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1.
Ann Neurol ; 93(3): 489-499, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36394101

RESUMEN

OBJECTIVE: Tenecteplase improves reperfusion compared to alteplase in patients with large vessel occlusions. To determine whether this improvement varies across the spectrum of thrombolytic agent to reperfusion assessment times, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates. METHODS: Patients with large vessel occlusion and treatment with thrombolysis were pooled from the Melbourne Stroke Registry, and the EXTEND-IA and EXTEND-IA TNK trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at imaging reassessment. We compared the treatment effect of tenecteplase and alteplase, accounting for thrombolytic to assessment exposure times, via Poisson modeling. We compared 90-day outcomes of patients who achieved reperfusion with a thrombolytic to patients who achieved reperfusion via endovascular therapy using ordinal logistic regression. RESULTS: Among 893 patients included in the primary analysis, thrombolytic-induced reperfusion was observed in 184 (21%) patients. Tenecteplase was associated with higher rates of reperfusion (adjusted incidence rate ratio [aIRR] = 1.50, 95% confidence interval [CI] = 1.09-2.07, p = 0.01). Findings were consistent in patient subgroups with first segment (aIRR = 1.41, 95% CI = 0.93-2.14) and second segment (aIRR = 2.07, 95% CI = 0.98-4.37) middle cerebral artery occlusions. Increased thrombolytic to reperfusion assessment times were associated with reperfusion (tenecteplase: adjusted risk ratio [aRR] = 1.08 per 15 minutes, 95% CI = 1.04-1.13 vs alteplase: aRR = 1.06 per 15 minutes, 95% CI = 1.00-1.13). No significant treatment-by-time interaction was observed (p = 0.87). Reperfusion via thrombolysis was associated with improved 90-day modified Rankin Scale scores (adjusted common odds ratio = 2.15, 95% CI = 1.54-3.01) compared to patients who achieved reperfusion following endovascular therapy. INTERPRETATION: Tenecteplase, compared to alteplase, increases prethrombectomy reperfusion, regardless of the time from administration to reperfusion assessment. Prethrombectomy reperfusion is associated with better clinical outcomes. ANN NEUROL 2023;93:489-499.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Tenecteplasa/uso terapéutico , Activador de Tejido Plasminógeno , Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Reperfusión/métodos , Resultado del Tratamiento
2.
Stroke ; 54(3): 706-714, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36727510

RESUMEN

BACKGROUND: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). METHODS: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015-2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. RESULTS: Tenecteplase was associated with higher odds of early reperfusion (75/369 [20%] versus alteplase: 9/96 [9%], adjusted odds ratio [aOR], 2.18 [95% CI, 1.03-4.63]). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 [25%] versus alteplase: 5/67 [7%], aOR, 3.93 [95% CI, 1.50-10.33]) when compared to high clot burden lesions (tenecteplase: 9/108 [8%] versus alteplase: 4/29 [14%], aOR, 0.58 [95% CI, 0.16-2.06]; Pinteraction=0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 [95% CI, 1.00-8.05] versus absent: aOR, 1.98 [95% CI, 0.65-6.03]; Pinteraction=0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 [30%] versus alteplase: 4/42 [10%], aOR, 3.73 [95% CI, 1.25-11.11]), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 [1%] versus alteplase 1/19 [5%], aOR, 0.22 [95% CI, 0.01-3.83]; Pinteraction=0.16). CONCLUSIONS: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.


Asunto(s)
Isquemia Encefálica , Enfermedades de las Arterias Carótidas , Accidente Cerebrovascular , Trombosis , Humanos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/inducido químicamente , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Fibrinolíticos , Reperfusión/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Tenecteplasa/uso terapéutico , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Trombosis/inducido químicamente , Activador de Tejido Plasminógeno , Resultado del Tratamiento
3.
Brain ; 145(4): 1285-1298, 2022 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-35333312

RESUMEN

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.


