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PURPOSE OF REVIEW: To review recent advances in the field of seizure detection in ambulatory patients with epilepsy. RECENT FINDINGS: Recent studies have shown that wrist or arm wearable sensors, using 3D-accelerometry, electrodermal activity or photoplethysmography, in isolation or in combination, can reliably detect focal-to-bilateral and generalized tonic-clonic seizures (GTCS), with a sensitivity over 90%, and false alarm rates varying from 0.1 to 1.2 per day. A headband EEG has also demonstrated a high sensitivity for detecting and help monitoring generalized absence seizures. In contrast, no appropriate solution is yet available to detect focal seizures, though some promising findings were reported using ECG-based heart rate variability biomarkers and subcutaneous EEG. SUMMARY: Several FDA and/or EU-certified solutions are available to detect GTCS and trigger an alarm with acceptable rates of false alarms. However, data are still missing regarding the impact of such intervention on patients' safety. Noninvasive solutions to reliably detect focal seizures in ambulatory patients, based on either EEG or non-EEG biosignals, remain to be developed. To this end, a number of challenges need to be addressed, including the performance, but also the transparency and interpretability of machine learning algorithms.
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Eletroencefalografia , Epilepsia , Humanos , Convulsões/diagnóstico , Algoritmos , Aprendizado de MáquinaRESUMO
BACKGROUND: Traumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy. METHODS: Plasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls. RESULTS: Plasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates. CONCLUSIONS: Plasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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Doença de Alzheimer , Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Humanos , Biomarcadores , Proteínas tau , Imageamento por Ressonância Magnética , Ubiquitina Tiolesterase , Atrofia , Peptídeos beta-AmiloidesRESUMO
BACKGROUND: Deep sedation may be indicated in the intensive care unit (ICU) for the management of acute organ failure, but leads to sedative-induced delirium. Whether processed electroencephalography (p-EEG) is useful in this setting is unclear. METHODS: We conducted a single-centre observational study of non-neurological ICU patients sedated according to a standardized guideline of deep sedation (Richmond Agitation Sedation Scale [RASS] between -5 and -4) during the acute phase of respiratory and/or cardio-circulatory failure. The SedLine (Masimo Incorporated, Irvine, California) was used to monitor the Patient State Index (PSI) (ranging from 0 to 100, <25 = very deep sedation and >50 = light sedation to full awareness) during the first 72 h of care. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). RESULTS: The median duration of PSI monitoring was 43 h. Patients spent 49% in median of the total PSI monitoring duration with a PSI <25. Patients with delirium (n = 41/97, 42%) spent a higher percentage of total monitored time with PSI <25 (median 67% [19-91] vs. 47% [12.2-78.9]) in non-delirious patients (p .047). After adjusting for the cumulative dose of analgesia and sedation, increased time spent with PSI <25 was associated with higher delirium (odds ratio 1.014; 95% CI 1.001-1.027, p = .036). CONCLUSIONS: A clinical protocol of deep sedation targeted to RASS at the acute ICU phase may be associated with prolonged EEG suppression and increased delirium. Whether PSI-targeted sedation may help reducing sedative dose and delirium deserves further clinical investigation. RELEVANCE TO CLINICAL PRACTICE: Patients requiring deep sedation are at high risk of being over-sedated and developing delirium despite the application of an evidence-based sedation guideline. Development of early objective measures are essential to improve sedation management in these critically ill patients.
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BACKGROUND: Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. METHODS: This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 h. Starting at day 3, automated infrared pupillometry-blinded to ICU caregivers-was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/s). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. RESULTS: A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/s) at day 3, and at all additional time-points tested (p < 0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p = 0.03). CONCLUSIONS: Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.
