A method for the development of cranial fracture histology slides.

Cranial vault fractures are of medicolegal interest as they have long-term impacts to someone's health and may contribute to an individual's death. The ability to distinguish antemortem from perimortem fractures and to assess the age of the injury is increasingly dependent on histology. Despite the increasing role of histology in assessing the microanatomy of osseous fractures, there are no methods currently available which account for the nuances and difficulties in creating high-quality histologic slides of cranial vault fractures that allow visualization of cellular features associated with healing bone. The authors present a modified method specific to slide development of human cranial vault fractures derived from the trial-and-error process of creating 730 such slides over a 3-year period which are suitable for the evaluation of the tissues, cells, and nuclei involved in fracture healing. This method adapts and troubleshoots typical histological procedures including sample excision, fixation, decalcification, dehydrating, clearing, embedding, microtomy, and staining, and introduces new procedures including preprocessing photography and cassette placement. By implementing these modifications, the number of poor-quality slides that required a new section to be sent to the histology laboratory was greatly reduced. Proactively implementing this new method into cranial fracture histologic slide development significantly reduces the number of slide rejections due to common issues like folding, chatter, or insufficient staining, saving both time and financial resources for forensic practitioners, researchers, and histotechnologists.

Neuropathology in Consecutive Forensic Consultation Cases with a History of Remote Traumatic Brain Injury.

Traumatic brain injury (TBI) is widely assumed to be causal in neurodegenerative disease, based on epidemiological surveys demonstrating an increased risk of Alzheimer disease (AD) following TBI, and on recent theories surrounding repetitive head movement. We tested this assumption by evaluating 30 consecutive forensic examinations in which neuropathology consultation was sought, and in which a history of remote TBI was uncovered during the course of the investigation. In this series, there was a high frequency of psychiatric co-morbidities (100%), remote contusion (90%), and seizures (63%). Extent of proteinopathy showed no differences with age-matched controls. A subset of the cases showed focal geographic tauopathy that correlated with older age at autopsy, but had no correlation with clinical signs, and was minimal in comparison with the encephalomalacia secondary to trauma. The results suggest that cerebral contusion and post-traumatic epilepsy may be over-represented in civilian TBI, while structural brain damage from trauma is the predominant cause of morbidity following TBI. We found no evidence that TBI initiates a progressive proteinopathy.

No Evidence of Increased Chronic Traumatic Encephalopathy Pathology or Neurodegenerative Proteinopathy in Former Military Service Members: A Preliminary Study.

It is presently unknown whether military service members are at risk for chronic traumatic encephalopathy (CTE) or Alzheimer's disease (AD) pathology, due to traumatic brain injury (TBI). Studies with respect to AD have had mixed results with respect to mild TBI, although an increased risk of clinical AD with moderate and severe TBI is more consistently demonstrated. No studies to date have demonstrated a longitudinal progression from TBI to autopsy. We therefore initiated a cross-sectional survey of former military service members. 18 brain specimens have been examined to date, with a mean age of 68.9±16 years (range 32-94). Twelve had a history of psychiatric problems; 10 had a history of PTSD specifically. Five had neurological problems including stroke and seizures. One subject had early-onset AD. Two subjects had a history of TBI and two had a history of blast exposure. Age-related proteinopathy, ranging from AD neuropathologic change A0B1C0 to A3B3C3 by NIA-AA guidelines, was identified. None of the cases showed changes specific for CTE pathology. There was no relationship between p-tau in the amygdala and psychiatric signs. There was no significant difference in phosphorylated tau (p-tau) or amyloid-ß burden compared to age-matched controls. These preliminary data suggest that military service per se is not a risk factor for CTE pathology or neurodegenerative proteinopathy. More research is needed to study the relationship, if any, between TBI and neurodegenerative proteinopathy.

Chronic Traumatic Encephalopathy Pathology After Shotgun Injury to the Brain.

Chronic traumatic encephalopathy (CTE) was initially conceptualized in boxers, but has extended to other athletes in recent years, albeit with limited clinical correlations. It is often asserted that CTE pathology represents the substrate for progressive neurodegenerative disease. We report the case of a shotgun injury to the brain with 42-year survival and no neurological disease progression until shortly before death. The decedent had no other traumatic brain injury (TBI) exposure and did not play football or other high energy collision sport. Neuropathological examination confirmed tissue damage, but additionally demonstrated localized patterns of phosphorylated tau (p-tau) meeting criteria for CTE pathology. P-tau and TDP-43 deposits within marginal tissue of damaged brain were also present focally. No amyloid-ß (Aß) deposits were present. These findings indicate that CTE pathology may occur following a single, severe TBI.

The development and validation of methods for evaluating the immune system in preweaning piglets.

The preweaning piglet has been found to be a valuable research model for testing ingredients used in infant formula. As part of the safety assessment, the neonates' immune system is an important component that has to be evaluated. In this study three concurrent strategies were developed to assess immune system status. The methods included (1) immunophenotying to assess circulating innate immune cell populations, (2) monitoring of circulating cytokines, particularly in response to a positive control agent, and (3) monitoring of localized gastrointestinal tissue cytokines using immunohistochemistry (IHC), particularly in response to a positive control agent. All assays were validated using white papers and regulatory guidance within a GLP environment. To validate the assays precision, accuracy and sample stability were evaluated as needed using a fit for purpose approach. In addition animals were treated with proinflammtory substances to detect a positive versus negative signal. In conclusion, these three methods were confirmed to be robust assays to evaluate the immune system and GIT-specific immune responses of preweaning piglets.

Infraorbital nerve surgical decompression for chronic infraorbital nerve hyperesthesia.

PURPOSE: To present three cases of chronic infraorbital nerve hyperesthesia relieved by surgical decompression of the infraorbital nerve. METHODS: Retrospective chart review. RESULTS: We identified three cases of chronic hyperesthesia of the infraorbital nerve. Two cases were related to previous blunt orbital trauma, whereas the third was associated with a long-standing anophthalmic socket with numerous previous surgeries. In each case, patients had dramatic relief of infraorbital nerve hyperesthesia and pain after surgical decompression of the infraorbital nerve. CONCLUSIONS: Surgical decompression of the infraorbital nerve can provide significant symptomatic improvement in patients with chronic infraorbital nerve hyperesthesia secondary to nerve compression.

Customized, single-incision, three-wall orbital decompression.

PURPOSE: To present the clinical outcome in 55 consecutive patients by using a customized, single-incision, 3-wall orbital decompression. METHODS: A retrospective chart review was performed of 97 customized, single-incision, 3-wall decompressions in 55 consecutive patients within one surgeon's practice. A standardized surgical technique featuring lateral small-incision, 3-wall decompression with specific "strut" preservation was used in all patients. Success of the procedure was assessed on the basis of the amount of proptosis reduction achieved, as measured by the difference in Hertel exophthalmometry measurements, and by improvement in or preservation of preoperative visual acuity and color vision in the setting of compressive optic neuropathy. Subjective diplopia was recorded before and after surgery, as was the presence of extraocular muscle restriction. RESULTS: A total of 97 orbital decompressions in 55 consecutive patients were reviewed. The majority of surgeries were performed for disfiguring proptosis with some degree of exposure-related symptoms (81%), with other indications including compressive optic neuropathy (17%), and pain (2%). The average amount of proptosis reduction achieved at 3 months was 5 mm (range, 1 to 11 mm). Visual acuity in patients with compressive optic neuropathy improved an average of 2 lines on the standard Snellen chart testing (range, 1 to 5). Color vision improved an average of 5 Ishihara plates (range, 0 to 13). Seventy-one percent of patients had subjective diplopia before surgery; 21% of these patients reported improvement or complete resolution of diplopia after surgery. Of the 29% of patients without preoperative subjective diplopia, all but one (1.8 of total patients) remained symptom free. CONCLUSIONS: We find that a customized, single-incision, 3-wall orbital decompression provides adequate decompression and proptosis reduction while minimizing postoperative strabismus and providing an aesthetically desirable result.