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Objectives The pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS. Methods Sixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis. Results Quantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (p Conclusion We found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.

Migraine is associated with a high individual level of suffering. Therefore, an effective preventive treatment is highly important. The spectrum of classical prophylactic drugs has now been expanded to include monoclonal antibodies against calcitonin gene-related peptide (CGRP) and its receptor. These antibodies have shown reliable efficacy compared to placebo and a rapid onset of action with a low rate of side effects and negligible interactions in pivotal studies. Recently, the efficacy of the antibody was shown in many studies even on drug-refractory migraine and migraine associated with medication overuse. Comprehensive head to head comparisons with previously established drugs and among the antibodies are not yet available; however, initial studies suggest better tolerability and efficacy compared to conventional drugs and other antibodies. The role of antibodies in established treatment cascades still needs to be clarified.Die Migräne geht mit einem starken individuellen Leidensdruck einher, weshalb einer effektiven prophylaktischen Behandlung hohe Bedeutung zukommt. Das Spektrum klassischer Prophylaktika wird nun durch monoklonale Antikörper gegen das „calcitonin gene-related peptide“ (CGRP) und dessen Rezeptor erweitert. Die Antikörper wiesen in den Zulassungsstudien eine zuverlässige Wirksamkeit gegenüber Placebo und einen raschen Wirkeintritt bei niedriger Nebenwirkungsrate und vernachlässigbaren Interaktionen auf. Zudem wurde in zahlreichen Studien unter anderem eine Wirkung der Antikörper auch bei therapierefraktärer Migräne nachgewiesen. Umfassende direkte Vergleiche der Antikörper untereinander und mit den bisher etablierten Medikamenten gibt es noch nicht. Erste Studien legen aber eine bessere Verträglichkeit und Wirksamkeit gegenüber etablierten Medikamenten oder anderen Antikörpern nahe. Die Rolle der Antikörper in den etablierten Therapiekaskaden bleibt zu klären.

Background The use of new concepts in patient care, such as video-consultations, reminder systems, and online evaluation portals, is becoming increasingly important in the physician–patient relationship and outpatient care. This study examines the acceptance of these approaches in a neurological setting and determines the patients’ preferences. Methods We analyzed 16 guideline-based qualitative interviews with neurological patients using qualitative content analysis (inductive category formation). Results The patients commented on the benefits and challenges of integrating new concepts of medical care. They identified advantages of telemedical care, including time savings (7 of 16; 43,8%) for both the patient and the physician, the prospect of more intensive (4 of 16; 25%) care, and the possibility for a quick response in case of urgent needs (3 of 16; 18.8%). Several challenges were reported, such as the limitations for patients with psychiatric (2 of 16; 12.5%) or complex diseases (4 of 16; 25%) and limited options for diagnostic procedures (such as physical examination (4 of 16; 25%)). For individual neurological patients' needs, telemedical and telecommunication structures could be discussed, which support the patients' specific requirements, such as answering questions while having a recall (2 of 16; 12.5%) and avoiding the journey (8 of 16; 50%). Also, patients are rejecting evaluation portals and are skeptical of telecare in the treatment of neurological diseases. Discussion The perception of telemedical care and the successful integration of new medical care concepts depend on fulfilling the individual patient’s needs. Regardless of the preferred nature of physician–patient interactions, there are specific instruments that can intensify the relationship. These individual needs of the patients must be inquired about and accommodated for. Conclusions For the first time, we could characterize the properties of optimal telemedical care for neurological patients. Interviews like the ones we conducted should be repeated during and after the pandemic, referring to our results and compare.

Background Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT. Methods In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity. Results The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder. Conclusion Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate. Trial registration NCT01892345 (ClinicalTrials.gov).

Migraine is a frequently underdiagnosed disease that is associated with a high burden on affected patients. There are a variety of prophylactic treatment options available, that have been expanded with the introduction of the CGRP-(receptor-)antibodies.Status of pharmacologic and nonpharmacologic preventive treatment in migraine therapy.Analysis and evaluation of internationally published articles concerning preventive treatment of episodic and chronic migraine.There are many approved medications for migraine prophylaxis with different evidence. The possibilities were further expanded with CGRP antibodies. Comparative studies of the new antibodies with previous prophylactic drugs have not yet been published, so it's unclear whether the antibodies are therapeutically superior. What should be emphasized is their rapid onset of action and their good tolerance. Basically, an individual choice of prophylaxis, which is based on affectedness, comorbidities and comedication, makes sense. In addition, a combination with nondrug measures is always mandatory.A variety of medicinal and non-medicinal measures are available for the treatment of migraine, which should be used multimodally.

Neuromodulatory approaches add to our armamentarium of therapeutic tools for the treatment of primary headaches. This review provides a comprehensive overview of current controlled studies on the different neuromodulation techniques and recommendations for clinical practice.Evidence for efficacy of transcutaneous vagal nerve stimulation (tVNS) is limited to acute use in migraine with ambiguous results and episodic cluster headache as well as chronic cluster headache if applied in addition to conventional treatment. Transcutaneous stimulation of the supraorbital and supratrochlear nerve was effective in both acute and preventive stimulation (the latter with ambiguous results) in episodic migraines. Thus, invasive procedures should be reserved for severe and refractory cases only. Occipital nerve stimulation for chronic refractory cluster headache is the only available invasive approach with a Conformité Européenne mark.Neuromodulation can complement conventional therapy, with noninvasive procedures being used preferably. Given the limited number of studies for each modality and the lack of head-to-head studies, it is difficult to place neuromodulation techniques in a conventional treatment algorithm.

Neuromodulatory approaches have enlarged the therapeutic armamentarium for the treatment of primary headaches such as migraine and cluster headache. While invasive devices are mainly used in patients with refractory and chronic conditions, non-invasive approaches are increasingly used in less severely affected patients with episodic headaches. This article critically reviews the literature focussing on recent controlled studies, provides recommendations on their use in clinical practice and strives to integrate them into present treatment regimes. As a relevant drawback, the number of controlled studies is limited with small cohorts included and marked methodological constraints, which hampers any direct comparison with pharmacological approaches.

The detection of Parkinson’s disease (PD) at stages earlier than current diagnostic criteria allow for may increase the efficacy of disease-modifying therapies. Here we studied the relationship between retrospectively reported prodromal non-motor and motor features of PD, their pre-diagnostic presentation to physicians, and the extrapolated potential of an earlier diagnosis of PD considering early diagnostic markers detected at presence. One hundred and fifteen PD patients (41 women; age 63.2 ± 8.6 years) underwent a structured face-to-face interview on 22 prediagnostic symptoms. Present olfactory function, motor symptoms, and substantia nigra hyperechogenicity (SN-h) were assessed using standardized tools. Most frequently self-perceived symptoms in the early and very early prediagnostic phase (>2, >7 years prior to diagnosis) were hyposmia (23, 10 %), musculoskeletal pain (21, 9 %), and depression/anxiety (14, 11 %). In the late prediagnostic phase (≤2 years) mild motor signs, especially asymmetric bradykinesia and rest tremor, increasingly dominated the self-perception. In the prediagnostic phase, 99 % of patients consulted a physician because of motor symptoms but only 36 % with non-motor symptoms, mostly pain (20 %), depression/anxiety (9 %), constipation, bladder urgency, insomnia, REM sleep behaviour disorder, sexual dysfunction, and malignant melanoma (each

Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. We validated this metric in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a European Medicines Agency–approved drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was also useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Furthermore, this metric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy. Our data indicate that relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with lysosomal disorders.