Publications by authors named "Mark Agostini"

21 Publications

  • Page 1 of 1

Non-lesional mesial temporal lobe epilepsy requires bilateral invasive evaluation.

Epilepsy Behav Rep 2021 27;15:100441. Epub 2021 Mar 27.

Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8508, USA.

Purpose: Mesial temporal lobe epilepsy (MTLE) usually responds well to surgical treatment, although in non-lesional cases up to 50% of patients experience seizure relapse. The possibility of bilateral independent seizure onset should be considered as a reason for epilepsy surgery failure.

Methods: In a cohort of 177 patients who underwent invasive presurgical evaluation with stereo-tactically placed electrodes in two level four epilepsy centers, 29 had non-lesional MTLE. Invasive evaluation results are described.

Results: Among 29 patients with non-lesional MRI and mesial temporal lobe seizure onset recorded during stereo-EEG (SEEG) evaluation, four patients with unilateral preimplantation hypothesis had independent bilateral mesial temporal seizures on SEEG despite of unilateral non-invasive evaluation data. Three of these patients were treated with bitemporal responsive neurostimulator system (RNS). Independent bilateral mesial temporal seizures have been confirmed on RNS ECoG (electrocorticography). The fourth patient underwent right anterior temporal lobectomy.

Conclusion: We propose that patients with non-lesional mesial temporal lobe epilepsy would benefit from bilateral invasive evaluation of mesial temporal structures to predict those patients who would be at most risk for surgical failure. Neurostimulaiton could be an initial treatment option for patients with independent bitemporal seizure onset.
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http://dx.doi.org/10.1016/j.ebr.2021.100441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058515PMC
March 2021

Physical activity status and quality of life in patients with epilepsy - Survey from level four epilepsy monitoring units.

Epilepsy Res 2021 Apr 9;173:106639. Epub 2021 Apr 9.

Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, TX, 75390, USA. Electronic address:

Purpose: People with epilepsy (PWE) tend to have sedentary lifestyles which may predispose them to a lower perceived quality of life (QOL). Moreover, the relationship between physical activity (PA) and QOL in populations of PWE with high disease burden has been under-studied. The goal of this study was to evaluate PA level and its impact on health-related QOL in PWE who were admitted to Level-4 epilepsy monitoring units (EMU).

Methods: In this prospective observational study, 200 patients from two EMUs in Dallas, Texas completed the following standard surveys: Rapid Assessment of Physical Activity (RAPA), the Quality of Life in Epilepsy (QOLIE-31), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) questionnaire. Information on self-reported epilepsy history, severity of disease, and socioeconomic status were also collected. The diagnosis of epilepsy was confirmed by video-EEG monitoring.

Results: Among the 200 who completed the survey, 113 had a diagnosis of epilepsy and 109 of them completed the RAPA. Ninety-two (84 %) of these PWE reported a sedentary level of physical activity (RAPA < 6) and 16 % reported an active level (RAPA ≥ 6). Self-reported QOL was slightly higher in PWE with an active level of PA compared to PWE with a sedentary level of PA (63.8 ± 15.0 vs 53.7 ± 17.9, p = 0.07), even though there was no difference in the severity of self-reported mood symptoms. After controlling for employment and seizure frequency, physical activity level measured by RAPA score was also positively related to QOL (r = 0.39, p = 0.01) and negatively correlated with anxiety symptoms (r = -0.28, p = 0.02) and depression symptoms (r = -0.25, p = 0.04).

Conclusion: The majority of PWE in this survey reported sedentary lifestyles despite most of them being young to middle-aged adults. Higher PA level was associated with fewer self-reported mood symptoms and higher QOL. In conjunction with the literature, these results suggest that PWE with a wide range of disease burden should be encouraged to participate in regular exercise to potentially improve QOL.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106639DOI Listing
April 2021

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Neurology 2020 09 20;95(9):e1244-e1256. Epub 2020 Jul 20.

