Predictors of left ventricular regional wall motion abnormalities after subarachnoid hemorrhage

Introduction  Cardiac abnormalities that have been reported after subarachnoid hemorrhage (SAH) include the release of cardiac biomarkers, electrocardiographic changes, and left ventricular (LV) systolic dysfunction. The mechanisms of cardiac dysfunction after SAH remain controversial. The aim of this study was to determine the prevalence of LV regional wall motion abnormalities (RWMA) after SAH and to quantify the independent effects of specific demographic and clinical variables in predicting the development of RWMA. Methods  Three hundred patients hospitalized with SAH were prospectively studied with serial echocardiography. The primary outcome measure was the presence of RWMA. The predictor variables included the admission Hunt & Hess grade, age, gender, cardiac risk factors, aneurysm location, plasma catecholamine levels, cardiac troponin I (cTi) level, heart rate (HR), blood pressure, and phenylephrine dose. Univariate and multivariate logistic regression was performed with adjustment for serial measurements, reporting olds ratios (OR) and 95% confidence intervals (CI). Results  In this study, 817 echocardiograms were analysed. RWMA were detected in 18% of those studied. The prevalence of RWMA in patients with Hunt & Hess grades 3–5 was 35%. Among patients with a peak cTi level grater than 1.0 μg/L, 65% had RWMA. Multivariate analysis demonstrated that high Hunt & Hess grade (OR 4.22 for grade 3–5 versus grade 1–2, p=0.046), a cTi level greater than 1.0 μg/L (OR 10.47, p=0.001), a history of prior cocaine or amphetamine use (OR 5.50, p=0.037), and higher HR (OR 1.34 per 10 bpm increase, p=0.024) were predictive of RWMA. Conclusions  RWMA were frequent after SAH. High-grade SAH, an elevation in cTi levels, a history of prior stimulant drug use, and tachycardia are independent predictors of RWMA.     

Increased cerebrospinal fluid concentrations of asymmetric dimethylarginine correlate with adverse clinical outcome in subarachnoid hemorrhage patients

Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been found in patients with subarachnoid hemorrhage (SAH). In addition, CSF levels of ADMA are associated with the severity of vasospasm. However, the relation between CSF ADMA levels and the clinical outcome of SAH patients is still unclear. We hypothesized that elevated ADMA levels in CSF might be related to the clinical outcome of SAH patients. CSF ADMA levels were measured in 20 SAH patients at days 3–5, days 7–9 and days 12–14 after SAH onset using high-performance liquid chromatography. Cerebral vasospasm was assessed by transcranial Doppler ultra sonography. Clinical outcome at 2 year follow-up was evaluated using the Karnofsky Performance Status scale (KPS). CSF ADMA concentrations in all SAH patients were significantly increased at days 3–5 (p = 0.002) after SAH, peaked on days 7–9 (p < 0.001) and remained elevated until days 12–14 (p < 0.001). In subgroup analysis, significant increases of CSF ADMA levels were found in patients both with and without vasospasm. The KPS scores significantly correlated with CSF levels of ADMA at days 7–9 (correlation coefficient = −0.55, p = 0.012; 95% confidence interval −0.80 to −0.14). Binary logistic regression analysis indicated that higher ADMA level at days 7–9 predicted a poor clinical outcome at 2 year follow-up after SAH (odds ratio = 1.722, p = 0.039, 95% confidence interval 1.029 to 2.882). ADMA may be directly involved in the pathological process and future adverse prognosis of SAH.     

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target

Objective

This study aimed to investigate the relationships of heart rate variability (HRV) with the presence, severity, and individual neuroimaging markers of cerebral small vessel disease (CSVD).

Method

A total of 4676 participants from the Third China National Stroke Registry (CNSR-III) study were included in this cross-sectional analysis. CSVD and its markers, including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA), were evaluated. Two common HRV parameters, including the square root of the mean of the sum of the squares of differences between adjacent N–N intervals (RMSSD) and the standard deviation of all N–N intervals (SDNN), were used to evaluate the function of the autonomic nervous system (ANS). Binary or ordinal logistic regression analyses were performed to investigate the association between HRV and CSVD. In addition, two-sample mendelian randomization (MR) analyses were performed to investigate the causality of HRV with CSVD.