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Estado Terminal , Delírio , Pupila , Respiração Artificial , Idoso , Estudos de Coortes , Cuidados Críticos , Delírio/diagnóstico , Delírio/etiologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pupila/fisiologia , Respiração Artificial/efeitos adversosRESUMO
OBJECTIVE: To evaluate the value of an adjuvant cisternostomy (AC) to decompressive craniectomy (DC) for the management of patients with severe traumatic brain injury (sTBI). METHODS: A single-center retrospective quality control analysis of a consecutive series of sTBI patients surgically treated with AC or DC alone between 2013 and 2018. A subgroup analysis, "primary procedure" and "secondary procedure", was also performed. We examined the impact of AC vs. DC on clinical outcome, including long-term (6 months) extended Glasgow outcome scale (GOS-E), the duration of postoperative ventilation, and intensive care unit (ICU) stay, mortality, Glasgow coma scale at discharge, and time to cranioplasty. We also evaluated and analyzed the impact of AC vs. DC on post-procedural intracranial pressure (ICP) and brain tissue oxygen (PbO2) values as well as the need for additional osmotherapy and CSF drainage. RESULTS: Forty patients were examined, 22 patients in the DC group, and 18 in the AC group. Compared with DC alone, AC was associated with significant shorter duration of mechanical ventilation and ICU stay, as well as better Glasgow coma scale at discharge. Mortality rate was similar. At 6-month, the proportion of patients with favorable outcome (GOS-E ≥ 5) was higher in patients with AC vs. DC [10/18 patients (61%) vs. 7/20 (35%)]. The outcome difference was particularly relevant when AC was performed as primary procedure (61.5% vs. 18.2%; p = 0.04). Patients in the AC group also had significant lower average post-surgical ICP values, higher PbO2 values and required less osmotic treatments as compared with those treated with DC alone. CONCLUSION: Our preliminary single-center retrospective data indicate that AC may be beneficial for the management of severe TBI and is associated with better clinical outcome. These promising results need further confirmation by larger multicenter clinical studies. The potential benefits of cisternostomy should not encourage its universal implementation across trauma care centers by surgeons that do not have the expertise and instrumentation necessary for cisternal microsurgery. Training in skull base and vascular surgery techniques for trauma care surgeons would avoid the potential complications associated with this delicate procedure.
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Lesões Encefálicas Traumáticas/cirurgia , Craniectomia Descompressiva/métodos , Complicações Pós-Operatórias/epidemiologia , Ventriculostomia/métodos , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Craniectomia Descompressiva/efeitos adversos , Feminino , Humanos , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Complicações Pós-Operatórias/prevenção & controle , Ventriculostomia/efeitos adversosRESUMO
Changes in emotional processing (EP) and in theory of mind (TOM) are central across treatment approaches for patients with borderline personality disorder (BPD). Although the assessment of EP relies on the observation of a patient's self-criticism in a two-chair dialogue, an individual's TOM assessments is made based on responses to humorous stimuli based on false beliefs. For this pilot study, we assessed eight patients with BPD before and after a 3-month-long psychiatric treatment, using functional magnetic resonance imaging and behavioral tasks. We observed arousal increase within the session of the two-chair dialogue (d = 0.36), paralleled by arousal decrease between sessions (d = 0.80). We found treatment-associated trends for neural activity reduction in brain areas central for EP and TOM. Our exploratory findings using an integrative assessment procedure of changes in EP and TOM point toward evidence for treatment effects at the brain systems level related to behavioral modulation.
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Transtorno da Personalidade Borderline/psicologia , Inteligência Emocional , Teoria da Mente , Transtorno da Personalidade Borderline/diagnóstico por imagem , Transtorno da Personalidade Borderline/fisiopatologia , Transtorno da Personalidade Borderline/terapia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Inteligência Emocional/fisiologia , Emoções , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Projetos Piloto , Autoimagem , Teoria da Mente/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Ketone bodies (such as ß-hydroxybutyrate or BHB) have been recently proposed as signals involved in brain regulation of energy homeostasis and obesity development. However, the precise role of ketone bodies sensing by the brain, and its impact on metabolic disorder development remains unclear. Nevertheless, partial deletion of the ubiquitous ketone bodies transporter MCT1 in mice (HE mice) results in diet-induced obesity resistance, while there is no alteration under normal chow diet. These results suggest that ketone bodies produced during the high fat diet would be important signals involved in obesity onset. METHODS: In the present study we used a specific BHB infusion of the hypothalamus and analyzed the energy homeostasis of WT or HE mice fed a normal chow diet. RESULTS: Our results indicate that high BHB levels sensed by the hypothalamus disrupt the brain regulation of energy homeostasis. This brain control dysregulation leads to peripheral alterations of energy expenditure mechanisms. CONCLUSIONS: Altogether, the changes induced by high ketone bodies levels sensed by the brain increase the risk of obesity onset in mice.
