Decreased Nighttime Heart Rate Variability and Progression of White Matter Hyperintensities of Presumed Vascular Origin. A Prospective Study in Community-Dwelling Older Adults

ObjectivesEvidence on the role of autonomic dysfunction on white matter hyperintensities (WMH) progression is limited. This study aims to assess the impact of a low nighttime heart rate variability (HRV) on WMH progression in community-dwelling older adults.Materials and methodsFollowing a prospective longitudinal study design, all individuals aged ≥60 years enrolled in the Atahualpa Project Cohort from 2012 to 2019 were invited to receive baseline HRV determinations through 24-h Holter monitoring, together with clinical interviews and brain MRIs. These individuals were periodically followed by means of annual door-to-door surveys, and those who also received brain MRIs at the end of the study (May 2021) were included in the analysis. Poisson regression models, adjusted for relevant confounders, were fitted to assess the incidence rate ratio (IRR) of WMH progression according to nighttime standard deviation of normal-to-normal R-R intervals (SDNN).ResultsThis study included 254 individuals aged ≥60 years (mean age: 65.4 ± 5.9 years; 55% women). The mean nighttime SDNN was 116.8 ± 36.3 ms. Follow-up MRIs showed WMH progression in 103 (41%) individuals after a median follow-up of 6.5 years. In unadjusted analyses, nighttime SDNN was lower among participants who developed WMH progression than in those who did not (p < 0.001). A Poisson regression model, adjusted for relevant covariates, disclosed a significantly inverse association between nighttime SDNN and WMH progression (IRR: 0.99; 95% C.I.: 0.98–0.99; p = 0.014).ConclusionsStudy results show an inverse association between nighttime SDNN and WMH progression, and provide support for the role of sympathetic overactivity in this relationship.     

Impact of obstructive sleep apnea on silent cerebral small vessel disease: a systematic review and meta-analysis

BackgroundCerebral small vessel disease (CSVD) is a well-known cause of vascular dementia, a leading medical morbidity in the aging population. Obstructive sleep apnea (OSA) has been validated as a cardiovascular risk factor. However, the relationship between these two clinical syndromes is not well established. We aimed to assess the association between OSA and CSVD.MethodsDatabases were searched from inception through May 2019. Studies that reported incidence or odd ratios of CSVD in patients with OSA were included. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird.ResultsA total of 14 observational studies comprising of 4335 patients were included into the analysis. Compared to patients without OSA, patients with OSA were significantly associated with CSVD magnetic resonance imaging (MRI) findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) with a pooled OR of 2.31 (95% confidence interval [CI], 1.46–3.66, I² = 79%) and 1.78 (95% CI, 1.06–3.01, I² = 41%), respectively. However, there was no significant association between OSA and findings of cerebral microbleeds (CMBs), with a pooled odds ratio (OR) of 2.15 (95% CI, 0.64–7.29, I² = 55%).ConclusionsOur study demonstrated the association between OSA and CSVD MRI findings of white matter hyperintensity (WMH) and asymptomatic lacunar infarction (ALI) when compared to patients without OSA. The absence of an association of CMBs findings with OSA could be due either by a lower sensitivity of neuroimaging techniques utilized to detect CMBs or a potentially different pathogenesis of CMBs.     

Cerebral small vessel disease burden and functional and radiographic outcomes in intracerebral hemorrhage

Objective

To examine the effect of individual cerebral small vessel disease (CSVD) markers and cumulative CSVD burden on functional independence, ambulation and hematoma expansion in spontaneous intracerebral hemorrhage (ICH).

Methods

Retrospective analysis of prospectively collected data from an observational study of consecutive patients with spontaneous ICH, brain MRI within 1 month from ictus, premorbid modified Rankin Scale (mRS) score?≤?2, available imaging data and 90-day functional status in a tertiary academic center. Functional outcomes included 90-day functional independence (mRS?≤?2) and independent ambulation; radiographic outcome was hematoma expansion (>?12.5 ml absolute or >?33% relative increase in ICH volume). We identified the presence and burden of individual CSVD markers (cerebral microbleeds (CMBs), enlarged perivascular spaces, lacunes, white matter hyperintensities) and composite CSVD burden score and explored their association with outcomes of interest in multivariable models adjusting for well-established confounders.

