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Objectives We aimed to confirm the sensitivity and specificity of contrast transcranial Doppler (cTCD) in the detection of right‐to‐left shunt (RLS) compared to the current reference standard (i.e., transesophageal echocardiography—TEE) in patients aged <55 years with a cryptogenic acute ischemic stroke (AIS) or high‐risk (ABCD2 score ≥4) transient ischemic attack (TIA), and to calculate the real life delay in detecting RLS by cTCD versus TEE in a tertiary care academic stroke center. Methods Consecutive 16‐ to 54‐year‐old patients with AIS or high‐risk TIA underwent complete diagnostic workup which included, in case of undetermined etiology, cTCD and TEE. Sensitivity and specificity of cTCD, RLS characteristics, and median delay between the two tests were calculated. Results Of the 98 included patients, 52 (53%) had a cryptogenic cerebrovascular ischemic event, which displayed a 56% prevalence of RLS related to a patent foramen ovale (PFO) mainly with a high‐grade shunt. When comparing TCD with “bubble test” to TEE, sensitivity and specificity were both 100%. Median delays from symptom onset to examination were 2 (min–max 1–10) and 21 (min–max 1–60) days, respectively, for cTCD and TEE. No adverse event occurred during or after cTDC examination. Conclusions Transcranial Doppler with “bubble test” appears as the best screening test for the detection of RLS in young and middle‐aged adults with cryptogenic acute cerebral ischemic events to select patients potentially suitable for closure procedure after TEE confirmation. Contrast transcranial Doppler (cTCD) showed 100% sensitivity and specificity in the detection of right‐to‐left shunt (RLS) compared to the current reference standard (i.e., transesophageal echocardiography—TEE) in consecutive patients aged <55 years with a cryptogenic acute ischemic stroke or high‐risk transient ischemic attack. Median delays from symptom onset to examination were 2 (min–max 1–10) and 21 (min–max 1–60) days, respectively, for cTCD and TEE. Transcranial Doppler with “bubble test” appears as the best screening test for the detection of RLS in young and middle‐aged adults with cryptogenic acute cerebral ischemic events to select patients potentially suitable for closure procedure after TEE confirmation.

Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS network found 32 patients receiving rituximab as first-line therapy. Main measures were number of relapse-free patients, changes in the annualized relapse rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO patients were 45 ± 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them had AQP4 antibodies. The median disease duration was 6.5 months (1–410), the mean EDSS was 5.8 ± 2.4 and the mean ARR was 3.8 ± 4.3. After rituximab with a mean follow-up of 28.7 ± 21 months, twenty-seven patients (84.3 %) were relapse free. Patients presented a 97 % decrease of ARR ( p  = 0.00001). EDSS decreased significantly to 3.9 ± 2.6 ( p  = 0.01). No relevant side effect was noted. New retrospective data are presented on RTX use in NMOSD. When used as first-line therapy RTX is highly effective and well tolerated.

Carotid stenting is a potential alternative to carotid endarterectomy but whether this technique is as safe as surgery and whether the long-term protection against stroke is similar to that of surgery are unclear. We previously reported that in patients in the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the rate of any stroke or death within 30 days after the procedure was higher with stenting than with endarterectomy. We now report the results up to 4 years. In this follow-up study of a multicentre, randomised, open, assessor-blinded, non-inferiority trial, we compared outcome after stenting with outcome after endarterectomy in 527 patients who had carotid stenosis of at least 60% that had recently become symptomatic. The primary endpoint of the EVA-3S trial was the rate of any periprocedural stroke or death (ie, within 30 days after the procedure). The prespecified main secondary endpoint was a composite of any periprocedural stroke or death and any non-procedural ipsilateral stroke during up to 4 years of follow-up. Other trial outcomes were any stroke or periprocedural death, any stroke or death, and the above endpoints restricted to disabling or fatal strokes. This trial is registered with ClinicalTrials.gov, number NCT00190398. 262 patients were randomly assigned to endarterectomy and 265 to stenting. The cumulative probability of periprocedural stroke or death and non-procedural ipsilateral stroke after 4 years of follow-up was higher with stenting than with endarterectomy (11·1% vs 6·2%, hazard ratio [HR] 1·97, 95% CI 1·06–3·67; p=0·03). The HR for periprocedural disabling stroke or death and non-procedural fatal or disabling ipsilateral stroke was 2·00 (0·75–5·33; p=0·17). A hazard function analysis showed the 4-year differences in the cumulative probabilities of outcomes between stenting and endarterectomy were largely accounted for by the higher periprocedural (within 30 days of the procedure) risk of stenting compared with endarterectomy. After the periprocedural period, the risk of ipsilateral stroke was low and similar in both treatment groups. For any stroke or periprocedural death, the HR was 1·77 (1·03–3·02; p=0·04). For any stroke or death, the HR was 1·39 (0·96–2·00; p=0·08). The results of this study suggest that carotid stenting is as effective as carotid endarterectomy for middle-term prevention of ipsilateral stroke, but the safety of carotid stenting needs to be improved before it can be used as an alternative to carotid endarterectomy in patients with symptomatic carotid stenosis. French Ministry of Health.

