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Idiopathic blepharospasm is a clinically heterogeneous dystonia also characterized by non motor symptoms.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.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.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.

Background and ObjectivesNeuroimaging studies suggest that changes in the cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit are a pathophysiologic feature of focal dystonia. However, it remains unclear whether structural and functional alterations vary in different forms of focal dystonia. Thus, in patients with cervical dystonia (CD) and blepharospasm (BSP), we aimed to investigate structural damage and resting-state functional alterations using whole-brain and seed-based approaches to test the hypothesis of possible functional connectivity (FC) alterations in specific circuits, including the cerebellum, basal ganglia, and cerebral cortex, in the context of preserved global FC.MethodsIn this cross-sectional study, we applied a multimodal 3T MRI protocol, including 3-dimensional T1-weighted images to extract brain volumes and cortical thickness, and fMRI at rest to study FC of the dentate nucleus and globus pallidus with a seed-based approach and whole-brain FC with a graph theory approach.ResultsThis study included 33 patients (17 with CD [14 female] age 55.7 ± 10.1 years, 16 with BSP [11 female] age 62.9 ± 8.8 years) and 16 age- and sex-matched healthy controls (HC) (7 female) 54.3 ± 14.3 years if age. Patients with CD, patients with BSP, and HC did not differ in terms of cortical or subcortical volume. Compared to HC, both patients with CD and patients with BSP had a loss of dentate FC anticorrelation with the sensorimotor cortex. Patients with CD and those with BSP showed increased pallidal FC with the cerebellum, supplementary motor area, and prefrontal cortices with respect to HC. Increased dentate FC with the cerebellum and thalamus and increased pallidal FC with the bilateral thalamus, sensorimotor and temporo-occipital cortices, and right putamen were present in patients with CD but not patients with BSP compared to HC. Measures of global FC, that is, global efficiency and small-worldness, did not differ between patients and HC.DiscussionBoth patients with CD and those with BSP showed altered dentate and pallidal FC with regions belonging to the integrated cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit, supporting the concept that focal dystonia is a disorder of specific networks and not merely a result of basal ganglia alterations in the context of a preserved whole-brain functional architecture. Differences in functional interplay among specific brain structures may distinguish CD and BSP.

Introduction Isolated head tremor, a pathological condition characterized by head tremor without dystonic postures or tremor in other body parts, has recently been suggested to be a form of dystonia. It is however still unclear whether isolated head tremor precedes dystonia or remains unmodified overtime. Methods We enrolled 20 patients with isolated head tremor. For each patient, we assessed videos recorded at enrollment and after 5 years. The videotapes were reviewed by two independent experienced movement disorder specialists who evaluated and scored tremor and CD severity using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor and the revised Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), respectively. Results Upon enrollment, all 20 patients showed isolated head tremor. Mean tremor severity was 2.7 ± 0.9 as measured using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor total score. At the 5-year follow-up examination, 15 (75%) of the 20 patients with isolated head tremor showed dystonic postures in the neck, while the remaining 5 patients (25%) had only isolated head tremor. Mean severity of dystonia as measured using the TWSTRS-2 total score was 11.8 ± 3.6. Head tremor severity was unchanged between baseline and the 5-year follow-up examination (p > 0.05). At the follow-up examination, no patients had tremor or dystonia in a body part other than the neck, nor did they develop bradykinesia or other parkinsonian signs. Conclusions Our longitudinal study demonstrated that patients with isolated head tremor may develop cervical dystonia over time.

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.

