Association of Ischemic Core Imaging Biomarkers With Post-Thrombectomy Clinical Outcomes in the MR CLEAN Registry

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice. Methods: We included EVT-treated patients (July 2016–November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days. Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01–1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78–0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS. Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS

Impact of Intracranial Volume and Brain Volume on the Prognostic Value of Computed Tomography Perfusion Core Volume in Acute Ischemic Stroke

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy.Results: In 200 patients, the median core volume was 13 (5–41) mL. Median ICV and TBV were 1377 (1283–1456) mL and 1108 (1020–1197) mL. Median ICVcore and TBVcore were 0.9 (0.4–2.8)% and 1.7 (0.5–3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33–0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35–0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33–0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. Conclusion:Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.</p

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype–phenotype correlations based on available evidence

Extramuscular myofascial force transmission alters substantially the acute effects of surgical aponeurotomy: assessment by finite element modeling

Effects of extramuscular myofascial force transmission on the acute effects of aponeurotomy were studied using finite element modeling and implications of such effects on surgery were discussed. Aponeurotomized EDL muscle of the rat was modeled in two conditions: (1) fully isolated (2) with intact extramuscular connections. The specific goal was to assess the alterations in muscle length-force characteristics in relation to sarcomere length distributions and to investigate how the mechanical mechanism of the intervention is affected if the muscle is not isolated. Major effects of extramuscular myofascial force transmission were shown on muscle length-force characteristics. In contrast to the identical proximal and distal forces of the aponeurotomized isolated muscle, substantial proximo-distal force differences were shown for aponeurotomized muscle with extramuscular connections (for all muscle lengths F dist > F prox after distal muscle lengthening). Proximal optimal length did not change whereas distal optimal length was lower (by 0.5 mm). The optimal forces of the aponeurotomized muscle with extramuscular connections exerted at both proximal and distal tendons were lower than that of isolated muscle (by 15 and 7%, respectively). The length of the gap separating the two cut ends of the intervened aponeurosis decreases substantially due to extramuscular myofascial force transmission. The amplitude of the difference in gap length was muscle length dependent (maximally 11.6% of the gap length of the extramuscularly connected muscle). Extramuscular myofascial force transmission has substantial effects on distributions of lengths of sarcomeres within the muscle fiber populations distal and proximal to the location of intervention: (a) Within the distal population, the substantial sarcomere shortening at the proximal ends of muscle fibers due to the intervention remained unaffected however, extramuscular myofascial force transmission caused a more pronounced serial distribution towards the distal ends of muscle fibers. (b) In contrast, extramuscular myofascial force transmission limits the serial distribution of sarcomere lengths shown for the aponeurotomized isolated muscle in the proximal population. Fiber stress distributions showed that extramuscular myofascial force transmission causes most sarcomeres within the aponeurotomized muscle to attain lengths favorable for higher force exertion. It is concluded that acute effects of aponeurotomy on muscular mechanics are affected greatly by extramuscular myofascial force transmission. Such effects have important implications for the outcome of surgery performed to improve impeded function since muscle in vivo is not isolated both anatomically and mechanically

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

A Novel Setup and Protocol to Measure the Range of Motion of the Wrist and the Hand

The human hand is important for the performance of activities of daily living which are directly related to quality of life. Various conditions, such as Duchenne muscular dystrophy (DMD) can affect the function of the human hand and wrist. The ability to assess the impairment in the hand and the wrist by measuring the range of motion (ROM), is essential for the development of effective rehabilitation protocols. Currently the clinical standard is the goniometer. In this study we explore the feasibility and reliability of an optical sensor (Leap motion sensor) in measuring active hand/wrist ROM. We measured the hand/wrist ROM of 20 healthy adults with the goniometer and the Leap motion sensor, in order to check the agreement between the two methods and additionally, we performed a test-retest of the Leap motion sensor with 12 of them, to assess its reliability. The results suggest low agreement between the goniometer and the leap motion sensor, yet showing a large decrease in measurement time and high reliability when using the later. Despite the low agreement between the two methods, we believe that the Leap motion sensor shows potential to contribute to the development of hand rehabilitation protocols and be used with patients in a clinical setting

Impact of Intracranial Volume and Brain Volume on the Prognostic Value of Computed Tomography Perfusion Core Volume in Acute Ischemic Stroke

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy.Results: In 200 patients, the median core volume was 13 (5–41) mL. Median ICV and TBV were 1377 (1283–1456) mL and 1108 (1020–1197) mL. Median ICVcore and TBVcore were 0.9 (0.4–2.8)% and 1.7 (0.5–3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33–0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35–0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33–0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. Conclusion:Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.</p