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Stroke pathophysiology: management challenges and new treatment advances

Fisiopatología del ictus: clásicos y nuevos tratamientos

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Abstract

Stroke is the second leading cause of death and the first cause of lost disability-adjusted years in developed countries. During the past decade, new developments in thrombolytic therapy have led to the implementation of emergency intervention protocols for the treatment of ischemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Treatment with rtPA has shown to be effective within the first 3 hours following stroke onset and the FDA and the European Medical Agency (EMEA) have approved its use. Acknowledging the urgency and intricacies of stroke, Stroke Units allow the monitoring of physiological parameters in the acute phase of stroke and are considered an important management tool that can significantly improve the quality of care provided to the patient. The concept of neuroprotective therapy for acute ischemic stroke to salvage tissue at risk and improve functional outcome is based on sound scientific principles and extensive preclinical animal studies demonstrating efficacy. However, most neuroprotective drugs in clinical trials have failed, possibly due to inadequate preclinical testing or flawed clinical development programs. Several new treatment strategies are under development and are being tested. This review is directed at understanding the management of acute ischemic stroke pathophysiology. We address the management challenges and new treatment advances by integrating the knowledge of possible pharmacological targets for acute ischemic stroke. We hope to shed new light upon the controversy surrounding the management of acute ischemic stroke in an attempt to elucidate why failed clinical trials continue to occur despite promising neuroprotective preclinical studies.

Resumen

El ictus representa la segunda causa de muerte y la primera de incapacidad en los países desarrollados. Pese a su frecuencia y gravedad, hasta hace pocos años no se disponía de tratamientos eficaces en la fase aguda, lo que condicionaba una actitud nihilista en todo el proceso terapéutico. En la última década se ha conseguido demostrar la efectividad de la administración precoz de tratamiento intravenoso trombolítico con rtPA en el ictus isquémico, por lo que tanto la FDA americana como la agencia europea del medicamento han autorizado su uso, si bien con restricciones diferentes. Además, la monitorización de los parámetros biológicos y estandarización de los cuidados médicos y de enfermería en los primeros días, realizados en las Unidades de Ictus, han demostrado también su eficacia terapéutica. En la actualidad el esfuerzo investigador en el ictus intenta encontrar moléculas que solas o en combinación trasladen a la práctica clínica la capacidad de neuroprotección que muchas de ellas ya han demostrado en el laboratorio o en los modelos animales. Sin embargo, hasta la fecha este esfuerzo no ha sido recompensado plenamente y científicos básicos y clínicos tendrán que intensificar su trabajo y comunicación para lograr al fin estrategias que permitan mantener viable el tejido cerebral sometido a agresión tras el ictus.

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Authors and Affiliations

  1. Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La, Mancha, Spain

    J. Jordán & T. Segura

  2. College of Medicine, SUNY Upstate Medical University, Syracuse, New York, U.S.A.

    I. Ikuta

  3. Departamento de Neurología, Hospital General Universitario de, Albacete, Spain

    J. García-García & T. Segura

  4. Departamento de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain

    S. Calleja

  5. Grupo de Neurofarmacología, Centro Regional de Investigaciones Biomédicas, Universidad Castilla-La Mancha, Spain

    J. Jordán

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Jordán, J., Ikuta, I., García-García, J. et al. Stroke pathophysiology: management challenges and new treatment advances. J. Physiol. Biochem. 63, 261–277 (2007). https://doi.org/10.1007/BF03165789

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