Levodopa Response in Patients With Early Parkinson Disease

In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude.

source: AAN

Summary

Further Observations of the LEAP Study

[Posted 23/Jan/2023]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier.

BACKGROUND: The Levodopa in Early Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease.

DETAILS: The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was -0.33 for bradykinesia, -0.29 for rigidity, and -0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, -0.49, -0.36, and -0.44 (small to medium effect); and from baseline to week 40, respectively, -0.32, -0.19, and -0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01).

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Source: Frequin, H. L., Schouten, J., Vershuur, C. V. M., et al. (2022). Levodopa Response in Patients With Early Parkinson Disease: Further Observations of the LEAP Study. American Academy of Neurology. 2023; 100(4). Published: January 24, 2023. DOI: 10.1212/WNL.0000000000201448.



Effect of Preoperative Low-Normal Cervical Length on Perinatal Outcome After Laparotomy-Assisted Fetoscopic Spina Bifida Repair

Low-normal cervical length (25-30 mm) as measured before in-utero laparotomy-assisted fetoscopic spina bifida repair may increase the risk of adverse perinatal outcomes, including PPROM and preterm birth, leading to higher rates of neonatal complications.

source: Ultrasound Obstet Gynecol

Summary

[Posted 27/Jan/2023]

AUDIENCE: Ob/Gyn, Neurology, Family Medicine

KEY FINDINGS: Low-normal cervical length (25-30 mm) as measured before in-utero laparotomy-assisted fetoscopic spina bifida repair may increase the risk of adverse perinatal outcomes, including PPROM and preterm birth, leading to higher rates of neonatal complications. These data warrant further research and are of critical relevance for clinical teams considering the eligibility of patients for in-utero spina bifida repair. Based on this evidence, patients with a low-normal cervical length should be aware of their increased risk for adverse perinatal outcome.

BACKGROUND: Aim of this study i to determine if preoperative cervical length in the low-normal range increases the risk of adverse perinatal outcome in patients undergoing fetoscopic spina bifida repair.

DETAILS: This was a retrospective cohort study of patients who underwent fetal spina bifida repair between September 2014 and May 2022 at a single center. Cervical length was measured on transvaginal ultrasound during the week before surgery. Eligibility for laparotomy-assisted fetoscopic spina bifida repair was as per the criteria of the Management of Myelomeningocele Study, although maternal body mass index (BMI) up to 40 kg/m2 was allowed. Laparotomy-assisted fetoscopic spina bifida repair was performed, with carbon dioxide insufflation via two 12-French ports in the exteriorized uterus. All patients received the same peri- and postoperative tocolysis regimen, including magnesium sulfate, nifedipine and indomethacin. Postoperative follow-up ultrasound scans were performed either weekly ( 32 weeks' gestation) or twice a week (< 32 weeks). Perinatal outcome was compared between patients with a preoperative cervical length of 25-30 mm vs those with a cervical length > 30 mm. Logistic regression analyses and generalized linear mixed regression analyses were used to predict delivery at less than 30, 34 and 37 weeks' gestation. The study included 99 patients with a preoperative cervical length > 30 mm and 12 patients with a cervix 25-30 mm in length. One further case which underwent spina bifida repair was excluded because cervical length was measured > 1 week before surgery. No differences in maternal demographics, gestational age (GA) at surgery, duration of surgery or duration of carbon dioxide uterine insufflation were observed between groups. Cases with low-normal cervical length had an earlier GA at delivery (median (range), 35.2 (25.1-39.7) weeks vs 38.2 (26.0-40.9) weeks; P = 0.01), higher rates of delivery at < 34 weeks (41.7% vs 10.2%; P = 0.01) and < 30 weeks (25.0% vs 1.0%; P < 0.01) and a higher rate of preterm prelabor rupture of membranes (PPROM) (58.3% vs 26.3%; P = 0.04) at an earlier GA (mean ± SD, 29.3 ± 4.0 weeks vs 33.0 ± 2.4 weeks; P = 0.05) compared to those with a normal cervical length. Neonates of cases with low-normal cervical length had a longer stay in the neonatal intensive care unit (20 (7-162) days vs 9 (3-253) days; P = 0.02) and higher rates of respiratory distress syndrome (50.0% vs 14.4%; P < 0.01), sepsis (16.7% vs 1.0%; P = 0.03), necrotizing enterocolitis (16.7% vs 0%; P = 0.01) and retinopathy (33.3% vs 1.0%; P < 0.01). There was an association between preoperative cervical length and risk of delivery at < 30 weeks which was significant only for patients with a maternal BMI < 25 kg/m2 (odds ratio, 0.37 (95% CI, 0.07-0.81); P = 0.02).

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Source: Corets, M. S., Corroenne, R., Johnson, B., et al. (2022). Effect of Preoperative Low-Normal Cervical Length on Perinatal Outcome After Laparotomy-Assisted Fetoscopic Spina Bifida Repair. Ultrasound Obstet Gynecol. 2023; 61(1): 74-80. Published: January, 2023. DOI: 10.1002/uog.26070.



The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression

The results demonstrate an increased resemblance in both autistic male and female individuals' neuroanatomy with male-characteristic patterns associated with typically sex-differential social cognitive features and related gene expression patterns.

source: Am J Psychiatry

Summary

[Posted 26/Jan/2023]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: The results demonstrate an increased resemblance in both autistic male and female individuals' neuroanatomy with male-characteristic patterns associated with typically sex-differential social cognitive features and related gene expression patterns. The findings hold promise for future research aimed at refining the quest for biological mechanisms underpinning the etiology of autism.

BACKGROUND: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression.

DETAILS: Using a novel deep learning framework trained to predict biological sex based on T1-weighted structural brain images, the authors compared sex prediction model performance across neurotypical and autistic males and females. Multiple large-scale data sets comprising T1-weighted MRI data were employed at four stages of the analysis pipeline: 1) pretraining, with the UK Biobank sample (>10,000 individuals); 2) transfer learning and validation, with the ABIDE data sets (1,412 individuals, 5-56 years of age); 3) test and discovery, with the EU-AIMS/AIMS-2-TRIALS LEAP data set (681 individuals, 6-30 years of age); and 4) specificity, with the NeuroIMAGE and ADHD200 data sets (887 individuals, 7-26 years of age). Across both ABIDE and LEAP, features positively predictive of neurotypical males were on average significantly more predictive of autistic males (ABIDE: Cohen's d=0.48; LEAP: Cohen's d=1.34). Features positively predictive of neurotypical females were on average significantly less predictive of autistic females (ABIDE: Cohen's d=1.25; LEAP: Cohen's d=1.29). These differences in sex prediction accuracy in autism were not observed in individuals with ADHD. In autistic females, the male-shifted neurophenotype was further associated with poorer social sensitivity and emotional face processing while also associated with gene expression patterns of midgestational cell types.

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Source: Floris, D. L., Peng, H., Warrier, V., et al. (2022). The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression. Am J Psychiatry. Published: January, 2023. DOI: 10.1176/appi.ajp.20220194.



Chronic Diseases and Comorbidities In Adults With and Without Intellectual Disabilities

This study identified a younger onset of chronic illness and a higher prevalence of multiple comorbidities among people with ID in general practice than those without ID. This underlines the complexity of people with ID and chronic diseases in general practice.

source: Family Practice

Summary

Comparative Cross-Sectional Study In Dutch General Practice

[Posted 2/Jan/2023]

AUDIENCE: Family Medicine, Neurology

KEY FINDINGS: This study identified a younger onset of chronic illness and a higher prevalence of multiple comorbidities among people with ID in general practice than those without ID. This underlines the complexity of people with ID and chronic diseases in general practice. As this study confirmed the earlier onset of chronic diseases and comorbidities, it is recommended to acknowledge these age differences when following chronic disease guidelines.

BACKGROUND: Chronic disease and comorbidity patterns in people with intellectual disabilities (ID) are more complex than in the general population. However, incomplete understanding of these differences limits care providers in addressing them. Aim of this study is to compare chronic disease and comorbidity patterns in chronically ill patients with and without ID in Dutch general practice.

DETAILS: In this population-based study, a multi-regional primary care database of 2018 was combined with national population data to improve identification of adults with ID. Prevalence was calculated using Poisson regression to estimate prevalence ratios and 95% confidence intervals for the highest-impact chronic diseases (ischemic heart disease (IHD), cerebrovascular disease (CVD), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD)) and comorbidities. Information from 18,114 people with ID and 1,093,995 people without ID was available. When considering age and sex, CVD (PR = 1.1), DM (PR = 1.6), and COPD (PR = 1.5) times more prevalent in people with than without ID. At younger age, people with ID more often had a chronic disease and multiple comorbidities. Males with ID most often had a chronic disease and multiple comorbidities. Comorbidities of circulatory nature were most common.

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Copyright © Oxford University Press. All rights reserved.

Source: van den Bemd, M., Schalk, B. W. M., Bischoff, E. W. M. A., et al. (2022). Chronic Diseases and Comorbidities In Adults With and Without Intellectual Disabilities: Comparative Cross-Sectional Study In Dutch General Practice. Family Practice. 2022; 39 (6): 1056-1062. Published: December, 2022. DOI: 10.1093/fampra/cmac042.



Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD

Contrary to the hypothesis, the study findings do not suggest that fMRI-NF of the rIFC is effective in improving clinical symptoms or cognition in boys with ADHD.

source: Am J Psychiatry

Summary

Double-Blind, Sham-Controlled Randomized Trial

[Posted 13/Dec/2022]

AUDIENCE: Psychiatry, Pediatric, Family Medicine

KEY FINDINGS: Contrary to the hypothesis, the study findings do not suggest that fMRI-NF of the rIFC is effective in improving clinical symptoms or cognition in boys with ADHD.

BACKGROUND: Functional MRI neurofeedback (fMRI-NF) could potentially be a novel, safe nonpharmacological treatment for attention deficit hyperactivity disorder (ADHD). A proof-of-concept randomized controlled trial of fMRI-NF of the right inferior frontal cortex (rIFC), compared to an active control condition, showed promising improvement of ADHD symptoms (albeit in both groups) and in brain function. However, comparison with a placebo condition in a larger trial is required to test efficacy.

DETAILS: This double-blind, sham-controlled randomized controlled trial tested the effectiveness and efficacy of fMRI-NF of the rIFC on symptoms and executive functions in 88 boys with ADHD (44 each in the active and sham arms). To investigate treatment-related changes, groups were compared at the posttreatment and 6-month follow-up assessments, controlling for baseline scores, age, and medication status. The primary outcome measure was posttreatment score on the ADHD Rating Scale (ADHD-RS). No significant group differences were found on the ADHD-RS. Both groups showed similar decreases in other clinical and cognitive measures, except for a significantly greater decrease in irritability and improvement in motor inhibition in sham relative to active fMRI-NF at the posttreatment assessment, covarying for baseline. There were no significant side effects or adverse events. The active relative to the sham fMRI-NF group showed enhanced activation in rIFC and other frontal and temporo-occipital-cerebellar self-regulation areas. However, there was no progressive rIFC upregulation, correlation with ADHD-RS scores, or transfer of learning.

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Source: Lam, S. L., Criaud, M., Lukito, S., et al. (2022). Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD. Am J Psychiatry. 2022; 179 (12): 947-958. Published: December, 2022. DOI: 10.1176/appi.ajp.21100999.



Cognitive-Driven Activities of Daily Living Impairment as a Predictor for Dementia in Parkinson Disease

The importance of differentiating between cognitive and motor aspects on ADL function in PD and monitoring cognitive ADL impairment in the prodromal stage of dementia is paramount.

source: AAN

Summary

A Longitudinal Cohort Study

[Posted 7/Dec/2022]

AUDIENCE: Neurology, Internal Medicine

KEY FINDINGS: The importance of differentiating between cognitive and motor aspects on ADL function in PD and monitoring cognitive ADL impairment in the prodromal stage of dementia is paramount. Patients with PD-MCI and cognitive IADL impairment may be a valuable target group for clinical trials aiming to slow down the development of dementia.

BACKGROUND: One-third of Parkinson disease (PD) patients with PD-mild cognitive impairment (PD-MCI) convert to dementia within a few years. Markers with a high prognostic value for dementia conversion are needed. Loss of everyday function primarily caused by cognitive dysfunction is the core criterion for the diagnosis of PD dementia, with an onset of more complex instrumental activities of daily living (IADL) dysfunction in the prodromal stage. This study evaluated the phenotype associated with cognitive IADL impairment and its predictive value for defining a high-risk group for PD dementia.

DETAILS: An observational longitudinal study using cognitive and clinical scores in addition to genetic and CSF biomarkers was conducted. The Functional Activities Questionnaire quotient (cut-off >=1), indicating more cognitive than motor-driven IADL impairment, defined cognitive IADL impairment status at baseline. Hazard ratios (HRs) were used to compare the impact of baseline classifications on dementia conversion. Of 268 patients with PD assessed at baseline, 108 (40.3%) had PD-MCI. After a period of 3.78 ± 0.84 years, 164 (61.2%) patients were reassessed. At follow-up, 93 (56.7%) patients had no cognitive impairment, 54 (32.9%) fulfilled PD-MCI criteria, and 17 (10.4%) had developed dementia. The HR of baseline cognitive IADL impairment (n = 37) for dementia conversion was descriptively higher than for PD-MCI, but highest in patients with both markers (HR = 12.01, 95% CI 4.47-32.22, p < 0.001). In the follow-up sample, nearly half of the patients (n = 10, 47.6%) with baseline classification of cognitive IADL impairment and PD-MCI converted to dementia. Baseline status of cognitive IADL impairment was associated with higher nonmotor burden, worse cognitive performance, and more severe IADL progression over the study period.

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Source: Becker, S., Bode, M., Brockmann, K., et al. (2022). Cognitive-Driven Activities of Daily Living Impairment as a Predictor for Dementia in Parkinson Disease: A Longitudinal Cohort Study. AAN. 2022; 99(23): e2548-e2560. Published: December 6, 2022. DOI: 10.1212/WNL.0000000000201201.



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