Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Prevalence and Predictors of Hemorrhagic Foci on Long-term Follow-up MRI of Recent Single Subcortical Infarcts.

Hemorrhagic foci surrounding the lacune in the long-term evolution of recent single subcortical infarcts (RSSIs) remains largely unexplored. We aimed to determine the prevalence, characteristics, and predictors of hemorrhagic foci in patients with RSSI. From a prospective, longitudinal study of RSSIs, we recruited patients who underwent multimodal MRI assessments both at baseline and approximately one year after the stroke onset. Hemorrhagic foci were identified using susceptibility-weighted imaging (SWI). Among 101 patients with RSSI, nearly half (n = 45, 44.6%) had hemorrhagic foci within the index RSSI lesions on follow-up SWI. RSSIs with hemorrhagic foci formation were associated with a longer time to follow-up imaging (median 449 versus 401 days, P = 0.005) and higher likelihood of being located in the anterior circulation compared to those without hemorrhagic foci (88.9% versus 64.3%, P = 0.003). Hemorrhagic foci were also associated with larger lesion size (P < 0.001), a higher proportion of cavitation formation (P = 0.003), higher baseline NIHSS scores (P = 0.004), and poorer functional outcomes (P = 0.001). In the subset of RSSIs in the lenticulostriate artery (LSA) territory, after adjustment for covariates, larger initial lesion volume (OR 1.80, 95% CI 1.13-2.87; P = 0.014) and greater decreases in LSA total length (OR 0.59, 95% CI 0.36-0.96; P = 0.035) were independently associated with hemorrhagic foci formation. The extent of ischemia in the initial infarct is predictive of the presence of hemorrhagic residues. Our findings contribute to the current understanding of the mechanisms underlying the evolution of RSSIs.

Multiple Hypointense Vessels are Associated with Cognitive Impairment in Patients with Single Subcortical Infarction.

We aimed to explore the relationship between multiple hypointense vessels and cognitive function in patients with single subcortical infarction (SSI) and the role of SSI with different etiological mechanisms in the above relationship. Multiple hypointense vessels were measured by the number of deep medullary veins (DMVs), DMVs score, and cortical veins (CVs) score. The Montreal Cognitive Assessment (MoCA), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) were assessed to evaluate cognitive function. SSI was dichotomized as branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI by whole-brain vessel-wall magnetic resonance imaging. We included a total of 103 acute SSI patients. After adjustments were made for related risk factors of cognitive function, the SSI patients with higher DMVs score were more likely to have longer STT-B (P = 0.001) and smaller STT-B-1 min (P = 0.014), and the SSI patients with higher CVs score were more likely to have shorter STT-A (P = 0.049). In subgroup analysis, we found that the negative relationship between DMVs scores and cognitive function and the positive relationship between CVs scores and cognitive function were significantly stronger in BAD patients. We provided valuable insights into the associations between DMVs, CVs, and multi-domain cognitive impairment in SSI patients, which underscored the necessity to further study the dynamic alterations of venules and their specific influence on post-stroke cognitive impairment.

Retinal microvascular and structural changes in intracranial hypertension patients correlate with intracranial pressure.

AIMS: We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We also investigated the association between clinical parameters and retinal changes in IH patients. METHODS: Intracranial hypertension patients were divided into eyes with papilledema (IH-P) and eyes without papilledema (IH-WP). IH patients underwent lumbar puncture to measure intracranial pressure (ICP); visual acuity was performed using the Snellen chart. Optical coherence tomography (OCT) was used to image and measure the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) while OCT angiography was used to image and measure the superficial vascular complex (SVC) and deep vascular complex (DVC). RESULTS: Intracranial hypertension patients showed reduced microvascular densities and thinner retinal thicknesses compared with the control group (all p < 0.001). Compared with the control group, IH-P showed reduced microvascular densities and thinner retinal thicknesses (all p < 0.001). IH-P showed reduced SVC density and thinner retinal thicknesses when compared with IH-WP (p = 0.008 for SVC, p = 0.025 for RNFL, and p = 0.018 for GCIPL). ICP correlated with the microvascular densities and GCIPL thickness in IH patients (p = 0.025 for GCIPL, p = 0.004 for SVC, and p = 0.002 for DVC). A significant association of ICP with SVC (p = 0.010) and DVC (p = 0.005) densities were also found in IH-P. CONCLUSIONS: Given the observed differences in these noninvasive retinal imaging markers, further research into their clinical utility in IH is needed.

Efficacy of Early Intensive Blood Pressure Management After Thrombectomy: Protocol for a Randomized Controlled Clinical Trial (IDENTIFY).

BACKGROUND: The optimal strategy for blood pressure management after thrombectomy remains unknown. The primary objective of The Early Intensive Blood Pressure Management after Endovascular Thrombectomy (IDENTIFY) study is to explore the efficacy and safety of early intensive blood pressure management strategies after thrombectomy compared with that of standard management. METHODS: The IDENTIFY study is a prospective, randomized, open-label, assessor-blinded multicenter clinical trial. Patients with acute anterior circulation ischaemic stroke who underwent endovascular thrombectomy within 6 h of stroke onset, achieved successful recanalization, and had two consecutive blood pressure readings > 130 mm Hg during the first 6 h after thrombectomy will be enrolled and centrally randomized into intensive or standard management groups in a 1:1 ratio. Continuous blood pressure monitoring will be initiated at the end of thrombectomy, and patients with high blood pressure during the transfer to the wards will also be enrolled. For patients in the intensive management group, the target blood pressure will be < 130 mm Hg, and the use of antihypertensive drugs will be discontinued if systolic blood pressure goes below 110 mm Hg. The target blood pressure for the standard management group will be < 180 mm Hg, and if systolic blood pressure decreases below 140 mm Hg, the use of antihypertensive drugs will be stepwise decreased until the systolic blood pressure reaches 140 mm Hg again or the infusion is discontinued. Patients will have their blood pressure reduced to the target range within 1 h from randomization and maintained until 24 h after thrombectomy with intravenous hypertensive drugs. A sample size of 600 was predicted. The primary outcome will be the rate of dependency (modified Rankin Scale scores 3-6) at 90 days. Secondary outcomes will include intracerebral hemorrhage (either symptomatic or asymptomatic) within 24 h and 7 days, malignant brain oedema, all-cause death, death and severe disability at 90 days, and quality of life at 90 days, which will be measured using the EuroQol-5 Dimensions-5 Level (EQ-5D-5L) and the 36-Item Short Form Health Survey (SF-36). Safety outcomes will include stroke recurrence within 24 h, early neurological deterioration, hypotension within 24 h, death within 7 days after endovascular thrombectomy, and all-cause acute kidney injury. Trial registration chictr.org.cn (identifier: ChiCTR2200057770). Registered March 17, 2022, http://www.chictr.org.cn/edit.aspx?pid=162575&htm=4.

Alterations of optic tract and retinal structure in patients after thalamic stroke.

Objectives: To investigate the association between degeneration of retinal structure and shrinkage of the optic tract in patients after thalamic stroke. Materials and methods: Patients with unilateral thalamic stroke were included. Structural magnetic resonance imaging (MRI) and optical coherence tomography (OCT) were performed to obtain parameters of optic tract shrinkage (lateral index) and retina structural thickness (retinal nerve fiber layer, RNFL; peripapillary retinal nerve fiber layer, pRNFL; ganglion cell-inner plexiform layer, GCIP), respectively. Visual acuity (VA) examination under illumination was conducted using Snellen charts and then converted to the logarithm of the minimum angle of resolution (LogMAR). We investigated the association between LI and OCT parameters and their relationships with VA. Results: A total of 33 patients and 23 age-sex matched stroke-free healthy controls were enrolled. Patients with thalamic stroke showed altered LI compared with control participants (P = 0.011) and a significantly increased value of LI in the subgroup of disease duration more than 6 months (P = 0.004). In these patients, LI were significantly associated with pRNFL thickness (ß = 0.349, 95% confidence interval [CI]: 0.134-0.564, P = 0.002) after adjusting for confounders (age, sex, hypertension, diabetes, dyslipidemia, and lesion volume). LI and pRNFL were both significantly associated with VA in all patients (LI: ß = -0.275, 95% CI: -0.539 to -0.011, P = 0.041; pRNFL: ß = -0.023, 95% CI: -0.046 to -0.001, P = 0.040) and in subgroup of disease duration more than 6 months (LI: ß = -0.290, 95% CI: -0.469 to -0.111, P = 0.002; pRNFL: ß = -0.041, 95% CI: -0.065 to -0.017, P = 0.003). Conclusion: Shrinkage of the optic tract can be detected in patients with thalamic stroke, especially after 6 months of stroke onset. In these patients, the extent of optic tract atrophy is associated with pRNFL thickness, and they are both related to visual acuity changes.

Association between Deep Medullary Veins in the Unaffected Hemisphere and Functional Outcome in Acute Cardioembolic Stroke: An Observational Retrospective Study.