Introduction To better understand the pathophysiology of isolated head tremor, we investigated somatosensory temporal discrimination threshold (STDT) and dopaminergic neurotransmission with 123I-FP-CIT (DAT-SPECT) in patients with isolated head tremor, as well as potential correlations with their clinical features. Methods We enrolled 14 patients with isolated head tremor who underwent clinical examination, STDT testing, and DAT-SPECT. Results We found normal radiotracer uptake in both striata as assessed with DAT-SPECT examination, but higher STDT values in patients as compared to healthy subjects. No significant correlations emerged between STDT values, specific binding ratios of radiotracer uptake, and demographic or clinical features. Conclusion Our study found normal radiotracer uptake with DAT-SPECT examination, suggesting dopaminergic neurotransmission integrity in patients with isolated head tremor. Patients with isolated head tremor exhibited an abnormally elevated STDT. Both results support the hypothesis that isolated head tremor should be considered a form of dystonia.

Objectives: The objective of this study was to evaluate the efficacy of equine therapy (ET) to detect changes in the activities of daily living, quality of life, mood, balance, and gait in individuals with Parkinson’s disease (PD). Material and Methods: In the study, 17 participants with PD were recruited to participate in 10 sessions of ET. The inclusion criteria of the study were: second and third stages of the Hoehn and Yahr scale, Mini-Mental State Examination (MMSE) greater than or equal to 24 points, and age up to 85 years. The outcome measures administered at the beginning and the end of treatment relied on measurements from the Rivermead ADL scale, Parkinson’s Disease Questionnaire-39 (PDQ-39), Zung Self-Rating Depression Scale (SDS), unified Parkinson’s disease rating scale (UPDRS), and Tinetti balance assessment. Data from the stabilometric platform were also collected to objectify the value obtained by the Tinetti balance assessment. The ET program included 10 biweekly 45 min sessions. Results: The results obtained included statistically significant increases in measurements from the Rivermead ADL, PDQ-39, UPDRS, SDS, and Tinetti balance assessment scales. The stabilometric platform did not report significant changes in data. Conclusion: ET that was used as a supportive therapy for traditional treatments resulted in statistically significant improvements in the occupational performance, mood, quality of life, gait, and balance of the participants. Data from the stabilometric platform did not show significant changes.

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.

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.To compare the measurement properties of four clinical scales in rating the severity of BSP in a large sample of patients from multiple sites.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.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.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.

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.

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.

We evaluated levels of serum neurofilament light chains (NfL), a known biomarker of neuroaxonal damage, in patients with cervical dystonia (CD) and healthy controls (HCs). CD patients had normal NfL levels supporting the hypothesis that CD may be considered as a functional network disorder rather than as a neurodegenerative disease.

Objective\ud We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs).\ud \ud Methods\ud In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 tertiary movement disorders centers in Italy. Each subject with FMDs underwent a comprehensive clinical assessment, including screening for different subtypes of functional gait disorders. Multivariate regression models were implemented in order to estimate the adjusted odds ratio (OR; 95% confidence interval) of having FGDs in relation to sociodemographic and clinical characteristics.\ud \ud Results\ud Out of 410 FMDs, 26.6% (n = 109) of patients exhibited FGDs. The most frequent FGDs were slow gait (n = 43, 39.4%), astasia-abasia (n = 26, 23.8%), and knee buckling (n = 24, 22%). They exhibited single FGDs in 51.4% (n = 56) or complex FGDs (more than one type of FGDs) in 48.6% (n = 53) of cases. On multivariate regression analysis, the presence of FGDs was more likely associated with older age (OR 1.03, 95% CI 1.01–1.04), functional visual symptoms (OR 2.19, 95% CI 1.08–4.45), and the diagnosis of somatic symptoms disorder (OR 2.97, 95% CI 1.08–8.17). FGDs were also more likely to undergo physiotherapy (OR 1.81, 95% CI 1.08–3.03).\ud \ud Conclusions\ud People with FMDs may present with different and overlapping types of FGDs, which may occur in older age. The association of FGDs with functional visual symptoms and somatic symptoms disorder opens up to new avenues to the understanding of the neural mechanisms of these disorders.

Background: Blink rate (BR) is considered a marker of dopaminergic activity in humans. BR is increased in patients with Mild Cognitive Impairment (MCI), but no study has yet investigated whether BR changes with the progression of cognitive decline from MCI to Alzheimer’s disease (AD) and whether BR abnormalities are present in subjects with Subjective Cognitive Decline (SCD). Objective: The aim of our study was to assess BR in patients with AD, MCI, and SCD and to correlate BR with demographic and clinical features of cognitive decline. Methods: We enrolled 22 subjects with SCD, 23 with MCI, and 18 with AD and a group of 20 age-matched healthy controls (HCs). Cognitive function was assessed by testing global cognitive status and frontal, attentional, memory, verbal, and visuospatial functions. BR was measured by counting the number of blinks per minute. Results: MCI subjects had an increased BR (p Conclusion: Increased BR in MCI likely reflects early compensatory mechanisms occurring before AD, whereas decreased BR in AD suggests dopaminergic system involvement in this condition.

Background There are no widely accepted criteria to aid the physician in diagnosing BSP. Objective To validate recently proposed diagnostic criteria for blepharospasm in a larger and geographically diverse population and to develop a screening system for blepharospasm. Methods Video-recordings from 211 blepharospasm patients and 166 healthy/disease controls were examined by 8 raters. Agreement for presence of orbicularis oculi spasms, sensory trick, and increased blinking was measured by k statistics. Inability to voluntarily suppress the spasms was asked by the examiner but not captured in the video. Patients/controls were also requested to fill a self-administered questionnaire addressing relevant blepharospasm clinical aspects. The diagnosis at each site was the gold standard for sensitivity/specificity. Results All the study items yielded satisfactory inter/intra-observer agreement. Combination of items rather than each item alone reached satisfactory sensitivity/specificity. The combined algorithm started with recognition of spasms followed by sensory trick. In the absence of a sensory trick, including “increased blinking” or “inability to voluntarily suppress the spasms” or both items yielded 88–92% sensitivity and 79–83% specificity. No single question of the questionnaire yielded high sensitivity/specificity. Serial application of the questionnaire to our blepharospasm and control subjects and subsequent clinical examination of subjects screening positive by the validated diagnostic algorithms yielded 78–81% sensitivity and 83–91% specificity. Conclusion These results support the use of proposed diagnostic criteria in multi-ethnic, multi-center cohorts. We also propose a case-finding procedure to screen blepharospasm in a given population with less effort than would be required by examination of all subjects.

Background and purpose\ud Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.\ud \ud Methods\ud Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation (“dystonia-only”) and one accepting dystonia OR tremor in any body part as disease manifestations (“dystonia OR tremor”). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping.\ud \ud Results\ud Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62–0.70 and 0.62–0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread.\ud \ud Conclusions\ud This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals’ risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

Patients with blepharospasm in addition to involuntary contraction of the orbicularis oculi muscle also have non-motor symptoms (psychiatric, sleep, cognitive, and ocular). In this paper, we investigated the relationship of non-motor with motor symptoms and the total burden of non-motor symptoms in patients with blepharospasm. Results were compared with those of age- and sex-matched healthy controls. We enrolled 60 patients with blepharospasm and 40 age-matched healthy controls. In all patients, the severity of blepharospasm was assessed clinically with the Blepharospasm Severity Rating Scale. All the participants underwent a psychiatric, sleep, cognitive, and ocular symptom evaluation. We investigated the correlations between motor, non-motor symptoms, and patients’ clinical and demographic features. The frequency of psychiatric, sleep, and cognitive disorders and ocular symptoms was higher in blepharospasm patients than in healthy controls. Non-motor symptoms coexisted in the majority of patients and there was no correlation between non-motor and motor symptoms. The total burden of non-motor symptoms did not associate with motor symptoms and demographic features in blepharospasm. Non-motor symptoms are independent of motor features and likely belong to the clinical spectrum of blepharospasm. The presence of non-motor symptoms possibly reflects a complex network disorder of blepharospasm.

