SUBARACHNOID HEMORRHAGE AND CEREBRAL INFARCTION IN ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE: A CASE REPORT AND REVIEW OF THE LITERATURE

Anti-glomerular basement membrane (anti-GBM) antibodies target the α3 chain of type IV collagen in pulmonary and renal basement membranes. Clinical manifestations typically involve the kidneys and lungs, whereas central nervous system (CNS) complications are rare. CNS complications in anti-GBM disease have been reported in 23 cases, most presenting with posterior reversible encephalopathy syndrome, and none with intracranial subarachnoid hemorrhage (SAH). Here, we describe a patient with anti-GBM disease who developed SAH and cerebral infarction. Despite persistently elevated antibody titers refractory to corticosteroids and plasma exchange (PE), rituximab (RTX) induction achieved a stable and sustained decline in antibody levels.

A 53-year-old woman presented with fever, headache, and progressive renal dysfunction. Anti-GBM antibody titers exceeded the detection limit (>350 U/mL), and C-reactive protein (CRP) was 25.55 mg/dL. Renal biopsy confirmed anti-GBM disease. Chest computed tomography (CT) showed no alveolar hemorrhage. She received intravenous methylprednisolone pulse followed by oral prednisolone and PE. Despite these treatments, renal function worsened, and hemodialysis was initiated. After three PE sessions, antibody titers remained >350 U/mL, and CRP was 19.97 mg/dL, prompting a second steroid pulse and administration of RTX. Three days after RTX administration, she developed impaired consciousness, bilateral tonic seizures, and severe hypertension (HT). Brain CT revealed SAH, and magnetic resonance imaging subsequently demonstrated a subacute cerebral infarction. Both conditions improved with blood pressure control and intensified immunosuppression. In total, she underwent 22 PE sessions and four RTX doses, reducing antibody titers to 83.0 U/mL. She was discharged dialysis-dependent but without neurological sequelae, and antibody titers continued to decline during follow-up.

To date, 23 cases of anti-GBM disease with CNS complications have been reported. Most patients had HT, high antibody titers, and poor renal survival (Table 1). In patients with severe renal dysfunction, anti-GBM antibodies may recognize a broader spectrum of antigens, including α1, α2, α4, and α5 chains. Expression of α1 and α2 chains in cerebral vascular basement membranes provides a potential mechanism for direct antibody-mediated vascular injury leading to cerebrovascular complications. The current standard treatment for anti-GBM disease includes PE, corticosteroids, and cyclophosphamide (CYC). However, CYC carries significant risks, including myelosuppression, infection, malignancy, and infertility. In our case, CYC was avoided owing to the absence of alveolar hemorrhage and poor renal prognosis. Although antibody titers remained elevated following PE and corticosteroids therapy, RTX induced a gradual decline in antibody levels. This reduction persisted even after discontinuation of PE, consistent with the prolonged B-cell–depleting effect of RTX.

This case represents the first report of intracranial SAH in anti-GBM disease. CNS complications may be associated with severe renal dysfunction, high antibody titers, and HT. Clinicians should be alert to potential neurological involvement in anti-GBM disease. Furthermore, our case suggests that RTX may serve as a therapeutic option when conventional therapy fails to sufficiently reduce antibody titers.