The first remission feels like a win — the dog’s seizures stop, balance improves, and the MRI finally looks clean. 

But weeks or months later, the familiar signs creep back: a sudden stumble, a tilted head, or new seizures. 

Relapse in meningoencephalitis of unknown origin (MUO) is often unpredictable and what’s worse, it rarely looks the same the second time around. 

Let’s break down how to recognize, confirm, and manage relapse — the way it unfolds in real clinical practice. 

Step 1: When the Signs Reappear 

Relapse often doesn’t mimic the first episode. 

A dog that initially had forebrain signs may now show cerebellar ataxia or cranial nerve deficits. 

Recent data show that over half of relapsing MUO cases demonstrate a shift in neuroanatomical localization — meaning new areas of the brain are affected during relapse¹. 

This pattern reflects the evolving, migratory nature of immune-mediated inflammation in the central nervous system. 

So, when new neurological deficits appear, think about relapse first — not a new disease. 

Act early, because delayed response allows the inflammation to spread. 

Step 2: Confirming Relapse — Why MRI and CSF Still Matter 

Once relapse is suspected, repeat imaging and CSF testing remain the gold standard. 

Studies show that most dogs (77%) develop new or persistent MRI lesions at relapse, particularly in the parietal and forebrain regions¹. 

Even clinically stable dogs can have silent disease progression — in one series, 44% had normal exams but active MRI lesions¹. 

CSF findings at relapse tend to be milder than at first presentation, often showing lower nucleated cell counts and fewer lymphocytes. 

This is likely due to ongoing immunomodulatory therapy that suppresses but doesn’t eliminate inflammation. 

Clinical takeaway: Less pleocytosis doesn’t mean less disease. 

Always interpret MRI, CSF, and clinical evolution together — not in isolation. 

Step 3: Adjusting Therapy Without Overreacting 

When relapse is confirmed, the reflex is often to raise the steroid dose. 

But evidence now supports a more strategic approach: a combination of immunosuppressive therapy provides better long-term control and survival². 

Dogs maintained on a second-line agent such as cytarabine, cyclosporine, or leflunomide alongside corticosteroids had significantly longer relapse-free intervals. 

Early relapse is often linked to short induction phases or premature tapering ². 

Therapy should therefore extend beyond the point of clinical remission — think of it as immune conditioning rather than temporary suppression. 

Practical tip: 

• Reinforce or reintroduce adjunct immunosuppressants rather than relying on high-dose steroids alone. 

• Continue dual therapy for at least 12 months after remission. 

• Reassess every 8–12 weeks, adjusting gradually based on clinical and laboratory stability. 

Step 4: Detecting the Silent Phase 

One of the most critical insights from recent data is that relapse can occur before clinical signs return. 

Lesions may silently evolve while the dog appears neurologically normal¹. 

This highlights the need for structured follow-up that includes: 

• Routine neurological exams 

• Periodic MRI (every 6–9 months if feasible) 

• CSF reassessment when subtle behavioral or coordination changes arise 

Encourage owners to record videos of minor changes — what seems insignificant at home often provides valuable clues during re-evaluation. 

Step 5: Communication and Compliance 

Relapse can deeply discourage owners who thought the condition was cured. 

Reframing the discussion helps: MUO behaves like chronic immune diseases such as multiple sclerosis; relapse is possible but manageable with consistent therapy. 

Informed owners make better partners. 

Share clear tapering schedules, adverse effect checklists, and red flags for relapse. 

Setting expectations early improves adherence, which directly impacts long-term stability. 

Step 6: Looking Forward — From Control to Customization 

Emerging evidence shows that MUO cannot be managed with a single protocol. 

The disease evolves dynamically; lesions resolve in some areas while new one's form elsewhere¹. Hence, treatment must evolve too. 

Future strategies include: 

• Tailored immunotherapy guided by MRI and CSF markers 

• Cytokine and microglial profiling to predict flares before they occur 

• Precision tapering using serial imaging to confirm true immune remission 

Such approaches aim to move from broad immune suppression to immune recalibration, preserving protection while preventing relapse. 

In Summary 

Relapse doesn’t mean treatment failure — it signals disease adaptation. 

The key lies in staying one step ahead with vigilant monitoring and individualized therapy. 

Practical summary for clinicians: 

• Suspect relapse when new neurological patterns emerge. 

• Confirm with MRI and CSF — mild inflammation can still be an active disease. 

• Extend combination therapy beyond remission to build durable immune control. 

• Schedule proactive follow-ups — catching subclinical relapse changes outcomes. 

With structured follow-up and adaptive therapy, long-term MUO care is evolving from reactive management to preventive medicine — guided by growing evidence and refined protocols^1,2. 

References 

1. Orgonikova I, Dancer S, Brocal J, De Decker S, Danciu CG, Martin L, Gutierrez-Quintana R, Gonçalves R, Faller KM. Relapsing meningoencephalitis of unknown origin in dogs results in changes in neuroanatomical localization, magnetic resonance imaging, and cerebrospinal fluid. J Am Vet Med Assoc. 2025 Sep 10;1(aop):1–10. 
2. Gonsalves R, Van Ham L, De Decker S, Bhatti SF. Long-term outcomes and relapse predictors in dogs with meningoencephalitis of unknown origin treated with combined immunosuppressive therapy: a multicentre retrospective study. Vet Rec. 2025;198(4):e2249.