From the Cleveland Clinic Foundation (D.R.N., A.V.A.), OH; California Pacific Medical Center (K.D.L., P.B.W.), San Francisco; Augusta University (A.M.M., Y.D.P.), GA; Henry Ford Hospital (G.L.B.), Detroit, MI; Ohio Health Neuroscience (B.J.S.), Columbus; Swedish Neuroscience Institute (R.P.G., M.J.D.), Seattle, WA; Mayo Clinic Arizona (K.H.N., R.S.Z.), Scottsdale; Johns Hopkins Medicine (G.K.B., W.S.A.), Baltimore, MD; Keck School of Medicine of USC (C.H., C.Y.L.), Los Angeles, CA; Via Christi Epilepsy Center (R.W.L., T.S.), Wichita, KS; Yale University School of Medicine (R.B.D., L.J.H.), New Haven, CT; Mayo Clinic Florida (R.E.W., W.T.), Jacksonville; Columbia University Medical Center (S.S., G.M.M.), New York, NY; University of Texas Southwestern Medical Center (M.A.A.), Dallas; Geisel School of Medicine at Dartmouth (B.C.J., D.W.R.), Hanover, NH; Indiana University School of Medicine (V.S., T.C.W.), Indianapolis; Massachusetts General Hospital (S.S.C., A.J.C.), Boston; Mayo Clinic Minnesota (G.A.W., B.N.L.), Rochester; Medical University of South Carolina (J.C.E., J.J.H.), Charleston; Oregon Health & Science University (D.C. Spencer, L.E.), Portland; Thomas Jefferson University (C.T.S., M.R.S.), Philadelphia, PA; Nicklaus Children's Hospital (I.M.), Miami, FL; Saint Barnabas Medical Center (E.B.G.), Livingston, NJ; University of Rochester Medical Center (M.J.B., A.J.F.), NY; University of Wisconsin Hospital and Clinics (P.R.), Madison; Baylor College of Medicine (A.M.G., E.M.M.), Houston, TX; Emory University School of Medicine (R.E.G.), Atlanta, GA; George Washington University School of Medicine and Health Sciences (D.C. Shields), Washington, DC; Weill Cornell Medical College (T.H.S., D.R.L.), New York, NY; University of Virginia School of Medicine (N.B.F., W.J.E.), Charlottesville; Louisiana State University Health Sciences Center (P.W.O., N.R.V.-P.), New Orleans; University of Florida (S.E., S.N.R.), Gainesville; Wake Forest University Health Sciences (J.G.B.), Winston-Salem, NC; NeuroPace, Inc (T.A.C., F.T.S., C.G.S., K.L.M., T.L.S., M.J.M.), Mountain View; and Stanford University (M.J.M.), Palo Alto, CA.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

Results: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% ( < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved ( < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators ( < 0.05, 1-tailed χ).

Conclusions: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.

Clinicaltrialsgov Identifier: NCT00572195.

Classification Of Evidence: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.
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http://dx.doi.org/10.1212/WNL.0000000000010154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538230PMC
September 2020

Invasion of microglia/macrophages and granulocytes into the Mauthner axon myelin sheath following spinal cord injury of the adult goldfish, Carassius auratus.

J Morphol 2020 01 27;281(1):135-152. Epub 2019 Nov 27.

Department of Biology, Williams College, Williamstown, Massachusetts.

Rapid activation of resident glia occurs after spinal cord injury. Somewhat later, innate and adaptive immune responses occur with the invasion of peripheral immune cells into the wound site. The activation of resident and peripheral immune cells has been postulated to play harmful as well as beneficial roles in the regenerative process. Mauthner cells, large identifiable neurons located in the hindbrain of most fish and amphibians, provided the opportunity to study the morphological relationship between reactive cells and Mauthner axons (M-axons) severed by spinal cord crush or by selective axotomy. After crossing in the hindbrain, the M-axons of adult goldfish, Carassius auratus, extend the length of the spinal cord. Following injury, the M-axon undergoes retrograde degeneration within its myelin sheath creating an axon-free zone (proximal dieback zone). Reactive cells invade the wound site, enter the axon-free dieback zone and are observed in the vicinity of the retracted M-axon tip as early as 3 hr postinjury. Transmission electron microscopy allowed the detection of microglia/macrophages and granulocytes, some of which appear to be neutrophil-like, at each of these locations. We believe that this is the first report of the invasion of such cells within the myelin sheath of an identifiable axon in the vertebrate central nervous system (CNS). We speculate that microglia/macrophages and granulocytes that are attracted within a few hours to the damaged M-axon are part of an inflammatory response that allows phagocytosis of debris and plays a role in the regenerative process. Our results provide the baseline from which to utilize immunohistochemical and genetic approaches to elucidate the role of non-neuronal cells in the regenerative process of a single axon in the vertebrate CNS.
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http://dx.doi.org/10.1002/jmor.21086DOI Listing
January 2020

Comparison of psychiatric comorbidities and impact on quality of life in patients with epilepsy or psychogenic nonepileptic spells.

Epilepsy Behav 2020 01 20;102:106649. Epub 2019 Nov 20.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, TX 75390, USA. Electronic address:

Objectives: Psychiatric comorbidity is common in people with epilepsy (PWE) and psychogenic nonepileptic spells (PNES). These comorbidities can be detrimental to quality of life (QOL) and are often underdiagnosed and undertreated. Some types of epilepsy, such as focal temporal lobe epilepsy (TLE), have been associated with higher rates of psychiatric comorbidity. This study examined the impact of psychiatric comorbidity on QOL in patients admitted to two level 4 epilepsy monitoring units (EMUs).

Methods: In this prospective observational study, 200 patients admitted to two level 4 EMUs completed standardized surveys including the Quality of Life in Epilepsy (QOLIE-31-P), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Beck Depression Inventory-II (BDI-II). Hierarchal multiple regression was performed to assess impact on QOL.

Results: Of the 200 participants, 113 had a diagnosis of epilepsy, 36 had a diagnosis of PNES, and 51 were excluded for nondiagnostic evaluation or dual diagnosis. Of those with epilepsy, 65 had TLE, 28 had focal extratemporal lobe epilepsy (ETLE), and 20 had nonfocal epilepsy. Patients with PNES had higher self-reported anxiety and depression levels (GAD-7: p = 0.04, PHQ-9: p < 0.01; BDI-II: p < 0.01) but similar QOL to PWE (p = 0.78). Using hierarchal multiple regression, symptoms of anxiety and depression were significant predictors of lower QOL in PWE but not in patients with PNES. There was no difference in QOL in those with ETLE and TLE.

Conclusions: Our findings suggest that self-reported anxiety and depression symptoms are common in patients admitted to level 4 EMUs regardless of diagnosis and play an important role in predicting QOL in PWE. Our findings emphasize the importance of routinely screening all EMU patients for psychiatric comorbidity.
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http://dx.doi.org/10.1016/j.yebeh.2019.106649DOI Listing
January 2020

Treatment of drug-resistant epilepsy in patients with periventricular nodular heterotopia using RNS® System: Efficacy and description of chronic electrophysiological recordings.

Clin Neurophysiol 2019 08 9;130(8):1196-1207. Epub 2019 May 9.

NeuroPace, Inc., Mountain View, CA, USA; Stanford University, Stanford, CA, USA.

Objectives: Describe changes in clinical seizure frequency and electrophysiological data recorded in patients with medically-intractable seizures and periventricular nodular heterotopias (PVNH) treated with the RNS® System (NeuroPace, Inc., Mountain View, CA).

Methods: Clinical seizures from eight patients (mean follow-up of 10.1 years) were analyzed pre- and post-treatment. Chronic ambulatory electrocorticograms (ECoGs) recorded from PVNHs, hippocampus and neocortex were evaluated to identify the earliest electrographic seizure onset type, pattern of spread, and interictal characteristics.

Results: Mean reduction in disabling seizures was 85.7 % (n = 8); seven patients had >50% seizure reduction and two were seizure-free in the final year of analysis. Seizure rate showed a progressive reduction over the course of the study with the highest rate of improvement in the first two to three years after implantation. Four of seven patients with one PVNH lead and a second lead in the hippocampus or neocortex had some electrographic seizures first recorded at either lead location, suggesting two foci or seizure propagation patterns. Low voltage fast type activity was the prominent seizure onset pattern. Interictal ECoG power was lower in PVNH than hippocampus.

Conclusions: RNS® System treatment substantially reduced clinical seizure frequency in patients with PVNH. Analysis of ictal ECoG records suggests PVNH may be involved in seizure generation.

Significance: Chronic ECoG recordings suggest PVNH tissue can actively participate in epileptogenic networks. Direct brain-responsive neurostimulation is a safe and effective treatment option in such patients, progressively reducing seizure rate over a period of years.
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http://dx.doi.org/10.1016/j.clinph.2019.04.706DOI Listing
August 2019

Diagnostic Yield of 2-Hour EEG Is Similar With 30-Minute EEG in Patients With a Normal 30-Minute EEG.

J Clin Neurophysiol 2019 May;36(3):204-208

Department of Neurology and Neurotherapeutics, University of Texas Southwestern, Dallas, U.S.A.

Purpose: Current literature suggests that longer duration of EEG recording increases the yield of detecting interictal epileptiform discharges. However, optimal duration for a repeat study in patients with initially normal 30-minute EEG is not clear. Thus, the purpose of this study is to determine whether a 2-hour EEG has a diagnostic advantage over a routine 30-minute EEG in detecting epileptiform abnormalities in patients who had a first normal 30-minute EEG.

Methods: This is a single-center, retrospective study done at UT Southwestern Medical Center at Dallas and Parkland Memorial Hospital. The data from 1997 to 2015 were extracted from the existing EEG report database for patients who had a first normal 30-minute EEG recording. EEG was interpreted by board-certified clinical neurophysiologists, who classified each EEG as normal or abnormal, with relevant subsequent subclassification.

