Search

Post COVID-19 conditions (PCC) present with a wide range of symptoms. Headache is one of the most frequently reported neurological symptoms by patients with PCC. We aimed to assess the prevalence of headache in patients with PCC who attended the Post-COVID LMU outpatient department at LMU University Hospital in Munich. We hypothesized that headaches occur more frequently in patients with PCC than in the control group. Patients answered a questionnaire containing sociodemographic characteristics, their current symptoms, and prior psychiatric and somatic diagnoses, the WHO Quality of Life assessment (WHOQOL-BREF), 9-item Patient Health Questionnaire (PHQ-9), and the Fatigue Severity Scale (FSS). 188 PCC patients were included in this study and compared to a control group of patients with a history of COVID-19 or a different infectious disease - but no consecutive post-infectious condition (n c =27). 115 (61%) of our PCC patients were female. The median age was 41 years. 60 (32%, p = 0.001) had a pre-existing psychiatric diagnosis. PCC was associated with worse outcomes in all four domains of the WHOQOL-BREF (p < 0.001), high levels of fatigue (FSS; p < 0.001), and a higher likeliness for symptoms of depression (PHQ-9; p < 0.001). We were able to confirm that psychiatric disorders are more frequently associated with headaches in PCC patients. Headache should be assessed and treated in the context of PCC not only by neurologists but by multi-professional teams and regarding all PCC symptoms., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the study was obtained from the Ethics Committee of the Medical Faculty of LMU Munich (21-1165). All potentially eligible participants were informed about the research in oral and written form. Furthermore, participants had to sign an informed consent form stating that all data would be treated anonymously. The Post-COVID-Care study was registered with the Deutsches Register Klinischer Studien (DRKS; registration number DRKS00030974). Consent for publication: All participants gave written informed consent. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest., (© 2024. The Author(s).)

Background: Visual snow is a disorder of visual perception that is manifested as a constant flickering or "TV-like" noise in the entire visual field. Visual snow syndrome (VSS) describes a combination with other additional visual symptoms, such as sensitivity to light, afterimages, night blindness and entoptic phenomena. Cases of VS have been described in the literature using a wide variety of terms, often misunderstood as persistent migraine aura. Established diagnostic criteria have existed for more than 10 years now; however, the pathophysiology is still incompletely understood. The exact prevalence also remains unknown and high numbers of unreported cases are suspected. This is the first detailed description of a cohort of VSS patients from Germany., Methods: Patients with VSS from several studies conducted at our center were pooled and retrospectively evaluated with respect to demographic, epidemiological and clinical data., Results: In this study 66 patients with VSS were included (age 31.3 ± 8.3 years, 30 women). The most commonly associated visual symptoms were photophobia (67%) and afterimages (65%). Of the patients 36 (54%) had comorbid migraine of whom 25 (70%) had migraine with aura, 26 (39%) reported depressive symptoms and 32 (48%) symptoms of an anxiety disorder. Tinnitus was reported by 32 (48%) patients., Conclusion: The characteristics of the German cohort described here are similar to other international descriptions. Due to the frequent psychological comorbidity there is still a risk of psychosomatic stigmatization., Competing Interests: Einhaltung ethischer Richtlinien Interessenkonflikt A. Straube; Für Vortragstätigkeit und Beratung: Allergan, Novartis, Lundbeck, Lilly, Sanofi, TEVA, Forschungsunterstützung: Novartis, Innovationsfonds, DFG, Universität München. R. Ruscheweyh : Für Vortragstätigkeit und Beratung, sowie Unterstützung von Kongressreisen: Allergan, Lilly, Lundbeck, Pfizer, Novartis, Teva. O.E. Eren Für Vortragstätigkeit und Beratung: Lilly, Novartis, Finanzielle Unterstützung für wissenschaftliche Tätigkeit: BMBF, Deutsche Migräne- und Kopfschmerzgesellschaft, Friedrich-Baur-Institut. F. Fay gibt an, dass kein Interessenkonflikt besteht.Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background and Aim: Migraine is a common disabling conditions which, globally, affects 15.2% of the population. It is the second cause of health loss in terms of years lived with disability, the first among women. Despite being so common, it is poorly recognised and too often undertreated. Specialty centres and neurologists with specific expertise on headache disorders have the knowledge to provide specific care: however, those who do not regularly treat patients with migraine will benefit from a synopsis on the most relevant and updated information about this condition. This paper presents a comprehensive view on the hallmarks of migraine, from genetics and diagnostic markers, up to treatments and societal impact, and reports the elements that identify migraine specific features., Main Results: The most relevant hallmark of migraine is that it has common and individual features together. Besides the known clinical manifestations, migraine presentation is heterogeneous with regard to frequency of attacks, presence of aura, response to therapy, associated comorbidities or other symptoms, which likely reflect migraine heterogeneous genetic and molecular basis. The amount of therapies for acute and for prophylactic treatment is really wide, and one of the difficulties is with finding the best treatment for the single patient. In addition to this, patients carry out different daily life activities, and might show lifestyle habits which are not entirely adequate to manage migraine day by day. Education will be more and more important as a strategy of brain health promotion, because this will enable reducing the amount of subjects needing specialty care, thus leaving it to those who require it in reason of refractory condition or presence of comorbidities., Conclusions: Recognizing the hallmarks of migraine and the features of single patients enables prescribing specific pharmacological and non-pharmacological treatments. Medical research on headaches today particularly suffers from the syndrome of single-disease approach, but it is important to have a cross-sectional and joint vision with other close specialties, in order to treat our patients with a comprehensive approach that a heterogeneous condition like migraine requires., (© 2024. The Author(s).)

Background: Headache disorders are among the most prevalent neurological disorders worldwide. However, whether groups differing in socioeconomic position (SEP) are disproportionately affected by headache disorders has not yet been adequately clarified. Our aim was to analyse (1) the headache prevalence by socioeconomic position (SEP) and (2) the attack frequency by SEP in a German population-based adult sample., Methods: Cross-sectional data from a random general population were used. The sample included N = 2,189 participants aged ≥ 18 years. SEP was measured using net equivalised income (NEI) and education. A binary logistic regression model tested the effect of SEP in predicting the prevalence of headache in general. Ordinal logistic regressions were modeled to predict the effect of SEP on the likelihood of attack frequency. Attack frequency was categorized in low frequency episodic headache (LFEH: 0-3 days per month), moderate frequency episodic headache (MFEH: 4-14 days per month) and chronic headache (CH: ≥ 15 days per month)., Results: Of the 2,189 participants, 891 reported headache in the last six months. Neither income nor education was associated with headache prevalence. However, significant differences between income groups were found for attack frequency. Compared to participants with NEI > 150%, those with NEI < 60% were 5.21 times more likely (95%CI 2.03, 13.36) to experience higher headache frequency, and those with NEI between 60 and 150% were 2.29 times more likely (95%CI 1.02, 5.11), with adjustments made for a set of potential confounders, including depressive symptoms., Conclusions: To reduce headache attacks, it is essential to address both low- and middle-income groups affected by headaches. Universal public health prevention campaigns are particularly appropriate., (© 2024. The Author(s).)

