Hypersensitivity to CGRP as a predictive biomarker of migraine prevention with erenumab.

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 (p = 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 (p = 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.Trial Registration: The study was registered at ClinicalTrials.gov (NCT04592952).

Hypersensitivity to BKCa channel opening in persistent post-traumatic headache.

BACKGROUND: Large conductance  calcium-activated potassium (BKCa) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could induce migraine-like headache in persons with PPTH. METHODS: This is a randomized double-blind, placebo-controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic saline) that was infused intravenously over 20 minutes. The two experiment sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. The secondary endpoint was the area under the curve (AUC) values for headache intensity scores between MaxiPost and placebo over the same 12-hour observation period. RESULTS: Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Furthermore, the median headache intensity scores, represented by AUC values, were higher following MaxiPost than after placebo (P < .001). CONCLUSIONS: Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. Additional investigations are nonetheless needed to confirm these insights and explore the therapeutic prospects of BKCa channel blockers in managing PPTH. GOV IDENTIFIER: NCT05378074.

Robotic-assisted Laparoscopic Repair of Kidney Transplant Ureteral Strictures.

OBJECTIVE: To evaluate outcomes of robotic-assisted transplant ureteral repair (RATUR) for the management of kidney transplant ureteral strictures (TUS). METHODS: We retrospectively analyzed 41 consecutive patients who underwent RATUR for TUS at multiple tertiary referral centers between January 2016 and December 2022. RATUR was performed utilizing a robotic-assisted transperitoneal approach. The primary outcome was stricture recurrence rate and secondary outcomes included postoperative complicate rate, determining factors impacting with allograft functional recovery, and rate of conversion to open surgery. Categorical and continuous variables are displayed as total number (Percentage) or median [Interquartile Range], respectively. Pearson correlation coefficient was utilized to assess categorical variable correlation with creatinine. RESULTS: The median age was 56years [44,66]. The female-to-male ratio was 1.1:1. Approximately 66% of patients were dialysis-dependent prior to kidney transplantation. TUS was identified at a median time of 4months [2, 15.5] following kidney transplant. Median stricture length was 2 cm [1.22, 2.9 cm]. There were no TUS recurrences with a median follow-up of 36months [24,48]. There were 3 Clavien grade 2 and 1 Clavien grade 3 complications (9.5%). No baseline characteristics or preoperative diagnostics were correlated with a long-term decline in renal allograft function. CONCLUSION: RATUR has excellent and durable outcomes with low complication rates. These findings encourage the use of a minimally invasive definitive repair as a first-line treatment option for the management of TUS.

Differences in Cortical Morphology in People With and Without Migraine: A Registry for Migraine (REFORM) MRI Study.

BACKGROUND AND OBJECTIVES: Structural imaging can offer insights into the cortical morphometry of migraine, which might reflect adaptations to recurring nociceptive messaging. This study compares cortical morphometry between a large sample of people with migraine and healthy controls, as well as across migraine subtypes. METHODS: Adult participants with migraine and age-matched and sex-matched healthy controls attended a single MRI session with magnetization-prepared rapid acquisition gradient echo and fluid-attenuated inversion recovery sequences at 3T. Cortical surface area, thickness, and volume were compared between participants with migraine (including subgroups) and healthy controls across the whole cortex within FreeSurfer and reported according to the Desikan-Killiany atlas. The analysis used cluster-determining thresholds of p < 0.0001 and cluster-wise thresholds of p < 0.05, adjusted for age, sex, and total intracranial volume. RESULTS: A total of 296 participants with migraine (mean age 41.6 years ± 12.4 SD, 261 women) and 155 healthy controls (mean age 41.1 years ± 11.7 SD, 133 women) were included. Among the participants with migraine, 180 (63.5%) had chronic migraine, 103 (34.8%) had migraine with aura, and 88 (29.7%) experienced a migraine headache during the scan. The total cohort of participants with migraine had reduced cortical surface area in the left insula, compared with controls (p < 0.0001). Furthermore, participants with chronic migraine (n = 180) exhibited reduced surface area in the left insula (p < 0.0001) and increased surface area in the right caudal anterior cingulate cortex (p < 0.0001), compared with controls. We found no differences specific to participants with aura or ongoing migraine headache. Post hoc tests revealed a positive correlation between monthly headache days and surface area within the identified anterior cingulate cluster (p = 0.014). DISCUSSION: The identified cortical changes in migraine were limited to specific pain processing regions, including the insula and caudal anterior cingulate gyrus, and were most notable in participants with chronic migraine. These findings suggest persistent cortical changes associated with migraine. TRIAL REGISTRATION INFORMATION: The REFORM study (clinicaltrials.gov identifier: NCT04674020).

