Comparison of MRI features and surgical outcome among the subtypes of focal cortical dysplasia

AbstractPurposeFocal cortical dysplasia (FCD) is the most common pathological diagnosis in patients who have undergone surgical treatment for intractable neocortical epilepsy. However, presurgical identification of MRI abnormalities in FCD patients remains difficult, and there are no highly sensitive imaging parameters available that can reliably differentiate among FCD subtypes. The purpose of our study was to investigate the surgical outcome in FCD patients with identifiable MRI abnormalities and to evaluate the prognostic role of the various MRI features and the characteristics of FCD pathology.MethodsWe retrospectively recruited epilepsy patients who had undergone surgical treatment for refractory epilepsy with focal MRI abnormalities and the pathological diagnosis of FCD. We evaluated the surgical outcome according to the pathological subtypes, and studied the prognostic roles of various MRI features. We used recently proposed three-tiered FCD classification system which included FCD type III when FCD occurs in association with other potentially epileptogenic pathologies.ResultsA total of 69 patients were included, and 68.1% of patients became seizure free. Patients with FCD type III had a lower chance for achieving seizure freedom (7/15) than in patients with isolated FCD (FCD types I and II) (40/54, p=0.044). Cortical thickness and blurring of gray–white matter junction were more common in isolated FCD than in FCD type III, but most MRI features failed to differentiate between FCD types I and II, and only the transmantle sign was specific for FCD type II. We failed to find a prognostic value of specific MRI abnormalities of prognostic value in terms of post-epilepsy surgery outcome in FCD patients.ConclusionsOur study showed that patients with FCD III have poor surgical outcome. Typical MRI features of isolated FCD such as cortical thickness and blurring of gray–white matter junction were less common in FCD type III and only transmantle sign was helpful in differentiating between FCD types I and II

Frontal lobe epilepsy: Clinical characteristics, surgical outcomes and diagnostic modalities

SummaryObjectiveTo identify surgical prognostic factors and to characterize clinical features according to the location of the intracranial ictal onset zone of frontal lobe epilepsy (FLE) in order to assess the role of various diagnostic modalities, including concordances with presurgical evaluations.MethodsWe studied 71 FLE patients who underwent epilepsy surgery and whose outcomes were followed for more than 2 years. Diagnoses were established by standard presurgical evaluation.ResultsClinical manifestations could be categorized into six types: initial focal motor (9 patients), initial versive seizure (15), frontal lobe complex partial seizure (14), complex partial seizure mimicking temporal lobe epilepsy (18), initial tonic elevation of arms (11), and sudden secondary generalized tonic–clonic seizure (4). Thirty-seven patients became seizure-free after surgery. Five patients were deleted in the analysis because of incomplete resection of ictal onset zones. The positive predictive value of interictal EEG, ictal EEG, MRI, PET, and ictal SPECT, respectively were 62.5%, 56.4%, 73.9%, 63.2%, and 63.6%, and the negative predictive value were 46.0%, 44.4%, 53.5%, 44.7%, and 51.7%. No significant relationship was found between the diagnostic accuracy of these modalities and surgical outcome, with the exception of MRI (p=0.029). Significant concordance of two or more modalities was observed in patients who became seizure-free (p=0.011). We could not find any clinical characteristic related to surgical outcome besides seizure frequency. No definite relationship was found between the location of intracranial ictal onset zone and clinical semiology.ConclusionAlthough various diagnostic methods can be useful in the diagnosis of FLE, only MRI can predict surgical outcome. Concordance between presurgical evaluations indicates a better surgical outcome

Loss of Autophagy Diminishes Pancreatic β Cell Mass and Function with Resultant Hyperglycemia

SummaryAutophagy is a cellular degradation-recycling system for aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in various diseases including neurodegeneration, its role in pancreatic β cells and glucose homeostasis has not been described. We produced mice with β cell-specific deletion of Atg7 (autophagy-related 7). Atg7 mutant mice showed impaired glucose tolerance and decreased serum insulin level. β cell mass and pancreatic insulin content were reduced because of increased apoptosis and decreased proliferation of β cells. Physiological studies showed reduced basal and glucose-stimulated insulin secretion and impaired glucose-induced cytosolic Ca2+ transients in autophagy-deficient β cells. Morphologic analysis revealed accumulation of ubiquitinated protein aggregates colocalized with p62, which was accompanied by mitochondrial swelling, endoplasmic reticulum distension, and vacuolar changes in β cells. These results suggest that autophagy is necessary to maintain structure, mass and function of pancreatic β cells, and its impairment causes insulin deficiency and hyperglycemia because of abnormal turnover and function of cellular organelles

Clinical Features of Probable Cluster Headache: A Prospective, Cross-Sectional Multicenter Study

Background: Epidemiological data of probable cluster headaches (CH) are scarce in the relevant literature. Here, we sought to assess the prevalence and clinical characteristics of probable CH in comparison with definite CH.Methods: Data used in this study were obtained from the Korean Cluster Headache Registry (KCHR), a prospective, cross-sectional, multicenter headache registry that collected data from consecutive patients diagnosed with CH.Results: In total, 159 patients were enrolled in this study; 20 (12.6%) were diagnosed with probable CH. The most common unfulfilled criterion in patients with probable CH was the duration of attack, which was found in 40% of patients with probable CH. Among clinical characteristics, the number of autonomic symptoms tended to be lower in probable CH than in definite CH (1.7 ± 1.2 vs. 2.4 ± 1.5, p = 0.051) and conjunctival injection and lacrimation showed an increased odds ratio (OR) [OR = 3.03; 95% confidence interval (CI): 1.03–8.33] in definite CH. The groups did not differ with regard to baseline demographic characteristics, disability, impact on life, or treatment response.Conclusions: Probable CH is relatively common among CH disorders, with a clinical impact similar to that of definite CH

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Pseudorapidity and transverse-momentum distributions of charged particles in proton-proton collisions at root s=13 TeV

The pseudorapidity (eta) and transverse-momentum (p(T)) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy root s = 13 TeV. The pseudorapidity distribution in vertical bar eta vertical bar <1.8 is reported for inelastic events and for events with at least one charged particle in vertical bar eta vertical bar <1. The pseudorapidity density of charged particles produced in the pseudorapidity region vertical bar eta vertical bar <0.5 is 5.31 +/- 0.18 and 6.46 +/- 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 <p(T) <20 GeV/c and vertical bar eta vertical bar <0.8 for events with at least one charged particle in vertical bar eta vertical bar <1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe