Supplementary Material for: Hypertrophic pachymeningitis with persistent intrathecal inflammation secondary to neurosarcoidosis treated with intraventricular chemotherapy: a case report

Background: Hypertrophic pachymeningitis (HP) is a rare immune-mediated disease characterized by thickening of the dura mater with consecutive cranial neuropathy. While HP is usually treated with systemic immunotherapies, response to therapy is variable and may be limited by insufficient drug concentrations in the brain. We report on a patient with HP and marked lymphocytic pleocytosis refractory to various systemic immunotherapies, who was treated with intraventricular chemotherapy. Methods: A 57-year-old patient with HP manifesting with vision and hearing loss had sustained clinical progression despite various systemic immunotherapies. Intraventricular chemotherapy with methotrexate, cytarabine and dexamethasone was initiated. We present clinical, imaging and cerebrospinal fluid (CSF) findings, including cytokine levels before and after intraventricular treatment. Results: Rapid decrease of cell count, lactate and pro-fibrotic cytokine levels in the CSF following intraventricular chemotherapy was paralleled by a mild reduction of dura thickness in MRI. The already severely impaired visual acuity and hearing loss did not progress further. Treatment was complicated by exacerbation of previously subtle psychiatric symptoms. Follow-up was terminated after 6 months as the patient suffered from a fatal ischemic stroke. Autopsy revealed neurosarcoidosis as the underlying cause of HP. Conclusion: This case report suggests that intrathecal chemotherapy can reduce the inflammatory milieu in the CNS and should be considered for treatment-refractory HP before irreversible damage of cranial nerves has occurred.

背景：肥厚性硬脑膜炎（Hypertrophic pachymeningitis, HP）是一种罕见的免疫介导性疾病，以硬脑膜增厚并继发颅神经病变为核心特征。尽管HP通常采用系统性免疫疗法治疗，但治疗应答存在显著个体差异，且可能因脑内药物浓度不足而受限。本文报告1例HP患者：该患者伴有显著脑脊液淋巴细胞增多症，对多种系统性免疫疗法均耐药，随后接受了脑室内化疗。
方法：1例57岁的HP患者，表现为视力与听力丧失，尽管接受多种系统性免疫疗法，临床症状仍持续进展。遂启动甲氨蝶呤（methotrexate）、阿糖胞苷（cytarabine）与地塞米松（dexamethasone）联合的脑室内化疗方案。本文呈现该患者的临床、影像学及脑脊液（cerebrospinal fluid, CSF）检查结果，包括脑室内治疗前后的细胞因子水平。
结果：脑室内化疗实施后，患者脑脊液中的细胞计数、乳酸及促纤维化细胞因子水平迅速下降，磁共振成像（MRI）显示硬脑膜厚度亦出现轻度降低。原本已严重受损的视力与听力未再进一步恶化。治疗过程中出现原有轻微精神症状加重的不良反应。随访6个月后，患者因致命性缺血性脑卒中终止随访。尸检结果显示，神经结节病（neurosarcoidosis）为HP的潜在致病原因。
结论：本病例报告提示，鞘内化疗可改善中枢神经系统的炎症微环境，在颅神经出现不可逆损伤前，可考虑将其用于治疗难治性HP。