Pavan S. Upadhyayula

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

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.

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.

A matched cohort comparison of cervical disc arthroplasty versus anterior cervical discectomy and fusion: Evaluating perioperative outcomes

OBJECTIVE Cervical disc arthroplasty (CDA) is a recent alternative to anterior cervical discectomy and fusion (ACDF) in patients suffering cervical disc herniation and degeneration. To date, a systematic analysis of their comparative advantages and risks following elective surgery remains elusive. METHODS Adult patients undergoing elective CDA or ACDF were extracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2011-2014. A total of 19,369 patients were matched 1:1 by age, sex, functional status, charlson comorbidity index, ASA classification, BMI classification, and number of vertebral levels operated on during surgery. This matching process led to a final sample of 588 subjects (294 CDA, 294 ACDF). Multivariable regression was performed for five outcome measures: operation time, early complications, reoperation rates, hospital length of stay (HLOS), and discharge destination. Mean differences (B), odds ratios (OR) and associated 95% confidence intervals (CI) are reported. RESULTS Compared to ACDF, CDA was associated with decreased mean operation time (B=-18.78-min, 95% CI [-29.13, -8.42]; p<0.001), decreased HLOS (B=-0.44-days [-0.77, -0.11]; p=0.009), and increased likelihood of discharge to home (OR=5.39 [1.14-25.43]; p=0.033). No differences in reoperation rates and complications were found. CONCLUSION In a matched cohort analysis, CDA performs comparably to ACDF and is associated with decreased operation time and HLOS, and increased likelihood of discharge to home, without differences in 30-day complications or reoperation rates. Future prospective studies are warranted.

345 Elective Anterior Cervical Discectomy and Fusion vs Cervical Artificial Disc Replacement: A Comparison of Perioperative Morbidity and Early Outcomes.

INTRODUCTION We conducted a retrospective cohort analysis of early outcomes after elective anterior cervical discectomy and fusion (ACDF) vs cervical artificial disc replacement (C-ADR) using the National Surgical Quality Improvement Program database. Risk factors associated with operation time, hospital length of stay, early complications, and discharge destination were studied. METHODS Adult patients undergoing elective ACDF or C-ADR were abstracted from American College of Surgeons National Surgical Quality Improvement Program years 2011 to 2014. Univariate analyses were performed by surgery cohort for each outcome, and corrected for demographic/clinical variables (age = 65, sex, race, body mass index (BMI), ASA score, functional status, inpatient/outpatient status, smoking, hypertension, Charlson Comorbidity Index) using multivariable regression. Means, standard errors, odds ratio (OR), and 95% confidence intervals (CIs) are reported. Significance was assessed at P < .05. RESULTS Of 18 067 subjects (ACDF = 17 296, C-ADR = 771), C-ADR subjects were on average younger (<65 years: 97.4% vs 84.2%; P < .001), less obese (nonobese: 6.10% vs 49.1%; P < .001), less physically burdened (ASA 1: 13.1% vs 4.3%; ASA 3-4: 17.9% vs 38.3%; P < .001), less functionally dependent (0.5% vs 2.2%; P < .001), and presented with fewer overall comorbidities (3.9% vs 6.4%; P < .001). Overall, 31 (0.17%) patients died. Univariate analyses showed that C-ADR had shorter operation time (111.27 ± 1.89-minutes vs 125.59 ± 0.53-minutes; P < .001), shorter hospital length of stay (HLOS) (1.06 ± 0.03 days vs 1.64 ± 0.04 days; P = .003), and higher likelihood of being discharged to home (99.5% vs 96.9%, P < .001). Multivariable analysis confirmed C-ADR association with shorter operation time (B = -9.37; 95% CI, -14.34 to -4.01) and with greater likelihood of returning home (OR, 2.74 [1.01, 7.41]), while a nonsignificant statistical trend was demonstrated for HLOS (B = -0.35; 95% CI, -0.73 to 0.03). Incidences of early complications did not differ between C-ADR and ACDF (1.4% vs 2.5%, P = .620). CONCLUSION Patients selected for elective C-ADR demonstrate lower comorbidity profiles than ACDF. Compared with ACDF, C-ADR is associated with decreased operative times and increased likelihood of being discharged home. Future studies are needed to confirm these findings.

Anterior Versus Transforaminal Lumbar Interbody Fusion: Perioperative Risk Factors and 30-Day Outcomes

ABSTRACT Background: Operative management of lower back pain often necessitates anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF). Specific pathoanatomic advantages and indications exist for both approaches, and few studies to date have characterized comparative early outcomes. Methods: Adult patients undergoing elective ALIF or TLIF operations were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) years 2011–2014. Univariate analyses were performed by surgery cohort for each outcome and adjusted for demographic/clinical variables (age ≥ 65, sex, race, body mass index, American Society of Anesthesiologists physical classification score, functional status, inpatient/outpatient status, smoking, hypertension, Charlson Comorbidity Index) using multivariable regression. Means, standard errors, mean differences (B), odds ratios (ORs), and associated 95% confidence intervals (CIs) are reported. Significance was assessed at P < .05. Results: Of 8263 subjects (ALIF: 4325, TLIF: 3938), ALIF subjects were younger, less obese, less physically impaired, and had significantly lower rates of hypertension, diabetes, coagulopathy, and previous cardiac surgery. On multivariable analysis, ALIF associated with shorter operative time (B = −11.80 minutes, 95% CI [−16.48, −7.12]; P < .001). Transforaminal lumbar interbody fusion was associated with increased incidence of urinary tract infections (UTIs; OR = 1.57, 95% CI [1.10, 2.26]; P = .013) and of blood transfusions (OR = 1.19, 95% CI [1.04, 1.37]; P = .012). Multivariate analysis also demonstrated TLIF associated with shorter hospital length of stay (B = −0.27 days, 95% CI [−0.54, −0.01]; P = .041), and fewer cases of pneumonia (OR = 0.55, 95% CI [0.32, 0.94]; P = .029) and prolonged ventilator dependency (OR = 0.33, 95% CI [0.12, 0.84]; P = .021). Conclusions: Comparatively, ALIF patients experienced decreased operative time and decreased incidence of postoperative UTIs and blood transfusions. Anterior lumbar interbody fusion patients were more likely to suffer postoperative pulmonary complications and longer hospital stays. Our data support the notion that both anterior and transforaminal surgical approaches perform comparably in context of 30-day perioperative outcomes.

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.