Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.

Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.

Other primary headache disorders: Data from the HEAD-MENA-A study in Africa, Asia, and the Middle East.

OBJECTIVE: Other primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries. METHODS: We analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria. RESULTS: Among patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD. CONCLUSIONS: Other primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches.

Physiological aspect of apoptosis-regulating microRNAs expressions during fasting.

OBJECTIVE: Fasting is an activity that requires a certain calorie restriction without consuming food or drinks for a certain period of daytime. However, fasting triggers many complex events, including activating cellular stress response pathways, autophagy promotion, apoptosis pathways, and a change in hormonal balance. Among the many events affecting the regulation of apoptosis, the expression of microRNAs (miRNAs) plays an important role. Therefore, we aimed to investigate the levels and importance of miRNA expression in fasting. PATIENTS AND METHODS: The expressions of 19 miRNAs regulating different pathways from saliva samples, isolated by matching healthy university students (n = 34) as group 1 (fasting for 17 consecutive hours) and group 2 (testing 70 minutes after meal consumption), were examined using the real-time PCR method. RESULTS: In fasting, modulation of apoptotic pathways by miRNAs triggers anti-pathogenic effects, and the adaptation of abnormal cells in the body decreases. For this reason, vital diseases, such as cancer, can be treated by preventing the proliferation and growth of cancerous cells by increasing programmed cell death due to the downregulation expression mechanism of miRNAs. CONCLUSIONS: Our study aims to improve the knowledge about the mechanisms and functions of miRNAs in various apoptosis pathways during fasting and may be a model for further future physiological and pathological studies.

Long-term results of scapulothoracic arthrodesis with multiple cable method for facioscapulohumeral dystrophy: do the results deteriorate over time?

Aims: The present study aimed to investigate the long-term functional results of scapulothoracic fusion using multifilament cables in patients with facioscapulohumeral dystrophy (FSHD) to identify if the early improvement from this intervention is maintained. Patients and Methods: We retrospectively investigated the long-term outcomes of 13 patients with FSHD (18 shoulders) in whom scapulothoracic fusion using multifilament cables was performed between 2004 and 2007. These patients have previously been reported at a mean of 35.5 months (24 to 87). There were eight men and five women with a mean age of 26 years. Their mean length of follow-up of our current study was 128 months (94 to 185). To evaluate long-term functional results, the range of shoulder flexion and abduction, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores were analyzed with a comparison of preoperatively, interim and at the final outcomes. The fusion was examined radiographically in all. Results: The complication rate was 33% (six of 18 scapulothoracic fusions) in 13 patients, which comprised failure of fusion in four shoulders (four patients) all occurring within the first year postoperatively. In two shoulders (one patient) wound problems arose due to attribution from the cables which required shortening but the fusion developed satisfactorily. At the final examination, the mean QuickDASH score and range of movement significantly improved in all but one patient (p < 0.001, p < 0.001 and p < 0.001). In the comparison of 13 patients' mid- and long-term results, the mean QuickDASH score decreased from 9.8 (sd 6.7; 3 to 26) in the third year to 9.1 (sd 5.6; 3 to 22) in the tenth year (p = 0.7); the mean range of shoulder flexion and abduction decreased from 129° (sd 22°; 90° to 160°) and 124° (sd 12; 100° to 150°) at the mid-term to 103° (sd 12°; 80° to 120°) and 101° (sd 8°; 80° to 120°) at the long-term, respectively (p = 0.78 and p = 0.65). Conclusion: Scapulothoracic fusion using a multiple cabling method can confer a considerable improvement in clinical and functional outcomes for most patients with FSHD after a long follow-up period. The technique requires careful execution to avoid complications. Cite this article: Bone Joint J 2018;100-B:953-6.

The effectiveness of the Latarjet procedure for shoulder instability in patients with epilepsy.

INTRODUCTION: Powerful contractions during epileptic seizures may cause shoulder dislocation and instability. The aim of the study is to evaluate the functional and radiographic results of the Latarjet procedure for anterior shoulder dislocation in patients with epilepsy and compare the functional results of these patients with the results of patients without epilepsy. HYPOTHESIS: Is latarjet procedure effective in epileptic patients as non-epileptic patients with anterior shoulder instability? MATERIAL AND METHOD: Eleven shoulders of 9 patients with epileptic seizures causing anterior shoulder instability were evaluated retrospectively. All patients had a Latarjet procedure after neurologic evaluation and treatment arrangement. Epileptic seizures after the operation and shoulder dislocation after a seizure were investigated. For functional evaluation, ROWE, ASES and Constant scores were utilized whereas standard X-ray views were used for radiologic evaluation. The results of epileptic patients with Latarjet procedure were compared with non-epileptic patients (53 patients, 54 shoulders) for anterior shoulder instability. RESULTS: Three (33%) of the 9 epileptic patients had recurrent seizures after Latarjet procedure, whereas 1 of the 11 shoulders (9%) had dislocation after an epileptic seizure. Functional scores were found to be significantly improved in epileptic (P<0.001) and non-epileptic patients (P<0.001). No significant differences for functional results were found between epileptic and non-epileptic patients after Latarjet procedure for anterior instability (P>0.05). One shoulder of 11 in the patients with epilepsy group (9%) and one shoulder of the 54 shoulders non-epileptic patients group (1.8%) had a redislocation. The rate of postoperative redislocation was significantly higher in patients with epilepsy (P=0.008). DISCUSSION: Epileptic patients have a high rate of recurrent seizures even with proper medical treatment. Significant functional improvements and shoulder stability may be achieved after Latarjet procedure in epileptic patients. These functional results were comparable with those of non-epileptic patients with Latarjet procedure for anterior shoulder instability. LEVEL OF EVIDENCE: III (case-control study).

Benefits of radial head excision in patients with haemophilia: mid-term functional results.

INTRODUCTION: Recurrent haemarthrosis in haemophilic patients result with arthropathy of the radiocapitellar joint and blockage of the forearm rotation. AIM: The aim of this study is to evaluate the mid-term results of radial head excision with partial synovectomy in severe haemophilic patients retrospectively. METHODS: Persistent pain and decreased forearm rotation were the main indications for radial head excision. Between 2002 and 2013, radial head excisions were performed for 14 elbows of 14 patients. Eleven patients were haemophilia A, whereas two patients were haemophilia B patients and the remaining one had von Willebrand (Type 3) disease. The mean age of the patients was 29 at the time of the surgery. The mean follow-up was 51 (12-155) months. VAS (visual analogue score) for pain, forearm rotation, qDASH and MEPS (Mayo Elbow Performance Score) were used as the primary outcome parameters. RESULTS: The mean VAS decreased significantly from 6.5 preoperatively to 2.2 at the final follow-up (P = 0.0003). The mean forearm rotation increased from 40° to 115° respectively (P = 0.0007). In two patients, efficacious rotation increase was not achieved due to distal radioulnar joint problems. The mean qDASH score and MEPS were 18.1 and 87.5 at the latest follow-up, respectively, where four patients had excellent and 10 patients had good results. CONCLUSIONS: Radial head excision is a safe and effective procedure for haemophiliac patients with radiocapitellar arthropathy and decreased forearm rotation. Distal radioulnar joint should be evaluated preoperatively which may impair the results.

Comparison of simple arm sling and figure of eight clavicular bandage for midshaft clavicular fractures: a randomised controlled study.

