J Neurocrit Care.  2021 Jun;14(1):46-51. 10.18700/jnc.200025.

Refractory brainstem encephalitis mimicking progressive cerebral infarction: infliximab and methotrexate as a salvage immunotherapy

• Ahn SH
• Roh J
• Woo KN
• Kim HS
• Park MG
• Park KP
• Baik SK
• Shin JH

• KMID: 2517132
• DOI: http://doi.org/10.18700/jnc.200025

Abstract

Background
Brainstem encephalitis is a rare, severe, and potentially life-threatening inflammation of the central nervous system, exhibiting various treatment responses and outcomes owing to multiple etiologies.
Case Report
We describe the favorable outcome of salvage immunotherapy using a combination of infliximab and methotrexate in a 62-year-old woman with refractory brainstem encephalitis. The patient was initially presumed to be at a subacute stage of medullary infarction but showed progressively worsening conditions involving cervical myelopathy, despite having completed the schedule of subsequent immunotherapy with intravenous methylprednisolone, immunoglobulin, and rituximab. After completion of four sessions of weekly rituximab injection, she was treated with 5 mg/kg of infliximab, scheduled at 0, 2, and 6 weeks, along with methotrexate (weekly 12.5 mg). After completion of infliximab injection and maintenance with methotrexate treatment, she showed an improving course of quadriplegia.
Conclusion
This case report provides evidence for the potential efficacy of infliximab with methotrexate in cases of refractory brainstem encephalitis.

Keyword

Brainstem encephalitis; Subacute cerebral infarction; Infliximab; Immunotherapy

Figure

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  Fig. 1. Magnetic resonance imaging (MRI) findings at admission. Baseline brain MRI revealing increased signals on the diffusion-weighted imaging sequence on the right anteromedial medulla (A) with a subtle signal change on apparent diffusion coefficient sequence (B) and increased signal intensity on T2-weighted (C) and T2-weighted fluid-attenuated inversion recovery (D) sequences.

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  Fig. 2. Magnetic resonance imaging (MRI) findings at 2 weeks of hospitalization during management for infarction. Follow-up brain spine MRI revealing further increased signals on the diffusion-weighted imaging sequence on the bilateral anteromedial medulla (A) with a subtle signal change on apparent diffusion coefficient sequence (B) and increased signal intensity on T2 sequence within C1 level of the medullar oblongata and spinal cord with increased enhancement (red arrows; C, D, respectively) during the therapeutic-induced hypertension and anti-thrombotic treatment, including triple anti-platelet agents and tirofiban infusion without evidence of intraventricular and periventricular ependymal lesions (E, F).

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  Fig. 3. Magnetic resonance imaging (MRI) findings at 2 months of hospitalization after completion of conventional immunotherapy. Follow-up brain MRI revealing expansion of diffusion-restricted lesions on the diffusion-weighted image sequence to both the anteromedial medulla (A) with a subtle signal change on apparent diffusion coefficient sequence (B) and increased perilesional signal intensity on T2-weighted (C) and T2-weighted fluid-attenuated inversion recovery (D) sequences, after completion of immunotherapy including intravenous methylprednisolone and immunoglobulin following completion of four sessions of weekly rituximab treatment.

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  Fig. 4. Magnetic resonance imaging (MRI) findings at 10 months after symptom onset. Follow-up brain MRI revealing a normalized diffusion-weighted image (A) and apparent diffusion coefficient (B) sequence on both the anteromedial medullar and cervical spinal cord with decreased perilesional signal intensity on T2-weighted (C) and T2-weighted fluid-attenuated inversion recovery (D) sequences, 6 months after completion of infliximab treatment.

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  Fig. 5. Clinical course of patient. The patient’s neurological deficit (measured by Medical Research Council [MRC] sumscore) and magnetic resonance imaging findings (blue circle) worsened until 18 weeks and gradually improved after completion of the scheduled escalation of immunotherapy until 16 weeks and maintenance of PO MTX and PD, following gradual tapering after discharge (blue square) at 26 weeks after symptom onset. MRC sumscore evaluates global muscle strength including manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) on both sides using the MRC scale. Summation of scores gives MRC sumscore, ranging from 0 to 60 (0–36, quadriplegia to severe quadriparesis; 36–48, mild quadriparesis; 48–60 [max], normal strength). IV, intravenous; DA, days after onset; PO, per oral; MTX, methotrexate; PD, prednisolone; MA, months after discharge.

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