Sequential Treatment of Guillain-Barré Syndrome with Extracorporeal Elimination and Intravenous Immunoglobulin

Abstract: Plasma exchange and administration of intravenous immunoglobulin (IgG) are established treatments for Guillain-Barré syndrome (GBS). Elimination of postulated pathogenetic factors by plasma exchange or selective adsorption treatment using affinity-type adsorption columns and subsequent immunomodulation by intravenous IgG may provide a more effective treatment. Forty-five patients with acute GBS were prospectively examined using a clinical score. We treated 11 patients by plasma exchange, 13 patients by selective adsorption using a tryptophan-linked polyvinyl alcohol gel adsorbent, and 21 patients by selective adsorption followed by intravenous IgG. The patients treated sequentially by selective adsorption and intravenous IgG improved significantly better than the patients who received plasma treatment only. The results suggest that sequential treatment of GBS may be superior to plasma treatment alone. The higher cost of combined treatment may be offset by lower overall expenditure.     

Long-Term Outcomes After PCI or CABG for Left Main Coronary Artery Disease According to Lesion Location

ObjectivesThe aim of this study was to investigate the impact of lesion site (ostial or shaft vs. distal bifurcation) on long-term outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease.BackgroundLong-term comparative data after PCI and CABG for LMCA disease according to lesion site are limited.MethodsPatients from the MAIN-COMPARE (Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry were analyzed, comparing adverse outcomes (all-cause mortality [a composite outcome of death, Q-wave myocardial infarction, or stroke] and target vessel revascularization) between PCI and CABG according to LMCA lesion location during a median follow-up period of 12.0 years.ResultsIn overall population, the adjusted risks for death and serious composite outcome were higher after PCI than after CABG for distal bifurcation disease, which was mainly separated beyond 5 years. These outcomes were not different for ostial or shaft disease. When comparing drug-eluting stents (DES) and CABG, the adjusted risks for death and serious composite outcome progressively diverged beyond 5 years after DES compared with CABG for distal bifurcation disease (death: hazard ratio: 1.78; 95% confidence interval: 1.22 to 2.59; composite outcome: hazard ratio: 1.94; 95% confidence interval: 1.35 to 2.79). This difference was driven mainly by PCI with a 2-stent technique for distal bifurcation. In contrast, the adjusted risks for these outcomes were similar between DES and CABG for ostial or shaft disease.ConclusionsAmong patients with distal LMCA bifurcation disease, CABG showed lower mortality and serious composite outcome rates compared with DES beyond 5 years. However, there were no between-group differences in these outcomes among patients with ostial or shaft LMCA disease.     

Effects of aging on neural connectivity underlying selective memory for emotional scenes

Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults' encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults' connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item.     

What's wrong with fear conditioning?

Fear conditioning is one of the prime paradigms of behavioural neuroscience and a source of tremendous insight in the fundamentals of learning and memory and the psychology and neurobiology of emotion. It is also widely regarded as a model for the pathogenesis of anxiety disorders in a diathesis-stress model of psychopathology. Starting from the apparent paradox between the adaptive nature of fear conditioning and the dysfunctional nature of pathological anxiety, we present a critique of the human fear conditioning paradigm as an experimental model for psychopathology. We discuss the potential benefits of expanding the human fear conditioning paradigm by (1) including action tendencies as an important index of fear and (2) paying more attention to “weak” (i.e., ambiguous) rather than “strong” fear learning situations (Lissek et al., 2006), such as contained in selective learning procedures. We present preliminary data that illustrate these ideas and discuss the importance of response systems divergence in understanding individual differences in vulnerability for the development of pathological anxiety.     

Emerging therapies for postmenopausal vaginal atrophy

Symptoms related to vaginal atrophy are a significant problem for postmenopausal women and estrogen has been the gold standard for its treatment. A number of recent reviews of vaginal estrogen products are available. This review will, therefore, focus on other products and potential products for this indication, including the tissue selective estrogen complex and selective estrogen receptor modulators. Additionally, lesser-studied approaches will be discussed.     

Initial delta and delayed theta/alpha pattern in the temporal region on ictal EEG suggests purely hippocampal epileptogenicity in patients with mesial temporal lobe epilepsy

ObjectiveTo determine whether the ictal scalp EEG findings suggest purely hippocampal epileptogenicity in patients with mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS).MethodsTwenty-three patients with mTLE with pathologically confirmed HS were divided into 12 with epileptogenicity only in the hippocampus (HS only group) and 11 with epileptogenicity in both the hippocampus and temporal neocortex or other locations (HS plus group), based on the combination of surgical procedures, postoperative outcome, and pathological findings. Sixteen underwent selective amygdalohippocampectomy (SelAH) and 7 received anterior temporal lobectomy. Ictal scalp EEG findings of 79 focal impaired awareness seizures were compared between the HS only and HS plus groups. We focused on the 1–4 Hz rhythmic delta activity at ictal onset followed by 5–9 Hz rhythmic theta/alpha activity 10–30 s after the onset in the temporal region.ResultsThe initial delta and delayed theta/alpha (ID-DT) pattern was observed in 8 of 12 patients in the HS only group, but in none of 11 patients in the HS plus group (p < 0.01).ConclusionsID-DT pattern on ictal EEG suggests purely hippocampal epileptogenicity in mTLE with HS.SignificancePatients with the ID-DT pattern are likely to become seizure-free after SelAH.     