Only a few randomised, controlled studies have compared different non-operative methods of treatment of mid-shaft fractures of the clavicle. In this prospective, randomised controlled study of 60 participants (mean age 31.6 years; 15 to 75) we compared the broad arm sling with the figure of eight bandage for the treatment of mid-shaft clavicle fractures. Our outcome measures were pain, Constant and American Shoulder and Elbow Surgeons scores and radiological union. The mean visual analogue scale (VAS) pain score on the first day after treatment was significantly higher (VAS 1 6.8; 4 to 9) in the figure of eight bandage group than the broad arm sling group (VAS 1 5.6; 3 to 8, p = 0.034). A mean shortening of 9 mm (3 to 17) was measured in the figure of eight bandage group, versus 7.5 mm (0 to 24) in the broad arm sling group (p = 0.30). The application of the figure of eight bandage is more difficult than of the broad arm sling, and patients experience more pain during the first day when treated with this option. We suggest the broad arm sling is preferable because of the reduction of early pain and ease of application.

Platelet-rich plasma for enhancing surgical rotator cuff repair: evaluation and comparison of two application methods in a rat model.

PURPOSE: Platelet-rich plasma (PRP) is a natural concentrate of autologous growth factors now being widely tested in different fields of medicine for its potential in enhancing the regeneration of tissue with low healing potential. However, studies of PRP in enhancing rotator cuff repair have been contradictory, perhaps because of how PRP is administered. The purpose of this study is to evaluate the effect of PRP and compare two different application methods of PRP on rotator cuff healing. METHODS: The supraspinatus tendons of 48 mature, male Wistar-Albino rats were detached from their insertion on the humerus. The animals were divided into four groups: (1) no repair, (2) primary repair, (3) repair plus PRP injections into the tendon-bone interface, and (4) repair plus PRP absorbed from a sponge carrier to the tendon-bone interface. The tendons were evaluated biomechanically and histologically at week 8. RESULTS: Cuffs repaired with PRP had significantly greater mean (SD) load-to-failure rates [11.1 (6.5) and 11.6 (3.9) N; P < 0.05] and stiffness [3.5 (2.3) and 1.6 (0.75) N; P < 0.05] than did cuffs repaired without PRP. The groups receiving PRP did not differ significantly on these variables. Histological evaluation showed no significant differences among the four groups. CONCLUSIONS: The application of PRP, independent of the application method, significantly improved biomechanical properties at the rotator cuff tendon-bone interface. The type of application, injection or absorption from a sponge did not influence the effect of PRP on rotator cuff healing.

A comparison of single-versus double-row suture anchor techniques in a simulated repair of the rotator cuff: an experimental study in rabbits.

We compared time-dependent changes in the biomechanical properties of single-and double-row repair of a simulated acute tear of the rotator cuff in rabbits to determine the effect of the fixation techniques on the healing process. A tear of the supraspinatus tendon was created in 80 rabbits which were separated into two equal groups. A single-row repair with two suture anchors was conducted in group 1 and a double-row repair with four suture anchors in group 2. A total of ten intact contralateral shoulder joints was used as a control group. Biomechanical testing was performed immediately post-operatively and at four and eight weeks, and histological analysis at four and eight weeks. The mean load to failure in group 2 animals was greater than in group 1, but both groups remained lower than the control group at all intervals. Histological analysis showed similar healing properties at four and eight weeks in both groups, but a significantly larger number of healed tendon-bone interfaces were identified in group 2 than in group 1 at eight weeks (p < 0.012). The ultimate load to failure increased with the number of suture anchors used immediately post-operatively, and at four and eight weeks. The increased load to failure at eight weeks seemed to be related to the increase in the surface area of healed tendon-to-bone in the double-row repair group.

A new detection method for capacitive micromachined ultrasonic transducers.

Capacitive micromachined ultrasonic transducers (cMUT) have become an alternative to piezoelectric transducers in the past few years. They consist of many small circular membranes that are connected in parallel. In this work, we report a new detection method for cMUTs. We model the membranes as capacitors and the interconnections between the membranes as inductors. This kind of LC network is called an artificial transmission line. The vibrations of the membranes modulate the electrical length of the transmission line, which is proportional to the frequency of the signal through it. By measuring the electrical length of the artificial line at a high RF frequency (in the gigahertz range), the vibrations of the membranes can be detected in a very sensitive manner. For the devices we measured, we calculated the minimum detectable displacement to be in the order of 10(-5) A/square root of Hz with a possible improvement to 10(-7) A/square root of Hz.

