Cerebellar syndrome: do not miss anti-Tr antibodies testing.

We report a case of a 19-year-old woman with a subacute onset of visual disturbance and gait instability in the last three months. The neurological examination revealed horizontal nystagmus in the lateral gaze with a change of phase. The patient also described double vision in various gaze positions, with no clear opthalmoparesis. In her next visits to our clinic, the symptoms had progressed. In this presentation, we discuss the approach of subacute cerebellar ataxia in a young adult patient.

Apraxia Patterns for the Differentiation between Alzheimer's Disease and Frontotemporal Dementia Variants.

Background and Objectives: Despite the increasing use of biomarkers, differentiation between Alzheimer's disease (AD), behavioral variant Frontotemporal Dementia (bvFTD), and Primary Progressive Aphasia (PPA) remains a challenge. Apraxia is a supportive feature for diagnosing AD but is underrepresented in other dementia types. Herein, we investigated the presence and characteristic profiles of limb, verbal, and non-verbal apraxia in three major dementia types. Materials and Methods: Test for Upper Limb Apraxia (TULIA) and Apraxia Battery for Adults-2 (ABA-2) were administered in patients with AD (n = 22), bvFTD (n = 41), and PPA (n = 22), with 20 individuals serving as healthy controls (HC). Composite and subdomain scores were compared between each patient group and the HC. Praxis profiles indicative of each dementia type and a possible predictive value were sought. Results: Apraxia provided high diagnostic accuracy for detecting dementia compared with HC (sensitivity: 63.6-100%, specificity: 79.2-100%). Patients with AD performed worse when imitating intransitive gestures as well as pantomiming transitive gestures (mean differences: 2.10 and 3.12, respectively), compared with bvFTD. PPA patients, compared with bvFTD, had comparable results in limb, verbal, and non-verbal praxis assessments, despite the greater deterioration in the outcome. Compared with patients with AD, PPA had increased pathological outcomes in verbal (86.4% vs. 40.9%) and non-verbal apraxia (31.8% vs. 0%), while bvFTD had increased pathological outcomes in verbal apraxia (85.4% vs. 44.5%). Finally, apraxia is correlated with cognitive decline. Conclusions: Apraxia profile evaluation could contribute to the differentiation between AD and Frontotemporal Dementia (FTD). Both TULIA and ABA-2 are reliable tools that can be performed as bed-side tests in clinical practice.

Analysis of insecticide resistance and de novo transcriptome assembly of resistance associated genes in the European grapevine moth, Lobesia botrana (Lepidoptera: Tortricidae).

The European grapevine moth Lobesia botrana (Denis & Shiffermüller 1776) is an economically important pest of the vine-growing areas worldwide. Chemical insecticides have been used for its control; however, its resistance status is largely unknown in many regions. We monitored the susceptibility of several L. botrana populations from Greece and Turkey. In addition, based on RNAseq transcriptome analysis, we identified and phylogenetically classify the cytochrome P450 genes of L. botrana, as well as analysed target site sequences and looked for the presence of known resistance mutations. Resistance against chlorantraniliprole, alpha-cypermethrin, spinetoram, etofenprox, and acetamiprid was very low (below 2.5-fold in all cases, compared to a reference strain from Greece) in all populations from Greece that were included in the study. However, resistance against indoxacarb (4-30-fold), spinosad (5-59-fold), and deltamethrin (18-30 fold) was detected in the L. botrana populations from Turkey, compared to a reference population from Turkey. De novo transcriptome assembly and manual annotation, and subsequent PCR-based analysis of insecticide target sequences (i.e. voltage-gated sodium channel - VGSC: target of pyrethroids and oxadiazines; nicotinic acetylcholine receptor subunit a6 - nAChR_α6: target of spinosad; ryanodine receptor - RyR: target of diamides; glutamate-gated chloride channel - GluCl: target of avermectins and; acetylcholinesterase - AChE: target of organophosphates) showed the absence of known resistance mutations in all specimens from both countries. Finally, the L. botrana CYPome (116 genes) was manually analysed and phylogenetically characterised, to provide resources for future studies that will aim the analysis of metabolic resistance.

Screening for Executive Impairment in Patients with Frontotemporal Dementia: Evidence from the Greek Version of the Frontier Executive Screen.

OBJECTIVES: The aim of the present study was to adjust the frontier executive screen (FES) for the Greek population, to develop normative data, and to investigate its ability to discriminate patients diagnosed with frontotemporal dementia from healthy individuals. METHODS: The FES was administered to 142 community-dwelling healthy adults (age: M = 65.9, SD = 8.5; education: M = 10.8, SD = 4.3; sex: 59% female) and 32 patients diagnosed with frontotemporal dementia (age: M = 69.3, SD = 8.6; education: M = 11.7, SD = 4.8; sex: 31% female). Correlation and regression analyses were performed to determine the association between the FES scores, demographic, and clinical characteristics. Cronbach's α coefficient was used to determine internal consistency. Group differences on the FES were examined with independent samples t-test and Mann-Whitney test. Discriminant and ROC analyses were used to determine diagnostic accuracy and to identify the optimal cutoff score for the discrimination between groups. RESULTS: Regression analyses indicated associations between demographic characteristics and FES scores (age: R2 = .08; education: R2 = .33). Internal consistency was marginally acceptable (α = .69). Patients scored lower than healthy participants on the total FES score (d = 1.91) and its three subscores (verbal fluency: η2 = .60; inhibition: η2 = .52; working memory: d = 0.90). The results indicated high diagnostic accuracy (94%) and the optimal cutoff score was 7 (91% sensitivity, 78% specificity). CONCLUSIONS: The Greek version of the FES is a useful tool for the brief evaluation of executive functions in patients diagnosed with frontotemporal dementia.

Box Lesion Isolation of the Left Atrial Posterior Wall with Radiofrequency Ablation Restricted in Predetermined Lines for the Treatment of Persistent Atrial Fibrillation: The Prognostic Role of Acute Interventional Outcome and Trigger Identification.

The left atrial posterior wall (PW) is known to be a critical substrate for the initiation and perpetuation of atrial fibrillation (AF) and has been explored as a target for catheter ablation, particularly in persistent AF (PerAF). In this retrospective study, we investigate the clinical outcome of patients with PerAF who underwent PW isolation (PWI) restricted in predetermined lines in addition to pulmonary vein isolation (PVI). One hundred consecutive patients (64 ± 9.1 years, 66% male, 20% with previous PVI ablation) underwent PWI in a box lesion setting for PerAF lasting >3 months (34% long-standing PerAF). PW triggers were defined as either foci from the PW that repeatedly induced AF or as isolated AF or atrial tachycardia (AT) within the PW. After a mean follow-up period of 25.6 ± 6.7 months, 61% of the patients remained in sinus rhythm after the last procedure. In 79 patients, the PW was successfully isolated, while, in 21 patients, complete isolation was not possible due to failure in completion of the roof line (n = 16), the floor line (n = 7), or both (n = 2). Patients with incomplete isolation had similar AF/AT recurrence rates compared to those with complete PWI. In 12 patients, PW triggers were identified, and PWI in these patients was shown to have a significantly better prognosis in terms of sinus rhythm maintenance (P = .031). Failure of complete PWI does not predispose a patient to an inferior outcome nor is it responsible for iatrogenic ATs. The presence of AF triggers within the PW leads to a particularly favorable result after box lesion isolation.

Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review.

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, a study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it is the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.

Detection and Prevention of Mild Cognitive Impairment and Dementia.

Mild cognitive impairment (MCI) is characterized by cognitive deficits alongside essentially preserved competence in activities of daily living [...].

Secondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review.

Secondary demyelinating diseases comprise a wide spectrum group of pathological conditions and may either be attributed to a disorder primarily affecting the neurons or axons, followed by demyelination, or to an underlying condition leading to secondary damage of the myelin sheath. In the elderly, primary demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis, are relatively uncommon. However, secondary causes of CNS demyelination may often occur and in this case, extensive diagnostic workup is usually needed. Infectious, postinfectious, or postvaccinal demyelination may be observed, attributed to age-related alterations of the immune system in this population. Osmotic disturbances and nutritional deficiencies, more commonly observed in the elderly, may lead to conditions such as pontine/extrapontine myelinolysis, Wernicke encephalopathy, and demyelination of the posterior columns of the spinal cord. The prevalence of malignancies is higher in the elderly, sometimes leading to radiation-induced, immunotherapy-related, or paraneoplastic CNS demyelination. This review intends to aid clinical neurologists in broadening their diagnostic approach to secondary CNS demyelinating diseases in the elderly. Common clinical conditions leading to secondary demyelination and their clinical manifestations are summarized here, while the current knowledge of the underlying pathophysiological mechanisms is additionally presented.

Metabolic syndrome and cognitive deficits in the Greek cohort of Epirus Health Study.

BACKGROUND: Metabolic syndrome is considered an important risk factor for cognitive decline and dementia. However, the evidence in middle-aged individuals is still conflicting. The aim of the study was to explore the association between metabolic syndrome and its individual components with cognitive function and to investigate possible interaction between sex, age and genetic predisposition for metabolic syndrome and Alzheimer's disease in a middle-aged Greek cohort. METHODS: A total of 2,077 healthy adults (mean age: 46.7 years) were included in the primary cross-sectional analysis and 305 of them in secondary prospective analyses. Metabolic syndrome was defined by the revised National Cholesterol Education-Adult Treatment Panel III and the International Diabetes Federation criteria. Cognitive function was measured primarily with the Trail Making, Verbal fluency and Logical Memory test, and in secondary prospective analyses with online versions of Posner cueing task, an emotional recognition task, Corsi block-tapping task and Stroop task. RESULTS: Multivariable linear regressions showed an association of metabolic syndrome with lower performance in attention (ß=1.62 seconds, 95% CI=0.20, 3.04) and memory (ß=-0.62 words, 95% CI=-1.19, -0.05) that could be driven by associations with elevated fasting glucose and abdominal obesity. Similar associations were observed in the secondary prospective analyses. CONCLUSION: In summary, metabolic syndrome was associated with cognitive deficits in domains related with the cognitive profile of vascular cognitive impairment.

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites.

The cognitive and behavioral correlates of functional status in patients with frontotemporal dementia: A pilot study.

Objective: Frontotemporal dementia (FTD) impinges significantly on cognition, behavior, and everyday functioning. Goal of the present study is the detailed description of behavioral disturbances and functional limitations, as well as the investigation of associations between cognition, behavior, and functional impairment among FTD patients. Given the importance of maintaining a satisfying functional status as long as possible, this study also aims to identify the cognitive correlates of compensatory strategy use in this clinical group. Methods: A total of 13 patients diagnosed with FTD (behavioral variant FTD = 9, non-fluent variant primary progressive aphasia = 3, semantic dementia = 1) were administrated a broad range of neuropsychological tests for the assessment of different cognitive abilities. Behavioral symptomatology and performance on everyday activities were rated with informant-based measures. Descriptive statistics were used for the delineation of behavioral and functional patterns, whereas stepwise multiple regression analyses were performed to identify associations between cognition, behavior, and functional status. Results: Negative symptoms, especially apathy, were found to predominate in the behavior of FTD patients. Instrumental tasks, such as housework and leisure activities, appeared to be the most impaired functional domains. Working memory was the strongest cognitive correlate of performance across various domains of everyday functioning, whereas working memory along with short-term verbal memory accounted for a great proportion of variance in compensatory strategy use. Behavioral disturbances and especially negative symptoms were also found to contribute significantly to functional impairment in FTD. Conclusions: Executive dysfunction, as well as behavioral disturbances contribute significantly to functional disability in FTD. Early interventions tailored at these domains may have the potential to improve functional outcomes and delay the rate of functional decline among FTD patients.

Functional characterization of cytochrome P450s associated with pyrethroid resistance in the olive fruit fly Bactrocera oleae.

Resistance to pyrethroid insecticides has evolved in Bactrocera oleae populations in Greece, threatening the efficacy of control interventions based on this insecticide class. Here we report the collection of populations from Crete, with resistance levels reaching up to 132-folds, compared to susceptible laboratory strains and show that pyrethroid resistance is substantially suppressed by the PBO synergist, suggesting the involvement of detoxification enzymes. To identify specific candidate genes implicated in resistance, we performed comparative transcriptomic analysis, between the pyrethroid resistant populations from Crete and the susceptible laboratory strains, using both whole bodies and Malpighian tubules. Several genes were found differentially transcribed between resistant and susceptible flies in each comparison, with P450s being among the most highly over-expressed detoxification genes in pyrethroid resistant populations. Four of the over-expressed P450s (Cyp6A61, Cyp6G6, Cyp4P6 and Cyp6G28) were recombinantly expressed in Escherichia coli and in vitro metabolism assays revealed that CYP6A61 is capable of metabolizing alpha-cypermethrin, while CYP6G6, CYP4P6 and CYP6G28 are capable of metabolizing deltamethrin. No metabolism of neonicotinoid insecticides was recorded. We further silenced CYP6G6 in vivo, via RNAi, which led to a small, but significant increase in deltamethrin toxicity. The study provides valuable information towards the development of molecular diagnostics and evidence-based insecticide resistance management strategies.

