A possible role for mitochondrial dysfunction in migraine

Migraine is a common neurological disorder characterised by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia and occasionally visual sensory disturbances. Migraine is a complex disease caused by an interplay between predisposing genetic variants and environmental factors. It affects approximately 12?% of studied Caucasian populations with affected individuals being predominantly female. Genes involved in neurological, vascular or hormonal pathways have all been implicated in predisposition towards developing migraine. All of these are nuclear encoded genes, but given the role of mitochondria in a number of neurological disorders and in energy production it is possible that mitochondrial variants may play a role in the pathogenesis of this disease. Mitochondrial DNA has been a useful tool for studying population genetics and human genetic diseases due to the clear inheritance shown through successive generations. Given the clear gender bias found in migraine patients it may be important to investigate X-linked inheritance and mitochondrial-related variants in this disorder. This paper explores the possibility that mitochondrial DNA changes may play a role in migraine. Few variants in the mitochondrial genome have so far been investigated in migraine and new studies should be aimed towards investigating the role of mitochondrial DNA in this common disorder.     

螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值

目的:探讨螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。方法:选取2014年1月至2016年1月期间来我院就诊的60例急性脑梗死患者作为观察组,另选同期来我院就诊的非急性脑梗死患者60例作为对照组。两组患者均进行螺旋CT头颈部血管成像检查,比较两组患者的颈动脉狭窄程度及各段血管斑块分布情况,并根据检查结果评价螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。结果:观察组轻度狭窄与中度狭窄检出率均显著高于对照组(P0.05),重度狭窄与闭塞检出率与对照组比较无统计学差异(P0.05),观察组总检出狭窄率高于对照组(P0.05)。观察组与对照组在颈动脉分叉处、颈总动脉、颈内动脉及颈外动脉均有斑块检出,观察组斑块总检出率为69.4%,显著高于对照组的41.2%(P0.05)。结论:临床上应用128层螺旋CT头颈部血管成像技术对急性脑梗死患者颈动脉狭窄情况可进行有效评估,该方法对患者轻、中度狭窄以及双侧颈动脉斑块检出率更高,在临床诊断及预后防治中具有应用推广价值。     

Studies on the Pathophysiology and Genetic Basis of Migraine

Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies.     

Identification of molecular genetic factors that influence migraine

Migraine is a common neurological disorder with a strong genetic basis. However, the complex nature of the disorder has meant that few genes or susceptibility loci have been identified and replicated consistently to confirm their involvement in migraine. Approaches to genetic studies of the disorder have included analysis of the rare migraine subtype, familial hemiplegic migraine with several causal genes identified for this severe subtype. However, the exact genetic contributors to the more common migraine subtypes are still to be deciphered. Genome-wide studies such as genome-wide association studies and linkage analysis as well as candidate genes studies have been employed to investigate genes involved in common migraine. Neurological, hormonal and vascular genes are all considered key factors in the pathophysiology of migraine and are a focus of many of these studies. It is clear that the influence of individual genes on the expression of this disorder will vary. Furthermore, the disorder may be dependent on gene–gene and gene–environment interactions that have not yet been considered. In addition, identifying susceptibility genes may require phenotyping methods outside of the International Classification of Headache Disorders II criteria, such as trait component analysis and latent class analysis to better define the ambit of migraine expression.     

From the "charretera" to the supraclavicular fascial island flap: revisitation and further evolution of a controversial flap

Wide tissue defects located on the face and neck area often require distant flaps or free flaps to achieve a tension-free reconstruction together with an acceptable aesthetic result. The supraclavicular island flap surely represents a versatile and useful flap that can be used in case of large tissue losses. Because of its wide arc of rotation, which ensures a 180-degree mobilization anteriorly and posteriorly, the flap can reach distant sites when harvested as a pure island flap. The main vascular supply of the flap, the supraclavicular artery, a branch of the transverse cervical artery or, less frequently, of the suprascapular artery, though reliable, is not a very large vessel. In some particular cases, when too much tension or angles that are too tight are present, the vascular supply of the flap can be difficult and special care must be taken to avoid flap failure. To avoid this problem, the authors started harvesting the flap not as a pure island flap but with a fascial pedicle, thin and resistant, which ensures good reliability; also, when a higher tension rate is present, it avoids the risk of excessive traction or kinking of the vessels. Twenty-five consecutive patients with various defects located on the head, neck, and thorax area were treated in the past 2 years using the modified supraclavicular island flap. There was no flap loss or distant necrosis of the flap, and there was marginal skin deepithelialization in only two cases, which only required minor surgery. Postoperative morbidity was low, similar to the classic supraclavicular island flap, with primarily closed donor sites, except for one case, and tension-free scars. The authors show how the modified supraclavicular island flap is a reliable and safe flap that gives a good aesthetic result with low risk concerning the viability of the transferred skin. The technique, similar to supraclavicular island flap harvesting, is easy to perform and is attractive in patients at risk for poor or delayed healing such as smokers or patients with complex medical histories.     

Temperature difference between the body core and arterial blood supplied to the brain during hyperthermia or hypothermia in humans

 A vascular heat transfer model is developed to simulate temperature decay along the carotid arteries in humans, and thus, to evaluate temperature differences between the body core and arterial blood supplied to the brain. Included are several factors, including the local blood perfusion rate, blood vessel bifurcation in the neck, and blood vessel pairs on both sides of the neck. The potential for cooling blood in the carotid artery by countercurrent heat exchange with the jugular veins and by radial heat conduction to the neck surface was estimated. Cooling along the common and internal carotid arteries was calculated to be up to 0.87 °C during hyperthermia by high environmental temperatures or muscular exercise. This model was also used to evaluate the feasibility of lowering the brain temperature effectively by placing ice pads on the neck and head surface or by wearing cooling garments during hypothermia treatment for brain injury or other medical conditions. It was found that a 1.1 °C temperature drop along the carotid arteries is possible when the neck surface is cooled to 0 °C. Thus, the body core temperature may not be a good indication of the brain temperature during hyperthermia or hypothermia. Received: 10 January 2002 / Accepted: 7 May 2002 This research was supported by a UMBC Summer Faculty Fellowship.     

Biology and therapy of fibromyalgia: pain in fibromyalgia syndrome

Fibromyalgia (FM) pain is frequent in the general population but its pathogenesis is only poorly understood. Many recent studies have emphasized the role of central nervous system pain processing abnormalities in FM, including central sensitization and inadequate pain inhibition. However, increasing evidence points towards peripheral tissues as relevant contributors of painful impulse input that might either initiate or maintain central sensitization, or both. It is well known that persistent or intense nociception can lead to neuroplastic changes in the spinal cord and brain, resulting in central sensitization and pain. This mechanism represents a hallmark of FM and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established only minimal nociceptive input is required for the maintenance of the chronic pain state. Additional factors, including pain related negative affect and poor sleep have been shown to significantly contribute to clinical FM pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of FM and other chronic pain syndromes.     

The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions

Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronic neuropathic pain, mood disorders, schizophrenia and various neuromuscular syndromes. In many of these conditions, as in epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated sodium and calcium channels or by promoting inhibition mediated by gamma-aminobutyric acid (GABA) A receptors. In neuropathic pain, chronic nerve injury is associated with the redistribution and altered subunit compositions of sodium and calcium channels that predispose neurons in sensory pathways to fire spontaneously or at inappropriately high frequencies, often from ectopic sites. AEDs may counteract this abnormal activity by selectively affecting pain-specific firing; for example, many AEDs suppress high-frequency action potentials by blocking voltage-activated sodium channels in a use-dependent fashion. Alternatively, AEDs may specifically target pathological channels; for example, gabapentin is a ligand of alpha2delta voltage-activated calcium channel subunits that are overexpressed in sensory neurons after nerve injury. Emerging evidence suggests that effects on signaling pathways that regulate neuronal plasticity and survival may be a factor in the delayed clinical efficacy of AEDs in some neuropsychiatric conditions, including bipolar affective disorder.     

Limitations on arteriovenous cooling of the blood supply to the human brain

Arteriovenous heat transfer (AVHT) is a thermoregulatory phenomenon which enhances tolerance to thermal stress in a variety of animals. Several authors have speculated that human responses to thermal stress reflect AVHT in the head and neck, even though primates lack the specialized vascular arrangements which characterize AVHT in other animals. We modeled heat transfer based on the anatonmical relationships and blood flows for the carotid artery and associated venous channels in the human neck and cavernous sinus. Heat transfer rate was predicted using the effectiveness-number of transfer units method for heat exchanger analysis. Modeling showed that AVHT is critically dependent upon (1) heat exchanger effectiveness and (2) arteriovenous inlet temperature difference. Predicted heat exchanger effectiveness is less than 5.5% for the neck and 0.3% for the cavernous sinus. These very low values reflect both the small arteriovenous interface for heat exchange and the high flow rate in the carotid artery. In addition, humans lack the strong venous temperature depression required to drive heat exchange; both the cavernous sinus and the internal jugular vein carry a large proportion of venous blood warmed by its passage through the brain as well as a small contribution from the face and scalp, whose temperature varies with environmental conditions. Under the most optimistic set of assumptions, carotid artery temperature would be lowered by less than 0.1° C during its passage from the aorta to the base of the brain. Physiologically significant cooling of the blood supply to the brain cannot occur in the absence of a suitably scaled site specialized for heat exchange.     

Comparative studies on the vascular organization of carotid labyrinths of anurans and caudates

The three-dimensional structures of the carotid labyrinth in five species of anurans representing four families (Rana nigromaculata, Rana catesbeiana, Bufo japonicus, Hyla arborea, and Xenopus laevis), and three species of caudates representing three families (Cynops pyrrhogaster, Hynobius nebulosus, Ambystoma mexicanum) were compared using vascular corrosion castings and scanning electron microscopy (SEM). Anuran carotid labyrinths are spherical in shape and are classified into two groups according to the origin of the external and internal carotid arteries. One group, which included Rana, Hyla, and Bufo, is characterized by the presence of a vascular ring at the proximal end and some vascular routes at the distal end of the labyrinth. The external and internal carotid arteries originate from these structures. The other group, which includes only Xenopus, is characterized by the external carotid artery opening directly from the central chamber or the common carotid artery, and by the internal carotid artery originating from within the vascular maze. The vascular maze is most complex in Xenopus, less so in Rana and Bufo, and simplest in Hyla. The carotid labyrinths in Cynops and Hynobius are oblong in shape. The fundamental organization in salamanders is similar to that in anurans. The vascular maze, however, is much simpler than in Hyla. There is no specialized swelling in Ambystoma mexicanum. The present findings suggest that most amphibian carotid labyrinths have the appropriate architecture for controlling vascular tone.     

Recent advances in understanding migraine mechanisms, molecules and therapeutics

Migraine is a complex, disabling disorder of the brain that manifests itself as attacks of often severe, throbbing head pain with sensory sensitivity to light, sound and head movement. There is a clear familial tendency to migraine, which has been well defined in a rare autosomal dominant form of familial hemiplegic migraine (FHM). FHM mutations so far identified include those in CACNA1A (P/Q voltage-gated Ca(2+) channel), ATP1A2 (N(+)-K(+)-ATPase) and SCN1A (Na(+) channel) genes. Physiological studies in humans and studies of the experimental correlate--cortical spreading depression (CSD)--provide understanding of aura, and have explored in recent years the effect of migraine preventives in CSD. Therapeutic developments in migraine have come by targeting the trigeminovascular system, with the most-recent being the proof-of-principle study of calcitonin gene-related peptide (CGRP) receptor antagonists in acute migraine. To understand the basic pathophysiology of migraine, brain imaging studies have firmly established reproducible changes in the brainstem in regions that include areas that are involved in sensory modulation. These data lead to the view that migraine is a form of sensory dysmodulatio--a system failure of normal sensory processing.     

The Stigma of Migraine

Background

People who have a disease often experience stigma, a socially and culturally embedded process through which individuals experience stereotyping, devaluation, and discrimination. Stigma has great impact on quality of life, behavior, and life chances. We do not know whether or not migraine is stigmatizing.

Methods

We studied 123 episodic migraine patients, 123 chronic migraine patients, and 62 epilepsy patients in a clinical setting to investigate the extent to which stigma attaches to migraine, using epilepsy as a comparison. We used the stigma scale for chronic illness, a 24-item questionnaire suitable for studying chronic neurologic diseases, and various disease impact measures.

Results

Patients with chronic migraine had higher scores (54.0±20.2) on the stigma scale for chronic illness than either episodic migraine (41.7±14.8) or epilepsy patients (44.6±16.3) (p<0.001). Subjects with migraine reported greater inability to work than epilepsy subjects. Stigma correlated most strongly with the mental component score of the short form of the medical outcomes health survey (SF-12), then with ability to work and migraine disability score for chronic and episodic migraine and the Liverpool impact on epilepsy scale for epilepsy. Analysis of covariance showed adjusted scores for the stigma scale for chronic illness were similar for chronic migraine (49.3; 95% confidence interval, 46.2 to 52.4) and epilepsy (46.5; 95% confidence interval, 41.6 to 51.6), and lower for episodic migraine (43.7; 95% confidence interval, 40.9 to 46.6). Ability to work was the strongest predictor of stigma as measured by the stigma scale for chronic illness.

Conclusion

In our model, adjusted stigma was similar for chronic migraine and epilepsy, which were greater than for episodic migraine. Stigma correlated most strongly with inability to work, and was greater for chronic migraine than epilepsy or episodic migraine because chronic migraine patients had less ability to work.     

Wall stress of the cervical carotid artery in patients with carotid dissection: a case-control study

Spontaneous internal carotid artery (ICA) dissection (sICAD) results from an intimal tear located around the distal carotid sinus. The mechanisms causing the tear are unknown. This case-control study tested the hypotheses that head movements increase the wall stress in the cervical ICA and that the stress increase is greater in patients with sICAD than in controls. Five patients with unilateral, recanalized, left sICAD and five matched controls were investigated before and after maximal head rotation to the left and neck hyperextension after 45° head rotation to the left. The anatomy of the extracranial carotid arteries was assessed by magnetic resonance imaging and used to create finite element models of the right ICA. Wall stress increased after head movements. Increases above the 80th and 90th percentile were located at the intimal side of the artery wall from 7.4 mm below to 10 mm above the cranial edge of the carotid sinus, i.e., at the same location as histologically confirmed tears in patients with sICAD. Wall stress increase did not differ between patients and controls. The present findings suggest that wall stress increases at the intimal side of the artery wall surrounding the distal edge of the carotid bulb after head movements may be important for the development of carotid dissection. The lack of wall stress difference between the two groups indicates that the carotid arteries of patients with carotid dissection have either distinct functional or anatomical properties or endured unusually heavy wall stresses to initiate dissection.     

The superior thyroid artery perforator flap: anatomical study and clinical series

The redundant tissues of the anterior neck are well suited as a donor site for fasciocutaneous flaps in head and neck reconstruction, with similar skin quality and numerous underlying perforators. However, historic cadaveric research has limited the use of this as a donor site for the design of long and/or large flaps for fear of vascular compromise. The authors undertook an anatomical study to identify the vascular basis for such flaps and have modified previous designs to offer the versatile and reliable superior thyroid artery perforator (STAP) flap. Forty-five consecutive computed tomographic angiograms of the neck were reviewed, assessing the vascular supply of the anterior skin of the neck. Based on these findings, eight consecutive patients underwent head and neck reconstruction using a flap based on the dominant perforator of the region. In all cases, a perforator larger than 0.5 mm was identified within a 2-cm radius of the midpoint of the sternocleidomastoid muscle at its anterior border. This perforator was seen to emerge through the investing layer of deep cervical fascia as a fasciocutaneous perforator and to perforate the platysma on its ipsilateral side of the neck, proximal to the midline. This was seen to be a superior thyroid artery perforator in 89 of 90 sides and an inferior thyroid artery perforator in one case. Eight consecutive patients underwent preoperative imaging and successful flap planning and execution based on this dominant perforator. The superior thyroid artery perforator (STAP) flap demonstrates reliable vascular anatomy and is well suited to reconstruction of a broad range of head and neck defects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.     

Extended lower trapezius island myocutaneous flap: a fasciomyocutaneous flap based on the dorsal scapular artery

The lower trapezius island myocutaneous flap is a useful flap in head and neck reconstruction. It is thin and pliable and can reach defects in most areas of the head and neck. Its usefulness in head and neck reconstruction has often been limited or discouraged by reports of significant failure rates. In this study, the vascular anatomy and clinical use of the extended lower trapezius myocutaneous flap based solely on the dorsal scapular artery system are elucidated, and experience gained performing 20 flaps over the past 5 years by using the extended lower trapezius myocutaneous flap is reported. The vascular anatomy of the dorsal scapular artery system is reviewed in 13 fresh cadaveric dissections by using methylene blue, latex injection studies, and radiologic examination.     

The exploration of mechanisms of comorbidity between migraine and depression

Migraine comorbid with depression is common and is often encountered in clinical practice. The comorbidity may lead to more serious conditions with other symptoms and a longer duration of treatment and it may impose heavy economic and social burdens, directly or indirectly, on patients and their families. Numerous studies have been published on the association of migraine with depression. Numerous literature have showed that the comorbidity may have a common complicated pathogenic mechanism involving biopsychosocial characteristics, including abnormal brain development and shared genetic basis, as well as neurotransmitters, sex hormones and stress. In addition, some studies have identified the multiple, bidirectional relationship between migraine and depressive disorder. We searched the literature for the possible common mechanisms between migraine and depression and classified the research results.     

Symptomatic carotid ischaemic events: safest and most cost effective way of selecting patients for angiography,before carotid endarterectomy.

OBJECTIVE: To determine the safest, least costly, and most effective way to select patients with symptomatic carotid ischaemic events for carotid angiography before carotid endarterectomy. DESIGN: Prospective cohort study. SETTING: University departments of clinical neurosciences and clinical neurology. PATIENTS: 485 Patients with carotid territory transient ischaemic attacks of the brain (n = 224) or eye (n = 162) or retinal infarction (n = 99) were referred to a single neurologist between 1976 and 1986. INTERVENTIONS: Clinical examination by auscultation over the precordium, supraclavicular fossae, and neck vessels (all patients). Cerebral angiography of patients suitable for carotid endarterectomy. MAIN OUTCOME MEASURES: Financial cost and number of disabling strokes after angiography. RESULTS: 296 Patients were investigated by cerebral angiography. Ischaemic symptoms had occurred in the distribution of 298 internal carotid arteries (symptomatic) that were imaged, two patients having bilateral symptoms. The presence or absence of a carotid bruit and the maximum percentage diameter stenosis of the origin of the symptomatic internal carotid artery were correlated. The prevalence of mild disease (diameter stenosis greater than or equal to 25%) of the symptomatic internal carotid artery was 57%, and if an ipsilateral carotid bruit was heard the probability of mild stenosis rose to 92%. The prevalence of moderate disease of the symptomatic internal carotid artery (stenosis greater than or equal to 50%) was 39%, and if a bruit was heard the probability doubled to 78%. The prevalence of severe internal carotid disease (stenosis greater than or equal to 75%) was 22%, and if a bruit was heard the probability was more than double, at 49%. The direct cost to both the NHS and the private health sector of investigating patients with symptomatic carotid ischaemia was estimated for several strategies of carotid artery imaging and expressed in terms of financial cost and number of strokes after angiography incurred in detecting all patients with diameter stenosis of the symptomatic internal carotid artery of greater than or equal to 25%, 50%, or 75%. To detect diameter stenosis of the internal carotid artery of greater than or equal to 25% it is most cost effective to proceed directly to cerebral angiography in patients with a carotid bruit over the symptomatic carotid bifurcation and to screen patients without a carotid bruit by duplex carotid ultrasonography; patients in whom duplex ultrasonography discloses stenosis of greater than or equal to 25% are then referred for cerebral angiography. To detect only more severe internal carotid disease (stenosis of greater than or equal to 50%) the same policy applies, unless the local duplex ultrasonographic service is particularly efficient and reliable, when it is probably most cost effective and safer to screen all patients by this method irrespective of the findings on cervical auscultation. To detect stenosis of 75% or greater it is most cost effective to screen all patients with duplex ultrasonography, whether a carotid bruit is present or not, because this approach reduces the number of angiograms required, is the least expensive, and results in the least number of strokes after angiography. CONCLUSIONS: Patients selection for cerebral angiography before carotid endarterectomy needs to be appropriate and cost effective. Sound clinical evaluation and duplex carotid ultrasound are required. The findings of this study should not be applied to other medical centres without first considering possible differences in the prevalence of carotid artery disease, the efficiency and reliability of duplex ultrasonography, the local complication rates of cerebral angiography, and the local costs of the imaging procedures.     

Disruption of the Hoxa3 homeobox gene results in anomalies of the carotid artery system and the arterial baroreceptors

Homeobox gene Hoxa3 is expressed in the third pharyngeal arch and pouch and is required for development of the third arch artery in addition to the thymus, parathyroid gland and carotid body. We therefore statistically analyzed malformations of the carotid artery system in Hoxa3 homozygous mutant mice, in comparison with wild-type and heterozygous littermates. To identify the carotid artery system, red carbon ink was injected, or vascular casts were made by injection of Mercox resin and observed by scanning electron microscopy. Furthermore, innervation of the carotid sinus and baroreceptor regions in the aortic arch and right subclavian artery were studied in the Hoxa3 null mutants having an abnormal carotid artery system by immunohistochemistry with TuJ1 and protein gene product (PGP) 9.5 antibodies, which recognize nerve fibers and neurons. The common carotid artery of Hoxa3 homozygous mutants was absent or very short and therefore the internal and external carotid artery arose from a more proximal level than those of wild types. The baroreceptor innervation, however, persisted in the mutants, although vascular targets were changed. These results indicate that Hoxa3 gene is crucial for the formation of the common carotid artery and the null mutant mice are the first useful animal models to show that the third arch arteries on both sides specifically degenerate but the fourth and sixth arch arteries are normal.     

Effects of Neck Radiation Therapy on Extra-Cranial Carotid Arteries Atherosclerosis Disease Prevalence: Systematic Review and a Meta-Analysis

Introduction

Radiation arteritis following neck irradiation as a treatment for head and neck malignancy has been well documented. The long-term sequelae of radiation exposure of the carotid arteries may take years to manifest clinically, and extra-cranial carotid artery (ECCA) stenosis is a well-recognised vascular complication. These carotid lesions should not be regarded as benign and should be treated in the same manner as standard carotid stenosis. Previous studies have noted increased cerebrovascular events such as stroke in this cohort of patients because of high-grade symptomatic carotid stenosis resulting in emboli.

Aim

To evaluate the effect of radiation therapy on ECCA atherosclerosis progression.

Methods

Online search for case-control studies and randomised clinical trials that reported on stenosis in extra-cranial carotid arteries in patients with neck malignancies who received radiation therapy (RT) comparing them to patients with neck malignancies who did not receive RT.

Results

Eight studies were included in the final analysis with total of 1070 patients – 596 received RT compared to 474 in the control group. There was statistically significant difference in overall stenosis rate (Pooled risk ratio  =  4.38 [2.98, 6.45], P  =  0.00001) and severe stenosis (Pooled risk ratio  =  7.51 [2.78, 20.32], P <0.0001), both being higher in the RT group. Pooled analysis of the five studies that reported on mild stenosis also showed significant difference (Pooled risk ratio  =  2.74 [1.75, 4.30], 95% CI, P  =  0.0001).

Conclusion

The incidence of severe ECCA stenosis is higher among patients who received RT for neck malignancies. Those patients should be closely monitored and screening programs should be considered in all patients who receive neck RT.     

Diencephalic and brainstem mechanisms in migraine

Migraine is a common and complex brain disorder. Although it is clear that head pain is a key manifestation of the disorder for most patients, what drives the activation of neuronal pain pathways in susceptible patients is less obvious. There is growing evidence that migraine pathophysiology may, in part, include dysfunction of subcortical structures. These include diencephalic and brainstem nuclei that can modulate the perception of activation of the trigeminovascular system, which carries sensory information from the cranial vasculature to the brain. Dysfunction of these nuclei, and their connections to other key brain centres, may contribute to the cascade of events that results in other symptoms of migraine - such as light and sound sensitivity - thus providing a comprehensive explanation of the neurobiology of the disorder.