Systemic LPS Administration Stimulates the Activation of Non-Neuronal Cells in an Experimental Model of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deficiency of the survival motor neuron (SMN) protein. Although SMA is a genetic disease, environmental factors contribute to disease progression. Common pathogen components such as lipopolysaccharides (LPS) are considered significant contributors to inflammation and have been associated with muscle atrophy, which is considered a hallmark of SMA. In this study, we used the SMNΔ7 experimental mouse model of SMA to scrutinize the effect of systemic LPS administration, a strong pro-inflammatory stimulus, on disease outcome. Systemic LPS administration promoted a reduction in SMN expression levels in CNS, peripheral lymphoid organs, and skeletal muscles. Moreover, peripheral tissues were more vulnerable to LPS-induced damage compared to CNS tissues. Furthermore, systemic LPS administration resulted in a profound increase in microglia and astrocytes with reactive phenotypes in the CNS of SMNΔ7 mice. In conclusion, we hereby show for the first time that systemic LPS administration, although it may not precipitate alterations in terms of deficits of motor functions in a mouse model of SMA, it may, however, lead to a reduction in the SMN protein expression levels in the skeletal muscles and the CNS, thus promoting synapse damage and glial cells' reactive phenotype.

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis.

Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis.

Morphosyntactic Abilities and Cognitive Performance in Multiple Sclerosis.

While cognitive abilities in people with multiple sclerosis (PwMS) have been studied in detail, little is known about linguistic abilities in PwMS and their relation to cognitive impairment. In this cross-sectional explorative study, we aim to investigate the morphosyntactic abilities of PwMS alongside their cognitive performance. Furthermore, we explore the effect of clinical factors, namely, the disease duration and MS type, on the linguistic and cognitive performance of PwMS. By so doing, we aim to shed light on neurocognitive and clinical correlates of linguistic performance in PwMS. We included 78 patients and 78 age-, sex- and education-matched healthy individuals. All participants were additionally administered the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, a verbal short-term memory task (non-word repetition) and questionnaires about mood, fatigue and quality of life. In addition, they underwent examinations with morphology and syntax tasks. PwMS were found to be impaired in morphology (past tense) and selectively impaired in syntax alongside cognitive impairments. Disease duration had the main impact on cognitive abilities. The MS type selectively impacted linguistic abilities, as shown by the remarkably deficient performance of the MS individuals with the progressive disease subtype. Linguistic impairments were predicted by only one measure of the BICAM test, namely, the Symbol Digit Modalities Test (SDMT), a measure of cognitive processing speed. Overall, this study contributes to the better understanding of the linguistic profile of PwMS by reporting selective deficits in their morphological and syntactical abilities. Furthermore, it provides insights into the clinical and cognitive correlates of linguistic performance. By so doing, it suggests clinical implications for the development of intervention programs for PwMS.

COVID-19 Vaccination and Disease Course in People with Multiple Sclerosis in Greece.

Over the past three years, humanity faced the abrupt spread of COVID-19, responsible for a worldwide health crisis. Initially, it was believed that individuals with chronic disorders, including multiple sclerosis, were more likely to be infected and suffer a worse degree of COVID-19 disease. Therefore, data with regard to COVID-19 disease outcomes in these populations may provide additional insight with regard to the management of chronic diseases during viral pandemics. The objective of this study is to evaluate COVID-19 disease course in people with multiple sclerosis (PwMS) during the COVID-19 pandemic in Greece and explore the impact of vaccination in the outcome of SARS-CoV-2 infection in this population. Anonymized data, extracted from nationwide administrative records between February 2020 and December 2021, were retrospectively analyzed in order to identify PwMS with SARS-CoV-2 infection. Demographic data, as well as data regarding COVID-19 infection and vaccination, were additionally collected. The study sample included 2351 PwMS (65.1% females, 51.2% unvaccinated at the time of infection). A total of 260 PwMS were hospitalized, while 25 PwMS died from COVID-19 disease and its complications. Older age, male sex and the presence of comorbidities were independently associated with a higher probability of hospitalization. The risk of hospitalization was decreased in PwMS receiving some disease-modifying treatments. Anti-CD20s demonstrated high odds ratios without reaching statistical significance. Regarding fatal outcome, only age reached statistical significance. Vaccination provided a significant protective effect against hospitalization but did not exhibit a statistically significant effect on mortality.

Association of cytokine gene polymorphisms with peripheral neuropathy susceptibility in people living with HIV in Greece.

