Multifocal multilobar focal cortical dysplasia type IIa in Febrile Infection Related Epilepsy Syndrome (FIRES).

A seven-year-old girl with history of type I diabetes and no history of seizures presented for altered mental status with convulsions nearly one week after a febrile illness. Serum and laboratory studies were normal with EEG showing biparietal fast activity and seizures originating from right occipital lobe consistent with FIRES. A collaborative decision was ultimately made to withdraw care. Post-mortem whole brain histopathological examination revealed diffuse abnormalities in multiple areas including both parietal lobes and the right parieto-occipital junction consistent with focal cortical dysplasia type IIa. We believe this to be the first report that describes focal cortical dysplasia type IIa co-localizing with epileptogenic areas on EEG in a case of FIRES, and recommend that focal cortical dysplasia be considered as an etiology early in the course of FIRES.

MicroRNAs as Candidate Biomarkers for Alzheimer's Disease.

The neurological damage of Alzheimer's disease (AD) is thought to be irreversible upon onset of dementia-like symptoms, as it takes years to decades for occult pathologic changes to become symptomatic. It is thus necessary to identify individuals at risk for the development of the disease before symptoms manifest in order to provide early intervention. Surrogate markers are critical for early disease detection, stratification of patients in clinical trials, prediction of disease progression, evaluation of response to treatment, and also insight into pathomechanisms. Here, we review the evidence for a number of microRNAs that may serve as biomarkers with possible mechanistic insights into the AD pathophysiologic processes, years before the clinical manifestation of the disease.

The efficacy of hydrogel foams in talc Pleurodesis.

BACKGROUND: Malignant pleural effusions are a serious complication of many late stage cancers that adversely affect quality of life. Pleurodesis with talc slurry is a standard treatment option, but clinical failures occur, possible due to poor talc delivery. A novel drug-delivery system was developed that fills the entire thoracic cavity with a liquid foam containing talc. The foam is designed to gel and adhere to the tissue walls at body temperature, to improve talc deposition and efficacy. METHODS: Rheology, foam stability, and ex-vivo coating and bio-adhesion studies were performed on three concentrations of a novel hydrogel talc foam system that was developed to improve delivery of talc to the pleural surfaces. A New Zealand rabbit model of pleurodesis was used to evaluate effectiveness of the foams at inducing adhesion formation and compared to talc slurry. The rabbits were recovered after they had one of the test agents instilled into their pleura, and then sacrificed after 28 days. Pleurodesis was assessed by a blinded pathologist using a standardized pathological scoring system. RESULTS: All talc foam formulations produced foams that gelled at physiological temperatures and were relatively stable for at least two hours. As the concentration of the formulation increased the gelation temperature decreased and the foam adhesiveness increased. Rabbits that received talc foam had significantly greater adhesion formation than talc slurry (mean score of 2.21 vs. 1.18 (p < 0.05)). Rabbits that received the 20% foam developed the most adhesions. CONCLUSIONS: This study demonstrates that our triblock copolymer hydrogel foam delivery system enhances adhesion formation in an experimental model. This novel approach can have important clinical impact, potentially improving efficacy of existing therapies and reducing the need for more invasive treatments.

An improved method of delivering a sclerosing agent for the treatment of malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a devastating sequela associated with cancer. Talc pleurodesis is a common treatment strategy for MPE but has been estimated to be unsuccessful in up to 20-50% of patients. Clinical failure of talc pleurodesis is thought to be due to poor dispersion. This monograph reports the development of a foam delivery system designed to more effectively coat the pleural cavity. METHODS: C57BL/6 mice were injected with Lewis lung carcinoma (LL/2) cells intrapleurally to induce MPE. The mice then received either normal saline (NS) control, foam control (F), talc slurry (TS, 2 mg/g) or talc foam (TF, 2 mg/g). Airspace volume was evaluated by CT, lungs/pleura were collected, and percent fibrosis was determined. RESULTS: The TF group had significantly better survival than the TS group (21 vs 13.5 days, p < 0.0001). The average effusion volume was less in the talc groups compared to the control group (140 vs 628 µL, p < 0.001). TF induced significant lung fibrosis (p < 0.01), similar to TS. On CT, TF significantly (p < 0.05) reduced loss of right lung volume (by 30-40%) compared to the control group. This was not seen with TS (p > 0.05). CONCLUSIONS: This report describes using a novel talc foam delivery system for the treatment of MPE. In the LL/2 model, mice treated with the TF had better survival outcomes and less reduction of lung volume than mice treated with the standard of care TS. These data provide support for translational efforts to move talc foam from animal models into clinical trials.