Juvenile Huntington disease
Oct. 24, 2022
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Functional movement disorders represent a challenge for the clinical practitioner as the diagnosis and treatment are usually difficult, and the prognosis may be poor in some patients. Sometimes also referred to as “functional,” “conversion,” or “psychogenic,” these disorders must be differentiated from “organic” disorders. Functional movement disorders may have several presentations, including tremor, dystonia, myoclonus, tics, parkinsonism, gait disorders, hemifacial spasm, opsoclonus, oculogyric crisis, stereotypies, painful legs, moving toes, etc. and are not uncommonly accompanied by functional speech and voice disorders. In this article, the author discusses current advances in the diagnosis, pathophysiology, and treatment of functional movement disorders.
• There is currently a lively debate whether the term functional or psychogenic should be used to describe these movements, with both terms having advantages and disadvantages.
• Functional movement disorders may have a wide variety of presentation; although tremor, dystonia, myoclonus, and gait disorders are among the most common, tics, parkinsonism, abnormal ocular movements, palatal tremor, stereotypies, and hemifacial spasm can also be observed.
• The diagnosis of functional movement disorders should be based on positive clinical findings rather than being a diagnosis of exclusion.
• The prognosis of functional movement disorders is usually poor; however, a short duration of the symptoms with an acceptable explanation and understanding of the disorder by the patient are considered important good prognostic factors.
• Current advances in the use of functional brain imaging are providing further information about the pathogenesis of these conditions.
The term hysteria was introduced in the Corpus Hippocraticum by Hippocrates of Kos (460-370 B.C.) to explain gynecological and other medical symptoms that were suspected to be linked with the womb (uterus). In the following centuries the concept of a “wandering womb” causing neurologic and psychiatric symptoms was predominant (214). However, in the second century Galen of Pergamon (130-210 A.D.) developed a theory emphasizing reciprocal influences between the mind and body to explain neuropsychiatric manifestations; however, such a remarkable advance was not further developed and in the Middle Ages “hysteria” was considered a sign of witchcraft and punished according to the instructions provided by the influential book Malleus Maleficarum: this view was dominant until Edward Jorden (1569-1633) recognized hysteria as a mental illness in his book A Disease Called the Suffocation of Mother (214). The conception of hysteria was not deeply studied until Pierre Briquet (1796-1881) published his book Traité clinique et thérapeutique de l’Hystérie, where he rejected theories attributing the neuropsychiatric symptoms to the womb. Briquet’s work had a great influence on Jean-Martin Charcot (1825-1893), who headed the French school in La Salpêtrière in Paris (85).
Charcot developed the anatomo-clinic method to study neuropsychiatric disorders through correlation between neurologic symptoms and abnormal pathology. Charcot discriminated disorders with an “organic” cause (ie, those with identifiable lesions in the nervous system) to those without an identifiable pathological lesion, called nevroses (neuroses), which included hysteria (85). Charcot dedicated several of his last years to the study of hysteria and proposed that hysteria was congenitally derived and a “dynamic lesion” from which its nature was unknown affected specific areas of the nervous system correlating with symptoms (85). He also used hypnosis as an experimental method to study hysterics; such proceedings are depicted in the famous painting “Une leçon clinique à la Salpêtrière” by Andre Brouillet. Charcot believed that prompt treatment of hysterical symptoms was important for good outcome and encouraged induction of second attacks using “hysterogenic points” or hypnosis for the diagnosis and treatment of many neurologic complaints. Many criticized this approach to treatment, as it would lead to imitations and behavior reinforcement. The English school headed by Gowers and Henry Head was critical on this point. Gowers observed that neurotics might suffer from many symptoms including spasm, palsy, and coma. He emphasized that there were few organic brain diseases not “imitated” by neurosis and the clinician must exclude any potential organic cause for the symptoms before concluding that they are functional in origin (87; 96).
Charcot and his followers used hypnosis as a powerful tool for demonstrating how, on occasion, subconscious motivations could generate a variety of disabilities resembling those seen in the context of bona fide neurologic disease (75). At that time, Janet emphasized the concept that “fixed ideas” could act in an unconscious level, and such unconscious mind may “dissociate” from the conscious mind under certain circumstances such as hypnosis or emotional states (196). Following the same line of thought, the term “hysteria” was replaced by “conversion” disorders, under the influence of Sigmund Freud who proposed that these symptoms result from a transformation (or conversion) of a psychological conflict into a symbolic physical manifestation because of repression of the unconscious mind, related to sexual conflicts (109). By the end of the 19th century Joseph Babinski, a Charcot’s student, aimed to identify clinical signs that distinguish “conversion” from organic disorders. He introduced the term “pithiathism” (from the Greek “persuasion”) following the observation that suggestion is characteristic in these patients (230; 198). Conversion disorders have been classified under the somatoform disorders (Briquet syndrome), a group of longstanding poly-symptomatic manifestations without evidence of an organic origin. Currently, the term "functional" is used to describe abnormal movements believed to derive from an underlying psychological or psychiatric disorder (92). However, a substantial proportion of patients with a movement disorder labeled "functional" does not always fit into an established psychiatric diagnosis (such as personality disorders, neurotic tendencies, or psychotic states), puzzling clinicians because of their apparent lack of appropriate characteristic psychosocial features or evidence for secondary gain (177). For these reasons some authors have proposed the term “functional movement disorders” (52); however, this term may also be misleading in part because patients suffering from these disorders are quite dysfunctional rather than functional (105). Furthermore, the term “functional” is not easily understood by patients, lacks scientific specificity, can be a disservice for patients, and it may delay treatment; but more importantly, the term functional could be a tactful way to lead the patient to acceptance of the diagnosis and to provide proper therapy (64; 105). In this review, we will use the term “functional” rather than “psychogenic,” but both terms are currently used in modern literature.