EEG-Neurofeedback as a Potential Therapeutic Approach for Cognitive Deficits in Patients with Dementia, Multiple Sclerosis, Stroke and Traumatic Brain Injury.

Memory deficits are common in patients with dementia, such as Alzheimer's disease, but also in patients with other neurological and psychiatric disorders, such as brain injury, multiple sclerosis, ischemic stroke and schizophrenia. Memory loss affects patients' functionality and, by extension, their quality of life. Non-invasive brain training methods, such as EEG neurofeedback, are used to address cognitive deficits and behavioral changes in dementia and other neurological disorders by training patients to alter their brain activity via operant activity. In this review paper, we analyze various protocols of EEG neurofeedback in memory rehabilitation in patients with dementia, multiple sclerosis, strokes and traumatic brain injury. The results from the studies show the effectiveness of the ΕΕG-NFB method in improving at least one cognitive domain, regardless of the number of sessions or the type of protocol applied. In future research, it is important to address methodological weaknesses in the application of the method, its long-term effects as well as ethical issues.

The Experience of a Tertiary Reference Hospital in the Study of Rare Neurological Diseases.

Background and Objectives: Rare diseases (RDs) are life-threatening or chronically impairing conditions that affect about 6% of the world's population. RDs are often called 'orphan' diseases, since people suffering from them attract little support from national health systems. Aim: The aim of this study is to describe the clinical characteristics of, and the available laboratory examinations for, patients who were hospitalized in a tertiary referral center and finally received a diagnosis associated with a Rare Neurological Disease (RND). Materials and Methods: Patients that were hospitalized in our clinic from 1 January 2014 to 31 March 2022 and were finally diagnosed with an RND were consecutively included. The RND classification was performed according to the ORPHAcode system. Results: A total of 342 out of 11.850 (2.9%) adult patients admitted to our department during this period received a diagnosis associated with an RND. The most common diagnosis (N = 80, 23%) involved an RND presenting with dementia, followed by a motor neuron disease spectrum disorder (N = 64, 18.7%). Family history indicative of an RND was present in only 21 patients (6.1%). Fifty-five (16%) people had previously been misdiagnosed with another neurological condition. The mean time delay between disease onset and diagnosis was 4.24 ± 0.41 years. Conclusions: Our data indicate that a broad spectrum of RNDs may reach a tertiary Neurological Center after a significant delay. Moreover, our data underline the need for a network of reference centers, both at a national and international level, expected to support research on the diagnosis and treatment of RND.

Emergence of artistic talent in logopenic variant of primary progressive aphasia: a case report.

The case report covers the investigation of a 59-year-old woman, with the diagnosis of logopenic variant of primary progressive aphasia (lvPPA), who presented de novo visual artistic talent after the onset of language deficits. Similar cases have been described in patients with semantic and non-fluent/agrammatic variants of primary progressive aphasia. However, this is the first related case with lvPPA reported in the literature. Upon her initial visit at the Neurology department in 2020, a neurological and neuropsychological assessment were conducted to establish the diagnosis. A neuropsychological reassessment was performed in 2022. Neuroimaging data indicated decreased blood flow of the left hemisphere, while neuropsychological deficits were diffuse with predominant language production disorder. A description of the patient's portraits and suggestions regarding possible neural mechanisms associated with the manifestation of this ability are provided.

Assess of Combinations of Non-Pharmacological Interventions for the Reduction of Irritability in Patients with Dementia and their Caregivers: A Cross-Over RCT.

INTRODUCTION: Dementia is a very common disorder that affects people over 65 years old all over the world. Apart from the cognitive decline, Behavioral and Psychological Symptoms of Dementia (BPSD) are a crucial matter in dementia, because they affect up to 90% of the patients during the course of their illness. Irritability has been found to be a common BPSD and one of the most distressing behaviors for the caregivers. The aim of the current study was to explore the efficacy of a combination of non-pharmacological interventions to treat irritability. METHODS: Sixty patients with different types and stages of dementia with irritability were participated in a cross-over RCT. Three non-pharmacological interventions were used; (a) Validation Therapy (VT)/Psycho-educational program, (b) Aromatherapy/massage and (c) Music Therapy (MT). The study assessed the three non-pharmacological interventions in order to find the most effective combination of the interventions. This study did not compare pharmacological and non-pharmacological treatments. The interventions lasted for five days. There was no drop-out rate. All patients were assessed at baseline using Mini Mental State of Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), Geriatric Depression Scale (GDS), Functional Rating Scale for symptoms in dementia (FRSSD), and Neuropsychiatric Inventory (NPI) (sub questions for irritability). Only NPI used for the assessment after each intervention. The analyses used categorical variables, Wilcoxon signed-rank test, Chi-square test and z value score. RESULTS: The most effective combination of non-pharmacological interventions was Aromatherapy/massage (p = 0.003)-VT plus Psycho-educational program (p = 0.014) plus MT (p = 0.018). The same combination was the most effective for the caregivers' burden, too (p = 0.026). CONCLUSIONS: The above combination of non-pharmacological interventions can reduce irritability in patients with dementia and caregivers' burden.

Comparison of the Greek Version of the Quick Mild Cognitive Impairment Screen and Montreal Cognitive Assessment in Older Adults.

Objective: Cognitive screening instruments (CSIs) are essential for everyday practice. The Quick Mild Cognitive Impairment (Qmci) screen, a short instrument designed to identify mild cognitive impairment, was recently translated into Greek (Qmci-Gr). The present study compared its diagnostic value against the Montreal Cognitive Assessment (MoCA) screen and examined its optimal cutoffs. Method: We recruited consecutive patients aged ≥55 years that presented with cognitive complaints from two outpatient clinics in Greece. The Qmci-Gr and MoCA were completed by all patients. Furthermore, they were assessed independently with a comprehensive flexible neuropsychological battery to establish a diagnostic classification. Results: In the current study, we assessed a total of 145 patients, with a median age of 70 years; 44 were classified as having Subjective Memory Complaints (SMC) but normal cognition, 32 with MCI and 69 with dementia. The Qmci-Gr had a higher accuracy compared to the MoCA in discriminating MCI from dementia, area under the curve (AUC) of 0.81 versus 0.75, respectively; however, this finding was marginally significant (p = 0.08). Its accuracy was marginally higher for distinguishing SMC from dementia, AUC of 0.94 versus 0.89 (p = 0.03). However, Qmci-Gr presented a lower accuracy than MoCa in differentiating SMC from MCI, AUC of 0.76 versus 0.94 (p = 0.006). Conclusions: The Qmci-Gr has comparable diagnostic accuracy to the MoCA regarding MCI and dementia groups. Further research, with larger and more diverse samples, may be necessary to ensure generalizability.

Dynamic interactions between the symbiont Candidatus Erwinia dacicola and its olive fruit fly host Bactrocera oleae.

The olive fruit fly, Bactrocera oleae, the most serious pest of olives, requires the endosymbiotic bacterium Candidatus Erwinia dacicola in order to complete its development in unripe green olives. Hence, a better understanding of the symbiosis of Ca. E. dacicola and its insect host may lead to new strategies for B. oleae control. The relative abundance of bacteria during the fly life cycle comparing black and green olives was estimated by real time quantitative PCR revealing significant fluctuations during development in black olives with a peak of the bacteria in the second instar larvae. By microscopy analysis of larvae, we show that the bacteria reside extracellularly in the gastric caeca. During the transition to late third instar larvae, the bacteria were discharged into the midgut concomitant with a change in caeca size and morphology due to the contraction of the muscles surrounding the caeca. A similar alteration was also observed in a laboratory strain devoid of bacteria. To further investigate the symbiotic interaction and the change in caeca morphology a comparative transcriptomics analysis was undertaken. Samples of dissected caeca from second and third instar larvae collected from the field as well as second instar larvae from a laboratory strain devoid of symbionts showed significant changes in transcript expression. This highlighted genes associated with the developmental changes revealed by the microscopic analysis as well as responses to microorganisms.