Showing papers by "Shengyuan Yu published in 2017"

Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis.

Abstract: The amygdala is a large grey matter complex in the limbic system, and it may contribute in the neurolimbic pain network in migraine. However, the detailed neuromechanism remained to be elucidated. The objective of this study is to investigate the amygdala structural and functional changes in migraine and to elucidate the mechanism of neurolimbic pain-modulating in the migraine pathogenesis. Conventional MRI, 3D structure images and resting state functional MRI were performed in 18 normal controls (NC), 18 patients with episodic migraine (EM), and 16 patients with chronic migraine (CM). The amygdala volume was measured using FreeSurfer software and the functional connectivity (FC) of bilateral amygdala was computed over the whole brain. Analysis of covariance was performed on the individual FC maps among groups. The increased FC of left amygdala was observed in EM compared with NC, and the decreased of right amygdala was revealed in CM compared with NC. The increased FC of bilateral amygdala was observed in CM compared with EM. The correlation analysis showed a negative correlation between the score of sleep quality (0, normal; 1, mild sleep disturbance; 2, moderate sleep disturbance; 3, serious sleep disturbance) and the increased FC strength of left amygdala in EM compared with NC, and a positive correlation between the score of sleep quality and the increased FC strength of left amygdala in CM compared with EM, and other clinical variables showed no significant correlation with altered FC of amygdala. The altered functional connectivity of amygdala demonstrated that neurolimbic pain network contribute in the EM pathogenesis and CM chronicization.

Depression and anxiety behaviour in a rat model of chronic migraine

Abstract: Epidemiological and clinical studies have demonstrated comorbidity between migraine and affective disorders. However, it is unclear whether chronic migraine can lead to affective disorders in other animals. A classical chronic migraine rat model (repeated dura mater inflammatory soup [IS] infusion) was used to evaluate depression and anxiety behaviour via weight, sucrose preference test, open field test and elevated plus maze test. We found that sucrose preference, locomotor and rearing behaviours, inner zoon distance percent, open-arm entries percent and serotonin and dopamine levels in the prefrontal cortex decreased significantly in the IS group compared with those in the control group; co-administration of low-dose amitriptyline ameliorated these deficits. However, no differences in weight, inner zone time percent, or open-arm time percent between the IS and control groups. These results were used to create new depression and anxiety scales to comprehensively assess and evaluate the degree of affective disorders in rats. Most of chronic migraine animals showed depression and anxiety like behaviors but a few didn’t. Most of the chronic migraine rats were present depression and anxiety like behaviors. The new scales we created are expected to use in the future studies to find out the potential mechanism of affective disorders’ comorbidity.

Disrupted functional connectivity of periaqueductal gray subregions in episodic migraine

Abstract: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the altered dysfunction of PAG subregions were not totally detected up to now. The aim of this study is to investigate the altered functional connectivity of PAG subregions in EM patients. The brain structural images and resting state functional MR imaging (rs-fMRI) data were obtained from 18 normal controls (NC) and 18 EM patients on 3.0 T MR system. Seven subregions of PAG were classified as bilateral ventrolateral PAG (vlPAG), lateral PAG (lPAG), dorsolateral PAG (dlPAG) and dorsomedial PAG (dmPAG). The functional connectivity maps of each PAG subregion were calculated, and Two sample t-test was applied with age and sex as covariables. Bilateral vlPAG and left dlPAG presented decreased functional connectivity, and the other subregions (bilateral lPAGs, right dlPAG and dmPAG) showed no significant altered functional connectivity in EM compared with NC. The brain regions with decreased functional connectivity mainly located in bilateral prefrontal cortex(PFC), middle temporal gyrus, primary motor area (PMA) and supplementary motor area (SMA) and right ventrolateral PFC (vlPFC) in EM patients in this study. Disease duration was positively related to the functional connectivity of bilateral vlPAG on the bilateral thalamus and putamen, left pallidum and right medial orbitofrontal gyrus in EM patients. The present study suggested that the dysfunction of bilateral vlPAG and left dlPAG presented in EM, and functional evaluation of PAG subregions may be help for the diagnosis and understanding of EM pathogenesis.

Mobile Phone Use and The Risk of Headache: A Systematic Review and Meta-analysis of Cross-sectional Studies

Abstract: Headache is increasingly being reported as a detrimental effect of mobile phone (MP) use. However, studies aimed to investigate the association between MP use and headache yielded conflicting results. To assess the consistency of the data on the topic, we performed a systematic review and meta-analysis of the available cross-sectional studies. Published literature from PubMed and other databases were retrieved and screened, and 7 cross-sectional studies were finally included in this meta-analysis. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated. We found that the risk of headache was increased by 38% in MP user compared with non-MP user (OR, 1.38; 95% CI, 1.18–1.61, p 15 min vs. 4 calls vs. <2 calls: OR, 2.52; 95% CI, 1.78–3.58, p < 0.001). Our data indicate that MP use is significantly associated with headache, further epidemiologic and experimental studies are required to affirm and understand this association.

Altered functional connectivity architecture of the brain in medication overuse headache using resting state fMRI.

Abstract: Functional connectivity density (FCD) could identify the abnormal intrinsic and spontaneous activity over the whole brain, and a seed-based resting-state functional connectivity (RSFC) could further reveal the altered functional network with the identified brain regions. This may be an effective assessment strategy for headache research. This study is to investigate the RSFC architecture changes of the brain in the patients with medication overuse headache (MOH) using FCD and RSFC methods. 3D structure images and resting-state functional MRI data were obtained from 37 MOH patients, 18 episodic migraine (EM) patients and 32 normal controls (NCs). FCD was calculated to detect the brain regions with abnormal functional activity over the whole brain, and the seed-based RSFC was performed to explore the functional network changes in MOH and EM. The decreased FCD located in right parahippocampal gyrus, and the increased FCD located in left inferior parietal gyrus and right supramarginal gyrus in MOH compared with NC, and in right caudate and left insula in MOH compared with EM. RSFC revealed that decreased functional connectivity of the brain regions with decreased FCD anchored in the right dorsal-lateral prefrontal cortex, right frontopolar cortex in MOH, and in left temporopolar cortex and bilateral visual cortices in EM compared with NC, and in frontal-temporal-parietal pattern in MOH compared with EM. These results provided evidence that MOH and EM suffered from altered intrinsic functional connectivity architecture, and the current study presented a new perspective for understanding the neuromechanism of MOH and EM pathogenesis.

Chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in rats

Abstract: Background Preclinical experimental studies revealed an acute alteration of pituitary adenylate cyclase-activating polypeptide in response to a single activation of the trigeminovascular system, which suggests a potential role of pituitary adenylate cyclase-activating polypeptide in the pathogenesis of migraine. However, changes in pituitary adenylate cyclase-activating polypeptide after repeated migraine-like attacks in chronic migraine are not clear. Therefore, the present study investigated chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulations in the rat. Methods A rat model of chronic migraine was established by repeated chemical dural stimulations using an inflammatory soup for a different numbers of days. The pituitary adenylate cyclase-activating polypeptide levels were quantified in plasma, the trigeminal ganglia, and the trigeminal nucleus caudalis using radioimmunoassay and Western blotting in trigeminal ganglia and trigeminal nucleus caudalis tissues. Western blot analysis and real-time polymerase chain reaction were used to measure the protein and mRNA expression of pituitary adenylate cyclase-activating polypeptide-related receptors (PAC1, VPAC1, and VPAC2) in the trigeminal ganglia and trigeminal nucleus caudalis to identify changes associated with repetitive applications of chemical dural stimulations. Results All rats exhibited significantly decreased periorbital nociceptive thresholds to repeated inflammatory soup stimulations. Radioimmunoassay and Western blot analysis demonstrated significantly decreased pituitary adenylate cyclase-activating polypeptide levels in plasma and trigeminal ganglia after repetitive chronic inflammatory soup stimulation. Protein and mRNA analyses of pituitary adenylate cyclase-activating polypeptide-related receptors demonstrated significantly increased PAC1 receptor protein and mRNA expression in the trigeminal ganglia, but not in the trigeminal nucleus caudalis, and no significant differences were found in the expression of the VPAC1 and VPAC2 receptors. Conclusions This study demonstrated the chronic alteration of pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in the rat, which suggests the crucial involvement of pituitary adenylate cyclase-activating polypeptide in the development of migraine. The selective increase in pituitary adenylate cyclase-activating polypeptide-related receptors suggests that the PAC1 receptor pathway is a novel target for the treatment of migraine.

Disrupted functional connectivity between the periaqueductal gray and other brain regions in a rat model of recurrent headache

Abstract: Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. We aimed to identify atypical FC between the periaqueductal gray (PAG) and other brain areas in rats induced by repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Quiescent and face-grooming behaviors were observed to assess nociceptive behavior. FC analysis seeded on the PAG was performed on rats 21 days after IS infusion. The rats exhibited nociceptive behavior correlates of human behaviors associated with migraine after IS infusion. The PAG showed increased FC with the prefrontal cortex, cingulate gyrus, and motor cortex but decreased FC with the basal ganglia, dorsal lateral thalamus, internal capsule and prelimbic cortex in the rat model. The atypical FC of the PAG with brain regions in the rat model that are involved in nociception, somatosensory processing, emotional processing, and pain modulation are consistent with the clinical data from migraineurs, indicate that resting-state FC changes in migraine patients may be a consequence of headache attacks, and further validate this rat model of chronic migraine.

Volume expansion of periaqueductal gray in episodic migraine: a pilot MRI structural imaging study

Abstract: The periaqueductal gray (PAG) dysfunction was recognized in migraine, and the nonspecific PAG lesions were also observed in episodic migraine (EM) recently. However, the PAG volume change was not totally detected in EM up to now. Herein, the aim of this study was to investigate altered PAG volume in EM patients based on high resolution brain structural image. The brain structural images were obtained from 18 normal controls (NC), 18 EM patients and 16 chronic migraine (CM) on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template using MRIcron, and the individual PAG was created by applying the deformation field to the PAG template after structural image segment. One-way analysis of covariance, partial correlation analysis and Receiver operating characteristics (ROC) curve were applied. EM had a larger PAG volume (0.35 ± 0.02 ml) than that (0.32 ± 0.02 ml) of NC (P = 0.017). The PAG volume of CM (0.33 ± 0.02 ml) was negatively related to the VAS score (P = 0.03). ROC analysis demonstrated that PAG volume has higher diagnostic efficacy (AUC, 0.731; Sensitivity, 0.556; Specificity, 0.889) for NC vs. EM compared with that NC vs. CM (AUC, 0.634; Sensitivity, 0.438; Specificity, 0.833) and EM vs. CM (AUC, 0.618; Sensitivity, 0.813; Specificity, 0.556). PAG volume expansion may be the direct impairment evidence on the brain in EM, and could be considered as a diagnostic and evaluated imaging biomarker in migraine.

Volume gain of periaqueductal gray in medication-overuse headache

Abstract: Periaqueductal gray (PAG) is a substantial descending pain modulatory center, and previous voxel-based morphometry study confirmed the clusters with increased volume in PAG region in medication-overuse headache (MOH). The aim of this study is to investigate altered PAG volume in MOH using an automated PAG segment method to measure the true PAG volume. High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 22 patients with MOH and 22 normal controls (NC). PAG template was created based on ICBM 152 gray template, and the individual PAG was generated by applying the deformation field from structural image segment to the PAG template, and individual PAG volume was calculated. There was a significant increased volume of PAG in MOH (0.366 ± 0.005 ml) than that in NC (0.341 ± 0.005 ml)(P 0.05). The area of receiver operating characteristic (ROC) curve was 0.845, and the cut-off of PAG volume was 0.341 ml with sensitivity 95.5% and specificity 63.6%. The present study demonstrated that the PAG volume gain was confirmed in MOH patients, and the automated individual PAG volume measure may be considered as a simple and effective imaging biomarker in MOH diagnosis.

Cardiac cephalalgia: one case with cortical hypoperfusion in headaches and literature review.

Abstract: Cardiac cephalalgia (CC) is a rare disease occurring during an episode of myocardial ischemia and relieved by nitroglycerine. Though more than 30 cases of CC have been reported since 1997, the mechanism is yet obscure. Herein, a case of CC is presented and discussed in relevance with previous literature to propose a novel hypothesis about the mechanism of CC. A CC patient with cortical hypoperfusion during headache attacks was presented, which has never been reported. All published cases of CC via PubMed ( http://www.ncbi.nlm.nih.gov/pubmed ) in English literature, between 1997 and 2016, were reviewed. A patient suffering from CC presented a cerebral hypoperfusion during a headache attack. This phenomenon had not been observed since CC was introduced in 1997. The literature review summarized the clinical presentations, neuroimaging features, ECG, and coronary angiography features of 35 CC patients. Based on the phenomenon of hypoperfusion in the event of a headache, the vessel constriction hypothesis was proposed including two potential physiological mechanisms underlying the pathophysiology of CC.

Cerebral aspergillosis: a retrospective analysis of eight cases.

Abstract: Purpose: Aspergillosis of the central nervous system is very rare. However with recent increases in the use of immunosuppressive agents and antibiotics, its incidence is increasing. We evaluated th...

Texture features of periaqueductal gray in the patients with medication-overuse headache.

Abstract: Periaqueductal gray (PAG) is the descending pain modulatory center, and PAG dysfunction had been recognized in migraine. Here we propose to investigate altered PAG texture features (quantitative approach for extracting texture descriptors for images) in the patients with medication-overuse headache (MOH) based on high resolution brain structural image to understand the MOH pathogenesis. The brain structural images were obtained from 32 normal controls (NC) and 44 MOH patients on 3.0 T MR system. PAG template was created based on the ICBM152 gray matter template, and the individual PAG segment was performed by applying the deformation field to the PAG template after structural image segment. Grey-level co-occurrence matrix (GLCM) was performed to measure the texture parameters including angular second moment (ASM), Contrast, Correlation, inverse difference moment (IDM) and Entropy. Contrast was increased in MOH patients (9.28 ± 3.11) compared with that in NC (7.94 ± 0.65) (P 0.05). The area under the ROC curve was 0.697 for Contrast in the distinction of MOH from NC, and the cut-off value of Contrast was 8.11 with sensitivity 70.5% and specificity 62.5%. The contrast was negatively with the sleep scores (r = -0.434, P = 0.003). Texture Contrast could be used to identify the altered MR imaging characteristics in MOH in understanding the MOH pathogenesis, and it could also be considered as imaging biomarker in for MOH diagnosis.

Lifting the burden of headache in China: managing migraine in a SMART way.

Abstract: With support from Lifting The Burden , a UK-registered charitable organization, a nationwide survey of headache disorders in the Chinese adult population was conducted in 2008–2009. This project, which was within the Global Campaign against Headache, showed that headache disorders have a major adverse impact on public health in China. Subsequently, as essential support for implementing headache services around the country, an enactment of stage 3 (intervention) of the Global Campaign against Headache − the continuing medical education (CME) program Headache Schools − was established. ‘SMART’ (Screen, Migraine, Aura, Red flag and Treatment), a systematic and operational disease management model, was introduced with the aims of enhancing neurologists’ knowledge of migraine, standardizing their diagnostic and treatment approaches, and improving their practices and outcomes. To date, 615 neurologists have been trained and 135 headache clinics have been established. In future, as we promote SMART in CME, we can use the database of our computerized clinical decision support systems to evaluate the impact on treatment outcomes.

Cortical damage in Wernicke's encephalopathy with good prognosis: a report of two cases and literature review.

Abstract: Wernicke’s encephalopathy (WE) is a thiamine deficiency-related condition, in which lesions are usually present in the periventricular and subcortical areas of the brain. However, lesions have also been found in atypical areas, such as the cerebral cortex. The present study summarizes the clinical outcomes and radiological features of WE with cortical impairment. We report two cases of cortical involvement in patients with WE, and review 22 similar cases from other reports. Among all 24 cases, 4 patients had a confirmed history of chronic daily alcohol abuse, and 19 of them had an identified causes of thiamine deficiency. 17 cases reported specific clinical information, among which 11 patients had symptoms of cortical impairment. 23 cases reported prognostic information at the end of treatment or at follow-up. The mortality rate was 26.1 % in our review. All patients had abnormal magnetic resonance imaging (MRI) signals or pathological findings in the bilateral cortex. Among patients with available MRI, 89.0 % had banding-like signs along the para-central sulcus. 13 cases underwent follow-up MRI examinations and 76.9 % displayed normal images. We suggest that WE with bilateral cortical involvement may have an acceptable prognosis, but that the mortality rate is higher than that among typical cases, especially if patients are not treated promptly and correctly. We identified the frontal and parietal lobes, especially around the central sulcus, to be the most susceptible areas, and suggest that the banding signs may be characteristic of WE. Persistent hyper-intensity on T2-weighted–fluid-attenuated inversion recovery, or gadolinium enhancement, may predict poor outcome.

Volumetric abnormalities of thalamic subnuclei in medication-overuse headache.

Abstract: The thalamus exerts a pivotal role in pain processing and cortical excitability control and a previous voxel-based morphometry study confirmed increased volume in bilateral thalamus in medication-overuse headache (MOH). The aim of this study is to investigate altered thalamic subnuclei volume in MOH compared with normal controls, and to evaluate the relationship of each thalamic subnuclei volume with the clinical variables. High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 27 patients with MOH and 27 normal controls (NC). Thalamic subnuclei templates were created based on Talairach template with MNI space transformation, and the individual thalamic subnuclei templates were generated by applying the deformation field from structural image segment to the thalamic subnuclei templates, and then individual thalamci subnuclei volume were calculated. The whole thalamus and each thalamic subnuclei presented increased volume compared with NC (P 0.05). Increased gray matter volume in the whole thalamus and all the thalamus subnuclei may reflect central sensitization and higher-order of pain alteration in MOH. These structural changes in the thalamus may also be influenced by mood disturbances related to the MOH.

Gender differences among Chinese patients with neuromyelitis optica spectrum disorders.

Abstract: Background Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune, inflammatory demyelinating diseases of the central nervous system, which have established variations in prevalence across different ethnicities and genders. The objective of this study was to investigate differences in clinical features among men and women with NMOSD, according to the 2015 diagnostic criteria. Methods A total of 97 patients with NMOSD were recruited from inpatient neurology clinics in this retrospective study. Demographic and clinical data were extracted from the various databases. Data on epidemiology, clinical signs, initial symptoms, and laboratory indices of men and women with NMOSD were compared. Results The cohort of this study had a female/male ratio of 5.47:1, with annualized relapse rates of 0.72 in female and 0.56 in male patients. Among female patients, 29.2% and 53.6% initially experienced acute optic neuritis and acute myelitis, respectively, while the prevalence of these symptoms was 46.6% and 53.3% among male patients. A total of 14.6% and 2.4% of female patients had area postrema symptoms and other brainstem signs, respectively on study enrollment. The prevalence of anti-AQP4-autoantibodies and anti-thyroid peroxidase autoantibodies/anti-thyroglobulin autoantibodies (TPO/TG-Ab) was significantly higher among women (77% and 45.7%) than among men (46.1% and 13.3%) ( P Conclusions Women with NMOSD have higher morbidity levels than men with this disease and are more likely to have autoimmune diseases and brainstem lesions, especially in the area postrema.

Alteration of gray matter texture features over the whole brain in medication-overuse headache using a 3-dimentional texture analysis

Abstract: Imaging studies have provided valuable information in understanding the headache neuromechanism for medication-overuse headache (MOH), and the aim of this study is to investigate altered texture features of MR structural images over the whole brain in MOH using a 3-dimentional texture analysis. Brain three-dimensional T1-weighted structural images were obtained from 44 MOH patients and 32 normal controls (NC). The imaging processing included two steps: gray matter (gray images) segment and a 3-dimensional texture features mapping. Voxel-based gray-level co-occurrence matrix (VGLCM) was performed to measure the texture parameters mapping including Contrast, Correlation, Energy, Entropy and inverse difference moment (IDM). The texture parameters of increased Contrast and Entropy, decreased Energy and IDM were identified in cerebellar vermis of MOH patients compared to NCs. Increased Contrast and decreased Energy were found in left cerebellum. Increased Correlation located in left dorsolateral periaqueductal gray (L-dlPAG), right parahippocampal gyrus (R-PHG), and left middle frontal gyrus (L-MFG) and decreased Correlation located in right superior parietal lobule(R-SPL). Disease duration was positively correlated with Contrast of vermis and negatively correlated with Correlation of R-SPL.HAMD score was negatively correlated with Correlation of R-PHG. MoCA score was positively correlated with Correlation of R-SPL. The altered textures in gray matter related to pain discrimination and modulation, affective and cognitive processing were helpful in understanding the pathogenesis of MOH. Texture analysis using VGLCM is a sensitive and efficient method to detect subtle gray matter changes in MOH.

Laugh-Induced Headache: Clinical Features and Literature Review.

Abstract: Background Laughing is a rare precipitating factor for headaches, and the pathogenesis underlying laugh-induced headache (LH) remains unclear. Methods Two cases of headache triggered predominantly by laughing were presented in this article. We also reviewed the published English literature regarding LH, summarized the clinical characteristics of LH, and discussed the probable pathophysiological mechanisms. Results In the first patient, magnetic resonance imaging of the brain revealed cerebellar tonsillar herniation through the foramen magnum. In the second patient, we did not find any evidence of intracranial disease. The literature review showed that LH is a mild to severe, non-pulsating headache. In most cases, the duration of each attack was limited to a few minutes. The headache usually bursts after laughing and reaches its peak almost immediately. In some cases, the headache can only be induced by mirthful laughing rather than by fake laughing. Conclusion LH can be categorized as primary LH and secondary LH. Changes in the spatial structure in the posterior cranial fossa and cerebrospinal fluid circulation may contribute to the development of secondary LH. Primary LH, primary cough headache, and primary exercise headache may share some common pathogenesis. And we speculate that the regions of the brain associated with the expression of mirth might be associated with LH.

Characteristics of Headache After an Intracranial Endovascular Procedure: A Prospective Observational Study.

Abstract: BACKGROUND Two editions of the International Classification of Headache Disorders (ICHD) diagnostic criteria for "Headache attributed to an intracranial endovascular procedure" have been published, in 2004 and 2013.1,2 Despite studies that have suggested that the former is not very practical, the ICHD-3 beta did not contain major changes. Moreover, so far no consensus exists regarding characteristics of headache after intracranial endovascular procedure. Thus, there is a need for sound suggestions to improve the ICHD-3 beta diagnostic criteria. METHODS Using a prospective design, we identified consecutive patients with unruptured intracranial aneurysms (UIAs) with neuroendovascular treatment from January 2014 to December 2014. RESULTS In total, 73 patients were enrolled, and 58 patients ultimately completed the 6-month follow-up. After the procedure, five of the 29 patients (17.2%) with pre-existing headache experienced marked worsening after the procedure, while seven of the 29 patients without prior headache developed new-onset headache post-procedurally. The headaches started within 24 hours, with a mean duration of 24-72 hours. The headaches were moderate to severe. The eligibility of these events to be considered headaches caused by neuroendovascular procedures according to the ICHD-3 beta diagnostic criteria for designation was far from ideal. CONCLUSIONS Most cases of markedly worsening headaches and new-onset headaches started within 24 hours and persisted longer than that specified in the ICHD-3 beta diagnostic criteria. Moreover, considering that some items are not very practical, the ICHD-3 beta diagnostic criteria should be revised in the light of recent literature reports.

Effect of Efflux Transporter Inhibition on the Distribution of Fluconazole in the Rat Brain.

Abstract: Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) are expressed on the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), preventing the entry of or the pumping out of numerous molecules. Fluconazole is widely used to treat fungal meningoencephalitis. The effect of these transporters on the distribution of fluconazole in the brain is unclear. We used microdialysis to compare the distribution of fluconazole in the rat brain with and without co-administration of probenecid, a MRP and OAT inhibitor. Additionally, we also observed the difference in fluconazole distribution between the two barriers. The results showed that probenecid increased the penetration of fluconazole into the BBB but did not alter the penetration of fluconazole into the BCSFB of rats. The penetration of the BBB and BCSFB by fluconazole did not statistically differ according to physiological condition. These results demonstrate that transporters that can be inhibited by probenecid may be involved in fluconazole resistance at the BBB and provide a laboratory basis for predicting brain extracellular fluid (ECF) concentration using the cerebrospinal fluid (CSF) concentration of fluconazole.

Letter by Yu et al Regarding Article, "Dynamic Arterial Compression in Pediatric Vertebral Arterial Dissection".

Abstract: We read with great interest the research by Rollins et al1 that investigated the possible associations between vertebral arterial dissection and dynamic vertebral artery (VA) compression in children. This article is meaningful because it provides important data on both pediatric vertebral arterial dissection and pediatric dynamic VA compression. We considered with interest the information in the article about stroke in dynamic VA compression. In this article, 7 boys with dynamic VA compression had cerebral infarction treated with systemic anticoagulation. We agree with the decision to administer anticoagulation therapy with heparin for these patients but think that the reasons were not clearly explained in this article. In our view, the selection of systemic anticoagulation may be associated with the possible …