Strategies for preservation of memory function in patients with brain metastases.

BACKGROUND: Cognitive decline, particularly in memory, is a side effect seen in patients with brain metastases and when severe, can have a significant impact on their quality of life. It is most often the result of multiple intersecting etiologic factors, including the use of whole brain radiation therapy, effects of which, in part, are mediated by damage within the hippocampus. A variety of clinical factors and comorbidities may impact the likelihood and severity of this cognitive decline, and affected patients should be considered for evaluation in a comprehensive neuro-rehabilitation or "brain fitness" program. PREVENTION STRATEGIES OF NEUROCOGNITIVE DECLINE DUE TO WHOLE BRAIN RADIOTHERAPY (WBRT): Avoiding WBRT is warranted for some patients with brain metastases; particularly those <50 years old. However, when WBRT is clinically indicated, hippocampal avoidance WBRT (HA-WBRT) has been shown to significantly reduce memory decline compared to historical controls without compromising treatment efficacy. Additionally, the NMDA receptor antagonist memantine and renin-angiotensin-aldosterone system (RAAS) blockers have shown promise as neuroprotective agents that could be used prophylactically with radiation. TREATMENT OF PATIENTS WITH NEUROCOGNITIVE DECLINE: After the onset of neurocognitive decline the treatment is largely symptom-driven, however simply screening for and treating depression, fatigue, anxiety, cognitive slowing, and other processes may alleviate some impairment. Stimulants such as methylphenidate may be useful in treating symptoms of fatigue and cognitive slowing. Other treatments including donepezil and cognitive rehabilitation have been extensively tested in the population at risk for dementia, although they have not been adequately studied in patients following cranial radiotherapy. An innovative hypothetical approach is the use of intranasal metabolic stimulants such as low dose insulin, which could be valuable in improving cognition and memory, by reversing impaired brain metabolic activity. CONCLUSIONS: Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in those in whom avoidance cannot be utilized. Likewise treatment will require a personalized combination of strategies optimized to address the patient's symptoms.

Estimation of tibial shaft defect volume using standard radiographs: development and validation of a novel technique.

BACKGROUND: No simple clinical technique with which to measure the volume of bone gaps in the treatment of open fractures or nonunions of the tibia is currently available. It is difficult to compare the three-dimensional magnitude of bone defects in research studies on bone grafting without such a tool, and clinicians have no way of determining the magnitude of defects in clinical practice. The purposes of this study were to develop and to validate a technique with which to accurately measure bone gap volumes of the tibial shaft by using only simple measurements on already available clinical radiographs and a simple equation. We hypothesized that a technique could be developed using anteroposterior- and lateral-view radiographs of the tibia to accurately determine the volume of a tibial shaft fracture. METHODS: We created standardized fracture gap models using 45 synthetic tibiae cut in different locations and orientations, rendering 135 gaps. We developed and validated a hydrostatic suspension technique to determine the volume of each bone, which underwent anteroposterior- and lateral-view radiography after each cut. Radiographic measurements were used to calculate defect volumes based on a simple equation. Predicted volumes were compared with measured volumes. RESULTS: The triangular prism equation matched well with the actual volumes. Linear regression analysis showed a slope of 0.92 and R(2) of 0.97. CONCLUSION: The equation provides a simple technique with which to calculate three-dimensional gap volumes based on standard radiographs. The simplicity of the equation and availability of standard radiographs make this a practical research and perhaps clinical tool that might be useful in quantifying volumes of the tibial shaft defect.