Publications by authors named "Aurelia Peraud"

38 Publications

Lamina cribrosa perforation during nasotracheal intubation in neonates: case series and review of the literature.

Clin Case Rep 2021 Sep 30;9(9):e04650. Epub 2021 Aug 30.

Division of Neonatology University Children's Hospital Dr. v. Hauner and Perinatal Center LMU Medical Hospital Munich Germany.

Intracranial penetration during attempted nasotracheal intubation is a potentially devastating complication, which should be carefully evaluated and the risk should be addressed in neonatal resuscitation trainings.
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http://dx.doi.org/10.1002/ccr3.4650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405422PMC
September 2021

Congruence and Discrepancy of Interictal and Ictal EEG With MRI Lesions in Pediatric Epilepsies.

Clin EEG Neurosci 2020 Nov 18;51(6):412-419. Epub 2020 May 18.

Ludwig Maximilians University (LMU) Munich, Epilepsy Center, Munich, Germany.

. To evaluate the congruence or discrepancy of the localization of magnetic resonance imaging (MRI) lesions with interictal epileptiform discharges (IEDs) or epileptic seizure patterns (ESPs) in surface EEG in lesional pediatric epilepsy patients. . We retrospectively analyzed presurgical MRI and video-EEG monitoring findings of patients up to age 18 years. Localization of MRI lesions were compared with ictal and interictal noninvasive EEG findings of patients with frontal, temporal, parietal, or occipital lesions. . A total of 71 patients were included. Localization of ESPs showed better congruence with MRI in patients with frontal lesions (n = 21, 77.5%) than in patients with temporal lesions (n = 24; 40.7%) ( = .009). No significant IED distribution differences between MRI localizations could be found. . MRI lesions and EEG findings are rarely fully congruent. Congruence of MRI lesions and ESPs was highest in children with frontal lesions. This is in contrast to adults, in whom temporal lesions showed the highest congruency with the EEG localization of ESP. Lesional pediatric patients should be acknowledged as surgical candidates despite incongruent findings of interictal and ictal surface EEG.
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http://dx.doi.org/10.1177/1550059420921712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457449PMC
November 2020

Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons.

Neurosurg Focus 2020 03;48(3):E13

1Meditech Foundation, Cali, Colombia.

Objective: Traumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons' training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons' careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world.

Methods: A committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation.

Results: The content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale.

Conclusions: An international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.
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http://dx.doi.org/10.3171/2019.12.FOCUS19850DOI Listing
March 2020

Compare and contrast: pediatric cancer versus adult malignancies.

Cancer Metastasis Rev 2019 12;38(4):673-682

Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Eythstrasse 24, 89075, Ulm, Germany.

Cancer is a leading cause of death in both adults and children, but in terms of absolute numbers, pediatric cancer is a relatively rare disease. The rarity of pediatric cancer is consistent with our current understanding of how adult malignancies form, emphasizing the view of cancer as a genetic disease caused by the accumulation and selection of unrepaired mutations over time. However, considering those children who develop cancer merely as stochastically "unlucky" does not fully explain the underlying aetiology, which is distinct from that observed in adults. Here, we discuss the differences in cancer genetics, distribution, and microenvironment between adult and pediatric cancers and argue that pediatric tumours need to be seen as a distinct subset with their own distinct therapeutic challenges. While in adults, the benefit of any treatment should outweigh mostly short-term complications, potential long-term effects have a much stronger impact in children. In addition, clinical trials must cope with low participant numbers when evaluating novel treatment strategies, which need to address the specific requirements of children.
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http://dx.doi.org/10.1007/s10555-019-09836-yDOI Listing
December 2019

Childhood haemorrhagic stroke: a 7-year single-centre experience.

Arch Dis Child 2019 12 20;104(12):1198-1202. Epub 2019 Jun 20.

University College London, Institute of Child Health, Clinical Neuroscience Section, London, UK.

Background: In recent years, there has been increasing research interest in improving diagnostic and management protocols in childhood arterial ischaemic stroke (AIS). However, childhood stroke comprises, in approximately equal parts, both arterial ischaemic and haemorrhagic stroke (HS).

Objective: The aim of this study was to focus on the aetiology, clinical presentation, treatment and short-term outcome of children with spontaneous intracranial bleeding in a university hospital and elucidate differences to childhood AIS.

Design: We performed a retrospective analysis of electronic medical records of children (28 days-18 years) diagnosed with HS between 2010 and 2016.

Results: We included 25 children (male child, n=11) with a median age of 8 years 1 month. The most common clinical presentations were vomiting (48%), headache (40%) and altered level of consciousness (32%). In more than half of the patients, HS was caused by vascular malformations. Other risk factors were brain tumour, coagulopathy and miscellaneous severe underlying diseases. Aetiology remained unclear in one child. Therapy was neurosurgical in most children (68%). Two patients died, 5 patients needed further (rehabilitation) treatment and 18 children could be discharged home.