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Ácido 3-Hidroxibutírico , Metabolismo Energético , Hipotálamo , Corpos Cetônicos , Camundongos Endogâmicos C57BL , Obesidade , Animais , Hipotálamo/metabolismo , Camundongos , Corpos Cetônicos/metabolismo , Masculino , Obesidade/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/etiologia , Homeostase , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Simportadores/metabolismo , Simportadores/genéticaRESUMO
Electroencephalography (EEG) is widely used to monitor epileptic seizures, and standard clinical practice consists of monitoring patients in dedicated epilepsy monitoring units via video surveillance and cumbersome EEG caps. Such a setting is not compatible with long-term tracking under typical living conditions, thereby motivating the development of unobtrusive wearable solutions. However, wearable EEG devices present the challenges of fewer channels, restricted computational capabilities, and lower signal-to-noise ratio. Moreover, artifacts presenting morphological similarities to seizures act as major noise sources and can be misinterpreted as seizures. This paper presents a combined seizure and artifacts detection framework targeting wearable EEG devices based on Gradient Boosted Trees. The seizure detector achieves nearly zero false alarms with average sensitivity values of [Formula: see text] for 182 seizures from the CHB-MIT dataset and [Formula: see text] for 25 seizures from the private dataset with no preliminary artifact detection or removal. The artifact detector achieves a state-of-the-art accuracy of [Formula: see text] (on the TUH-EEG Artifact Corpus dataset). Integrating artifact and seizure detection significantly reduces false alarms-up to [Formula: see text] compared to standalone seizure detection. Optimized for a Parallel Ultra-Low Power platform, these algorithms enable extended monitoring with a battery lifespan reaching 300 h. These findings highlight the benefits of integrating artifact detection in wearable epilepsy monitoring devices to limit the number of false positives.
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Epilepsia , Dispositivos Eletrônicos Vestíveis , Humanos , Algoritmos , Artefatos , Eletroencefalografia , Epilepsia/diagnóstico , Convulsões/diagnósticoRESUMO
The long-term, continuous analysis of electroencephalography (EEG) signals on wearable devices to automatically detect seizures in epileptic patients is a high-potential application field for deep neural networks, and specifically for transformers, which are highly suited for end-to-end time series processing without handcrafted feature extraction. In this work, we propose a small-scale transformer detector, the EEGformer, compatible with unobtrusive acquisition setups that use only the temporal channels. EEGformer is the result of a hardware-oriented design exploration, aiming for efficient execution on tiny low-power micro-controller units (MCUs) and low latency and false alarm rate to increase patient and caregiver acceptance.Tests conducted on the CHB-MIT dataset show a 20% reduction of the onset detection latency with respect to the state-of-the-art model for temporal acquisition, with a competitive 73% seizure detection probability and 0.15 false-positive-per-hour (FP/h). Further investigations on a novel and challenging scalp EEG dataset result in the successful detection of 88% of the annotated seizure events, with 0.45 FP/h.We evaluate the deployment of the EEGformer on three commercial low-power computing platforms: the single-core Apollo4 MCU and the GAP8 and GAP9 parallel MCUs. The most efficient implementation (on GAP9) results in as low as 13.7 ms and 0.31 mJ per inference, demonstrating the feasibility of deploying the EEGformer on wearable seizure detection systems with reduced channel count and multi-day battery duration.
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Eletroencefalografia , Convulsões , Processamento de Sinais Assistido por Computador , Dispositivos Eletrônicos Vestíveis , Humanos , Eletroencefalografia/instrumentação , Eletroencefalografia/métodos , Convulsões/diagnóstico , Convulsões/fisiopatologia , Processamento de Sinais Assistido por Computador/instrumentação , Algoritmos , Redes Neurais de ComputaçãoRESUMO
Following traumatic brain injury (TBI), cerebral metabolic dysfunction, characterized by an elevated cerebral microdialysis (CMD) lactate/pyruvate (LP) ratio, is associated with poor outcome. However, the exact pathophysiological mechanisms underlying this association are not entirely established. In this pre-planned analysis of the BIOmarkers of AXonal injury after Traumatic Brain Injury (BIO-AX-TBI) prospective study, we investigated any associations of LP ratio with brain structure volume change rates at 1 year. Fourteen subjects underwent acute-phase (0-96 h post-TBI) CMD monitoring and had longitudinal magnetic resonance imaging (MRI) quantification of brain volume loss between the subacute phase (14 days to 6 weeks) and 1 year after TBI, recalculated as an annual rate. On average, CMD showed an elevated (>25) LP ratio (31 [interquartile range (IQR) 24-34]), indicating acute cerebral metabolic dysfunction. Annualized whole brain and total gray matter (GM) volume change rates were abnormally reduced (-3.2% [-9.3 to -2.2] and -1.9% [-4.4 to 1.7], respectively). Reduced annualized total GM volume correlated significantly with elevated CMD LP ratio (Spearman's ρ = -0.68, p-value = 0.01) and low CMD glucose (ρ = 0.66, p-value = 0.01). After adjusting for age, admission Glasgow Coma Scale (GCS) score and CT Marshall score, CMD LP ratio remained strongly associated with 1-year total GM volume change rate (p < 0.001; multi-variable analysis). No relationship was found between WM volume changes and CMD metabolites. We demonstrate a strong association between acute post-traumatic cerebral metabolic dysfunction and 1-year gray matter atrophy, reinforcing the role of CMD LP ratio as an early biomarker of poor long-term recovery after TBI.
