Headache最新文献

Background: Migraine is the most common neurological disorder and the second most disabling human condition. Autotaxin (ATX) is a plasma enzyme that leads to the formation of lysophosphatidic acid (LPA), which is involved in different functions involved in migraine, such as vascular tone control, inflammation, neuronal excitation, endothelial dysfunction, and neuropathic pain, among others. Most patients with migraine are females and, interestingly, ATX is physiologically higher in the serum of females compared to males.

Objective: As ATX may be a link between common mechanisms associated with migraine, we aimed to determine the potential role of ATX in migraine by studying its concentrations in serum between patients with episodic (EM) and chronic migraine (CM) compared to healthy controls, as well as the correlation of ATX with clinical outcomes, and other biomarkers described in migraine.

Methods: In this cross-sectional study, healthy controls (n = 62), and patients with EM (n = 45), and CM (n = 38) were studied. Clinical outcomes, such as migraine intensity as assessed on a visual analog scale (VAS), frequency of headaches (days/month), evolution time (months), and the duration of attacks (h) were investigated together with the serum biomarkers for inflammation (interleukin 6 [IL-6] and IL-10), trigeminovascular system activation (calcitonin gene-related peptide [CGRP]), endothelial dysfunction (pentraxin 3 [PTX3], cellular fibrinogen [cFN], soluble tumor necrosis factor-like weak inducer of apoptosis [sTWEAK]), and ATX. Additionally, the serum lipidomic biomarkers profile was also analyzed.

Results: Serum ATX levels were found to be significantly elevated in both patients with EM (mean [standard deviation, SD] 310.7 [79.7] ng/mL) and CM (mean [SD] 336.7 [66.9] ng/mL) compared to controls (mean [SD] 212.3 [53.2] ng/mL) (p < 0.001). Elevated ATX levels were associated with migraine outcomes in CM, such as VAS score (Spearman's coefficient = 0.405, p < 0.05), frequency (Spearman's coefficient = 0.718, p < 0.001), and evolution time (Spearman's coefficient = 0.2257, p < 0.01). ATX was correlated with CGRP (Pearson's coefficient = 0.278, p < 0.001), PTX3 (Pearson's coefficient = 0.468, p < 0.001), sTWEAK (Pearson's coefficient = 0.242, p < 0.001), cFN (Pearson's coefficient = 0.252, p < 0.01), and IL-6 serum levels (Pearson's coefficient = 0.159, p < 0.001). A drastic decrease in serum lysophosphatidylcholine levels indicates high ATX activity in patients with migraine.

Conclusions: Serum levels of ATX were significantly increased in patients with EM and CM. In addition, ATX correlates with clinical outcomes, as well as CGRP, endothelial dysfunction and inflammation biomarkers. Further studies are necessary to elucidate the potential role of ATX as a therapeutic target for migraine.

Objective: To estimate the real-world risk of cardiovascular events among patients with migraine treated with erenumab and other migraine preventive medications.

Background: Migraine preventive treatment with calcitonin gene-related peptide (CGRP) pathway inhibitors, such as erenumab and others, may theoretically result in cardiovascular effects due to a lack of compensatory vasodilation with CGRP pathway inhibition.

Methods: In this retrospective observational cohort study, we estimated the unadjusted cumulative risk (CR) of new-onset hypertension, acute myocardial infarction (MI), or stroke among patients with migraine newly treated with erenumab, other anti-CGRP pathway monoclonal antibodies (mAbs), standard oral preventive medications, and onabotulinumtoxinA using data from the MarketScan® Commercial and Medicare Supplemental medical claims database. Comparative analyses to assess the relative risk (RR) of vascular events were gated on the comparability of treatment groups with respect to baseline demographics and clinical characteristics. Potential bias due to unmeasured confounding was evaluated via negative control outcome (NCO) analyses. Confounding based on measured covariates and differential informative censoring were addressed with inverse probability weights.

Results: A total of 108,019 new users of migraine preventive medications were included. Unadjusted CR (95% confidence interval [CI]) of hypertension at 12 months of treatment was: erenumab, 9.34% (8.79-9.89%); other anti-CGRP pathway mAbs, 9.42% (8.92-9.92%); standard oral preventive medications, 9.09% (8.77-9.41%); and onabotulinumtoxinA, 9.10% (8.39-9.81%). NCO analyses identified minimal concerns related to unmeasured confounding in erenumab versus other mAbs and erenumab versus onabotulinumtoxinA comparisons. Adjusted RRs (95% CIs) of acute MI and stroke, respectively, at 36 months of treatment were 1.02 (0.45-1.59) and 0.90 (0.56-1.25) for erenumab versus other mAbs and 0.87 (0.19-1.55) and 0.97 (0.42-1.52) for erenumab versus onabotulinumtoxinA.

Conclusions: In this analysis of the MarketScan medical claims database, we found no difference in the risk of vascular events in patients treated with erenumab versus other anti-CGRP pathway mAbs or onabotulinumtoxinA.

Skull base metastases, including those from small-cell lung carcinoma (SCLC), can present with various syndromes depending on the site of involvement, such as orbital syndrome, parasellar syndrome, middle fossa syndrome, jugular foramen syndrome, and occipital condyle syndrome (OCS). One such example is OCS, which consists of unilateral occipital headache accompanied with ipsilateral hypoglossal palsy. This case report describes a 51-year-old man initially diagnosed with OCS, which led to the discovery of systemic bone metastases from SCLC. Magnetic resonance imaging showed lesions in the occipital condyle and hypoglossal canal, while positron emission tomography-computed tomography identified a lung mass and widespread metastases. SCLC is highly aggressive and metastatic, with the bone being a common site of spread. In this case, the OCS preceded the diagnosis of the underlying malignancy. Prompt diagnosis and treatment are crucial, as patients with OCS often have advanced disease. This case highlights the importance of considering SCLC as a potential etiology for OCS, given the propensity for bone metastases. Early recognition and evaluation of OCS is essential to initiate appropriate management.

Objective: To assess patient reported outcomes of patients with migraine receiving preventative medications, and to compare patient reported outcomes and unplanned care of patients on calcitonin gene-related peptide inhibitors (CGRPi) with those on other preventative medications.

Background: Patient reported outcome measures can be useful in conditions such as migraine with frequent disability. CGRPi are newer migraine preventative medications that can improve patients' quality of life.

Methods: This was a retrospective cohort analysis of Patient Reported Outcomes Measurement Information System (PROMIS) data combined with administrative claims data from a large regional health plan for adult patients (≥18 years) with migraine who were on preventative medications from January 2019 to March 2022. PROMIS scores of patients on CGRPi were compared to scores of patients who switched from other preventative medications to CGRPi (pre vs. post), between patients adherent to CGRPi versus non-adherent, and changes in all-cause/migraine-related unplanned care (emergency department) use by the CGRPi cohort.

Results: There were 1245 patients on other preventative medications (antiseizure [532/1245 (43%)], antidepressants [316/1245 (25%)], and beta-blockers [397/1245 (32%)]), 148 who were on CGRPi, and 112 who had switched from other preventative medications to CGRPi. The mean age was 44 years old, 88% were females, 50% were married, and 75% were on commercial insurance. Patients with migraine had higher T-scores in pain, fatigue, anxiety, and sleep disturbance than the general population. Patients on CGRPi had a statistically significant reduction in pain T-scores (60.4 [standard deviation (SD) 7.4] to 58.4 [SD 8.2], p = 0.003) post initiation of medications, especially those who switched from other preventative medications to CGRPi (61.4 [SD 6.9] to 58.7 [SD 8.3], p < 0.001). The pain T-score reduction occurred only among the adherent group. There was a lower proportion of patients with all-cause unplanned care among patients on CGRPi (43% [64/148] to 32% [47/148], p < 0.001), but the reduction in migraine-related unplanned care was not statistically significant (9% [14/148] to 6% [9/148], p = 0.197).

Conclusion: Our findings suggest that patients had an improvement in pain reduction scores after initiating CGRPi. PROMIS scores could provide important information about quality-of-life improvement for prescribers.

Objective: To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants.

Background: Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks.

Methods: In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles.

Results: The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases.

Conclusion: During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Objective: To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.

Background: Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.

Methods: A literature search identified RCTs evaluating the efficacy (2-h pain relief [2hPR]) of different DHE dosage forms. The PK profiles for these DHE dosage forms were determined from published literature. Univariate regression analyses were performed to determine the PK parameters that best predicted 2hPR across DHE dosage forms. The relationship between maximum plasma concentration (C_max) and nausea incidence for various dosage forms was determined from published Phase 1 trials.

Results: The literature search identified nine RCTs with DHE dosage forms that reported 2hPR: DHE liquid nasal spray (four studies), DHE administered subcutaneously (three), and DHE administered via oral pulmonary inhalation (two). The DHE PK parameters that best predicted 2hPR rates were C_max and area under the curve from time zero to 0.5 h post-dose (AUC_0-0.5h) (R² = 0.59 for each). Across Phase 1 trials, nausea incidence was minimal when C_max was <2500 pg/mL but increased in a log-linear manner when C_max exceeded ~2500 pg/mL.

Conclusions: The maximum concentration and AUC over the first 30 min following DHE administration were associated with increasing rates of 2hPR and a C_max below ~2500 pg/mL was associated with low incidences of nausea. We suggest that this may be an optimal profile for a DHE delivery form. Further research to test this hypothesis is warranted.

Objective: The aim of this study was to provide long-term clinical results-including "sweet spot" identification and connectomic imaging analysis-in a series of patients treated with deep brain stimulation for refractory chronic cluster headache.

Background: Deep brain stimulation is a relatively recent indication for the treatment of refractory chronic cluster headache. This indication has generated substantial debate in recent years due to uncertainty surrounding the mechanism of action and the lack of long-term efficacy data.

Methods: Case retrospective series of adult patients diagnosed with refractory chronic cluster headache and treated with deep brain stimulation. Demographic and clinical data were registered preoperatively and at 3, 6, 12, and 24 months. The primary endpoint was reduction in headache load, a composite score of frequency, severity, and duration of each attack. Imaging analyses (sweet spot and connectomic analyses) were performed to identify the brain regions most closely correlated with the reduction in headache load and to identify the structural networks involved. Treatment response was categorized according to the reduction in headache load, as follows: poor (<30% reduction), partial (30-50%), or high (>50%).

Results: A total of 14 patients were included, with a mean (standard deviation [SD]) age of 42.4 (10.7) years and mean (SD) headache duration of 8.0 (5.8) years. Headache load scores decreased significantly from baseline to Month 24: mean (SD) 424.2 (325.9) versus 135.9 (155.7) (p = 0.001). In most patients (eight patients [58.0%]), headache load scores decreased by 50% after treatment. The other six patients showed either a partial (three [21.0%]) or poor (three [21.0%]) response. The optimized sweet spot was the lateral ventral tegmental area ((Montreal Neurological Institute) MNI coordinates of the center of mass: x = ± 9.0 mm, y = -10.6 mm, z = -3.5 mm). The connectomic analysis pointed to the probable implication of corticorubral tracts.

Conclusion: These findings suggest that a substantial proportion of patients with refractory chronic cluster headache obtain significant long-term clinical benefits from deep brain stimulation. Good responders were characterized by a robust improvement in headache load within 3-6 months after surgery. The lateral ventral tegmental area was identified as the best target for this indication, with the likely participation of corticorubral tracts.

Objective: To explore the relationships among anxiety, depression, and headache-related disability in a pediatric clinic-based retrospective cross-sectional study.

Background: Anxiety and depression are commonly considered comorbidities of headache disorders and are frequently seen in children and adolescents. These conditions can contribute to disability and may have a cumulative impact. In this study, we tested whether self-reported anxiety and/or depression in youth were associated with headache-related disability.

Methods: This was a retrospective cross-sectional study of children ages 6-17 years old who completed a headache intake questionnaire at the time of a new outpatient neurology visit. Those who reported on behavioral health symptoms, involvement of a behavioral health provider (i.e., yes/no), and the PedMIDAS (a validated metric of headache-related disability) were included. The relationship between anxiety and/or depression and headache-related disability was examined.

Results: Of the 12,660 questionnaires queried, 9118 met criteria for inclusion. Respondents were 64.0% female and had a median age of 13.5 years (interquartile range [IQR] 10.3, 15.7). Compared to patients without self-reported anxiety/depression, patients with anxiety and depression reported higher headache-related disability (M = 17.0, [IQR 6.0, 41.0]) even after accounting for covariates (estimated difference = 6.0, 95% confidence interval [CI: 4.4-7.5]). For participants with anxiety and/or depression, having a behavioral health provider was associated with greater headache-related disability (estimated difference = 7.0; 95% CI 4.6-9.3).

Conclusions: Patients with self-reported anxiety and/or depression reported higher headache-related disability. Having a behavioral health provider was associated with greater headache-related disability, indicating the complexity and high level of need for this population. Further research is needed to understand the directionality of these results; however, patients with headache as well as depression and or anxiety are a vulnerable group who may benefit from an integrated care model.