BACKGROUND:
Glutamic acid decarboxylase 65 (GAD-65) antibody spectrum disorders encompass a range of autoimmune neurological conditions associated with impaired GABAergic inhibition, leading to syndromes such as stiff-person syndrome, cerebellar ataxia, and epilepsy. Ocular motor abnormalities including nystagmus and saccadic dysmetria are recognized features; however, lid lag and von Graefe’s sign are classically linked to thyrotoxicosis. Their occurrence in GAD-65 autoimmunity without thyroid dysfunction has not been previously reported.
CASE PRESENTATION:
We describe the case of a 51-year-old woman with known GAD-65 antibody spectrum disorder who presented with progressive gait instability and new ocular findings. Ocular exam revealed bilateral lid lag and von Graefe’s sign, rotatory nystagmus, and impaired smooth pursuit. Thyroid function tests and thyroid autoantibodies were normal. Serum GAD-65 antibody levels remained elevated (634 nmol/L). There was no evidence of neuromuscular junction or motor neuron disease on EMG.
DISCUSSION:
GAD-65 antibodies disrupt GABAergic inhibitory control within cerebellar and brainstem circuits resulting in neuronal hyperexcitability and which can lead to ocular motor disturbances classically seen in GAD-65 spectrum disorder. Within the oculomotor system, GABAergic modulation also plays a role in eyelid control by regulating motoneuron excitability. GABAA receptors mediate inhibition in oculomotor motoneurons, including those innervating the levator palpebrae superioris (the muscle responsible for elevating the upper eyelid). We propose that the reduction of GABAergic inhibition, as seen in GAD65-associated autoimmune syndromes, may heighten motoneuron excitability and disrupt normal eyelid control, potentially manifesting clinically as lid lag.
CONCLUSIONS:
Recognition of lid lag as a potential manifestation of GAD-65 antibody syndromes may prompt consideration of autoimmune neurological disease in patients presenting with other features of stiff-person syndrome or cerebellar dysfunction. The finding emphasizes the importance of a comprehensive neurological evaluation in patients with lid lag in the absence of thyroid dysfunction to avoid misattribution to endocrine causes alone.