The DSM-5 (03) classification of psychiatric disorders includes additional categories under which a functional movement disorder might reside, such as somatic symptom disorder, conversion disorder, illness anxiety disorder, and factitious disorders. In a minority of cases, the primary psychiatric disorders are factitious disorders or malingering, in which the abnormal movements are feigned (29; 02). However, the term “malingering,” has been removed from DSM-5 as it is thought to represent a voluntary condition rather than a mental illness.
General features of functional movement disorders. The growth of the clinical literature defining the various movement disorders has enhanced clinical expertise and the criteria for recognizing functional movement disorders (19).
Functional movement disorders can be among the most challenging neurologic conditions. The diagnosis is based on positive findings and it is not a diagnosis of exclusion. There has been an exponential growth of manuscripts detailing the phenomenology of functional movement disorders (19). However, there are general features suggesting that a movement disorder may be functional (66; 210; 89). These features can be divided into historical, clinical, and therapeutic ones (Table 1). Historical features include an abrupt onset or a static course, unexplained spontaneous remissions, obvious psychiatric disturbances, multiple somatizations, the presence of potential secondary gain, pending litigation, or compensation. Clinical clues suggesting a potential functional movement disorder include: inconsistent features with an “organic” movement disorder (variable amplitude, frequency, distribution, and selective disability), worsening with attention and improving with distraction (209); selected disabilities such as preserving the ability to write despite marked tremor or functional disability out of proportion to neurologic examination. Other signs include false weakness, false or inconsistent sensory complaints, self-induced injuries, and deliberate slowness of movement (89).
Distractibility is 1 of the most characteristic features of functional movement disorders, particularly tremor (105). In a group of 28 subjects with functional movement disorders, 86% exhibited distractibility (62). In half of them, the condition developed abruptly, and more than one third demonstrated disabilities that were more selective than should be experienced with the usual presentations of the disorder (62).
Examiners maneuvers (also known as sensory tricks) are episodic and specific maneuvers that temporarily improve (alleviating maneuvers) or worsen (aggravating maneuvers) dystonia in a manner not based in counteracting the involuntary movements. In patients with functional movement disorders a variety of stimuli can influence functional movements, including tactile, proprioceptive, nociceptive, kinetic, and auditory or complex stimuli; however, vibration with a 128 Hz tuning fork was the most common (23). Aggravating maneuvers were detected in 20% of patients with functional movements; 12% had alleviating maneuvers, and few patients were influenced by both types of maneuvers in a large cohort (23). It is unclear to which degree this represents suggestion or abnormal somatosensory processing as discussed below.
The “whack-a-mole” sign refers to the suppression of involuntary movements in 1 body part when holding it, and, in apparent reaction, the involuntary movement increases in other limbs (166). Convergence spasm is another phenomenon that can be observed in patients with functional movement disorders. Convergence spasm is defined as a transient ocular convergence, miosis, and accommodation resembling abducens palsy (70). Convergence spasm was observed in 69% of patients with functional movement disorders using blinded evaluations; this feature was found in 36% and 33% of patients with organic movement disorders and normal controls, respectively (70). The presence of marked convergence spasm showed a high specificity (87%), although a low sensitivity (15%) for the diagnosis of functional movement disorders.
Finally, therapeutic clues to the functional nature of the abnormal movement include a prominent placebo effect, unresponsiveness to medications that usually improve the same organic movements, and remission or marked clinical improvement with psychotherapy (77).
Functional tremor. Tremor is 1 of the most common presentations in most series of functional movement disorders (63; 62). In a review, the most common functional movement disorder was tremor (49%), followed by more bizarre and difficult-to-classify abnormal movements (25.5%) and an equal frequency of dystonia (21%), myoclonus/jerks (21%), tic-like movements (21%), and functional gaits (21%) (10). Other less common disorders included functional hemifacial spasm, functional chorea/ballism, and restlessness. Patients with functional tremor usually show marked variability in amplitude, frequency, and direction of the shaking; changing distribution of the tremor is another feature. Increased variability drawing spirals have been recognized in patients with functional tremor compared with subjects with organic tremor (98).
Entrainment or ceasing of tremor to externally cued rhythmic movement is a typical feature of functional tremor (105).
In a series of 24 patients with functional tremor, Koller and colleagues reported that the majority had an abrupt onset, often with a complex interplay of resting, postural, and action tremor qualities (115). Dual task interference has been proven as a feature of functional tremor (120). Other features highly suggestive of functional tremor are presented in Table 2 (111).
• More common in women
Some of the clinical features of functional tremor may be demonstrated using neurophysiology (see section below).
Functional dystonia. Functional dystonia is a well-recognized form of functional movement disorders (65; 66; 126). Two types of functional dystonia have been recognized: mobile and fixed dystonia. Mobile dystonia represents about two thirds of patients with functional dystonia; these patients have frequently a fluctuating clinical course with axial localization of dystonia and comorbid functional neurologic disorders (171). Fixed dystonia is the typical presentation of functional dystonia; most patients have involvement of the lower extremities and a peripheral injury precedes the onset in about two thirds of cases (187). Another series showed that functional dystonia is more often associated with pain (47.4%) than functional tremor (213). Most patients have comorbid pain (125). Long duration fixed dystonia may lead to secondary joint contractures (235). Criteria for complex regional pain syndrome is met by about one fifth of cases (187). Some patients with limb dystonia may request amputation of the affected limbs, but such procedures have an unfavorable outcome (49). Functional dystonia has been identified by polysomnography in a patient during stages 1 and 2 of non-REM sleep and REM sleep (13). The movements caused night arousals and excessive daytime sleepiness (13).
• Women are overrepresented
Functional myoclonus. Functional myoclonus is a common presentation of functional movement disorders, with similar gender distribution. They were observed in 20% among 89 patients with functional movement disorders (141). Functional myoclonus shares features of other functional movements such as distractibility, spontaneous remissions, improvement with placebo, and associated psychopathology (141). Entrainment or full suppressibility of movements to externally cued movements is also observed in functional myoclonus. Axial distribution is common in patients with functional myoclonus, but multifocal involvement including the facial muscles is not uncommon (55). Propriospinal myoclonus is a form of axial myoclonus characterized by painless, usually flexor arrhythmic jerks of the trunk, hips, and knees, which are often stimulus-sensitive and increase when the patient is supine (218). It has been assumed that propriospinal myoclonus originates from a spinal generator and spreads up and down the spinal cord via intrinsic proprioceptive pathways, therefore, the slow conduction velocities (5-15 m/s) recorded in these cases (05). In a clinical reappraisal of 179 cases, 104 (58%) were diagnosed as having functional propriospinal myoclonus (218). Functional myoclonus may be stimulus-sensitive with variable latency. Such stimulus-sensitive jerks, particularly following auditive stimuli, may mimic pathological startle response (212; 127). Although patients with functional movements may have enlarged response probabilities of the early and late startle responses, they usually show a normal recruitment of involved muscles (48). Patients with functional myoclonus have normal spine imaging, an inconsistent EMG pattern of muscle activation, and presence of the motor preparation potential or Bereitschaftspotential (218). The “jumpy stump” is another possible presentation of functional muscle jerks, characterized by sudden onset of paroxysmal rhythmical stump jerking associated with distractibility and variability of the movements (234).
• Gender distribution is about equal
Functional palatal tremor. Palatal tremor (also known as palatal myoclonus) is another presentation of functional movement disorders (134; 110). Palatal tremor is classified as “essential” when such tremor is the only clinical manifestation and imaging studies are normal, and as “symptomatic” when a structural or degenerative cause is identified, usually by neuroimaging. In a retrospective study of 10 patients with essential palatal tremor, a functional cause was identified in 7 of them (197). Such patients were mostly female, younger than patients with symptomatic palatal tremor, and frequently reported a precipitant event. These patients also complained of ear clicking, multiple somatizations, as well as variable entrainment and distractibility of palatal movements. Treatment with oral medications usually fails, but improvement with botulinum toxin has been observed in selective cases (15).
Functional paroxysmal dyskinesia. Among patients presenting with paroxysmal nonkinesigenic dyskinesia, a functional etiology has been described (45). In 1 study, 11 of 25 subjects were diagnosed as having a psychogenic (or functional) etiology (32). In another study of 26 patients with paroxysmal functional movement disorders, dystonia was the most common single movement disorder presentation but complex movements were the most common phenomenology (78). The age at onset is usually much later than in hereditary paroxysmal dyskinesias; other features include: high phenomenological variability between attacks, atypical and variable duration of attacks, multiple atypical triggers, odd precipitating factors, unusual relieving maneuvers, and unusual response to medications are typical among patients with functional paroxysmal dyskinesia (78).
Functional tics. Cases of functional movements resembling tics have been reported in the literature (122). