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

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

Repetitive Peripheral Magnetic Stimulation (rPMS) in Subjects With Migraine-Setup Presentation and Effects on Skeletal Musculature.

Purpose: Repetitive peripheral magnetic stimulation (rPMS) has been successfully applied recently in migraineurs to alleviate migraine symptoms. Symptom relief has been achieved by stimulating myofascial trigger points (mTrPs) of the trapezius muscles, which are considered part of the trigemino-cervical complex (TCC). However, effects on musculature have not been assessed in detail, and the specificity of effects to muscles considered part of the TCC yet has to be elucidated. Against this background, this study presents the setup of rPMS in migraine and evaluates effects on skeletal musculature. Materials and Methods: Thirty-seven adults (mean age: 25.0 ± 4.1 years, 36 females) suffering from migraine and presenting mTrPs according to physical examination underwent rPMS either to mTrPs in the trapezius muscles (considered part of the TCC; n = 19) or deltoid muscles (considered not part of the TCC; n = 18) during six sessions over the course of 2 weeks. Standardized questionnaires were filled in to assess any adverse events and experience with rPMS as well as satisfaction and benefits from stimulation. Algometry was performed to evaluate changes in pressure pain thresholds (PPTs). Results: All stimulation sessions were successfully performed without adverse events, with 84.2% of subjects of the trapezius group and 94.4% of subjects of the deltoid group describing rPMS as comfortable (p = 0.736). Muscular pain or tension improved in 73.7% of subjects of the trapezius group and in 61.1% of subjects of the deltoid group (p = 0.077). PPTs of the trapezius muscles clearly increased from the first to the last stimulation sessions-regardless of the stimulated muscle (rPMS to the trapezius or deltoid muscles). However, depending on the examined muscles the increase of PPTs differed significantly (subjects with stimulation of trapezius muscles: p = 0.021; subjects with stimulation of deltoid muscles: p = 0.080). Conclusion: rPMS is a comfortable method in migraineurs that can improve local muscular pain or tension. Furthermore, it is able to increase directly and indirectly the PPTs of the trapezius muscles (considered part of the TCC) when applied over mTrPs, supporting the role of the TCC in migraineurs.

Quantitative magnetic resonance imaging of the upper trapezius muscles - assessment of myofascial trigger points in patients with migraine.

BACKGROUND: Research in migraine points towards central-peripheral complexity with a widespread pattern of structures involved. Migraine-associated neck and shoulder muscle pain has clinically been conceptualized as myofascial trigger points (mTrPs). However, concepts remain controversial, and the identification of mTrPs is mostly restricted to manual palpation in clinical routine. This study investigates a more objective, quantitative assessment of mTrPs by means of magnetic resonance imaging (MRI) with T2 mapping. METHODS: Ten subjects (nine females, 25.6 ± 5.2 years) with a diagnosis of migraine according to ICHD-3 underwent bilateral manual palpation of the upper trapezius muscles to localize mTrPs. Capsules were attached to the skin adjacent to the palpated mTrPs for marking. MRI of the neck and shoulder region was performed at 3 T, including a T2-prepared, three-dimensional (3D) turbo spin echo (TSE) sequence. The T2-prepared 3D TSE sequence was used to generate T2 maps, followed by manual placement of regions of interest (ROIs) covering the trapezius muscles of both sides and signal alterations attributable to mTrPs. RESULTS: The trapezius muscles showed an average T2 value of 27.7 ± 1.4 ms for the right and an average T2 value of 28.7 ± 1.0 ms for the left side (p = 0.1055). Concerning signal alterations in T2 maps attributed to mTrPs, nine values were obtained for the right (32.3 ± 2.5 ms) and left side (33.0 ± 1.5 ms), respectively (p = 0.0781). When comparing the T2 values of the trapezius muscles to the T2 values extracted from the signal alterations attributed to the mTrPs of the ipsilateral side, we observed a statistically significant difference (p = 0.0039). T2 hyperintensities according to visual image inspection were only reported in four subjects for the right and in two subjects for the left side. CONCLUSIONS: Our approach enables the identification of mTrPs and their quantification in terms of T2 mapping even in the absence of qualitative signal alterations. Thus, it (1) might potentially challenge the current gold-standard method of physical examination of mTrPs, (2) could allow for more targeted and objectively verifiable interventions, and (3) could add valuable models to understand better central-peripheral mechanisms in migraine.

Surviving murine experimental sepsis affects the function and morphology of the inner ear.

Severe sepsis is known to result in various neurological long-term deficits in human. Recently, a link between severe, lethal sepsis and significant hearing loss with correlating histomorphological inner ear changes in mice (C57BL/6) was observed. However, if similar observations can be made in severe, non-lethal sepsis in mice is unclear. This study evaluates mice after severe, non-lethal sepsis for analogue functional and histomorphological alterations of the inner ear.A total of 63 C57BL/6 mice were included in the study. All underwent an initial hearing test with auditory brainstem response on day 1. In 35 mice sepsis was induced by cecal ligation and puncture (CLP), in 15 sham surgery was performed and 13 served as healthy control. A second hearing test was performed on day 7. All mice were sacrificed afterwards for further histomorphological evaluation of the inner ears. Immunohistochemical analysis with apoptotic markers Cleaved-caspase 3, BAX and BCL-2 were performed to identify structural inner ear damage.Of all CLP mice, 21/35 (60.0%) died due to the induced sepsis. Of the surviving CLP mice, 14/35 (40.0%), post-treatment hearing thresholds differed significantly from the sham and control mice (P<0.001). Positive immunostaining at different inner ear structures, like the spiral ligament or the supporting cells could be observed. The percentage of the immunostained positive area in the spiral ligament significantly correlated with the grade of hearing loss for BAX (P=0.027) and Cleaved-caspase 3 (P=0.024) but not for BCL 2 (P>0.05).The present data suggests that severe, non-lethal sepsis in mice results in significantly elevated hearing thresholds. A positive labelling for the pro-apoptotic markers BAX and Cleaved-caspase 3 suggested the induction of apoptosis in inner ear.