Functional movement disorder (FMD) is a common manifestation of functional neurological disorder presenting with diverse phenotypes such as tremor, weakness and gait disorder. Our current understanding of the basic epidemiological features of this condition is unclear. We aimed to describe and examine the relationship between age at onset, phenotype and gender in FMD in a large meta-analysis of published and unpublished individual patient cases. An electronic search of PubMed was conducted for studies from 1968 to 2019 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Individual patient data were collected through a research network. We described the distribution of age of onset and how this varied by gender and motor phenotype. A one-stage meta-analysis was performed using multilevel mixed-effects linear regression, including random intercepts for country and data source. A total of 4905 individual cases were analysed (72.6% woman). The mean age at onset was 39.6 years (SD 16.1). Women had a significantly earlier age of onset than men (39.1 years vs 41.0 years). Mixed FMD (23.1%), tremor (21.6%) and weakness (18.1%) were the most common phenotypes. Compared with tremor (40.7 years), the mean ages at onset of dystonia (34.5 years) and weakness (36.4 years) were significantly younger, while gait disorders (43.2 years) had a significantly later age at onset. The interaction between gender and phenotype was not significant. FMD peaks in midlife with varying effects of gender on age at onset and phenotype. The data gives some support to ‘lumping’ FMD as a unitary disorder but also highlights the value in ‘splitting’ into individual phenotypes where relevant.

Background and purpose The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases (“comorbid FMDs”), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases (“pure FMDs”). Methods For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables). Results Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non‐neurological comorbidities, paroxysmal non‐epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non‐neurological comorbidities. Conclusions Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non‐neurological diseases.

Background Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated. Objective To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19. Methods We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin’ Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire. Results Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic. Conclusion Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19.

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Background: Olfactory dysfunctions and hallucinations are considered common nonmotor symptoms in Parkinson’s disease (PD). Visual and auditory hallucinations are well-known; however, olfactory hallucinations (OHs) are not fully investigated. The aim of this study was to evaluate OHs in PD patients, and their correlation to motor impairment, cognitive abilities, visual and auditory hallucinations, and olfactory and gustatory function. Methods: A sample of 273 patients was enrolled: 141 PD patients (mean age ± SD: 70.1 ± 9.5 years) and 132 healthy controls (mean age ± SD: 69.4 ± 9.6 years). In all patients, the following parameters were evaluated: motor symptoms (UPDRS-III), olfactory function, cognitive abilities, and occurrence of OH, gustatory hallucinations (GHs), and visual/auditory hallucinations. Results: OHs were found only in PD patients with a percentage of 11.3%. Among PD patients with OHs, 2.8% also presented GHs. High significant frequencies of females, the presence of visual/auditory hallucinations, and a high mean UPDRS-III score were found in patients with OHs related to patients without them. Binary logistic regression evidenced the presence of visual/auditory hallucinations and sex as main variables predicting the presence of OHs. Conclusions: Our data indicated that OHs occur frequently in PD patients, especially in women, and often concomitant with visual and auditory hallucinations, without any association with olfactory impairment.

Objective:To perform a simultaneous evaluation of potential risk/protective factors of Parkinson’s disease (PD) in order to identify independent risk/protective factors, assess interaction among factors and determine whether identified risk factors predict etiological subtypes of PD.Methods:We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbidities, and drugs. The study enrolled 694 PD patients and 640 healthy controls from six neurological centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis.Results:The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR]: 0.6; 95% confidence interval [CI]: 0.4-0.9), smoking (OR: 0.7; 95% CI: 0.6-0.9), physical activity (OR: 0.8; 95% CI: 0.7-0.9), family history of PD (OR: 3.2; 95% CI: 2.2- 4.8), dyspepsia (OR: 1.8; 95% CI:1.3-2.4), exposure to pesticides (OR: 2.3; 95% CI:1.3- 4.2), oils (OR: 5.6; 95% CI: 2.3-13.7), metals (OR: 2.8; 95% CI: 1.5-5.4), and general anesthesia (OR: 6.1; 95% CI: 2.9-12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified four subtypes with different risk factor profiles. In Group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents were present in 30% of patients. In Group 2 and 3, a family history of PD was lacking, while exposure to toxic agents (Group 2) and dyspepsia (Group 3) played major roles. Group 4 consisted of patients with no risk factors.Conclusions:This study demonstrated that nine factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same subject.

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.

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