A non-invasive biomechanical model of mild TBI in larval zebrafish

A mild traumatic brain injury is a neurological dysfunction caused by biomechanical forces transmitted to the brain in physical impacts. The current understanding of the neuropathological cascade resulting in the manifested clinical signs and symptoms is limited due to the absence of sensitive brain imaging methods. Zebrafish are established models for the reproduction and study of neurobiological pathologies. However, all available models mostly recreate moderate-to-severe focal injuries in adult zebrafish. The present work has induced a mild brain trauma in larval zebrafish through a non-invasive biomechanical approach. A custom-made apparatus with a commercially available motor was employed to expose larvae to rapidly decelerating linear movements. The neurophysiological changes following concussion were assessed through behavioural quantifications of startle reflex locomotor distance and habituation metrics. Here we show that the injury was followed, within five minutes, by a transient anxiety state and CNS dysfunction manifested by increased startle responsivity with impaired startle habituation, putatively mirroring the human clinical sign of hypersensitivity to noise. Within a day after the injury, chronic effects arose, as evidenced by an overall reduced responsivity to sensory stimulation (lower amplitude and distance travelled along successive stimuli), reflecting the human post-concussive symptomatology. This study represents a step forward towards the establishment of a parsimonious (simple, less ethically concerning, yet sensitive) animal model of mild TBI. Our behavioural findings mimic aspects of acute and chronic effects of human concussion, which warrant further study at molecular, cellular and circuit levels. While our model opens wide avenues for studying the underlying cellular and molecular pathomechanisms, it also enables high-throughput testing of therapeutic interventions to accelerate post-concussive recovery

Sex differences in the use of mechanical ventilation in a neurointensive care population: a retrospective study

Background: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. Methods: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. Results: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. Conclusion: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm

Dizziness and benign paroxysmal positional vertigo among retirement home residents: a cross-sectional descriptive and interventional study

BACKGROUND The prevalence of dizziness increases with age. We aimed to determine the point prevalence of dizziness and, in particular, of benign paroxysmal positional vertigo (BPPV) among retirement home residents. Furthermore, we aimed to evaluate the efficacy of a 2-axis turntable based BPPV treatment. METHODS We contacted all large retirement homes in or around the city of Zurich (Switzerland). 10 retirement homes (with a total of 536 residents) agreed to participate in this study. 83 rejected inquiries by residents led to a potential study population of 453 residents. After a structured interview evaluating the presence and characteristics of dizziness, all willing patients were tested for positional vertigo and nystagmus on a portable and manually operated 2-axis turntable that was transported to the retirement home. Testing consisted of the Dix-Hallpike and supine roll maneuvers to both sides. Participants were immediately treated with the appropriate liberation maneuver whenever BPPV was diagnosed. Otherwise, taking the resident's medical history, a neuro-otological bedside examination, and a review of the available medical documentation was used to identify other causes of dizziness. RESULTS Out of the 453 residents, 75 (16.6%; average age: 87.0 years; 68% female) were suffering from dizziness presently or in the recent past and gave their consent to participate in this study. Among the participants tested on the turntable (n = 71), BPPV was present in 11.3% (point prevalence). Time-related properties, triggering factors and qualitative attributes of vertigo or dizziness were not significantly different between the dizzy participants with and those without BPPV. In all BPPV patients, appropriate liberation maneuvers were successful. CONCLUSIONS BPPV could be demonstrated in about one tenth of retirement home residents with dizziness or recent dizziness. Such point prevalence of BPPV translates to a much higher yearly prevalence if one assumes that BPPV is not present on every day. Our finding suggests that retirement home residents suffering from dizziness should be regularly tested for BPPV and treated with appropriate liberation maneuvers, ideally on turntable to reduce strain. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT03643354

Sex-related differences in extracranial complications in patients with traumatic brain injury

