The white matter was unremarkable with normal cell density, normal appearing myelin sheets, and no staining abnormalities for proteolipid protein, myelin basic protein, and myelin oligodendroglial glycoprotein. work-up of CNS toxicity and irAEs related to immune checkpoint inhibitor treatment. development of autoimmune reactions, patients with pre-existing autoimmune disorders were excluded from clinical trials. Still, immune-related adverse events (irAEs) distinct from side-effects observed with conventional cytotoxic chemotherapy. They arise from systemic inflammation and included dermatologic, gastrointestinal, hepatic, respiratory, renal, and endocrine manifestations (16). In this regard, transverse myelitis, meningitis, posterior reversible encephalopathy syndrome (PRES), and limbic encephalitis were observed in the clinical trials of nivolumab (Opdivo?, Bristol-Myers-Squibb, New York, NY, USA) (17). Cases of detrimental and fatal irAEs of the central nervous system (CNS) in the post-marketing phase such as immune-mediated encephalitis and myelitis sparked further interest in these conditions (18C23). There is insufficient understanding of the pathomechanisms leading to CNS toxicity and subsequent management (24). Thus, the U.S. Food and Drug Administration issued an ongoing post-marketing requirement for enhanced pharmacovigilance to evaluate incidence, severity and outcomes. Here, we expand the spectrum of checkpoint inhibitor-related toxicity to the CNS by reporting a fatal and histologically proven case of necrotizing encephalopathy after two cycles of nivolumab as second-line treatment for squamous NSCLC. Case Presentation A 67-year-old woman was diagnosed with squamous NSCLC 1?year before 3-Methoxytyramine the current admission, details of the subsequent clinical course are CDC25C outlined in Figure ?Figure1.1. The work-up including PET/CT and analysis of the specimen removed by partial resection of the lower lobe of the right lung, pleura, and specimens of the sixth rib staged the tumor as pT3; pN0 (0/14); L0, V0; G2-G3; R0. Further immunohistological analyses showed the following reactivities: CK-5/6 (+), ALK D5-F3 (?), c-MET (++ to +++), PD-L1, and PD-1 (?), PI3K (?). Her comorbidities included hypertension, chronic renal insufficiency, recurrent hyponatremia, hypercholesterinemia, peripheral arterial occlusive disease, depression/anxiety disorder, and smoking (25 pack years). She developed nausea, vomiting, and generalized weakness in the postoperative course and was treated for hypertension and hyponatremia. Brain CT revealed wide-spread bilateral hypodense lesion in the subcortical 3-Methoxytyramine white matter of the frontal, parietal, and occipital lobe (Figures ?(Figures2A,B),2A,B), which had vanished on follow-up 8?days later. Our patient recovered within a few days, and the episode was classified as reversible encephalopathy syndrome. The subsequent 24?h blood pressure monitoring revealed mean systolic day- and nighttime blood pressure of 135 and 142?mmHg, respectively. Open in a separate window Figure 1 Clinical, therapeutic, and radiological course. Abbreviations: CSF cerebrospinal fluid; d, days; EEG, electroencephalography; GE, gadolinium-enhancement; IVIG, intravenous 3-Methoxytyramine immunoglobulin; JCV-PCR John Cunningham virus-polymerase chain reaction; MP, methylprednisolone; MRI, magnetic resonance imaging; NCSE, non-convulsive status epilepticus. Open in a separate window Figure 2 Neuroimaging. Brain CT in the postoperative course after the patient developed nausea, vomiting, and generalized weakness. The red arrows point at revealing wide-spread bilateral hypodensities in the subcortical white matter of the frontal, parietal, and occipital lobe (A,B). Brain MRI findings on day 14 of month 1 of the first nivolimab course. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) showing multiple bilateral hyperintensities in gray cerebellar matter [(C), red arrows]. (D) T1-contrast enhanced images on the same level as image [(A) (red arrow)]. (D) MRI FLAIR images showing bilateral thalamic hyperintensities with corresponding T1-contrast enhancement left.
- One unit of SOD activity was defined as the amount of enzyme that inhibits the photochemical reduction of nitroblue tetrazolium to 50%, considering the absorbance of the control mixture as 100%
- We thank Dr