Discussion
quadriparesis, death, seizures, epilepsy, fatigue, infections, ALS, quadriplegia, skin infection, paralysis, infection, tetraplegia, NORSE, weakness, disorders of mood or cognition, disability
ADVERSE EVENT, MOVEMENT DISORDERS, EPILEPSY, PARKINSON DISEASE, INFECTIONS, QUADRIPLEGIA, SKIN INFECTION, INFECTION, STERILE, CORTEX, TETRAPLEGIA, SAID, COMPLICATIONS
The investigational BrainGate Neural Interface system has an encouraging safety record, with more than 17,000 person-array implant-days of data. All 12 participants who were enrolled for more than 1 year met the primary safety endpoint of not having the device removed for safety reasons during the 1-year postimplant evaluation. Although 6 SAEs were classified as possible, probably, or definitely device-related or procedure-related, there were no device-related SAEs that resulted in death or permanently increased disability during the 1-year postimplant evaluation period (Two participants died of complications from ALS before the 1-year evaluation). Device safety has also remained reassuring over the 2 to 5+ years that 8 participants have been enrolled.The most common AE (Detailed Adverse Event Summary TableThe participant who experienced NORSE illustrates how medical device research can raise dilemmas at the interface of research ethics and medical ethics. Similar to many trials of novel medical devices, the ethical premise under which participants are recruited and provide informed consent to this study is that there This work has some limitations warranting discussion. The most significant, from a clinical trials standpoint, is the lack of a control arm; for myriad ethical and logistical reasons, an experimental control (e.g., surgery without device use) would not be feasible. We are nonetheless reassured by our findings that the percutaneous BrainGate system has a safety profile, to date, in a population of people with tetraplegia, which is comparable with fully implanted deep brain stimulation (DBS) devices approved for the treatment of certain movement disorders and the responsive neurostimulation (RNS) device approved for the treatment of partial-onset seizures refractory to 2 or more antiepileptic medications. Large studies with more than 100 patients undergoing DBS implantation have reported infection rates between 3% and 5% of patients,Our clinical research experience with a percutaneously connected intracortical neural recording system has included only a single device-related skin infection and no bone or CNS infections. We ascribe this to a thorough preoperative skin cleansing protocol (consisting of 3 days of a daily pre-operative full body wash with chlorhexidine soap); careful intraoperative attention to sterile procedure; a rigorous caregiver protocol for maintaining an aseptic environment around the percutaneous pedestals; and chlorhexidine-impregnated patches (BioPatch) around the pedestal site (Anti-infective Procedures/ProtocolsA second limitation in comparing the safety profile of this device with other chronically implanted neurotechnologies is that the people enrolled in the BrainGate trial have different neurologic conditions than the populations enrolled in other neurotechnology trials. People with quadriparesis may have greater contact with caregivers attending to health-related needs than those with epilepsy or Parkinson disease; consequently, comparisons with devices intended for ambulatory populations are imperfect. In addition, while our participants consented to the risk of worsening paralysis because of array placement on motor cortex (which has not been observed), given the significant baseline weakness required to enroll, subtle changes in motor function may occur below the threshold of clinical perception. With that said, the ongoing BrainGate trial and subsequent studies using similar research protocols and the Blackrock NeuroPort array were informed by numerous animal studies of safety, histology, and chronic device functionWhile safety is the While an exhaustive review of the potential benefits of the iBCI approach is beyond the scope of this article, the “risk/benefit” analysis—particularly as considered by an individual with paralysis contemplating the use of different assistive technologies—will be central to the future success of these devices. For example, some participants have entered the study frustrated, for a host of reasons, by the utility of their eye-gaze systems. Despite relative preservation of eye movements in the earlier stages of ALS, subtle changes in motor control, slowness of saccades, fatigue in supporting musculature, and progressive ophthalmoparesis can all affect performance with these systems.Furthermore, for a person with severe speech and motor impairments, the ability to use an assistive technology while visually engaging with their dialog partner—which itself has communication value—is also important. Consequently, iBCIs provide not only theoretical advantages over eye-gaze systems but also over other BCIs (implanted or EEG based) that encumber eye movements specifically to navigate communication interfaces. Given iBCIs' early demonstrations of the ability to support multidimensional, dexterous reach-and-grasp movements, to restore sensation (with some further improvement in, for example, assistive robot control),Overall, we are reassured by our findings over the past 17 years that the investigational BrainGate Neural Interface System is being deployed safely. The development of a fully implantable system, which would reduce the infection concern presented by a percutaneous component and provide more acceptable cosmesis for many users, remains an important goal of our group and others. Moreover, this trial has been conducted during and continues to benefit from a revolution in machine learning/artificial intelligence and microprocessor technology. Advances in these fields have contributed to the ongoing improvement in performance that we have observed, and we anticipate that these technical gains will only accelerate in the coming years. Of importance, these same technological advances have led to improvements in consumer assistive technology available to people with paralysis. Voice control platforms such as Siri and Alexa may allow a person with quadriplegia and intact speech naturalistic control over their consumer electronics and home environment, and head-mounted virtual reality/augmented reality technology may provide additional channels of communication for people who have lost the ability to speak. However, no one technological solution will work best for everyone. Indeed, many able-bodied individuals prefer to type or text rather than use voice recognition to maintain the privacy of their communication from the people in their immediate surroundings, and much of the drive for iBCIs is not only to restore communication but also to restore mobility through intuitively controlled functional electrical stimulation or soft/wearable robotics. Intracortical BCIs also are being developed as key components of closed-loop neuromodulation therapies that may improve the management of disorders of mood or cognition.