Results

111 patients were included, 65% lobar ICH, with a median volume 20.8 ml. 43 (38.7%) achieved functional independence and 71 (64%) independent ambulation. In multivariable adjusted models, there was higher total CSVD burden (OR 0.61, 95% CI 0.37–0.96, p?=?0.03) and CMBs presence (OR 0.32, 95% CI 0.1–0.88, p?=?0.04) remained independently inversely associated with functional independence. Individual CSVD markers or total CSVD score had no significant relation with ambulation and ICH expansion. Larger ICH volume and deep ICH location were the major determinants of lack of independent ambulation.

Conclusions

Our findings suggest that in ICH patients without previous functional dependence, total CSVD burden and particularly presence of CMBs significantly affect functional recovery. The latter is a novel finding and merits further exploration.

     

Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors

Objective

The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice.

Methods

We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables.

Results

The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28–3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p = .016).

Significance

In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.     

Loneliness and cardiovascular disease and the role of late‐life depression

Objective

Loneliness and depression have a strong reciprocal influence, and both predict adverse health outcomes at old age. Therefore, this study examines whether loneliness is associated with the presence of cardiovascular diseases taking into account the role of late‐life depression.

Methods

Cross‐sectional data of 477 older adults in the Netherlands Study of Depressed Older Persons were used. Logistic regression analysis was performed to examine the relation between loneliness and cardiovascular disease. Depression was added to the regression model to examine whether depression is an explanatory factor in the association between loneliness and cardiovascular disease. Interaction terms between loneliness and depression and between loneliness and sex were introduced in the regression model to investigate whether depressed and non‐depressed participants, and men and women differed in their association between loneliness and cardiovascular disease.

Results

Of the overall group, 61% were lonely, 28% had a history of cardiovascular disease and 74% were depressed. Loneliness and cardiovascular disease were not associated in the overall group after adjustment for confounders (continuous: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.98–1.10), p = 0.25; dichotomous: OR = 1.27, 95% CI = 0.80–2.03, p = 0.32). For women, there was an association between loneliness and cardiovascular diseases (continuous: OR = 1.13, 95% CI = 1.06–1.21, p < 0.001; dichotomous: OR = 2.64, 95% CI = 1.50–4.65, p = 0.001), but this association was not present in men (OR = 0.96, 95% CI = 0.88–1.05, p = 0.38). This association remained significant after adjustment for confounders, but it lost significance after adding depression to the model.

Conclusion

For women only, there was an association between loneliness and cardiovascular disease. However, this association was explained by depression, indicating that loneliness in its own right seems not related with cardiovascular disease. Copyright © 2017 John Wiley & Sons, Ltd.     

Measuring change in perceived well‐being of family caregivers: validation of the Spanish version of the Perceived Change Index (PCI‐S) in Chilean dementia caregivers

Objective

Few instruments evaluate family caregiver perceptions of challenges caring for persons with dementia and improvement or worsening in these areas. To address this measurement gap, we examine psychometric properties of a Spanish version of the 13‐item Perceived Change Index (PCI‐S), originally validated with English‐speaking caregivers.

Methods

Cross‐sectional study with 94 caregivers of persons with mild to moderate dementia in Chile. Interviews included caregiver demographics, burden, health perception, distress with behaviours, dementia severity, behavioural symptoms and functionality.

Results

Caregiver mean age was 55.9 (SD ± 14.14) years and mean years caregiving was 3 (SD ± 2.60). The scale had strong internal consistency (Cronbach α = 0.94), and inter‐observer consistency (CCI = 0.99; 95% CI = 0.95–0.99). Two factors were identified: Management skills (α = 0.89), and somatic well‐being and affects (α = 0.92), explaining 63% of scale variance. Significant associations supporting convergent validity were observed for PCI‐S and subscales with caregiver burden (p < 0.01), health perceptions (p < 0.01), depressive symptoms (p < 0.01) and distress with behaviours (p < 0.01); and in persons with dementia, functionality (p < 0.05), dementia severity (p < 0.05) and behavioural symptoms (p < 0.01) in expected directions. In logistic regression models, perceived worsening (PCI‐S and subscale scores) was associated with more behavioural symptoms (OR = 1.07; 95% CI = 1.03–1.15) and caregiver burden (OR = 1.48; 95% CI = 1.18–1.86); whereas perceived improvement was associated with higher physical functioning (OR = 0.95; 95% CI = 0.91–0.99) in persons with dementia. PCI‐S scores were not associated with socio‐demographic characteristics reflecting divergent validity.

Conclusions

Spanish version of the 13‐item Perceived Change Index and its two‐factor solution is a valid and reliable measure with clinical utility to detect improvement or worsening in caregivers concerning daily care challenges. Copyright © 2017 John Wiley & Sons, Ltd.     

