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We study the impact of coil orientation on the motor threshold (MT) and present an optimal coil orientation for stimulation of the foot. The result can be compared to results of models that predict this orientation from electrodynamic properties of the media in the skull and from orientations of cells, respectively. We used a robotized TMS system for precise coil placement and recorded motor-evoked potentials with surface electrodes on the abductor hallucis muscle of the right foot in 8 healthy control subjects. First, we performed a hot-spot search in standard (lateral) orientation and then rotated the coil in steps of 10° or 20°. At each step we estimated the MT. For navigated stimulation and for correlation with the underlying anatomy a structural MRI scan was obtained. Optimal coil orientation was 33.1 ± 18.3° anteriorly in relation to the standard lateral orientation. In this orientation the threshold was 54 ± 18% in units of maximum stimulator output. There was a significant difference of 8.0 ± 5.9% between the MTs at optimal and at standard orientation. The optimal coil orientations were significantly correlated with the direction perpendicular to the postcentral gyrus ([Formula: see text]). Robotized TMS facilitates sufficiently precise coil positioning and orientation to study even small variations of the MT with coil orientation. The deviations from standard orientation are more closely matched by models based on field propagation in media than by models based on orientations of pyramidal cells.

Introduction As sensitivity of a test can be increased at the expense of specificity, a quality measure taking into account both parameters is desirable. The “predictive summary index” (PSI) is calculated from the prevalence of the disease, sensitivity and specificity. We characterize diagnostic yield of repetitive nerve stimulation (RNS) and stimulated concentric needle jitter (CNJ) in the diagnosis of myasthenia gravis (MG) with PSI. From PSI, the number of tests that is required for the prediction of one correct diagnosis (“number needed to predict” [NNP] in analogy to the number needed to treat) can be calculated as 1/PSI. Methods Among patients consecutively referred to the electrophysiology laboratory for a workup of a disorder of the neuromuscular junction (NMJ), we identified 35 patients with MG (clinical diagnosis supported by antibody findings or treatment response) and 85 patients with diagnosis unrelated to the NMJ in whom both RNS and stimulated CNJ had been performed. Results The PSI was 0.82 and 0.53 for CNJ and RNS, respectively. The NNPs were 1.22 for CNJ and 1.89 for RNS. This means that 1.49 patients have to be tested with CNJ instead of RNS to arrive at one correct diagnosis. In data from the literature, PSI illustrates that 7% as a cut‐off in RNS can be helpful and that amplitude decrement is more reliable than area decrement. Conclusion CNJ was more reliable in the diagnosis of MG than RNS. PSI provides a rational quantitative framework to discuss both the validity of different techniques and their cost in terms of time spent to arrive at a correct diagnosis. We use retrospective data from our electrophysiology laboratory to show that to diagnose or rule out myasthenia gravis one in every 1.22 concentric needle jitter tests and one in 1.89 repetitive nerve stimulations tests leads to the correct prediction.

Background Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. Methods The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a ‘natural’ background progression-rate of 10% without radiotherapy (null hypothesis). Discussion If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. Trial registration clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.

Background Myasthenia gravis has a variable disease course. Early identification of patients with a highly active disease is crucial to prevent myasthenic exacerbations and crisis, necessitating more aggressive immunotherapy. However, no biomarkers currently exist to identify patients at risk for highly active disease course. Objective The PROGNO-MG study aims to identify blood-based biomarker signatures associated with a highly active disease course in immunotherapy-naïve patients with acetylcholine-receptor-antibody positive (AChR + ) generalized Myasthenia gravis (gMG). Methods This is an investigator-initiated prospective, multicentric, observational study. Seventy newly diagnosed immunotherapy-naïve AChR + gMG patients will be enrolled and followed up for 24 months. Blood samples and clinical data will be collected biannually. Biomarkers (calprotectin, neurofilament light chain, ITIH3, complement activation, kappa free light chains, and exploratory proteome-analyses and immune cell phenotyping) will be measured and their association with clinical outcomes will be evaluated. Perspective The results will provide evidence for prognostic biomarkers, supporting risk stratification and early individualized treatment for AChR + gMG patients. Trial registration The study is registered in the German clinical trial register (DRKS00035457).

