Associate Program Director Loma Linda University Loma Linda, California, United States
Case Diagnosis: Anti-glutamic acid decarboxylase 65 (GAD65) autoimmune encephalitis (AE)
Case Description: A 32-year-old left-handed female stage manager with a past medical history of hypothyroidism presented with acute left hand dystonia and epilepsy. A year later, she was admitted for worsening right-sided headache and bilateral vision loss. vEEG revealed lateral periodic discharges and focal occipital seizures. Initial brain MRI showed cortical and subcortical T2/FLAIR hyperintensity of the left occipital lobe. Workup returned positive for GAD65 antibodies. After extensive workup, Rituximab and IVIG were initiated for suspected AE, with concomitant anti-epileptics. She was transferred to Neurology for status epilepticus, intubation, and tracheostomy. She was admitted to acute inpatient rehabilitation for neurologic monitoring and daily therapy. She continued to experience hand dystonia, visual changes, and hallucinations. Her function improved globally from substantial maximum assistance to supervision-independence in 26 days.
Discussions: We present a complicated case of anti-GAD65 AE, a rare but increasingly recognized disease. Autoantibodies targeting GAD65, an intracellular enzyme in presynaptic inhibitory neurons, have been associated with stiff person syndrome, cerebellar ataxia, epilepsy, and limbic encephalitis. While no controlled studies of immunotherapies for anti-GAD65 AE exist, our patient benefited from IVIG, anti-epileptics, and Rituximab, consistent with other retrospective reports. After intensive physical, occupational, and speech therapy, her functional mobility, blurriness, and visual hallucinations improved. An initial trial of carbidopa/levodopa was not successful in treating her dystonia, but baclofen yielded notable improvement. Interestingly, she displayed psychosomatic improvement in hand movement and vision in the absence of an audience.
Conclusions: Anti-GAD65 AE may present with a unique constellation of focal seizures, dystonia, and neuro-ophthalmic symptoms. These signs, along with imaging and lumbar puncture evidence of inflammation, should prompt early antibody testing and immunotherapy. Our patient responded to IVIG, Rituximab, and comprehensive inpatient multidisciplinary rehabilitation to improve her functional neurologic outcome.