Surgical hematoma evacuation of cortical intracerebral hemorrhage ≥10 ml reduces risk of subsequent epilepsy by more than 70%: A retrospective monocenter study

Aim

The aim of this study was to re-evaluate risk factors for post-ICH epilepsy (PICHE) and examine the impact of surgical hematoma evacuation on epilepsy development after ICH.

Background and purpose

Epilepsy is a common complication after intracerebral hemorrhage (ICH). Information on risk factors is still scarce and the role of ICH evacuation remains uncertain.

Methods

We retrospectively included patients with spontaneous ICH treated in our hospital in 2006–2019. Patients' medical records were analyzed. In addition, mailed questionnaires and telephone interviews were used to complete the dataset. Uni- and multivariable hazard ratios (HRs) were applied to investigate risk factors for PICHE and the impact of surgical ICH evacuation.

Results

Among 587 ICH patients available for analyses, 139 (23.7%) developed PICHE (mean follow-up 1795 ± 1378 days). The median time of epilepsy onset was 7 months after ICH (range 1–132 months). Risk factors associated with PICHE were cortical hemorrhage (multivariable HR 1.65 [95% CI 1.14–2.37]; p = 0.008), ICH volume > 10 ml (multivariable HR 1.91 [95% CI 1.33–2.73]; p < 0.001) and acute symptomatic seizures (multivariable HR 1.81 [95% CI 1.20–2.75]; p = 0.005). Patients with cortical ICH > 10 ml who underwent surgical hematoma evacuation were less likely to develop epilepsy than those with conservative treatment alone (multivariable HR 0.26 [95% CI 0.08–0.84]; p = 0.025).

Conclusions

Post-ICH epilepsy is frequent and predicted by large cortical ICH and acute symptomatic seizures. Hematoma evacuation reduced the risk of PICHE by more than 70% in patients with large cortical ICH. This finding could be considered in the clinical decision making on the acute treatment of ICH.     

A systematic review and meta-analysis of respiratory dysfunction in Parkinson's disease

Introduction

Respiratory dysfunction in Parkinson's disease (PD) is common and associated with increased hospital admission and mortality rates. Central and peripheral mechanisms have been proposed in PD. To date no systematic review identifies the extent and type of respiratory impairments in PD compared with healthy controls.

Methods

PubMed, EMBASE, CINAHL, Web of Science, Pedro, MEDLINE, Cochrane Library and OpenGrey were searched from inception to December 2021 to identify case–control studies reporting respiratory measures in PD and matched controls.

Results

Thirty-nine studies met inclusion criteria, the majority with low risk of bias across Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) domains. Data permitted pooled analysis for 26 distinct respiratory measures. High-to-moderate certainty evidence of impairment in PD was identified for vital capacity (standardised mean difference [SMD] 0.75; 95% CI 0.45–1.05; p < 0.00001; I² = 10%), total chest wall volume (SMD 0.38; 95% CI 0.09–0.68; p = 0.01; I² = 0%), maximum inspiratory pressure (SMD 0.91; 95% CI 0.64–1.19; p < 0.00001; I² = 43%) and sniff nasal inspiratory pressure (SMD 0.58; 95% CI 0.30–0.87; p < 0.00001; I² = 0%). Sensitivity analysis provided high-moderate certainty evidence of impairment for forced vital capacity and forced expiratory volume in 1 s during medication ON phases and increased respiratory rate during OFF phases. Lower certainty evidence identified impairments in PD for maximum expiratory pressure, tidal volume, maximum voluntary ventilation and peak cough flow.

Conclusions

Strong evidence supports a restrictive pattern with inspiratory muscle weakness in PD compared with healthy controls. Limited data for central impairment were identified with inconclusive findings.     

Epilepsy center characteristics and geographic region influence presurgical testing in the United States

Objective

Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy.

Methods

We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank-sum, Kruskal–Wallis, and chi-squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables.

Results

The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2–6.86; p = .018) and fluorodeoxyglucose–positron emission tomography (OR = 2.74, 95% CI = = 1.14–6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23–.93; p = .031) and West (OR = .41, 95% CI = .19–.87; p = .022), odds of performing single-photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates.

Significance

Presurgical testing for drug-resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.     

Physical activity and brain health in patients with atrial fibrillation

Background and purpose

Vascular brain lesions, such as ischemic infarcts, are common among patients with atrial fibrillation (AF) and are associated with impaired cognitive function. The role of physical activity (PA) in the prevalence of brain lesions and cognition in AF has not been investigated.

Methods

Patients from the multicenter Swiss-AF cohort study were included in this cross-sectional analysis. We assessed regular exercise (RE; at least once weekly) and minutes of weekly PA using a validated questionnaire. We studied associations with ischemic infarcts, white matter hyperintensities, cerebral microbleeds, and brain volume on brain magnetic resonance imaging and with global cognition measured with a cognitive construct (CoCo) score.

Results

Among 1490 participants (mean age = 72 ± 9 years), 730 (49%) engaged in RE. In adjusted regression analyses, RE was associated with a lower prevalence of ischemic infarcts (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.63–0.98, p = 0.03) and of moderate to severe white matter hyperintensities (OR = 0.78, 95% CI = 0.62–0.99, p = 0.04), higher brain volume (β-coefficient = 10.73, 95% CI = 2.37–19.09, p = 0.01), and higher CoCo score (β-coefficient = 0.08, 95% CI = 0.03–0.12, p < 0.001). Increasing weekly PA was associated with higher brain volume (β-coefficient = 1.40, 95% CI = 0.65–2.15, p < 0.001).

Conclusions

In AF patients, RE was associated with a lower prevalence of ischemic infarcts and of moderate to severe white matter disease, with larger brain volume, and with better cognitive performance. Prospective studies are needed to investigate whether these associations are causal. Until then, our findings suggest that patients with AF should be encouraged to remain physically active.     

Evaluation of abdominal gas by plain abdominal radiographs

Background

Our aim was to determine the reliability of plain abdominal radiographs for the evaluation of abdominal gas content in patients with functional digestive symptoms.

Methods

Abdominal CT scan scout views, mimicking a conventional plain abdominal radiograph, were obtained from 30 patients both during episodes of abdominal distension and basal conditions. Physicians (n = 50) were instructed to rate the estimated volume of gas in the 60 images presented in random sequence using a scale graded from 0 to ≥600 ml.

Key Results

The gas volumes estimated in the scout views differed from those measured by CT by a median of 90 (95% CI 70–102) ml, and the misestimation was not related to the absolute volume in the image. The accuracy of the observers, measured by their mean misestimation, was not related to their specialty or the training status (misestimation by 96 (95% CI 85–104) ml in staff vs 78 (70–106) ml in residents; p = 0.297). The accuracy was independent of the order of presentation of the images. Gas volume measured by CT in the images obtained during episodes of abdominal distension differed by a median of 39 (95% CI 29–66) ml from those during basal conditions, and this difference was misestimated by a median of 107 (95% CI 94–119) ml. The accuracy of these estimations was not related to the absolute gas volumes (R = −0.352; p < 0.001) or the magnitude of the differences.

Conclusions & Inferences

Plain abdominal radiographs have limited value for the evaluation of abdominal gas volume in patients with functional gut disorders.     

Outcomes in minor stroke patients treated with intravenous thrombolysis

Aims

Our study aimed to describe the short-, medium-, and long-term outcomes of intravenous thrombolysis in minor stroke, and to explore the relationship between thrombolysis and clinical outcomes.

Methods

Our study included ischemic minor stroke patients (National Institutes of Health Stroke Scale score ≤ 5) within 4.5 h from symptom onset from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–1 at 3 months. The secondary outcomes included mRS score of 0–1 at discharge, 6 months, and 1 year. The safety outcomes were symptomatic intracerebral hemorrhage (sICH) at 24–36 h and all-cause mortality. The association between intravenous thrombolysis and clinical outcomes was studied using multivariable models.

Results

A total of 1905 minor ischemic stroke patients were included. Overall 527 patients (28%) received intravenous t-PA (IV t-PA) and 1378 patients (72%) in the non-IV t-PA group. Of them, 18.85% (359/1905) participants had a disabled outcome (defined as mRS score ≥ 2) at discharge, 12.8% (242/1885) at 3 months, 13.9% (262/1886) at 6 months, and 13.9% (260/1871) at 1 year. In multivariable analysis, IV t-PA was associated with favorable functional outcomes at discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.13–1.96; p = 0.004), 3 months (aOR 1.51; 95% CI 1.09–2.10; p = 0.01), 6 months (aOR 1.64; 95% CI 1.19–2.27; p = 0.003), and 1 year (aOR 1.52; 95% CI 1.10–2.10; p = 0.01). Symptomatic ICH occurred in 3 (0.6%) patients in IV t-PA versus 2 (0.1%) in the non-IV t-PA group. No significant differences were found in all-cause mortality between the two groups.

Conclusions

Intravenous t-PA may be safe and effective in minor stroke (NIHSS ≤ 5) within a 4.5-h window and further randomized controlled trials are warranted.     

Factors affecting the outcomes of tirofiban after endovascular treatment in acute ischemic stroke: Experience from a single center

Aims

To investigate the predicted factors influencing the outcomes in acute ischemic stroke (AIS) patients who received tirofiban after endovascular treatment (EVT) and the optimal administration of tirofiban.

Methods

In this retrospective study, AIS patients who received EVT followed by tirofiban between January 2017 and October 2021 were enrolled. The dose and duration of tirofiban were adjusted by trained clinicians according to the patient's clinical status. A reduction of at least four points on the National Institutes of Health Stroke Scale (NIHSS) after tirofiban compared with that before tirofiban was defined as an effective response. A modified ranking scale (mRS) of 0–2 was defined as a favorable outcome at a 90-day follow-up.

Results

A total of 260 consecutive patients were enrolled, and 36.5% of patients achieved a favorable outcome. The modified thrombolysis in cerebral infarction (mTICI) 2b-3 occurred in 93.5% of patients. Symptomatic intracerebral hemorrhage (sICH) occurred in 6.2% of patients, and the mortality at 90-day follow-up was 16.9%. Duration of tirofiban >24 h (adjusted OR: 2.545; 95% CI: 1.008–6.423; p = 0.048) and effective response to tirofiban (adjusted OR: 25.562; 95% CI: 9.794–66.715; p < 0.001) were related to the favorable outcome (mRS 0–2). Higher NIHSS (adjusted OR: 0.855; 95% CI: 0.809–0.904; p < 0.001) and glucose level on admission (adjusted OR: 0.843; 95% CI: 0.731–0.971; p = 0.018) were predictive for the unfavorable outcome (mRS 3–6).

Conclusions

An effective response to tirofiban is an independent factor in predicting the long-term efficacy outcome, and extending the duration of tirofiban is beneficial for neurological improvement.     

Volume of White Matter Hyperintensities,and Cerebral Micro-Bleeds

PurposeIn the past years the significance of white matter hyperintensities (WMH) has gained raising attention because it is considered a marker of severity of different pathologies. Another condition that in the last years has been assessed in the neuroradiology field is cerebral microbleeds (CMB). The purpose of this work was to evaluate the association between the volume of WMH and the presence and characteristics of CMB.Material and methodsSixty-five consecutive (males 45; median age 70) subjects were retrospectively analyzed with a 1.5 Tesla scanner. WMH volume was quantified with a semi-automated procedure considering the FLAIR MR sequences whereas the CMB were studied with the SWI technique and CMBs were classified as absent (grade 1), mild (grade 2; total number of CMBs: 1–2), moderate (grade 3; total number of CMBs: 3–10), and severe (grade 4; total number of CMBs: >10). Moreover, overall number of CMBs and the maximum diameter were registered.ResultsPrevalence of CMBs was 30.76% whereas WMH 81.5%. Mann–Whitney test showed a statistically significant difference in WMH volume between subjects with and without CMBs (p < 0.001). Pearson analysis showed significant correlation between CMB grade, number and maximum diameter and WMH. The better ROC area under the curve (Az) was obtained by the hemisphere volume with a 0.828 (95% CI from 0.752 to 0,888; SD = 0.0427; p value = 0.001). The only parameters that showed a statistically significant association in the logistic regression analysis were Hemisphere volume of WMH (p = 0.001) and Cholesterol LDL (p = 0.0292).ConclusionIn conclusion, the results of this study suggest the presence of a significant correlation between CMBs and volume of WMH. No differences were found between the different vascular territories.     

Amyotrophic lateral sclerosis regional progression intervals change according to time of involvement of different body regions

Background and purpose

The prediction of disease course is one of the main targets of amyotrophic lateral sclerosis (ALS) research, particularly considering its wide phenotypic heterogeneity. Despite many attempts to classify patients into prognostic categories according to the different spreading patterns at diagnosis, a precise regional progression rate and the time of involvement of each region has yet to be clarified. The aim of our study was to evaluate the functional decline in different body regions according to their time of involvement during disease course.

Methods

In a population-based dataset of ALS patients, we analysed the functional decline in different body regions according to time and order of regional involvement. We calculated the regional progression intervals (RPIs) between initial involvement and severe functional impairment using the ALS Functional Rating Scale revised (ALSFRS-r) subscores for the bulbar, upper limb, lower limb and respiratory/thoracic regions. Time-to-event analyses, adjusted for age, sex, ALSFRS-r pre-slope (ΔALSFRS-R), cognitive status, and mutational status were performed.

Results

The duration of RPI differed significantly among ALS phenotypes, with the RPI of the first region involved being significantly longer than the RPIs of regions involved later. Cox proportional hazard models showed that in fact a longer time between disease onset and initial regional involvement was related to a reduced duration of the RPI duration in each different body region (bulbar region: hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.06–1.16, p < 0.001; upper limb region: HR 1.16, 95% CI 1.06–1.28, p = 0.002; lower limb region: HR 1.11, 95% CI 1.03–1.19, p = 0.009; respiratory/thoracic region: HR 1.10, 95% CI 1.06–1.14, p = 0.005).

Conclusions

We found that the progression of functional decline accelerates in regions involved later during disease course. Our findings can be useful in patient management and prognosis prediction.     

Dysphagia treatments in Parkinson's disease: A systematic review and meta-analysis

Background

The majority of patients with Parkinson's disease (PD) develop oropharyngeal dysphagia during the course of their disease. However, the efficacy of dysphagia treatments for these patients remains controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate treatment efficacy based on the evidence from randomized controlled trials (RCTs).

Methods

Five electronic databases were systematically searched from inception date to April 2022. Two reviewers independently extracted and analyzed the data. The outcome measures were changes in swallowing-related characteristics based on instrumental swallowing assessments.

Key Results

An initial search identified 187 RCT studies of relevance. After screening, nine studies with a total sample size of 286 were included in the meta-analysis. The pooled effect size for all dysphagia treatments compared with control comparators was significant and medium (SMD [95% CI] = 0.58 [0.22, 0.94], p = 0.001; I² = 50%). Subgroup analysis revealed a significant and medium pooled effect size for stimulation treatments (brain stimulation, peripheral neurostimulation and acupuncture) (SMD [95% CI] = 0.54 [0.15, 0.92]; p = 0.006; I² = 22%). Specifically, the effect sizes for the single RCTs on neuromuscular stimulation (SMD [95% CI] = 1.58 [0.49, 2.86]; p = 0.005) and acupuncture (SMD [95% CI] = 0.82 [0.27, 1.37]; p = 0.003) were significant and large.

Conclusions and Inferences

Our results showed that overall, dysphagia treatments, particularly stimulation treatments, can potentially benefit PD patients. However, given the limited number of small RCTs for each type of treatment, the evidence remains weak and uncertain. Further large-scale, multicenter RCTs are warranted to fully explore their clinical efficacy in the PD population.     

First-line levetiracetam versus enzyme-inducing antiseizure medication in glioma patients with epilepsy

Objective

This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients.

Methods

In this nationwide retrospective observational cohort study, Grade 2–4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders.

Results

In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20–2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78–2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89–12.55, p = .001).

Significance

In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.     

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis

Background and purpose

This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS).

Methods

From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral-domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models.

Results

We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12–93). Mean pRNFL thickness was 92.6 μm (SD = 12.1), and mean GCIPL thickness was 81.4 μm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9–92). EDSS ≥ 3 was predicted with GCIPL < 77 μm (HR = 2.7, 95% CI = 1.6–4.2, p < 0.001) and pRNFL thickness ≤ 88 μm (HR = 2.0, 95% CI = 1.4–3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease-modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated.

Conclusions

Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers.     

Retinal ganglion cell loss is associated with future disability worsening in early relapsing–remitting multiple sclerosis

Background and purpose

Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event.

Methods

This observational cohort study included 201 patients with recently diagnosed clinically isolated syndrome or relapsing–remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, magnetic resonance imaging, and OCT at baseline and at yearly follow-up visits.

Results

Patients were included at a median disease duration of 2.0 months. During a median follow-up of 59 (interquartile range = 43–71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity 3 (NEDA-3) criteria, and 19% presented with confirmed disability worsening. A GCIP threshold of ≤77 μm at baseline identified patients with a high risk for NEDA-3 failure (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1–2.8, p = 0.04), and GCIP measures of ≤69 μm predicted disability worsening (HR = 2.2, 95% CI = 1.2–4.3, p = 0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (HR = 2.5 per 1 μm/year increase of GCIP loss, p = 0.03).

Conclusions

Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression.