Idiopathic Generalized Epilepsy: Misunderstandings, Challenges, and Opportunities

The idiopathic generalized epilepsies (IGE) make up a fifth of all epilepsies, but <1% of epilepsy research. This skew reflects misperceptions: diagnosis is straightforward, pathophysiology is understood, seizures are easily controlled, epilepsy is outgrown, morbidity and mortality are low, and surgical interventions are impossible. Emerging evidence reveals that patients with IGE may go undiagnosed or misdiagnosed with focal epilepsy if EEG or semiology have asymmetric or focal features. Genetic, electrophysiologic, and neuroimaging studies provide insights into pathophysiology, including overlaps and differences from focal epilepsies. IGE can begin in adulthood and patients have chronic and drug-resistant seizures. Neuromodulatory interventions for drug-resistant IGE are emerging. Rates of psychiatric and other comorbidities, including sudden unexpected death in epilepsy, parallel those in focal epilepsy. IGE is an understudied spectrum for which our diagnostic sensitivity and specificity, scientific understanding, and therapies remain inadequate.

A novel paradigm examining the remote induction of nocebo effects online.

OBJECTIVE: Side effect information is routinely communicated online. However, limited experimental evidence exists regarding the role of this information in generating maladaptive health outcomes (i.e., the nocebo effect). A novel paradigm was developed to remotely induce the nocebo effect via provision of online side effect information. METHOD: Participants were given information regarding the positive effects of low frequency noise (LFN). A proportion were additionally warned of LFN-induced side effects. Study 1 (N = 423) investigated the source of information (listed vs. socially communicated side effects), while Study 2 (N = 560) investigated the role of positive and negative affects on attenuating and exacerbating the nocebo effect. Pooled analysis (N = 983) explored the effect of negative and positive expectations on both the nocebo effect and positive outcomes. RESULTS: Across studies, a significant nocebo effect in the warned side effects occurred after LFN exposure. This did not vary by source of information (Study 1) nor was it attenuated via the induction of positive affect (Study 2). Both studies demonstrated a reduction in positive outcomes among those receiving side effect information. Pooled analysis revealed that negative, but not positive, expectations mediated the nocebo effect. Positive and negative expectations interacted to predict positive outcomes. Holding negative expectations appeared to block positive health outcomes. Specifically, when negative expectations were above average, there was no effect of positive expectations on positive outcomes. CONCLUSIONS: Nocebo effects were remotely generated via minimal provision of side effect information. Pooled analysis revealed that future interventions should target positive and negative expectations to reduce side effects. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

BACKGROUND AND OBJECTIVES: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. METHODS: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. RESULTS: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. DISCUSSION: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.

Interictal EEG and ECG for SUDEP Risk Assessment: A Retrospective Multicenter Cohort Study.

Objective: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Although lots of effort has been made in identifying clinical risk factors for SUDEP in the literature, there are few validated methods to predict individual SUDEP risk. Prolonged postictal EEG suppression (PGES) is a potential SUDEP biomarker, but its occurrence is infrequent and requires epilepsy monitoring unit admission. We use machine learning methods to examine SUDEP risk using interictal EEG and ECG recordings from SUDEP cases and matched living epilepsy controls. Methods: This multicenter, retrospective, cohort study examined interictal EEG and ECG recordings from 30 SUDEP cases and 58 age-matched living epilepsy patient controls. We trained machine learning models with interictal EEG and ECG features to predict the retrospective SUDEP risk for each patient. We assessed cross-validated classification accuracy and the area under the receiver operating characteristic (AUC) curve. Results: The logistic regression (LR) classifier produced the overall best performance, outperforming the support vector machine (SVM), random forest (RF), and convolutional neural network (CNN). Among the 30 patients with SUDEP [14 females; mean age (SD), 31 (8.47) years] and 58 living epilepsy controls [26 females (43%); mean age (SD) 31 (8.5) years], the LR model achieved the median AUC of 0.77 [interquartile range (IQR), 0.73-0.80] in five-fold cross-validation using interictal alpha and low gamma power ratio of the EEG and heart rate variability (HRV) features extracted from the ECG. The LR model achieved the mean AUC of 0.79 in leave-one-center-out prediction. Conclusions: Our results support that machine learning-driven models may quantify SUDEP risk for epilepsy patients, future refinements in our model may help predict individualized SUDEP risk and help clinicians correlate predictive scores with the clinical data. Low-cost and noninvasive interictal biomarkers of SUDEP risk may help clinicians to identify high-risk patients and initiate preventive strategies.