BackgroundExtracranial complications after traumatic brain injury (TBI) are common. Their influence on outcome is uncertain. Furthermore, the role of sex on the development of extracranial complications following TBI remains poorly investigated. We aimed to investigate the incidence of extracranial complications after TBI with particular focus on sex-related differences with regard to complications and their influence on outcome.MethodsThis retrospective, observational study was conducted in a level I universitary swiss trauma center. Consecutive patients with TBI admitted to the intensive care unit (ICU) between 2018 and 2021 were included. Patients’ and trauma characteristics, in-hospital complications (i.e., cardiovascular, respiratory, renal, metabolic, gastrointestinal, hematological, and infectious) as well as functional outcome 3 months after trauma were analyzed. Data was dichotomized by sex or by outcome. Univariate as well as multivariate logistic regression was performed to reveal possible associations between sex, outcome and complications.ResultsOverall, 608 patients were included (male n = 447, 73.5%). Extracranial complications occurred most frequently in cardiovascular, renal, hematological and infectious systems. Men and women suffered similarly from extracranial complications. While men needed correction of coagulopathies more often (p = 0.029), women suffered more frequently from urogenital infections (p = 0.001). Similar results were found in a subgroup of patients (n = 193) with isolated TBI. A multivariate analysis did not show extracranial complications to be independent predictors of unfavorable outcome.ConclusionExtracranial complications following TBI occur frequently during the ICU-stay, can affect almost all organ systems but are not independent predictors of unfavorable outcome. The results suggest that sex-specific strategies for early recognition of extracranial complications might not be needed in patients with TBI

Limitation of life sustaining measures in neurocritical care: sex, timing, and advance directive

Background: The limitation of life sustaining treatments (LLST) causes ethical dilemmas even in patients faced with poor prognosis, which applies to many patients admitted to a Neurocritical Care Unit (NCCU). The effects of social and cultural aspects on LLST in an NCCU population remain poorly studied. Methods: All NCCU patients between 01.2018 and 08.2021 were included. Medical records were reviewed for: demographics, diagnosis, severity of disease, and outcome. Advance directives (AD) and LLST discussions were reviewed evaluating timing, degree, and reason for LLST. Social/cultural factors (nationality, language spoken, religion, marital status, relationship to/sex of legal representative) were noted. Associations between these factors and the patients’ sex, LLST timing, and presence of AD were evaluated. Results: Out of 2975 patients, 12% of men and 10.5% of women underwent LLST (p=0.30). Women, compared to men, more commonly received withdrawal instead of withholding of life sustaining treatments (57.5 vs. 45.1%, p=0.028) despite comparable disease severity. Women receiving LLST were older (73±11.7 vs. 69±14.9 years, p=0.005) and often without a partner (43.8 vs. 25.8%, p=0.001) compared to men. AD were associated with female sex and early LLST, but not with an increased in-hospital mortality (57.1 vs. 75.2% of patients with and without AD respectively). Conclusions: In patients receiving LLST, the presence of an AD was associated with an increase of early LLST, but not with an increased in-hospital mortality. This supports the notion that the presence of an AD is primarily an expression of the patients’ will but does not per se predestine the patient for an unfavorable outcome. Key words: Redirection of Care, Palliation, Neurocritical Care, Sex Difference

Sex-related differences in extracranial complications in patients with traumatic brain injury

Background: Extracranial complications after traumatic brain injury (TBI) are common. Their influence on outcome is uncertain. Furthermore, the role of sex on the development of extracranial complications following TBI remains poorly investigated. We aimed to investigate the incidence of extracranial complications after TBI with particular focus on sex-related differences with regard to complications and their influence on outcome. Methods: This retrospective, observational study was conducted in a level I universitary swiss trauma center. Consecutive patients with TBI admitted to the intensive care unit (ICU) between 2018 and 2021 were included. Patients' and trauma characteristics, in-hospital complications (i.e., cardiovascular, respiratory, renal, metabolic, gastrointestinal, hematological, and infectious) as well as functional outcome 3 months after trauma were analyzed. Data was dichotomized by sex or by outcome. Univariate as well as multivariate logistic regression was performed to reveal possible associations between sex, outcome and complications. Results: Overall, 608 patients were included (male n = 447, 73.5%). Extracranial complications occurred most frequently in cardiovascular, renal, hematological and infectious systems. Men and women suffered similarly from extracranial complications. While men needed correction of coagulopathies more often (p = 0.029), women suffered more frequently from urogenital infections (p = 0.001). Similar results were found in a subgroup of patients (n = 193) with isolated TBI. A multivariate analysis did not show extracranial complications to be independent predictors of unfavorable outcome. Conclusion: Extracranial complications following TBI occur frequently during the ICU-stay, can affect almost all organ systems but are not independent predictors of unfavorable outcome. The results suggest that sex-specific strategies for early recognition of extracranial complications might not be needed in patients with TBI

Sex-related differences in symptom presentation of patients with aneurysmal subarachnoid hemorrhage

Background: In patients with myocardial infarction, atypical symptoms at onset have been demonstrated in women. We aimed to investigate the presence of sex-related differences in symptom presentation in patients with aneurysmal subarachnoid hemorrhage (aSAH) to enable earlier diagnosis and treatment. Methods: We assessed symptoms on admission to hospital in 343 patients with aSAH in this retrospective single-center cohort-study. Univariate statistical analysis was performed by comparing sexes including the whole study population and subgroups (dichotomized using Fisher scale 1-2 vs. 3-4, WFNS grade 1-3 vs. 4-5, and anterior vs. posterior circulation aneurysms, respectively). Results: The majority of patients was female (63.6%, n=218, vs. 36.4%, n=125), the mean age 57.4 years (standard deviation (SD) 13.3) with older women compared to men (59.2, SD 13.8, vs. 54.4, SD 11.6; p=0.003). Anterior communicating artery (AcomA) aneurysms were most common (30.9%, n=106), predominantly in men (43.2%, n=54, vs. 23.9%, n=52; p=0.0002), whereas posterior communicating artery (PcomA) aneurysms were more frequent in women (19.3%, n=42, vs. 8.8%, n=11; p=0.005). Exercise-induced headache was more often reported by men (10.4%, n=13, vs. 5%, n=11; p=0.04) in all patients as well as in the subgroup of WFNS 1-3. Anisocoria was more frequent in women within the subgroup of severely impaired consciousness (WFNS 4-5; 25.3%, n=22, vs. 10.7%, n=6; p=0.032). For all other symptoms, there was no evidence for sex-specific differences in the whole study group as well as in subgroups. Conclusion: Our results show no evidence for relevant sex-related differences in symptom presentation at onset in aSAH patients. Women presenting with an acute onset anisocoria should be screened even more carefully for an underlying ruptured Pcom aneurysm

Sex-specific extracerebral complications in patients with aneurysmal subarachnoid hemorrhage

Background: Extracerebral complications in patients with aneurysmal subarachnoid hemorrhage (aSAH) often occur during their stay at the neurocritical care unit (NCCU). Their influence on outcomes is poorly studied. The identification of sex-specific extracerebral complications in patients with aSAH and their impact on outcomes might aid more personalized monitoring and therapy strategies, aiming to improve outcomes.MethodsConsecutive patients with aSAH admitted to the NCCU over a 6-year period were evaluated for the occurrence of extracerebral complications (according to prespecified criteria). Outcomes were assessed with the Glasgow Outcome Scale Extended (GOSE) at 3 months and dichotomized as favorable (GOSE 5–8) and unfavorable (GOSE 1–4). Sex-specific extracerebral complications and their impact on outcomes were investigated. Based on the results of the univariate analysis, a multivariate analysis with unfavorable outcomes or the occurrence of certain complications as dependent variables was performed.ResultsOverall, 343 patients were included. Most of them were women (63.6%), and they were older than men. Demographics, presence of comorbidities, radiological findings, severity of bleeding, and aneurysm-securing strategies were compared among the sexes. More women than men suffered from cardiac complications (p = 0.013) and infection (p = 0.048). Patients with unfavorable outcomes were more likely to suffer from cardiac (p < 0.001), respiratory (p < 0.001), hepatic/gastrointestinal (p = 0.023), and hematological (p = 0.021) complications. In the multivariable analysis, known factors including age, female sex, increasing number of comorbidities, increasing World Federation of Neurosurgical Societies (WFNS), and Fisher grading were expectedly associated with unfavorable outcomes. When adding complications to these models, these factors remained significant. However, when considering the complications, only pulmonary and cardiac complications remained independently associated with unfavorable outcomes.ConclusionExtracerebral complications after aSAH are frequent. Cardiac and pulmonary complications are independent predictors of unfavorable outcomes. Sex-specific extracerebral complications in patients with aSAH exist. Women suffered more frequently from cardiac and infectious complications potentially explaining the worse outcomes

Long-term outcome in new onset refractory status epilepticus: a retrospective study

BACKGROUND: New onset refractory status epilepticus (NORSE) is a neurologic emergency without an immediately identifiable cause. The complicated and long ICU stay of the patients can lead to perceiving a prolongation of therapies as futile. However, a recovery is possible even in severe cases. This retrospective study investigates ICU treatments, short- and long-term outcome and ethical decisions of a case series of patients with NORSE. METHODS: Overall, 283 adults were admitted with status epilepticus (SE) to the Neurocritical Care Unit of the University Hospital Zurich, Switzerland, between 01.2010 and 12.2022. Of them, 25 had a NORSE. We collected demographic, clinical, therapeutic and outcome data. Descriptive statistics was performed. RESULTS: Most patients were female (68%), previously healthy (Charlson comorbidity index 1 [0-4]) and relatively young (54 ± 17 years). 96% presented with super-refractory SE. Despite extensive workup, the majority (68%) of cases remained cryptogenic. Most patients had a long and complicated ICU stay. The in-hospital mortality was 36% (n = 9). The mortality at last available follow-up was 56% (n = 14) on average 30 months after ICU admission. The cause of in-hospital death for 89% (n = 8) of the patients was the withholding/withdrawing of therapies. Medical staff except for one patient triggered the decision. The end of life (EOL) decision was taken 29 [12-51] days after the ICU admission. Death occurred on day 6 [1-8.5] after the decision was taken. The functional outcome improved over time for 13/16 (81%) hospital survivors (median mRS at hospital discharge 4 [3.75-5] vs. median mRS at last available follow-up 2 [1.75-3], p < 0.001). CONCLUSIONS: Our data suggest that the long-term outcome can still be favorable in NORSE survivors, despite a prolonged and complicated ICU stay. Clinicians should be careful in taking EOL decisions to avoid the risk of a self-fulfilling prophecy. Our results encourage clinicians to continue treatment even in initially refractory cases

Sex-related differences of invasive therapy in patients with aneurysmal subarachnoid hemorrhage

Background: Sex-related differences in patients with aneurysmal subarachnoid hemorrhage (aSAH) exist. More females than males are affected. Aneurysm location is associated to sex. The relationship between sex and outcome, however, is unclear. Possible differences in management might influence the occurrence of primary and secondary brain injury and thus outcome. The study compares demographics, intensity of treatment, complications, and outcome among females and males with aSAH. Methods: All consecutive patients with aSAH admitted to the neurocritical care unit, University Hospital Zurich over a 5-year period were eligible in this retrospective study. Patients’ characteristics, comorbidities, aSAH severity, frequency of vasospasm/delayed cerebral ischemia, frequency of invasive interventions, and 3-month outcome were compared by sex. Univariate analysis was performed with the data dichotomized by sex, and outcome. Multivariate analysis for prediction of outcomes was performed. Results: Three hundred forty-eight patients were enrolled (64% females). Women were older than men. Comorbidities, scores at admission, and treatment modality were comparable among males and females. Vasospasm and DCI occurred similarly among females and males. Interventions and frequency of intraarterial spasmolysis were comparable between sexes. In the multivariate analysis, increasing age, female sex, increasing comorbidities, WFNS and Fisher grade, and presence of delayed cerebral ischemia were predictors of unfavorable outcome when considering all patients. However, after excluding death as a possible outcome, sex did not remain a predictor of unfavorable outcome. Conclusions: In the study population, women with aSAH might have present a worse outcome at 3 months. However, no differences by sex that might explain this difference were found in intensity of treatment and management