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Byline: Steffen. Naegel, Mark. Obermann Background: Key structures for the pathophysiology of primary headache disorders such as migraine, cluster headache, and other trigeminal autonomic cephalalgias were identified by imaging in [...]

Background: Digitalization and electronic health (eHealth) offer new treatment approaches for patients with migraine. Current smartphone applications (apps) for migraine patients include a wide spectrum of functions ranging from digital headache diaries to app-based headache treatment by, among others, analysis of the possible triggers, behavioral therapy approaches and prophylactic non-drug treatment methods with relaxation therapy or endurance sport. Additional possibilities arise through the use of modern, location-independent communication methods, such as online consultations. However, there is currently insufficient evidence regarding the benefits and/or risks of these electronic tools for patients. To date, only few randomized controlled trials have assessed eHealth applications. Methods: SMARTGEM is a randomized controlled trial assessing whether the provision of a new digital integrated form of care consisting of the migraine app M-sense in combination with a communication platform (with online consultations and medically moderated patient forum) leads to a reduction in headache frequency in migraine patients, improving quality of life, reducing medical costs and work absenteeism (DRKS-ID: DRKS00016328). Discussion: SMARTGEM constitutes a new integrated approach for migraine treatment, which aims to offer an effective, location-independent, time-saving and cost-saving treatment. The design of the study is an example of how to gather high quality evidence in eHealth. Results are expected to provide insightful information on the efficacy of the use of electronic health technology in improving the quality of life in patients suffering from migraine and reducing resource consumption. [ABSTRACT FROM AUTHOR]

Objective: To identify grey matter alterations in patients suffering new daily persistent headache to enrich the pathophysiological concept of this rare headache disorder characterised by a distinct, clearly remembered onset and its instant chronification. Method: Magnetic resonance-based voxel-based and surface-based morphometry was used to investigate 23 patients suffering from new daily persistent headache and 23 age- and gender-matched healthy controls with 1.5 Tesla MRI. Independent statistical analysis was performed at three sites using statistical parametric mapping, as well as FSL(FMRIB Software Library)-based approaches. Results: No grey matter changes were detected using this sophisticated and cross-checked method. Conclusion: The absence of structural brain changes in patients with new daily persistent headache contribute to the recent discussion regarding structural alterations in primary headache disorders in general and does not provide evidence for grey matter changes being associated with the pathophysiology of new daily persistent headache. Future research will have to determine the underlying pathophysiological mechanisms of this disorder. [ABSTRACT FROM AUTHOR]

Background and purpose: Vestibular migraine (VM) patients are ictally and interictally hypersensitive for self‐motion and visual perception. Increased cortical excitability of the vestibular system represented by lowered motion perception thresholds might play an important role in the pathophysiology of VM. We aimed to compare motion perception thresholds and the vegetative response to rotatory motion, as well as the vestibulo‐ocular reflex (VOR) during rotation in VM patients compared to healthy controls (HC). Methods: In this cross‐sectional study, 28 female VM patients in the interictal state and 33 age‐ and gender‐matched HC were investigated sitting in a motorized rotary chair shielded regarding visual and acoustic stimuli for 20 min with slowly increasing velocity (maximum = 72°/s). The motion perception threshold was indicated by the participants by pushing a button. During and after rotation, participants rated the presence and extent of motion sickness using a sickness rating scale. Results: We detected lower motion perception thresholds (7.54°/s vs. 23.49°/s; p < 0.001) in VM patients compared to HC but no difference at the basic VOR thresholds. Furthermore, the patients showed enhanced susceptibility to motion sickness during and after the rotation. Conclusions: We provide evidence for decreased motion perception thresholds and pronounced susceptibility to motion sickness in VM patients in the interictal state, which could indicate alterations in higher levels of vestibular processing. Future studies should determine whether this could be the pathophysiological hallmark of VM either as a unique disease entity or in differentiation from other forms of migraine. [ABSTRACT FROM AUTHOR]

The article presents the case of a young female with mitochondrial encephalopathy, lactate acidosis, and stroke-like episodes (MELAS) syndrome with a stroke-like episode to discuss the efficacy of erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, as a treatment of migraine. Topics include the pathophysiology of mitochondrial vasculopathy and erenumab as treatment of highly refractory migrainous headache.

Objective To investigate headache-related serum melatonin levels and melatonin excretion rhythmicity in patients with hypnic headache (HH). Background Strict sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal role in the pathophysiology of HH. Methods Serum melatonin levels were acquired in nine patients with HH and nine age- and gender-matched healthy controls over a 20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am). Results No significant changes of melatonin levels could be detected comparing HH patients and healthy controls. Melatonin excretion rhythmicity was not significantly altered in patients with HH (Mean melatonin level in ng/mL ± SD, patients vs controls at 12 pm: 21.5 ± 9.5 vs 13.6 ± 6.3 [ P = .077], 4 pm: 18.4 ± 8.4 vs 14.0 ± 4.7 [ P = .222], 7 pm: 19.4 ± 5.1 vs 15.1 ± 4.5 [ P = .094], 10 pm: 59.5 ± 45.0 vs 29.4 ± 12.7 [ P =.136], headache time: 96.9 ± 68.3 vs 49.1 ± 22.8 [ P = .94], and 8 am: 31.6 ± 18.3 vs 26.7 ± 15.6 [ P = .489]). Conclusion This study is not able to confirm a significant role of melatonin concentration changes in the pathophysiology of HH and vetoes that melatonin deficiency plays a major role in the pathophysiology of the disorder. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging studies using voxel-based morphometry (VBM) detected structural changes in the human brain within periods of months or weeks. The underlying molecular mechanisms of VBM findings remain unresolved. We showed that simple visual stimulation by an alternating checkerboard leads to instant, short-lasting alterations of the primary and secondary visual cortex detected by VBM. The rapidness of occurrence (i.e., within 10 minutes) rather excludes most of the proposed physiological mechanism such as neural or glial cell genesis/degeneration or synapse turnover. We therefore favour cerebral fluid shifts to be the underlying correlate of the here observed VBM gray matter changes. Fast onset gray matter changes might be one important explanation for the inconsistency of VBM study results that often raise concern in regard to the validity of presented data. This study shows that changes detectable by VBM may occur within a few minutes after physiological stimulation and must be considered in future VBM experiments to avoid misinterpretation of results. [ABSTRACT FROM AUTHOR]

Objective: Persistent postural-perceptual dizziness (PPPD) is the most common vestibular disorder in the age group between 30 and 50 years. It is considered to be based on a multisensory maladjustment involving alterations of sensory response pattern including vestibular, visual and motion stimuli. Previous data supported a link between vestibular and pain mechanism. The aim of the study was to investigate whether other sensory inputs such as pain stimuli might be altered in terms of a more widespread central perception dysfunction in this disorder. Methods: Nociceptive blink reflex was measured in 27 patients with PPPD and compared with 27 healthy, age and gender matched controls. The habituation of the R2 component of the blink reflex was evaluated as the percentage area-under-the curve (AUC) decrease in ten consecutive blocks of five averaged rectified responses. Additionally, clinical characteristics were evaluated. Results: In patients with PPPD a lack of habituation was observed compared to healthy controls. Relative AUC decreased between the first and the tenth block by 19.48% in PPPD patients and by 31.63% (p = 0.035) in healthy controls. There was no correlation between clinical data (course of disease, comorbid depression, medication, trigger factors) or electrophysiological data (perception threshold, pain threshold, stimulus intensity) and habituation pattern. No trigeminal sensitization in terms of facilitation of absolute values could be detected. Conclusion: Our study results supports the hypothesis of the multisensory dimension of impaired sensory processing in patients with PPPD extends beyond vestibular/visual motion stimuli and reflexive postural/oculomotor control mechanisms to other sensory inputs such as pain perception in terms of a more generalized disturbed habituation pattern. [ABSTRACT FROM AUTHOR]

Recent studies from the UK give the debate about how to deal best with patients suffering from whiplash injury new impetus. Following whiplash injury, about 90% of patients complain about head and/or neck pain, as well as dizziness, sleep problems and anxiety. These symptoms are often referred to as whiplash-associated disorders. In the majority of cases, these complaints develop within a few days or weeks following the accident. However, 30–50% of patients experience prolonged symptoms for more than 6 months, with headache as the main complaint. In accordance with the bio-psycho-social model of chronic post-traumatic headache, the following treatment options have been suggested: (1) proper patient education with detailed explanation of the condition; (2) support of normal movement; (3) avoiding immobilization; (4) resumption of work; and (5) targeted physiotherapy. Based on current study data, intensified physiotherapy seems not to be superior to standard therapy with simple patient education and can therefore not be recommended considering cost–benefit aspects. [ABSTRACT FROM AUTHOR]

With regard to frequency, duration, intensity and concomitant vegetative symptoms of migraine headache and vertigo attacks, VM is a complex disorder with various facets. However, we do not have information regarding the latency of our examination to the next migraine headache or vertigo attack. Last but not least, future studies should document the timing of migraine headache and vertigo attacks immediately before and after stimulation to better understand the cyclic pattern of thresholds in VM since this could also lead to biased measurements. [Extracted from the article]

The article offers a discussion on the pathophysiologic mechanism of hypnic headache (HH), a rare primary headache disorder. It cited several factors considered to determine underlying pathophysiologic mechanisms including cerebral imaging, drug efficacy and types of symptomatic headache. Topics covered include the diagnostic criteria of HH, role of trigeminal facilitation and habituation in HH, and symptoms of brain tumors that resemble HH.

.Background: Hypnic headache (HH) is a rare primary headache disorder that is characterised by strictly sleep-related headache attacks. Purpose: Because of the low prevalence of this headache disorder, disease information is mainly based on case reports and small case series. This review summarises current knowledge on HH in regard to clinical presentation, pathophysiology, symptomatic causes and therapeutic options. Method:We review all reported HH cases since its first description in 1988 by Raskin. Broadened diagnostic criteria were applied for patient selection that slightly deviate from the current ICHD-II criteria. Patients were allowed to describe the headache character to be other than dull. Additionally, accompanying mild trigemino-autonomic symptoms were permitted. Conclusions: Mainly elderly patients are affected, but younger patients and even children might also suffer from HH. Headache attacks usually last between 15 and 180 minutes, but some patients report headache attacks up to 10 hours. Almost all patients report motor activity during headache attacks. Cerebral MRI and 24-hour blood pressure monitoring should be performed in the diagnostic work-up of HH. Other primary headache disorders such as migraine and cluster headache may also present with sleep-related headache attacks and should be considered first. Caffeine taken as a cup of strong coffee seems to be the best acute and prophylactic treatment option. [ABSTRACT FROM AUTHOR]

Background: Hypnic headache (HH) is a rare primary headache disorder that is characterized by exclusively sleep-related headache attacks. Because of its low prevalence, clinical features and therapeutic options are widely unknown or under discussion.Methods: Twenty patients with HH were examined and interviewed using a standardized questionnaire in regard to their clinical characteristics and effective treatment regimens. Data were evaluated according to current International Headache Society (IHS) diagnostic criteria. Individual treatment history and effective treatment options were compared with expected efficacy based on current literature.Results: In conflict to current IHS criteria, 15% of patients reported trigemino-autonomic symptoms. All patients showed distinct motor behavior during their headache attacks. In acute pain attacks caffeine was most effective. Lithium, topiramate, melatonin, amitriptyline and indomethacin were sometimes useful prophylactic treatment options but were often associated with side effects.Conclusions: Our results underline the need for modification of the IHS diagnostic criteria of HH to better reflect the actual clinical characteristics of this headache. Caffeine should be considered as first-line acute therapy. Prophylactic medical treatment should be carefully evaluated in regard to side effects in this aged patient population, as this seems to be a major concern of patients apart from pure pain reduction. [ABSTRACT FROM AUTHOR]

Mitochondrial processes may play a role in the pathophysiology of migraine. Serum levels of two biomarkers, Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15), are typically elevated in patients with mitochondrial disorders. The study investigated whether the presence of migraine may influence FGF-21 and GDF-15 serum levels considering vascular and metabolic disorders as possible confounders. A cross-sectional study in two headache centers was conducted analyzing GDF-15 and FGF-21 serum concentration in 230 patients with episodic and chronic migraine compared to a control group. Key clinical features of headache were evaluated, as well as health-related life quality, anxiety and depression using SF-12 and HADS-questionnaires. Elevated GDF-15 values were detected in the migraine group compared to the control group (506.65 ± 275.87 pg/mL vs. 403.34 ± 173.29 pg/mL, p < 0.001, Mann–Whitney U test). A strong correlation between increasing age and higher GDF-15 levels was identified (p < 0.001, 95%-CI elevation of GDF-15 per year 5.246–10.850 pg/mL, multiple linear regression). Mean age was different between the groups, and this represents a confounding factor of the measurements. FGF-21 levels did not differ between migraine patients and controls (p = 0.635, Mann–Whitney U test) but were significantly influenced by increasing BMI (p = 0.030, multiple linear regression). Neither biomarker showed correlation with headache frequency. Higher FGF-21 levels were associated with a higher mean intensity of headache attacks, reduced health-related life quality and anxiety. When confounding factors were considered, increased serum levels of FGF-21 and GDF-15 were not detected in migraine patients. However, the results show an age-dependence of GDF-15 in migraine patients, and this should be considered in future studies. Similar findings apply to the relationship between FGF-21 and BMI. Previous studies that did not adjust for these factors should be interpreted with caution. [ABSTRACT FROM AUTHOR]

The article examines on the risk of vestibular migraine from the combination of dizziness, vertigo and balance disturbance with migraine. It highlights the knowledge on vestibular migraine associated with epidemiology, clinical presentation differential diagnosis of migraine. It also emphasizes the rates of patients who were diagnosed with vertigo and headache in clinical neurology.

Background: The prevalence of migraine and non-migraine headache declines with age.Methods: Data from the third visit (2011-2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65-86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression.Results: The lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had "episodic infrequent migraine, 0-8 headache days/month", 10 (0.5%) had "episodic frequent migraine, 9-14 headache days/month", and five (0.2%) had "chronic migraine, ≥15 headache days/month". Overall, 10 (0.5%) had "chronic headache, any headache on ≥15 days/month". Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity.Conclusions: Headaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission. [ABSTRACT FROM AUTHOR]

The article presents a study aimed at identifying structural brain alterations linked to vestibular migraine (VM) to show involvement of somatosensory-, pain- and migraine-related structural changes as well as changes related to central vestibular control, dizziness and vertigo. Topics discussed include the theories on the pathogenesis of VM, the presence of grey matter (GM) volume reduction in brain regions showing structural changes in patients, and the study's clinical implications.

Background: Analysis of habituation patterns in patients wi+ primary headache disorders allows +e detection of changes to +e excitability level of +e trigeminal nociceptive system. Previous studies demonstrated a habituation deficit to painful stimuli in migraine and it was suggested +at similar observations could be made in cluster headache (CH). Me+ods: Habituation of +e ''nociceptive'' blink reflex (nBR) (R2 response) was studied in 66 CH patients (18 episodic CH inside bout, 28 episodic CH outside bout, 20 chronic CH) as well as in 30 heal+y controls in a case-control study design. Results: Habituation behaviour was similar in CH and heal+y controls as well as in CH subtypes. No side-to-side differences of habituation between headache side and non-headache side were detected. Conclusion: Our results did not detect an altered habituation in CH patients. Despite clinical similarities, migraine and CH seem not to share +e same pa+ophysiological mechanisms in +is regard. [ABSTRACT FROM AUTHOR]

Background: Hypnic headache (HH) is a rare primary headache disorder characterized by strictly sleep-related headache attacks. Most patients are over the age of 50 and usually awake at the same time at night with dull bilateral head pain. The pathophysiology of this headache disorder is still enigmatic but association with rapid eye movement (REM) sleep and sleep-disordered breathing (SDB) has been suggested.Methods: Six patients with HH according to the current International Classification of Headache Disorders (ICHD-II) criteria (code 4.5) were investigated. Serial polysomnography (PSG) was performed in each patient for four consecutive nights.Results: A total of 22 HH attacks were recorded from all patients during PSG. Six of the monitored headache attacks arose from REM sleep; 16 attacks, however, arose from different non-REM (NREM) sleep stages. Five patients showed an increased apnoea/hypopnoea index (>" xbd="863" xhg="831" ybd="1443" yhg="1407"/>5), indicating obstructive sleep apnoea (OSA) on some but not the majority of nights. Headache onset and occurrence of SDB were not temporally connected.Conclusions: This prospective study shows that the onset of HH was not associated with sleep stage. These results contradict the current belief that REM sleep and SDB play a crucial role in the pathophysiology of HH. [ABSTRACT FROM PUBLISHER]