Revision by S2-alar-iliac instrumentation reduces caudal screw loosening while improving sacroiliac joint pain-a group comparison study.

Lumbosacral instrumentation continues to be challenging due to complex biomechanical force distributions and poor sacral bone quality. Various techniques have therefore been established. The aim of this study was to investigate the outcome of patients treated with S2-alar-iliac (S2AI), S2-alar (S2A), and iliac (I) instrumentation as the most caudal level. Sixty patients underwent one of the 3 techniques between January 2012 and June 2017 (S2AI 18 patients, S2A 20 patients, I 22 patients). Mean age was 70.4 ± 8.5 years. Screw loosening (SL) and sacroiliac joint (SIJ) pain were evaluated during the course at 3-month and maximum follow-up (FU). All patients completed 3-month FU, the mean FU period was 2.5 ± 1.5 years (p = 0.38), and a median of 5 segments was operated on (p = 0.26), respectively. Bone mineral density (BMD), derived opportunistically from computed tomography (CT), did not significantly differ between the groups (p = 0.66), but cages were more frequently implanted in patients of the S2A group (p = 0.04). SL of sacral or iliac screws was more common in patients of the S2A and I groups compared with the S2AI group (S2AI 16.7%, S2A 55.0%, I 27.3% of patients; p = 0.03). SIJ pain was more often improved in the S2AI group not only after 3 months but also at maximum FU (S2AI 61.1%, S2A 25.0%, I 22.7% of patients showing improvement; p = 0.02). Even in shorter or mid-length lumbar or thoracolumbar constructs, S2AI might be considered superior to S2A and I instrumentation due to showing lower incidences of caudal SL and SIJ pain.

Completeness and accuracy of data in spine registries: an independent audit-based study.

PURPOSE: Clinical registries are used for quality management and clinical research. Due to the importance and implications of both aims, completeness and high quality of data are of paramount importance. However, this remains uncertain, as none of these registries have implemented independent monitoring. The aim of this study was to determine the accuracy and completeness of registry data o the example of the German Spine Society (DWG) registry. METHODS: In a prospective study, audits by a board-certified neurosurgeon were conducted at certified spine centers with mandatory registry input, a setting comparable to most existing registries worldwide. A 2-week period was analyzed, and any discrepancy between patients' charts and the registry entry was evaluated. A median of 31 items per patient was evaluated including completeness and accuracy of data. RESULTS: Out of 17 centers willing to participate, 4 were still lacking any data entries. Even in the remaining 13 centers eligible for audits, 28.50% (95%-CI = [22.46-34.55]) of entries were finalized only after the audits were announced. Only 82.55% (95%-CI = [79.12-85.98]) of surgeries were documented, and on average 14.95% (95%-CI = [10.93-19.00]) of entries were not accurate with a wide variation (range; 6.21-27.44%) between centers. Aspects for improvement of the situation were identified. CONCLUSION: Due to the high inaccuracy, the high number of centers lacking mandatory entries at all and the number of false entries, these data alert us to advocate unannounced audits and further measures to improve the situation. Data should not be used for the time being, since wrong conclusion will be drawn. These slides can be retrieved under Electronic Supplementary Material.

[Migraine in childhood and adolescence-neurostimulation as a future innovative approach in terms of a multimodal treatment regimen]. / Migräne im Kindes- und Jugendalter ­ Ausblick auf innovative Behandlungsansätze im Rahmen multimodaler Therapiekonzepte.

Although migraine is a relevant health issue in children and adolescents, clinical care and research are still underrepresented and underfunded in this field. Quality of life can be significantly reduced when living with frequent episodes of pain. Due to the high level of vulnerability of the developing brain during adolescence, the risk of chronification and persistence into adulthood is high. In this narrative review, we describe the corner stones of a patient-centered, multimodular treatment regimen. Further, an update on the pathophysiology of migraine is given considering the concept of a periodically oscillating functional state of the brain in migraine patients ("migraine is a brain state"). Besides central mechanisms, muscular structures with the symptoms of muscular pain, tenderness, or myofascial trigger points play an important role. Against this background, the currently available nonpharmacological and innovative neuromodulating approaches are presented focusing on the method of repetitive peripheral magnetic stimulation.

