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Schematic view of white matter tract changes of association, commisural, projection, and brainstem pathways in patients with migraine headache compared to healthy controls. The fiber tract visualization was adopted from the Human Connectome Project population-based atlas (available at https://brain.labsolver.org/hcp_trk_atlas.html). The study population, in which changes were observed, are reported in brackets. Upward arrrow means an increase and downward arrow means a decrease in diffusion parameters. Reference 23 reported a trend toward increased FA in CC; reference 25 reported a trends toward decreased AD in CC and decreased MD in SLF tracts in patients. Abbreviations: ACR: anterior corona radiata, AD: axial diffusivity, CAB: cingulum–angular bundle, CCG: cingulum cingulate gyrus, CC: corpos callosum, CMWoA: chronic migraine without aura, CST: corticospinal tract, FA: fractional anisotropy, ILF: inferior longitudinal fasciculus, MD: mean diffusivity, MWoA: migraine without aura, PCR: posterior corona radiata, SCR: superior corona radiata, SDS+: self-rating depression scale > 49; SDS-: self-rating depression scale < 049; RD: radial diffusivity, SLF: superior longitudinal fasciculus
Source publication
The pathophysiology of migraine as a headache disorder is still undetermined. Diffusion tensor imaging (DTI) has significantly improved our knowledge about brain microstructure in this disease. Here, we aimed to systematically review DTI studies in migraine and survey the sources of heterogeneity by investigating diffusion parameter changes associa...
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The term Headache Disorders (HD) refers to a number of nervous system pathologies characterised by recurrent headaches. Despite the serious impact HD have on the health system, society, and the economy, these are an underestimated, underdiagnosed, and, hence, undertreated phenomenon. Triptans are the first-line therapy for the acute treatment of mo...
Citations
... Similar to sleep disruption, a recent systematic review demonstrated that chronic headache is associated with widespread reductions in white matter microstructure (Rahimi et al., 2022). However, the majority of participants included in these studies were middle-aged. ...
Chronic headache (persistent or recurrent headache for 3-months or longer) is highly prevalent among youth. While sleep disturbances have been associated with headache, their inter-relationship with brain connectivity remains unknown. This observational study examined whether self-report and actigraphy measures of sleep were associated with alterations to white matter tracts (i.e., uncinate fasciculus and cingulum) in youth with chronic headache versus healthy controls. Thirty youth aged 10–18 years with chronic headache and thirty controls underwent an MRI. Diffusion tensor images were obtained and mean fractional anisotropy values of the cingulum and uncinate were extracted. One-week prior to their MRI, youth wore an actigraph to obtain sleep duration, wake after sleep onset and sleep efficiency measures. Moreover, they completed questionnaires regarding their sleep quality and pain symptomatology. Linear regression was applied to examine the relationships between sleep (self-report and actigraphy), fractional anisotropy, and number of headache days per month. Self-report and actigraphy measures of sleep did not differ between patients and controls. However, poorer self-reported sleep quality was associated with lower fractional anisotropy values in the left uncinate (P = 0.05). Lower left uncinate fractional anisotropy was related to increased headache frequency (P = 0.002) in youth with chronic headache. Therefore, alterations to connectivity may be associated with the relationship between altered perceptions of sleep and headache chronicity.
... The results of brain white matter (WM) variation representing the brain SC in previous migraine studies have been inconsistent (17,26,27). In a follow-up study spanning 9 years, whole-brain WM difference was not detected between migraine and control cases by using magnetic resonance (MR) dual echo T2-weighted imaging or by fluid-attenuated inversion recovery (FLAIR) imaging, but focal WM alteration was detected in migraine cases (26). ...
... In a follow-up study spanning 9 years, whole-brain WM difference was not detected between migraine and control cases by using magnetic resonance (MR) dual echo T2-weighted imaging or by fluid-attenuated inversion recovery (FLAIR) imaging, but focal WM alteration was detected in migraine cases (26). Another study reported no significant WM microstructural difference between MwA and MwoA (27). Meanwhile, differences of WM alterations between chronic and episodic migraine have also shown inconsistency across studies (27). ...
... Another study reported no significant WM microstructural difference between MwA and MwoA (27). Meanwhile, differences of WM alterations between chronic and episodic migraine have also shown inconsistency across studies (27). However, higher and lower SC involving subcortical and cortical regions associated with pain processing and brain excitability have been identified in chronic and episodic migraine (17). ...
Background
Cortical spreading depression (CSD) has been considered the prominent theory for migraine with aura (MwA). However, it is also argued that CSD can exist in patients in a silent state, and not manifest as aura. Thus, the MwA classification based on aura may be questionable. This study aimed to capture whole-brain connectome-based imaging markers with identifiable signatures for MwA and migraine without aura (MwoA).
Methods
A total of 88 migraine patients (32 MwA) and 49 healthy controls (HC) underwent a diffusion tensor imaging and resting-state functional magnetic resonance imaging scan. The whole-brain structural connectivity (SC) and functional connectivity (FC) analysis was employed to extract imaging features. The extracted features were subjected to an all-relevant feature selection process within cross-validation loops to pinpoint attributes demonstrating substantial efficacy for patient categorization. Based on the identified features, the predictive ability of the random forest classifiers constructed with the 88 migraine patients’ sample was tested using an independent sample of 32 migraine patients (eight MwA).
Results
Compared to MwoA and HC, MwA showed two reduced SC and six FC (five increased and one reduced) features [all P<0.01, after false discovery rate (FDR) correction], involving frontal areas, temporal areas, visual areas, amygdala, and thalamus. A total of four imaging features were significantly correlated with clinical rating scales in all patients (r=−0.38 to 0.47, P<0.01, after FDR correction). The predictive ability of the random forest classifiers achieved an accuracy of 78.1% in the external sample to identify MwA.
Conclusions
The whole-brain connectivity features in our results may serve as connectome-based imaging markers for MwA identification. The alterations of SC and FC strength provide possible evidence in further understanding the heterogeneity and mechanism of MwA which may help for patient-specific decision-making.
... 5,51 With the standard analysis approaches of tract-based spatial statistics, region of interest analysis, or whole brain voxel-wise analysis, the measures obtained from DTI include fractional anisotropy (FA), mean diffusivity (MD) or apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). [51][52][53] Differences in these measures between migraineurs and healthy controls reflect white matter microstructural differences associated with migraine. FA is highly sensitive to changes to axonal integrity, fiber density, and myelin but often nonspecific, suggesting cell death, cell shrinkage or swelling, axonal loss, demyelination, and more. ...
... FA is highly sensitive to changes to axonal integrity, fiber density, and myelin but often nonspecific, suggesting cell death, cell shrinkage or swelling, axonal loss, demyelination, and more. 29,53 MD is often measured in conjunction with FA, indicating changes in the extracellular space due to cell shrinkage or loss of axonal or dendritic connections. 29,53 AD is reflective of axonal integrity and affected by axonal injury and brain maturation, while RD is more reflective of axonal myelination and susceptible to demyelination and axonal degeneration. ...
... 29,53 MD is often measured in conjunction with FA, indicating changes in the extracellular space due to cell shrinkage or loss of axonal or dendritic connections. 29,53 AD is reflective of axonal integrity and affected by axonal injury and brain maturation, while RD is more reflective of axonal myelination and susceptible to demyelination and axonal degeneration. 53,54 It is debated whether such changes contribute to a predisposition to migraine or result from repeated attacks, which may be explained as maladaptive plastic modifications, accumulated white matter damage, or secondary functional alterations after repeated stimulation. ...
Migraine is a complex and heterogenous disorder whose disease mechanisms remain disputed. This narrative review summarizes functional MRI (fMRI) and diffusion tensor imaging (DTI) findings and interprets their association with migraine symptoms and subtype to support and expand our current understanding of migraine pathophysiology. Our PubMed search evaluated and included fMRI and DTI studies involving comparisons between migraineurs vs healthy controls, migraineurs with vs without aura, and episodic vs chronic migraineurs. Migraineurs demonstrate changes in functional connectivity (FC) and regional activation in numerous pain-related networks depending on migraine phase, presence of aura, and chronicity. Changes to diffusion indices are observed in major cortical white matter tracts extending to the brainstem and cerebellum, more prominent in chronic migraine and associated with FC changes. Reported changes in FC and regional activation likely relate to pain processing and sensory hypersensitivities. Diffuse white matter microstructural changes in dysfunctional cortical pain and sensory pathways complement these functional differences. Interpretations of reported fMRI and DTI measure trends have not achieved a clear consensus due to inconsistencies in the migraine neuroimaging literature. Future fMRI and DTI studies should establish and implement a uniform methodology that reproduces existing results and directly compares migraineurs with different subtypes. Combined fMRI and DTI imaging may provide better pathophysiological explanations for nonspecific FC and white matter microstructural differences.
