Quinn, Terence J.

English

Enlighten: Publications

 
 
 
 
Quinn, T. J.  (2018) Stroke literature synopses: clinical science. Stroke, 
49(5), e200-e201. (doi:10.1161/STROKEAHA.118.021008) 
 
 
This is the author’s final accepted version. 
 
There may be differences between this version and the published version. 
You are advised to consult the publisher’s version if you wish to cite from 
it. 
 
http://eprints.gla.ac.uk/158542/    
                    
 
 
 
 
 
 
Deposited on: 06 March 2018 
 
Enlighten – Research publications by members of the University of Glasgow 
http://eprints.gla.ac.uk  
 Stroke Literature Synopses:Clinical Science 
Terence J Quinn MD, 
Institute of Cardiovascular and Medical Sciences, University of Glasgow 
 
 
 
Word count:849 
 
Keywords:cerebral amyloid angiopathy, cognition, dementia, vascular cognitive impairment  
 
Address for correspondence: 
Dr Terry Quinn 
Institute of Cardiovascular and Medical Sciences  
Room 2.44, New Lister Campus, Glasgow Royal Infirmary  
Glasgow, UK, G4 0SF  
Email:terry.quinn@glasgow.ac.uk 
@DrTerryQuinn 
 
  
Stroke Literature Synopses:Clinical Science  
(vascular cognitive impairment) 
 
Historically the cognitive consequences of stroke have received limited research attention.  Yet, 
neuropsychological issues are common following stroke and stroke-survivors consistently state that 
cognitive decline is their biggest concern.  For this Clinical Synopsis I have selected papers themed 
around vascular cognitive impairment (VCI).  These papers are not trials  - there have been 
depressingly few intervention trials in this field.  Rather, I have chosen papers with a methodological 
flavour.  I believe, if we get the methods correct in VCI trials then positive results will follow.     
 
One of the fundamental barriers to progressing VCI research, is that we have no agreed definition of 
the condition. Many classification systems are available but the content of each differs and the 
resulting diagnoses can be contradictory.  To try and bring some consistency, the VICCS group 
propose a novel VCI classification system. (Skrobot OA The Vascular Impairment of Cognition 
Classification Consensus Study. Alzheimer’s and Dementia. 2017; 13:624-633.) 
Rather than create a classification from scratch, the VICCS group collated and appraised all the 
published materials on VCI classification.  They then developed their new guidance through an 
iterative process of anonymous review, feedback and amendment (Delphi process).  After several 
rounds of review, the VICCS group settled on a conceptualisation of VCI that recognises distinct 
entities of ‘Post Stroke Dementia’, ‘Subcortical’ or ‘Cortical Ischaemic Dementia’ and ‘Mixed 
Dementia’.  
The robust VICCS process provides a template for future studies looking at clinical classification. The 
group followed best practice in study conduct; they involved a diverse, international group of 
experts and they tried to harmonise the outputs with existing guidance.  It remains to be seen 
whether the VICCS system will gain traction in the research or clinical arenas.  Hopefully it can, I will 
be disappointed if in a few years the Clinical Synopsis section reports on another attempt to 
standardise VCI.  
 
Dementia is a progressive condition. In Alzheimer’s disease we often think of a pathway that begins 
with clinically occult pathology and then progresses through mild cognitive impairment (MCI) to 
frank dementia.  Whether this paradigm is valid or useful for VCI is less clear.  An early stage is 
described as ‘vascular cognitive impairment no dementia’ (VCI-ND) but unlike MCI there is no 
consensus definition of VCI-ND.  Sound familiar?   
In a UK study, the authors used a prospective, cognitive cohort of over 13,000 participants to try and 
operationalise an approach to VCI-ND.  (Stephan et al Neuropsychological profiles of vascular disease 
and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND) 
Age Ageing 2017; 46:755-60.). The population had a mix of differing vascular comorbidity and after 
excluding all participants with prevalent dementia, they were followed with cognitive and dementia 
assessment over two years.  
By the authors own admission, this study does not provide the last word on VCI-ND but provides 
interesting results that could inform future studies.  At baseline, cognitive impairment was not 
uniform across vascular diseases, diabetes mellitus and previous stroke seemed to be particularly 
associated with multi-domain cognitive issues.  Over time, all vascular diseases increased risk of 
dementia.  However, the neuropsychological profiles of cognitive problems differed between 
conditions. This finding has biological plausibility. The potential pathophysiology and expression of 
cognitive decline in cardiac disease is likely to differ from the patterns seen in diabetes mellitus and 
hypertension.  Perhaps using the umbrella term VCI is unhelpful and future studies should try and 
characterise the cognitive characteristics expected from vascular disease. 
 
