Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke
The findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.
KEY FINDINGS: These findings provide new insights into the subcortical anatomy of apraxia after LH stroke, suggesting a specific contribution of caudate nucleus lesions to apraxic deficits.
BACKGROUND: Apraxia is commonly attributed to left hemisphere (LH) lesions of the cortical fronto-temporo-parietal praxis networks or white matter lesions causing disconnections between cortical nodes. By contrast, the contribution of lesions to the subcortical gray matter, that is, basal ganglia or thalamus, to apraxic deficits remains controversial. Here, we investigate whether damage to these subcortical gray matter structures (i.e., caudate nucleus, putamen, globus pallidus, and thalamus) or the adjacent white matter tracts was associated with apraxic deficits.
DETAILS: Identified patients with distinct subcortical lesions with and without apraxia from a large retrospective sample of subacute LH ischemic stroke patients (n = 194). To test which subcortical structures (caudate nucleus, putamen, globus pallidus, thalamus, and adjacent white matter tracts), when lesioned, contributed to apraxic deficits, we statistically compared the proportion of lesioned voxels within subcortical gray and white matter structures between the apraxic and nonapraxic patients. Of the 194 stroke patients screened, 39 (median age = 65 years, range 30-82 years; median time poststroke at the apraxia assessment = 7 days, range 1-44 days) had lesions confined to subcortical regions (gray and white matter). Eleven patients showed apraxic deficits when imitating gestures or pantomiming object use. Region-wise statistical lesion comparison (controlled for lesion size) revealed a more significant proportion of damage ('lesion load') in the caudate nucleus in apraxic stroke patients (mean difference = 6.9%, 95% CI 0.4-13.3, p = 0.038, ηp2 = 0.11). By contrast, apraxic patients had lower lesion load in the globus pallidus (mean difference = 9.9%, 95% CI 0.1-19.8, p = 0.048, ηp2 = 0.10), whereas the lesion load in other subcortical structures (putamen, thalamus, and adjacent white matter tracts) did not differ significantly between the apraxic and nonapraxic patients.
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Source: Schmidt, C. C., Achilles, E. I. S., Bolte, K., et al. (2023). Association of Circumscribed Subcortical Gray and White Matter Lesions With Apraxic Deficits in Patients With Left Hemisphere Stroke. American Academy of Neurology. 2023; 101 (11): Published: September 12, 2023. DOI: 10.1212/WNL.0000000000207598.
A Pilot Randomized Control Trial of Holding During Hypothermia and Effects on Maternal and Infant Salivary Cortisol Levels
Authors demonstrate positive effects of holding during TH as evidenced by lower salivary cortisol for both mother and infant and decreased heart rate, respiratory rate, and blood pressure for the infant on day-2. Further research is needed to replicate these results, to understand the lack of infant response on day-3 and to assess correlation with cumulative morphine exposure.
KEY FINDINGS: Authors demonstrate positive effects of holding during TH as evidenced by lower salivary cortisol for both mother and infant and decreased heart rate, respiratory rate, and blood pressure for the infant on day-2. Further research is needed to replicate these results, to understand the lack of infant response on day-3 and to assess correlation with cumulative morphine exposure.
BACKGROUND: The lack of physical contact during therapeutic hypothermia (TH) is challenging for parents of newborns with hypoxic ischemic encephalopathy. Holding is often avoided due to concerns for effects on infant temperature and for dislodging equipment. Authors assessed the effect of holding during TH on maternal and infant salivary cortisol levels and on infant vital signs.
DETAILS: Prospective crossover study with infants randomized to a 30-minute session of holding on day-2 versus day-3 of TH. "No-holding" occurred on the alternate day at the same time. Pre- and post-holding salivary cortisol levels were compared between holding and no-holding conditions. Vital signs were collected at 2-minute intervals. Data was analyzed using mixed-effects models. Thirty-four mothers and infants were recruited. The median gestational age was 39 weeks, 16 (94%) had moderate encephalopathy and all were on morphine during TH. Salivary cortisol levels decreased after holding for infants on day-2 (P = .02) and mothers on day-2 and day-3 (P = .01). Infants held on day-2, but not on day-3, had lower heart rates, respiratory rates, and mean arterial pressures. Temperature and oxygen saturations were stable on both days.
