Functional motor disorders (FMDs) are part of a wide spectrum of functional neurological disorders (FNDs) [e.g., psychogenic non-epileptic seizures (PNES) and sensory and visual disturbances] characterized by abnormal movements (e.g., functional limb weakness, tremor, and dystonia) which can be altered by distractive maneuvers and are incongruent with movement disorders seen in typical neurological diseases (1, 2). Highly disabling non-motor symptoms (e.g., pain, fatigue, and anxiety) besides motor symptoms are also present (3). FMDs account for more than 50% of FNDs (prevalence 50/100,000 cases) mainly in young and middle-aged adults (35–50 years), in which they are a cause of disability and diminished quality of life (4) and a reason for leaving work or for reduced independence (5).

Over the past decade, despite advances in our understanding of the pathophysiology of FMDs (1, 6–8), clinical correlates (3, 9), and evidence-based treatment (8, 10), the illness is neither adequately diagnosed nor treated, as evidenced by the dissatisfaction expressed by neurologists (11) and by patients who feel misunderstood and abandoned by their healthcare providers (12). Such dissatisfaction reflects inadequacies within current clinical services for patients with FMDs (8, 12) and the lack of early diagnosis and disease-specific, evidence-based management. The difficulty in diagnosing and managing FMDs originates from a poor understanding of how symptoms are produced. The features that are generally associated with voluntary movement (distractibility and placebo resolution) have led neurologists to mistakenly think that simulation is the main mechanism underlying the disorders (1). Patients with FMDs differ from simulators, however, and report these disorders as involuntary and uncontrolled (6). The dissociation between the voluntary and the involuntary nature of FMDs perceived by patients stems from an altered perception of control of actions and their consequences (i.e., sense of agency) (7). Another crucial element is that FMDs have been conventionally considered secondary to emotional–psychological trauma (i.e., conversion disorders) (13). Recent epidemiological studies have demonstrated an overlap of stressful life events and psychological/psychiatric comorbidity between organic and functional disorders (14, 15). Accordingly, the causal role of psychological factors in FMDS has been removed from the Diagnostic and Statistical Manual of Mental Disorders (DSM V) where they are now defined as risk factors (2).

The literature emphasizes the importance of multidisciplinary three-stage stepped care to manage the phenomenological complexity of FMDs (16, 17). According to the Scottish model, the first step in successful management (step 1) is to diagnose FNDs symptoms early and appropriately explain them by a neurologist expert in the field. Step 2 entails brief therapy usually delivered by a physiotherapist for FMDs, and step 3 includes more complex multidisciplinary care involving the full rehabilitation team and psychiatry/psychology treatment. Wider acceptance of this stepped care model could enhance the care of patients with FMDs and reduce healthcare costs (17). The model is designed to guide healthcare providers, and its recommendations are not intended as prescriptive. In many cases, a revised approach will require (i.e., different national contexts and clinical frameworks) an established care pathway that is already working well.

Data from the first year (2018–2019) of the Italian Registry of Functional Motor Disorders (RI-FMDS) showed that the model is not currently operational in Italy: three physicians (range 1–25) on an average evaluated 80% of patients before a correct diagnosis was established, and about 73% of patients received one or more misdiagnoses of organic neurological disease (3, 9), with a diagnostic delay of about 6 years. Patients are often improperly referred to psychological and psychotherapy (rarely to physiotherapy) and leave their job due to an undiagnosed condition (3). The reasons for such poor management are grounded on two main issues: (1) an inappropriate referral to first-line specialists and lack of rehabilitation care (18).

There is limited information about health care costs in patients with FNDs because they are difficult to calculate, particularly for a complex disorder with a substantial delay to diagnosis (19, 20). Very recently, Stephen et al. (19) have provided national estimates of resource use and spending for FNDs in adults and children using national data on Emergency department and inpatient visits in the US in the period 2008–2017. They showed that patients with FNDs incurred total charges to the US health care system of more than $1.2 billion annually ($1.2 billion in adult FNDs and $88 million in pediatric FNDs), similar to those of neurological conditions that require high health care resource use.

Single-center studies on FNDs including a small sample of patients (from 25 to 73) have mainly focused on PNES and reported higher healthcare utilization due to a delay in correct diagnosis and appropriate patient management (20–24). No information on health care use and costs in FMDs patients is available although they represent the highest proportion of patients with FNDs.

In this work, we wanted to provide a real-world overview of the economic burden of FMDs from a cohort of patients of a specialized clinic in Italy before they had obtained a correct diagnosis. To do this, we defined medical resource consumption as the costs for specialist visits, diagnostic tests, emergency room (ER) visits, hospital admissions, and rehabilitation services in a period of up to 5 years before diagnosis, based on Italian healthcare costs (21). Estimation of utilization volumes and costs associated with delayed FMDs diagnosis can underline the importance of earlier diagnosis of FMDs for achieving better health outcomes, less unnecessary resource consumption, and lower costs. Adopting an early disease-specific care network model could improve the quality and the effectiveness of healthcare processes and bring savings to the national healthcare system.

This pilot retrospective study involved 40 patients with a clinically definite diagnosis of FMDs (25), referred to the Parkinson's Disease and Movement Disorders Unit of Verona (Italy) and that were included in the Verona dataset of IR-FMDs (Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona; Italian Academy for the Study of Parkinson's Disease and other Movement Disorders), satisfying the inclusion and exclusion criteria. Inclusion criteria were a detailed medical and medication history as documented by medical records or statements from informed relatives during a period of up to 5 years (3, 21); age ≥16 years; a clinically definite diagnosis of FMDs based on Gupta and Lang's diagnostic criteria (25); the presence of distractibility maneuvers and demonstration of positive signs (2); the presence of one (isolated FMDs) or more clinical motor symptoms (combined FMDs), including weakness, tremor, jerks, dystonia, gait disorders, parkinsonism, and facial motor disorders (3). Exclusion criteria were the presence of cognitive or physical impairments that precluded signing the informed consent form for participation in the study (3). For details see Table 1.

Sociodemographic information (age, sex, education level, and work status), clinical history (previous organic and non-organic diagnosis predating the final diagnosis, number of examining physicians, diagnostic tests), and clinical manifestations (isolated/combined FMDs, associated FNDs, psychiatric comorbidities, neurological comorbidities, and childhood predisposing factors) were collected.

With this study, we explored the volume and the direct medical costs of delayed diagnosis of FMDs in a cohort of patients during a period of up to 5 years before they received correct diagnosis and management at a specialized tertiary clinic in Italy. The direct medical cost before diagnosis was estimated at €2,302 per patient per year, divided into €1,524 to the NHS and €778 to the patient for out-of-pocket expenses. Major cost drivers were hospitalization (40% of total costs), rehabilitation services, and diagnostic testing. The costs of diagnostic tests and hospitalization are direct costs for the NHS, whereas the costs for specialist visits and rehabilitation services are covered by the patient.

A recent study assessing US emergency department (ED) and inpatient use and charges for FNDs using national data in the period 2008–2017 underlies the importance of increasing information on health care and costs in patients with FNDs, pointing out that unnecessary investigations and iatrogenic harm inflate costs in the face of neglected rehabilitative treatments (19). Previous literature focused on single-center studies on PNES (20–24) showing a considerable burden of healthcare utilization costs due to a delay in the correct diagnosis, unnecessary therapy, and iatrogenic consequences. Our study cannot be compared with this previous literature due to differences in the patients' selection (adults and pediatric with FNDs and adults with PNES), methodology used in retrospectively retrieving economic data (International Classification of Disease codes, questionnaires, EMR), and settings (emergency department, inpatient use, single medical centers). However, in our pilot single-center retrospective study on a small cohort of patients with FMDs from a specialized clinic in Italy, we reported for the first time evidence of considerable direct healthcare volumes and costs before the correct diagnosis also in patients with FMDs.

In our work, the mean time lag between the onset of symptoms and FMDs diagnosis (6.63 years) is in line with previous studies (3, 20, 21). Often inappropriate procedures, such as psychotherapy for example, translated into a steady additional cost year by year until a definite diagnosis was established.

