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1.
Nat Med ; 29(12): 3162-3174, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38049620

RESUMO

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .


Assuntos
Lesões Encefálicas Traumáticas , Estimulação Encefálica Profunda , Humanos , Lesões Encefálicas Traumáticas/terapia , Estimulação Encefálica Profunda/métodos , Estudos de Viabilidade , Qualidade de Vida , Tálamo/fisiologia
2.
Radiology ; 304(2): 385-394, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35471108

RESUMO

Background After severe traumatic brain injury (sTBI), physicians use long-term prognostication to guide acute clinical care yet struggle to predict outcomes in comatose patients. Purpose To develop and evaluate a prognostic model combining deep learning of head CT scans and clinical information to predict long-term outcomes after sTBI. Materials and Methods This was a retrospective analysis of two prospectively collected databases. The model-building set included 537 patients (mean age, 40 years ± 17 [SD]; 422 men) from one institution from November 2002 to December 2018. Transfer learning and curriculum learning were applied to a convolutional neural network using admission head CT to predict mortality and unfavorable outcomes (Glasgow Outcomes Scale scores 1-3) at 6 months. This was combined with clinical input for a holistic fusion model. The models were evaluated using an independent internal test set and an external cohort of 220 patients with sTBI (mean age, 39 years ± 17; 166 men) from 18 institutions in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study from February 2014 to April 2018. The models were compared with the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model and the predictions of three neurosurgeons. Area under the receiver operating characteristic curve (AUC) was used as the main model performance metric. Results The fusion model had higher AUCs than did the IMPACT model in the prediction of mortality (AUC, 0.92 [95% CI: 0.86, 0.97] vs 0.80 [95% CI: 0.71, 0.88]; P < .001) and unfavorable outcomes (AUC, 0.88 [95% CI: 0.82, 0.94] vs 0.82 [95% CI: 0.75, 0.90]; P = .04) on the internal data set. For external TRACK-TBI testing, there was no evidence of a significant difference in the performance of any models compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.90) in the prediction of mortality. The Imaging model (AUC, 0.73; 95% CI: 0.66-0.81; P = .02) and the fusion model (AUC, 0.68; 95% CI: 0.60, 0.76; P = .02) underperformed as compared with the IMPACT model (AUC, 0.83; 95% CI: 0.77, 0.89) in the prediction of unfavorable outcomes. The fusion model outperformed the predictions of the neurosurgeons. Conclusion A deep learning model of head CT and clinical information can be used to predict 6-month outcomes after severe traumatic brain injury. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Haller in this issue.


Assuntos
Lesões Encefálicas Traumáticas , Aprendizado Profundo , Adulto , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/cirurgia , Escala de Coma de Glasgow , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
3.
J Neurotrauma ; 36(16): 2423-2429, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30827167

RESUMO

Outcome measures are essential components of natural history studies of recovery and treatment effects after traumatic brain injury (TBI). The Glasgow Outcome Scale (GOS) and its revised version, the Glasgow Outcome Scale Extended (GOSE), are well accepted and widely used for both observational and intervention studies, but there are concerns about their psychometric properties and aptness as outcome measures for TBI. The present study compares the Functional Status Examination (FSE) with the GOSE to assess outcome after TBI in a sample of 533 participants with TBI from the Magnesium Sulfate study and the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study by evaluating the sensitivity of each measure to severity of brain injury and recovery of function over time. The results indicate that both measures are strongly correlated with TBI severity. At three months, the correlation strengths between injury severity and each outcome measure do not differ (p = 0.88 for Glasgow Coma Scale [GCS], p = 0.13 for computed tomography [CT] abnormalities) but at six months, the FSE is more strongly related to TBI severity indices than is the GOSE (p = 0.045 for GCS, p = 0.014 for CT abnormalities). In addition, the FSE generally shows significantly more improvement over time than the GOSE (p < 0.001). Detailed, structured administration rules and a wider score range of the FSE likely yields more sensitive and precise assessment of functional level than the GOSE. The FSE may be a valuable alternative to the GOSE for assessing functional outcome after TBI.


Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Escala de Resultado de Glasgow , Qualidade de Vida , Recuperação de Função Fisiológica/fisiologia , Adolescente , Adulto , Lesões Encefálicas Traumáticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Índices de Gravidade do Trauma , Resultado do Tratamento , Adulto Jovem
4.
Exp Neurol ; 224(2): 369-88, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20420832

RESUMO

The use of electrocorticography (ECoG) with etiologically realistic epilepsy models promises to facilitate the discovery of better anti-epileptic drugs (AEDs). However, this novel approach is labor intensive, and must be optimized. To this end, we employed rostral parasagittal fluid percussion injury (rpFPI) in the adolescent rat, which closely replicates human contusive closed head injury and results in posttraumatic epilepsy (PTE). We systematically examined variables affecting the power to detect anti-epileptic effects by ECoG and used a non-parametric bootstrap strategy to test several different statistics, study designs, statistical tests, and impact of non-responders. We found that logarithmically transformed data acquired in repeated-measures experiments provided the greatest statistical power to detect decreases in seizure frequencies of preclinical interest with just 8 subjects and with up to approximately 40% non-responders. We then used this optimized design to study the anti-epileptic effects of acute exposure to halothane, and chronic (1 week) exposures to carbamazepine (CBZ) and valproate (VPA) 1 month post-injury. While CBZ was ineffective in all animals, VPA induced, during treatment, a progressive decrease in seizure frequency in animals primarily suffering from non-spreading neocortical seizures, but was ineffective in animals with a high frequency of spreading seizures. Halothane powerfully blocked all seizure activity. The data show that rpFPI and chronic ECoG can conveniently be employed for the evaluation of AEDs, suggest that VPA may be more effective than CBZ to treat some forms of PTE, and support the theory that pharmacoresistance may depend on the severity of epilepsy. The data also demonstrate the utility of chronic exposures to experimental drugs in preclinical studies and highlight the need for greater attention to etiology in clinical studies of AEDs.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , Epilepsia do Lobo Frontal/tratamento farmacológico , Halotano/uso terapêutico , Traumatismos Cranianos Fechados/complicações , Ácido Valproico/uso terapêutico , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Eletrodos , Eletrofisiologia , Epilepsia do Lobo Frontal/etiologia , Epilepsia do Lobo Frontal/fisiopatologia , Masculino , Método de Monte Carlo , Ratos , Ratos Sprague-Dawley
5.
J Head Trauma Rehabil ; 24(4): 272-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19625866

RESUMO

OBJECTIVE: To determine preferences for depression treatment modalities and settings among persons with traumatic brain injury (TBI). DESIGN: Telephone survey. Depression status was determined using the Patient Health Questionnaire-9. SETTING: Harborview Medical Center, Seattle, Washington, the level I trauma center serving Washington, Idaho, Montana, and Alaska. PARTICIPANTS: One hundred forty-five adults, English-speaking consecutive patients admitted with complicated mild to severe TBI. MAIN OUTCOME MEASURES: Telephone survey within 12 months post-TBI ascertaining preferences for depression treatment modalities and settings. RESULTS: More patients favored physical exercise or counseling as a depression treatment than other treatment modalities. Group therapy was the least favored modality. Patients favored speaking with a clinician in the clinic or over the telephone and were less likely to communicate with a clinician over the Internet. Subjects with probable major depression or a history of antidepressant use or outpatient mental health treatment were more likely to express a preference for antidepressants for treatment of depression. CONCLUSIONS: This study underscores the importance of understanding patient preferences and providing patient education in selecting a treatment for depression after TBI. Future studies should examine psychotherapy and alternative treatment modalities and delivery models for the management of depression in this vulnerable population.


Assuntos
Lesões Encefálicas/psicologia , Depressão/terapia , Satisfação do Paciente , Adulto , Antidepressivos/uso terapêutico , Atitude Frente a Saúde , Comportamento de Escolha , Terapias Complementares , Aconselhamento , Depressão/psicologia , Exercício Físico , Feminino , Processos Grupais , Humanos , Internet , Entrevistas como Assunto , Masculino , Psicoterapia , Índice de Gravidade de Doença
6.
Epilepsia ; 50 Suppl 2: 10-3, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19187289

RESUMO

Posttraumatic epilepsy presents an ideal target for prevention efforts. Traumatic brain injury (TBI) is common, characteristics that put people at high risk such as penetrating injury or subdural hematoma or provoked seizures are easily identified, and the latency between the injury and the onset of epileptic seizures is frequently short. Several drugs have been tested for their ability to prevent provoked seizures and epilepsy after TBI. We describe the design of those studies and their results. Phenytoin and carbamazepine significantly reduce the incidence of provoked seizures. Phenobarbital and the combination of phenobarbital and phenytoin also look promising for reducing provoked seizures, but small sample sizes in the studies evaluating these drugs do not allow definitive conclusions. None of the drugs studied (phenytoin, phenobarbital, their combination, carbamazepine, valproate, or magnesium) have shown reliable evidence that they prevent, or even suppress, epileptic seizures after TBI. For most of the regimens tested (the phenytoin/phenobarbital combination being the exception), the best estimate of effect is under a 25% reduction in posttraumatic seizures, well less than the 50% reduction most studies were designed to detect. The evaluation of the tested drugs has serious limitations, however, and antiepileptic drugs (AEDs) developed since 1980 and other compounds have barely been tested at all. Better understanding the process of epileptogenesis, testing treatments that demonstrate antiepileptogenic effects in the laboratory, and performing thorough preclinical and phase II evaluations before attempting definitive trials should greatly improve the chance of identifying ways to prevent posttraumatic epilepsy, providing the ultimate cure for this condition.


Assuntos
Anticonvulsivantes/uso terapêutico , Lesões Encefálicas/complicações , Epilepsia Pós-Traumática/prevenção & controle , Animais , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Eletroencefalografia/efeitos dos fármacos , Epilepsia Pós-Traumática/tratamento farmacológico , Traumatismos Cranianos Penetrantes/complicações , Hematoma Subdural/complicações , Humanos , Fenobarbital/uso terapêutico , Fenitoína/uso terapêutico , Prognóstico , Convulsões/complicações
7.
Lancet Neurol ; 6(1): 29-38, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17166799

RESUMO

BACKGROUND: Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients. METHODS: In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number . FINDINGS: Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect. INTERPRETATION: Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Sulfato de Magnésio/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Adolescente , Adulto , Idoso , Lesões Encefálicas/complicações , Lesões Encefálicas/mortalidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Escala de Coma de Glasgow , Humanos , Magnésio/sangue , Sulfato de Magnésio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Testes Neuropsicológicos , Edema Pulmonar/epidemiologia , Edema Pulmonar/etiologia , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Convulsões/epidemiologia , Convulsões/etiologia , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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