Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Increase in repulsive guidance molecule-a (RGMa) in lacunar and cortical stroke patients is related to the severity of the insult.

Repulsive guidance molecule-a (RGMa) inhibits angiogenesis and increases inflammation. Animal models of cerebral ischemia have shown that an increased expression of RGMa leads to larger infarction and its inhibition attenuates effects of ischemia. We report on the relationship of RGMa to stroke types and severity. This is a prospective study in patients admitted to the stroke service in Qatar. We collected the clinical determinants, including NIHSS at admission, imaging and outcome at discharge and 90-days. RGMa levels were determined by measuring mRNA levels extracted from peripheral blood mononuclear cells (PBMCs) within 24 h of onset and at 5 days. There were 90 patients (lacunar: 64, cortical: 26) and 35 age-matched controls. RGMa mRNA levels were significantly higher in the stroke patients: day 1: 1.007 ± 0.13 versus 2.152 ± 0.19 [p < 0.001] and day-5: 3.939 ± 0.36 [p < 0.0001]) and significantly higher in patients with severe stroke (NIHSS ≥ 8) compared to milder symptoms (NIHSS < 8) at day 1 (NIHSS ≥ 8: 2.563 ± 0.36; NIHSS < 8: 1.947 ± 0.2) and day 5 (NIHSS ≥ 8: 5.25 ± 0.62; NIHSS < 8: 3.259 ± 0.419). Cortical stroke patients had marginally higher RGMa mRNA levels compared to lacunar stroke at day 1 (cortical stroke: 2.621 ± 0.46 vs lacunar stroke: 1.961 ± 0.19) and day 5 (cortical stroke: 4.295 ± 0.76 vs lacunar stroke: 3.774 ± 0.39). In conclusion, there is an increase in the level of RGMa mRNA in patients with acute stroke and seen in patients with lacunar and cortical stroke. The increase in RGMa mRNA levels is related to the severity of the stroke and increases over the initial 5 days. Further studies are required to determine the effects of the increase in RGMa on stroke recovery.

Night-Time Non-dipping Blood Pressure and Heart Rate: An Association With the Risk of Silent Small Vessel Disease in Patients Presenting With Acute Ischemic Stroke.

Background and Purpose: Nocturnal non-dipping blood pressure and heart rate are associated with an increased risk of cardiovascular disease. The effects of such variance on cerebrovascular disease have not been well studied. Methods: The 24-h ambulatory blood pressure (ABPM) and heart rate were monitored with B-pro in patients with acute stroke within the initial week of hospital admission. The risk factor profiles, clinical presentation, imaging, and short-term prognosis were compared in nocturnal dippers and non-dippers (more than 10% nocturnal decrease) of blood pressure and heart rate. Results: We enrolled 234 patients in whom ABPM and MRI data were available. Heart rate data were available in 180 patients. Lacunar sub-cortical stroke was the most common acute lesion (58.9%), while hypertension (74%) and diabetes (41.5%) were the most common associated risk factors. ABPM revealed non-dipping in 69% of patients. On univariate analysis, Small Vessel Disease (SVD) was significantly more frequent in non-dippers vs. dippers (BP: 56.8 vs. 40.3% p = 0.02; heart rate: 57.9 vs. 40.7% p = 0.03). Silent strokes were also more frequent in non-dippers vs. dippers (BP: 40.7 vs. 26.4% p = 0.35; heart rate: 44.6 vs. 25.4% p = 0.01). Multivariate analysis revealed SVD to be significantly related to age, hypertension, blood pressure non-dipping, and severity of symptoms at index event. Conclusions: The presence of nocturnal non-dipping of blood pressure and heart rate are associated with an increased risk of silent stroke and SVD. Increased use of ABPM may allow for improved diagnosis of non-dippers.

Stroke Mimics: A five-year follow-up study from the Qatar Stroke Database.

BACKGROUND AND PURPOSE: Mimics comprise a third of patients presenting with an acute stroke. There is limited information on their natural history. METHODS: We evaluate long term major cardiovascular events (MACE) in stroke mimics in a prospective database from Qatar. RESULTS: Between Feb 2014 and Jan 2019, 481 patients (male: 238; female: 243) mean age 57.5 years (±18.0), with 399 (83%) medical mimics and 82 (17%) functional mimics were evaluated. Imaging revealed previous old stroke in 26.6% and small vessel disease in 5%. MACE occurred in 57 (11.9%) and there were 31 deaths (6.4%) with majority of deaths (5.6%) from cardiovascular causes. MACE was significantly higher in patients with previous stroke, p < 0.0001), coronary artery disease, p = 0.002), diabetic, p = 0.01), and hypertensive on admission, p < 0.0001. MACE were also significantly higher in patients where imaging showed a previous stroke, p = 0.006). CONCLUSION: The occurrence of MACE during follow-up suggests that patients with existing vascular disease require aggressive management of vascular risk factors.

Sex-Specific Differences in Short-Term and Long-Term Outcomes in Acute Stroke Patients from Qatar.

