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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Article info
Publication history
Published online: July 20, 2022
Accepted:
July 14,
2022
Received in revised form:
July 12,
2022
Received:
March 23,
2022
Identification
Copyright
© 2022 Elsevier B.V. All rights reserved.
