Thymoma-associated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with Myasthenia Gravis

Morise, Satoshi; Nakamura, Masataka; Morita, Jun-ichi; Miyake, Kousuke; Kunieda, Takenobu; Kaneko, Satoshi; Kusaka, Hirofumi

doi:10.2169/internalmedicine.56.7979

Cited by 14 publications

(11 citation statements)

References 11 publications

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“… 13 In contrast, the presence of thymoma did not affect the prognosis of patients with other antibody-related syndromes; for example, the 3 patients with PERM and GlyR antibodies made an excellent recovery similar to that observed in idiopathic cases and in 6 of 7 previously reported patients with thymoma. 14 , 24 , 38 …”

Section: Discussionmentioning

confidence: 99%

Thymoma and Autoimmune Encephalitis

Guasp

Landa

Martínez‐Hernández

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo report the clinical, neuroimaging, and antibody associations in patients with autoimmune encephalitis (AE) and thymoma.MethodsA retrospective cohort study of 43 patients was conducted. Antibody determination and immunoprecipitation to characterize novel antigens were performed using reported techniques.ResultsPatients' median age was 52 years (range: 23–88 years). Forty (93%) had neuronal surface antibodies: gamma-aminobutyric acid receptor A (GABAAR) (15), amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) (13), contactin-associated protein-like 2 (CASPR2) (4), leucine-rich, glioma inactivated 1 (LGI1) (3), glycine receptor (GlyR) (3), and unknown antigens (2). Concurrent antibodies against intracellular antigens occurred in 13 (30%; 9 anti–collapsin response mediator protein 5 [CRMP5]) and were more frequent in anti-AMPAR encephalitis (54% vs 20%; p = 0.037). The most common clinical presentation was encephalitis with multiple T2/fluid-attenuated inversion recovery hyperintense lesions in 23 (53%) patients (15 GABAAR, 5 AMPAR, and 1 unknown neuropil antibody), followed by encephalitis with peripheral nerve hyperexcitability in 7 (16%; 4 CASPR2, 2 LGI1, and 1 unknown antibody), limbic encephalitis in 6 (14%; 4 AMPAR, 1 LGI1, and 1 antibody negative), progressive encephalomyelitis with rigidity and myoclonus in 4 (9%; 3 GlyR and 1 AMPAR antibodies), and encephalitis with normal MRI in 3 (7%; AMPAR antibodies). Anti-GABAAR encephalitis was more prevalent in Japanese patients compared with Caucasians and other ethnicities (61% vs 16%; p = 0.003). In anti-AMPAR encephalitis, 3/4 patients with poor and 0/6 with good outcome had concurrent CRMP5 antibodies (p = 0.033). Immunoprecipitation studies identified metabotropic glutamate receptor 3 antibodies that were additionally found in 5 patients (3 with and 2 without encephalitis).ConclusionsAE in patients with thymoma include several clinical-radiologic syndromes that vary according to the associated antibodies. Anti-GABAAR encephalitis was the most frequent AE and occurred more frequently in Japanese patients.

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Section: Discussionmentioning

confidence: 99%

Thymoma and Autoimmune Encephalitis

Guasp

Landa

Martínez‐Hernández

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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“…This sample was from a MG patient [MG (+) T24, Table 1 ] positive for anti-AChR, -titin and -ryanodine receptor antibodies, having concomitant stiff-person syndrome associated with glutamic acid decarboxylase (GAD) antibodies, and transient myositis. Although rare, some cases of MG patients with stiff-person syndrome associated with anti-GAD antibodies have been previously described [ 43 , 44 ]. Positivity of the MG (+) T24 patient for several autoantibodies, suggest a polyclonal B cell activation, likely as a consequence of EBV-induced autoimmunity [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

et al. 2017

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The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas. EBV DNA and EBV-encoded small nuclear RNA (EBER) 1 transcript were detected in 14/26 (53.8%) and 22/26 (84.6%) MG thymomas, and only in 3 of 14 (21.4%) non-MG thymomas. Latent EBNA2 and late gp350/220 lytic transcripts were undetectable in all, but one, thymomas, and early lytic BZLF1 transcript was absent in all samples, suggesting that early infection events and EBV reactivation were very rare in thymomas. EBER1 and 2-positive cells were detected in MG, but not in non-MG, thymomas, as well as cells expressing EBV latency proteins (EBNA1, LMP1, LMP2A), that were mainly of B cell phenotype, indicating EBV association with MG rather than with thymoma. Toll-like receptor (TLR) 3 transcriptional levels were higher in MG than non-MG thymomas and positively correlated with EBER1 levels, suggesting a role for EBERs in TLR3 activation. Our findings show that EBV is commonly present in thymoma-infiltrating B cells of myasthenic patients, indicating a contribution of EBV to B cell-mediated autoreactivity in MG associated with thymic tumor.

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“…1B). The case reported by Morise et al is the only case of PERM and MG with anti‐GlyR and ‐AChR antibodies associated with thymoma 5 (Fig. 1C).…”

Section: Discussionmentioning

confidence: 74%

Progressive Encephalomyelitis with Rigidity and Myoclonus and Myasthenia Gravis Comorbid Status with Thymoma

Ogawa

Ogaki

Daida

et al. 2021

Movement Disord Clin Pract

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Thymoma-associated Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with Myasthenia Gravis

Cited by 14 publications

References 11 publications

Thymoma and Autoimmune Encephalitis

Thymoma and Autoimmune Encephalitis

Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

Progressive Encephalomyelitis with Rigidity and Myoclonus and Myasthenia Gravis Comorbid Status with Thymoma

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