Retrospective
not developed yet
safety and usefullness of short-term anticoagulation in the setting of acute ischemic stroke
- Studies-overview:
- advantage:
- disadvantage:
- further investigations:
Use of neuromonitoring to predict outcome and to guide therapeutic decision-making in patients with brainstem haemorrhages
- studies overview:
SSEPs and MEPs reliable and useful tool for preciding functional recovery in patients with brainstem haemorrhages - advantages:
- disadvantsges:
- further investigstions:
Stroke recidive -> Same cause or differente cause ? How to treat it specificaly
- studies-overview:
- advantages
- disadvantages
- further investigations:
Role of IVT in promoting or limiting infarcts in initially unaffected territories -> IVT in patients with AF lead to fragmentation of cardiac thrombus
Improvement of stroke treatment after publishment of the stroke guidelines from Bern:
1) in Bern itself
2) in peripheral hospital
3) according to the news treatments across the time
4) regarding to the version
Segmentation study in stroke -> Need more reading
Correlation between inflammatory disease and stroke -> Which type of inflammatory disease are more found in stroke patient, Stroke rate by compliants vs. non compliants patients
theorical background -> Microglia is activated after brain dammage -> Secretion of IL-1b and TNF-a, release free radicals and activation of molecular pathways such as NF-kB -> neuronal death.
IL-1b production depends on inflamasome activation (especially NLRP3). MCC950 (selective antagonist of NLRP3) prevents inflammasome activation and IL-1b
release from microglia
studies-overview:
- advantage:
- disadvantage:
- furthers investigations:
Examination of indications/findings/consequence of standardized (routine controlle) and non standardized (emergency imaging) after acute ischaemic stroke:
- studies overview:
- advantages:
- disadvantages:
- further investigations:
“It is unclear if antiplatelet drugs worsen the outcome of hemorrhagic stroke” -> Retrospective Analysis
Investigations of TIA:
1) Clinical presentation of TIA -> relation with plausible etiology
Examples:
1) sensomotoric hemisymptomatic with aphasia -> anterior LVO -> embolic -> AF?
2) isolated speak disorder -> small vessel occlusion -> hypertensiv -> microangiopathic lesions/ leukenzephalopathy -> hypertension or diabetes.
- studies overview:
- advantages:
- disadvantages:
- further investigations:
Correlation between length, diameter, morphology of ICA and risk of ICA-occlusion vs. distal occlusion in embolic stroke, response to IVT and EVT
Predilection factors for stroke after interruption of oral anticoagulation (according to anticoagulation-type) for surgical or other purpose
- studies-overview:
- advantages:
- disadvantages:
- further investigations:
Development of neurovascular (Aneurysma, Dursley’s arteriovenous Fistulae) and others neurological conditions ( MS, Parkinson, Epilepsy, Headache, Memory Disorders, Brain tumor or spinal cord tumor, periphereal neuropathy, post-herpetic neuralgia) after stroke
- according to personal experience by ongoing very long-term follow-up after EVT study: development of neurogical conditions doesn’t seem really frequent.
- further litterature-research concerning vascular changes after stroke needed
Occurrence and description of in-patients hemorrhagic stroke
studies overview:
advantages: evidence lacking on this subject disadvantages: Field of David, doctor thesis of Martina ?
further investigations:
IVT in low NIHSS with/without disabling Symptomes -> Investigation of outcomes and comparison with stroke with disabling symptoms.
- Studies overview:
1) Thrombolysis for Acute Minor Stroke: Outcome and Barriers to Management. Results from the RESUVAL Stroke Network. Laurencin et al.
