Complement-dependent neuroinflammation in spinal cord injury: from pathology to therapeutic implications.

ABSTRACT: Spinal cord injury remains a major cause of disability in young adults, and beyond acute decompression and rehabilitation, there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population. Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation, a similar role for complement in spinal neuroinflammation is a focus of ongoing research. In this work, we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins, triggers of complement activation, and role of effector functions in the pathology. We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris, and or activation via antibody binding to damage-associated molecular patterns. Several effector functions of complement have been implicated in spinal cord injury, and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury. Following this pathophysiological review, we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects. This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury, to evaluate the phases of involvement of opsonins and anaphylatoxins, and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

Decreased readmission rates following use of modified trauma-specific frailty index in older trauma patients: A follow-up study.

INTRODUCTION: Post-discharge readmission rates using modified Trauma-Specific Frailty Index (mTSFI) compared to the Emergency Severity Index (ESI) are unknown. In our pilot study, we demonstrated that mTSFI usage more accurately triages older trauma patients. In the current study, we hypothesized that adult trauma patients triaged using mTSFI would have lower readmission rates at the 30-day interval post discharge. METHODS: Retrospective review of readmission rates for 96 trauma patients ≥ 50 years old was performed. The two study groups were categorized as mTSFI-concordant and ESI-concordant. Fisher's exact test was performed. RESULTS: Mean ages for ESI and mTSFI groups were 63.8 (SD 10.6) and 65.2 (SD 10.8) years. The 30-day readmission rate was 0% (0/32) in the mTSFI group vs 11% (7/64) in the ESI group (p = 0.104). CONCLUSIONS: Utilization of mTSFI for adult trauma patients may lead to lower 30-day readmission rates compared to using ESI, despite our sample sizes being too small to demonstrate a statistically significant difference.

Systematic Review of Syndrome of the Trephined and Reconstructive Implications.

Syndrome of the trephined (SoT) is a severe complication following decompressive craniectomy resulting in neurological decline which can progress to aphasia, catatonia, and even death. While cranioplasty can reverse neurological symptoms of SoT, awareness of SoT is poor outside of the neurosurgery community. The authors performed a systematic review of the literature on SoT with a focus on reconstructive implications. Search terms "syndrome of the trephined" and "sunken flap syndrome" were applied to PubMed to identify primary studies through October 2021. Full-text review yielded 11 articles discussing SoT and reconstructive techniques or implications with 56 patients undergoing cranial reconstruction. Average age of the patients was 41.8±9.5 years. Sixty-three percent of the patients were male. The most common indication for craniectomy was traumatic brain injury (43%), followed by tumor resection (23%), intracerebral hemorrhage (11%), and aneurysmal subarachnoid hemorrhage (2%). Patients most commonly suffered from motor deficits (52%), decreased wakefulness (30%), depression or anxiety (21%), speech deficits (16%), headache (16%), and cognitive difficulties (2%). Time until presentation of symptoms following decompression was 4.4±8.9 months. Patients typically underwent cranioplasty with polyetheretherketone (48%), titanium mesh (21%), split thickness calvarial bone (16%), full thickness calvarial bone (14%), or split thickness rib graft (4%). Eight percent of patients required free tissue transfer for soft tissue coverage. Traumatic Brain Injury (TBI) was a risk factor for development of SoT when adjusting for age and sex (odds ratio: 8.2, 95% confidence interval: 1.2-8.9). No difference significant difference was observed between length until initial improvement of neurological symptoms following autologous versus allograft reconstruction (P=0.47). SoT can be a neurologically devastating complication of decompressive craniectomy which can resolve following urgent cranioplasty. Familiarity with this syndrome and its reconstructive implications is critical for the plastic surgery provider, who may be called upon to assist with these urgent cases.

Traumatic Brain Injury as a Potential Risk Factor for Diabetes Mellitus in the Veteran Population.

This review examines various aspects of traumatic brain injury (TBI) and its potential role as a causative agent for type 2 diabetes mellitus (T2DM) in the veteran population. The pituitary glands and the hypothalamus, both housed in the intracranial space, are the most important structures for the homeostatic regulation of almost every hormone in the human body. As such, TBI not only causes psychological and cognitive impairments but can also disrupt the endocrine system. It is well established that in addition to having a high prevalence of chronic traumatic encephalopathy (CTE), veterans have a very high risk of developing various chronic medical conditions. Unfortunately, there are no measures or prophylactic agents that can have a meaningful impact on this medically complex patient population. In this review, we explore several important factors pertaining to both acute and chronic TBI that can provide additional insight into why veterans tend to develop T2DM later in life. We focus on the unique combination of risk factors in this population not typically found in civilians or other individuals with a non-military background. These include post-traumatic stress disorder, CTE, and environmental factors relating to occupation and lifestyle.

Open Retroperitoneal Inferior Vena Cava Cannulation for Distal Ventriculoatrial Shunt Catheter Placement.

Multiple alternative sites for distal ventriculoperitoneal shunts have been described including pleural, atrial, ureteral, fallopian, and gallbladder placement. In medically complex patients the sites for cerebrospinal fluid (CSF) diversion can be exhausted. We present a case where open retroperitoneal inferior vena cava cannulation was used for successful atrial catheter placement in a 17-month-old female. The patient had a complex abdominal, pulmonary, and vascular history precluding placement of the distal catheter in other sites or atrial placement through more peripheral venous cannulation. The patient underwent uncomplicated open retroperitoneal exposure of her inferior vena cava (IVC) with cannulation and placement of atrial catheter under fluoroscopic guidance. At the follow-up one year after surgery, the patient did not require revision with appropriate placement of the distal atrial catheter.