Asunto(s)
Conectoma , Epilepsia del Lóbulo Temporal , Adulto , Atrofia/patología , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética
4.
Aust N Z J Psychiatry ; 57(4): 594-602, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-35196886

RESUMEN

OBJECTIVE: Amyloid-beta often co-exists in dementia with Lewy bodies, but its clinical relevance in dementia with Lewy bodies remains unclear. This study aimed to investigate the clinical and imaging correlates of amyloid-beta deposition in dementia with Lewy bodies, particularly its relationship with cortical thickness in Alzheimer's disease-prone regions and hippocampal volume. METHODS: Twenty-four participants with probable dementia with Lewy bodies underwent high-resolution magnetic resonance imaging and amyloid-beta positron emission tomography imaging using the radiotracer 18F-NAV4694. Amyloid-beta deposition was quantified and reported using the Centiloid method. RESULTS: Amyloid-beta positivity, defined as Centiloid > 50, was present in 45.8% of dementia with Lewy bodies participants. There were no statistically significant differences in clinical characteristics between Aß+ and Aß- dementia with Lewy bodies. Compared with the Aß- group, Aß+ dementia with Lewy bodies exhibited greater global cortical thinning as well as in the Alzheimer's disease-prone region of interest, adjusted for age, sex and years of education. A mean cortical thickness of 5.12 mm across a combined meta-region of interest has a sensitivity of 88.9% and specificity of 90.0% in discriminating Aß+ from Aß- dementia with Lewy bodies. Hippocampal volume was not different between groups. CONCLUSION: Early structural changes in cortical thickness, but not hippocampal volume, were observed in dementia with Lewy bodies with significant amyloid-beta burden. This may represent an early Alzheimer's disease-related neurodegenerative process.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad por Cuerpos de Lewy , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/diagnóstico por imagen , Enfermedad por Cuerpos de Lewy/patología , Péptidos beta-Amiloides/metabolismo , Tomografía de Emisión de Positrones/métodos , Hipocampo/diagnóstico por imagen , Hipocampo/patología
5.
Stroke ; 53(6): 1915-1923, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35135319

RESUMEN

BACKGROUND: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. METHODS: In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. RESULTS: In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75-0.98]; P=0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. CONCLUSIONS: In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Procedimientos Endovasculares/métodos , Fibrinolíticos/uso terapéutico , Humanos , Infarto , Reperfusión/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Tenecteplasa/uso terapéutico , Trombectomía/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento
6.
Stroke ; 53(5): 1597-1605, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34937423

RESUMEN

BACKGROUND: Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24-72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy. METHODS: We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible (<1 mm), mild (≥1 to <5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere. RESULTS: Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00-1.028), 1.03 (IQR, 1.01-1.077), and 1.15 (IQR, 1.08-1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days (P<0.002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 [95% CI, 1.03-1.20], P=0.005; rHV ß, 0.39 [95% CI, 0.24-0.55], P<0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 [95% CI, 0.10-0.58], P=0.001; rHV ß, -2.95 [95% CI, -4.61 to -11.29], P=0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 [95% CI, 0.14-0.98], P=0.045; rHV ß, -2.59 [95% CI, -4.32 to -0.86], P=0.004). CONCLUSIONS: BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.


Asunto(s)
Edema Encefálico , Isquemia Encefálica , Barrera Hematoencefálica/diagnóstico por imagen , Edema Encefálico/complicaciones , Edema Encefálico/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Infarto Cerebral/complicaciones , Circulación Cerebrovascular , Humanos
7.
N Engl J Med ; 380(19): 1795-1803, 2019 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-31067369

RESUMEN

BACKGROUND: The time to initiate intravenous thrombolysis for acute ischemic stroke is generally limited to within 4.5 hours after the onset of symptoms. Some trials have suggested that the treatment window may be extended in patients who are shown to have ischemic but not yet infarcted brain tissue on imaging. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving patients with ischemic stroke who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging. The patients were randomly assigned to receive intravenous alteplase or placebo between 4.5 and 9.0 hours after the onset of stroke or on awakening with stroke (if within 9 hours from the midpoint of sleep). The primary outcome was a score of 0 or 1 on the modified Rankin scale, on which scores range from 0 (no symptoms) to 6 (death), at 90 days. The risk ratio for the primary outcome was adjusted for age and clinical severity at baseline. RESULTS: After 225 of the planned 310 patients had been enrolled, the trial was terminated because of a loss of equipoise after the publication of positive results from a previous trial. A total of 113 patients were randomly assigned to the alteplase group and 112 to the placebo group. The primary outcome occurred in 40 patients (35.4%) in the alteplase group and in 33 patients (29.5%) in the placebo group (adjusted risk ratio, 1.44; 95% confidence interval [CI], 1.01 to 2.06; P = 0.04). Symptomatic intracerebral hemorrhage occurred in 7 patients (6.2%) in the alteplase group and in 1 patient (0.9%) in the placebo group (adjusted risk ratio, 7.22; 95% CI, 0.97 to 53.5; P = 0.05). A secondary ordinal analysis of the distribution of scores on the modified Rankin scale did not show a significant between-group difference in functional improvement at 90 days. CONCLUSIONS: Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 and 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo. There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group. (Funded by the Australian National Health and Medical Research Council and others; EXTEND ClinicalTrials.gov numbers, NCT00887328 and NCT01580839.).


