What is the early fate of adjacent segmental lordosis compensation at L3-4 and L5-S1 following a lateral versus transforaminal lumbar Interbody Fusion at L4-5?

INTRODUCTION: Degenerative spondylolisthesis causes translational and angular malalignment, resulting in a loss of segmental lordosis. This leads to compensatory adjustments in adjacent levels to maintain balance. Lateral lumbar interbody fusion (LLIF) and transforaminal lumbar interbody fusion (TLIF) are common techniques at L4-5. This study compares compensatory changes at adjacent L3-4 and L5-S1 levels six months post LLIF versus TLIF for grade 1 degenerative spondylolisthesis at L4-5. METHODS: A retrospective study included patients undergoing L4-5 LLIF or TLIF with posterior pedicle screw instrumentation (no posterior osteotomy) for grade 1 spondylolisthesis. Pre-op and 6-month post-op radiographs measured segmental lordosis (L3-L4, L4-L5, L5-S1), lumbar lordosis (LL), and pelvic incidence (PI), along with PI-LL mismatch. Multiple regressions were used for hypothesis testing. RESULTS: 113 patients (61 LLIF, 52 TLIF) were studied. TLIF showed less change in L4-5 lordosis (mean = 1.04°, SD = 4.34) compared to LLIF (mean = 4.99°, SD = 5.53) (p = 0.003). L4-5 angle changes didn't correlate with L3-4 changes, and no disparity between LLIF and TLIF was found (all p > 0.16). In LLIF, greater L4-5 lordosis change predicted reduced compensatory L5-S1 lordosis (p = 0.04), while no significant relationship was observed in TLIF patients (p = 0.12). CONCLUSION: LLIF at L4-5 increases lordosis at the operated level, with compensatory decrease at L5-S1 but not L3-4. This reciprocal loss at adjacent L5-S1 may explain inconsistent improvement in lumbar lordosis (PI-LL) post L4-5 fusion.

Deep Brain Stimulation for Primary Refractory Tinnitus: A Systematic Review.

BACKGROUND: tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. METHODS: a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. RESULTS: seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). CONCLUSIONS: DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice.

Implementation of the Modified Brain Injury Guidelines Might Be Feasible and Cost-Effective Even in a Nontrauma Hospital.

INTRODUCTION: The modified Brain Injury Guidelines (mBIG) provide a framework to stratify traumatic brain injury (TBI) patients based on clinical and radiographic factors in level 1 and 2 trauma centers. Approximately 75% of all U.S. hospitals do not carry any trauma designation yet could also benefit from these guidelines. To the best of our knowledge, this is the first report of applying the mBIG protocol in a community hospital without any trauma designation. METHODS: All adult patients with a TBI in a single center from 2020 to 2022 were retrospectively classified into mBIG categories. The primary outcomes included neurological deterioration, progression on computed tomography of the head, and surgical intervention. Additional outcomes included the hospital costs incurred by the mBIG 1 and mBIG 2 groups. RESULTS: Of the 116 included patients, 35 (30%) would have stratified into mBIG 1, 23 (20%) into mBIG 2, and 58 (50%) into mBIG 3. No patient in mBIG 1 had a decline in neurological examination findings or progression on computed tomography of the head or required neurosurgical intervention. Three patients in mBIG 2 had radiographic progression and one required surgical decompression. Two patients in mBIG 3 demonstrated a neurological decline and six had radiographic progression. Of the 21 patients who received surgical intervention, 20 were stratified into mBIG 3. Implementation of the mBIG protocol could have reduced costs by >$250,000 during the 2-year period. CONCLUSIONS: The mBIG protocol can safely stratify patients in a nontrauma hospital. Because nontrauma centers tend to see more patients with minor TBIs, implementation could result in significant cost savings, reduce unnecessary hospital and intensive care unit resources, and reduce transfers to a tertiary institution.

Successful Implantation of a Ventricular Shunt With Termination in the Iliac Bone in the Adult Patient With Obstructive Hydrocephalus.

