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.

中文翻译：

---

自身免疫性 GFAP 星形细胞病、MOGAD 和 AQP4-IgG+ NMOSD 以模拟颅内感染为初始表现的临床和放射学特征比较

客观的

几种自身免疫性中枢神经系统炎症性疾病，包括自身免疫性胶质纤维酸性蛋白星形细胞病 (A-GFAP-A)、髓鞘少突胶质细胞糖蛋白抗体相关疾病 (MOGAD) 和水通道蛋白-4-免疫球蛋白-G 阳性视神经脊髓炎谱系疾病 (AQP4-IgG ⁺ NMOSD) 最初常表现为类似颅内感染的症状，在缺乏自身抗体检测的早期发病时不易鉴别。

方法

在我们的单中心队列中，回顾性纳入了以颅内感染为初始症状的患者，包括 9 例 A-GFAP-A、17 例 MOGAD 和 11 例 AQP4-IgG ⁺ NMOSD。通过基于细胞的测定法检测自身抗体。总结了临床、免疫学和放射学特征。

结果

在该队列中，震颤和阳性 Kernig 征在 A-GFAP-A（分别为 44.4% 和 77.8%）高于 MOGAD（5.9%，p  = 0.034；29.4%，p  = 0.038）和 AQP4-IgG ⁺ NMOSD（ 0，p  = 0.026；18.2%，p  = 0.022）。10 例患者（A-GFAP-A，4 例；MOGAD，5 例；AQP4-IgG ⁺ NMOSD，1 例）最初被误诊为结核性或病毒性脑膜脑炎，但对经验性抗结核或抗病毒治疗耐药，最终进入调整治疗后，免疫治疗可部分或完全缓解。在脑脊液（CSF）检查中，A-GFAP-A 队列中 CSF 中的白细胞计数较高（中位数，90×10 ⁶/L [IQR，41-209]）与 AQP4-IgG ⁺ NMOSD（中位数，6 × 10 ⁶ /L [IQR，1-10]，p  = 0.018）相比。重要的是，脑脊液蛋白 (1319 mg/L [IQR, 1035-1519])、乳酸脱氢酶 (LDH, 53.9 ± 37.2 U/L)、乳酸 (3.50 ± 0.88 mmol/L)、IgG (130.9 ±与 MOGAD（CSF 蛋白：441 mg/L [IQR，330– 776]，p  = 0.004；LDH：53.9 ± 37.2 U/L，p  = 0.005；乳酸：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) 和 AQP4-IgG ⁺NMOSD（CSF 蛋白：386 mg/L [IQR，369-453]，p  = 0.002；LDH：23.7 ± 11.0 U/L，p  = 0.048；乳酸：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)。值得注意的是，超过一半的 A-GFAP-A 患者 (5/8, 62.5%) 出现了较小 (< 2 cm) 的对称性神经节和丘脑病变 (5/8, 62.5%)，但在 MOGAD 中从未出现(0%, p  = 0.001) 和 AQP4-IgG ⁺ NMOSD (0%, p  = 0.026)。此外，与 MOGAD (5, 29.4%, p  = 0.011) 和 AQP4-IgG相比，A-GFAP-A (8, 88.9%) 中弥漫性脑膜增强更常见⁺ NMOSD (1/6, 16.7%, p  = 0.011)，分别。急性播散性脑脊髓炎 (ADEM) 样病变在 MOGAD 中更常见（6/16, 37.5%），但在 A-GFAP-A 和 AQP4-IgG ⁺ NMOSD 中从未出现（p  = 0.02）。

结论

我们的研究表明，在 A-GFAP-A 中常见一些明显的特征，包括震颤症状、较高的 CSF 免疫学特征、双侧对称性神经节病变和弥漫性脑膜强化，而 ADEM 样病变似乎主要发生在 MOGAD。这些体征为那些以颅内感染为初始症状的患者的鉴别诊断提供了重要的临床意义。临床医生应考虑这些自身免疫性中枢神经系统炎性疾病伪装成颅内感染的可能性。