Dataset Information

Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

ABSTRACT:

Objective

Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) were reviewed for studies investigating olfactory dysfunction in persons with moderate to severe TBI. Of the 5,223 studies reviewed, 19 met our inclusion criteria for the systematic review and 11 met inclusion criteria for meta-analysis. We calculated effect sizes (Hedges' g) to characterize the degree of olfactory dysfunction between patients with moderate to severe TBI and controls.

Results

A total of 951 moderate-severe TBI patients from 19 studies were included in the systematic review, which largely demonstrated poorer olfactory psychophysical performances in this patient population. Meta-analysis demonstrated a large effect size for olfactory dysfunction in moderate-severe TBI relative to healthy controls (g=-2.43, 95%CI: -3.16 < δ<-1.69). The magnitude of the effect was moderated by age and patient sex, with larger effect sizes associated with older age (following exclusion of a pediatric population) and larger compositions of women in the patient group.

Conclusion

Moderate to severe TBI is associated with prominent olfactory dysfunction. Significant research gaps remain regarding the mechanism, recovery and natural history of olfactory dysfunction following moderate to severe TBI, which has significant clinical implications for the identification and treatment for those with post-traumatic olfactory dysfunction.

SUBMITTER: Tai K

PROVIDER: S-EPMC10040093 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Tai Katherine K Leland Evelyn M EM Seal Stella M SM Schneider Andrea L C ALC Rowan Nicholas R NR Kamath Vidyulata V

Neuropsychology review 20220907 4

<h4>Objective</h4>Reports of smell loss following traumatic brain injury (TBI) are a well-documented but understudied phenomenon. Given the broad consequences of olfactory loss, we characterized psychophysical olfactory dysfunction in individuals with moderate to severe TBI using systematic review and meta-analytic methods.<h4>Methods</h4>Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol, five databases (PubMed, EMBASE, Cochrane Library, Web of Scienc ...[more]

PMID: 36070126

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Project description:ImportanceTraumatic brain injury (TBI) is a leading cause of death and disability worldwide. Hypotension in patients with TBI is associated with poorer outcomes. A comprehensive review examining adverse outcomes of hypotension in patients with TBI is needed.ObjectiveTo investigate the mortality and incidence of hypotension in patients with TBI.Data sourcesA search of studies published before April 2024 was conducted using MEDLINE, MEDLINE In Process, ePubs, Embase, Classic+Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for primary research articles in English, including randomized control trials, quasirandomized studies, prospective cohorts, retrospective studies, longitudinal studies, and cross-sectional surveys.Study selectionInclusion criteria were patients aged at least 10 years with moderate to severe TBI with hypotension. The exclusion criteria were mild TBI (due to the differences in management principles from moderate to severe TBI). Data were screened using Covidence software with multiple reviewers.Data extraction and synthesisThis meta-analysis conforms to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines for assessing data quality and validity. Primary outcomes (unadjusted and adjusted odds ratios [ORs]) were calculated using a random-effect model with 95% CIs. Incidence of hypotension was derived using logit transformation.Main outcomes and measuresMain outcomes were association of hypotension with death and/or vegetative state within 6 months and incidence of hypotension. Vegetative state was not reported due to lack of data from included studies. Hypothesis testing occurred before data collection.ResultsThe search strategy identified 17 676 unique articles. The final review included 51 studies (384 329 patients). Pooled analysis of found a significant increase in mortality in patients with hypotension and moderate to severe TBI (crude OR, 3.82; 95% CI, 3.04-4.81; P < .001; I2 = 96.98%; adjusted OR, 2.22; 95% CI, 1.96-2.51; P < .001; I2 = 92.21%). The overall hypotension incidence was 18% (95% CI, 12%-26%) (P < .001; I2 = 99.84%).Conclusions and relevanceThis meta-analysis of nearly 400 000 patients with TBI found a significant association of greater than 2-fold odds of mortality in patients with hypotension and TBI. This comprehensive analysis can guide future management recommendations, specifically with respect to blood pressure threshold management to reduce deaths when treating patients with TBI.

Project description:ObjectivesAfter traumatic brain injury, continuous electroencephalography is widely used to detect electrographic seizures. With the development of standardized continuous electroencephalography terminology, we aimed to describe the prevalence and burden of ictal-interictal patterns, including electrographic seizures after moderate-to-severe traumatic brain injury and to correlate continuous electroencephalography features with functional outcome.DesignPost hoc analysis of the prospective, randomized controlled phase 2 multicenter INTREPID study (ClinicalTrials.gov: NCT00805818). Continuous electroencephalography was initiated upon admission to the ICU. The primary outcome was the 3-month Glasgow Outcome Scale-Extended. Consensus electroencephalography reviews were performed by raters certified in standardized continuous electroencephalography terminology blinded to clinical data. Rhythmic, periodic, or ictal patterns were referred to as "ictal-interictal continuum"; severe ictal-interictal continuum was defined as greater than or equal to 1.5 Hz lateralized rhythmic delta activity or generalized periodic discharges and any lateralized periodic discharges or electrographic seizures.SettingTwenty U.S. level I trauma centers.PatientsPatients with nonpenetrating traumatic brain injury and postresuscitation Glasgow Coma Scale score of 4-12 were included.InterventionsNone.Measurements and main resultsAmong 152 patients with continuous electroencephalography (age 34 ± 14 yr; 88% male), 22 (14%) had severe ictal-interictal continuum including electrographic seizures in four (2.6%). Severe ictal-interictal continuum burden correlated with initial prognostic scores, including the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (r = 0.51; p = 0.01) and Injury Severity Score (r = 0.49; p = 0.01), but not with functional outcome. After controlling clinical covariates, unfavorable outcome was independently associated with absence of posterior dominant rhythm (common odds ratio, 3.38; 95% CI, 1.30-9.09), absence of N2 sleep transients (3.69; 1.69-8.20), predominant delta activity (2.82; 1.32-6.10), and discontinuous background (5.33; 2.28-12.96) within the first 72 hours of monitoring.ConclusionsSevere ictal-interictal continuum patterns, including electrographic seizures, were associated with clinical markers of injury severity but not functional outcome in this prospective cohort of patients with moderate-to-severe traumatic brain injury. Importantly, continuous electroencephalography background features were independently associated with functional outcome and improved the area under the curve of existing, validated predictive models.

Project description:Blood biomarkers are an emerging diagnostic and prognostic tool that reflect a range of neuropathological processes following traumatic brain injury (TBI). Their effectiveness in identifying long-term neuropathological processes after TBI is unclear. Studying biomarkers in the chronic phase is vital because elevated levels in TBI might result from distinct neuropathological mechanisms during acute and chronic phases. Here, we examine plasma biomarkers in the chronic period following TBI and their association with amyloid and tau PET, white matter microarchitecture, brain age and cognition. We recruited participants ≥40 years of age who had suffered a single moderate-severe TBI ≥10 years previously between January 2018 and March 2021. We measured plasma biomarkers using single molecule array technology [ubiquitin C-terminal hydrolase L1 (UCH-L1), neurofilament light (NfL), tau, glial fibrillary acidic protein (GFAP) and phosphorylated tau (P-tau181)]; PET tracers to measure amyloid-β (18F-NAV4694) and tau neurofibrillary tangles (18F-MK6240); MRI to assess white matter microstructure and brain age; and the Rey Auditory Verbal Learning Test to measure verbal-episodic memory. A total of 90 post-TBI participants (73% male; mean = 58.2 years) were recruited on average 22 years (range = 10-33 years) post-injury, and 32 non-TBI control participants (66% male; mean = 57.9 years) were recruited. Plasma UCH-L1 levels were 67% higher {exp(b) = 1.67, P = 0.018, adjusted P = 0.044, 95% confidence interval (CI) [10% to 155%], area under the curve = 0.616} and P-tau181 were 27% higher {exp(b) = 1.24, P = 0.011, adjusted P = 0.044, 95% CI [5% to 46%], area under the curve = 0.632} in TBI participants compared with controls. Amyloid and tau PET were not elevated in TBI participants. Higher concentrations of plasma P-tau181, UCH-L1, GFAP and NfL were significantly associated with worse white matter microstructure but not brain age in TBI participants. For TBI participants, poorer verbal-episodic memory was associated with higher concentration of P-tau181 {short delay: b = -2.17, SE = 1.06, P = 0.043, 95% CI [-4.28, -0.07]; long delay: bP-tau = -2.56, SE = 1.08, P = 0.020, 95% CI [-4.71, -0.41]}, tau {immediate memory: bTau = -6.22, SE = 2.47, P = 0.014, 95% CI [-11.14, -1.30]} and UCH-L1 {immediate memory: bUCH-L1 = -2.14, SE = 1.07, P = 0.048, 95% CI [-4.26, -0.01]}, but was not associated with functional outcome. Elevated plasma markers related to neuronal damage and accumulation of phosphorylated tau suggest the presence of ongoing neuropathology in the chronic phase following a single moderate-severe TBI. Plasma biomarkers were associated with measures of microstructural brain disruption on MRI and disordered cognition, further highlighting their utility as potential objective tools to monitor evolving neuropathology post-TBI.

Dataset Information

Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Objective

Methods

Results

Conclusion

Publications

Olfactory Dysfunction Following Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

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