BACKGROUND AND IMPORTANCE: With the exception of the 3 classic shunt placement options (ventriculoperitoneal, ventriculopleural, and ventriculoatrial), surgically feasible alternative sites for distal catheter placement remain limited and often require the assistance of an access surgeon. Tubbs et al suggested the possibility of intraosseous cerebrospinal fluid diversion in the ilium, noting that ilium infusion in cadaveric specimens was possible without the development of body edema or fluid overflow. Since this publication, limited case reports have been published on the success of ventriculo-ilium (VI) shunt placement. Here, we describe the technique used for successful VI shunt placement in 2 adult patients. CLINICAL PRESENTATION: Here, we describe 2 patients with differing etiologies of hydrocephalus (obstructive and nonobstructive) and complex medical and surgical problems precluding traditional distal shunt termini. Both patients underwent successful placement of a VI shunt with distal catheter placement into the right iliac crest using a small right-angle connector and small cranial fixation plate to prevent backout of the catheter. DISCUSSION AND CONCLUSION: We report the first demonstration of successful placement of a VI shunt in 2 adult patients with evidence of shunt functionality and improved neurological outcome. We propose that the placement of a VI shunt is an easy and viable option when more traditional shunt methods are not available for use.

Ten-Year Durability of Hypothalamic Deep Brain Stimulation in Treatment of Chronic Cluster Headaches: A Case Report and Literature Review.

Chronic cluster headache (CCH) is a debilitating primary headache that causes excruciating pain without remission. Various medical and surgical treatments have been implemented over the years, yet many provide only short-term relief. Deep brain stimulation (DBS) is an emerging treatment alternative that has been shown to dramatically reduce the intensity and frequency of headache attacks. However, reports of greater than 10-year outcomes after DBS for CCH are scant. Here, we report the durability of DBS in the posterior inferior hypothalamus after 10 years on a patient with CCH. Our patient experienced an 82% decrease in the frequency of headaches after DBS, which was maintained for over 10 years. The side effects observed included depression, irritability, anxiety, and dizziness, which were alleviated by changing programming settings. In the context of current literature, DBS shows promise for long-term relief of cluster headaches when other treatments fail.

Clinical Guidelines for the Evaluation and Treatment of Lumbar Disc Herniations: How Accurate is the Internet?

OBJECTIVE: To compare information online regarding lumbar disc herniation (LDH) on commonly searched websites and compare those findings with the evidence-based recommendations listed in the North American Spine Society (NASS) clinical practice guidelines. METHODS: NASS Clinical Practice Guidelines, Internet searches were performed utilizing three common search engines (Google, Bing, Yahoo) and keywords associated with LDH. The top 20 websites from each search were selected. The content regarding diagnosis and treatment of LDH was compared to the NASS clinical practice guidelines. RESULTS: On average, websites mentioned only 59% of recommendations supported by Level I evidence. Websites included an average of 3 recommendations not discussed in the NASS guidelines out of an average of 12 total recommendations. Muscle and sensory testing and physical therapy were the most frequent recommendations, appearing on over 80% of websites. Websites were equally likely to contain recommendations backed by high-quality evidence as recommendations not included in NASS guidelines. CONCLUSIONS: This study demonstrates that websites regarding LDH contain a mix of information, with only a fraction of recommendations aligning with NASS clinical guidelines. Patients who use these websites are presented with unsubstantiated information, conceivably impacting their understanding, expectations and decision-making in physician offices.

The Surgeon Ergonomic Impact of a Tubular-Based Digital Camera to Perform a Seated Posterior Cervical Foraminotomy.

BACKGROUND: Posterior cervical decompression is a common spine procedure that can be performed with the patient in prone or sitting position. The sitting position provides the potential benefits of more facile retraction of surrounding soft tissues, increased operative field and fluoroscopic visualization, and decreased epidural bleeding. However, the surgeon's ergonomics of this positioning can be quite challenging when using the standard operative microscope to perform the procedure and may cause musculoskeletal harm to the surgeon. METHODS: A sterile digital camera was brought into the field to perform a sitting foraminotomy completed through the tube retractor at both C6-7 and C7-T1 levels. For half of the procedure, a typical neurosurgical operative microscope was brought into the field to evaluate surgeon ergonomics using baseline Rapid Entire Body Assessment (REBA) scores for 2 surgeons of differing stature. The digital camera was inserted onto the tubular retractor, and REBA scores were calculated. RESULTS: With a microscope, the surgeon with taller stature scored a 5 on the initial REBA scale, and the surgeon with shorter stature scored a 6, placing both in the medium-risk category. Once the tubular-based camera was placed, repeated REBA score of both surgeons was 3, placing them in the low-risk category. CONCLUSIONS: Using a tubular-based digital camera system, the ergonomics of the surgery are substantially improved. The surgeon can stand closer to the operative field and look directly at a front-facing screen, allowing increased relaxation of the upper extremity and cervical musculature; improving overall ergonomic function.

