Sarto Jordi, Caballol Berta, Berenguer Joan, Aldecoa Iban, Carbayo Álvaro, Santana Daniel, Archilla Ivan, Gaig Carles, Graus Francesc, Panés Julián, Saiz Albert
Neurology Service, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Department of Gastroenterology, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Ther Adv Neurol Disord. 2022 Feb 24;15:17562864221079682. doi: 10.1177/17562864221079682. eCollection 2022.
Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23 approved for the treatment of Crohn's disease, has shown to be an effective therapy with a favourable safety profile. Clinical trials and real-world studies have reported very few neurological adverse events, including posterior reversible encephalopathy syndrome, idiopathic intracranial hypertension and headache. We describe the case of a 48-year-old man with Crohn's disease who initiated treatment with ustekinumab on top of ongoing treatment with methotrexate 25 mg/week who presented with an acute-onset encephalopathy that rapidly evolved to severe tetraparesis and akinetic mutism, associated with extensive leukoencephalopathy and restricted diffusion on brain magnetic resonance imaging (MRI), 1 month after the second dose of ustekinumab. Comprehensive in-patient diagnostic testing ruled out vascular, demyelinating, metabolic, tumoral and infectious etiologies. Brain biopsy showed patchy infiltrates of foamy histiocytes with perivascular distribution, associated with edema, diffuse astrocytic gliosis and focal perivascular axonal destruction without demyelination, and ustekinumab-induced neurotoxicity was suspected. After drug discontinuation, the patient presented a complete clinical recovery despite the persistence of leukoencephalopathy. In conclusion, in an era in which biological therapies are continually evolving and expanding, knowledge about the potential neurotoxicity of these new therapies and their management becomes crucial. Although ustekinumab-induced encephalopathy is uncommon, the recognition of this potentially serious side effect is important because prompt withdrawal is associated with a favourable outcome. Whether methotrexate played an additional contributing role is currently unknown, but it is a factor that should be considered.
优特克单抗是一种获批用于治疗克罗恩病的抗白细胞介素（IL）-12和IL-23单克隆抗体，已被证明是一种安全有效的治疗方法。临床试验和真实世界研究报告的神经系统不良事件极少，包括后部可逆性脑病综合征、特发性颅内高压和头痛。我们描述了一名48岁克罗恩病男性患者的病例，该患者在持续接受每周25毫克甲氨蝶呤治疗的基础上开始使用优特克单抗治疗，在第二次注射优特克单抗1个月后出现急性脑病，迅速发展为严重四肢瘫痪和运动不能性缄默症，脑磁共振成像（MRI）显示广泛的白质脑病和扩散受限。全面的住院诊断检查排除了血管性、脱髓鞘性、代谢性、肿瘤性和感染性病因。脑活检显示泡沫状组织细胞呈血管周围分布的斑片状浸润，伴有水肿、弥漫性星形细胞胶质增生和局灶性血管周围轴突破坏但无脱髓鞘，怀疑是优特克单抗诱导的神经毒性。停药后，尽管白质脑病持续存在，患者仍实现了完全临床康复。总之，在生物疗法不断发展和扩展的时代，了解这些新疗法的潜在神经毒性及其管理变得至关重要。尽管优特克单抗诱导的脑病并不常见，但认识到这种潜在的严重副作用很重要，因为及时停药与良好的预后相关。甲氨蝶呤是否起到了额外的作用目前尚不清楚，但这是一个应考虑的因素。
