Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventy-two symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task ( Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.

Background: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. Methods: In NF1 patients (n = 11; 19–44 years) and healthy controls (HC; n = 11; 19–31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. Results: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. Conclusions: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option.

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. 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. 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. 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.

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. 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. 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. 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.