Treatment of L5-S1 spondyloptosis with stand-alone anterior lumbar interbody fusion in a patient with neurofibromatosis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder that causes multiple tumor formations throughout the nervous system. Common spinal dysplasias seen with NF1, such as dural ectasia (DE), often undergo modulation and predispose these patients to spondylolisthesis, making surgical treatment challenging. CASE DESCRIPTION: A patient with NF1 presented with a 12-year-history of back and left lower extremity radicular pain. Lumbar spine magnetic resonance imaging revealed developmental anomalies with severe DE and associated scalloping of the L4-S1 vertebral bodies and severe L5-S1 Meyerding grade 4 spondylolisthesis. During surgery, post-positioning x-rays demonstrated a grade 5 spondyloptosis. The patient underwent an L5-S1 stand-alone anterior lumbar interbody fusion (ALIF). The final construct was an ALIF cage with one screw into S1, without an anterior plate. By 3-months post-operative, there was complete resolution of preoperative symptoms and at 2 year follow-up the patient was asymptomatic with stable hardware and solid bony fusion. To the authors' knowledge, this is the first report of spondyloptosis treated with a stand-alone ALIF in a patient with NF1 and severe DE.

The Impact of Surgical Approach on Sagittal Plane Alignment in Patients Undergoing One- or Two- Level Fusions for Degenerative Pathology: A Multicenter Radiographic Evaluation 6 Months Following Surgery.

OBJECTIVE: Interbody fusion procedures, including transforaminal (TLIF), posterior (PLIF), anterior (ALIF), and lateral (LLIF), effectively treat lumbar degenerative pathology and provide spinopelvic balance. The objective of this study is to compare changes in spinopelvic parameters 6 months following 1-2 level TLIF, PLIF, ALIF, and LLIF. METHODS: This retrospective study included 18 centers across the United States. Patients were included in the study if they underwent a 1- or 2-level primary lumbar fusion for degenerative pathology. Preoperative and 6-month postoperative lumbar anteroposterior and lateral lumbar plain radiograph measurements included: pelvic incidence, pelvic tilt, lumbar lordosis from L1-S1, and segmental lordosis of each segment between L1 and S1. RESULTS: A total of 474 patients met inclusion criteria, with 632 levels that underwent fusion. Of these, 181 patients underwent an ALIF/LLIF on 381 levels, and 188 underwent a TLIF/PLIF on 252 levels. ALIF/LLIF procedures resulted in significantly more segmental lordosis (P < 0.001) and global lumbar lordotic alignment change (P < 0.01) compared with TLIF/PLIF procedures. Whether patients' alignment was preserved versus worsened was not significantly predicted by type of procedure. Similarly, whether patients' alignment was restored versus not corrected was not significantly predicted by procedure. CONCLUSIONS: In this large-scale multicenter study of lumbar fusion patients presenting with degenerative lumbar pathology, anteriorly placed grafts (ALIF/LLIF) led to a greater likelihood of patients being preserved rather than worsened in their spinopelvic mismatch. Posteriorly placed TLIF or PLIF grafts tended to worsen lordosis both segmentally and globally, yet even the anterior grafts only modestly improved those 2 same measurements.

The impact of interbody approach and lumbar level on segmental, adjacent, and sagittal alignment in degenerative lumbar pathology: a radiographic analysis six months following surgery.

BACKGROUND CONTEXT: Interbody fusion, including: transforaminal (TLIF), posterior (PLIF), anterior (ALIF), and lateral (LLIF); effectively treat lumbar degenerative pathology and provide spinopelvic balance. Although the decision on surgical approach and technique are multifactorial and patient specific, the impact of the interbody approach on segmental and adjacent level lordosis could be an important factor to consider during pre-operative planning to achieve pre-specified alignment goals. PURPOSE: The purpose of this study is to compare the 6-month postoperative radiographic outcomes in the lumbar spine following 1 to 2 level transforaminal (TLIF), posterior (PLIF), anterior (ALIF), and lateral (LLIF) interbody fusions at the L3-4, L4-5, and L5-S1 levels. As our primary outcome, we evaluated the change in segmental lordosis at the level of fusion in ALIF/LLIF approaches compared to TLIF/PLIF. Secondarily, we evaluated the pelvic incidence to lumbar lordosis (PI-LL) mismatch and examined the compensatory lordotic changes at the adjacent levels 6 months following surgery. STUDY DESIGN: Retrospective cohort. PATIENT SAMPLE: This retrospective study included 18 centers of various practice settings across the United States. Patients were included in the study if they underwent a one- or two-level primary lumbar fusion for degenerative pathology. OUTCOMES MEASURES: Measurements of the pre-operative and 6-month post-operative lumbar AP and lateral lumbar plain radiographs included: pelvic incidence (PI), pelvic tilt, lumbar lordosis from L1-S1 (LL), as well as segmental lordosis (SL) of each segment between L1-S1. METHODS: Due to there being 2 evaluated time points, patients were then grouped based on alignment into categories of preserved, restored, not corrected, and worsened. RESULTS: 474 patients underwent 608 levels of fusion. ALIF/LLIF resulted in significantly more segmental lordosis compared to TLIF/PLIF procedures at both L4-5 and L5-S1 (p<.001). Overall, ALIF/LLIF resulted in significantly more global lumbar lordotic alignment change compared to TLIF/PLIF (p=.01). Whether patients' alignment was preserved versus worsened was not significantly predicted by type of procedure. Similarly, whether patients' alignment was restored versus not corrected was not significantly predicted by type of procedure. Finally, anterior approaches resulted in decreased lordosis at adjacent levels, thus resulting in a more neutral position. CONCLUSION: In this large multicenter retrospective study of 1 to 2 level interbody fusion surgeries, we identified that A/LLIF procedures at L4-L5 and L5-S1 resulted in greater segmental lordosis restoration and PI-LL mismatch improvement compared to T/PLIF procedures. A/LLIF may also significantly reduce lordosis (compared to T/PLIF) at the adjacent levels in a fashion that serves to reduce the lumbar lordosis that may have been increased at the fused level.

Transforaminal Endoscopic Lumbar Discectomy and Foraminotomy with Modified Radiofrequency Nerve Stimulator and Continuous Electromyography Under General Anesthesia.

BACKGROUND: Transforaminal endoscopic lumbar approaches involve working in Kambin's triangle. These procedures are performed on awake patients or under general anesthesia with continuous electromyography. Potential morbidity of this approach includes injury to exiting and traversing nerve roots, as substantial dissection or cauterization of overlying tissues is required for visualization. METHODS: We developed a novel connection system that accepts input from a bipolar radiofrequency probe to allow direct nerve stimulation in conjunction with electromyography. This study included 30 consecutive patients undergoing transforaminal endoscopic lumbar approaches for discectomies (73.3%), foraminal stenosis (23.3%), or lateral recess stenosis (3.3%). Demographic, operative, and outcomes data were collected. RESULTS: Average age of patients was 61.4 years, and the L4-5 segment was most commonly treated (65.6%). Electrophysiologic mapping of the exiting nerve root was attempted in 28 patients with an average stimulation threshold of 8.6 ± 0.9 mA. Mapping of the traversing nerve root was attempted in 12 patients with an average stimulation threshold of 6.0 ± 0.8 mA. There were no instances of new postoperative sensorimotor deficits or dysesthesia. These findings persisted through mean and median follow-up of 294 days and 165 days, respectively. No patient required subsequent lumbar surgery. CONCLUSIONS: Our modified instrumentation and technique allow for accurate identification of the exiting and traversing nerve roots with minimal changes to the workflow of transforaminal endoscopic lumbar approaches. Modification of a bipolar radiofrequency device connection arrangement is simple, inexpensive, and reusable. In this study, no patients developed injury or pain related to nerve root dysfunction.

Intraoperative neuromonitoring for one-level lumbar discectomies is low yield and cost-ineffective.

