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A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression

24 Mar

A Controlled Single-Centre Pilot Study to Evaluate the Effect of Prophylactic Surgery in Asymptomatic Degenerative Cervical Cord Compression

Study DesignSingle-centre controlled pilot study.ObjectivesTo evaluate the effect of prophylactic surgery and to review the biases of a therapeutic trial in asymptomatic degenerative cervical cord compression (ADCC) patients.MethodsPatients with ADCC and at least 1 predictor of progression to symptomatic degenerative cervical cord myelopathy (DCM) were offered either prophylactic surgery or standard structured rehabilitation. Recruited patients were clinically followed to detect the development of symptomatic DCM.ResultsForty-one patients treated surgically and 68 patients treated non-surgically completed the minimum 36 months' follow-up; 3 recruited patients were lost from evaluation. The surgical group had a higher Neck Disability Index score and more severe MRI compression. A matched subgroup of 41 non-surgical patients was created to reduce potential bias. During the follow-up period we observed progression to symptomatic DCM in 1 surgical case (2.4%) compared to 9 patients in the non-surgical group (13.2%, P = 0.054) and 7 cases in the matched non-surgical group (17.1%, P = 0.029). We observed non-serious early postoperative complications in 4 patients, which resolved spontaneously or after surgical revision. In 9 patients with progression to DCM, the myelopathy was mild with mJOA scale 15-17. One patient in the non-surgical group and 1 patient in the surgical group who progressed to DCM underwent surgery with a good outcome.ConclusionsProphylactic surgery led to a significant decrease in proportion of ADCC patients with progression to DCM.

Altered Patterns of Dynamic Functional Connectivity Underpin Reduced Expressions of Social-Emotional Reciprocity in Autistic Adults

24 Mar

Altered Patterns of Dynamic Functional Connectivity Underpin Reduced Expressions of Social-Emotional Reciprocity in Autistic Adults

To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)-an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male-male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social-emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior.

Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia

24 Feb

Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia

Dystonia is a rare-disease trait for which large-scale genomic investigations are still underrepresented. Genetic heterogeneity among patients with unexplained dystonia warrants interrogation of entire genome sequences, but this has not yet been systematically evaluated. To significantly enhance our understanding of the genetic contribution to dystonia, we (re)analyzed 2,874 whole-exome sequencing (WES), 564 whole-genome sequencing (WGS), as well as 80 fibroblast-derived proteomics datasets, representing the output of high-throughput analyses in 1,990 patients and 973 unaffected relatives from 1,877 families. Recruitment and precision-phenotyping procedures were driven by long-term collaborations of international experts with access to overlooked populations. By exploring WES data, we found that continuous scaling of sample sizes resulted in steady gains in the number of associated disease genes without plateauing. On average, every second diagnosis involved a gene not previously implicated in our cohort. Second-line WGS focused on a subcohort of undiagnosed individuals with high likelihood of having monogenic forms of dystonia, comprising large proportions of patients with early onset (81.3%), generalized symptom distribution (50.8%) and/or coexisting features (68.9%). We undertook extensive searches for variants in nuclear and mitochondrial genomes to uncover 38 (ultra)rare diagnostic-grade findings in 37 of 305 index patients (12.1%), many of which had remained undetected due to methodological inferiority of WES or pipeline limitations. 

Maternal depression during the perinatal period and its relationship with emotion regulation in young adulthood: An fMRI study in a prenatal birth cohort

14 Feb

Maternal depression during the perinatal period and its relationship with emotion regulation in young adulthood: An fMRI study in a prenatal birth cohort

Background: Maternal perinatal mental health is essential for optimal brain development and mental health of the offspring. We evaluated whether maternal depression during the perinatal period and early life of the offspring might be selectively associated with altered brain function during emotion regulation and whether those may further correlate with physiological responses and the typical use of emotion regulation strategies.

Methods: Participants included 163 young adults (49% female, 28-30 years) from the ELSPAC prenatal birth cohort who took part in its neuroimaging follow-up and had complete mental health data from the perinatal period and early life. Maternal depressive symptoms were measured mid-pregnancy, 2 weeks, 6 months, and 18 months after birth. Regulation of negative affect was studied using functional magnetic resonance imaging, concurrent skin conductance response (SCR) and heart rate variability (HRV), and assessment of typical emotion regulation strategy.

Results: Maternal depression 2 weeks after birth interacted with sex and showed a relationship with greater brain response during emotion regulation in a right frontal cluster in women. Moreover, this brain response mediated the relationship between greater maternal depression 2 weeks after birth and greater suppression of emotions in young adult women (ab = 0.11, SE = 0.05, 95% CI [0.016; 0.226]). 

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