Occult cervical spinal dural arteriovenous fistula masquerading as acute spinal cord ischemia

Acute presentation of upper and lower extremity motor weakness is commonly attributed to intracerebral ischemic infarct upon initial examination. For those that exhibit acute onset of bilateral weakness, it is important to expand the differential diagnosis to include spinal cord ischemic involvement. One cause of ischemic lesions is spinal dural arteriovenous (AV) fistulas which are generally found in the thoraco-lumbar region. They present with progressive paraplegia or quadriplegia due to changes in the spinal venous pressure and eventual myelopathy. We present a 60 year old gentleman with bilateral upper extremity weakness and right lower extremity weakness preceded by upper back and neck pain. Initial studies included both Magnetic resonance imagine (MRI) of the brain and also the cervical spine that demonstrated abnormal signal intensity within the anterior cervical cord from C3-C7 levels concerning for spinal cord infarct. In our case there were no flow voids to suggest dilated perimedullary vessels that usually prompt further diagnostic evaluation through a spinal angiogram. However, given the clinical suspicion, a spinal angiogram was obtained that demonstrated a cervical dural AV fistula supplied by a dural branch vessel originating from the left vertebral artery. We will highlight the importance of recognizing the clinical presentation of spinal dural AV fistulas; the usual findings on imaging, the value of considering further diagnostic tests if clinical suspicion is high, and provide an overview of the spinal dural AV treatment

BRAIN TOPiC Study: Assessing Variability in Traumatic Brain Injury (TBI) Outcome Prognostication – Do Self-Fulfilling Prophecies Exist in TBI, Too?

OBJECTIVE: In this study, we surveyed clinicians caring for patients with moderate-severe traumatic brain injury (msTBI) to assess (1) possible variability in outcome prognostication in TBI, varying by clinicians level of training and medical specialty, (2) possible biases and self-fulfilling prophecies, and (3) whether specific ICU medical complications may influence clinicians in their outcome prognostication. BACKGROUND: Patients with msTBI commonly die from withdrawal of support, likely as a consequence of an unfavorable outcome prognosis provided to the family by the treating physician. It is unknown whether prognostication may lead to self-fulfilling prophecies, and whether the presence of intensive care unit (ICU) complications may accentuate possible provider bias. DESIGN/METHODS: We conducted an anonymous electronic survey of clinicians, including faculty members (Neurology, Neurosurgery, Trauma, Anesthesia/Critical Care), neurology house staff, ICU affiliate practitioners and neuroICU nurses at a single Level I trauma center. The survey included three TBI case vignettes and their respective ICU courses. Questions were designed to assess the utilization of known TBI prognostic models, relative importance of ICU complications for outcome prognostication and aggressiveness of care recommended by the survey participant. RESULTS: The survey response rate was 72% (106 surveys returned). In all 3 cases, the majority of participants did not recommend withdrawal of care, but did predict unfavorable 6-month outcomes. 51% of participants consider medical ICU complications as very important in TBI prognostication. Age, ICU course and head CT findings are the prognostic variables considered most important to outcomes. CONCLUSIONS: We have discovered great variability in outcome predictions made by clinicians with different levels of experience in treating msTBI. Self-fulfilling prophecies may exist in msTBI outcomes. Outcome estimates should focus not only on admission variables, but also on ICU complications in order to guide clinicians in providing prognostication

Severity of Pre-existing Cerebral Small Vessel Disease is Associated with Outcome after Traumatic Brain Injury

Background and purpose: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of pre-existing white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of pre-existing cerebral small vessel disease related white matter rarefaction (leukoaraiosis) is independently associated with outcome after TBI. Methods: We retrospectively analyzed consecutive, prospectively enrolled patients of ≥50 years (n=136) that were admitted to a single neurological-trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) via telephone interview at 3 and 12 months, respectively. Results: After adjustment for other factors, leukoaraiosis-severity was significantly associated with a poor outcome at 3 and 12 months as defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and a poor outcome remained when the analysis was restricted to patients that survived to 3 months, had moderate-to-severe TBI (enrolment Glasgow Coma Scale [GCS] ≤12; p=0.001), or had mild TBI (GCS 13-15; p=0.002), respectively. Conclusion: We provide first evidence that pre-existing cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization

Association Between Concussion Burden During Professional American-Style Football and Postcareer Hypertension

Previous work has demonstrated an association between American-style football (ASF) and the development of hypertension among collegiate athletes.1 In addition, hypertension prevalence has been shown to be higher among active professional ASF athletes compared with similarly aged members of the general population.2 Whereas causal factors including deliberate weight gain, repetitive isometric strength training, sleep apnea, and nonsteroidal anti-inflammatory drug use have been suggested, definitive mechanisms remain incompletely understood. Recent studies in general populations have shown associations between brain injury and subsequent hypertension.3 Given that ASF players are at particular risk for recurrent head injury, the relationship between concussion history and later life hypertension deserves focused exploration

Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage – a Randomized Placebo-Controlled Trial to assess Safety, Tolerability and Feasibility

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos \u3e5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusions: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences

Elucidating the neuroimmunology of traumatic brain injury: methodological approaches to unravel intercellular communication and function

The neuroimmunology of traumatic brain injury (TBI) has recently gained recognition as a crucial element in the secondary pathophysiological consequences that occur following neurotrauma. Both immune cells residing within the central nervous system (CNS) and those migrating from the periphery play significant roles in the development of secondary brain injury. However, the precise mechanisms governing communication between innate and adaptive immune cells remain incompletely understood, partly due to a limited utilization of relevant experimental models and techniques. Therefore, in this discussion, we outline current methodologies that can aid in the exploration of TBI neuroimmunology, with a particular emphasis on the interactions between resident neuroglial cells and recruited lymphocytes. These techniques encompass adoptive cell transfer, intra-CNS injection(s), selective cellular depletion, genetic manipulation, molecular neuroimaging, as well as in vitro co-culture systems and the utilization of organoid models. By incorporating key elements of both innate and adaptive immunity, these methods facilitate the examination of clinically relevant interactions. In addition to these preclinical approaches, we also detail an emerging avenue of research that seeks to leverage human biofluids. This approach enables the investigation of how resident and infiltrating immune cells modulate neuroglial responses after TBI. Considering the growing significance of neuroinflammation in TBI, the introduction and application of advanced methodologies will be pivotal in advancing translational research in this field

A genome-wide association study of outcome from traumatic brain injury

Background Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias. Methods We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography. Findings The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10−8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10−5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10−4). Interpretation While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available.Additional co-authors: Ramon Diaz-Arrastia, Aarno Palotie, Samuli Ripatti, Jonathan Rosand, and David K. Menon on behalf of The Genetic Associations In Neurotrauma (GAIN) Consortium (with contribution from the CENTER-TBI, TRACK-TBI, CABI, MGB, and TBIcare studies

A rare presentation of hypertrophic olivary degeneration secondary to primary central nervous system lymphoma

Case report: A 71-year-old man presented with a 2-week history of nausea, vomiting, unsteady gait, and diplopia

Severe leukoaraiosis portends a poor outcome after traumatic brain injury

BACKGROUND AND PURPOSE: It is now well accepted that traumatic white matter injury constitutes a critical determinant of post-traumatic functional impairment. However, the contribution of preexisting white matter rarefaction on outcome following traumatic brain injury (TBI) is unknown. Hence, we sought to determine whether the burden of preexisting leukoaraiosis of presumed ischemic origin is independently associated with outcome after TBI. METHODS: We retrospectively analyzed consecutive, prospectively enrolled patients of \u3e /=50 years (n = 136) who were admitted to a single neurological/trauma intensive care unit. Supratentorial white matter hypoattenuation on head CT was graded on a 5-point scale (range 0-4) reflecting increasing severity of leukoaraiosis. Outcome was ascertained according to the modified Rankin Scale (mRS) and Glasgow outcome scale (GOS) at 3 and 12 months, respectively. RESULTS: After adjustment for other factors, leukoaraiosis severity was significantly associated with a poor outcome at 3 and 12 months defined as mRS 3-6 and GOS 1-3, respectively. The independent association between leukoaraiosis and poor outcome remained when the analysis was restricted to patients who survived up to 3 months, had moderate-to-severe TBI [enrollment Glasgow Coma Scale (GCS) \u3c /=12; p = 0.001], or had mild TBI (GCS 13-15; p = 0.002), respectively. CONCLUSION: We provide first evidence that preexisting cerebral small vessel disease independently predicts a poor functional outcome after closed head TBI. This association is independent of other established outcome predictors such as age, comorbid state as well as intensive care unit complications and interventions. This knowledge may help improve prognostic accuracy, clinical management, and resource utilization