Publications by authors named "Philipp Reif"

62 Publications

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.

J Neurol Neurosurg Psychiatry 2021 Apr 26. Epub 2021 Apr 26.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, and Chalfont Centre for Epilepsy, Gerrard Cross, UK

Objective: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.

Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.

Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).

Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
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http://dx.doi.org/10.1136/jnnp-2020-325932DOI Listing
April 2021

Postoperative outcomes and surgical ratio at a newly established epilepsy center: The first 100 procedures.

Epilepsy Behav 2021 03 22;116:107715. Epub 2021 Jan 22.

Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Purpose: To describe the patients' characteristics, surgical ratio, and outcomes following epilepsy surgery at the newly established Epilepsy Center Frankfurt Rhine-Main.

Methods: We retrospectively studied the first 100 consecutive patients, including adult (n = 77) and pediatric (n = 23) patients, with drug-resistant epilepsy who underwent resective or ablative surgical procedures at a single, newly established epilepsy center. Patient characteristics, seizure and neuropsychological outcomes, histopathology, complications, and surgical ratio were analyzed.

Results: The mean patient age was 28.8 years (children 10.6 years, adults 34.2 years). The mean epilepsy duration was 11.9 years (children 3.9 years, adults 14.3 years), and the mean follow-up was 1.5 years. At the most recent visit, 64% of patients remained completely seizure free [Engel IA]. The rates of perioperative complications and unexpected new neurological deficits were 5%, each. The proportion of patients showing deficits in one or more cognitive domains increased six months after surgery and decreased to presurgical proportions after two years. Symptoms of depression were significantly decreased and quality of life was significantly increased after surgery. The surgical ratio was 25.3%.

Conclusion: Similar postsurgical outcomes were achieved at a newly established epilepsy center compared with long-standing epilepsy centers. The lower time to surgery may reflect a general decrease in time to surgery over the last decade or the improved accessibility of a new epilepsy center in a previously underserved area. The surgical ratio was not lower than reported for established centers.
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http://dx.doi.org/10.1016/j.yebeh.2020.107715DOI Listing
March 2021

DIagnostic Subdural EEG electrodes And Subdural hEmatoma (DISEASE): a study protocol for a prospective nonrandomized controlled trial.

Neurol Res Pract 2020 15;2:50. Epub 2020 Dec 15.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany.

Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.

Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.

Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.

Trial Registration: ClinicalTrials.gov identifier no. NCT04211233.
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http://dx.doi.org/10.1186/s42466-020-00096-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737265PMC
December 2020

NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns.

Genet Med 2021 02 4;23(2):363-373. Epub 2020 Nov 4.

Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.

Purpose: Pathogenic variants in the X-linked gene NEXMIF (previously KIAA2022) are associated with intellectual disability (ID), autism spectrum disorder, and epilepsy. We aimed to delineate the female and male phenotypic spectrum of NEXMIF encephalopathy.

Methods: Through an international collaboration, we analyzed the phenotypes and genotypes of 87 patients with NEXMIF encephalopathy.

Results: Sixty-three females and 24 males (46 new patients) with NEXMIF encephalopathy were studied, with 30 novel variants. Phenotypic features included developmental delay/ID in 86/87 (99%), seizures in 71/86 (83%) and multiple comorbidities. Generalized seizures predominated including myoclonic seizures and absence seizures (both 46/70, 66%), absence with eyelid myoclonia (17/70, 24%), and atonic seizures (30/70, 43%). Males had more severe developmental impairment; females had epilepsy more frequently, and varied from unaffected to severely affected. All NEXMIF pathogenic variants led to a premature stop codon or were deleterious structural variants. Most arose de novo, although X-linked segregation occurred for both sexes. Somatic mosaicism occurred in two males and a family with suspected parental mosaicism.

Conclusion: NEXMIF encephalopathy is an X-linked, generalized developmental and epileptic encephalopathy characterized by myoclonic-atonic epilepsy overlapping with eyelid myoclonia with absence. Some patients have developmental encephalopathy without epilepsy. Males have more severe developmental impairment. NEXMIF encephalopathy arises due to loss-of-function variants.
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http://dx.doi.org/10.1038/s41436-020-00988-9DOI Listing
February 2021

A 10 year comparative study of caesarean deliveries using the Robson 10 group classification system in a university hospital in Austria.

PLoS One 2020 16;15(10):e0240475. Epub 2020 Oct 16.

Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Objective: The Robson ten group classification system is used as a global standard for assessing, monitoring and comparing caesarean delivery (CD) rates within and between maternity services. Our objective was to compare the changes of CD rates at our institution between the years 2008-2010 and 2017-2019 using the Robson ten group classification system.

Study Design: Data was collected retrospectively and all women were classified using the obstetric concepts and parameters described in the Robson ten group classification system.

Results: During 2008-2010 7,832 deliveries were performed, increasing to 9,490 in 2017-2019. The CD rate also increased from 29.1% to 32.2% (p<.05) during this 10 year period. In both observed periods group 5 (single cephalic multiparous women at term with a previous CD) was the largest contributor to the overall CD rate accounting for 20.2% of all CD during 2008-2010 and increasing to 26.9% in 2017-2019 (p<.001). The overall size of group 5 also increased from 8.3% to 11.6% (p<.001). Furthermore, an increase in CD rate in group 7 (multiparous women with a single breech pregnancy, including women with a uterine scar) from 92.9% to 98.2% (p = .752) could be observed. In group 8 (women with multiple pregnancies, including women with a uterine scar) a slight shift towards vaginal delivery (VD) can be reported with CD rates decreasing from 82% to 79.2% (p = .784). There was no observed difference with CD rates in group 1 although the group size decreased from 29.4% in 2008-2010 to 24.2% in 2017-2019 (p<.001). The CD rate in group 10 experienced a slight elevation, in 2008-2010 46.2% were delivered per CD and in 2017-2019 48.8% (p = .553). The overall size of group 10 decreased, contributing 8.9% in 2008-2010 and 8% in 2017-2019 (p<.05) to the overall birthrate.

Conclusion: The biggest contributors to the CD rate in our hospital remain multiparous women at term with a previous CD. The CD rates, as well as the overall size of this group, keep rising, resulting in a need to establish more effective ways to motivate women with one previous CD towards vaginal birth after caesarean delivery (VBAC). Furthermore, the CD rate in preterm deliveries is increasing and approaching 50%. This illustrates the need to discuss whether CD is the appropriate mode of delivery in half of the preterm infants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240475PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567372PMC
December 2020

Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring.

CNS Drugs 2020 05;34(5):545-553

Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, Goethe-University Frankfurt, University Hospital Frankfurt, Schleusenweg 2-16, Haus 95, 60528, Frankfurt am Main, Germany.

Background: An efficient, well tolerated, and safe emergency treatment with a rapid onset of action is needed to prevent seizure clusters and to terminate prolonged seizures and status epilepticus.

Objectives: This study aimed to examine the efficacy, tolerability, and safety of intranasal midazolam (in-MDZ) spray in clinical practice.

Methods: In this retrospective, multicenter observational study, we evaluated all patients with peri-ictal application of in-MDZ during video-EEG monitoring at the epilepsy centers in Frankfurt and Marburg between 2 014 and 2017. For every patient, we analyzed the recurrence of any seizure or generalized tonic-clonic seizures after index seizures with and without in-MDZ administration. Treatment-emergent adverse events (TEAEs) were also evaluated.

Results: In-MDZ was used in 243 patients with epilepsy (mean age 35.5 years; range 5-76 years; 46.5% female) for treatment of 459 seizures. A median dose of in-MDZ 5 mg (i.e., two puffs; range 2.5-15 mg) was administered within a median time from EEG seizure onset until in-MDZ application of 1.18 min [interquartile range (IQR) 1.27], while median time from clinical seizure onset until in-MDZ administration was 1.08 min (IQR 1.19). In-MDZ was given within 1 min after EEG seizure onset in 171 seizures. An intraindividual comparison of seizures with and without application of in-MDZ was feasible in 171 patients, demonstrating that in-MDZ reduced the occurrence of any (Cox proportional-hazard model p < 0.001) and generalized tonic-clonic seizure (Cox proportional-hazard model p = 0.0167) over a period of 24 h. The seizure-free timespan was doubled from a median of 5.0 h in controls to a median of 10.67 h after in-MDZ administration. We additionally clustered in-MDZ administrations for the 119 patients who received in-MDZ more than once, comparing them with the index cases without in-MDZ. Even when considering subsequent seizures with in-MDZ administration, a patient receiving in-MDZ is still half as likely to incur another seizure in the upcoming 24 h as compared with when the same patient does not receive in-MDZ (hazard ratio 0.50; 95% CI 0.42-0.60; p < 0.01). In-MDZ was well tolerated without major adverse events. The most common side effects were irritation of the nasal mucosa [37 cases (8.1%)], prolonged sedation [26 cases (5.7%)], and nausea and vomiting [12 cases (2.6%)]. A decline in oxygen saturation was measured after 78 seizures (17%).

Conclusion: We conclude that in-MDZ is a safe and efficient treatment option to prevent short-term recurrence of seizures. In-MDZ can be administered very quickly by trained staff within 1-2 min after seizure onset. No major cardiocirculatory or respiratory adverse events were observed.
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http://dx.doi.org/10.1007/s40263-020-00720-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198639PMC
May 2020

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Seizure 2020 May 5;78:31-37. Epub 2020 Mar 5.

Neurocenter Bellevue, Zurich, Switzerland.

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".
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http://dx.doi.org/10.1016/j.seizure.2020.02.018DOI Listing
May 2020

Prone, lateral, or supine positioning at seizure onset determines the postictal body position: A multicenter video-EEG monitoring cohort study.

Seizure 2020 Feb 21;76:173-178. Epub 2020 Feb 21.

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized and Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany; Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany. Electronic address:

Purpose: Most patients who die from sudden unexpected death in epilepsy (SUDEP) are found in the prone position. We evaluated whether changes in body position occur during generalized convulsive seizures (GCSs).

Method: GCSs in patients undergoing video-EEG-monitoring between 2007 and 2017 at epilepsy centers in Frankfurt and Marburg were analyzed in relation to changes in body position.

Results: A total of 494 GCSs were analyzed among 327 patients. At seizure onset, positions included supine (48.2 %), right lateral (19.0 %), left lateral (15.6 %), sitting or standing (14.0 %), and prone (3.2 %). Between seizure onset and the start of generalization, 57.5 % of participants altered body positions. During four seizures, patients adopted a prone position, while, in five seizures, patients moved from a prone position. Patients who experienced GCS onset while in a nonprone position had a 2.1 % risk of entering the prone position by the end of their seizure. In contrast, 56.2 % of those in an initial prone position remained so at the end of the GCS, with an odds ratio for maintaining that position of 60.2 (95 % confidence interval: 29.1-124.3; p < 0.001). The likelihood of ending up in the prone position post-GCS did not vary among patients with different nonprone starting positions (p = 0.147).

Conclusions: Seizures in prone position occur during sleep and the highest risk for postictal prone positioning appears to be being in the prone position at GCS onset. Epilepsy patients should therefore be advised to go to sleep in a supine or lateral position to reduce their SUDEP risk.
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http://dx.doi.org/10.1016/j.seizure.2020.02.008DOI Listing
February 2020

Predicting outcome of epilepsy surgery in clinical practice: Prediction models vs. clinical acumen.

Seizure 2020 Feb 1;76:79-83. Epub 2020 Feb 1.

Epilepsy Center Hessen, Department of Neurology, University Hospitals Giessen & Marburg, Philipps-University Marburg, Marburg, Germany; Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Center of Neurology and Neurosurgery, University Hospital, Goethe-University Frankfurt, Germany; Center for Personalized Translational Epilepsy Research (CePTER), Goethe University, Frankfurt, Germany; Departments of Clinical Neurosciences, Medical Genetics and Community Health Sciences, Hotchkiss Brain Institute & Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address:

Purpose: Epilepsy surgery is an evidence-based treatment for drug-refractory focal epilepsy. We aimed to evaluate how well preoperative outcome estimates of epilepsy surgery in clinical practice correlated with postoperative outcome and to compare prediction by the clinical team with available scores (m-SFS, ESN).

Method: Retrospective cohort study including patients with drug-refractory focal epilepsy who underwent resective epilepsy surgery at Epilepsy Center Hessen, Marburg, between 1998-2016. Patients were categorized into four groups based on their estimated chance of postoperative seizure freedom documented in preoperative medical records. Variables required for calculation of m-SFS and ESN were also extracted from presurgical medical records. Seizure outcome using Engel/ILAE classifications was extracted from postoperative medical records.

Results: 148 patients were included and 98 had follow-up at 5 years. 69 (70%) had Engel I and 50 (51%) ILAE 1 outcome. Observed 5-year outcome for very good candidates was 20/22 (91%) Engel I and 14/22 (64%) ILAE 1, for good candidates 29/40 (73%) Engel I and 21/40 (53%) ILAE 1, for candidates with slightly reduced chance 11/18 (61%) Engel I and 9/18 (50%) ILAE 1 and for candidates with considerably reduced chance 1/5 (20%) Engel I and 1/5 (20%) ILAE 1.There were no significant differences in discrimination or overall performance between predictions by the clinical team, ESN and m-SFS.

Conclusions: Preoperative outcome estimates corresponded well with observed outcome indicating adequate patient counseling.
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http://dx.doi.org/10.1016/j.seizure.2020.01.016DOI Listing
February 2020

Factorial validity of a neuropsychological test battery and its ability to discern temporal lobe epilepsy from frontal lobe epilepsy - A retrospective study.

Seizure 2020 Jan 27;74:81-88. Epub 2019 Nov 27.

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, University Hospital Frankfurt and Goethe University, Frankfurt Am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe University, Frankfurt Am Main, Germany.

Purpose: Firstly, to evaluate the validity of a neuropsychological test battery in epilepsy patients, i.e. whether its tests sufficiently allow the assessment of the required cognitive domains in this specific group. Secondly, to examine its ability to differentiate between cognitive profiles of different subgroups of focal epilepsy.

Methods: The test battery suggested by the German ILAE Chapter was performed on 207 epilepsy patients, and its factor structure was investigated by principal component analysis (PCA). To further examine its accuracy in two matched subgroups of patients with temporal lobe epilepsy (TLE, n = 35) and frontal lobe epilepsy (FLE, n = 35), a discriminant function analysis (DFA) was used.

Results: PCA revealed eleven interpretable factors, accounting for 69.1% of total variance: Divided Attention, Reaction Time, Verbal Learning, Verbal Memory, Contextual Memory, Short-term- and Working Memory, Visuospatial Functioning, Space Perception, Verbal Fluency, Response Monitoring and Cognitive Flexibility. DFA identified six test to be most appropriate to discern TLE from FLE: WMS-IV Logical Memory, recognition; WMS-R Digit Span, backwards; VLMT, repetitions; VOSP Silhouettes; VLMT, delayed recall; and RWT Phonemic verbal fluency. Group membership was correctly predicted for 78.6% of patients using cross-validation.

Conclusions: As neuropsychological assessments are central in clinical decision-making in presurgical work-up of epilepsy patients, the appropriateness of the test battery in use is essential. The majority of cognitive domains are sufficiently measurable by the test battery and it is highly sensitive to differentiate between the cognitive profiles of TLE and FLE. However, the selection of tests assessing nonverbal memory functions requires further improvement.
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http://dx.doi.org/10.1016/j.seizure.2019.11.012DOI Listing
January 2020

Detection of cortical malformations using enhanced synthetic contrast images derived from quantitative T1 maps.

NMR Biomed 2020 02 3;33(2):e4203. Epub 2019 Dec 3.

Brain Imaging Center, Goethe University, Frankfurt am Main, Germany.

The detection of cortical malformations in conventional MR images can be challenging. Prominent examples are focal cortical dysplasias (FCD), the most common cause of drug-resistant focal epilepsy. The two main MRI hallmarks of cortical malformations are increased cortical thickness and blurring of the gray (GM) and white matter (WM) junction. The purpose of this study was to derive synthetic anatomies from quantitative T1 maps for the improved display of the above imaging characteristics in individual patients. On the basis of a T1 map, a mask comprising pixels with T1 values characteristic for GM is created from which the local cortical extent (CE) is determined. The local smoothness (SM) of the GM-WM junctions is derived from the T1 gradient. For display of cortical malformations, the resulting CE and SM maps serve to enhance local intensities in synthetic double inversion recovery (DIR) images calculated from the T1 map. The resulting CE- and/or SM-enhanced DIR images appear hyperintense at the site of cortical malformations, thus facilitating FCD detection in epilepsy patients. However, false positives may arise in areas with naturally elevated CE and/or SM, such as large GM structures and perivascular spaces. In summary, the proposed method facilitates the detection of cortical abnormalities such as cortical thickening and blurring of the GM-WM junction which are typical FCD markers. Still, subject motion artifacts, perivascular spaces, and large normal GM structures may also yield signal hyperintensity in the enhanced synthetic DIR images, requiring careful comparison with clinical MR images by an experienced neuroradiologist to exclude false positives.
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http://dx.doi.org/10.1002/nbm.4203DOI Listing
February 2020

Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study.

Ann Clin Transl Neurol 2019 12 4;6(12):2413-2425. Epub 2019 Nov 4.

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany.

Objective: We sought to evaluate the efficacy and tolerability of intranasal midazolam (in-MDZ) as first-line inhospital therapy in patients with status epilepticus (SE) during continuous EEG recording.

Methods: Data on medical history, etiology and semiology of SE, anticonvulsive medication usage, efficacy and safety of in-MDZ were retrospectively reviewed between 2015 and 2018. Time to end of SE regarding the administration of in-MDZ and ß-band effects were analyzed on EEG and with frequency analysis.

Results: In total, 42 patients (mean age: 52.7 ± 22.7 years; 23 females) were treated with a median dose of 5 mg of in-MDZ (range: 2.5-15 mg, mean: 6.4 mg, SD: 2.6) for SE. The majority of the patients suffered from nonconvulsive SE (n = 24; 55.8%). In total, 24 (57.1%) patients were responders, as SE stopped following the administration of in-MDZ without any other drugs being given. On average, SE ceased on EEG at 05:05 (minutes:seconds) after the application of in-MDZ (median: 04:56; range: 00:29-14:53; SD:03:13). Frequency analysis showed an increased ß-band on EEG after the application of in-MDZ at 04:07 on average (median: 03:50; range: 02:20-05:40; SD: 01:09). Adverse events were recorded in six patients (14.3%), with nasal irritations present in five (11.9%) and prolonged sedation occurring in one (2.6%) patient.

Conclusions: This pharmaco-EEG-based study showed that in-MDZ is effective and well-tolerated for the acute treatment of SE. EEG and clinical effects of in-MDZ administration occurred within 04:07 and 5:05 on average. Intranasal midazolam appears to be an easily applicable and rapidly effective alternative to buccal or intramuscular application as first-line treatment if an intravenous route is not available.
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http://dx.doi.org/10.1002/acn3.50932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6917318PMC
December 2019

Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.

Nat Commun 2019 10 29;10(1):4919. Epub 2019 Oct 29.

Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France.

Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
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http://dx.doi.org/10.1038/s41467-019-12763-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820781PMC
October 2019

Fractures in Parkinson's Disease: injury patterns, hospitalization, and therapeutic aspects.

Eur J Trauma Emerg Surg 2021 Apr 14;47(2):573-580. Epub 2019 Oct 14.

Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Goethe University Frankfurt, Frankfurt am Main, Germany.

Aim: The primary aim of this study was to analyze the frequency and characteristic patterns of fall-related fractures as well as consecutive hospitalization and management relating to such fractures. In addition, important pathognomonic and therapeutic aspects are discussed.

Methods: This retrospective mono-center study was conducted at the University Hospital Frankfurt am Main, Germany. Between 2007 and 2017, a total of 145 PD patients with fall-related fractures were identified via a retrospective systematic query in the hospital information system using the ICD-10 German modification codes G20.0-G20.9. Patients with unclear or falsely coded PD were strictly excluded.

Results: The mean age of the cohort was 77.7 years (± 7.5, median 77.) and 57.9% of the cohort were females (n = 84). A total number of 151 fractures were reported, with 140 patients (96.6%) suffering from one, four patients from two (2.8%), and one patient from three fractures (0.6%) at a time. For 43.9% (n = 65) of the cohort, fractures concerned lower extremities (LE) followed by trunk (38.1%, n = 58) and upper extremities (UE, 17.9%, n = 27). Most common fracture types in LE were femoral neck fractures (52.3%, n = 34). Mean length of hospital stay (LOS) was 13.6 days (95% CI 12.4-14.7). In 43.4% (n = 63) of cases, an interim admission to an intensive-care unit (ICU) was necessary. Mean ICU LOS was 2.3 days (95% CI 1.5-3.0), and mean LOS for normal care unit was 10.5 days (95% CI 10.3-12.4). Surgical treatment was necessary in 75.9% of the cases (n = 110). Patients undergoing surgical treatment showed significantly longer LOS compared to conservatively treated patients (p < 0.001). Moreover, fractures of the LE (p = 0.018) and UE (p = 0.010) were associated with a significant longer LOS.

Conclusion: Fall-related fractures are a common and relevant complication in PD patients leading to increased immobility, frequent hospitalization, and immediate surgical care. Fractures of the lower extremities and trunk were the most common in the cohort for this study. A PD patient presenting to the emergency room or at the general practitioner with a fracture should always be checked for osteoporosis and a fall-related injury should be seen as a red flag for reviewing a patient's individual therapeutic regime.
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http://dx.doi.org/10.1007/s00068-019-01240-zDOI Listing
April 2021

Drug-Resistant Juvenile Myoclonic Epilepsy: Misdiagnosis of Progressive Myoclonus Epilepsy.

Front Neurol 2019 10;10:946. Epub 2019 Sep 10.

Center for Personalized Translational Epilepsy Research (CePTER), Frankfurt am Main, Germany.

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criteria. 87/168 identified JME patients were seizure-free at last follow-up including 61 drug-responsive patients (group NDR). Seventy-eight patients were not seizure-free including 26 drug-resistant patients (group DR). Valproate was the most efficacious AED. The JME diagnosis was revised in 7 patients of group DR including 6 in whom the diagnosis had already been questioned or revised during clinical follow-up. One of these was finally diagnosed with PME (genetically confirmed Lafora disease) based on genetic testing. She was initially reviewed at age 29 yrs and considered to be inconsistent with PME. Intellectual disability ( = 0.025), cognitive impairment ( < 0.001), febrile seizures in first-degree relatives ( = 0.023) and prominent dialeptic seizures ( = 0.009) where significantly more frequent in group DR. Individuals with PME are rarely found among drug-resistant alleged JME patients in a tertiary epilepsy center. Even a very detailed review by experienced epileptologists may not identify the presence of PME before the typical features evolve underpinning the need for early genetic testing in drug-resistant JME patients.
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http://dx.doi.org/10.3389/fneur.2019.00946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746890PMC
September 2019

Does third trimester cervical length predict duration of first stage of labor?

Wien Klin Wochenschr 2019 Oct 16;131(19-20):468-474. Epub 2019 Jul 16.

Department of Obstetrics and Gynecology, Medical University of Graz, Auenbruggerplatz 14, 8036, Graz, Austria.

Objective: To examine the association between third trimester cervical length (CL) measurement and duration of the first stage of labor.

Methods: This prospective cohort study included women with a singleton pregnancy who had routine CL measurements taken by transvaginal ultrasonography between 37 and 39 weeks gestation. Subjective duration of the first stage of labor was defined as the duration of contractions that the women subjectively had from the onset of regular contractions to full effacement of the cervix. Objective duration of first stage of labor was defined as 3 cm cervical dilation independent of cervical effacement until full effacement of the cervix. Associations between variables were analyzed using nonparametric correlations coefficients. A model relating the duration of labor to predictors was built using linear regression.

Results: In this analysis a total of 129 women were included. There was no significant correlation between CL and subjective duration of labor (ρ = -0.037, p = 0.695); however, a reduction in CL increased the objective duration of the first stage of labor (ρ = -0.269, p = 0.013). In univariate analysis parity (p = 0.018), hypertensive disorders (p = 0.013) and induction of labor (p = 0.022) were significantly associated with subjective duration of the first stage of labor.

Conclusion: A long cervix in the third trimester is not associated with a prolonged first stage of labor. Induction of labor and multiparity were associated with a shorter first stage of labor while hypertension was associated with a longer duration of labor.
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http://dx.doi.org/10.1007/s00508-019-1527-0DOI Listing
October 2019

Seizure management and prescription patterns of anticonvulsants in Dravet syndrome: A multicenter cohort study from Germany and review of literature.

Epilepsy Behav 2019 09 10;98(Pt A):88-95. Epub 2019 Jul 10.

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany; Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany. Electronic address:

Objective: The aim of this study was to describe the treatment pattern of patients with Dravet syndrome (DS) in Germany with routine antiepileptic drugs (AEDs) and emergency medication, and to review the literature of real-world evidence on medicine utilization of patients with DS in Europe.

Methods: Patient use of routine AEDs and emergency medications over 3-6 months was analyzed from a 2018 multicenter survey of 93 caregivers of patients with DS throughout Germany. Results were contextualized in a review of real-world evidence on medicine utilization of patients with DS in Europe.

Results: The variety of medications and the most frequent combinations routinely used by patients with DS (AEDs and others) are described. Patients use a large number of pharmaceutical treatments to manage seizures. The five most commonly used AEDs were sodium valproate (66% of the patients; mean daily dose: 660 mg; 24.5 mg per kg bodyweight), bromide (44%; 1462 mg; 51.2 mg per kg), clobazam (41%; 10.4 mg; 0.32 mg per kg), stiripentol (35%; 797 mg; 27.6 mg per kg), and topiramate (24%; 107 mg; 3.5 mg per kg). Ninety percent had reported using emergency medications in the last 3 months;, with the most common medications being Buccolam (40%, an oromucosal form of midazolam) and diazepam (20%, mostly rectal application). No discernable relationships between current medication and age or seizure frequency were observed.

Significance: This is the first comprehensive report of routine AEDs and emergency medication use in a large sample of patients with DS in Germany over a period of 3-6 months and shows that despite the most common AED combinations being in line with clinical guidelines/best practice, there is no discernable impact of best treatment on seizure frequency. We find a higher use of bromide in Germany compared with other real-world evidence in Europe.
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http://dx.doi.org/10.1016/j.yebeh.2019.06.021DOI Listing
September 2019

Characteristics of bilateral versus unilateral temporal encephalocele-associated epilepsy.

Seizure 2019 Oct 29;71:13-19. Epub 2019 May 29.

Epilepsy Center Frankfurt Rhine Main and Department of Neurology, Goethe University Frankfurt, Frankfurt, Germany; LOEWE Center for Personalized Translational Research (CePTER), Goethe University Frankfurt, Frankfurt, Germany.

Purpose: To characterise bilateral temporal encephalocele (BTE)-associated epilepsy relative to unilateral temporal encephalocele (UTE)-associated epilepsy as a rare but curable cause of structural epilepsy using demographics, epilepsy status and imaging findings.

Method: In this single-centre retrospective study we included all patients from June 2015 to August 2018, who suffered from epilepsy and were diagnosed with a temporal encephalocele. Data were systematically collected and analysed for differences between BTE and UTE.

Results: Seventeen epilepsy patients diagnosed with temporal encephaloceles (TE) were identified. One-third exhibited BTE. The age of epilepsy onset was higher in patients with BTE compared to UTE (median 51 vs. 37 years, p = 0.074). Latency between epilepsy diagnosis and definitive TE diagnosis differed considerably with a median five-fold shorter duration for the BTE-group when compared to the UTE-group (2-10 years, p = 0.02). Five of seven (81%) patients with BTE were pharmacoresistant, while this applied to only five out of ten (50%) patients with a UTE.

Conclusion: When compared to UTE-associated epilepsy, BTE-associated epilepsy is characterised by a later age at onset, shorter delay in TE diagnosis and more frequent drug-resistance. As epilepsy surgery is a valid treatment option for both syndromes, a standardised diagnostic workup should be implemented for temporal lobe epilepsy (TLE) patients with unknown aetiology to facilitate early detection of UTE and BTE.
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http://dx.doi.org/10.1016/j.seizure.2019.05.022DOI Listing
October 2019

Statement by the OEGGG with Review of the Literature on the Mode of Delivery of Premature Infants at the Limit of Viability.

Geburtshilfe Frauenheilkd 2018 Dec 14;78(12):1212-1216. Epub 2018 Dec 14.

Universitätsklinik für Frauenheilkunde und Geburtshilfe, Medizinische Universität Graz, Graz, Austria.

In 2017, the Austrian Society for Paediatric and Adolescent Medicine (ÖGKJ) published a guideline on the primary care of premature infants at the limit of viability. In this guideline, it is recommended that a Caesarean section be preferred as mode of delivery with regard to an early preterm birth (22 + 0 - 24 + 6 weeks of pregnancy) due to an allegedly lower perinatal risk of cerebral haemorrhage. In contrast to this, the Austrian Society for Gynaecology and Obstetrics (OEGGG) considers there to be no clinical and scientific basis for this recommendation and the mode of delivery in the case of early preterm birth must be adapted to the individual maternal and foetal clinical situation. The international data available from the generally retrospective investigations show heterogeneous results regarding the mode of delivery. The prospective and randomised data in this regard are insufficient. A Cochrane analysis does not show any advantage in favour of a Caesarean delivery. The German-language guidelines (AWMF and Switzerland) make analogous recommendations for adapting the mode of delivery with regard to an early preterm birth individually to the respective clinical situation. In the case of an early preterm birth and a singleton in cephalic presentation, the OEGGG therefore recommends individual management of the delivery which takes the maternal and foetal clinical situation into account and also includes vaginal delivery as a mode of delivery in the clinical decision process.
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http://dx.doi.org/10.1055/a-0669-1480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294639PMC
December 2018

Efficacy, Retention, and Tolerability of Brivaracetam in Patients With Epileptic Encephalopathies: A Multicenter Cohort Study From Germany.

Front Neurol 2018 23;9:569. Epub 2018 Jul 23.

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe University Frankfurt, Frankfurt, Germany.

To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE). A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017. Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free ( = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% ( = 4; 9%) or 50% ( = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%. In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.
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http://dx.doi.org/10.3389/fneur.2018.00569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064736PMC
July 2018

Use of Emergency Medication in Adult Patients with Epilepsy: A Multicentre Cohort Study from Germany.

CNS Drugs 2018 08;32(8):771-781

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16, Haus 95, 60528, Frankfurt am Main, Germany.

Background: Emergency treatment with benzodiazepines is indicated in prolonged seizures, seizure clusters and status epilepticus.

Objective: The aim of this study was to evaluate the use of emergency medication in adult patients with epilepsy.

Patients And Methods: All adult epilepsy patients attending the epilepsy outpatient clinics of the university hospitals in Frankfurt and Marburg in 2015 were asked to participate in this questionnaire-based, retrospective survey.

Results: A total of 481 patients with a mean age of 43.4 years (range 18-94 years, 54% female) participated in the study. Among them, 134 patients (27.9%) reported on the prescription of an emergency medication during the last year. Patients receiving emergency medication were younger and exhibited a lower age at epilepsy onset, a higher seizure frequency and a higher number of regularly taken antiepileptic drugs. The most frequently taken emergency drugs were oral lorazepam tablets (65.7%; n = 88 out of 134), followed by buccal midazolam (23.9%, n = 32) and rectal diazepam (17.9%, n = 24). The most common indications for administering the emergency medication were seizures continuing for several minutes (35.1%, n = 47), but almost the same number of patients (33.6%, n = 45) stated that the rescue medication was given during or after every seizure. Regarding adverse events, sedation was named as a major (18.7%, n = 25) or moderate (29.1%; n = 39) problem by a substantial number of patients. Difficulties in administration were reported by 17 (13%) patients. Two-thirds assessed the efficacy of their emergency medication as good (50.7%, n = 68) or as very good (15.7%, n = 21). For multivariate logistic regression analysis, aspects such as young age at onset, active epilepsy, structural etiology, presence of generalised tonic-clonic seizures, past medical history of status epilepticus and living with another person independently predicted prescription of emergency medication.

