Associations of Perioperative Variables With the 30-Day Risk of Stroke or Death in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

Background and Purpose- This analysis was performed to assess the association between perioperative and clinical variables and the 30-day risk of stroke or death after carotid endarterectomy for symptomatic carotid stenosis. Methods- Individual patient-level data from the 5 largest randomized controlled carotid trials were pooled in the Carotid Stenosis Trialists' Collaboration database. A total of 4181 patients who received carotid endarterectomy for symptomatic stenosis per protocol were included. Determinants of outcome included carotid endarterectomy technique, type of anesthesia, intraoperative neurophysiological monitoring, shunting, antiplatelet medication, and clinical variables. Stroke or death within 30 days after carotid endarterectomy was the primary outcome. Adjusted risk ratios (aRRs) were estimated in multilevel multivariable analyses using a Poisson regression model. Results- Mean age was 69.5±9.2 years (70.7% men). The 30-day stroke or death rate was 4.3%. In the multivariable regression analysis, local anesthesia was associated with a lower primary outcome rate (versus general anesthesia; aRR, 0.70 [95% CI, 0.50-0.99]). Shunting (aRR, 1.43 [95% CI, 1.05-1.95]), a contralateral high-grade carotid stenosis or occlusion (aRR, 1.58 [95% CI, 1.02-2.47]), and a more severe neurological deficit (mRS, 3-5 versus 0-2: aRR, 2.51 [95% CI, 1.30-4.83]) were associated with higher primary outcome rates. None of the other characteristics were significantly associated with the perioperative stroke or death risk. Conclusions- The current results indicate lower perioperative stroke or death rates in patients operated upon under local anesthesia, whereas a more severe neurological deficit and a contralateral high-grade carotid stenosis or occlusion were identified as potential risk factors. Despite a possible selection bias and patients not having been randomized, these findings might be useful to guide surgeons and anesthetists when treating patients with symptomatic carotid disease.

Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors.

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 Parasutterella sp. 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 JNK or the MC4R 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.

Clinical Course and Monitoring Parameters After Continuous Interventional Intra-Arterial Treatment in Patients with Refractory Cerebral Vasospasm.

BACKGROUND: In aneurysmal subarachnoid haemorrhage cerebral vasospasm leads to clinical worsening and poor outcome. Interventional treatment with nimodipine might be a therapeutic option. OBJECTIVE: To evaluate the clinical course of patients with different interventional treatment types. METHODS: A retrospective, observational analysis was performed. Inclusion criteria were aneurysmal subarachnoid haemorrhage, clinical and/or radiologic evidence of vasospasm and interventional intra-arterial treatment. Patients were divided into 3 groups: continuous nimodipine infusion, repetitive nimodipine infusions, and singular nimodipine infusion. Pre- and postinterventional parameters were analyzed to evaluate the efficacy of the procedure in terms of responder status. Outcome was determined using the modified Rankin scale. RESULTS: A total of 163 interventions (97 patients) were examined. Patients with continuous treatment showed a greater World Federation of Neurological Surgeons grade. Response to intra-arterial nimodipine in the continuous group was comparatively worse. Transcranial Doppler monitoring as well as brain tissue oxygenation measuring showed good correlation with imaging results. The rate of intraprocedural complications in the continuous treatment group was significantly greater. We observed a worse clinical outcome in the patients who underwent continuous treatment. None of the patients in the continuous group achieved favorable outcome after 3 months. CONCLUSIONS: Facing the poor clinical outcome and the greater complication rate, continuous intra-arterial infusion of nimodipine in patients with angiographically refractory cerebral vasospasm has to be indicated strictly. Transcranial Doppler and brain tissue oxygenation monitoring seem to be reliable tools for evaluation of the clinical postinterventional course.

Simultaneous EEG-fMRI in drug-naive children with newly diagnosed absence epilepsy.

PURPOSE: In patients with idiopathic generalized epilepsy (IGE), blood oxygen level dependent (BOLD) EEG during functional MRI (EEG-fMRI) has been successfully used to link changes in regional neuronal activity to the occurrence of generalized spike-and-wave (GSW) discharges. Most EEG-fMRI studies have been performed on adult patients with long-standing epilepsy who were on antiepileptic medication. Here, we applied EEG-fMRI to investigate BOLD signal changes during absence seizures in children with newly diagnosed childhood absence epilepsy (CAE). METHODS: Ten drug-naive children with newly diagnosed CAE underwent simultaneous EEG-fMRI. BOLD signal changes associated with ictal EEG activity (i.e., periods of three per second GSW) were analyzed in predefined regions-of-interests (ROIs), including the thalamus, the precuneus, and caudate nucleus. RESULTS: In 6 out of 10 children, EEG recordings showed periods of three per second GSW during fMRI. Three per second GSW were associated with regional BOLD signal decreases in parietal areas, precuneus, and caudate nucleus along with a bilateral increase in the BOLD signal in the medial thalamus. Taking into account the normal delay in the hemodynamic response, temporal analysis showed that the onset of BOLD signal changes coincided with the onset of GSW. DISCUSSION: In drug-naive individuals with CAE, ictal three per second GSW are associated with BOLD signal changes in the same striato-thalamo-cortical network that changes its regional activity during primary and secondary generalized paroxysms in treated adults. No BOLD signal changes in the striato-thalamo-cortical network preceded the onset of three per second GSW in unmediated children with CAE.

Changes in activity of striato-thalamo-cortical network precede generalized spike wave discharges.

The pathophysiology of generalized spike wave discharges (GSW) is not completely understood. Thalamus, basal ganglia and neocortex have been implicated in the generation of GSW, yet the specific role of each structure remains to be clarified. In six children with idiopathic generalized epilepsy (IGE), we performed combined EEG-fMRI to identify GSW-related changes in blood oxygen level-dependent (BOLD) signal in the striato-thalamo-cortical network. In all patients, within-subject analysis demonstrated BOLD signal changes that preceded the GSW. An increase in BOLD signal in the medial thalamus started 6 s before the onset of the GSW. Decreases in cortical BOLD signal were mainly found in frontoparietal areas and precuneus starting 6 to 3 s before the GSW. All patients showed a decrease in BOLD signal in the head of the caudate nucleus with a variable onset. The temporospatial pattern of BOLD signal changes suggests that GSW on the cortical surface is preceded by a sequence of neuronal events in the thalamo-cortical-striatal network. Approximately 6 s before the GSW, the thalamus shows an increase in neuronal activity along with regional decreases in cortical activity. These changes in thalamo-cortical activity are followed by a deactivation of the caudate nucleus. These early changes in BOLD signal may reflect changes in neuronal activity that contribute to the generation of GSW and may contribute to the transition from a normal to a generalized hypersynchronous pattern of neuronal activity. Our preliminary findings warrant further studies on a larger number of patients to explore the influence of age, medication and type of epileptic syndrome.

Different neuronal networks are associated with spikes and slow activity in hypsarrhythmia.

PURPOSE: West syndrome is a severe epileptic encephalopathy of infancy characterized by a poor developmental outcome and hypsarrhythmia. The pathogenesis of hypsarrhythmia is insufficiently understood. METHODS: We investigated eight patients with infantile spasms and hypsarrhythmia (group I) and 8 children with complex partial seizures (group II) using simultaneous recordings of electroencephalogram (EEG) and functional MRI. Hemodynamic responses to epileptiform discharges and slow wave activity (EEG delta power) were analyzed separately. RESULTS: In group I (mean age, 7.82 +/- 2.87 months), interictal spikes within the hypsarrhythmia were associated with positive blood oxygenation level-dependent (BOLD) changes in the cerebral cortex (especially occipital areas). This was comparable with cortical positive BOLD responses in group II (mean age, 20.75 +/- 12.52 months). Slow wave activity in group I correlated significantly with BOLD signal in voxels, which were localized in brainstem, thalamus, as well as different cortical areas. There was no association between BOLD effect and EEG delta power in group II. Moreover, as revealed by group analysis, group I differed from group II according to correlations between BOLD signal and slow wave activity in putamen and brainstem. CONCLUSIONS: This study demonstrates that multifocal interictal spikes and high-amplitude slow wave activity within the hypsarrhythmia are associated with the activation of different neuronal networks. Although spikes caused a cortical activation pattern similar to that in focal epilepsies, slow wave activity produced a hypsarrhythmia-specific activation in cortex and subcortical structures such as brainstem, thalamus, and putamen.