---
title: "Efgartigimod for anti-GAD65 antibody–positive epilepsy and cerebellar ataxia: case report overview"
id: "frontiers-in-immunology-15-treatment-of-anti-gad65-antibody-positive-epilepsy-and-cerebellar-ataxia-with"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-treatment-of-anti-gad65-antibody-positive-epilepsy-and-cerebellar-ataxia-with"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1849117"
published_at: "2026-08-04T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Efgartigimod for anti-GAD65 antibody–positive epilepsy and cerebellar ataxia: case report overview
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-treatment-of-anti-gad65-antibody-positive-epilepsy-and-cerebellar-ataxia-with
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1849117)
- **Published At:** 2026-08-04T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source article is titled “Treatment of **anti-GAD65 antibody**-positive **epilepsy** and **cerebellar ataxia** with **efgartigimod**: a case report and literature review” and is published in Frontiers in Immunology. - The available source content supplied here contains only website navigation and journal scaffolding; the body of the case report and review was not included. - Specific clinical details — including patient demographics, clinical course, diagnostic testing results, antibody titers, therapeutic regimen, dosing, treatment duration, clinical endpoints, adverse events, and outcomes — were not reported in the provided source text. - The provided source does not include the case presentation, methods, literature review findings, or authors’ interpretations; therefore study-specific results and conclusions cannot be summarized from this input. - Because the article is described as a case report and literature review, readers would normally expect sections on patient presentation, diagnostic work-up, rationale for use of **efgartigimod**, treatment details, response and follow-up, and a contextual literature review; these expected elements were not present in the supplied content. - Any interpretation beyond the article title and journal citation would be speculative; the supplied source does not permit confirmation of efficacy, safety, or recommendations regarding **efgartigimod** for anti-GAD65-related neurologic disease. - Users should consult the full article on Frontiers in Immunology or contact the journal to obtain the complete report, including methods, results, and the authors’ discussion and conclusions.
## Clinical Analysis & Structured Key Points
Frontiers | Treatment of anti-GAD65 antibody-positive epilepsy and cerebellar ataxia with efgartigimod: a case report and literature review ORIGINAL RESEARCH article Front. Immunol. , 04 August 2026 Sec. Multiple Sclerosis and Neuroimmunology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1849117 Published in Frontiers in Immunology Multiple Sclerosis and Neuroimmunology 7 impact factor 11.3 citescore Part of a Research Topic Seizures in Autoimmune and Systemic Inflammatory Disorders: Immunologic, Genetic, Metabolic, and Lifestyle Modifiers Submission open 772 views 1 articles Editor & Reviewers Edited by M G Maria Guadalupe Zavala-Cerna Reviewed by M R Marina Romozzi D M Deepinder Maini Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Table 1 Results of GAD65 antibody in serum. View in article Table 2 Results of GAD65 antibody in CSF. View in article Table 3 Summary of clinical course, auxiliary examinations, treatment regimens and clinical response. View in article ORIGINAL RESEARCH article Front. Immunol. , 04 August 2026 Sec. Multiple Sclerosis and Neuroimmunology Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1849117 Treatment of anti-GAD65 antibody-positive epilepsy and cerebellar ataxia with efgartigimod: a case report and literature review L X Lulu Xie 1 J Z Junqin Zuo 2 L L Le Luo 3 D Z Duo Zhang 3 Z M Zhuang Ma 3 Z W Zihan Wang 1 C D Chunying Deng 1,2,3 * 1. Tianjin Academy of Traditional Chinese Medicine, Tianjin, China 2. First Department of Neurology, North China University of Science and Technology Affiliated Hospital, Tangshan, China 3. Department of Neurology II, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, China See more Article metrics View details Abstract Background: Anti-glutamic acid decarboxylase 65 (GAD65) antibody-associated neurological syndrome is a rare autoimmune disorder with heterogeneous clinical manifestations, including epilepsy and cerebellar ataxia. Standard treatment strategies remain limited. This report aimed to describe a rare case presenting with combined epilepsy and cerebellar ataxia, and to evaluate the efficacy of efgartigimod followed by mycophenolate mofetil. Methods: We present a 62-year-old female with slowly progressive recurrent epileptic seizures and cerebellar ataxia. Clinical, neurological, neuroimaging (PET/CT, MRI), and laboratory examinations (serum and cerebrospinal fluid GAD65 antibodies) were analyzed. The patient was treated with efgartigimod (10 mg/kg weekly for 3 doses) plus maintenance mycophenolate mofetil. Clinical outcomes and follow-up data were assessed. Results: Neurological examination showed left-sided dysmetria, dysdiadochokinesia, and a positive Romberg sign. Brain PET/CT revealed hypometabolism in the bilateral temporal lobes, right hippocampus, and left frontoparietal regions, accompanied by mild right hippocampal atrophy. Serum and cerebrospinal fluid (CSF) examinations were positive for GAD65 antibodies at titers of 1:1000 and 1:100, respectively, confirming the diagnosis of GAD65 antibody-associated neurological syndrome. After treatment, seizures completely resolved, gait ataxia improved significantly, and daily activities were fully restored at 1-month follow-up. Antiseizure medications were gradually tapered. No clinical relapse occurred during the 1-year follow-up period. Conclusions: This case demonstrates that anti-GAD65 antibody syndrome can present as concurrent refractory epilepsy and cerebellar ataxia. The sequential regimen of efgartigimod induction combined with mycophenolate mofetil maintenance appears effective and safe. This therapeutic strategy may provide a valuable reference for the clinical management of such rare autoimmune neurological disorders. Introduction Glutamic acid decarboxylase-65 (GAD65) is a key enzyme responsible for the biosynthesis of gamma-aminobutyric acid, the primary inhibitory neurotransmitter in the central nervous system ( 1 ). GAD65 antibodies serve as a biomarker for autoimmune disorders, which are characterized by immune-mediated attack on the nervous and endocrine systems by anti-GAD65 antibodies. Anti-GAD65 antibody-related autoimmune disorders can be categorized into neurological and non-neurological manifestations. Neurological phenotypes mainly include stiff-person syndrome (SPS), autoimmune epilepsy, limbic encephalitis (LE), and cerebellar ataxia (CA), whereas non-neurological manifestations predominantly consist of diabetes mellitus type 1 (T1DM) ( 2 ). Space-occupying lesions are present in only a minority of cases. Given the low incidence and heterogeneous clinical spectrum of anti-GAD65 antibody-associated disorders, standardized treatment protocols have not yet been established, and current management largely relies on combined immunotherapy. Adjunctive measures include seizure control, antineoplastic therapy, and other symptomatic interventions, which should be individually optimized according to patient-specific clinical features. Based on previous reports, immunotherapy is the established mainstay for anti-GAD65-related diseases ( 3 ). Early and intensive immunotherapy is correlated with a more favorable prognosis. Immunotherapeutic strategies are generally classified into first-line, second-line, long-term maintenance, escalation, and additive regimens. It is broadly recommended that all patients with newly diagnosed encephalitis receive first-line immunotherapy, to which more than half of affected individuals exhibit a satisfactory response ( 4 ). However, conventional immunotherapy frequently demonstrates limited efficacy in reducing seizure frequency and ameliorating cognitive impairment. As illustrated in the current case, second-line immunotherapy should be promptly initiated in patients who fail to achieve substantial clinical improvement following adequate trials of two or more first-line agents ( 5 ). Given the intracellular localization of the GAD65 antigen, systemic immunotherapies generally yield poor clinical effects in most patients, and no unified standard immunotherapy protocols are available for these diseases at present. This report describes the clinical features and therapeutic management of a patient with anti-GAD65 antibody-associated epilepsy and cerebellar ataxia, with the aim of improving clinical recognition and providing novel references for treatment strategies. Case presentation A 62-year-old female was admitted to our hospital on October 8, 2024, with a chief complaint of episodic loss of consciousness and focal clonic activity involving the limbs for 20 years. Three months before admission, the patient developed progressive cerebellar ataxia, presenting as persistent unsteady gait with lateral swaying that required assistive devices for ambulation. This was accompanied by dizziness, vertigo, nausea and vomiting, leading to multiple falls during this period. The patient’s medical history and treatment process are described as follows: Her initial neurological manifestations onset in 2004, presenting as brief staring spells (duration: tens of seconds) accompanied by drooling from the left oral commissure. She visited a local hospital at that time without a clear diagnosis. Oral carbamazepine of unknown dosage was prescribed but failed to relieve her symptoms, with seizures occurring 50–60 times per year. The clinical course was progressively deteriorating, with subsequent evolution into bilateral tonic-clonic seizures, characterized by generalised seizures, frothy saliva, cyanosis, tongue biting and urinary incontinence. In the postictal phase, the patient suffered from left temporal and occipital headache, whose frequency and intensity were aggravated by emotional stress and sleep disturbance. In 2015, brain MRI and 24-hour EEG ( Figure 1 ) were completed, and epilepsy was diagnosed. She was treated sequentially with multiple antiseizure medications: oxcarbazepine 450 mg twice daily, levetiracetam 1 g twice daily, valproate 500 mg twice daily and zonisamide 150 mg twice daily, none of which yielded effective seizure control. Figure 1 Brain EEG. In 2022, the patient’s antiseizure medication regimen was optimized at Beijing Tiantan Hospital. She was prescribed oral lacosamide 300 mg twice daily, oral levetiracetam 0.5 g twice daily, and oral perampanel 4 mg once nightly. Notably, the patient frequently adjusted her medication dosage without medical guidance. Despite this combination therapy, episodes of blank staring and teeth grinding persisted, occurring 3–4 times monthly. On October 12, 2023, brain PET/CT imaging revealed hypometabolism suggestive of focal lesions in the anterior right temporal lobe, reduced metabolic activity in the right hippocampus, mild volumetric atrophy of the right hippocampus and right temporal lobe, hypometabolism within the left temporal lobe, and multifocal FDG hypometabolism in the left frontal and parietal lobes with the most prominent changes in the left frontal lobe. Positive anti-GAD65 antibodies were detected at a titer of 1:320, leading to a final diagnosis of autoimmune encephalitis. Intravenous human immunoglobulin was administered during hospitalization, which partially reduced seizure frequency. After discharge, the patient adhered to a stable regimen of oral lacosamide 300 mg twice daily, oral levetiracetam 0.5 g twice daily, and oral perampanel 4 mg once nightly. The patient had a 12-year history of type 2 diabetes mellitus. Her regular hypoglycemic regimen consisted of oral acarbose 50 mg three times daily, oral metformin 0.5 g three times daily, and subcutaneous glargine insulin 13 units once nightly, yet her glycemic control remained suboptimal. Despite sequential therapeutic trials of multiple antiseizure medications, including carbamazepine, oxcarbazepine, levetiracetam, sodium valproate, zonisamide, lacosamide and perampanel, satisfactory seizure control was not achieved. On admission, vital signs were stable: temperature 36.2 °C, pulse 80 beats/min, respiratory rate 20 breaths/min, and blood pressure 130/77 mmHg. General physical examination showed no abnormal findings in the cardiovascular, respiratory, or abdominal systems. Neurological examination revealed clear consciousness, fluent speech, intact extraocular movements without nystagmus, and bilaterally normal-sized pupils with preserved light reaction. Facial symmetry was intact, and the tongue protruded midline. Muscle strength was graded 5 throughout all extremities, with normal muscle tone. Deep tendon reflexes were absent at the knees and ankles bilaterally; plantar responses were flexor (negative Babinski and Chaddock signs). Sensory examination was unremarkable. Cerebellar evaluation demonstrated left-sided dysmetria on finger-to-nose and heel-knee-shin testing, along with ipsilateral dysdiadochokinesia. The Romberg sign was positive both with eyes open and closed. No meningeal irritation signs were observed. The Scale for the Assessment and Rating of Ataxia (SARA) score on admission was 17. Brain PET/CT performed on October 12, 2023, demonstrated hypometabolism involving the anterior right temporal lobe, right hippocampus, and left temporal lobe, accompanied by mild volumetric reduction of the right hippocampus ( Figure 2 ). Cranial MRI conducted on October 12, 2024, revealed multiple chronic ischemic infarcts and diffuse cerebral atrophy. Serological and CSF analyses obtained on October 9, 2024, confirmed positivity for glutamic acid decarboxylase 65 (GAD65) antibodies, with serum ( Table 1 ) and CSF ( Table 2 ) titers of 1:1000 and 1:100 respectively. The immunofluorescence image of GAD65 is shown in Figure 3 . CSF protein was mildly elevated at 0.44 g/L. Combining the clinical presentations of refractory epilepsy and progressive cerebellar ataxia, characteristic neuroimaging alterations, and serologically verified GAD65 antibody positivity, a definitive diagnosis of GAD65 antibody-associated neurological syndrome was rendered. Figure 2 Brain PET/CT. Table 1 Item Testing method Result Reference range NMDAR antibody CBA method Negative (-) Negative (-) AMPA1 antibody CBA method Negative (-) Negative (-) AMPA2 antibody CBA method Negative (-) Negative (-) LGI1 antibody CBA method Negative (-) Negative (-) CASPR2 antibody CBA method Negative (-) Negative (-) GlyR1 antibody CBA method Negative (-) Negative (-) GABAA antibody CBA method Negative (-) Negative (-) GABAB antibody CBA method Negative (-) Negative (-) IgLON5 antibody CBA method Negative (-) Negative (-) DPPX antibody CBA method Negative (-) Negative (-) DRD2 antibody CBA method Negative (-) Negative (-) GAD65 antibody CBA method Positive (1:1000+++) Negative (-) Results of GAD65 antibody in serum. Bold values denote positive test results of GAD65 Antibody in serum. Table 2 Item Testing method Result Reference range Titin antibody CBA method Negative (-) Negative (-) Recoverin antibody CBA method Negative (-) Negative (-) PKCγ antibody CBA method Negative (-) Negative (-) NMDAR antibody CBA method Negative (-) Negative (-) AMPA1 antibody CBA method Negative (-) Negative (-) AMPA2 antibody CBA method Negative (-) Negative (-) LGI 1 antibody CBA method Negative (-) Negative (-) CASPR2 antibody CBA method Negative (-) Negative (-) GlyR1 antibody CBA method Negative (-) Negative (-) GABAA antibody CBA method Negative (-) Negative (-) GABAB antibody CBA method Negative (-) Negative (-) GAD65 antibody CBA method Positive (1:100+++) Negative (-) Results of GAD65 antibody in CSF. Bold values denote positive test results of GAD65 Antibody in CSF. Figure 3 Fluorescence image results of GAD65 antibody. Following admission, the patient received efgartigimod infusions at a dosage of 10 mg/kg weekly for a total of three doses. This therapeutic intervention led to a marked reduction in seizure frequency and significant improvement in cerebellar ataxia, as reflected by a decrease in the SARA score from 17 to 8. The patient subsequently regained independent ambulation. Upon discharge, maintenance immunosuppressive treatment with mycophenolate mofetil dispersible tablets (0.5g twice daily) was instituted, with regular surveillance of complete blood count and immunological parameters. At the one-month follow-up evaluation, the patient had fully resumed normal daily activities. At four months post-discharge (February 17, 2025), serum anti-GAD65 antibody titers remained positive at 1:1000, while IgG levels and peripheral B-cell proportions exhibited a decreasing trend. No clinical relapse was documented throughout the one-year follow-up period. Summary of clinical course, auxiliary examinations, treatment regimens and clinical response ( Table 3 ). Table 3 Time point Key clinical manifestations Examinations Treatment regimens Clinical response 2004 (Initial onset, 20 years before admission) Brief staring spells, drooling from left mouth; later developed bilateral tonic-clonic seizures (frothing, lip cyanosis, tongue biting, urinary incontinence); left temporal-occipital headache; seizure frequency: 50–60 times/year Not tested Carbamazepine (unknown dosage) No seizure relief 2015 Persistent refractory seizures Brain MRI + 24 h EEG: diagnosed epilepsy Oxcarbazepine 450 mg twice daily; levetiracetam 1 g twice daily; valproate 500 mg twice daily; zonisamide 150 mg twice daily Failed seizure control 2022 Frequent blank staring, teeth grinding; seizures 3–4 times/month No repeat neuroimaging Lacosamide 300 mg twice daily; levetiracetam 0.5 g twice daily; perampanel 4 mg once nightly (patient self-adjusted dosage irregularly) Seizures persisted 12 Oct 2023 Seizures unchanged FDG PET/CT: hypometabolism of anterior right temporal lobe, right hippocampus, left temporal lobe, left frontoparietal lobe; mild right hippocampal atrophySerum anti-GAD65 antibody 1:320 lacosamide 300 mg twice daily, oral levetiracetam 0.5 g twice daily, and oral perampanel 4 mg once;nightlyIntravenous human immunoglobulin Partial reduction of seizure frequency Admission (8 Oct 2024) Refractory focal seizures; severe cerebellar ataxia, SARA score = 17; left dysmetria, dysdiadochokinesia, positive Romberg sign Brain MRI: multiple chronic ischemic infarcts, diffuse cerebral atrophy Serum anti-GAD65 1:1000; CSF anti-GAD65 1:100; all other neuronal autoantibodies negative; CSF protein 0.44 g/L Lacosamide 300 mg twice daily; levetiracetam 0.5 g twice daily; perampanel 4 mg once nightly Efgartigimod 10 mg/kg weekly × 3 doses Marked improvement of seizures and ataxia; SARA decreased to 8; independent walking recovered 1-month follow-up (Nov 2024) No seizure recurrence; normal daily activities Not rechecked Tapering ASMs gradually Continuous mycophenolate mofetil Complete recovery of daily living ability 4-month follow-up (17 Feb 2025) No seizures; stable gait function Serum anti-GAD65 still positive 1:1000; IgG and peripheral B cell count declined Low-dose maintenance ASMs Continuous mycophenolate mofetil Sustained remission 1-year follow-up (Oct 2025) No clinical relapse No repeated antibody testing Long-term low-dose ASMsContinuous mycophenolate mofetil No recurrence of seizures Summary of clinical course, auxiliary examinations, treatment regimens and clinical response. Discussion GAD65 is widely expressed throughout the nervous system. In patients with anti-GAD65 antibodies, brain MRI frequently shows temporal lobe and hippocampal involvement. The main clinical manifestations include epileptic seizures and cognitive impairment, while cerebellar ataxia is also a well-recognized phenotype. The disease usually follows a subacute or chronic progressive course, is mostly sporadic, and predominantly affects middle-aged to elderly women ( 6 ). Gait ataxia is the most common presentation, followed by limb ataxia, diplopia, and brainstem-related dysarthria ( 2 ). These symptoms can occur simultaneously or sequentially during disease progression ( 7 ). Our patient initially presented with seizures and subsequently developed cerebellar ataxia. The treatment strategy reported herein provides clinical reference for the management of anti-GAD65 antibody-positive patients complicated by both epilepsy and cerebellar ataxia. Anti-GAD65 antibodies disrupt the conversion of glutamate to GABA via humoral immunity, leading to increased glutamate levels, enhanced neuronal excitability, and reduced seizure threshold ( 8 , 9 ). Recent studies suggest anti-GAD65 antibodies may directly promote epileptogenesis ( 10 , 11 ). In contrast, some research proposes cytotoxic T-cell-mediated neuronal injury as the primary mechanism, with anti-GAD65 antibodies acting only as an immunological marker rather than directly pathogenic ( 12 ). In anti-GAD65–associated autoimmune epilepsy, temporal lobe epilepsy is the typical phenotype, often accompanied by chronic encephalopathy. Focal to bilateral tonic-clonic seizures and focal non-motor seizures are the most common seizure types ( 13 ). Multiple seizure types may develop over time, as seen in our patient. Cerebellar atrophy has been reported in some patients with anti-GAD65 associated ataxia ( 14 ), but was not obvious in our case. The definite relationship between anti-GAD65 antibodies and cerebellar atrophy, as well as its underlying mechanism, requires further large-scale studies. Approximately half of patients with anti-GAD65 antibodies have concomitant systemic autoimmune diseases, mainly type 1 diabetes, followed by autoimmune thyroiditis ( 15 , 16 ). The absence of systemic autoimmunity in our patient suggests a relatively favorable prognosis. Current treatment for anti-GAD65 related neurological syndromes combines immunotherapy, antiseizure medications. First-line immunotherapy includes high-dose intravenous methylprednisolone, intravenous immunoglobulin, and plasma exchange ( 17 ). Second-line options include rituximab and cyclophosphamide. However, first-line treatments carry side effects or high costs, and ritux
## Related Clinical Research

- [GLP-1 receptor agonists and PMOS: evidence, mechanisms, and who may benefit](https://medichelpline.com/clinical-feed/medical-news-today-0-can-glp-1s-really-help-treat-pmos-experts-answer-3-key-questions.md)
- [GLP-1 Receptor Agonists and Long-Term Pancreatic Cancer Risk: TriNetX Propensity-Matched Analysis](https://medichelpline.com/clinical-feed/pubmed-42745130.md) (DOI: 10.1007/s12029-026-01523-w)
- [Modified Huanglian Wendan Decoction protects prediabetic kidneys via AMPK/ULK1‑mediated autophagy](https://medichelpline.com/clinical-feed/pubmed-42259235.md) (DOI: 10.1016/j.intimp.2026.116966)
- [NIH awards $4.6M to multi-university team to model hormones and improve women's health](https://medichelpline.com/clinical-feed/endocrine-news-0-nih-awards-multi-university-team-over-4m-to-improve-women-s-health.md)
- [Antidiabetic regimens and risk of cognitive disorders in type 2 diabetes: large retrospective coho](https://medichelpline.com/clinical-feed/plos-one-23-antidiabetic-medications-and-risk-of-cognitive-disorders-in-type-2-diabetes-a.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.