Conclusions: In most cases, unsuitable benzodiazepines with slow absorption due to oral administration were prescribed, or buccal midazolam solution was used off-label in adults. Furthermore, inappropriate use of emergency medication at every seizure was reported by a substantial number of participating patients.
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http://dx.doi.org/10.1007/s40263-018-0544-2DOI Listing
August 2018

Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus.

Epilepsia 2018 08 25;59(8):1549-1556. Epub 2018 Jun 25.

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University, Frankfurt am Main, Germany.

Objective: The objective of this study was to evaluate effectiveness, retention, and tolerability of brivaracetam (BRV) in genetic generalized epilepsies (GGE) in clinical practice.

Methods: A multicenter, retrospective cohort study recruiting all patients that started BRV in 2016 and 2017.

Results: A total of 61 patients (mean age = 29.8, range = 9-90 years, 41 female [67%]) were treated with BRV. They were difficult to control, with 2.4 failed antiepileptic drugs (AEDs) in the past, taking 1.9 AEDs on average at baseline. The length of exposure to BRV ranged from 7 days to 24 months, with a mean retention time of 7.9 months, resulting in a total exposure time to BRV of 483 months. The retention rate was 82% at 3 months and 69% at 6 months. Efficacy at 3 months was 36% (50% responder rate), with 25% seizure-free for 3 months. Patients with juvenile myoclonic epilepsy showed a responder rate of 60%, with 40% being free of any seizures. Long-term 50% responder rate was present in 17 patients (28%; 11 seizure-free [18%]) for >6 months and in 14 patients (23%; 10 seizure-free [16%]) for >12 months. Treatment-emergent adverse events were observed in 26% of the patients, with the most common being somnolence, ataxia, and psychobehavioral adverse events. Use of intravenous BRV with bolus injection of 200-300 mg in two females with absence status epilepticus was well tolerated, but did not result in cessation of status epilepticus.

Significance: Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV-induced adverse events.
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http://dx.doi.org/10.1111/epi.14476DOI Listing
August 2018

The role of mTOR inhibitors in preventing epileptogenesis in patients with TSC: Current evidence and future perspectives.

Epilepsy Behav 2019 02 22;91:94-98. Epub 2018 Jun 22.

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University, Frankfurt am Main, Germany.

Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Mutations in the TSC1 or TSC2 genes lead to the dysregulation of the mechanistic target of rapamycin (mTOR) pathway. This mTOR pathway hyperactivation is associated with several processes resulting in epileptic conditions. The occurrence of seizures and their treatment outcomes seem to play a crucial role in cognitive and behavioral developments in patients with TSC. Mechanistic target of rapamycin inhibitors have been proven to be effective in epilepsy treatment in individuals with TSC. Specifically, because of their disease-modifying mechanism of action, they have the capability to prevent epileptogenesis in patients with TSC. This article will provide an overview of the current evidence of and delineate future perspectives for mTOR inhibitors and their role in preventing epileptogenesis.
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http://dx.doi.org/10.1016/j.yebeh.2018.05.039DOI Listing
February 2019

Invasive EEG-electrodes in presurgical evaluation of epilepsies: Systematic analysis of implantation-, video-EEG-monitoring- and explantation-related complications, and review of literature.

Epilepsy Behav 2019 02 13;91:30-37. Epub 2018 Jun 13.

Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe-University, Frankfurt am Main, Germany; LOEWE Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University, Frankfurt am Main, Germany.

Introduction: Stereoelectroencephalography (sEEG) is a diagnostic procedure for patients with refractory focal epilepsies that is performed to localize and define the epileptogenic zone. In contrast to grid electrodes, sEEG electrodes are implanted using minimal invasive operation techniques without large craniotomies. Previous studies provided good evidence that sEEG implantation is a safe and effective procedure; however, complications in asymptomatic patients after explantation may be underreported. The aim of this analysis was to systematically analyze clinical and imaging data following implantation and explantation.

Results: We analyzed 18 consecutive patients (mean age: 30.5 years, range: 12-46; 61% female) undergoing invasive presurgical video-EEG monitoring via sEEG electrodes (n = 167 implanted electrodes) over a period of 2.5 years with robot-assisted implantation. There were no neurological deficits reported after implantation or explantation in any of the enrolled patients. Postimplantation imaging showed a minimal subclinical subarachnoid hemorrhage in one patient and further workup revealed a previously unknown factor VII deficiency. No injuries or status epilepticus occurred during video-EEG monitoring. In one patient, a seizure-related asymptomatic cross break of two fixation screws was found and led to revision surgery. Unspecific symptoms like headaches or low-grade fever were present in 10 of 18 (56%) patients during the first days of video-EEG monitoring and were transient. Postexplantation imaging showed asymptomatic and small bleedings close to four electrodes (2.8%).

Conclusion: Overall, sEEG is a safe and well-tolerated procedure. Systematic imaging after implantation and explantation helps to identify clinically silent complications of sEEG. In the literature, complication rates of up to 4.4% in sEEG and in 49.9% of subdural EEG are reported; however, systematic imaging after explantation was not performed throughout the studies, which may have led to underreporting of associated complications.
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http://dx.doi.org/10.1016/j.yebeh.2018.05.012DOI Listing
February 2019

[Psychogenic non epileptic seizures : Differential diagnostic features].

Herzschrittmacherther Elektrophysiol 2018 Jun 14;29(2):155-160. Epub 2018 May 14.

Epilepsiezentrum Frankfurt Rhein-Main, Zentrum der Neurologie und Neurochirurgie, Universitätsklinikum Frankfurt, Schleusenweg 2-16, 60528, Frankfurt am Main, Deutschland.

Psychogenic nonepileptic seizures (PNES) are to be considered in the differential diagnosis of a transient loss of consciousness. Their discrimination from syncope, epileptic seizures or vascular events can be difficult and requires profound knowledge about the semiology and clinical presentation of PNES and their differential diagnoses. Erroneous diagnoses and the resulting therapies lead to elevated morbidity, elevated costs and a poorer outcome. The aim of the present article is to provide an overview on PNES and their delineation from the clinical pictures of epilepsy and syncope.
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http://dx.doi.org/10.1007/s00399-018-0557-zDOI Listing
June 2018

Noncompliance of patients with driving restrictions due to uncontrolled epilepsy.

Epilepsy Behav 2019 02 9;91:86-89. Epub 2018 May 9.

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University, Frankfurt am Main, Germany; Epilepsy Center Hessen and Department of Neurology, Philipps-University, Marburg, Germany.

Epilepsies are a common and chronic neurological disorder characterized by sustained risk of recurrent seizures. Because of paroxysmal and often unpredictable occurrence of seizures, patients with uncontrolled epilepsy are subject to disease-specific restrictions in daily life, such as their career choice or specific work limitations. According to German law and many other European and international guidelines, driving is strictly prohibited in patients with uncontrolled epilepsy so as to increase active and passive safety in public road traffic. Nevertheless, a significant percentage of patients probably do not comply with these legal restrictions and drive on a regular basis. For this study, we analyzed a representative German cohort with 302 patients (mean age: 45.0 years ± 16.4; 48% male) with established epilepsy to identify the number of patients driving without permission. Overall, 58.6% (n = 177) of patients had a driving license, 71.1% (n = 69/97) of patients were in seizure remission, and 52.7% (n = 108/205) of patients had uncontrolled epilepsy. Among patients in seizure remission, 54.6% (n = 53/97) reported regular driving while, among patients with uncontrolled epilepsy, 15.1% (n = 31/205) reported driving on a regular basis. No patient in the cohort stated driving without a valid license. Permanent employment, freelance work, the absence of a relevant disability, and living alone were identified as significant risk factors, which underlines the already existing evidence for the importance of a possible restricted access to the labor market as motive for disregarding legal driving restrictions. In our opinion, specialized and generally available social counseling with a special focus on vocational and career guidance is urgently needed to improve compliance with epilepsy-caused driving restrictions and the underlying reasons for violating these rules. In addition, more effort has to be spent on improving diagnostics and treatment of epilepsy to reduce the number of patients with uncontrolled seizures. Comprehensive introduction of self-driving vehicles may also help to improve mobility of patients with refractory epilepsy.
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http://dx.doi.org/10.1016/j.yebeh.2018.04.008DOI Listing
February 2019

Prenatal acupuncture: Women's expectations and satisfaction and influence on labor.

Birth 2018 06 1;45(2):210-216. Epub 2018 Feb 1.

Department of Obstetrics and Gynecology, Medical University of Graz, Graz, Austria.

Background: Use of prenatal acupuncture for labor preparation is common, but there is still conflicting evidence with respect to its objective obstetric benefits. There is little information on women's expectations and subjective experiences with acupuncture treatments.

Methods: In this retrospective cohort study, a validated questionnaire on women's treatment satisfaction was sent to women who had received prenatal acupuncture at the obstetric clinic of the Medical University of Graz, Austria within the last 3 years. The electronic obstetric database was used to extract detailed clinical and obstetric data of women who received acupuncture and delivered at the hospital. For comparison, obstetric data were matched with a control group of women without prenatal acupuncture, who had given birth at the hospital during the study period.

Results: The questionnaire was sent to 150 women, out of which 70 (46.7%) completed and returned the questionnaire. Analysis of the questionnaire indicated good overall satisfaction (mean sum score 26.22 ± 4.72) with acupuncture treatment-97.1% indicated that they were very or quite satisfied. Responders did not differ from nonresponders, except for the time between delivery and questionnaire (P = .015). Comparisons between the deliveries after prenatal acupuncture (n = 144) and the matched control deliveries (n = 576) showed no statistical significant differences in the length of labor and use of analgesics.

Conclusion: Prenatal acupuncture is likely to have positive effects on pregnant women, aside from an objective influence on labor duration and pain.
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http://dx.doi.org/10.1111/birt.12336DOI Listing
June 2018

Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches.

Epilepsy Behav 2017 11 13;76:13-18. Epub 2017 Sep 13.

Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt, Germany; Center for Personalized Translational Epilepsy Research (CePTER), 60528 Frankfurt, Germany(1).

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1].
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http://dx.doi.org/10.1016/j.yebeh.2017.06.041DOI Listing
November 2017

Personalized translational epilepsy research - Novel approaches and future perspectives: Part II: Experimental and translational approaches.

Epilepsy Behav 2017 11 14;76:7-12. Epub 2017 Sep 14.

Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt, Germany; Center for Personalized Translational Epilepsy Research (CePTER), 60528 Frankfurt, Germany(1).

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1].
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http://dx.doi.org/10.1016/j.yebeh.2017.06.040DOI Listing
November 2017