RESUMO
BACKGROUND AND PURPOSE: This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities. METHODS: Data from the ATTENTION cohort were used to perform a post-hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90-day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied. RESULTS: Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78-26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28-6.92; pinteraction = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44-2.81; pinteraction = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (pinteraction = 0.042). CONCLUSION: An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO.
Assuntos
Circulação Colateral , Trombectomia , Insuficiência Vertebrobasilar , Humanos , Trombectomia/métodos , Masculino , Circulação Colateral/fisiologia , Feminino , Idoso , Pessoa de Meia-Idade , Insuficiência Vertebrobasilar/cirurgia , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/fisiopatologia , Resultado do Tratamento , Índice de Gravidade de Doença , Recuperação de Função Fisiológica/fisiologia , Idoso de 80 Anos ou mais , Estado Funcional , Angiografia por Tomografia Computadorizada , Artéria Basilar/cirurgia , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/fisiopatologiaRESUMO
Attention deficit hyperactivity disorder (ADHD) is associated with reduction of cortical and subcortical gray matter volumes (GMVs). The kinectin 1 gene (KTN1) has recently been reported to significantly regulate GMVs and ADHD risk. In this study, we aimed to identify sex-specific, replicable risk KTN1 alleles for ADHD and to explore their regulatory effects on mRNA expression and cortical and subcortical GMVs. We examined a total of 1020 KTN1 SNPs in one discovery sample (ABCD cohort: 5573 males and 5082 females) and three independent replication European samples (Samples #1 and #2 each with 802/122 and 472/141 male/female offspring with ADHD; and Sample #3 with 14,154/4945 ADHD and 17,948/16,246 healthy males/females) to identify replicable associations within each sex. We examined the regulatory effects of ADHD-risk alleles on the KTN1 mRNA expression in two European brain cohorts (n = 348), total intracranial volume (TIV) in 46 European cohorts (n = 18,713) and the ABCD cohort, as well as the GMVs of seven subcortical structures in 50 European cohorts (n = 38,258) and of 118 cortical and subcortical regions in the ABCD cohort. We found that four KTN1 variants significantly regulated the risk of ADHD with the same direction of effect in males across discovery and replication samples (0.003 ≤ p ≤ 0.041), but none in females. All four ADHD-risk alleles significantly decreased KTN1 mRNA expression in all brain regions examined (1.2 × 10-5 ≤ p ≤ 0.039). The ADHD-risk alleles significantly increased basal ganglia (2.8 × 10-22 ≤ p ≤ 0.040) and hippocampus (p = 0.010) GMVs but reduced amygdala GMV (p = 0.030) and TIV (0.010 < p ≤ 0.013). The ADHD-risk alleles also significantly reduced some cortical (right superior temporal pole, right rectus) and cerebellar but increased other cortical (0.007 ≤ p ≤ 0.050) GMVs. To conclude, we identified a set of replicable and functional risk KTN1 alleles for ADHD, specifically in males. KTN1 may play a critical role in the pathogenesis of ADHD, and the reduction of specific cortical and subcortical, including amygdalar but not basal ganglia or hippocampal, GMVs may serve as a neural marker of the genetic effects.
RESUMO
BACKGROUND: The bi-tensor free water imaging may provide more specific information in detecting microstructural brain tissue alterations than conventional single tensor diffusion tensor imaging. The study aimed to investigate microstructural changes in deep gray matter (DGM) nuclei of Wilson's disease (WD) using a bi-tensor free water imaging and whether the findings correlate with the neurological impairment in WD patients. METHODS: The study included 29 WD patients and 25 controls. Free water and free water corrected fractional anisotropy (FAT) in DGM nuclei of WD patients were calculated. The correlations of free water and FAT with the Unified WD Rating Scale (UWDRS) neurological subscale of WD patients were performed. RESULTS: Free water and FAT values were significantly increased in multiple DGM nuclei of neurological WD patients compared to controls. WD patients with normal appearing on conventional MRI also had significantly higher free water and FAT values in multiple DGM nuclei than controls. Positive correlations were noted between the UWDRS neurological subscores and free water values of the putamen and pontine tegmentum as well as FAT values of the dentate nucleus, red nucleus, and globus pallidus. In addition, the measured free water and FAT values of specific structures also showed a positive correlation with specific clinical symptoms in neurological WD patients, such as dysarthria, parkinsonian signs, tremor, dystonia, and ataxia. CONCLUSIONS: Free water imaging detects microstructural changes in both normal and abnormal appearing DGM nuclei of WD patients. Free water imaging indices were correlated with the severity of neurological impairment in WD patients.
Assuntos
Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico por imagem , Estudos Transversais , Imagem de Tensor de Difusão , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Biomarcadores , ÁguaRESUMO
Nondopaminergic neurotransmitters such as adenosine, norepinephrine, serotonin, glutamate, and acetylcholine are all involved in Parkinson's disease (PD) and promote its symptoms. Therefore, nondopaminergic receptors are key targets for developing novel preparations for the management of motor and non-motor symptoms in PD, without the potential adverse events of dopamine replacement therapy. We reviewed English-written articles and ongoing clinical trials of nondopaminergic treatments for PD patients till 2014 to summarize the recent findings on nondopaminergic preparations for the treatment of PD patients. The most promising research area of nondopaminergic targets is to reduce motor complications caused by traditional dopamine replacement therapy, including motor fluctuations and levodopa-induced dyskinesia. Istradefylline, Safinamide, and Zonisamide were licensed for the management of motor fluctuations in PD patients, while novel serotonergic and glutamatergic agents to improve motor fluctuations are still under research. Sustained- release agents of Amantadine were approved for treating levodopa induced dyskinesia (LID), and serotonin 5HT1B receptor agonist also showed clinical benefits to LID. Nondopaminergic targets were also being explored for the treatment of non-motor symptoms of PD. Pimavanserin was approved globally for the management of hallucinations and delusions related to PD psychosis. Istradefylline revealed beneficial effect on daytime sleepiness, apathy, depression, and lower urinary tract symptoms in PD subjects. Droxidopa may benefit orthostatic hypotension in PD patients. Safinamide and Zonisamide also showed clinical efficacy on certain non-motor symptoms of PD patients. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs may lead to new approaches with positive clinical implications.
