BackgroundLow-glycaemic diet may alleviate migraine; however, individual blood glucose variability can affect efficacy. In this open-label randomised controlled trial in Germany, we assessed whether the digital therapeutic (DTx) sinCephalea, which delivers personalised low-glycaemic nutritional recommendations supported by intermittent continuous glucose monitoring (CGM), reduces migraine frequency compared with a design-matched control application.MethodsThis open-label trial in Germany assessed the DTx sinCephalea for migraine prevention. Adults aged 18-65 years with episodic migraine were randomised 1:1 (in addition to standard treatment) to the digital therapeutic (intervention) or a design-matched control application. Patients completed a daily headache and medication diary, and 4-weekly patient-reported outcome questionnaires. Adherence to nutritional recommendations was monitored. Primary endpoint (Week 12): change from baseline in monthly migraine days (every 4 weeks) for intervention versus control. Secondary endpoints: change from baseline in monthly migraine days in patients with ≥50% adherence to nutritional recommendations, 30% response rates, migraine- and headache-related impairment, quality-of-life, and acute medication use for intervention versus control. Adverse events were recorded.Results842 patients were randomised between July 2021 and August 2023 (full analysis set: intervention = 416; control = 419). There were significantly greater reductions in monthly migraine days at week 12 for intervention versus control (mean [SD] change: 1.7 [3.4] versus 1.2 [3.2] days; between-group difference estimate: -0.53 [95% CI -0.98 to -0.09]; p = 0.0195) with similar monthly migraine days reductions observed in adherent patients (p = 0.0062; adjusted α = 0.05). Response rate was 54.9% (185/337) in intervention versus 42.9% (168/392) in control (odds ratio: 1.63 [95% CI 1.21-2.19]; p = 0.0012; adjusted α = 0.0125). Migraine- and headache-related impairment were lower at week 12 for intervention versus control (p = 0.0247, adjusted α = 0.0167and p = 0.0001, adjusted α = 0.01, respectively). There was no significant difference in quality-of-life or acute medication use and no digital therapeutic-related adverse events.ConclusionPersonalised nutrition, supported by intermittent CGM, via the DTx sinCephalea, was efficacious for migraine prevention without DTx-related adverse events. This study provides evidence in support of the link between diet and migraine frequency and symptoms. Additionally, as this is a non-pharmacological treatment with no DTx-related side effects, it may be an attractive option for patients. DTx could also reduce the burden of migraine on healthcare systems by providing a scalable, remote, non-invasive and convenient treatment option.

Unter trigeminoautonomen Kopfschmerzen versteht man eine Gruppe von Kopfschmerzerkrankungen, die mit stärksten attackenartigen periorbitalen Schmerzen verbunden mit autonomen Begleitsymptomen wie Augentränen oder Nasenlaufen einhergehen. Insgesamt werden vier solcher Kopfschmerzarten (Clusterkopfschmerz, paroxysmale Hemikranie, SUNA/SUNCT, Hemicrania continua) unterschieden, wobei sich diese v. a. im Zeitmuster unterscheiden. Die Trigeminusneuralgie gehört ausdrücklich nicht zu diesen Erkrankungen. Heutzutage liegen evidenzbasierte Therapieempfehlungen vor, mit denen die meisten Betroffenen gut behandelt werden können. Dabei kommen sowohl medikamentöse als auch interventionelle Verfahren zum Einsatz. Einen besonderen Stellenwert hat das Schmerzmittel Indometacin, das bei einigen dieser Formen spezifisch und vollständig wirksam ist. Bei attackenartigen schwersten Kopfschmerzerkrankungen, die nicht typisch für das eigene Fachgebiet sind, sollte immer eine Vorstellung bei einem Neurologen oder in einer Schmerzambulanz erwogen werden.

Background Autonomic symptoms are mandatory for making the diagnosis of a trigemino-autonomic cephalalgia (TAC). These symptoms can occasionally also occur in migraine and facial pain disorders. This leads to the question whether the trigeminal pain itself can induce autonomic symptoms also in healthy subjects. Methods We enrolled healthy subjects without a history of migraine or a TAC and provoked severe trigeminal pain by injection of 0.05 ml capsaicin (0.01%) into the right forehead. Autonomic symptoms occurring at the right eye or right nostril were registered until they disappeared. We also calculated an autonomic score for the frequency and duration of autonomic symptoms in an individual. Results We enrolled 60 healthy volunteers (30 male, 30 female; mean age 28 +/- 5 years). All but two subjects developed at least one autonomic symptom after injection of capsaicin. One minute after injection, the pain was rated as 9.2 +/- 1.1 and 8.5 +/- 1.2 (scale from 0 to 10) in female and male subjects, respectively. The autonomic score was 4.4 +/- 1.6 and 1.7 +/- 0.9 for female and male subjects, respectively. All differences between female and male subjects were significant. Pain rating and autonomic score showed a significant positive correlation which remained significant even after adjusting for sex. Conclusions Severe trigeminal pain was accompanied by autonomic symptoms in almost all subjects in this experiment. The pain rating and the severity of autonomic symptoms were significantly higher in female subjects than in male. The higher the pain the more severe was this autonomic activation. We conclude that activation of autonomic symptoms is an unspecific consequence of severe trigeminal pain. This does, however, not exclude the possibility that primary headache disorders might have an independent anatomic pathway to induce autonomic symptoms because these symptoms can, although very rarely, also occur without pain.

BACKGROUND:Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear. METHODS:This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024. The study included 4552 adults (2005 female; median age, 73 years) with ischemic stroke and no seizure history. Seizures were classified using International League Against Epilepsy definitions. We examined ASyS occurring within 7 days after stroke. The main outcomes were all-cause mortality and epilepsy. Validation of the updated SeLECT score (SeLECT-ASyS) was performed in 3 independent cohorts (Switzerland, Argentina, and Japan) collected between 2012 and 2024, including 74 adults with ASyS. RESULTS:The 10-year risk of poststroke epilepsy ranged from 41% to 94%, and mortality from 36% to 100%, depending on ASyS type and timing. ASyS on stroke onset day had a higher epilepsy risk (adjusted hazard ratio [aHR], 2.3 [95% CI, 1.3-4.0]; P=0.003) compared with later ASyS. Status epilepticus had the highest epilepsy risk (aHR, 9.6 [95% CI, 3.5-26.7]; P<0.001), followed by focal to bilateral tonic-clonic seizures (aHR, 3.4 [95% CI, 1.9-6.3]; P<0.001). Mortality was higher in those with ASyS presenting as focal to bilateral tonic-clonic seizures on day 0 (aHR, 2.8 [95% CI, 1.4-5.6]; P=0.004) and status epilepticus (aHR, 14.2 [95% CI, 3.5-58.8]; P<0.001). The updated SeLECT-ASyS model, available as an application, outperformed a previous model in the derivation cohort (concordance statistics, 0.68 versus 0.58; P=0.02) and in the validation cohort (0.70 versus 0.50; P=0.18). CONCLUSIONS:ASyS timing and type significantly affect epilepsy and mortality risk after stroke, improving epilepsy prediction and guiding patient counseling.

Cluster headache (CH) is a rare primary headache disorder characterized by recurrent episodes of strictly unilateral excruciating pain accompanied by trigemino-autonomic signs, which significantly impacts the quality of life, social interactions, and occupational functioning of those who are affected. To promote a better understanding of this disabling condition and to foster research on the topic, this review provides a comprehensive description of the hallmarks of CH, including its clinical presentation, diagnostic challenges, pathophysiology, and current and novel therapeutic targets. It concludes by describing the disease burden and advocating for significant improvements in healthcare systems, and promoting health equity, as well as reducing stigma. Despite its distinctive clinical and chronobiological features, CH may be mistaken for other primary headache disorders or different types of orofacial pain. Key pathogenic characteristics include the activation of the trigeminal-autonomic system with the release of several neuropeptides, the involvement of the hypothalamus in regulating the circadian rhythm, genetic variants, and the mesolimbic system. Both invasive and non-invasive neuromodulation treatments have been used to target the trigemino-cervical, parasympathetic, and hypothalamic systems. Additionally, novel therapeutic targets are currently being study. Alongside canonical therapies, several complementary approaches have been explored over the years, with most evidence deriving from uncontrolled research involving individuals who do not respond to standard pharmacological treatments. Despite advancements in our understanding of this complex disease, CH continues to pose considerable social, economic, and psychological challenges. Advocacy is essential and should prioritize early diagnosis, alleviate stigma, provide specialized training for healthcare professionals, and offer support to and through patient associations. CH is characterised by a complex, multifactorial, pathophysiology that is still not fully understood. Precise diagnosis, additional research studies, and robust psychosocial and institutional support are necessary to improve the quality of life for individuals affected by this debilitating condition.

Epilepsy or epileptic seizures have only rarely been described in the classical opera. Four operas were detected, in which epileptic seizures are described also by musical means. Three of them (“Der Golem” by Eugen d'Albert; “Idiot” by Mieczyslaw Weinberg; “Otello” by Giuseppe Verdi) describe a generalized tonic-clonic epileptic seizure by a descending chromatic scale. One opera (“The turn of the screw” by Benjamin Britten) describes temporal lobe seizures by overtone music played by the instrument celesta.

OnabotulinumtoxinA is a potent inhibitor of muscle contraction that acts by preventing the release of acetylcholine at the neuromuscular junction. In pain states such as migraine, its mechanism of action is not yet fully elucidated and probably relates to the phenomena of central and peripheral sensitization within the trigeminal system. Migraine is a prevalent and disabling disorder and, especially in its variant of chronic migraine (CM), is associated with relevant symptomatic and socioeconomic burden, the objective of preventive treatment being to reduce the frequency, duration, or severity of migraine attacks. OnabotulinumtoxinA, administered by intramuscular injection, is approved for the prevention of CM and is among the most utilized preventive treatments in CM and fundamental to clinical practice. The efficacy and safety of OnabotulinumtoxinA in the treatment of CM have been verified by the PREEMPT 1 and 2 studies and confirmed by the real-world studies that followed, including the COMPEL, REPOSE, and CM PASS. OnabotulinumtoxinA not only reduces headache days but also leads to improvement in functioning and quality of life, thereby reducing migraine impact. Data about its pathophysiology, efficacy, and its place in CM treatment in the era of CGRP monoclonal antibodies are reviewed and discussed here.

The ObserVational survey of the Epidemiology, tReatment and Care Of MigrainE (OVERCOME) European Union (EU) is part of an overarching population-based study program that also includes the United States and Japan. Here, we report data on the migraine/severe headache burden and the use of acute medication and healthcare resources in Spain and Germany. OVERCOME (EU) was an online, non-interventional, cross-sectional survey conducted in adults in Spain and Germany between October 2020 and February 2021. A total migraine cohort was established based on health survey participants who reported headache/migraine in the last 12 months AND identified as having migraine based on modified International Classification of Headache Disorders, third edition criteria OR self-reported physician diagnosis. Data were analyzed for the total migraine cohort and the subcohort with moderate to severe headache attacks, with average pain severity ≥ 5 points, pain duration ≥ 4 h, and at least moderate disability due to migraine [Migraine Disability Assessment (MIDAS) score ≥ 11] over the past 3 months. Pain of moderate or severe intensity was the most frequent symptom in the total migraine cohort (n = 19,103/20,756; 92.0

ZUSAMMENFASSUNGEin Zusammenhang zwischen Sport und Kopfschmerz ergibt sich im Wesentlichen auf 2 Ebenen: Kann Sport zu Kopfschmerzen führen? Kann Sport in der Therapie von Kopfschmerzen eingesetzt werden? Der Artikel beleuchtet diesen Zusammenhang am Anfang aus historischer und systematischer Sicht. Die Frage der Kopfschmerzauslösung beim Sport und der Reaktion von Kopfschmerzpatienten auf körperliche Belastung sowie Geschlechtsunterschiede werden diskutiert. Schließlich wird die Evidenz für den Einsatz von Sport in der Kopfschmerztherapie kritisch dargestellt, nicht zuletzt vor dem Hintergrund, dass die aktuelle DGN-DMKG-Leitlinie für die Behandlung der Migräne regelmäßigen Ausdauersport zur Prophylaxe empfiehlt. Abschließend sollen in einem Expertenkonsens solche Empfehlungen dann differenziert vorgestellt werden.

Objective: The impact of listening to music on pain perception has been evaluated using questionnaires and numeric/visual analogue scales. In this study, the impact of music perception on sensory pain functions was measured by means of quantitative sensory testing. Methods: We enrolled 10 female and 10 male healthy subjects (10 of them were professional musicians). All subjects underwent, in total, four quantitative sensory testing measures (first: baseline; second: after pleasant music [Johannes Brahms, 3rd symphony, 3rd movement]; third: after unpleasant music [Krzysztof Penderecki, Threnos]; fourth: after a longer break). The pleasantness of music was evaluated using the Ertel differential scale. Results: After the participants listened to pleasant music, an increased sensitivity to cold stimuli (both threshold and pain), to mechanical stimuli (only for threshold), and to repeated stimuli (wind-up reaction) was noted. Listening to unpleasant music was not associated with changes in sensitivity. We did not observe any significant differences between male and female subjects or between musicians and non-musicians. There was no significant correlation between the rating of the music as pleasant/unpleasant and the different quantitative sensory testing measures. Conclusions: Our data show that listening to music inducing a pleasant feeling can increase the sensitivity to stimuli applied during a quantitative sensory testing session. This should be considered when performing or interpreting quantitative sensory testing examinations. Interestingly, this finding is in contrast to the observation that listening to music can decrease pain perception during painful procedures.

ZUSAMMENFASSUNG Die neue ICD-11 bringt im Kapitel der Neurologie einige Änderungen. So finden sich die Schlaf-Wach-Störungen und die infektiösen Erkrankungen des Nervensystems nicht mehr in dem Kapitel der Neurologie. Dagegen sind die zerebrovaskulären Krankheiten in das Kapitel der Neurologie übergeleitet worden. Die Einteilung der einzelnen Krankheitsbilder erfolgt jetzt nach den großen klassischen Gruppen, z. B. den Bewegungsstörungen oder den demyelinisierenden Krankheiten. Insgesamt geht der Trend dahin, dass klinisch und pathophysiologisch ähnliche Krankheiten in ein Unterkapitel zusammengefasst werden. Gerade in der Neurologie können sehr viele Querverweise und Doppeldiagnosen vergeben werden. Insbesondere in der Schlaganfallmedizin bietet die neue ICD-11 vielfältige Möglichkeiten der Kodierung auf klinischer und parallel auf pathophysiologischer Ebene. Derzeit befindet sich die deutsche Übersetzung der ICD-11 in Bearbeitung, hier könnten (und sollten) noch einige Verbesserungen vorgenommen werden.