Martin E. Weinand

The human brain consists of multiple interacting neuronal networks that interleave at fine spatial and temporal scales. This complexity presents a challenge for scalp EEG and other noninvasive mapping techniques to accurately identify seizures and abnormal current patterns from background activity. To address this unmet need, this study investigates Transcranial Acoustoelectric Brain Imaging (tABI) with neuronavigation as a new method for mapping EEG-derived currents through the skull. In tABI, ultrasound (US) is focused and steered in the brain as surface electrodes record an acoustoelectric (AE) interaction signal. Space and time varying current maps are then generated at a resolution determined by the US focus. To test the efficacy of this method, a human skull was filled with conductive agarose gel, and a clinical depth electrode array was implanted 43 mm below the skull surface to generate artificial current waveform segments taken from normal and seizure activity. A 0.6 MHz 2D array was used to electronically focus and steer US through the skull while gold cup electrodes recorded high frequency AE signals and low frequency surface potentials. A 2D Wiener filter (WF) was introduced during preprocessing to enhance SNR followed by Singular Value Decomposition (SVD) to selectively identify pixels correlated with different temporal patterns. Whereas the WF enhanced SNR up to 16.9 dB at 6.4 mA of current, SVD enabled color-coding of tABI to highlight activation patterns correlated with different current waveforms with a spatial resolution of 5 mm. Finally, the current detection limit depended on the duration and bandwidth of the selected currents with the ictal waveform yielding the lowest detection (28 µA and 78 µA/cm2*MPa, p<0.05). These results support the development of tABI for noninvasive mapping of neuronal currents in epilepsy patients for surgical planning and other applications.

Background/Objectives: For patients with medically refractory temporal lobe epilepsy (TLE), surgery is an effective strategy. However, post-operative seizure recurrence occurs in 20–30% of patients, and it remains challenging to predict outcomes solely based on clinical variables. Here, we ask to what extent differences in gene expression in epileptic tissue can predict the outcome after resective epilepsy surgery. Methods: We performed RNAseq on hippocampal tissue resected from eight patients who underwent anterior temporal lobectomy with amygalohippocampectomy (ATL/AH), half of whom became seizure free (SF) or non-seizure free (NSF). Results: Bioinformatic analyses revealed 1548 differentially expressed genes and statistical enrichment analyses identified a distinct set of pathways in NSF and SF cohorts that were associated with neuroinflammation, neurotransmission, synaptic plasticity, and extracellular matrix (ECM) reorganization. Resected tissue exhibiting strong pro-inflammatory processes are associated with better post-surgery seizure outcomes than patients exhibiting cellular signaling processes related to ECM reorganization, autoantibody production, and neural circuit formation. Conclusions: The results suggest that post-operative targeting of both inhibitory aspects of the ECM remodeling and the autoimmune/inflammatory components may be helpful in promoting repair and preventing the recurrence of seizures.

Background/Objectives: For patients with medically refractory temporal lobe epilepsy (TLE), surgery is an effective strategy. However, post-operative seizure-recurrence occurs in 20-30% of patients and it remains challenging to predict outcome solely based on clinical variables. Here we ask to what extent differences in gene expression in epileptic tissue can predict outcome after resective epilepsy surgery. Methods: We perform RNAseq on hippocampal tissue resected from 8 patients who underwent anterior temporal lobectomy with amygalohippocampectomy (ATL/AH), half of whom became seizure free (SF) or non-seizure free (NSF). Results: Bioinformatic analyses revealed 1548 differentially ex-pressed genes and statistical enrichment analyses identified a distinct set of pathways in NSF and SF cohorts that were associated with neuroinflammation, neurotransmission, synaptic plasticity, and extracellular matrix (ECM) reorganization. Resected tissue ex-hibiting strong proinflammatory processes are associated with better post-surgery seizure outcomes than patients exhibiting cellular signaling processes related to ECM reorgan-ization, autoantibody production and neural circuit formation. Conclusions: The results suggest that postoperative targeting of both inhibitory aspects of the ECM remodeling and the autoimmune/inflammatory components may be helpful in promoting repair and preventing the recurrence of seizures.

Introduction: Spinal cord stimulation (SCS) for chronic abdominal pain is not novel. However, this has been explored only when the pain has a clear dermatomal association such as the right upper quadrant for sphincter of Oddi dysfunction or the left upper quadrant for post-traumatic splenectomy. The present report thereby discusses the utility of SCS when the visceral pain is diffusely distributed across all four quadrants of the abdomen. Case Presentation: A patient in their 70s presented with a 30-year history of chronic abdominal pain diffusely located in all four quadrants. The patient had a pancreatic cyst removed via pancreaticoduodenectomy in 1991 complicated by chronic pancreatitis and visceral hyperalgesia. After failed pharmacological management and various outpatient nerve blocks and trigger point injections, the patient underwent SCS placement via five 4-contact paddle leads at the mid- to superior thoracic 7 level. At 1-month follow-up, the patient’s visual analog scale score decreased from 8/10 (prior to implantation) to 0/10. The patient also discontinued his chronic opioid regimen post-SCS placement but continued duloxetine. Device settings remained the same throughout the postoperative period: pulse width of 500 microseconds (inter-burst) and 1,000 microseconds, frequency of 40 Hertz, and current of 1.7 milliamperes. At 12-month follow-up, the patient continued to report >90% pain relief at nearly the same SCS settings as the initial programming. Conclusion: SCS may be a reliable treatment option for chronic abdominal, visceral hyperalgesia when the pain is diffusely located in all 4 quadrants and without a clear dermatomal pattern.

OBJECTIVE: Nonaccidental trauma (NAT) is a major cause of traumatic death during infancy and early childhood. Several findings are known to raise the index of clinical suspicion: subdural hematoma (SDH), retinal hemorrhage (RH), fracture, and external trauma. Combinations of certain injury types, determined via statistical frequency associations, may assist clinical diagnostic tools when child abuse is suspected. The present study sought to assess the statistical validity of the clinical triad (SDH + RH + fracture) in the diagnosis of child abuse and by extension pediatric NAT. METHODS: A retrospective review of The University of Arizona Trauma Database was performed. All patients were evaluated for the presence or absence of the components of the clinical triad according to specific International Classification of Diseases (ICD)–10 codes. Injury type combinations included some variation of SDH, RH, all fractures, noncranial fracture, and cranial fracture. Each injury type was then correlated with the ICD-10 codes for child abuse or injury comment keywords. Statistical analysis via contingency tables was then conducted for test characteristics such as sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: There were 3149 patients younger than 18 years of age included in the quantitative analysis, all of whom had at least one component of the clinical triad. From these, 372 patients (11.8%) had a diagnosis of child abuse. When compared to a single diagnosis of either SDH, RH, all fractures, noncranial fracture, or cranial fracture, the clinical triad had a significantly greater correlation with the diagnosis of child abuse (100% of cases) (p < 0.0001). The dyad of SDH + RH also had a significantly greater correlation with a child abuse diagnosis compared to single diagnoses (88.9%) (p < 0.0001). The clinical triad of SDH + RH + fracture had a sensitivity of 88.8% (95% CI 87.6%–89.9%), specificity of 100% (95% CI 83.9%–100%), and positive predictive value of 100% (95% CI 99.9%–100%). The dyad of SDH + RH had a sensitivity of 89.1% (95% CI 87.9%–90.1%), specificity of 88.9% (95% CI 74.7%–95.6%), and positive predictive value of 99.9% (95% CI 99.6%–100%). All patients with the clinical triad were younger than 3 years of age. CONCLUSIONS: When SDH, RH, and fracture were present together, child abuse and by extension pediatric NAT were highly likely to have occurred.