Event-related potentials to rare visual targets and negative symptom severity in a transdiagnostic psychiatric sample

ObjectivesNegative psychiatric symptoms are often resistant to treatments, regardless of the disorder in which they appear. One model for a cause of negative symptoms is impairment in higher-order cognition. The current study examined how particular bottom-up and top-down mechanisms of selective attention relate to severity of negative symptoms across a transdiagnostic psychiatric sample.MethodsThe sample consisted of 130 participants: 25 schizophrenia-spectrum disorders, 26 bipolar disorders, 18 unipolar depression, and 61 nonpsychiatric controls. The relationships between attentional event-related potentials following rare visual targets (i.e., N1, N2b, P2a, and P3b) and severity of the negative symptom domains of anhedonia, avolition, and blunted affect were evaluated using frequentist and Bayesian analyses.ResultsP3b and N2b mean amplitudes were inversely related to the Positive and Negative Syndrome Scale-Negative Symptom Factor severity score across the entire sample. Subsequent regression analyses showed a significant negative transdiagnostic relationship between P3b amplitude and blunted affect severity.ConclusionsResults indicate that negative symptoms, and particularly blunted affect, may have a stronger association with deficits in top-down mechanisms of selective attention.SignificanceThis suggests that people with greater severity of blunted affect, independent of diagnosis, do not allocate sufficient cognitive resources when engaging in activities requiring selective attention.     

Region-specific vulnerability in neurodegeneration: lessons from normal ageing

A number of age-associated neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), possess a shared characteristic of region-specific neurodegeneration. However, the mechanisms which determine why particular regions within the nervous system are selectively vulnerable to neurodegeneration, whilst others remain relatively unaffected throughout disease progression, remain elusive. Here, we review how regional susceptibility to the ubiquitous physiological phenomenon of normal ageing might underlie the vulnerability of these same regions to neurodegeneration, highlighting three regions archetypally associated with AD, PD and ALS (the hippocampus, substantia nigra pars compacta and ventral spinal cord, respectively), as especially prone to age-related alterations. Placing particular emphasis on these three regions, we comprehensively explore differential regional susceptibility to nervous system tissue, cellular and molecular level ageing to provide an integrated perspective on why age-related neurodegenerative diseases exhibit region-selective vulnerability. Combining these principles with increasingly recognised differences between chronological and biological ageing (termed differential or ‘delta’ ageing) might ultimately guide therapeutic approaches for these devastating neurodegenerative diseases, for which a paucity of disease modifying and/or life promoting treatments currently exist.     

Substantial regional differences in the biomechanical behavior of molar treated with selective caries tissue removal technique: a finite element study

ObjectivesSelective caries removal (SCR) is recommended over non-selective removal for managing deep carious lesions to avoid pulp exposure and maintain pulp vitality. During SCR, residual carious dentin is left behind and sealed beneath the restoration. The biomechanical effects of such residual lesions on the restored tooth remain unclear and were assessed using finite element modeling (FEM).MethodsBased on μ-CT images of a healthy permanent human third molar, we developed five finite element models. Generic class I and II cavity restorations were modeled where residual lesions of variable sizes were either left or fully removed on occlusal and proximal surfaces. The cavities were restored with adhesive composite. All 3D-FE models were compared with a model of a healthy, non-treated molar. A vertical load of 100 N was applied onto the occlusal surface.ResultsRegardless of the lesion size, in molars with occlusal lesions higher mean stresses were predicted along the filling-lesion interface than in all other models. The smallest occlusal lesion (Ø₁ = 1 mm) resulted in the highest maximum stresses at the filling-lesion interface with large stress concentrations at the filling walls indicating failure risk. In conclusion, lesion site and extent are influencing parameters affecting the filling-lesion interactions and thus the biomechanical behavior of the tooth after SCR.SignificanceRetaining carious lesions around the pulpal floor affects the deformation and stress states in tooth-filling complexes. The higher stresses observed in molars with occlusal lesions may affect restoration stability and longevity. Suprisingly, more extended occlusal lesions may provide a more favorable tooth performance than less extended ones. In contrast, in molars with proximal lesions the residual lesion had only limited effect on the tooth’s biomechanical condition.