RESUMEN
Persistent symptoms following a minor head injury can cause significant morbidity, yet the underlying mechanisms for this are poorly understood. The shortcomings of the current terminology that refer to non-specific symptom clusters is discussed. This update considers the need for a multi-dimensional approach for the heterogenous mechanisms driving persistent symptoms after mild traumatic brain injury. Relevant pathophysiology is discussed to make the case for mild traumatic brain injury to be conceptualized as an interface disorder spanning neurology, psychiatry and psychology. The relevance of pre-injury factors, psychological co-morbidities and their interaction with the injury to produce persistent symptoms are reviewed. The interplay with psychiatric diagnoses, functional and somatic symptom disorder presentations and the influence of the medicolegal process is considered. The judicious use and interpretation of investigations given the above complexity is discussed, with suggestions of how the explanation of the diagnostic formulation to the patient can be tailored, including insight into the above processes, to aid recovery. Moving beyond the one-dimensional concept of 'postconcussional syndrome' and reframing the cause of persistent symptoms following mild traumatic brain injury in a bio-psycho-socio-ecological model will hopefully improve understanding of the underlying contributory mechanistic interactions and facilitate treatment.
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Conmoción Encefálica , Trastornos Mentales , Neurología , Síndrome Posconmocional , Psiquiatría , Conmoción Encefálica/diagnóstico , Humanos , Trastornos Mentales/etiología , Síndrome Posconmocional/diagnóstico , Síndrome Posconmocional/etiología , Síndrome Posconmocional/psicologíaRESUMEN
Cognitive impairment after traumatic brain injury remains hard to predict. This is partly because axonal injury, which is of fundamental importance, is difficult to measure clinically. Advances in MRI allow axonal injury to be detected after traumatic brain injury, but the most sensitive approach is unclear. Here, we compare the performance of diffusion tensor imaging, neurite orientation dispersion and density-imaging and volumetric measures of brain atrophy in the identification of white-matter abnormalities after traumatic brain injury. Thirty patients with moderate-severe traumatic brain injury in the chronic phase and 20 age-matched controls had T1-weighted and diffusion MRI. Neuropsychological tests of processing speed, executive functioning and memory were used to detect cognitive impairment. Extensive abnormalities in neurite density index and orientation dispersion index were observed, with distinct spatial patterns. Fractional anisotropy and mean diffusivity also indicated widespread abnormalities of white-matter structure. Neurite density index was significantly correlated with processing speed. Slower processing speed was also related to higher mean diffusivity in the corticospinal tracts. Lower white-matter volumes were seen after brain injury with greater effect sizes compared to diffusion metrics; however, volume was not sensitive to changes in cognitive performance. Volume was the most sensitive at detecting change between groups but was not specific for determining relationships with cognition. Abnormalities in fractional anisotropy and mean diffusivity were the most sensitive diffusion measures; however, neurite density index and orientation dispersion index may be more spatially specific. Lower neurite density index may be a useful metric for examining slower processing speed.
RESUMEN
Following hyperacute management after traumatic brain injury (TBI), most patients receive treatment which is inadequate or inappropriate, and delayed. This results in suboptimal rehabilitation outcome and avoidable detrimental chronic effects on patients' recovery. This worsens long-term disability, and magnifies costs to the individual and society. We believe that accurate diagnosis (at the level of pathology, impairment and function) of the causes of disability is a prerequisite for appropriate care and for accessing effective rehabilitation. An expert-led, integrated care pathway is needed to deliver accurate and timely diagnosis and optimal treatment at all stages during a TBI patient's care.We propose the introduction of a specialist interdisciplinary traumatic brain injury team, led by a neurosciences-trained brain injury consultant. This team would engage acutely and for a longer term after TBI to provide accurate diagnoses, which guides subsequent management and rehabilitation. This approach would also encourage more efficient collaboration between research and the clinic. We propose that the current major trauma network is leveraged to introduce and evaluate this proposal. Improvements to patient outcomes through this approach would lead to reduced personal, societal and economic impact of TBI.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Neurociencias , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/terapia , Humanos , Medicina Estatal , Resultado del TratamientoRESUMEN
Cognitive impairment is common following traumatic brain injury. Dopaminergic drugs can enhance cognition after traumatic brain injury, but individual responses are highly variable. This may be due to variability in dopaminergic damage between patients. We investigate whether measuring dopamine transporter levels using 123I-ioflupane single-photon emission computed tomography (SPECT) predicts response to methylphenidate, a stimulant with dopaminergic effects. Forty patients with moderate-severe traumatic brain injury and cognitive impairments completed a randomized, double-blind, placebo-controlled, crossover study. 123I-ioflupane SPECT, MRI and neuropsychological testing were performed. Patients received 0.3 mg/kg of methylphenidate or placebo twice a day in 2-week blocks. Subjects received neuropsychological assessment after each block and completed daily home cognitive testing during the trial. The primary outcome measure was change in choice reaction time produced by methylphenidate and its relationship to stratification of patients into groups with normal and low dopamine transporter binding in the caudate. Overall, traumatic brain injury patients showed slow information processing speed. Patients with low caudate dopamine transporter binding showed improvement in response times with methylphenidate compared to placebo [median change = -16 ms; 95% confidence interval (CI): -28 to -3 ms; P = 0.02]. This represents a 27% improvement in the slowing produced by traumatic brain injury. Patients with normal dopamine transporter binding did not improve. Daily home-based choice reaction time results supported this: the low dopamine transporter group improved (median change -19 ms; 95% CI: -23 to -7 ms; P = 0.002) with no change in the normal dopamine transporter group (P = 0.50). The low dopamine transporter group also improved on self-reported and caregiver apathy assessments (P = 0.03 and P = 0.02, respectively). Both groups reported improvements in fatigue (P = 0.03 and P = 0.007). The cognitive effects of methylphenidate after traumatic brain injury were only seen in patients with low caudate dopamine transporter levels. This shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy.
