Excitatory-inhibitory imbalance is central to epilepsy pathophysiology. Current surgical therapies for epilepsy, such as brain resection, laser ablation, and neurostimulation, target epileptic networks on macroscopic scales, without directly correcting the circuit-level aberrations responsible for seizures. The transplantation of inhibitory cortical interneurons represents a novel neurobiological method for modifying recipient neural circuits in a physiologically corrective manner. Transplanted immature interneurons have been found to disperse in the recipient brain parenchyma, where they develop elaborate structural morphologies, express histochemical markers of mature interneurons, and form functional inhibitory synapses onto recipient neurons. Transplanted interneurons also augment synaptic inhibition and alter recipient neural network synchrony, two physiological processes disrupted in various epilepsies. In rodent models of epilepsy, interneuron transplantation corrects recipient seizure phenotypes and associated behavioral abnormalities. As such, interneuron transplantation may represent a novel neurobiological approach to the surgical treatment of human epilepsy. Here, the authors describe the preclinical basis for applying interneuron transplantation to human epilepsy, discuss its potential clinical applications, and consider the translational hurdles to its development as a surgical therapy.
Stephen C. Harward and Derek G. Southwell
Theresa L. Williamson, Andrew Cutler, Mary I. Cobb, Shervin Rahimpour, Eric R. Butler, Stephen C. Harward, Thomas J. Cummings, and Allan H. Friedman
This study describes a patient with an autograft-derived spinal cord mass following transplantation of olfactory mucosa for treatment of cervical spine injury. The authors report the case of a 35-year-old man who suffered a complete spinal cord injury (SCI) at C5–6 in 2001. The patient underwent an olfactory mucosal cell implantation at the location of injury 4 years following initial trauma. Twelve years later, the patient presented with rapidly progressive decline in upper-extremity function as well as neuropathic pain. Imaging revealed a heterogeneously enhancing intramedullary mass from C3 to C7. At surgery, the patient was found to have a posttransplant mucinous mass. Each mucinous cyst was drained and a portion of the cyst wall was removed. Histological examination demonstrated ciliated epithelium-lined fibrous tissue, submucosal glands, and mucoid material, consistent with a transplant-derived tumor. This case report both documents a rare long-term complication of olfactory mucosal cell transplantation and serves as a cautionary tale encouraging prudent use of novel treatments in a vulnerable population of patients with severe SCI.