Stroke - Acute intervention and secondary prevention – Niaz Ahmed's research group

Stroke is the number one cause of neurological disability in adults and the second leading cause of death worldwide. Around 85% of stroke cases are caused by cerebral infarcts due to occlusion of cerebral arteries, 15% are caused by spontaneous intracerebral haemorrhages.



Research area
Stroke- Acute intervention and secondary prevention
 

Background
Stroke is the number one cause of neurological disability in adults and the second leading cause of death worldwide. Around 85% of stroke cases are caused by cerebral infarcts due to occlusion of cerebral arteries, 15% are caused by spontaneous intracerebral haemorrhages.

Acute Intervention

Reperfusion therapy 
Reperfusion therapy by iv thrombolysis and/or endovascular thrombectomy are evidence-based treatments for acute ischemic stroke. In spite of these combined revascularisation therapies, up to 40% of treated patients will be functionally dependent or die within three months of index stroke. Moreover, <15% of all patients with acute ischaemic stroke receive reperfusion therapies. Still a number of issues regarding recanalisation therapy remain unanswered. The SITS (Safe Implementation of Treatment in Stroke) is an International Stroke Registry with its base at Karolinska Institutet and Stroke Research Unit at Karolinska University Hospital (www.sitsinternational.org). The SITS registry has several data entry protocol such as IV thrombolysis, endovascular thrombectomy, general stroke registry and quality registry. A number of projects are ongoing to answer some of these unanswered questions on recanalisation therapy based on SITS data.

Treatment to restore Blood brain barrier disruption
In the 1980s and 90s, another treatment paradigm, neuroprotection, was explored extensively. Unfortunately, numerous neuroprotective trials in humans with a number of potential drugs have failed to show benefit in the treatment of acute ischaemic stroke. Far less attention has been given to protecting the vascular endothelium from the deleterious effects of ischaemia, and blocking or reversing blood brain barrier (BBB) disruption in stroke. Imatinib, a tyrosine kinase inhibitor, can restore the integrity of the BBB by blocking the signalling of platelet-derived growth factor alpha (PDGF-alpha) receptors on perivascular astrocytes. We have received funding from the Swedish Research Council to perform a phase III study to evaluate the effect of Imatinib in patients with acute ischaemic stroke. The study is expected to start on Q3 2018.

Secondary stroke prevention
Atrial fibrillation (AF) is the most common cardiac arrhythmia and patients with AF have a 5-fold increased risk of ischemic stroke. Guidelines recommend that patients with AF suffering an ischemic stroke or transient ischemic attack (TIA) should receive long-term anticoagulation therapy unless contraindicated. However, optimal timing of early oral anticoagulation initiation for secondary prevention of ischemic stroke has not been established. We are collecting data on timing of oral anticoagulation initiation in the SITS international registry and we hope these data will shed some light in this uncertainty.

Research Projects

  • Efficacy of Imatinib in acute ischaemic stroke, a phase 3, multicentre, parallel-arm randomised, double-blind placebo-controlled trial
  • Effect of Imatinib on the occurrence of epileptic seizures in patients with acute ischaemic stroke
  • Cerebral oedema after acute ischaemic stroke: Risk factors, prognosis and treatment
  • Subtypes of Ischemic Stroke – analysis of revascularization therapy, thrombi composition, and the role of blood pressure
  • Safety and efficacy of routine endovascular thrombectomy in acute occlusive stroke.
  • Safe implementation of oral anticoagulation therapy for secondary stroke prevention in atrial fibrillation
  • Recanalization therapy in acute ischaemic stroke for patients taking oral anticoagulants.
  • A mobile-phone based method for increasing follow-up after acute stroke

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Publications

Selected publications

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