Prognostic information of gaze deviation in acute ischemic stroke patients.

INTRODUCTION: Gaze deviation (GD) in acute ischemic stroke patients has been suggested to be associated with poor outcome and with the presence of large vessel occlusion. Our aim was to study the prognostic significance of GD in ischemic stroke patients submitted to acute revascularization treatments. METHODS: Retrospective single-center study of consecutive anterior circulation ischemic stroke patients submitted to thrombolysis and/or endovascular revascularization between 2007 and 2017. The groups of patients with and without GD were compared concerning baseline clinical and imagiological variables, functional outcome at 3 months, and survival at 1 year. RESULTS: Among a study population of 711 patients, 332 (46.7%) presented GD. Patients with GD were more frequently of female sex (p = 0.048), had higher baseline NIHSS scores (p < 0.001), had lower ASPECTS on baseline CT (p < 0.001), more frequently had ischemia of the right hemisphere (p < 0.001), presented higher NIHSS 24 hours after treatment (p < 0.001), and more frequently presented cardioembolic stroke (p = 0.003). In the unadjusted analyses, GD was associated with decreased 3-month functional independence and increased 1-month and 1 year mortality (p < 0.001). After adjustment for variables of interest, namely, for NIHSS 24 hours after treatment, GD was no longer associated with functional outcome or survival. CONCLUSIONS: GD in patients with acute ischemic stroke is associated with increased clinical and imagiological severity at baseline. However, in patients submitted to acute revascularization treatments, this does not appear to be independent predictor of functional outcome or survival.

A role for prolyl isomerase PIN1 in the phosphorylation-dependent modulation of PRRXL1 function.

Prrxl1 encodes for a paired-like homeodomain transcription factor essential for the correct establishment of the dorsal root ganglion - spinal cord nociceptive circuitry during development. Prrxl1-null mice display gross anatomical disruption of this circuitry, which translates to a markedly diminished sensitivity to noxious stimuli. Here, by the use of an immunoprecipitation and mass spectrometry approach, we identify five highly conserved phosphorylation sites (T110, S119, S231, S233 and S251) in PRRXL1 primary structure. Four are phospho-S/T-P sites, which suggest a role for the prolyl isomerase PIN1 in regulating PRRXL1. Accordingly, PRRXL1 physically interacts with PIN1 and displays diminished transcriptional activity in a Pin1-null cell line. Additionally, these S/T-P sites seem to be important for PRRXL1 conformation, and their point mutation to alanine or aspartate down-regulates PRRXL1 transcriptional activity. Altogether, our findings provide evidence for a putative novel role of PIN1 in the development of the nociceptive system and indicate phosphorylation-mediated conformational changes as a mechanism for regulating the PRRXL1 role in the process.