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Meningoencephalomyelitis of unknown origin
Synonym(s): MUO, meningo-encephalo-myelitis, meningoencephalitis
Introduction
- Inflammatory diseases of the central nervous system (CNS) are one of the common causes of neurological dysfunction in the dog.
- Inflammatory CNS disease can be grouped into two broad categories; those of a known infectious etiology and those causing meningoencephalomyelitis of unknown origin (MUO).
- The MUO group consists of diseases such as steroid responsive meningitis-arteritis (SRMA), eosinophilic meningoencephalomyelitis, and the numerous encephalitides including granulomatous meningoencephalomyelitis (GME) and the specific meningoencephalitides (ie necrotizing encephalitis (NE) including necrotizing meningoencephalomyelitis [NME] and necrotizing leucoencephalitis (NLE)).
- These conditions require histopathological confirmation of a CNS biopsy to form a diagnosis. However, limited tissue access, risks of morbidity and mortality together with its limited availability make it an impractical tool.
- The term ‘meningoencephalomyelitis of unknown origin’ has been coined to describe those cases in which MRI and cerebrospinal fluid (CSF) alterations indicate inflammatory non-infectious (immune-mediated) CNS disease but definitive histopathological analysis is lacking.
- In using the term MUO we have a more clinically useful group of dogs to analyze in order to ensure the best treatments are given in spite of our inability to establish a histopathological diagnosis.
- Small breeds, notably terriers are most commonly affected, although any breed can develop the disease.
- Highest incidence occurs in dogs between 4-8 years age although any age dog can be affected.
- Signs: generally, the disease causes multifocal lesions, causing a range of possible clinical presentations.
- Diagnosis: cerebrospinal fluid analysis, and CT/MRI scans.
- Treatment: corticosteroids at immunosuppressive doses, and/or other immunosuppressive drugs therapy.
- Prognosis: guarded to fair but relapses may occur. Dogs with multifocal signs, signs of raised intracranial pressure and/or herniation on MRI have a poorer prognosis.
Presenting signs
- Multifocal or disseminated (CNS) signs.
- Focal CNS signs.
- Optic neuritis Optic neuritis.
Age predisposition
- 3-7 years old most commonly, although dogs of any age can be affected.
Gender predisposition
- Females may be slightly predisposed.
Breed/Species predisposition
- Small breeds, notably terriers, more commonly affected. However, any breed can develop GME.
Cost considerations
- High costs can be incurred in diagnostic work-up.
- Immunosuppressive drugs.
- Corticosteroids.
- Repeat examinations and hematology testing if using adjunctive immunosuppressives.
- Repeat imaging and spinal fluid sampling.
- Antiepileptic medication where seizures present.
Special risks
General anesthesia
- Monitor oxygen supply carefully. Hypoxia due to seizure activity and compromise of airway may → cytoxic brain edema → raised intracranial pressure.
- Monitor PCO2 Arterial blood gas sampling. Lesions = cytotoxic edema, raided intra-cranial pressure, reduced perfusion, vasogenic edema, hypoxia,cytotoxic edema, etc → leading to brain herniation.
CSF collection
- May result in brain herniation Brain: tentorial herniation and death if clinical signs of increased intracranial pressure are present.
Pathogenesis
Pathophysiology
- MUO is assumed to have an autoimmune and genetic pathogenesis.
- In general, major factors that contribute to the development of autoimmunity are genetic susceptibility and environmental factors.
- Suspected agents include environmental or infectious antigenic triggers that might activate autoreactive cells in the CNS, although no such agent has yet been identified in the development of MUO.
- Susceptibility genes may confer susceptibility or protection for autoimmunity by influencing the maintenance of self-tolerance. Data from inbred rodent studies have identified a strong influence of genetic background as a competing influence in the variability of lymphocyte responses in clearing pathogens from the CNS and promoting neuroprotection.
- Histiocytes, or monocytes, which are derived from circulating monocytes → invade white matter following breakdown of blood-brain barrier → immune-mediated damage and general loss of structural detail and can develop into → discrete masses, especially cerebral white matter, thalamus, brain stem, cerebellum, spinal cord → increased production of intrathecal immunoglobulin.
Timecourse
- Multifocal GME Granulomeningoencephalitis typically is characterized clinically by sub-acute to acute onset and rapid progression of multifocal neurologic signs.
- Focal GME tends to have a more insidious or slower progression of neurologic signs that may suggest a space-occupying lesion.
- Ocular GME, clinically manifests with acute signs of blindness attributable to optic neuritis.
Diagnosis
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Treatment
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Prevention
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Outcomes
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Further Reading
Publications
Refereed Papers
- Recent references from PubMed and VetMedResource.
- Paušová T K, Tomek A, Šrenk P, Belašková S (2021) Clinical Presentation, Diagnostic Findings, and Long-term Survival Time in 182 Dogs With Meningoencephalitis of Unknown Origin From Central Europe That Were Administered Glucocorticosteroid Monotherapy. Top Companion Anim Med 44, 100539 doi.org/10.1016/j.tcam.2021.100539.
- Brady S L, Woodward A P, le Chevoir M (2020) Survival time and relapse in dogs with meningoencephalomyelitis of unknown origin treated with prednisolone and ciclosporin: a retrospective study. Aust Vet J 98(10), 491-498 PubMed.
- Stee K, Broeckx B J G, Targett M, Gomes S A, Lowrie M (2020) Cytosine arabinoside constant rate infusion without subsequent subcutaneous injections for the treatment of dogs with meningoencephalomyelitis of unknown origin. Vet Rec 187(11), e98 PubMed.
- Cornelis I, Van Ham L, Gielen I, De Decker S, Bhatti S F M (2019) Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: A review. Vet J 244, 37-44 PubMed.
- Lowrie M, Thomson S, Smith P, Garosi L (2016) Effect of a constant rate infusion of cytosine arabinoside on mortality in dogs with meningoencephalitis of unknown origin. Vet J 213, 1-5 PubMed.
- Coates J R, Jeffery N D (2014) Perspectives on meningoencephalomyelitis of unknown origin. Vet Clin North Am Small Anim Pract 44(6), 1157-1185 PubMed.
- Lowrie M, Smith P M, Garosi L (2013) Meningoencephalitis of unknown origin: investigation of prognostic factors and outcome using a standard treatment protocol. Vet Rec 172(20), 527 PubMed.
- Granger N, Smith P M, Jeffery N D (2010) Clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: a systematic review of 457 published cases from 1962 to 2008. Vet J 184(3), 290-297 PubMed.
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