Lesion location impact on functional recovery of the hemiparetic upper limb.

The effect of stroke topography on the recovery of hemiparetic upper limb (HUL) function is unclear due to limitations in previous studies-examination of lesion effects only in one point of time, or grouping together patients with left and right hemispheric damage (LHD, RHD), or disregard to different lesion impact on proximal and distal operations. Here we used voxel-based lesion symptom mapping (VLSM) to investigate the impact of stroke topography on HUL function taking into consideration the effects of (a) assessment time (subacute, chronic phases), (b) side of damaged hemisphere (left, right), (c) HUL part (proximal, distal). HUL function was examined in 3 groups of patients-Subacute (n = 130), Chronic (n = 66), and Delta (n = 49; patients examined both in the subacute and chronic phases)-using the proximal and distal sub-divisions of the Fugl-Meyer (FM) and the Box and Blocks (B&B) tests. HUL function following LHD tended to be affected in the subacute phase mainly by damage to white matter tracts, the putamen and the insula. In the chronic phase, a similar pattern was shown for B&B performance, whereas FM performance was affected by damage only to the white matter tracts. HUL function following RHD was affected in both phases, mainly by damage to the basal ganglia, white matter tracts and the insula, along with a restricted effect of damage to other cortical structures. In the chronic phase HUL function following RHD was affected also by damage to the thalamus. In the small Delta groups the following trends were found: In LHD patients, delayed motor recovery, captured by the B&B test, was affected by damage to the sensory-motor cortex, white matter association fibers and parts of the perisilvian cortex. In the RHD patients of the Delta group, delayed motor recovery was affected by damage to white matter projection fibers. Proximal and distal HUL functions examined in LHD patients (both in the subacute and chronic phases) tended to be affected by similar structures-mainly white matter projection tracts. In RHD patients, a distinction between proximal and distal HUL functions was found in the subacute but not in the chronic phase, with proximal and distal HUL functions affected by similar subcortical and cortical structures, except for an additional impact of damage to the superior temporal cortex and the retro-lenticular internal capsule only on proximal HUL function. The current study suggests the existence of important differences between the functional neuroanatomy underlying motor recovery following left and right hemisphere damage. A trend for different lesion effects was shown for residual proximal and distal HUL motor control. The study corroborates earlier findings showing an effect of the time after stroke onset (subacute, chronic) on the results of VLSM analyses. Further studies with larger sample size are required for the validation of these results

Neutrophil Extracellular Traps Are Increased in Chronic Myeloid Leukemia and Are Differentially Affected by Tyrosine Kinase Inhibitors

Cardiovascular complications are increasingly reported with the use of certain tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML). We studied neutrophil extracellular trap (NET) formation in CML and evaluated the effect of TKIs on NET formation. Neutrophils isolated from treatment-naïve patients with CML showed a significant increase in NET formation compared to matched controls at baseline and after stimulation with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA). Expression of citrullinated histone H3 (H3cit), peptidyl arginine deiminase 4 (PAD4) and reactive oxygen species (ROS) was significantly higher in CML samples compared to controls. Pre-treatment of neutrophils with TKIs was associated with a differential effect on NET formation, and ponatinib significantly augmented NET-associated elastase and ROS levels as compared to controls and other TKIs. BCR-ABL1 retroviral transduced HoxB8-immortalized mouse hematopoietic progenitors, which differentiate into neutrophils in-vitro, demonstrated increased H3cit & myeloperoxidase (MPO) expression consistent with excess NET formation. This was inhibited by Cl-amidine, a PAD4 inhibitor, but not by the NADPH inhibitor diphenyleneiodonium (DPI). Ponatinib pre-exposure significantly increased H3cit expression in HoxB8-BCR-ABL1 cells after stimulation with IO. In summary, CML is associated with increased NET formation, which is augmented by ponatinib, suggesting a possible role for NETs in promoting vascular toxicity in CML

Psychophysic-psychological dichotomy in very early acute mTBI pain: a prospective study

To characterize the pain-related somatosensory and psychological presentation of very early acute patients with a mild traumatic brain injury (mTBI).Patients with an mTBI participated in a prospective observational study undergoing clinical, psychophysic, and psychological assessment within 72 hours after the accident. Healthy controls underwent similar protocol.One hundred acute patients with an mTBI (age 36 ± 12.5 [SD] years, range 19-67 years, 42 women) and 80 healthy controls (age 43 ± 14.3 years, range 24-74 years, 40 women) participated. Patients with an mTBI demonstrated a pronociceptive psychophysic response in most tests such as less efficient pressure-pain threshold-conditioned pain modulation (0.19 ±0.19±.09 vs. 0.91±.10 kg, < 0.001) and lower temperature needed to elicit a Pain50 response (44.72 ± 0.26°C vs 46.41 ± 0.30°C, < 0.001). Their psychophysic findings correlated with clinical pain measures, e.g., Pain50 temperature and mean head ( = -0.21, = 0.045) and neck ( = -0.26, = 0.011) pain. The pain-catastrophizing magnification subscale was the only psychological variable to show a difference from the controls, while no significant correlations were found between any psychological measures and the clinical or psychophysic pain measures.There appears to be a dichotomy between somatosensory and psychological findings in the very early acute post-mTBI stage; while the first is altered and is associated with the clinical picture, the second is unchanged. In the context of the ongoing debate on the pathophysiologic nature of the post-mTBI syndrome, our findings support its "physical" basis, free of mental influence, at least in the short time window after the injury