Autobiographical memories in our lives are critically dependent on temporal lobe structures. However, the contribution of CA1 neurons in the human hippocampus to the retrieval of episodic ...autobiographical memory remains elusive. In patients with a rare acute transient global amnesia, highly focal lesions confined to the CA1 field of the hippocampus can be detected on MRI. We studied the effect of these lesions on autobiographical memory using a detailed autobiographical interview including the remember/know procedure. In 14 of 16 patients, focal lesions in the CA1 sector of the hippocampal cornu ammonis were detected. Autobiographical memory was significantly affected over all time periods, including memory for remote periods. Impairment of episodic memory and autonoetic consciousness exhibited a strong temporal gradient extending 30 to 40 y into the past. These results highlight the distinct and critical role of human hippocampal CA1 neurons in autobiographical memory retrieval and for re-experiencing detailed episodic memories.
The CA1 (cornu ammonis) region of hippocampus is selectively vulnerable to a variety of metabolic and cytotoxic insults, which is mirrored in a delayed neuronal death of CA1 neurons. The basis and ...mechanisms of this regional susceptibility of CA1 neurons are poorly understood, and the correlates in human diseases affecting the hippocampus are not clear. Adopting a translational approach, the lesion evolution, temporal course, pattern of diffusion changes, and damage in hippocampal CA1 in acute neurologic disorders were studied using high-resolution magnetic resonance imaging. In patients with hippocampal ischemia (n = 50), limbic encephalitis (n = 30), after status epilepticus (n = 17), and transient global amnesia (n = 53), the CA1 region was selectively affected compared with other CA regions of the hippocampus. CA1 neurons exhibited a maximum decrease of apparent diffusion coefficient (ADC) 48 to 72 hours after the insult, irrespective of the nature of the insult. Hypoxic-ischemic insults led to a significant lower ADC suggesting that the ischemic insult results in a stronger impairment of cellular metabolism. The evolution of diffusion changes show that CA1 diffusion lesions mirror the delayed time course of the pathophysiologic cascade typically observed in animal models. Studying the imaging correlates of hippocampal damage in humans provides valuable insight into the pathophysiology and neurobiology of the hippocampus.
Soft-tissue sarcomas (STS) are rare tumors of the soft tissue. Recent diagnostic studies on STS mainly dealt with only few cases of STS and did not investigate the post-therapeutic performance of MRI ...in a routine clinical setting. Therefore, we assessed the long-term diagnostic accuracy of MRI for detecting recurrent STS at a multidisciplinary sarcoma center.
In all, 1055 postoperative follow-up MRIs of 204 patients were included in the study. MRI follow-up scans were systematically reviewed for diagnostic values (true-positive/-negative and false-positive/-negative results) in detecting recurrences. Pathological reports and follow-up MRIs were set as baseline references.
The median age of the patients was 55.3 ± 18.2 years. Of the patients, 34.8% presented with recurrences. Here, 65 follow-up scans were true positive, 23 false positive, 6 false negative, and 961 true negative. The overall sensitivity and specificity of MRI for detecting recurrences were 92 and 98%, respectively, with an accuracy of 97%. For intramuscular lesions and after surgery alone the sensitivity was higher (95 and 97%, respectively) than for subcutaneous lesions and surgery with additional radiation therapy (83 and 86%, respectively), at similarly high specificities (96-98%). The 6 false-negative results were found in streaky (n = 2) and small ovoid/nodular (n = 4) recurring lesions. The false-positive lesions imitated streaky (n = 14), ovoid/nodular (n = 8), and polycyclic/multilobulated recurring tumors (n = 1). All false-positive results were found in patients in whom the primary tumors were polycyclic/multilobulated in appearance.
MRI shows a high diagnostic accuracy for detecting recurrent STS, with a high sensitivity and specificity. The diagnostic accuracy decreases in subcutaneous lesions and after surgery with radiation therapy, compared to intramuscular lesions and surgery alone. Radiologists should pay particular attention to streaky and small ovoid/nodular recurring lesions and patients with polycyclic/multilobulated primary tumors.
The original version of this consensus statement on mechanical thrombectomy was approved at the European Stroke Organisation (ESO)-Karolinska Stroke Update conference in Stockholm, 16–18 November ...2014. The statement has later, during 2015, been updated with new clinical trials data in accordance with a decision made at the conference. Revisions have been made at a face-to-face meeting during the ESO Winter School in Berne in February, through email exchanges and the final version has then been approved by each society. The recommendations are identical to the original version with evidence level upgraded by 20 February 2015 and confirmed by 15 May 2015. The purpose of the ESO-Karolinska Stroke Update meetings is to provide updates on recent stroke therapy research and to discuss how the results may be implemented into clinical routine. Selected topics are discussed at consensus sessions, for which a consensus statement is prepared and discussed by the participants at the meeting. The statements are advisory to the ESO guidelines committee. This consensus statement includes recommendations on mechanical thrombectomy after acute stroke. The statement is supported by ESO, European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), and European Academy of Neurology (EAN).
Summary Background Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes ...than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. Methods In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. Findings Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65–69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13–4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90–2·88) for patients aged 65–69 years and an HR of 2·09 (1·32–3·32) for patients aged 70–74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). Interpretation In these RCTs, CEA was clearly superior to CAS in patients aged 70–74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. Funding None.
Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex- matched ...nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of
in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the
or the
gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.
This analysis examined the frequency of dural arteriovenous fistulae (dAVF) after cerebral venous thrombosis (CVT) in patients included in a randomized controlled trial comparing dabigatran etexilate ...with dose-adjusted warfarin (RE-SPECT CVT A Clinical Trial Comparing Efficacy and Safety of Dabigatran Etexilate With Warfarin in Patients With Cerebral Venous and Dural Sinus Thrombosis), who had systematic follow-up magnetic resonance (MR) imaging.
RE-SPECT CVT was a Phase 3, prospective, randomized, parallel-group, open-label, multicenter, exploratory trial with blinded end point adjudication. We allocated patients with acute CVT to dabigatran 150 mg twice daily or dose-adjusted warfarin, for 24 weeks and obtained a standardized MR protocol including time-of-flight MR angiography, 3-dimensional phase-contrast venography, and 3-dimensional contrast-enhanced MR venography at the end of the treatment period. A blinded adjudication committee assessed the presence of dAVF in a predefined substudy of the trial.
We analyzed development of dAVF in 112 of 120 randomized patients; 57 allocated to dabigatran and 55 to warfarin. For 3 (2.7%) of these 112 patients, quality of follow-up imaging was insufficient to evaluate dAVF. A dAVF (Borden I) was found in 1 patient (0.9%) allocated to warfarin; however, this dAVF was already present at baseline. The patient did not present with hemorrhage at baseline or during the trial and was asymptomatic at follow-up.
Despite systematic imaging, we found no new dAVF 6 months after CVT. Routine follow-up cerebral MR angiography aiming to detect new dAVF 6 months after CVT has a very low yield. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02913326.
Although the modified Rankin Scale (mRS) is the most commonly used primary end point in acute stroke trials, its power is limited when analyzed in dichotomized fashion and its indication of effect ...size challenging to interpret when analyzed ordinally. Weighting the 7 Rankin levels by utilities may improve scale interpretability while preserving statistical power.
A utility-weighted mRS (UW-mRS) was derived by averaging values from time-tradeoff (patient centered) and person-tradeoff (clinician centered) studies. The UW-mRS, standard ordinal mRS, and dichotomized mRS were applied to 11 trials or meta-analyses of acute stroke treatments, including lytic, endovascular reperfusion, blood pressure moderation, and hemicraniectomy interventions.
Utility values were 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6. For trials with unidirectional treatment effects, the UW-mRS paralleled the ordinal mRS and outperformed dichotomous mRS analyses. Both the UW-mRS and the ordinal mRS were statistically significant in 6 of 8 unidirectional effect trials, whereas dichotomous analyses were statistically significant in 2 to 4 of 8. In bidirectional effect trials, both the UW-mRS and ordinal tests captured the divergent treatment effects by showing neutral results, whereas some dichotomized analyses showed positive results. Mean utility differences in trials with statistically significant positive results ranged from 0.026 to 0.249.
A UW-mRS performs similar to the standard ordinal mRS in detecting treatment effects in actual stroke trials and ensures the quantitative outcome is a valid reflection of patient-centered benefits.
Summary Background The SPACE trial is a multinational, prospective, randomised study to test the hypothesis that carotid artery stenting is not inferior to carotid endarterectomy for treating ...patients with severe symptomatic carotid artery stenosis. We did not prove non-inferiority of carotid artery stenting compared with carotid endarterectomy for the 30-day complication rate, and we now report the results at 2 years. Methods Between March, 2001, and February, 2006, patients with symptomatic, severe (≥70%) carotid artery stenosis were recruited to this non-inferiority trial and randomly assigned with a block randomisation design to have carotid artery angioplasty with stenting or carotid artery endarterectomy. 2-year endpoints include several clinical endpoints and the incidence of recurrent carotid stenosis of at least 70%. Clinical and vascular follow-up was done by a certified neurologist. Analyes were by intention to treat and per protocol. This trial is registered with ISRCTN, number 57874028.12. Findings 1 214 patients were randomly assigned (613 were randomly assigned to carotid angioplasty with stenting and 601 were randomly assigned to carotid endarterectomy). In both the intention-to-treat and per-protocol analyses the Kaplan-Meier estimates of ipsilateral ischaemic strokes up to 2 years after the procedure and any periprocedural stroke or death do not differ between the carotid artery stenting and the carotid endarterectomy groups (intention to treat 9·5% vs 8·8%; hazard ratio (HR) 1·10, 95%CI 0·75 to 1·61; log-rank p=0·62; per protocol 9·4% vs 7·8%; HR 1·23, 95%CI 0·82 to 1·83; log-rank p=0·31). In both the intention-to-treat and per-protocol populations, recurrent stenosis of 70% or more is significantly more frequent in the carotid artery stenting group compared with the carotid endarterectomy group, with a life-table estimate of 10·7% versus 4·6% (p=0·0009) and 11·1% versus 4·6% (p=0·0007), respectively. Only two incidences of recurrent stenoses after carotid artery stenting led to neurological symptoms. Interpretation After 2 years' follow-up, the rate of recurrent ipsilateral ischaemic strokes reported in the SPACE trial is similar for both treatment groups. The incidence of recurrent carotid stenosis at 2 years, as defined by ultrasound, is significantly higher after carotid artery stenting. However, it cannot be excluded that the degree of in-stent stenosis is slightly overestimated by conventional ultrasound criteria. Funding Federal Ministry of Education and Research; German Research Foundation; The German Society of Neurology; The German Society of Neuroradiology; The German Radiological Society; Boston Scientific; Guidant; Sanofi-Aventis.
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