Hansen Deng

Selective Serotonin Reuptake Inhibitors for Treating Neurocognitive and Neuropsychiatric Disorders Following Traumatic Brain Injury: An Evaluation of Current Evidence

The prevalence of neuropsychiatric disorders following traumatic brain injury (TBI) is 20%–50%, and disorders of mood and cognition may remain even after recovery of neurologic function is achieved. Selective serotonin reuptake inhibitors (SSRI) block the reuptake of serotonin in presynaptic cells to lead to increased serotonergic activity in the synaptic cleft, constituting first-line treatment for a variety of neurocognitive and neuropsychiatric disorders. This review investigates the utility of SSRIs in treating post-TBI disorders. In total, 37 unique reports were consolidated from the Cochrane Central Register and PubMed (eight randomized-controlled trials (RCTs), nine open-label studies, 11 case reports, nine review articles). SSRIs are associated with improvement of depressive but not cognitive symptoms. Pooled analysis using the Hamilton Depression Rating Scale demonstrate a significant mean decrease of depression severity following sertraline compared to placebo—a result supported by several other RCTs with similar endpoints. Evidence from smaller studies demonstrates mood improvement following SSRI administration with absent or negative effects on cognitive and functional recovery. Notably, studies on SSRI treatment effects for post-traumatic stress disorder after TBI remain absent, and this represents an important direction of future research. Furthermore, placebo-controlled studies with extended follow-up periods and concurrent biomarker, neuroimaging and behavioral data are necessary to delineate the attributable pharmacological effects of SSRIs in the TBI population.

Circadian variability of the initial Glasgow Coma Scale score in traumatic brain injury patients

Introduction The Glasgow Coma Scale (GCS) score is the primary method of assessing consciousness after traumatic brain injury (TBI), and the clinical standard for classifying TBI severity. There is scant literature discerning the influence of circadian rhythms or emergency department (ED) arrival hour on this important clinical tool. Methods Retrospective cohort analysis of adult patients suffering blunt TBI using the National Sample Program of the National Trauma Data Bank, years 2003–2006. ED arrival GCS score was characterized by midday (10 a.m.–4 p.m.) and midnight (12 a.m.–6 a.m.) cohorts (N=24548). Proportions and standard errors are reported for descriptive data. Multivariable regressions using odds ratios (OR), mean differences (B), and their associated 95% confidence intervals [CI] were performed to assess associations between ED arrival hour and GCS score. Statistical significance was assessed at p<0.05. Results Patients were 42.48±0.13-years-old and 69.5% male. GCS score was 12.68±0.13 (77.2% mild, 5.2% moderate, 17.6% severe-TBI). Overall, patients were injured primarily via motor vehicle accidents (52.2%) and falls (24.2%), and 85.7% were admitted to hospital (33.5% ICU). Injury severity score did not differ between day and nighttime admissions. Nighttime admissions associated with decreased systemic comorbidities (p<0.001) and increased likelihood of alcohol abuse and drug intoxication (p<0.001). GCS score demonstrated circadian rhythmicity with peak at 12 p.m. (13.03±0.08) and nadir at 4am (12.12±0.12). Midnight patients demonstrated lower GCS (12 a.m.–6 a.m.: 12.23±0.04; 10 a.m.–4 p.m.: 12.95±0.03, p<0.001). Multivariable regression adjusted for demographic and injury factors confirmed that midnight-hours independently associated with decreased GCS (B=−0.29 [−0.40, −0.19]). In patients who did not die in ED or go directly to surgery (N=21862), midnight-hours (multivariable OR 1.73 [1.30–2.31]) associated with increased likelihood of ICU admission; increasing GCS score (per-unit OR 0.82 [0.80–0.83]) associated with decreased odds. Notably, the interaction factor ED GCS score*ED arrival hour independently demonstrated OR 0.96 [0.94–0.98], suggesting that the influence of GCS score on ICU admission odds is less important at night than during the day. Conclusions Nighttime TBI patients present with decreased GCS scores and are admitted to ICU at higher rates, yet have fewer prior comorbidities and similar systemic injuries. The interaction between nighttime hours and decreased GCS score on ICU admissions has important implications for clinical assessment/triage.