Results

RMSSD was significantly associated with total burden of CSVD (Wardlaw's scale, common odds ratio [cOR] 0.80, 95% confidence interval [CI] 0.67–0.96, p = 0.02; Rothwell's scale, cOR 0.75, 95% CI 0.60–0.93, p = 0.008) and the presence of CSVD (Rothwell, OR 0.75, 95% CI 0.60–0.93, p = 0.008). However, no significant associations between SDNN and the presence or total burden of CSVD were observed. Moreover, RMSSD was related to WMH burden (OR 0.80, 95% CI 0.66–0.96, p = 0.02), modified WMH burden (cOR 0.82, 95% CI 0.69–0.97, p = 0.02), and Deep-WMH (OR 0.75, 95% CI 0.62–0.91, p = 0.003), while SDNN was related to Deep-WMH (OR 0.80, 95% CI 0.66–0.96, p = 0.02) and BA (cOR 0.80, 95% CI 0.68–0.95, p = 0.009). Furthermore, adding HRV to the conventional model based on vascualr risk factors enhanced the predictive performance for CSVD, as validated by the integrated discrimination index (p < 0.05). In addition, no causality between HRV and CSVD was observed in two-sample MR analyses.

Conclusion

Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.     

LDL-C/HDL-C ratio and risk of all-cause mortality in patients with intracerebral hemorrhage

Background: The low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio has been recognized as a strong risk predictor of cardiovascular diseases. However, the association between the LDL-C/HDL-C ratio and the prognosis of acute intracranial hemorrhage (ICH) is unclear. Thus, we prospectively investigated whether a low LDL-C/HDL-C ratio could predict all-cause mortality and whether LDL-C/HDL-C ratio is superior to traditional lipid profiles in predicting mortality among Chinese patients with acute ICH.

Methods: A prospective cohort study of 356 patients with acute ICH was conducted, and the mean follow-up time point was 80.4 days. Participants were divided into four categories based on LDL-C/HDL-C ratio quartiles. Three-month outcomes were evaluated by in-person or telephone interviews with patients or their family members. The end point was three-month mortality from all causes.

Results: Forty-seven deaths from all causes were documented. The multivariate analysis found that LDL-C/HDL-C ratio [hazard ratio (HR) = 0.49, p = 0.008] and LDL-C (HR = 0.27, p = 0.044) were significantly associated with all-cause mortality. The Kaplan–Meier curves show that patients in the lowest quartiles had the highest cumulative incidence rates (log-rank p = 0.027). After adjusting for covariates, a low LDL-C/HDL-C ratio was associated with a 3.55-fold increase in the risk of all-cause mortality (HR, 3.55 [95% confidence interval, 1.04–12.14]; P-trend = 0.011) when the highest and lowest quartiles were compared. The C-statistic of the LDL-C/HDL-C ratio was significantly larger than other traditional lipid profiles (all p < 0.05).

Conclusions: A low LDL-C/HDL-C ratio was independently associated with an increased risk of all-cause mortality at three months in patients with ICH. Moreover, the LDL-C/HDL-C ratio appeared to be a best lipid predictor of all-cause mortality than traditional lipid profiles.     

Genetically predicted insomnia and lung cancer risk: a Mendelian randomization study

BackgroundThe relationship between insomnia and lung cancer is scanty. The Mendelian randomization approach provides the rationale for evaluating the potential causality between genetically-predicted insomnia and lung cancer risk.MethodsWe extracted 148 insomnia-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from published genome-wide association studies (GWASs). Summary data of individual-level genetic information of participants were obtained from the International Lung Cancer Consortium (ILCCO) (29,266 cases and 56,450 controls). MR analyses were performed using the inverse-variance-weighted approach, MR pleiotropy residual sum and outlier (MR-PRESSO) test, weighted median estimator, and MR-Egger regression. Sensitivity analyses were further performed using Egger intercept analysis, leave-one-out analysis, MR-PRESSO global test, and Cochran's Q test to verify the robustness of our findings.ResultsThe results of the MR analysis indicated an increased risk of lung cancer in insomnia patients (OR = 1.1671; 95% CI 1.0754–1.2666, p = 0.0002). The subgroup analyses showed increased risks of lung adenocarcinoma (OR = 1.1878; 95% CI 1.0594–1.3317, p = 0.0032) and squamous cell lung cancer (OR = 1.1595; 95% CI 1.0248–1.3119, p = 0.0188).ConclusionOur study indicated that insomnia is a causal risk factor in the development of lung cancer. Due to the lack of evidence on both the epidemiology and the mechanism level, more studies are needed to better elucidate the results of the study.     

Cerebral venous sinus thrombosis in pregnancy and puerperium: A pooled,systematic review

Pregnancy and puerperium are risk factors for cerebral venous sinus thrombosis (CVST); however studies describing diagnosis and management in this population are limited. The objective of this study was to amalgamate published case reports and series regarding diagnosis and management of CVST in pregnancy and puerperium. Searches of PubMed and the Cochrane library were performed using search terms “pregnancy”/“puerperium” and “sinus occlusion”/“sinus thrombosis”. Studies were included in our pooled analysis if they included individual patient symptoms, management approach and follow-up condition. Multivariate regression was utilized to assess the effect of non-modifiable factors on excellent outcome (mRS 0). Sixty-six patients were included. Mean duration of symptom onset to diagnosis was 5.9 days (95% CI 4.2–7.6). Clot involvement of the superior sagittal sinus was seen in 67% of cases, the transverse/sigmoid in 64% and of the deep venous system in 15% of cases. Management approaches included anticoagulation (91% of patients), IA (intra-arterial) thrombolysis alone (26%), and IA thrombectomy with IA thrombolysis (8%). Fifty-nine percent of patients were mRS 0 at follow-up; 94% were mRS 0-2. Presentation with headache alone was associated with excellent outcome on multivariate analysis (p = 0.04); coma/obtundation predicted against excellent outcome (p = 0.03). As compared to IA thrombolysis alone, patients undergoing IA thrombolysis with IA thrombectomy demonstrated a trend toward better outcome (p = 0.10).     

Evaluation of the utility of early routine computed tomography angiography in subarachnoid hemorrhage patient outcomes

ObjectivesThe role of an early CTA approach in neurologically stable patients with nontraumatic SAH has not been assessed. This study explored the use of CTA in clinically stable SAH patients to pre-emptively identify cerebral vasospasm, to evaluate whether this approach is associated with improved clinical outcomes.MethodsWe conducted a retrospective chart review of SAH patients presenting between July 2007 and December 2016 in a single academic center. Patients were divided into two groups: (1) Early CTA (stable patients who underwent a CTA between days 5–8 post-SAH), and (2) Standard Protocol. The co-primary outcomes were a composite of the mRS at discharge and last clinical follow-up (good = 0–2; poor = 3–6). A multivariable binary logistic regression was conducted to compare both groups against outcomes, controlling for potential confounders.ResultsA total of 415 patients were included, 103 (24.8%) with early CTA, and 312 (75.2%) undergoing the standard protocol; the mean age was 57 years and 248 (59.8%) patients were female. Patients in the early CTA group had a higher modified Fisher grade (3–4) (87.4% vs 63.1%; p < 0.02). The multivariable analysis showed that early CTA was independently associated with lower poor outcomes at discharge (OR = 0.21, 95% CI 0.07–0.61, p = 0.004). Plus, vasospasm detection was associated with an increased risk of poor outcomes (OR = 4.77, 95% CI 1.41 – 16.10, p = 0.01). Early CTA was not associated with outcomes at clinical follow-up.ConclusionThe early CTA surveillance approach was associated with better functional outcomes at discharge when compared to the current imaging standard practice.     

Terson’s syndrome – Pathophysiologic considerations of an underestimated concomitant disease in aneurysmal subarachnoid hemorrhage

Terson syndrome (TS) is a common and underestimated concomitant disease in patients suffering from subarachnoid hemorrhage (SAH). Aim of this study was to evaluate the influence of an initial unconsciousness and raised intracranial pressure (ICP) on the development of TS. We performed a retrospective analysis of 213 prospective collected SAH patients screened for TS to investigate the impact of an initial unconsciousness and raised ICP on the development of TS. A univariate analysis followed by a multivariate logistic regression model was performed to identify risk factors that are associated with TS. The findings are all discussed and correlated with the present pathophysiologic considerations of TS. The rate of TS in this study was 23.9%. A higher risk of TS in the univariate analysis was associated with a Glasgow Coma scale ⩽ 7 (p = 0.001), higher Hunt and Hess grade (p = 0.001), Fisher grade IV (p = 0.002), intracerebral hemorrhage (p = 0.011), initial unconsciousness (p = 0.013) and an ICP of ⩾25 mmHg (p < 0.001). An ICP of ⩾25 mmHg was the only independent predictor for TS in the multivariate analysis (p = 0.007). TS patients had a higher mortality (p = 0.012) and a higher risk for a worse long-term outcome (p = 0.002). Notable that 5 of 51 TS patients (9.8%) in this study developed TS with no raised ICP or initial unconsciousness. Terson syndrome is a common concomitant disease in SAH patients. The pathomechanism leading to TS is not exclusively related to raised ICP levels and/or unconsciousness. However, these factors may be associated with a high percentage of TS.     

Cardiac Troponin-I: A Predictor of Prognosis in Subarachnoid Hemorrhage

Background  Release of cardiac biomarkers is reported in patients with subarachnoid hemorrhage (SAH). Data addressing the impact of cardiac injury on outcome in these patients is sparse. This study was conducted to ascertain the association of elevation of serum cardiac Troponin-I (cTnI) with mortality and neurological outcome in patients with SAH. Methods  Medical records of all patients admitted with a diagnosis of SAH and at least one measured cTnI were reviewed. Demographic and clinical variables including admission neurological status were collected. Conservative and non-parametric statistics were used to assess association between cTnI and death or neurological outcome at discharge. Results  The study group comprised of 83 patients with a mean age of 59 years. There was a female (60%) and African-American (60%) preponderance. At admission, the median Glasgow Coma Scale (GCS) was 9, and 47% had a severe Hunt–Hess grade (HHG) of ≥4. Elevation of cTnI was found in 31 (37%) patients and was associated with worse baseline Fisher grade (p=0.01) and neurological status: GCS score (p=0.006) and HHG (p=0.007). Patients with abnormal cTnI were more likely to die (55% vs.27%; odds ratio 1.3–8.4, p = 0.01) and had a worse GCS score (p = 0.008) and HHG (p = 0.004) on discharge. On multivariate analysis, peak cTnI (p = 0.04) and admission GCS score of <12 (p = 0.02) were independent predictors of death at discharge. Conclusion  Patients with subarachnoid hemorrhage and elevated cTnI are found to have worse neurological status at admission. These patients have a worse neurological outcome and in-hospital mortality.     

Lipids and amyotrophic lateral sclerosis: A two-sample Mendelian randomization study

Objective

Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and the risk of amyotrophic lateral sclerosis (ALS), potentially prone to bias. Therefore, we aimed to study whether lipid metabolism involves genetically determined risk factors for ALS through Mendelian randomization (MR) analysis.

Methods

Using genome-wide association study summary-level data for total cholesterol (TC) (n = 188,578), high-density lipoprotein cholesterol (HDL-C) (n = 403,943), low-density lipoprotein cholesterol (LDL-C) (n = 440,546), apolipoprotein A1 (ApoA1) (n = 391,193), apolipoprotein B (ApoB) (n = 439,214), and ALS (12,577 cases and 23,475 controls), we implemented a bidirectional MR study to evaluate a genetic relation between lipids and ALS risk. We performed a mediation analysis to assess whether LDL-C is a potential mediator on the pathway from traits of LDL-C-related polyunsaturated fatty acids (PUFAs) to ALS risk.

Results

We identified genetically predicted increased lipid levels to be associated with the risk of ALS, whereby elevated LDL-C had the most potent effect (OR 1.028, 95% CI 1.008–1.049, p = 0.006). The effect of increased levels of apolipoproteins on ALS was similar to their corresponding lipoproteins. ALS did not cause any changes in lipid levels. We found no relation between LDL-C-modifying lifestyles and ALS. The mediation analysis revealed that LDL-C could act as an active mediator for linoleic acid, with the mediation effect estimated to be 0.009.

Conclusions

We provided high-level genetic evidence verifying the positive link between preclinically elevated lipid and ALS risk that had been described in previous genetic and observational studies. We also demonstrated the mediating role of LDL-C in the pathway from PUFAs to ALS.     

Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fisher’s exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8–14 (8–14 versus 3–7, p = 0.016; 15 versus 3–7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8–14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3–7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8–14. To clarify and strengthen these observations, prospective, randomized trials are needed.     

Clinical predictors of early second event in patients with clinically isolated syndrome

This study aimed to determine the predictors of increased risk of a second demyelinating event within the first year of an initial demyelinating event (IDE) suggestive of early multiple sclerosis (MS). Patients with MS or clinically isolated syndrome (CIS) seen at the UCSF MS Center within one year of the IDE were studied. Univariate and multivariate Cox models were used to analyze predictors of having a second event within 1 year of the IDE. Of 330 patients with MS/CIS, 111 had a second event within 1 year. Non-white race/ethnicity (HR = 2.39, 95% CI [1.58, 3.60], p < 0.0001) and younger age (HR for each 10-year decrease in age = 1.51, 95% CI [1.28, 1.80], p < 0.0001) were strongly associated with an increased risk of having a second event within one year of onset. Having a lower number of functional systems affected by the IDE was also associated with an increased risk of early second event (HR for every one less FS involved = 1.31, 95% CI [1.06, 1.61], p = 0.011). These results were similar after adjusting for treatment of the IDE with steroids and disease-modifying therapy. Non-white race/ethnicity, younger age, and a lower number of FS affected by the IDE are associated with a substantially increased hazard ratio for a second demyelinating event within 1 year. Since early relapse is predictive of worse long-term outcome, identifying and treating such patients after the IDE may be of benefit to them.     

Developmental and Behavioral Performance of Internationally Adopted Preschoolers: A Pilot Study

Most international adoptees (IA) have rapid catch-up of the delays common at arrival. However, it is not known whether development at arrival predicts later abilities or school readiness. Therefore, we comprehensively evaluated language, fine motor, visual reception (VR), executive function (EF), attention (ATT), and sensory skills (SS) in IA preschoolers. We hypothesized that pre-adoptive risk factors, development at arrival, and the post-adoptive environment (time in day care) would predict developmental and behavioral outcomes and school readiness. 37 IA (12M:25F), currently age 4–5 years and previously seen in our clinic (mean arrival age 12 months), were evaluated with standardized tests of development, language, EF, ATT, and SS, along with demographic information, parent interview, and review of arrival clinic records. Fine motor and VR skills at arrival ranged from average to very below average. At followup, most IA were average or above average in fine motor, VR, and language skills, but many had concerning scores for ATT (42%), EF (11%) and SS (48%). Arrival expressive language T scores (Mullen) predicted follow-up scores for expressive language (PLS-4, r = .44, p = .005). Arrival fine motor scores (Mullen) correlated with follow-up auditory comprehension scores (PLS-4, r = .47, p = .002) and inversely with inattention scores (Conners’, r = −.48, p = .003). Arrival visual reception scores correlated inversely with global measures of attention (Conners’ opposition r = −.45, p = .005, ADHD scores r = −.49, p = .002, and to a lesser extent hyperactivity r = −.35, p = .03). Age at arrival was a very strong predictor of many of the outcome measures tested, including language performance, attention regulation, executive function, and sensory processing. Children who spent more time in daycare had significantly more difficulty with emotional control (p = .005). Although IA have good catch-up in specific areas of development, difficulties with ATT regulation, EF, and sensory processing may increase the risk of later school problems.     

Sex differences in limbic network and risk-taking propensity in healthy individuals

Little is known about the structural neural substrates that may contribute to sex differences in risk-taking propensity (RTP). A close association between risk-seeking behavior and the emotional-regulation network led us to hypothesize that the sex differences in RTP would be associated with sex differences in brain morphometry of the limbic network (LN). We collected RTP scores using the bubble sheet version of the evaluation of risk (EVAR) scale and neuroanatomical data from 57 healthy individuals (29 males). The EVAR scale included sub-scales measuring recklessness/impulsivity, self-confidence, and need for control (NFC). We observed significant sex differences in NFC showing greater desire for control and dominance in males than females (multivariate analysis of covariance, MANCOVAN: p = .01). Morphometry analysis showed that it was only the right LN, which showed significant sex differences in normalized surface area, normalized cortical volume, and adjusted mean curvature index (females > males) at p < .01 (MANCOVAN, corrected for multiple comparisons). Correlation analysis showed that greater curvature of the right LN was significantly associated with lower desire for control in high-risk events (r = −.31, p = .02 at 95% CI of [−0.53, –0.05]). Our findings suggest that the normalized cortical measures could indicate specific sex differences in brain morphometry, particularly within the LN. The curvature index was the only differentiating factor for greater/lower propensity for risk-taking behavior in overall sample. Therefore, the LN and the curvature measures could be key biomarkers, which play an important role in predicting risk-taking behavior.     

Ventricular Arrhythmia Risk After Subarachnoid Hemorrhage

Introduction  Cardiac morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH) are attributable to myocardial injury, decreased ventricular function, and ventricular arrhythmia (VA). Our objective was to test the relationships between QTc prolongation, VA, and survival after SAH. Methods  In 200 subjects with acute aneurysmal SAH, electrocardiograms, echocardiograms, and telemetry were evaluated. Serum electrolytes and troponin were also evaluated. Results  Initial QTc (mean 460 ± 45 ms) was prolonged (≥470 ms) in 38% of subjects and decreased on follow-up (469 ± 49 initial vs. 435 ± 31 ms follow-up; N = 89; P < 0.0001). VA was present in 14% of subjects, 52% of subjects with VA had QTc ≥ 470 ms, and initial QTc trended toward longer duration in subjects with VA (474 ± 61 vs. 457 ± 42 ms; P = 0.084). Multivariate analysis demonstrated significant predictors of VA after SAH were increasing age (OR 1.3/5 years; P = 0.025), increasing stroke severity (OR 1.8; P = 0.009), decreasing heart rate (OR 0.5/10 beats/min; P= 0.006), and the absence of angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist use at SAH onset (OR 0.10; P = 0.027). All-cause mortality was 19% (25/135) at 3 months and subjects with VA had significantly higher mortality than those without VA (37% vs. 16%; P = 0.027). Conclusions  These data demonstrate that QTc prolongation and arrhythmias are frequently noted after SAH, but arrhythmias are often not associated with QTc prolongation. In addition, the presence of VA identified subjects at greater risk of mortality following their SAH.     

Peripheral Inflammation Is Associated with Dopaminergic Degeneration in Parkinson's Disease

Background

Peripheral inflammatory immune responses are suggested to play a major role in dopaminergic degeneration in Parkinson's disease (PD). The neutrophil-to-lymphocyte ratio (NLR) is a well-established biomarker of systemic inflammation in PD. Degeneration of the nigrostriatal dopaminergic system can be assessed in vivo using [¹²³I]FP-CIT single photon emission computed tomography imaging of striatal dopamine transporter (DAT) density.

Objectives

To assess the relationship between the peripheral immune profile (NLR, lymphocytes, and neutrophils) and striatal DAT density in patients with PD.

Methods

We assessed clinical features, the peripheral immune profile, and striatal [¹²³I]FP-CIT DAT binding levels of 211 patients with PD (primary-cohort). Covariate-controlled associations between the immune response and striatal DAT levels were assessed using linear regression analyses. For replication purposes, we also studied a separate cohort of 344 de novo patients with PD enrolled in the Parkinson's Progression Markers Initiative (PPMI-cohort).

Results

A higher NLR was significantly associated with lower DAT levels in the caudate (primary-cohort: β = −0.01, p < 0.001; PPMI-cohort: β = −0.05, p = 0.05) and the putamen (primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = −0.06, p = 0.02). Intriguingly, a lower lymphocyte count was significantly associated with lower DAT levels in both the caudate (primary-cohort: β = +0.09, p < 0.05; PPMI-cohort: β = +0.11, p = 0.02) and the putamen (primary-cohort: β = +0.09, p < 0.05, PPMI-cohort: β = +0.14, p = 0.01), but an association with the neutrophil count was not consistently observed (caudate; primary-cohort: β = −0.05, p = 0.02; PPMI-cohort: β = 0, p = 0.94; putamen; primary-cohort: β = −0.04, p = 0.08; PPMI-cohort: β = −0.01, p = 0.73).

Conclusions

Our findings across two independent cohorts suggest a relationship between systemic inflammation and dopaminergic degeneration in patients with PD. This relationship was mainly driven by the lymphocyte count. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Improvement in patient outcomes following endovascular treatment of WFNS grade V subarachnoid haemorrhage from 2000 to 2014

Patient outcomes following grade V subarachnoid haemorrhage (SAH) have been dismal, although they may have improved following recent technological advances in endovascular treatment (EVT). A single-centre, retrospective study was conducted to evaluate whether outcomes have improved from 2000 to 2014 for patients with World Federation of Neurosurgical Societies (WFNS) grade V SAH. Coiling has been the preferred first-line treatment for grade V SAH patients in our institution since 2000. Patients who underwent EVT (n = 115) were grouped on the basis of their hospital admission year: 2000–2004 (n = 44), 2005–2009 (n = 37) and 2010–2014 (n = 34). Patient demographics, outcomes and in-hospital mortality rates were compared between the groups. Patient outcomes at discharge were evaluated using the Glasgow Outcome Scale (GOS), with GOS scores of 4–5 defined as favourable outcomes. There were no significant intergroup differences in patient demographics. In addition, there were no significant differences in the frequencies of favourable outcomes (14% in 2000–2004, 16% in 2005–2009 and 26% in 2010–2014). Mortality rates were 52% in 2000–2004, 43% in 2005–2009 and 24% in 2010–2014, with a significantly lower mortality rate in 2010–2014 than in 2000–2004 (p = 0.01). Both perioperative rebleeding and delayed cerebral ischaemia decreased over time; however, multivariate regression analysis showed that the former contributed more to the decrease in mortality. Age was the only variable associated with favourable outcomes. The results of this study indicate that EVT is an appropriate therapeutic option for grade V SAH patients. However, multi-centre, prospective trials are required to provide evidence-based verification of the efficacy of EVT.     

An exploratory study of serum urate levels in patients with amyotrophic lateral sclerosis

Urate is a natural antioxidant, and high serum urate levels could be protective against the development of amyotrophic lateral sclerosis (ALS). To determine if serum urate concentrations were lower in ALS patients than in healthy controls, we compared serum urate levels in 132 ALS patients and 337 age/sex-matched controls. Median urate levels were lower in ALS patients compared to controls (4.2mgl/dL [range:1.4–8.2], vs. 4.7 [1.7–13.1]; p = 0.04). In univariate analysis, high urate levels were less likely to be associated with ALS (odds ratio [OR]: 0.53; 95% CI: 0.29–0.97; p = 0.04), but after adjusting for age, sex and kidney function, the association was not statistically significant (OR: 0.63; 95% CI: 0.32–1.24; p = 0.18). Urate levels were lower in bulbar-onset ALS (3.9 mg/dL), compared to limb-onset ALS (4.3; p = 0.001), and in cases with longer disease duration compared to controls (4.1 mg/dL, vs. 4.7; p = 0.01). In this cross-sectional study, lower levels of serum urate were evident in ALS cases with bulbar-onset and longer disease duration, but were likely to be related to the malnutrition induced by ALS.     

Effect of cilostazol in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis

Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR = 0.47; 95% CI, 0.31–0.72; p < 0.001), severe vasospasm (RR = 0.48; 95% CI, 0.28–0.82; p = 0.007), vasospasm-related new cerebral infarctions (RR = 0.38; 95% CI, 0.22–0.67; p = 0.001), and poor outcome (RR = 0.57; 95% CI, 0.37–0.88; p = 0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm-related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH.     

The impact of serum magnesium and calcium on the risk of epilepsy: A mendelian randomization study

Aims

To investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach.

Methods

Single nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary-level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta-analysis was then conducted.

Results

The result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12–0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10–0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31–1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17–0.74, p = 0.006).

Conclusion

The current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.