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Encefalopatias , Lesões Encefálicas Traumáticas , Humanos , Estudos Prospectivos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Escala de Coma de Glasgow , BiomarcadoresRESUMO
BACKGROUND AND OBJECTIVES: Neurologic complications have been associated with COVID-19, including delirium. Such complications have been reported to be frequent among intensive care unit (ICU)-admitted patients. We hypothesized that the rate of neurologic complications would be higher in COVID-19 associated acute respiratory distress syndrome (ARDS) than those who develop ARDS from a different cause. METHODS: We conducted a retrospective cohort study in the adult ICU of Lausanne University Hospital, including all consecutive patients fulfilling the Berlin criteria for ARDS hospitalized between December 2017 and June 2021, stratifying exposure between COVID-19 or not. The primary outcome was delirium onset during ICU stay, defined by the confusion assessment method (CAM-ICU). Exploratory outcomes included development of neurologic complications of the central nervous system (stroke, hemorrhage, and vasculitis), critical illness weakness, and 30- and 180-day all-cause mortality. RESULTS: Three hundred eleven patients were included in the study (253 with COVID-19 and 58 with other causes) and CAM-ICU could be assessed in 231 (74.3% in COVID-19 vs 74.1% in non-COVID-19). The proportion of patients developing delirium was similar in patients with COVID-19 and controls in univariate comparison (69.1% vs 60.5%, p = 0.246). Yet, patients with COVID-19 had a higher body mass index, lower ICU severity, longer mechanical ventilation, and higher sedation doses (propofol and dexmedetomidine). After adjusting for these factors in a multivariable analysis, the risk of delirium remained comparable across groups (adjusted OR [95% CI]: 0.86 [0.35-2.1]). Similarly, COVID-19-related ARDS had no effect on all-cause mortality at 30 days (adjusted OR: 0.87 [0.39-1.92]) and 180 days (adjusted OR: 0.67 [0.33-1.35]). Finally, neurologic complications affecting the CNS (adjusted OR: 1.15 [0.25-5.29]) and critical illness weakness (adjusted OR: 2.99 [0.97-9.1]) were not higher in the COVID-19 group. DISCUSSION: Compared with other etiologies, patients with COVID-19 did not have higher incidence of delirium and other neurologic complications, after accounting for underlying disease severity in patients with ARDS. Management of COVID-19-associated ARDS needed longer invasive ventilation and higher sedation, which could explain higher rates of delirium in uncontrolled studies.
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COVID-19 , Delírio , Síndrome do Desconforto Respiratório , Humanos , Adulto , Estado Terminal , Estudos Retrospectivos , COVID-19/complicações , Síndrome do Desconforto Respiratório/epidemiologia , Síndrome do Desconforto Respiratório/etiologia , Unidades de Terapia Intensiva , Respiração Artificial , Delírio/epidemiologia , Delírio/etiologiaRESUMO
In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016−March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPialone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictorsto prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1−3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90−100)) at day 3 (sensitivity 24% (15−35), negative predictive value 36% (34−39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information.
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Hypertonic lactate (HL) is emerging as alternative treatment of intracranial hypertension following acute brain injury (ABI), but comparative studies are limited. Here, we examined the effectiveness of HL on main cerebral and systemic physiologic variables, and further compared it to that of standard hypertonic saline (HS). Retrospective cohort analysis of ABI subjects who received sequential osmotherapy with 7.5% HS followed by HL-given at equi-osmolar (2400 mOsmol/L) and isovolumic (1.5 mL/kg) bolus doses-to reduce sustained elevations of ICP (> 20 mmHg). The effect of HL on brain (intracranial pressure [ICP], brain tissue PO2 [PbtO2], cerebral microdialysis [CMD] glucose and lactate/pyruvate ratio [LPR]) and blood (chloride, pH) variables was examined at different time-points (30, 60, 90, 120 min vs. baseline), and compared to that of HS. A total of 34 treatments among 17 consecutive subjects (13 traumatic brain injury [TBI], 4 non-TBI) were studied. Both agents significantly reduced ICP (p < 0.001, at all time-points tested): when comparing treatment effectiveness, absolute ICP decrease in mmHg and the duration of treatment effect (median time with ICP < 20 mmHg following osmotherapy 183 [108-257] vs. 150 [111-419] min) did not differ significantly between HL and HS (all p > 0.2). None of the treatment had statistically significant effects on PbtO2 and CMD biomarkers. Treatment with HL did not cause hyperchloremia and resulted in a more favourable systemic chloride balance than HS (Δ blood chloride - 1 ± 2.5 vs. + 4 ± 3 mmol/L; p < 0.001). This is the first clinical study showing that HL has comparative effectiveness than HS for the treatment of intracranial hypertension, while at the same time avoiding hyperchloremic acidosis. Both agents had no significant effect on cerebral oxygenation and metabolism.