Conclusion: Study provided evidence of safety and suggested potential benefit of thrombolysis in patients with NIHSS score ≤4. A majority of these patients exhibited arterial occlusion before thrombolysis. Most often, patients with mild stroke are not given priority in terms of the mode of transport, direct admission to stroke unit and rapid imaging, resulting in an increased delay from onset to thrombolysis - advantage:
- disadvantage:
- further investigations:
Comparison of outcomes between ischemic stroke with (asymptomatic/symptomatic) hemorrhagic transformation vs. ischemic stroke without hemorrhagic transformation
- Acceptance of risk for asymptomatic hemorrhage in IVT/EVT indication -> subsubject
- studies-overview:
- advantage:
- disadavantage:
- further investigations:
« Starting out on your quest for a doctorate with a bad research idea is, well, a bad idea. Whether it’s that you run out of places to go because the idea was too shallow, or you find yourself unable to even begin because its objectives were unrealistic, you will find yourself wishing you had chosen something better. »
Correlation EVT-method and Thrombus-typ
- „Further research to guide the selection of endovascular devices and techniques suited for specific thrombi volume and composition is imperative”
- advantage: retrospective design
- disadvantage: possible lack of sequences, single center -> normaly only 1-2 method used routinely
FINER: feasible, interesting, novel, ethical, and relevant
“Maintaining your adviser means asking for what you need rather than hoping that he or she will know what to provide.”
1
Brain and inflammation
- Theory of focal vs. global brain inflammation.
Clinical evidence supporting a role for astrocytes in global brain inflammation after a stroke is still absent. One reason might be the absence of a specific astrocyte biomarker feasible for invivo imaging in patients who
have had a stroke. Chronic elevation of systemic inflammatory mediators such as Creactive protein, IL6, and TNFα is reported in patients, which is associated with decline of cognition and stroke recurrence. This evidence indicates that systemic inflammatory response might influence chronic brain inflammation.
« Diaschisis », the alteration of structural and functional connectivity between brain areas distant from the lesion, is often reported after stroke in both patients and corresponding animal models.
- Ischemic vs. hemorrhagic stroke: focal brain inflammation is sustained longer in intracerebral haemorrhage relative to acute ischaemic stroke, wherein focal brain inflammation subsides after about 1 week. Inflammation is triggered through a common pathway shared by both acute ischaemic stroke and intracerebral haemorrhage.
- Mobilisation of peripheral immune cells after stroke: Accumulation of T cells within the thalamus, which is distal to primary injury and known to develop secondary neurodegeneration after a stroke, has been observed. Experimental studies suggest that B cells have a small role in the formation of focal brain injury during the acute phase. However, the evidence of immunoglobulin synthesis in CSF of patients with stroke suggests that the humoral immune response is activated in stroke.
- Cerebral microvascular endothelial cells are swiftly activated after a stroke and upregulate a
series proinflammatory and procoagulation factors, including vascular cell adhesion molecule (VCAM1) and matrix metalloproteinase 9. These molecules sub sequently promote the adhesion and migration of per pheral leukocytes, activation of the coagulation system, and blood–brain barrier disruption. Similar to acute ischaemic stroke, molecular imaging of VCAM1 in intracerebral haemorrhage models also suggest a wide distribution of vascular inflammation in the acute phase of intracerebral haemorrhage.
Neuroinflammation is accompanied by disruption of the blood–brain barrier. Global vascular inflammation and disruption of the blood–brain barrier have been reported in the acute and chronic phases of experimental stroke animal models and patients with ischaemic stroke.
- The potential clinical relevance of global brain inflammation: Dementia after a stroke occurs in 15–30% of patients with ischaemic stroke. Longitudinal studies posit that several plasma inflammatory markers are predictors of dementia after a stroke, including IL6, IL12, erythrocyte sedimentation rate, and Creactive protein. In a phase 2 trial that included 161 European patients with ischaemic stroke, administration of an α4 integrin monoclonal antibody natalizumab, which inhibits the interaction between endothelial cells and leukocytes during the acute stage of acute ischaemic stroke, improved cognitive and other brain functions at 3 months despite no reduction in infarct volume relative to placebo.
- Advantages: Cooperation with neuroimmunologis
- Disadvantages: Prospective design certainlx mandatory, small patient cohort depending from the investigations, clinical investigations difficult to perform.
- further investigations:
Future longterm (ie, over years) monitoring of glial activation by imaging or postmortem pathological study would be crucial to answer whether the global glial activation is persistent after a stroke.
Future research must not only aim to understand how global brain inflammation is initiated and maintained but also clarify the role of global brain inflammation in the longterm sequelae of stroke and its roles in neurological recovery and brain tissue regeneration (panel).
Brain and inflammation 2
Conclusion: Clinical trials have yielded encouraging outcomes, and include the evaluation of natalizumab in acute ischaemic stroke, fingolimod in acute ischaemic stroke and in intracerebral haemorrhage and glyburide in acute hemispheric infarction. Several new largescale clinical trials based on the insights derived from these studies are ongoing.
These approaches prevent further fuelling of inflammation but do not alter ongoing insitu processes. Direct interference of molecules that trigger brain inflammation locally is likely to curb injury expansion within the brain. The successful management of patients with stroke might require coupling of focal and systemic approaches to modulate brain inflammation.
further investigations: Intrathecal administration of anti-inflammation drugs to cut down the focal inflammation cascade.
Poststroke fatigue (PSF) and inflammation
Article: Poststroke Fatigue: Emerging Evidence and Approaches to Management. Janice L. Hinkle et al.
A role for inflammation in the genesis of PSF is implicated by several key observations. First, fatigue is a common symptom in patients with immune-mediated diseases. Second, fatigue occurs in otherwise healthy individuals who develop infections. Third, administration of proinflammatory cytokines to healthy individuals leads to the perception of fatigue. Finally, modulation of inflammation with cytokine antagonists improves fatigue in several different diseases.
-> Actual data to support a role for inflammation in PSF are more limited.
“Data suggest that most postulated causes of PSF are related and share a common denominator in the immune system.”
Further investigations
-> 2018: Large studies controlling for baseline comorbidities and stroke characteristics are needed to adequately address the relationship between C-reactive protein and PSF.
-> 2018: Given the limitations of research done to date, it is apparent that definitive biomarkers for PSF have not been identified. Furthermore, it seems unlikely that there will be a single biomarker linked to PSF. The data suggest, however, that perturbations in the immune response after stroke may contribute to the perception of PSF.
1
Perfusion- Study
1) No-reflow phenomen
- Recanalization without reperfusion after EVT or IVT: no reflow phenomen.
2) Prediction of core growth (especially for patients transferred to thrombectomy)
3) „Contralateral Hemispheric Cerebral Blood Flow (cCBF) Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke“
Thamm & Guo et al.
4) „Vascular Hyperintensity on Fluid-Attenuated Inversion Recovery Indicates the Severity of Hypoperfusion in Acute Stroke.“ Nomura et al.: Recent studies suggested that identification of FLAIR vascular hyperintensity (FVHs) beyond the boundaries of a DWI cortical lesion (ie, FVH- DWI mismatch) might be an easy and reproducible way to identify patients with a large penumbra (ie, a large PWI-DWI mismatch indicated large infarct growth). In support of the previous research, our quantitative analyses showed extensive hypoperfusion in the DWI- ASPECTS regions, beyond the DWI lesions. We could not find any reports that used the Tmax or MTT parameters for quantitative assessment of brain perfusion status in the DWI-ASPECTS regions. Furthermore, no studies have quantitatively compared FVH-based hypoperfusion between the FVHlow (hypo- and isointensity) and FVHhigh (hyperintensity) in the MCA-M2.
Therefore, failure to improve hypoperfusion by recanalization early after imaging can result in relatively worse outcomes in the FVHhigh group, if the DWI lesions expand or additional DWI lesions appear over time. In the FVHlow group, the high DWI-ASPECTS indicated relatively less severe hypoperfusion in the FVH-DWI mismatch regions; these results implied more potentially salvageable regions in the ischemic penumbra, compared with those in the FVHhigh group. Based on these results, categorizing patients as FVHhigh or FVHlow, in the setting of acute MCA-M1 occlusion, might be helpful in quantitatively estimating the degree of hypoperfusion.
Advantages: Collaboration with neuroradiologist
Disadvantages: new or completing imaging sequences/technic potentially needed -> organisation and prospectiv design.
Further investigations:
1) Further studies on perfusion Imaging techniques after EVT needed -> Article: Imaging findings after mechanical thrombectomy in acute ischemic stroke -> "Further studies evaluating the role of microvascular dysfunction in reperfusion injury with angiographic and perfusion Imaging are warranted". Further investigation of the no reflow phenomen in general.
3) open questions of the study:
– If stenosis or occlusion at the carotid bifurcation is associated with low cCBF. (No cervical imaging in the study–design).
– A comparison of ASL (arterial spin labeling)-cCBF with other imaging techniques related to blood flow, such as multiphase CT, would be valuable. –> no ASL in our stroke–protocol...?