Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study.

Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis. In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre. Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43). ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death.

Müller-Jensen L ，Zierold S ，Versluis JM ，Boehmerle W ，Huehnchen P ，Endres M ，Mohr R ，Compter A ，Blank CU ，Hagenacker T ，Meier F ，Reinhardt L ，Gesierich A ，Salzmann M ，Hassel JC ，Ugurel S ，Zimmer L ，Banks P ，Spain L ，Soon JA ，Enokida T ，Tahara M ，Kähler KC ，Seggewiss-Bernhardt R ，Harvey C ，Long GV ，Schöberl F ，von Baumgarten L ，Hundsberger T ，Schlaak M ，French LE ，Knauss S ，Heinzerling LM ... -  《-》

Dataset of a retrospective multicenter cohort study on characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis.

Over the past decade, cancer immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved the outcome of many malignancies. However, with the broad use of ICIs, neurological immune related adverse events (irAE) are increasingly recognized. ICI-induced encephalitis (ICI-iE) is a particularly severe irAE, often leading to treatment termination, long-term sequalae or death. Despite its high morbidity and mortality, data on clinical features and diagnostic criteria are limited. We aimed to define clinical, radiologic and laboratory characteristics of ICI-iE and identify factors that discriminate it from anti-leucine-rich glioma-inactivated (anti-LGI)-1 encephalitis and herpes simplex virus (HSV)-1 encephalitis - two alternative causes of encephalitis - to increase the awareness of ICI-iE and improve its diagnosis and management. To that end, we retrospectively collected 30 cases of ICI-iE that were reported to the Side Effect Registry Immuno-Oncology (SERIO) and 46 cases of anti-LGI1 encephalitis or herpes simplex virus (HSV)-1 encephalitis that presented to a large German neurological referral center (Charité Universitätsmedizin Berlin) between January 2015 and September 2021. Signs and symptoms, imaging and electroencephalogram features, laboratory findings and outcome measures were assessed using standardized case report forms as well as patients' medical records and compared between the groups. The data reported here represents the largest primary cohort of patients with ICI-iE to date and the first comparison with other types of encephalitis. As all three disorders - ICI-iE, HSV-1 encephalitis and anti-LGI1 encephalitis - are rare neurological entities, this dataset can be used as a reference in future clinical studies on ICI-induced neurotoxicity, neurological autoimmune disorders, and central nervous system infections.

Müller-Jensen L ，Zierold S ，Versluis JM ，Boehmerle W ，Huehnchen P ，Endres M ，Mohr R ，Compter A ，Blank CU ，Hagenacker T ，Meier F ，Reinhardt L ，Gesierich A ，Salzmann M ，Hassel JC ，Ugurel S ，Zimmer L ，Banks P ，Spain L ，Soon JA ，Enokida T ，Tahara M ，Kähler KC ，Seggewiss-Bernhardt R ，Harvey C ，Long GV ，Schöberl F ，von Baumgarten L ，Hundsberger T ，Schlaak M ，French LE ，Knauss S ，Heinzerling LM ... -  《Data in Brief》

Encephalitis Induced by Immune Checkpoint Inhibitors: A Systematic Review.

Velasco R ，Villagrán M ，Jové M ，Simó M ，Vilariño N ，Alemany M ，Palmero R ，Martínez-Villacampa MM ，Nadal E ，Bruna J ... -  《-》

CHI3L1 in the CSF is a potential biomarker for anti-leucine-rich glioma inactivated 1 encephalitis.

Anti-leucine-rich glioma inactivated 1(LGI1) encephalitis is one rare autoimmune encephalitis which is accompanied by inflammatory responses. (Anti-leucine-rich glioma inactivated 1 (anti-LGI1) encephalitis is an autoimmune disease mediated by inflammatory responses.)This study aimed to investigate the Chitinase 3-like 1(CHI3L1) in anti-LGI1encephalitis patients and evaluate its association with modified Rankin Scale (mRS) score in anti-LGI1 encephalitis at admission and 6 months follow-up.(This study looked into the relationship between Chitinase 3-like 1 (CHI3L1) and the modified Ranking Scale (mRS) score in anti-LGI1 encephalitis patients at admission and 6 months later.). Thirty-five patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease were enrolled in this study. (We enrolled 35 patients with anti-LGI1 encephalitis and 22 patients with non-inflammatory neurological disease.)Cerebrospinal fluid (CSF) and serum levels of CHI3L1 were measured by enzyme-linked immunosorbent assay. (We quantified CHI3L1 in the serum and cerebrospinal fluid (CSF) by performing an enzyme-linked immunosorbent assay.)Patients were evaluated for mRS score at admission and at 6 months follow-up.(We recorded the mRS score of the patients at admission and 6 months later.). CHI3L1 levels in CSF and serum were highly elevated in patients with anti-LGI1 encephalitis at admission compared those with the controls.(At admission, patients with anti-LGI1 encephalitis had elevated CHI3L1 levels in the CSF and serum.) Additionally, patients presenting with cognitive impairment had significantly higher CSF CHI3L1 levels and mRS scores than those without cognitive impairment symptoms. Patients presenting with only faciobrachial dystonic seizures at admission had lower CSF CHI3L1 levels than those with other symptoms. Finally, CSF CHI3L1 levels were positively correlated with CSF lactate levels. CHI3L1 level in CSF is correlated with the severity and prognosis of anti-LGI1 encephalitis. (CSF CHI3L1 levels are correlated with the severity and prognosis of anti-LGI1 encephalitis.).

Li J ，Li H ，Wang Y ，Zhao X ，Wang S ，Li L ... -  《Frontiers in Immunology》

Cytokines/chemokines and immune checkpoint molecules in anti-leucine-rich glioma-inactivated 1 encephalitis.

We aimed to investigate levels of cytokines/chemokines and immune checkpoint molecules in patients with anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. The study recruited 12 patients with anti-LGI1 encephalitis and six non-inflammatory controls from the Qilu Hospital of Shandong University treated between January 2019 and December 2020. Serum levels of 30 cytokines/chemokines and 10 checkpoint molecules were measured in participants of both the groups. In contrast to those in the control group, 24 cytokines/chemokines and 5 immune checkpoint molecules were differentially expressed in patients with anti-LGI1 encephalitis, with 14 cytokines being upregulated and 10 being downregulated. There were 1033 enriched biological processes and 61 enriched Kyoto Encyclopedia of Genes and Genomes signaling pathways. A wide range of cytokines/chemokines and immune checkpoint molecules are implicated in immune regulation in anti-LGI1 encephalitis, indicating that they may serve as important targets in the development and treatment of the disease.

Qiao S ，Zhang SC ，Li HY ，Wang ZH ，Jin Y ，Wang AH ，Liu XW ... -  《-》