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Acute anti-Ma2 paraneoplastic encephalitis associated to pembrolizumab: a case report and review of literature.

ABSTRACT: Anti-Ma2 encephalitis is a rare neurological disorder with a predominant involvement of brainstem, limbic and diencephalic structures. Although an unspecific encephalopathy is the usual form of presentation, acute-onset neurologic symptoms and other atypical manifestations have been described and account for the challenging diagnosis of this entity. Despite being usually detected as a paraneoplastic syndrome in patients with early-stage tumors or without a previous history of malignancy, a growing concern has arisen from several cases reported in metastatic patients under treatment with immune checkpoint inhibitors. We report what to our knowledge is the first known case of anti-Ma2 encephalitis associated to pembrolizumab and presenting as an acute-onset focal neurological syndrome, consisting on acute global aphasia, right upper limb paresia, hypoacusia, sleep disorder, decreased conscious level and a motor focal status that was refractory to anticonvulsant therapy. A brain MRI scan showed a focal alteration of the cortical-subcortical signal on the left parietal lobe. CSF study found a significant hyperproteinorrhachia and electroencephalography showed lateralized periodic discharges (LPDs), suggestive of a diffuse encephalopathy. A positive result for anti-Ma2 antibodies was obtained both in blood and CSF samples through indirect immune-fluorescence (IFI) and later confirmed by western-blot technique. Our patient obtained a mild response to steroid therapy and a significant improvement after the administration of intravenous immunoglobulins. The hypothesis that checkpoint inhibitors may trigger the expression of previously subclinical paraneoplastic events, through the strengthening of cytotoxic T cells-mediated immune response, is supported by our finding of preexisting anti-Ma2 antibodies in preserved blood samples obtained before the initiation of pembrolizumab in our patient. Further research is needed to reveal if the detection of onconeural antibodies prior to a treatment with checkpoint inhibitors may be used as a predictive biomarker of neurologic immune-related high-grade toxicity.

SUBMITTER: Albarran V

PROVIDER: S-EPMC8350103 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Acute anti-Ma2 paraneoplastic encephalitis associated to pembrolizumab: a case report and review of literature.

Albarrán Víctor V Pozas Javier J Rodríguez Fernando F Carrasco Ángela Á Corral Elena E Lage Yolanda Y Álvarez-Ballesteros Pablo P Soria Ainara A Garrido Pilar P

Translational lung cancer research 20210701 7

Anti-Ma2 encephalitis is a rare neurological disorder with a predominant involvement of brainstem, limbic and diencephalic structures. Although an unspecific encephalopathy is the usual form of presentation, acute-onset neurologic symptoms and other atypical manifestations have been described and account for the challenging diagnosis of this entity. Despite being usually detected as a paraneoplastic syndrome in patients with early-stage tumors or without a previous history of malignancy, a growi ...[more]

PMID: 34430366

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Project description:Introduction18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis.MethodsThe cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities.ResultsThe three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery.ConclusionsThe distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool.

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Dataset Information

Acute anti-Ma2 paraneoplastic encephalitis associated to pembrolizumab: a case report and review of literature.

Publications

Acute anti-Ma2 paraneoplastic encephalitis associated to pembrolizumab: a case report and review of literature.

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