Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.

BACKGROUND: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. METHODS: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. RESULTS: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. CONCLUSIONS: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.

AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization.

BACKGROUND: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. METHODS: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. RESULTS: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1ß, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. CONCLUSIONS: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Migraine-like headache in subjects with isolated Lambl's excrescences: a case series and literature review.

AIM: Lambl's excrescences are mobile, thin, fibrinous connective tissue strands typically found on left-sided cardiac values. Migraine is positively associated with structural cardiac anomalies. However, it remains unclear whether Lambl's excrescences are associated with migraine. METHODS: Retrospective review of 182 inpatients with Lambl's excrescences confirmed by transesophageal echocardiogram in Chinese PLA General Hospital since January 2010. Among them, those with isolated Lambl's excrescences presented with migraine-like headache were included. We collected information on the demographics and clinical profiles of all participants, and performed follow-up visits. RESULTS: A total of 8 patients presented with migraine-like headache among 15 patients with isolated Lambl's excrescences. They included 2 men and 6 women, with an average age of 44.63 ± 12.24 years. Among these patients, 3 had visual aura, and 6 manifested infarct-like lesions on magnetic resonance imaging, of which 2 developed lesions after first visit. During follow-up, 4 patients suffering from intervention for Lambl's excrescences dramatically reduced headache recurrence compared to the other 4 patients only receiving migraine preventive medications. CONCLUSIONS: This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache. And intervention for Lambl's excrescences may be crucial for preventing headache recurrence.

This study supports the hypothesis that microemboli from isolated Lambl's excrescences could cause migraine-like headache.The small sample size study fails to make management recommendations.

Prevalence of depression and its correlation with anxiety, headache and sleep disorders among medical staff in the Hainan Province of China.

Objective: This cross-sectional survey aimed to investigate the prevalence of depression among medical staff and its risk factors as well as the association between depression, anxiety, headache, and sleep disorders. Methods: Stratified random cluster sampling was used to select medical staff from various departments of four hospitals in Sanya City. The Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI) were used to quantitatively assess depression, anxiety, and sleep disorders. Correlation and regression analyses were performed to determine factors affecting the depression occurrence and scores. Results: Among 645 medical staff members, 548 (85%) responded. The 1-year prevalence of depression was 42.7% and the prevalence of depression combined with anxiety, headache, and sleep disorders was 23, 27, and 34.5%, respectively. The prevalence of depression in women, nurses, the unmarried or single group, and the rotating-shift population was significantly higher than that in men (48.3% vs. 27.1%, odds ratio OR = 2.512), doctors (55.2% vs. 26.7%, OR = 3.388), the married group (50.5% vs. 35.8%, OR = 1.900), and the day-shift population (35.2% vs. 7.5%, OR = 1.719). The occurrence of depression was correlated with anxiety, sleep disorders, headache, and migraines, with anxiety having the highest correlation (Spearman's Rho = 0.531). The SDS was significantly correlated with the SAS and PSQI (Spearman's Rho = 0.801, 0.503) and was also related to the presence of headache and migraine (Spearman Rho = 0.228, 0.159). Multiple logistic regression indicated that nurse occupation and anxiety were risk factors for depression, while grades of anxiety, sleep disorders and nurse occupation were risk factors for the degree of depression in multiple linear regression. Conclusion: The prevalence of depression among medical staff was higher than that in the general population, especially among women, nurses, unmarried people, and rotating-shift workers. Depression is associated with anxiety, sleep disorders, headache, and migraines. Anxiety and nursing occupation are risk factors for depression. This study provides a reference for the promotion of occupational health among medical professionals.

Ginkgo biloba extract EGb 761® improves cognition and overall condition after ischemic stroke: Results from a pilot randomized trial.

Background: Patients who experienced an ischemic stroke are at risk for cognitive impairment. Quantified Ginkgo biloba extract EGb 761® has been used to treat cognitive dysfunction, functional impairment and neuropsychiatric symptoms in mild cognitive impairment and dementia. Objectives: To assess the cognitive-related effects of EGb 761® treatment in patients after acute ischemic stroke, as well as the feasibility of patient selection and outcome measures. Methods: We conducted a randomized, multicentric, open-label trial at 7 centers in China. Patients scoring 20 or lower on the National Institutes of Health Stroke Scale were enrolled between 7 and 14 days after stroke onset and randomly assigned to receive 240 mg per day of EGb 761® or no additional therapy for 24 weeks in a 1:1 ratio. Both groups received standard treatments for the prevention of recurrent stroke during the trial. General cognitive function and a battery of cognitive tests for sub-domains were evaluated at 24 weeks. All patients were monitored for adverse events. Results: 201 patients ≥50 years old were included, with 100 assigned to the EGb 761® group and 101 to the reference group. The mean change from baseline on the global cognitive function as assessed by the Montreal Cognitive Assessment score was 2.92 in the EGb 761® group and 1.33 in the reference group (between-group difference: 1.59 points; 95% confidence interval [CI], 0.51 to 2.67; p < 0.005). For cognitive domains, EGb 761® showed greater effects on the Hopkins Verbal Learning Test Total Recall (EGb 761® change 1.40 vs. reference -0.49) and Form 1 of the Shape Trail Test (EGb 761® change -38.2 vs. reference -15.6). Potentially EGb 761®-related adverse events occurred in no more than 3% of patients. Conclusion: Over the 24-week period, EGb 761® treatment improved overall cognitive performance among patients with mild to moderate ischemic stroke. Our findings provide valuable recommendations for the design of future trials, including the criteria for patient selection. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN11815543.

The applicability research of the diagnostic criteria for 10.2 Heamodialysis-related headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Headache during hemodialysis (HDH) is prevalent but not negligible. Despite the high prevalence of dialysis headaches, they have rarely been studied. Therefore, this study aimed to evaluate the prevalence, risk factors, and clinical characteristics of HDH and reappraise the HDH diagnostic criteria in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: One hundred and fifty-four patients completed this randomized cross-sectional study. Consecutive patients who underwent haemodialysis were assessed using a semi-structured questionnaire. The patients were administered face-to-face questionnaires while undergoing dialysis. RESULTS: This study included 154 patients. Before commencing dialysis, 3.24% (5/154) of the patients had migraine without aura, 1.29% (2/154) had menstrual-related migraine, 0.6% (1/154) had tension-type headaches, and 0.6% (1/154) had an unclassifiable headache. One case (0.6%) of headache resolved after dialysis treatment. HDH was diagnosed in 9.09% (14/154) of the patients. Headache after haemodialysis (HAH) was reported in 6.49% (10/154) of patients. The most prevalent features of HDH were frontal or temporal location, bilateral headaches, dull and throbbing nature, and moderate severity. HDH started at a mean of 2.33 ± 0.79 h after dialysis commenced. The average headache duration was 6.56 ± 1.57 h (median = 3.0 h), with 66.67% of the patients reporting a duration of ≤4 h. HDH was more prevalent in females than males (P = 0.01, P < 0.05). Female sex was a risk factor for HDH (P = 0.01，P < 0.05). CONCLUSIONS: The diagnostic criteria for 10.2 HDH in ICHD-3 may miss several HAH. Therefore, ICHD-3 should be revised according to the literature and further studies.

Acute sleep deprivation aggravates nitroglycerin-evoked hyperalgesia in mice.

Sleep deprivation can trigger migraine, and migraineurs often choose to sleep to relieve headaches during acute migraine. This study aimed to explore the effect of acute sleep deprivation on hyperalgesia induced by nitroglycerin in mice. In part one, after either 6-h sleep deprivation or 6-h normal sleep, mice were intraperitoneally injected with nitroglycerin or saline. The mechanical pain threshold and withdrawal latency of the hindpaw were measured every 30 min for 6 h. Next, the same sleep deprivation and injection procedure was performed with new mice, and mice were sacrificed 4.5 h after injection. The trigeminal nucleus caudalis and upper cervical spinal segments were taken for immunofluorescence Fos staining. In part two, after injection of saline or nitroglycerin, the mice were either deprived of sleep for 6 h or allowed to sleep without interference. The mechanical and thermal pain threshold were measured after 6 h. In part three, we compared the sleep time of mice after intraperitoneal injection of saline or nitroglycerin without interference. Sleep deprivation for 6 h did not cause any changes in the baseline pain thresholds in mice. However, pretreatment with 6-h sleep deprivation significantly prolonged the duration of hyperalgesia induced by nitroglycerin. Additionally, the expression of Fos at 4.5 h was significantly higher in the 6-h sleep deprivation and nitroglycerin group than in the other three groups. When intraperitoneal injection was given first, the mechanical pain threshold of the hind paw was significantly lower in the group that received nitroglycerin with 6-h sleep deprivation than in the other groups. Compared to the saline injection, one-time nitroglycerin injection would result in a significant increase in sleep latency and decrease in sleep duration for the normal mice. Acute sleep deprivation significantly aggravated the hyperalgesia induced by nitroglycerin in mice, which highlights the importance of sleep disorders for migraine.

