4-Aminopyridine Toxicity Mimics Autoimmune-Mediated Limbic Encephalitis

4-Aminopyridine (4-AP) is a potassium channel blocker which increases motor performance and walking speed in multiple sclerosis (MS) and spinal cord injury.1 It enhances action potentials by blocking open potassium channels. 4-AP toxicity can cause dizziness, nausea, weakness, psychosis, and seizures.2 In limbic encephalitis, antibodies bind voltage-gated potassium channels (VGKC) and damage peripheral and central neurons.3 VGKC subtypes exist in brain, peripheral nerves, vascular endothelium, and all muscle types.4 We document that severe 4-AP overdose causes significant abulia, cognitive impairment, and prominent myopathic changes in heart and skeletal muscle. The temporal lobe MRI signal and clinical presentation have parallels to the seemingly distinct disease, limbic encephalitis. ### Case report. A 22-year-old man with MS ingested 30 10-mg tablets of 4-AP. He had agitated behavior but was oriented, conversant, and without focal neurologic deficits or muscle fibrillations. He had cool, flushed, diaphoretic skin with temperature of 38.9°C. Blood pressure was 209/108 mm Hg, with runs of supraventricular tachycardia to 170 beats per minute. Intubation for airway protection led to intensive care unit admission. EEG exhibited frequent diffuse polyspike and spike-wave discharges that normalized over time. There were no electrographic or clinical seizures. Transthoracic echocardiogram revealed diffuse hypokinesis, and an ejection fraction of 24%. CSF …