Results
calcification, fever, traumatic brain injury, seizures, stroke, traumatic brain injuries, subarachnoid hemorrhage, respiratory distress, death, headaches, infections, neurologic disease, tightness, pulmonary embolus, quadriparesis, nausea, antiseizure, ALS, arachnoid, pulmonary embolism, headache, hypertension, disability
PULMONARY EMBOLISM, BRAINSTEM STROKE, SINGLE SEIZURE, ADVERSE EVENTS, STROKE, EVENT, NEW-ONSET REFRACTORY STATUS EPILEPTICUS, INFECTIONS, CORTEX, SUBARACHNOID HEMORRHAGE, FOCAL MOTOR SEIZURES, PULMONARY EMBOLUS, HYPERTENSION, SEQUELAE, LOCALIZED SKIN INFECTION, COMPLICATIONS
Between 2004 and December 2021, 14 people enrolled in the BrainGate trial (Summary of Demographic and Safety DataThree participants were female and 11 were male. Eleven participants identified as White, 1 as Asian, 1 as Black, and 1 as Other. One participant identified as Hispanic ethnicity. All participants had quadriparesis, including 6 with SCI, 6 with ALS, and 2 with brainstem stroke. The median age at array implantation was 51 years (range 24–66). For participants with SCI or brainstem stroke, the median time from injury or stroke to implant was 8.5 years (range 3–11). For participants with ALS, the median time from diagnosis to implant was 5.5 years (range 2–7); we note that people with ALS often have symptoms for months or years before receiving a formal diagnosis. The median duration of device implantation was 774 days (range 296–1,994). There were 12,203 implant-days across all 14 participants (or 17,927 array-implant-days, counting participants with 2 arrays twice). Six participants underwent elective explant of the BrainGate device at the conclusion of their participation in the trial; 1 participant requested removal of the percutaneous pedestal but not the intracranial microelectrode array. Six participants died of progression of their underlying neurologic disease while enrolled. In no case was a participant’s death related to the investigational device or clinical trial; there were no unanticipated adverse device effects. Other than transitioning in 2013 from placing 1 to 2 arrays per participant and the introduction of a wireless signal transmitter in 2017,Among the 14 participants, there were 342 adverse events (AEs); the median number of AEs per participant was 21, and the range was from 0–62 AEs (Of the 68 device-related AEs (median 2 per participant, range 0–17), approximately half (35/68) were related to irritation, sensitivity, a sense of tightness, or other changes of the skin around the surgical incision or pedestal site. In many cases, these were caused by overly enthusiastic preventive care of the pedestal site by a caretaker or family member, and these resolved after reeducating caregivers. One participant was treated with oral antibiotics for a localized skin infection around a pedestal site and required no further treatment. In more than 17,000 array-days of implant, there were no intracranial or deep tissue (e.g., bone) infections related to the investigational device or any device-related infections requiring hospitalization, intravenous antibiotics, or device removal.Seven participants had perioperative AEs. In most cases, these were common postoperative problems such as low-grade fever, nausea, or headache. One participant had postoperative hypertension that required treatment with intravenous antihypertensives. A participant with a history of pulmonary embolism who was on chronic anticoagulation developed respiratory distress on postoperative day 3 (before the planned resumption of therapeutic anticoagulation on postoperative day 14). He was diagnosed with recurrent pulmonary embolus and restarted therapeutic anticoagulation with resolution of his symptoms. Given that anticoagulation was held for device placement, this event was classified as related to the study.In 3 of the 5 participants who had elective array explantation after more than a year (a sixth participant had the pedestal but not the array explanted), array removal was without complications or AEs. In all participants who had elective array removal, it was noted that the arachnoid had grown over the array. For 1 participant who had the BrainGate array explanted at the conclusion of her participation in the trial, surgery revealed that the array was well adhered to the brain and that, as expected, a thin, semitranslucent layer of arachnoid had grown over the array. The arachnoid was incised to partially expose the array, which was then removed. A small piece of tissue secured within the forceps (approximately 5 × 5 × 1 mm intact; measured after dislodgement from the sensor as a triangular piece of tissue 7.0 mm in its longest dimension) was lightly adherent to the electrode side of the array. Histology confirmed that the tissue included meninges and underlying superficial cortex. There was no clinical impact on the participant, who returned to her residence and usual activities on the first postoperative day. In another participant who underwent explantation at the conclusion of trial participation, after removal of the array and all visible portions of reference wires, the surgical investigator noted that the dura was densely adherent to the brain in the area surrounding the array; it was felt unsafe to perform further dissection to retrieve the full length of the 2 15 cm × 0.127-mm diameter reference wires. Postoperative CT imaging demonstrated a short curvilinear hyperdensity within the extra-axial space, suggestive of either a short length of retained reference wire or calcification along the track of the prior location of a reference wire. There were no clinical sequelae.Two participants, both of whom had a history of traumatic brain injury in addition to SCI, had seizures in the postimplantation period. In one case, the participant was noted intraoperatively to have a small but nonetheless atypical quantity (approximately 2 mL) of subarachnoid hemorrhage around 1 of the 2 implanted arrays. Four days later, he experienced 2 self-limited focal motor seizures, for which he was hospitalized and treated with levetiracetam. He continued levetiracetam as an outpatient, experienced no further seizures, and subsequently participated in the trial for 17 months without any other neurologic AEs. This participant had not received a prophylactic antiseizure medication postoperatively because this practice had not yet been incorporated into the study protocol. Another participant had a single seizure on postoperative day 4; he too was admitted to the hospital, started on levetiracetam, and had no further seizures. He remains enrolled in the clinical trial and has been participating in research sessions for more than 2 years. He had been prescribed a prophylactic antiseizure medication, but 2 doses were missed during the transition from hospital to home. These participants' prior traumatic brain injuries were believed to have increased their risk for seizures.Before the 2 postoperative seizures described earlier, 1 participant experienced new-onset refractory status epilepticus (NORSE).While not an AE, we also note that for the participants who had the investigational device (array(s) and/or pedestal) electively explanted at their conclusion of participation in the trial, additional surgical consideration was required to close the well-healed scalp site(s) after removal of the pedestal(s). In participants with a thicker scalp, clean debridement and closure of the healed pedestal site was directly achieved. In a participant with a thinner scalp, additional loosening of the underlying tissue was necessary to close the site, which contributed to postoperative headaches. In addition, and while also not AEs, 2 participants in the first IDE had unexpected abrupt changes (or initial absence) of recording quality. In 1 participant, nonoperative provisional repair of an external component of the percutaneous pedestal was performed 6 months after device placement; the wire bonds had failed at the landing grid assembly within the pedestal, and conductive epoxy was manually placed on each bond site to attempt to restore connections. The initial source of this failure was attributed to the method of sterilization of the devices, which was subsequently changed. Approximately 4.5 months later, the number of useable signals recorded from the array again dropped abruptly, with moderate recovery of signals. There was no clinical change in the participant coinciding with this change in signals nor was this event believed to represent a risk to the health, safety, or welfare of the participant, and it was reported as an unexpected change in device performance. It is unknown whether this loss of signals was due to failure of the previous repair or an unrelated event, such as array dislodgement/displacement from coughing (which the patient had reported) or other participant-specific factors. After the initial device failure and discussion with the device manufacturer, modifications were made to the sterilization procedures used before delivery to investigators. In a second participant during this early period, caregivers inadvertently applied a sudden axial force to the participant's head and pedestal while placing the participant back into bed (by too forcefully contacting the headrest of the bed with the participant's head). There was a substantial return of recording quality within a month, though with considerably more day-to-day variability than previously seen. Overall, this study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs, defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.