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Source: Fox, L., Cutler, A., Kaneko-Tarui, T., et al. (20245). A Pilot Randomized Control Trial of Holding During Hypothermia and Effects on Maternal and Infant Salivary Cortisol Levels. Advances in Neonatal Care. 2025; 25(2): 173-180. Published: April, 2025. DOI: 10.1097/ANC.0000000000001239.
Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia
In this phase 3, double-blind, randomized, placebo-controlled trial in 256 people with schizophrenia, xanomeline-trospium was associated with a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale total score compared with placebo. Xanomeline-trospium was generally well tolerated; the most common adverse events were primarily gastrointestinal effects, which were mild or moderate in intensity and generally transient in nature.
KEY FINDINGS: Xanomeline-trospium was efficacious and well tolerated in people with schizophrenia experiencing acute psychosis. These findings, together with the previously reported and consistent results from the EMERGENT-1 and EMERGENT-2 trials, support the potential of xanomeline-trospium to be the first in a putative new class of antipsychotic medications without D2 dopamine receptor blocking activity.
BACKGROUND: A significant need exists for new antipsychotic medications with different mechanisms of action, greater efficacy, and better tolerability than existing agents. Xanomeline is a dual M1/M4 preferring muscarinic receptor agonist with no direct D2 dopamine receptor blocking activity. KarXT combines xanomeline with the peripheral muscarinic receptor antagonist trospium chloride with the goal of reducing adverse events due to xanomeline-related peripheral muscarinic receptor activation. In prior trials, xanomeline-trospium chloride was effective in reducing symptoms of psychosis and generally well tolerated in people with schizophrenia. Purpose of this study is to evaluate the efficacy and safety of xanomeline-trospium vs placebo in adults with schizophrenia.
DETAILS: EMERGENT-3 (NCT04738123) was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 5-week trial of xanomeline-trospium in people with schizophrenia experiencing acute psychosis, conducted between April 1, 2021, and December 7, 2022, at 30 inpatient sites in the US and Ukraine. Data were analyzed from February to June 2023. Participants were randomized 1:1 to receive xanomeline-trospium chloride (maximum dose xanomeline 125 mg/trospium 30 mg) or placebo for 5 weeks. The prespecified primary end point was change from baseline to week 5 in Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measures were change from baseline to week 5 in PANSS positive subscale score, PANSS negative subscale score, PANSS Marder negative factor score, Clinical Global Impression-Severity score, and proportion of participants with at least a 30% reduction in PANSS total score. Safety and tolerability were also evaluated. A total of 256 participants (mean [SD] age, 43.1 [11.8] years; 191 men [74.6%]; 156 of 256 participants [60.9%] were Black or African American, 98 [38.3%] were White, and 1 [0.4%] was Asian) were randomized (125 in xanomeline-trospium group and 131 in placebo group). At week 5, xanomeline-trospium significantly reduced PANSS total score compared with placebo (xanomeline-trospium , -20.6; placebo, -12.2; least squares mean difference, -8.4; 95% CI, -12.4 to -4.3; P < .001; Cohen d effect size, 0.60). Discontinuation rates due to treatment-emergent adverse events (TEAEs) were similar between the xanomeline-trospium (8 participants [6.4%]) and placebo (7 participants [5.5%]) groups. The most common TEAEs in the xanomeline-trospium vs placebo group were nausea (24 participants [19.2%] vs 2 participants [1.6%]), dyspepsia (20 participants [16.0%] vs 2 participants [1.6%]), vomiting (20 participants [16.0%] vs 1 participant [0.8%]), and constipation (16 participants [12.8%] vs 5 participants [3.9%]). Measures of extrapyramidal symptoms, weight gain, and somnolence were similar between treatment groups.
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Source: Kaul, I., Sawchak, S., Walling, D. P., et al. (2024). Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. 2024; 81(8): 749-756. Published: August, 2024. DOI: 10.1001/jamapsychiatry.2024.0785.
Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke
While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.
KEY FINDINGS: While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.
BACKGROUND: Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%.
DETAILS: Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high.
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Source: Bailey, A. M., Baum, R., Nestor, M .,et al. (2024). Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series. Advanced Emergency Nursing Journal. 2024; 46(2): 101-107. Published: April/June, 2024. DOI: 10.1097/TME.0000000000000512.
Worldwide Incidence of Suicides in Prison
Prison services worldwide, and particularly in Europe, should prioritise suicide prevention. Assessment and management of suicide risk in female individuals living in prison need particular attention due to excess mortality relative to community-based populations.
Summary
A Systematic Review With Meta-Regression Analyses
[Posted 3/Jun/2024]
AUDIENCE: Psychiatry, Ob/gyn
KEY FINDINGS: Prison services worldwide, and particularly in Europe, should prioritise suicide prevention. Assessment and management of suicide risk in female individuals living in prison need particular attention due to excess mortality relative to community-based populations. Interpretation of synthesised data needs to be done with caution due to high heterogeneity between jurisdictions.
BACKGROUND: Suicide is a leading cause of death during imprisonment. This systematic review aimed to synthesise available evidence of prison suicide incidence worldwide.
DETAILS: Authors systematically searched the scientific literature, data repositories, and prison system reports, supplemented by correspondence with prison administrations. Authors included reports on people living in prison but excluded studies in preselected groups (by age or offence type). Absolute numbers and incidence rates of suicide mortality per 100,000 person-years by sex and country were extracted from 2000 to 2021. IQRs were used to describe the suicide incidence in different world regions. Incidence rate ratios comparing suicides of people living in prison with age-standardised general populations were calculated. Authors conducted meta-regression analyses on national-level and prison-level factors to examine heterogeneity. Authors included three scientific studies, 124 official reports, and 11 datasets from email correspondence. Between 2000 and 2021, there were 29,711 reported suicides during 91.2 million person-years of imprisonment in 82 jurisdictions worldwide (sex-specific data available for 13,289 individuals: 12,544 [94.4%] male and 745 [5.6%] female individuals). There were large variations between countries, with most studies reporting suicide rates in the range of 24-89 per 100,000 person-years in both sexes (22-86 in male individuals and 25-107 in female individuals). In meta-regression analyses, Europe (vs other regions), high-income countries (vs low-income and middle-income countries), and countries with lower incarceration rates (vs those with higher incarceration rates) had higher suicide rates. Incidence rate ratios between people who are incarcerated and age-standardised general populations in the same jurisdictions were typically in the range of 1.9-6.0 in male and 10.4-32.4 in female individuals.
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Source: Mundt, A. P., Cifuentes-Gramajo, P. A., Baranyi, G. et al. (2024). Worldwide Incidence of Suicides in Prison: A Systematic Review With Meta-Regression Analyses. The Lancet. 2024; Published: May 29, 2024. DOI: 10.1016/S2215-0366(24)00134-2.
GPi-DBS-Induced Brain Metabolic Activation in Cervical Dystonia
GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.
KEY FINDINGS: GPi-DBS increases metabolic activity at the stimulation site and sensorimotor network. The clinical benefit and adverse effects are mediated by modulation of specific networks.
BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a highly efficacious treatment for cervical dystonia, but its mechanism of action is not fully understood. Here, we investigate the brain metabolic effects of GPi-DBS in cervical dystonia.
DETAILS: Eleven patients with GPi-DBS underwent brain 18F-fluorodeoxyglucose positron emission tomography imaging during stimulation on and off. Changes in regional brain glucose metabolism were investigated at the active contact location and across the whole brain. Changes in motor symptom severity were quantified using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), executive function using trail making test (TMT) and parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS). The mean (SD) best therapeutic response to DBS during the treatment was 81 (22)%. The TWSTRS score was 3.2 (3.9) points lower DBS on compared with off (p=0.02). At the stimulation site, stimulation was associated with increased metabolism, which correlated with DBS stimulation amplitude (r=0.70, p=0.03) but not with changes in motor symptom severity (p>0.9). In the whole brain analysis, stimulation increased metabolism in the GPi, subthalamic nucleus, putamen, primary sensorimotor cortex (PFDR0.05). Acute improvement in TWSTRS correlated with metabolic activation in the sensorimotor cortex and overall treatment response in the supplementary motor area. Worsening of TMT-B score was associated with activation of the anterior cingulate cortex and parkinsonism with activation in the putamen.
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Source: Honkanen E. A., Rönkä J., Pekkonen E., et al. (2024). GPi-DBS-Induced Brain Metabolic Activation in Cervical Dystonia. Journal of Neurology, Neurosurgery & Psychiatry. 2024; 95(4): 300-308. Published: April, 2024. DOI: 10.1136/jnnp-2023-331668.
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