# Case Report: Thymoma-associated myasthenia gravis, myositis, myocarditis, and anti-GAD65 autoimmune encephalitis: a unique case of paraneoplastic polyautoimmunity

**Authors:** Enmanuel A. Leiva-Murillo, Eugenia Martínez-Hernández, Iban Aldecoa, Pedro Castro, Valeria Richart, José C. Milisenda, Ana Matas-García

PMC · DOI: 10.3389/fimmu.2026.1763320 · Frontiers in Immunology · 2026-02-10

## TL;DR

A 41-year-old woman with thymoma developed multiple rare autoimmune conditions, including myasthenia gravis, myositis, myocarditis, and anti-GAD65 autoimmune encephalitis, which responded well to aggressive treatment.

## Contribution

This is the first reported case of paraneoplastic polyautoimmunity involving myasthenia gravis, myositis, myocarditis, and anti-GAD65 autoimmune encephalitis in a thymoma patient.

## Key findings

- The patient exhibited a rare combination of autoimmune conditions associated with thymoma.
- Anti-GAD65 antibodies were detected, which is exceptional in this clinical context.
- Aggressive treatment led to significant clinical improvement, highlighting the importance of early recognition.

## Abstract

Neurological and autoimmune muscle comorbidities are rare in thymoma-associated myasthenia gravis (TAMG). The incidence of myositis is likely underestimated due to its clinical similarity. Few cases of autoimmune encephalitis (AE) have been reported in TAMG, most of which are associated with neuronal surface antibodies. We present the case of a 41-year-old woman with weakness and bulbar dysfunction, and elevated muscle and cardiac enzyme levels, who developed seizures and a decreased level of consciousness. Among the complementary tests, electromyography revealed a postsynaptic neuromuscular junction disorder. Muscle biopsy revealed inflammatory myopathy (IM), and cardiac magnetic resonance imaging (MRI) showed myocardial edema. Electroencephalography showed epileptiform activity, while brain MRI revealed bilateral T2/FLAIR hyperintensities in the medial temporal lobe. Neuroimmunological studies detected anti-acetylcholine receptor and anti-glutamic acid decarboxylase 65 (anti-GAD65) antibodies. Chest computed tomography (CT) revealed a mediastinal mass, which was later confirmed as a thymoma. The patient received corticosteroids, intravenous immunoglobulin, plasma exchanges, and rituximab. The simultaneous coexistence of myasthenia, myositis, myocarditis, and AE in a patient with thymoma has not been previously described in the medical literature. The presence of anti-GAD65 in this context is exceptional. In this case, early recognition and aggressive treatment led to a remarkable recovery. Clinicians should maintain a high index of suspicion for the coexistence of autoimmune disorders in patients with TAMG. IM may indicate a more serious disease, and myocarditis can be life-threatening. Neurological signs, such as memory loss, confusion, and seizures, may indicate the development of AE.

## Linked entities

- **Diseases:** myasthenia gravis (MONDO:0009688), myocarditis (MONDO:0004496), autoimmune encephalitis (MONDO:0020640), thymoma (MONDO:0006456)

## Full-text entities

- **Genes:** GAD2 (glutamate decarboxylase 2) [NCBI Gene 396929] {aka GAD65}, AIRE (autoimmune regulator) [NCBI Gene 326] {aka AIRE1, APECED, APS1, APSI, PGA1}, MCH (Mean corpuscular hemoglobin content) [NCBI Gene 104798092], CNTNAP2 (contactin associated protein 2) [NCBI Gene 26047] {aka AUTS15, CASPR2, CDFE, NRXN4, PTHSL1}, MUSK (muscle associated receptor tyrosine kinase) [NCBI Gene 4593] {aka CMS9, FADS}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, RYR1 (ryanodine receptor 1) [NCBI Gene 6261] {aka CCO, CMYO1A, CMYO1B, CMYP1A, CMYP1B, KDS}, GAD2 (glutamate decarboxylase 2) [NCBI Gene 2572] {aka GAD65}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 397286], PDCD1 (programmed cell death 1) [NCBI Gene 100533201], CD274 (CD274 molecule) [NCBI Gene 574058] {aka PDL1}, LGI1 (leucine rich glioma inactivated 1) [NCBI Gene 9211] {aka ADLTE, ADPAEF, ADPEAF, DEE121, EPITEMPIN, EPT}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, KCNA4 (potassium voltage-gated channel subfamily A member 4) [NCBI Gene 3739] {aka HBK4, HK1, HPCN2, HUKII, KCNA4L, KCNA8}, TTN (titin) [NCBI Gene 7273] {aka CMD1G, CMH9, CMPD4, CMYO5, CMYP5, EOMFC}, LRP4 (LDL receptor related protein 4) [NCBI Gene 4038] {aka CLSS, CMS17, LRP-4, LRP10, MEGF7, SOST2}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}
- **Diseases:** myocardial edema (MESH:D004487), malignancy (MESH:D009369), ischemic (MESH:D002545), axial and proximal limb weakness (MESH:D018908), dyspnea (MESH:D004417), acute coronary syndrome (MESH:D054058), girdle muscles (MESH:D019042), myasthenic crises (MESH:D013224), AE (MESH:D020274), inflammatory (MESH:D007249), myasthenia (MESH:D020294), dysphonia (MESH:D055154), encephalitic (MESH:D010301), dermatomyositis (MESH:D003882), bulbar dysfunction (MESH:D010244), status epilepticus (MESH:D013226), paraneoplastic (MESH:D010257), pulmonary embolism (MESH:D011655), weakness of the neck extensors and shoulder (MESH:D000070599), Seizure (MESH:D012640), junction (MESH:D020511), metabolic abnormalities (MESH:D008659), confusion (MESH:D003221), Myocarditis (MESH:D009205), tetraparesis (MESH:C565722), myocardial injury (MESH:D009202), IM (MESH:D009220), thymic hyperplasia (MESH:D013952), Autoimmune limbic encephalitis (MESH:C531729), obesity (MESH:D009765), and muscular autoimmune comorbidities (MESH:D001327), arrhythmias (MESH:D001145), ventilatory (MESH:D012131), diastolic dysfunction (MESH:D018487), palpebral ptosis (MESH:C564553), lymphocytic pleocytosis (MESH:D007964), Myocardial involvement (MESH:C564676), PM (MESH:D017285), ischemic heart disease (MESH:D017202), encephalitis (MESH:D004660), infection (MESH:D007239), hypokinesia (MESH:D018476), diplopia (MESH:D004172), neurological damage (MESH:D020196), dysphagia (MESH:D003680), epileptic (MESH:D004827), cerebellar ataxia (MESH:D002524), PE (MESH:D054219), memory loss (MESH:D008569), AChR-MG (MESH:D009157), MSA (MESH:C537381), right eye exotropia (MESH:D005099), limbic encephalitis (MESH:D020363), cognitive impairment (MESH:D003072), neurological deterioration (MESH:D009422), Brain MRI abnormalities (MESH:C564543), acute central nervous system infection (MESH:D002494), hypersensitivity (MESH:D004342), granulomatous myopathy (MESH:D009135), Thymoma (MESH:D013945)
- **Chemicals:** methylprednisolone (MESH:D008775), rituximab (MESH:D000069283), Hematoxylin (MESH:D006416), ganglioside (MESH:D005732), N-terminal pro-brain natriuretic peptide (-), eosin (MESH:D004801), pyridostigmine (MESH:D011729)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929398/full.md

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Source: https://tomesphere.com/paper/PMC12929398