scholarly journals Acute cerebellar ataxia due to Epstein-Barr virus under administration of an immune checkpoint inhibitor

2019 ◽  
Vol 12 (12) ◽  
pp. e231520 ◽  
Author(s):  
Hirotaka Saikawa ◽  
Hiromi Nagashima ◽  
Tetsuya Maeda ◽  
Makoto Maemondo

A 71-year-old male patient with adenocarcinoma of the lung and contralateral lung metastasis under administration of pembrolizumab had symptoms of cerebellar ataxia. We suspected that the symptoms were immune-related adverse events (irAE), but the patient was subsequently diagnosed as cerebellitis due to Epstein-Barr virus (EBV) infection. After steroid pulse therapy, the symptoms of cerebellar ataxia improved immediately. Immune checkpoint inhibitors (ICI) can induce neurological adverse events and cause acute cerebellar ataxia. Initially, irAEs were suspected in this case. His clinical data suggested that reactivation of the virus had occurred because the ICI affected his immune system. This is the first report of a case of acute cerebellar ataxia due to EBV under administration of an ICI.

Neurology ◽  
1994 ◽  
Vol 44 (8) ◽  
pp. 1506-1506 ◽  
Author(s):  
H. Ito ◽  
S. Sayama ◽  
S. Irie ◽  
N. Kanazawa ◽  
T. Saito ◽  
...  

2019 ◽  
Vol 90 (e7) ◽  
pp. A14.1-A14
Author(s):  
Stephanie L Barnes ◽  
Bruce J Brew

IntroductionInfectious aetiologies such as acute Epstein-Barr virus (EBV) infection are in the differential diagnosis for acute cerebellar ataxia (ACA). This syndrome remains exceptionally rare and not well characterised in adults.e.g. 1 2MethodsA retrospective case review of a patient diagnosed with ACA following EBV infection with implications for pathogenesis and treatment.ResultsA 29-year-old Caucasian male presented with a three day history of ACA. Seven days prior he was diagnosed with infectious mononucleosis; bloodwork was consistent with acute EBV infection. These symptoms improved rapidly with oral prednisolone. He took no regular medications, drank alcohol moderately and had no significant family history.On examination, he was afebrile, ataxic and mildly dysarthric. Sensory examination was normal, particularly proprioception. Romberg’s test was negative. Remaining neurological and general examination was normal.Bloodwork showed mild liver dysfunction and positive ANA (titre 1/320, homogenous and speckled patterns). Immune screen was otherwise negative. Antineuronal antibody panel was negative in serum and CSF. CSF glucose was 3.1 mmol/L, protein 751 mg/L, albumin 523 mg/L, neopterin 24 nmol/L and B2 microglobulin 1.1 mg/L. The sample was acellular with negative EBV PCR (<500 copies/mL). Other infective serology and PCRs were also negative. MRI brain with gadolinium showed no abnormality.The patient received supportive care and was neurologically normal within three months.ConclusionsACA related to EBV is rare in adults. This report is important because it documents an adult case, other ACA causes have been rigorously excluded, resolution without antiviral therapy is detailed, and investigations support an immune-mediated pathogenesis.ReferencesMcCarthy CL, McColgan P, Martin P. Acute cerebellar ataxia due to Epstein-Barr virus. Pract Neurol 2012;12:238–240.Lascelles RG, Longson M, Johnson PJ, Chiang A. Infectious mononucleosis presenting as acute cerebellar syndrome. Lancet 1973;2:707.


2016 ◽  
pp. bcr2016215303
Author(s):  
Benjamin Davies ◽  
Nicholas Machin ◽  
Timothy Lavin ◽  
Mian Ayaz ul Haq

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15509-e15509
Author(s):  
Raghav Sundar ◽  
Aditi Qamra ◽  
Angie Lay Keng Tan ◽  
Shenli Zhang ◽  
Cedric Chuan Young Ng ◽  
...  

e15509 Background: We recently elicited the role of epigenetic promoter alterations as a mechanism of immune-evasion and primary resistance to immune checkpoint inhibition in gastric cancer. High prevalence of epigenetic modifications are known to occur in Epstein-Barr virus associated gastric cancer (EBVaGC). EBVaGC has high response rates to anti-PD-1 immune checkpoint inhibitors and is associated with high levels of PD-L1 expression. However, not all EBVaGC express PD-L1 and mechanisms that mediate these phenomena are unknown. Methods: We performed NanoString profiling and PD-L1 immunohistochemistry (using Dako PD-L1 IHC 22C3) on tissue from gastric cancer patients undergoing primary tumor resections at Samsung Medical Centre, South Korea. NanoString panel was designed for 90 recurrent somatic alternate promoter-related genes, and immune-related genes including PD-L1. EBV status was determined using EBV-encoded RNA in situ hybridization and categorized as EBVaGC and EBV-negative. Samples in the top-quartile of alternate promoter utilization were classified as APhigh and the remaining APlow. Results: A total of 272 samples (EBVaGC n = 79; EBV-negative n = 193) were included in this study. EBVaGC had significantly higher PD-L1 expression (p < 0.001) compared to EBV-negative samples. APhigh group (n = 67) consisted of 61 EBV-negative and 6 EBVaGC samples. EBVaGC APhigh tumors had significantly lower PD-L1 transcript expression compared to EBVaGC APlow tumors (p = 0.011, Wilcoxon-rank sum). Similar correlation was also found with PD-L1 IHC combined positive score (CPS)(median CPS score 1 vs 8, p = 0.047). There was a trend towards poorer survival for EBVaGC APhigh tumors (vs EBVaGC APlow; HR 0.23, 95% CI: 0.046 – 1.23, p = 0.087). EBV-negative APhigh tumors also had lower PD-L1 expression (vs EBV-negative APlow; p = 0.046, Wilcoxon-rank sum). Conclusions: Increased utilization of epigenetic alternate promoter isoforms correlates with lower transcriptomic and protein expression of PD-L1 in EBVaGC. Here we describe a potential mechanism of immune-evasion to explain low immune-infiltration and PD-L1 expression that occurs in a group of EBVaGC that is traditionally considered highly immunogenic.


2012 ◽  
Vol 12 (4) ◽  
pp. 238-240 ◽  
Author(s):  
Claire Louise McCarthy ◽  
Peter McColgan ◽  
Peter Martin

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