Faculty Bibliography

Background/UNASSIGNED:F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. Methods/UNASSIGNED:F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. Results/UNASSIGNED:F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood-brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen. Conclusions/UNASSIGNED:F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, we summarize the rationale for using tES techniques, specifically transcranial Direct Current Stimulation (tDCS), across the COVID-19 clinical course, and index ongoing efforts to evaluate the inclusion of tES optimal clinical care.

Sudden Unexplained Death in Childhood (SUDC) is the unexpected death of a child over age 12 months that remains unexplained after a thorough case investigation, including review of the child's medical history, circumstances of death, a complete autopsy and ancillary testing (1). First defined in 2005, SUDC cases are more often male, with death occurring during a sleep period, being found prone, peak winter incidence, associated with febrile seizure history in ~28% of cases and mild pathologic changes insufficient to explain the death (1, 2). There has been little progress in understanding the causes of SUDC and no progress in prevention. Despite reductions in sudden unexpected infant death (SUID) and other causes of mortality in childhood, the rate of SUDC has increased during the past two decades (3-5). In Ireland, SUID deaths were cut in half from 1994 to 2008 while SUDC deaths more than doubled (4). Surveillance issues, including lack of standardized certification practices, affect our understanding of the true magnitude of unexplained child deaths. Mechanisms underlying SUDC, like SUID, remain largely speculative. Limited and inconsistent evidence implicates abnormalities in brainstem autonomic and serotonergic nuclei, critical for arousal, cardiorespiratory control, and reflex responses to life-threatening hypoxia or hypercarbia in sleep (6). Abnormalities in medullary serotonergic neurons and receptors, as well as cardiorespiratory brainstem nuclei occur in some SUID cases, but have never been studied in SUDC. Retrospective, small SUDC studies with non-standardized methodologies most often demonstrate minor hippocampal abnormalities, as well as focal cortical dysplasia and dysgenesis of the brainstem and cerebellum. The significance of these findings to SUDC pathogenesis remains unclear with some investigators and forensic pathologists labeling these findings as normal variants, or potential causes of SUDC. The development of preventive strategies will require a greater understanding of underlying mechanisms.

Background/UNASSIGNED:Spine surgeons encounter occasional complex cerebrospinal fluid fistulas/dural tears (CSF/DT) during lumbar spinal surgery. In some cases, these leaks are found during the index procedure, but others may appear postoperatively, or in the course of successive procedures. Here we asked, whether these complex CSF fistulas/DT could be more readily repaired utilizing a "bone suture anchor" technique, particularly where there is no residual dural margin/remnant. Methods/UNASSIGNED:With the combined expertise of the orthopedist and neurosurgeon, mini/micro bone suture anchors, largely developed for hand surgery, facilitated repair of complex DT occurring during lumbar spine surgery. This technique was utilized to suture in place fascia, periosteal, or muscle grafts, and was followed by the application of microfibrillar collagen, and a fibrin sealant. Results/UNASSIGNED:This mini/micro suture anchor technique has now been utilized to repair multiple significant intraoperative and/or postoperative recurrent DT, largely avoiding the need to place lumbar drains and/or lumbo- peritoneal shunts. Conclusions/UNASSIGNED:Here, we reviewed how to directly suture dural grafts utilizing a mini/micro bone suture anchor technique to repair complex intraoperative primary/recurrent DT occurring during lumbar spine surgery. The major advantages of this technique, in addition to obtaining definitive occlusion of the DT, largely avoids the need to place lumbar drains and/or lumbo-peritoneal shunts with their attendant risks and complications.

Pediatric multiple sclerosis (MS) is an increasingly recognized rare subgroup of patients presenting with a unique set of diagnostic challenges. Understanding the early development of MS may offer a window into the pathogenesis of disease; however further research is needed, particularly within the field of genetics and to understand the complex environmental and biological interactions at work. Acute disseminated encephalomyelitis (ADEM) remains a hallmark presentation of early pediatric disease and can be a monophasic illness or end up being reclassified as a relapsing disorder. The clinical expression is shaped in part by the prepubertal or postpubertal state of the patient. Other syndromes can also present with ADEM, and a specific differential diagnosis exists for children presenting with any initial demyelinating event (IDE). New definitions and criteria have allowed early detection of MS. However applying adult criteria to very young children should be approached with caution. There is now a major effort in studying disease-modifying therapy (DMT) in children due to requirements from regulatory authorities. Pediatric patients respond well to therapy and often do best with an interdisciplinary approach focusing on social aspects, cognition, and fatigue which enhances the achievement of successful outcomes.
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