CHA2DS2-VASc Score as Predictor of New-Onset Atrial Fibrillation and Mortality in Critical COVID-19 Patients.

BACKGROUND: Pre-existing and new-onset atrial fibrillation (NOAF) is a common arrhythmia in COVID-19 patients and is related to increased mortality. CHA2DS2-VASc score was initially developed to evaluate thromboembolic risk in patients with AF. Moreover, it predicted adverse outcomes in other clinical conditions, including SARS-CoV-2 infection. We aimed to evaluate the association of CHA2DS2-VASc with NOAF, ICU length of stay (LOS) and mortality in critically ill COVID-19 patients. We also examined the relationship of NOAF with mortality. We reviewed the literature to describe the link between cardiovascular risk factors and inflammatory response of severe COVID-19. METHODS AND RESULTS: We retrospectively studied 163 COVID-19 patients admitted to a level 3 general ICU from March 2020 to April 2022. Patients were of advanced age (median 64 years, IQR 56.5-71) and the majority of them were male (67.5%). Regarding NOAF, we excluded 12 patients with AF history. In this group, CHA2DS2VASc score was significantly elevated (3 IQR (1-4) versus 1 IQR (1-2.75), p = 0.003). Specifically, three components of CHA2DS2VASc were notably increased: age (p < 0.001), arterial hypertension (p = 0.042) and stroke (p = 0.047). ICU mortality was raised in the NOAF group [75.8% versus 34.8%, p < 0.001 OR 5.87, 95% CI (2.43, 14.17)]. This was significant even after adjusting for ICU clinical scores (APACHE II and SOFA). About mortality in the entire sample, survivors were younger (p = 0.001). Non-survivors had greater APACHE II (p = 0.04) and SOFA (p = 0.033) scores. CHA2DS2VASc score was positively associated with mortality [p = 0.031, OR 1.28, 95% CI (1.03, 1.6)]. ICU length of stay was associated with mortality (p = 0.016) but not with CHA2DS2VASc score (p = 0.842). CONCLUSIONS: NOAF and CHA2DS2VASc score were associated with higher mortality in COVID-19 ICU patients. CHA2DS2VASc score was also associated with NOAF but not with ICU LOS.

Tumefactive cerebral amyloid angiopathy - related inflammation.

INTRODUCTION: Cerebral amyloid angiopathy-related inflammation (CAA-ri) derives from inflammatory response to ß-amyloid (Aß) protein deposition within the cerebral blood vessel walls. We report a case that accentuates those clinical and imaging features that can contribute to raise suspicion for the condition and lead to early treatment initiation. CASE PRESENTATION: A 72-year-old man was referred with one-month history of cognitive decline along with behavioral alterations. Brain MRI showed fluid attenuated inversion recovery (FLAIR) asymmetrical multifocal white matter hyperintensities (WMHs) along with multiple cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on T2*-weighted gradient-recalled echo (T2*-GRE) images. Metabolic, infectious, and neoplastic causes were excluded, and subsequently corticosteroids were administered to the patient resulting in clinical recovery. Imaging on follow-up disclosed remission of WMHs, while CMBs load increased significantly. DISCUSSION: Clinical neurologists' acquaintance with the clinical and imaging features of CAA-ri allows prompt diagnosis and medication initiation, that is essential for a conceivably treatable condition.

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.

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.

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.

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.

Developmental plasticity shapes social traits and selection in a facultatively eusocial bee.

Developmental plasticity generates phenotypic variation, but how it contributes to evolutionary change is unclear. Phenotypes of individuals in caste-based (eusocial) societies are particularly sensitive to developmental processes, and the evolutionary origins of eusociality may be rooted in developmental plasticity of ancestral forms. We used an integrative genomics approach to evaluate the relationships among developmental plasticity, molecular evolution, and social behavior in a bee species (Megalopta genalis) that expresses flexible sociality, and thus provides a window into the factors that may have been important at the evolutionary origins of eusociality. We find that differences in social behavior are derived from genes that also regulate sex differentiation and metamorphosis. Positive selection on social traits is influenced by the function of these genes in development. We further identify evidence that social polyphenisms may become encoded in the genome via genetic changes in regulatory regions, specifically in transcription factor binding sites. Taken together, our results provide evidence that developmental plasticity provides the substrate for evolutionary novelty and shapes the selective landscape for molecular evolution in a major evolutionary innovation: Eusociality.

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.

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.

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.

A spatiotemporal atlas of the lepidopteran pest Helicoverpa armigera midgut provides insights into nutrient processing and pH regulation.

BACKGROUND: Caterpillars from the insect order Lepidoptera are some of the most widespread and destructive agricultural pests. Most of their impact is at the larval stage, where the midgut epithelium mediates the digestion and absorption of an astonishing amount of food. Although this tissue has been the subject of frequent investigation in Lepidoptera, a comprehensive expression atlas has yet to be generated. RESULTS: Here, we perform RNA-sequencing and proteomics on the gut of the polyphagous pest Helicoverpa armigera across, life stages, diet types, and compartments of the anterior-posterior axis. A striking relationship between the structural homology and expression pattern of a group of sugar transporters was observed in the early larval stages. Further comparisons were made among the spatial compartments of the midgut, which suggested a putative role for vATPases and SLC9 transporters in the generation of alkaline conditions in the H. armigera midgut. CONCLUSIONS: This comprehensive resource will aid the scientific community in understanding lepidopteran gut physiology in unprecedented resolution. It is hoped that this study advances the understanding of the lepidopteran midgut and also facilitates functional work in this field.

Genetic causes of acute encephalopathy in adults: beyond inherited metabolic and epileptic disorders.

Acute encephalopathy is a widely used term, implying a rapidly progressive multifocal or diffuse brain dysfunction, caused by acute structural disturbance or a myriad of metabolic, toxic, epileptic, or infection-related factors. Apart from the more common acquired causes, a broad range of rare inherited disorders may produce spells of encephalopathy in adulthood, posing diagnostic challenges to clinicians. Among the latter, neurometabolic disorders and epileptic syndromes constitute typical examples. Interestingly, certain genetic entities have the potential to provoke episodic changes of cognition, via alternative, neither metabolic nor epileptic, mechanisms. Our aim is to provide a short and focused overview of their clinicoradiological features and potential pathophysiology. As the neurogenetic landscape is rapidly evolving, it is important to be familiar with these chameleons, in order to provide swift diagnosis and proper genetic counselling.

Neuropsychological correlates of cerebellar volumes in multiple sclerosis: an MRI volumetric analysis study.

The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.

Functionally characterized arthropod pest and pollinator cytochrome P450s associated with xenobiotic metabolism.

The cytochrome P450 family (P450s) of arthropods includes diverse enzymes involved in endogenous essential physiological functions and in the oxidative metabolism of xenobiotics, insecticides and plant allelochemicals. P450s can also establish insecticide selectivity in bees and pollinators. Several arthropod P450s, distributed in different phylogenetic groups, have been associated with xenobiotic metabolism, and some of them have been functionally characterized, using different in vitro and in vivo systems. The purpose of this review is to summarize scientific publications on arthropod P450s from major insect and mite agricultural pests, pollinators and Papilio sp, which have been functionally characterized and shown to metabolize xenobiotics and/or their role (direct or indirect) in pesticide toxicity or resistance has been functionally validated. The phylogenetic relationships among these P450s, the functional systems employed for their characterization and their xenobiotic catalytic properties are presented, in a systematic approach, including critical aspects and limitations. The potential of the primary P450-based metabolic pathway of target and non-target organisms for the development of highly selective insecticides and resistance-breaking formulations may help to improve the efficiency and sustainability of pest control.

The genome of the stable fly, Stomoxys calcitrans, reveals potential mechanisms underlying reproduction, host interactions, and novel targets for pest control.

BACKGROUND: The stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies. RESULTS: This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways. CONCLUSIONS: The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (horn flies and Glossina) and non-blood-feeding flies (house flies, medflies, Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.

Alzheimer's disease research progress in the Mediterranean region: The Alzheimer's Association International Conference Satellite Symposium.

As research and services in the Mediterranean region continue to increase, so do opportunities for global collaboration. To support such collaborations, the Alzheimer's Association was due to hold its seventh Alzheimer's Association International Conference Satellite Symposium in Athens, Greece in 2021. Due to the COVID-19 pandemic, the meeting was held virtually, which enabled attendees from around the world to hear about research efforts in Greece and the surrounding Mediterranean countries. Research updates spanned understanding the biology of, treatments for, and care of people with Alzheimer's disease (AD_ and other dementias. Researchers in the Mediterranean region have outlined the local epidemiology of AD and dementia, and have identified regional populations that may expedite genetic studies. Development of biomarkers is expected to aid early and accurate diagnosis. Numerous efforts have been made to develop culturally specific interventions to both reduce risk of dementia, and to improve quality of life for people living with dementia.

SPECT analysis and language profile in Greek speaking patients with subtypes of frontotemporal dementia.

OBJECTIVE: We aimed to examine if single photon emission computed tomography (SPECT) can discriminate between variants of frontotemporal dementia (FTD). As a secondary investigation we identify and establish the linguistic differences between those variants. MATERIALS AND METHODS: Nine patients with semantic variant primary progressive aphasia (svPPA), 8 with non-fluent variant primary progressive aphasia (nfvPPA) and 17 with behavioral variant of frontotemporal dementia (bvFTD) were compared on Addenbrooke's cognitive examination-revised (ACE-R), auditory comprehension, oral expression and verbal fluency. All patients were also compared with healthy controls. Patients were evaluated using technetium-99m-hexamethylproyleneamine oxime (99mTc-HMPAO) brain SPECT as a measure of regional cerebral flow. RESULTS: Significant group differences between all patients and controls were found for ACE-R, auditory comprehension and oral expression. Semantic variant primary progressive aphasia patients performed higher in letter compared to category fluency with significant deficits in auditory comprehension and oral expression. Non-fluent variant primary progressive aphasia patients showed significant deficits in auditory comprehension but not oral expression while performed lightly worse in letter fluency compared to category. Behavioral variant of frontotemporal dementia patients showed deficits in auditory comprehension and oral expression and performed similar in category and letter fluency. Single photon emission computed tomography analysis revealed left frontotemporal hypoperfusion extending to the right frontotemporal region in svPPA patients. Non-fluent variant primary progressive aphasia patients presented left frontotemporal hypoperfusion with participation of the left parietal and right frontotemporal regions. Behavioral variant of frontotemporal dementia patients showed bilateral frontotemporal hypoperfusion compared to parietal and visual cortices. CONCLUSION: Our findings suggest that SPECT may assist in the discrimination of the FTD variants. We also confirmed that bvFTD patients share similar language deficits with svPPA patients.

Transcriptomic analysis of s-methoprene resistance in the lesser grain borer, Rhyzopertha dominica, and evaluation of piperonyl butoxide as a resistance breaker.

BACKGROUND: The lesser grain borer, Rhyzopertha dominica is a serious pest of stored grains. Fumigation and contact insecticides play a major role in managing this pest globally. While insects are developing genetic resistance to chemicals, hormonal analogues such as s-methoprene play a key role in reducing general pest pressure as well as managing pest populations that are resistant to fumigants and neurotoxic contact insecticides. However, resistance to s-methoprene has been reported in R. dominica with some reports showing a remarkable high resistance, questioning the use of this compound and other related analogues in grain protection. The current study attempts to identify possible molecular mechanisms that contribute in resistance to s-methoprene in R. dominica. RESULTS: Transcriptome analysis of resistant and susceptible strains of this pest species identified a set of differentially expressed genes related to cytochrome P450s, indicating their potential role in resistance to s-methoprene. Laboratory bioassays were performed with s-methoprene treated wheat grains in presence and absence of piperonyl butoxide (PBO), a cytochrome P450 inhibitor. The results indicate that PBO, when applied alone, at least at the concentration tested here, had no effect on R. dominica adult emergence, but has a clear synergistic effect to s-methoprene. The number of produced progeny decreased in presence of the inhibitor, especially in the resistant strain. In addition, we also identified CYP complement (CYPome) of R. dominica, annotated and analysed phylogenetically, to understand the evolutionary relationships with other species. CONCLUSIONS: The information generated in current study suggest that PBO can effectively be used to break resistance to s-methoprene in R. dominica.

Hereditary diffuse leukoencephalopathy with spheroids mimicking primary progressive aphasia: report of a Greek case.

INTRODUCTION: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an adult onset leukodystrophy, causally related to mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We report the unique case of a Greek HDLS patient, demonstrating an unusual phenotype, reminiscent of primary progressive aphasia (PPA). METHODS: A 63-year-old woman was referred with a 2-year history of deteriorating language and memory deficits, apathy, and two generalized tonic-clonic seizures. Neurological and neuropsychological examination revealed prominent aphasia with a pattern consistent with nonfluent variant of PPA. However, brain MRI disclosed confluent T2 and FLAIR white matter hyperintensities with frontal emphasis, whereas genetic testing corroborated the diagnosis of HDLS. DISCUSSION: PPA-like patterns may rarely develop in the context of HDLS. Prompt diagnosis of this leukoencephalopathy is essential, since preliminary data suggest that it could represent a potentially treatable disorder.

Selective executive impairments as neuroimmunological manifestations of the human immunodeficiency virus.

Executive processes that predominantly effect people living with human immunodeficiency virus remain to be understood. In the present case-control study, components summarizing executive functions were empirically determined to clarify the nature of executive difficulties observed in individuals with human immunodeficiency virus. One hundred and five seropositive and 62 seronegative healthy adults without comorbidities underwent a comprehensive executive function assessment. Test data were reduced via principal components analysis and component scores were used to investigate whether seropositive adults exhibit selective difficulties in specific executive processes. A three-component solution was found, consisting of updating, inhibition and set-shifting. Group differences between seropositive and seronegative participants were observed only in the updating component. In the present exploratory analyses, significant findings emerged that suggest a selective executive impairment associated with the updating/working memory process in young to middle adulthood seropositive individuals without comorbidities.