzu, Coton de Tulear, and papillon breeds.
♦Necrotizing encephalitis (NE): Canine NE was first described in 1993 in Yorkshire terriers and has been reported in other breeds, including French bulldogs.
Signalment
Age
- GME affects dogs older than 6 months of age, and is most prevalent in dogs between 4 and 8 years of age.
- Onset of NME is 6 months to 7 years of age, with a mean onset age of 29 months.
- NE typically manifests between 4 months and 10 years of age, with 4.5 years as a mean onset age.
Breed & Sex Predilection
- GME affects all sizes and breeds of dogs (with toy and terrier breeds overrepresented), whereas NME and NE affect predominantly small-breed dogs.
- Both males and females are affected, although females may be at higher risk for developing the disease.
CNS = central nervous system; CSF = cerebrospinal fluid; GME = granulomatous meningoencephalomyelitis; NE = necrotizing encephalitis; NME = necrotizing meningoencephalitis; PCR = polymerase chain reaction
Causes
- Obscure, although an autoimmune or immune-mediated/immune-dysregulatory cause is suspected.
- PCR-based screening for viral DNA (eg, herpes, adeno- or parvoviruses) has been negative.
Pathophysiology
Suggested possible mechanisms include autoimmune encephalitis induced by anti-GFAP (glial fibrillary acidic protein) antibodies in CSF and T-cell-mediated delayed hypersensitivity mechanisms.
Signs
- Signs of neurologic dysfunction reflect the location of the lesion(s) within the CNS.
- Multifocal involvement of the cerebrum, brainstem, cerebellum, and spinal cord (GME only) is common.
- Clinical signs of GME may include visual disturbances (ie, the ophthalmic form of GME affects the optic nerve), cranial nerve deficits (particularly central vestibular signs), seizures, apparent cervical pain, ataxia, and paresis.
- NME and NE frequently affect the forebrain, resulting in abnormal mentation, seizures, blindness, circling, and behavior changes, or brainstem, resulting in cranial nerve deficits, changes in mentation, and difficulty walking.
Diagnosis
Definitive Diagnosis
- A tentative antemortem diagnosis may be based on analysis of a combination of the patient’s:
♦Signalment, history, and clinical signs
♦Neurologic examination findings
♦Blood analysis results
♦Infectious disease titers (eg, Toxoplasma, Neospora, fungal organisms, canine distemper)
♦CSF analysis (including culture and PCR analysis)
♦Advanced imaging (CT and MRI)
- Neurologic signs, CSF analysis results, and neuroimaging findings will vary with intensity and location of pathologic lesions.
- Definitive antemortem diagnosis is based on characteristic findings on histopathology of brain and/or spinal cord tissue obtained by surgical biopsy.
- Definitive postmortem diagnosis is based on characteristic findings on histopathology of brain and spinal cord.
►Possible Causes of Brain Dysfunction in Dogs
Degenerative
- Lysosomal storage diseases
- Leukodystrophy/spongy degeneration
- Cognitive dysfunction syndrome
Anomalous/Developmental
- Congenital hydrocephalus
- Caudal occipital malformation
- Intracranial arachnoid cyst
Metabolic
- Hepatic encephalopathy
- Renal-associated encephalopathy
- Hypoglycemic encephalopathy
- Electrolyte-associated encephalopathy
- Endocrine-related encephalopathies
- Encephalopathy associated with acid-base disturbances
- Mitochondrial encephalopathy
Neoplastic
- Primary brain tumors
- Secondary brain tumors
Nutritional
- Thiamine deficiency
Inflammatory/Infectious/Immune-Mediated
- Bacterial meningoencephalitis
- Fungal encephalitis
- Viral meningoencephalitis
- Protozoal meningoencephalitis
- Rickettsial meningoencephalitis
- Verminous meningoencephalitis
- Granulomatous meningoencephalomyelitis
- Necrotizing meningoencephalitis
- Necrotizing encephalitis
- Eosinophilic meningoencephalitis
Toxic
- Pyrethrins, lead, methylxanthines, zinc phosphate, & metaldehyde
Vascular
- Ischemic encephalopathy
- Hemorrhagic encephalopathy
Differential Diagnosis
See Box for other causes of focal and multifocal CNS dysfunction of dogs.
Laboratory Findings
- CSF from dogs with inflammatory CNS disease is usually abnormal, although normal CSF may be present (particularly if corticosteroids have been administered up to 6 weeks prior to CSF collection).
- Typical findings consist of an elevated total nucleated cell count and elevated CSF protein. Lymphocytes are the predominant cell type, with smaller numbers of neutrophils and macrophages present (Figure 1).
- Infectious causes of CSF abnormalities should be considered, and culture, serologic testing, electrophoresis, or PCR analysis (of CSF and/or serum) for the presence of infectious agents may be appropriate (eg, canine distemper virus), although results of these tests are unlikely to contribute to a diagnosis.