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Fibrinolíticos/uso terapéutico , Imagen de Perfusión , Accidente Cerebrovascular/tratamiento farmacológico , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Angiografía por Tomografía Computarizada , Femenino , Fibrinolíticos/efectos adversos , Humanos , Infusiones Intravenosas , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/prevención & control , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/mortalidad , Equipoise Terapéutico , Activador de Tejido Plasminógeno/efectos adversos
8.
Epilepsia ; 63(5): 1081-1092, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35266138

RESUMEN

OBJECTIVES: Around 30% of patients undergoing surgical resection for drug-resistant mesial temporal lobe epilepsy (MTLE) do not obtain seizure freedom. Success of anterior temporal lobe resection (ATLR) critically depends on the careful selection of surgical candidates, aiming at optimizing seizure freedom while minimizing postoperative morbidity. Structural MRI and FDG-PET neuroimaging are routinely used in presurgical assessment and guide the decision to proceed to surgery. In this study, we evaluate the potential of machine learning techniques applied to standard presurgical MRI and PET imaging features to provide enhanced prognostic value relative to current practice. METHODS: Eighty two patients with drug resistant MTLE were scanned with FDG-PET pre-surgery and T1-weighted MRI pre- and postsurgery. From these images the following features of interest were derived: volume of temporal lobe (TL) hypometabolism, % of extratemporal hypometabolism, presence of contralateral TL hypometabolism, presence of hippocampal sclerosis, laterality of seizure onset volume of tissue resected and % of temporal lobe hypometabolism resected. These measures were used as predictor variables in logistic regression, support vector machines, random forests and artificial neural networks. RESULTS: In the study cohort, 24 of 82 (28.3%) who underwent an ATLR for drug-resistant MTLE did not achieve Engel Class I (i.e., free of disabling seizures) outcome at a minimum of 2 years of postoperative follow-up. We found that machine learning approaches were able to predict up to 73% of the 24 ATLR surgical patients who did not achieve a Class I outcome, at the expense of incorrect prediction for up to 31% of patients who did achieve a Class I outcome. Overall accuracies ranged from 70% to 80%, with an area under the receiver operating characteristic curve (AUC) of .75-.81. We additionally found that information regarding overall extent of both total and significantly hypometabolic tissue resected was crucial to predictive performance, with AUC dropping to .59-.62 using presurgical information alone. Incorporating the laterality of seizure onset and the choice of machine learning algorithm did not significantly change predictive performance. SIGNIFICANCE: Collectively, these results indicate that "acceptable" to "good" patient-specific prognostication for drug-resistant MTLE surgery is feasible with machine learning approaches utilizing commonly collected imaging modalities, but that information on the surgical resection region is critical for optimal prognostication.


Asunto(s)
Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Fluorodesoxiglucosa F18 , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética , Convulsiones , Resultado del Tratamiento
9.
Epilepsia ; 63(8): 2081-2095, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35656586

RESUMEN

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Atrofia/patología , Biomarcadores , Estudios Transversales , Epilepsia/complicaciones , Epilepsia del Lóbulo Temporal/patología , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis/complicaciones
10.
Neuroradiology ; 64(8): 1557-1567, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35094103

