The Impact of Cytomegalovirus Infection on Natural Killer and CD8+ T Cell Phenotype in Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating neurological disease that has been classified as an immune-mediated attack on myelin, the protective sheath of nerves. Some aspects of its pathogenesis are still unclear; nevertheless, it is generally established that viral infections influence the course of the disease. Cytomegalovirus (CMV) is a major pathogen involved in alterations of the immune system, including the expansion of highly differentiated cytotoxic CD8+ T cells and the accumulation of adaptive natural killer (NK) cells expressing high levels of the NKG2C receptor. In this study, we evaluated the impact of latent CMV infection on MS patients through the characterization of peripheral NK cells, CD8+ T cells, and NKT-like cells using flow cytometry. We evaluated the associations between immune cell profiles and clinical features such as MS duration and MS progression, evaluated using the Expanded Disability Status Scale (EDSS). We showed that NK cells, CD8+ T cells, and NKT-like cells had an altered phenotype in CMV-infected MS patients and displayed high levels of the NKG2C receptor. Moreover, in MS patients, increased NKG2C expression levels were found to be associated with higher EDSS scores. Overall, these results support the hypothesis that CMV infection imprints the immune system by modifying the phenotype and receptor repertoire of NK and CD8+ T cells, suggesting a detrimental role of CMV on MS progression.

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.

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.

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.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

BACKGROUND: Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. OBJECTIVE: To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. METHODS: We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. RESULTS: Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). CONCLUSIONS: These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

Cladribine and ocrelizumab induce differential miRNA profiles in peripheral blood mononucleated cells from relapsing-remitting multiple sclerosis patients.

Background and objectives: Multiple sclerosis (MS) is a chronic, progressive neurological disease characterized by early-stage neuroinflammation, neurodegeneration, and demyelination that involves a spectrum of heterogeneous clinical manifestations in terms of disease course and response to therapy. Even though several disease-modifying therapies (DMTs) are available to prevent MS-related brain damage-acting on the peripheral immune system with an indirect effect on MS lesions-individualizing therapy according to disease characteristics and prognostic factors is still an unmet need. Given that deregulated miRNAs have been proposed as diagnostic tools in neurodegenerative/neuroinflammatory diseases such as MS, we aimed to explore miRNA profiles as potential classifiers of the relapsing-remitting MS (RRMS) patients' prospects to gain a more effective DMT choice and achieve a preferential drug response. Methods: A total of 25 adult patients with RRMS were enrolled in a cohort study, according to the latest McDonald criteria before (pre-cladribine, pre-CLA; pre-ocrelizumab, pre-OCRE, time T0) and after high-efficacy DMTs, time T1, 6 months post-CLA (n = 10, 7 F and 3 M, age 39.0 ± 7.5) or post-OCRE (n = 15, 10 F and 5 M, age 40.5 ± 10.4) treatment. A total of 15 age- and sex-matched healthy control subjects (9 F and 6 M, age 36.3 ± 3.0) were also selected. By using Agilent microarrays, we analyzed miRNA profiles from peripheral blood mononuclear cells (PBMC). miRNA-target networks were obtained by miRTargetLink, and Pearson's correlation served to estimate the association between miRNAs and outcome clinical features. Results: First, the miRNA profiles of pre-CLA or pre-OCRE RRMS patients compared to healthy controls identified modulated miRNA patterns (40 and seven miRNAs, respectively). A direct comparison of the two pre-treatment groups at T0 and T1 revealed more pro-inflammatory patterns in the pre-CLA miRNA profiles. Moreover, both DMTs emerged as being capable of reverting some dysregulated miRNAs toward a protective phenotype. Both drug-dependent miRNA profiles and specific miRNAs, such as miR-199a-3p, miR-29b-3p, and miR-151a-3p, emerged as potentially involved in these drug-induced mechanisms. This enabled the selection of miRNAs correlated to clinical features and the related miRNA-mRNA network. Discussion: These data support the hypothesis of specific deregulated miRNAs as putative biomarkers in RRMS patients' stratification and DMT drug response.

Phenotypic Variability in Acquired and Idiopathic Dystonia.