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Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/análisis , Metilfenidato/uso terapéutico , Neuroimagen/métodos , Adulto , Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto JovenRESUMEN
Traumatic brain injury can reduce striatal dopamine levels. The cause of this is uncertain, but is likely to be related to damage to the nigrostriatal system. We investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane single-photon emission computed tomography (SPECT) scans and their relationship to nigrostriatal damage and clinical features. We studied 42 moderate-severe traumatic brain injury patients with cognitive impairments but no motor parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to assess dopamine transporter levels. Clinical scan reports were compared to quantitative dopamine transporter results. Advanced MRI methods were used to assess the nigrostriatal system, including the area through which the nigrostriatal projections pass as defined from high-resolution Human Connectome data. Detailed clinical and neuropsychological assessments were performed. Around 20% of our moderate-severe patients had clear evidence of reduced specific binding ratios for the dopamine transporter in the striatum measured using 123I-Ioflupane SPECT. The caudate was affected more consistently than other striatal regions. Dopamine transporter abnormalities were associated with reduced substantia nigra volume. In addition, diffusion MRI provided evidence of damage to the regions through which the nigrostriatal tract passes, particularly the area traversed by dopaminergic projections to the caudate. Only a small percentage of patients had evidence of macroscopic lesions in the striatum and there was no relationship between presence of lesions and dopamine transporter specific binding ratio abnormalities. There was also no relationship between reduced volume in the striatal subregions and reduced dopamine transporter specific binding ratios. Patients with low caudate dopamine transporter specific binding ratios show impaired processing speed and executive dysfunction compared to patients with normal levels. Taken together, our results suggest that the dopaminergic system is affected by a moderate-severe traumatic brain injury in a significant proportion of patients, even in the absence of clinical motor parkinsonism. Reduced dopamine transporter levels are most commonly seen in the caudate and this is likely to reflect the pattern of nigrostriatal tract damage produced by axonal injury and associated midbrain damage.
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Lesiones Traumáticas del Encéfalo/patología , Encéfalo/diagnóstico por imagen , Dopamina/metabolismo , Adulto , Anciano , Encéfalo/efectos de los fármacos , Encéfalo/patología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Usos Diagnósticos de Compuestos Químicos , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Nortropanos/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients.
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Lesiones Traumáticas del Encéfalo/complicaciones , Núcleo Caudado/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Función Ejecutiva/fisiología , Giro del Cíngulo/diagnóstico por imagen , Adulto , Anciano , Animales , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/psicología , Mapeo Encefálico , Estudios de Casos y Controles , Conectoma , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = -23.30%, 95% confidence interval -40.9 to -5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
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Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Microglía/efectos de los fármacos , Minociclina/uso terapéutico , Enfermedades Neurodegenerativas/etiología , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Estudios Transversales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Microglía/patología , Persona de Mediana Edad , Enfermedades Neurodegenerativas/inducido químicamente , Proteínas de Neurofilamentos/metabolismo , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Pirimidinas/farmacocinética , Estadísticas no Paramétricas , Adulto JovenRESUMEN
OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum insulin-like growth factor-I (IGF-I) may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male, median age = 30.5 years, 87.2% moderate-severe, median time since TBI = 16.3 months, n = 4 with GHD) were scanned twice, 13.3 months (range = 12.1-14.9) apart, and 35 healthy controls were scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n = 33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC) and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above versus below the median for age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that the growth hormone/IGF-I system may be a potential therapeutic target following TBI. Ann Neurol 2017;82:30-43.
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Lesiones Traumáticas del Encéfalo/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Sustancia Blanca/patología , Adulto , Anisotropía , Estudios de Casos y Controles , Imagen de Difusión Tensora , Femenino , Hormona del Crecimiento/deficiencia , Humanos , Cápsula Interna/patología , Estudios Longitudinales , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Músculos Paraespinales/patología , Calidad de Vida , Adulto JovenRESUMEN
SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.
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Amnesia/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Giro del Cíngulo/fisiopatología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/fisiopatología , Giro Parahipocampal/fisiopatología , Adulto , Amnesia/diagnóstico por imagen , Amnesia/etiología , Aprendizaje por Asociación/fisiología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Giro Parahipocampal/diagnóstico por imagen , Memoria Espacial/fisiología , Adulto JovenRESUMEN
Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner.
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Lesiones Traumáticas del Encéfalo/metabolismo , Catecolaminas/metabolismo , Disfunción Cognitiva/metabolismo , Lesiones Traumáticas del Encéfalo/complicaciones , Disfunción Cognitiva/etiología , HumanosRESUMEN
OBJECTIVES: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinical studies suggest that vitamin D status influences the recovery after TBI. However, there is no published clinical data on links between vitamin D status and TBI outcomes. The aim was to determine the (i) prevalence of vitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors and TBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI. DESIGN: Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25-hydroxy-cholecalciferol) was categorized as deficient (<40 nmol/l), insufficient (40-70 nmol/l) or replete (>70 nmol/l). PATIENTS: A total of 353 adults seen in tertiary hospital clinic (75·4% lighter skinned, 74·8% male, age median 35·1 year, range 26·6-48·3 year), 0·3-56·5 months after TBI (74·5% moderate-severe). MEASUREMENTS: Serum vitamin D concentrations; Addenbrooke's Cognitive Examination (ACE-R), Beck Depression Inventory-II (BDI-II), SF-36 Quality of Life, Pittsburgh Sleep Quality Index. RESULTS: In total, 46·5% of patients after TBI had vitamin D deficiency and 80·2% insufficiency/deficiency. Patients with vitamin D deficiency had lower ACE-R scores than those of vitamin D replete (mean effect size ± SEM 4·5 ± 2·1, P = 0·034), and higher BDI-II scores than those of vitamin D insufficient (4·5 ± 1·6, P = 0·003), correcting for age, gender, time since TBI and TBI severity. There was no association between vitamin D status and markers of TBI severity, sleep or quality of life. CONCLUSION: Vitamin D deficiency is common in patients after TBI and associated with impaired cognitive function and more severe depressive symptoms.
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Lesiones Traumáticas del Encéfalo/complicaciones , Deficiencia de Vitamina D/etiología , Adulto , Disfunción Cognitiva/etiología , Depresión/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Calidad de Vida , Estudios Retrospectivos , SueñoRESUMEN
It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of 'concussed' individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms.
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Conmoción Encefálica/diagnóstico , Confusión , Manejo de la Enfermedad , Conmoción Encefálica/complicaciones , Conmoción Encefálica/historia , Conmoción Encefálica/terapia , Lesiones Encefálicas/etiología , Trastornos del Conocimiento/etiología , Historia del Siglo XX , Historia del Siglo XXI , Historia Medieval , Humanos , Trastornos Mentales/etiología , NeuroimagenRESUMEN
Pulmonary embolism (PE) continues to be associated with significant mortality despite advances in the diagnostic techniques available for its detection. Anticoagulation remains standard treatment in PE although there is a consensus view that 'step-up' to thrombolytic therapy in addition to anticoagulation is indicated in those patients who are systemically shocked at presentation--a group defined as having suffered 'massive pulmonary embolism'. Considerable research has been directed at attempting to identify further groups of patients with PE who are at high risk of morbidity and mortality--notably those who are labelled as having suffered 'sub-massive pulmonary embolism' where this is defined as the presence of right-heart strain in the absence of systemic shock. In particular, the potential benefit of extending thrombolytic therapy to include those patients with sub-massive PE has been the subject of much enquiry and debate. This review examines the evidence for thrombolytic therapy and explores the potential for risk stratification in PE.
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Anticoagulantes/uso terapéutico , Fibrinolíticos/uso terapéutico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamiento farmacológico , Terapia Trombolítica , Humanos , Embolia Pulmonar/fisiopatología , Medición de RiesgoRESUMEN
The global burden of stroke, the undisputed success of intravenous thrombolysis in the management of myocardial infarction and subsequent evidence from animal models of cerebral infarction have all fuelled intense interest in the potential role for thrombolytic agents in the acute management of stroke in clinical practice. Before any clinical treatment is introduced universally its safety and efficacy must be demonstrated in the routine clinical environment and not just within the ideal conditions of controlled clinical trials. Similarly, the cost effectiveness of a new treatment modality is an essential consideration before its use is promulgated. This paper reviews the current scientific evidence for thrombolysis in stroke with reference to issues of safety, efficacy and cost effectiveness.