BACKGROUND: Sex differences may determine presentation, utility of treatment, rehabilitation, and occurrences of major adverse cardiovascular events (MACEs) in acute stroke (AS). OBJECTIVE: The purpose of the study was to evaluate the short-term prognosis and long-term outcomes in MACEs in Qatari nationals admitted with AS. METHODS: All AS patients admitted between January 2014 and February 2019 were included. We evaluated the preadmission modified Rankin scale (mRS) score, etiology and severity of symptoms, complications, and functional recovery at discharge and 90 days. MACEs were recorded for 5 years. RESULTS: There were 891 admissions for AS (mean age 64.0 ± 14.2 years) (male, n = 519 [mean age ± SD 62.9 ± 14.1 years]; female, n = 372 [mean age ± SD 65.6 ± 14.2 years] p = 0.005). There were no differences in the preadmission mRS and severity of symptoms as measured on National Institute of Stroke Scale. At discharge, the outcome was better (mRS 0-2) in men (57.8 vs. 46.0%), p = 0.0001. This difference persisted at the 90-day follow-up (mRS 0-2, male 69.4% vs. female 53.2%, p = 0.0001). At the 90-day follow-up, more women died (total deaths 70; women 38 [10.2%] versus men 32 [6.2%], p = 0.03). MACEs occurred in 25.6% (133/519) males and 30.9% (115/372) females over the 5-year follow-up period (odds ratio 0.77, 95% confidence interval 0.57-1.0, p = 0.83). CONCLUSIONS: Female patients have a poor short-term outcome following an AS when corrected for age and comorbidities. While our study cannot explain the reasons for the discrepancies, higher poststroke depression and social isolation in women may be important contributory factors, and requires further studies are required to confirm these findings.

Progression of stroke deficits in patients presenting with mild symptoms: The underlying etiology determines outcome.

BACKGROUND AND PURPOSE: Patients with acute stroke and mild or rapidly improving symptoms frequently show progression. The role of reperfusion treatment in such patients is not clear. We hypothesized that progression was most likely in patients with cortical localization and such patients may benefit from thrombolysis. MATERIAL AND METHODS: We interrogated Hamad Stroke Database to evaluate 90-days outcome in patients with acute ischemic stroke admitted within 4 hours and a NIHSS score of ≤6. Evaluation was based on localization (lacunar or cortical), multi-model imaging abnormalities and whether they received rt-PA. The 90-day mRS was used to determine outcome. RESULTS: During study period 6381 patients were admitted with acute stroke. Mild stroke within 4 hours was diagnosed in 506 [no thrombolysis: 381(lacunar: 213; cortical: 168), thrombolysis: 125 (lacunar: 45; cortical: 80)]. The rt-PA treated patients had significantly higher NIHSS (2.94±3.9 versus 1.28±2.46, p<0.0001), increased rates of complications (16.0% versus 3.9%, p<0.0001) and longer hospital stay (6.05±8.1 versus 3.78±3.6 days; p<0.001). In patients with cortical stroke, intracranial arterial occlusions (11.6% vs 3.9%, p<0.0001) and CTP mismatch (22.2% vs 4.4%, p<0.0001) were more frequent in rt-PA treated patients. Discharge mRS (33.6% versus 13.9%, p<0.001) and 90-days mRS (23.2% versus 11.8%, p = 0.002) was significantly worse in patients with cortical stroke (rt-PA-treated and untreated patients). CONCLUSIONS: The outcome in patients with mild stroke depends on lesion location (lacunar versus cortical) and severity of symptoms. Patients who receive rt-PA have significantly larger deficits, increased imaging abnormalities and higher rates of hospital complication, explaining the poor outcome in such subjects.

The Impact of Diabetes on Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND: Stroke in diabetics may delay recovery and increases the risk of early recurrence of stroke. We compared the outcomes of patients (with and without diabetes) admitted with an acute ischemic stroke (AIS) in the state of Qatar. PATIENTS AND METHODS: We prospectively compared the clinical presentation, complications, discharge outcome, and stroke recurrence at 90 days in patients with and without diabetes. RESULTS: Five thousand two hundred twenty-eight stroke patients were admitted between January 2014 and December 2017. Two thousand nine hundred sixty-one had confirmed AIS, 1695 (57.2%) had diabetes, 429 (14.5%) had prediabetes and 873 (29.5%) had no diabetes. Comparing diabetic patients to prediabetic and nondiabetics, they were significantly older (58.5 ± 11.9 versus 54.0 ± 12.9 versus 49.5 ± 13.8, P = .0001), had higher rates of hypertension (80.8% versus 67.4% versus 59.2%), previous stroke (18.0% versus 5.4% versus 6.2%), and coronary artery disease (12.9% versus 5.6% versus 5.0%; P = .001 for all). The percentage of patients with modified Rankin scale 3-6 at discharge (39.7% versus 32.6% versus 30.2%; P = .0001) and 90 days (26.7% versus 18.8% versus 21.4%, P = .001); 90-day mortality (6.2% versus 2.2% versus 5.2%; P = .03) and stroke recurrence (4.2% versus .7% versus 2.2%; P = .005) was significantly higher in diabetic patients. CONCLUSIONS: Patients with diabetes and AIS have more in-hospital complications, worse discharge outcomes, higher mortality and stroke recurrence at 90 days, compared to prediabetes and no diabetes.

Synthesis of organo cobalt-aluminum layered double hydroxide via a novel single-step self-assembling method and its use as flame retardant nanofiller in PP.

Synthesis of polypropylene/organo-layered double hydroxide (PP/OLDH) has been carried out based on self-assembled organocobalt-aluminum LDH (O-CoAl-LDH). The novel method of synthesizing self-assembled CoAl-LDH and its characterization have also been reported in details. This method is proven to be very efficient way of producing OLDH in a single step with homogeneous composition and structure. As flame-retardant nanofiller, O-CoAl-LDH shows significant decrease in heat release rate (HRR), the total heat release (THR) and the heat release capacity (HRC) of the PP composites, though the thermal stability of the compounds decreases slightly compared to the base polymer. Morphological analyses show that the LDH particles are dispersed in PP matrix in a partially exfoliated form. The activation energy calculation based on the Kissinger method reveals that O-CoAl-LDH has a positive effect on the activation energy of thermal decomposition of PP. However, in the presence of this filler, decomposition of the composites starts at an earlier stage than that of pure PP.