Effects of PDE-3 inhibition in persistent post-traumatic headache: evidence of cAMP-dependent signaling.

BACKGROUND: Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. METHODS: We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window. RESULTS: Twenty-one persons underwent randomization and completed both experiment days. The mean participants' age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P <.001). CONCLUSIONS: Our results provide novel evidence showing that PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Given that PDE-3 inhibition increases intracellular cAMP levels, our findings allude to the potential therapeutic value of targeting cAMP-dependent signaling pathways in the management of PPTH. Further investigations are imperative to substantiate these insights and delineate the importance of cAMP-dependent signaling pathways in the neurobiologic mechanisms underlying PPTH. GOV IDENTIFIER: NCT05595993.

Clinical features of migraine with aura: a REFORM study.

BACKGROUND: About one-third of persons with migraine experience transient neurologic symptoms, referred to as aura. Despite its widespread prevalence, comprehensive clinical descriptions of migraine with aura remain sparse. Therefore, we aimed to provide an in-depth phenotypic analysis of aura symptoms and characteristics in a cross-sectional study of a large sample of adults diagnosed with migraine with aura. METHODS: Data were extracted from the baseline characteristics of participants in the Registry for Migraine (REFORM) study - a single-center, prospective, longitudinal cohort study. Participants were adults diagnosed with migraine aura, reporting ≥ 4 monthly migraine days in the preceding 3 months. Trained personnel conducted in-person semi-structured interviews, capturing details on the nature, duration, localization, and progression of individual aura symptoms. RESULTS: Of the 227 enrolled participants with migraine with aura, the mean age was 41.1 years, with a predominant female representation (n = 205 [90.3%]). Visual aura was present in 215 (94.7%) participants, somatosensory aura in 81 (35.7%), and speech and/or language aura in 31 (13.7%). A single type of aura was observed in 148 (65.2%) participants, whilst 79 (34.8%) reported multiple aura types. Most participants (n = 220 [96.9%]) described their aura symptoms as positive or gradually spreading. Headache in relation to aura was noted by 218 (96.0%) participants, with 177 (80.8%) stating that the onset of aura symptoms preceded the onset of headache. CONCLUSIONS: This study offers a detailed clinical depiction of persons with migraine with aura, who were predominantly enrolled from a tertiary care unit. The findings highlight potential gaps in the available literature on migraine with aura and should bolster clinicians' acumen in diagnosing migraine with aura in clinical settings.

Premonitory symptoms in migraine: A REFORM Study.

BACKGROUND: Estimates of proportions of people with migraine who report premonitory symptoms vary greatly among previous studies. Our aims were to establish the proportion of patients reporting premonitory symptoms and its dependency on the enquiry method. Additionally, we investigated the impact of premonitory symptoms on disease burden using Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) and World Health Organization Disability Assessment 2.0 (WHODAS 2.0), whilst investigating how various clinical factors influenced the likelihood of reporting premonitory symptoms. METHODS: In a cross-sectional study, premonitory symptoms were assessed among 632 patients with migraine. Unprompted enquiry was used first, followed by a list of 17 items (prompted). Additionally, we obtained clinical characteristics through a semi-structured interview. RESULTS: Prompted enquiry resulted in a greater proportion reporting premonitory symptoms than unprompted (69.9% vs. 43.0%; p < 0.001) and with higher symptom counts (medians 2, interquartile range = 0-6 vs. 1, interquartile range = 0-1; p < 0.001). The number of symptoms correlated weakly with HIT-6 (ρ = 0.14; p < 0.001) and WHODAS scores (ρ = 0.09; p = 0.041). Reporting postdromal symptoms or triggers increased the probability of reporting premonitory symptoms, whereas monthly migraine days decreased it. CONCLUSIONS: The use of a standardized and optimized method for assessing premonitory symptoms is necessary to estimate their prevalence and to understand whether and how they contribute to disease burden.

Postdromal symptoms in migraine: a REFORM study.

BACKGROUND: Migraine is a multiphasic neurovascular disorder, where headache can be succeeded by postdromal symptoms. However, there are limited research on postdromal symptoms. This study aimed to investigate the proportion of individuals with migraine from a tertiary care unit reporting postdromal symptoms in adherence with the ICHD-3 definition. We also aimed to examine how the means of enquiry might influence the estimated proportions. Additionally, we explored whether any clinical features might affect the likelihood of reporting postdromal symptoms. Finally, we assessed to what extend the postdromal symptoms might impact the disease burden. METHODS: In a cross-sectional study, we enrolled adult participants diagnosed with migraine who were asked to report their postdromal symptoms (i.e., unprompted reporting). Subsequently, a 16-item list was used to further ascertain the occurrence of postdromal symptoms (i.e., prompted reporting). Clinical characteristics were obtained through a semi-structured interview. Moreover, electronic questionnaires were used to assess the disease burden, i.e., the Six-Item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and the World Health Organization Disability Assessment 2.0 (WHODAS 2.0). RESULTS: Among 631 participants with migraine, a higher proportion experienced at least one postdromal symptom when prompted (n = 509 [80.7%]) compared with unprompted reporting (n = 421 [66.7%], P < 0.001). Furthermore, the total number of postdromal symptoms experienced was greater with prompted than unprompted reporting (medians 3 [IQR 1 - 6] versus 1 [IQR 0 - 2]; P < 0.001). Furthermore, the likelihood of reporting postdromal symptoms increased with the presence of premonitory symptoms and decreased with higher number of monthly migraine days. Weak correlations were identified between the number of postdromal symptoms reported and both HIT-6 (ρ = 0.14; P < 0.001) and WHODAS scores (ρ = 0.15; P < 0.001), whilst no correlation was observed with MIDAS score (ρ = 0.08; P = 0.054). CONCLUSIONS: Postdromal symptoms are prevalent in individuals with migraine from a tertiary care unit. However, reported estimates warrant cautious interpretation as they depend on the means of enquiry, presence of premonitory symptoms, and frequency of monthly migraine days. Moreover, a weak correlation was identified between the number of postdromal symptoms and both HIT-6 and WHODAS scores, indicating only a marginal influence on the disease burden.

Epidemiology and clinical features of paroxysmal hemicrania: A systematic review and meta-analysis.

