Meral A Tubi

Bio: Meral A Tubi is an academic researcher from University of Southern California. The author has contributed to research in topics: Traumatic brain injury & Population. The author has an hindex of 5, co-authored 9 publications receiving 228 citations. Previous affiliations of Meral A Tubi include University of California, Los Angeles.

Metabolic crisis occurs with seizures and periodic discharges after brain trauma.

Abstract: OBJECTIVE Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post-traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis. METHODS A prospective multicenter study of surface and intracortical depth EEG were performed in conjunction with cerebral microdialysis in a cohort of severe TBI patients with time-locked analysis of the neurochemical response to seizures and pseudoperiodic discharges. RESULTS Seizures or PDs occurred in 61% of 34 subjects, with 42.9% of these seizures noted only on intracortical depth EEG and in some cases lasted for many hours. Metabolic crisis as measured by elevated cerebral microdialysis lactate/pyruvate ratio occurred during seizures or PDs but not during electrically nonepileptic epochs. Interpretation In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study. This article is protected by copyright. All rights reserved. Language: en

Traumatic hemorrhagic brain injury: impact of location and resorption on cognitive outcome.

Abstract: OBJECTIVE Hemorrhagic contusions are often the most visible lesions following traumatic brain injury. However, the incidence, location, and natural history of traumatic parenchymal hemorrhage and its impact on neurological outcome have been understudied. The authors sought to examine the location and longitudinal evolution of traumatic parenchymal hemorrhage and its association with cognitive outcome. METHODS Sixteen patients with hemorrhagic contusions due to acceleration-deceleration injuries underwent MRI in the acute (mean 6.3 days postinjury) and chronic (mean 192.9 days postinjury) phases. ImageJ was used to generate GRE and FLAIR volumes. To account for the effect of head-size variability across individuals, the authors calculated each patient's total brain tissue volume using SIENAX. GRE and FLAIR volumes were normalized to the total brain tissue volume, and values for absolute and percent lesion volume and total brain volume change were generated. Spearman's rank correlations were computed to determine associations between neuroimaging and 6-month postinjury neuropsychological testing of attention (Symbol Digit Modalities Test [SDMT], oral [O] and written [W] versions), memory (Selective Reminding Test, total learning and delayed recall), and executive function (Trail Making Test Part B [TMT-B]). RESULTS The patients' mean age was 31.4 ± 14.0 years and their mean Glasgow Coma Scale score at admission was 7.9 ± 2.8. Lesions were predominantly localized to the frontal (11 lesions) and temporal (9 lesions) lobes. The average percent reductions in GRE and FLAIR volumes were 44.2% ± 46.1% and 80.5% ± 26.3%, respectively. While total brain and frontal lesion volumes did not correlate with brain atrophy, larger temporal lobe GRE and FLAIR volumes were associated with larger volumes of atrophy (GRE: acute, -0.87, p < 0.01, chronic, -0.78, p < 0.01; FLAIR: acute, -0.81, p < 0.01, chronic, -0.88, p < 0.01). Total percent volume change of GRE lesions correlated with TMT-B (0.53, p < 0.05) and SDMT-O (0.62, p < 0.05) scores. Frontal lobe lesion volume did not correlate with neuropsychological outcome. However, robust relationships were seen in the temporal lobe, with larger acute temporal lobe GRE volumes were associated with worse scores on both oral and written versions of the SDMT (SDMT-W, -0.85, p < 0.01; SDMT-O, -0.73, p < 0.05). Larger absolute change in temporal GRE volume was strongly associated with worse SDMT scores (SDMT-W, 0.88, p < 0.01; SDMT-O, 0.75, p < 0.05). The same relationships were also seen between temporal FLAIR lesion volumes and neuropsychological outcome. CONCLUSIONS Traumatic parenchymal hemorrhages are largely clustered in the frontal and temporal lobes, and significant residual blood products are present at 6 months postinjury, a potential source of ongoing secondary brain injury. Neuropsychological outcome is closely tied to lesion volume size, particularly in the temporal lobe, where larger GRE and FLAIR volumes are associated with more brain atrophy and worse SDMT scores. Interestingly, larger volumes of hemorrhage resorption were associated with worse SDMT and TMT-B scores, suggesting that the initial tissue damage had a lasting impact on attention and executive function.