Alteration of gut microbiota in migraine patients with irritable bowel syndrome in a Chinese Han population.

Objective: Migraine is frequently reported in patients with irritable bowel syndrome (IBS), and emerging evidence suggests that gut microbiota plays a role in migraine and IBS. However, alterations in the gut microbiome in migraine patients with IBS remain unknown. This study aimed to explore the compositions of gut microbiota in migraine patients with IBS in a Chinese Han population. Methods: Sixteen migraine patients with IBS and thirteen age- and gender-matched IBS patients with similar dietary and lifestyle habits were enrolled in this pilot study. Demographic data, clinical data, eating habits, lifestyle habits, comorbidities, and medications were recorded using a unified case registration form. Questionnaires for the Migraine Disability Assessment (MIDAS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD) were completed. Fecal samples were collected, and microbial DNA was extracted. Gut microbiota 16S ribosomal RNA (16S rRNA) gene sequencing targeting the V4 region was performed using the Illumina HiSeq 2500 high-throughput sequencing platform. The relationships between gut microbiota and clinical characteristics of migraine were analyzed. Results: The structure of gut microbiota differed between migraine patients with IBS and patients with IBS, while the richness and diversity of gut microbiota in migraine patients with IBS showed no significant difference from that of patients with IBS. We found a higher relative abundance of the genus Parabacteroides and a lower relative abundance of the genera Paraprevotella, Lachnospiraceae_UCG-010, Lactococcus, Collinsella, and Comamonas in migraine patients with IBS than in patients with IBS. According to random forest predictive models, the phylum Bacteroidota shows the most important role in migraine patients with IBS. Furthermore, no statistical correlation was found between significantly different taxa at the genus level and migraine clinical data. Conclusion: This study identified that altered gut microbiota occurred in Chinese Han migraine patients with IBS, but no correlation was found between gut microbiota and the clinical characteristics of migraine. Further study is needed to better understand the role of gut microbiota in the pathogenesis of migraine in IBS.

Diffusion-weighted imaging hyperintensities during the chronic stage of intracerebral hemorrhage with surgery: A new clinical situation or post-surgery artifact?

Background and objective: Diffusion-weighted imaging (DWI) hyperintensities were occasionally seen at previous hematoma in patients several months after intracerebral hemorrhage with surgery. Whether they are newly occurred clinical situations or post-surgery changes is unknown. This study aims to investigate the prevalence and possible mechanisms for this phenomenon. Methods: We retrospectively reviewed the MRI database for intracerebral hemorrhage with surgery after 3 months of disease onset in our hospital. We also prospectively performed repeated multimodal MRI scans for two patients at the chronic stage after surgery for intracerebral hemorrhage. Results: We found that 14 out of 23 patients (60.9%) had DWI hyperintensities at the site of previous hematoma 3 months after intracerebral hemorrhage with surgery. All the DWI lesions were hyperintense on T1- and T2-weighted imaging, most of which appeared long and narrow in shape. The DWI lesions were usually located adjacent to the thin wall of the previous hematoma cavity close to the lateral ventricle. They were more associated with the basal ganglia hemorrhage than with the lobar hemorrhage (P = 0.02) and were more frequently seen for those with intraventricular hemorrhage than without (P = 0.02). Prospectively repeated MRI exams of two patients revealed unchanged DWI hyperintensity during the 18- and 2-month follow-up, respectively. Conclusion: The DWI lesions at previous hematoma were commonly seen in patients after surgery for intracerebral hemorrhage at the chronic stage which would persist for years. We hypothesized a possible mechanism by which extracellular methemoglobin "islands" are formed with delayed or no absorption by macrophages from adjacent thin residual brain tissue. Unnecessary further examinations and treatment would be avoided by realizing this imaging phenomenon.

