Institute of Psychiatry and Neurology

Introduction: The spot sign identified on CT angiography (CTA), is a well-established predictor of hematoma expansion (HE), but its role in FXai-related intracerebral hemorrhage (ICH) remains poorly explored. We investigated the association between spot sign and HE in patients with acute FXai-associated ICH and to assess whether its presence modified the treatment effect of andexanet alfa. Methods: Participants with a qualifying ICH on baseline brain imaging and available CTA at baseline were included in this post-hoc analysis of the ANNEXa-I trial. Imaging analyses assessed the presence of spot sign and its features (e.g., number, maximum diameter, maximum density, co-localization with hypodensity). HE was defined as a hematoma volume increase of ≥12.5 mL or ≥35% between baseline and 12 hours after randomization. The association between spot sign presence and its characteristics with HE was assessed with logistic regression analysis adjusted for time from symptom onset to scan, baseline hematoma volume, and diastolic blood pressure. The treatment effect modification of andexanet on HE by these imaging variables was assessed with a multivariable regression analysis. Results: Of the 530 patients in the intention-to-treat population, 156 had CTA performed and were included in this study (66 [42.3%] female, mean [ + SD] age 78.5 [±7.8]) ( Table 1 ). HE was observed in 55 (35.7%) patients and 31 (20.1%) patients had a spot sign. Spot sign presence (adjusted odds ratio [aOR] 4.24 [95% CI=1.55-11.56]), as well as some of its features, such as diameter >5 mm (aOR 5.40 [95% CI=1.39-20.97]), central location (aOR 7.76 [95%CI=1.63-37.03]), and co-localization with a hypodensity (aOR 6.56, [95%CI=1.46-29.50]) were associated with HE following multivariable adjustment ( Table 2 ). HE occurred in 36 (29.3%) patients with no spot sign (andexanet 20% vs. usual care 38.1%; NNT with andexanet to prevent HE: 5.6) and in 19 (61.3%) with a spot sign (andexanet 45% vs. usual care 90.9%; NNT with andexanet to prevent HE: 2.2). No significant heterogeneity in the proportional reduction of HE with andexanet was observed based on spot sign presence (p-interaction=0.150) or its characteristics ( Figure 1 ). Conclusions: The presence of the spot sign and its features were significantly associated with HE in FXai-associated ICH. The treatment effect of andexanet was still consistent regardless of the presence of the spot sign and its features

In this article, we present genetic studies of apolipoproteins associated with Alzheimer’s disease in the frontal cortex after ischemia and discuss their involvement in the development of neurodegeneration. Gene expression was assessed using an RT-PCR protocol at 2, 7, and 30 days and at 6, 12, 18, and 24 months after an episode of 10 min total cerebral ischemia. ApoA1 expression (encoding apolipoprotein A1) in the ischemic frontal cortex was lower than control values after 2 days, 6 and 12 months, while its overexpression was observed after 7 and 30 days and 18 and 24 months. In the case of ApoE (encoding apolipoprotein E) expression, it was lower than control values after 2 and 30 days and after 6 months; in the remaining periods after ischemia, the expression was above control values. A similar expression pattern after ischemia was revealed for ApoJ (encoding apolipoprotein J). The data indicate that the observed changes in gene expression may reflect the activation and inhibition of various pathological processes involved in the development of post-ischemia neurodegeneration. Thus, overexpression of ApoA1 may be associated with the induction of neuroprotective mechanisms, whereas increased expression of ApoE may have harmful effects. Regarding the overexpression of ApoJ, the data indicate a dual behavior: in the early stages after ischemia, it has a protective effect, whereas in the later stages, it participates in the progression of neurodegenerative processes.

PurposeNeuroimaging and biological predictors of response to electroconvulsive therapy (ECT) are still being sought, so as to enable a full understanding of its therapeutic effects. The present study aims to determine the role of functional near-infrared spectroscopy (fNIRS) as a potential predictor of response to treatment with and efficacy of ECT.ViewsEach of the currently used neuroimaging methods has its limitations; however, the advantages of fNIRS provide a starting point for the widespread use of this method in the assessment of ECT. Studies using fNIRS for measurement have shown that prior to undergoing ECT depressed patients have a bilaterally lower frontal oxyhaemoglobin response to cognitive tasks compared to healthy subjects. After ECT, there is a change in oxyhaemoglobin (oxy-Hb) values compared to pre-treatment ones. However, the results regarding changes in oxy-Hb values obtained by different groups of investigators were not consistent.ConclusionsHigher oxy-Hb values are achieved in healthy subjects than in patients. Apart from that, oxy-Hb values in patients are altered after ECT. For this reason the use of fNIRS can be an objective assessment of its therapeutic effect on patients. However, for fNIRS to become a biomarker for ECT treatment, studies need to be conducted on a larger patient population, considering the time since the last ECT and various disease entities.

