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Reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) are both rare disorders. The pathophysiology of both diseases is not yet fully understood. We report the unique case of a 19-year-old comatose woman who was brought to the ER after a series of generalized tonic–clonic seizures 6 days post peridural anesthesia for cesarean section. Vital signs and initial laboratory testing including urine analysis and drug screening were unremarkable. Initial cranial CT scan showed an acute small subdural hematoma (17 mm length × 6 mm width × 30 mm height), cerebral edema with slit ventricles, and slight cerebellar tonsillar herniation as signs of intracranial hypotension. CT angiography depicted narrowing of the proximal intracranial vessels consistent with RCVS. MR imaging was also suggestive of both intracranial hypotension and RCVS and showed, in addition, vasogenic edema consistent with PRES. An extensive CSF leakage involving T1 to L2/L3 was confirmed by spinal MRI. The patient underwent conservative therapy for intracranial hypotension (e.g., head-down position) as well as epidural blood patch, which led to regression of the clinical symptoms within a few days. Follow-up MRI showed complete resolution of all radiological changes. In summary, our patient developed clinical and neuroradiological signs of intracranial hypotension and a combination of PRES and RCVS associated with a CSF leakage caused by peridural anesthesia; by treating the intracranial hypotension, the other syndromes resolved. From a clinical point of view, it is important to look for CSF leakage as a treatable possible cause of PRES and/or RCVS triggered by intracranial hypotension as in our patient postpartum. Moreover, it is vital to obtain a good history as, in cases of suspected CSF leakage with classic postural headache, a recent spinal/cranial procedure is typically present.

Although the diagnostic performance of whole-brain computed tomographic perfusion (WB-CTP) in the detection of supratentorial infarctions is well established, its value in the detection of infratentorial strokes remains less well defined. We examined its diagnostic accuracy in the detection of infratentorial infarctions and compared it to nonenhanced computed tomography (NECT), aiming to identify factors influencing its detection rate. Out of a cohort of 1380 patients who underwent WB-CTP due to suspected stroke, we retrospectively included all patients with MRI-confirmed infratentorial strokes and compared it to control patients without infratentorial strokes. Two blinded readers evaluated NECT and four different CTP maps independently for the presence and location of infratentorial ischemic perfusion deficits. The study was designed as a retrospective case-control study and included 280 patients (cases/controls = 1/3). WB-CTP revealed a greater diagnostic sensitivity than NECT (41.4 vs. 17.1 %, P = 0.003). The specificity, however, was comparable (93.3 vs. 95.0 %). Mean transit time (MTT) and time to drain (TTD) were the most sensitive (41.4 and 40.0 %) and cerebral blood volume (CBV) the most specific (99.5 %) perfusion maps. Infarctions detected using WB-CTP were significantly larger than those not detected (15.0 vs. 2.2 ml; P = 0.0007); infarct location, however, did not influence the detection rate. The detection of infratentorial infarctions can be improved by assessing WB-CTP as part of the multimodal stroke workup. However, it remains a diagnostic challenge, especially small volume infarctions in the brainstem are likely to be missed.

Background Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. Several reports have demonstrated that the clinical features of THS are not specific to one causal aetiology and can lead to misdiagnosis. Case report We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low-penetrance mutation (Q703K) of the cryopyrin/ NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome. Discussion This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin-associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients.

To assess symptoms and objective parameters of autonomic dysfunction (AD) in patients with ANCA-associated vasculitides. Symptoms and objective parameters of AD were assessed in patients with ANCA-associated vasculitis and in age-matched healthy controls. Autonomic symptoms were explored by COMPASS31, a validated questionnaire addressing symptoms of six autonomic domains (orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor, and bladder dysfunction). Objective autonomic parameters consisted of expiratory/inspiratory (E/I) ratio during the deep breathing test (DBT), blood pressure response to cold pressor test (CPT), and skin conductance changes during mental arithmetic. 27 patients and 27 healthy controls have been enrolled. 27 patients and 27 controls completed COMPASS31. 21 patients and 18 controls underwent objective autonomic testing. Vasculitis patients had significantly higher COMPASS31 total scores than controls (median 10.4 vs 3.0; p = 0.005). In the sub-domain analysis, significant differences were seen in the vasomotor and the bladder domain (p = 0.004; p

OBJECTIVE We tested the hypotheses (i) that autoimmune encephalitis is associated with new-onset headache, and (ii) that the occurrence of headache is associated with the presence of anti-N-methyl-D-aspartate (NMDA)-receptor antibodies. BACKGROUND Autoimmune encephalitis presents with cognitive dysfunction as well as neuro-psychiatric symptoms. Its pathophysiology might involve antibody-mediated dysfunction of the glutamatergic system as indicated by the presence of anti-NMDA-receptor antibodies in some patients. METHODS In this cross-sectional study, patients with autoimmune encephalitis were assessed with a standardized interview for previous headache and headache associated with autoimmune encephalitis. Headache was classified according to the International Classification of Headache Disorders, second edition. Clinical and paraclinical findings were correlated with the occurrence of headache. RESULTS Of 40 patients with autoimmune encephalitis, 19 did not have a history of headache. Of those, nine suffered from encephalitis-associated headache. Seven of these nine had anti-NMDA-receptor antibodies in contrast to only two among the remaining 10 patients without new-onset headache (P = .023, odds ratio: 14, 95% confidence interval: 1.5; 127). In most patients headache occurred in attacks on more than 15 days/month, was severe, and of short duration (less than 4 hours). International Headache Society criteria for migraine were met in three patients. CONCLUSIONS New-onset headache is a relevant symptom in patients with autoimmune encephalitis who have no history of previous headache, especially in the subgroup with anti-NMDA-receptor antibodies. This indicates a thorough investigation for secondary headaches including anti-NMDA-R antibodies for patients with new-onset headache and neuropsychiatric findings. Glutamatergic dysfunction might be important for the generation of head pain but may only occasionally be sufficient to trigger migraine-like attacks in nonmigraineurs.

Chronic pain represents a great challenge; according to epidemiological data increasing numbers of patients should be expected. Based on recent advances, a better understanding of the pathophysiology of chronic pain has been achieved and neurologists have made a major contribution to this understanding. Chronic pain is accompanied by substantial maladaptive plastic alterations in both the peripheral and central nervous systems; therefore, neurological knowledge is of paramount importance for pain therapists but this contrasts with the current treatment situation of pain patients in Germany. There are basically too few departments and practices undertaking treatment, and neurologists are an exception in most pain centers. Furthermore, due to economic reasons neurological hospitals are currently experiencing a dearth of inpatients suffering from chronic pain. Diagnostic and/or treatment procedures for neurological pain entities (e.g. headaches or neuropathic pain) are insufficiently represented in the German diagnosis-related groups (DRG) reimbursement system and the obstacles for an efficient pain therapy in neurological practices are too high. Finally, there are too few academic positions for pain medicine in neurological hospitals; therefore, career opportunities for motivated young neurologists with an interest in pain are lacking. In order to address the unmet therapeutic needs of patients with chronic pain there is a high demand for (i) establishment of departments for neurological pain medicine, (ii) modification of the German DRG system and (iii) education of young neurologists with expertise in pain. Pain medicine in particular should be especially appealing to neurologists .

Bei der Entstehung primarer Kopfschmerzen spielt das autonome Nervensystem eine wichtige Rolle. Daraus ergeben sich auch neue Ansatze fur die Therapie, die etwa Patienten mit Clusterkopfschmerzen oder mit Migrane zugute kommen konnen. Erste klinische Studien mit verschiedenen Verfahren der Vagusstimulation sind vielversprechend.

Physical inactivity is a major but modifiable risk factor for morbidity and mortality. Regular physical activity has preventive and therapeutic effects on numerous diseases including neurological disorders. Therefore, it is desirable that physicians motivate their patients to increase their physical and sports activities and that they help them to overcome barriers to exercising. The present study is a survey of neurologists who are members of the German Neurological Society with their own practices; they were asked whether they advised their patients on the benefits of physical activity. Details on physician counseling on physical activity were obtained, such as the frequency of counseling, the neurological disorders considered by the practitioners to be worth the effort of counseling, and the barriers to exercise on the part of patients. More than 80 % of the participants who responded to the survey stated that they frequently provide their patients with advice on the preventive and therapeutic aspects of physical activity. Almost all of them recommended endurance sports; this was followed by Far Eastern types of sport such as tai chi or yoga (70 % of all physicians who advice sports activities). The frequency of counseling about physical activity significantly correlated to the physician's own sports activity. Frequency of counseling was reduced if the physician assessed the patients to be incapable of adopting and maintaining a lifestyle of habitual physical activity. Lack of time as well as an insufficient reimbursement of the counseling, however, did not significantly influence the frequency of counseling. The physician's own sports activity matched that of individuals with similar social status. Thus, a selection bias does not seem to be of importance regarding the results of the survey. However, since only 169 of the 784 invited neurologists (21.6 %) responded to the questionnaire, the representativeness of the survey may be limited. Counseling about physical activity seems to be an essential part of consultations in neurological practices.

Background White noise galvanic vestibular stimulation (GVS) is thought to enhance the sensitivity of vestibular organs. Objective To examine the effects of noise-enhanced vestibular input on the walking performance in healthy subjects walking with eyes closed. Methods Walking performance of 17 healthy subjects (mean age 28.8 ± 1.7 years) at slow, preferred, and fast speeds was examined during three different conditions: (1) walking with eyes open (EO) as baseline condition, (2) walking with eyes closed and sham noisy GVS (EC), and (3) walking with eyes closed and non-zero amplitude noisy GVS set to 80% of the individual sensory threshold for GVS (EC-GVS). Ten gait parameters were examined: stride time, stride length, base of support, swing time percentage, double support time percentage as well as gait asymmetry, bilateral phase coordination and the coefficient of variation (CV) of stride time, stride length and base of support. Results Noisy GVS improved stride time CV by 36% ( p 0.034), stride length CV by 31% ( p 0.037), base of support CV by 14% ( p 0.009), and bilateral phase coordination by 23% ( p 0.034). The ameliorating effects of noisy GVS on locomotion function were primarily observable during slow walking speeds. Conclusion Noise-enhanced vestibular input is effective in improving locomotion function and is accompanied by a subjectively felt improvement of walking balance. It predominantly targets the variability and bilateral coordination characteristics of the walking pattern, which are critically linked to dynamic walking stability. Noisy GVS might present an effective treatment option to improve walking performance in patients with bilateral vestibular dysfunction.

ZusammenfassungNach der 2013 überarbeiteten IHS-Klassifikation werden der episodische und chronische Cluster-Kopfschmerz, die episodisch und chronisch paroxysmale Hemikranie und SUNCT-Syndrom (short-lasting unilateral neuralgiform headache with conjunctival injection and tearing) und das SUNA-Syndrom (short-lasting unilateral neuralgiform headache with autonomic symptoms) sowie die Hemicrania continua unter dem Begriff trigemino-autonome Kopfschmerzen (TAK) zusammengefasst. Sie unterscheiden sich in Dauer, Frequenz und Rhythmik der Schmerzattacken. Autonome Begleitsymptome wie ipsilaterale Lakrimation, konjunktivale Injektion, Rhinorrhoe, nasale Kongestion, Gesichtsschwitzen, Völlegefühl im Ohr und Lidschwellung treten mehr oder weniger stark ausgeprägt auf. Ein wesentliches weiteres Unterscheidungsmerkmal liegt in dem unterschiedlichen Ansprechen auf Indometacin: Der Cluster-Kopfschmerz und das SUNCT- und SUNA-Syndrom sprechen nicht auf Indometacin an, bei den anderen TAK ist Indometacin per definitionem effektiv. Grundsätzlich unterteilt sich die Therapie der TAK in eine Akuttherapie und eine medikamentöse Prophylaxe. Aufgrund der relativen Kürze der Attacken ist bei der paroxysmalen Hemicranie und beim SUNCT/SUNA-Syndrom keine Akuttherapie möglich, beim Cluster-Kopfschmerz sind orale Substanzen in der Regel nicht ausreichend rasch wirksam. Das größte Augenmerk der Therapie liegt daher stets auf der Prophylaxe. Die Therapie der TAK erfordert eine individuell auf den Patienten zugeschnittene Kombination der verschiedenen Therapieoptionen. Obwohl ausreichend gute, vergleichende Studien rar sind, kann in der Praxis in der Mehrzahl der Fälle eine positive Beeinflussung der Schmerzattacken erreicht werden. Nur in seltenen Fällen ist eine invasive Therapie nötig. Die Therapieempfehlungen stützen sich, soweit möglich, auf Kriterien der evidenzbasierten Medizin (EBM).

Patienten mit Lasionen des Prafrontalkortex als Folge frontaler Hirntumoren (intra- und extraaxial) konnen Beeintrachtigungen der Exekutivfunktionen zeigen 1 2 3 4 . Obwohl eine umfangreiche Zahl testpsychologischer Verfahren existiert, ist die routinemasige Erfassung von Beeintrachtigungen alltagsrelevanter Exekutivfunktionen bei diesen Patienten nach wie vor auserst schwierig. Bei 30 Patienten mit Raumforderungen des Prafrontalkortex wurden die Exekutivfunktionen mit dem Behavioural Assessment of Dysexecutive Syndrome (BADS) untersucht, 21 konnten auch postoperativ nachuntersucht werden. Erganzend wurden, wenn moglich, der Wisconsin Card Sorting Test (WCST) als weit verbreiteter Exekutivfunktionstest sowie der Wechsler-Intelligenztest fur Erwachsene (WIE) fur die allgemeine kognitive Leistungsfahigkeit durchgefuhrt. Pra- und postoperativ konnten insgesamt 16 Patienten vollstandig mit allen drei Tests nachverfolgt werden. Das Ziel war es, die neuropsychologische Diagnostik praoperativ und postoperativ hinsichtlich Defiziten und Leistungsveranderungen zu evaluieren und auch postoperativ sicherzustellen, dass keine alltagsrelevanten neuen kognitiven Defizite entstanden sind. Praoperativ zeigte im BADS lediglich ein Patient, der nicht postoperativ getestet werden konnte, einen reduzierten Gesamtprofilwert. Fur alle Patienten, die sowohl pra- als auch postoperativ getestet wurden, konnte gezeigt werden, dass in keiner der verwendeten Testungen Hinweise auf eine Verschlechterung des kognitiven Status 8 – 12 Wochen postoperativ erkennbar waren. Fur die Zukunft sollten weiterfuhrende Untersuchung mittels fMRT die Frage klaren, ob die fehlenden Defizite als neuroplastische Adaptationen der prafrontal reprasentierten kognitiven Funktionen interpretiert werden mussen oder eine Erfassung von doch vorhandenen Defiziten aufgrund der zu geringen Sensitivitat der genutzten Testverfahren nicht gelang.

We have recently shown that subjects can learn to use cognitive-emotional strategies to suppress their spinal nociceptive flexor reflex (RIII reflex) under visual RIII feedback and proposed that this reflects learned activation of descending pain inhibition. Here, we investigated whether learned RIII suppression also affects supraspinal nociception and whether previous relaxation training increases success. Subjects were trained over 3 sessions to reduce their RIII size by self-selected cognitive-emotional strategies. Two groups received true RIII feedback (with or without previous relaxation training) and a sham group received false feedback (15 subjects per group). RIII reflexes, late somatosensory evoked potentials (SEPs), and F-waves were recorded and pain intensity ratings collected. Both true feedback groups achieved significant (P < 0.01) but similar RIII suppression (to 79% ± 21% and 70% ± 17% of control). Somatosensory evoked potential amplitude (100-150 milliseconds after stimulation) was reduced in parallel with the RIII size (r = 0.57, P < 0.01). In the sham group, neither RIII size nor SEP amplitude was significantly reduced during feedback training. Pain intensity was significantly reduced in all 3 groups and also correlated with RIII reduction (r = 0.44, P < 0.01). F-wave parameters were not affected during RIII suppression. The present results show that learned RIII suppression also affects supraspinal nociception as quantified by SEPs, although effects on pain ratings were less clear. Lower motor neuron excitability as quantified by F-waves was not affected. Previous relaxation training did not significantly improve RIII feedback training success.

Metastasis to the brain is a frequent complication in lung cancer and is still associated with a dismal prognosis. Current treatment strategies not only target tumor cells but also focus on cells of the tumor microenvironment like tumor associated microglia/macrophages (TAMs). The interactions between tumor cells and TAMs during different steps of cerebral metastasis formation of lung cancer brain metastasis are poorly characterized. Moreover, the role of CX3CR1 in this process remains unclear. We established a syngeneic cerebral metastasis mouse model by combining a chronic cranial window and two-photon laser scanning microscopy (TPLSM), which allows the tracking of single fluorescent metastasizing tumor cells and the tumor microenvironment on a cellular resolution in vivoover time for a period of weeks. Transgenic CX3CR1 proficient and deficient mice (CX3CRGFP/wt and CX3CR1GFP/GFP) were injected with red fluorescent Lewis lung carcinoma cells. During different steps of metastasis formation (extravasation, formation of micro- and macrometastasis) the density and cell body volume of TAMs, their interaction with tumor cells and possible influence on the fate of single metastatic tumor cells were investigated using serial TPLSM. We found that during metastasis formation TAM density was significantly lower in CX3CR1 deficient mice. However, activation as assessed by TAM morphology did not differ in the absence of CX3CR1. Strikingly, CX3CR1 deficiency was associated with a significant increase of tumor cells successfully extravasating the cerebral vasculature. However, subsequent steps (mirco- and macrometastasis formation) were observed less frequent in CX3CR1 deficient mice. In summary, our results highlight a complex role of CX3CR1 for TAMs during cerebral metastasis formation, indicating anti-tumorous properties of CX3CR1 at early steps and possible pro-tumorous effects at later stages (micro- and macrometastasis formation).

Bone marrow edema (BME) is a descriptive term for a common finding in magnetic resonance imaging (MRI). Although pain is the major symptom, BME differs in terms of its causal mechanisms, underlying disease, as well as treatment and prognosis. This complexity together with the lack of evidence-based guidelines, frequently makes the identification of underlying conditions and its management a major challenge. Unnecessary multiple consultations and delays in diagnosis as well as therapy indicate a need for interdisciplinary clinical recommendations. Therefore, an interdisciplinary task force was set up within our large osteology center consisting of specialists from internal medicine, endocrinology/diabetology, hematology/oncology, orthopedics, pediatrics, physical medicine, radiology, rheumatology, and trauma surgery to develop a consenus paper. After review of literature, review of practical experiences (expert opinion), and determination of consensus findings, an overview and an algorithm were developed with concise summaries of relevant aspects of the respective underlying disease including diagnostic measures, clinical features, differential diagnosis and treatment of BME. Together, our single-center consensus review on the management of BME may help improve the quality of care for these patients.

Significance Primary central nervous system lymphoma (PCNSL) is a highly malignant brain tumor with limited treatment options. Here, we show that genetically engineered T cells, expressing a chimeric antigen receptor, thoroughly infiltrate these tumors in mice. Combining intravital 2-photon microscopy with chronic cranial windows, we were able to visualize their intratumoral proliferation and intracerebral persistence for up to 159 d, leading to the eradication of large, established PCNSL and to long-term survival., T cells expressing anti-CD19 chimeric antigen receptors (CARs) demonstrate impressive efficacy in the treatment of systemic B cell malignancies, including B cell lymphoma. However, their effect on primary central nervous system lymphoma (PCNSL) is unknown. Additionally, the detailed cellular dynamics of CAR T cells during their antitumor reaction remain unclear, including their intratumoral infiltration depth, mobility, and persistence. Studying these processes in detail requires repeated intravital imaging of precisely defined tumor regions during weeks of tumor growth and regression. Here, we have combined a model of PCNSL with in vivo intracerebral 2-photon microscopy. Thereby, we were able to visualize intracranial PCNSL growth and therapeutic effects of CAR T cells longitudinally in the same animal over several weeks. Intravenous (i.v.) injection resulted in poor tumor infiltration of anti-CD19 CAR T cells and could not sufficiently control tumor growth. After intracerebral injection, however, anti-CD19 CAR T cells invaded deeply into the solid tumor, reduced tumor growth, and induced regression of PCNSL, which was associated with long-term survival. Intracerebral anti-CD19 CAR T cells entered the circulation and infiltrated distant, nondraining lymph nodes more efficiently than mock CAR T cells. After complete regression of tumors, anti-CD19 CAR T cells remained detectable intracranially and intravascularly for up to 159 d. Collectively, these results demonstrate the great potential of anti-CD19 CAR T cells for the treatment of PCNSL.

Background The role of avoidance and endurance behaviour is well established in chronic musculoskeletal pain, but less is known about its significance in migraine. Methods The Avoidance-Endurance Questionnaire behavioural subscales, the Pain Disability Index (PDI), the Migraine Disability Assessment Scale (MIDAS) and the Hospital Anxiety and Depression Scale (HADS) were obtained from 128 migraine patients (90 episodic, 38 chronic). Sixty nine of them were re-evaluated after 3–6 months. Results At baseline, there were positive relations between avoidance (especially social avoidance behaviour) and pain-related disability as assessed by the PDI (Wald χ2 [1] = 32.301, p

Autonomic dysfunction (AD) has been described in various chronic inflammatory diseases. Studies of AD in patients with familial Mediterranean fever (FMF) are inconclusive. We aimed to assess AD in a cohort of FMF patients.Signs and symptoms of AD were investigated in patients with FMF and compared to age and gender matched healthy controls. Symptoms of AD were assessed by COMPASS-31, a validated questionnaire to evaluate orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor and bladder function domains. Assessment of objective AD comprised heart rate variability during deep breathing, skin conductance changes during mental arithmetic, blood pressure response to pain and dynamic infrared pupillometry.25 patients and 25 healthy controls were included and evaluated by COMPASS-31 and objective testing of AD. FMF patients had higher median COMPASS-31 total scores than controls (23.7 vs. 1.6, p=0.024). Significant differences were also found in the secretomotor and gastrointestinal sub-domains (4.2 vs. 0.0; p0.001 and 8.0 vs. 0.0; p=0.004, respectively). Symptoms of autonomic dysfunction were correlated with patient reported global disease activity (r=0.71; p0.001) and pain level (r=0.68; p0.001). There were no differences in heart rate variability (HRV), skin conductance, blood pressure response to pain or sympathetic pupillomotor function between patients and controls. FMF patients revealed impaired parasympathetic pupillomotor function that was not associated with clinical parameters. However, patients that were on IL-1-blocking therapy had better parasympathetic pupillary function than patients on conventional treatment.FMF patients have AD in terms of symptoms and parasympathetic pupillomotor function. Dynamic pupillometry can provide additional information on autonomic regulation in patients with FMF.

Patients with migraine often also suffer from gastrointestinal disorders such as irritable bowel syndrome, inflammatory bowel disease or celiac disease. All these diseases share increased intestinal permeability ("leaky gut") and thus increased inflammatory activity. There is an increase in proinflammatoric cytokines in the serum, which in turn can trigger migraine attacks. Probiotics can have a positive effect on the intestinal epithelium and reduce inflammatory activity. A first uncontrolled, small study of 39 migraineurs showed a decrease in the rate of attacks under the daily intake of a probiotic.In an uncontrolled observational study, the influence of a specially formulated multispecies probiotic on the frequency of migraine attacks and the intensity of migraine-associated complaints was recorded. The self-assessment of 1,020 patients was evaluated.Over the treatment period of 8 weeks, the number of headache days was reduced from 2 to 1.4 days per week. The headache intensity decreased from 5.1 to 2.1 points (0 = not present to 6 = very intensive). The migraine-associated complaints were reduced and the use of painkillers halved. All results were statistically significant (p ≤ 0.001).It can be suggested that this multispecies probiotic formulation has a positive influence on intensity and frequency of migraine attacks. However, randomized, placebo-controlled trials are required for further confirmation.

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.

Objective To determine if migraine patients with high achievement motivation have an increased use of acute headache medication. Background It has been hypothesized that high achievement-motivated migraine patients have an increased use of acute headache medication to be able to perform at work and during daily life, putting them at risk for medication overuse headache (MOH). Methods The Achievement Motivation Inventory and use of acute headache medication were assessed in 117 migraine patients (60 episodic, 57 chronic) at their first appointment at our tertiary headache center. Results Patients with low vs high achievement motivation were not significantly different in acute headache medication days per month (10.8 ± 6.9 vs 10.9 ± 7.8, P = .98), in acute headache medication use in the absence of headache (to prevent occurrence of headache later that day: 51.8% vs 48.2%, P = .38), in having a diagnosis of MOH (37.9 vs 23.7%, P = .12), or in reduction of acute headache medication days at 3 and 6 months follow-up (both P > .20). Conclusions High achievement motivation in migraine patients was not associated with increased acute headache medication use or more frequent diagnosis of MOH.

Bedingt durch die stetig zunehmende Lebenserwartung sind auch die Demenzerkrankungen, d. h., Erkrankungen, bei denen es zu einer anhaltenden Einschrankung der Hirnleistung mit dadurch bedingten Einschrankungen im Alltag kommt, ein zunehmend diskutiertes Problem in der Gesellschaft. Neben einer gesunden Lebensfuhrung mit einer entsprechenden Ernahrung, der konsequenten Behandlung von Risikoerkrankungen wie arterieller Hypertonie, Diabetes mellitus und Fettstoffwechselstorungen, ist eine regelmasige und ausreichende korperliche Aktivierung eine der wesentlichen vorbeugenden Masnahmen. Daneben zeigt sich aber auch, dass auch bei vorliegender Hirnleistungsstorung regelmasiges korperliches Training zu einer Verbesserung der Ausfallssymptome fuhrt. Als besonders sinnvoll zeigen sich dabei Programme, die neben dem korperlichen Training auch kognitive Aufgaben und soziale Interaktion beinhalten.

Die Multiple Sklerose und verwandte Erkrankungen verlaufen typischerweise chronisch uber viele Jahre und konnen individuell verschieden zu weniger oder mehr korperlicher Einschrankung fuhren. Ein regelmasiges Training fuhrt nicht zu vermehrten Schuben oder Krankheitsaktivitat, hilft aber, Symptome wie die rasche Ermudbarkeit („Fatigue“) zu lindern und den Abbau von Muskelmasse zu verhindern. Auch einem Knochenschwund (Osteoporose), der haufig durch eine Inaktivitat gemeinsam mit wiederholter Gabe von Cortison bedingt ist, wird durch korperliches Training vorgebeugt. Welches Training bevorzugt werden sollte, hangt ganz entscheidend von der individuellen Einschrankung ab. Entsprechend angepasste Vorschlage werden im Text diskutiert.

Objective Habituation of visual-evoked potentials (VEPs) is typically described as deficient interictally in migraine patients, supposedly indicating altered cortical excitability. Use of this parameter for monitoring changes over time, e.g. under treatment, requires demonstration of test-retest reliability. Methods VEPs were recorded interictally in 41 episodic migraine patients and 40 controls. N75–P100 amplitudes were measured over six consecutive blocks of 75 VEPs each. Amplitude regression slopes and block ratios were used to quantify VEP habituation. Test-retest reliability was assessed over 15 minutes and two to three weeks. Results Controls showed significantly more negative VEP habituation slopes than migraine patients (−0.21 ± 0.40 vs. 0.04 ± 0.46 µV/block, p Conclusions Deficient VEP habituation in migraine was confirmed. However, the test-retest reliability of VEP habituation was rather weak. Therefore, we suggest that VEP habituation should be used for evaluation of cortical excitability under treatment only at the group level and only when a control group with sham treatment is included.

Background Chronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH. Methods PREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS ( n = 48) with standard of care (SoC) alone (control ( n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed. Results During the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS ( n = 45) had a significantly greater reduction in the number of attacks per week vs controls ( n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p Conclusion Adjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.

The starting point for German headache research and clinical education was the engagement of D. Soyka in the 1970s, which enabled the foundation of the German Headache Society (DMKG) on 28 June 1979 and, some years later, the founding congress of the International Headache Society (IHS) in Munich 1982. As a result of these activities, in 1988 the first international classification of headache disorders was published. This classification was one of the major milestones in the development of basic as well as clinical headache research. In the following years, epidemiological studies all over the world showed a 1-year prevalence for headache of approximately 60%, making headaches one of the most frequent medical complaints. Basic research showed an involvement of serotonergic mechanisms in migraine pain and triptans were one of the first drugs designed to influence these mechanisms. Functional brain imaging studies in migraine patients further showed a cyclic modulation of the activity of brainstem areas independent of the current pain state. Various research groups were involved in the clarification of the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache. A specific development in the German headache scene is the establishment of integrated headache centers and reflects the primarily multimodal treatment approach in Germany which contrasts with the settings in other countries. These successful developments are increasingly being undermined by the fact that the low financial support of headache research, for example, by the German science council is causing a decreasing interest in headache research, with the consequence that the clinical education of students as well as young medical doctors shows increasing deficits. The consequence for the future will be a deficit in the clinical care of the population.

In natural life pain automatically draws attention towards the painful body part suggesting that it interacts with different attentional mechanisms such as visual attention. Complex regional pain syndrome (CRPS) patients who typically report on chronic distally located pain of one extremity may suffer from so-called neglect-like symptoms, which have also been linked to attentional mechanisms. The purpose of the study was to further evaluate how continuous pain conditions influence visual attention. Saccade latencies were recorded in two experiments using a common visual attention paradigm whereby orientating saccades to cued or uncued lateral visual targets had to be performed. In the first experiment saccade latencies of healthy subjects were measured under two conditions: one in which continuous experimental pain stimulation was applied to the index finger to imitate a continuous pain situation, and one without pain stimulation. In the second experiment saccade latencies of patients suffering from CRPS were compared to controls. The results showed that neither the continuous experimental pain stimulation during the experiment nor the chronic pain in CRPS led to an unilateral increase of saccade latencies or to a unilateral increase of the cue effect on latency. The results show that unilateral, continuously applied pain stimuli or chronic pain have no or only very limited influence on visual attention. Differently from patients with visual neglect, patients with CRPS did not show strong side asymmetries of saccade latencies or of cue effects on saccade latencies. Thus, neglect-like clinical symptoms of CRPS patients do not involve the allocation of visual attention.

ZusammenfassungKopfschmerzen bei Kindern und Jugendlichen in Deutschland sind häufig und nehmen Richtung Jugendalter deutlich zu: Die Prävalenzen liegen zwischen 38% bei jüngeren Kindern und 84% bei Jugendlichen (Migräne: 6% bis 31%; Spannungskopfschmerz: 18% bis 51%; häufige Kopfschmerzen: 4% bis 10%). Dabei wird ein allgemeiner Anstieg der Kopfschmerzprävalenz bei Kindern und Jugendlichen in den letzten Jahren beschrieben, eine Aussage, die aber – bezogen auf alle Studien zu diesem Thema – inkonsistent bleibt. Stress, Rauchen, Koffeinkonsum und dysfunktionale muskuläre Anspannung und Schmerzen im Bereich von Schulter und Nacken wurden auch bei Kindern und Jugendlichen in allen Studien als Risikofaktoren für primäre Kopfschmerzen bestätigt.

Zusammenfassung80% der Schüler berichten über Kopfschmerzen im Laufe von 90 Tagen. Eine frühe Erkrankung an häufigen Kopfschmerzen bedingt eine höhere Wahrscheinlichkeit auch später im Erwachsenenalter an Kopfschmerzen zu leiden. Es ist deshalb sinnvoll, über Möglichkeiten einer Prävention von Kopfschmerzen im Schulalter nachzudenken. In der vorliegenden Übersicht werden die Ergebnisse von Studien, die die Umsetzbarkeit von meist psychologischen Interventionen wie Entspannungsübungen, Verhaltenstherapie oder Psychoedukation über Kopfschmerzen untersuchten, vorgestellt. Meist relativ kleine Studien weisen darauf hin, dass internetbasierte Verfahren oder Programme, die vorwiegend auf Selbststudium basieren, zu einer signifikanten Besserung führen. Vor diesem Hintergrund führten wir eine Studie zu dem Einfluss einer einstündigen Psychoedukation über Risikofaktoren, den Zusammenhang zu Muskelspannung der peri - kraniellen Muskulatur mit Demonstration von Dehnübungen und Wachheit gegenüber Stressoren durch. Diese bei 12 bis 19 Jahre alten Schülern durchgeführte Studie konnte zeigen, dass niedrigschwellige Intervention zur signifikanten Reduktion von Kopfschmerzen in der Gruppe führte, ein auch noch nach 7 Monaten nachweisbarer Effekt. Der Ansatz, über eine Gesundheitsaufklärung in der Schule, eine nachhaltige Besserung der Kopfschmerzen zu erreichen, wird mit unseren aktuellen Daten unterstützt.

ZusammenfassungZur psychologischen Behandlung von Kopfschmerzen bei Kindern und Jugendlichen bieten sich mehrere hocheffektive Therapieverfahren an. Neben Beratung und Entspannung können Biofeedbackverfahren, operante Schmerzbehandlung, Schmerzbewältigung und kognitive Verhaltenstherapie angewendet werden. Dazu kommen multimodale Verfahren, die aus Kombinationen dieser Einzelbehandlungen und physiotherapeutischen Verfahren bestehen. Diese Behandlungsansätze können Verbesserungen von bis zu 50%, in Kombination bis zu 75% bewirken. Damit sind diese Verfahren hocheffektiv, deren Wirkung vergleichbar mit der von Schmerzmedikamenten und sollten bei der Behandlung von kindlichen Kopfschmerzen berücksichtigt werden.

Objective. There is increasing evidence that the cerebellum has a role in pain processing. The present study investigates whether chronic pain patients, who are likely to have altered pain processing, exhibit signs of subtle cerebellar dysfunction. We used oculomotor tasks to assess dysfunction of the associated neuronal networks, including the cerebellum. Methods. Thirty patients with chronic nonspecific spinal pain and 30 age-and sex-matched controls were enrolled. Using a head-mounted eye tracker (EyeSeeCam), eye movements were quantified during predictable and unpredictable saccade and smooth pursuit tasks in the horizontal plane. Results. The initial latency and the velocity variability of smooth pursuit were significantly increased in the chronic spinal pain patients compared with controls (initial latency: 198 +/- 20 vs 185 +/- 11 ms, P

Background The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. Methods Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. Results A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3–17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p

Objectives To assess potential risk factors for vertigo and dizziness in adolescents and to evaluate their variability by different vertigo types. The role of possible risk factors for vertigo and dizziness in adolescents and their population relevance needs to be addressed in order to design preventive strategies. Study design The study population consisted of 1482 school-children between the age of 12 and 19 years, who were instructed to fill out a questionnaire on different vertigo types and related potential risk factors. The questionnaire specifically asked for any vertigo, spinning vertigo, swaying vertigo, orthostatic dizziness, and unspecified dizziness. Further a wide range of potential risk factors were addressed including gender, stress, muscular pain in the neck and shoulder region, sleep duration, migraine, coffee and alcohol consumption, physical activity and smoking. Results Gender, stress, muscular pain in the neck and shoulder region, sleep duration and migraine were identified as independent risk factors following mutual adjustment: The relative risk was 1.17 [1.10 - 1.25] for female sex, 1.07 [1.02 - 1.13] for stress, 1.24 [1.17 - 1.32] for muscular pain, and 1.09 [1.03 - 1.14] for migraine. The population attributable risk explained by these risk factors was 26%, with muscular pain, stress, and migraine accounting for 11%, 4%, and 3% respectively. Conclusion Several established risk factors in adults were also identified in adolescents. Risk factors amenable to prevention accounted for 17% of the total population risk. Therefore, interventions targeting these risk factors may be warranted.

To assess autonomic function by infrared dynamic pupillometry in patients with ANCA-vasculitis (AAV) in correlation to autonomic symptoms, disease specific clinical parameters and cardiovascular reflex tests. Patients with AAV and healthy controls underwent pupillometry at rest and after sympathetic stimulation (cold pressor test). Three parasympathetic parameters (amplitude, relative amplitude, maximum constriction velocity) and one sympathetic parameter (late dilatation velocity) were assessed. Results were correlated with clinical parameters, symptoms of autonomic dysfunction (COMPASS31 questionnaire), heart rate variability during deep breathing test and blood pressure response to pain. 23 patients and 18 age-matched controls were enrolled. Patients had a smaller amplitude (1.44 vs. 1.70 mm; p = 0.009) and a slower constriction velocity (4.15 vs. 4.71 mm/s; p = 0.028) at baseline and after sympathetic stimulation (1.47 vs. 1.81 mm, p = 0.001; 4.38 vs. 5.19 mm/s, p = 0.006, respectively). Relative amplitude was significantly smaller in patients after sympathetic stimulation (28.6 vs. 32.5%; p = 0.043), but not at baseline. There was no difference in sympathetic pupillary response between the groups. In patients, parasympathetic pupil response was correlated negatively with age and positively with parasympathetic cardiac response. After adjusting for age, no significant correlation was observed with clinical parameters. However, there was a trend towards a negative correlation with disease duration, vasculitis damage index and CRP. Patients with AAV exhibit parasympathetic pupillary autonomic dysfunction. Although correlations were weak and not significant, pupillary autonomic dysfunction is rather linked to chronic damage than to active inflammation or symptoms of autonomic dysfunction.

Headache disorders are the most occuring symptoms in human population. Basis for a successful therapy of headaches is a definite diagnosis, which needs in turn valid criteria for the graduation of headaches. Corresponding to the classification of the International Headache Society (IHS) especially relevant questions about patient's history and clinical examination lead to a diagnosis.

Background In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study. Findings After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P

Kopfschmerzerkrankungen gehoren zu den haufigsten neurologischen Krankheitsbildern. Zudem besteht oft eine erhebliche Einschrankung der Lebensqualitat mit auch groser soziookonomischer Belastung. Dieses spiegelte sich in den Versorgungsstrukturen nur eingeschrankt wider. Aufgrund der resultierenden Unterversorgung wurde seit Mitte der 90er Jahre das Konzept der Integrierten Versorgung fur Kopfschmerzpatienten punktuell in Deutschland etabliert und ausgebaut. Dabei ist die Multidisziplinaritat sowohl fur das Patienten-Assessment als auch fur die Therapie der zentrale Bestandteil dieser Versorgungsstruktur. Dieser Artikel gibt detaillierte Einblicke in die Zusammenarbeit von Arzten, Psychologen und Physiotherapeuten in der Behandlung von Kopfschmerzpatienten. Dabei werden Grundsatze und Details der Versorgung sowie Outcome-Daten der beteiligten Zentren in Essen, Munchen, Jena, Berlin und Kiel strukturiert dargestellt. Aufbauend auf den Erfahrungen der IV sollte die zukunftige Versorgung sektorenubergreifend, multidisziplinar mit koordiniertem Behandlungsablauf organisiert werden.

Decades of research have implicated both cortical and subcortical areas, such as the cerebellum, as playing an important role in motor learning, and even more recently, in predicting the sensory consequences of movement. Still, it is unknown whether the cerebellum also plays a role in recalibrating sensory estimates of hand position following motor learning. To test this, we measured proprioceptive estimates of static hand position in 19 cerebellar patients with local ischemic lesions and 19 healthy controls, both before and after reach training with altered visual feedback of the hand. This altered visual feedback, (30° cursor-rotation) was gradually introduced in order to facilitate reach adaptation in the patient group. We included two different types of training (in separate experiments): the typical visuomotor rotation training where participants had full volition of their hand movements when reaching with the cursor, and sensory exposure training where the direction of participants׳ hand movements were constrained and gradually deviated from the cursor motion (Cressman, E. K., Henriques, D. Y., 2010. Reach adaptation and proprioceptive recalibration following exposure to misaligned sensory input. J. Neurophysiol., vol. 103, pp. 1888–1895). We found that both healthy individuals and patients showed equivalent shifts in their felt hand position following both types of training. Likewise, as expected given that the cursor-rotation was introduced gradually, patients showed comparable reach aftereffects to those of controls in both types of training. The robust change in felt hand position across controls and cerebellar patients suggests that the cerebellum is not involved in proprioceptive recalibration of the hand.

Background Descending pain modulatory systems control transmission of nociceptive information at the spinal level, and their activity can be modified by cognitive and emotional processes. Thus, it may be possible to learn using cognitive–emotional strategies to specifically target descending pathways in order to achieve pain reduction. Methods The present study used visual feedback of the nociceptive flexor reflex (RIII reflex) to train healthy subjects over three sessions to reduce their spinal nociception (RIII reflex size) by self-selected cognitive–emotional strategies. The study included two feedback groups (fixed vs. random stimulation intervals) and a control group without feedback (15 subjects each). Results While all three groups successfully reduced their RIII reflexes (p

Background and Purpose— Vertebral artery hypoplasia (VAH) is supposed to be a risk factor for posterior circulation ischemia (PCI), particularly in the territory of the posterior inferior cerebellar artery (PICA). The aim of our study was to determine whether VAH impedes perfusion in the dependent PICA territory even in the absence of manifest PCI. Methods— VA diameter was retrospectively measured in 934 consecutive patients who underwent whole-brain multimodal computed tomography because of suspected stroke. VAH was defined by a diameter of ≤2 mm and an asymmetry ratio of ≤1:1.7 of both VAs. We performed blinded computed tomography perfusion reading in patients with VAH without PCI (MRI-confirmed) and in control patients (ratio 1:2) with normal VAs. Four different perfusion maps were evaluated for a relative hypoperfusion in the PICA territory. Results— VAH was found in 146 of 934 patients (15.6%). It was more frequent on the right side (66.1%). Of 146 patients, 59 without PCI qualified for computed tomography perfusion analysis. Depending on the perfusion map, ≤42.4% (25/59) of patients with VAH, but only 7.6% (9/118) without VAH, showed an ipsilateral PICA hypoperfusion ( P mean transit time 39.0% (23/59)>cerebral blood flow 25.4% (15/59). Cerebral blood volume was never affected. Conclusions— VAH is a frequent vascular variant that can lead to a relative regional hypoperfusion in the PICA territory. Additional research should clarify the pathophysiological role of VAH in PCI.

This consensus paper introduces a classification of headache care facilities on behalf of the German Migraine and Headache Society. This classification is based on the recommendations of the International Association for the Study of Pain (IASP) and the European Headache Federation (EHF) and was adapted to reflect the specific situation of headache care in Germany. It defines three levels of headache care: headache practitioner (level 1), headache outpatient clinic (level 2) and headache centers (level 3). The objective of the publication is to define and establish reliable criteria in the field of headache care in Germany.