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Lesões Encefálicas/complicações , Hipertensão Intracraniana/tratamento farmacológico , Hipertensão Intracraniana/etiologia , Lactatos/administração & dosagem , Adulto , Feminino , Humanos , Soluções Hipertônicas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Solução Salina Hipertônica/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.
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Traumatismos da Medula Espinal , Substância Branca , Encéfalo , Tronco Encefálico , Humanos , Imageamento por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/diagnóstico por imagemRESUMO
Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.
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Lesões Encefálicas Traumáticas , Filamentos Intermediários , Axônios , Biomarcadores , Encéfalo , Lesões Encefálicas Traumáticas/complicações , HumanosRESUMO
BACKGROUND: Venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) after refractory cardiogenic shock or cardiac arrest has significant morbidity and mortality. Early outcome prediction is crucial in this setting, but data on neuroprognostication are limited. We examined the prognostic value of clinical neurologic examination, using an automated device for the quantitative measurement of pupillary light reactivity. METHODS: An observational cohort of sedated, mechanically ventilated VA-ECMO patients was analyzed during the early phase after ECMO insertion (first 72 h). Using the NPi-200 automated infrared pupillometer, pupillary light reactivity was assessed repeatedly (every 12 h) by calculating the Neurological Pupil index (NPi). Trends of NPi over time were correlated to 90-day mortality, and the prognostic performance of the NPi, alone and in combination with the 12-h PREDICT VA-ECMO score, was evaluated. RESULTS: One hundred consecutive patients were studied (51 with refractory cardiogenic shock and 49 with refractory cardiac arrest; 12-h PREDICT VA-ECMO, 40%; observed 90-day survival, 43%). Nonsurvivors (n = 57) had significantly lower NPi than did survivors at all time points (all P < .01). Abnormal NPi (< 3, at any time from 24 to 72 h) was 100% specific for 90-day mortality, with 0% false positives. Adding the 12-h PREDICT VA-ECMO score to the NPi provided the best prognostic performance (specificity, 100% [95% CI, 92%-100%]; sensitivity, 60% [95% CI, 46%-72%]; area under the receiver operating characteristic curve, 0.82). CONCLUSIONS: Quantitative NPi alone had excellent ability to predict a poor outcome from day 1 after VA-ECMO insertion, with no false positives. Combining NPi and 12-h PREDICT-VA ECMO score increased the sensitivity of outcome prediction, while maintaining 100% specificity.
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Oxigenação por Membrana Extracorpórea , Parada Cardíaca/terapia , Exame Neurológico/métodos , Reflexo Pupilar , Choque Cardiogênico/terapia , Idoso , Coma , Feminino , Parada Cardíaca/mortalidade , Humanos , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Choque Cardiogênico/mortalidade , Taxa de Sobrevida , SuíçaRESUMO
Adaptive metabolic response to injury includes the utilization of alternative energy substrates - such as ketone bodies (KB) - to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n = 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and ß-hydroxybutyrate). Nutrition - from fasting vs. stable nutrition state - was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] µmol/L vs. 13.1 [6.5-64.3] µmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] µmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p = 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.
Assuntos
Lesões Encefálicas Traumáticas/metabolismo , Corpos Cetônicos/metabolismo , Adulto , Fatores Etários , Encéfalo/metabolismo , Metabolismo Energético , Feminino , Humanos , Corpos Cetônicos/sangue , Cetonas/metabolismo , Masculino , Microdiálise , Pessoa de Meia-IdadeRESUMO
INTRODUCTION AND AIMS: Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome. METHODS AND ANALYSIS: BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6 weeks, at 6 and 12 months after injury. ETHICS AND DISSEMINATION: The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d'éthique de la recherche sur l'être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit. TRIAL REGISTRATION NUMBER: NCT03534154.