Surgical treatment of distal intraarticular humeral fractures in adults.

We reviewed 17 patients with distal intraarticular humeral type C fractures, treated by open reduction and internal fixation, followed by an early rehabilitation programme. The results, as judged by the criteria of Jupiter, were excellent in ten, good in five and fair in two. Non-union of the olecranon osteotomy occurred in one patient.

Time-dependent reduction in load to failure of wedge-type polyglyconate suture anchors.

SUMMARY: Thirty-two absorbable (polyglyconate) and 24 nonabsorbable (polyacetal) wedge-type suture anchors (TAG; Acufex, Mansfield, MA) were implanted into sheep tibiae. Load to failure tests were performed on the day of insertion and at weeks 3, 6, and 12, followed by macroscopic examination. Failure type was suture breakage for nonabsorbable anchors in all groups, with average forces of 142.5 +/- 4.8 N on the first day, 138.0 +/- 6.6 N in week 6, and 135.6 +/- 2.9 N in week 12. In the absorbable group, suture breakage occurred on the first day with a mean force of 133.5 +/- 4. 2 N. In weeks 3, 6, and 12, suture cutout occurred with average forces of 33.75 +/- 5.0 N, 23.25 +/- 2.2 N, and 23.25 +/- 5.9 N, respectively. For absorbable anchors, results at weeks 3, 6, and 12 were significantly lower compared with initial results (P <.001). These results show that wedge-type polyglyconate anchors lose 75% of their initial pullout strength within the first 3 weeks and 84% in 6 weeks.

Synovial chondromatosis of the subcoracoid bursa.

Synovial chondromatosis, is the chondroid metaplasia of the synovial membrane. Large joints such as the knee and hip are most commonly involved. Extraarticular involvement is rarely described. Synovial chondromatosis may be associated with impingement syndrome of the shoulder. We report a case of synovial chondromatosis of the subcoracoid bursa, which resulted in impingement symptoms.

Theory and analysis of electrode size optimization for capacitive microfabricated ultrasonic transducers.

Theoretical analysis and computer simulations of capacitive microfabricated ultrasonic transducers indicate that device performance can be optimized through judicious patterning of electrodes. The conceptual basis of the analysis is that electrostatic force should be applied only where it is most effective, such as at the center of a circular membrane. If breakdown mechanisms are ignored, an infinitesimally small electrode with an infinite bias voltage results in the optimal transducer. A more realistic design example compares the 3-dB bandwidths of a fully metalized transducer and a partially metalized transducer, each tuned with a lossless Butterworth network. It is found that the bandwidth of the optimally metalized device is twice that of the fully metalized device.

Primary replacement of the humeral head in iatrogenically displaced fracture-dislocations of the shoulder: a report about six cases.

Dislocation of the shoulder is a common injury and may be associated with a variety of complications. We report six cases of primary replacement of the humeral head where closed reduction of a shoulder dislocation associated with an undisplaced fracture of the humeral neck led to displacement of the neck fracture. All dislocations examined were anterior with a displaced greater tubercle fracture. The patients had undergone closed reduction at other medical centres and were referred to us because of iatrogenically displaced fracture-dislocations of the shoulder. Three were women and three were men with a mean age of 52.8 years (range 38-72). Primary replacement of the humeral head was done in an average of 9.3 days (range 2-30 days) following the injury. The average follow-up period was 30.2 months (range 12-55 months). Postoperative pain, active range of motion and function were evaluated with the American Shoulder and Elbow Surgeons Criteria. The forward flexion averaged 124 degrees, active external rotation averaged 29 degrees and internal rotation (achieved movement) to the second lumbar vertebra. Because of the high risk of avascular necrosis and severe collapse of the humeral head, we conclude that the primary replacement of the humeral head is the superior treatment option in iatrogenically displaced fracture dislocations of the shoulder.

Surface micromachined capacitive ultrasonic transducers.