Conclusions: HS differs from AIS in aetiology (vascular malformations as number one risk factor), number of risk factors ('mono-risk' disease), clinical presentation (vomiting, headache and altered level of consciousness) and (emergency) therapy.
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http://dx.doi.org/10.1136/archdischild-2018-316749DOI Listing
December 2019

Accuracy of oscillometric noninvasive blood pressure compared with intra-arterial blood pressure in infants and small children during neurosurgical procedures: An observational study.

Eur J Anaesthesiol 2019 06;36(6):400-405

From the Department of Anaesthesiology (ASM, MT, TKH, PB, JB), the Department of Neurosurgery, University Hospital of Munich (LMU), Munich, Germany (AP), and the Department of Neurosurgery, University Hospital Ulmm, Ulm, Germany (AP).

Background: General anaesthesia in children results in a significant decrease of arterial pressure. Hypotension in neonates and infants reduces cerebral perfusion; therefore, an accurate arterial pressure measurement is of utmost importance. Although arterial pressure measured via an arterial catheter is considered to be the gold standard, in most children undergoing anaesthesia, arterial pressure is monitored by an upper arm cuff using an oscillometric technique. Data on the accuracy of these devices in such young patients are rare.

Objective: The aim of this study was to assess the accuracy of oscillometric blood pressure measurement compared with intra-arterial measurement.

Design: An observational comparison study.

Setting: A single-centre study, conducted in a German university hospital from November 2015 to January 2018.

Patients: Twenty-five children of 2 years old or less (median age 6 [IQR, 5 to 11]) months undergoing neurosurgical procedures requiring invasive arterial pressure determination.

Main Outcome Measures: Arterial pressure was measured invasively and also oscillometrically by an upper arm cuff every 10 min. Simultaneously measured pairs of mean arterial pressures were analysed by the Bland-Altman method; the correlation coefficient, percentage error and concordance were calculated.

Results: Data from 21 children were analysed. Mean, (standard deviation) and [range] of invasive and noninvasive mean arterial pressures were 54 (8) [30 to 94] and 57 (8) [40 to 108] mmHg, respectively. The overall bias between invasive and noninvasive arterial pressure was -3 (7) mmHg, with 95% limits of agreement from -17 to +10 mmHg. The correlation coefficient, percentage error and concordance were 0.65, 25% and 0.77, respectively. For hypotensive invasive arterial pressure values below 45 mmHg, the mean bias (invasive arterial pressure - noninvasive arterial pressure) was -9 (5) mmHg.

Conclusion: Arterial pressure derived by the oscillometric device showed acceptable levels of agreement. However, during hypotension, a clinically relevant overestimation of arterial pressure occurred when measured by an upper arm cuff.
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http://dx.doi.org/10.1097/EJA.0000000000000984DOI Listing
June 2019

Epilepsy surgery in the first months of life: a large type IIb focal cortical dysplasia causing neonatal drug-resistant epilepsy.

Epileptic Disord 2019 Feb;21(1):122-127

Department of Neurosurgery, Section for Pediatric Neurosurgery, University of Ulm, Germany.

Focal cortical dysplasia is a common cause of medically refractory epilepsy in infancy and childhood. We report a neonate with seizures occurring within the first day of life. Continuous video-EEG monitoring led to detection of left motor seizures and a right frontal EEG seizure pattern. Brain MRI revealed a lesion within the right frontal lobe without contrast enhancement. The patient was referred for epilepsy surgery due to drug resistance to vitamin B6 and four antiepileptic drugs. Lesionectomy was performed at the age of two and a half months, and histopathological evaluation confirmed the diagnosis of focal cortical dysplasia type IIb (FCD IIb). The patient is free of unprovoked seizures without medication (Engel Class I) and is normally developed at 36 months after surgery. The case study demonstrates that FCD IIb may cause seizures within the first day of life and that epilepsy surgery can be successfully performed in medically intractable patients with a clearly identifiable seizure onset zone within the first three months of life. Although radical surgery such as hemispherectomy and multi-lobar resections are over-represented in early infancy, this case also illustrates a favourable outcome with a more limited resection in this age group.
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http://dx.doi.org/10.1684/epd.2019.1037DOI Listing
February 2019

Outcome after individualized stereoelectroencephalography (sEEG) implantation and navigated resection in patients with lesional and non-lesional focal epilepsy.

J Neurol 2019 Apr 30;266(4):910-920. Epub 2019 Jan 30.

Department of Neurosurgery, University Hospital of Munich, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany.

Background: Refined localization of the epileptogenic zone (EZ) in patients with pharmacoresistant focal epilepsy proceeding to resective surgery might improve postoperative outcome. We here report seizure outcome after stereo EEG (sEEG) evaluation with individually planned stereotactically implanted depth electrodes and subsequent tailored resection.

Methods: A cohort of consecutive patients with pharmacoresistant focal epilepsy, evaluated with a non-invasive evaluation protocol and invasive monitoring with personalized, stereotactically implanted depth electrodes for sEEG was analyzed. Co-registration of post-implantation CT scan to presurgical MRI data was used for 3D reconstructions of the patients' brain surface and mapping of neurophysiology data. Individual multimodal 3D maps of the EZ were used to guide subsequent tailored resections. The outcome was rated according to the Engel classification.

