Stroke recovery enhancing therapies: lessons from recent clinical trials

Abstract

Poststroke recovery processes include restoration or compensation of function, respectively functions initially lost or new functions acquired after an injury. Therapeutic interventions can enhance these processes and/or reduce processes impeding regeneration. Numerous experimental studies suggest great opportunities for such treatments, but the results from recent large clinical trials using neuromodulators such as dopamine and fluoxetine are disappointing. The reasons for this are manifold affecting forward translation of results from animals models into the human situation. This “translational road block” is defined by differences between animals and humans with regard to the genetic and epigenetic background, size and anatomy of the brain, cerebral vascular anatomy, immune system, as well as clinical function and behavior. Backward blockade includes the incompatible adaption of targets and outcomes in clinical trials with regard to prior preclinical findings. For example, the design of clinical recovery trials varies widely and was characterized by the selection of different clinical endpoints, the inclusion a broad spectrum of stroke subtypes and clinical syndromes as well as different time windows for treatment initiation after infarct onset. This review will discuss these aspects based on the results of the recent stroke recovery trials with the goal to contribute to the currently biggest unmet need in stroke research - the development of a recovery enhancing therapy that improves the functional outcome of a chronic stroke patient.

Therapien zur Verbesserung der Schlaganfall-Regeneration – Ergebnisse klinischer Studien im wissenschaftlichen Kontext

“…In zahlreichen präklinischen und klinischen Studien wurde insbesondere die Wirkung von Dopamin, d-Amphetamin und Serotonin-Wiederaufnah-mehemmern untersucht. Die Primärdaten der jüngsten großen klinischen Studien wurden in einer Synopsis zusammengeführt [9], die hier in ▶tab. 1 zu finden ist.…”

“…Klinisch-pharmakologische Behandlung zur Erholung nach einem Schlaganfall (basierend auf Rogalewski, Schäbitz[9]) funktionelle Ergebnisskalen ausgewertet. Es gelang leider nicht mit dem groben Ergebnisparameter "modifizierte Rangskala nach 6 Monaten" einen Unterschied zwischen Fluoxetin und Placebo zu zeigen[13][14][15].…”

A scoping review in Indian post-stroke patients

“…The caregivers are not being educated by the nursing staff or the clinicians about poststroke care which can be pivotal in enhancing the quality of life (QoL) of the stroke patients postdischarge from the critical care unit. 27,28 Rehabilitation is essential to reduce the recurrence of stroke-related complications and patients who receive ongoing professional and systematic rehabilitation after the acute phase of the stroke tend to recover quickly. 29 Currently, drug and rehabilitation therapy is practiced as a rehabilitation treatment for stroke.…”

The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke

“…Several pharmacological agents have been explored for their ability to promote neuroplasticity and neurogenesis during the later stages of stroke, including antidepressants, amphetamines, and neurotrophins ( 138 ). However, randomized controlled trials for these agents have failed to meet their efficacy endpoints ( 139 ).…”