Hubs disruption in mesial temporal lobe epilepsy. A resting‐state fMRI study on a language‐and‐memory network

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language‐and‐memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure‐related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN‐FC using two methods: pairwise correlations (region of interest [ROI]‐to‐ROI) and graph theory. The cognitive efficiency of the LMN‐FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L‐mTLE) than in right (R‐mTLE) patients. The LMN‐FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of “connectome” would gain to be associated with a “cognitome” concept.     

Multi‐scale network regression for brain‐phenotype associations

Brain networks are increasingly characterized at different scales, including summary statistics, community connectivity, and individual edges. While research relating brain networks to behavioral measurements has yielded many insights into brain‐phenotype relationships, common analytical approaches only consider network information at a single scale. Here, we designed, implemented, and deployed Multi‐Scale Network Regression (MSNR), a penalized multivariate approach for modeling brain networks that explicitly respects both edge‐ and community‐level information by assuming a low rank and sparse structure, both encouraging less complex and more interpretable modeling. Capitalizing on a large neuroimaging cohort (n = 1, 051) , we demonstrate that MSNR recapitulates interpretable and statistically significant connectivity patterns associated with brain development, sex differences, and motion‐related artifacts. Compared to single‐scale methods, MSNR achieves a balance between prediction performance and model complexity, with improved interpretability. Together, by jointly exploiting both edge‐ and community‐level information, MSNR has the potential to yield novel insights into brain‐behavior relationships.     

Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases

BACKGROUND: Maternal alloantibodies against the five common human platelet antigen (HPA) systems (HPA-1 to -3, -5, and -15) are found in only 20% of cases referred for fetal and neonatal thrombocytopenia (FMAIT) investigations. The question asked was whether mismatches for the remaining 11 low-frequency HPAs (HPA-4 and -6bw to -17bw) might in part explain the remaining 80% of cases.
STUDY DESIGN AND METHODS: A total of 1054 paternal DNA samples from referred FMAIT cases (among which 223 cases where antibodies against a common HPA were found) were genotyped for 11 low-frequency HPAs as well as a recently discovered polymorphism ( ITGA2B -C2320T). The initial genotyping was carried out by TaqMan and potential heterozygotes were confirmed by DNA sequencing. Clinical and serologic data were collected for each case with a heterozygote father.
RESULTS: In total, eight heterozygous fathers were identified: four for HPA-6w, one each for HPA-10w and -11w, and two for HPA-12w. Maternal antibodies against the corresponding antigen were identified in four of the eight cases. In two of these cases, antibodies against HPA-1a and HPA-1b were also found.
CONCLUSION: It was concluded that the minor alleles of HPA-4 and -6bw to -17bw are exceptionally rare in the Caucasian population and therefore do not explain the large number of FMAIT referrals which test negative for the common HPA antibodies.     

Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review

The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from academic centers. Evaluations by faculty and students have been overwhelmingly positive. Requests to use the CPPS units in various clinical pharmacology teaching programs were received from numerous schools within the United States and from abroad. The third teaching clinic in September 1995 included a follow-up focused on the uses of drug information databases in case problem exercises. These examples are presented to demonstrate the variety of educational activities the American College of Clinical Pharmacology is sponsoring to fulfill its strategic initiative dedicated to offer innovative teaching programs and to develop new teaching materials in clinical pharmacology. Collectively, all of the teaching clinics, symposia, and workshop efforts, sponsored by the various academic professional societies alone or together over the past decade, are necessary if new and innovative teaching materials in the field of basic science and in the fields of pharmacology and clinical pharmacology are to be continuously developed to keep pace with the new, rapidly changing developments in medicine to provide the best treatment for patients in the 21st century.     

Safety and efficacy of intravenous valproate in pediatric status epilepticus and acute repetitive seizures

Summary: Purpose: To evaluate the safety and efficacy of intravenous valproate (VPA) loading in children with status epilepticus (SE) or acute repetitive seizures. Methods: Retrospective review was performed on 40 pediatric patients with intravenous VPA loading. Patients were classified into two groups: SE (n = 18) and acute repetitive seizures (n = 22). Thirty‐one patients were VPA naïve and received a full loading dose of 25 mg/kg; nine had subtherapeutic plasma VPA levels and received a partial loading dose. Average infusion rate was 2.8 mg/kg/min. Heart rate and blood pressure were measured before, during, and after infusion. Results: Intravenous VPA loading stopped seizures in 18 patients with SE within 20 min. All 18 patients regained baseline mental status within 1 h of seizure cessation. Among 22 patients with acute repetitive seizures, only one had further seizures after VPA infusion. One patient in the SE group complained of transient tremors. No significant changes in blood pressure or heart rate were found in either group. Postinfusion plasma VPA levels ranged from 51 to 138 μg/ml (mean ± SD = 88 ± 21.5 μg/ml). Conclusions: Intravenous VPA loading is safe and effective for treating acute seizure emergencies in children.