Results: Out of 914 patients who underwent non-invasive presurgical evaluation, 85 underwent sEEG, and 70 were included in the outcome analysis. Median follow-up was 31.5 months. Seizure-free outcome (Engel class I A-C, ILAE class 1-2) was achieved in 83% of the study cohort. Patients exhibiting lesional and non-lesional (n = 42, 86% vs. n = 28, 79%), temporal and extratemporal (n = 45, 80% vs. n = 25, 84%), and right- and left-hemispheric epilepsy (n = 44, 82% vs. n = 26, 85%) did similarly well. This remains also true for those with an EZ adjacent to or distant from eloquent cortex (n = 21, 86% vs. n = 49, 82%). Surgical outcome was independent of resected tissue volume.

Conclusion: Favourable post-surgical outcome can be achieved in patients with resistant focal epilepsy, using individualized sEEG evaluation and tailored navigated resection, even in patients with non-lesional or extratemporal focal epilepsy.
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http://dx.doi.org/10.1007/s00415-019-09213-3DOI Listing
April 2019

Multimodal Imaging in Extratemporal Epilepsy Surgery.

Cureus 2018 Mar 18;10(3):e2338. Epub 2018 Mar 18.

Epilepsy Center, Dept. of Neurology, University of Munich Hospital, Ludwig-Maximilians-University Munich.

Neuroimaging is crucial for the evaluation of patients considered for resective epilepsy surgery. Multimodal image fusion is a new tool to integrate all available localizing information on the individual epileptogenic network in a three-dimensional (3D) manner to plan invasive EEG recordings and delineate the epileptogenic zone from the eloquent cortex for the neurosurgical planning of a tailored resection. Here, we illustrate the multimodal fusion of images from different modalities in a patient with medically intractable non-lesional frontal lobe epilepsy who underwent partial frontal lobe resection, rendering him seizure-free.
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http://dx.doi.org/10.7759/cureus.2338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959727PMC
March 2018

Decompression in Chiari Malformation: Clinical, Ocular Motor, Cerebellar, and Vestibular Outcome.

Front Neurol 2017 22;8:292. Epub 2017 Jun 22.

Department of Neurosurgery, University Hospital Munich, Munich, Germany.

Background: Treatment of Chiari malformation can include suboccipital decompression with resection of one cerebellar tonsil. Its effects on ocular motor and cerebellar function have not yet been systematically examined.

Objective: To investigate whether decompression, including resection of one cerebellar tonsil, leads to ocular motor, vestibular, or cerebellar deficits.

Patients And Methods: Ten patients with Chiari malformation type 1 were systematically examined before and after (1 week and 3 months) suboccipital decompression with unilateral tonsillectomy. The work-up included a neurological and neuro-ophthalmological examination, vestibular function, posturography, and subjective scales. Cerebellar function was evaluated by ataxia rating scales.

Results: Decompression led to a major subjective improvement 3 months after surgery, especially regarding headache (5/5 patients), hyp-/dysesthesia (5/5 patients), ataxia of the upper limbs (4/5 patients), and paresis of the triceps and interosseal muscles (2/2 patients). Ocular motor disturbances before decompression were detected in 50% of the patients. These symptoms improved after surgery, but five patients had new persisting mild ocular motor deficits 3 months after decompression with unilateral tonsillectomy (i.e., smooth pursuit deficits, horizontally gaze-evoked nystagmus, rebound, and downbeat nystagmus) without any subjective complaints. Impaired vestibular (horizontal canal, saccular, and utricular) function improved in five of seven patients with impaired function before surgery. Posturographic measurements after surgery did not change significantly.

Conclusion: Decompression, including resection of one cerebellar tonsil, leads to an effective relief of patients' preoperative complaints. It is a safe procedure when performed with the help of intraoperative electrophysiological monitoring, although mild ocular motor dysfunctions were seen in half of the patients, which were fortunately asymptomatic.
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http://dx.doi.org/10.3389/fneur.2017.00292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479925PMC
June 2017

Lateralization of cortical negative motor areas.

Clin Neurophysiol 2016 10 10;127(10):3314-21. Epub 2016 Aug 10.

Epilepsy Center, Department of Neurology, University of Munich, Germany. Electronic address:

Objective: The lateral and mesial aspects of the central and frontal cortex were studied by direct electrical stimulation of the cortex in epilepsy surgery candidates in order to determine the localization of unilateral and bilateral negative motor responses.

Methods: Results of electrical cortical stimulation were examined in epilepsy surgery candidates in whom invasive electrodes were implanted. The exact localization of subdural electrodes was defined by fusion of 3-dimensional reconstructed MRI and CT images in 13 patients and by analysis of plane skull X-rays and intraoperative visual localization of the electrodes in another 7 patients.

Results: Results of electrical stimulation of the cortex were evaluated in a total of 128 patients in whom invasive electrodes were implanted for planning resective epilepsy surgery. Twenty patients, in whom negative motor responses were obtained, were included in the study. Bilateral upper limb negative motor responses were more often elicited from stimulation of the mesial frontal cortex whereas stimulation of the lateral central cortex leads to contralateral upper limb negative motor responses (p<0.0001). Bilateral negative motor responses were exclusively found in the superior frontal gyrus whereas contralateral negative motor responses localized predominantly in the anterior part of the precentral gyrus (p<0.0001).

