Zhang L, Micael Chopp M, Teng H, Ding G, Jiang Q, Yang XP, et al. Combination Treatment With N-Acetyl-Seryl-Aspartyl-Lysyl-Proline andTissue Plasminogen Activator Provides Potent Neuroprotection in RatsAfter Stroke. Stroke 2014.
Infections can cause stroke, and stroke increases the rate of infections. In fact, infection is the most common complication after stroke and contributes to poor functional outcome. Pneumonia for instance occurs in upto 22% of patients and is the leading cause of death after stroke. This bidirectional relationship is complex. Recall the parts of the immune system, it comprises the innate and adaptive immune systems, each differing with respect to how quickly and for how long it responds, central effector cell types and its specificity for pathogens. The association between the adaptive system and stroke has been well investigated, but the function of the innate system in stroke is unknown.
Factors such as aspiration, crural weakness, bedridden state, urinary incontinence etc. alone cannot entirely explain the increased risk of infection. Immunodeficiency of the innate and adaptive systems in addition offers a better explanation. This raises the question of short-term prophylactic antibiotics. The ESPIAS and PANTHERIS trials that studied this question found no benefit in outcomes, but may have been related to fluroquinolone neurotoxicity. In contrast, studies where minocycline, and mezlocillin/sulbactam (Mannheim Infection in Stroke Study) prophylaxis was used showed improved clinical outcomes. Lets hope that further knowledge of the immune system in stroke may aid in optimally selecting an antimicrobial regimen for prophylaxis, that can be tested in future trials.
Favre I, Zeffiro TA, Detante O, Krainik A, Hommel M, and Jaillard A. Upper Limb Recovery After Stroke Is Associated With Ipsilesional PrimaryMotor Cortical Activity: A Meta-Analysis. Stroke. 2014
Interpreting the results of functional imaging studies to explore post-stroke plasticity can be challenging. Invariably these studies include only a small sample of subjects. As a result, many functional imaging studies conflict on the exact location of increased brain activity in the recovery period. In this article, Favre and colleagues bring clarity to post-stroke brain remodeling by combining the results of multiple fMRI and PET studies. In subjects with good functional recovery they found increased activity in the ipsilesional M1 and medial-premotor cortex (PMC). Subjects with poor recovery had increased activity in the cerebellar vermis.
The authors performed activation likelihood estimation to assess cortical activation patterns in 24 prior fMRI and PET studies. Subjects had motor impairments of the upper limb with either partial or complete recovery. 89% had subcortical strokes. Studies were separated into acute (<35 days post-stroke) and chronic (>3 mo. post-stroke) stages. The authors found an increase in cortical activation in contralesional dorsolateral PMC in the acute stage that faded with time. This acute contralesional shift did not correlate with recovery. In contrast, during the chronic stage there was a ventral shift in ipsilesional M1 activation that occurred in those with good recovery.
This meta-analysis consolidates the evidence from prior functional imaging studies and suggests that functional imaging may be a useful biomarker for stroke recovery. Many prior studies show a contralesional shift in cortical activation in the acute phase post-stroke. Whether this shift is adaptive or maladaptive remains unclear; the present meta-analysis found no association with recovery. What is more clear is that later in the recovery process a shift in activation patterns back to the lesional side and particularly a ventral shift in M1 occurs in those with good recovery. The authors also discovered increased activity in the cerebellar vermis in those with poor recovery – a novel finding that requires further confirmation. Studies like this increase our confidence in using functional imaging as a biomarker for stroke recovery. Time to return of ipsilesional activation and ventral shift in ipsilesional M1 may emerge as important endpoints in future stroke rehabilitation trials.
Outcomes of a Contemporary Cohort Of 536 Consecutive Acute Ischemic Stroke Patients Treated With Endovascular Therapy
This observational, population-based, post SYNTHESIS, IMS-III and the MR RESCUE study, comes at a perfect time.
Rozanski M, Richter TB, Grittner U, Endres M, Fiebach JB, and Jungehulsing GJ. Elevated Levels of Hemoglobin A1c Are Associated With Cerebral White Matter Disease in Patients With Stroke. Stroke. 2014
“Patchy, nonspecific T2/FLAIR hyperintense white matter disease that is greater than expected for age.” These words, or something similar grace many an MRI read. A number of studies have found consistent correlations between white matter disease (WMD), age and HTN, however there has been inconsistent or even contradictory correlations between WMD and other factors such as DM, HL, smoking and renal function. In this study, Rozanski et al found that in patients with first acute ischemic stroke (AIS), WMD was significantly associated with age, HTN and higher levels of HbA1c, but not elevated levels of TG, LDL, or total cholesterol.
512 patients with first AIS were enrolled in the study. Standard screening labs were drawn at admission, and fasting lipids and HbA1c on day 2. The mean age was 68.5, 37% were women, and the median NIHSS was 3. MRI imaging was performed during workup, and WMD burden was measured utilizing the Wahlund score (WS). Of all patients, 77% had HTN, 49.5% had HL, 24% had AFib and 23% had DM.
Per the authors, this is the first study that they know of that shows a correlation between elevated HbA1c and WMD burden. Median levels of HbA1c were 5.7 to 5.9% in patients with any sign of WMD, vs. 5.3% in patients without hyperintensities. Interestingly, DM alone did not correlate as strongly, which the authors felt may be explained by the fact that patients diagnosed with DM may be under better control, thus have lower HbA1c’s.
WMD has gained interest in the potential role it may play in cognitive decline and as a risk factor in stroke, and by all accounts appears related to ongoing microvascular damage. This study reaffirms the role of age and HTN play in the process, but in this case at least, also points to elevated HbA1c as another key causative factor—even independent of a diagnosis of DM. All this underscores, yet again, the critical importance of risk factor monitoring and management, hopefully long before a first AIS.