Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

An Examination of Pain's Relationship to Sleep Fragmentation and Disordered Breathing Across Common Sleep Disorders.

Objective: Short sleep duration and insomnia have been linked to higher pain and an increased risk of developing chronic pain, but relatively little research has examined the contribution of sleep disordered breathing (SDB) to pain. This study examined the unique contributions of SDB and insomnia to chronic pain. Subjects: Adult patients referred to an academic sleep center for overnight polysomnography were invited to participate. Methods: Participants (N = 105) completed questionnaires about their sleep and pain, including the Insomnia Severity Index, Medical College of Virginia Pain Questionnaire, and two weeks of sleep/pain diaries. Results: Most participants (80.00%) reported chronic pain, and the likelihood of having chronic pain did not differ by sleep disorder. However, there was a significant difference in pain intensity; individuals with comorbid obstructive sleep apnea (OSA)/insomnia reported an average pain intensity that was 20 points (out of 100) higher than individuals with insomnia or no diagnosis and 28 points higher than those with OSA, controlling for participant sex (Ps < 0.05). In a hierarchical regression, pain was unrelated to measures of sleep fragmentation (apnea-hypopnea index, spontaneous arousals, periodic leg movement arousals) and nocturnal hypoxemia (SaO2 nadir, time at or below 88% SaO2). Conclusions: Polysomnography measures of SDB severity and sleep fragmentation were unrelated to pain intensity. However, comorbid OSA/insomnia was associated with significantly higher pain (compared with either disorder in isolation), a finding that has implications for the treatment of chronic pain and possibly for understanding the mechanisms of chronic pain.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

OBJECTIVE: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. METHODS: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. RESULTS: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

OBJECTIVE: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. METHODS: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. RESULTS: All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SIGNIFICANCE: Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures.

Obstructive Sleep Apnea and Stroke: Determining the Mechanisms Behind their Association and Treatment Options.

Sleep-disordered breathing (SDB) can be a sequela of stroke caused by vascular injury to vital respiratory centers, cerebral edema, and increased intracranial pressure of space-occupying lesions. Likewise, obstructive sleep apnea (OSA) contributes to increased stroke risk through local mechanisms such as impaired ischemic cerebrovascular response and systemic effects such as promoting atherosclerosis, hypercoagulability, cardiac arrhythmias, vascular-endothelial dysfunction, and metabolic syndrome. The impact of OSA on stroke outcomes has been established, yet it receives less attention in national guidelines on stroke management than hyperglycemia and blood pressure dysregulation. Furthermore, whether untreated OSA worsens stroke outcomes is not well-described in the literature. This scoping review provides an updated investigation of the correlation between OSA and stroke, including inter-relational pathophysiology. This review also highlights the importance of OSA treatment and its role in stroke outcomes. Knowledge of pathophysiology, the inter-relationship between these common disorders, and the impact of OSA therapy on outcomes affect the clinical management of patients with acute ischemic stroke. In addition, understanding the relationship between stroke outcomes and pre-existing OSA will allow clinicians to predict outcomes while treating acute stroke.

Duration of Prophylactic Levetiracetam After Surgery for Brain Tumor: A Prospective Randomized Trial.

BACKGROUND: Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors. OBJECTIVE: To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression. METHODS: Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence. RESULTS: A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period. CONCLUSION: The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Construction of a neuroanatomical shape complex atlas from 3D MRI brain structures.

Brain atlas construction has attracted significant attention lately in the neuroimaging community due to its application to the characterization of neuroanatomical shape abnormalities associated with various neurodegenerative diseases or neuropsychiatric disorders. Existing shape atlas construction techniques usually focus on the analysis of a single anatomical structure in which the important inter-structural information is lost. This paper proposes a novel technique for constructing a neuroanatomical shape complex atlas based on an information geometry framework. A shape complex is a collection of neighboring shapes - for example, the thalamus, amygdala and the hippocampus circuit - which may exhibit changes in shape across multiple structures during the progression of a disease. In this paper, we represent the boundaries of the entire shape complex using the zero level set of a distance transform function S(x). We then re-derive the relationship between the stationary state wave function ψ(x) of the Schrödinger equation [formula in text] and the eikonal equation [formula in text] satisfied by any distance function. This leads to a one-to-one map (up to scale) between ψ(x) and S(x) via an explicit relationship. We further exploit this relationship by mapping ψ(x) to a unit hypersphere whose Riemannian structure is fully known, thus effectively turn ψ(x) into the square-root of a probability density function. This allows us to make comparisons - using elegant, closed-form analytic expressions - between shape complexes represented as square-root densities. A shape complex atlas is constructed by computing the Karcher mean ψ¯(x) in the space of square-root densities and then inversely mapping it back to the space of distance transforms in order to realize the atlas shape. We demonstrate the shape complex atlas computation technique via a set of experiments on a population of brain MRI scans including controls and epilepsy patients with either right anterior medial temporal or left anterior medial temporal lobectomies.