Conclusions: Exact localization using 3-D fusion methods revealed that negative motor areas are widely distributed throughout the precentral gyrus and the mesial fronto-central cortex showing functional differences with regard to unilateral and bilateral upper limb representation.

Significance: The lateral fronto-central negative motor area serves predominantly contralateral upper limb motor control whereas the mesial frontal negative motor area represents bilateral upper limb movement control.
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http://dx.doi.org/10.1016/j.clinph.2016.08.001DOI Listing
October 2016

Falsely low values of oxygen saturation measured by pulse oximetry in a boy treated with Chinese herb tea.

J Clin Monit Comput 2017 Apr 25;31(2):481-484. Epub 2016 Mar 25.

Department of Anaesthesiology, Klinikum der Universität München, Marchioninistraße 15, 81377, Munich, Germany.

An 8-year-old boy suffering from progressive glioblastoma was scheduled for neurosurgery. Prior to induction of anaesthesia pulse oximetry measured 64 % saturation of oxygen (SpO). Arterial blood gas analysis revealed normal oxygen saturation and normal oxygen partial pressure. After having ruled out technical problems of pulse oximetry the neurosurgical procedure was halted. Meticulous examination of the child's history and medication did not explain a possible interaction of drugs with pulse oximetry. A Chinese herb tea had been given to the child, but was then stopped on the day of admission. The surgical procedure took place the next day without any complications. During the subsequent inpatient stay, repeated blood gas analyses showed normal oxygenation, but pulse oximetry measured initially SpO values of 64 %, gradually increasing over 7 days up to 91 % by the time of discharge from hospital. Blood samples were taken and analysed. Absorption spectroscopy from the patient's blood showed an uncommon absorption maximum at 684 nm besides the normal maxima. The normalisation of SpO values after stopping Chinese herb tea administration leads to the conclusion that one of its ingredients caused the distorted pulse oximetry measurement.
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http://dx.doi.org/10.1007/s10877-016-9865-1DOI Listing
April 2017

Walking assessment after lumbar puncture in normal-pressure hydrocephalus: a delayed improvement over 3 days.

J Neurosurg 2017 Jan 18;126(1):148-157. Epub 2016 Mar 18.

German Center for Vertigo and Balance Disorders.

OBJECTIVE The determination of gait improvement after lumbar puncture (LP) in idiopathic normal-pressure hydrocephalus (iNPH) is crucial, but the best time for such an assessment is unclear. The authors determined the time course of improvement in walking after LP for single-task and dual-task walking in iNPH. METHODS In patients with iNPH, sequential recordings of gait velocity were obtained prior to LP (time point [TP]0), 1-8 hours after LP (TP1), 24 hours after LP (TP2), 48 hours after LP (TP3), and 72 hours after LP (TP4). Gait analysis was performed using a pressure-sensitive carpet (GAITRite) under 4 conditions: walking at preferred velocity (STPS), walking at maximal velocity (STMS), walking while performing serial 7 subtractions (dual-task walking with serial 7 [DTS7]), and walking while performing verbal fluency tasks (dual-task walking with verbal fluency [DTVF]). RESULTS Twenty-four patients with a mean age of 76.1 ± 7.8 years were included in this study. Objective responder status moderately coincided with the self-estimation of the patients with subjective high false-positive results (83%). The extent of improvement was greater for single-task walking than for dual-task walking (p < 0.05). Significant increases in walking speed were found at TP2 for STPS (p = 0.042) and DTVF (p = 0.046) and at TP3 for STPS (p = 0.035), DTS7 (p = 0.042), and DTVF (p = 0.044). Enlargement of the ventricles (Evans Index) positively correlated with early improvement. Gait improvement at TP3 correlated with the shunt response in 18 patients. CONCLUSIONS Quantitative gait assessment in iNPH is important due to the poor self-evaluation of the patients. The maximal increase in gait velocity can be observed 24-48 hours after the LP. This time point is also best to predict the response to shunting. For dual-task paradigms, maximal improvement appears to occur later (48 to 72 hours). Assessment of gait should be performed at Day 2 or 3 after LP.
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http://dx.doi.org/10.3171/2015.12.JNS151663DOI Listing
January 2017

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

Cancer Med 2016 Mar 29;5(3):442-53. Epub 2015 Dec 29.

Department of Neurosurgery, Ludwig-Maximilians-University, Munich, Germany.

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen. Temporary Iodine-125 seeds were used (median reference dose: 54 Gy). Treatment response was estimated with the modified MacDonald criteria. Analysis of functional outcome included ophthalmological, endocrinological and neurological evaluation. Survival was analyzed with the Kaplan-Meier method. Prognostic factors were obtained from proportional hazards models. Toxicity was categorized according to the Common Terminology Criteria for Adverse Events. Fifty-eight patients were included treated either with SBT alone (n = 39) or with SBT plus microsurgery (n = 19). Five-year progression-free survival was 87%. Two patients had died due to tumor progression. Among survivors, improvement/stabilization/deterioration of functional deficits was seen in 20/14/5 patients, respectively. Complete/partial response had beneficial impact on functional scores (P = 0.02). The 5-year estimated risk to receive adjuvant radiotherapy/chemotherapy was 5.2%. The overall early (delayed) toxicity rate was 8.6% (10.3%), respectively. No permanent morbidity occurred. In complex located PLGGs, early SBT alone or combined with best safe resection preserves/improves functional scores and results in tumor control rates usually achieved with complete resection. Long-term analysis is necessary for confirmation of these results.
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http://dx.doi.org/10.1002/cam4.605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799958PMC
March 2016

Intraoperative electrical stimulation of the cortex reveals the speech area missed by extraoperative stimulation because of epicortical hematoma.

Acta Neurochir (Wien) 2015 Sep 31;157(9):1585-6. Epub 2015 Jul 31.

Epilepsy Center, Department of Neurology, University of Munich, Marchioninistr.15, 81337, Munich, Germany.

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http://dx.doi.org/10.1007/s00701-015-2517-2DOI Listing
September 2015

Anomia produced by direct cortical stimulation of the pre-supplementary motor area in a patient undergoing preoperative language mapping.

Epileptic Disord 2015 Jun;17(2):184-7

Department of Neurology, Germany.

There is sparse data on the analysis of supplementary motor area in language function using direct cortical stimulation of the supplementary motor area. Here, we report a patient who experienced isolated anomia during stimulation of the anterior supplementary motor area and discuss the role of the supplementary motor area in speech production. The role of the pre-supplementary motor· area in word selection, observed in fMRI studies, can be confirmed by direct cortical stimulation.
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http://dx.doi.org/10.1684/epd.2015.0750DOI Listing
June 2015

The underestimated complication rate of decompressive craniectomy in pediatric traumatic brain injury.

Authors:
Aurelia Peraud

Neuropediatrics 2015 Feb 24;46(1):3-4. Epub 2014 Oct 24.

Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.

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http://dx.doi.org/10.1055/s-0034-1389899DOI Listing
February 2015

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

Acta Neurochir (Wien) 2014 Dec 24;156(12):2315-24. Epub 2014 Sep 24.

Department of Neurosurgery, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany,

Background: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Methods: Information on patient characteristics, MRI characteristics of tumors, histology, fluorescence qualities, and outcomes were requested. Surgeons were further asked to indicate whether fluorescence was "useful", i.e., leading to changes in surgical strategy or identification of residual tumor. Recursive partitioning analysis (RPA) was used for defining cohorts with high or low likelihoods for useful fluorescence.

Results: Data on 78 patients <18 years of age were submitted by 20 centers. Fluorescence was found useful in 12 of 14 glioblastomas (85 %), four of five anaplastic astrocytomas (60 %), and eight of ten ependymomas grades II and III (80 %). Fluorescence was found inconsistently useful in PNETs (three of seven; 43 %), gangliogliomas (two of five; 40 %), medulloblastomas (two of eight, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.1 %).

Conclusions: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study.
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http://dx.doi.org/10.1007/s00701-014-2234-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232748PMC
December 2014

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

Neuropediatrics 2014 Oct 4;45(5):294-308. Epub 2014 Sep 4.

KBO Children's Centre, Munich, Germany.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.
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http://dx.doi.org/10.1055/s-0034-1387818DOI Listing
October 2014

Neurodevelopmental and esthetic results in children after surgical correction of metopic suture synostosis: a single institutional experience.

Childs Nerv Syst 2014 Jun 13;30(6):1075-82. Epub 2013 Dec 13.

Department of Neurosurgery, Klinikum Großhadern, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377, Munich, Germany.

Introduction: Metopic suture synostosis leading to trigonocephaly is considered the second most frequent type of craniosynostosis. Besides esthetic results, we present 25 consecutive pediatric cases operated upon metopic suture synostosis with a focus on the child's motor, speech, and neurocognitive development.

Methods: Twenty-five children (aged 6 to 33 months; median 9.2 months) with trigonocephaly were operated upon between 2002 and 2012 with fronto-orbital advancement including frontal bone cranioplasty and fronto-orbital bandeau remodeling. Neurodevelopmental deficits were evaluated by a standardized questionnaire including gross motor function, manual coordination, speech, and cognitive function performed by independent pediatric/developmental neurologists before surgery and at 6 and 12 months of time interval postoperatively.

Results: Twenty-one (84 %) boys and four (16 %) girls were included in this study. Mean follow-up period was 33 ± 28 months. Outcome analysis for esthetic results showed a high degree of satisfaction by the parents and treating physicians in 23 cases (92 %). Preoperative evaluation revealed neurodevelopmental deficits in 10 children (40 %; six mild, four moderate degree). Twelve children (48 %) were proven to have a normal preoperative neuropediatric development. Mild or moderate developmental restraints were no longer apparent in 6/13, improved but still apparent in 3/13, and stable in 4/13, 6 months after cranial vault reconstruction. At 12 months of follow-up, deficits were no longer present in 9/13 and improved in 4/13. Apart from this cohort, two children were diagnosed with a syndromic form, and one child had a fetal valproate syndrome. In these three children, neurodevelopmental deficits were more pronounced. Neurocognitive progress was obvious, but was comparably slower, and major deficits were still apparent at last follow-up. All children with proven mild/moderate/severe deficits received intensive physiotherapy, logopedic, or neurobehavioral support.