Background: To date, a few studies have systematically investigated differences in the clinical spectrum between acquired and idiopathic dystonias. Objectives: To compare demographic data and clinical features in patients with adult-onset acquired and idiopathic dystonias. Methods: Patients were identified from among those included in the Italian Dystonia Registry, a multicenter Italian dataset of patients with adult-onset dystonia. Study population included 116 patients with adult-onset acquired dystonia and 651 patients with isolated adult-onset idiopathic dystonia. Results: Comparison of acquired and idiopathic dystonia revealed differences in the body distribution of dystonia, with oromandibular dystonia, limb and trunk dystonia being more frequent in patients with acquired dystonia. The acquired dystonia group was also characterized by lower age at dystonia onset, greater tendency to spread, lower frequency of head tremor, sensory trick and eye symptoms, and similar frequency of neck pain associated with CD and family history of dystonia/tremor. Conclusions: The clinical phenomenology of dystonia may differ between acquired and idiopathic dystonia, particularly with regard to the body localization of dystonia and the tendency to spread. This dissimilarity raises the possibility of pathophysiological differences between etiologic categories.

Neurophysiological and clinical biomarkers of secondary progressive multiple sclerosis: A cross-sectional study.

Timely diagnosis of secondary progressive multiple sclerosis (SPMS) represents a clinical challenge. The Frailty Index, a quantitative frailty measure, and the Neurophysiological Index, a combined measure of sensorimotor cortex inhibitory mechanism parameters, have recently emerged as promising tools to support SPMS diagnosis. The aim of this study was to explore the possible relationship between these two indices in MS. MS participants underwent a clinical evaluation, Frailty Index administration, and neurophysiological assessment. Frailty and Neurophysiological Index scores were found to be higher in SPMS and correlated with each other, thus suggesting that they may capture similar SPMS-related pathophysiological mechanisms.

Evaluation of BAFF, APRIL and CD40L in Ocrelizumab-Treated pwMS and Infectious Risk.

BACKGROUND: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. METHODS: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. RESULTS: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p < 0.0001), APRIL (p = 0.0223) and CD40L (p < 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p < 0.0001 and p < 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p < 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p < 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk.

Cortico-Subcortical White Matter Bundle Changes in Cervical Dystonia and Blepharospasm.

Dystonia is thought to be a network disorder due to abnormalities in the basal ganglia-thalamo-cortical circuit. We aimed to investigate the white matter (WM) microstructural damage of bundles connecting pre-defined subcortical and cortical regions in cervical dystonia (CD) and blepharospasm (BSP). Thirty-five patients (17 with CD and 18 with BSP) and 17 healthy subjects underwent MRI, including diffusion tensor imaging (DTI). Probabilistic tractography (BedpostX) was performed to reconstruct WM tracts connecting the globus pallidus, putamen and thalamus with the primary motor, primary sensory and supplementary motor cortices. WM tract integrity was evaluated by deriving their DTI metrics. Significant differences in mean, radial and axial diffusivity between CD and HS and between BSP and HS were found in the majority of the reconstructed WM tracts, while no differences were found between the two groups of patients. The observation of abnormalities in DTI metrics of specific WM tracts suggests a diffuse and extensive loss of WM integrity as a common feature of CD and BSP, aligning with the increasing evidence of microstructural damage of several brain regions belonging to specific circuits, such as the basal ganglia-thalamo-cortical circuit, which likely reflects a common pathophysiological mechanism of focal dystonia.

Frailty and relapse activity in multiple sclerosis: A longitudinal observation.

Recent cross-sectional investigations suggest a relationship between frailty, as measured by Frailty Index (FI), and multiple sclerosis (MS). However, if and how frailty is associated with relapse activity in MS is still unknown. To explore this issue, a one-year follow-up study involving 471 patients was conducted. A univariate regression model showed an inverse association between baseline FI score and the presence of relapse, which was also confirmed in the multivariate model. These results suggest that frailty may reflect pathophysiological mechanisms involved in MS disease activity and that the FI may be used as an enrichment criterion in clinical trials.

Neural bases of motor fatigue in multiple sclerosis: A multimodal approach using neuromuscular assessment and TMS-EEG.

