Dong H, Ding H, Young K, Blaivas M, Christensen PJ, Wang MM. Advanced Intimal Hyperplasia Without Luminal Narrowing of Leptomeningeal Arteries in CADASIL. Stroke. 2013
CADASIL is the most common form of heritable stroke and vascular dementia. The clinical presentation is very well known, although less is known about the pathophysiology of the disease. In this issue, Dong et al. investigated leptomeningeal arteries of 6 patients with genetically diagnosed CADASIL, 6 controls within the age range that those with CADASIL and 6 aged controls. The authors obtained morphometric and immunological arterial characteristics in cases and controls. The authors found that in arteries from patients with CADASIL, the intima was 5 fold thicker, the media was thinner and the sclerotic index was greater than in those without CADASIL. Surprisingly, the lumen was not significantly smaller despite the intima hyperplasia. The hyperplastic intima expressed muscle-like proteins.
If the intima was 5 times thicker and the lumen remained the same, why do patients ultimately develop strokes? How could an intact lumen be associated with cortical dysfunction that eventually leads to dementia as the authors suggested? Several explanations come to mind. We don’t know based on the published data if all leptomeningeal arteries had the same size across groups. This is important, because the proportion of the intima and the media vary according to arterial size. Also, these specimens might represent a very early form of intima hyperplasia. According to the classic model of atherosclerosis by Glagov et al. we know that coronary arteries enlarge to compensate for up to 40% of intima thickening before the lumen becomes compromised. Although this is less well-established in brain arteries, it could be an explanation. If these findings are confirmed in larger datasets, one might think of potential ways treat this disease. Antiproliferative measures could be imagined to arrest the intima thickening and preserve the lumen. If we could identify the process even earlier, more aggressive controls of concomitant vascular risk factor might be warranted to avoid further intima thickening. The work by Dong et al. broadens the horizons to imagine new treatments of this and other arteriopathies that cause stroke and vascular dementia.
This is a very large retrospective study. As expected, the authors find that hypertension is highly prevalent in patients with ischemic stroke (over 70% of patients in their registry had hypertension). They also find an association between HTN and stroke recurrence. After controlling for various factors, they only find solid evidence of the relationship with small vessel disease and not with other subtypes. This is important because in order to address stroke recurrence we need to tackle the risk factors responsible for that. But when interpreting this finding we need to remember that this was a retrospective study.
Prospective trials such as WASID and SAMPRIS have clearly found an association between hypertension control and lower stroke recurrence. The current study provides some food for thought: ischemic stroke is a heterogeneous disease with heterogeneous risk factors and in order to address recurrence we need to concentrate on specific risk factors for that stroke sub-type. It also makes a case for investigating ischemic stroke cause thoroughly as that might help differentiate the stroke sub-type leading to change in the management.
MRI-DRAGON score is an adaptation of CT DRAGON score to predict 3 month outcome in acute anterior circulation stroke patients who had MRI as initial diagnostic workup and were treated with IV t-PA within 4.5 hours.
One point each is given for M1 occlusion, DWI ASPECTS ≤ 5, prestroke mRS >1, Age 65-79, Glucose level >8mmol/l prior to t-PA, Onset to treat time >90 min and NIHSS 5-9 prior to IV t-PA. Two points each is given for age ≥ 80 and NIHSS 10-15. Patients with NIHSS>15 get 3 points. With MRI-DRAGON score total of 10 points is possible.
Among 228 patients evaluated with the MRI-DRAGON score in the study all patients with total score ≤ 2 (n=22) had a good outcome (mRS 0-2) while those with score ≥ 8 (n=11) had poor outcome (mRS 5-6). Poor outcome was significantly associated with all parameters considered in the MRI-DRAGON score except onset to treat time and prestroke mRS>1 which only had a nonsignificant trend towards poor outcome.
It is well known from previous studies that the odds of good outcome is higher for those patients treated within 90 min of symptom onset compared to those treated in 90-180 min and 180-270min of symptom onset. However it is interesting to note in this study that onset to treat time>90min had only a nonsignificant trend for association with poor outcome.
This tool incorporates only information that is available prior to IV t-PA administration. Therefore it may be helpful in selecting patients for therapeutic interventions in clinical trials, for example, excluding patients with higher MRI-DRAGON score (≥ 8) due to increased probability of poor outcome at 3 months in these patients.
de Rooij NK, Greving JP, Rinkel GJE, Frijns CJM. Early prediction of delayed cerebral ischemia after SAH: development and validation of a practical risk chart. Stroke. 2013.
Delayed cerebral ischemia (DCI) is a common complication in the setting of subarachnoid hemorrhage and it may be a major determinant of morbidity and mortality. De Rooij et al. report the development and validation of a risk chart that incorporates only variables collected at admission and aims to predict the risk of infarcts related to delayed cerebral ischemia.
The authors carefully studied data derived from 371 prospectively collected patients in order to create a prognostic model, and validated the findings in an additional cohort of 255 patients. Not unexpectedly, the variables that more robustly predicted DCI-related infarcts were poor clinical grade, larger amount of blood on CT, and age. Based on these factors, the chart predicted a chance as low as 12% of developing DCI-related infarct in patients with low Fisher Scale/ low World Federation of Neurological Surgeons Scale (WFNS) grade and age ≥55, and as high as 61% in patients with thick subarachnoid hemorrhage, high WFNS grade and younger age. The authors suggest that lower risk patients could be considered for an earlier discharge from the unit, and state that the chart should be used to “predict absolute risks of DCI in individual patients”.
In practice, it works as a well-ordered paradigm, however it is intriguing to consider its application to certain “individual” cases, such as a 60 years-old patient with modified Fisher II and WFNS V (in whom the risk of infarct from DCI would be read as low). Moreover, multiple medical variables such as fever, anemia, hyperglycemia, cardiac and pulmonary issues, hemodynamic and/or electrolyte changes, etc, are considered to influence the morbidity of these patients and need to be intensively followed. Therefore, the benefit of early identification of an increased risk of DCI/infarct based on admission variables would not be relatively so important, and providers could have time to incorporate variables collected within the few days into the risk stratification. In summary, Rooij et al. provide us with solid and meticulously analyzed data that may aid in the decision making of such a commonly encountered scenario.
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