Longitudinal quantification and visualization of intracerebral haemorrhage using multimodal magnetic resonance and diffusion tensor imaging

Abstract: Objective: To demonstrate a set of approaches using diffusion tensor imaging (DTI) tractography whereby pathology-affected white matter (WM) fibres in patients with intracerebral haemorrhage (ICH) can be selectively visualized.Methods: Using structural neuroimaging and DTI volumes acquired longitudinally from three representative patients with ICH, the spatial configuration of ICH-related trauma is delineated and the WM fibre bundles intersecting each ICH lesion are identified and visualized. Both the extent of ICH lesions as well as the proportion of WM fibres intersecting the ICH pathology are quantified and compared across subjects.Results: This method successfully demonstrates longitudinal volumetric differences in ICH lesion load and differences across time in the percentage of fibres which intersect the primary injury.Conclusions: Because neurological conditions such as intracerebral haemorrhage (ICH) frequently exhibit pathology-related effects which lead to the exertion of mechanical press...

Clinical Diagnosis of Alzheimer's Disease

Abstract: There are a number of ways in which a clinical diagnosis of dementia of the Alzheimer type can be made – the application of clinical criteria is the commonest but ancillary techniques such as neuroima

Poststroke Dementia

Abstract: Stroke is a major cause of death in the elderly, and risk of dementia increases after stroke. Poststroke dementia （PSD） covers all types of dementia after stroke, and is an important cause of disability in the elderly. The prevalence of PSD varies from 31.4% to 21.5% in 3 months to 4 years after the stroke. Its incidence increases with time after the stroke. Stroke and dementia share a number of risk factors. Stroke can be the direct cause of dementia and may also produce dementia by precipitating the onset of degenerative disease. Key words: stroke ; dementia ; Alzheimer＇s disease ; risk factor

Severe traumatic brain injury: targeted management in the intensive care unit

Abstract: Summary Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical–surgical approach. Treatment aims to prevent additional brain damage and to optimise conditions for brain recovery. TBI is typically considered and treated as one pathological entity, although in fact it is a syndrome comprising a range of lesions that can require different therapies and physiological goals. Owing to advances in monitoring and imaging, there is now the potential to identify specific mechanisms of brain damage and to better target treatment to individuals or subsets of patients. Targeted treatment is especially relevant for elderly people—who now represent an increasing proportion of patients with TBI—as preinjury comorbidities and their therapies demand tailored management strategies. Progress in monitoring and in understanding pathophysiological mechanisms of TBI could change current management in the intensive care unit, enabling targeted interventions that could ultimately improve outcomes.

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Abstract: The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likely primary drivers of epileptogenesis, namely inflammation, neuron loss, plasticity, and circuit reorganization. This review suggests a path to identify neuronal and molecular targets for clinical testing of specific hypotheses about epileptogenesis and its prevention or modification. Acquired human epilepsies with different etiologies share some features with animal models. We identify these commonalities and discuss their relevance to the development of successful epilepsy prevention or disease modification strategies. Risk factors for developing epilepsy that appear common to multiple acute injury etiologies include intracranial bleeding, disruption of the blood-brain barrier, more severe injury, and early seizures within 1 week of injury. In diverse human epilepsies and animal models, seizures appear to propagate within a limbic or thalamocortical/corticocortical network. Common histopathologic features of epilepsy of diverse and mostly focal origin are microglial activation and astrogliosis, heterotopic neurons in the white matter, loss of neurons, and the presence of inflammatory cellular infiltrates. Astrocytes exhibit smaller K+ conductances and lose gap junction coupling in many animal models as well as in sclerotic hippocampi from temporal lobe epilepsy patients. There is increasing evidence that epilepsy can be prevented or aborted in preclinical animal models of acquired epilepsy by interfering with processes that appear common to multiple acute injury etiologies, for example, in post-status epilepticus models of focal epilepsy by transient treatment with a trkB/PLCγ1 inhibitor, isoflurane, or HMGB1 antibodies and by topical administration of adenosine, in the cortical fluid percussion injury model by focal cooling, and in the albumin posttraumatic epilepsy model by losartan. Preclinical studies further highlight the roles of mTOR1 pathways, JAK-STAT3, IL-1R/TLR4 signaling, and other inflammatory pathways in the genesis or modulation of epilepsy after brain injury. The wealth of commonalities, diversity of molecular targets identified preclinically, and likely multidimensional nature of epileptogenesis argue for a combinatorial strategy in prevention therapy. Going forward, the identification of impending epilepsy biomarkers to allow better patient selection, together with better alignment with multisite preclinical trials in animal models, should guide the clinical testing of new hypotheses for epileptogenesis and its prevention.