Conclusions: As shown in a single-center observation, surgical correction of metopic suture synostosis not only refines esthetic appearance but also might improve neurodevelopmental outcome if deficits are apparent, even in syndromic forms of the deformity under additional physiotherapy, logopedic, or neurobehavioral support.
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http://dx.doi.org/10.1007/s00381-013-2340-0DOI Listing
June 2014

Dynamic regulation of P-glycoprotein in human brain capillaries.

Mol Pharm 2013 Sep 7;10(9):3333-41. Epub 2013 Aug 7.

Institute of Pharmacology, Toxicology, and Pharmacy, Ludwig-Maximilians-University , 80539 Munich, Germany.

Considering its role as a major blood-brain barrier gatekeeper, the dynamic regulation of the efflux transporter P-glycoprotein is of considerable functional relevance. In particular, disease-associated alterations in transport function might affect central nervous system drug efficacy. Thus, targeting regulatory signaling cascades might render a basis for novel therapeutic approaches. Using capillaries freshly prepared from patient tissue resected during epilepsy surgery, we demonstrate dynamic regulation of P-glycoprotein in human brain capillaries. Glutamate proved to up-regulate P-glycoprotein efflux transport in a significant manner via endothelial NMDA receptors. Both inhibition of cyclooxygenase-2 and antagonism at the glycine-binding site of the NMDA receptor prevented the glutamate-mediated induction of P-glycoprotein transport function in human capillaries. In conclusion, the data argue against species differences in the signaling factors increasing endothelial P-glycoprotein transport function in response to glutamate exposure. Targeting of cyclooxygenase-2 and of the NMDA receptor glycine-binding site was confirmed as an efficacious approach to control P-glycoprotein function. The findings might render a basis for translational development of add-on approaches to improve brain penetration and efficacy of drugs.
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http://dx.doi.org/10.1021/mp4001102DOI Listing
September 2013

Magnetic resonance-based estimation of intracranial pressure correlates with ventriculoperitoneal shunt valve opening pressure setting in children with hydrocephalus.

Invest Radiol 2013 Jul;48(7):543-7

Institute for Clinical Radiology, University of Munich, Germany.

Objectives: The aim of this study was to investigate the relationship between the pressure setting of the ventriculoperitoneal (VP) shunt valve and a magnetic resonance (MR)-based estimate of intracranial pressure (ICP) in children with shunt-treated hydrocephalus without clinical signs of shunt malfunction.

Materials And Methods: Institutional review board approval was obtained before the study, and all subjects and/or their legal guardians provided written informed consent. In this prospective study, 15 consecutive patients (median age, 8.25 years; range, 2.2-18.4 years; 6 girls and 9 boys) with shunt-treated hydrocephalus without signs of shunt malfunction were examined with retrospectively gated phase contrast sequences to quantify arterial inflow, venous outflow, and cerebrospinal fluid (CSF) flow to and from the cranial vault. The ratio of the maximal intracranial volume change and the pulse pressure gradient change was used to derive MR-ICP. Spearman ρ was used to test for the association of setting of the shunt valve opening pressure and MR-ICP.

Results: Shunt valve opening pressure settings and MR-ICP were positively correlated (Spearman ρ = 0.64, P < 0.01). Median MR-ICP was 8.67 mm Hg (interquartile range [IQR], 1.59 mm Hg) and median setting of the VP-shunt valve was 6.62 mm Hg (IQR, 1.47 mm Hg). The median MR-ICP was 1.9 mm Hg (IQR, 0.73 mm Hg) higher than the setting of the shunt valve.

Conclusion: There is a positive correlation between MR-ICP and VP shunt valve opening pressure setting. The systematically higher assessment of MR-ICP is most likely a result of outflow resistance within the shunt tubing system and well within the known fluctuation rates of VP shunt systems.
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http://dx.doi.org/10.1097/RLI.0b013e31828ad504DOI Listing
July 2013

Microsurgical outlet restoration in isolated fourth ventricular hydrocephalus: a single-institutional experience.

Childs Nerv Syst 2012 Dec 16;28(12):2101-7. Epub 2012 Aug 16.

Department of Neurosurgery, Klinikum Großhadern, Marchioninistrasse 15, 81377 Munich, Germany.

Purpose: Isolated fourth ventricles as a consequence of shunted posthemorrhagic hydrocephalus can cause significant brainstem compression and subsequent clinical deficits in children. Several treatment options have been described. We report the clinical and radiological outcome after microsurgical fenestration of fourth ventricular outlet foramen via a suboccipital approach.

Methods: In nine patients (age, 9 to 87 months; median age, 21 months), microsurgical reopening of formerly occluded outlet foramen of the fourth ventricle was performed under electrophysiological monitoring. Pre- and postoperative clinical outcome as well as radiological results are reported.

Results: Mean follow-up for all children was 25 months. Three children older than 3 years were less significantly involved, the remaining six showed tremendous long tract signs and lower cranial nerve deficits. All children exhibited a remarkable improvement of their preexisting neurological deficits post-surgery. Despite successful fenestration, one child required additional internal drainage of fourth ventricle to the lateral ventricles due to malabsorption. Median diameters of the fourth ventricle changed markedly after surgery with anterior-posterior (a.p.) extension from 3.8 to 2.9 cm, lateral extension from 4.2 to 2.8 cm (p = 0.018), and craniocaudal extension from 5.8 to 4.7 cm, respectively. Also, the pontine a.p. diameter increased significantly from 0.8 to 1.5 cm (p = 0.022).

Conclusion: The clinical and radiological outcomes after microsurgical fenestration in children with an isolated fourth ventricle are very promising. This treatment modality is a safe and effective shunt-free option when electrophysiological monitoring and thorough preoperative neuroradiological work-up are applied.
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http://dx.doi.org/10.1007/s00381-012-1887-5DOI Listing
December 2012

Intramedullary pilomyxoid astrocytoma with intracerebral metastasis exhibiting oligoden-droglioma-like features.

Rare Tumors 2012 Apr 31;4(2):e30. Epub 2012 May 31.

Center for Neuropathology.

Intramedullary glioma are rare and their biological behaviour can differ from their cerebral counterparts. Pilomyxoid astrocytoma (PMA, WHO grade II), predominantly occur in the hypothalamic/chiasmatic region of infants and children. The few reported cases of pediatric intramedullary PMA displayed a particularly aggressive behavior. Here, we report a diagnostically challenging case of a five year old female patient presenting with intramedullary glioma and local tumor recurrence three years later. Twelve years after the initial manifestation, a second tumor was found intracerebrally. We performed a comprehensive histological, molecular pathological and imaging analysis of the tumors from both localizations. The results revealed a metastasizing PMA with unique histological and genetic features. Our study indicates that PMA comprise a heterogeneous group including aggressive subtypes which may not be compatible with the current classification according to WHO grade II. Furthermore, the case emphasizes the increasing relevance of molecular pathological markers complementing classic histo-logical diagnosis.
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http://dx.doi.org/10.4081/rt.2012.e30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401158PMC
April 2012

Proper cerebellar development requires expression of β1-integrin in Bergmann glia, but not in granule neurons.

Glia 2012 May 28;60(5):820-32. Epub 2012 Feb 28.

Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.

β1-class integrins play essential roles both in developmental biology as well as in cancer. Particularly, a Nestin-driven deletion of β1-integrin receptors results in severe abnormalities of brain development including a laminar disorganization of cerebellar granule neurons. However, since Nestin is expressed in all kinds of neural precursors, these data do not allow conclusions to be drawn about the role of β1-integrins in distinct neuronal and glial cell types. By generating conditional knockout mice using granule cell-specific Math1-promoter sequences, we show here that the expression of β1-integrins in granule neurons is dispensable for the development of the cerebellum. Also, deletion of β1-integrin from tumors that arise in a mouse model of granule cell precursor-derived medulloblastoma did not result in a significant survival benefit. Last, expression levels of β1-integrin in human medulloblastoma samples did not predict patient's outcome. However, a β1-integrin knockout using hGFAP-promoter sequences led to cerebellar hypoplasia, inappropriate positioning of Bergmann glia cells in the molecular layer, undirected outgrowth of radial glia fibers, and granule cell ectopia. We therefore conclude that β1-integrin expression in cerebellar granule neurons is not essential during normal development or medulloblastoma formation. In fact, it is the expression of β1-integrin in glia that is crucial for the proper development of the cerebellar cortex.
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http://dx.doi.org/10.1002/glia.22314DOI Listing
May 2012

IDH1 mutations in grade II astrocytomas are associated with unfavorable progression-free survival and prolonged postrecurrence survival.

Cancer 2012 Jan 29;118(2):452-60. Epub 2011 Jun 29.

Department of Neurosurgery, Ludwig Maximilians University, Munich, Germany.

Background: The favorable prognostic impact of mutations in the IDH1 gene is well documented for malignant gliomas; its influence on World Health Organization (WHO) grade II astrocytomas, however, is still under debate.

Methods: A previously published database of 127 predominantly surgically treated patients harboring WHO grade II astrocytomas was revisited. Patients were screened for TP53 mutations (sequencing analysis), IDH1 mutations (pyrosequencing), and MGMT promoter methylation (methylation-specific polymerase chain reaction and bisulfite sequencing). Endpoints were overall survival, progression-free survival (PFS), time to malignant transformation, and postrecurrence survival. Radiotherapy was usually withheld until tumor progression/malignant transformation occurred.

