Publications by authors named "Jeffrey W Britton"

89 Publications

Antiseizure Medication use in Gastric Bypass Patients and Other Post-Surgical Malabsorptive States.

Epilepsy Behav Rep 2021 22;16:100439. Epub 2021 Mar 22.

Department of Neurology, Mayo Clinic, Rochester, MN, United States.

Healthcare professionals are encountering an increasing number of patients who have undergone bariatric surgeries. Antiseizure medications (ASM) have a narrow therapeutic window, and patients with malabsorptive states receiving ASM present a complex situation as the pharmacokinetics of these drugs have only been studied in patients with a normal functioning gastrointestinal tract. Patients with malabsorptive states may have altered pharmacokinetics, and there is limited literature to guide drug selection and dosage adjustment in patients with malabsorptive states. This review highlights pharmacokinetic parameters of common ASM, and considerations when managing patients on them. The effect of pH, lipophilicity, absorption, and metabolism should be taken into account when selecting and managing ASMs in this patient population. Based on these parameters, levetiracetam, and topiramate have fewer issues referable to absorption related to bariatric surgery while oral formulations of phenytoin, carbamazepine, oxcarbamazepine and valproic acid have reduced absorption due to effects of bariatric surgery based on the pharmacokinetic properties of these medications. Extended formulations should be avoided and ASM serum concentrations should be checked before and after surgery. The care of patients with epilepsy who are scheduled to undergo bariatric surgery should be guided by a multidisciplinary team including a pharmacist and a neurologist who should be involved in the adjustment of the ASMs throughout the pre-surgical and post-surgical periods.
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http://dx.doi.org/10.1016/j.ebr.2021.100439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093413PMC
March 2021

Hyperammonemia in Patients With Status Epilepticus Treated With or Without Valproic Acid.

Neurologist 2021 May 5;26(3):80-82. Epub 2021 May 5.

Department of Neurology, Mayo Clinic, Rochester, MN.

Background: Hyperammonemia is a common side effect of valproic acid (VPA) and can occur after generalized seizures, but the clinical significance is unclear. The aim of this study was to better understand the clinical practice and utility of ammonia testing in status epilepticus (SE) treated with or without VPA.

Methods: Charts of adult patients with SE from St. Mary's Hospital Intensive Care Units (ICUs) (Mayo Clinic, Rochester, MN) from 2011 to 2016 were reviewed. Clinical factors were compared between patients who had ammonia checked versus those who did not, and those with normal ammonia versus hyperammonemia (>50 µg/dL). Charts were reviewed to determine if hyperammonemia changed clinical management and if it was felt to be symptomatic.

Results: There were 304 patients identified: 94 received VPA, 142 had ammonia checked and receiving VPA was associated with ammonia testing (P<0.001). Hyperammonemia was identified in 32 and associated with younger age, being in a non-neurological intensive care unit, and liver disease, but was not statistically associated with VPA. Only one patient had valproate-induced hyperammonemic encephalopathy; however, many patients received treatment for hyperammonemia such as lactulose, levocarnitine, or VPA dose reductions.

Conclusions: This study demonstrated variability in ammonia testing and management changes in SE but does not support the routine monitoring of ammonia levels and showed that hyperammonemic encephalopathy was rare in this clinical setting.
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http://dx.doi.org/10.1097/NRL.0000000000000335DOI Listing
May 2021

Clinical Neurophysiology Fellowship Program Directors Survey on a Standardized Fellowship Match Process: A Call for Action.

J Clin Neurophysiol 2021 Apr 14. Epub 2021 Apr 14.

Department of Neurology, Emory University, Atlanta, Georgia, U.S.A.; Department of Neurology, University of Rochester, Rochester, New York, U.S.A.; Department of Neurology, University of Kentucky, Lexington, Kentucky, U.S.A.; Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, U.S.A.; Department of Neurology and Neurosurgery, Stanford University, Stanford, California, U.S.A.; Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, U.S.A.; Department of Neurology, Mayo Clinic, Rochester, Minnesota, U.S.A.; Department of Neurology, University of California, Los Angeles, California, U.S.A.; Department of Neurology, Mayo Clinic, Jacksonville, Florida, U.S.A.; and Department of Neurology, Duke University School of Medicine, Durham, North Carolina, U.S.A.

Purpose: To survey US Clinical Neurophysiology (CNP) fellowship program directors on the nature of CNP and related training programs, current recruitment cycle, and views for a standardized process.

Methods: A 23-question electronic survey was sent to all 93 US Accreditation Council for Graduate Medical Education-accredited CNP fellowship program directors from December 2020 to January 2021.

Results: The response rate was 60%. There was great variability in the number of CNP positions and CNP tracks offered. The following tracks were identified: 48% EEG dominant, 26% EMG dominant, 22% split equally between EEG and EMG, and 2% and 1% were neurophysiologic intraoperative monitoring and autonomic dominant, respectively. Of the responding institutions, 43% offered a second year of training options to CNP fellows, mainly in conjunction with Epilepsy fellowship, which was pursued by 25% of CNP fellows. Many programs indicated flexibility in their design between different CNP tracks or between CNP and other related training programs based on the available candidates. The median percentage of CNP fellowship positions filled over the last 5 years was 80%, and there was great variation in the recruitment timeline across institutions. Overall, 86% of program directors favored a universal timeline and 71% favored a formal match for CNP. The respondents were split between an independent CNP match (39%) and joining the initiatives of affiliate societies on a standardized process (61%).

Conclusions: There is significant heterogeneity in the makeup of the CNP fellowship programs and the recruitment process. The majority of CNP program directors are in favor of standardization of the recruitment process.
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http://dx.doi.org/10.1097/WNP.0000000000000852DOI Listing
April 2021

Musicogenic epilepsy: Expanding the spectrum of glutamic acid decarboxylase 65 neurological autoimmunity.

Epilepsia 2021 May 25;62(5):e76-e81. Epub 2021 Mar 25.

Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.

The objective of this study was to describe serological association of musicogenic epilepsy and to evaluate clinical features and outcomes of seropositive cases. Through retrospective chart review, musicogenic epilepsy patients were identified. Among 16 musicogenic epilepsy patients, nine underwent autoantibody evaluations and all had high-titer glutamic acid decarboxylase 65-immunoglobulin G (GAD65-IgG; >20 nmol·L , serum, normal ≤ .02 nmol·L , eight women). Median GAD65-IgG serum titer was 294 nmol·L (20.3-3005 nmol·L ), and median cerebrospinal fluid titer (n = 4) was 14.7 nmol·L . All patients had temporal lobe epilepsy, and bitemporal epileptiform abnormalities were common. Right temporal lobe seizures were most frequently captured when seizures were induced by music on electroencephalogram (3/4; 75%). Intravenous (IV) methylprednisolone and/or IV Ig (IVIG) was utilized in four patients, with one having greater than 50% reduction. Rituximab (n = 2) and mycophenolate (n = 1) were ineffective. Two patients underwent right temporal lobe resections but continued to have seizures. Vagus nerve stimulation was effective at reducing seizures in one patient by 50%, and an additional patient was seizure-free by avoiding provoking music. Right temporal lobe epilepsy was more common among patients with musicogenic epilepsy when compared to nonmusicogenic GAD65 epilepsies (n = 71, 89% vs. 47%, p = .03). GAD65-IgG should be tested in patients with musicogenic epilepsy, given implications for management and screening for comorbid autoimmune conditions.
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http://dx.doi.org/10.1111/epi.16888DOI Listing
May 2021

Outcomes following surgical management of vagus nerve stimulator-related infection: a retrospective multi-institutional study.

J Neurosurg 2020 Dec 18:1-9. Epub 2020 Dec 18.

Departments of1Neurologic Surgery and.

Objective: Surgical site infection (SSI) is a rare but significant complication after vagus nerve stimulator (VNS) placement. Treatment options range from antibiotic therapy alone to hardware removal. The optimal therapeutic strategy remains open to debate. Therefore, the authors conducted this retrospective multicenter analysis to provide insight into the optimal management of VNS-related SSI (VNS-SSI).

Methods: Under institutional review board approval and utilizing an institutional database with 641 patients who had undergone 808 VNS-related placement surgeries and 31 patients who had undergone VNS-related hardware removal surgeries, the authors retrospectively analyzed VNS-SSI.

Results: Sixteen cases of VNS-SSI were identified; 12 of them had undergone the original VNS placement procedure at the authors' institutions. Thus, the incidence of VNS-SSI was calculated as 1.5%. The mean (± standard deviation) time from the most recent VNS-related surgeries to infection was 42 (± 27) days. Methicillin-sensitive staphylococcus was the usual causative bacteria (58%). Initial treatments included antibiotics with or without nonsurgical procedures (n = 6), nonremoval open surgeries for irrigation (n = 3), generator removal (n = 3), and total or near-total removal of hardware (n = 4). Although 2 patients were successfully treated with antibiotics alone or combined with generator removal, removal of both the generator and leads was eventually required in 14 patients. Mild swallowing difficulties and hoarseness occurred in 2 patients with eventual resolution.

Conclusions: Removal of the VNS including electrode leads combined with antibiotic administration is the definitive treatment but has a risk of causing dysphagia. If the surgeon finds dense scarring around the vagus nerve, the prudent approach is to snip the electrode close to the nerve as opposed to attempting to unwind the lead completely.
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http://dx.doi.org/10.3171/2020.7.JNS201385DOI Listing
December 2020

Use of diffusion-weighted imaging to distinguish seizure-related change from limbic encephalitis.

J Neurol 2020 Nov 24;267(11):3337-3342. Epub 2020 Jun 24.

Department of Neurology, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA.

Objective: To determine whether diffusion-weighted imaging (DWI) can help differentiate peri-ictal signal abnormality from limbic encephalitis (LE) among patients with medial temporal lobe T2-hyperintensity.

Methods: We retrospectively identified patients with peri-ictal medial temporal lobe T2-hyperintensity using a Mayo Clinic database, and reviewed their DWI to look for unique diffusion restriction patterns. We then identified patients with medial temporal lobe T2-hyperintensity and LE, and reviewed their DWI to see if these patterns were ever present. Presence of diffusion restriction patterns was confirmed by a blinded neuro-radiologist.

Results: We identified 10 patients without LE who had peri-ictal unilateral medial temporal lobe T2-hyperintensity, ipsilateral to focal seizure onset. Nine of 10 (90%) had at least one of two diffusion restriction patterns potentially unique to seizure activity; four had gyriform hippocampal diffusion restriction ("Pattern 1"), three had diffuse hippocampal diffusion restriction that spared the most medial temporal lobe structures ("Pattern 2"), and two had both diffusion restriction patterns. The median patient age was 62 years (range 2-76 years) and 3/9 (33%) were female. In comparison, among patients with medial temporal lobe T2-hyperintensity and LE, only 5/57 (9%) had one of the diffusion restriction patterns ("Pattern 2") identified (P < 0.0001); all five had seizures reported.

Conclusions: In patients with medial temporal lobe T2-hyperintensity and one of the diffusion restriction patterns described herein, the signal abnormality may be a peri-ictal phenomenon rather than indicative of LE and should prompt investigation for seizure. Even in patients with LE, these patterns should raise concern for seizure.
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http://dx.doi.org/10.1007/s00415-020-10007-1DOI Listing
November 2020

Electroencephalogram Changes During Cheyne-Stokes Respiration in Acutely Ill Hospitalized Patients.

Neurocrit Care 2020 12;33(3):829-834

Department of Neurology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.

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http://dx.doi.org/10.1007/s12028-020-00937-zDOI Listing
December 2020

Headache in epilepsy: A prospective observational study.

Epilepsia Open 2019 Dec 21;4(4):593-598. Epub 2019 Oct 21.

Department of Neurology Mayo Clinic Rochester Rochester Minnesota.

Objective: To assess the frequency and characteristics of interictal and postictal headaches (using International Classification of Headache Disorders, 3rd edition criteria) in a population of patients with epilepsy admitted to the Mayo Clinic Rochester epilepsy monitoring unit and assess their localizing value.

Methods: This was a cross-sectional study. Participants were voluntarily recruited upon admission to the epilepsy monitoring unit. Two separate questionnaires were then administered. The first was to assess the presence and character of headaches experienced in the past 12 months. The second was to assess characteristics of postictal headaches experienced during their admission including localization.

Results: One-hundred and twenty subjects (77%) met inclusion criteria and completed the initial questionnaire. Mean age was 38.1 years (range 18-82), and 67 (55.8%) were female. Interictal headaches were reported in 97 of 120 (81%) subjects, and these met ICHD3 criteria for migraine in 48 (50%). Postictal headaches were reported by 75 of 120 (63%) subjects on the initial admission questionnaire, representing migraine in 38 (51%). Thirty-nine (32%) subjects completed the secondary questionnaire related to postictal headaches experienced during admission, of which nine (23%) met criteria for migraine. There was no seizure lateralizing or localizing value noted based on postictal headache localization.

Significance: Migraine was frequent in this cohort and appears to be the dominant interictal and postictal headache type in patients with epilepsy. In this study, the first to assess incident postictal headache in the setting of an ictal EEG, headache localization was of no seizure localizing value. Few patients were being actively treated; suggesting headache management is often overlooked in the epilepsy population.
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http://dx.doi.org/10.1002/epi4.12363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885695PMC
December 2019

Tau deposition in young adults with drug-resistant focal epilepsy.

Epilepsia 2019 12 29;60(12):2398-2403. Epub 2019 Oct 29.

Department of Neurology, Mayo Clinic, Rochester, Minnesota.

Objective: To evaluate the presence of tau deposition and pathologic features of chronic traumatic encephalopathy (CTE) in young adult patients treated with focal cortical resections for drug-resistant epilepsy.

Methods: Sixty consecutive patients who had undergone surgical treatment for drug-resistant focal epilepsy between 18 and 45 years of age were identified (2010-2017). Medical records were reviewed to determine clinical factors, including history of head trauma, age at seizure onset, age at surgical resection, seizure type(s) and frequency, imaging findings, and surgical outcome. All formalin-fixed, paraffin-embedded blocks from the surgical specimens from each subject were sectioned and stained with hematoxylin and eosin and antibodies to tau (Thermo Fisher Scientific Clone AT8), and examined blindly for tau pathology, including lesions characteristic of CTE.

Results: The median age at resection was 29.5 years (range = 19-45). A history of head trauma was reported in 19 patients. Although none of the patients had pathological findings characteristic of CTE, 23 patients (38%) demonstrated tau-immunoreactive lesions, including neurites, neurofibrillary pretangles, neurofibrillary tangles, subpial tau, and/or glial tau. In 4 of the 23 patients (7% of the cohort; 17% of those with tau pathology), substantial tau burden was identified. Three of these 4 patients had no significant history of head trauma; 1 patient had multiple sports-related concussions. No specific clinical factors correlated with the presence of tau pathology.

Significance: Tau-immunoreactive lesions were found in 38% of 60 patients who underwent a focal cortical resection for drug-resistant focal epilepsy. Diagnostic features of CTE were not detected in any patient; however, the pathological evaluation for CTE was limited to a surgical specimen. The prominent and excessive tau deposition in 23 patients (38%) is abnormal in this age group and warrants further investigation.
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http://dx.doi.org/10.1111/epi.16375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973032PMC
December 2019

Transient Epileptic Amnesia: A Treatable Cause of Spells Associated With Persistent Cognitive Symptoms.

Front Neurol 2019 28;10:939. Epub 2019 Aug 28.

Department of Neurology, Mayo Clinic-Rochester, Rochester, MN, United States.

To characterize the clinical, EEG, and neuroimaging profiles of transient epileptic amnesia (TEA). We performed a retrospective analysis of patients diagnosed with TEA at the Mayo Clinic Minnesota from January 1, 1998 to September 21, 2017. Diagnostic criteria included the presence of recurrent episodes of transient amnesia with preservation of other cognitive functions and evidence for epilepsy [epileptiform abnormalities on EEG, clinical features of seizures, or symptomatic response to anti-seizure medications (ASMs)]. Nineteen patients were identified (14 men, 5 women) with median onset age 66 years and median time to diagnosis 2 years. Thirteen patients (68%) reported persistent cognitive/behavioral symptoms, including 4 (21%) for whom these were the chief presenting complaints. EEG revealed epileptiform abnormalities involving the frontal and/or temporal regions in 12/19 individuals (63%), including activation during sleep in all of these cases. In numerous cases, sleep and prolonged EEG evaluations identified abnormalities not previously seen on shorter or awake-state studies. Brain MRI revealed focal abnormalities in only 4/19 cases (21%). FDG-PET identified focal hypometabolism in 2/8 cases where it was performed, both involving the frontal and/or temporal regions. Anti-seizure therapy, most often with a single agent, resulted in improvement (reduction in spell frequency and/or subjective improvement in interictal cognitive/behavioral complaints) in all 17 cases with available follow-up. TEA is a treatable cause of amnestic spells in older adults. This syndrome is frequently associated with persistent interictal cognitive/behavioral symptoms and thus can be mistaken for common mimics. In the appropriate clinical context, our findings support the use of early prolonged EEG with emphasis on sleep monitoring as a key diagnostic tool. FDG-PET may also complement MRI in distinguishing TEA from neurodegenerative disease when suspected.
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http://dx.doi.org/10.3389/fneur.2019.00939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724577PMC
August 2019

Segmentation errors and intertest reliability in automated and manually traced hippocampal volumes.

Ann Clin Transl Neurol 2019 09 6;6(9):1807-1814. Epub 2019 Sep 6.

Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Objective: To rigorously compare automated atlas-based and manual tracing hippocampal segmentation for accuracy, repeatability, and clinical acceptability given a relevant range of imaging abnormalities in clinical epilepsy.

Methods: Forty-nine patients with hippocampal asymmetry were identified from our institutional radiology database, including two patients with significant anatomic deformations. Manual hippocampal tracing was performed by experienced technologists on 3T MPRAGE images, measuring hippocampal volume up to the tectal plate, excluding the hippocampal tail. The same images were processed using NeuroQuant and FreeSurfer software. Ten subjects underwent repeated manual hippocampal tracings by two additional technologists blinded to previous results to evaluate consistency. Ten patients with two clinical MRI studies had volume measurements repeated using NeuroQuant and FreeSurfer.

Results: FreeSurfer raw volumes were significantly lower than NeuroQuant (P < 0.001, right and left), and hippocampal asymmetry estimates were lower for both automatic methods than manual tracing (P < 0.0001). Differences remained significant after scaling volumes to age, gender, and scanner matched normative percentiles. Volume reproducibility was fair (0.4-0.59) for manual tracing, and excellent (>0.75) for both automated methods. Asymmetry index reproducibility was excellent (>0.75) for manual tracing and FreeSurfer segmentation and fair (0.4-0.59) for NeuroQuant segmentation. Both automatic segmentation methods failed on the two cases with anatomic deformations. Segmentation errors were visually identified in 25 NeuroQuant and 27 FreeSurfer segmentations, and nine (18%) NeuroQuant and six (12%) FreeSurfer errors were judged clinically significant.

Interpretation: Automated hippocampal volumes are more reproducible than hand-traced hippocampal volumes. However, these methods fail in some cases, and significant segmentation errors can occur.
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http://dx.doi.org/10.1002/acn3.50885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764491PMC
September 2019

Medial Temporal Encephalocele and Medically Intractable Epilepsy: A Tailored Inferior Temporal Lobectomy and Case Report.

Oper Neurosurg (Hagerstown) 2020 01;18(1):E19-E22

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Background And Importance: Temporal lobe encephaloceles are increasingly recognized as a potential cause of medically refractory epilepsy and surgical treatment has proven effective. Resection of the encephalocele and associated cortex is often sufficient to provide seizure control. However, it is difficult to determine the extent of adjacent temporal lobe that should be resected. We present a case report and our technique of a tailored inferior temporal pole resection.

Clinical Presentation: A 32-yr-old man with an 11-yr history of medically refractory epilepsy. Prolonged electroencephalography (EEG) revealed frequent left and rare right frontotemporal sharp waves. Numerous seizures were captured with EEG, all of which originated from the left temporal region. Statistical parametric mapping (SPM) subtraction ictal-interictal SPECT coregistered with magnetic resonance imaging (MRI) (SISCOM) demonstrated ictal hyperperfusion in the anterior left temporal lobe. MRI showed 2 encephaloceles in the left anterior temporal lobe with the accompanying bony defects in the floor of the middle cranial fossa apparent on the computed tomography scan. The patient underwent left temporal craniotomy with intraoperative electrocorticography, resection of the encephaloceles, and a tailored inferior temporal lobectomy (IFTL) and repair of the middle fossa defects. At 7 mo follow up he reported seizure-freedom since surgery.

Conclusion: Resection of temporal encephalocele and adjacent cortex is safe and effective procedure for select patients with medically refractory epilepsy. This video demonstrates our technique which provides a more standardized approach to the resection.
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http://dx.doi.org/10.1093/ons/opz098DOI Listing
January 2020

Recognizing autoimmune encephalitis as a cause of seizures: Treating cause and not effect.

Neurology 2019 05 12;92(19):877-878. Epub 2019 Apr 12.

From the Division of Epilepsy (J.W.B.) and ICREA and Institut d'Investigacions Biomèdiques August Pi i Sunyer Hospital Clínic (J.D.), Universitat de Barcelona, Spain; and Department of Neurology(J.D.), University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1212/WNL.0000000000007444DOI Listing
May 2019

Targeting analysis of a novel parietal approach for deep brain stimulation of the anterior nucleus of the thalamus for epilepsy.

Epilepsy Res 2019 07 19;153:1-6. Epub 2019 Mar 19.

Department of Neurosurgery, Mayo Clinic, Rochester, MN, USA. Electronic address:

Purpose: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising treatment for refractory epilepsy; however, it remains challenging to successfully target the ANT. The results of Medtronic Registry for Epilepsy (MORE) supported a frontal transventricular(TV) compared to frontal extraventricular (EV) lead trajectory for ANT DBS may have better coverage of the ANT. Here we report the safety and targeting efficacy of a novel, posterior parietal extraventricular (PEV) approach to the ANT.

Methods: We conducted a retrospective analysis of ten patients who underwent bilateral ANT DBS (20 total trajectories) for medically-refractory epilepsy. Similar targeting methodology as the MORE trial was used, and the DBS Intrinsic Template Atlas (DISTAL) was utilized for ANT localization and contact position relative to ANT. Clinical data were assessed for DBS targeting efficacy and surgical complications.

Results: The demonstrated PEV trajectory showed a successful ANT targeting rate of 90% bilaterally. Two or more contacts within ANT were presented in 75% of all leads. Mean contact number in ANT was 2.2+ 1.2. There were no intracranial hemorrhages, cerebrospinal fluid leakage, or permanent neurologic deficits.

Conclusion: In this small series, the novel PEV for ANT DBS is feasible with good targeting accuracy and potential safety advantages. The high accuracy of the PEV trajectory suggests that it is a reasonable alternative trajectory for ANT DBS. Larger studies will be needed to assess this trajectory on clinical outcome of DBS treatment to epilepsy.
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http://dx.doi.org/10.1016/j.eplepsyres.2019.03.010DOI Listing
July 2019

Reassessing the impact of intraoperative electrocorticography on postoperative outcome of patients undergoing standard temporal lobectomy for MRI-negative temporal lobe epilepsy.

J Neurosurg 2019 02;132(2):605-614

Departments of2Neurologic Surgery.

Objective: Almost 30% of the patients with suspected temporal lobe epilepsy (TLE) have normal results on MRI. Success rates for resection of MRI-negative TLE are less favorable, ranging from 36% to 76%. Herein the authors describe the impact of intraoperative electrocorticography (ECoG) augmented by opioid activation and its effect on postoperative seizure outcome.

Methods: Adult and pediatric patients with medically resistant MRI-negative TLE who underwent standardized ECoG at the time of their elective anterior temporal lobectomy (ATL) with amygdalohippocampectomy between 1990 and 2016 were included in this study. Seizure recurrence comprised the primary outcome of interest and was assessed using Kaplan-Meier and multivariable Cox regression analysis plots based on distribution of interictal epileptiform discharges (IEDs) recorded on scalp electroencephalography, baseline and opioid-induced IEDs on ECoG, and extent of resection.

Results: Of the 1144 ATLs performed at the authors' institution between 1990 and 2016, 127 (11.1%) patients (81 females) with MRI-negative TLE were eligible for this study. Patients with complete resection of tissue generating IED recorded on intraoperative ECoG were less likely to have seizure recurrence compared to those with incomplete resection on univariate analysis (p < 0.05). No difference was found in seizure recurrence between patients with bilateral independent IEDs and unilateral IEDs (p = 0.15), presence or absence of opioid-induced epileptiform activation (p = 0.61), or completeness of resection of tissue with opioid-induced IEDs on intraoperative ECoG (p = 0.41).

Conclusions: The authors found that incomplete resection of IED-generating tissue on intraoperative ECoG was associated with an increased chance of seizure recurrence. However, they found that induction of epileptiform activity with intraoperative opioid activation did not provide useful intraoperative data predictive of improving operative results for temporal lobectomy in MRI-negative epilepsy.
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http://dx.doi.org/10.3171/2018.11.JNS182124DOI Listing
February 2019

Late-onset Lennox-Gastaut syndrome: Diagnostic evaluation and outcome.

Neurol Clin Pract 2018 Oct;8(5):397-402

Department of Neurology, Mayo Clinic, Rochester, MN.

Background: We describe the clinical features and outcome in patients with late-onset Lennox-Gastaut syndrome (LGS).

Methods: Adult patients evaluated between January 1, 2000, and March 1, 2017, who presented with onset of LGS ≥10 years were identified. Data abstracted included age at seizure onset, seizure types, etiology, treatments, EEG and neuroimaging results, cerebrospinal fluid (CSF) findings, and autoimmune evaluation.

Results: Ten patients (8 females) were identified. The mean age at onset of seizures consistent with LGS was 16.5 years (range, 10-32 years). Seizure types included tonic, atonic, and tonic-clonic seizures (all), myoclonic seizures (n = 3), and atypical absence seizures (n = 7). Five patients had normal intellectual function at onset. Prolonged video-EEG monitoring recorded seizures and generalized interictal epileptiform discharges in all. All patients had drug-resistant epilepsy (range of antiseizure drugs tried, 7-16). Two patients had a history of intrathecal methotrexate to treat acute lymphoblastic leukemia. Two patients had malformations of cortical development. CSF analysis (n = 5) showed a mild elevation in the protein level without other abnormalities. Autoantibody determinations in the serum (n = 4) or the CSF (n = 5) and genetic testing (n = 5) were negative. At final follow-up, all but 1 patient was disabled and required a caregiver, and none were driving. One patient died of probable sudden unexpected death in epilepsy (SUDEP).

Conclusions: Late-onset LGS represents a rare, treatment-resistant generalized epilepsy that is disabling and may be associated with progressive cognitive impairment. The elevated CSF protein level in our cohort could have been due to high seizure burden but increases the possibility of an inflammatory component to the pathophysiology of this disorder.
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http://dx.doi.org/10.1212/CPJ.0000000000000527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276343PMC
October 2018

Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy.

Epilepsia 2018 10 24;59(10):1973-1981. Epub 2018 Sep 24.

Mayo Center for Sleep Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.

Objective: We aimed to determine the frequency of probable obstructive sleep apnea (pOSA) in refractory epilepsy monitoring unit inpatients and clinical features associated with pOSA, including risk for sudden unexpected death in epilepsy (SUDEP).

Methods: We prospectively recruited 49 consecutive adult patients admitted to the Mayo Clinic Epilepsy Monitoring Unit with focal, generalized, or unclassified epilepsy syndromes. pOSA was identified using oximetric oxyhemoglobin desaturation index (ODI) and the Sleep Apnea-Sleep Disorders Questionnaire (SA-SDQ) and STOP-BAG screening tools. Revised SUDEP Risk Inventory (rSUDEP-7) scores were calculated, and epilepsy patients with and without pOSA were compared with Wilcoxon signed-rank tests. Correlation and regression analyses were utilized to determine relationships between pOSA and rSUDEP-7 scores.

Results: Thirty-five percent of patients had pOSA, with a mean ODI of 11.3 ± 5.1/h (range = 5.1-22.8). Patients with pOSA were older and heavier, and more frequently had a focal epilepsy syndrome and longer epilepsy duration, with higher SA-SDQ and STOP-BAG scores (all P < 0.05). Median rSUDEP-7 score was 3 ± 1.4 (range = 0-6). Higher rSUDEP-7 scores were positively correlated with higher ODI (P = 0.036). rSUDEP-7 score ≥ 5 was associated with pOSA by ODI, SA-SDQ, and STOP-BAG questionnaire criteria (P < 0.05).

Significance: Our pilot study identified a high frequency of pOSA in refractory epilepsy monitoring patients, finding that pOSA patients were older and heavier, with higher screening symptoms for sleep apnea and more frequent focal seizures with a longer epilepsy duration. We also found a possible association between OSA and SUDEP risk. Identification and treatment of OSA in patients with epilepsy could conceivably provide a novel approach toward preventing the risk of SUDEP. Future studies with polysomnography are needed to confirm predictive features for OSA in epilepsy populations, and to determine whether OSA is associated with SUDEP risk.
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http://dx.doi.org/10.1111/epi.14548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855247PMC
October 2018

Bilateral independent periodic discharges are associated with electrographic seizures and poor outcome: A case-control study.

Clin Neurophysiol 2018 11 29;129(11):2284-2289. Epub 2018 Aug 29.

Department of Neurology, Yale University School of Medicine, New Haven, CT, USA; Service de Neurologie et Centre de Référence pour le Traitement de l'Epilepsie Réfractaire, Université Libre de Bruxelles - Hôpital Erasme, Bruxelles, Belgium. Electronic address:

Objective: To determine the clinical correlates bilateral independent periodic discharges (BIPDs) and their association with electrographic seizures and outcome.

Methods: Retrospective case-control study of patients with BIPDs compared to patients without periodic discharges ("No PDs") and patients with lateralized periodic discharges ("LPDs"), matched for age, etiology and level of alertness.

Results: We included 85 cases and 85 controls in each group. The most frequent etiologies of BIPDs were stroke, CNS infections, and anoxic brain injury. Acute bilateral cerebral injury was more common in the BIPDs group than in the No PDs and LPDs groups (70% vs. 37% vs. 35%). Electrographic seizures were more common with BIPDs than in the absence of PDs (45% vs. 8%), but not than with LPDs (52%). Mortality was higher in the BIPDs group (36%) than in the No PDs group (18%), with fewer patients with BIPDs achieving good outcome (moderate disability or better; 18% vs. 36%), but not than in the LPDs group (24% mortality, 26% good outcome). In multivariate analyses, BIPDs remained associated with mortality (OR: 3.0 [1.4-6.4]) and poor outcome (OR: 2.9 [1.4-6.2]).

Conclusion: BIPDs are caused by bilateral acute brain injury and are associated with a high risk of electrographic seizures and of poor outcome.

Significance: BIPDs are uncommon but their identification in critically ill patients has potential important implications, both in terms of clinical management and prognostication.
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http://dx.doi.org/10.1016/j.clinph.2018.07.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785981PMC
November 2018

Predictors of neural-specific autoantibodies and immunotherapy response in patients with cognitive dysfunction.

J Neuroimmunol 2018 10 25;323:62-72. Epub 2018 Jul 25.

Department of Neurology, Mayo Clinic, Rochester, United States; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, United States.

Recognition of autoimmunity as a cause of encephalopathy has increased. Recent studies have validated the use of Antibody-Prevalence-in-Epilepsy (APE) and Responsive-to-immunotherapy-in-Epilepsy (RITE) scores in the evaluation and management of autoimmune-epilepsy. We aim to assess the utility of these models for patients with cognitive dysfunction. Among the evaluated patients, 17% had antibodies universally associated with autoimmune-encephalopathy. NMDA-R-IgG and LGI1-IgG were the most common antibody specificities. Antibody-Prevalence-in-Epilepsy-and-Encephalopathy (APE) score ≥ 4 was 99% sensitive and 93% specific for neural-specific-antibodies. Responsive-to-immunotherapy-in-Epilepsy-and-Encephalopathy (RITE) score ≥ 7 had 96% sensitivity and 86% specificity for favorable initial immunotherapy response. Application of these models may optimize autoantibody evaluations and immunotherapeutic trials.
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http://dx.doi.org/10.1016/j.jneuroim.2018.07.009DOI Listing
October 2018

Antiepileptic drug therapy in autoimmune epilepsy associated with antibodies targeting the leucine-rich glioma-inactivated protein 1.

Epilepsia Open 2018 Sep 25;3(3):348-356. Epub 2018 Jun 25.

Department of Neurology Mayo Clinic Rochester Minnesota U.S.A.

Objective: To characterize seizure semiology and the utility of antiepileptic drug (AED) therapy in leucine-rich glioma inactivated-1 ( LGI1-Ab) autoimmune epilepsy (AE).

Methods: Patients with voltage-gated potassium channel complex (VGKCc) titers higher than 0.02 nmol/L who were evaluated between May 2008 and June 2016 at the 3 Mayo Clinic sites (Arizona, Florida, or Minnesota) were identified. We then performed a retrospective review of those who were LGI1-Ab positive and were treated for seizures.

Results: A total of 1,095 patients with VGKCc titers higher than 0.02 nmol/L were identified, in which 77 were LGI1 positive. Of these, 56 patients with seizures were included in the analysis. Mean age at symptom onset was 62.9 years; 66% (n = 37) were male. The most common seizure semiology was focal faciobrachial dystonic seizures with preserved awareness (FBDS) (n = 35, 63%), followed by focal with impaired awareness (FIA) (n = 29, 52%), generalized tonic-clonic (GTCs) (n = 28, 50%), and focal non-motor seizures with preserved awareness (n = 28, 50%). The majority had more than one seizure type (n = 49, 88%; median = 2.5). Thirty-eight patients (68%) became seizure free: 29 (76%) with immunotherapy, 3 (5%) with AEDs alone, 2 (3%) with AEDs before any immunotherapy, and 4 (7%) with AEDs after immunotherapy. Levetiracetam (n = 47, 84%) and valproic acid (n = 21, 38%) were the most commonly used AEDs, but neither were associated with seizure freedom. Sodium channel blocking (NCB) AEDs were associated with seizure freedom in 4 patients compared to none treated with non-NCB AEDs. Regardless of class, AEDs prior to or apart from immunotherapy were associated with seizure freedom in only five patients (9%). In patients with FBDS, seizure freedom was more often associated with immunotherapy than AEDs (20/30 vs. 3/34, p = 0.001).

Significance: Although FBDS are the most characteristic seizure type seen in LGI1-Ab AE, other seizure types including FIA and GTCs also occur. Immunotherapy was the treatment most frequently associated with seizure freedom in LGI1-Ab AE. In general, AEDs seemed to confer a very low chance for seizure freedom, although AEDs with NCB-blocking properties were associated with seizure freedom in a limited number. Levetiracetam in particular appears to be ineffective in this patient population.
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http://dx.doi.org/10.1002/epi4.12226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119747PMC
September 2018

Jeavons Syndrome: Clinical Features and Response to Treatment.

Pediatr Neurol 2018 09 10;86:46-51. Epub 2018 Jul 10.

Department of Neurology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: Jeavons syndrome is an underreported epileptic syndrome characterized by eyelid myoclonia, eyelid closure-induced seizures or electroencephalography paroxysms, and photosensitivity. Drug-resistant epilepsy is common, but the prognostic factors and clinical course leading to drug resistance have not been well characterized.

Methods: We identified 30 patients who met the diagnostic criteria of Jeavons syndrome at a single institution between January 1, 2000 and December 15, 2016. Criteria for Jeavons syndrome included all of the following: (1) eyelid myoclonia with or without absences, (2) eye-closure-induced seizures or electroencephalography paroxysms, and (3) seizure onset after 12 months of age. We reviewed and described the epilepsy history, antiepileptic drug trials, and response to treatments.

Results: Mean age at seizure onset was 7.3 years, and 80% were female. Absence seizures (63%) and generalized tonic-clonic seizures (23%) were most common at onset. Diagnosis was delayed by an average of 9.6 years. After a median follow-up of two years, 80% of patients had drug resistant epilepsy and 70% experienced generalized tonic-clonic seizures. Generalized tonic-clonic seizures and seizure types other than absence seizures increased the risk of drug-resistant epilepsy (P values 0.049 and 0.03, respectively). Valproic acid, lamotrigine, ethosuximide, and levetiracetam were the most effective in reducing seizures by more than 50%.

Conclusions: The diagnosis of Jeavons syndrome is often delayed. Generalized tonic-clonic seizures and seizure types other than absence seizures may be predictors of drug-resistant epilepsy among patients with Jeavons syndrome.
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http://dx.doi.org/10.1016/j.pediatrneurol.2018.06.001DOI Listing
September 2018

Unusual seizure evolution: Focal-general-focal-general.

Epilepsy Behav Case Rep 2018 14;10:54-56. Epub 2018 Mar 14.

Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA.

Seizure types have been described that do not conform to traditional classification schemes. We present another unusual type characterized by focal onset with secondary generalization, that is followed immediately by continued focal activity that generalizes again without an intervening break. Better understanding of these seizure types may allow improved targeted therapies and help shed light on the mechanistic underpinnings of epilepsy.
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http://dx.doi.org/10.1016/j.ebcr.2018.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031237PMC
March 2018

Frequent sleep-related bitemporal focal seizures in transient epileptic amnesia syndrome: Evidence from ictal video-EEG.

Epilepsia Open 2017 06 7;2(2):255-259. Epub 2017 Feb 7.

Department of Neurology Mayo Clinic College of Medicine Rochester Minnesota U.S.A.

Two patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep-activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case 1 is a 59-year-old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct 8-h-long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case 2 is a 50-year-old woman with known focal epilepsy also presented with memory complaints. Over the course of 1 year, she had two discrete 2-h-long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. Although the etiology of accelerated long-term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep-related seizures may contribute, and they highlight the importance of video-EEG monitoring.
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http://dx.doi.org/10.1002/epi4.12040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719851PMC
June 2017

Electrical Stimulation Mapping With Stereo-EEG Electrodes.

J Clin Neurophysiol 2018 Mar;35(2):110-114

Epilepsy Division and Professor of Neurology, Mayo Clinic, Rochester, Minnesota, U.S.A.

The practice of stereo-EEG (SEEG) is expanding. Electrical stimulation mapping remains an important part of the surgical evaluation process in SEEG, as it is in subdural electrocorticography cases. Because the technique and electrodes used in SEEG and electrocorticography are distinct, the clinician needs to be aware of the important differences between these techniques when performing electrical stimulation mapping. In this review, the advantages, disadvantages, and potential safety concerns related to electrical stimulation mapping in SEEG are discussed. A case is presented illustrating the utility of SEEG cortical stimulation and safety concerns that need to be considered when performing these evaluations.
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http://dx.doi.org/10.1097/WNP.0000000000000443DOI Listing
March 2018

Chronic traumatic encephalopathy in an epilepsy surgery cohort: Clinical and pathologic findings.

Neurology 2018 02 10;90(6):e474-e478. Epub 2018 Jan 10.

From the Department of Neurology (A.L.J., J.W.B., J.E.P., G.D.C.), Division of Epilepsy (A.L.J., J.W.B., G.D.C.), and Department of Laboratory Medicine and Pathology (M.M.B., J.E.P.), Mayo Clinic, Rochester, MN.

Objective: To determine the occurrence of chronic traumatic encephalopathy (CTE) in young adult patients undergoing epilepsy surgery.

Methods: Ten patients who underwent epilepsy surgery were randomly selected for this retrospective study. The patients were 18-45 years of age, had preoperative neuropsychological evaluation, and had 1 year postoperative follow-up. Microscopic sections from resections were evaluated for the presence of CTE with standard stains and antibodies to tau (clone AT8).

Results: The median age at resection was 32.5 years (range 23-43) and the median duration of seizures was 23.5 years (range 3-28). Eight had a history of head injury. Preoperative neuropsychological testing showed mild to moderate cognitive impairment in 8 patients (80%). Pathologic examination in one patient showed focal sparse tau-immunoreactive lesions along descending rami and cortical gyral depths of the resected frontal lobe. Nine patients had no evidence of CTE. All focal cortical resections showed variable subpial and subcortical gliosis commonly identified in patients with chronic seizure disorders.

Conclusions: The present small retrospective observational study suggests that CTE may occur, but appears uncommon, in young adult patients undergoing surgical treatment for drug-resistant focal epilepsy. The significance of these findings requires further investigation to define the relative importance of tau accumulation in younger adult patients with drug-resistant focal epilepsy and cognitive decline.
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http://dx.doi.org/10.1212/WNL.0000000000004927DOI Listing
February 2018

Chronic subthreshold cortical stimulation for adult drug-resistant focal epilepsy: safety, feasibility, and technique.

J Neurosurg 2018 08 20;129(2):533-543. Epub 2017 Oct 20.

Departments of1Neurosurgery and.

OBJECTIVE Epilepsy surgery is effective for lesional epilepsy, but it can be associated with significant morbidity when seizures originate from eloquent cortex that is resected. Here, the objective was to describe chronic subthreshold cortical stimulation and evaluate its early surgical safety profile in adult patients with epilepsy originating from seizure foci in cortex that is not amenable to resection. METHODS Adult patients with focal drug-resistant epilepsy underwent intracranial electroencephalography monitoring for evaluation of resection. Those with seizure foci in eloquent cortex were not candidates for resection and were offered a short therapeutic trial of continuous subthreshold cortical stimulation via intracranial monitoring electrodes. After a successful trial, electrodes were explanted and permanent stimulation hardware was implanted. RESULTS Ten patients (6 males) who underwent chronic subthreshold cortical stimulation between 2014 and 2016 were included. Based on radiographic imaging, intracranial pathologies included cortical dysplasia (n = 3), encephalomalacia (n = 3), cortical tubers (n = 1), Rasmussen encephalitis (n = 1), and linear migrational anomaly (n = 1). The duration of intracranial monitoring ranged from 3 to 20 days. All patients experienced an uneventful postoperative course and were discharged home with a median length of stay of 10 days. No postoperative surgical complications developed (median follow-up length 7.7 months). Seizure severity and seizure frequency improved in all patients. CONCLUSIONS The authors' institutional experience with this small group shows that chronic subthreshold cortical stimulation can be safely and effectively performed in appropriately selected patients without postoperative complications. Future investigation will provide further insight to recently published results regarding mechanism and efficacy of this novel and promising intervention.
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http://dx.doi.org/10.3171/2017.5.JNS163134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286090PMC
August 2018

Antiepileptic drug therapy in patients with autoimmune epilepsy.

Neurol Neuroimmunol Neuroinflamm 2017 Jul 10;4(4):e353. Epub 2017 May 10.

Department of Neurology (A.M.F., A.S.L.C.), Mayo Clinic, Jacksonville, FL; and Department of Neurology (J.W.B.), Mayo Clinic, Rochester, MN.

Objective: We aimed to report the pattern of usage and efficacy of antiepileptic drugs (AEDs) in patients with autoimmune epilepsy (AE).

Methods: We retrospectively studied the Mayo Clinic's electronic medical record of patients with AE in which seizures were the main presenting feature. Clinical data, including demographics, seizure characteristics, type of AED and immunotherapy used, presence of neural antibody, and treatment outcomes, were reviewed.