Results: Over 18 years, a total of 12,425 individual 30-minute EEGs were performed. Of these, 1,023 patients had at least one repeated EEG after the first normal EEG. Among these patients, 763 had a 30-minute EEG as the second study and 260 had a 2-hour EEG as the second study. The yield of epileptiform discharges was 3.3% in the 30-minute EEG group and 4.2% in the 2-hour EEG group (P = 0.5) in the repeating studies.

Conclusions: Two-hour EEG has a similar yield as 30-minute EEG to detect epileptiform discharges in patients with a normal 30-minute EEG.
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http://dx.doi.org/10.1097/WNP.0000000000000567DOI Listing
May 2019

Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology.

JAMA Neurol 2017 04;74(4):397-402

Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, Texas2Department of Neurology, Parkland Health and Hospital System, Dallas, Texas.

Importance: Autoimmune epilepsy is an underrecognized condition, and its true incidence is unknown. Identifying patients with an underlying autoimmune origin is critical because these patients' condition may remain refractory to conventional antiseizure medications but may respond to immunotherapy.

Objective: To determine the prevalence of neurological autoantibodies (Abs) among adult patients with epilepsy of unknown etiology.

Design, Setting, And Participants: Consecutive patients presenting to neurology services with new-onset epilepsy or established epilepsy of unknown etiology were identified. Serum samples were tested for autoimmune encephalitis Abs as well as thyroperoxidase (TPO) and glutamic acid decarboxylase 65 (GAD65) Abs. An antibody prevalence in epilepsy (APE) score based on clinical characteristics was assigned prospectively. Data were collected from June 1, 2015, to June 1, 2016.

Main Outcomes And Measures: Presence of neurological Abs. A score based on clinical characteristics was assigned to estimate the probability of seropositivity prior to antibody test results. Good seizure outcome was estimated on the basis of significant reduction of seizure frequency at the first follow-up or seizure freedom.

Results: Of the 127 patients (68 males and 59 females) enrolled in the study, 15 were subsequently excluded after identification of an alternative diagnosis. Serum Abs suggesting a potential autoimmune etiology were detected in 39 (34.8%) cases. More than 1 Ab was detected in 7 patients (6.3%): 3 (2.7%) had TPO-Ab and voltage-gated potassium channel complex (VGKCc) Ab, 2 (1.8%) had GAD65-Ab and VGKCc-Ab, 1 had TPO-Ab and GAD65-Ab, and 1 had anti-Hu Ab and GAD65-Ab. Thirty-two patients (28.6%) had a single Ab marker. Among 112 patients included in the study, 15 (13.4%) had TPO-Ab, 14 (12.5%) had GAD65-Ab, 12 (10.7%) had VGKCc (4 of whom were positive for leucine-rich glioma-inactivated protein 1 [LGI1] Ab), and 4 (3.6%) had N-methyl-D-aspartate receptor (NMDAR) Ab. Even after excluding TPO-Ab and low-titer GAD65-Ab, Abs strongly suggesting an autoimmune cause of epilepsy were seen in 23 patients (20.5%). Certain clinical features, such as autonomic dysfunction, neuropsychiatric changes, viral prodrome, faciobrachial dystonic spells or facial dyskinesias, and mesial temporal sclerosis abnormality on magnetic resonance imaging, correlated with seropositivity. The APE score was a useful tool in predicting positive serologic findings. Patients who were Ab positive were more likely to have good seizure outcome than were patients with epilepsy of unknown etiology (15 of 23 [65.2%] vs 24 of 89 [27.0%]; odds ratio, 4.8; 95% CI, 1.8-12.9; P = .002). In patients who were seropositive, reduction in seizure frequency was associated with use of immunomodulatory therapy.

Conclusions And Relevance: Among adult patients with epilepsy of unknown etiology, a significant minority had detectable serum Abs suggesting an autoimmune etiology. Certain clinical features (encoded in the APE score) could be used to identify patients with the highest probability of harboring neurological Abs.
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http://dx.doi.org/10.1001/jamaneurol.2016.5429DOI Listing
April 2017

Predictors of Postoperative Seizure Recurrence: A Longitudinal Study of Temporal and Extratemporal Resections.

Epilepsy Res Treat 2016 16;2016:7982494. Epub 2016 Mar 16.

Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections. At last follow-up (mean 48 months; range 24-87 months), the outcome was Engel class I in 84% (n = 59) of patients. Seizure recurrence followed two patterns: recurrence was "early" (within 2 years) in 82% of patients, of whom 83% continued to have seizures despite optimum medical therapy; recurrence was "late" (after 2 years) in 18%, of whom 25% continued to have seizures subsequently. Among the variables of interest, only resection site and ictal EEG remained as independent predictors of seizure recurrence over the long term (p < 0.05). Extratemporal resection and discordance between ictal EEG and resection area were associated with 4.2-fold and 5.6-fold higher risk of seizure recurrence, respectively. Conclusions. Extratemporal epilepsy and uncertainty in ictal EEG localization are independent predictors of unfavorable outcome. Seizure recurrence within two years of surgery indicates poor long-term outcome.
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http://dx.doi.org/10.1155/2016/7982494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812270PMC
April 2016

The Prevention of Epilepsy.