Background: Idiopathic intracranial hypertension (IIH) is typically characterized by headaches and vision loss. However, neurocognitive deficits are also described. Our study aimed to test the influence of therapeutic lumbar puncture on the latter., Methods: A total of 15 patients with IIH were tested with a battery of neurocognitive tests at baseline and after therapeutic lumbar drainage. Hereby, Logical Memory of the Wechsler Memory Scale-Revised Edition (WMS-R), the California Verbal Learning Test Short Version (CVLT), alertness, selective attention, and word fluency were used. Changes in cognitive functioning in the course of CSF pressure lowering were analysed and compared with age, sex, and education-matched healthy controls., Results: Before intervention, scores of Logical Memory, the RWT, and the HADS-D were significantly lower in IIH patients compared to matched controls. After short-term normalization of CSF pressure, the RWT improved significantly. Additionally, significant positive correlations were found between headache intensity and subjective impairment, as well as between BMI and CSF opening pressure., Conclusions: Our findings confirm lower performance in terms of long-term verbal memory and word fluency compared to controls, as well as depressive symptoms in IIH patients. Significant improvement after short-term normalization of intracranial pressure by means of CSF drainage was seen only for word fluency. This indicates that short-term normalization of CSF pressure is not sufficient to normalize observed neurocognitive deficits.

Homotrinuclear complexes of the C 3 -symmetric tris(ferrocenyl)arene-based tris-phosphanes 1a-d with ruthenium(ii) ([1a-d(Ru) 3 ]) and rhodium(i) ([1a-d(Rh) 3 ]) were prepared and fully characterised. Complexes [1a-d(Ru) 3 ] and [1a-d(Rh) 3 -triazine allows to fine-tune the exact oxidation potentials for tailoring the electrochemical response. With a BAr s -based supporting electrolyte, a distinct separation of the three iron-centred oxidations of the ligand backbone is observable. Under these conditions, these oxidations are mostly reversible but, especially for the third oxidation, already show signs of irreversibility. In general, while the coordinated metal complex fragment does not strongly alter the electrochemical response of the arene-trisferrocenyl core 1a-d, there are observable differences. Rhodium(i) complexes are oxidised at slightly higher potentials than ruthenium(ii) complexes. In both cases, individual oxidation states for the C F 4 - -based supporting electrolyte, a distinct separation of the three iron-centred oxidations of the ligand backbone is observable. Under these conditions, these oxidations are mostly reversible but, especially for the third oxidation, already show signs of irreversibility. In general, while the coordinated metal complex fragment does not strongly alter the electrochemical response of the arene-trisferrocenyl core 1a-d, there are observable differences. Rhodium(i) complexes are oxidised at slightly higher potentials than ruthenium(ii) complexes. In both cases, individual oxidation states for the C 6 H 3 (CH 2 ) 3 -based ligand (1d) are difficult to address and the C 3 N 3 -based ligand (1c) shows the most complicated and least reversible electrochemistry with severely broadened third oxidations and reduced reversibility in cyclic voltammetry. The most well-suited system for potential applications in redox-switchable catalysis, in all cases, is the C 6 H 3 -based ligand (1a), showing entirely reversible and well-separated redox events., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Cluster headache (CH) is associated with high disability. The Cluster Headache Impact Questionnaire (CHIQ) is a short, disease-specific disability questionnaire first developed and validated in German. Here, we validated the English version of this questionnaire., Methods: The CHIQ was assessed together with nonspecific headache-related disability questionnaires in CH patients from a tertiary headache center and an American self-help group., Results: 155 active episodic and chronic CH patients were included. The CHIQ showed good internal consistency (Cronbach's α = 0.91) and test-retest reliability (ICC = 0.93, n = 44). Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test™ (HIT-6™, ρ = 0.72, p < 0.001), the Hospital Anxiety and Depression Scale (HADS depression: ρ = 0.53, HADS anxiety: ρ = 0.61, both p < 0.001), the Perceived Stress Scale (PSS-10, ρ = 0.61, p < 0.001) and with CH attack frequency (ρ = 0.29, p < 0.001). Chronic CH patients showed the highest CHIQ scores (25.4 ± 7.9, n = 76), followed by active episodic CH and episodic CH patients in remission (active eCH: 22.2 ± 8.7, n = 79; eCH in remission: 14.1 ± 13.1, n = 127; p < 0.001). Furthermore, the CHIQ was graded into 5 levels from "no to low impact" to "extreme impact" based on the patients' perception. Higher CHIQ grading was associated with higher attack and acute medication frequency, HIT-6™, HADS and PSS scores., Conclusion: The English version of the CHIQ is a reliable, valid, and disease-specific patient-reported outcome measure to assess the impact of headaches on CH patients., (© 2024. The Author(s).)

Background: The adverse events (AEs) after a Coronavirus disease 2019 (Covid-19) Pfizer-Biotech mRNA vaccination present a medical and epidemiological issue of increasing interest. Headache is the most frequent neurological adverse effect and generally the third most common adverse event after a Covid-19 vaccination, but only a few studies focus on the link between headache and other AEs after vaccination. This study aims to investigate the correlation between headaches and Covid-19 vaccination, as well as the possible links between headaches and other AEs after Covid-19 vaccination, thereby helping the management of AEs and avoiding further occurrences., Methods: This study is based on a published questionnaire survey of 1,402 healthcare workers. Our study focused on the 5 questions including 12 AEs and headaches extracted from the questionnaire post the first and second Covid-19 vaccination. The severity of the 12 AEs and headaches could be classified by the participants on a five-step scale: "Not at all", "Little", "Average", "Quite", and "Very" (abbreviated as "N", "L", "A", "Q", "V"). We used the Bowker test to study the comparison of headache severity, indicated on a 5-point Likert scale between the first and second vaccinations. We applied an ordinal logistic regression to the 5 categories with headache severity serving as the dependent variable and the ratings of the other 12 AEs serving as the independent variable to further explore to what extent the severity of the 12 AEs is associated with the severity of headaches. Receiver Operating Characteristic (ROC) analysis was conducted to evaluate the predictive value of the ratings of the 12 AEs to headache severity., Results: We found that participants rated their headaches as more severe after the second vaccination, and participants who reported experiencing fatigue, flu-like symptoms, pain at the injection site, known tension-type headache, fever, dizziness/balance problems and known migraine are associated with headache symptoms., Conclusions: There are clusters of headache-associated AEs post Covid-19 vaccination. The association of various AEs with headaches may be due to similar causative mechanisms., (© 2024. The Author(s).)

Preterm birth is the leading cause of infant morbidity and mortality. There has been an interest in developing prostaglandin F 2α (PGF 2α ) antagonists as a new treatment for preterm birth, although much of the rationale for their use is based on studies in rodents where PGF 2α initiates labour by regressing the corpus luteum and reducing systemic progesterone concentrations. How PGF 2α antagonism would act in humans who do not have a fall in systemic progesterone remains unclear. One possibility, in addition to an acute stimulation of contractions, is a direct alteration of the myometrial smooth muscle cell state towards a pro-labour phenotype. In this study, we developed an immortalised myometrial cell line, MYLA, derived from myometrial tissue obtained from a pregnant, non-labouring patient, as well as a novel class of PGF 2α receptor (FP) antagonist. We verified the functionality of the cell line by stimulation with PGF 2α , resulting in Gα q -specific coupling and Ca 2+ release, which were inhibited by FP antagonism. Compared to four published FP receptor antagonists, the novel FP antagonist N582707 was the most potent compound [F max 7.67 ± 0.63 (IC 50 21.26 nM), AUC 7.30 ± 0.32 (IC 50 50.43 nM), and frequency of Ca 2+ oscillations 7.66 ± 0.41 (IC 50 22.15 nM)]. RNA-sequencing of the MYLA cell line at 1, 3, 6, 12, 24, and 48 h post PGF 2α treatment revealed a transforming phenotype from a fibroblastic to smooth muscle mRNA profile. PGF 2α treatment increased the expression of MYLK , CALD1 , and CNN1 as well as the pro-labour genes OXTR , IL6 , and IL11 , which were inhibited by FP antagonism. Concomitant with the inhibition of a smooth muscle, pro-labour transition, FP antagonism increased the expression of the fibroblast marker genes DCN , FBLN1 , and PDGFRA . Our findings suggest that in addition to the well-described acute contractile effect, PGF 2α transforms myometrial smooth muscle cells from a myofibroblast to a smooth muscle, pro-labour-like state and that the novel compound N582707 has the potential for prophylactic use in preterm labour management beyond its use as an acute tocolytic drug., Competing Interests: Authors WW, JY, YY, PP, AS, and GF were employed by Ferring Research Institute Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hamshaw, Straube, Stark, Baxter, Alam, Wever, Yin, Yue, Pinton, Sen, Ferguson and Blanks.)

People continuously adapt their movements to ever-changing circumstances, and particularly in skills training and rehabilitation, it is crucial that we understand how to optimize implicit adaptation in order for these processes to require as little conscious effort as possible. Although it is generally assumed that the way to do this is by introducing perturbations gradually, the literature is ambivalent on the effectiveness of this approach. Here, we tested whether there are differences in motor performance when adapting to an abrupt compared to a ramped visuomotor rotation. Using a within-subjects design, we tested this question under 3 different rotation sizes: 30-degrees, 45-degrees, and 60-degrees, as well as in 3 different populations: younger adults, older adults, and patients with mild cerebellar ataxia. We find no significant differences in either the behavioural outcomes, or model fits, between abrupt and gradual learning across any of the different conditions. Neither age, nor cerebellar ataxia had any significant effect on error-sensitivity either. These findings together indicate that error-sensitivity is not modulated by introducing a perturbation abruptly compared to gradually, and is also unaffected by age or mild cerebellar ataxia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Accumulating evidence demonstrates a role of the cerebellum in nociception. Some studies suggest that this is mediated via endogenous pain modulation. Here, we used t-DCS to test the effects of modulation of cerebellar function on nociception and endogenous pain modulation. Anodal, cathodal, and sham cerebellar t-DCS were investigated in a cross-over design in 21 healthy subjects. The nociceptive flexor (RIII) reflex, conditioning pain modulation (CPM), and offset analgesia (OA) paradigms were used to assess endogenous pain modulation. Somatosensory evoked potentials (SEPs) and pain ratings were used to assess supraspinal nociception and pain perception, respectively. No significant t-DCS effects were detected when including all t-DCS types and time points (baseline, 0, 30, 60 min post t-DCS) in the analysis. Exploratory analysis revealed an increased RIII reflex size immediately after cathodal t-DCS (compared to sham, P = 0.046, η 2  = 0.184), in parallel with a trend for a decrease in electrical pain thresholds (P = 0.094, η p  = 0.184), in parallel with a trend for a decrease in electrical pain thresholds (P = 0.094, η 2 p  = 0.134), and increased N120 SEP amplitudes 30 min after cathodal compared to anodal t-DCS (P = 0.007, η 2 p  = 0.374). OA was increased after anodal compared to sham stimulation (P = 0.023, η 2 p  = 0.232). Exploratory results suggested that cathodal (inhibitory) cerebellar t-DCS increased pain perception and reduced endogenous pain inhibition while anodal (excitatory) t-DCS increased endogenous pain inhibition. Results are principally compatible with activation of endogenous pain inhibition by cerebellar excitation. However, maybe due to limited t-DCS skull penetration, effects were small and unlikely to be clinically significant., (© 2022. The Author(s).)

Background: Migraine is a brain disorder with recurrent headache attacks and altered sensory processing. Introvision is a self-regulation method based on mindfulness-like perception techniques, developed at the University of Hamburg. Here, we examined the effect of Introvision in migraine prevention., Methods: Migraineurs with at least five headache days per month were block-randomized to the experimental group (EG) or waiting list group (WL), the latter starting Introvision training six weeks after the EG. Participants learned Introvision in six weekly on-site group sessions with video-conference support followed by three individual video-conference sessions. Headache diaries and questionnaires were obtained before Introvision training and three months after the last individual Introvision session., Results: Fifty-one patients completed the study. The primary outcome, headache days of the EG after Introvision training compared to those of the WL before the training, showed no significant effect (10.6 ± 7.7, n = 22; vs. 10.9 ± 6.3, n = 29, p = 0.63; Mann-Whitney-U-Test). The secondary outcome, comparing pooled EG and WL data before and after Introvision training, revealed a significant reduction of headache days (from 11.7 ± 6.5 to 9.8 ± 7.0; p = 0.003; Wilcoxon-paired-Test) as well as of acute medication intake and Headache-Impact-Test 6 (HIT-6) scores and increased self-efficacy as quantified by increased FKMS-scores (FKMS: german short form of the Headache Management Self-Efficacy Scale (HMSE))., Conclusion: Although the study did not reach its primary endpoint, several secondary outcome parameters in the pooled (non-controlled) pre-post analysis showed an improvement with a decrease in monthly headache days by 1.9 days/ month. A larger randomized controlled trial has to corroborate these preliminary findings., Trial Registration: NCT03507400, Registration date 09.03.2018., (© 2023. The Author(s).)

Multivalent interactions are common in biology at many different length scales, and can result in the directional motion of multivalent cargo along substrates. Here, a general analytical model has been developed that can describe the directional motion of multivalent cargo as a response to position dependence in the binding and unbinding rates exhibited by their interaction sites. Cargo exhibit both an effective velocity, which acts in the direction of increasing cargo-substrate binding rate and decreasing cargo-substrate unbinding rate, and an effective diffusivity. This model can reproduce previously published experimental findings using only the binding and unbinding rate distributions of cargo interaction sites, and without any further parameter fitting. Extension of the cargo binding model to two dimensions reveals an effective velocity with the same properties as that derived for the one-dimensional case.

Background: Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'., Methods: We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure., Results: A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% (n = 970) had failed ≥ 1 triptan, 13.1% (n = 300) had failed ≥ 2 triptans (meeting the EHF definition of 'triptan resistance'), and 3.9% (n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency (p < 0.001), intensity (p < 0.05), and disability (p < 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan., Conclusion: In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class., Trial Registration: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081)., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Introduction: In the setting of acute COVID-19 infection, headache occurs in 10-60% of patients and may last for days and, in a smaller proportion of patients, weeks (about 10%). However, it is less recognized that headache may also occur after vaccination with a short latency and may persist for a longer period in a still unclear number of patients., Methods: Retrospective description of headache and course in a case series of 32 outpatients with headache that changed or recurred after COVID-19 vaccination., Results: The majority of patients experienced an exacerbation of migraine headache; rare headache syndromes such as intracranial hypertension or thunderclap headache occurred in 2 patients. Headache manifested in more than 50% of patients within the first 48 h after vaccination. Over 50% of patients who received a triptan improved., Conclusion: The pathophysiological relationship between vaccination and persistent headache is not yet clearly understood. The short latency, partial efficacy of cortisone, and initial findings showing an increase of various inflammatory markers during the course of headache in COVID infection suggest a possible involvement of the innate immune system and here the inflammasome. Furthermore, the response to triptan in a proportion of patients also indicates activation of the trigeminovascular system., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Monoclonal antibodies targeting the CGRP pathway are effective and safe for prophylactic treatment of episodic (EM) and chronic migraine (CM). In case of treatment failure of a CGRP pathway targeting mAb, physician has to decide whether using another anti-CGRP pathway mAb is useful. This interim analysis of Finesse Study evaluates effectiveness of the anti-CGRP mAb fremanezumab in patients with a history of other prior anti-CGRP pathway mAb treatments (switch patients)., Methods: FINESSE, a non-interventional, prospective, multicentre, two-country (Germany-Austria) study observing migraine patients receiving fremanezumab in clinical routine. This subgroup analysis presents data on documented effectiveness over 3 months after the first dose of fremanezumab in switch patients. Effectiveness was evaluated based on reduction in average number of migraine days per month (MMDs), MIDAS and HIT-6 scores changes as well as in number of monthly days with acute migraine medication use., Results: One hundred fifty-three out of 867 patients with a history of anti-CGRP pathway mAb treatment prior to initiation of fremanezumab were analysed. Switch to fremanezumab led to ≥ 50% MMD reduction in 42.8% of migraine patients, with higher response rate in EM (48.0%) than in CM patients (36.5%). A ≥ 30% MMD reduction was achieved by 58.7% in CM patients. After three months, monthly number of migraine days decreased by 6.4 ± 5.87 (baseline: 13.6 ± 6.5; p < 0.0001) in all patients, 5.2 ± 4.04 in EM and 7.7 ± 7.45 in CM patients. MIDAS scores decreased from 73.3 ± 56.8 (baseline) to 50.3 ± 52.9 (after 3 months; p = 0.0014), HIT-6 scores decreased from 65.9 ± 5.0 to 60.9 ± 7.2 (p < 0.0001). Concomitant use of acute migraine medication had decreased from 9.7 ± 4.98 (baseline) to 4.9 ± 3.66 (3 months) (p < 0.0001)., Conclusions: Our results show that about 42.8% of anti-CGRP pathway mAb-non-responder benefit from switching to fremanezumab. These results suggest that switching to fremanezumab may be a promising option for patients experiencing poor tolerability or inadequate efficacy with prior other anti-CGRP pathway mAb use., Trial Registration: FINESSE Study is registered on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS44606)., (© 2023. The Author(s).)

Background: Most migraine patients need an effective acute medication. Real-world data can provide important information on the performance of acute migraine medication in clinical practice., Methods: We used data from the German Migraine and Headache Society Headache Registry, where patients rate efficacy and tolerability of and satisfaction with each of their acute headache medications., Results: A total of 1756 adult migraine patients (females: 85%, age: 39.5 ± 12.8 years, headache days per month: 13.5 ± 8.1) were included. Of these, 93% used acute medication, most frequently triptans (59.3%) and/or non-opioid analgesics (56.4%), and 58.5% rated efficacy as good or very good. This was more frequent for triptans (75.4%) than for non-opioid analgesics (43.6%, p < 0.001). Among non-opioid analgesics, naproxen was rated most effective (61.9% very good or good, p < 0.001 compared to ibuprofen, acetylsalicylic acid and paracetamol). Patient-rated efficacy significantly declined with higher headache frequencies (p < 0.001), and this effect remained significant after omitting patients overusing acute medication., Conclusion: In the present population recruited at specialized headache centers, patients rated triptans as more effective than non-opioid analgesics, naproxen as more effective than ibuprofen, and acute medication efficacy decreased with increasing headache frequency.Trial registration: The German Migraine and Headache Society Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Backgound: Headache disorders are not only among the most prevalent, they are also among the most disabling disorders worldwide. This paper investigates the association between headache impact on daily life and the socioeconomic status (SES) of headache sufferers., Methods: Data stem from a random general population sample in Germany. Respondents who reported having headache for at least a year and were aged ≥ 18 years were included in the study. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey. The impact of headache on daily life was measured using the German version of the Headache Impact Test (HIT-6)., Results: Higher headache impact was found in low and medium SES compared to high SES. After adjustment for sociodemographics, headache-related factors (analgesic use, headache duration, headache frequency, migraine diagnosis), depressive symptoms, physical inactivity and obesity, an increased odds ratio of having higher headache impact in low SES compared to high SES was found: OR = 1.83, 95% CI [1.43, 2.23], p = .014. When the interactions "SES*obesity", "SES*depressive symptoms", and "SES*physical inactivity" were added, the results showed a significant interaction effect of "SES*obesity". Obese persons with low SES were 3.64 times more likely to have higher headache impact than non-obese persons with low SES. No significant differences between obese and non-obese persons were found in the medium and high SES groups., Conclusions: SES is an important factor that should not be neglected in headache awareness campaigns and headache treatment. Longitudinal studies are needed in the future to investigate whether lifestyle interventions, such as weight reduction, can help to reduce headache impact in people in lower SES., (© 2023. The Author(s).)

Temporary and persistent visual phenomena are a frequent reason for a neurological presentation. The diagnosis can usually be made with the help of a structured anamnesis with determination of the time of onset, the course and symptoms as well as the monocular vs. binocular manifestation. The visual aura in migraine is certainly the most frequent entity to be differentiated. In particular, persistent visual phenomena such as visual snow syndrome, hallucinogen persisting perception disorder and the Charles Bonnet syndrome (CBS) seem to be underdiagnosed in clinical practice for various reasons and are probably not that rare. Instrumental diagnostics are mostly used for exclusion diagnostics and are a component of a complete patient education, but can be indicative for certain questions (CBS, epilepsy). This article presents the most frequent visual phenomena from the neurological practice and their differential diagnoses, guided by a case history., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Lung cancer patients are at risk for brain metastases and often succumb to their intracranial disease. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful cell-based immunotherapy for hematological malignancies; however, it remains unclear whether CAR T-cells represent a viable therapy for brain metastases. Here, we established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning-microscopy. This approach enabled in vivo -characterization of fluorescent CAR T-cells and tumor cells on a single-cell level over weeks. Intraparenchymal injection of Lewis lung carcinoma cells (expressing the tumor cell-antigen EpCAM) was performed, and EpCAM-directed CAR T-cells were injected either intravenously or into the adjacent brain parenchyma. In mice receiving EpCAM-directed CAR T-cells intravenously, we neither observed substantial CAR T-cell accumulation within the tumor nor relevant anti-tumor effects. Local CAR T-cell injection, however, resulted in intratumoral CAR T-cell accumulation compared to controls treated with T-cells lacking a CAR. This finding was accompanied by reduced tumorous growth as determined per in vivo -microscopy and immunofluorescence of excised brains and also translated into prolonged survival. However, the intratumoral number of EpCAM-directed CAR T-cells decreased during the observation period, pointing toward insufficient persistence. No CNS-specific or systemic toxicities of EpCAM-directed CAR T-cells were observed in our fully immunocompetent model. Collectively, our findings indicate that locally (but not intravenously) injected CAR T-cells may safely induce relevant anti-tumor effects in brain metastases from lung cancer. Strategies improving the intratumoral CAR T-cell persistence may further boost the therapeutic success., Competing Interests: Tao Xu, No disclosures; Philipp Karschnia, No disclosures; Bruno L. Cadilha, No disclosures; Sertac Dede, No disclosures; Michael Lorenz, No disclosures; Niklas Seewaldt, No disclosures; Elene Nikolaishvili, No disclosures; Katharina Müller, No disclosures; Jens Blobner, No disclosures; Nico Teske, No disclosures; Julika J. Herold, No disclosures; Kai Rejeski, Kite/Gilead: Research funding and travel support, Novartis: Honoraria, BMS/CELGENE: Consultancy, Honoraria; Sigrid Langer, No disclosures; Hannah Obeck, No disclosures; Theo Lorenzini, No disclosures; Matthias Mulazzani, No disclosures; Wenlong Zhang, No disclosures; Hellen Ishikawa-Ankerhold, No disclosures; Veit R. Buchholz, No disclosures; Marion Subklewe, No disclosures; Niklas Thon, No disclosures; Andreas Straube, No disclosures; Joerg-Christian Tonn, Research grants from Novocure and Munich Surgical Imaging, and Royalties from Springer Publisher Intl; Sebastian Kobold, S.K. has received honoraria from TCR2 Inc, Novartis, BMS and GSK, S.K. is an inventor of several patents in the field of immuno-oncology, S.K. received license fees from TCR2 Inc and Carina Biotech, S.K. received research support from TCR2 Inc. and Arcus Bioscience for work unrelated to the manuscript. Louisa von Baumgarten, No disclosures., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Intracellular transport is essential for neuronal function and survival. The most effective plus-end-directed neuronal transporter is the kinesin-3 KIF1C, which transports large secretory vesicles and endosomes. 1-4 Mutations in KIF1C cause hereditary spastic paraplegia and cerebellar dysfunction in human patients. 5-8 In contrast to other kinesin-3s, KIF1C is a stable dimer and a highly processive motor in its native state. 9 Here, we establish a baseline for the single-molecule mechanics of Kif1C. We show that full-length KIF1C molecules can processively step against the load of an optical trap and reach average stall forces of 3.7 pN. Compared with kinesin-1, KIF1C has a higher propensity to slip backward under load, which results in a lower maximal single-molecule force. However, KIF1C remains attached to the microtubule while slipping backward and re-engages quickly, consistent with its super processivity. Two pathogenic mutations, P176L and R169W, that cause hereditary spastic paraplegia in humans , 10 Here, we establish a baseline for the single-molecule mechanics of Kif1C. We show that full-length KIF1C molecules can processively step against the load of an optical trap and reach average stall forces of 3.7 pN. Compared with kinesin-1, KIF1C has a higher propensity to slip backward under load, which results in a lower maximal single-molecule force. However, KIF1C remains attached to the microtubule while slipping backward and re-engages quickly, consistent with its super processivity. Two pathogenic mutations, P176L and R169W, that cause hereditary spastic paraplegia in humans 7 , 8 maintain fast, processive single-molecule motility in vitro but with decreased run length and slightly increased unloaded velocity compared with the wild-type motor. Under load in an optical trap, force generation by these mutants is severely reduced. In cells, the same mutants are impaired in producing sufficient force to efficiently relocate organelles. Our results show how its mechanics supports KIF1C's role as an intracellular transporter and explain how pathogenic mutations at the microtubule-binding interface of KIF1C impair the cellular function of these long-distance transporters and result in neuronal disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20 min. Using group-independent component analysis and dual regression, we extracted the subjects' time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN., Methods: This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition., Discussion: The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER., Trial Registration: The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 ., (© 2022. The Author(s).)

Background: Chiari I malformation typically presents with cough headache. However, migraine-like or tension-type-like headaches may also occur. There are limited publications on Chiari I malformation-associated headache semiologies and the effect of foramen magnum decompression on different headache types., Methods: A retrospective analysis complemented by structured phone interviews was performed on 65 patients with Chiari I malformation, treated at our hospital between 2010 and 2021. Headache semiology (according to ICHD-3), frequency, intensity, and radiological characteristics were evaluated pre- and postoperatively., Results: We included 65 patients. 38 patients were female and 27 male. Mean age was 43.9 ± 15.7 years. Headache was predominant in 41 patients (63.0%). Twenty-one patients had cough headache and 20 had atypical headache (12 migrainous, eight tension-type headache-like). Thirty-five patients with headache underwent surgery. Frequency, intensity, and analgesic use was significantly reduced in cough headache ( p  < 0.001). Atypical headaches improved less ( p  = 0.004 to 0.176). Exploratory analysis suggested that larger preoperative tonsillar descent correlated with larger postoperative headache intensity relief ( p  = 0.025)., Conclusion: Decompression was effective in Chiari I malformation-related cough headache. Atypical headache responded less well, and the causal relation with Chiari I malformation remains uncertain. For atypical headache, decompression should only be considered after failed appropriate preventive therapy and within an interdisciplinary approach involving a neurologist.

Objectives: Recently, a novel clearing system for interstitial solutes of the brain was described as a perivascular pathway named the glymphatic system. Furthermore, lymphatic vessels were found in the meninges to drain interstitial fluids. It is hypothesized that interstitial solutes, such as amyloid β, are firstly processed through the brain by the glymphatic system and secondly drained out of the brain by lymphatic vessels (glymphatic-lymphatic fluid transport system [GLS]). Since then, various neurological disorders, such as Alzheimer disease, have been associated with a dysfunction of the GLS. In the current study, we aimed to establish a clinical magnetic resonance imaging (MRI) study protocol for visualizing lymphatic vessels as part of the GLS in humans. More importantly, we aimed to describe the dynamic changes of a contrast agent in these lymphatic vessels over time., Materials and Methods: Twenty volunteers with an unremarkable neurological/psychiatric history were included in this 3T MRI study. Serial MRI sequence blocks were performed at 3 predefined time points (TPs): TP 1, precontrast MRI before administration of a gadolinium-based contrast agent (GBCA); TP 2, immediately post-GBCA (early ce-MRI); and TP 3, 60 minutes post-GBCA (late ce-MRI). Each MRI block contained the following sequences obtained in the same order: whole-brain 3D T1-MPRAGE, whole-brain 3D T2-FLAIR, focused 2D T2-FLAIR, and whole-brain 3D T1-SPACE. Signal intensity (SI) in compartments of the GLS adjacent to the superior sagittal sinus, gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was calculated by manually placed regions of interest. The time course of the signal intensities was examined by generalized linear mixed models. The data were adjusted for age, cognitive function (Montreal-Cognitive-Assessment test), and sleep quality (Pittsburgh Sleep Quality Index questionnaire)., Results: The GLS was best visualized in the 2D T2-FLAIR and 3D T1-SPACE sequences, enabling further SI measurement. In precontrast (TP 1), the SI within the GLS was significantly higher than in CSF and significantly lower than in GM and WM. In post-GBCA, a significant increase (TP 2) and decrease (TP 3), respectively, of the GLS SI values were noted (86.3 ± 25.2% increase and subsequent decrease by 25.4 ± 9% in the 3D T1-SPACE sequence). The SI values of CSF, GM, and WM did not change significantly between the 3 TPs., Conclusions: A clinical MRI study protocol was established for the visualization of lymphatic vessels as an important part of the GLS and therefore the brain's clearing mechanism of interstitial solutes. Furthermore, dynamic changes in the GLS were described over time, possibly reflecting the clearing function of the GLS. This might constitute the basis for evaluating the GLS function in manifold neurological pathologies in the future., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This study investigates visuospatial memory in patients with unilateral lesions of the temporal lobe and the hippocampus resulting from surgery to treat drug-resistant epilepsy. To detect impairments of visuospatial memory in these individuals, a memory test should be specific to episodic memory, the type of memory in which the hippocampus is crucially involved. However, most known visuospatial memory tests do not focus on episodic memory. We hypothesized that a new sequential visuospatial memory test, which has been previously developed and applied only in healthy subjects, might be suitable to fill this gap. The test requires the subject to reproduce a memorized sequence of target locations in ordered recall by typing on a blank graphics tablet. The length of the memorized sequence extended successively after repeated presentation of a sequence of 20 target positions. The test was done twice on day one and again after one week. Visual working memory was tested with the Corsi block-tapping task. The performance in the new test was also related to the performance of the patients in the standard test battery of the neuropsychological examination in the clinical context. Thirteen patients and 14 controls participated. Patients showed reduced learning speed in the new sequential visuospatial memory task. Right-sided lesions induced stronger impairments than left-sided lesions. After one week, retention was reduced in the patients with left-sided lesions. The performance of the patients in commonly used tests of the neuropsychological standard battery did not differ compared to healthy subjects, whereas the new test allowed discrimination between patients and controls at a high correct-decision rate of 0.89. The Corsi block-span of the patients was slightly shorter than that of the controls. The results suggest that the new test provides a specific investigation of episodic visuospatial memory. Hemispheric asymmetries were consistent with the general hypothesis of right hemispheric dominance in visuospatial processing., Competing Interests: The authors have declared that no competing interests exist.

Background: Although good treatment options exist for many headache disorders, not all patients benefit and disability continues to be large. To design strategies for improving headache care, real-world data observing standard care is necessary. Therefore, the German Migraine and Headache Society (DMKG) has established the DMKG Headache Registry. Here we present methods and baseline data., Methods: Accredited German headache centers (clinic-based or private practice) can offer participation to their patients. Patients provide headache history, current headache load (including a mobile headache diary), medication and comorbidities and answer validated questionnaires, prior to their physician appointment. Physicians use these data as the base of their history taking, and add, change or confirm some central information. Before the next visit, patients are asked to update their data. Patients will continuously be included over the next years., Results: The present analysis is based on the first 1,351 patients (1110 females, 39.6 ± 12.9 years) with a completed first visit. Most participants had a migraine diagnosis. Participants had 14.4 ± 8.5 headache days and 7.7 ± 6.1 acute medication days per month and 63.9% had a migraine disability assessment (MIDAS) grade 4 (severe disability). 93.6% used at least one acute headache medication, most frequently a triptan (60.0%) or non-opioid analgesic (58.3%). 45.0% used at least one headache preventive medication, most frequently an antidepressant (11.4%, mostly amitriptyline 8.4%) or a CGRP(receptor) antibody (9.8%). Most common causes for discontinuation of preventive medication were lack of effect (54.2%) and side effects (43.3%)., Conclusion: The DMKG Headache Registry allows to continuously monitor headache care at German headache centers in both a cross-sectional and a longitudinal approach., Trial Registration: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081 )., (© 2022. The Author(s).)

Introduction: The aim of this analysis is to determine whether regular physical activity is associated with less analgesic use in men and women suffering from headache disorders based on population-based cross-sectional data., Methods: We used data from a random general population sample in Germany that comprised 2477 participants aged ≥ 14 years. A standardized questionnaire addressing headache and headache treatment was filled in during the face-to-face survey., Results: Thirty-nine percent of the participants reported headache. Of these, 37.5% of men and 33.6% of women were physically active. Of the participants with headache, 43.3% reported taking analgesics on < 2 days a month, 40.7% on 2-5 days a month, 10.1% on 6-10 days a month, and 5.9% on > 10 days a month. Frequent headache, severe impact of headache on daily life, and depressive symptoms were associated with higher analgesic use in both men and women. For women, physical inactivity was associated with the frequency of analgesic use adjusted for sociodemographic and headache-related variables. For men, results did not suggest any association between physical inactivity and frequency of analgesic use., Conclusions: There are both sex-unspecific and sex-specific factors associated with analgesic use among men and women with headache. In women with increased analgesic use, promoting physical activity may reduce analgesic use. For men, education about the therapeutic effects of physical activity for headaches is an important resource., (© 2022. The Author(s).)

Friedreich's ataxia (FA) is a hereditary system degeneration, which progressively affects sensory functions such as proprioceptive feedback, which causes progressive ataxia in FA patients. While major clinical features of movement disorders in FA patients have been identified, the underlying impaired neural control is not sufficiently understood. To elucidate the underlying control mechanism, we investigated single-joint movements of the upper limb in FA patients. Small, tolerable force perturbations were induced during voluntary single-joint arm movements to examine the compensatory reaction of the FA patient's motor system. Movement kinematics were measured, and muscle torques were quantified. We first found that as in healthy subjects, unperturbed single-joint movements in FA patients preserved similar temporal profiles of hand velocity and muscle torques, however, scaled in duration and amplitude. In addition, the small perturbations were compensated for efficiently in both groups, with the endpoint error < 0.5° (maximum displacement of 5-15°). We further quantified the differences in movement time, torque response, and displacement between patients and controls. To distinguish whether these differences were caused by a malfunction of top-down control or a malfunction of feedback control, the responses were fitted with a detailed model of the stretch reflex. The model simulations revealed that the feedback delay, but not the feedback gain was affected in FA patients. They also showed that the descending control signal was scaled in time and amplitude and co-contraction was smaller in FA patients. Thus, our study explains how the motor deficits of FA patients result from pathological alterations of both top-down and feedback control., (© 2022. The Author(s).)

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. At group level, we found that the intensity of pain in patients with chronic back pain is encoded in the anterior insular cortex, the frontal operculum, and the pons; the change of pain in chronic back pain and chronic migraine patients is mainly encoded in the anterior insular cortex. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results bridge between clinical observations and neuroimaging; they add to the understanding of chronic pain as a complex and multifaceted disease., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Cluster headache (CH) is a severe, highly disabling primary headache disorder. However, there is little research on CH-related disability, and most of it is based on non CH-specific questionnaires. The aim of this study was to develop a short, CH-specific disability questionnaire., Methods: The 8-item Cluster Headache Impact Questionnaire (CHIQ) was developed based on a literature review and patient and expert interviews. The questionnaire was tested in 254 CH patients (171 males; 47.5 ± 11.4 years; 111 chronic CH, 85 active episodic CH, 52 episodic CH in remission) from our tertiary headache center or from a German support group., Results: Reliability and validity of the CHIQ was evaluated in active episodic and chronic CH patients (n = 196). Internal consistency (Cronbach's α = 0.88) and test-retest reliability (ICC 0.91, n = 41) were good. Factor analysis identified a single factor. Convergent validity was shown by significant correlations with the Headache Impact Test (HIT-6, r = 0.58, p < 0.001), subscales of the depression, anxiety and stress scales (DASS, r = 0.46-0.62; p < 0.001) and with CH attack frequency (r = 0.41; p < 0.001). CHIQ scores significantly differentiated between chronic CH (25.8 ± 6.5), active episodic CH (23.3 ± 6.9) and episodic CH patients in remission (13.6 ± 11.9, p < 0.05 for all 3 comparisons)., Conclusions: The CHIQ is a short, reliable, valid, and easy to administer measure of CH-related disability, which makes it a useful tool for clinical use and research., (© 2022. The Author(s).)

Introduction: Migraine is a neurological disease with a considerable economic and societal burden that negatively impacts quality of life and productivity. Triptans are potent serotonin receptor agonists widely used to treat migraine attacks. Little is known about German patients with migraine diagnosed with triptan contraindications or those who discontinue triptans., Methods: This retrospective observational study identifies adults with migraine from a German sickness fund database (2010-2018). Migraine prevalence was calculated for the database population and extrapolated to the German Statutory Health Insurance (SHI) population. Medication use, proportion and demographics of patients with triptan contraindications, prevalence of triptan discontinuation and use of triptans by patients with contraindications were analysed., Results: In total 120,170 patients with migraine were identified in the database population, of whom 77.7% were female; migraine prevalence was 2.0% (male) and 7.3% (female), leading to an extrapolated 2,923,979 patients with migraine in the entire German SHI population (2019); of these, 14.5% had ≥ 1 triptan contraindication. The most frequent contraindication was a history of stroke/transient ischaemic attack. However, an extrapolated 25.9% of patients who had a triptan contraindication received a triptan prescription following diagnosis. We calculated that 975,698 patients in the entire German SHI population had ever received a triptan, of whom 596,364 did not receive a triptan prescription in the follow-up year. Of these 596,364 individuals, 96.6% continued to receive a migraine diagnosis after their last triptan prescription. These 'triptan discontinuers' were predominantly female (82.6%). Most patients utilized only one specific triptan, with a large majority of ongoing triptan users who had used this specific triptan receiving > 4 prescriptions., Conclusion: We confirm the existence of German patients with migraine and unmet therapeutic needs. These are patients diagnosed with triptan contraindications or patients who have discontinued triptan use despite continued migraine attacks. More research is needed to ascertain reasons for triptan discontinuation and the risk of triptan use by patients with contraindications., (© 2021. The Author(s).)

This study examined saccade adaptation induced by intrasaccadic target steps (ITS). By manipulating the ITS, we investigated potential effects of the consistency of the feedback error on saccade adaptation, which would provide evidence against the linearity of standard models of visuomotor adaptation. Previous studies addressing saccade adaptation arrived at different interpretations, but in these experiments only a single saccade amplitude was trained rather than a variety of saccade amplitudes in random order (mixed training). We extend previous studies by testing for effects of error consistency under additional control conditions described by the factors training protocol (single-amplitude/mixed), ITS direction (onward/backward), and adaptation phase (training/washout). Adaptation dynamics were assessed using a model of "multi-gainfield adaptation" developed by tailoring an existing linear model for visuomotor adaptation of movements with multiple target positions to gain adaptation of saccades with multiple amplitudes. The total adaptive change did not depend on the consistency of the ITS in either mixed or single-amplitude training. The initial adaptation speed was lower with inconsistent ITS. However, the effect on adaptation speed occurred only during amplitude reduction and not during enlargement or washout. These results corroborate the linearity of saccade adaptation in that the mean error is the main factor determining the total adaptive change, independent of error consistency. The multi-gainfield adaptation model was confirmed in that the retention rate and error sensitivity did not depend on the training protocol. The absence of effects of error consistency on saccade adaptation is relevant in the context of adaptive deficits in movement disorders., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Several psychological cofactors of migraine have been identified, but relationships to different headache parameters (e.g., headache frequency vs. headache-related disability) are only incompletely understood., Methods: We cross-sectionally assessed 279 migraine patients at their first presentation at our tertiary headache center. We obtained headache and acute medication frequency, pain intensity, the Migraine Disability Assessment Scale (MIDAS), and the Pain Disability Index (PDI) as headache-related outcomes as well as scores of the Hospital Anxiety and Depression Scale (HADS), the Pain Catastrophizing Scale (PCS), Pain-Related Control Scale (PRCS), and Avoidance Endurance Questionnaire (AEQ) as psychological factors., Results: Linear regression models revealed the highest associations of the psychological factors with the PDI (adjusted R 2  = 0.296, p < 0.001, independent predictors: PCS, AEQ social avoidance, depression) followed by the MIDAS (adjusted R 2  = 0.137, p < 0.001, predictors: depression, AEQ social avoidance) and headache frequency (adjusted R 2  = 0.083, p < 0.001, predictors: depression, AEQ humor/distraction). Principal component analysis corroborated that psychological factors were preferentially associated with the PDI, while the MIDAS loaded together with headache frequency., Conclusion: Our results suggest that psychological factors are more strongly associated with the subjective degree of headache-related disability measured by the PDI than with the days with disability (MIDAS) or the more objective parameter of headache frequency. This once again highlights the need for comprehensive assessment of migraine patients with different headache parameters and the need for considering psychological treatment, especially in patients with high disability., (© 2021. The Author(s).)

Objective: Patients with visual snow syndrome (VSS) suffer from a debilitating continuous ("TV noise-like") visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient's history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds., Methods: Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases., Results: The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20)., Conclusions: This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS., (© 2021. The Author(s).)

First clinical observations of the therapeutic effect of vagus nerve stimulation were of patients who were treated for refractory epilepsy with a fully implanted vagus nerve stimulator, who also reported an improvement of their migraine and cluster headache. With the development of non-invasive vagus nerve stimulation, first clinical studies concerning a possible therapeutic effect in migraine and cluster headache were performed. In a controlled study, transcutaneous cervical vagus nerve stimulation (tcVNS) showed a significant but limited effect in acute treatment of a migraine attack. There was no significant prophylactic effect in episodic migraine. Concerning cluster headache, there was a clear beneficial effect in the prophylaxis of chronic cluster headache and in the attack treatment in episodic cluster headache. There are fewer studies in the literature on the effect of transcutaneous auricular vagus nerve stimulation (taVNS), with a partial overlap with studies on electrical ear acupuncture. In a small controlled clinical trial, there was a significant effect of taVNS in the prevention of chronic migraine. In less defined clinical studies, there were some positive signs that the method may be beneficial in chronic back pain and in unspecific gastro-intestinal pain in adolescents. Based on the available evidence, it is probable that vagus nerve stimulation can have a clinically meaningful influence on pain syndromes, but there are still several questions (e.g. frequency of the stimulation; duration of the stimulation; differential effects of auricular vagus stimulation and cervical vagus stimulation) to answer before vagus stimulation can be used widely in the clinic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Health care costs of migraine constitute a major issue in health economics. Several publications analyzed health care costs for adult migraine patients, based on questionnaires or secondary (health insurance) data. Although migraine often starts already in primary school age, data on migraine related costs in children is scarce. In this paper we aimed to assess the migraine-related health care costs in 6 to 11 year old children in Germany., Methods: Using claims data of a large German health insurer (BARMER), overall annual health care costs of 6 to 11 year old children with a diagnosis of migraine in 2017 (n = 2597) were compared to a control group of 6 to 11 year old children without a headache diagnosis between 2013 and 2017 (n = 306,926). The association of migraine and costs was modeled by generalized linear regression (Gamma regression) with adjustment for sex, age and comorbidities., Results: Children with migraine caused considerably higher annual per capita health care costs than children without a headache diagnosis (migraine group: € 1018, control group: € 618). Excess costs directly related to migraine amounted to € 115. The remaining excess costs were related to comorbidities, which were more frequent in the migraine group. Mental and behavioural disorders constituted the most expensive comorbidity, accounting for € 105 of the € 400 annual excess costs in the migraine group., Conclusion: 6 to 11 year old children with a migraine diagnosis cause significant direct and comorbidity related excess costs in the German health care system., (© 2021. The Author(s).)