These preliminary results shed some light on the high healthcare services volume and direct healthcare costs of FMDs patients from clinic to clinic for visits, unnecessary tests, and prescribed treatments (3, 19). Most (78%) reported multiple consultations and numerous diagnostic tests before they received a correct diagnosis of FMDs. A plausible explanation is “doctor shopping,” which we believe reflects issues associated with the diagnosis of FMDs, including miscommunication between physicians and patients, a reluctance/failure to accept the diagnosis, and the lack of a therapeutic plan and clear treatment goals (3, 18, 30, 31). Before diagnosis, many specialist visits involved neurologists first, then psychiatrists. Around half of all specialist visits were not a consultation with a neurologist, but rather a psychologist or a psychiatrist. This indicates a lack of recognition of the disorders by neurologists and other healthcare providers who wrongly referred the patient for inappropriate and unnecessary diagnostic testing and specialist visits (“doctor shopping”). The same problem concerns the type of therapy and treatment: only 37% of the patients underwent rehabilitative treatment (motor/neuromotor), which was ineffective because it did not address the physiopathology of the disorder. This phenomenon is further confirmed by the reported incorrect use of rehabilitation services, where psychotherapy accounted for 32% and physical therapy 28% of the services delivered. In brief, the diagnostic delay generates unjustified costs for diagnostic testing, ineffective treatment, and hospital admission. Referring to an FMDs specialist would reduce the latency to diagnosis and lower cost, thereby avoiding unnecessary multiple consultations and tests (3, 30, 31).

Moreover, on an average the cost of health services used is steady year after year with no peak for any services except ER. In the 2 years before the establishment of correct diagnosis, the data show repeated ER visits and hospital admission when the diagnosis is finally made (the use and costs of the last hospitalization have not been included in resource analysis). The data show that because primary healthcare services do not solve the problem, patients are admitted to the hospital where costs are higher. Considering only direct medical costs (excluding medications) and an average delay of 6 years, the total cost before diagnosis is around €14,000 per patient. The total cost is a conservative estimation because, to avoid recall bias, we reported only resource use data that could be confirmed by documents or hospital EMR. Actually, we calculated only direct medical costs, excluding costs for medications and non-healthcare direct and indirect costs. Moreover, costs do not take into account the costs of medications, transportation, and caregiving and, in particular, the cost of informal care and the loss of productivity due to time taken off (paid) work. While the cost of medications may not be relevant compared to PNES, for example, FMDs still incur considerable indirect costs.

Obtaining earlier diagnosis, increasing health professionals' knowledge of FMDs can improve health outcomes and reduce unnecessary resource consumption and costs. Due to its engendered costs, the economic burden of illness is acutely underexplored, yet essential for public health policy makers.

This work is the first which would attempt to fill this gap when healthcare systems are increasingly under pressure to enhance the choice of value for money in healthcare programs. The Scottish three-stage stepped care model constitutes a reference in offering healthcare providers guidance to deal with FNDs. However, it needs to be tailored to the specific cultural and NHS framework of the Italian context.

First, early and thorough assessment by healthcare providers and by general practitioners (GPs) (primary care) is needed to refer the patient toward correct diagnosis as soon as possible (18). Educational efforts should involve all professional categories (i.e., GPs, physiatrists, psychiatrists, physiotherapists, psychologists) and all levels of healthcare professional training and continuing education (i.e., undergraduate and post-graduate education pathways) to share knowledge on the pathophysiology, clinical correlates, and management principles of FMDs (8, 18). This would aid in the development of shared (partially overlapping) expertise and catalyze interdisciplinary management of FMDs.

Second, patients should be promptly referred to a neurologist expert in FMDs (or to a general neurologist who can refer the patient to an experienced neurologist) for correct diagnosis and communication, and to triage the patient toward the most suitable treatment according to available options and phenomenological complexity, including physiotherapy, skills-based psychotherapy, and/or multidisciplinary interventions (8, 10, 32, 33). Rehabilitation followed by home-based management can play a crucial role in the multidisciplinary management of these patients through education, movement retraining, and self-management strategies in a positive and a non-judgmental context (8, 10, 32, 33).

Finally, complicated patients with combined FMD phenotypes (3), paroxysmal symptoms, and psychiatric comorbidities or overlapping organic neurological disease (9) may require a further third-line interdisciplinary and multidisciplinary approach (16). More advanced diagnostic testing and specialist visits might be focused on evaluating only organic symptoms paroxysms, thus averting a waste of unnecessary healthcare resources.

Scattered evidence suggests that rehabilitation might further decrease healthcare costs by reducing symptom severity and improving quality of life (34, 35). Nielsen et al. (2017) found an improvement in motor symptoms in 72% of the patients attending physiotherapy (n = 30) compared with 18% of patients who did not (n = 30) over 6 months (34). The improvement was associated with moderate-to-large treatment effects across various clinical outcomes, such as quality of life as measured by Short Form 36. In addition, this feasibility study showed that rehabilitation had a high probability of being cost-effective, with a mean incremental cost per quality-adjusted life-year gained at £12,087 (34).

Whether disease-specific multidisciplinary three-stage stepped care is truly cost-effective needs to be explored by cost-effectiveness studies. The results of this work are an initial step to determine whether reducing unnecessary medical testing through accurate and early diagnosis followed by patient-centered multidisciplinary care can improve patient outcomes and save health costs.

The main strength of our study is that for the first time the economic burden of FMDs has been estimated in a cohort of patients with a clinically definite diagnosis made at the same clinic for movement disorders. The analysis of health services resources was used because neurological symptoms showed that the main drivers of utilization volume and cost are the broad categories of services, testing, rehabilitation, and hospitalization, as well as the specific type of service (neurology, psychology, etc.). The variety of services reflect the patient's difficulties in seeking a definite diagnosis that may take up to 5 years before it is established.

Our data should be interpreted cautiously given the small sample size, also including patients with FMD with comorbid organic neurological and psychiatric disorders, which may have lengthened time to diagnosis and increased healthcare costs. However, our cohort's proportion of these comorbidities is consistent with those reported in a larger sample of FMD patients (3, 9, 29), thus indicating that our patient's sample is representative. Data from a larger sample of FMDs stratifying patients with and without neurological/psychiatric comorbidity would generalize the present results.

Other significant limitations of this work are the lack of an instrument designed/validated for assessing costs in FMDs and the lack of a control group with “organic” motor disorders hampers having a typical healthcare expenditure to compare with. The lack of patient-reported outcome measures and reported experience measures does not allow us to assess the patients' dissatisfaction about their pathway care. Moreover, the retrospective design did not allow us to retrieve indirect medical costs or evaluate informal care and productivity loss for high recall bias risks. Finally, we could not determine the severity of the recorded symptoms and quality of life as we did not employ an instrument for rating them (i.e., simplified functional movement disorders rating scale and SF36).

Notwithstanding these limitations, our study provides a starting point for future studies to statistically test and quantify cost reduction after implementing appropriate healthcare pathways to analyze an economic comparison between a diagnostic protocol in practice vs. none. The goal is to understand the economic burden of undiagnosed FMDs and the magnitude of increasing/decreasing cost overtime before/after diagnosis.

Future studies would (1) validate the questionnaire specifically for patients with FMDs to improve the quality of resource use data generated, (2) evaluate whether there exists meaningful differences in cost between different phenotypes, and (3) consider the number of individual providers, as opposed to specialist visits, to detail how many different opinions motor FMDs might have.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee Verona and Rovigo Province (CESC) (Project Number 132 1757CESC). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

MT: design, conceptualization and execution of the study, review, and critique of the statistical analyses and manuscript. MG: execution of the study, acquisition of clinical data, drafting the manuscript, and review and critique of the manuscript. SL: execution of the statistical analyses, drafting the manuscript, and review and critique of the manuscript. CL: design, conceptualization of the study, review and critique of the statistical analyses and manuscript. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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