Spinal Arachnoid Webs: Presentation, Natural History, and Outcomes in 38 Patients.

BACKGROUND: Spinal arachnoid webs are rarely described bands of thickened arachnoid tissue in the dorsal thoracic spine. Much is unknown regarding their origins, risk factors, natural history, and outcomes. OBJECTIVE: To present the single largest case series, detailing presenting symptoms and outcomes amongst operative and nonoperative patients, to better understand the role of intervention. METHODS: This retrospective chart review identified 38 patients with arachnoid webs. Patient demographics, radiologic signs, symptoms, and surgical history data were extracted from the electronic medical record. Symptoms were divided by location and character. 28 patients were successfully contacted for follow up outcome surveys. RESULTS: 26 patients (68%) underwent surgical intervention, 12 (32%) were managed non-operatively. 15 (39%) patients had undergone a previous unsuccessful surgery at a different site for their symptoms prior to arachnoid web diagnosis. Commonly presenting symptoms included myelopathy (68%), focal thoracic back pain (68%), lower extremity weakness (45%), numbness and sensory changes (58%), and lower extremity radicular pain (42%), upper extremity weakness (24%), and radicular pain (37%). Focal thoracic pain was associated with thoracic level (P < .02). Myelopathic symptoms were less common in postoperative patients. Postoperative patients described significantly more upper extremity (P < .01) and thoracic (P < .01) numbness and paresthesias. Surveyed nonoperative patients universally described their symptoms as either stable or worsening. CONCLUSION: Spinal arachnoid webs present with thoracic myelopathy and back pain but can also present with upper extremity symptoms. Surgical intervention stabilizes or improves symptoms and is well received. Nonoperative patients do not spontaneously improve.

Differential effect of mechanical thrombectomy and intravenous thrombolysis in atrial fibrillation associated stroke.

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke has worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Limited data exist about the effect of AF on procedural and clinical outcomes after mechanical thrombectomy (MT). OBJECTIVE: To determine whether recanalization efficacy, procedural speed, and clinical outcomes differ in AF associated stroke treated with MT. METHODS: We performed a retrospective cohort study of the Stroke Thrombectomy and Aneurysm Registry (STAR) from January 2015 to December 2018 and identified 4169 patients who underwent MT for an anterior circulation stroke, 1517 (36.4 %) of whom had comorbid AF. Prospectively defined baseline characteristics, procedural outcomes, and clinical outcomes were reported and compared. RESULTS: AF predicted faster procedural times, fewer passes, and higher rates of first pass success on multivariate analysis (p<0.01). AF had no effect on intracranial hemorrhage (aOR 0.69, 95% CI 0.43 to 1.12) or 90-day functional outcomes (aOR 1.17, 95% CI 0.91 to 1.50) after MT, although patients with AF were less likely to receive IVT (46% vs 54%, p<0.0001). CONCLUSIONS: In patients treated with MT, comorbid AF is associated with faster procedural time, fewer passes, and increased rates of first pass success without increased risk of intracranial hemorrhage or worse functional outcomes. These results are in contrast to the increased hemorrhage rates and worse functional outcomes observed in AF associated stroke treated with supportive care and or IVT. These data suggest that MT negates the AF penalty in ischemic stroke.

Cranioplasty Infection and Resorption Are Associated with the Presence of a Ventriculoperitoneal Shunt: A Systematic Review and Meta-Analysis.

BACKGROUND: Following decompressive craniectomy, hydrocephalus is a common complication often necessitating placement of a ventriculoperitoneal shunt (VPS). Complications in the presence of a VPS have been reported, but a clear association has not been established. METHODS: PRISMA guidelines were used to perform a literature search using PubMed to identify articles that published the complication rates associated with staged or simultaneous cranioplasty and VPS placement. From these event rates, odds ratios (ORs) with 95% confidence intervals (CIs) of complications were calculated. Data were pooled using the Mantel-Haenszel method. The Oxford Center for Evidence-Based Medicine guidelines were used to assess the quality of individual articles and studies. The Newcastle-Ottawa Scale was used to assess the risk of bias in studies. RESULTS: Of the 30 papers reviewed for complications in the presence and absence of a VPS, 7 studies, with a total of 1635 patients, were eligible for meta-analysis. Overall rates of complications (n = 1635; OR, 9.75; 95% CI, 4.8-20.1), infection (OR, 4.9; 95% CI, 2.2-10.7), and bone resorption (OR, 10.6; 95% CI, 4.9-23.0) were increased when a VPS was placed at the time of cranioplasty. Simultaneous procedures were associated with increased complication rates (n = 283; OR, 4.3; 95% CI, 2.3-8.2) compared with staged procedures. CONCLUSIONS: Cranioplasty in the presence of a VPS is associated with a higher rate of overall complications, including infection and bone resorption. Performing cranioplasty and VPS placement in the same operation is associated with an increased rate of complications compared with staged procedures. Surgeons should consider staging these procedures when possible and counsel patients about these risks.