... The structural integrity of white matter pathways such as the STR and FAT (connecting sensorimotor processing centers) or the anterior thalamic radiation or UF (connecting emotional processing centers) were also affected in the FD/MAS cohort. Across these pathways, lower FA was associated with greater pain severity, which aligns with prior findings made in patients with migraine, persistent headache, or trigeminal neuralgia (49)(50)(51)(52)(53). Interestingly, a correlation with neuropathic pain scores and lower FA values in pathways implicated in orofacial movements (ie, FAT) was observed (54). ...
Context
Pain is a poorly managed aspect in fibrous dysplasia/McCune-Albright Syndrome (FD/MAS) due to uncertainties regarding the clinical, behavioral, and neurobiological underpinnings that contribute to pain in these patients.
Objective
Identify neuropsychological and neurobiological factors associated pain severity in FD/MAS.
Design
Prospective, single-site study
Patients
20 FD/MAS patients and 16 age-sex matched healthy controls (HCs)
Intervention
Assessments of pain severity, neuropathic pain, pain catastrophizing (pain rumination, magnification, and helplessness), emotional health, and pain sensitivity with thermal quantitative sensory testing [QST]). Central nervous system (CNS) properties were measured with diffusion tensor imaging, structural magnetic resonance imaging, and functional MRI.
Main outcome measures
Questionnaire responses, detection thresholds and tolerances to thermal stimuli, and structural and functional CNS properties.
Results
Pain severity in FD/MAS patients was associated with more neuropathic pain quality, and higher levels of pain catastrophizing, and depression. QST revealed normal detection of non-noxious stimuli in patients. Individual with FD/MAS had higher pain tolerances relative to HCs. From neuroimaging studies, greater pain severity, neuropathic pain quality, and psychological status of the patient were associated with reduced structural integrity of white matter pathways (superior thalamic radiation and uncinate fasciculus), reduced gray matter thickness (pre-/paracentral gyri), and heightened responses to pain (precentral, temporal, and frontal gyri). Thus, properties of CNS circuits involved in processing sensorimotor and emotional aspects of pain were altered in FD/MAS.
Conclusions
These results offer insights into pain mechanisms in FD/MAS, while providing a basis for implementation of comprehensive pain management treatment approaches that addresses neuropsychological aspects of pain.
... In spite of extensive research work and a great number of studies, the mechanisms underlying the development of the attacks of migraine headache, are still not clearly understood [26] and a great amount of controversy still exists regarding the physiological, metabolic and microstructural changes in the brain of migraine patients [27,28,29,30]. ...
... The majority of previous studies have included migraine patients with aura or a mixture of patients with and without aura and some studies even included patients with chronic migraine. Specific studies of migraine patients without aura were remarkably few [28,30,31,32]. So, our study included only migraine patients without aura to investigate these brain changes in this particular clinically entity. ...
Background: Migraine is a very common disease. Studying the pathological changes in the brain is important for understanding the mechanisms underlying migraine headache. Previous research work has given conflicting results. This study aimed to investigate the functional, metabolic and microstructural changes in the brain of migraine patients without aura. Methods: This study included 42 migraine patients without aura in the interictal period and 11 age and sex matched controls. All participants were subjected to clinical assessment, assessment of the habituation to visual evoked potentials, assessment of the peak metabolic ratios by H-MRS and diffusion tensor imaging of the brain to test for regional microstructural changes. Results: The amplitudes of VEPs showed significant reduction in control subjects (P < 0.01), but not in migraine patients after repeated stimulation and significant increase in migraine patients compared to controls (P < 0.01). H-MRS showed significant decrease of NAA/Cr (P < 0.01) and increase of Mi/NAA (P < 0.001) and Cho/Cr (P < 0.05) PMRs in the thalamus and occipital lobes in migraine patients compared to controls. DTI showed significant changes in the FA, AD, MD, RD values in the thalamus, occipital lobe and insula in migraine patients indicating microstructural changes in these areas. All changes showed significant correlation with the intensity, frequency and duration of migraine episodes, but not with the duration of migraine disease. Conclusion: Migraine patients without aura showed increased excitability to visual stimulation and significant metabolite and microstructural brain changes that correlated with the severity, not the duration of the disease. These changes need to be confirmed in a large scale longitudinal studies.
... For the MD and also the radial diffusivity, as with AD, both trends with higher and lower values in MP compared to controls have been detected, but with a higher number of studies reporting the higher values in MP. A detailed description of these results and further comparisons with a higher number of references is available elsewhere (Rahimi et al., 2022). ...
The objective of this study is to evaluate the efficacy of deep learning (DL) techniques in improving the quality of diffusion MRI (dMRI) data in clinical applications. The study aims to determine whether the use of artificial intelligence (AI) methods in medical images may result in the loss of critical clinical information and/or the appearance of false information. To assess this, the focus was on the angular resolution of dMRI and a clinical trial was conducted on migraine, specifically between episodic and chronic migraine patients. The number of gradient directions had an impact on white matter analysis results, with statistically significant differences between groups being drastically reduced when using 21 gradient directions instead of the original 61. Fourteen teams from different institutions were tasked to use DL to enhance three diffusion metrics (FA, AD and MD) calculated from data acquired with 21 gradient directions and a b-value of 1000 s/mm2. The goal was to produce results that were comparable to those calculated from 61 gradient directions. The results were evaluated using both standard image quality metrics and Tract-Based Spatial Statistics (TBSS) to compare episodic and chronic migraine patients. The study results suggest that while most DL techniques improved the ability to detect statistical differences between groups, they also led to an increase in false positive. The results showed that there was a constant growth rate of false positives linearly proportional to the new true positives, which highlights the risk of generalization of AI-based tasks when assessing diverse clinical cohorts and training using data from a single group. The methods also showed divergent performance when replicating the original distribution of the data and some exhibited significant bias. In conclusion, extreme caution should be exercised when using AI methods for harmonization or synthesis in clinical studies when processing heterogeneous data in clinical studies, as important information may be altered, even when global metrics such as structural similarity or peak signal-to-noise ratio appear to suggest otherwise.
... The temporal pole and the dorsolateral occipital lobe are connected by the ILF, which lies within the inferior temporal lobe [50]. Of significant note, Rahimi et al. documented alterations in the white matter of these tracts in patients with migraine [51]. This suggests that the SLF and ILF might contribute to the neuropathology of migraines, perhaps by influencing the perception and processing of pain associated with these conditions. ...
Background
New daily persistent headache (NDPH) is a rare primary headache disorder characterized by daily and persistent sudden onset headaches. The pathogenesis of NDPH remains unclear, and there are few white matter imaging studies related to NDPH. The purpose of this study was to investigate the micro-structural abnormalities of white matter in NDPH and provided insights into the pathogenesis of this disease based on tract-based spatial statistics (TBSS).
Methods
Twenty-one patients with NDPH and 25 healthy controls (HCs) were included in this study. T1 structural and diffusion magnetic resonance imaging (MRI) were acquired from all participants. Differences in the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) between patients with NDPH and HCs were investigated using TBSS analysis.
Results
Significantly decreased FA, increased MD and RD were found in patients with NDPH compared to HCs. White matter regions overlaid with decreased FA, increased MD and RD were found in 16 white matter tracts from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas and Johns Hopkins University White-Matter Tractography Atlas. Specifically, these white matter regions included the right anterior thalamic radiation (ATR), body of the corpus callosum (BCC), bilateral cingulum, left hippocampal cingulum (CGH), left corticospinal tract (CST), forceps major, fornix, left inferior fronto-occipital fasciculus (IFOF), bilateral inferior longitudinal fasciculus (ILF), left posterior limb of the internal capsule (PLIC), right retrolenticular part of the internal capsule (RPIC), splenium of the corpus callosum (SCC), right superior longitudinal fasciculus (SLF) and left uncinate fasciculus (UF). After Bonferroni correction, there were no correlations between the FA, MD, AD and RD values and the clinical characteristics of patients with NDPH (p > 0.05/96).
Conclusion
The results of our research indicated that patients with NDPH might have widespread abnormalities in the white matter of the brain.
... The mechanism of WMLs is unclear and is speculated to be due to disruption of blood-brain barrier, release of proinflammatory markers during a migraine attack, associated hypercoagulability, susceptibility for frequent CSD, and resultant cerebral hypoperfusion during a migraine attack, as well as genetic predisposition. Recent diffusion tensor imaging studies showed microstructural changes with widespread alteration of white matter tracts, thalamic radiations, corpus callosum, and brainstem in migraine [112], suggesting neuronal damage and impairment of axonal integrity [113]. ...
Purpose of Review
Uncommon causes of stroke merit specific attention; when clinicians have less common etiologies of stoke in mind, the diagnosis may come more easily. This is key, as optimal management will in many cases differs significantly from “standard” care.
Recent Findings
Randomized controlled trials (RCT) on the best medical therapy in the treatment of cervical artery dissection (CeAD) have demonstrated low rates of ischemia with both antiplatelet and vitamin K antagonism. RCT evidence supports the use of anticoagulation with vitamin K antagonism in “high-risk” patients with antiphospholipid antibody syndrome (APLAS), and there is new evidence supporting the utilization of direct oral anticoagulation in malignancy-associated thrombosis. Migraine with aura has been more conclusively linked not only with increased risk of ischemic and hemorrhagic stroke, but also with cardiovascular mortality. Recent literature has surprisingly not provided support the utilization of l-arginine in the treatment of patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); however, there is evidence at this time that support use of enzyme replacement in patients with Fabry disease. Additional triggers for reversible cerebral vasoconstriction syndrome (RCVS) have been identified, such as capsaicin. Imaging of cerebral blood vessel walls utilizing contrast-enhanced MRA is an emerging modality that may ultimately prove to be very useful in the evaluation of patients with uncommon causes of stroke. A plethora of associations between cerebrovascular disease and COVID-19 have been described. Where pertinent, authors provide additional tips and guidance.
Summary
Less commonly encountered conditions with updates in diagnosis, and management along with clinical tips are reviewed.
... For this reason, more reports of accurate descriptions of the clinical features of visual aura in children and adolescents are needed to better define symptoms and distinctive features in both conditions. Deep knowledge of pathophysiology mechanisms involved in cortical excitatory-inhibitory balance, promotion of hyper-reactivity to pain, and advancements in comprehending the potential neural mechanisms linked with migraine are necessary to understand and provide specific treatment options [76]. Some interesting data belong to the diffusion-weighted imaging (DWI) sequences, based on the difference in magnitude of water diffusion. ...
Since the earliest descriptions of the simple visual hallucinations in migraine patients and in subjects suffering from occipital lobe epilepsy, several important issues have arisen in recognizing epileptic seizures of the occipital lobe, which often present with symptoms mimicking migraine. A detailed quantitative and qualitative clinical scrutiny of timing and characteristics of visual impairment can contribute to avoiding mistakes. Differential diagnosis, in children, might be challenging because of the partial clinical, therapeutic, and pathophysiological overlaps between the two diseases that often coexist. Ictal elementary visual hallucinations are defined by color, shape, size, location, movement, speed of appearance and duration, frequency, and associated symptoms and their progression. The evaluation of the distinctive clinical features of visual aura in migraine and visual hallucinations in occipital epilepsy could contribute to understanding the pathogenetic mechanisms of these two conditions. This paper aims to critically review the available scientific evidence on the main clinical criteria that address diagnosis, as well as similarities and differences in the pathophysiological mechanisms underlying the visual impairment in epilepsy and migraine.
... Several migraine DTI studies had showed broader alterations in white matter tracts, subcortical and cortical areas, such as changes in the corpus callosum, thalamic radiations, coronal radiation, and the brainstem, which presented a high degree of variability during the migraine cycle phase [11][12][13][14]. DTI studies indicated that migraine had been linked to microstructural changes in a wide range of regions including the thalamic radiations, corpus callosum and brainstem which could accentuate neuronal damage and neuronal plasticity mechanisms [15]. All these studies suggested that resting-state functional magnetic resonance imaging could provide some objective imaging evidence for the diagnosis of migraine and assist clinicians at the imaging level in the management of the disease. ...
Migraine is a common, chronic dysfunctional disease with recurrent headaches. Its etiology and pathogenesis have not been fully understood and there is a lack of objective diagnostic criteria and biomarkers. Meanwhile, resting-state functional magnetic resonance imaging (RS-fMRI) is increasingly being used in migraine research to classify and diagnose brain disorders. However, the RS-fMRI data is characterized by a large amount of data information and the difficulty of extracting high-dimensional features, which brings great challenges to relevant studies. In this paper, we proposed an automatic recognition framework based on static functional connectivity (sFC) strength features and dynamic functional connectome pattern (DFCP) features of migraine sufferers and normal control subjects, in which we firstly extracted sFC strength and DFCP features and then selected the optimal features using the recursive feature elimination based on the support vector machine (SVM−RFE) algorithm and, finally, trained and tested a classifier with the support vector machine (SVM) algorithm. In addition, we compared the classification performance of only using sFC strength features and DFCP features, respectively. The results showed that the DFCP features significantly outperformed sFC strength features in performance, which indicated that DFCP features had a significant advantage over sFC strength features in classification. In addition, the combination of sFC strength and DFCP features had the optimal performance, which demonstrated that the combination of both features could make full use of their advantage. The experimental results suggested the method had good performance in differentiating migraineurs and our proposed classification framework might be applicable for other mental disorders.