Associations between clinical tests and simulated driving performance in persons with epilepsy.

People with epilepsy (PWE) may experience seizures that constitute a risk to road safety. Consequently, many states have instituted restrictions, such as being seizure-free for intervals of 3 to 12 months, before driving can be resumed. However, 30% of drivers with recurrent seizures still drive despite having a restricted license. As a result of recurrent and uncontrolled seizures, PWE may have impairments in motor, visual and cognitive abilities, as well as impaired driving performance. No studies to date have prospectively examined factors associated with driving performance in PWE. The primary objective of this study was to determine which tests, from a clinical battery, are correlated with driving errors in PWE using a simulator. The sample consisted of 16 drivers with epilepsy (mean age 44.3±12.0; 63% women) recruited from the epilepsy monitoring unit at the University of Florida. All participants completed a clinical battery of cognitive, visual and motor tests, as well as a 35-minute drive on a simulator. Significant correlations emerged between: visual acuity with visual scanning (r=.69, p<.01) and adjustment to stimuli (r=.60, p<.05); contrast sensitivity with lane maintenance (r=-.54, p>.05), vehicle position (r=-.61, p>.05) and total number of errors (r=-.72, p>.01); and useful field of view scores (subtest 2) with visual scanning (r=.57, p>.05) and vehicle position (r=.63, p>.05). Limitations and future implications are addressed. The preliminary findings suggest visual and visual-cognitive tests are associated with driving errors in a simulated driving environment.

Evidence-based review on epilepsy and driving.

OBJECTIVE: The aim of this study was to synopsize the evidence on predictors of crashes and driving status in people with epilepsy (PWE). METHODS: Evidence-based review of the published English literature was the method used. We searched various databases and extracted data from 16 (of 77) primary studies. On the basis of American Academy of Neurology criteria, we assigned each study a class of evidence (I-IV, where I indicates the highest level of evidence) and made recommendations (Level A: predictive or not; Level B: probably predictive or not; Level C: possibly predictive or not; Level U: no recommendations). RESULTS: For PWE, the following characteristics are considered useful: For identifying crash risk, epilepsy (level B) and short seizure-free intervals (≥3 months) (Level C) are not predictive of motor vehicle crash (MVC). For self/proxy-reported crash risk, epilepsy surgery (Level B), seizure-free intervals (6-12 months) (Level B), few prior non-seizure-related crashes (Level B), and regular antiepileptic drug adjustments (Level B) are protective against crashes; seizures contribute to MVCs (Level C); mandatory reporting does not contribute to reduced crashes (Level C). No recommendations for reliable auras, age, and gender (Level U), as data are inadequate to make determinations. For self-reported driving or licensure status, employment and epilepsy surgery are predictive of driving (Level C); there are no recommendations for antiepileptic drug use, self-reported driving, gender, age, receiving employment benefits, or having reduced seizure frequency (Level U). CONCLUSION: Limitations, that is, heterogeneity among studies, examining the English literature from 1994 to 2010, must be considered. Yet, this is the first evidence-based review to synopsize the current PWE and driving literature and to provide recommendation(s) to clinicians and policy makers. Class I studies, matched for age and gender, yielding Level A recommendations are urgently needed to define the risks, benefits, and causal factors underlying driving performance issues in PWE.

Group-wise Point-set registration using a novel CDF-based Havrda-Charvát Divergence.

This paper presents a novel and robust technique for group-wise registration of point sets with unknown correspondence. We begin by defining a Havrda-Charvát (HC) entropy valid for cumulative distribution functions (CDFs) which we dub the HC Cumulative Residual Entropy (HC-CRE). Based on this definition, we propose a new measure called the CDF-HC divergence which is used to quantify the dis-similarity between CDFs estimated from each point-set in the given population of point sets. This CDF-HC divergence generalizes the CDF based Jensen-Shannon (CDF-JS) divergence introduced earlier in the literature, but is much simpler in implementation and computationally more efficient.A closed-form formula for the analytic gradient of the cost function with respect to the non-rigid registration parameters has been derived, which is conducive for efficient quasi-Newton optimization. Our CDF-HC algorithm is especially useful for unbiased point-set atlas construction and can do so without the need to establish correspondences. Mathematical analysis and experimental results indicate that this CDF-HC registration algorithm outperforms the previous group-wise point-set registration algorithms in terms of efficiency, accuracy and robustness.

Seizure recurrence following epilepsy surgery: is post-operative EEG helpful?

OBJECTIVES: We examined whether the relationship between interictal epileptiform discharges (IED) on post-operative EEG and seizure recurrence after epilepsy surgery was different in patients with neocortical and mesiotemporal resections. METHODS: We reviewed the records of 93 consecutive patients who underwent epilepsy surgery at our center and who had adequate post-operative follow-up and a post-operative EEG to determine the type of surgery, the recurrence of seizures and the presence of IED on post-operative EEG. RESULTS: Chi-square test revealed that for the entire group, there was a significant relationship between the presence of IED and seizure recurrence. However, this relationship was significant in neocortical surgery but not in mesiotemporal surgery. Time distribution of seizure recurrence revealed that in more than half the cases, seizures recurred with the first 3 months. Time distribution was not influenced by the presence of IED. CONCLUSIONS: This study revealed that IED on early post-operative EEG correlate with seizure recurrence in neocortical but not mesiotemporal surgeries and may be used to guide patient counseling in this group of patients.

Quetiapine improves visual hallucinations in Parkinson disease but not through normalization of sleep architecture: results from a double-blind clinical-polysomnography study.

Polysomnographic studies of Parkinson's disease (PD) patients with visual hallucinations (VH) usually reveal short, fragmented rapid eye movement (REM) sleep, with lower sleep efficiency and reduced total REM sleep. Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD. To confirm quetiapine's efficacy in improving VH, and to determine whether the mechanism was due to its effect on REM sleep architecture, we performed a pilot, double-blind, placebo-controlled study. Sixteen PD patients experiencing VH were recruited. Eight patients were randomized to quetiapine and eight patients to placebo. Patients underwent pre- and post-treatment polysomnography. The Clinical Global Impression Scale (CGIS), Brief Psychiatric Rating Scale (BPRS), and Unified Parkinson Disease Rating Scale (UPDRS) motor subscale were obtained. There were no differences in baseline characteristics between the treatment arms except that the placebo group had more sleep in stage REM (74.7 min vs. 40.1 min; p < .001). Data were imputed for all patients who prematurely discontinued (four quetiapine and one placebo) in an intention-to-treat analysis. The average quetiapine dose was 58.3 mg/day. While there was no significant difference in the change in REM duration pre- vs. post-treatment in either arm, patients randomized to quetiapine improved on the CGIS (p = .03) and the hallucination item of the BPRS (p = .02). No difference was noted in the UPDRS motor scores. Despite the small sample, this is the first double-blind trial to show quetiapine's efficacy over placebo in controlling VH in the PD population. However, normalization of sleep architecture was not supported as the mechanism.

Diagnosis of nonconvulsive status epilepticus (NCSE) in adults with altered mental status: clinico-electroencephalographic considerations.

The high incidence of nonconvulsive status epilepticus (NCSE) and difficulties encountered in rapid diagnosis have only recently become apparent and most neurophysiology textbooks have yet to fully address this topic. There is an immediate need to provide neurologists, neurology residents, and electroneurodiagnostic technologists with information to assist them in achieving early, accurate diagnosis of NCSE in patients they encounter on a daily basis. Instead of attempting to write a comprehensive review of the topic, we examined over 90 NCSE publications since 1972 and focused our efforts on extracting and summarizing those EEG and clinical considerations we found most useful for accurate diagnosis of NCSE in an adult population. The wide overlap between the clinical symptoms of NCSE and many other disorders causing change in mental status limits the usefulness of clinical measures for diagnosis. Those clinical parameters which have some utility are outlined. EEG testing and accurate interpretation is needed to identify NCSE in most instances. EEG patterns of NCSE are detailed and examples provided in order of progressive complexity. Timely treatment reduces patient risk for morbidity attributed to NCSE. Electroneurodiagnostic technologists who learn to recognize the entire spectrum of NCSE EEG patterns are better able to alert electroencephalographers to EEGs likely needing expedited review. This may facilitate early diagnosis if electroencephalographers determine that NCSE is indeed present. Electroencephalographers correlate the EEG pattern, clinical activity, and other diagnostic information to provide the treating medical doctors with an interpretation and recommendation in a timely manner. Lastly, EEG and clinical checklists and an algorithm which uses benzodiazepine response in conjunction with continuous EEG monitoring are provided to help reduce uncertainty in interpretation of equivocal EEG patterns of NCSE.