BACKGROUND: Intraoperative neuromonitoring is a common, well-established modality used in spine surgery to prevent intraoperative neural injury. Neuromonitoring use in lumbar discectomy, however, is based on surgeon preference, without evidence-based data. The purpose of this research was to determine intraoperative utility and overall cost effectiveness of neuromonitoring for lumbar discectomy. METHODS: We retrospectively reviewed adult patients who underwent a lumbar discectomy, with at least 1 month of follow-up at a single tertiary care center. Patient age, sex, body mass index (BMI), lumbar level operated, and operative time and cost were collected. Neuromonitoring and operative reports were reviewed for any electromyography (EMG) abnormalities noted intraoperatively, pre- and post-operative motor exam and post-operative pain relief were collected. RESULTS: Ninety-one (47 with and 44 without neuromonitoring) lumbar discectomy cases were reviewed. There was no significant difference between mean age, sex, and BMI between the two groups. There was a significant (p = 0.006) increase in operating room time (174 min; with vs. 144 min; without neuromonitoring). Neuromonitoring was associated with a significant (p = 0.006) overall operative cost ($21,949; with vs. $18,064; without). Of the 47 cases with neuromonitoring; one had abnormal intraoperative EMG activity, which returned to normal by case conclusion. No patient in either group demonstrated new post-operative motor weakness. There was no difference in the number of patients who endorsed post-operative pain relief between the two groups. CONCLUSIONS: Neuromonitoring for lumbar discectomy confers greater operative time and cost, without any difference in neurological outcome.

Two-level reverse Bohlman transsoseous approach for treatment of symptomatic pseudarthrosis.

Surgical treatment for high-grade spondylolisthesis with high sacral slope remains controversial and no definitive gold standard procedure has been identified. The Bohlman technique, in which a fibular strut is reamed posteriorly across the L5-S1 disc space in an oblique, inferior to superior trajectory, has been increasingly utilized. Recently, a Reverse Bohlman technique has been described, in which a graft is reamed anteriorly across a single disc space in a superior to inferior trajectory. Case Report A 55 year-old male with complete lumbarization of S1 (referred to as L6) and previous L5-L6-S1 posterior instrumented fusion presented, with progressively worsening low back pain and lower extremity radicular pain. After failing conservative management, he underwent a 2-level Reverse Bohlman approach to place a titanium mesh interbody graft (cage) anteriorly from L5 to S1, crossing the L5-6 and L6-S1 disc spaces. Here we describe for the first time a Reverse Bohlman technique spanning two disc spaces in a patient with a transitional lumbosacral anomaly and high sacral slope. At 6 months post-operative follow up, the patient reported near complete resolution of symptoms.

Novel Use of Responsive Neurostimulation (RNS System) in the Treatment of Super Refractory Status Epilepticus.

There are very few randomized controlled trials studying treatment of super refractory status epilepticus (SE), despite estimated occurrence in about 15% of SE cases and its association with high morbidity and mortality rates. Small case series and case reports have described use of neurostimulation, including vagal nerve stimulation, transcranial magnetic stimulation, and deep brain stimulation, to treat super refractory SE when medical interventions have failed. To our knowledge, this is the first reported case of responsive neurostimulation being used to successfully treat a case of super refractory SE. A 37-year-old man with refractory focal epilepsy and a known focal cortical dysplasia involving motor cortex was implanted with an RNS System device after being in super refractory SE for 20 days. Responsive neurostimulation strip and depth electrodes were placed targeting the cortical dysplasia. Detection and stimulation parameters were adjusted over a 14-day period, as medications were gradually weaned. Seizures abated 15 days after implant, 24 hours after stimulation parameters were configured to mimic seizure offset pattern. Seizure remission was sustained, allowing the patient to be weaned off sedating medications and discharged to a rehabilitation facility. At 6 weeks of follow-up, the patient was near his neurologic baseline with no focal deficits.

Fivefold higher rate of pseudarthrosis with polyetheretherketone interbody device than with structural allograft used for 1-level anterior cervical discectomy and fusion.

In BriefThe authors examined fusion rates after single-level anterior cervical discectomy and fusion, comparing use of a structural allograft with use of polyetheretherketone (PEEK) interbody devices packed with bone graft. The results demonstrate superior results of structural allograft in terms of arthrodesis rates and reoperation rates. Currently, reimbursement rates substantially favor the use of PEEK and other synthetic devices, which the authors believe should be changed based on the results of this study.

Incidence of symptomatic tethered spinal cord in pediatric patients presenting with neurofibromatosis types 1 and 2.