Background The temporal processing of sensory information can be evaluated by testing the somatosensory temporal discrimination threshold (STDT), which is defined as the shortest interstimulus interval needed to recognize two sequential sensory stimuli as separate in time. The STDT requires the functional integrity of the basal ganglia and of the somatosensory cortex (S1). Although there is evidence that time processing is impaired in patients with Alzheimer's disease (AD), no study has yet investigated STDT in patients with various degree of cognitive impairment. Objective The aim of our study was to understand how cognition and attention deficits affect STDT values in patients with cognitive abnormalities. Methods We enrolled 63 patients: 28 had mild-moderate AD, 16 had mild cognitive impairment (MCI), and the remaining 19 had subjective cognitive deficit (SCD). A group of 45 age-matched healthy subjects acted as controls. Paired tactile stimuli for STDT testing consisted of square-wave electrical pulses delivered with a constant current stimulator through surface electrodes over the distal phalanx of the index finger. Results STDT values were higher in AD and MCI patients than in SCD subjects or healthy controls. Changes in the STDT in AD and MCI were similar in both conditions and did not correlate with disease severity. Conclusions STDT alterations in AD and MCI may reflect a dysfunction of the dopaminergic system, which signals salient events and includes the striatum and the mesocortical and mesolimbic circuits.

Introduction Suicidal ideation is increased in Parkinson's disease (PD) patients. The possible relationship between parkinsonian motor and non-motor symptoms and suicidal ideation in PD is unknown. The aim of the study was to evaluate suicidal ideation in patients with PD in a controlled study specifically designed to identify the clinical correlates of PD suicidal ideation. Methods We consecutively enrolled 100 patients with PD, 76 patients with psoriasis and 80 healthy subjects. Motor symptoms and complications were evaluated by using the International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale. Non-motor symptoms were evaluated by means of the Non-Motor Symptoms assessment scale for PD. All patients also underwent a psychiatric evaluation that included the administration of the Columbia-Suicide Severity Rating Scale. Results Suicidal ideation was present in 31% of PD patients, 16% of patients with psoriasis and 2% of healthy controls. PD patients showing suicidal ideation have more frequent motor complications, more severe non-motor symptoms and a higher perceived disability than patients without suicidal ideation. Suicidal ideation correlated with the presence of motor complications as well as with non-motor symptom severity, perceived disability severity and the presence of psychiatric disorders. Conclusions Our findings showed that suicidal ideation is increased in PD patients compared with healthy controls and patients with psoriasis and that several clinical PD features, including motor complications and non-motor symptoms, are associated with suicidal ideation in PD. The results suggest a multi-factorial origin of PD suicidal ideation.

The introduction of oral disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) changed the therapeutic landscape and algorithms of RRMS treatment (1). In Europe, dimethyl fumarate (DMF) and teriflunomide (TRF) are approved as first-line agents and are often used as the initial therapeutic choice (2, 3). Pivotal trials showed the efficacy of both DMTs on controlling clinical relapses, disability accrual and magnetic resonance imaging (MRI) activity (4-8). Both DMTs had overall good tolerability. There have been no head-to-head randomized trials to compare these two DMTs; however, several real-world evidence (RWE) studies have compared DMF and TRF and provided useful information to guide the selection of either drug for MS patients (9, 10). Although different statistical methods were used, both drugs demonstrated an ability to control disease activity (11-13). In some RWE studies, patients on DMF had a lower relapse rate and a higher relapse-free survival time (11, 12). In this registry-based nationwide cohort Cox-model study, we compared the clinical and radiological activity between patients treated with DMF or TRF.

