Mechanisms of post-radiation injury: cerebral microinfarction not a significant factor.

Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined. The annual incidence of CMI was calculated. Only 2 definite CMI were found (2/685, 0.3 %). The calculated annual incidence of CMI was 0.11. This incidence is similar to the normal population, and lower than the reported incidence in patients with intracerebral hemorrhage or cognitive impairment. CMI incidence in patients treated with brain RT is similar to the general population. This finding suggests that post-radiation leukoencephalopathy and cognitive impairment are not due to active SVD solely but rather secondary to other causes such as inflammation, metabolic or direct cell damage.

Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis.

Leptomeningeal disease (LMD) occurs in 5 % of breast cancer patients. The aim of this study was to identify risk factors related to survival and time to development of LMD in breast cancer patients. A retrospective analysis of breast cancer patients with LMD, evaluated in MDACC between 1995 and 2011. 103 patients with diagnosis of breast cancer and LMD were identified (one male). The median age at LMD diagnosis was 49.2 years. 78.2 % had invasive ductal carcinoma. Hormone receptors (HRs) were positive in 55.3 % of patients, 47.4 % were human epidermal growth factor receptor 2-positive and 22.8 % were triple negative. 52 % of the patients were treated with WBRT, 19 % with spinal radiation, 36 % with systemic chemotherapy and 55 % with intrathecal chemotherapy. Estimated median overall survival from time of breast cancer diagnosis was 3.66 years. Median survival from time of LMD diagnosis was 4.2 months. Time from breast cancer diagnosis to LMD was 2.48 years. In multivariate analysis, HR status and stage at diagnosis were significantly associated with time to LMD diagnosis (p < 0.05). In triple negative patients, time to LMD was shorter. In patients who were HR positive, time to LMD was longer. Survival from LMD diagnosis was significantly associated with both treatment, as well as positive HR status (multivariate analysis p < 0.05). In conclusion LMD has dismal prognosis in breast cancer patients. HR status contributes to time to LMD diagnosis and survival from LMD diagnosis. The impact of treatment aimed at LMD cannot be ascertained in our retrospective study due to the inherent bias associated with the decision to treat.

Clinical characteristics of Parkinson's disease among Jewish Ethnic groups in Israel.

Yemenite Jews in Israel are a distinctive ethnic division of the Jewish diaspora. Clinical findings, disease course and genetic tests for the LRRK2 6055G > A (G2019S) mutation were compared between Ashkenazi and Yemenite Israeli patients with Parkinson's disease (PD). Age of onset was significantly younger in the Yemenites (P < 0.001). There were no differences in the distribution of initial symptoms, environmental risk factors or rate of motor/non-motor phenomena. The Yemenite group had a more severe disease (P < 0.001), and a more rapid disease course (P = 0.006). The frequency of Lrrk2 substitution was 12.7% in the Ashkenazi group and was not observed in the Yemenites. These results show that there are differences between Israeli Jewish ethnic groups in the severity and progression of PD, but not in clinical symptoms. The high frequency of Lrrk2 G2019S in the Ashkenazi and its absence in the Yemenite Jews suggests a specific ancestral pattern of inheritance in Ashkenazi Jews.

Mass antibiotic treatment to stop an outbreak of meningococcal disease: a molecular analysis.

The occurrence of three cases of meningococcal disease among children in a small community, two of whom attended the same day-care centre, prompted a programme of mass antibiotic prophylaxis. Nasopharyngeal and throat swabs were obtained on three occasions from all children registered at the day-care centre. Serogroup B Neisseria meningitidis was isolated from 13 of 61 children before prophylaxis, from three children after 2 weeks, and from 19 children after 3 months. Repetitive extragenic palindromic PCR analysis identified several meningococcal strains before treatment, one of which became predominant after 3 months. Mass antibiotic prophylaxis initially suppressed meningococcal carriage, but the carriage rate subsequently rebounded.