Hereditary spastic paraplegias (HSPs) are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may also be produced by inborn errors of metabolism. We performed next-generation sequencing of 4813 genes in one adult twin pair with HSP and severe muscular weakness occurring at the same age. We found two pathogenic compound heterozygous variants in MTHFR, including a variant not referenced in international databases, c.197C>T (p.Pro66Leu) and a known variant, c.470G>A (p.Arg157Gln), and two heterozygous pathogenic variants in POLG, c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile). MTHFR and POLG mutations were consistent with the severe muscle weakness and the metabolic changes, including hyperhomocysteinemia and decreased activity of both N(5,10)methylenetetrahydrofolate reductase (MTHFR) and complexes I and II of the mitochondrial respiratory chain. These data suggest the potential role of MTHFR and POLG mutations through consequences on mitochondrial dysfunction in the occurrence of spastic paraparesis phenotype with combined metabolic, muscular, and neurological components.

Objectives: To describe different sleep disorders and daytime sleepiness in a French population of randomly selected young women during pregnancy and to evaluate the frequency of these sleep disorders according to the three trimesters of pregnancy. Methods: Cross-sectional design with retrospective survey of pre-pregnancy, symptoms and prospective survey of current symptoms. Mothers were interviewed during pregnancy with a questionnaire to evaluate their sleep before pregnancy and to assess alterations in their sleep according to the trimester. Results: 871 pregnant women completed the questionnaire. The rate of pregnant women with insomnia with non-refreshing sleep and frequent awakenings increases during the second and the third trimester reaching more than 75% of the women, essentially due to an urge to urinate, movements of the fetus, backache and restless legs syndrome. Snoring also increases throughout the pregnancy with more than 18% of them snoring every night. Conversely, more than 75% of the women complained of a decrease in their vigilance and a need to nap inreased during the pregnancy. Conclusions: The subjective quality of sleep is disturbed as early as the first trimester of pregnancy and increases throughout the pregnancy, except for excessive daytime sleepiness which was more frequent during the first trimester.

Abstract Study Objectives Sleep deprivation alters inspiratory endurance by reducing inspiratory motor output. Vagal tone is involved in exercise endurance. This study aimed to investigate the effect of sleep deprivation on vagal tone adaptation in healthy subjects performing an inspiratory effort. Methods Vagal tone was assessed using Heart Rate Variability normalized units of frequency domain component HF (high frequency) before, at the start, and the end of an inspiratory loading trial performed until exhaustion by 16 volunteers after one night of sleep deprivation and one night of normal sleep, where sleep deprivation reduced the inspiratory endurance by half compared to the normal sleep condition (30 min vs 60 min). Results At rest, heart rate was similar in sleep deprivation and normal sleep conditions. In normal sleep condition, heart rate increased during inspiratory loading task; this increase was greater in sleep deprivation condition. In normal sleep condition, vagal tone increased at the beginning of the trial. This vagal tone increase was absent in sleep deprivation condition. Conclusions Sleep deprivation abolished vagal tone response to inspiratory load, possibly contributing to a higher heart rate during the trial and to a reduced inspiratory endurance. Clinical Trial Registration NCT02725190.

In this randomized trial of patients with symptomatic carotid stenosis of 60% or more, patients who underwent endarterectomy had lower rates of death or stroke at 1 month and 6 months than patients who underwent stenting. In this randomized trial of patients with symptomatic carotid stenosis of 60% or more, patients who underwent endarterectomy had lower rates of death or stroke at 1 month and 6 months than patients who underwent stenting. Findings from two large randomized, clinical trials 1 – 3 have established endarterectomy as the standard treatment for severe symptomatic carotid-artery stenosis. As compared with endarterectomy, stenting avoids the need for general anesthesia and an incision in the neck that could lead to nerve injury and wound complications. The costs may be less than those of surgery, mainly because the hospital stay is shorter. However, stenting also carries a risk of stroke and local complications, and the long-term efficacy of this technique is not well known. A systematic review 4 of five randomized trials comparing stenting with endarterectomy 5 – 10 concluded that the current . . .

Aims: To describe the frequency of restless legs syndrome (RLS) in a French population of randomly selected women during their third trimester of pregnancy and its evolution up to 3 months after delivery and to identify potential factors associated with the improvement of RLS after delivery. Methods: A cross-sectional questionnaire survey. Results: 186 pregnant women living in a French town were included. 32% of women were affected by RLS during the third trimester of their pregnancy. Multiple pregnancies and iron intake during pregnancy were significantly associated with RLS during the third trimester. RLS disappeared after delivery among 64.8% of the women, and by less than 2 weeks after delivery in half of them. This improvement after delivery was not associated with the number of previous pregnancies, the RLS severity and iron intake during pregnancy, peridural anaesthesia, caesarean section, delivery complications, newborn weight, breastfeeding, dopaminergic agent intake after delivery, and with the absence of RLS before pregnancy. Conclusions: RLS affects one third of pregnant women during their third trimester and usually improves after delivery. Although there is no allowed treatment, most of the time only counselling and iron status assessment should be provided.

In France, two therapeutic strategies can be offered after fingolimod (FNG) withdrawal to highly active relapsing–remitting multiple sclerosis (RRMS) patients: natalizumab (NTZ) or anti-CD20. We compared the effectiveness of these two strategies as a switch for FNG within the OFSEP database. The primary endpoint was the time to first relapse. Other outcomes were the relapse rates over 3-month periods, time to worsening the EDSS score, proportion of patients with worsened 24-month MRI, time to treatment discontinuation, and incidence rates of serious adverse events. The dynamics of event rates over time were modeled using multidimensional penalized splines, allowing the possibility to model the effects of covariates in a flexible way, considering non-linearity and interactions. A total of 740 patients were included (337 under anti-CD20 and 403 under NTZ). There was no difference between the two treatments regarding the dynamic of the first occurrence of relapse, with a monthly probability of 5.0% at initiation and 1.0% after 6 months. The rate of EDSS worsening increased in both groups until 6 months and then decreased. No difference in the proportion of patients with new T2 lesions at 24 months was observed. After 18 months of follow-up, a greater risk of NTZ discontinuation was found compared to anti-CD20. This study showed no difference between NTZ and anti-CD20 after the FNG switch regarding the clinical and radiological activity. The effect of these treatments was optimal after 6 months and there was more frequent discontinuation of NTZ after 18 months, probably mainly related to JC virus seroconversions.

ImportanceThere is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).ObjectivesTo report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.Design, Setting, and ParticipantsThe KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019.ExposureIVT and/or EVT.Main Outcomes and MeasuresPrimary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]).ResultsOverall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P < .01). Median time from stroke onset to imaging was higher in the EVT group at 3 hours and 7 minutes (IQR, 2 hours and 3 minutes to 6 hours and 24 minutes) vs 2 hours and 39 minutes (IQR, 1 hour and 51 minutes to 4 hours and 13 minutes) (P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P < .01). Death occurred in 3 patients (4.4%). Median pedNIHSS reduction at 24 hours was 4 (IQR, 0-9) points. Intracerebral hemorrhage occurred in 4 patients and symptomatic intracerebral hemorrhage occurred in 1 patient, all in the EVT group. The median mRS was 2 (IQR, 0-3) at day 90 and 1 (IQR, 0-2) at 1 year, which was not significantly different between EVT and IVT only groups, although different in initial severity.Conclusions and RelevanceThe findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS.