Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Predictors of functional outcome after symptomatic intracranial hemorrhage complicating intravenous thrombolysis: results from the SITS-ISTR.

BACKGROUND AND PURPOSE: Several risk factors of symptomatic intracerebral hemorrhage (SICH) following intravenous thrombolysis for acute ischaemic stroke have been established. However, potential predictors of good functional outcome post-SICH have been less studied. METHODS: Patient data registered in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Register (SITS-ISTR) from 2005 to 2021 were used. Acute ischaemic stroke patients who developed post intravenous thrombolysis SICH according to the SITS Monitoring Study definition were analyzed to identify predictors of functional outcomes. RESULTS: A total of 1679 patients with reported SICH were included, out of which only 2.8% achieved good functional outcome (modified Rankin Scale scores of 0-2), whilst 80.9% died at 3 months. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score and 24-h ΔNIHSS score were independently associated with a lower likelihood of achieving both good and excellent functional outcomes at 3 months. Baseline NIHSS and hematoma location (presence of both SICHs, defined as remote and local SICH concurrently; n = 478) were predictors of early mortality within 24 h. Independent predictors of 3-month mortality were age, baseline NIHSS, 24-h ΔNIHSS, admission serum glucose values and hematoma location (both SICHs). Age, baseline NIHSS score, 24-h ΔNIHSS, hyperlipidemia, prior stroke/transient ischaemic attack, antiplatelet treatment, diastolic blood pressure at admission, glucose values on admission and SICH location (both SICHs) were associated with reduced disability at 3 months (≥1-point reduction across all modified Rankin Scale scores). Patients with remote SICH (n = 219) and local SICH (n = 964) had comparable clinical outcomes, both before and after propensity score matching. CONCLUSIONS: Symptomatic intracerebral hemorrhage presents an alarmingly high prevalence of adverse clinical outcomes, with no difference in clinical outcomes between remote and local SICH.

Rescue aortic valvuloplasty for severe aortic stenosis is simple and effective in severely hemodynamically compromised patients presenting to centers without on-site heart surgery or TAVI facilities.

Management of high-risk patients with severe aortic stenosis (AS) is a challenging issue. The prognosis of patients with AS presenting with therapy-refractory pulmonary edema (RPE) or cardiogenic shock (CS) remains poor. The purpose of this study was to assess the 30-day mortality of rescue percutaneous balloon aortic valvuloplasty (PBAV) in AS patients presenting with RPE or CS in a community-based hospital without on-site heart surgery. From January 2016 to February 2019, we identified consecutively admitted patients with CS or RPE related to severe AS who underwent emergent PBAV. The primary end point was 30-day mortality. Secondary end points included procedural adverse events according to the Valve Academic Research Consortium (VARC)-2 criteria and predictive factors of the primary end point. We identified 51 patients with either CS (n = 22) or RPE (n = 29). All PBAV procedures were successful with a significant reduction in peak-to-peak gradient (median, [IQR] from 40 [27] mmHg to 15 [20] mmHg, p < 0.001). No procedural deaths occurred, while adverse events included stroke (4%), minor vascular complications (6%), minor (4%) and major bleedings (4%), and no life-threatening bleeding. Overall, 15 deaths (29%) were noted at 30 days after PBAV, while 53% of the surviving patients were successfully bridged to transcatheter aortic valve implantation (TAVI). 30-day mortality was significantly higher in the CS group compared to the RPE (n = 10 (45%) vs n = 5 (7%), p = 0.029), and was significantly associated with the presence of acute kidney injury (OR 9.09, 95% CI 2.13-38.77, p = 0.003) and elevated pulmonary artery systolic pressure (OR 1.06, 95% CI 1.0-1.12, p = 0.047). Rescue PBAV in patients with severe AS presenting with RPE or CS is a feasible and effective therapeutic option, even in a community-based hospital without on-site heart surgery. Rescue PBAV resulted in 30-day survival of more than 70%, with more than half of the surviving patients having been successfully bridged to TAVI.

CADASIL in Greece: Mutational spectrum and clinical characteristics based on a systematic review and pooled analysis of published cases.

BACKGROUND: Differences have been noted in the clinical presentation and mutational spectrum of CADASIL among various geographical areas. The aim of the present study was to investigate the mode of clinical presentation and genetic mutations reported in Greece. METHODS: After a systematic literature search, we performed a pooled analysis of all published CADASIL cases from Greece. RESULTS: We identified 14 studies that reported data from 14 families comprising 54 patients. Migraine with aura was reported in 39%, ischemic cerebrovascular diseases in 68%, behavioral-psychiatric symptoms in 47% and cognitive decline in 60% of the patients. The mean (±SD) age of onset for migraine with aura, ischemic cerebrovascular diseases, behavioral-psychiatric symptoms and cognitive decline was 26.2 ± 8.7, 49.3 ± 14.6, 47.9 ± 9.4 and 42.9 ± 10.3, respectively; the mean age at disease onset and death was 34.6 ± 12.1 and 60.2 ± 11.2 years. With respect to reported mutations, mutations in exon 4 were the most frequently reported (61.5% of all families), with the R169C mutation being the most common (30.8% of all families and 50% of exon 4 mutations), followed by R182C mutation (15.4% of all families and 25% of exon 4 mutations). CONCLUSIONS: The clinical presentation of CADASIL in Greece is in accordance with the phenotype encountered in Caucasian populations, but differs from the Asian phenotype, which is characterized by a lower prevalence of migraine and psychiatric symptoms. The genotype of Greek CADASIL pedigrees is similar to that of British pedigrees, exhibiting a high prevalence of exon 4 mutations, but differs from Italian and Asian populations, where mutations in exon 11 are frequently encountered.

Withholding or withdrawing life support in long-term neurointensive care patients: a single-centre, prospective, observational pilot study.

PURPOSE: Scarce evidence exists regarding end-of-life decision (EOLD) in neurocritically ill patients. We investigated the factors associated with EOLD making, including the group and individual characteristics of involved healthcare professionals, in a multiprofessional neurointensive care unit (NICU) setting. MATERIALS AND METHODS: A prospective, observational pilot study was conducted between 2013 and 2014 in a 10-bed NICU. Factors associated with EOLD in long-term neurocritically ill patients were evaluated using an anonymised survey based on a standardised questionnaire. RESULTS: 8 (25%) physicians and 24 (75%) nurses participated in the study by providing their 'treatment decisions' for 14 patients at several time points. EOLD was 'made' 44 (31%) times, while maintenance of life support 98 (69%) times. EOLD patterns were not significantly different between professional groups. The individual characteristics of the professionals (age, gender, religion, personal experience with death of family member and NICU experience) had no significant impact on decisions to forgo or maintain life-sustaining therapy. EOLD was patient-specific (intraclass correlation coefficient: 0.861), with the presence of acute life-threatening disease (OR (95% CI): 18.199 (1.721 to 192.405), p=0.038) and low expected patient quality of life (OR (95% CI): 9.276 (1.131 to 76.099), p=0.016) being significant and independent determinants for withholding or withdrawing life-sustaining treatment. CONCLUSIONS: Our findings suggest that EOLD in NICU relies mainly on patient prognosis and not on the characteristics of the healthcare professionals.

Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies.

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn.

Delayed recurrent enhancing white matter lesions complicating coiling of intracranial aneurysm.

BACKGROUND AND PURPOSE: In recent years, the use of coiling has gained increased popularity for the treatment of intracranial aneurysms, and stroke physicians are confronted with rare pathologies associated with this relatively new and evolving treatment method, such as embolization of pieces of the polymeric filaments from the coils and a subsequent inflammatory response. In particular, white matter enhancing lesions are a rare complication after aneurysm endovascular therapy (EVT), suggesting a foreign body reaction to shedding of hydrophilic coating from the endovascular devices into the blood stream. The description of such a case aims to raise the clinicians' awareness of the symptomatic delayed and recurring inflammatory changes that may occur after endovascular aneurysmal treatment with the use of coiling devices. CASE DESCRIPTION: A 64-year-old woman underwent coiling of a ruptured right posterior communicating artery aneurysm. She was asymptomatic after EVT. One year later, she presented with headache, acoustic hallucinations, paresthesias and left arm weakness. Brain magnetic resonance imaging (MRI) revealed multiple enhancing white matter lesions in the right hemisphere. She was treated with pulse intravenous methylprednisolone, followed by oral prednisolone; all clinical symptoms resolved and imaging findings improved substantially. Two years after tapering the steroids, follow-up symptoms recurred and repeat brain MRI revealed new enhancing white matter lesions. DISCUSSION AND CONCLUSIONS: There is an increasing number of similar reports of enhancing white matter lesions after coiling of intracranial aneurysms, with the incidence estimated to be between 0.5% and 2.3% in different cohort studies. Close monitoring for the appearance of new neurologic symptoms that could suggest delayed brain reactivity should be recommended.

Delirium REduction after administration of melatonin in acute ischemic stroke (DREAMS): A propensity score-matched analysis.

BACKGROUND AND PURPOSE: Poststroke delirium (PSD) comprises a common and severe complication after stroke. However, treatment options for PSD remain insufficient. We investigated whether prophylactic melatonin supplementation may be associated with reduced risk for PSD. METHODS: Consecutive patients admitted to the Tübingen University Stroke Unit, Tübingen, Germany, with acute ischemic stroke (AIS), who underwent standard care between August 2017 and December 2017, and patients who additionally received prophylactic melatonin (2 mg per day at night) within 24 h of symptom onset between August 2018 and December 2018 were included. Primary outcomes were (i) PSD prevalence in AIS patients and (ii) PSD risk and PSD-free survival in patients with cerebral infarction who underwent melatonin supplementation compared to propensity score-matched (PSM) controls. Secondary outcomes included time of PSD onset and PSD duration. RESULTS: Out of 465 (81.2%) patients with cerebral infarction and 108 (18.8%) transient ischemic attack (TIA) patients, 152 (26.5%) developed PSD (median time to onset [IQR]: 16 [8-32] h; duration 24 [8-40] h). Higher age, cerebral infarction rather than TIA, and higher National Institutes of Health Stroke Scale score and aphasia on admission were significant predictors of PSD. After PSM (164 melatonin-treated patients with cerebral infarction versus 164 matched controls), 42 (25.6%) melatonin-treated patients developed PSD versus 60 (36.6%) controls (odds ratio, 0.597; 95% confidence interval, 0.372-0.958; p = 0.032). PSD-free survival differed significantly between groups (p = 0.027), favoring melatonin-treated patients. In patients with PSD, no between-group differences in the time of PSD onset and PSD duration were noted. CONCLUSIONS: Patients prophylactically treated with melatonin within 24 h of AIS onset had lower risk for PSD than patients undergoing standard care. Prospective randomized trials are warranted to corroborate these findings.

Prevalence, clinical characteristics and outcomes of Guillain-Barré syndrome spectrum associated with COVID-19: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach. METHODS: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients. RESULTS: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I2  = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I2  = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I2  = 46%) and 42.8% (95% CI 32.8%-53%; I2  = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls. CONCLUSION: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.

The shaky ground truth of real-time phase estimation.

Instantaneous phase of brain oscillations in electroencephalography (EEG) is a measure of brain state that is relevant to neuronal processing and modulates evoked responses. However, determining phase at the time of a stimulus with standard signal processing methods is not possible due to the stimulus artifact masking the future part of the signal. Here, we quantify the degree to which signal-to-noise ratio and instantaneous amplitude of the signal affect the variance of phase estimation error and the precision with which "ground truth" phase is even defined, using both the variance of equivalent estimators and realistic simulated EEG data with known synthetic phase. Necessary experimental conditions are specified in which pre-stimulus phase estimation is meaningfully possible based on instantaneous amplitude and signal-to-noise ratio of the oscillation of interest. An open source toolbox is made available for causal (using pre-stimulus signal only) phase estimation along with a EEG dataset consisting of recordings from 140 participants and a best practices workflow for algorithm optimization and benchmarking. As an illustration, post-hoc sorting of open-loop transcranial magnetic stimulation (TMS) trials according to pre-stimulus sensorimotor µ-rhythm phase is performed to demonstrate modulation of corticospinal excitability, as indexed by the amplitude of motor evoked potentials.

Early Administration of Desmopressin and Platelet Transfusion for Reducing Hematoma Expansion in Patients With Acute Antiplatelet Therapy Associated Intracerebral Hemorrhage.

OBJECTIVES: To investigate the hemostatic efficacy of combined desmopressin (1-deamino-8-D-arginine vasopressin) and platelet transfusion in reducing hematoma expansion in acute, spontaneous intracerebral hemorrhage under antiplatelet treatment. DESIGN: Single-center, nonrandomized study, performed between 2006 and 2014. SETTING: Tertiary University Hospital of Tuebingen, Germany. PATIENTS: Adult patients with intracerebral hemorrhage under antiplatelet treatment and follow-up CT at 24 ± 12 hours were included. Exclusion criteria included other intracerebral hemorrhage causes, anticoagulation, coagulopathy, or immediate surgery after baseline-CT. INTERVENTIONS: Treatment with IV 1-deamino-8-D-arginine vasopressin (0.4 µg/kg) + platelet transfusion (2 U) within 60 minutes of intracerebral hemorrhage under antiplatelet treatment diagnosis on brain imaging. MEASUREMENTS AND MAIN RESULTS: Primary outcome was relative hematoma expansion from baseline to follow-up CT. Secondary outcomes included secondary intraventricular hemorrhage or hydrocephalus upon follow-up CT, thromboembolic events before discharge, and the 3-month functional outcome (assessed by modified Rankin Scale). One-hundred forty patients were included, 72 treated versus 68 controls. Times of symptom-onset-to-baseline-CT (hr) (median [interquartile range]: 3 [4] vs 5 [5]; p = 0.468) and follow-up CT (26 [18] vs 19 [12]; p = 0.352) were similar between groups. No between-group differences of total intracerebral hematoma expansion (%) (median [interquartile range]: 8.5 [12.4] vs 9.1 [16.5]; p = 0.825), intraparenchymal (10.7 [23.1] vs 9.2 [20.7]; p = 0.900), and intraventricular hematoma expansion (14.5 [63.2] vs 6.1 [40.4]; p = 0.304) were noted. Among patients with hematoma expansion greater than or equal to 33% compared with baseline, 16 (52%) received treatment versus 15 (48%) controls. The occurrence of hematoma expansion greater than or equal to 33% was similar between groups (p = 0.981). Rates of secondary intraventricular hemorrhage, hydrocephalus, and thromboembolic events were similar between groups. Treatment with 1-deamino-8-D-arginine vasopressin + platelet transfusion was not associated with the 3-month functional outcome (adjusted odds ratio, 1.570; 95% CI, 0.721-3.419; p = 0.309). CONCLUSIONS: In line with the randomized Platelet Transfusion Versus Standard Care After Acute Stroke Due to Spontaneous Cerebral Hemorrhage Associated With Antiplatelet Therapy trial, our results suggest no hemostatic efficacy of early platelet transfusion in intracerebral hemorrhage under antiplatelet treatment. Contrary to results of preclinical and clinical nonintracerebral hemorrhage studies, adjunct 1-deamino-8-D-arginine vasopressin showed no benefit in limiting hematoma expansion or improving functional outcome.

Point-of-care testing of coagulation in patients treated with edoxaban.

Edoxaban, alongside other direct oral anticoagulants (DOAC), is increasingly used for prevention of thromboembolism, including stroke. Despite DOAC therapy, however, annual stroke rate in patients with atrial fibrillation remains 1-2%. Rapid exclusion of relevant anticoagulation is necessary to guide thrombolysis or reversal therapy but, so far, no data exists on the effect of edoxaban on available point-of-care test systems (POCT). To complete our previous investigation on global coagulation-POCT for the detection of DOAC, we evaluated whether CoaguChek®-INR (CC-INR) is capable of safely ruling out edoxaban concentrations above the current treatment thresholds of 30/50 ng/mL in a blood sample. We studied patients receiving a first dose of edoxaban; excluding subjects receiving other anticoagulants. Six blood samples were collected from each patient: before drug intake, 0.5, 1, 2 and 8 h after intake, and at trough (24 h). CC-INR and mass spectrometry for edoxaban concentrations were performed for each time-point. One hundred and twenty blood samples from 20 patients contained 0-302 ng/mL of edoxaban. CC-INR ranged from 0.9 to 2.3. Pearson's correlation coefficient showed strong correlation between CC-INR and edoxaban concentrations (r = 0.73, p < 0.001). Edoxaban concentrations > 30 and > 50 ng/mL were ruled out by CC-INR ≤ 1.0 and ≤ 1.1, respectively, with high specificity (> 95%), and a sensitivity of 44% (95%-confidence interval: 30-59%) and 86% (74-93%), respectively. Our study represents the first evaluation of coagulation-POCT in edoxaban-treated patients. CC-POCT is suitable to safely exclude clinically relevant edoxaban concentrations prior to thrombolysis, or guide reversal therapy in stroke patients.

Phase Synchronicity of µ-Rhythm Determines Efficacy of Interhemispheric Communication Between Human Motor Cortices.

The theory of communication through coherence predicts that effective connectivity between nodes in a distributed oscillating neuronal network depends on their instantaneous excitability state and phase synchronicity (Fries, 2005). Here, we tested this prediction by using state-dependent millisecond-resolved real-time electroencephalography-triggered dual-coil transcranial magnetic stimulation (EEG-TMS) (Zrenner et al., 2018) to target the EEG-negative (high-excitability state) versus EEG-positive peak (low-excitability state) of the sensorimotor µ-rhythm in the left (conditioning) and right (test) motor cortex (M1) of 16 healthy human subjects (9 female, 7 male). Effective connectivity was tested by short-interval interhemispheric inhibition (SIHI); that is, the inhibitory effect of the conditioning TMS pulse given 10-12 ms before the test pulse on the test motor-evoked potential. We compared the four possible combinations of excitability states (negative peak, positive peak) and phase relations (in-phase, out-of-phase) of the µ-rhythm in the conditioning and test M1 and a random phase condition. Strongest SIHI was found when the two M1 were in phase for the high-excitability state (negative peak of the µ-rhythm), whereas the weakest SIHI occurred when they were out of phase and the conditioning M1 was in the low-excitability state (positive peak). Phase synchronicity contributed significantly to SIHI variation, with stronger SIHI in the in-phase than out-of-phase conditions. These findings are in exact accord with the predictions of the theory of communication through coherence. They open a translational route for highly effective modification of brain connections by repetitive stimulation at instants in time when nodes in the network are phase synchronized and excitable.SIGNIFICANCE STATEMENT The theory of communication through coherence predicts that effective connectivity between nodes in distributed oscillating brain networks depends on their instantaneous excitability and phase relation. We tested this hypothesis in healthy human subjects by real-time analysis of brain states by electroencephalography in combination with transcranial magnetic stimulation of left and right motor cortex. We found that short-interval interhemispheric inhibition, a marker of interhemispheric effective connectivity, was maximally expressed when the two motor cortices were in phase for a high-excitability state (the trough of the sensorimotor µ-rhythm). We conclude that findings are consistent with the theory of communication through coherence. They open a translational route to highly effectively modify brain connections by repetitive stimulation at instants in time of phase-synchronized high-excitability states.

Neuroaesthetical Changes in Sculpture: The Case of Yannoulis Halepas (1851-1938).

The theoretical conceptualization of artistic ingenuity and creativity, as reflections of the highest-level cognitive functions in the human brain, has recently evolved from a purely philosophical pursuit to a compelling neuroscientific undertaking. Changes in artistic style have been extensively studied in association with brain dysfunction in the presence of neurological and psychiatric diseases in famous artists. This paper presents the case of Yannoulis Halepas (1851-1938), who is widely regarded as the most influential sculptor of modern Greek art. At the age of 27, already at the peak of his fame, Halepas abruptly abandoned the sculpture world after developing schizoaffective disorder, only to resurge onto the art scene after an almost 40-year-long hiatus with a fundamentally reformed artistic style. Two distinct periods have preoccupied art critics: Halepas's early premorbid years (1870-1878), which were imbued with the principles of neoclassicism, and the later postmorbid years (1918-1938), which mark the artist's transcendence to expressionism and contemporary art. From a neuroaesthetical perspective, the extensive and multifaceted oeuvre that Halepas produced in his lifetime allows a close study of his artistic development throughout and beyond mental disease. In addition, his lifework is a unique account in the history of art of the struggle of artistic genius with the limits of the rational mind and its conscious reality.

Angelos Katakouzenos (1902-1982): A Lifework of Neurology and Art.

Angelos Katakouzenos, a Greek neurologist and prolific medical writer at the beginning of the 20th century, belonged to a group of artists and scholars that formed the "generation of the 30s," a cultural movement that emerged after World War I and introduced modernism in Greek art and literature. Born in 1902, Katakouzenos studied medicine in France at the Universities of Montpellier and Paris, where he trained in neurology and -psychiatry under Georges Guillain, Henri Claude, Jean-Athanase Sicard, Pierre Marie, Clovis Vincent and Théophile -Alajouanine. In Paris, he attended to Freud's patients, collaborating with the psychoanalyst Marie Bonaparte, while he was introduced to the contemporary avant-garde movements of this time, developing long-lasting friendships with artists and intellectuals, including Marc Chagall and Tériade. Although Professor of Neurology and Psychiatry at the University of -Paris, Commandeur of the Légion d'honneur and founder of the first neuropsychiatric clinics in Greece, Katakouzenos lived far from the limelight. Despite his numerous publications, his scientific work remained largely unacknowledged. Yet, as a -psychoanalyst he gained international fame and treated patients including William Faulkner who later would write, "To the wise scientist, the in-depth judge of the human soul, my friend Dr. Katakouzenos, who has helped me like no one else to redeem myself from the tortuous questions that troubled me for years - from the depths of my heart, many, very many thanks". In this paper, the rediscovery of Katakouzenos's remarkable work in the field of neuroscience aims to tell the story of a great physician whose lifework in bridging art and science may, in retrospect, reinstate him as one of the most captivating neurologists of the 20th century.

Tensor and non-tensor tractography for the assessment of the corticospinal tract of children with motor disorders: a comparative study.

INTRODUCTION: Non-invasive measures of corticospinal tract (CST) integrity may help to guide clinical interventions, particularly in children and young people (CAYP) with motor disorders. We compared diffusion tensor imaging (DTI) metrics extracted from the CST generated by tensor and non-tensor based tractography algorithms. METHODS: For a group of 25 CAYP undergoing clinical evaluation, the CST was reconstructed using (1) deterministic tensor-based tractography algorithm, (2) probabilistic tensor-based, and (3) constrained spherical deconvolution (CSD)-derived tractography algorithms. RESULTS: Choice of tractography algorithm significantly altered the results of tracking. Larger tracts were consistently defined with CSD, with differences in FA but not MD values for tracts to the pre- or post-central gyrus. Differences between deterministic and probabilistic tensor-based algorithms were minimal. Non-tensor reconstructed tracts appeared to be more anatomically representative. Examining metrics along the tract, difference in FA values appeared to be greatest in voxels with predominantly single-fibre orientations. Less pronounced differences were seen outwith of these regions. CONCLUSION: With an increasing interest in the applications of tractography analysis at all stages of movement disorder surgery, it is important that clinicians remain alert to the consequences of choice of tractography algorithm on subsequently generated tracts, including differences in volumes, anatomical reconstruction, and DTI metrics, the latter of which will have global as well as more regional effects. Tract-wide analysis of DTI based metrics is of limited utility, and a more segmental approach to analysis may be appropriate, particularly if disruption to a focal region of a white matter pathway is anticipated.

Association of gut dysbiosis with first­episode psychosis (Review).

The gut­microbiota­brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut­microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early­life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first­episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP.