Evidence for a single-layer van der Waals multiferroic.

Multiferroic materials have attracted wide interest because of their exceptional static1-3 and dynamical4-6 magnetoelectric properties. In particular, type-II multiferroics exhibit an inversion-symmetry-breaking magnetic order that directly induces ferroelectric polarization through various mechanisms, such as the spin-current or the inverse Dzyaloshinskii-Moriya effect3,7. This intrinsic coupling between the magnetic and dipolar order parameters results in high-strength magnetoelectric effects3,8. Two-dimensional materials possessing such intrinsic multiferroic properties have been long sought for to enable the harnessing of magnetoelectric coupling in nanoelectronic devices1,9,10. Here we report the discovery of type-II multiferroic order in a single atomic layer of the transition-metal-based van der Waals material NiI2. The multiferroic state of NiI2 is characterized by a proper-screw spin helix with given handedness, which couples to the charge degrees of freedom to produce a chirality-controlled electrical polarization. We use circular dichroic Raman measurements to directly probe the magneto-chiral ground state and its electromagnon modes originating from dynamic magnetoelectric coupling. Combining birefringence and second-harmonic-generation measurements with theoretical modelling and simulations, we detect a highly anisotropic electronic state that simultaneously breaks three-fold rotational and inversion symmetry, and supports polar order. The evolution of the optical signatures as a function of temperature and layer number surprisingly reveals an ordered magnetic polar state that persists down to the ultrathin limit of monolayer NiI2. These observations establish NiI2 and transition metal dihalides as a new platform for studying emergent multiferroic phenomena, chiral magnetic textures and ferroelectricity in the two-dimensional limit.

Position and momentum mapping of vibrations in graphene nanostructures.

Propagating atomic vibrational waves-phonons-determine important thermal, mechanical, optoelectronic and transport characteristics of materials. Thus a knowledge of phonon dispersion (that is, the dependence of vibrational energy on momentum) is a key part of our understanding and optimization of a material's behaviour. However, the phonon dispersion of a free-standing monolayer of a two-dimensional material such as graphene, and its local variations, have remained elusive for the past decade because of the experimental limitations of vibrational spectroscopy. Even though electron energy loss spectroscopy (EELS) in transmission has recently been shown to probe local vibrational charge responses1-4, such studies are still limited by momentum space integration due to the focused beam geometry; they are also restricted to polar materials such as boron nitride or oxides1-4, in which huge signals induced by strong dipole moments are present. On the other hand, measurements on graphene performed by inelastic X-ray (neutron) scattering spectroscopy5-7 or EELS in reflection8,9 do not have any spatial resolution and require large microcrystals. Here we provide a new pathway to determine phonon dispersions down to the scale of an individual free-standing graphene monolayer by mapping the distinct vibrational modes for a large momentum transfer. The measured scattering intensities are accurately reproduced and interpreted with density functional perturbation theory10. Additionally, a nanometre-scale mapping of selected momentum-resolved vibrational modes using graphene nanoribbon structures has enabled us to spatially disentangle bulk, edge and surface vibrations. Our results are a proof-of-principle demonstration of the feasibility of studying local vibrational modes in two-dimensional monolayer materials at the nanometre scale.

Clinical, prognostic and pathophysiological implications of MOG-IgG detection in the CSF: the importance of intrathecal MOG-IgG synthesis.

BACKGROUND: Cerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS). METHODS: We retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF- and ITS+/ITS- patients. RESULTS: MOG-IgG were found in 55/960 patients (5.7%; serum+/CSF-: 58.2%, serum+/CSF+: 34.5%; serum-/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI -0.46 to -0.65), p=0.65). There were no clinical-paraclinical differences between MOG-IgG CSF+ vs CSF- patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01). CONCLUSIONS: Consistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

Does sex influence the natural history of idiopathic adult-onset dystonia?

BACKGROUND: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread. OBJECTIVE: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD. METHODS: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed. RESULTS: Women predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia. CONCLUSIONS: Our findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.

Direct Current Stimulation of Prefrontal Cortex Is Not Effective in Progressive Supranuclear Palsy: A Randomized Trial.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare 4R-tauopathy. Transcranial direct current stimulation (tDCS) may improve specific symptoms. OBJECTIVES: This randomized, double-blinded, sham-controlled trial aimed at verifying the short-, mid-, and long-term effect of multiple sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) cortex in PSP. METHODS: Twenty-five patients were randomly assigned to active or sham stimulation (2 mA for 20 minute) for 5 days/week for 2 weeks. Participants underwent assessments at baseline, after the 2-week stimulation protocol, then after 45 days and 3 months from baseline. Primary outcomes were verbal and semantic fluency. The efficacy was verified with analysis of covariance. RESULTS: We failed to detect a significant effect of active stimulation on primary outcomes. Stimulation was associated to worsening of specific behavioral complaints. CONCLUSIONS: A 2-week protocol of anodal left DLPFC tDCS is not effective in PSP. Specific challenges in running symptomatic clinical trials with classic design are highlighted. © 2024 International Parkinson and Movement Disorder Society.

Psychometric properties of the Caregiver's inventory neuropsychological diagnosis dementia (CINDD) in mild cognitive impairment and dementia.

OBJECTIVES: The Caregiver's Inventory Neuropsychological Diagnosis Dementia (CINDD) is an easy tool designed to quantify cognitive, behavioural and functional deficits of patients with cognitive impairment. Aim of the present study was to analyse the psychometric properties of the CINDD in Mild Cognitive Impairment (MCI) and Dementia (D). DESIGN, SETTING AND PARTICIPANTS: The CINDD, composed by 9 sub-domains, was administered to fifty-six caregivers of patients with different types of dementia (D) and 44 caregivers of patients with MCI. All patients underwent an extensive neuropsychological assessment, the Neuropsychiatric Inventory (NPI) and functional autonomy scales. The reliability, convergent construct validity and possible cut-off of CINND were measured by Cronbach's alpha (α), Pearson's correlation and ROC analysis, respectively. RESULTS: The D and MCI patients differed only for age (p=0.006). The internal consistency of CINDD was high (α= 0.969). The α-value for each CINDD domain was considered acceptable, except the mood domain (α=0.209). The CINDD total score correlated with cognitive screening tests; each domain of the CINDD correlated with the corresponding score from either tests or NPI (p<0.05), except for visuo-spatial perception skills and apathy. A screening cut-off equal to 59, can be used discriminate D from MCI (Sensitivity=0.70, Specificity=0.57). CONCLUSION: The CINDD is a feasible, accurate and reliable tool for the assessment of cognitive and behavioural difficulties in patients with different degree of cognitive impairment. It may be used to quantify and monitor caregiver-reported ecological data in both clinical and research settings.

Validation of the Italian version of the Parkinson's Disease- Cognitive Functional Rating Scale.

A key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson's disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson's Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the influence of motor impairment. The aim of this multicenter study was to (i) validate the Italian version of the PD-CFRS in PD, (ii) determine optimal cut-off scores for detecting MCI and dementia in PD, (iii) compare its performances with the most established functional assessment tool (IADL). Six hundred and sixty nine PD participants were recruited from 4 Italian Movement Disorders centers (Venice, Milan, Gravedona, and Salerno). They underwent Level-II cognitive evaluation, which resulted in 282 PD-NC, 310 PD-MCI, and 77 PDD. The PD-CFRS's psychometric and clinimetric properties, applicability, and responsiveness were analyzed. The PD-CFRS showed high acceptability. Floor and ceiling effects were acceptable. It also displayed strong internal consistency (Cronbach's α = 0.738), and test-retest reliability (ICC = .854). The PD-CFRS demonstrated higher coefficient of variation to detect dysfunction in PD-MCI patients in comparison to the IADL scale (PD-CFRS 96% vs IADL 22.5%). Convergent validity with the IADL was r = - 0.638 and - 0.527 in males and females, respectively. PD-CFRS total score negatively correlated with global cognition (MoCA corrected score r = - 0.61; p < 0.001). A cut-off score > 6.5 identified PDD with a sensitivity of 90% and specificity of 88% (AUC = .959). A cut-off value of > 1 detected PD-MCI with a sensitivity of 68% and specificity of 69% (AUC = .695). The Italian version of the PD-CFRS demonstrated to be an easy, valid and reliable tool that properly captures functional impairment due to cognitive decline in PD. It also proved to be particularly effective in the advanced stages of PD, and would be a useful support for the diagnosis of PD-MCI and PDD.

Does thyroid diseases contribute to the natural history of idiopathic adult-onset dystonia? Data from the Italian Dystonia Registry.

A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5-12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99-3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.

Electron doping as a handle to increase the Curie temperature in ferrimagnetic Mn3Si2X6 (X = Se, Te).

By analysing the results of ab initio simulations performed for Mn3Si2X6 (X = Se, Te), we first discuss the analogies and the differences in electronic and magnetic properties arising from the anion substitution, in terms of size, electronegativity, band widths of p electrons and spin-orbit coupling strengths. For example, through mean-field theory and simulations based on density functional theory, we demonstrate that magnetic frustration, known to be present in Mn3Si2Te6, also exists in Mn3Si2Se6 and leading to a ferrimagnetic ground state. Building on these results, we propose a strategy, electronic doping, to reduce the frustration and thus to increase the Curie temperature (TC). To this end, we first study the effect of electronic doping on the electronic structure and magnetic properties and discuss the differences in the two compounds, along with their causes. Secondly, we perform Monte-Carlo simulations, considering from the first to the fifth nearest-neighbor magnetic interactions and single-ion anisotropy, and show that electron doping efficiently raises the TC.

Development of the Digital Inclusion Questionnaire (DIQUEST) in Parkinson's Disease.

BACKGROUND: No tool is currently able to measure digital inclusion in clinical populations suitable for telemedicine. We developed the "Digital Inclusion Questionnaire" (DIQUEST) to estimate access and skills in Parkinson's Disease (PD) patients and verified its properties with a pilot study. METHODS: Thirty PD patients completed the initial version of the DIQUEST along with the Mobile Device Proficiency Questionnaire (MDPQ) and a practical computer task. A Principal Components Analysis (PCA) was conducted to define the DIQUEST factor structure and remove less informative items. We used Cronbach's α to measure internal reliability and Spearman's correlation test to determine the convergent and predictive validity with the MDPQ and the practical task, respectively. RESULTS: The final version of the DIQUEST consisted of 20 items clustering in five components: "advanced skills," "navigation skills," "basic skills/knowledge," "physical access," and "economical access." All components showed high reliability (α > 0.75) as did the entire questionnaire (α = 0.94). Correlation analysis demonstrated high convergent (rho: 0.911; p<0.001) and predictive (rho: 0.807; p<0.001) validity. CONCLUSIONS: We have here presented the development of the DIQUEST as a screening tool to assess the level of digital inclusion, particularly addressing the access and skills domains. Future studies are needed for its validation beyond PD.

Longitudinal change of energy expenditure, body composition and dietary habits in Progressive Supranuclear Palsy patients.

INTRODUCTION: Alterations in metabolic status, body composition, and food intake are present in all neurodegenerative diseases. Aim of this study was to detect the progression of these changes in Progressive Supranuclear Palsy (PSP). METHODS: We conducted a longitudinal study of 15 patients with PSP. The assessments were performed at baseline (T0) and after 7(IQR = 5) months of follow-up (T1). We collected anthropometric measures including body weight, height, body mass index and waist circumference, metabolic parameters through indirect calorimeters, body composition using bioimpedance analysis, and dietary habits with a validated questionnaire. PSP-rating scale (PSP-rs) was used to evaluate disease severity and dysphagia. RESULTS: The majority of patients (66.66%) presented PSP-Richardson Syndrome and 33.33% the other variant syndromes of the disease. At T1 there was a decrease in intake of total daily calories (p < 0.001), proteins (p < 0.001), fibers (p = 0.001), calcium (p = 0.008), iron (p < 0.001), zinc (0.034), vitamin E (p = 0.006) and folates (p = 0.038) compared to T0. No other changes were found. As for T1 data, no significant differences were shown according to disease phenotypes or the presence of clinically significant dysphagia for solids. CONCLUSIONS: Within a mid-term follow up, PSP patients presented reduced caloric and proteins intake regardless the presence of dysphagia. The PSP-rs is likely not adequate to assess dysphagia, which should be investigated by specific clinical scales or instrumental examinations. With the goal of maintaining adequate nutritional status, the administration of protein and vitamin supplements should be considered even in the absence of dysphagia evidenced by the rating scales.

Bariatric surgery and dimethyl fumarate-induced lymphopenia in patients with multiple sclerosis.

INTRODUCTION: Lymphopenia is a known side effect of dimethyl fumarate (DMF), a disease-modifying therapy (DMT) for patients with multiple sclerosis (pwMS). A body mass index ≥ 30 kg/m2 has been identified as a protective factor; however, no data are available on lymphopenia in pwMS undergoing to weight loss due to bariatric surgery. METHODS: We described two pwMS with history of bariatric surgery who started DMF as DMT. RESULTS: The two pwMS experienced persistent lymphopenia during DMF-treatment, which was resolved after its discontinuation. CONCLUSIONS: Several mechanisms might modify DMF pharmacokinetic profiles after bariatric surgery and its bioavailability. Absolute lymphocyte count should be monitored in pwMS treated with DMF and history of bariatric surgery and weight loss.

Anti-pan-neurofascin nodopathy: cause of fulminant neuropathy.

Autoimmune nodopathies are inflammatory diseases of the peripheral nervous system with clinical and neurophysiological peculiar characteristics. In this nosological category, we find patients with autoantibodies against Neurofascin 140/186 and 155, Contactin1, and Caspr1 directed precisely towards nodal and paranodal structures. These antibodies are extremely rare and cause severe clinical symptoms. We describe the clinical case of a patient with autoimmune nodopathy caused by the coexistence of anti-neurofascin (NF) 186/140 and 155, characterized by progressive weakness in all limbs leading to tetraplegia, involving cranial nerves, and respiratory insufficiency. Response to first-line treatments was good followed by rapid dramatic clinical relapse. There are few reported cases of anti-pan NF neuropathy in the literature, and they present a clinical phenotype similar to our patient. In these cases, early recognition of clinical red flags of nodopathies and serial neurophysiological studies can facilitate the diagnosis. However, the severe clinical relapse suggests a possible early use of immunosuppressive therapies for this rare category of patients.

Oromandibular dystonia: from onset to spread a multicenter italian study.

BACKGROUND: Detailed information about the epidemiological and phenomenological differences among the aetiological subtypes of oromandibular dystonia (OMD) is lacking. Moreover, the OMD tendency to spread to other body sites has never been investigated. AIM: To compare the main demographic and clinical features of OMD in different aetiological groups and assess the risk of spread. MATERIALS AND METHODS: We retrospectively analysed data from patients contained in the Italian Dystonia Registry. The risk of spread was assessed by Kaplan Meyer curves and Cox regression analysis. RESULTS: The study included 273 patients (175 women) aged 55.7 years (SD 12.7) at OMD onset. Female predominance was observed. Idiopathic dystonia was diagnosed in 241 patients, acquired dystonia in 22. In 50/273 patients, dystonia started in the oromandibular region (focal OMD onset); in 96/273 patients the onset involved the oromandibular region and a neighbouring body site (segmental/multifocal OMD onset); and in 127/273 patients OMD was a site of spread from another body region. Sensory trick (ST) and positive family history predominated in the idiopathic group. No dystonia spread was detected in the acquired group, whereas spread mostly occurred within the first five years of history in 34% of the focal OMD onset idiopathic patients. Cox regression analysis revealed ST as a significant predictor of spread (HR, 12.1; 95% CI, 2.5 - 18.8; P = 0.002). CONCLUSION: This large study provides novel information about the clinical phenomenology of idiopathic and acquired OMD. We pointed out a possible role of oestrogens in favouring dystonia development. Moreover, we described for the first time the association between ST and dystonia spread, revealing possible common pathophysiological mechanisms. Our findings may be suggested as a referral point for future pathophysiological and therapeutic studies on OMD.

Excitonic Effects in Energy-Loss Spectra of Freestanding Graphene.

In this work, we perform electron energy-loss spectroscopy (EELS) of freestanding graphene with high energy and momentum resolution to disentangle the quasielastic scattering from the excitation gap of Dirac electrons close to the optical limit. We show the importance of many-body effects on electronic excitations at finite transferred momentum by comparing measured EELS to ab initio calculations at increasing levels of theory. Quasi-particle corrections and excitonic effects are addressed within the GW approximation and the Bethe-Salpeter equation, respectively. Both effects are essential in the description of the EEL spectra to obtain a quantitative agreement with experiments, with the position, dispersion, and shape of both the excitation gap and the π plasmon being significantly affected by excitonic effects.

Magnetic Resonance T1w/T2w Ratio in the Putamen and Cerebellum as a Marker of Cognitive Impairment in MSA: a Longitudinal Study.

The exact pathophysiology of cognitive impairment in multiple system atrophy (MSA) is unclear. In our longitudinal study, we aimed to analyze (I) the relationships between cognitive functions and some subcortical structures, such as putamen and cerebellum assessed by voxel-based morphometry (VBM) and T1-weighted/T2-weighted (T1w/T2w) ratio, and (II) the neuroimaging predictors of the progression of cognitive deficits. Twenty-six patients with MSA underwent a comprehensive neuropsychological battery, motor examination, and brain MRI at baseline (T0) and 1-year follow-up (T1). Patients were then divided according to cognitive status into MSA with normal cognition (MSA-NC) and MSA with mild cognitive impairment (MCI). At T1, we divided the sample according to worsening/non worsening of cognitive status compared to baseline evaluation. Logistic regression analysis showed that age (ß = - 9.45, p = .02) and T1w/T2w value in the left putamen (ß = 230.64, p = .01) were significant predictors of global cognitive status at T0, explaining 65% of the variance. Logistic regression analysis showed that ∆-values of WM density in the cerebellum/brainstem (ß = 2188.70, p = .02) significantly predicted cognitive worsening at T1, explaining 64% of the variance. Our results suggest a role for the putamen and cerebellum in the cognitive changes of MSA, probably due to their connections with the cortex. The putaminal T1w/T2w ratio may deserve further studies as a marker of cognitive impairment in MSA.

Frequency and imaging correlates of neuropsychiatric symptoms in Progressive Supranuclear Palsy.

Neuropsychiatric symptoms are intrinsic to Progressive Supranuclear Palsy (PSP) and a spoonful of studies investigated their imaging correlates. Describe (I) the frequency and severity of neuropsychiatric symptoms in PSP and (II) their structural imaging correlates. Twenty-six PSP patients underwent Neuropsychiatric Inventory (NPI) and brain 3D T1-weighted MRI. Spearman's rho with Bonferroni correction was used to investigate correlations between NPI scores and volumes of gray matter regions. More than 80% of patients presented at least one behavioral symptom of any severity. The most frequent and severe were depression/dysphoria, apathy, and irritability/lability. Significant relationships were found between the severity of irritability and right pars opercularis volume (p < 0.001) as well as between the frequency of agitation/aggression and left lateral occipital volume (p < 0.001). Depression, apathy, and irritability are the most common neuropsychiatric symptoms in PSP. Moreover, we found a relationship between specific positive symptoms as irritability and agitation/aggression and greater volume of the right pars opercularis cortex and lower volume of the left occipital cortex, respectively, which deserve further investigations.

Synthesis and Magnetic Properties of the Multiferroic [C(NH2)3]Cr(HCOO)3 Metal-Organic Framework: The Role of Spin-Orbit Coupling and Jahn-Teller Distortions.

We report for the first time the synthesis of [C(NH2)3]Cr(HCOO)3 stabilizing Cr2+ in formate perovskite, which adopts a polar structure and orders magnetically below 8 K. We discuss in detail the magnetic properties and their coupling to the crystal structure based on first-principles calculations, symmetry, and model Hamiltonian analysis. We establish a general model for the orbital magnetic moment of [C(NH2)3]M(HCOO)3 (M = Cr, Cu) based on perturbation theory, revealing the key role of the Jahn-Teller distortions. We also analyze their spin and orbital textures in k-space, which show unique characteristics.

Higher Health Service Costs Associated With Delayed Diagnosis of Functional Neurological Disorder.

OBJECTIVE: Functional neurological disorder (FND) is frequently encountered in clinical practice but commonly misdiagnosed, which might lead to higher direct costs for the health care system. The investigators analyzed the direct costs associated with the diagnosis of FND compared with costs associated with other neurological conditions and explored possible cost trends related to the clinical and demographic features of FND. METHODS: Consecutive patients attending a general neurology clinic were recruited and underwent a structured assessment aimed to collect information pertaining to their demographic and clinical characteristics, as well as data regarding their prior diagnostic processes (e.g., the number of consulted specialists, number and type of investigations, emergency department visits, etc.). The costs were hence calculated and compared between the study groups. RESULTS: A total of 155 consecutive patients were recruited; of these, 18.6% had FND, 55.84% had one or more other neurological disorder (OND), and 27.10% presented with comorbid FND and OND. The total prediagnostic costs (in euros [€]) were higher in the FND group compared with the OND group (median=€289, interquartile range [IQR] €385 vs. median=€98, IQR €216; Mann-Whitney U=879.5, p=0.04). There was a higher diagnostic delay in the FND group compared with the OND group (median=48 months, IQR 60 months vs. median=12 months, IQR 6 months; Mann-Whitney U=162.00, p<0.01). Diagnostic delay significantly correlated with the total costs in the entire study sample (Spearman's ρ=0.25, p=0.003) but more strongly in the FND group (Spearman's ρ=0.81, p<0.001). In the FND group, higher numbers of investigations and costs were associated with the presence of a physiological or psychological trigger and multiple symptoms. CONCLUSIONS: Delayed diagnosis of FND significantly affects health care system costs, and raising awareness about FND to improve the diagnostic process and outcomes is necessary.