Apolipoprotein E epsilon 4 (APOE-ε4) genotype is associated with decreased 6-month verbal memory performance after mild traumatic brain injury

The apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear.

Update on critical care for acute spinal cord injury in the setting of polytrauma

Traumatic spinal cord injury (SCI) often occurs in patients with concurrent traumatic injuries in other body systems. These patients with polytrauma pose unique challenges to clinicians. The current review evaluates existing guidelines and updates the evidence for prehospital transport, immobilization, initial resuscitation, critical care, hemodynamic stability, diagnostic imaging, surgical techniques, and timing appropriate for the patient with SCI who has multisystem trauma. Initial management should be systematic, with focus on spinal immobilization, timely transport, and optimizing perfusion to the spinal cord. There is general evidence for the maintenance of mean arterial pressure of > 85 mm Hg during immediate and acute care to optimize neurological outcome; however, the selection of vasopressor type and duration should be judicious, with considerations for level of injury and risks of increased cardiogenic complications in the elderly. Level II recommendations exist for early decompression, and additional time points of neurological assessment within the first 24 hours and during acute care are warranted to determine the temporality of benefits attributable to early surgery. Venous thromboembolism prophylaxis using low-molecular-weight heparin is recommended by current guidelines for SCI. For these patients, titration of tidal volumes is important to balance the association of earlier weaning off the ventilator, with its risk of atelectasis, against the risk for lung damage from mechanical overinflation that can occur with prolonged ventilation. Careful evaluation of infection risk is a priority following multisystem trauma for patients with relative immunosuppression or compromise. Although patients with polytrauma may experience longer rehabilitation courses, long-term neurological recovery is generally comparable to that in patients with isolated SCI after controlling for demographics. Bowel and bladder disorders are common following SCI, significantly reduce quality of life, and constitute a focus of targeted therapies. Emerging biomarkers including glial fibrillary acidic protein, S100β, and microRNAs for traumatic SCIs are presented. Systematic management approaches to minimize sources of secondary injury are discussed, and areas requiring further research, implementation, and validation are identified.

Vasopressor support in managing acute spinal cord injury: a knowledge update.

INTRODUCTION Managing neurogenic shock following acute traumatic spinal cord injury (SCI) is challenging. Current guidelines target mean arterial pressure (MAP) above 85-90 mmHg to maintain cord perfusion and reduce ischemia/secondary injury. While early vasopressor utilization has been associated with improved outcomes, recent updates regarding indications of specific vasopressors for refinement of existing guidelines are needed. EVIDENCE ACQUISITION A comprehensive search was conducted using the National Library of Medicine PubMed database between 01/2010 and 01/2017 targeting vasopressor use in the setting of neurogenic/spinal shock and/or hypotension following acute SCI in adult patients. Special focus was provided for endpoints of comparative advantage, complications, and adjunctive agents. EVIDENCE SYNTHESIS Seven reports met inclusion criteria. In complete and incomplete SCI, rates of vasopressor-associated complications were greater for dopamine compared to phenylephrine. Norepinephrine provided a comparative 2-mmHg increase to spinal cord perfusion pressure without differential MAP effects versus dopamine. In elderly SCI, more vasopressor and dopamine-specific complications were observed. A case series found adjunct oral pseudoephedrine to be successful in wean off intravenous vasopressors. One study of various MAP thresholds 65-90 mmHg found no correlations with neurological outcome. CONCLUSIONS Class III evidence has been augmented regarding vasopressor usage following acute SCI, however comparative benefits between vasopressors remain in need of elucidation due to small sample sizes and/or inadequate specificity to spine injury levels. Large prospective multicenter studies targeting age cohorts, and characterizing associated comorbidities and complication profiles, are of high priority in order to determine judicious use criteria of specific vasopressors for relevant subpopulations.

Emergency department blood alcohol level associates with injury factors and six-month outcome after uncomplicated mild traumatic brain injury

The relationship between blood alcohol level (BAL) and mild traumatic brain injury (mTBI) remains in need of improved characterization. Adult patients suffering mTBI without intracranial pathology on computed tomography (CT) from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with emergency department (ED) Glasgow Coma Scale (GCS) 13-15 and recorded blood alcohol level (BAL) were extracted. BAL≥80-mg/dl was set as proxy for excessive use. Multivariable regression was performed for patients with six-month Glasgow Outcome Scale-Extended (GOSE; functional recovery) and Wechsler Adult Intelligence Scale Processing Speed Index Composite Score (WAIS-PSI; nonverbal processing speed), using BAL≥80-mg/dl and <80-mg/dl cohorts, adjusting for demographic/injury factors. Overall, 107 patients were aged 42.7±16.8-years, 67.3%-male, and 80.4%-Caucasian; 65.4% had BAL=0-mg/dl, 4.6% BAL<80-mg/dl, and 30.0% BAL≥80-mg/dl (range 100-440-mg/dl). BAL differed across loss of consciousness (LOC; none: median 0-mg/dl [interquartile range (IQR) 0-0], <30-min: 0-mg/dl [0-43], ≥30-min: 224-mg/dl [50-269], unknown: 108-mg/dl [0-232]; p=0.002). GCS<15 associated with higher BAL (19-mg/dl [0-204] vs. 0-mg/dl [0-20]; p=0.013). On univariate analysis, BAL≥80-mg/dl associated with less-than-full functional recovery (GOSE≤7; 38.1% vs. 11.5%; p=0.025) and lower WAIS-PSI (92.4±12.7, 30th-percentile vs. 105.1±11.7, 63rd-percentile; p<0.001). On multivariable regression BAL≥80-mg/dl demonstrated an odds ratio of 8.05 (95% CI [1.35-47.92]; p=0.022) for GOSE≤7 and an adjusted mean decrease of 8.88-points (95% CI [0.67-17.09]; p=0.035) on WAIS-PSI. Day-of-injury BAL>80-mg/dl after uncomplicated mTBI was associated with decreased GCS score and prolongation of reported LOC. BAL may be a biomarker for impaired return to baseline function and decreased nonverbal processing speed at six-months postinjury. Future confirmatory studies are needed.

Predictors of 30-Day Outcomes in Octogenarians with Traumatic C2 Fractures Undergoing Surgery

BACKGROUND Predictors of surgical outcomes following traumatic axis (C2) fractures in octogenarians remain undercharacterized. METHODS Patients age ≥80 years undergoing cervical spine surgery following traumatic C2 fractures were extracted from the National Sample Program of the National Trauma Data Bank (2003-2012). Outcomes include overall inpatient complications, individual complications with an incidence >1%, hospital length of stay (HLOS), discharge disposition, and mortality. Demographics, comorbidities, and injury predictors were analyzed using multivariable regression. Odds ratios (OR), mean differences, and 95% confidence intervals (CIs) were calculated. Statistical significance was assessed at P < 0.05. RESULTS The cohort of 442 patients was 48.6% male and had a mean age of 84.3 ± 2.7 years. The distribution of admissions was 42.3% to the hospital floor, 40.3% to the intensive care unit (ICU), 7.7% to telemetry, 2.0% to the operating room, and 7.7% to other/unknown. Mortality was 9.7%, mean HLOS was 13.1 ± 9.2 days, the rate of complications was 38.5%, and 81.5% of survivors were discharged to a nonhome facility. Injury severity was predictive of mortality and overall complications. History of bleeding disorder/coagulopathy predicted mortality (OR, 4.02; 95% CI, 1.07-15.05), overall complications (OR, 3.01; 95% CI, 1.09-8.32), cardiac arrest (OR, 8.19; 95% CI, 1.06-63.54), and renal complications (OR, 10.36; 95% CI, 2.13-50.38). History of congestive heart failure predicted mortality (OR, 3.10; 95% CI, 1.10-8.69). ICU admission (vs. floor) predicted overall complications (OR, 2.01; 95% CI, 1.23-3.27) and pneumonia (OR, 4.65; 95% CI, 1.91-11.30). Telemetry admission (vs. floor) predicted unplanned intubation (OR, 7.76; 95% CI, 1.24-48.49). CONCLUSIONS In this cohort of octogenarians undergoing surgery for traumatic C2 fracture, injury severity and a history of bleeding disorder/coagulopathy were identified as risk factors for inpatient complications and mortality. Heightened surveillance should be considered for ICU and/or telemetry admissions for the development of complications. These findings warrant consideration by the clinician, patient, and family to inform clinical decisions and goals of care.

Temporal lobe contusions on computed tomography are associated with impaired 6-month functional recovery after mild traumatic brain injury: a TRACK-TBI study

ABSTRACT Introduction: Mild traumatic brain injury (MTBI) can cause persistent functional deficits and healthcare burden. Understanding the association between intracranial contusions and outcome may aid in MTBI treatment and prognosis. Methods: MTBI patients with Glasgow Coma Scale 13–15 and 6-month outcomes [Glasgow Outcome Scale-Extended (GOSE)], without polytrauma from the prospective TRACK-TBI Pilot study were analyzed. Intracranial contusions on computed tomography (CT) were coded by location. Multivariable regression evaluated associations between intracranial injury type (temporal contusion [TC], frontal contusion, extraaxial [epidural/subdural/subarachnoid], other-intraaxial [intracerebral/intraventricular hemorrhage, axonal injury]) and GOSE. Odds ratios (OR) are reported. Results: Overall, 260 MTBI subjects were aged 44.4 ± 18.1-years; 67.7% were male. Ninety-seven subjects were CT-positive and 46 had contusions (41.3%–frontal, 30.4%–temporal, 21.7%–frontal + temporal, 2.2% each-parietal/occipital/brainstem); 95.7% had concurrent extraaxial hemorrhage. Mortality was 0% at discharge and 2.3% by 6-months. GOSE distribution was 2.3%–death, 1.5%–severe disability, 27.7%–moderate disability, 68.5%–good recovery. Forty-six percent of TC-positive subjects suffered moderate disability or worse (GOSE ≤6) and 41.7% were unable to return to baseline work capacity (RTBWC), compared to 29.1%/20.4% for CT-negative and 26.1%/20.9% for CT-positive subjects without TC. On multivariable regression, TC associated with OR = 3.33 (95% CI [1.16–9.60], p = 0.026) for GOSE ≤6, and OR = 4.48 ([1.49–13.51], p = 0.008) for inability to RTBWC. Conclusions: Parenchymal contusions in MTBI are often accompanied by extraaxial hemorrhage. TCs may be associated with 6-month functional impairment. Their presence on imaging should alert the clinician to the need for heightened surveillance of sequelae complicating RTBWC, with low threshold for referral to services.

Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the Development of Chronic Traumatic Encephalopathy

The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10–15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI.

Emergent neurosurgical management of a rapidly deteriorating patient with acute intracranial hemorrhage and alcohol-related thrombocytopenia

Alcohol intoxication is a common risk factor of traumatic brain injury (TBI) and carries a significant health-care burden on underserved patients. Patients with chronic alcohol use may suffer a spectrum of bleeding diatheses from hepatic dysfunction not well studied in the context of TBI. A feared sequela of TBI is the development of coagulopathy resulting in worsened intracranial bleeding. We report the clinical course of an intoxicated patient found down with blunt head trauma and concurrent alcoholic cirrhosis who was awake and responsive in the field. Hospital course was characterized by a rapidly deteriorating neurological examination with progressive subdural and subarachnoid hemorrhage and precipitating neurosurgical decompression and critical care management. Our experience dictates the need for timely consideration of the possibility of rapid deterioration from coagulopathic intracranial bleeding in the initial assessment of intoxicated patients with head trauma of unknown severity, for which a high index of suspicion for extra-axial hemorrhage should be maintained, along with the immediate availability of operating room and the necessary medical personnel.