Establishing a multidisciplinary specialist centre for fetal alcohol spectrum disorders-Lessons learned from a model project in Germany.

BACKGROUND: Inadequate coordination between relevant professionals hampers the provision of appropriate care for individuals with fetal alcohol spectrum disorder (FASD). Integrated, multidisciplinary care is thus urgently required. Hence, we aimed at establishing the first university-bound, interdisciplinary specialist centre for FASD in Germany, systematically collecting data on its utilisation and evaluation by attendees. METHODS: After our centre started to provide consultation and support services in July 2019 until May 2021, we collected 233 questionnaires on the centre's utilisation (including attendees' sociodemographic characteristics and the topics on which they requested consultation, e.g., general information about FASD, consultation on therapy options, and educational consultation). Ninety-four of 136 individuals who received consultation at our centre submitted an evaluation questionnaire that recorded attendees' satisfaction with the support they had received (e.g., the extent to which the consultation met their needs). RESULTS: Of 233 participants who completed the utilisation questionnaire, 81.8% were female, and 56.7% were aged 40 to 60 years. Moreover, 42% were foster parents, while 38% were professionals. Most attendees had questions on FASD in general as well as on a specific child or adolescent with FASD. Almost three quarters of the attendees requested consultation on adequate therapies for FASD patients, while 64% had questions on parenting issues. The overall quality of the consultation was rated very well. DISCUSSION: Our service was used by both caregivers and professionals who reported numerous and complex concerns and needs. Professionally sound and multidisciplinary services are viable instruments to meet those needs, bearing the potential for quick and notable relief among individuals affected. We propose further advancement of networking and coordination between care providers, the expansion of multidisciplinary services, and securing early diagnosis and consistency of care as relevant steps to even better support children and adolescents with FASD and their families in the future.

Headache frequency and neck pain are associated with trapezius muscle T2 in tension-type headache among young adults.

BACKGROUND: Tension-type headache (TTH) is the most prevalent primary headache disorder. Neck pain is commonly associated with primary headaches and the trigemino-cervical complex (TCC) refers to the convergence of trigeminal and cervical afferents onto neurons of the brainstem, thus conceptualizes the emergence of headache in relation to neck pain. However, no objective biomarkers exist for the myofascial involvement in primary headaches. This study aimed to investigate the involvement of the trapezius muscles in primary headache disorders by quantitative magnetic resonance imaging (MRI), and to explore associations between muscle T2 values and headache frequency and neck pain. METHODS: This cohort study prospectively enrolled fifty participants (41 females, age range 20-31 years): 16 subjects with TTH only (TTH-), 12 with mixed-type TTH plus migraine (TTH+), and 22 healthy controls (HC). The participants completed fat-suppressed T2-prepared three-dimensional turbo spin-echo MRI, a headache diary (over 30 days prior to MRI), manual palpation (two weeks before MRI), and evaluation of neck pain (on the day of MRI). The bilateral trapezius muscles were manually segmented, followed by muscle T2 extraction. Associations between muscle T2 and the presence of neck pain as well as the number of days with headache (considering the 30 days prior to imaging using the headache calendar) were analyzed using regression models (adjusting for age, sex, and body mass index). RESULTS: The TTH+ group demonstrated the highest muscle T2 values (right side: 31.4 ± 1.2 ms, left side: 31.4 ± 0.8 ms) as compared to the TTH- group or HC group (p < 0.001). Muscle T2 was significantly associated with the number of headache days (ß-coefficient: 2.04, p = 0.04) and the presence of neck pain (odds ratio: 2.26, p = 0.04). With muscle T2 as the predictor, the area under the curve for differentiating between HC and the TTH+ group was 0.82. CONCLUSIONS: Increased T2 of trapezius muscles may represent an objective imaging biomarker for myofascial involvement in primary headache disorders, which could help to improve patient phenotyping and therapy evaluation. Pathophysiologically, the increased muscle T2 values could be interpreted as a surrogate of neurogenic inflammation and peripheral sensitization within myofascial tissues.

Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood.

INTRODUCTION: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. MATERIALS AND METHODS: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). RESULTS: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. CONCLUSION: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient's risks and potential medical and psychosocial problems might improve the long-term outcome significantly.

Patients with episodic migraine show increased T2 values of the trapezius muscles - an investigation by quantitative high-resolution magnetic resonance imaging.

BACKGROUND: Neck pain is frequent in patients with migraine. Likewise, evidence for inflammatory processes in the trapezius muscles is accumulating. However, non-invasive and objectively assessable correlates are missing in vivo. METHODS: Twenty-one subjects with episodic migraine (mean age: 24.6 ± 3.1 years, 18 females) and 22 controls (mean age: 23.0 ± 2.2 years, 17 females) without any history of headache prospectively underwent physical examination and quantitative magnetic resonance imaging of the trapezius muscles. A T2-prepared turbo spin-echo sequence was acquired for manual segmentation of the trapezius muscles and extraction of mean T2 values. RESULTS: There were no statistically significant differences regarding age, sex, body mass index, or number of myofascial trigger points (mTrPs) between groups. All patients with migraine presented with mTrPs in the trapezius muscles. T2 of the entire trapezius muscles was significantly higher in the migraine group when compared to controls (31.1 ± 0.8 ms vs. 30.1 ± 1.1 ms; p = 0.002). CONCLUSIONS: Elevated T2 values of the trapezius muscles may indicate subtle inflammatory processes within musculature among patients with migraine because T2 increase is likely to stem from edematous changes. Future work may validate this finding in larger cohorts, but muscle T2 might have potential to develop into a viable in vivo biomarker for muscular affection in migraine.

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized-controlled trial in Germany: "moma - modules on migraine activity".

BACKGROUND: Migraine is common in childhood, peaks in adolescents and persists into adulthood in at least 40% of patients. There is need for early interventions to improve the burden of disease and, if possible, reduce chronification. The aim of the project is to compare two types of ambulatory treatment strategies regarding their effect on headache days and quality of life in 6 to 11 year old children with migraine: 1) the routine care in pediatricians' practices (intervention group A) and 2) a structured interdisciplinary multimodal intervention administered at social pediatric centers (intervention group B). METHODS: The study is a nation-wide cluster-randomized study. Based on the postal codes the regions are randomly assigned to the two intervention-strategies. Children with migraine are recruited in the pediatric practices, as common outpatient-care in the German health-care system. Parents rate headache frequency, intensity and acute medication intake at a daily basis via a digital smartphone application specifically designed for the study. Migraine-related disability and quality of life are assessed every 3 months. Study duration is 9 months for every participant: 3 months of baseline at the pediatric practice (both groups); 3 months of intervention at the pediatric practice (intervention group A) or at the social pediatric center (intervention group B), respectively; 3 months of follow-up at the pediatric practice (both groups). DISCUSSION: Results of the planned comparison of routine care in pediatric practices and interdisciplinary social pediatric centers will be relevant for treatment of children with migraine, both for the individual and for the health care system. TRIAL REGISTRATION: The study was approved by the ethics committee at the Ludwig-Maximilians-University Munich (number 18-804) and was retrospectively registered on 27 April 2021 in the WHO approved German Clinical Trials Register (number DRKS00016698 ).

Total health insurance costs in children with a migraine diagnosis compared to a control group.

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.

[Fetal alcohol spectrum disorders-diagnosis, prognosis, and prevention]. / Fetale Alkoholspektrumstörungen ­ Diagnose, Prognose und Prävention.

Fetal alcohol spectrum disorder is one of the most common chronic diseases at birth. It is very often not or falsely diagnosed. This leads to inadequate, ineffective care and treatment of the affected children as well as to insufficient support of their families. The result is not only a high rate of secondary disorders, but it also leads to fewer opportunities for secondary and tertiary prevention for each child and family. With the right diagnosis these opportunities are guaranteed. The primary prevention in the field of alcohol consumption during pregnancy and fetal alcohol spectrum disorder should be planned and performed by the medical and political partners in a structured interdisciplinary and scientifically based way. Besides health promotion and education of the general population, the knowledge transfer to doctors and other medical, psychological, and pedagogical professionals is of particular relevance.

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

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

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

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

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.

[Fetal alcohol spectrum disorders (FASD) ­ diagnosis, neuropsychological assessment, and symptom-orientated therapy]. / Fetale Alkoholspektrumstörungen ­ Diagnose, neuropsychologische Testung und symptomorientierte Förderung.

According to the GEDA study (Study of Health in Germany), 20 % of all pregnant women show moderate and 8 % risky alcohol consumption. Of the pregnant women, 12 % engage in binge drinking (≥ 5 drinks per occasion less than once per month, 4 % every month and 0.1 % at least every week). According to conservative estimates, approximately 1 % of all children are affected by intrauterine exposure to alcohol. In total, approximately 800,000 million people, thereof 130,000 children, suffer from a fetal alcohol spectrum disorder in Germany. Many of the affected children, however, remain undiagnosed or are properly diagnosed only very late. To date, professionals in the healthcare and social system have not been sufficiently informed about the symptoms and the necessary diagnosis. This review illustrates the medical and psychological possibilities and necessities regarding children and adolescents with FASD. Early diagnosis and living in a supportive and violence-free environment are the most important protective factors for the long-term outcome of patients with FASD.

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

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

Vestibular Migraine in Children and Adolescents.

PURPOSE OF REVIEW: The goal of this review is to provide an actualized overview on vestibular migraine in childhood and adolescence, with focus on the epidemiology and clinical presentation as well as its treatment. RECENT FINDINGS: Vertigo spells in childhood can evolve into other periodic syndromes and/or migraine types and persist even into adulthood. Vestibular migraine (VM) and benign paroxysmal vertigo are the most common causes of vertigo in children and adolescents. The diagnostic criteria for VM are dizziness and vertigo, headache, phonophobia and photophobia, and visual aura. The prevention of attacks is the treatment for children and adolescents with VM, as is recommended for migraine with or without aura. Thus, non-pharmacological measures are the first-line option; when these measures fail or daily activities are notably affected, drugs are administrated. Psychological assessment and cognitive behavioral therapy are also important therapeutic measures in this patient group. There is still insufficient research on VM in children and adolescents; future studies on clinical presentation, evolvement, and specific treatment are necessary.

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

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

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

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

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

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

Prognostic factors for long-term outcome in children with fetal alcohol spectrum disorders.

INTRODUCTION: Known protective factors for long-term outcome in children with fetal alcohol spectrum disorders (FASD) are early diagnosis and a stable, non-violent supportive environment. Which factors contribute to the stability of care is not yet known. Thus, the aim of our study was to evaluate whether the age at diagnosis and the complexity of brain dysfunction play a role for placement changes in children with FASD. MATERIALS AND METHODS: An online survey was conducted among caregivers and professionals caring for children with FASD and seeking help at the German FASD Competence Centre Bavaria (N = 232). The survey collected information about diagnosis, brain dysfunctions, behavioural factors influencing everyday life and changes of placement. The association of timing of diagnosis, brain dysfunctions and neurobehavioral impairment with changes of placement (<2 vs. 2 or more changes) was evaluated via logistic regression models. RESULTS: About 50% of the children received their diagnosis of FASD after the age of 5 years. The complexity of brain dysfunctions in children with FASD affecting everyday life was high. 15% of the children experienced four or more changes of placement. Children with more neuropsychological impairments experienced more changes of placement (OR: 2.53, 95% CI: 1.36-4.71). CONCLUSIONS: Even though our results need to be interpreted with caution due to methodological limitations such as the use of a convenience sample and limited statistical power, they imply that severely affected children with FASD experience a less stable environment. These children may therefore be at high risk for a negative prognosis. To warrant a better prognosis for the affected children, professionals urgently need to pay attention to early recognition and the complexity of neuropsychological impairments in children with FASD as well as to the support that caregivers urgently need.

