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Cureus May 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in...
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an uncommon genetic disorder that affects small blood vessels in the brain. It leads to neurological symptoms, disability-adjusted life years, and difficult emotional and physical situations for patients and their families. As unusual brain symptoms appear, it becomes important to understand the different clinical manifestations of CADASIL. Our case report and review examine several cases to demonstrate different presentations and management strategies of CADASIL. A 52-year-old male with a family history of strokes at a young age from his father and paternal grandfather presented to a neurology clinic for left facial droop and drooling. Brain magnetic resonance imaging showed extensive periventricular and subcortical white matter disease, including the external capsule and subcortical white matter of the temporal lobe. Findings were suggestive of small vessel vasculopathy. A cerebral angiogram showed that all large extra- and intracranial vessels were patent without evidence of aneurysm formation. There was no obvious evidence of beading of the distal intracranial vessels. Cerebrospinal fluid studies were normal. The NOTCH3 mutation was sent to test for CADASIL, which came back positive. The patient was started on aspirin (81 mg) and atorvastatin (20 mg) daily. The patient was counseled on the possibility of having an ischemic or hemorrhagic stroke. Aspirin and atorvastatin were continued, a neuropsychological evaluation was ordered, and CADASIL genetic counseling and testing were offered to him and his children. Over several years, patients developed several strokes and seizures due to infarcts. He also developed intraparenchymal hemorrhage complicated by dysphagia, requiring a feeding tube. Due to his severe physical debility, he was discharged to a nursing home for rehabilitation, where he did not improve with therapy and remained bedbound. He was discharged and sent home with his family. CADASIL can present as a diagnostic challenge due to its common presentation with migraines, transient ischemic attacks, and strokes, with or without risk factors. This unique presentation of CADASIL with facial palsy highlights the importance of emerging atypical presentations and the need for a detailed history of neuroimaging, family history, and personal history of neurovascular events. By accurately diagnosing the condition, patients and families can be counseled on the disease course and genetics. Management requires a multidisciplinary approach with neurology, genetic counseling, physical therapy, psychology, and psychiatry if depression or anxiety is present, with the aim of improving the patient's quality of life.
PubMed: 38868233
DOI: 10.7759/cureus.60165 -
The Journal of Headache and Pain Jun 2024Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets....
BACKGROUND
Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine.
METHODS
We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs.
RESULTS
We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels.
CONCLUSIONS
This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs.
Topics: Humans; Migraine Disorders; Mendelian Randomization Analysis; Genome-Wide Association Study; Quantitative Trait Loci; Genetic Predisposition to Disease; Brain
PubMed: 38867170
DOI: 10.1186/s10194-024-01805-3 -
Clinical Ophthalmology (Auckland, N.Z.) 2024To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may...
PURPOSE
To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity.
METHODOLOGY
This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF.
RESULTS
In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively).
CONCLUSION
Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.
PubMed: 38863678
DOI: 10.2147/OPTH.S463016 -
NMC Case Report Journal 2024Stroke-like migraine attacks after radiation therapy (SMART) syndrome, a delayed sequela of cranial radiotherapy encountered rarely, occurs due to transient neurological...
Stroke-like migraine attacks after radiation therapy (SMART) syndrome, a delayed sequela of cranial radiotherapy encountered rarely, occurs due to transient neurological deficits coupled with migraine episodes. This case report describes an occurrence of SMART syndrome in an individual 8 years after receiving medulloblastoma treatment. The subject, a 21-year-old male, experienced abrupt aphasia and right-sided hemiparesis. Arterial spin labeling (ASL) revealed initial cerebral hypoperfusion in the left temporal and parietal regions, with no tumor resurgence or notable ischemic alterations. Two days later, the symptoms disappeared completely; nevertheless, at that time, ASL presented cerebral hyperperfusion in the same lobule. The subject experienced a pulsating headache and nausea the next day. In the context of SMART syndrome, this fluctuation in cerebral blood flow indicated by ASL is a unique finding. The significance of this case lies in the documentation of the dynamic evolution of cerebral perfusion in SMART syndrome via ASL, thereby elucidating its underlying pathophysiology. As hemiplegic migraine shows a similar cerebral perfusion pattern to SMART syndrome, we inferred an unexplored but shared pathophysiology among hemiplegic migraine and SMART syndrome. Through this successful capture of these distinct cerebral blood flow alterations, from hypoperfusion to hyperperfusion, our understanding of the pathophysiological intricacies inherent to SMART syndrome will be enhanced.
PubMed: 38863579
DOI: 10.2176/jns-nmc.2024-0037 -
Frontiers in Neurology 2024This cross-sectional study aims to investigate migraineurs' preferred complementary and alternative medicine (CAM) types and the factors influencing their usage.
OBJECT
This cross-sectional study aims to investigate migraineurs' preferred complementary and alternative medicine (CAM) types and the factors influencing their usage.
MATERIALS AND METHODS
An anonymous e-survey was distributed to Lithuanian Migraine Association members, and social media migraine support communities. The collected data consisted of demographic, migraine-related questions, personal qualities, CAM habits.
RESULTS
470 respondents were analyzed. 95.96% were women with a median age of 37 (IQR 31, 44). The median duration of migraine was 17.5 years (IQR 10, 25) and the median headache severity was rated 8 (IQR 7, 10) out of 10. 68.90% of participants had one or more headache days per week. 71.49% of respondents were triptan users, 27.66% used medical prophylaxis, and 17.87% used monoclonal antibodies. 52.55% of respondents used CAM in the past 12 months. Physical activity (36.17%), dietary changes/fasting (27.02%), relaxation/meditation (26.60%) were the most used CAM types. Reasons for CAM use included dissatisfaction with conventional treatment effectiveness (42.51%), concerns about safety (48.18%) and adverse effects (37.25%). Factors associated with the decision to explore CAM included longer headache duration ( = 0.017, Mann-Whitney U test), frequent sick leaves ( < 0.001, Mann-Whitney U test), current preventive medication use ( = 0.016, chi-square test), positive views on CAM safety/naturality ( = 0.001/ < 0.001, Mann-Whitney U test), belief of having a healthy diet (p < 0.001, chi-square test), food-related worries ( = 0.011, Mann-Whitney U test) and Big-five personality trait of openness to experience ( = 0.049, chi-square test). After logistic regression, the frequent need to take sick leaves, having a healthy diet, food-associated fears maintained statistical significance. CAM use was not associated with non-adherence to conventional medicine. 48.99% of CAM consumers disclosed CAM use to their doctors.
CONCLUSION
CAM is explored by a significant proportion of migraineurs, less than half communicate this to their doctors. In our sample, physical activity, dietary changes, and relaxation techniques were the most common. Many patients opted for CAM due to previously experienced side effects/ineffectiveness of conventional migraine treatment or the fear of potential harm from standard medication. Individual factors, such as openness of personality can be an important contributing factor.
PubMed: 38863511
DOI: 10.3389/fneur.2024.1378532 -
Cephalalgia : An International Journal... Jun 2024
REPLY to Comment on Correlation between endometriosis and migraine features: Results from a prospective case-control study'': Correlation between endometriosis and migraine features is not based on a broad strokes results.
Topics: Humans; Endometriosis; Migraine Disorders; Female; Case-Control Studies; Stroke; Prospective Studies
PubMed: 38863218
DOI: 10.1177/03331024241254821 -
The Journal of Headache and Pain Jun 2024Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance...
Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance imaging (MRI) is a powerful tool for investigating whole-brain connectivity patterns; however, systematic assessment of structural connectome organization has rarely been performed. In the present study, we aimed to examine the changes in structural connectivity in patients with episodic migraines using diffusion MRI. First, we computed structural connectivity using diffusion MRI tractography, after which we applied dimensionality reduction techniques to the structural connectivity and generated three low-dimensional eigenvectors. We subsequently calculated the manifold eccentricity, defined as the Euclidean distance between each data point and the center of the data in the manifold space. We then compared the manifold eccentricity between patients with migraines and healthy controls, revealing significant between-group differences in the orbitofrontal cortex, temporal pole, and sensory/motor regions. Between-group differences in subcortico-cortical connectivity further revealed significant changes in the amygdala, accumbens, and caudate nuclei. Finally, supervised machine learning effectively classified patients with migraines and healthy controls using cortical and subcortical structural connectivity features, highlighting the importance of the orbitofrontal and sensory cortices, in addition to the caudate, in distinguishing between the groups. Our findings confirmed that episodic migraine is related to the structural connectome changes in the limbic and sensory systems, suggesting its potential utility as a diagnostic marker for migraine.
Topics: Humans; Migraine Disorders; Connectome; Female; Adult; Male; Limbic System; Diffusion Tensor Imaging; Young Adult
PubMed: 38862883
DOI: 10.1186/s10194-024-01806-2 -
Cephalalgia : An International Journal... Jun 2024Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to... (Randomized Controlled Trial)
Randomized Controlled Trial
Acupuncture plus topiramate placebo versus topiramate plus sham acupuncture for the preventive treatment of chronic migraine: A single-blind, double-dummy, randomized controlled trial.
BACKGROUND
Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine.
METHODS
This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100 mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12.
RESULTS
Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, = 0.007]). No severe adverse events were reported.
CONCLUSIONS
Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine.
TRIAL REGISTRATION
ISRCTN.org Identifier 13563102.
Topics: Humans; Topiramate; Migraine Disorders; Female; Male; Middle Aged; Adult; Acupuncture Therapy; Chronic Disease; Treatment Outcome; Single-Blind Method; Young Adult; Combined Modality Therapy; Adolescent; Aged
PubMed: 38860524
DOI: 10.1177/03331024241261080 -
Cephalalgia : An International Journal... Jun 2024Real-world data on the effectiveness and safety of lasmiditan, a new medication for acute migraine attacks, is necessary. (Observational Study)
Observational Study
BACKGROUND
Real-world data on the effectiveness and safety of lasmiditan, a new medication for acute migraine attacks, is necessary.
METHODS
We performed a prospective, observational, multi-center, real-world study. A total of 48 patients with migraine (44 females, 44.6 ± 12.9 years old) were included in this study.
RESULTS
Twenty-three patients (47.9%) reported they were headache-free two hours after taking lasmiditan and were categorized into the responder group. In total, 44 patients (91.7%) experienced at least one side effect within two hours of taking the medication. Dizziness, somnolence, malaise, nausea, and palpitations were reported by 56.3% (n = 27), 45.8% (n = 22), 37.5% (n = 18), 20.8% (n = 10), and 14.6% (n = 7) of patients respectively. Of 48 patients, 20 (41.7%) indicated that they preferred lasmiditan to their previous acute treatment. There were no predictive factors for efficacy.
CONCLUSION
This real-world study demonstrated the efficacy and safety of lasmiditan. More than 90% of patients experienced side effects from lasmiditan. Approximately 40% of patients preferred lasmiditan despite the occurrence of side effects.
Topics: Humans; Migraine Disorders; Female; Male; Adult; Middle Aged; Japan; Prospective Studies; Treatment Outcome; Pyridines; Piperidines; Benzamides; Serotonin Receptor Agonists
PubMed: 38859749
DOI: 10.1177/03331024241258695 -
Cephalalgia : An International Journal... Jun 2024The present study aimed to investigate the predictive value of calcitonin gene-related peptide (CGRP)-induced migraine attacks for effectiveness to erenumab treatment in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The present study aimed to investigate the predictive value of calcitonin gene-related peptide (CGRP)-induced migraine attacks for effectiveness to erenumab treatment in people with migraine.
METHODS
In total, 139 participants with migraine underwent a single experimental day involving a 20-min infusion with CGRP. Following this, the participants entered a 24-week treatment period with erenumab. The primary endpoints were the predictive value of CGRP-induced migraine attacks on the effectiveness of erenumab, defined as ≥50% reduction in monthly migraine days, or ≥ 50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity.
RESULTS
Among participants with CGRP-induced migraine attacks, 60 of 99 (61%) achieved ≥50% reduction in monthly migraine days during weeks 13-24 with erenumab. Conversely, 13 of 25 (52%) where CGRP infusion did not induce a migraine achieved the same endpoint ( = 0.498). There were no significant differences between the ≥50% reduction in either monthly migraine or monthly headache days of moderate to severe intensity between CGRP-sensitive and non-sensitive participants ( = 0.625).
CONCLUSIONS
Our findings suggest that the CGRP-provocation model cannot be used to predict erenumab's effectiveness. It remains uncertain whether this finding extends to other monoclonal antibodies targeting the CGRP ligand or to gepants. The study was registered at ClinicalTrials.gov (NCT04592952).
Topics: Migraine Disorders; Humans; Calcitonin Gene-Related Peptide; Antibodies, Monoclonal, Humanized; Male; Female; Adult; Calcitonin Gene-Related Peptide Receptor Antagonists; Middle Aged; Biomarkers; Double-Blind Method; Predictive Value of Tests
PubMed: 38859744
DOI: 10.1177/03331024241258734