Background Adult-onset focal dystonia can spread to involve one, or less frequently, two additional body regions. Spread of focal dystonia to a third body site is not fully characterized. Materials and methods We retrospectively analyzed data from the Italian Dystonia Registry, enrolling patients with segmental/multifocal dystonia involving at least two parts of the body or more. Survival analysis estimated the relationship between dystonia features and spread to a third body part. Results We identified 340 patients with segmental/multifocal dystonia involving at least two body parts. Spread of dystonia to a third body site occurred in 42/241 patients (17.4%) with focal onset and 10/99 patients (10.1%) with segmental/multifocal dystonia at onset. The former had a greater tendency to spread than patients with segmental/multifocal dystonia at onset. Gender, years of schooling, comorbidity, family history of dystonia/tremor, age at dystonia onset, and disease duration could not predict spread to a third body site. Among patients with focal onset in different body parts (cranial, cervical, and upper limb regions), there was no association between site of focal dystonia onset and risk of spread to a third body site. Discussion and conclusion Spread to a third body site occurs in a relative low percentage of patients with idiopathic adult-onset dystonia affecting two body parts. Regardless of the site of dystonia onset and of other demographic/clinical variables, focal onset seems to confer a greater risk of spread to a third body site in comparison to patients with segmental/multifocal dystonia at onset.

Background Patients with essential tremor have upper limb postural and action tremor often associated with voice tremor. The objective of this study was to objectively examine voice tremor and its response to symptomatic pharmacological treatment in patients with essential tremor using voice analysis consisting of power spectral analysis and machine learning. Methods We investigated 58 patients (24 men; mean age ± SD, 71.7 ± 9.2 years; range, 38-85 years) and 74 age- and sex-matched healthy subjects (20 men; mean age ± SD, 71.0 ± 12.4 years; range, 43-95 years). We recorded voice samples during sustained vowel emission using a high-definition audio recorder. Voice samples underwent sound signal analysis, including power spectral analysis and support vector machine classification. We compared voice recordings in patients with essential tremor who did and did not manifest clinically overt voice tremor and in patients who were and were not under the symptomatic effect of the best medical treatment. Results Power spectral analysis demonstrated a prominent oscillatory activity peak at 2-6 Hz in patients who manifested a clinically overt voice tremor. Voice analysis with support vector machine classifier objectively discriminated with high accuracy between controls and patients who did and did not manifest clinically overt voice tremor and between patients who were and were not under the symptomatic effect of the best medical treatment. Conclusions In patients with essential tremor, voice tremor is characterized by abnormal oscillatory activity at 2-6 Hz. Voice analysis, including power spectral analysis and support vector machine classification, objectively detected voice tremor and its response to symptomatic pharmacological treatment in patients with essential tremor. © 2021 International Parkinson and Movement Disorder Society.

Most patients with multiple sclerosis presenting with a relapsing–remitting disease course at diagnosis transition to secondary progressive multiple sclerosis (SPMS) 1–2 decades after onset. SPMS is characterized by predominant neurodegeneration and atrophy. These pathogenic hallmarks result in unsatisfactory treatment response in SPMS patients. Therefore, early diagnosis of SPMS is necessary for prompt treatment decisions. The aim of this review was to assess neurophysiological and fluid biomarkers that have the potential to monitor disease progression and support early SPMS diagnosis. We performed a systematic review of studies that analyzed the role of neurophysiological techniques and fluid biomarkers in supporting SPMS diagnosis using the preferred reporting items for systematic reviews and meta-analyses statement. From our initial search, we selected 24 relevant articles on neurophysiological biomarkers and 55 articles on fluid biomarkers. To date, no neurophysiological or fluid biomarker is sufficiently validated to support the early diagnosis of SPMS. Neurophysiological measurements, including short interval intracortical inhibition and somatosensory temporal discrimination threshold, and the neurofilament light chain fluid biomarker seem to be the most promising. Cross-sectional studies on an adequate number of patients followed by longitudinal studies are needed to confirm the diagnostic and prognostic value of these biomarkers. A combination of neurophysiological and fluid biomarkers may be more sensitive in detecting SPMS conversion.

