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As the field of neurogenetics is expanding rapidly and variant classification criteria evolve, genetic variants in databases are re‐evaluated overtime allowing updated classifications of pathogenicity predication. When caring for patients with genetic disorders, it is important to obtain the original genetic report and also consider an updated reanalysis., As the field of neurogenetics is expanding rapidly and variant classification criteria evolve, the clinical utility of reanalysis to obtain updated classification of pathogenicity predication is described in a pregnant patient with a diagnosis of familial hemiplegic migraine.

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked urea cycle disorder. Maternal OTCD can lead to life-threatening hyperammonemia if untreated. We aimed to compare the outcomes of maternal OTCD when diagnosis is known prior to pregnancy to when diagnosis is made during pregnancy. We performed a systematic literature review on maternal OTCD using the databases Ovid MEDLINE and PubMed from 1982 through 2018. Studies were included if addressed maternal OTCD signs, symptoms, and detailed pregnancy outcomes. We calculated the median or the mean for continuous variables and percentages for categorical variables. Of 36 cases of maternal OTCD, 20 (55%) were diagnosed prior to pregnancy while 16 (45%) were not. In the 20 patients diagnosed prior to pregnancy, 7 (35%) had either a neurologic or psychiatric presentation during pregnancy or postpartum. Two hyperammonemic patients (11%) experienced ICU admission, dialysis, and coma with no maternal deaths. All had a favorable outcome. In the 16 patients not known to have maternal OTCD prior to pregnancy, 13 (81%) had neurologic or psychiatric presentation during pregnancy or postpartum. Four presented with hyperemesis gravidarum. Eleven (69%) hyperammonemic patients had ICU admission and coma and 7 (47%) of them had dialysis. There were 5 (31%) maternal deaths. Three patients (19%) had prolonged hospitalization course. Overall, three male neonatal deaths were reported. Three other male children had liver transplant. Maternal OTCD is associated with high maternal and neonatal morbidity and mortality when diagnosis is made during pregnancy compared to when diagnosis is known prior to pregnancy.

Knee injuries cause structural damage and acute inflammation that initiates the development of post-traumatic osteoarthritis (PTOA). NADPH oxidase 4 (Nox4), a member of a family of enzymes that generates reactive oxygen species (ROS), plays a pivotal role in normal development of the musculoskeletal system, but may increase ROS production to harmful levels after joint injury. The role of ROS in both normal joint homeostasis and injury is poorly understood, but inhibition of excessive ROS production by Nox4 after joint injury could be protective to the joint, decreasing oxidative stress, and initiation of PTOA. Knee injuries were simulated using inflammatory cytokines in cultured primary human chondrocytes and a non-invasive mouse model of PTOA in C57BL/6N and Nox4 knockout mice. There is an acute decrease in Nox4 activity within 24 h after injury in both systems, followed by a subsequent sustained low-level increase, a novel finding not seen in any other system. Inhibition of Nox4 activity by GKT137831 was protective against early structural changes after non-invasive knee injury in a mouse model. Nox4 knockout mice had significant differences in structural and mechanical properties of bone, providing further evidence for the role of Nox4 in development of joint tissues and biochemical response after joint injury. Nox4 plays a significant role in the acute phase after joint injury, and targeted inhibition of inflammation caused by Nox4 may be protective against early joint changes in the pathogenesis of PTOA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2429-2436, 2019.

Background. The pseudopapillary pattern of granulosa cell tumor is rare. Case. We describe the case of a 35-year-old woman who presented with an initial diagnosis of papillary serous cystadenocarcinoma. Results. Evaluation, including immunohistochemistry, led to the diagnosis of pseudopapillary granulosa cell tumor. Conclusion. The pseudopapillary pattern of granulosa cell tumor is rare and must be suspected in order to utilize appropriate immunohistochemistry and reach the correct diagnosis. Inhibin positivity is particularly helpful.

Radiotherapy is a versatile tool used in the treatment of various types of benign and malignant neoplasms. However, conventional radiation therapy for cancerous conditions often results in collateral damage to healthy tissues due to involvement of oversized radiation fields. Over the last decade one type of precision based radiation treatment has developed. This new treatment, known as Stereotactic Radiosurgery (SRS), involves highly accurate beams of high-energy radiation that are used to destroy abnormal cells by permanently damaging their DNA. As technology progressed stereotactic cranial radiosurgery developed into a successful method for certain tumorous conditions of the head and skull. The success of stereotactic cranial radiosurgery led to further radiation application research to widen the spectrum of treatable conditions to include those located extracranially. The result of this continued research led to the development of stereotactic body radiation therapy (SBRT), a radiotherapy technique based upon principles of SRS that is used to treat small or moderate sized tumors of the body with a limited number of treatments. Stereotactic body radiation therapy combines the use of the latest tumor imaging technology as well as precision based radiation delivery mechanisms to overcome physiological barriers of normal radiation therapy such as movement of tumors in tissues. The net effect of SBRT is that a dose of radiation much larger than normal can be administered in a very precise manner, over smaller time frame, bringing about a dramatic tumor response. In this review the authors will attempt to briefly cover the subject of stereotactic body radiation therapy as well as its applications and effectiveness.