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

“It is unclear if antiplatelet drugs worsen the outcome of hemorrhagic stroke” -> Retrospective Analysis

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:

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:

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

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.