Impact of dementia status on intravenous thrombolysis and endovascular treatment for acute ischemic stroke: Retrospective study.

INTRODUCTION: Individuals with dementia are underrepresented in interventional studies for acute ischemic stroke (AIS). This research gap creates a bias against their treatment in clinical practice. Our goal was to compare the safety and efficacy of intravenous-thrombolysis (t-PA) and endovascular treatment (EVT) in individuals with or without pre-AIS dementia. METHOD: A retrospective study of AIS patients receiving t-PA or EVT between 2019 and 2022. Patients were classified as dementia on a case-by-case review of baseline assessment. Additional variables included demographic, vascular risk factors, AIS severity and treatment. Outcomes of interest were intracerebral hemorrhage, mortality in 90-days, and the difference in modified rankin scale (mRS) before AIS and in 90-days follow-up. Outcomes were compared across non-matched groups and following propensity-score matching. RESULTS: Altogether, 628 patients were included, of which 68 had pre-AIS dementia. Compared to non-dementia group, dementia group were older, had a higher rate of vascular risk factors, higher pre-stroke mRS and higher baseline NIHSS. Individuals with dementia had higher rates of mortality (25% vs.11%,p < 0.01) on non-matched comparison. All cohort and restricted t-PA EVT matched analysis showed no difference in any outcome. Regression analysis confirmed that AIS severity at presentation and its treatment, not dementia, were the chief contributors to patients' outcomes. DISCUSSION: Our results indicate that pre-AIS dementia does not impact the efficacy or safety of EVT or t-PA for AIS. We thus call for more inclusive research on stroke therapy with regards to baseline cognitive status. Such studies are urgently required to inform stroke guidelines and enhance care.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A phase 2 study of ibrutinib maintenance following first-line high-dose methotrexate-based chemotherapy for elderly patients with primary central nervous system lymphoma.

BACKGROUND: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression-free survival (PFS) of 6-16 months. Ibrutinib penetrates the blood-brain barrier and has shown activity in PCNSL. METHODS: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2-year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60-85 years old who responded to first-line high-dose methotrexate (HDMTX)-based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. RESULTS: Twenty patients were enrolled, with a median age of 72 years (range, 61-80). Median time on ibrutinib maintenance was 12.5 (range, 2-46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1- and 2-year PFS are 90% and 72.6%, respectively, and the 2-year OS is 89%. CONCLUSIONS: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly.

A new perspective on the role of the frontoparietal regions in Stroop-like conflicts.

Humans are goal-directed; however, goal-unrelated information still affects us, but how? The Stroop task is often used to answer this question, relying on conflict (incongruency) between attributes, one targeted by the task and another irrelevant to the task. The frontal regions of the brain are known to play a crucial role in processing such conflict, as they show increased activity when we encounter incongruent stimuli. Notably, the Stroop stimuli also consist of conceptual dimensions, such as semantic or emotional content, that are independent of the attributes that define the conflict. Since the non-targeted attribute usually refers to the same conceptual dimension as the targeted-attribute, it is relevant to the task at hand. For example, when naming the emotion of an emotional face superimposed by an emotional word, both the targeted-attribute and the non-targeted attribute refer to the conceptual dimension "emotion". We designed an fMRI paradigm to investigate how conflicts between different conceptual dimensions impact us. Even though the conflict was task-irrelevant, incongruent stimuli resulted in longer reaction times, indicating a behavioral congruency effect. When examining the neural mechanisms that underlie this effect, we found that the frontal regions exhibited repetition suppression, while the bilateral intraparietal sulcus (IPS) showed a congruency effect linked to the behavioral effect. Taken together, these findings suggest that individuals are unable to completely ignore task-irrelevant information, and that the IPS plays a crucial role in processing such information.

EEG p-adic quantum potential accurately identifies depression, schizophrenia and cognitive decline.

No diagnostic or predictive instruments to help with early diagnosis and timely therapeutic intervention are available as yet for most neuro-psychiatric disorders. A quantum potential mean and variability score (qpmvs), to identify neuropsychiatric and neurocognitive disorders with high accuracy, based on routine EEG recordings, was developed. Information processing in the brain is assumed to involve integration of neuronal activity in various areas of the brain. Thus, the presumed quantum-like structure allows quantification of connectivity as a function of space and time (locality) as well as of instantaneous quantum-like effects in information space (non-locality). EEG signals reflect the holistic (nonseparable) function of the brain, including the highly ordered hierarchy of the brain, expressed by the quantum potential according to Bohmian mechanics, combined with dendrogram representation of data and p-adic numbers. Participants consisted of 230 participants including 28 with major depression, 42 with schizophrenia, 65 with cognitive impairment, and 95 controls. Routine EEG recordings were used for the calculation of qpmvs based on ultrametric analyses, closely coupled with p-adic numbers and quantum theory. Based on area under the curve, high accuracy was obtained in separating healthy controls from those diagnosed with schizophrenia (p<0.0001), depression (p<0.0001), Alzheimer's disease (AD; p<0.0001), and mild cognitive impairment (MCI; p<0.0001) as well as in differentiating participants with schizophrenia from those with depression (p<0.0001), AD (p<0.0001) or MCI (p<0.0001) and in differentiating people with depression from those with AD (p<0.0001) or MCI (p<0.0001). The novel EEG analytic algorithm (qpmvs) seems to be a useful and sufficiently accurate tool for diagnosis of neuropsychiatric and neurocognitive diseases and may be able to predict disease course and response to treatment.

The First Word Recalled Measure - A Potential Addition to Clinical Exams.

Characterizing episodic memory abilities is highly important in the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI), and usually includes wordlist learning and recall tasks. Clinical evaluations typically focus on the number of words recalled, ignoring additional information, like serial position. Here, we tested the potential value of two serial positioning measures for clinical diagnosis - how retrieval is initiated, as measured by the first word recalled, and how it proceeds - using data from patients with AD and MCI that completed a wordlist learning and recall task. Our results show that during the early stages of learning, patients with AD are less prone to retrieve the first word from the wordlist, manifested as lower primacy effect in the first word recalled, compared with MCI patients. The first word recalled measure adds to the differentiation between the groups over and above the total number of words learned. Thus, the first word recalled during word list learning and recall tasks may be used as a simple complementary measure to distinguish between MCI and AD during standard neuropsychological evaluations.

Paroxysmal slow cortical activity in Alzheimer's disease and epilepsy is associated with blood-brain barrier dysfunction.

A growing body of evidence shows that epileptic activity is frequent but often undiagnosed in patients with Alzheimer's disease (AD) and has major therapeutic implications. Here, we analyzed electroencephalogram (EEG) data from patients with AD and found an EEG signature of transient slowing of the cortical network that we termed paroxysmal slow wave events (PSWEs). The occurrence per minute of the PSWEs was correlated with level of cognitive impairment. Interictal (between seizures) PSWEs were also found in patients with epilepsy, localized to cortical regions displaying blood-brain barrier (BBB) dysfunction, and in three rodent models with BBB pathology: aged mice, young 5x familial AD model, and status epilepticus-induced epilepsy in young rats. To investigate the potential causative role of BBB dysfunction in network modifications underlying PSWEs, we infused the serum protein albumin directly into the cerebral ventricles of naïve young rats. Infusion of albumin, but not artificial cerebrospinal fluid control, resulted in high incidence of PSWEs. Our results identify PSWEs as an EEG manifestation of nonconvulsive seizures in patients with AD and suggest BBB pathology as an underlying mechanism and as a promising therapeutic target.

Non-Ashkenazi Jewish Origin is Associated with Early Onset Alzheimer's Disease.

Early-onset Alzheimer's disease (EOAD) accounts for 1-5% of Alzheimer's disease cases and is associated with specific ethnicities. It has been our impression that non-Ashkenazi Jews have a higher rate of EOAD and we therefore explored this hypothesis. We performed a retrospective case control study of EOAD cases referred to our cognitive neurology clinic between January 1999 and December 2016. Patients (n = 129) were compared to age- and geographically-matched controls generated from the Second Israeli National Health Survey (n = 1,811). Data on country of origin, education, dementia family history, depression, and vascular risk factors were compared between the groups. The association of non-Ashkenazi Jewish heritage and country of origin with EOAD was calculated using a logistic multivariate regression model. The EOAD group's mean age was 59.6±4.1 years, with a female predominance (64.3%). The EOAD group had a higher percentage of individuals of non-Ashkenazi Jewish origin (64.3% versus 51.4%, p = 0.003) and of Yemenite descent in particular (16.28% versus 6.24%, p < 0.001). On multiple logistic regression analysis, Yemenite Jewish origin was an independently associated with EOAD (OR 2.54, 95% CI 1.4-4.8). There were no significant differences in parameters between non-Ashkenazi and Ashkenazi Jews. Only 4.6% of EOAD cases had a positive EOAD family history. In conclusion, EOAD is over-represented among non-Ashkenazi Jews. Yemenite origin is independently associated with EOAD and the majority of patients with EOAD have no family history of Alzheimer's disease. Further evaluation with genetic studies is warranted.

Clinical Experience With Deferiprone Treatment for Friedreich Ataxia.

Friedreich ataxia is an inherited disorder characterized by degeneration of the peripheral and central nervous system and hypertrophic cardiomyopathy. Homozygous mutations in the frataxine (FXN) gene reduce expression of frataxin and cause accumulation of iron in the mitochondria. Deferiprone, an oral iron chelator, has been shown effective in cell and animal models of Friedreich ataxia. The results of a 6-month randomized, double blind placebo-controlled study suggested that deferiprone 20 mg/kg/day may reduce disease progression. The authors present their experience of 5 Friedreich ataxia patients treated with deferiprone (20 mg/kg/day), in addition to idebenone treatment, followed over a period of 10-24 months, under off-label authorization. The patients were monitored for laboratory parameters, cardiac assessment, neurological evaluations, and quality of life. The authors conclude that combined therapy of a low dose of deferiprone with idebenone is relatively safe, might improve neurological function, and seems to improve heart hypertrophy, warranting further studies.

Lateral Sinus Thrombosis: The Importance of the Unaffected Sinus.

BACKGROUND AND PURPOSE: Intracranial hypertension develops in only some patients with lateral sinus thrombosis (LST), for reasons that are unclear. The purpose of this study was to evaluate a possible association between patency of the unaffected sinus and clinical presentation of unilateral LST. METHODS: A computerized search identified patients with LST, hospitalized in Soroka Medical Center. Patients with signs of increased intracranial pressure (iICP) and those with normal intracranial pressure (nICP) were compared. CT venography or MR venography confirmed the diagnosis, located the thrombosis, and determined the dominant lateral sinus (LS). Diameters of the right and left LSs (the occluded and unaffected) were compared to the diameter of the distal superior sagittal sinus (SSS). RESULTS: Of the 50 patients identified, 30 had iICP and 20 nICP. The dominant LS was the right one in 39 (78%) and the left one in 8 (16%); 3 (6%) had equal LS dominance. The dominant sinus was affected in 32 (70%) and the non-dominant in 15 (30%) patients. iICP was detected in 28/32 (81%) of patients with the dominant side affected, and 3/15 (20%) of those with non-dominant thrombotic sinus (P = .002). The unaffected sinus was narrower in iICP patients (size relative to SSS diameter = 43% in iICP vs. 86% in nICP [P = .0002]; size grading, according to Farb's method was 1.86 in the iICP vs. 3.57 in the nICP group [P = .0001]). CONCLUSIONS: Thrombosis was more common in the dominant LS. Unaffected LS patency appears to be associated with the development of increased ICP.

Essential tremor might be less frequent than Parkinson's disease in North Israel Arab villages.

Essential tremor (ET) is much more prevalent than Parkinson's disease (PD) in Western countries. We estimated ET and PD prevalence in Wadi Ara Arabic villages in Northern Israel. In this door-to-door survey, all consenting residents aged >or=65 years were systematically examined by an Arabic speaking team. No prescreening questionnaires were used. A random sample of 900 subjects [437 males, mean age (SD) = 72.6 years (6.6)] of the 2,163 eligible residents were evaluated. Sixteen subjects had an action, intentional tremor. Tremor prevalence was estimated as 1.78% (95% CI 1.1-2.87). Nine of these had another likely cause of tremor. Only 7 patients were diagnosed as ET [prevalence 0.78% (95% CI 0.38-1.6)]. PD was diagnosed in 13 subjects. PD prevalence was 1.44% (95% CI 0.84-2.45). ET is unusually uncommon in this population and possibly even less frequent than PD. The PD prevalence in Wadi Ara is similar to that reported in Western countries.

Psychosis, short stature in benign hereditary chorea: a novel thyroid transcription factor-1 mutation.

Benign hereditary chorea (BHC) is a rare autosomal dominant nonprogressive movement disorder. In some cases the phenotype includes, besides choreoathetosis, thyroid dysfunction and pulmonary infections in infancy, as expressed by the name "Brain-Thyroid-Lung syndrome". Mutations in the thyroid transcription factor-1 (TITF-1) gene have been identified in some BHC families. We present the phenotypic features of a family with chorea, hypothyroidism, and lung dysfunction. All affected individuals suffered from a nonprogressive chorea with infancy onset. All showed short stature and some webbed neck. One patient suffered from psychosis at the age of 27 years another from lung carcinoma. In all affected individuals, a novel mutation consisting of heterozygous C to A substitution at position 650 of the coding sequence of the TITF-1 gene, exon 3 was detected, leading to a premature stop at codon 217 (S217X). We describe the unique phenotypic features and intrafamilial variability expressing this novel mutation.

T lymphocytes: the "cellular" arm of acquired immunity in the peritoneum.

T cells are an important part of the acquired immune response and target specific antigen with their T cell receptor. The peritoneum is a special milieu within which T cells react. We describe briefly the anatomy important for T cell function. T cell biology including antigen presentation, T cell activation, and the different T cell subpopulations are reviewed. We also define innate and acquired immunity and describe the role of polymorphonuclear cells and peritoneal mesothelial cells in the regulation of leukocyte population recruitment during peritonitis. We focus particularly on peritoneal lymphocytes and compare them to the regular lymphocyte populations in the circulation. We illustrate the role of PMCs in antigen presentation and discuss the changes of CD4+ helper T cell subtypes (Th1 and Th2) during peritoneal dialysis. The role of CD8+ cytotoxic T lymphocytes and their possible destructive role for the peritoneal membrane modified by advanced glycation end products are discussed. Polymorphonuclear cells play an important role in the regulation of inflammation and immunity. We describe their possible role in supporting T cells and particularly for generating memory CD8+ T cells by secretion of interleukin-15, a potent T cell growth factor. Light is shed on gamma8T cells, a special T cell population that is able to recognize antigens without the restriction of antigen presentation. We end our review with a description of regulatory T cells. This cell population is extremely important in preventing autoimmunity and in the regulation of acquired immunity.

CD40 ligand expression correlates with resolution of peritonitis and mononuclear cell recruitment.

BACKGROUND: CD40 belongs to the tumor necrosis factor receptor family and its ligation is a central event in major inflammatory and immune reactions. We have previously demonstrated that CD40 ligation upregulates the secretion of mononuclear chemokines from peritoneal mesothelial cells (PMC), and that blocking the CD40 ligand (CD154) reduced the mononuclear infiltrate in a model of peritonitis. OBJECTIVE: To characterize the kinetics of CD154 expression on peritoneal Leukocytes and examine the correlation of this occurrence with the mononuclear transition at the resolution phase of peritonitis. METHODS: Leukocytes were collected from the effluent of 11 patients during episodes of peritonitis while undergoing peritoneal dialysis (PD). The effluent was then analyzed by flow cytometry to characterize CD154 expression. RESULTS: CD154 expression on peritoneal mononuclear cells gradually increased during the resolution phase of peritonitis, peaking first on T cells (CD4+ and CD8* cells at 20-45 hours) and then on macrophages (CD14' at 20-50 hours). The maximal expression of CD154 on macrophages, CD4* cells, and CD8* cells during peak hours reached values of 33% * 23%, 4%-3%, and 24%-17%, respectively. The increase in CD154 expression was in-negative correlation (r= -0.44, p = 0.032) with total Leukocyte numbers and in positive correlation (r = 0.52, p = 0.009) with the increase of mononuclear cells. Deterioration of peritonitis was associated with a decrease in CD154 levels, while recurrence of peritonitis was related to high CD154 Levels. CONCLUSION: Our data, which show a positive correlation between CD154 Levels and mononuclear dominance, suggest that CD40-CD154 Ligation plays an important role in the transition to mononuclear predominance in the late phase of peritonitis.