The applicability research of the diagnostic criteria for 6.7.2 angiography headache in the international classification of headache disorders-3rd edition.

BACKGROUND: Angiography headache (AH) is common but not negligible, and the criteria for AH have been based on only a few studies. The purpose of this study was to investigate the incidence, risk factors and possible mechanism of AH and reappraise the diagnostic criteria for AH in the International Classification of Headache Disorders 3 (ICHD-3). METHODS: Two hundred and seventy-nine patients completed this prospective, non-randomized study, including 107 patients who underwent cerebral angiography, 101 patients who underwent coronary intervention and 71 patients who underwent extremities arterial intervention. Patients were followed up with questionnaires immediately after the procedure and 24 h, 72 h, 1 week and 2 weeks after the procedure. RESULTS: The incidence of headache was 22.4% (24/107) in cerebral angiography group, 23.8% (24/101) in coronary intervention group, and 16.9% (12/71) in extremities arterial intervention group. Headache still occurred in 12.1% (13/107), 14.9% (15/101) and 11.3% (8/71) of patients 24 h after the procedure in the three groups, respectively. Two types of headache were observed in cerebral angiography group and coronary intervention group, one during and one after the procedure, while only postoperative headache was observed in extremities arterial intervention group. Previous headache history was a risk factor for headache in the three groups (p = 0.003 in cerebral angiography group, p = 0.006 in coronary intervention group, and p = 0.016 in extremities arterial intervention group). In addition, female (p = 0.008) was a risk factor for cerebral angiography group. Headache characteristics were described in detail. CONCLUSIONS: The diagnostic criteria for 6.7.2 angiography headache in ICHD-3 may miss a number of cerebral AH with onset later than 24 h after the procedure. Therefore, it is recommended to revise it according to the literature and further studies. The incidence of headache was high during and after angiography and interventional procedure. It was suggested that the definition of headache due to coronary intervention and headache due to extremities arterial intervention should be added in ICHD.

Temporal characteristics of astrocytic activation in the TNC in a mice model of pain induced by recurrent dural infusion of inflammatory soup.

BACKGROUND: Astrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release. METHODS: We used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A). RESULTS: Recurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d. CONCLUSIONS: Our results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release.

Characteristics of headache during and/or after coronary intervention: A prospective observational study.

INTRODUCTION: Headache during and/or after coronary intervention is common but has received little attention from cardiologists and neurologists. The purpose of this study was to investigate the incidence, risk factors, and possible mechanism of coronary intervention-related headache. METHODS: Using a prospective observational design, we identified consecutive patients with coronary intervention from May 2020 to August 2020. Patients were followed up with questionnaires immediately after coronary intervention and 24 h, 72 h, 1 week and 2 weeks after the intervention. RESULTS: In total, 94 patients were enrolled, and 71 patients ultimately completed the 2-week follow-up. Among 71 patients, headache developed during and/or after coronary intervention in 18 (25.4%) patients. Two different types of headache related to coronary intervention were observed: One during and another after coronary intervention. Headache characteristics are described in detail. A history of previous headache was an independent risk factor for coronary intervention-related headache (p < 0.01). CONCLUSIONS: Coronary intervention-related headache has an incidence of 25.4%, and previous headache history was an independent risk factor. Moreover, considering that there are no relevant diagnostic criteria, it is suggested that the definition of coronary intervention-related headache should be established in the International Classification of Headache Disorders.

Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms.

BACKGROUND: Mutations in ATP1A2, the gene encoding the α2 subunit of Na+/K+-ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear. METHODS: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na+/K+-ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations. RESULTS: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na+/K+-ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na+/K+-ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na+/K+-ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain. CONCLUSIONS: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na+/K+-ATPase. Mutations associated with intellectual disability presented with severe impairment of Na+/K+-ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function.

Paroxysmal dysarthria-ataxia syndrome: Literature review on MRI findings and report of a peculiar case with clinically isolated syndrome coexisting with anti-N-methyl-d-aspartate receptor antibodies.

Paroxysmal dysarthria and ataxia (PDA) syndrome constitutes a rare neurological disorder, and is generally reported in cases of multiple sclerosis (MS) involving the midbrain. We present an illustrative case of 32-year-old female who developed clinically isolated syndrome manifested paroxysmal dysarthria, ataxia, ptosis and diplopia, coexisting with anti-N-methyl-d-aspartate receptor antibodies. We review the literature and identify 23 other cases with brain MRI examinations to summarize the lesion locations and clinical characteristics of PDA syndrome, and ultimately provide a new framework for understanding this rare condition. The current case expands the spectrum of symptoms in PDA syndrome, which was including but not limited to dysarthria and ataxia. Caudal paramedian midbrain lesions involving decussation of the superior cerebellar peduncles appear to be critical for PDA syndrome.

Prevalence and risk factors associated with headache amongst medical staff in South China.

BACKGROUND: A previous study by our team reported the prevalence of primary headache disorders and factors associated with headache among nurses in three hospitals in North China. The aim of this cross-sectional survey was to learn more about how medical nurses in South China were affected by headache. Additionally, we determined the prevalence of headache and measured the impact of headache among doctors in mainland China for the first time. METHODS: Stratified random cluster sampling was used to select 280 physicians and 365 nurses from various departments in four hospitals in Sanya, which is one of southernmost cities in China. Information was collected on demographic data, occupational factors and headache characteristics by using a structured questionnaire. RESULTS: Among 645 medical staff, 548 (85%) responded (doctors = 240, nurses = 308). Among the medical staff, the 1-year prevalence of primary headache disorders was 50%, with 25.9% experiencing migraine and 24.1% experiencing tension-type headache (TTH). The prevalence of migraine in female doctors was higher than that in female nurses, although this difference was not significant (32.4% vs. 29.8%, P = 0.628). Multivariate analysis showed that being female and working in other specialties (Emergency Department & Radiology Department) remained independent risk factors for migraine in doctors (OR 2.314 and 3.223). In nurses, being married was a risk factor for migraine (OR 3.728), and job titles remained an independent risk factor for migraine and TTH (OR 2.294 and 4.695). Working more than 6 night-shifts per month was associated with an increased prevalence of migraine and TTH in doctors; the same was true in nurses for migraine, but not for TTH. CONCLUSION: The prevalence of primary headache disorders in both nurses and doctors is higher than that in the general population in South China. Our study shows that occupation, geography and sex may play an important role. Further, female doctors are more susceptible than female nurses to migraine. The risk factors relevant to headache that were found in this study should provide an important reference for promoting occupational health in medical staff, especially female doctors in China.

Isolated lymphomatoid granulomatosis of the central nervous system: A case report and literature review.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive lymphoproliferative disease which can involve multiple organs of the body and is most common in the lungs. Its pathological features are proliferation of large atypical B-cells related to Epstein-Barr virus, T-cell infiltration and tissue necrosis. This disease is rare, and LYG which uniquely involves the central nervous system (CNS) is extremely rare. In this paper, we report a case of isolated lymphomatoid granulomatosis of the CNS (iCNS-LYG) diagnosed by histological biopsy and we review the clinical features of all similar cases reported in the past 46 years. A total of 49 cases of iCNS-LYG have been reported to date. The clinical, imaging and pathological features of iCNS-LYG are discussed in combination with a literature review.

Headache attributed to cranial venous sinus stenting: A case series and literature review.

BACKGROUND: The diagnostic criteria for headache attributable to cranial venous sinus stenting were first formalized in the recently published third edition of the International Classification of Headache Disorders (ICHD-3). However, the diagnostic criteria for headache caused by cranial venous sinus stenting are based on very few data and the condition is poorly characterized. OBJECTIVES: To validate the diagnostic criteria for cranial venous sinus stenting headache by retrospectively studying the characteristics of headache in patients with isolated pulsatile tinnitus who underwent curative cranial venous sinus stenting and who had not previously complained of headache. PATIENTS AND METHODS: We retrospectively studied clinical, radiological, and manometric data from patients with isolated venous pulsatile tinnitus who had not previously reported headache. All patients underwent lateral sinus stenting in our institution between October 2010 and February 2018. RESULTS: Forty eight patients, 47 females and one male, were enrolled. The mean age at symptom onset was 36.2 ± 8.7 years and the mean body mass index was 24.0 ± 3.2 kg/m2. Lateral sinus stenosis was evident in 47 patients and a sigmoid diverticulum in one. Fourteen patients experienced headaches after recovering from general anesthesia. All were female, with a mean age of 35.5 ± 9.6 years. Headache persisted for less than 3 days in six patients (42.8%); for 3 days to 3 months in four (28.6%); and for longer than 3 months in four (28.6%). The headaches were located on the same sides as the cranial venous sinus stents in 13 patients (92.9%) and were principally occipital, being oppressive in nine patients (64.3%) and of moderate intensity in seven (50%). Age at onset of pulsatile tinnitus and body mass index were significantly associated with headache (p < 0.05; t-test). CONCLUSION: To the best of our knowledge, this is the first study to describe cranial venous sinus stenting headache in detail. We found that de novo headache developed after cranial venous sinus stenting, and was usually mild to moderate, unilateral, but oppressive; almost one-third of such headaches persisted for more than 3 months. Researchers and clinicians must become familiar with this headache spectrum; further prospective studies are required.

Unnecessary Neuroimaging for Patients With Primary Headaches.

Background - Headache may be due to either a primary or secondary disorder, and neuroimaging assessments can play an important role when differentiating between these types of headache. Although many studies have reported no significant differences between primary headache patients and the general population in terms of abnormal neuroimaging findings, others have shown that neuroimaging may be employed to rule out secondary causes of headache that could impact morbidity and mortality. This issue remains under debate. Thus, the present study compared the neuroimaging findings of headache patients and healthy controls. Methods - This study recruited 1070 healthy controls and 1070 primary headache patients from the Chinese People's Liberation Army General Hospital. The primary headache patients were diagnosed by computerized clinical decision support systems, and re-diagnosed by a specialist. All participants were assessed with either computed tomography or magnetic resonance imaging (MRI) scans. The neuroimaging findings were classified as significant abnormalities, non-significant abnormalities, or normal. Results - All the significant abnormalities were found using MRI scans. Significant abnormalities were identified in 4 primary headache patients (0.58%) and 5 healthy controls (0.73%); the rate of significant abnormalities was not significant different between both groups (P > .05). Conclusions - The present study found that neuroimaging was unnecessary for the primary headache patients.

Comparison of Therapeutic Efficacy Between Isolated Encephaloduroarteriosynangiosis and Medical Treatment in Patients with Atherosclerotic Middle Cerebral Artery Occlusion.

BACKGROUND: Encephaloduroarteriosynangiosis (EDAS) as a form of indirect revascularization has been recently proposed as a potentially promising alternative for patients with intracranial atherosclerotic disease (ICAD). The object of this study was to compare the prognostic roles between isolated EDAS and medical therapy in patients with atherosclerotic middle cerebral artery occlusion (MCAO). METHODS: From January 2014 to June 2017, 125 patients with atherosclerotic MCAO were enrolled in this prospective nonrandomized controlled cohort study. Patients who underwent EDAS (n = 60) were compared with those treated medically (n = 65). Early and late adverse events and functional outcomes including memory ability were compared between groups. RESULTS: During 23.7 months of mean follow-up, rates of adverse events, including ischemic events in the territory of the qualifying middle cerebral artery, and death from any causes, were not significantly different in patients treated with EDAS and with medical therapy (6.7% vs. 12.3%; P = 0.285). Landmark analyses showed that at initial 6-month follow-up, there was no significant difference for adverse event rates, whereas the opposite finding was shown for the subsequent period (EDAS 1/57 [1.7%] vs. medical management 7/64 [10.9%]; P = 0.024). The P value for the interaction between time (first 6 months vs. subsequent period) was 0.044. No significant differences were found with respect to neural function status and cognitive ability. CONCLUSIONS: In the long-term, isolated EDAS can be considered effective and safe for patients with atherosclerotic MCAO, whereas it may need additional medical therapy support in the short-term.