Do pre-school episodic syndromes predict migraine in primary school children? A retrospective cohort study on health care data.

OBJECTIVE: To assess the relative risk, predictive value and population attributable risk fraction of pre-school episodic syndromes for later migraine in primary school age children. METHODS: This retrospective cohort study used health insurance data on 55,035 children born in 2006 with no diagnosis of migraine up to the age of 5 years. The relative risk, probability and population attributable risk fraction of migraine prompting a physician visit at the age of 6-10 years in children with episodic syndromes included in the International Classification of Headache Disorders (benign paroxysmal torticollis, benign paroxysmal vertigo, cyclic vomiting syndrome, recurrent abdominal symptoms and abdominal migraine) and those not included in the International Classification of Headache Disorders (pavor nocturnus, somnabulism and bruxism) diagnosed up to the age of 5 years were determined. RESULTS: The period prevalence of individual episodic syndromes ranged between 0.01% and 1.40%. For episodic syndromes included in the International Classification of Headache Disorders (recurrent abdominal symptoms and abdominal migraine) and for the episodic syndromes not included in the International Classification of Headache Disorders (somnambulism), the risk for later migraine was increased by factors of 2.08, 21.87 and 3.93, respectively. The proportion of risk for migraine in primary school children explained by any episodic syndromes included in the International Classification of Headache Disorders was 2.18% and for any episodic syndromes not included in the International Classification of Headache Disorders it was 0.59%. CONCLUSION: Several pre-school episodic syndromes are risk factors for migraine in primary school age children. The fraction of migraine in primary school age children explained by prior episodic syndromes, however, is below 3%. A probability to develop primary school age migraine above 50% was only observed for abdominal migraine.

Age- and sex-specific first health care use for migraine in 2016 in children and adolescents from prospectively collected health insurance data in Germany.

BACKGROUND: Migraine in children and adolescents is associated with significant disability and a high risk of persistence into adulthood. OBJECTIVE: Data on migraine incidence in children and adolescents are few and relatively coarse. To tailor interventions starting shortly after disease onset, detailed information on age- and sex-specific incidence of migraine in children and adolescents is needed. METHODS: We used health care data prospectively collected by the BARMER statutory health insurance, representing ∼11% of the German population. The incidence of migraine diagnoses (International Classification of Diseases (ICD)-10 code G43) in the year 2016 was assessed in subjects aged 0-19 years, who had been continuously insured with the BARMER between 2005 and 2016 or during their entire lifespan. RESULTS: Data from ∼1.2 million children and adolescents were available. The incidence of migraine diagnoses steadily increased with age, reaching ∼1% per year around the age of 10 for both sexes, and 3.49% per year in females and 1.72% per year in males at the age of 19. Incidences in males and females were similar up to the age of 13 and higher in females from there on. The proportion of incident migraine diagnoses specified as "definite" versus "probable" migraine increased with age. CONCLUSION: The present study provides a representative estimation of the first documented health care use for migraine in children and adolescents in Germany within 1-year age bins, separately for boys and girls. These data will be helpful for tailoring early healthcare interventions to reduce disability and prevent migraine chronification.

Pediatric Chronic Inflammatory Bowel Disease in a German Statutory Health INSURANCE-Incidence Rates From 2009 to 2012.

OBJECTIVE: The incidence of pediatric inflammatory bowel disease (PIBD) varies over time and geographic region. We attempted to generate incidence rates form German health insurance data. METHODS: We used health care data for 2009-2015 provided by BARMER, a major statutory health insurance company in Germany, insuring approximately 8% of the pediatric population. We applied a Canadian case definition for PIBD based on International Classification of Diseases coding, documentation of (ileo)colonoscopy and the number of PIBD related visits, without external validation for Germany. An internal validation of the specificity of the diagnosis by checking whether the identified incident cases had also prescriptions of PIPD specific drugs was performed. RESULTS: In 2012, 187 pediatric patients were newly diagnosed, accounting for an overall PIBD incidence of 17.41 (95% CI 15.08-20.10) per 100,000 insured children and adolescents from 0 to 17.9 years per year compared with 13.65/100,000 (95% CI 11.63-16.01) in 2009. The age-specific incidence showed a steep increase as of the age of 7 years. The PIBD prevalence in 2012 was 66.29/100,000. CONCLUSIONS: In conclusion, the incidence of PIBD in 0 to 17.9-year-olds in Germany with health BARMER health insurance in 2012 is among the highest reported in the literature.

Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysis.

BACKGROUND/OBJECTIVES: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear. SUBJECT/METHODS: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. RESULTS: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. CONCLUSIONS: A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

Association of decision-making in spinal surgery with specialty and emotional involvement-the Indications in Spinal Surgery (INDIANA) survey.

BACKGROUND: Although recent trials provided level I evidence for the most common degenerative lumbar spinal disorders, treatment still varies widely. Thus, the Indications in Spinal Surgery (INDIANA) survey explores whether decision-making is influenced by specialty or personal emotional involvement of the treating specialist. METHOD: Nationwide, neurosurgeons and orthopedic surgeons specialized in spine surgery were asked to answer an Internet-based questionnaire with typical clinical patient cases of lumbar disc herniation (DH), lumbar spinal stenosis (SS), and lumbar degenerative spondylolisthesis (SL). The surgeons were assigned to counsel a patient or a close relative, thus creating emotional involvement. This was achieved by randomly allocating the surgeons to a patient group (PG) and relative group (RG). We then compared neurosurgeons to orthopedic surgeons and the PG to the RG regarding treatment decision-making. RESULTS: One hundred twenty-two spine surgeons completed the questionnaire (response rate 78.7%). Regarding DH and SS, more conservative treatment among orthopedic surgeons was shown (DH: odds ratio [OR] 4.1, 95% confidence interval [CI] 1.7-9.7, p = 0.001; SS: OR 3.9, CI 1.8-8.2, p < 0.001). However, emotional involvement (PG vs. RG) did not affect these results for any of the three cases (DH: p = 0.213; SS: p = 0.097; SL: p = 0.924). CONCLUSIONS: The high response rate indicates how important the issues raised by this study actually are for dedicated spine surgeons. Moreover, there are considerable variations in decision-making for the most common degenerative lumbar spinal disorders, although there is high-quality data from large multicenter trials available. Emotional involvement, though, did not influence treatment recommendations.

Health-Related Quality of Life of Children/Adolescents with Vertigo: Retrospective Study from the German Center of Vertigo and Balance Disorders.

Purpose To assess the impact of vertigo on health-related quality of life (HrQoL) of children/adolescents and to assess if the impact on HrQoL varies by age group, gender, and type of vertigo diagnoses. Methods A retrospective analysis was performed on the clinical and HrQoL data of children and adolescents referred to the German Center of Vertigo and Balance Disorders (n = 32; male = 17; female = 15; age range: 8-18 years), using the KIDSCREEN-52 questionnaire. For each scale, means of the Z-scores with 95% confidence intervals of the study and norm sample were compared. By nonparametric Kruskal-Wallis statistics differences between diagnostic groups were assessed. To assess the gender- and age-specific impact of vertigo on quality of life, Wilcoxon signed-rank test was used. Results The means of the physical well-being, psychological well-being, autonomy scale, and the general HrQoL index of patients were considerably lower than the means of the norm sample. The physical well-being seemed to be most affected by vertigo. The reduction of HrQoL was not related to gender and vertigo types but seemed to be higher in children suffering from vertigo aged 12 to 18 years than children aged 8 to 11 years. Conclusion These are the first data to demonstrate impaired HrQoL in children with chronic vertigo.

Self-reported neck and shoulder pain in adolescents is associated with episodic and chronic migraine.

AIM: The aim of this study was to verify the association between self-reported neck/shoulder pain and migraine and to compare findings of chronic and episodic migraine in adolescents. METHODS: In this cross-sectional study, 601 secondary-school students filled in questionnaires about headache appearance, type and frequency, neck and shoulder pain and lifestyle factors. RESULTS: The adjusted strength of the association between reported neck and shoulder pain and migraine (assessed in multinomial regression models) increased with the frequency of migraine: less than once a week (OR = 1.40; 95% CI = (0.85-2.30)), weekly (OR = 2.14; 95% CI = (1.42-3.24)), and at least 15 days/month (OR = 7.27; 95% CI = (3.42-15.44)). CONCLUSION: In adolescents the association between self-reported neck and shoulder pain and migraine is most pronounced in migraine with a high attack frequency.

Headache in school children: is the prevalence increasing?

The objectives of this systematic review were to examine age dependency of headache prevalence in school age children and to assess secular trends of headache prevalence in the last decade, gender and regional differences. A literature search was performed in MEDLINE to identify all prevalence studies in children and adolescents. Five hundred seventy studies were found, of which 37 studies could be included for this review. Headache prevalence in school children increases with their age as demonstrated in cohorts of identical children and cross-sectional surveys covering different age groups of children in one population. Regarding a potential general increase in the prevalence of headache in children and adolescents in the last decade, there are four studies which all show some increase of headache prevalence; however, the degree of increase is varying. Prevalence of headache in girls appears to be higher than in boys. There were no clear regional differences in the prevalence of headache.

Migraine and tension type headache in adolescents at grammar school in Germany - burden of disease and health care utilization.

BACKGROUND: Tension-type headache and migraine are among the most prevalent chronic disorders in children/adolescents. Data on health care utilization for headache in this age group, however, are sparse. METHODS: In 1399 grammar school students (aged 12-19 years) with headache in the last six months in Germany a) the burden of disease for headache (mean intensity, mean frequency in the last three months and PedMIDAS means), b) medical care utilization defined by proportion of students consulting a physician in the last 12 months and/or taking analgetic drugs in the last three months by headache types (migraine and tension-type headache) and by burden of disease were assessed. RESULTS: Primary headache substantially impaired daily living activities in adolescents which was mainly related to migraine. Medical care utilization and drug use, however, was low (consulting a physician: 12.0 %, 95 %-CI = [10.3-13.8]; taking analgetic drugs: 29.9 %, 95 %-CI = [27.5-32.4]) - even among students with severe headache (physician consultation: <35 %; taking analgetic drugs: <63 %). Two thirds of students with any headache and 40 % of those with migraine had neither seen a physician nor used analgetic drugs because of their headache in the preceding 12 months. CONCLUSIONS: Adolescents with headache might too rarely seek professional help for treatment of headache. Health promotion in adolescents should increase awareness for evidence-based treatment options for headache.

Self-reported neck pain is associated with migraine but not with tension-type headache in adolescents.

AIM: The aim of the present analysis is to confirm or refute the association of neck pain to migraine or tension-type headache and to assess whether this association is independent of other risk factors for headache. METHODS: Secondary school students were invited to complete a questionnaire on headache and lifestyle factors in a cross-sectional study. Neck pain was assessed via (a) a screening question concerning neck pain and (b) denoting affected areas in schematic drawings of the human body. RESULTS: Absolute increment in prevalence of headache with pain in the shoulder-neck region was between 7.5% and 9.6%. Gender, grade, stress and lifestyle factors were assessed as potential confounding factors. Nearly all factors were associated with shoulder-neck pain and most with headache. After adjustment for confounders, the association of neck pain with headache was almost completely confined to migraine (OR 2.39; 95% CI 1.48-3.85) and migraine + tension-type headache (OR 2.12; 95% CI 1.50-2.99), whereas the association with isolated tension-type headache was negligible (OR 1.22, 95% CI 0.87-1.69). CONCLUSION: Neck pain is associated with migraine but not with tension-type headache. A possible link between migraine and neck pain may be the cervico-trigeminal convergence of neck and meningeal sensory afferents or a disturbed descending inhibition in migraine.

High diagnostic stability of confirmed migraine and confirmed tension-type headache according to the ICHD-3 beta in adolescents.

BACKGROUND: Stable headache diagnosis classification is a prerequisite for identification of headache type specific risk factors. Does the stability of a headache diagnosis over time vary between migraine and tension-type headache (TTH)? Are there differences in diagnosis stability between a probable and a definite headache diagnosis? FINDINGS: In a sample of 783 students (ages 12 to 18 years) participating in a headache intervention study in greater Munich, the stability of headache classification according to the International Classification of Headache Disorder - third edition (beta version) (ICHD-3 beta) after a follow-up of 7 months was examined. Differences in stability of probable or definite migraine and probable or definite TTH were assessed. The stability of the headache diagnosis was assessed as predictive value of headache diagnosis with regard to confirmation of the headache type using the same diagnostic instrument 7 months later. Predictive values with 95% confidence intervals (CI) are reported.Of students with initial migraine, a diagnosis of migraine was confirmed in 65.71% of students after 7 months (95%-CI [59.40-71.64]). A clear distinction between probable (44.71%, 95%-CI [33.91-53.89]) and confirmed diagnosis (76.88% 95%-CI [69.56-83.17]) of migraine was observed. For TTH the predictive value was 62.66% (95%-CI [57.07-68.01]) overall with a lower stability for probable (46.10%, 95%-CI [37.68-54.69]) compared to the confirmed diagnosis (69.71%, 95%-CI [23.58-37.67]). CONCLUSION: While confirmed migraine and confirmed TTH diagnoses seem stable over time, stability of a probable diagnosis for either headache type was lower. TRIAL REGISTRATION: The trial was registered at the German Clinical Trial Register with the ID DRKS00003308.

Prevention of headache in adolescents: population-attributable risk fraction for risk factors amenable to intervention.

INTRODUCTION: Several risk factors for headache have been identified, some of which are potentially amenable to interventions. The potential effect of such interventions can be predicted by the population-attributable risk fraction (PARF). We assessed PARFs of the the following risk factors: neck muscle pain, chronic stress, alcohol consumption, smoking, coffee consumption, and physical inactivity. We studied the maximal possible effect achievable by avoidance of these risk factors. METHODS: Two approaches to estimate PARFs are compared, which assess their cumulative and individual impact of risk factors by age: the Levin formula and the average attributable fraction. RESULTS: The overall impact for removal of all six risk factors amounts to 19.7% for the average attributable fraction. Neck tension and consumption of alcohol ranked as the strongest population-attributable risk factor for any headache. The potential impact for migraine was considerably higher (43.8%). With increasing age, the overall impact of risk factors on headache increases by 18.9%. CONCLUSION: Based on the estimations of the most appropriate approach, up to 20% of headaches in general and up to 43% of migraine in adolescents might be preventable by removing risk factors amenable to intervention, with increasing proportions by age.

Burden of disease and lifestyle habits in adolescents and young adults prone to frequent episodic migraine: A secondary comparative analysis.

The objective of this study was to assess the burden of disease and prevalence of lifestyle factors for adolescents and young adults with frequent episodic migraine. We conducted a secondary comparative analysis of data collected during two previous studies. Inclusion criteria for this analysis were age 15-35 years, 15 to 44 migraine episodes within 12 weeks, and completeness of Migraine Disability Assessment and lifestyle questionnaire data. Datasets of 37 adults (median age [interquartile range]: 25 [6]) and 27 adolescents (median age [interquartile range]: 15 [1]) were analyzed. 81% (n = 30) of adults reported severe disability (16% [n = 3] of adolescents; p < 0.001). Headache frequency (24 vs. 17 days; p = 0.005) and prevalence of regular analgesic use (60% [n = 22] vs. 18% [n = 5]; p = 0.002) were significantly higher in adults. In adults, sleep duration on weekdays was significantly lower (8.5 vs. 10 h; p < 0.001). Any consumption of caffeine tended to be higher in adolescents and alcohol consumption tended to be higher in adults (p > 0.05). This study underlines the importance of educating adolescents and young adults with migraine about lifestyle habits that are likely to interfere with the condition.

Anterior Pituitary Hormones in Blood and Cerebrospinal Fluid of Patients in Neurocritical Care.

BACKGROUND: Anterior pituitary hormones in blood follow a circadian rhythm, which may be influenced by various factors such as intracranial pathologies. In cerebrospinal fluid (CSF), pituitary hormones have been collected only selectively and circadian rhythm has not yet been investigated. This pilot study analysed diurnal variations of anterior pituitary hormones in patients in neurocritical care to determine whether circadian rhythmicity exists in these patients. Possible influences of intracranial pathologies were also investigated. Blood and CSF concentrations were assessed simultaneously to explore the value of blood concentrations as a surrogate parameter for CSF levels. METHODS: Blood and CSF samples of 20 non-sedated patients were collected at 06:00, noon, 18:00 and midnight, and analysed for adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) concentrations at each of the four time points. ACTH and IGF-1 were measured by sandwich chemiluminescence immunoassay. Cortisol and TSH were measured by electrochemiluminescence immunoassay. RESULTS: Results showed inconsistent circadian rhythms. Less than 50% of the patients showed a circadian rhythmicity of ACTH, cortisol, TSH or IGF-1. Significance of diurnal variations was only present for blood concentrations of TSH. Correlations between blood and CSF concentrations were strong for cortisol and TSH. CONCLUSIONS: CSF concentrations were only in the measurable range in some of the patients. No clear circadian rhythmicity could be identified, except for TSH in blood. Absence of significant diurnal variations could be explained by the underlying pathologies or disturbing influences of the intensive care unit. Blood concentrations of cortisol and TSH may be suitable surrogate parameters for CSF.

Response Predictors of Repetitive Neuromuscular Magnetic Stimulation in the Preventive Treatment of Episodic Migraine.

Background: Repetitive neuromuscular magnetic stimulation (rNMS) of the trapezius muscles showed beneficial effects in preventing episodic migraine. However, clinical characteristics that predict a favorable response to rNMS are unknown. The objective of this analysis is to identify such predictors. Methods: Thirty participants with a diagnosis of episodic migraine (mean age: 24.8 ± 4.0 years, 29 females), who were prospectively enrolled in two non-sham-controlled studies evaluating the effects of rNMS were analyzed. In these studies, the interventional stimulation of the bilateral trapezius muscles was applied in six sessions and distributed over two consecutive weeks. Baseline and follow-up assessments included the continuous documentation of a headache calendar over 30 days before and after the stimulation period, the Migraine Disability Assessment Score (MIDAS) questionnaire (before stimulation and 90 days after stimulation), and measurements of pain pressure thresholds (PPTs) above the trapezius muscles by algometry (before and after each stimulation session). Participants were classified as responders based on a ≥25% reduction in the variable of interest (headache frequency, headache intensity, days with analgesic intake, MIDAS score, left-sided PPTs, right-sided PPTs). Post-hoc univariate and multivariate binary logistic regression analyses were performed. Results: Lower headache frequency (P = 0.016) and intensity at baseline (P = 0.015) and a migraine diagnosis without a concurrent tension-type headache component (P = 0.011) were significantly related to a ≥25% reduction in headache frequency. Higher headache frequency (P = 0.052) and intensity at baseline (P = 0.014) were significantly associated with a ≥25% reduction in monthly days with analgesic intake. Lower right-sided PPTs at baseline were significantly related to a ≥25% increase in right-sided PPTs (P = 0.015) and left-sided PPTs (P =0.030). Performance of rNMS with higher stimulation intensities was significantly associated with a ≥25% reduction in headache intensity (P = 0.046). Conclusions: Clinical headache characteristics at baseline, the level of muscular hyperalgesia, and stimulation intensity may inform about how well an individual patient responds to rNMS. These factors may allow an early identification of patients that would most likely benefit from rNMS.

Non-Invasive Mapping for Effective Preoperative Guidance to Approach Highly Language-Eloquent Gliomas-A Large Scale Comparative Cohort Study Using a New Classification for Language Eloquence.

Objective: A considerable number of gliomas require resection via direct electrical stimulation (DES) during awake craniotomy. Likewise, the feasibility of resecting language-eloquent gliomas purely based on navigated repetitive transcranial magnetic stimulation (nrTMS) has been shown. This study analyzes the outcomes after preoperative nrTMS-based and intraoperative DES-based glioma resection in a large cohort. Due to the necessity of making location comparable, a classification for language eloquence for gliomas is introduced. Methods: Between March 2015 and May 2019, we prospectively enrolled 100 consecutive cases that were resected based on preoperative nrTMS language mapping (nrTMS group), and 47 cases via intraoperative DES mapping during awake craniotomy (awake group) following a standardized clinical workflow. Outcome measures were determined preoperatively, 5 days after surgery, and 3 months after surgery. To make functional eloquence comparable, we developed a classification based on prior publications and clinical experience. Groups and classification scores were correlated with clinical outcomes. Results: The functional outcome did not differ between groups. Gross total resection was achieved in more cases in the nrTMS group (87%, vs. 72% in the awake group, p = 0.04). Nonetheless, the awake group showed significantly higher scores for eloquence than the nrTMS group (median 7 points; interquartile range 6-8 vs. 5 points; 3-6.75; p < 0.0001). Conclusion: Resecting language-eloquent gliomas purely based on nrTMS data is feasible in a high percentage of cases if the described clinical workflow is followed. Moreover, the proposed classification for language eloquence makes language-eloquent tumors comparable, as shown by its correlation with functional and radiological outcomes.

Navigated repetitive transcranial magnetic stimulation improves the outcome of postsurgical paresis in glioma patients - A randomized, double-blinded trial.

BACKGROUND: Navigated repetitive transcranial magnetic stimulation (nrTMS) is effective therapy for stroke patients. Neurorehabilitation could be supported by low-frequency stimulation of the non-damaged hemisphere to reduce transcallosal inhibition. OBJECTIVE: The present study examines the effect of postoperative nrTMS therapy of the unaffected hemisphere in glioma patients suffering from acute surgery-related paresis of the upper extremity (UE) due to subcortical ischemia. METHODS: We performed a randomized, sham-controlled, double-blinded trial on patients suffering from acute surgery-related paresis of the UE after glioma resection. Patients were randomly assigned to receive either low frequency nrTMS (1 Hz, 15 min) or sham stimulation directly before physical therapy for 7 consecutive days. We performed primary and secondary outcome measures on day 1, on day 7, and at a 3-month follow-up (FU). The primary endpoint was the change in Fugl-Meyer Assessment (FMA) at FU compared to day 1 after surgery. RESULTS: Compared to the sham stimulation, nrTMS significantly improved outcomes between day 1 and FU based on the FMA (mean [95% CI] +31.9 [22.6, 41.3] vs. +4.2 [-4.1, 12.5]; P = .001) and the National Institutes of Health Stroke Scale (NIHSS) (-5.6 [-7.5, -3.6] vs. -2.4 [-3.6, -1.2]; P = .02). To achieve a minimal clinically important difference of 10 points on the FMA scale, the number needed to treat is 2.19. CONCLUSION: The present results show that patients suffering from acute surgery-related paresis of the UE due to subcortical ischemia after glioma resection significantly benefit from low-frequency nrTMS stimulation therapy of the unaffected hemisphere. CLINICAL TRIAL REGISTRATION: Local institutional registration: 12/15; ClinicalTrials.gov number: NCT03982329.