A condition that is frequently associated with dementia is cerebral amyloid angiopathy (CAA).  A 
diagnosis of CAA has prognostic and treatment implications but making an in-vivo diagnosis of CAA is 
challenging.  MRI based criteria are available, but access to MRI is not always feasible or possible.  As 
CT imaging remains the work-horse of international stroke services, a CT based diagnostic algorithm 
for CAA could have substantial clinical utility.  
The team from Edinburgh, UK offer such an algorithm.  (Rodrigues MA et al. The Edinburgh CT and 
genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid 
angiopathy. Lancet Neurol 2018; 17: 232–40.)  In this study of 110 patients with intracerebral 
haemorrhage who had post mortem assessment for CAA, the authors developed a multi-item 
prediction tool.  The authors assessed the discriminative ability of various CT features and combined 
those most strongly associated with CAA into a three item model: a) presence of subarachnoid 
blood; b) finger like projections of the bleed and c) presence of ApoE4 genotype.  The tool had 
impressive accuracy offering near perfect CAA ‘rule out’ and ‘rule in’.     
For those of you, like me, who aren’t sure if they could distinguish ‘finger like projections’, the 
authors offer an on-line training resource. (https://radiopaedia.org/articles/edinburgh-criteria-for-
lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy)   
I suspect we will all start using the Edinburgh criteria in our clinical work. Diagnostic and prediction 
rules don’t always work so well when applied in populations beyond the parent study and so the 
authors plan to externally validate their rule in other datasets.  The other important, but difficult to 
answer, question is whether using the rule (or any of the classifications discussed in this Synopsis) 
will make any difference to patient outcomes.   


Stroke literature synopses: clinical science

Enlighten

      Quinn, T. J. (2017) Stroke literature synopses: clinical science. Stroke, 48(9), e243-e244.     There may be differences between this version and the published version. You are advised to consult the publisher’s version if you wish to cite from it.    http://eprints.gla.ac.uk/145018/            Deposited on: 29 August 2017                       Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk  Stroke Literature Synopsis: Clinical Science  STROKE/2017/018510 October 2017  Author: Dr Terence J Quinn MD Word Count: 890 in text Disclosures: Nil            Contact details:  Dr Terence J Quinn  Institute of Cardiovascular and Medical Sciences University of Glasgow  Glasgow, UK  Terry.quinn@glasgow.ac.uk +44 (0)141 201 8510   Recent clinical stroke research has predominantly focussed on hyperacute interventions.  These treatments are life-saving and life-changing at the individual level, but are only applicable to a proportion of those affected by stroke.  At a population level, effective primary and secondary prevention of stroke is the most important intervention.  Three recent studies have given us important insights into one of the fundamental aspects of prevention, antithrombotic treatment.  Cardiologists have been using increasingly potent antiplatelets for the management of acute coronary syndrome for years. A large randomised controlled trial of the P2Y12 receptor antagonist ticagrelor suggested that the benefits of intensive antiplatelet that have been seen in cardiology may not translate to stroke. Across 13,199 participants randomly allocated ticagrelor or aspirin following stroke or TIA, there was no statistically significant difference in rate of cardiovascular events between the groups, albeit there was a strong trend in favour of ticagrelor. In this new paper, the authors present a pre-planned subgroup analysis of the main trial, restricted to participants with large vessel atherosclerotic disease as defined by ‘ASCO’ grading. Amerenco et al Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. Lancet Neurol. 2017;16:301-310 http://dx.doi.org/10.1016/S1474-4422(17)30038-8 This time there was a significant between group difference with 168 (6·8%) patients in the ticagrelor group and 208 (8·3%) in the aspirin group having a cardiovascular event (HR:0.79[95%CI:0.65-0.97].) Analyses describing rates of recurrent stroke and mortality were also in favour of ticagrelor.  We always have to be wary of ‘positive’ subgroup analyses when the main trial is neutral. However, stroke is a syndrome and not a distinct disease process and so it makes sense that certain treatments may only show efficacy for certain types of stroke. Future trials of secondary prevention may wish to stratify or restrict inclusion by underlying stroke pathology. Ongoing trials of anticoagulant in presumed cardioembolic stroke are already adopting this approach. Of course, all of this is dependent on robust classification of the index stroke event and in the messy reality of acute stroke this is not always straightforward.   With increasing potency of antiplatelet comes increasing risk of adverse events.  An elegant study from Oxford, UK suggests that we may be underestimating the risk associated with antiplatelet. Linxin Li et al Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet 2017 online before print DOI: http://dx.doi.org/10.1016/S0140-6736(17)30770-5. In this population based cohort study, the authors described rates of bleeding in patients prescribed antiplatelet (usually aspirin) following stroke, TIA or myocardial infarction. The average annual risk of bleeding was 3.36% (95%CI:3.04-3.70). Risk of major bleed, severity of bleeding and poor outcomes from bleeding were all also higher in older adults.  The risk of bleeding did not substantial decrease with increasing duration of exposure. There are many salutary lessons from this paper. The bleeding risk in this real world cohort was higher than described in previous clinical trials where recruitment has tended to focus on younger patients with less comorbidity. Risk of cardiovascular events following stroke and TIA is highest in the first days to weeks but risk of bleeding seems to be maintained over time. Perhaps for older adults who are taking antiplatelet for a vascular event that occurred in the distant past we need to rethink the risk-balance of continuing the antiplatelet treatment.  Although the most common bleeding event in the Oxford study was gastrointestinal bleeding, the most feared bleeding event (amongst stroke physicians) is intracerebral haemorrhage (ICH). Patients with bleeding episodes are not immune to future cardiovascular events, in fact they may be at increased risk so any guidance on antithrombotic prescribing in this group is welcome. A recent meta-analysis looked at the evidence around antithrombotic treatment following an intracerebral bleeding event. Perry LA et al Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2017 DOI: 10.1002/14651858.CD012144.pub2 The authors collated all controlled trials looking at antithrombotic treatment following ICH. For such a common and important question, the available evidence was modest at best. Despite a rigorous search strategy, in total there were only two RCTs with a combined participant population of 121. Both studies were judged at risk of bias in a number of areas and generalizability was limited as the interventions studied were parenteral anticoagulants and follow up was limited to the short term.  Accepting all these caveats, the use of anticoagulants following ICH appeared safe with no increase in mortality or bleeding but equally there was no decrease in thrombotic events. Clearly the available evidence is not sufficient to guide practice and the review authors’ call for large scale RCTS seems well founded. Several such trials are currently recruiting. One could argue that we don’t need the trials as we have a number of studies from observational registries that report safety of reintroduction of anticoagulant following ICH.  However, a properly conducted randomised trial remains the gold standard as stroke medicine has many examples of interventions that appeared efficacious or safe in observational cohorts but were subsequently proven to be ineffective or harmful in RCTs. For now, when we are faced with a patient who has ICH but also an indication for antiplatelet then perhaps the best course of action is to randomise to one of the trials.    

 
 
 
 
Quinn, T. J. (2018) Stroke literature synopses: clinical science. Stroke, 
49(1), e5-e6. (doi:10.1161/STROKEAHA.117.019655) 
 
This is the author’s final accepted version. 
 
There may be differences between this version and the published version. 
You are advised to consult the publisher’s version if you wish to cite from 
it. 
 
 
 
 
http://eprints.gla.ac.uk/153951/ 
     
 
 
 
 
 
 
Deposited on: 23 January 2018 
 
 
 
 
 
 
 
 
 
 
 
 
Enlighten – Research publications by members of the University of Glasgow 
http://eprints.gla.ac.uk 
Stroke Literature Synopsis: Clinical Science 
(diagnosis and prognosis) 
 
STROKE/2017/019655 
December 2017 
Author: Dr Terence J Quinn MD 
Word Count: 839 in text 
Disclosures: Nil 
Contact details: 
Dr Terence J Quinn 
Institute of Cardiovascular and Medical Sciences 
University of Glasgow 
Glasgow, UK 
Terry.quinn@glasgow.ac.uk 
@DrTerryQuinn 
+44 (0)141 201 8510 
 
In acute stroke we are lucky to have a number of efficacious treatments supported by a robust 
evidence-base. However, before we think about treatment we first need to make the diagnosis of 
stroke and make some estimate of likely outcome. This is not always straightforward and much of 
the skill, challenge and reward of stroke medicine comes from the diagnostic and prognostic 
decision making required for each patient. For this month’s Literature Synopsis I have selected 
articles that are themed around diagnosis and prognosis. This is an area of stroke where I feel we 
need more research and I hope to see, and discuss, more articles on these themes in future 
Synopses. 
 
 
I consider myself an evidence-based practitioner but there will always be areas of practice where we 
have limited research to guide decision making. In this context it is reassuring to see results that 
confirm something I had, based on experience, always assumed to be the case. Most stroke 
physicians will recognise that patients who have made recovery from a previous disabling stroke can 
appear to show a re-emergence of clinical deficits when they are subject to physiological stressors 
such as infection or metabolic disturbance. In a registry based case-control analysis using data from 
the Massachusetts General Hospital, the existence of this syndrome was proven (Topcuoglu et al 
Recrudescence of Deficits After Stroke Clinical and Imaging Phenotype, Triggers, and Risk Factors. 
JAMA Neurol. 2017;74(9):1048–1055) and was given a new name and abbreviation - post stroke 
recrudescence (PSR). The description of a typical case of PSR may give clinicians more certainty in 
making this diagnosis. In the case series, patients with PSR had a symptom complex that could occur 
many years after the index stroke. Symptoms were generally mild and lasted less than twenty-four 
hours. This is a nice diagnostic study, but I was left wondering about prognosis. Does a systemic 
illness with associated PSR have a poorer prognosis than a similar illness with no PSR? 
 
One of the most difficult prognostic decisions is when to withhold or withdraw active stroke 
treatment. In a study of 60 patients with severe stroke admitted to two centres in the Netherlands, 
stroke physicians’ estimates of prognosis were compared to the actual six month patient outcomes. 
(Geurts et al Predictive accuracy of physicians' estimates of outcome after severe stroke. PLOSOne. 
2017 ONE12(9): e0184894) Physicians were relatively good at predicting death, one patient 
predicted to die, survived and one patient predicted to survive was dead at six months. However, 
predictions around functional outcome were less good and generally too optimistic (false positive 
rate 0.3). Predictions around quality of life were even less accurate. For a cohort with very severe 
initial stroke, I was surprised at the high proportions of patients reporting favourable quality of life. 
This suggests that my predictive accuracy is also limited and is a salient reminder of the dangers of 
making prognostic decisions too early. 
 
 Atrial fibrillation (AF) and stroke is an exemplar of an area where we are increasingly aware of the 
shortcomings in our prognostic understanding. Patients with ‘true’ paroxysmal AF, the definition of 
which varies from guideline to guideline, are at greater risk of cardioembolic stroke than those with 
sinus rhythm. Frustratingly, the most common result from ambulatory cardiac monitoring is neither 
sustained sinus nor AF, but bursts of atrial arrhythmia that are too short to meet any diagnostic 
after use.  The Find-AF investigators used their data to describe the implications of supraventricular 
runs (Weber-Kruger et al Relevance of supraventricular runs detected after cerebral ischaemia. 
Neurology.2017,89:1545-1552.) The results of 3.7 years follow-up confirmed that even short 
supraventricular runs were associated with more stroke events and more incident AF. Given the 
frequency of these short runs of arrhythmia on ambulatory monitoring (around a third of patients in 
this study) this is an important finding. Now the important question is, what should we do with 
patients who have this abnormality? Anticoagulation would seem intuitive but the efficacy and 
economics of anticoagulation in patients who do not fulfil AF diagnostic criteria remains to be 
proven. 
 
Can we better stratify the risk of incident AF? Certainly various modifiable risk factors for incident 
AF have been described. We know that high levels of alcohol consumption can predispose to AF, but 
the importance of moderate alcohol remains a subject of debate. We will never see a randomised 
controlled trial of therapeutic alcohol and so we are reliant on observational research, with all the 
caveats that come with such studies. A national registry based study from Norway (47002 
participants, 1697 new AF diagnoses) gives a reasonably precise estimate of risk. (Gemes et al Does 
Moderate Drinking Increase the Risk of AF? JAHA2017;6:e007094) The authors describe a curvilinear 
relationship between alcohol and incident AF, but the risk of moderate alcohol (defined in this study 
as 1 drink per day for women and 2 drinks per day for men) was negligible, with a population 
attributable risk of 0.07 (95%CI:-0.01 to 0.13). This is reassuring news for my quality of life, so I’ll 
drink to that. Cheers! 
 Terry.quinn@glasgow.ac.uk 
@DrTerryQuinn 


Terence J. Quinn

Crossref

Stroke

<i>Stroke</i>
            Literature Synopses: Clinical Science

     Quinn, T. J. (2018) Stroke literature synopses: clinical science. Stroke, 49(10), e299-e300. (doi:10.1161/strokeaha.118.022324).  This is the author’s final accepted version.  There may be differences between this version and the published version. You are advised to consult the publisher’s version if you wish to cite from it.  http://eprints.gla.ac.uk/172565/                              Deposited on: 23 December 2019         Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk    Stroke Literature Synopses: Clinical Science Terence J Quinn MD, Institute of Cardiovascular and Medical Sciences, University of Glasgow    Word count:  Keywords: cerebral amyloid angiopathy, cognition, dementia, vascular cognitive impairment   Address for correspondence: Dr Terry Quinn Institute of Cardiovascular and Medical Sciences  Room 2.44, New Lister Campus, Glasgow Royal Infirmary  Glasgow, UK, G4 0SF  Email:terry.quinn@glasgow.ac.uk   Stroke Literature Synopses: Clinical Science  (Dementia and vascular cognitive impairment)  Historically the cognitive consequences of stroke have received less research attention than the physical aspects.  Yet, neuropsychological issues are incredibly common following stroke and people affected by stroke consistently state that post stroke cognitive decline is their biggest concern.  For this Clinical Synopsis I have selected three important papers themed around vascular cognitive impairment (VCI).  The papers chosen are not trials of interventions to prevent or reverse VCI, as there have been depressingly few positive trials in this field.  Rather, I have chosen papers with a methodological flavour.  I believe, if we can get the methods correct in VCI trials then the positive results will follow.      One of the fundamental barriers to progressing VCI interventional research, is that we have no agreed definition of VCI. Many operationalised definitions of various VCI presentations are available but the content of each classification system differs and the resulting diagnoses can be contradictory.  To try and bring some consistency to VCI assessment, the VICCS group propose a novel classification system. (Skrobot OA The Vascular Impairment of Cognition Classification Consensus Study. Alzheimer’s and Dementia. 2017; 13:624-633.) Rather than create a VCI classification from scratch, the VICCS group collated and appraised all the published guidance on VCI classification.  Based on this they developed new guidance for application through an iterative and circular process of anonymous review, feedback and amendment (a Delphi process).  After many rounds of review, the VICCS group settled on a conceptulaisation of VCI that recognises distinct entities of Post Stroke Dementia, subcortical or cortical ischaemic dementia and mixed dementia.  The VICCS process provides a template for future studies looking at clinical classification. The group followed best practice in the conduct of the study; they involved a diverse, international group of experts and they tried to harmonise the outputs with existing, high profile guidance. It remains to be seen whether the VICCS system will gain traction in the research or clinical arenas.  I hope that a consensus can be reached. I will be disappointed if in a few years the Clinical Synopsis section reports on another attempt to standardise VCI.     Dementia is a progressive condition. In Alzheimer’s disease and undifferentiated dementia, we often think of a pathway that begins with clinically occult pathological process and then progresses through a mild cognitive impairment (MCI) to frank dementia.  Whether this paradigm is valid or useful for the syndrome of vascular dementias is less clear.  An early stage of disease is described, vascular cognitive impairment, no dementia (VCI-ND) but unlike MCI there is no consensus on how this condition should be defined.  In a UK study, the authors used a prospective, cognitive cohort of over 13,000 participants to try and operationalise an approach to VCI-ND.  (Stephan et al Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia(VCI-ND) Age Ageing 2017; 46:755-60.). The population had a mix of differing vascular comorbidity and after excluding all participants with prevalent dementia, they were followed with cognitive and dementia assessment over two years.  By the authors own admission, this study does not provide the last word on VCI-ND but provides interesting results that could inform future studies.  At baseline, cognitive impairment was not uniform across vascular diseases, diabetes mellitus and previous stroke seemed to be particularly associated with multi-domain cognitive issues.  Over time, all vascular diseases increased risk of dementia.  However, the neuropsychological profiles of cognitive problems differed between conditions. This finding has biological plausibility. The potential pathophysiology and expression of cognitive decline in cardiac disease is likely to differ from the patterns seen in diabetes mellitus and hypertension.  Perhaps using the umbrella term vascular dementia is unhelpful and future studies should try and characterise the cognitive characteristics expected from vascular disease. This is easier said than done.      A condition that is frequently associated with dementia is cerebral amyloid angiopathy (CAA).  A diagnosis of CAA has important prognostic and treatment implications but making an in-vivo diagnosis of CAA is not straightforward.  MRI based criteria are available, but access to MRI is not always feasible or possible.  As CT imaging remains the work-horse of international stroke services, a CT based diagnostic algorithm for CAA could have substantial clinical utility.  The team from Edinburgh, UK offer such an algorithm.  (Rodrigues MA et al. The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy. Lancet Neurol 2018; 17: 232–40.)  In this study of 110 patients with intracerebral haemorrhage who had post mortem assessment for CAA, the authors developed a multi-item prediction tool.  The authors assessed the discriminative ability of various CT features and combined those most strongly associated with CAA into a three item model. The final model included a) presence of subarachnoid blood; b) finger like projections of the bleed and c) presence of ApoE4 genotype.  The tool had impressive accuracy offering near perfect CAA ‘rule out’ and ‘rule in’.     I suspect we will all start using the Edinburgh criteria in our day to day clinical work. Diagnostic and prediction rules don’t always work so well when applied in populations beyond the parent study and so the authors plan to externally validate their rule in other datasets.  The other important, but difficult to answer, question is whether using the rule will make any difference to patient outcomes.  For those of you, like me, who aren’t sure if they could distinguish ‘finger like projections’, the authors even offer an on-line training resource. (https://radiopaedia.org/articles/edinburgh-criteria-for-lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy)   

    Quinn, T. J. (2018) Stroke literature synopses: clinical science. Stroke, 49(1), e5-e6. (doi:10.1161/STROKEAHA.117.019655)  This is the author’s final accepted version.  There may be differences between this version and the published version. You are advised to consult the publisher’s version if you wish to cite from it.     http://eprints.gla.ac.uk/153951/            Deposited on: 23 January 2018             Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Stroke Literature Synopsis: Clinical Science (diagnosis and prognosis)  STROKE/2017/019655 December 2017 Author: Dr Terence J Quinn MD Word Count: 839 in text Disclosures: Nil Contact details: Dr Terence J Quinn Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow, UK Terry.quinn@glasgow.ac.uk @DrTerryQuinn +44 (0)141 201 8510  In acute stroke we are lucky to have a number of efficacious treatments supported by a robust evidence-base. However, before we think about treatment we first need to make the diagnosis of stroke and make some estimate of likely outcome. This is not always straightforward and much of the skill, challenge and reward of stroke medicine comes from the diagnostic and prognostic decision making required for each patient. For this month’s Literature Synopsis I have selected articles that are themed around diagnosis and prognosis. This is an area of stroke where I feel we need more research and I hope to see, and discuss, more articles on these themes in future Synopses.   I consider myself an evidence-based practitioner but there will always be areas of practice where we have limited research to guide decision making. In this context it is reassuring to see results that confirm something I had, based on experience, always assumed to be the case. Most stroke physicians will recognise that patients who have made recovery from a previous disabling stroke can appear to show a re-emergence of clinical deficits when they are subject to physiological stressors such as infection or metabolic disturbance. In a registry based case-control analysis using data from the Massachusetts General Hospital, the existence of this syndrome was proven (Topcuoglu et al Recrudescence of Deficits After Stroke Clinical and Imaging Phenotype, Triggers, and Risk Factors. JAMA Neurol. 2017;74(9):1048–1055) and was given a new name and abbreviation - post stroke recrudescence (PSR). The description of a typical case of PSR may give clinicians more certainty in making this diagnosis. In the case series, patients with PSR had a symptom complex that could occur many years after the index stroke. Symptoms were generally mild and lasted less than twenty-four hours. This is a nice diagnostic study, but I was left wondering about prognosis. Does a systemic illness with associated PSR have a poorer prognosis than a similar illness with no PSR?  One of the most difficult prognostic decisions is when to withhold or withdraw active stroke treatment. In a study of 60 patients with severe stroke admitted to two centres in the Netherlands, stroke physicians’ estimates of prognosis were compared to the actual six month patient outcomes. (Geurts et al Predictive accuracy of physicians' estimates of outcome after severe stroke. PLOSOne. 2017 ONE12(9): e0184894) Physicians were relatively good at predicting death, one patient predicted to die, survived and one patient predicted to survive was dead at six months. However, predictions around functional outcome were less good and generally too optimistic (false positive rate 0.3). Predictions around quality of life were even less accurate. For a cohort with very severe initial stroke, I was surprised at the high proportions of patients reporting favourable quality of life. This suggests that my predictive accuracy is also limited and is a salient reminder of the dangers of making prognostic decisions too early.   Atrial fibrillation (AF) and stroke is an exemplar of an area where we are increasingly aware of the shortcomings in our prognostic understanding. Patients with ‘true’ paroxysmal AF, the definition of which varies from guideline to guideline, are at greater risk of cardioembolic stroke than those with sinus rhythm. Frustratingly, the most common result from ambulatory cardiac monitoring is neither sustained sinus nor AF, but bursts of atrial arrhythmia that are too short to meet any diagnostic after use.  The Find-AF investigators used their data to describe the implications of supraventricular runs (Weber-Kruger et al Relevance of supraventricular runs detected after cerebral ischaemia. Neurology.2017,89:1545-1552.) The results of 3.7 years follow-up confirmed that even short supraventricular runs were associated with more stroke events and more incident AF. Given the frequency of these short runs of arrhythmia on ambulatory monitoring (around a third of patients in this study) this is an important finding. Now the important question is, what should we do with patients who have this abnormality? Anticoagulation would seem intuitive but the efficacy and economics of anticoagulation in patients who do not fulfil AF diagnostic criteria remains to be proven.  Can we better stratify the risk of incident AF? Certainly various modifiable risk factors for incident AF have been described. We know that high levels of alcohol consumption can predispose to AF, but the importance of moderate alcohol remains a subject of debate. We will never see a randomised controlled trial of therapeutic alcohol and so we are reliant on observational research, with all the caveats that come with such studies. A national registry based study from Norway (47002 participants, 1697 new AF diagnoses) gives a reasonably precise estimate of risk. (Gemes et al Does Moderate Drinking Increase the Risk of AF? JAHA2017;6:e007094) The authors describe a curvilinear relationship between alcohol and incident AF, but the risk of moderate alcohol (defined in this study as 1 drink per day for women and 2 drinks per day for men) was negligible, with a population attributable risk of 0.07 (95%CI:-0.01 to 0.13). This is reassuring news for my quality of life, so I’ll drink to that. Cheers!  Terry.quinn@glasgow.ac.uk @DrTerryQuinn 

    Quinn, T. J.  (2018) Stroke literature synopses: clinical science. Stroke, 49(5), e200-e201. (doi:10.1161/STROKEAHA.118.021008)   This is the author’s final accepted version.  There may be differences between this version and the published version. You are advised to consult the publisher’s version if you wish to cite from it.  http://eprints.gla.ac.uk/158542/                              Deposited on: 06 March 2018  Enlighten – Research publications by members of the University of Glasgow http://eprints.gla.ac.uk   Stroke Literature Synopses:Clinical Science Terence J Quinn MD, Institute of Cardiovascular and Medical Sciences, University of Glasgow    Word count:849  Keywords:cerebral amyloid angiopathy, cognition, dementia, vascular cognitive impairment   Address for correspondence: Dr Terry Quinn Institute of Cardiovascular and Medical Sciences  Room 2.44, New Lister Campus, Glasgow Royal Infirmary  Glasgow, UK, G4 0SF  Email:terry.quinn@glasgow.ac.uk @DrTerryQuinn    Stroke Literature Synopses:Clinical Science  (vascular cognitive impairment)  Historically the cognitive consequences of stroke have received limited research attention.  Yet, neuropsychological issues are common following stroke and stroke-survivors consistently state that cognitive decline is their biggest concern.  For this Clinical Synopsis I have selected papers themed around vascular cognitive impairment (VCI).  These papers are not trials  - there have been depressingly few intervention trials in this field.  Rather, I have chosen papers with a methodological flavour.  I believe, if we get the methods correct in VCI trials then positive results will follow.      One of the fundamental barriers to progressing VCI research, is that we have no agreed definition of the condition. Many classification systems are available but the content of each differs and the resulting diagnoses can be contradictory.  To try and bring some consistency, the VICCS group propose a novel VCI classification system. (Skrobot OA The Vascular Impairment of Cognition Classification Consensus Study. Alzheimer’s and Dementia. 2017; 13:624-633.) Rather than create a classification from scratch, the VICCS group collated and appraised all the published materials on VCI classification.  They then developed their new guidance through an iterative process of anonymous review, feedback and amendment (Delphi process).  After several rounds of review, the VICCS group settled on a conceptualisation of VCI that recognises distinct entities of ‘Post Stroke Dementia’, ‘Subcortical’ or ‘Cortical Ischaemic Dementia’ and ‘Mixed Dementia’.  The robust VICCS process provides a template for future studies looking at clinical classification. The group followed best practice in study conduct; they involved a diverse, international group of experts and they tried to harmonise the outputs with existing guidance.  It remains to be seen whether the VICCS system will gain traction in the research or clinical arenas.  Hopefully it can, I will be disappointed if in a few years the Clinical Synopsis section reports on another attempt to standardise VCI.   Dementia is a progressive condition. In Alzheimer’s disease we often think of a pathway that begins with clinically occult pathology and then progresses through mild cognitive impairment (MCI) to frank dementia.  Whether this paradigm is valid or useful for VCI is less clear.  An early stage is described as ‘vascular cognitive impairment no dementia’ (VCI-ND) but unlike MCI there is no consensus definition of VCI-ND.  Sound familiar?   In a UK study, the authors used a prospective, cognitive cohort of over 13,000 participants to try and operationalise an approach to VCI-ND.  (Stephan et al Neuropsychological profiles of vascular disease and risk of dementia: implications for defining vascular cognitive impairment no dementia (VCI-ND) Age Ageing 2017; 46:755-60.). The population had a mix of differing vascular comorbidity and after excluding all participants with prevalent dementia, they were followed with cognitive and dementia assessment over two years.  By the authors own admission, this study does not provide the last word on VCI-ND but provides interesting results that could inform future studies.  At baseline, cognitive impairment was not uniform across vascular diseases, diabetes mellitus and previous stroke seemed to be particularly associated with multi-domain cognitive issues.  Over time, all vascular diseases increased risk of dementia.  However, the neuropsychological profiles of cognitive problems differed between conditions. This finding has biological plausibility. The potential pathophysiology and expression of cognitive decline in cardiac disease is likely to differ from the patterns seen in diabetes mellitus and hypertension.  Perhaps using the umbrella term VCI is unhelpful and future studies should try and characterise the cognitive characteristics expected from vascular disease.  A condition that is frequently associated with dementia is cerebral amyloid angiopathy (CAA).  A diagnosis of CAA has prognostic and treatment implications but making an in-vivo diagnosis of CAA is challenging.  MRI based criteria are available, but access to MRI is not always feasible or possible.  As CT imaging remains the work-horse of international stroke services, a CT based diagnostic algorithm for CAA could have substantial clinical utility.  The team from Edinburgh, UK offer such an algorithm.  (Rodrigues MA et al. The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy. Lancet Neurol 2018; 17: 232–40.)  In this study of 110 patients with intracerebral haemorrhage who had post mortem assessment for CAA, the authors developed a multi-item prediction tool.  The authors assessed the discriminative ability of various CT features and combined those most strongly associated with CAA into a three item model: a) presence of subarachnoid blood; b) finger like projections of the bleed and c) presence of ApoE4 genotype.  The tool had impressive accuracy offering near perfect CAA ‘rule out’ and ‘rule in’.     For those of you, like me, who aren’t sure if they could distinguish ‘finger like projections’, the authors offer an on-line training resource. (https://radiopaedia.org/articles/edinburgh-criteria-for-lobar-intracerebral-haemorrhage-associated-with-cerebral-amyloid-angiopathy)   I suspect we will all start using the Edinburgh criteria in our clinical work. Diagnostic and prediction rules don’t always work so well when applied in populations beyond the parent study and so the authors plan to externally validate their rule in other datasets.  The other important, but difficult to answer, question is whether using the rule (or any of the classifications discussed in this Synopsis) will make any difference to patient outcomes.   

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Stroke literature synopses: clinical science

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