Faculty Bibliography

Introduction: To date, only very few series have aimed to assess the outcomes of botulinum toxin injections in patients with Parkinson's Disease (PD). The aim of this study was to assess the safety and efficacy of intradetrusor onabotulinum toxin A injections for the treatment of overactive bladder (OAB) in patients with PD.
Method(s): All PD patients who underwent intradetrusor injections of onabotulinum toxin A (BoNT-A) for storage symptoms between 2010 and 2017 were included in a retrospective study. A 100 U dose of BoNT-A (Botox, Allergan Irvine, CA) was used for the first injection in all patients. The primary endpoint was clinical success defined as any subjective improvement in OAB symptoms self-assessed by the patients four weeks after the injections.
Result(s): Out of 24 patients analyzed, 19 reported improvement of their OAB symptoms four weeks after the first injection (79.2%) with complete resolution of urgency urinary incontinence in 7 patients (29.1%; p<0.001). The average post-void residual (PVR) increased significantly after the first injection from 17.6 to 125.3 ml (p<0.001). Three of the patients had to start clean intermittent catheterization (CIC) after the first injection (12.5%). Out of 49 injections in total, only five caused incomplete bladder emptying requiring the use of CIC (10.2%). Higher pre-injection PVR was significantly associated with both a lower chance of symptomatic improvement (p=0.04) and a higher risk of incomplete bladder emptying with institution of CIC (p=0.047).
Conclusion(s): Botox appeared effective in PD patients with a relatively low rate of retention requiring CIC. Higher preoperative PVR was the stronger predictor of both treatment failure and postoperative urinary retention requiring CIC while urodynamic obstruction was also associated with treatment failure in male patients. Intradetrusor injections of BoNT-A 100 U appeared as a safe and effective option in PD patients with OAB symptoms and a low PVR before the injection

N-Methyl-d-aspartate (NMDA) receptors are ligand and voltage-gated heteromeric ion channel receptors. Excessive activation of NMDA receptors is implicated in many neurological and psychiatric disorders, including ischemic stroke, neuropathic pain, epilepsy, drug addition, Alzheimer's disease, and schizophrenia. [¹⁸F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or 'open' channel) with a high binding affinity (K_d = 2.4 nM). Here, we report the production of the NMDA receptor radioligand [¹⁸F]GE179 in a current Good Manufacturing Practice (cGMP) facility through a one-pot two-step strategy. [¹⁸F]GE179 was produced in approximately 110 min with a radiochemical yield of 12 ± 6% (n = 4, decay corrected), radiochemical purity >95%, molar activity of 146 ± 32 GBq/μmol (at the end of synthesis), an average mass of GE179 at 2.2 μg/batch, and total impurities less than 0.5 μg/batch (n = 4). The radiopharmaceutical dose meets all quality control (QC) criteria for human use, and is suitable for clinical PET studies of activated NMDA receptor ion channels.

Mental health emergencies require a rapid, effective response. We searched the literature on mental health emergencies in athletes and found five papers. None of these addressed elite athletes. Nonetheless, common mental health emergencies may present in the sports environment and may place the athlete and others at risk. Sports teams and organisations should anticipate which emergencies are likely and how medical and support staff can best respond. Responses should be based on general non-sporting guidelines. We stress the importance of clinicians following standard procedures.

Status dystonicus (SD) is a rare and potentially life-threatening condition requiring intensive care management. Deep brain stimulation (DBS) has emerged as an effective treatment for SD refractory to medical management, but its application in this field is still limited. Here, we report the long-term outcome of four pediatric patients treated with DBS at the University Hospital of Padua, Italy, for SD refractory to medications. In addition, we present the results of a systematic literature review aimed at identifying published cases of SD treated with DBS, with focus on motor outcome. In our cohort, two children were affected by methylmalonic acidemia and suffered acute basal ganglia lesions, while the other two carried a pathogenic mutation in GNAO1 gene. DBS target was subthalamic nucleus (STN) in one case and globus pallidus internus (GPi) in three. All patients experienced SD resolution within 8-19 days after surgery. Mean post-operative follow-up was 5 years. We identified in the literature 53 additional SD cases treated with DBS (median age at DBS implantation: 12 years) with reported positive outcome in 51 and resolution of SD in a mean of 17 days after surgery. Our findings indicate that DBS is an effective treatment for SD refractory to medications, even in patients with acute basal ganglia lesions; STN can be an appropriate target when GPi is damaged. Moreover, data from long-term follow-up show that SD recurrences can be significantly reduced in frequency or abolished after DBS implantation.

BACKGROUND:There have been a number of recent prominent lawsuits challenging the use of neurologic criteria to declare death in the United States. METHODS:To put these lawsuits into perspective, we conducted a search of Nexis Uni® to identify cases from the past 50 years that involved objections to the use of neurologic criteria to declare death in the United States. RESULTS:We identified lawsuits about 67 decedents (59 state and 8 federal) from 34 different regions which were filed for crime related issues (n=42), hospital related issues (n=20), insurance related issues (n=2) and other issues related to time of death (n=3). The judicial opinions about the lawsuits addressed: 1) acceptance of the use of neurologic criteria to declare death (n=55), 2) criteria to declare death (n=3), 3) management of decedents after death by neurologic criteria (n=13), 4) identification of the time of death (n=4) and 5) rights of the dead (n=3). The outcomes of these cases were heterogeneous. CONCLUSION/CONCLUSIONS:Since the incorporation of neurologic criteria into the medical practice of declaration of death, there have been a number of legal objections to its use. To avoid the rendering of variable opinions by the courts, there is a need for consistent legislative modification throughout the country to address 1) the specific criteria to employ when declaring death by neurologic criteria, 2) management of religious objections to use of neurologic criteria to declare death and 3) management after declaration of death by neurologic criteria.

OBJECTIVES/OBJECTIVE:To present an overview of the existing epidemiological evidence regarding the occurrence of mental health symptoms and disorders among current and former elite athletes. DESIGN/METHODS:Systematic review and meta-analysis. DATA SOURCES/METHODS:Five electronic databases were searched from inception to November 2018: PubMed (MEDLINE), SportDiscus via EBSCO, PSycINFO via ProQuest, Scopus and Cochrane. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/UNASSIGNED:We included original quantitative studies that were written in English, were conducted exclusively among current or former elite athletes, and presented incidence or prevalence rates of symptoms of mental disorders. RESULTS:Twenty-two relevant original studies about mental health symptoms and disorders among current elite athletes were included: they presented data especially on symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 2895 to 5555 current elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression. Fifteen relevant original studies about mental health symptoms and disorders among former elite athletes were included: they similarly presented data especially about symptoms of distress, sleep disturbance, anxiety/depression and alcohol misuse. Meta-analyses comprising 1579 to 1686 former elite athletes showed that the prevalence of mental health symptoms and disorders ranged from 16% for distress to 26% for anxiety/depression. CONCLUSIONS:Our meta-analyses showed that the prevalence of mental health symptoms and disorders ranged from 19% for alcohol misuse to 34% for anxiety/depression for current elite athletes, and from 16% for distress to 26% for anxiety/depression for former elite athletes.

OBJECTIVE:Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). We evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability. METHODS:Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, we identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, we identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, we removed three "boilerplate" standard text phrases from away notes and repeated performance. RESULTS:We observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data. SIGNIFICANCE/CONCLUSIONS:Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. Our methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling.

Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.