A fibril-specific, conformation-dependent antibody recognizes a subset of Abeta plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain.

Beta-amyloid (Abeta) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Abeta have been identified that may be neurotoxic. Abeta oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Abeta deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = -0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Abeta deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Abeta pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought.

Conditions associated with giant pituitary tumors at the time of surgery effecting outcome morbidity and mortality.

BACKGROUND: Surgical outcome prediction has assisted physicians in discussing surgical intervention or expectant management. While increasing pituitary tumor size would seem to be associated with increasing challenge of removal and associated complications, that relationship has not been borne in the literature. METHODS: We performed a retrospective review of a consecutive cohort of pituitary surgeries completed at our institution. Data included age at the time of surgery, presenting symptoms and Glasgow Coma scale (GCS), GCS at discharge or 7 days postoperatively, GCS at 6 months, adenoma size, imaging characteristics of the tumor and brain before resection, postoperative complications, the presence of preoperative hydrocephalus, brainstem compression, and patient mortality. RESULTS: Patients with giant adenomas were more likely to present with a cranial nerve palsy (P = 0.019), altered mental status (P = 0.0001), hydrocephalus (P = 0.002), and mass effect on the brainstem (P = 0.020). Patients who experienced a postoperative decline in mental status were more likely to present with altered mental (P = 0.006), had an increased prevalence of mass effect on the brainstem (P = 0.005), and were more likely to have either an ischemic stroke (P = 0.0001) and vasospasms or new intraparenchymal hemorrhage (P = 0.013). CONCLUSION: The results of this study demonstrate that postoperative mental status declines after pituitary adenoma resection can be directly related to brainstem compression and further surgical irritation of the surrounding vasculature. The intraoperative irritation can be multifactorial and may result as the decompressed brain structures assume their anatomical position.

Anti-epileptic prophylaxis in traumatic brain injury: A retrospective analysis of patients undergoing craniotomy versus decompressive craniectomy.

BACKGROUND: Seizures account for significant morbidity and mortality early in the course of traumatic brain injury (TBI). Although there is sufficient literature suggesting short-term benefits of antiepileptic drugs (AEDs) in post-TBI patients, there has been no study to suggest a time frame for continuing AEDs in patients who have undergone a decompressive craniectomy for more severe TBI. We examined trends in a level-II trauma center in southern California that may provide guidelines for AED treatment in craniectomy patients. METHODS: A retrospective analysis was performed evaluating patients who underwent decompressive craniectomy and those who underwent a standard craniotomy from 2008 to 2012. RESULTS: Out of the 153 patients reviewed, 85 were included in the study with 52 (61%) craniotomy and 33 (39%) craniectomy patients. A total of 78.8% of the craniotomy group used phenytoin (Dilantin), 9.6% used levetiracetam (Keppra), 5.8% used a combination of both, and 3.8% used topiramate (Topamax). The craniectomy group used phenytoin 84.8% and levetiracetam 15.2% of the time without any significant difference between the procedural groups. Craniotomy patients had a 30-day seizure rate of 13.5% compared with 21.2% in craniectomy patients (P = 0.35). Seizure onset averaged on postoperative day 5.86 for the craniotomy group and 8.14 for the craniectomy group. There was no significant difference in the average day of seizure onset between the groups P = 0.642. CONCLUSION: Our study shows a trend toward increased seizure incidence in craniectomy group, which does not reach significance, but suggests they are at higher risk. Whether this higher risk translates into a benefit on being on AEDs for a longer duration than the current standard of 7 days cannot be concluded as there is no significant difference or trend on the onset date for seizures in either group. Moreover, a prospective study will be necessary to more profoundly evaluate the duration of AED prophylaxis for each one of the stated groups.