The current state of novel technology, surface microfabricated ultrasonic transducers, is reported. Experiments demonstrating both air and water transmission are presented. Air-coupled longitudinal wave transmission through aluminum is demonstrated, implying a 110 dB dynamic range for transducers at 2.3 MHz in air. Water transmission experiments from 1 to 20 MHz are performed, with a measured 60 dB SNR at 3 MHz. A theoretical model is proposed that agrees well with observed transducer behavior. Most significantly, the model is used to demonstrate that microfabricated ultrasonic transducers constitute an attractive alternative to piezoelectric transducers in many applications.

VLSI circuits for adaptive digital beamforming in ultrasound imaging.

For phased-array ultrasound imaging, alternative beamforming techniques and their VLSI circuits are studied to form a fully digital receive front-end hardware. In order to increase the timing accuracy in beamforming, a computationally efficient interpolation scheme to increase the sampling rate is examined. For adaptive beamforming, a phase aberration correction method with very low computational complexity is described. Image quality performance of the method is examined by processing the non-aberrated and aberrated phased-array experimental data sets of an ultrasound resolution phantom. A digital beamforming scheme based on receive focusing at the raster focal points is examined. The sector images of the resolution phantom, reconstructed from the phased-array experimental data by beamforming at the radial and raster focal points, are presented for comparison of the image resolution performances of the two beamforming schemes. VLSI circuits and their implementations for the proposed techniques are presented.

A phase aberration correction method for ultrasound imaging.

A computationally efficient method for phase aberration correction in ultrasound imaging is presented. The method is based on time delay estimation via minimization of the sum of absolute differences between radio frequency samples of adjacent array elements. Effects of averaging estimated aberration patterns over scan angle and truncation to a single bit wordlength are examined. Phase distortions due to near-field inhomogeneities are simulated using silicone rubber aberrators. Performance of the method is tested using experimental data. Simulation studies addressing different factors affecting efficiency of the method, such as the number of iterations, window length, and the number of scan angles used for averaging, are presented. Images of a standard resolution phantom are reconstructed and used for qualitative testing.

A Lamb wave lens for acoustic microscopy.

In a conventional scanning acoustic microscope the excited leaky modes contribute significantly to the high contrast obtained in the images. However, all such modes exist simultaneously, and the interpretation of the images is not straightforward, especially in layered media. A lens geometry is proposed that can be used with acoustic microscopes to image layered solid structures. This lens can focus the acoustic waves in only one of the Lamb wave modes of the layered solid with a high efficiency. V(Z) curves obtained from this lens are more sensitive to material properties compared to that obtained from conventional lens. Measuring the return signal as a function of frequency results in another characteristic curve, V(f). The Lamb wave lens and the associated characterization methods for the layered structures are described. The results presented show that the Lamb wave lens is at least an order of magnitude more sensitive than the conventional lens and can easily differentiate between a good bond and disbond in a layered structure.

Improvement of anisotropy sensitivity in the scanning acoustic microscope.

The response of the conventional scanning acoustic microscope (SAM) to anisotropic materials is theoretically investigated. For this purpose, the reflection coefficient of plane acoustic waves incident on a liquid-solid interface is numerically calculated for a general anisotropic solid oriented in any arbitrary direction. In general, the reflection coefficient depends on polar and azimuthal angles of incidence. For the case of a circularly symmetric acoustic microscope lens, a mean reflectance function can be defined that depends only on the polar angle. With this mean reflectance function, it is very easy to predict the anisotropic material response of the acoustic microscope. It is found that, under certain conditions, the amplitude response of the acoustic microscope can depend heavily on the orientation of the solid material under investigation. The amplitude of the acoustic microscope signal is influenced by the orientation of the material because there is a cancellation of acoustic rays reflected from the object surface at different azimuthal angles. This cancellation is revealed as a minimum in the mean reflectance function. It is shown by numerical simulation that the sensitivity to orientation can be increased by the use of a ring-shaped insonification at the back of the acoustic lens.