In a 47‑day intensive care unit (ICU) patient with schizophrenia, alcohol excess, seizures, low Glasgow Coma Scale (GCS), magnetic resonance imaging (MRI)‑confirmed rhombencephalitis, lung consolidation, positive GQ1b antibody, hypercalcemia, and myositis ossificans, what is the likely cause of the rhombencephalitis and what is the clinical significance of the myositis ossificans?

Rhombencephalitis in a Complex ICU Patient: Etiology and Clinical Significance

Most Likely Cause of Rhombencephalitis

The combination of rhombencephalitis with positive GQ1b antibody in this critically ill patient most likely represents either Listeria monocytogenes infection (given the prolonged ICU course, immunocompromised state from alcohol excess, and lung consolidation) or an autoimmune Bickerstaff brainstem encephalitis (BBE) triggered by antecedent infection, though the two can occasionally overlap. 1, 2

Primary Differential: Listeria vs. Autoimmune

Listeria monocytogenes is the most common infectious cause of rhombencephalitis and should be your top consideration given: 1

• Alcohol excess creates immunocompromise predisposing to Listeria infection 1
• Prolonged ICU course (47 days) with lung consolidation suggests possible bacteremic seeding 1
• Seizures and low GCS are consistent with Listeria rhombencephalitis, which typically presents with brainstem dysfunction 1, 2
• Listeria rhombencephalitis occurs in 75% with CSF pleocytosis and nearly 100% with abnormal brain MRI 1

However, the positive GQ1b antibody complicates this picture significantly: 2, 3, 4

• GQ1b antibody positivity typically indicates Bickerstaff brainstem encephalitis (BBE), an autoimmune condition characterized by external ophthalmoplegia, ataxia, and altered consciousness 4
• BBE often follows respiratory or gastrointestinal infections (50% of cases), which could explain the lung consolidation 4
• Critically, one case report documented Listeria rhombencephalitis WITH GQ1b antibody positivity, suggesting Listeria infection may trigger autoimmune responses 2
• This patient initially received immunosuppressive therapy for presumed BBE but only improved with antimicrobial therapy targeting Listeria 2

Diagnostic Algorithm

Immediate actions required: 1

1. Review blood and CSF cultures - Listeria grows in standard cultures; positive cultures are most specific for diagnosis 1
2. Review CSF PCR results - HSV PCR should have been sent (HSV is third most common cause of rhombencephalitis) 1
3. Assess MRI pattern - Listeria typically shows brainstem and cerebellar signals, sometimes with hemorrhagic foci 2
4. Check if empiric ampicillin was started - This is critical for Listeria coverage 1

Treatment decision tree: 1, 2

• If cultures positive for Listeria OR high clinical suspicion: Continue ampicillin (or meropenem) plus trimethoprim-sulfamethoxazole for 4-6 weeks minimum 2
• If cultures negative but GQ1b positive with typical BBE features: Consider IVIG or plasma exchange 4
• If uncertain: Treat BOTH possibilities - continue antibiotics while adding immunotherapy, as the case report showed limited efficacy of immunosuppression alone when Listeria was the underlying cause 2

Other Etiologies to Consider

Herpes simplex virus (HSV): 1

• Third most common infectious cause of rhombencephalitis (80% HSV-1,20% HSV-2) 1
• 50% have isolated brainstem involvement, 50% also involve temporal/frontal lobes 1
• Mortality 22% with acyclovir vs. 75% without 1
• Should have received empiric acyclovir 10 mg/kg IV every 8 hours at presentation 5, 1

Enterovirus 71: 1

• Second most common infectious cause globally, but 95% of cases in Asian-Pacific region 1
• No specific treatment available 1

Behçet disease (autoimmune): 1

• Over 90% have abnormal MRI, 94% have CSF pleocytosis 1
• Treatment with corticosteroids and immunosuppressives, but only 25% achieve complete recovery 1

Clinical Significance of Myositis Ossificans

The myositis ossificans in this patient is almost certainly a complication of prolonged immobilization and ICU care, NOT directly related to the rhombencephalitis etiology. 6

Why Myositis Ossificans Developed

Prolonged ICU immobilization is the primary risk factor: 6

• This patient has been immobilized for 47 days in ICU 6
• Myositis ossificans typically occurs in skeletal muscle (most commonly quadriceps, adductors, brachialis) following trauma or prolonged immobility 6
• The condition represents benign, self-limiting ossification of soft tissue 6

Clinical Implications

Impact on rehabilitation and recovery: 6

• Pain and swelling at affected sites will limit range of motion 6
• Delayed mobilization - patients typically progress to light activity at 2-3 months, full activity by 6 months, pre-injury level by 1 year 6
• Conservative management is appropriate for most cases with excellent outcomes 6
• Surgical excision only indicated for persistent symptoms or progressive disease 6

Diagnostic considerations: 6

• Plain radiographs may miss early lesions 6
• MRI is gold standard for imaging soft tissue masses 6
• Ultrasound can serve as early screening modality 6

No Direct Connection to Rhombencephalitis

The myositis ossificans is a separate complication of critical illness, not a clue to the encephalitis etiology: 6

• It does not help differentiate between infectious vs. autoimmune causes 6
• It represents a musculoskeletal complication of prolonged immobilization rather than a neurological manifestation 6
• Management should focus on preventing further ossification through gentle range-of-motion exercises once the acute encephalitis is controlled 6

Critical Management Priorities

Address the hypercalcemia urgently: 6

• Hypercalcemia may be related to myositis ossificans (heterotopic ossification can cause calcium dysregulation) or represent a separate paraneoplastic process 6
• Severe hypercalcemia worsens mental status and can confound neurological assessment 6
• Aggressive hydration and bisphosphonates if severe 6

Ensure adequate antimicrobial coverage: 1, 2

• Ampicillin 2g IV every 4 hours (or meropenem if penicillin-allergic) PLUS trimethoprim-sulfamethoxazole for Listeria coverage 2
• Acyclovir 10 mg/kg IV every 8 hours should have been started empirically and continued until HSV definitively excluded 5, 1
• Duration: minimum 4-6 weeks for Listeria rhombencephalitis 2

Consider immunotherapy if cultures remain negative: 2, 4

• IVIG 0.4 g/kg/day for 5 days or plasma exchange 5-10 sessions 4
• However, the case report showed limited efficacy when Listeria was the underlying cause 2
• Do not stop antibiotics even if starting immunotherapy 2