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Objectives: The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed‐based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting‐state functional magnetic resonance imaging (MRI). Methods: The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well‐matched healthy controls (HCs) with 3.0 Tesla MRI. The 76 nuclei in the brainstem atlas were defined as ROIs. Furthermore, we explored the correlations between FC and patients' clinical characteristics and neuropsychological evaluations. Results: Patients with NDPH exhibited reduced FC in multiple brainstem nuclei compared to HCs (including right inferior medullary reticular formation, right mesencephalic reticular formation, bilateral locus coeruleus, bilateral laterodorsal tegmental nucleus‐central gray of the rhombencephalon, median raphe, left medial parabrachial nucleus, periaqueductal gray, and bilateral ventral tegmental area‐parabrachial pigmented nucleus complex) and increased FC in periaqueductal gray. No significant correlations were found between the FC of these brain regions and clinical characteristics or neuropsychological evaluations after Bonferroni correction (p > 0.00016). Conclusions: Our results demonstrated that patients with NDPH have abnormal FC of brainstem nuclei involved in the perception and regulation of pain and emotions. [ABSTRACT FROM AUTHOR]

Objective: To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods: A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results: The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation: This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the glymphatic function in patients with new daily persistent headache (NDPH) using the diffusion tensor image analysis along the perivascular space (DTI‐ALPS) method. Background: NDPH, a rare and treatment‐refractory primary headache disorder, is poorly understood. There is limited evidence to suggest that headaches are associated with glymphatic dysfunction. Thus far, no studies have evaluated glymphatic function in patients with NDPH. Methods: In this cross‐sectional study conducted in the Headache Center of Beijing Tiantan Hospital, patients with NDPH and healthy controls were enrolled. All participants underwent brain magnetic resonance imaging examinations. Clinical characteristics and neuropsychological evaluation were examined in patients with NDPH. ALPS indexes for both hemispheres were measured to determine the glymphatic system function in patients with NDPH and healthy controls. Results: In total, 27 patients with NDPH (14 males, 13 females; age [mean ± standard deviation (SD)]: 36.6 ± 20.6) and 33 healthy controls (15 males, 18 females; age [mean ± SD]: 36.0 ± 10.8) were included in the analysis. No significant differences between groups were observed in the left ALPS index (1.583 ± 0.182 vs. 1.586 ± 0.175, mean difference = 0.003, 95% confidence interval [CI] of difference = −0.089 to 0.096, p = 0.942), or right ALPS index (1.578 ± 0.230 vs. 1.559 ± 0.206, mean difference = −0.027, 95% CI of difference = −0.132 to 0.094, p = 0.738). Additionally, ALPS indexes were not correlated with clinical characteristics or neuropsychiatric scores. Conclusion: No glymphatic dysfunction was detected in patients with NDPH by means of the ALPS method. Additional studies with larger samples are needed to confirm these preliminary findings and improve the understanding of glymphatic function in NDPH. [ABSTRACT FROM AUTHOR]

Objective: To explore gamma‐aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine. Background: Migraine affects approximately 1 billion people worldwide, with 2.5%–3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. Methods: In this cross‐sectional study, patients with EM and CM were recruited. Mescher‐Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs). Results: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age‐ and sex‐matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = −0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < −0.1, and p = 0.034, MD < −0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1) (p = 0.024; MD = −0.1). The area under the curve for GABA+/Water levels in differentiating patients with CM from HCs was 0.83 (95% confidence interval 0.68, 0.98; p = 0.004). Correlation analyses within the migraine group revealed no significant correlation between metabolite concentration levels and headache characteristics after Bonferroni correction. Conclusion: Reduced GABA+/Water levels and imbalance of excitation/inhibition in the right thalamus may contribute to migraine chronification. [ABSTRACT FROM AUTHOR]

Nocturnal trough systolic blood pressure (NTSBP) and Time Point of Nocturnal Trough Systolic Blood Pressure (T‐NTSBP) were important parameters of nocturnal blood pressure, the predictive values of which are unclear for stroke outcome. This study aimed to examine the relationship between NTSBP/T‐NTSBP and stroke outcome. The authors used data from a nationwide ambulatory blood pressure monitoring cohort study conducted in China, which recruited 2348 ischemic stroke and transient ischemic attack (TIA) patients. NTSBP was defined as the lowest SBP during nighttime (22:00–6:00), and T‐NTSBP was defined as the corresponding time point of NTSBP. The associations between NTSBP/T‐NTSBP and stroke outcome (stroke recurrence and combined vascular event [CVE]) at 90 days or 1 year were analyzed using cox regression models. According to NTSBP classified by quartile, hazard ratio (HR) with 95% confidence interval (CI) for NTSBP quartile 4 (>129 mm Hg) was 2.727 (1.148–6.478) for CVE at 90‐day, compared with quartile 1 (≤102 mm Hg). However, an attenuated association between NTSBP and CVE was observed at 1 year. In addition, we observed the group of T‐NTSBP at 4:00–6:00 had a lowest CVE incidence at 90 days among four groups (22:00–23:59, 00:00–1:59 2:00–3:59, 4:00–6:00). After multivariable adjustment, T‐NTSBP was significantly associated with CVE incidence at 90 days (T‐NTSBP at the 4:00–6:00 versus the 22:00–23:59 group: HR, 0.433; 95%CI, 0.190–0.986), independent of NTSBP and average nocturnal SBP. Both of NTSBP and T‐NTSBP were important predictors for short‐term cardiovascular risk in ischemic stroke and TIA patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: QT dispersion (QTd) abnormalities are widely documented in stroke patients. This study aims to investigate the association between QTd and clinical outcomes in IS patients. Methods: IS patients registered in the Blood Pressure and Clinical Outcome in transient ischemic attack (TIA) or IS (BOSS) registry between 2012 and 2014 within 24 h of onset were analyzed. In this prospective observational study, we identified 1,522 IS cases with adequate electrocardiographic evaluations to assess QTd after the index stroke. Patients were classified into four groups based on the quartile of QTd, with the lowest group as the reference. The primary stroke outcome was defined as a modified Rankin Scale score ≥3 at 1-year. Multiple logistic regressions were utilized to investigate the association between QTd and outcome events. Results: The mean QTd across all cases was 57 ms (40–83). Functional dependency or death was documented in 214 (14.98%) cases at 1 year. After adjusting for confounders, the prevalence of death and major disability (mRS ≥ 3) showed significant differences according to the quartile of QTd, with the risk of death and major disability (mRS ≥ 3) at 1 year being significantly higher for patients in Q4 than for those in Q1 (adjusted OR = 1.626, 95% CI:1.033–2.560). However, there were no significant correlation between QTd and the event outcomes at 1 year. Conclusions: QTd was associated with poor functional outcomes at 1 year. QTd is a useful surrogate marker for adverse functional prognosis, which might help to stratify risk in patients with acute IS. [ABSTRACT FROM AUTHOR]

The white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD , and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, and c.179C>A chr6-44280882 p.P60H) with varying expression in 4 independent Chinese families with leukodystrophy. These single nucleotide variants (SNVs), or deletion mutations, each induced a frameshift, causing a missense mutation in alanyl-tRNA synthetase 2. These findings suggested that all mutations might contribute to the development of leukodystrophy in the examined family members. Combined with previous findings, our data confirmed that the novel mutations are located in leukodystrophy-related risk genes. We also summarized all the alanyl-tRNA synthetase 2 mutations related to the onset of leukodystrophies in adults. [ABSTRACT FROM AUTHOR]

Background and objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best known and the most common monogenic small vessel disease (SVD). Cognitive impairment is an inevitable feature of CADASIL. Total SVD score and global cortical atrophy (GCA) scale were found to be good predictors of poor cognitive performance in community-dwelling adults. We aimed to estimate the association between the total SVD score, GCA scale and the cognitive performance in patients with CADASIL. Methods: We enrolled 20 genetically confirmed CADASIL patients and 20 controls matched by age, gender, and years of education. All participants underwent cognitive assessments to rate the global cognition and individual domain of executive function, information processing speed, memory, language, and visuospatial function. The total SVD score and GCA scale were rated. Results: The CADASIL group performed worse than the controls on all cognition measures. Neither global cognition nor any separate domain of cognition was significantly different among patients grouped by total SVD score. Negative correlations between the GCA score and cognitive performance were observed. Approximately 40% of the variance was explained by the total GCA score in the domains of executive function, information processing speed, and language. The superficial atrophy score was associated with poor performance in most of the domains of cognition. Adding the superficial atrophy score decreased the prediction power of the deep atrophy score on cognitive impairment alone. Conclusions: The GCA score, not the total SVD score, was significantly associated with poor cognitive performance in patients with CADASIL. Adding the superficial atrophy score attenuated the prediction power of the deep atrophy score on cognitive impairment alone. [ABSTRACT FROM AUTHOR]

Glycyl-tRNA synthetase (GARS) gene mutations have been reported to be associated with Charcot-Marie-Tooth disease 2D and distal hereditary motor neuropathy type V (dHMN-V). In this study, we report a novel GARS mutation in a Chinese family with dHMN-V. Clinical, electromyogram, genetic, and functional data were explored. The proband was an 11-year-old girl presented with progressive distal limb muscle weakness and atrophy due to peripheral motor neuropathy for 1 year. Another five members from three successive generations of the family showed similar symptoms during their first to second decades and demonstrated an autosomal dominant inheritance. The results of genetic testing revealed a novel c.383T>G mutation in the GARS gene in the affected individuals, showing apparent genetic cosegregation. Further bioinformatic analyses showed that the c.383T > G mutation resulted in L128R alteration in the second functional protein domain, and the mutation site was well conserved among different species. In silico analysis predicted that this mutation probably affected protein function. In vitro, this GARS mutation led to a different protein localization pattern than that of the wild-type enzyme. The study found a novel GARS mutation of c.383T > G causing dHMN-V with subcellular localization abnormity in a genetic cosegregation family. These findings broaden the mutational spectrum of GARS. [ABSTRACT FROM AUTHOR]

Whether cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL) is a risk factor for spontaneous intracerebral hemorrhage ( ICH) and influences outcomes remains unclear. In this study, we report two cases of CADASIL presenting with cerebral hemorrhages. These cases suggest that a CADASIL vasculopathy by itself mainly results in ICH, as indicated by slight vascular risk factors and prominent neuroimaging abnormalities, suggesting that CADASIL should be considered a risk factor for ICH. Interestingly, decreased perihematomal edema was noted in ICH patients with CADASIL in this study. [ABSTRACT FROM AUTHOR]