OBJECTIVE: To assess the prevalence or relative frequency of paroxysmal hemicrania and its clinical features in the adult general population and among adult patients evaluated for headache in tertiary care. BACKGROUND: Paroxysmal hemicrania is a rare trigeminal autonomic cephalalgia with characteristic attacks of headache, associated cranial autonomic symptoms and signs, and an absolute response to indomethacin. Its epidemiological burden remains unknown in both the adult general population and among adult patients evaluated for headache in a tertiary care setting. Moreover, the frequencies of the clinical features associated with paroxysmal hemicrania have not been well established. METHODS: A literature search of PubMed and Embase was conducted from January 1, 1988, to January 20, 2023. Eligible for inclusion were observational studies reporting the point prevalence or relative frequency of paroxysmal hemicrania or its clinical features in the adult general population or among adult patients evaluated for headache in tertiary care. Two independent investigators (M.J.H. and J.G.L.) performed the title, abstract, and full-text article screening. Each included study's risk of bias was critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Estimates of prevalence or relative frequency were calculated using a random-effects meta-analysis. The between-study heterogeneity was assessed using the I2 statistic and further explored with meta-regression. This study was pre-registered on PROSPERO (identifier: CRD42023391127). RESULTS: A total of 17 clinic-based studies and one population-based study met the eligibility criteria. Importantly, an overall high risk of bias was observed across the eligible studies. The relative frequency of paroxysmal hemicrania was estimated to be 0.3% (95% CI, 0.2%-0.5%) among adult patients evaluated for headache in tertiary care with considerable heterogeneity (I2 = 76.4%). No cases with paroxysmal hemicrania were identified among 1,838 participants in a population-based sample. Moreover, the most prevalent cranial autonomic symptoms were lacrimation (77.3% [95% Cl, 62.7%-87.3%]), conjunctival injection (75.0% [95% Cl, 60.3%-85.6%]), and nasal congestion (47.7% [95% Cl, 33.6%-62.3%]). CONCLUSIONS: Our findings suggest that paroxysmal hemicrania is a rare disorder among adults evaluated for headache in tertiary care, while its prevalence in the general population remains unknown. Further studies focusing on the clinical features of paroxysmal hemicrania are warranted.

Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury. Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10 pmol/kg/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period. Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P < 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P < 0.001). These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH.

Induction of cluster headache after opening of adenosine triphosphate-sensitive potassium channels: a randomized clinical trial.

ABSTRACT: Activation of adenosine triphosphate-sensitive potassium (K ATP ) channels has been implicated in triggering migraine attacks. However, whether the opening of these channels provoke cluster headache attacks remains undetermined. The hallmark of cluster headache is a distinct cyclical pattern of recurrent, severe headache episodes, succeeded by intervals of remission where no symptoms are present. In our study, we enrolled 41 participants: 10 with episodic cluster headaches during a bout, 15 in the attack-free remission period, and 17 diagnosed with chronic cluster headaches. Over 2 distinct experimental days, participants underwent a continuous 20-minute infusion of levcromakalim, a K ATP channel opener, or a placebo (isotonic saline), followed by a 90-minute observational period. The primary outcome was comparing the incidence of cluster headache attacks within the postinfusion observation period between the levcromakalim and placebo groups. Six of 10 participants (60%) with episodic cluster headaches in bout experienced attacks after levcromakalim infusion, vs just 1 of 10 (10%) with placebo ( P = 0.037). Among those in the remission phase, 1 of 15 participants (7%) reported attacks after levcromakalim, whereas none did postplacebo ( P = 0.50). In addition, 5 of 17 participants (29%) with chronic cluster headache had attacks after levcromakalim, in contrast to none after placebo ( P = 0.037). These findings demonstrate that K ATP channel activation can induce cluster headache attacks in participants with episodic cluster headaches in bout and chronic cluster headache, but not in those in the remission period. Our results underscore the potential utility of K ATP channel inhibitors as therapeutic agents for cluster headaches.

Hypersensitivity to opening of ATP-sensitive potassium channels in post-traumatic headache.

OBJECTIVE: To investigate whether levcromakalim (a KATP channel opener) induces migraine-like headache in people with persistent post-traumatic headache who had no known history of migraine. METHODS: In a randomized, double-blind, placebo-controlled, 2-way crossover trial, participants were randomly assigned to receive a 20-minute continuous intravenous infusion of levcromakalim (50 µg/mL) or placebo (isotonic saline) on two separate experimental days with a 1-week wash-out period in between. The primary endpoint was the difference in incidence of migraine-like headache between levcromakalim and placebo during a 12-hour observational period after infusion start. The secondary endpoint was the difference in area under the curve for baseline-corrected median headache intensity scores between levcromakalim and placebo during the 12-hour observational period. RESULTS: A total of 21 participants with persistent post-traumatic headache were randomized and completed the trial. During the 12-hour observational period, 12 (57%) of 21 participants reported experiencing migraine-like headache following the levcromakalim infusion, compared with three after placebo (P = 0.013). Moreover, the baseline-corrected median headache intensity scores were higher following the levcromakalim infusion than after placebo (P = 0.003). CONCLUSION: Our findings suggest that KATP channels play an important role in the pathogenesis of migraine-like headache in people with persistent post-traumatic headache. This implies that KATP channel blockers might represent a promising avenue for drug development. Further research is warranted to explore the potential therapeutic benefits of KATP channel blockers in managing post-traumatic headache.Trial Registration: ClinicalTrials.gov Identifier: NCT05243953.

An exploratory analysis of clinical and sociodemographic factors in CGRP-induced migraine attacks: A REFORM study.

OBJECTIVE: To investigate whether clinical and sociodemographic factors are associated with calcitonin gene-related peptide (CGRP) induced migraine attacks. METHODS: A total of 139 participants with migraine received a 20-minute intravenous infusion of CGRP (1.5 µg/min) on a single experiment day. The incidence of CGRP-induced migraine attacks was recorded using a headache diary during the 12-hour observational period post-infusion. Univariable and multivariable regression analyses were conducted to examine potential predictors' relationship with CGRP-induced migraine attacks. RESULTS: CGRP-induced migraine attacks were reported in 110 (79%) of 139 participants. Univariable analysis revealed that participants with cutaneous allodynia had higher odds of developing CGRP-induced migraine attacks, compared with those without allodynia (OR, 2.97, 95% CI, 1.28 to 7.43). The subsequent multivariable analysis confirmed this association (OR, 3.26, 95% CI, 1.32 to 8.69) and also found that participants with migraine with aura had lower odds of developing CGRP-induced migraine attacks (OR, 0.32, 95% CI, 0.12 to 0.84). CONCLUSION: Our results suggest that cutaneous allodynia and aura play a role in CGRP-induced migraine attacks, while other clinical and sociodemographic factors do not seem to have any noticeable impact. This indicates that the CGRP provocation model is robust, as the CGRP hypersensitivity remained unaffected despite differences among a heterogeneous migraine population.Trial Registration: ClinicalTrials.gov Identifier: NCT04592952.

Calcitonin gene-related peptide causes migraine aura.

BACKGROUND: Although the involvement of calcitonin gene-related peptide (CGRP) in migraines is well-established, its specific role in investigating the aura phase, which often precedes the headache, remains largely unexplored. This study aims to instigate CGRP's potential in triggering aura, thus establishing its role in the early stages of migraine. METHODS: In this open-label, non-randomized, single-arm trial, 34 participants with migraine with aura received continuous intravenous infusion of CGRP (1.5 µg/min) over 20 min on a single experimental day. Participants were required to be free of headache and report no use of acute medications 24 h before infusion start. The primary endpoint was the incidence of migraine aura during the 12-hour observational period after the start of infusion. RESULTS: Thirteen (38%) of 34 participants developed migraine aura after CGRP infusion. In addition, 24 (71%) of 34 participants developed migraine headache following CGRP infusion. CONCLUSIONS: Our findings suggest that CGRP could play an important role in the early phases of a migraine attack, including during the aura phase. These insights offer a new perspective on the pathogenesis of migraines with aura. They underscore the need for additional research to further explore the role of CGRP in these initial stages of a migraine attack, and potentially inform future development of therapeutic interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04592952.

Comparative study of articaine 4% versus lidocaine 2% in the local anesthesia of permanent mandibular first molars affected by MIH: a randomized controlled trial.

PURPOSE: The current study compares articaine 4% with lidocaine 2% in terms of injection pain and effectiveness of anesthesia when treating permanent mandibular first molars (PMFMs) affected by molar incisor hypomineralization (MIH). In addition to comparing the complications of local anesthesia for both solutions. METHODS: The sample included 20 children. Each child was randomly assigned to either articaine 4% or lidocaine 2% in their first session with the other solution being used at the subsequent session. Injection pain and the effectiveness of anesthesia were assessed using the Wong-Baker Faces® Pain Rating Scale and the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. Parents were asked to report any complications of local anesthesia. The Wilcoxon-matched pairs signed-rank test was used to analyze the data. RESULTS: Patients experienced greater pain when receiving articaine 4% injections according to both scales, differences were statistically significant when using the Wong-Baker Faces® Pain Rating scale (p < 0.05). Whereas, the FLACC scale did not show such differences (P > 0.05). Although there were no significant differences between the two solutions regarding the effectiveness of local anesthesia according to both scales (P > 0.05), articaine 4% was clinically found to be more effective than lidocaine 2%. No complications of local anesthesia were reported. CONCLUSIONS: Articaine 4% injection was more painful than lidocaine 2%. However, both solutions were effective in anesthetizing PMFMs affected by MIH and without anesthetic complications in the studied sample. TRIAL REGISTRATION: Clinical trial, NCT05200884, ( https://clinicaltrials.gov/ct2/show/NCT05200884 ).

Hemicrania Continua: An Update.

PURPOSE OF REVIEW: Hemicrania Continua (HC) is a rare and disabling primary headache disorder that is characterized by persistent, unilateral headache with ipsilateral, cranial autonomic symptoms and restlessness or agitation. The diagnosis requires patients to experience an absolute response to therapeutic doses of indomethacin. RECENT FINDINGS: HC is diagnosed in in about 1.8% of adult patients who were evaluated for headache in tertiary care services, albeit this estimate should be interpreted with caution. The most prevalent accompanying symptoms appear to be lacrimation, conjunctival injection and restlessness or agitation. However, the available literature is limited by methodologic issues, and the current diagnostic criteria lack clarity on what defines absolute response to indomethacin. More rigorous studies are thus needed to improve our understanding of HC which, in turn, will facilitate better disease management in clinical practice. Here, we provide a comprehensive overview of HC, including its epidemiology, clinical presentation, diagnostic evaluation, and management.

Pediatric Gastrointestinal Basidiobolomycosis: A Retrospective Study from Jazan Province, Saudi Arabia.

Introduction: Basidiobolomycosis is a rare fungal infection caused by Basidiobolus ranarum, and its incidence is poorly understood due to its rarity. Gastrointestinal Basidiobolomycosis (GIB) is an uncommon presentation with limited reports in Saudi Arabia. This retrospective study aims to describe risk factors, clinical findings, diagnosis, and management of GIB in the pediatric population. Methods: We conducted a retrospective analysis of all pediatric patients diagnosed with GIB at a tertiary hospital between 2010 and 2022. Patients were identified based on their diagnosis of GIB. A self-administered questionnaire was distributed to assess risk factors associated with GIB. Results: We analyzed 25 cases of pediatric GIB, with approximately half of the cases (56%) occurring during the COVID-19 pandemic. The mean age of affected patients was 6.6 years, with a male predominance (60%, n=15). About 100% of parents acknowledged gecko existence in their residence, and their children were exposed to insect bites. Poor appetite was reported in all patients, and high counts of eosinophils and erythrocyte sedimentation rate were observed. Thrombocytosis was present in approximately 90% of patients, and 87% had anemia. Abdominal computerized tomography scans and ultrasound-guided biopsies were the most used diagnostic tools, with cases being diagnosed based on histopathological findings and confirmed via fungal culture. Conclusion: Our study provides valuable information on the potential risk factors, clinical features, diagnosis, and management of pediatric GIB in the Jazan region. The observed increase in cases during the COVID-19 pandemic highlights the need for continued surveillance and research to understand better the epidemiology and associated risk factors with this rare fungal infection. These findings emphasize the need for heightened awareness, early detection, and effective prevention strategies to mitigate the impact of pediatric GIB.

Neck pain and headache: Pathophysiology, treatments and future directions.

INTRODUCTION: Neck pain is a prevalent neurologic and musculoskeletal complaint in the general population and is often associated with primary headache disorders such as migraine and tension-type headache (TTH). A considerable proportion, ranging from 73% to 90%, of people with migraine or TTH also experience neck pain, and there is a positive correlation between headache frequency and neck pain. Furthermore, neck pain has been identified as a risk factor for migraine and TTH. Although the exact underlying mechanisms linking neck pain to migraine and TTH remain uncertain, pain sensitivity appears to play an important role. People with migraine or TTH exhibit lower pressure pain thresholds and higher total tenderness scores compared with healthy controls. PURPOSE: This position paper aims to provide an overview of the current evidence on the relationship between neck pain and comorbid migraine or TTH. It will encompass the clinical presentation, epidemiology, pathophysiology, and management of neck pain in the context of migraine and TTH. IMPLICATIONS: The relationship between neck pain and comorbid migraine or TTH is incompletely understood. In the absence of robust evidence, the management of neck pain in people with migraine or TTH relies mostly on expert opinion. A multidisciplinary approach is usually preferred, involving pharmacologic and non-pharmacologic strategies. Further research is necessary to fully dissect the linkage between neck pain and comorbid migraine or TTH. This includes the development of validated assessment tools, evaluation of treatment effectiveness, and exploration of genetic, imaging, and biochemical markers that might aid in diagnosis and treatment.

The Effect of Different Obturation Techniques in Primary Teeth on the Apical Microleakage using Endoflas: A Comparative In Vitro Study.

Objectives: This study was carried out to quantitatively evaluate and compare the sealing ability of Endoflas by using different obturation techniques. Materials and Methods: After 42 extracted primary maxillary incisors and canines were decoronated, their canals were instrumented with K files of size ranging from #15 to #50. In accordance with the obturation technique, the samples were divided into three experimental groups, namely, group I: endodontic pressure syringe, group II: modified disposable syringe, and group III: reamer technique, and two control groups. Dye extraction method was used for leakage evaluation. Data were analyzed using one-way ANOVA and Dunnett's T3 post hoc tests. The level of significance was set at p < 0.05. Results: Endodontic pressure syringe had significantly less leakage than the modified disposable syringe and reamer techniques (p < 0.05). Meanwhile, no significant difference was found in the mean leakage between the modified disposable syringe and the reamer techniques. Conclusion: Amongst all the techniques used in this study, endodontic pressure syringe could be preferred as an obturation technique in primary teeth when used with Endoflas obturation material because of its potential to provide good apical seal.

Preventive effect of combined Er, Cr: YSGG and fluoride gel on acid resistance of the permanent tooth enamel: An in vitro study.

Background: Increasing the resistance of enamel to acids may prevent dental erosion and diminish microhardness alterations in the enamel. This study aimed to evaluate the preventive effect of erbium, chromium: yttrium, scandium, gallium, and garnet laser combined with 1.23% acidulated phosphate fluoride gel on enamel resistance to demineralization. Material and Methods: Thirty-four human maxillary first premolars were randomly assigned to three groups. Group I (control group), group II were treated with fluoride gel for 4-minutes and group III received ten seconds of laser treatment; then fluoride has applied. Each sample was immersed in a soft drink for 2 minutes, then washed and kept in deionized water. Four consecutive cycles were carried out at 6 hours intervals. The effects were studied utilizing the Vickers microhardness test and scanning electron microscopy. Data analyses were performed by Levene test and General Linear Model Repeated Measure Factorial ANOVA with Bonferonni post hoc test, the accepted level of significance was 0.05. Results: Microhardness was increased statistically in groups II and III after treatment, with the highest value for group III. After demineralization, the control group had the lowest microhardness score, followed by group II and group III, which showed the least reduction in microhardness with a statistical significance (p<0.05). There was a correlation between the morphological alterations in enamel surfaces and the increased enamel resistance. Conclusions: Both fluoride and the combined laser fluoride treatment had an advantage in protecting the enamel and increasing enamel resistance to acids, with a more significant benefit for the combined laser fluoride group. Key words:Prevention, Er, Cr: YSGG, enamel demineralization, fluoride, microhardness.