OBJECTIVE The relationship between a tethered cord (TC) and neurofibromatosis type 1 (NF1) and NF2 is not known. The purpose of this study was to define the incidence of TC in pediatric neurosurgical patients who present with NF. METHODS The authors performed a single-institution (tertiary care pediatric hospital) 10-year retrospective analysis of patients who were diagnosed with or who underwent surgery for a TC and/or NF. Clinical and radiological characteristics were analyzed, as was histopathology. RESULTS A total of 424 patients underwent surgery for a TC during the study period, and 67 patients with NF were seen in the pediatric neurosurgery clinic. Of these 67 patients, 9 (13%) were diagnosed with a TC, and filum lysis surgery was recommended. Among the 9 patients with NF recommended for TC-release surgery, 4 (44%) were female, the mean age was 8 years (range 4-14 years), the conus position ranged from L1-2 to L-3, and 3 (33%) had a filum lipoma, defined as high signal intensity on T1-weighted MR images. All 9 of these patients presented with neuromotor, skeletal, voiding, and/or pain-related symptoms. Histopathological examination consistently revealed dense fibroconnective tissue and blood vessels. CONCLUSIONS Despite the lack of any known pathophysiological relationship between NF and TC, the incidence of a symptomatic TC in patients with NF1 and NF2 who presented for any reason to this tertiary care pediatric neurosurgery clinic was 13%. Counseling patients and families regarding TC symptomatology might be indicated in this patient population.

Contributions of the pre-Bötzinger complex and the Kölliker-fuse nuclei to respiratory rhythm and pattern generation in awake and sleeping goats.

We investigated in three groups of awake and sleeping goats whether there are differences in ventilatory responses after injections of Ibotenic acid (IA, glutamate receptor agonist and neurotoxin) into the pre-Bötzinger complex (preBötC), lateral parabrachial (LPBN), medial (MPBN) parabrachial, or Kölliker-Fuse nuclei (KFN). In one group, within minutes after bilateral injection of 10µl IA (50mM) into the preBötC, there was a 10-fold increase in breathing frequency, but 1.5h later, the goats succumbed to terminal apnea. These data are consistent with findings in reduced preparations that the preBötC is critical to sustaining normal breathing. In a second group, increasing volumes (0.5-10µl) of IA injected at weekly intervals into the preBötC elicited a near-dose-dependent tachypnea and irregular breathing that lasted at least 5h. There were apneas restricted to wakefulness, but none were terminal. Postmortem histology revealed that the preBötC was 90% destroyed, but there was a 25-40% above normal number of neurons in the presumed parafacial respiratory group that may have contributed to maintenance of arterial blood gas homeostasis. In a third group, bilateral injections (1 and 10µl) of IA into the LPBN, MPBN, or KFN did not significantly increase breathing in any group, and there were no terminal apneas. However, 3-5h after the injections into the KFN, breathing frequency was decreased and the three-phase eupneic breathing pattern was eliminated. Between 10 and 15h after the injections, the eupneic breathing pattern was not consistently restored to normal, breathing frequency remained attenuated, and there were apneas during wakefulness. Our findings during wakefulness and NREM sleep warrant concluding that (a) the preBötC is a primary site of respiratory rhythm generation; (b) the preBötC and the KFN are determinants of respiratory pattern generation; (c) after IA-induced lesions, there is time-dependent plasticity within the respiratory control network; and (d) ventilatory control mechanisms are state dependent.

Enhancing the informed consent process for critical care research: strategies from a thromboprophylaxis trial.

BACKGROUND: Critically ill patients lack capacity for decisions about research participation. Consent to enrol these patients in studies is typically obtained from substitute decision-makers. OBJECTIVE: To present strategies that may optimise the process of obtaining informed consent from substitute decision-makers for participation of critically ill patients in trials. We use examples from a randomised trial of heparin thromboprophylaxis in the intensive care unit (PROTECT, clinicaltrials.gov NCT00182143). METHODS: 3764 patients were randomised, with an informed consent rate of 82%; 90% of consents were obtained from substitute decision-makers. North American PROTECT research coordinators attended three meetings to discuss enrolment: (1) Trial start-up (January 2006); (2) Near trial closure (January 2010); and (3) Post-publication (April 2011). Data were derived from slide presentations, field notes from break-out groups and plenary discussions, then analysed inductively. RESULTS: We derived three phases for the informed consent process: (1) Preparation for the Consent Encounter; (2) The Consent Encounter; and (3) Follow-up to the Consent Encounter. Specific strategies emerged for each phase: Phase 1 (four strategies); Phase 2 (six strategies); and Phase 3 (three strategies). CONCLUSION: We identified 13 strategies that may improve the process of obtaining informed consent from substitute decision-makers and be generalisable to other settings and studies.