Item Response Theory (IRT) describes a set of statistical models describing how individual items in a test or questionnaire relate to the underlying characteristic or trait that the test claims to measure. Until now IRT models have not been applied to the Positive and Negative Syndrome Scale (PANSS) in forensic and general psychiatric samples to establish its psychometric properties and explore the link between psychotic symptom severity and violent behavior in schizophrenia. This study investigated patients with schizophrenia spectrum disorders and a history of violence from forensic institutions and non-violent patients from general psychiatric settings in five European countries. A total of 398 participants were assessed using the PANSS. IRT analysis revealed a poor model fit for the Partial Credit Model (PCM) with considerably disordered thresholds for most items. Differential item functioning (DIF) revealed significant differences between the two groups, notably for items hypothetically linked to violence risk, such as delusions and hostility. These findings reveal potential limitations when trying to compare PANSS scores across these two clinical populations.

Pathogenic GRN variants that reduce progranulin (PGRN) levels cause frontotemporal dementia (FTD). To facilitate model development, we generated induced pluripotent stem cells (iPSCs) from dermal fibroblasts of two family members carrying the GRN c.1009C>T (p.Q337X) pathogenic variant—one symptomatic and one asymptomatic—as well as a non-carrier first-degree relative serving as a genetically matched control. The obtained iPSC lines were validated for pluripotency markers (Nanog, Sox2, Oct4, and TRA1-1-81), genomic integrity, and differentiation potential. The obtained iPSC lines were subsequently directed toward neuroepithelial stem (NES) cells. NES identity was confirmed by the expression of lineage-specific markers, including Nestin and Sox2 (assessed by immunocytochemistry), as well as SOX1, PLAGL1, and MKI67 (evaluated by real-time PCR). Furthermore, GRN mRNA levels were significantly reduced in iPSC and NES lines derived from mutation carriers compared to control cells. The established iPSC and NES cell lines represent a platform for modeling progranulin-deficient FTD. The symptomatic and asymptomatic carrier-derived lines obtained from the same family offer a unique opportunity to study disease progression across clinical phases. The control line, derived from a related (first-degree) non-carrier, minimizes genetic background variability. Their utility of the established cell lines extends to therapeutic drug screening and further differentiation into neuronal, non-neuronal, and organoid models.

Background and Clinical Significance: Wilson’s disease (WD) is an inherited, multisystem disorder of copper metabolism, resulting in pathological copper accumulation in various tissues (predominantly the liver and brain) and leading to secondary organ damage and corresponding clinical manifestations. Sleep disorders are frequent in neurodegenerative disorders, but remain underdiagnosed and poorly characterized in WD. Case presentation: We describe the case of a 51-year-old patient with WD presenting predominantly with neurological symptoms, who underwent routine video-polysomnography (v-PSG). The examination revealed shortened sleep latency, reduced rapid eye movement (REM) sleep latency, and sleep fragmentation—features of sleep architecture frequently observed in narcolepsy. These abnormalities worsened at follow-up despite the introduction of anti-copper treatment and concomitant neurological improvement. However, the patient did not report clinical symptoms of narcolepsy, and none were confirmed by the evaluating sleep specialist. Conclusions: This case highlights that sleep disorders (SDs) are common in patients with WD. Such patients may experience a wide range of SDs, and anti-copper treatment may improve sleep quality in addition to alleviating neurological symptoms. Narcolepsy is a rare but possible manifestation of SDs in WD. Therefore, whenever symptoms suggestive of sleep disturbances occur, WD patients should be referred to a sleep specialist, as accurate diagnosis and targeted treatment may profoundly improve quality of life, daily functioning, and long-term disease management.

Background/Objectives: Electroconvulsive therapy (ECT) is used for treatment-resistant depression (TRD). Despite high effectiveness, its most prevalent side effect is memory loss, particularly autobiographical memory deficits. Some patients and physicians might associate post-ECT improvement in depressive symptoms with a higher risk of autobiographical amnesia or even consider this side effect ECT’s mechanism of action. Here, we aimed to study the association between improvement in depressive symptoms and the severity of autobiographical amnesia, as well as identify factors associated with the degree of memory loss. Methods: In this prospective naturalistic observational pilot study, we included 20 patients who underwent ECT for TRD. Attending psychiatrists decided on the electrode placement. Electrical dosage was based on the seizure-titration procedure. Depressive symptoms (Hamilton Depression Scale-21) and autobiographical memory (AMI-SF) were assessed before and after the full course of ECT. The correlation between symptomatic improvements and severity of memory loss was studied using Spearman’s correlation. Demographic and clinical baseline data were examined to look for associations with the decline in autobiographical memory. Results: Symptomatic improvement was not correlated with autobiographical memory loss (r = −0.14, p = 0.58) or any of its domains. Suicidal ideation at baseline was associated with a stronger decline in autobiographical memory (r = −0.53, p = 0.016). Patients treated with bilateral electrode placement had worse amnesia than those treated with right unilateral treatment, though the difference was not significant (MD = −17.4 vs. −13.1, p = 0.2). Conclusions: ECT improved depressive symptoms irrespective of autobiographical amnesia severity. Patients with suicidal ideation at baseline might experience worse post-ECT amnesia than those without.