Immune-Related Cerebellar Ataxia: A Rare Adverse Effect of Checkpoint Inhibitor Therapy

Sebbag, E.; Psimaras, Dimitri; Baloglu, Seyyid; Bourgmayer, Agathe; Moinard-Butot, Fabien; Barthélémy, Philippe; Tranchant, Christine; Honnorat, Jérôme; Bender, Laura

doi:10.1007/s11481-021-10026-3

Cited by 8 publications

(11 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A case of acute cerebellar ataxia due to Epstein-Barr virus (EBV) infection following ICI administration was interpreted as activation of the virus under the affected immune system (13). Autoimmune antibodies, including anti-Zic4, anti-TRIM9, and GAD65, have been detected in some cases (4,14,15). Additionally, obvious cognitive impairment supports parenchymal involvement, which is not limited to the cerebellum.…”

Section: Discussionmentioning

confidence: 99%

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

et al. 2022

View full text Add to dashboard Cite

Toripalimab (Junshi Bioscience Co., Ltd) is a new immune checkpoint inhibitor (ICI) that targets programmed cell death protein 1 (PD-1) in various cancers, including metastatic melanoma. No neurological immune-related adverse events (n-irAEs) of toripalimab have been reported, except for neuromuscular involvement. We report a case of a 63-year-old woman who presented with severe vertigo, vomiting, nystagmus, cerebellar ataxia, and cognitive impairment after toripalimab treatment for metastatic melanoma. Compared with the concomitant cognitive dysfunction and a pathological reflex involving the cerebral cortex, the signs and symptoms of cerebellar involvement were much more prominent. Anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody was positive in both serum and cerebrospinal fluid (CSF). After intravenous immunoglobulin (IVIG) and methylprednisolone (IVMP) administration, the symptoms of vertigo and vomiting resolved, with cognitive impairment and cerebellar ataxia remaining. This is the first report of autoimmune encephalitis (AIE) as an n-irAE of toripalimab.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Therefore, we tested whether immunoblot is as sensitive as CBA. Cases 2, 3, and 4 were previously shown to recognize the 95 and 72kDa bands 1,2 . CSF from newly reported Cases 1 and 5 primarly recognized the 95 and 72kDa bands, whereas Cases 9 and 11 recognized TRIM9/67 and additional bands, suggesting the presence of other antineural antibodies.…”

Section: Resultsmentioning

confidence: 87%

“…Seven of 10 (Cases 1–6 and 10) presented with subacute cerebellar syndrome, 3 of which (Cases 2–4) were previously published 1,2 . All cerebellar syndrome cases developed a pancerebellar syndrome over 3 to 4 weeks.…”

Section: Resultsmentioning

confidence: 98%

“…Cases 2, 3, and 4 were previously shown to recognize the 95 and 72kDa bands. 1,2 CSF from newly reported Cases 1 and 5 primarly recognized the 95 and 72kDa bands, whereas Cases 9 and 11 recognized TRIM9/67 and additional bands, suggesting the presence of other antineural antibodies. In contrast, Cases 7 and 8 both produced a lower band of approximately 60kDa but no bands at the expected molecular weights (see Fig 3E).…”

Section: Detection Of Trim9/67-igg By Immunoblotmentioning

confidence: 89%

“…ANN NEUROL 2023;94:1086-1101 C o-occurring TRIM9/67 autoantibodies (TRIM9/ 67-IgG) are proposed paraneoplastic biomarkers that are associated with a subacute pancerebellar syndrome, typically in the setting of lung cancer. [1][2][3] Importantly, TRIM9/67-IgG has not been detected in the sera or cerebrospinal fluid (CSF) of small cell lung cancer (SCLC) patients without a paraneoplastic neurological syndrome (PNS), autoimmune encephalitis patients, or patients with noninflammatory neurodegenerative disorders. 1 Therefore, TRIM9/67-IgG is not a general marker of cancer or neural injury.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Detection of High‐Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins

Bartley,

Ngo,

et al. 2023

Annals of Neurology

View full text Add to dashboard Cite

Co‐occurring anti‐tripartite motif‐containing protein 9 and 67 autoantibodies (TRIM9/67‐IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67‐IgG detection are not known. We performed a retrospective, multi‐center study to evaluate the cerebrospinal fluid (CSF) and serum of candidate TRIM9/67‐IgG cases by tissue‐based immunofluorescence (TBIF), peptide phage display immunoprecipitation sequencing (PhIP‐Seq), overexpression cell‐based assay (CBA), and immunoblot. Cases in whom TRIM9/67‐IgG was detected by at least two assays were considered TRIM9/67‐IgG positive. Among these cases (N=13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67‐IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (N = 7/10), followed by encephalitis (N = 3/10). Of these ten, 70% had comorbid cancer (7/10), 85% of whom (N = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (N = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. TRIM9/67‐IgG are rare but likely high‐risk paraneoplastic biomarkers for which CBA appears to be the most sensitive diagnostic assay.This article is protected by copyright. All rights reserved.

show abstract

Anti-inflammatories/atezolizumab

2023

Reactions Weekly

View full text Add to dashboard Cite

Immune-Related Cerebellar Ataxia: A Rare Adverse Effect of Checkpoint Inhibitor Therapy

Cited by 8 publications

References 12 publications

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

Anti-GAD65 Antibody-Associated Autoimmune Encephalitis With Predominant Cerebellar Involvement Following Toripalimab Treatment: A Case Report of a Novel irAE of Toripalimab

Detection of High‐Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins

Anti-inflammatories/atezolizumab

Contact Info

Product

Resources

About