Neuromodulation in Pediatric Migraine using Repetitive Neuromuscular Magnetic Stimulation: A Feasibility Study.

Migraine has a relevant impact on pediatric health. Non-pharmacological modalities for its management are urgently needed. This study assessed the safety, feasibility, acceptance, and efficacy of repetitive neuromuscular magnetic stimulation (rNMS) in pediatric migraine. A total of 13 patients with migraine, ≥6 headache days during baseline, and ≥1 myofascial trigger point in the upper trapezius muscles (UTM) received six rNMS sessions within 3 weeks. Headache frequency, intensity, and medication intake were monitored using headache calendars; headache-related impairment and quality of life were measured using PedMIDAS and KINDL questionnaires. Muscular involvement was assessed using pressure pain thresholds (PPT). Adherence yielded 100%. In 82% of all rNMS sessions, no side effects occurred. All participants would recommend rNMS and would repeat it. Headache frequency, medication intake, and PedMIDAS scores decreased from baseline to follow-up (FU), trending towards statistical significance (p = 0.089; p = 0.081, p = 0.055). A total of 7 patients were classified as responders, with a ≥25% relative reduction in headache frequency. PPT above the UTM significantly increased from pre- to post-assessment, which sustained until FU (p = 0.015 and 0.026, respectively). rNMS was safe, feasible, well-accepted, and beneficial on the muscular level. The potential to reduce headache-related symptoms together with PPT changes of the targeted UTM may underscore the interplay of peripheral and central mechanisms conceptualized within the trigemino-cervical complex.

Transcranial magnetic stimulation as a feasible, non-invasive, neuromodulatory intervention in fetal alcohol spectrum disorders. A very first proof of concept.

INTRODUCTION: A neurobiological feature of Fetal Alcohol Spectrum Disorder (FASD) is a global decrease in neuronal connectivity, which leads to significant impairments in everyday functionality. Non-invasive repetitive transcranial magnetic stimulation (rTMS) could potentially positively influence neuronal plasticity but has not yet been studied in FASD. The present trial addresses this gap, making it the first-ever study of rTMS in FASD. MATERIALS AND METHODS: The prospective clinical trial was conducted at the LMU University Hospital Munich and enrolled eight FASD participants aged 6-16. Six sessions of 1 Hz-rTMS over the left dorsolateral prefrontal cortex were administered two times a week for three weeks consisting of 1500 pulses at 90 % of resting motor threshold in four trains of 375s. Outcome measures investigated feasibility and treatment response of rTMS on executive functions, attention/impulsivity, social-emotional regulation and quality of life (QoL) via standardized tests and the FASD parents' app. RESULTS: Adherence and retention rate were 100 %. Adverse events (AEs) were mild and self-limiting, resulting in a per-session risk of 53.3 %, with local paraesthesia accounting for 54.2 % of the AEs. There were individual relevant but no significant group-level improvements in the investigated functional cerebral domains or participants' QoL. The FASD parents' app showed no significant change in participants' daily functioning or caregivers' QoL. Caregivers' parental stress decreased significantly. CONCLUSION: FASD is a very complex disorder that is difficult to treat. In addition, comorbidities as atypical responses to pharmacotherapies are frequent. For this reason, non-invasive, innovative therapies for children with FASD have to be developed. For the first time, rTMS was shown to be safe, tolerable, and acceptable and thus well feasible in paediatric patients with FASD. Further clinical studies with larger samples are needed to identify effective stimulation protocols and to evaluate treatment response.