Cytogenetic guided therapy using blinatumomab and inotuzumab ozogamicin in a patient with relapse/refractory acute lymphoblastic leukemia.

INTRODUCTION: Acute Lymphoblastic Leukemia (ALL) is an aggressive cancer that requires intense chemotherapy and has a high rate of recurrence. Treatments of Relapse/Refractory (R/R) B-cell ALL are limited. Blinatumomab, a bispecific T-cell engager (CD19/CD3) monocolonal antibody, and Inotuzumab Ozogamicin, an anti-CD22 antibody conjugate, are current recommended options. CASE REPORT: To describe a R/R B-cell ALL patient who failed blinatumomab therapy. Subsequently she received inotuzumab ozogamicin achieving a complete response. MANAGEMENT & OUTCOME: Our patient was initially treated with CALGB 10403 regimen but did not achieve a complete response. Blinatumomab was given for relapse/refractory disease however she had an incomplete response despite having 100% expression in CD19 markers. Consequently, she received inotuzumab ozogamicin attributable to 70% expression of CD22. She responded with a complete response and transitioned to a successful hematopoietic stem cell transplant. DISCUSSION: There is limited clinical guidance on the preferred treatment of adult R/R B-Cell ALL. Currently, there are no randomized head-to-head trials comparing efficacy of blinatumomab and inotuzumab ozogamicin. Clinical patterns of blinatumomab resistance has been reported. Our case study remains unclear of why our patient had unsuccessful outcomes with blinatumomab regardless of having CD19 positivity of 100%. Future prospective analysis and comparative studies are needed to determine proper sequencing of these therapies.

Managing Multiple Myeloma in the Face of Drug-Induced Adverse Drug Reaction.

Drug-induced liver injury has been reported to cause up to 10% of adverse drug reactions in the United States. Risk factors for druginduced liver injury include female gender, older age, interacting medications and drugs that are metabolized by the liver. This case report describes a patient who was newly initiated on tizanidine, an alpha2 adrenergic agonist used for muscle spasm and musculoskeletal pain, and bortezomib, a proteasome inhibitor used for multiple myeloma. Both medications are metabolized by cytochrome P450 isoenzyme 1A2. The medications were suspected of causing acute hepatitis based on the timing of their initiation and evidence to suggest that they can cause acute hepatitis. The Naranjo adverse drug reaction scale was scored as possible. In addition, the drugs' blood levels may have been increased by acyclovir and hydralazine, both inhibitors of cytochrome P450 isoenzyme 1A2. A dilemma for the team was how to best manage bortezomib. It is part of first line treatment for multiple myeloma when combined with lenalidomide and dexamethasone. Other proteasome inhibitors are available for multiple myeloma treatment. When starting chemotherapy, it is important to be aware of medications that cause a rise in liver enzymes, potential drug interactions, and how best to manage the clinical consequences.

Clinical and EEG factors associated with antiseizure medication resistance in idiopathic generalized epilepsy.