Objective: To explore whether deep medullary veins (DMVs) in the unaffected hemisphere were associated with functional outcome in acute cardioembolic stroke patients. Methods: Acute cardioembolic stroke patients at a single center were retrospectively included. DMVs visibility in the unaffected hemisphere was assessed using a well-established four-grade scoring method based on susceptibility-weighted imaging (SWI): grades 0−3 (grade 0 for no visible DMVs; grade 1 for the numbers of conspicuous DMVs < 5; grade 2 for numbers raging from 5 to 10; grade 3 for more than 10). Patients were further divided into mild-to-moderate (grade 0−2) and severe DMVs (grade 3) groups. Functional outcomes were evaluated using the modified Rankin scale (mRS) score at three months. Poor outcome was defined as mRS ≥ 3. Binary logistic regression analysis was used to explore the association between DMVs grade and functional outcome. Results: A total of 170 patients were finally included. Compared with the mild-to-moderate DMVs group (149 patients), the severe DMVs group (21 patients) had higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.002), lower levels of admission systolic blood pressure (BP) (p = 0.031), and elevated rates of large infarction (p = 0.003). At three months, the severe DMVs group had higher mRS (p = 0.002). Patients in the poor outcome group (82/170, 48.2%) had older age, higher baseline NIHSS score, lower admission diastolic BP, higher rates of hemorrhagic transformation and large infarction, and an increased proportion of severe DMVs (all p < 0.05). After adjusting for confounders, multivariable regression analysis showed that the severe DMVs grade (adjusted odds ratio [OR] = 5.830, 95% confidence interval [CI] = 1.266−26.856, p = 0.024) was significantly associated with three-month functional outcomes without interaction with other potential risk factors (p for interaction > 0.05). Conclusions: DMVs grade in the unaffected hemisphere was independently associated with three-month functional outcome in acute cardioembolic stroke patients. Patients with severe DMVs were more likely to have a poor functional outcome at three months.

Characterization of Macular Structural and Microvascular Changes in Thalamic Infarction Patients: A Swept-Source Optical Coherence Tomography-Angiography Study.

Background: The retina and brain share similar neuronal and microvascular features. We aimed to investigate the retinal thickness and microvasculature in patients with thalamic infarcts compared with control participants. Material and methods: Swept-source optical coherence tomography (SS-OCT) was used to image the macular thickness (retinal nerve fiber layer, RNFL; ganglion cell-inner plexiform layer, GCIP), while OCT angiography was used to image the microvasculature (superficial vascular plexus, SVP; intermediate capillary plexus, ICP; deep capillary plexus, DCP). Inbuilt software was used to measure the macular thickness (µm) and microvascular density (%). Lesion volumes were quantitively assessed based on structural magnetic resonance images. Results: A total of 35 patients with unilateral thalamic infarction and 31 age−sex-matched controls were enrolled. Compared with control participants, thalamic infarction patients showed a significantly thinner thickness of RNFL (p < 0.01) and GCIP (p = 0.02), and a lower density of SVP (p = 0.001) and ICP (p = 0.022). In the group of patients, ipsilateral eyes showed significant reductions in SVP (p = 0.033), RNFL (p = 0.01) and GCIP (p = 0.043). When divided into three groups based on disease duration (<1 month, 1−6 months, and >6 months), no significant differences were found among these groups. After adjusting for confounders, SVP, ICP, DCP, RNFL, and GCIP were significantly correlated with lesion volume in patients. Conclusions: Thalamic infarction patients showed significant macular structure and microvasculature changes. Lesion size was significantly correlated with these alterations. These findings may be useful for further research into the clinical utility of retinal imaging in stroke patients, especially those with damage to the visual pathway.

Lymphocyte-to-monocyte ratio and risk of hemorrhagic transformation in patients with acute ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke (AIS), and inflammation has been found to play an important role in the occurrence of HT. We aimed to investigate the impact of lymphocyte-to-monocyte ratio (LMR), a maker of inflammatory status, on HT in patients with AIS. METHODS: Consecutive AIS patients within 7 days from stroke onset were enrolled between January 2016 and October 2017. LMR was calculated according to lymphocyte and monocyte counts obtained within 24 h on admission. Patients were categorized into three groups according to LMR tertiles. HT was detected by follow-up computed tomography (CT) or magnetic resonance imaging (MRI) during hospitalization. The multivariate logistic analysis was used to evaluate the independent relationship between LMR and HT. RESULTS: A total of 1005 patients were finally included. HT was observed in 99 (9.9%) patients, with 51 (5.1%) hemorrhagic infarction (HI) and 48 (4.8%) parenchymal hematoma (PH). After adjustment for potential confounders, the odds ratio (OR) of HT was 0.523 (95% confidence interval [CI] 0.293-0.936, P = 0.029) for the highest LMR tertile compared with the lowest tertile. Multiple-adjusted spline regression model showed a nonlinear approximately L-shaped relationship between LMR levels and HT (P for nonlinear trend = 0.030). There was no significant association of baseline LMR with PH (OR 0.562, 95% CI 0.249-1.268, P = 0.165). CONCLUSION: Lower LMR was independently related to higher risk of HT in patients with AIS. Admission LMR may be used as one of the predictors for HT. Further prospective multicenter studies are needed to validate our findings.