Motor fatigue is one of the most common symptoms in multiple sclerosis (MS) patients. Previous studies suggested that increased motor fatigue in MS may arise at the central nervous system level. However, the mechanisms underlying central motor fatigue in MS are still unclear. This paper investigated whether central motor fatigue in MS reflects impaired corticospinal transmission or suboptimal primary motor cortex (M1) output (supraspinal fatigue). Furthermore, we sought to identify whether central motor fatigue is associated with abnormal M1 excitability and connectivity within the sensorimotor network. Twenty-two patients affected by relapsing-remitting MS and 15 healthy controls (HCs) performed repeated blocks of contraction at different percentages of maximal voluntary contraction with the right first dorsal interosseus muscle until exhaustion. Peripheral, central, and supraspinal components of motor fatigue were quantified by a neuromuscular assessment based on the superimposed twitch evoked by peripheral nerve and transcranial magnetic stimulation (TMS). Corticospinal transmission, excitability and inhibition during the task were tested by measurement of motor evoked potential (MEP) latency, amplitude, and cortical silent period (CSP). M1 excitability and connectivity was measured by TMS-evoked electroencephalography (EEG) potentials (TEPs) elicited by M1 stimulation before and after the task. Patients completed fewer blocks of contraction and showed higher values of central and supraspinal fatigue than HCs. We found no MEP or CSP differences between MS patients and HCs. Patients showed a post-fatigue increase in TEPs propagation from M1 to the rest of the cortex and in source-reconstructed activity within the sensorimotor network, in contrast to the reduction observed in HCs. Post-fatigue increase in source-reconstructed TEPs correlated with supraspinal fatigue values. To conclude, MS-related motor fatigue is caused by central mechanisms related explicitly to suboptimal M1 output rather than impaired corticospinal transmission. Furthermore, by adopting a TMS-EEG approach, we proved that suboptimal M1 output in MS patients is associated with abnormal task-related modulation of M1 connectivity within the sensorimotor network. Our findings shed new light on the central mechanisms of motor fatigue in MS by highlighting a possible role of abnormal sensorimotor network dynamics. These novel results may point to new therapeutical targets for fatigue in MS.

Exploring the Central Mechanisms of Botulinum Toxin in Parkinson's Disease: A Systematic Review from Animal Models to Human Evidence.

Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory-motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD.

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry.

Introduction: Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping. Methods: Data were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or "combined" FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables. Results: From a study population of n = 410 subjects with FMDs, we selected n = 188 subjects [women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years] presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (n = 82; 43.6%) and Cluster C2 (n = 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants. Conclusion: Using a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.

Diagnostic and therapeutic recommendations in adult dystonia: a joint document by the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Motor and psychiatric features in idiopathic blepharospasm: A data-driven cluster analysis.

INTRODUCTION: Idiopathic blepharospasm is a clinically heterogeneous dystonia also characterized by non motor symptoms. METHODS: We used a k-means cluster analysis to assess 188 patients with idiopathic blepharospasm in order to identify relatively homogeneous subpopulations of patients, using a set of motor and psychiatric variables to generate the cluster solution. RESULTS: Blepharospasm patients reached higher scores on scales assessing depressive- and anxiety-related disorders than healthy/disease controls. Cluster analysis suggested the existence of three groups of patients that differed by type of spasms, overall motor severity, and presence/severity of psychiatric problems. The greater severity of motor symptoms was observed in Group 1, the least severity in Group 3, while the severity of blepharospasm in Group 2 was between that observed in Groups 1 and 3. The three motor subtypes also differed by psychiatric features: the lowest severity of psychiatric symptoms was observed in the group with least severe motor symptoms (group 3), while the highest psychiatric severity scores were observed in group 2 that carried intermediate motor severity rather than in the group with more severe motor symptoms (group 1). The three groups did not differ by disease duration, age of onset, sex or other clinical features. CONCLUSIONS: The present study suggests that blepharospasm patients may be classified in different subtypes according to the type of spasms, overall motor severity and presence/severity of depressive symptoms and anxiety.

Measurement Properties of Clinical Scales Rating the Severity of Blepharospasm: A Multicenter Observational Study.

Background: Several scales have been proposed to clinically evaluate the Motor Severity of Blepharospasm (BSP) but information about their measurement properties as a multicenter instrument is limited. Objective: To compare the measurement properties of four clinical scales in rating the severity of BSP in a large sample of patients from multiple sites. Methods: The Burke-Fahn-Marsden Scale (BFMS), the Global Dystonia Severity Rating Scale (GDRS), the Jankovic Rating Scale (JRS), and the Blepharospasm Severity Rating Scale (BSRS) were administered to 211 patients across 10 sites who were also requested to self-complete the Blepharospasm Disability Index (BDI). Measurement properties to be assessed included inter-/intra-observer agreement, item-to-total correlation, internal consistency, floor and ceiling effect, convergent/discriminant validity, and adherence to the distribution of BDI. Results: The BFMS had unsatisfactory measurement properties, the GDRS had acceptable reliability but other properties could not be completely testable; the JRS had satisfactory measurement properties but the scale did not accurately reflect the distribution of disability parameter (BDI) in the sample, and the BSRS had satisfactory measurement properties and also showed the best adherence to the distribution of BDI in the assessed sample. Conclusion: The comparison of the measurement properties of four rating scales to assess the motor state of the BSP in a large sample of patients from multiple sites showed that the GDRS should be used to simultaneously assess BSP and dystonia in other body parts, while the JRS (easier to use) and BSRS (better to discriminate severity) should be used to assess BSP alone.

Clinical Features and Evolution of Blepharospasm: A Multicenter International Cohort and Systematic Literature Review.

Objective: Blepharospasm is a type of dystonia where the diagnosis is often delayed because its varied clinical manifestations are not well recognized. The purpose of this study was to provide a comprehensive picture of its clinical features including presenting features, motor features, and non-motor features. Methods: This was a two-part study. The first part involved a systematic literature review that summarized clinical features for 10,324 cases taken from 41 prior reports. The second part involved a summary of clinical features for 884 cases enrolled in a large multicenter cohort collected by the Dystonia Coalition investigators, along with an analysis of the factors that contribute to the spread of dystonia beyond the periocular region. Results: For cases in the literature and the Dystonia Coalition, blepharospasm emerged in the 50s and was more frequent in women. Many presented with non-specific motor symptoms such as increased blinking (51.9%) or non-motor sensory features such as eye soreness or pain (38.7%), photophobia (35.5%), or dry eyes (10.7%). Non-motor psychiatric features were also common including anxiety disorders (34-40%) and depression (21-24%). Among cases presenting with blepharospasm in the Dystonia Coalition cohort, 61% experienced spread of dystonia to other regions, most commonly the oromandibular region and neck. Features associated with spread included severity of blepharospasm, family history of dystonia, depression, and anxiety. Conclusions: This study provides a comprehensive summary of motor and non-motor features of blepharospasm, along with novel insights into factors that may be responsible for its poor diagnostic recognition and natural history.

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset.

Evaluation of the Psychometric Properties of the Revised Piper Fatigue Scale in Patients with Multiple Sclerosis.

BACKGROUND: Fatigue is one of the most common symptoms in patients with multiple sclerosis (MS), and has a major impact on their quality of life. Measurement tools that assess the patient's condition are commonly used in the neurological field, though diagnostic tools are currently unable to distinguish potential alternative causes of fatigue in individual patients. The Revised Piper Fatigue Scale (PFS-R) is a self-administered assessment scale that is internationally used for fatigue measurement. AIM: This study aimed to evaluate the reliability and validity of the Italian version of the PFS-R in patients with MS. METHODS: Forty-one individuals were included in this study. Each participant in the study was given a dossier, in paper format, containing the informed consent form, a personal data sheet, the Fatigue Symptoms and Impacts Questionnaire in Relapsing Multiple Sclerosis (FSIQ-RMS), the Fatigue Severity Scale (FSS), and the PFS-R. RESULTS: The PFS-R was found to have strong internal consistency, with a value of α equal to 0.977. Correlations between PFS-R, FSS, and FSIQ-RMS scores were analyzed using the Pearson correlation coefficient, and all scales showed statistically significant correlations. CONCLUSION: The PFS-R is a new self-administered tool to assess fatigue in patients with MS. It evaluates fatigue characteristics, difficulty in carrying out daily life activities, and how the individual feels as a result of this symptom. This tool was previously validated for use in cancer patients, which also allows us to make a comparison between different pathologies and rehabilitation treatments.