Relatively little research has been done in recent years to understand what leads to the unceasingly high rates of HIV sensory neuropathy despite successful antiretroviral treatment. In vivo and in vitro studies demonstrate neuronal damage induced by HIV and increasingly identified ART neurotoxicity involving mitochondrial dysfunction and innate immune system activation in peripheral nerves, ultimately all pathways resulting in enhanced pro-inflammatory cytokine secretion. Furthermore, many infectious/autoimmune/malignant diseases are influenced by the production-profile of pro-inflammatory and anti-inflammatory cytokines, due to inter-individual allelic polymorphism within cytokine gene regulatory regions. Associations of cytokine gene polymorphisms are investigated with the aim of identifying potential genetic markers for susceptibility to HIV peripheral neuropathy including ART-dependent toxic neuropathy. One hundred seventy-one people living with HIV in Northern Greece, divided into two sub-groups according to the presence/absence of peripheral neuropathy, were studied over a 5-year period. Diagnosis was based on the Brief Peripheral Neuropathy Screening. Cytokine genotyping was performed by sequence-specific primer-polymerase chain reaction. Present study findings identify age as an important risk factor (p < 0.01) and support the idea that cytokine gene polymorphisms are at least involved in HIV peripheral-neuropathy pathogenesis. Specifically, carriers of IL1a-889/rs1800587 TT genotype and IL4-1098/rs2243250 GG genotype disclosed greater relative risk for developing HIV peripheral neuropathy (OR: 2.9 and 7.7 respectively), while conversely, carriers of IL2+166/rs2069763 TT genotype yielded lower probability (OR: 3.1), all however, with marginal statistical significance. The latter, if confirmed in a larger Greek population cohort, may offer in the future novel genetic markers to identify susceptibility, while it remains significant that further ethnicity-oriented studies continue to be conducted in a similar pursuit.

Prevention, Intervention and Care of Neurodegenerative Diseases.

Chronic neurodegenerative diseases encompass a wide spectrum of disorders and affect millions of people worldwide [...].

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.

Epidemiological Insights on Medication Concurrency and Polypharmacy in People With Multiple Sclerosis in Greece.

BACKGROUND: Besides disease-modifying therapies, various pharmacologic agents are frequently prescribed to people with multiple sclerosis (MS) for symptom treatment and for comorbid conditions. The present study aims to investigate the types and frequencies of agents prescribed to people with MS in Greece using records from the nationwide digital prescription database. METHODS: Prescription records for 21,218 people (65.9% women) with MS were included in the study. The criterion for study inclusion was a minimum of 3 months of continuous prescription of an agent. Identified treatments were further examined by age group. RESULTS: Antispasticity agents (17.5%) and fampridine (14.5%) were the most regularly prescribed symptomatic medications. Antihypertensives (21.1%) and drugs for affective disorders, including antidepressants (36.1%) and anxiolytics (16.2%), were the most frequently prescribed medications for comorbid conditions. Antidepressants were prescribed at almost equally high rates among individuals older than 40 years. Hypertension was one of the leading comorbidities among the study sample, with rates rising significantly after age 40 years and plateauing after age 60 years. Polypharmacy was observed in 22.5% of the study sample, with a higher incidence among people with MS older than 60 years (46.98%). CONCLUSIONS: Agents prescribed for the treatment of disease symptoms and other medical conditions are expected to positively affect quality of life in people with MS. However, polypharmacy seems to be particularly high, especially in the aged population. The potential implications of polypharmacy in the disease course should further be explored.

The impact of SARS-CoV-2 immunization on COVID-19 disease course in people with myasthenia gravis.

INTRODUCTION/AIMS: There is limited knowledge regarding the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines οn coronavirus disease 2019 (COVID-19) disease course in people with myasthenia gravis. In this study, we aimed to investigate whether SARS-CoV-2 vaccination influences hospitalization and mortality due to COVID-19 in this population. METHODS: This is a retrospective analysis of administrative data extracted from the Greek nationwide database that holds the COVID-19 disease and vaccination registry, as well as all medical prescription records. The study period extended from the onset of the pandemic (February 2020) until the 10th of January 2022. RESULTS: We identified 278 people with myasthenia gravis (mean age 58.1 ± 17.2, 47.5% males) who tested positive for SARS-CoV-2. Of those, 139 (50%) were not vaccinated at the time of infection. Multivariable binary logistic regression analysis showed that the probability of hospitalization increased with age (odds ratio [OR]: 1.058; 95% confidence interval [CI], 1.036-1.080; p < .001) and immunosuppressive treatment (OR: 2.872; 95% CI 1.412-5.839; p = .004), and decreased with vaccination (OR: 0.244; 95% CI 0.132-0.453; p < .001). The probability of a fatal outcome increased with age (OR: 1.085; 95% CI 1.043-1.129; p < .001) and decreased with vaccination (OR: 0.315; 95% CI 0.125-0.791; p = .014). DISCUSSION: SARS-CoV-2 vaccination significantly reduces hospitalization and mortality due to COVID-19 in people with myasthenia gravis. This study regarding the efficacy of these vaccines, together with previous studies regarding their safety, provide evidence to support their use in people with myasthenia gravis.

Translation, cross-cultural adaptation, and validation of the Greek version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-19.

INTRODUCTION: Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) explores optimally impact of MS on sexual activity/satisfaction/intimacy. AIM: The present study aims to provide the only validation of the Greek Version of MSISQ-19, and compare results to validation studies in other languages. METHODS: The original/English version of the MSISQ-19 was translated into Greek according to standardized guidelines, while validity/reliability, correlations with other scales and sexual dysfunction prevalence were tested. Subjects were requested to complete all questionnaires and MSISQ-19, being re-tested three weeks later. Construct-validity of the Greek version of the MSISQ-19 was confirmed with principal-component-analysis. Bartlett's test assessed correlation-adequacy between items. Pearson's correlation explored internal-construct-validity between subscales and overall score, and external-construct-validity with disease-status variables, cognitive testing and patient-reported outcomes regarding fatigue, depression/anxiety, MS impact, and quality of life. RESULTS: 201 PwMS (130 female). Mean age was 39.3 ± 11.8 years with median disease-duration 11.7 ± 7.9 years. 79.1% RRMS, PPMS (10.4%) and SPMS (10.4%). Cronbach's alpha coefficient was 0.949. MSISQ-19 correlations between items were large. Significant associations of sexual dysfunction were identified with age (rho = 0.392, p < 0.01), years of education (rho=-0.199, p = 0.006), the Expanded Disability Status Scale (rho = 0.518, p < 0.01) and MS duration (rho = 0.354, p < 0.01). Correlations were disclosed with the Brief International Cognitive Assessment for MS (rho=-0.247, p < 0.05), Modified Fatigue Impact Scale (rho = 0.374, p < 0.05), Depression Anxiety Stress Scale (rho = 0.375, p < 0.05), Multiple Sclerosis Impact Scale (rho = 0.442, p < 0.05), and EuroQoL-five-dimensional instrument (rho = 0.375, p < 0.05). Internal consistency of the Greek version of the MSISQ-19 was confirmed with Cronbach's alpha. Test-retest reliability (31 PwMS) was excellent with intraclass-correlation-coefficients > 0.90. CONCLUSION: Besides Greek MSISQ-19 satisfactory validity/reliability/reproducibility and being first to include cognitive-testing, authors estimated sexual-dysfunction prevalence affecting half PwMS.HIGHLIGHTSThis study provides the only validation of the Greek Version of the MSISQ-19.The latter was found with satisfactory validity, reliability and reproducibility.50% of the Greek PwMS sample was found to be afflicted with sexual dysfunction.This is also the first validation study to examine associations with cognitive testing.Sexual function is still an underestimated functionality parameter upon examination.

Epidemiology of HIV-associated peripheral neuropathy in people living with human immunodeficiency virus infection in Greece.

BACKGROUND: Peripheral neuropathy is among the most common complications among people with HIV with prevalence rates varying widely among studies (10-58%). OBJECTIVE: This study aims to assess the prevalence of HIV-associated peripheral neuropathy among HIV-positive people in Northern Greece monitored during the last 5-year period and investigate possible correlations with antiretroviral therapy, disease staging, and potential risk factors, as there is no prior epidemiological record in Greek patients. METHODS: Four hundred twenty patients were divided into a group with peripheral neuropathy (n = 269), and those without (n = 151). Peripheral neuropathy was assessed with a validated Peripheral Neuropathy Screening tool. Statistical analyses were performed with SPSS, were two-tailed, and p-value was set at 0.05. RESULTS: The incidence of peripheral neuropathy was estimated at 35.9%. Age was found to correlate with higher odds of developing HIV-peripheral neuropathy, rising by 4%/year. Females encountered 77% higher probability to develop peripheral neuropathy. Stage 3 of the disease associated with higher occurrence of peripheral neuropathy (96% as compared to stage-1 patients). Among patients with peripheral neuropathy, the duration of antiretroviral therapy was found to be longer than in those without. CONCLUSIONS: Peripheral neuropathy remains one of the most common complications regardless of the antiretroviral-therapy type, indicating the involvement of other risk factors in its occurrence, such as the stage of the disease, age and gender. Therefore, the treating physician should screen patients as early and frequently as possible upon HIV-diagnosis to prevent the progression of this debilitating condition so that prolonged life-expectancy is accompanied by a good quality of life.

Optical Coherence Tomography and Optical Coherence Tomography with Angiography in Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative, potentially disabling disease of the central nervous system. OCT (Optical Coherence Tomography) and OCT-A (Optical Coherence Tomography with Angiography) are imaging techniques for the retina and choroid that are used in the diagnosis and monitoring of ophthalmological conditions. Their use has recently expanded the study of several autoimmune disorders, including MS. Although their application in MS remains unclear, the results seem promising. This review aimed to provide insight into the most recent OCT and OCT-A findings in MS and may function as a reference point for future research. According to the current literature, the retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform complex (GC-IPL) are significantly reduced in people with MS and are inversely correlated with disease duration. The use of OCT might help distinguish between MS and neuromyelitis optica spectrum disorders (NMOSD), as the latter presents with more pronounced thinning in both the RNFL and GC-IPL. The OCT-A findings in MS include reduced vessel density in the macula, peripapillary area, or both, and the enlargement of the foveal avascular zone (FAZ) in the setting of optic neuritis. Additionally, OCT-A might be able to detect damage in the very early stages of the disease as well as disease progression in severe cases.

What scans see when patients see defects: neuroimaging findings in body dysmorphic disorder.

Body dysmorphic disorder (BDD) is characterized by an individual's preoccupation with a perceived defect in their appearance which to others may be barely noticeable or even completely unnoticed. It confers significant disturbances of everyday functioning in affected persons. The present review study provides an overview of neuroimaging findings on BDD. Literature on three platforms, PubMed, Google Scholar and PsycArticles of APA PsycNet, was searched for studies on patients with BBD compared with healthy controls (HCs), with a focus on neuroimaging findings. Out of an initial yield of 414 articles, 23 fulfilled inclusion criteria and were reviewed. Among the most remarkable findings were functional abnormalities in visual processing, frontostriatal and limbic systems, reduced global efficiency of White Matter (WM) connectivity, reduced cortical thickness in temporal and parietal lobes, and correlations between these neuroimaging findings and clinical variables such as symptom severity and degree of insight. Structural, volumetric and functional neuroimaging findings in BDD affected persons may help shed light on the pathophysiology and neurobiological underpinnings of this condition. Future studies should further investigate the use of imaging findings as potential prognostic biomarkers of treatment efficacy and disease outcome.

Psychopharmacology of patients with multiple sclerosis in Greece during the period 2017-2019.

Multiple Sclerosis (MS) is highly comorbid with mental disorders in any disease stage, while psychiatric manifestations may precede the onset of neurological symptoms as well as diagnosis. Neuropsychiatric comorbidities are associated with an elevated risk of MS disability progression, and therefore, people with multiple sclerosis (PwMS) with psychiatric comorbidities often experience a significantly lower functional status, perform worse in objective neuropsychological assessment, are less likely to adhere to pharmacological treatment, and exhibit higher levels of disruption of their supportive social environment as compared with "non-psychiatric" PwMS. The present study aims to estimate the nationwide use of psychopharmacological agents by PwMS in Greece. Prescription records of the nationwide digital prescription database were analyzed, in order to identify PwMS that have received prescriptions of an antipsychotic, an antidepressant, an anxiolytic or a psychostimulant during a 2-year study period. Pseudo-anonymized prescription records of PwMS (n=21218) were extracted from the Greek nationwide prescription database, dating from June 2017 to May 2019. According to this national level study, psychopharmacological agents are frequently prescribed in PwMS. Antidepressants were prescribed in 36.1% of the study sample, followed by anxiolytics (16.23%), psychostimulants (4.97%) and antipsychotics (3.76%). The proportion of patients under treatment with these agents was increasing with age. Selective serotonin reuptake inhibitors, second generation antipsychotics and benzodiazepines were the most often prescribed agents in each drug category and especially in younger age groups, possibly indicating a better efficacy/side-effect equilibrium, while modafinil was the only psychostimulant prescribed aiming to ameliorate levels of fatigue. A pharmacological preference for antidepressants and psychostimulants was observed in the 40-60 age group (p = 0.02), while antipsychotics and anxiolytics were more frequently prescribed in the >60 age group (p<0.001). Serotonin-norepinephrine reuptake inhibitors were mostly prescribed within the 40-60 age-group. Benzodiazepines were less favored among the >60 age-group. This study highlights the increased prevalence of mental disorders in this patient group. Adequate treatment and monitoring of psychiatric symptomatology, may improve long-term outcomes of the disease, however caution is needed regarding potential drug interactions and side effects.

Oxidative Stress and Neurodegeneration: Interconnected Processes in PolyQ Diseases.

Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.

A Greek Validation Study of the Multiple Sclerosis Work Difficulties Questionnaire-23.

The Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23) is a self-report instrument developed to assess barriers faced by People with Multiple Sclerosis (PwMS) in the workplace. The aim of this study was to explore the psychometric properties of the Greek version of the MSWDQ-23. The study sample consisted of 196 PwMS, all currently working in part- or full-time jobs. Participants underwent clinical examination and cognitive screening with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and completed self-report measures of fatigue, psychological functioning, and quality of life, along with the MSWDQ-23 questionnaire. Confirmatory Factor Analysis (CFA) was performed, and goodness-of-fit measures were used to evaluate construct validity. Convergent validity was checked by correlating MSWDQ-23 scores with study measures. Cronbach's alpha value was produced to assess internal consistency. CFA yielded a model with a fair fit confirming the three-factor structure of the instrument. Higher work difficulties were associated with higher Expanded Disability Status Scale (EDSS) scores, poorer cognitive function, more fatigue, stress, anxiety, and depression, and poorer health status, supporting the convergent validity of MSWDQ-23. Internal consistency (Cronbach's alpha = 0.94) and test-retest reliability (ICC = 0.996, 95%, CI = 0.990-0.998) were excellent. The Greek MSWDQ-23 can be considered a valid patient-reported outcome measure and can be used in interventions aiming to improve the vocational status of PwMS.

Spastic gait, intellectual disability and seizures due to a rare mutation causing hyperargininemia.

Hyperargininemia is an autosomal recessive disorder caused by a defect in the arginase I enzyme. We present a case of a 20-year-old male with severe spastic gait, intellectual disability and seizures. Metabolic tests revealed high levels of arginine in blood serum. Hyperargininemia was attributed to a likely pathogenic rare mutation of ARG1 gene [Chr6: g131905002_131905002 G>A (p.Arg308Gln) homozygous] detected in Whole Exome Sequencing resulting in deficiency in arginase I enzyme. Following the diagnosis, the patient has been treated with low protein diet, aminoacid and vitamin supplements. The accumulation of arginine, may contribute to the pathogenesis of severe neurological manifestations, however, low protein intake diet may lead to a favorable outcome. Therefore, clinicians should screen for hyperargininemia in early childhood in case of strong clinical suspicion.

Brief international cognitive assessment for multiple sclerosis (BICAMS) cut-off scores for detecting cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) affects 35-65% of multiple sclerosis (MS) patients. The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been proposed as a highly feasible and cost-effective tool for cognitive impairment (CI) screening in MS. The tool yields scores that should, ideally, readily convey patients' cognitive status to the clinicians. METHODS: To this aim, this study sought for cut-off scores of the three BICAMS test in a sample of 960 MS patients. We used three definitions for CI: 1.5, 1,65 and 2 standard deviations below the mean. Receiver operating characteristic (ROC) statistics helped us determine the capacity of BICAMS to diagnose CI. Optimal cut-offs were determined by the delta distance. Positive and negative predictive values, along with overall accuracy were also calculated. RESULTS: Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test-II (CVLT-II) showed a diagnostic accuracy ranging from 74.6 to 77.4%, across the three CI definitions. The accuracy of Brief Visuospatial Memory Test-Revised (BVMT-R) was over 88%. SDMT had a balanced sensitivity, while CVLT-II and BVMT-R had higher specificities than sensitivities at detecting CI. More specifically, BVMT-R showed 100% specificity for all CI definitions. Raw cut-off scores for BICAMS tests are also provided within the manuscript, along with the diagnostic calculations. CONCLUSIONS: In this study, we confirmed that BICAMS is a good screening tool for CI and that simple cut-offs can be used in the everyday neurological practice.