To describe a patient with antiGAD65 positive Stiff Person Spectrum Disorder, initially mimicking serotonin syndrome.

Stiff person syndrome (SPS) is a rare autoimmune disorder, characterized by progressive rigidity and painful muscular spasms, most commonly due to antiGAD antibodies, impairing GABA synthesis, leading to loss of inhibitory neurotransmission and continuous motor-unit firing. PERM represents a severe form within this spectrum, often involving brainstem and autonomic dysfunction. Although PERM is often associated with glycine receptor antibodies, anti–GAD–positive cases highlight the overlap of autoimmune GABAergic disorders and the expanding GAD antibody–associated neurological spectrum.

We present a case of A 47-year-old woman with no medical history who presented with painful muscle cramps and stimulus-triggered jerks initially thought to be functional. She was started on paroxetine and tizanidine, after which she developed profound rigidity, tremor, and hyperthermia (Tmax 107 °F) with encephalopathy and autonomic instability contributing to intubation and ICU admission. Despite benzodiazepines and cyproheptadine for suspected serotonin syndrome, she remained encephalopathic with persistent progressive rigidity and myoclonus. Infectious and metabolic workups were negative; MRI brain and EEG were unremarkable. Serum anti–GAD65 antibody came back strongly positive (40 SI; ref <11), CSF showed mild protein elevation (65 mg/dL). She received IV methylprednisolone (5 days), IVIG (5 days), plasma exchange (5 sessions), and rituximab (1g × 2 doses), eventually with gradual improvement.

Following immunotherapy and gradual steroid taper, her myoclonus and rigidity markedly improved. She regained independent ambulation with PT and has remained free of recurrent spasms on prednisone 10 mg daily, diazepam 5 mg q6h, and levetiracetam 1500 mg BID. At her 6 month follow-up, she reported rare transient facial tremors.

This case illustrates that anti–GAD65–associated PERM can present with hyperthermia and AMS, mimicking serotonin syndrome. Recognition of persistent rigidity and stimulus-induced myoclonus with negative EEG correlation should prompt autoimmune evaluation and early multimodal immunotherapy.