Anti-GM2 IgG-positive autoimmune brainstem encephalitis presenting as a stroke mimic: a case report and literature review

Technical Summary: Anti-GM2 IgG-positive Autoimmune Brainstem Encephalitis Presenting as a Stroke Mimic

Problem Statement
Autoimmune encephalitis involving the brainstem is a rare and diagnostically challenging condition. It frequently presents with acute focal neurological deficits that closely mimic cerebrovascular disease (stroke). While anti-ganglioside antibodies are well-recognized in peripheral nervous system disorders (e.g., Miller Fisher syndrome), their role in central nervous system (CNS) inflammatory diseases, particularly those associated with Anti-GM2 antibodies, remains incompletely understood. A significant clinical dilemma arises when patients present with severe brainstem syndromes but lack corresponding abnormalities on standard neuroimaging (MRI and CTA), leading to potential misdiagnosis as ischemic stroke or other etiologies.

Methodology
This study employs a single-case report design combined with a literature review.

• Case Subject: A 28-year-old previously healthy male presenting with a 2-day history of acute vertigo, diplopia, right-sided facial numbness, and gait ataxia.
• Diagnostic Workup:
  • Neuroimaging: Brain MRI (T1, T2-FLAIR, DWI) and Computed Tomography Angiography (CTA) were performed to rule out acute infarction, structural lesions, or vascular occlusion.
  • Cerebrospinal Fluid (CSF) Analysis: Lumbar puncture was conducted to assess protein levels, lactate dehydrogenase (LDH), and immunoglobulins (IgG, IgA).
  • Serology and Immunology: Extensive screening included testing for anti-GM2 IgG, other ganglioside antibodies (anti-GQ1b), demyelinating antibodies (MOG-IgG, AQP4-IgG), autoimmune encephalitis panels (NMDAR, LGI1, CASPR2), and paraneoplastic syndromes.
  • Infectious and Systemic Screening: Comprehensive workup for viral (EBV, CMV, HSV, Toxoplasma) and bacterial infections, alongside systemic malignancy screening.
  • Electrophysiology: Nerve conduction studies, somatosensory evoked potentials, and EEG were utilized.
• Intervention: The patient was treated with intravenous methylprednisolone (80 mg/day for 3 days) followed by an oral corticosteroid taper.
• Literature Review: The authors synthesized data from previously reported cases of Anti-GM2 associated CNS involvement to contextualize the current findings.

Key Results

• Clinical Presentation: The patient exhibited a classic brainstem syndrome (bilateral abducens nerve palsy, right trigeminal sensory impairment, limb ataxia) with an abrupt onset suggestive of posterior circulation stroke.
• Imaging Discrepancy: A critical finding was the "clinicoradiological dissociation." Despite severe neurological deficits, MRI sequences (including DWI) and CTA revealed no evidence of acute infarction, structural abnormalities, or vascular stenosis.
• Laboratory Findings:
  • CSF showed mildly elevated protein (0.46 g/L), elevated LDH (71 U/L), and slight elevations in IgG and IgA.
  • Serum testing was positive for Anti-GM2 IgG antibodies (30 AU).
  • All other autoimmune, demyelinating, paraneoplastic, and infectious markers were negative.
• Treatment Outcome: The patient demonstrated significant clinical improvement following corticosteroid therapy, with resolution of vertigo and sensory symptoms and marked recovery of ocular movements and coordination.
• Literature Synthesis: The review identified a spectrum of Anti-GM2 associated CNS disorders, including rhombencephalitis and Bickerstaff brainstem encephalitis (BBE)-like syndromes. While some cases involved multiple antibodies or paraneoplastic contexts, this case represents a distinct presentation of isolated Anti-GM2 IgG positivity mimicking an acute stroke.

Key Contributions

• Expansion of Clinical Spectrum: This report documents a rare instance of Anti-GM2 IgG-positive autoimmune brainstem encephalitis in a young male, expanding the known clinical manifestations of Anti-GM2 antibodies beyond peripheral neuropathies and typical BBE presentations.
• Diagnostic Paradigm: The study highlights the critical importance of considering autoimmune etiologies in young patients with "stroke-like" presentations when neuroimaging is incongruent with clinical severity.
• Therapeutic Validation: It provides evidence that corticosteroid therapy can be effective for Anti-GM2 associated brainstem encephalitis, even in the absence of overt radiological lesions.

Significance and Claims
The authors claim that this case underscores the limitations of conventional neuroimaging in detecting antibody-mediated neuronal dysfunction. They posit that the presence of Anti-GM2 antibodies can drive severe neurological deficits without visible structural damage on MRI.

The significance of this work lies in its call for increased clinical awareness:

1. Diagnostic Vigilance: Autoimmune brainstem encephalitis should be a primary differential diagnosis for young patients with acute focal deficits and normal imaging.
2. Expanded Testing: In atypical brainstem syndromes where standard evaluations are unrevealing, expanded antibody panels, including antiganglioside antibodies, may provide necessary diagnostic insights.
3. Outcome Optimization: Early recognition and prompt initiation of immunotherapy (such as corticosteroids) can lead to favorable outcomes and prevent unnecessary interventions for presumed cerebrovascular disease.

The paper concludes that while standardized treatment strategies for antiganglioside antibody-associated encephalitis are not yet defined, this case supports the utility of early immunotherapy in improving patient outcomes.