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Comparison of clinical and radiological characteristics in autoimmune GFAP astrocytopathy, MOGAD and AQP4-IgG+ NMOSD mimicking intracranial infection as the initial manifestation

  • Author Footnotes
    1 These authors contributed equally to the work.
    Jun Xiao
    Footnotes
    1 These authors contributed equally to the work.
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to the work.
    Shuo-Qi Zhang
    Footnotes
    1 These authors contributed equally to the work.
    Affiliations
    Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to the work.
    Xin Chen
    Footnotes
    1 These authors contributed equally to the work.
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Yue Tang
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Man Chen
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Ke Shang
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Gang Deng
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Chuan Qin
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Dai-Shi Tian
    Correspondence
    Corresponding authors.
    Affiliations
    Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Author Footnotes
    1 These authors contributed equally to the work.

      Highlights

      • Symptom of tremor and meningeal irritation signs are distinct features in A-GFAP-A.
      • Higher CSF immunological profiles might be distinct features in A-GFAP-A.
      • ADEM-like lesions seemed to occur only in MOGAD.
      • Ganglia bilateral lesions, diffuse enhancement are characteristics in A-GFAP-A.
      • The three diseases masquerading as intracranial infection must be considered.

      Abstract

      Objective

      Several autoimmune CNS inflammatory diseases, including autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD) often presented initially with similar symptoms mimicking intracranial infection, are not easy to be differentiated during early-onset lacking the detection of autoantibody.

      Methods

      In our single-center cohorts, those patients mimicking intracranial infection as initial symptoms, including 9 with A-GFAP-A, 17 with MOGAD and 11 with AQP4-IgG+NMOSD, were retrospectively included. The autoantibodies were detected by cell-based assays. The clinical, immunological and radiological characteristics were summarized.

      Results

      In the cohort, tremor and positive Kernig's sign were predominated in A-GFAP-A (44.4% and 77.8%, respectively) over MOGAD (5.9%, p = 0.034; 29.4%, p = 0.038) and AQP4-IgG+NMOSD (0, p = 0.026; 18.2%, p = 0.022). Ten patients (A-GFAP-A, 4; MOGAD, 5; AQP4-IgG+NMOSD, 1) were initially misdiagnosed as tubercular or viral meningoencephalitis, however, resistant to empiric anti-tuberculosis or anti-viral treatment, and finally were in partial or complete remission with the immunotherapy when adjusted treatments. On cerebrospinal fluid (CSF) examination, white blood cell counts in CSF was higher in A-GFAP-A cohort (median, 90×106/L [IQR, 41-209]) compared to AQP4-IgG+ NMOSD (median, 6 × 106/L [IQR, 1-10], p = 0.018). Importantly, the higher increase in CSF protein (1319 mg/L [IQR, 1035-1519]), lactate dehydrogenase (LDH, 53.9 ± 37.2 U/L), lactic acid (3.50 ± 0.88 mmol/L), IgG (130.9 ± 60.4 mg/L), IgM (8.6 ± 6.1 mg/L) and IgA (23.0 ± 11.4 mg/L) levels in A-GFAP-A was found compared to MOGAD (CSF protein: 441 mg/L [IQR, 330–776], p = 0.004; LDH: 53.9  ±  37.2 U/L, p = 0.005; lactic acid: 2.15 ± 0.62 mmol/L, p = 0.001; IgG: 77.9 ± 71.3 mg/L, p = 0.018; IgM, 2.7 ± 2.9 mg/L, p = 0.015) and AQP4-IgG+ NMOSD (CSF protein: 386 mg/L [IQR, 369-453], p = 0.002; LDH: 23.7 ± 11.0 U/L, p = 0.048; lactic acid: 2.40  ±  0.66 mmol/L, p = 0.040; IgG, 53.2 ± 30.3 mg/L, p = 0.015; IgM, 2.1 ± 3.9 mg/L, p = 0.004; IgA, 5.2 ± 5.0 mg/L, p < 0.001). Of Note, smaller (< 2 cm), symmetrical lesions in ganglia and thalamus (5/8, 62.5%) were showed in over half of the A-GFAP-A patients (5/8, 62.5%), but never in MOGAD (0%, p = 0.001) and AQP4-IgG+NMOSD (0%, p = 0.026). In addition, diffuse meningeal enhancement was more common in A-GFAP-A (8, 88.9%) compared to MOGAD (5, 29.4%, p = 0.011) and AQP4-IgG+NMOSD (1/6, 16.7%, p = 0.011), respectively. Acute disseminated encephalomyelitis (ADEM) -like lesions occurred more frequently in MOGAD (6/16, 37.5%) but never in A-GFAP-A and AQP4-IgG+NMOSD (p = 0.02).

      Conclusion

      Our study demonstrates that several distinct features including the symptom of tremor, higher CSF immunological profiles, bilateral symmetrical lesions in ganglia, and diffuse meningeal enhancement are frequent in A-GFAP-A, whereas ADEM-like lesions seem to occur mainly in MOGAD. These signs provide crucial clinical implications in differential diagnosis for those mimicking intracranial infection as initial symptoms. Clinicians should consider the possibility of these autoimmune CNS inflammatory diseases masquerading as intracranial infection.

      Keywords

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