OBJECTIVE: We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)-resistant vs ASM-responsive outcome for patients with idiopathic generalized epilepsy (IGE). METHODS: This was a case-control study of ASM-resistant cases and ASM-responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient. We then compared characteristics of cases vs controls using multivariable logistic regression to develop a predictive model of ASM-resistant IGE. RESULTS: We identified 118 ASM-resistant cases and 114 ASM-responsive controls with IGE. First, we confirmed our recent finding that catamenial epilepsy is associated with ASM-resistant IGE (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.32-10.41, for all study subjects) after covariate adjustment. Other independent factors seen with ASM resistance include certain seizure-type combinations (absence, myoclonic, and generalized tonic-clonic seizures [OR 7.06, 95% CI 2.55-20.96]; absence and generalized tonic-clonic seizures [OR 4.45, 95% CI 1.84-11.34]), as well as EEG markers of increased generalized spike-wave discharges (GSWs) in sleep (OR 3.43, 95% CI 1.12-11.36 for frequent and OR 7.21, 95% CI 1.50-54.07 for abundant discharges in sleep) and the presence of generalized polyspike trains (GPTs; OR 5.49, 95% CI 1.27-38.69). The discriminative ability of our final multivariable model, as measured by area under the receiver-operating characteristic curve, was 0.80. SIGNIFICANCE: Multiple clinical and EEG characteristics independently predict ASM resistance in IGE. To improve understanding of a patient's prognosis, clinicians could consider asking about specific seizure-type combinations and track whether they experience catamenial epilepsy. Obtaining prolonged EEG studies to record the burden of GSWs in sleep and assessing for the presence of GPTs may provide additional predictive value.

Immune-checkpoint inhibitor toxicity during a pandemic: Overcoming patient fears to provide care. A case report.

BACKGROUND: Pembrolizumab is a humanized monoclonal antibody that is used to treat a variety of cancers. It exerts its mechanism of action by blocking the programmed death receptor-1 (PD-1). Toxicity concerns include immune-related toxicities, including colitis, hepatitis, pneumonitis, nephritis, endocrine toxicities and more rarely, myocarditis and other organ system toxicities. OBJECTIVE: To review a real-world case involving immunotherapy induced myocarditis after a patient received pembrolizumab and discuss how the current pandemic created complexity in toxicity management. DISCUSSION: An 83 year old male with metastatic lung cancer developed fatal myocarditis after receiving 2 doses of pembrolizumab. Applying the Naranjo score, the likelihood of pembrolizumab causing the myocarditis is probable, with a score of 6. Severe cardiac toxicities are rare with pembrolizumab, but can still occur. It is vital to be aware of these toxicities, and educate patients on signs and symptoms. Complicating the situation even further was the global pandemic, which created fear and hesitation in the patient and the patient's family to seek medical treatment out of fear of exposure. This pandemic adds another layer to the complexity of care for patients with cancer and management of toxicities. Pharmacists play a significant role in ensuring the safety and efficacy of medications, especially oncology agents. CONCLUSION: Proper education of patients regarding symptoms and when to report are paramount to assisting in early detection and intervention for immunotherapy-related adverse events. New management and treatment strategies will need to be discussed and implemented considering the changing landscape around the SARS-CoV-2 pandemic.

The impact of medications and medical comorbidities on sexual function in people with epilepsy.

OBJECTIVE: People with epilepsy experience increased rates of sexual dysfunction, often affecting quality of life. Sexual dysfunction may result from the underlying disorder, antiseizure or other medications, or comorbid psychosocial factors. This study evaluated the incidence and clinical associations of sexual dysfunction in adult epilepsy patients. METHODS: 89 epilepsy patients 18 years and older admitted to the New York University Comprehensive Epilepsy Center epilepsy monitoring unit between 2016 and 2018 completed a survey on sexual functioning. The survey included demographic, clinical, and sexual functioning information with a validated measure of sexual function (the Arizona Sexual Experiences Scale (ASEX). RESULTS: Of 89 surveys completed, 15 (16.9 %) patients had discussed sexual functioning with a medical professional and 20 (22.5 %) reported sexual dysfunction. For the group, the mean ASEX score was 13.6 (SD 4.8). 59 (66.3 %) participants reported not being asked about sexual health by their doctor or nurse practitioner in the last year. The two independent predictors of sexual dysfunction were self-identifying as overweight/obese (OR 6.1, CI 1.4-26.5, P = 0.02) or taking strong enzyme-inducing antiseizure medications (OR 7.8, CI 1.4-44.9, P = 0.02). Other factors such as age, relationship status, duration of epilepsy, the presence of depression or anxiety, cardiovascular risk factors, and opioid/stimulant use, did not predict sexual dysfunction. SIGNIFICANCE: Our study showed that sexual dysfunction is common in epilepsy patients but infrequently discussed by medical professionals. Two modifiable risk factors, being overweight or taking strong enzyme-inducing antiseizure medications, were independently associated with sexual dysfunction, suggesting interventions to potentially improve sexual health.