Authors:
Mark Agostini

JAMA Neurol 2016 Apr;73(4):375-6

Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas.

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http://dx.doi.org/10.1001/jamaneurol.2015.4780DOI Listing
April 2016

Temporal lobe volume predicts Wada memory test performance in patients with mesial temporal sclerosis.

Epilepsy Res 2016 Feb 28;120:25-30. Epub 2015 Nov 28.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8508, USA. Electronic address:

The Wada test is widely used in the presurgical evaluation of potential temporal lobectomy patients to predict postoperative memory function. Expected asymmetry (EA), defined as Wada memory lateralized to the nonsurgical hemisphere, or a higher score after injection of the surgical hemisphere would be considered favorable in terms of postoperative memory outcome. However, in some cases, nonlateralized memory (NM) results, with no appreciable asymmetry, may occur because of impaired scores after both injections, often leading to denial of surgery. The reason for such nonlateralized Wada memory in patients with intractable temporal lobe epilepsy (TLE) remains unclear. Given that quantitative morphometric magnetic resonance imaging studies in TLE patients have shown bilateral regional atrophy in temporal and extratemporal structures, we hypothesized that the volume loss in contralateral temporal structures could contribute to nonlateralized Wada memory performance. To investigate this, we examined the relationship between the volume changes of temporal structures and Wada memory scores in patients with intractable TLE with mesial temporal sclerosis (MTS) using an age- and gender-matched control group. Memory was considered nonlateralized if the absolute difference in the total correct recall scores between ipsilateral and contralateral injections was <11%. Among 21 patients, Wada memory was lateralized in 15 and nonlateralized in 6 patients, with all the nonlateralized scores being observed in left TLE. The recall scores after ipsilateral injection were significantly lower in patients with an NM profile than an EA profile (23 ± 14% vs. 59 ± 18% correct recall, p ≤ 0.001). However, the recall scores after contralateral injection were low but similar between the two groups (25 ± 17% vs. 25 ± 15% correct recall, p=0.97). Compared to controls, all the patients showed greater volume loss in the temporal regions. However, patients with a NM profile showed significantly more volume loss than those with a lateralized memory profile in both contralateral and ipsilateral temporal regions (p<0.05). Left hemispheric Wada memory performance correlated positively with the size of the left mesial and neocortical temporal structures (r=0.49-0.63, p=0.005-0.04). Our study suggests that volume loss in the nonsurgical temporal structures is associated with nonlateralized Wada memory results in patients with intractable TLE.
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http://dx.doi.org/10.1016/j.eplepsyres.2015.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740193PMC
February 2016

Retrospective case series of the clinical features, management and outcomes of patients with autoimmune epilepsy.

Seizure 2015 Jul 30;29:143-7. Epub 2015 Apr 30.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, United States.

Purpose: Analyze clinical and electrographic characteristics of patients with autoimmune epilepsy, and evaluate the effect of early diagnosis and treatment on reduction of seizure frequency.

Methods: Observational retrospective case series, conducted using electronic medical data from two teaching hospitals. Clinical data was collected from 2008 to 2013. Cases of new onset seizures were selected based on the presence of laboratory evidence of autoimmunity.

Results: 34 hospitalized patients who presented predominantly due to seizures with concern for autoimmune etiology were identified. Mean age of patients was 44.94 years and 64.7% were males. Autoimmune antibodies were detected in 76.5% (26) of patients as follows: VGKc (8); NMDA-R (7); anti-thyroid (5); GAD (4); GABAB (2). 22 patients had unilateral temporal lobe onset and 4 had bilateral temporal lobe onset, while 8 had extra-temporal onset/multiple ictal foci. Median number of seizures during initial prolonged vEEG monitoring was 8 (range 0-48); median number of anti-seizure medications used was 2 (range 1-5). 9 patients had an underlying malignancy. 94.1% (32) patients received immunomodulation, as follows: high dose corticosteroids (96.8%), plasmapheresis (62.5%), IVIG (34.4%), rituximab (21.8%), mycophenolate (15.6%), cyclophosphamide (12.5%). 63.3% (19) participants achieved ≥ 50% seizure reduction (Responder Rate) at first clinic visit. Patients without malignancy had better seizure control (p < 0.05). Time from symptom onset to diagnosis (p < 0.005) and symptom onset to immunomodulation (p < 0.005) was significantly lower among patients who achieved responder rate (RR).