Assuntos
Discinesias , Doença de Parkinson , Humanos , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologia , Dopamina , Discinesias/tratamento farmacológico , Levodopa/efeitos adversos , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Serotonina/uso terapêutico , Zonisamida/uso terapêuticoRESUMO
Dopamine (DA) agonists, as an excellent dopamine replacement therapy for patients with early and advanced Parkinson's disease (PD), play a vital role in controlling motor and several nonmotor symptoms. Besides, the application of DA agonists may delay levodopa therapy and the associated risk of motor complications. Indeed, each DA agonist has unique pharmacokinetic and pharmacodynamic characteristics and therefore has different therapeutic efficacy and safety profile. The comorbidities, significant non-motor manifestations, concomitant medications, and clinical features of PD individuals should guide the selection of a specific DA agonist to provide a more patient-tailored treatment option. Thorough knowledge of DA agonists helps clinicians better balance clinical efficacy and side effects. Therefore, this review refers to recent English-written articles on DA agonist therapy for PD patients and summarizes the latest findings on non-ergot DA agonists as well as the advantages and disadvantages of each compound to help clinicians in the selection of a specific DA agonist. In addition, novel D1/D5 partial agonists and new formulations of DA agonists are also discussed.
Assuntos
Agonistas de Dopamina , Doença de Parkinson , Humanos , Agonistas de Dopamina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/complicações , Antiparkinsonianos/uso terapêutico , Antiparkinsonianos/farmacologia , Dopamina , Levodopa/uso terapêuticoRESUMO
Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10-5, and right p = 9.4 × 10-5; α = 2.1 × 10-4) and modestly increased other subcortical and cortical GMVs in both sexes (α < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 × 10-7 ≤ p < α; Top two: left pallidum and putamen) and males (3.5 × 10-6 ≤ p < α), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Encéfalo/diagnóstico por imagem , Criança , Feminino , Estudo de Associação Genômica Ampla , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Proteínas de Membrana , Caracteres SexuaisRESUMO
Background: Histopathological studies in Wilson's disease (WD) have revealed increased copper and iron concentrations in the deep gray matter nuclei. However, the commonly used mean bulk susceptibility only reflects the regional metal concentration rather than the total metal content, and regional atrophy may affect the assessment of mean bulk susceptibility. Our study aimed to quantitatively assess the changes of metal concentration and total metal content in deep gray matter nuclei by quantitative susceptibility mapping to distinguish patients with neurological and hepatic WD from healthy controls. Methods: Quantitative susceptibility maps were obtained from 20 patients with neurological WD, 10 patients with hepatic WD, and 25 healthy controls on a 3T magnetic resonance imaging system. Mean bulk susceptibility, volumes, and total susceptibility of deep gray matter nuclei in different groups were compared using a linear regression model. The area under the curve (AUC) was calculated by receiver characteristic curve to analyze the diagnostic capability of mean bulk susceptibility and total susceptibility. Results: Mean bulk susceptibility and total susceptibility of multiple deep gray matter nuclei in patients with WD were higher than those in healthy controls. Compared with patients with hepatic WD, patients with neurological WD had higher mean bulk susceptibility but similar total susceptibility in the head of the caudate nuclei, globus pallidus, and putamen. Mean bulk susceptibility of putamen demonstrated the best diagnostic capability for patients with neurological WD, the AUC was 1, and the sensitivity and specificity were all equal to 1. Total susceptibility of pontine tegmentum was most significant for the diagnosis of patients with hepatic WD, the AUC was 0.848, and the sensitivity and specificity were 0.7 and 0.96, respectively. Conclusion: Brain atrophy may affect the assessment of mean bulk susceptibility in the deep gray matter nuclei of patients with WD, and total susceptibility should be an additional metric for total metal content assessment. Mean bulk susceptibility and total susceptibility of deep gray matter nuclei may be helpful for the early diagnosis of WD.
RESUMO
Sjögren's syndrome is an autoimmune disease that can affect multiple systems. Sjögren's syndrome with motor neuron disease is rarely reported. Herein, we describe a patient with rapidly progressive motor neuron disease secondary to Sjögren's syndrome. A 42-year-old woman was admitted to our hospital with a 2-month history of progressive limb weakness. Neurological assessment revealed fasciculation in the lower limbs and amyotrophy in the bilateral supraspinatus, interosseous, and thenar muscles. Serological examination and labial gland biopsy revealed Sjögren's syndrome. In addition, electromyography demonstrated neurogenic damage to the upper and lower limbs. The patient received a short course of high-dose corticosteroids, intravenous immunoglobulins, and immunosuppressant treatment, including a weekly dose of 0.4 g cyclophosphamide and a daily dose of 0.2 g hydroxychloroquine. However, the patient's limb weakness was further aggravated and her respiratory function was compromised. Electromyography re-examination demonstrated extensive neurogenic damage, and she was diagnosed with Sjögren's syndrome with motor neuron disease. The patient died of respiratory failure after 2 months. We suggest that more effective maintenance treatments should be sought. Further investigation is required to elucidate the association between autoimmune motor neuron disease and Sjögren's syndrome.