Results: The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed. Seizure was the initial presentation in 50 patients (20%). Serum and/or CSF autoantibodies were detected in 41 (82%) patients, and 38 (76%) patients had neural autoantibodies. The majority (n = 43, 86%) received at least 1 form of immunotherapy in combination with AEDs, while the remainder received AEDs alone. Twenty-seven patients (54%) became seizure free: 18 (36%) with immunotherapy, 5 (10%) with AEDs alone, and 4 (8%) with AEDs after immunotherapy failure. Levetiracetam was the most commonly used (42/50); however, it was associated with 0% seizure-free response. AED seizure-free responses occurred with carbamazepine (n = 3) [3/16, 18.8%], lacosamide (n = 3) [3/18, 16.6%] with phenytoin (n = 1) [1/8, 12.5%], or oxcarbazepine (n = 2) [2/11, 18.1%]. Regardless of the type of therapy, voltage-gated potassium channel-complex antibody-positive patients were more likely to become seizure free compared with glutamic acid decarboxylase 65 antibody-positive cases (12/17 vs 2/10, = 0.0183).

Conclusions: In select patients, AEDs alone were effective in controlling seizures. AEDs with sodium channel blocking properties resulted in seizure freedom in a few cases. Prospective studies are needed to clarify AED selection and to elucidate their immunomodulatory properties in AE.
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http://dx.doi.org/10.1212/NXI.0000000000000353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489139PMC
July 2017

Dacrystic seizures-a cry for help.

Neurol Neuroimmunol Neuroinflamm 2017 Jul 16;4(4):e372. Epub 2017 Jun 16.

Department of Laboratory Medicine and Pathology (A.G., E.P.F., S.J.P.) and Department of Neurology (A.G., J.S., J.W.B., E.P.F., S.J.P.), Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1212/NXI.0000000000000372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473955PMC
July 2017

Predictive models in the diagnosis and treatment of autoimmune epilepsy.

Epilepsia 2017 07 26;58(7):1181-1189. Epub 2017 May 26.

Department of Neurology, Mayo Clinic, Rochester, Minnesota, U.S.A.

Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy.

Methods: We conducted a retrospective study of epilepsy cases at Mayo Clinic (Rochester-MN; Scottsdale-AZ, and Jacksonville-FL) in whom autoimmune encephalopathy/epilepsy/dementia autoantibody testing profiles were requested (06/30/2014-06/30/2016). An Antibody Prevalence in Epilepsy (APE) score, based on clinical characteristics, was assigned to each patient. Among patients who received immunotherapy, a Response to Immunotherapy in Epilepsy (RITE) score was assigned. Favorable seizure outcome was defined as >50% reduction of seizure frequency at the first follow-up.

Results: Serum and cerebrospinal fluid (CSF) from 1,736 patients were sent to the Mayo Clinic Neuroimmunology Laboratory for neural autoantibody evaluation. Three hundred eighty-seven of these patients met the diagnostic criteria for epilepsy. Central nervous system (CNS)-specific antibodies were detected in 44 patients. Certain clinical features such as new-onset epilepsy, autonomic dysfunction, viral prodrome, faciobrachial dystonic seizures/oral dyskinesia, inflammatory CSF profile, and mesial temporal magnetic resonance imaging (MRI) abnormalities had a significant association with positive antibody results. A significantly higher proportion of antibody-positive patients had an APE score ≥4 (97.7% vs. 21.6%, p < 0.01). Sensitivity and specificity of an APE score ≥4 to predict presence of specific neural auto-antibody were 97.7% and 77.9%, respectively. In the subset of patients who received immunotherapy (77), autonomic dysfunction, faciobrachial dystonic seizures/oral dyskinesia, early initiation of immunotherapy, and presence of antibodies targeting plasma membrane proteins (cell-surface antigens) were associated with favorable seizure outcome. Sensitivity and specificity of a RITE score ≥7 to predict favorable seizure outcome were 87.5% and 83.8%, respectively.

Significance: APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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http://dx.doi.org/10.1111/epi.13797DOI Listing
July 2017

Electroencephalography Predicts Poor and Good Outcomes After Cardiac Arrest: A Two-Center Study.

Crit Care Med 2017 Jul;45(7):e674-e682

1Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV) and Université de Lausanne (UNIL), Lausanne, Switzerland.2Department of Neurology, Mayo Clinic, Rochester, MN.3Department of Anesthesiology, Mayo Clinic, Rochester, MN.4Department of Intensive Care Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and Université de Lausanne (UNIL), Lausanne, Switzerland.

Objective: The prognostic role of electroencephalography during and after targeted temperature management in postcardiac arrest patients, relatively to other predictors, is incompletely known. We assessed performances of electroencephalography during and after targeted temperature management toward good and poor outcomes, along with other recognized predictors.

Design: Cohort study (April 2009 to March 2016).

Setting: Two academic hospitals (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Mayo Clinic, Rochester, MN).

Patients: Consecutive comatose adults admitted after cardiac arrest, identified through prospective registries.

Interventions: All patients were managed with targeted temperature management, receiving prespecified standardized clinical, neurophysiologic (particularly, electroencephalography during and after targeted temperature management), and biochemical evaluations.

Measurements And Main Results: We assessed electroencephalography variables (reactivity, continuity, epileptiform features, and prespecified "benign" or "highly malignant" patterns based on the American Clinical Neurophysiology Society nomenclature) and other clinical, neurophysiologic (somatosensory-evoked potential), and biochemical prognosticators. Good outcome (Cerebral Performance Categories 1 and 2) and mortality predictions at 3 months were calculated. Among 357 patients, early electroencephalography reactivity and continuity and flexor or better motor reaction had greater than 70% positive predictive value for good outcome; reactivity (80.4%; 95% CI, 75.9-84.4%) and motor response (80.1%; 95% CI, 75.6-84.1%) had highest accuracy. Early benign electroencephalography heralded good outcome in 86.2% (95% CI, 79.8-91.1%). False positive rates for mortality were less than 5% for epileptiform or nonreactive early electroencephalography, nonreactive late electroencephalography, absent somatosensory-evoked potential, absent pupillary or corneal reflexes, presence of myoclonus, and neuron-specific enolase greater than 75 µg/L; accuracy was highest for early electroencephalography reactivity (86.6%; 95% CI, 82.6-90.0). Early highly malignant electroencephalography had an false positive rate of 1.5% with accuracy of 85.7% (95% CI, 81.7-89.2%).

Conclusions: This study provides class III evidence that electroencephalography reactivity predicts both poor and good outcomes, and motor reaction good outcome after cardiac arrest. Electroencephalography reactivity seems to be the best discriminator between good and poor outcomes. Standardized electroencephalography interpretation seems to predict both conditions during and after targeted temperature management.
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http://dx.doi.org/10.1097/CCM.0000000000002337DOI Listing
July 2017