Conclusion: This study highlights certain important clinical and electrographic aspects of autoimmune epilepsy, and the significance of early diagnosis and initiation of immunomodulatory therapy.
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http://dx.doi.org/10.1016/j.seizure.2015.04.007DOI Listing
July 2015

Effectiveness of multimodality treatment for autoimmune limbic epilepsy.

Epileptic Disord 2014 Dec;16(4):494-9

Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

We evaluated the outcome of multimodality treatment in autoimmune limbic epilepsy in 3 consecutive patients (2 male and 1 female; age 33-55 years) presenting with a combination of focal non-convulsive status epilepticus, memory impairment, and psychosis. MRI showed right or bitemporal T2 or FLAIR hyperintensity. Video-EEG showed seizures of right temporo-occipital or bitemporal independent onset. Extensive workup failed to reveal infectious aetiology or an underlying tumour. However, the autoantibody panel was positive for one or more of these antibodies: anti-VGKC, anti-GABAB, anti-VGCC (P/Q, N types), and anti-GAD65. All patients received: (1) conventional antiepileptic drugs including levetiracetam, lacosamide, phenobarbital, lamotrigine, and valproate; (2) immunomodulatory therapy including methylprednisolone, plasmapheresis, and intravenous immunoglobulin; and (3) rituximab. After a 4-6-week in-hospital course, the seizures resolved in all patients but 2 had persistent memory impairment. None had treatment-related complications. At the time of last follow-up, 2-3 months later, 2 patients remained seizure-free while 2 had residual memory impairment. Our findings suggest that multimodality treatment with a combination of conventional AEDs, immunomodulatory therapy, and rituximab is effective and safe in autoimmune limbic epilepsy.
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http://dx.doi.org/10.1684/epd.2014.0703DOI Listing
December 2014

Subtypes of post-traumatic epilepsy: clinical, electrophysiological, and imaging features.

J Neurotrauma 2014 Aug 28;31(16):1439-43. Epub 2014 Jul 28.

1 Department of Neurology and Neurotherapeutics, The University of Texas Southwestern Medical Center , Dallas, Texas.

Post-traumatic epilepsy (PTE) is a consequence of traumatic brain injury (TBI), occurring in 10-25% of patients with moderate to severe injuries. The development of animal models for testing antiepileptogenic therapies and validation of biomarkers to follow epileptogenesis in humans necessitates sophisticated understanding of the subtypes of PTE, which is the objective of this study. In this study, retrospective review was performed of patients with moderate to severe TBI with subsequent development of medically refractory epilepsy referred for video-electroencephalography (EEG) monitoring at a single center over a 10-year period. Information regarding details of injury, neuroimaging studies, seizures, video-EEG, and surgery outcomes were collected and analyzed. There were 123 patients with PTE identified, representing 4.3% of all patients evaluated in the epilepsy monitoring unit. Most of them had localization-related epilepsy, of which 57% had temporal lobe epilepsy (TLE), 35% had frontal lobe epilepsy (FLE), and 3% each had parietal and occipital lobe epilepsy. Of patients with TLE, 44% had mesial temporal sclerosis (MTS), 26% had temporal neocortical lesions, and 30% were nonlesional. There was no difference in age at injury between the different PTE subtypes. Twenty-two patients, 13 of whom had MTS, proceeded to surgical resection. At a mean follow-up of 2.5 years, Engel Class I outcomes were seen in 69% of those with TLE and 33% of those with FLE. Our findings suggest PTE is a heterogeneous condition, and careful evaluation with video-EEG monitoring and high resolution MRI can identify distinct syndromes. These results have implications for the design of clinical trials of antiepileptogenic therapies for PTE.
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http://dx.doi.org/10.1089/neu.2013.3221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132580PMC
August 2014

Axon cap morphology of the sea robin (Prionotus carolinus): Mauthner cell is correlated with the presence of "signature" field potentials and a C-type startle response.

J Comp Neurol 2011 Jul;519(10):1979-98

Department of Biology, Williams College, Williamstown, Massachusetts 01267, USA.

Studies on the Mauthner cell (M-cell) of goldfish, Carassius auratus, have facilitated our understanding of how sensory information is integrated in the hindbrain to initiate C-type fast startle responses (C-starts). The goldfish M-cell initial segment/axon hillock is surrounded by a composite axon cap consisting of a central core and a peripheral zone covered by a glial cell layer. The high resistivity of the axon cap results in "signature" field potentials recorded on activation of the M-cell, allowing unequivocal physiological identification of the M-cell and of its feedback and reciprocal inhibitory networks that are crucial in ensuring that only one M-cell is active and that it fires only once. Phylogenetic mapping of axon cap morphology to muscle activity patterns and behavior predicts that teleost fishes that have a composite axon cap, like that of the goldfish, will perform C-start behavior with primarily unilateral muscle activity. We have chosen to study these predictions in the northern sea robin, Prionotus carolinus, a percomorph fish. Although sea robins have a very different phylogenetic position, body form, and habitat compared with the goldfish, they display the correlation of axon cap morphology to physiology and C-start behavior. Differences in response parameters suggest some evolutionary trade-offs in sea robin C-start behavior compared with that of the goldfish, but the correlations in morphology, physiology, and behavior are common features of both otophysan and nonotophysan teleosts. The M-cell will continue to provide an unprecedented opportunity to study the evolution of a neural circuit in the context of behavior.
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http://dx.doi.org/10.1002/cne.22617DOI Listing
July 2011

Attitudes and performance of third- vs fourth-year neurology clerkship students.

Arch Neurol 2010 May;67(5):548-51

Department of Neurology, University of Texas Southwestern Medical School, Dallas, TX 75390-9036, USA.

Objective: To compare student performance, attitudes, and career plans based on whether the neurology clerkship was taken in the third or fourth year.

Design: During the 1-year transition when the neurology clerkship was officially moved from the fourth to the third year at our institution, students took the identical clinical clerkship and were mixed together at each clinical site where faculty were blinded to student's year.

Setting: University of Texas Southwestern Medical School.

Participants: Third- and fourth-year medical students.

Main Outcome Measures: Performance, enthusiasm, and match results were analyzed by year of medical school for differences.

Results: There was a statistical trend toward better performance of third-year students as measured by the clinical evaluation grade (88.4 vs 87.4; P = .051) but this represented only a 1% difference. No difference was noted on the National Board of Medical Examiners neurology shelf examination score (73.8 vs 74.9; P = .20). Students' enthusiasm for neurologic learning was significantly higher in third- as compared with fourth-year students (P = .004). The probability that students would choose a career in neurology was higher for third- than fourth-year students (P < .001), but there was no correlation between year and matching for a neurology residency (P = .17).

Conclusions: Our findings support the belief among academic neurologists that students who take the neurology clerkship in the third year have greater enthusiasm for the field and look more favorably on neurology as a possible career than those taking the neurology clerkship in their fourth year. Nevertheless, our findings do not support the notion that third-year placement results in superior achievement.
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http://dx.doi.org/10.1001/archneurol.2010.64DOI Listing
May 2010

Posttraumatic epilepsy: the endophenotypes of a human model of epileptogenesis.

Epilepsia 2009 Feb;50 Suppl 2:14-20

Department of Neurology, University of Texas Southwestern Medical Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital, Dallas, Texas 75390-9036, USA.

Posttraumatic epilepsy is a common complication of traumatic brain injury (TBI), occurring in up to 15-20% of patients with severe brain trauma. Trauma accounts for approximately 5% of chronic epilepsy in the community. Because it is a common condition, and because of the relatively short latency period between injury and onset of chronic seizures, posttraumatic epilepsy represents a good model to test antiepileptogenic therapies. However, several well-conducted clinical trials have failed to demonstrate antiepileptogenic efficacy for several common anticonvulsants. Posttraumatic epilepsy can arise through a number of mechanisms, which often coexist within a single patient. Penetrating brain injury produces a cicatrix in the cortex and is associated with a risk of posttraumatic epilepsy of approximately 50%, whereas nonpenetrating head injury may produce focal contusions and intracranial hemorrhages, and is associated with a risk of posttraumatic epilepsy of up to 30%. Furthermore, closed head injury often produces diffuse concussive injury, with shearing of axons and selective damage to vulnerable brain regions, such as the hippocampus. The clinical, neurophysiologic, imaging, and neuropathologic features or epileptogenicity differ between these alternate mechanisms. It is likely that better understanding of the subtypes of epilepsy resulting from brain trauma will be required to successfully identify antiepileptogenic therapies.
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http://dx.doi.org/10.1111/j.1528-1167.2008.02006.xDOI Listing
February 2009

Evaluation of seizure-like episodes in survivors of moderate and severe traumatic brain injury.

J Head Trauma Rehabil 2004 Jul-Aug;19(4):290-5

Department of Physical Medicine and Rehabilitation, University of Texas Southwestern Medical Center, Dallas, 75390, USA.

Background: Transient paroxysmal alterations of consciousness or behavior are common sequelae of moderate and severe traumatic brain injury (TBI). Clinicians caring for patients with such episodes often diagnose them as epileptic seizures, a frequent and well-studied complication of TBI. As it is difficult to confirm this diagnosis, antiepileptic drugs are often used empirically. However, as such therapy is frequently ineffective, we studied the usefulness of prolonged video electroencephalogram (VEEG) monitoring in the clinical management of paroxysmal behaviors in TBI survivors.

Methods: Records of patients referred evaluation in an epilepsy monitoring unit for management of medically intractable epilepsy were retrospectively reviewed. Patients with a documented history of moderate-to-severe brain injury preceding the onset of epilepsy were identified. These patients were studied by simultaneous videotape and scalp electroencephalographic recordings, and the majority also underwent magnetic resonance imaging and neuropsychologic studies.

Results: Of the 1858 consecutive admissions over a 66-month period, 127 (7%) fulfilled enrollment criteria. VEEG monitoring was conducted for an average of 4.6 days. Monitoring was successful in establishing a diagnosis in 82% of the cases referred: 62% had focal seizures, 6% had generalized seizures, and 33% had psychogenic nonepileptic seizures. Of those with temporal lobe epilepsy, 53% had mesial temporal sclerosis, as shown by magnetic resonance imaging.

Conclusions: VEEG is a useful procedure in the evaluation of TBI survivors with spells. The yield of diagnoses that may alter treatment is substantial. Additionally, mesial temporal sclerosis is associated with TBI. Given the variety of seizure types found in survivors of moderate-to-severe TBI, obtaining specific diagnosis of seizure type by VEEG monitoring impacts treatment options.
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http://dx.doi.org/10.1097/00001199-200407000-00003DOI Listing
November 2004

Increased risk of late posttraumatic seizures associated with inheritance of APOE epsilon4 allele.

Arch Neurol 2003 Jun;60(6):818-22

Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Background: Late posttraumatic seizures are a common complication of moderate and severe traumatic brain injury. Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with increased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury.

Objective: To determine whether inheritance of APOE epsilon4 is associated with increased risk of developing late posttraumatic seizures.

Design: Prospective study.

Setting: Neurosurgical service at an urban level I trauma center.Patients Patients admitted with a diagnosis of moderate and severe traumatic brain injury were enrolled.

Methods: Six months after injury, patients were contacted to determine functional outcome (according to the Glasgow Outcome Scale-Expanded [GOS-E]) and the presence of late posttraumatic seizures. Genotype at the APOE locus was determined by restriction fragment length polymorphism analysis.

Results: DNA and outcome information was obtained from 106 subjects. Six months after injury, 31 (29%) had a poor outcome (GOS-E score, 1-4), 47 (44%) had an intermediate outcome (GOS-E score, 5-6), and 28 (26%) had a favorable outcome (GOS-E score, 7-8). Twenty-one patients (20%) had at least 1 late posttraumatic seizure. The relative risk of late posttraumatic seizures for patients with the epsilon4 allele was 2.41 (95% confidence interval, 1.15-5.07; P =.03). In this cohort, inheritance of APOE epsilon4 was not associated with an unfavorable GOS-E score 6 (P =.47).

Conclusions: Inheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizures. In this cohort, this risk appears to be independent of an effect of epsilon4 on functional outcome. A better understanding of the molecular role of APOE in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.
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http://dx.doi.org/10.1001/archneur.60.6.818DOI Listing
June 2003

Bilateral Memory Dysfunction in Epilepsy Surgery Candidates Detected by the Intracarotid Amobarbital Procedure (Wada Memory Test).

Epilepsy Behav 2002 Feb;3(1):82-91

The intracarotid amobarbital procedure (IAP) is widely used in the evaluation of candidates for resective epilepsy surgery, in part to identify patients at risk for postoperative amnesia. Yet there is no widely accepted standardized protocol, and there is a paucity of quantitative data to assess the factors associated with poor IAP performance. This report summarizes our findings on 110 patients with intractable focal epilepsy who underwent IAP testing at our center. Ipsilateral IAP scores for patients with left-sided seizure foci were significantly lower than those for patients with right-sided seizure foci. Falsely and poorly lateralizing scores were also significantly more common in subjects with left-sided seizure onsets. Twenty-four percent of subjects failed the IAP bilaterally, and patients who failed the IAP bilaterally had significantly lower scores on neuropsychologic measures. There was no difference between patients who passed and failed in the location, etiology, duration, or age of onset of epilepsy. We conclude that bilateral memory dysfunction is common in patients with intractable partial epilepsy. Whether memory dysfunction detected by IAP testing as performed at our center is predictive of functionally limiting postoperative amnesia remains to be determined.
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http://dx.doi.org/10.1006/ebeh.2001.0298DOI Listing
February 2002

Evolving treatment strategies for epilepsy.

JAMA 2002 Jun;287(22):2917-20

Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Room F2.302, Dallas, TX 75390-9036, USA.

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http://dx.doi.org/10.1001/jama.287.22.2917DOI Listing
June 2002