Simultaneous registration and parcellation of bilateral hippocampal surface pairs for local asymmetry quantification.

In clinical applications where structural asymmetries between homologous shapes have been correlated with pathology, the questions of definition and quantification of "asymmetry" arise naturally. When not only the degree but the position of deformity is thought relevant, asymmetry localization must also be addressed. Asymmetries between paired shapes have already been formulated in terms of (nonrigid) diffeomorphisms between the shapes. For the infinity of such maps possible for a given pair, we define optimality as the minimization of deviation from isometry under the constraint of piecewise deformation homogeneity. We propose a novel variational formulation for segmenting asymmetric regions from surface pairs based on the minimization of a functional of both the deformation map and the segmentation boundary, which defines the regions within which the homogeneity constraint is to be enforced. The functional minimization is achieved via a quasi-simultaneous evolution of the map and the segmenting curve, conducted on and between two-dimensional surface parametric domains. We present examples using both synthetic data and pairs of left and right hippocampal structures and demonstrate the relevance of the extracted features through a clinical epilepsy classification analysis.

Motor Impairments in Transient Ischemic Attack Increase the Odds of a Subsequent Stroke: A Meta-Analysis.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) increases the risk for a subsequent stroke. Typical symptoms include motor weakness, gait disturbance, and loss of coordination. The association between the presence of motor impairments during a TIA and the chances of a subsequent stroke has not been examined. In the current meta-analysis, we examine whether the odds of a stroke are greater in TIA individuals who experience motor impairments as compared with those who do not experience motor impairments. METHODS: We conducted a systematic search of electronic databases as well as manual searches of the reference lists of retrieved articles. The meta-analysis included studies that reported an odds ratio relating motor impairments to a subsequent stroke, or the number of individuals with or without motor impairments who experienced a subsequent stroke. We examined these studies using rigorous meta-analysis techniques including random effects model, forest and funnel plots, I2, publication bias, and fail-safe analysis. RESULTS: Twenty-four studies with 15,129 participants from North America, Australia, Asia, and Europe qualified for inclusion. An odds ratio of 2.11 (95% CI, 1.67-2.65, p = 0.000) suggested that the chances of a subsequent stroke are increased by twofolds in individuals who experience motor impairments during a TIA compared with those individuals who have no motor impairments. CONCLUSION: The presence of motor impairments during TIA is a significantly high-risk clinical characteristic for a subsequent stroke. The current evidence for motor impairments following TIA relies exclusively on the clinical reports of unilateral motor weakness. A comprehensive examination of motor impairments in TIA will enhance TIA prognosis and restoration of residual motor impairments.

Joint registration and segmentation of neuroanatomic structures from brain MRI.

RATIONALE AND OBJECTIVES: Segmentation of anatomic structures from magnetic resonance brain scans can be a daunting task because of large inhomogeneities in image intensities across an image and possible lack of precisely defined shape boundaries for certain anatomical structures. One approach that has been quite popular in the recent past for these situations is the atlas-based segmentation. The atlas, once constructed, can be used as a template and can be registered nonrigidly to the image being segmented thereby achieving the desired segmentation. The goal of our study is to segment these structures with a registration assisted image segmentation technique. MATERIALS AND METHODS: We present a novel variational formulation of the registration assisted image segmentation problem which leads to solving a coupled set of nonlinear Partial Differential Equations (PDEs) that are solved using efficient numeric schemes. Our work is a departure from earlier methods in that we can simultaneously register and segment in three dimensions and easily cope with situations where the source (atlas) and target images have very distinct intensity distributions. RESULTS: We present several examples (20) on synthetic and (3) real data sets along with quantitative accuracy estimates of the registration in the synthetic data case. CONCLUSION: The proposed atlas-based segmentation technique is capable of simultaneously achieve the nonrigid registration and the segmentation; unlike previous methods of solution for this problem, our algorithm can accommodate for image pairs having very distinct intensity distributions.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.