Nystagmus and Imbalance as the Presenting Symptoms of Anti-GAD Antibody Syndrome in a 67-Year-Old Female

This case report describes a rare presentation of anti-GAD (glutamic acid decarboxylase) antibody syndrome in a 67-year-old female who presented with severe downbeat nystagmus, imbalance, and diplopia, with concomitant seronegative rheumatoid arthritis. The study was published in the Journal of Ophthalmology Research Reviews & Reports in 2024. It highlights the importance of keeping autoimmune encephalitis on the differential diagnosis when patients present with non-specific neurological and ocular symptoms.

Background

Autoimmune encephalitis is a serious condition that causes brain inflammation, typically mediated by antibodies directed against various neuronal antigens. Anti-GAD antibodies target the glutamic acid decarboxylase enzyme, which converts glutamate to GABA -- the nervous system's primary inhibitory neurotransmitter. When this pathway is disrupted, the resulting loss of inhibitory signaling can produce a range of neurological symptoms related to prolonged excitation, including seizures, nystagmus, and ataxia.

Anti-GAD antibody syndrome is a rare form of autoimmune encephalitis with a wide spectrum of clinical presentations. Because its symptoms are non-specific and overlap with many common neurological conditions, it involves a complex differential diagnosis. Elevated anti-GAD antibodies have been associated with stiff-person syndrome, cerebellar ataxia, epilepsy, and limbic encephalitis. Treatment ranges from corticosteroids to monoclonal antibody infusions, and the medication regimen often needs to be tailored to the individual patient's response.

The Patient

A 67-year-old female presented to the neuro-ophthalmology clinic with:

• Dizziness and imbalance confirmed on neurology exam
• Severe nystagmus (downbeat pattern, worsened in side gazes bilaterally)
• Headaches
• Reported diplopia, though she was orthotropic in all gazes on sensorimotor exam
• Pain and swelling in her hands and wrists, which had been gradually worsening
• Ocular history significant for prior myopic LASIK correction

Neurology examination was unremarkable for sensory loss but confirmed imbalance.

Diagnostic Workup

Ophthalmic Examination

• Visual field testing was unremarkable, showing only slightly enlarged blind spots OU consistent with peripapillary atrophy of a myopic fundus
• OCT of the optic nerve showed RNFL thickness of 83 microns OD and 75 microns OS -- within normal range for her eyes
• Sensorimotor exam revealed orthotropia in all gazes despite diplopia complaints
• Severe downbeat nystagmus worsening in lateral gazes OU

Laboratory Studies

• Anti-GAD antibody: >250 IU/mL (normal <5 IU/mL) -- significantly elevated
• HbA1c: 7.4 (elevated, indicating poorly controlled diabetes)
• Vitamin B12: 5.8 nmol/L (low)
• Normal results: Anti-acetylcholine receptor antibodies, rheumatoid factor, QuantiFERON-TB Gold, ESR/CRP, Hepatitis B

Brain Imaging

• MRI brain was unremarkable, with no parenchymal lesions

Results

The patient was diagnosed with seronegative rheumatoid arthritis and autoimmune encephalopathy due to anti-GAD antibodies.

Treatment Course

1. Initial treatment: Oral prednisone 30 mg daily -- no improvement in any symptoms
2. Rheumatology referral: IV methylprednisolone infusion plus vitamin B12 supplementation -- nystagmus and balance improved following infusion
3. Maintenance regimen: Rituximab (Rituxan) infusion every 4 months and IVIG (Gammagard) infusion every month

Outcomes on Current Therapy

• Full ocular motility restored
• Nystagmus significantly improved
• Muscle weakness improved
• Joint pain improved
• Balance improved
• Patient continues on rituximab and IVIG with consistent follow-up with neurologist and rheumatologist

Clinical Significance

This case is notable for several reasons that expand the understanding of anti-GAD antibody syndrome:

• Concomitant rheumatoid arthritis and autoimmune encephalitis: A prior case report of this combination in a 57-year-old male showed significant parenchymal brain lesions on MRI, while this patient's MRI was entirely normal -- demonstrating that autoimmune encephalitis can occur without visible structural changes on imaging
• Ocular symptoms as presenting features: Unlike many previously reported cases of anti-GAD encephalitis that lacked ocular findings, this patient presented primarily with severe downbeat nystagmus and diplopia
• Treatment failure with oral steroids: The patient did not respond to oral prednisone, highlighting the importance of escalating therapy and using a multidisciplinary team approach
• Successful treatment with rituximab and IVIG: This combination achieved significant improvement in both neurological and rheumatological symptoms, whereas a prior case of anti-GAD encephalitis with nystagmus treated with plasma exchange and IV steroids showed improvement in balance but no improvement in ocular symptoms

Citation

Khachikyan N, Manasyan A, Hashemi N. Nystagmus and imbalance as the presenting symptoms of anti-GAD antibody syndrome in a 67-year-old female. J Opht Res Rev Rep. 2024;5(2):1-2. DOI: 10.47363/JORRR/2024(5)158

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