RESUMEN

PURPOSE: Development of a freely available stroke population-specific anatomical CT/MRI atlas with a reliable normalisation pipeline for clinical CT. METHODS: By reviewing CT scans in suspected stroke patients and filtering the AIBL MRI database, respectively, we collected 50 normal-for-age CT and MRI scans to build a standard-resolution CT template and a high-resolution MRI template. The latter was manually segmented into anatomical brain regions. We then developed and validated a MRI to CT registration pipeline to align the MRI atlas onto the CT template. Finally, we developed a CT-to-CT-normalisation pipeline and tested its reliability by calculating Dice coefficient (Dice) and Average Hausdorff Distance (AHD) for predefined areas in 100 CT scans from ischaemic stroke patients. RESULTS: The resulting CT/MRI templates were age and sex matched to a general stroke population (median age 71.9 years (62.1-80.2), 60% male). Specifically, this accounts for relevant structural changes related to aging, which may affect registration. Applying the validated MRI to CT alignment (Dice > 0.78, Average Hausdorff Distance < 0.59 mm) resulted in our final CT-MRI atlas. The atlas has 52 manually segmented regions and covers the whole brain. The alignment of four cortical and subcortical brain regions with our CT-normalisation pipeline was reliable for small/medium/large infarct lesions (Dice coefficient > 0.5). CONCLUSION: The newly created CT-MRI brain atlas has the potential to standardise stroke lesion segmentation. Together with the automated normalisation pipeline, it allows analysis of existing and new datasets to improve prediction tools for stroke patients (free download at https://forms.office.com/r/v4t3sWfbKs ).


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Anciano , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Reproducibilidad de los Resultados , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X
11.
Stroke ; 52(10): 3163-3166, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34187178

RESUMEN

Background and Purpose: Mobile stroke units (MSUs) improve reperfusion therapy times in acute ischemic stroke (AIS). However, prehospital management options for intracerebral hemorrhage (ICH) are less established. We describe the initial Melbourne MSU experience in ICH. Methods: Consecutive patients with ICH and AIS treated by the Melbourne MSU were included. We describe demographics, proportions of patients receiving specific therapies, and bypass to comprehensive/neurosurgical centers. We also compare operational time metrics between patients with MSU-ICH and MSU-AIS. Results: During a 2-year period, the Melbourne MSU managed 49 patients with ICH, mean (SD) age 74 (12) years, median (interquartile range) National Institutes of Health Stroke Scale 17 (12­20). Intravenous antihypertensives were the commonest treatment provided (46.9%). Bypass of a primary center to a comprehensive center with neurosurgical expertise occurred in 32.7% of patients with MSU-ICH compared with 20.5% of patients with MSU-AIS. Compared with patients with MSU-AIS, patients with MSU-ICH had faster onset-to-emergency-call, and onset-to-scene-arrival times at the median and 75th percentiles. Conclusions: MSUs can facilitate ultra-early ICH diagnosis, management, and triage.


Asunto(s)
Ambulancias , Hemorragia Cerebral/terapia , Servicios Médicos de Urgencia/métodos , Accidente Cerebrovascular Hemorrágico/terapia , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Manejo de Caso , Femenino , Accidente Cerebrovascular Hemorrágico/cirugía , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Tiempo de Tratamiento , Triaje , Victoria
12.
Brain ; 143(8): 2454-2473, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32814957

RESUMEN

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.


Asunto(s)
Encéfalo/patología , Síndromes Epilépticos/patología , Sustancia Blanca/patología , Adulto , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad
13.
J Comput Assist Tomogr ; 45(1): 37-51, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32976265

RESUMEN

ABSTRACT: Gadolinium-based contrast agents for clinical magnetic resonance imaging are overall safe. However, the discovery of nephrogenic systemic fibrosis in patients with severe renal impairment and gadolinium deposition in patients receiving contrast have generated developments in contrast-free imaging of the vasculature, that is, noncontrast magnetic resonance angiography. This article presents an update on noncontrast magnetic resonance angiography techniques, with comparison to other imaging alternatives. Potential benefits and challenges to implementation, and evidence to date for various clinical applications are discussed.


Asunto(s)
Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Dermopatía Fibrosante Nefrogénica/diagnóstico por imagen , Humanos , Angiografía por Resonancia Magnética , Dermopatía Fibrosante Nefrogénica/complicaciones
14.
Stroke ; 51(3): 922-930, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32078483

RESUMEN

Background and Purpose- Mobile stroke units (MSUs) are increasingly used worldwide to provide prehospital triage and treatment. The benefits of MSUs in giving earlier thrombolysis have been well established, but the impacts of MSUs on endovascular thrombectomy (EVT) and effect on disability avoidance are largely unknown. We aimed to determine the clinical impact and disability reduction for reperfusion therapies in the first operational year of the Melbourne MSU. Methods- Treatment time metrics for MSU patients receiving reperfusion therapy were compared with control patients presenting to metropolitan Melbourne stroke units via standard ambulance within MSU operating hours. The primary outcome was median time difference in first ambulance dispatch to treatment modeled using quantile regression analysis. Time savings were subsequently converted to disability-adjusted life years avoided using published estimates. Results- In the first 365-day operation of the Melbourne MSU, prehospital thrombolysis was administered to 100 patients (mean age, 73.8 years; 62% men). The median time savings per MSU patient, compared with the control cohort, was 26 minutes (P<0.001) for dispatch to hospital arrival and 15 minutes (P<0.001) for hospital arrival to thrombolysis. The calculated overall time saving from dispatch to thrombolysis was 42.5 minutes (95% CI, 36.0-49.0). In the same period, 41 MSU patients received EVT (mean age, 76 years; 61% men) with median dispatch-to-treatment time saving of 51 minutes ([95% CI, 30.1-71.9], P<0.001). This included a median time saving of 17 minutes ([95% CI, 7.6-26.4], P=0.001) for EVT hospital arrival to arterial puncture for MSU patients. Estimated median disability-adjusted life years saved through earlier provision of reperfusion therapies were 20.9 for thrombolysis and 24.6 for EVT. Conclusions- The Melbourne MSU substantially reduced time to reperfusion therapies, with the greatest estimated disability avoidance driven by the more powerful impact of earlier EVT. These findings highlight the benefits of prehospital notification and direct triage to EVT centers with facilitated workflow on arrival by the MSU.


Asunto(s)
Ambulancias , Servicios Médicos de Urgencia , Unidades Móviles de Salud , Reperfusión , Accidente Cerebrovascular/terapia , Trombectomía , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Angiografía por Tomografía Computarizada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Victoria
15.
Lancet ; 394(10193): 139-147, 2019 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-31128925

RESUMEN

BACKGROUND: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. METHODS: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FINDINGS: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66). INTERPRETATION: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. FUNDING: None.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica , Tiempo de Tratamiento , Hemorragia Cerebral/inducido químicamente , Imagen de Difusión por Resonancia Magnética , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Humanos , Imagen de Perfusión , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
16.
Hum Brain Mapp ; 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32468614

RESUMEN

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

17.
Ann Neurol ; 85(2): 241-250, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30609109

RESUMEN

OBJECTIVE: We investigated the relationship between the interictal metabolic patterns, the extent of resection of 18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) hypometabolism, and seizure outcomes in patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) following anterior temporal lobe (TL) resection. METHODS: Eighty-two patients with hippocampal sclerosis or normal magnetic resonance imaging (MRI) findings, concordant 18 FDG-PET hypometabolism, and at least 2 years of postoperative follow-up were included in this 2-center study. The hypometabolic regions in each patient were identified with reference to 20 healthy controls (p < 0.005). The resected TL volume and the volume of resected TL PET hypometabolism (TLH) were calculated from the pre- and postoperative MRI scans coregistered with interictal 18 FDG-PET. RESULTS: Striking differences in metabolic patterns were observed depending on the lateralization of the epileptogenic TL. The extent of the ipsilateral TLH was significantly greater in left MTLE patients (p < 0.001), whereas right MTLE patients had significantly higher rates of contralateral (CTL) TLH (p = 0.016). In right MTLE patients, CTL hypometabolism was the strongest predictor of an unfavorable seizure outcome, associated with a 5-fold increase in the likelihood of seizure recurrence (odds ratio [OR] = 4.90, 95% confidence interval [CI] = 1.07-22.39, p = 0.04). In left MTLE patients, greater extent of resection of ipsilateral TLH was associated with lower rates of seizure recurrence (p = 0.004) in univariate analysis; however, its predictive value did not reach statistical significance (OR = 0.96, 95% CI = 0.90-1.02, p = 0.19). INTERPRETATION: The difference in metabolic patterns depending on the lateralization of MTLE may represent distinct epileptic networks in patients with right versus left MTLE, and can guide preoperative counseling and surgical planning. Ann Neurol 2019; 1-10 ANN NEUROL 2019;85:241-250.


Asunto(s)
Epilepsia Refractaria/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Adulto , Lobectomía Temporal Anterior , Estudios de Casos y Controles , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Fluorodesoxiglucosa F18 , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos , Estudios Retrospectivos , Esclerosis , Resultado del Tratamiento
18.
Epilepsia ; 61(12): 2785-2794, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33111330

RESUMEN

OBJECTIVE: The posterior cingulate cortex (PCC)/precuneus is a key hub of the default mode network, whose function is known to be altered in epilepsy. Glutamate and γ-aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters in the central nervous system, respectively. Glutathione (GSH) is the most important free radical scavenging compound in the brain. Quantification of these molecules by magnetic resonance spectroscopy (MRS) up to 4 T is limited by overlapping resonances from other molecules. In this study, we used ultra-high-field (7 T) MRS to quantify their concentrations in patients with different epilepsy syndromes. METHODS: Nineteen patients with temporal lobe epilepsy (TLE) and 16 with idiopathic generalized epilepsy (IGE) underwent magnetic resonance imaging scans using a 7-T research scanner. Single-voxel (8 cm3 ) MRS, located in the PCC/precuneus, was acquired via stimulated echo acquisition mode. Their results were compared to 10 healthy volunteers. RESULTS: Mean concentrations of glutamate, GABA, and the glutamate/GABA ratio did not differ between the IGE, TLE, and healthy volunteer groups. The mean ± SD concentration of GSH was 1.9 ± 0.3 mmol·L-1 in healthy controls, 2.0 ± 0.2 mmol·L-1 in patients with TLE, and 2.2 ± 0.4 mmol·L-1 in patients with IGE. One-way analysis of variance with post hoc Tukey-Kramer test revealed a significant difference in the concentration of GSH between patients with IGE and controls (P = .03). Short-term seizure freedom in patients with epilepsy was predicted by an elevated concentration of glutamate in the PCC/precuneus (P = .01). In patients with TLE, the concentration of GABA declined with age (P = .03). SIGNIFICANCE: Patients with IGE have higher concentrations of GSH in the PCC/precuneus than healthy controls. There is no difference in the concentrations of glutamate and GABA, or their ratio, in the PCC/precuneus between patients with IGE, patients with TLE, and healthy controls. Measuring the concentration of glutamate in the PCC/precuneus may assist with predicting drug response.


Asunto(s)
Epilepsia/metabolismo , Ácido Glutámico/análisis , Glutatión/análisis , Giro del Cíngulo/química , Lóbulo Parietal/química , Ácido gamma-Aminobutírico/análisis , Adulto , Anciano , Estudios de Casos y Controles , Epilepsia Generalizada/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Epilepsy Behav ; 111: 107308, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32698105

RESUMEN

The default mode network (DMN) is a major neuronal network that deactivates during goal-directed tasks. Recent advances in neuroimaging have shed light on its structure and function. Alterations in the DMN are increasingly recognized in a range of neurological and psychiatric conditions including epilepsy. This review first describes the current understanding of the DMN in health, normal aging, and disease as it is acquired via resting-state functional magnetic resonance imaging (MRI), before focusing on how it is affected in various types of focal and generalized epilepsy. These findings support the potential use of DMN parameters as future biomarkers in epilepsy research, diagnosis, and management.


Asunto(s)
Encéfalo/diagnóstico por imagen , Red en Modo Predeterminado/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Descanso , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Red en Modo Predeterminado/fisiopatología , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Descanso/fisiología
20.
N Engl J Med ; 372(11): 1009-18, 2015 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-25671797

RESUMEN

BACKGROUND: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS: We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS: The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).


Asunto(s)
Procedimientos Endovasculares , Fibrinolíticos/uso terapéutico , Arteria Cerebral Media/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Trombectomía , Activador de Tejido Plasminógeno/uso terapéutico , Anciano , Angiografía de Substracción Digital , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Arteria Carótida Interna/diagnóstico por imagen , Terapia Combinada , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Imagen de Perfusión , Reperfusión , Método Simple Ciego , Stents , Trombectomía/instrumentación , Tomografía Computarizada de Emisión
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