The usefulness of brain imaging studies in dizzy patients presenting to the emergency department (ED) is controversial. We aimed to assess the ‘real-world’ probability of ischemic stroke and other acute brain lesions (ABLs) in these patients to create an algorithm that helps decision-making on whether which and when brain imaging is needed. By reviewing medical records, we identified 610 patients presenting with dizziness, vertigo or imbalance to our university hospital’s ED and receiving neurological workup. We collected timing/triggers of symptoms, ABCD 2 score, focal neurological abnormalities, HINTS (head impulse, nystagmus, test-of-skew) and other central oculomotor signs. ABLs were extracted from CT/MRI reports. Uni-/multivariate logistic regression analyses investigated associations between clinical parameters and ABLs. Finally, the likelihood of ABLs was assessed for different clinically defined subgroups (‘dizziness syndromes’). Early CT (day 1) was performed in 539 (88%) and delayed MR imaging (median: day 4) in 299 (49%) patients. ABLs (89% ischemic stroke) were revealed in 75 (24%) of 318 patients with adequate imaging (MRI or lesion-positive CT). The risk for ABLs increased with the presence of central oculomotor signs (odds ratio 2.8, 95% confidence interval 1.5–5.2) or focal abnormalities (OR 3.3, 95% CI 1.8–6.2). The likelihood of ABLs differed between dizziness syndromes, e.g., HINTS-negative acute vestibular syndrome: 0%, acute imbalance syndrome with ABCD 2 -score ≥ 4: 50%. We propose a clinical pathway, according to which patients with HINTS-negative acute vestibular syndrome should not receive brain imaging, whereas imaging is suggested in dizzy patients with acute imbalance, central oculomotor signs or focal abnormalities.

Purpose To prospectively assess the incidence of Dropped Head Syndrome (DHS) in childhood cancer survivors (CCS) and to develop and evaluate a diagnostic algorithm for DHS. Methods A systematic literature search for DHS in combination with neck radiotherapy (RT) exposure was performed. Analyses and a combination of the most common examination methods were integrated into a diagnostic algorithm. Almost all CCSs visiting the local late effects clinic between May 2020 and April 2022 were included in the study. CCS exposed to neck RT with doses ≥ 19 Gy received standardized clinical and neurological assessment and, in case of abnormal results, an MRI scan to confirm muscle atrophy. Results Two hundred and five CCS were included of whom 41 received RT to the neck with ≥ 19 Gy. In the entire cohort and in the subgroup receiving RT, 2.4% and 12% of CCS were affected by DHS, respectively. Results of clinical and neurological assessment correlated well with MRI results. Neck circumference and neck/thigh ratio were lower after neck RT. Over 50% of CCS experienced neck disability and pain. Conclusions A relevant proportion of CCS exposed to neck RT is affected by DHS. High concordance of MRI results with the neurological examination supports the clinical value of the diagnostic algorithm. Measurement of neck circumference might be an easy tool for assessment of neck muscle atrophy in survivors at risk. Implications for cancer survivors Integration of a diagnostic algorithm for DHS in standard long-term follow-up care facilitates diagnosis as well as initiation of early treatment and obviates the need for invasive examinations.

Standard radiotherapy (RT) for glioblastoma lasts 6 weeks. We aimed to identify patients who would benefit from a hypofractionated approach. In 167 patients receiving standard fractionation, 10 factors were analyzed for local control (LC) and overall survival (OS). A survival score was developed and compared to a previous instrument. On multivariate analysis, better LC was significantly associated with the presence of only one lesion and O -methylguanine-DNA methyltransferase (MGMT) promoter methylation. Better OS was associated with one lesion, better performance status, MGMT promoter methylation, and receipt of chemotherapy. Lesion diameter ≤40 mm and upfront resection were associated with improved OS on univariate analyses. Based on assigning scores to these six factors, three groups, with 32-35, 36-44 and 45-48 points, were designed with 12-month OS-rates of 0%, 56%, and 92%, respectively. Accuracy in predicting death within 12 months and survival ≥12 months was 100% and 92%, respectively, versus 67% and 83% with the previous scoring system. A new survival score with higher accuracy was developed for patients with glioblastoma. Our model can be utilized to individualize RT dose-fractionation recommendations for glioblastoma.

Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.

ObjectiveAntibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD).MethodsCoded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1).ResultsResults of tests on 92 controls identified 12assays as highly specific (0–1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5–100%) of all 21 assays. The specificities (85.8–100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples.ConclusionsThe cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.