Introduction Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. Objective To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities. Methods Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted. Results A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors. Conclusions Our data support the evidence of a large overlap between FMD phenotypes.

(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD), and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus.

ObjectiveTo assess the clinical manifestations and predictors of different types of tremors in individuals with different types of isolated dystonia.MethodsClinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2,362 individuals with all types of isolated dystonia (focal, segmental, multifocal, and generalized) recruited through the Dystonia Coalition.ResultsMethodical and standardized assessments of all participants in this cohort revealed the overall prevalence of any type of tremor was 53.3%. The prevalence of dystonic tremor varied from 36.9% to 48.4%, depending on criteria used to define it. To identify the factors associated with tremors in dystonia, the data were analyzed by generalized linear modeling and cluster analyses. Generalized linear modeling indicated 2 of the strongest factors associated with tremor included body region affected by dystonia and recruitment center. Tremor was also associated with severity of dystonia and duration of dystonia, but not with sex or race. The cluster analysis distinguished 8 subgroups within the whole cohort; defined largely by body region with dystonia, and secondarily by other clinical characteristics.ConclusionThe large number of cases evaluated by an international team of movement disorder experts facilitated the dissection of several important factors that influence the apparent prevalence and phenomenology of tremor in dystonia. These results are valuable for understanding the many differences reported in prior studies, and for guiding future studies of the nosology of tremor and dystonia.

Background Movement execution in healthy individuals increases the somatosensory temporal discrimination threshold. These changes are a result of mechanisms of sensory gating at the subcortical level. Although the somatosensory temporal discrimination threshold is abnormally increased in patients with focal dystonias, the effect of movement execution on somatosensory temporal discrimination in dystonic patients is unknown. Objectives The objective of this study was to determine whether somatosensory temporal discrimination threshold modulation induced by voluntary movement is normal in different forms of focal dystonia. Methods We enrolled 71 dystonic patients (24 with blepharospasm, 31 with cervical dystonia, and 16 with focal hand dystonia) and 39 age-matched healthy participants. Paired stimuli for the somatosensory temporal discrimination threshold were triggered by movement execution at movement onset and at various time intervals thereafter. We analyzed the kinematic features of the motor task to ascertain whether tactile input induces changes in movement parameters. Results Movement execution led to greater and longer lasting increases in somatosensory temporal discrimination threshold values, both upon movement onset and at various time intervals thereafter, in patients with cervical dystonia and focal hand dystonia than in those with blepharospasm or the healthy participants. Somatosensory temporal discrimination testing did not induce any changes in the mean velocity of index finger movements in either patients or healthy participants. Conclusions Somatosensory temporal discrimination threshold changes induced by movement execution are abnormal in focal dystonias. This abnormality is related to the type of dystonia. Abnormal gating of sensory information is likely involved in movement-induced triggering or worsening of different forms focal dystonia. © 2018 International Parkinson and Movement Disorder Society.

BACKGROUND AND PURPOSE: Adult-onset laryngeal dystonia (LD) can be isolated or can be associated with dystonia in other body parts. Combined forms can be segmental at the onset or can result from dystonia spread to or from the larynx. The aim of this study was to identify the main clinical and demographic features of adult-onset idiopathic LD in an Italian population with special focus on dystonia spread. METHODS: Data were obtained from the Italian Dystonia Registry (IDR) produced by 37 Italian institutions. Clinical and demographic data of 71 patients with idiopathic adult-onset LD were extracted from a pool of 1131 subjects included in the IDR. RESULTS: Fifty of 71 patients presented a laryngeal focal onset; the remaining subjects had onset in other body regions and later laryngeal spread. The two groups did not show significant differences of demographic features. 32% of patients with laryngeal onset reported spread to contiguous body regions afterwards and in most cases (12 of 16 subjects) dystonia started to spread within 1 year from the onset. LD patients who remained focal and those who had dystonia spread did not show other differences. CONCLUSIONS: Data from IDR show that dystonic patients with focal laryngeal onset will present spread in almost one-third of cases. Spread from the larynx occurs early and is directed to contiguous body regions showing similarities with clinical progression of blepharospasm. This study gives a new accurate description of LD phenomenology that may contribute to improving the comprehension of dystonia pathophysiology.

Patients with cervical dystonia (CD) may display non-motor symptoms, including psychiatric disturbances, pain, and sleep disorders. Intramuscular injection of botulinum toxin type A (BoNT-A) is the most efficacious treatment for motor symptoms in CD, but little is known about its effects on non-motor manifestations. The aim of the present study was to longitudinally assess BoNT-A’s effects on CD non-motor symptoms and to investigate the relationship between BoNT-A-induced motor and non-motor changes. Forty-five patients with CD participated in the study. Patients underwent a clinical assessment that included the administration of standardized clinical scales assessing dystonic symptoms, psychiatric disturbances, pain, sleep disturbances, and disability. Clinical assessment was performed before and one and three months after BoNT-A injection. BoNT-A induced a significant improvement in dystonic symptoms, as well as in psychiatric disturbances, pain, and disability. Conversely, sleep disorders were unaffected by BoNT-A treatment. Motor and non-motor BoNT-A-induced changes showed a similar time course, but motor improvement did not correlate with non-motor changes after BoNT-A. Non-motor symptom changes after BoNT-A treatment are a complex phenomenon and are at least partially independent from motor symptom improvement.

Objective The aim of this five-year longitudinal study was to investigate whether patients with increased blinking develop orbicularis oculi muscle spasms. Methods Eleven patients who initially manifested increased blinking alone were clinically and neurophysiologically re-evaluated five years later. Results By the five-year follow-up assessment, nine of the 11 patients had developed orbicularis oculi muscle spasms. The blink reflex recovery cycle became abnormal whereas somatosensory temporal discrimination, already abnormal at the first evaluation, did not significantly change. Conclusions Our longitudinal study demonstrates that increased blinking may precede blepharospasm and that an abnormal blink reflex recovery cycle reflects the development of orbicularis oculi muscle spasms. This article is protected by copyright. All rights reserved.

Background\ud Functional motor disorders (FMDs) are abnormal movements that are significantly altered by distractive maneuvers and are incongruent with movement disorders seen in typical neurological diseases.\ud \ud Objective\ud The objectives of this article are to (1) describe the clinical manifestations of FMDs, including nonmotor symptoms and occurrence of other functional neurological disorders (FND); and (2) to report the frequency of isolated and combined FMDs and their relationship with demographic and clinical variables.\ud \ud Methods\ud For this multicenter, observational study, we enrolled consecutive outpatients with a definite diagnosis of FMDs attending 25 tertiary movement disorders centers in Italy. Each patient underwent a detailed clinical evaluation with a definition of the phenotype and number of FMDs (isolated, combined) and an assessment of associated neurological and psychiatric symptoms.\ud \ud Results\ud Of 410 FMDs (71% females; mean age, 47 ± 16.1 years) the most common phenotypes were weakness and tremor. People with FMDs had higher educational levels than the general population and frequent nonmotor symptoms, especially anxiety, fatigue, and pain. Almost half of the patients with FMDs had other FNDs, such as sensory symptoms, nonepileptic seizures, and visual symptoms. Patients with combined FMDs showed a higher burden of nonmotor symptoms and more frequent FNDs. Multivariate regression analysis showed that a diagnosis of combined FMDs was more likely to be delivered by a movement disorders neurologist. Also, FMD duration, pain, insomnia, diagnosis of somatoform disease, and treatment with antipsychotics were all significantly associated with combined FMDs.\ud \ud Conclusions\ud Our findings highlight the need for multidimensional assessments in patients with FMDs given the high frequency of nonmotor symptoms and other FNDs, especially in patients with combined FMDs.