Saddle pulmonary embolism with fluorouracil: A case report.

INTRODUCTION: As a single agent, fluorouracil has been documented to have a small but present chance of causing extravasation of the port when not properly administered. It has also been shown that cancer patients receiving chemotherapy are at increased risk of deep vein thrombosis, symptomatic or silent. CASE REPORT: A 43-year-old male patient with stage III colon cancer receiving FOLFOX developed a saddle pulmonary embolism involving possible extravasation that was discovered following cycle 3 of chemotherapy. CT scan and lower extremity Doppler confirmed non-occlusive deep vein thrombosis along with saddle pulmonary embolism.Management and outcome: For acute management, patient underwent bilateral pulmonary artery thrombolysis. Following this, the patient was initiated on rivaroxaban indefinitely. The right subclavian port was removed, and a new port was placed in the left subclavian. Patient went on to receive three more cycles of chemotherapy. DISCUSSION: Fluorouracil, an inflammitant, has been shown to have damaging potential, especially in terms of the integrity of the endothelium. Over time, this can lead to serious complications such as cardiotoxicity, including deep vein thrombosis formation. Based on how and when the thrombi were discovered, it is not possible to deduce whether the port, the 5-FU, extravasation or other factors were the precipitators of the formation of the thrombi. The combination of chemotherapy treatment along with CVC placement appears to have an additive risk to the formation of a thrombus. Practitioners should take caution when evaluating for extravasation and CVC integrity and note other potential differentials for causes, including deep vein thrombosis/saddle pulmonary embolism formation.

Front-line use of tyrosine kinase inhibitors in chronic phase chronic myeloid leukemia: Practice considerations.

The development of BCR-ABL-targeting tyrosine kinase inhibitors has transformed chronic phase chronic myeloid leukemia (CP CML) from a disease with a terminal prognosis to a treatable chronic illness. Long-term treatment with tyrosine kinase inhibitors means that patients have to be clinically managed and monitored over extended periods of time, thus a patient-centered, medically integrated, and multidisciplinary oncology healthcare team is required to support patients through their journey. Pharmacists work with patients, physicians, and the wider support team to select the optimum therapy plan for a given patient. These decisions are based on risk factors, comorbidities, concomitant medications, and personal circumstances and pharmacists advise on the efficacy and safety of different treatment options. Additionally, pharmacists are a key point-of-contact and resource for monitoring patient response to treatment, identifying and managing adverse events and drug-drug interactions, any subsequent therapy plan modifications, and, potentially, treatment-free remission. Pharmacists also assist with patient education, medication adherence, and financial discussions with patients throughout the long course of the disease. This review provides an overview of BCR-ABL tyrosine kinase inhibitors, discusses the role of the medically integrated pharmacy team, and suggests strategies that pharmacists can use in patient management and clinical decision-making to optimize the treatment of CP CML.

Hand posture as localizing sign in adult focal epileptic seizures.

OBJECTIVE: The aim of this study was to identify specific ictal hand postures (HPs) as localizing signs of the epileptogenic zone (EZ) in patients with frontal or temporal lobe epilepsy. METHODS: In this study, we retrospectively analyzed ictal semiology of 489 temporal lobe or frontal lobe seizures recorded over a 6-year period at the Seizure Disorder Center at University of California, Los Angeles in the USA (45 patients) or at the C. Munari Epilepsy Surgery Center at Niguarda Hospital in Milan, Italy (34 patients). Our criterion for EZ localization was at least 2 years of seizure freedom after surgery. We analyzed presence and latency of ictal HP. We then examined whether specific initial HPs are predictive for EZ localization. RESULTS: We found that ictal HPs were present in 72.5% of patients with frontal and 54.5% of patients with temporal lobe seizures. We divided HPs into 6 classes depending on the reciprocal position of the fingers ("fist," "cup," "politician's fist," "pincer," "extended hand," "pointing"). We found a striking correlation between EZ localization and ictal HP. In particular, fist and pointing HPs are strongly predictive of frontal lobe EZ; cup, politician's fist, and pincer are strongly predictive of temporal lobe EZ. INTERPRETATION: Our study offers simple ictal signs that appear to clarify differential diagnosis of temporal versus frontal lobe EZ localization. These results are meant to be used as a novel complementary tool during presurgical evaluation for epilepsy. At the same time, they give us important insight into the neurophysiology of hand movements. ANN NEUROL 2019;86:793-800.

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment-resistant multifocal epilepsy.

Electrical stimulation in the anterior nucleus of the thalamus (ANT) has previously been found to be efficacious for reducing seizure frequency in patients with epilepsy. Bilateral deep brain stimulation (DBS) of the ANT is an open-loop system that can be used in the management of treatment-resistant epilepsy. In contrast, the responsive neurostimulation (RNS) system is a closed-loop device that delivers treatment in response to prespecified electrocorticographic triggers. The efficacy and safety of RNS targeting the ANT is unknown. We describe 3 patients with treatment-resistant multifocal epilepsy who were implanted with an RNS system, which included unilateral stimulation of the ANT. After >33 months of follow-up, there were no adverse effects on mood, memory or behavior. Two patients had ≥50% reduction in disabling seizures and one patient had a 50% reduction compared to pretreatment baseline. Although reduction in seizure frequency has been modest to date, these findings support responsive neurostimulation of the ANT as feasible, safe, and well-tolerated. Further studies are needed to determine optimal stimulation parameters.

Precision Pharmacotherapy: Integrating Pharmacogenomics into Clinical Pharmacy Practice.

Precision pharmacotherapy encompasses the use of therapeutic drug monitoring; evaluation of liver and renal function, genomics, and environmental and lifestyle exposures; and analysis of other unique patient or disease characteristics to guide drug selection and dosing. This paper articulates real-world clinical applications of precision pharmacotherapy, focusing exclusively on the emerging field of clinical pharmacogenomics. This field is evolving rapidly, and clinical pharmacists now play an invaluable role in the clinical implementation, education, and research applications of pharmacogenomics. This paper provides an overview of the evolution of pharmacogenomics in clinical pharmacy practice, together with recommendations on how the American College of Clinical Pharmacy (ACCP) can support the advancement of clinical pharmacogenomics implementation, education, and research. Commonalities among successful clinical pharmacogenomics implementation and education programs are identified, with recommendations for how ACCP can leverage and advance these common themes. Opportunities are also provided to support the research needed to move the practice and application of pharmacogenomics forward.

A finite element modeling study of peripheral nerve recruitment by percutaneous tibial nerve stimulation in the human lower leg.

Percutaneous tibial nerve stimulation (PTNS) is a clinical therapy for treating overactive bladder (OAB), where an un-insulated stainless steel needle electrode is used to target electrically the tibial nerve (TN) in the lower leg. Recent studies in anesthetized animals not only confirm that bladder-inhibitory reflexes can be evoked by stimulating the TN, but this reflex can also be evoked by stimulating the adjacent saphenous nerve (SAFN). Although cadaver studies indicate that the TN and major SAFN branch(es) overlap at the location of stimulation, the extent to which SAFN branches are co-activated is unknown. In this study, we constructed a finite element model of the human lower leg and applied a numeric axon model (MRG model) to simulate the electrical recruitment of TN and SAFN fibers during PTNS. The model showed that up to 80% of SAFN fibers (located at the level of the needle electrode) can be co-activated when electrical pulses are applied at the TN activation threshold, the standard therapeutic amplitude. Both the location of the inserted electrode and stimulation amplitude were important variables that affected the recruitment of SAFN branches. This study suggests further work is needed to investigate the potential therapeutic effects of SAFN stimulation in OAB patients.

Post-contractile BOLD contrast in skeletal muscle at 7 T reveals inter-individual heterogeneity in the physiological responses to muscle contraction.

Muscle blood oxygenation-level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre-contraction signal intensity were observed in the soleus muscle. We observed considerable inter-subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (TR : 1000 and 2500 ms) to determine the potential of T1 -related inflow effects on the magnitude of the post-contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two TR values (3.8 ± 0.9 versus 4.0 ± 0.6% for TR  = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post-contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.

Isolated Abducens Nerve Palsy: Update on Evaluation and Diagnosis.

Abducens nerve palsy is a common clinical finding in neurology practice. In many instances, the origin is obvious and management straightforward; however, the list of possible etiologies and mimics is vast and diverse and diagnostic decisions can be challenging and even controversial. This is especially true when the abducens nerve is affected in isolation, since in the current era of cost-effective medicine, it is critical to accurately diagnose etiologies that may lead to major morbidity or mortality with efficiency. Topics for highlighted updates in this review include management of isolated abducens nerve palsy with a high likelihood of a microvascular ischemic etiology; common imaging pitfalls and current state-of-the-art neuroimaging; and abducens palsy mimics.

Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla.

PURPOSE: The purpose of this study was to determine the feasibility of muscle BOLD (mBOLD) imaging at 7 Tesla (T) by comparing the changes in R2* of muscle at 3 and 7T in response to a brief period of tourniquet-induced ischemia. METHODS: Eight subjects (three male), aged 29.5 ± 6.1 years (mean ± standard deviation, SD), 167.0 ± 10.6 cm tall with a body mass of 62.0 ± 18.0 kg, participated in the study. Subjects reported to the lab on four separate occasions including a habituation session, two MRI scans, and in a subset of subjects, a session during which changes in blood flow and blood oxygenation were quantified using Doppler ultrasound (U/S) and near-infrared spectroscopy (NIRS) respectively. For statistical comparisons between 3 and 7T, R2* rate constants were calculated as R2* = 1/T2*. RESULTS: The mean preocclusion R2* value was greater at 7T than at 3T (60.16 ± 2.95 vs. 35.17 ± 0.35 s(-1), respectively, P < 0.001). Also, the mean ΔR2 *END and ΔR2*POST values were greater for 7T than for 3T (-2.36 ± 0.25 vs. -1.24 ± 0.39 s(-1), respectively, Table 1). CONCLUSION: Muscle BOLD contrast at 7T is as much as six-fold greater than at 3T. In addition to providing greater SNR and CNR, 7T mBOLD studies may offer further advantages in the form of greater sensitivity to pathological changes in the muscle microcirculation.

Co-activation of saphenous nerve fibers: a potential therapeutic mechanism of percutaneous tibial nerve stimulation?

Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive and effective treatment for overactive bladder (OAB). However, clinical trials show that positive therapeutic outcomes among patients are difficult to predict (failure rate = 35% to 50%). Inconsistencies in the stimulation amplitudes used clinically and those used in preclinical animal studies led us to hypothesize that OAB therapy involves a secondary bladder-inhibitory pathway. In this paper, we implemented and tested a computer model of the human lower leg that investigated the differential activation of the saphenous nerve (SAFN) and tibial nerve (TN) during percutaneous electrical stimulation. Our preliminary findings show that concomitant activation of SAFN branches occurs during PTNS, which suggests the possibility that the SAFN may influence the clinical outcome of treatment.

Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans.

Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities.