IMPORTANCE: Predicting the duration of poststroke dysphagia is important to guide therapeutic decisions. Guidelines recommend nasogastric tube (NGT) feeding if swallowing impairment persists for 7 ...days or longer and percutaneous endoscopic gastrostomy (PEG) placement if dysphagia does not recover within 30 days, but, to our knowledge, a systematic prediction method does not exist. OBJECTIVE: To develop and validate a prognostic model predicting swallowing recovery and the need for enteral tube feeding. DESIGN, SETTING, AND PARTICIPANTS: We enrolled participants with consecutive admissions for acute ischemic stroke and initially severe dysphagia in a prospective single-center derivation (2011-2014) and a multicenter validation (July 2015-March 2018) cohort study in 5 tertiary stroke referral centers in Switzerland. EXPOSURES: Severely impaired oral intake at admission (Functional Oral Intake Scale score <5). MAIN OUTCOMES AND MEASURES: Recovery of oral intake (primary end point, Functional Oral Intake Scale ≥5) or return to prestroke diet (secondary end point) measured 7 (indication for NGT feeding) and 30 (indication for PEG feeding) days after stroke. RESULTS: In total, 279 participants (131 women 47.0%; median age, 77 years interquartile range, 67-84 years) were enrolled (153 54.8% in the derivation study; 126 45.2% in the validation cohort). Overall, 64% (95% CI, 59-71) participants failed to recover functional oral intake within 7 days and 30% (95% CI, 24-37) within 30 days. Prolonged swallowing recovery was independently associated with poor outcomes after stroke. The final prognostic model, the Predictive Swallowing Score, included 5 variables: age, stroke severity on admission, lesion location, initial risk of aspiration, and initial impairment of oral intake. Predictive Swallowing Score prediction estimates ranged from 5% (score, 0) to 96% (score, 10) for a persistent impairment of oral intake on day 7 and from 2% to 62% on day 30. Model performance in the validation cohort showed a discrimination (C statistic) of 0.84 (95% CI, 0.76-0.91; P < .001) for predicting the recovery of oral intake on day 7 and 0.77 (95% CI, 0.67-0.87; P < .001) on day 30, and a discrimination for a return to prestroke diet of 0.94 (day 7; 95% CI, 0.87-1.00; P < .001) and 0.71 (day 30; 95% CI, 0.61-0.82; P < .001). Calibration plots showed high agreement between the predicted and observed outcomes. CONCLUSIONS AND RELEVANCE: The Predictive Swallowing Score, available as a smartphone application, is an easily applied prognostic instrument that reliably predicts swallowing recovery. It will support decision making for NGT or PEG insertion after ischemic stroke and is a step toward personalized medicine.
Objective
Information about rivaroxaban plasma level (RivLev) may guide treatment decisions in patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) taking rivaroxaban.
Methods
...In a multicenter registry‐based study (Novel Oral Anticoagulants in Stroke Patients collaboration; ClinicalTrials.gov: NCT02353585) of patients with stroke while taking rivaroxaban, we compared RivLev in patients with AIS and ICH. We determined how many AIS patients had RivLev ≤ 100ng/ml, indicating possible eligibility for thrombolysis, and how many ICH patients had RivLev ≥ 75ng/ml, making them possibly eligible for the use of specific reversal agents. We explored factors associated with RivLev (Spearman correlation, regression models) and studied the sensitivity and specificity of international normalized ratio (INR) thresholds to substitute RivLev using cross tables and receiver operating characteristic curves.
Results
Among 241 patients (median age = 80 years, interquartile range IQR = 73–84; median time from onset to admission = 2 hours, IQR = 1–4.5 hours; median RivLev = 89ng/ml, IQR = 31–194), 190 had AIS and 51 had ICH. RivLev was similar in AIS patients (82ng/ml, IQR = 30–202) and ICH patients (102ng/ml, IQR = 51–165; p = 0.24). Trough RivLev(≤137ng/ml) occurred in 126/190 (66.3%) AIS and 34/51 (66.7%) ICH patients. Among AIS patients, 108/190 (56.8%) had RivLev ≤ 100ng/ml. In ICH patients, 33/51 (64.7%) had RivLev ≥ 75ng/ml. RivLev was associated with rivaroxaban dosage, and inversely with renal function and time since last intake (each p < 0.05). INR ≤ 1.0 had a specificity of 98.9% and a sensitivity of 25.7% to predict RivLev ≤ 100ng/ml. INR ≥ 1.4 had a sensitivity of 59.3% and specificity of 90.1% to predict RivLev ≥ 75ng/ml.
Interpretation
RivLev did not differ between patients with AIS and ICH. Half of the patients with AIS under rivaroxaban had a RivLev low enough to consider thrombolysis. In ICH patients, two‐thirds had a RivLev high enough to meet the eligibility for the use of a specific reversal agent. INR thresholds perform poorly to inform treatment decisions in individual patients. Ann Neurol 2018;83:451–459
The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS ...patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome CIS 5.5%, relapsing-remitting MS RRMS 85.8%, primary progressive MS PPMS 3.5%, secondary progressive MS SPMS 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Central retinal artery occlusion (CRAO) often leads to permanent monocular blindness. Hence, early recognition and rapid re-perfusion is of paramount importance. This study aims to describe ...prehospital pathways in CRAO compared to stroke and study the knowledge about CRAO.
(1) Description of baseline characteristics, prehospital pathways/delays, and acute treatment (thrombolysis/thrombectomy vs. standard of care) of patients with CRAO and ischemic stroke registered in the Swiss Stroke Registry. (2) Online survey about CRAO knowledge amongst population, general practitioners (GPs) and ophthalmologists in Eastern Switzerland.
Three hundred and ninety seven CRAO and 32,816 ischemic stroke cases were registered from 2014 until 2019 in 20 Stroke Centers/Units in Switzerland. In CRAO, 25.6% arrived at the hospital within 4 h of symptom onset and had a lower rate of emergency referrals. Hence, the symptom-to-door time was significantly longer in CRAO compared to stroke (852 min. vs. 300 min). The thrombolysis/thrombectomy rate was 13.2% in CRAO and 30.9% in stroke. 28.6% of the surveyed population recognized CRAO-symptoms, 55.4% of which would present directly to the emergency department in contrast to 90.0% with stroke symptoms. Almost 100% of the ophthalmologist and general practitioners recognized CRAO as a medical emergency and 1/3 of them considered IV thrombolysis a potentially beneficial therapy.
CRAO awareness of the general population and physician awareness about the treatment options as well as the non-standardized prehospital organization, seems to be the main reason for the prehospital delays and impedes treating CRAO patients. Educational efforts should be undertaken to improve awareness about CRAO.
Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce.
We assessed prevalence of pre-specified ICH etiologies and their association with ...outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019).
We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 interquartile range, 3 to 15). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio aOR, 1.33; 95% confidence interval CI, 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031).
Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.
Abstract Context Cancer cachexia occurs in most patients suffering from solid malignancies. Recent works suggest paraneoplastic mechanisms. Empirical studies also found autonomic dysfunction in ...cancer patients, but comprehensive evaluation of the peripheral nervous system is lacking. Objectives To further understand the role of the autonomic and peripheral nervous system in cancer cachexia to guide treatment. Methods We prospectively investigated cachectic cancer patients for parasympathetic autonomic dysfunction with a time-domain–based analysis of heart rate variability (breathing at rest, deep breath, and in response to the Valsalva maneuver). Blood pressure changes after the Valsalva maneuver were used as a marker of the sympathetic noradrenergic system. Orthostatic hypertension was investigated in response to active standing. We used a noninvasive continuous beat-to-beat heart rate assessment and blood pressure monitoring. The sympathetic cholinergic nervous system was evaluated with the sympathetic skin response. A detailed neurological examination, nerve conduction studies, and electromyography also were conducted. Results A total of 13 patients were enrolled (median age 66 years). Median time from inclusion until death was 3.5 months. About 12 of the 13 patients showed abnormal results in at least one autonomic test. Sympathetic noradrenergic and cholinergic abnormalities were discovered in six patients each and five patients had orthostatic hypotension. Only one patient showed abnormal results in parasympathetic cholinergic tests. Asymptomatic large fiber polyneuropathy was detected in eight patients. Conclusion Large fiber polyneuropathy coincides with autonomic dysfunction in cachectic cancer patients. Our findings suggest a relevant role of sympathetic impairment in cancer cachexia.
Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with ...multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies.
For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry.
We obtained 10 133 blood samples from 5390 people (median samples per patient 1 IQR 1–2 in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 IQR 3·0–8·0). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35–4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08–6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry.
The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials.
Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche.
Objective
Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases ...causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).
Methods
sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross‐sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow‐up = 3.1 years, interquartile range IQR = 2.0–4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.
Results
sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2–65.3) or both brain and spinal gadolinium‐enhancing lesions (62.5pg/ml, IQR = 42.7–71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9–41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease‐modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC‐based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval CI = 1.21–3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07–5.42, p = 0.034).
Interpretation
These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857–870
In a large trial, the estimated incidence of stroke, systemic embolism, hemorrhage, or death was 2.8 percentage points lower to 0.5 percentage points higher with early than with later use of direct ...oral anticoagulants.
Objective
The aim was to evaluate, in patients with atrial fibrillation (AF) and acute ischemic stroke, the association of prior anticoagulation with vitamin K antagonists (VKAs) or direct oral ...anticoagulants (DOACs) with stroke severity, utilization of intravenous thrombolysis (IVT), safety of IVT, and 3‐month outcomes.
Methods
This was a cohort study of consecutive patients (2014–2019) on anticoagulation versus those without (controls) with regard to stroke severity, rates of IVT/mechanical thrombectomy, symptomatic intracranial hemorrhage (sICH), and favorable outcome (modified Rankin Scale score 0–2) at 3 months.
Results
Of 8,179 patients (mean SD age, 79.8 9.6 years; 49% women), 1,486 (18%) were on VKA treatment, 1,634 (20%) on DOAC treatment at stroke onset, and 5,059 controls. Stroke severity was lower in patients on DOACs (median National Institutes of Health Stroke Scale 4, interquartile range 2–11) compared with VKA (6, 2–14) and controls (7, 3–15, p < 0.001; quantile regression: β −2.1, 95% confidence interval CI −2.6 to −1.7). The IVT rate in potentially eligible patients was significantly lower in patients on VKA (156 of 247 63%; adjusted odds ratio aOR 0.67; 95% CI 0.50–0.90) and particularly in patients on DOACs (69 of 464 15%; aOR 0.06; 95% CI 0.05–0.08) compared with controls (1,544 of 2,504 74%). sICH after IVT occurred in 3.6% (2.6–4.7%) of controls, 9 of 195 (4.6%; 1.9–9.2%; aOR 0.93; 95% CI 0.46–1.90) patients on VKA and 2 of 65 (3.1%; 0.4–10.8%, aOR 0.56; 95% CI 0.28–1.12) of those on DOACs. After adjustments for prognostic confounders, DOAC pretreatment was associated with a favorable 3‐month outcome (aOR 1.24; 1.01–1.51).
Interpretation
Prior DOAC therapy in patients with AF was associated with decreased admission stroke severity at onset and a remarkably low rate of IVT. Overall, patients on DOAC might have better functional outcome at 3 months. Further research is needed to overcome potential restrictions for IVT in patients taking DOACs. ANN NEUROL 2021;89:42–53
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