Results: IDH1 mutations, TP53 mutations, and methylated MGMT promoters were seen in 78.1%, 51.2%, and 80.0% of the analyzed tumors, respectively. IDH1 mutations, which were significantly associated with TP53 mutations and/or MGMT promoter methylation (P < .001), resulted in shortened PFS (median, 47 vs 84 months; P = .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; P = .006). Overall survival was not affected by IDH1. A similar pattern of influence was seen for MGMT promoter methylation. Methylated tumors did significantly worse (better) in terms of PFS (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. Conversely, TP53 mutations were stringently associated with a worse prognosis throughout the course of the disease.

Conclusions: IDH1 mutations are associated with a Janus headlike phenomenon; unfavorable prognostic influence on PFS turns into favorable impact on postrecurrence survival. A similar pattern of influence might exist for MGMT methylation.
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http://dx.doi.org/10.1002/cncr.26298DOI Listing
January 2012

Children with tethered cord syndrome of different etiology benefit from microsurgery-a single institution experience.

Childs Nerv Syst 2011 May 6;27(5):803-10. Epub 2011 Jan 6.

Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.

Purpose: The term "tethered cord syndrome" (TCS) illustrates, according to the literature, both a separate diagnosis, as well as a combination of symptoms in the context of dysraphic conditions. The common denominator is the increased tension and abnormal stretching of the spinal cord, caused by tissue attachments that limit its movement in the spinal canal. In light of the fact that no real data exists regarding the management of these patients, the purpose of this single institutional study is to underscore management strategies and discuss the results, pitfalls, and the treatment of pediatric patients with tethered cord syndrome.

Methods And Results: The clinical outcome in 20 pediatric patients was studied retrospectively. Ten children with closed spinal dysraphism, nine with tethering after postpartum myelomeningocele repair, and one child with an infected open dermal sinus were included. A total of 22 detethering procedures were performed. The most common symptoms prior to surgery were muscle weakness and urinary dysfunction, followed by foot deformities and pain. Of all symptoms, pain responded most favorably to surgical treatment. There was improvement in 11 out of 15 patients with preoperative motor deficits, while that was the case in 11 out of 16 patients with urinary dysfunction.

Conclusions: In view of the lack of evidence regarding the treatment of children with tethered cord syndrome, the best way to aim for a favorable outcome is correct indication for surgical intervention, combined with the implementation of technical advancements, such as intraoperative neurophysiological monitoring and ultrasound.
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http://dx.doi.org/10.1007/s00381-010-1374-9DOI Listing
May 2011

Epidural and foramen-ovale electrodes in the diagnostic evaluation of patients considered for epilepsy surgery.

Epileptic Disord 2010 Mar 1;12(1):48-53. Epub 2010 Mar 1.

Epilepsy Center, Dept. of Neurology.

Purpose: To evaluate the clinical utility of epidural and foramen-ovale recordings and associated morbidity in the pre-surgical evaluation of epilepsy.

Methods: We retrospectively analysed 59 epilepsy patients, who underwent recordings with epidural (n = 59) and foramen-ovale electrodes (n = 46) as part of their pre-surgical evaluation between 1990-1999. The epidural and foramen-ovale evaluation was based on the results of the non-invasive EEG-video recordings in patients, in whom non-invasive evaluation failed to localise seizure onset (75%, 44 patients) or where EEG, and imaging studies were discrepant (25%, 15 patients) but allowed a testable hypothesis on the seizure onset zone.

Results: Most patients (n = 57) were evaluated between 1990-1994. Only two patients were evaluated later. The results of the epidural (n = 559) and foramen-ovale (n = 83) electrode recordings allowed us to proceed to resective epilepsy surgery in 31% (n = 18) and to exclude further invasive evaluation in 15% (n = 9) of the patients. In 49% (n = 29) of the patients the results guided further invasive recordings using subdural and/or depth electrodes. For only three patients no additional information was gained by the electrode recordings. Temporary morbidity included local infection (epidural; n = 1) and facial pain (foramen ovale; n = 1) but no permanent complication occurred.

Discussion: Epidural and foramen-ovale electrodes have almost been abandoned in recent years, most likely because of the improvement of neuroimaging techniques such as MRI, PET and ictal SPECT. However, in selected patients, epidural electrodes and foramen-ovale electrodes are either useful as a measure to avoid invasive evaluation or serve to guide invasive evaluation.
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http://dx.doi.org/10.1684/epd.2010.0297DOI Listing
March 2010

Ictal SPECT in Sturge-Weber syndrome.

Epilepsy Res 2008 Feb 25;78(2-3):240-3. Epub 2008 Jan 25.

University of Munich, Klinikum Grosshadern; Department of Neurology, Germany.

We report on a patient with right-sided Sturge-Weber syndrome (SWS), in whom earlier functional hemispherectomy failed. Subtraction of ictal and interictal single-photon-emission-computed-tomography (SPECT) superimposed on individual MRI showed a right fronto-orbital hyperperfusion, with a left-sided EEG seizure pattern. Ictal SPECT supported our assumption that right frontal originated seizure pattern propagated to left hemisphere via the remaining right frontal bridge. Right orbito-frontal resection and disconnection from corpus callosum resulted in seizure freedom.
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http://dx.doi.org/10.1016/j.eplepsyres.2007.12.006DOI Listing
February 2008
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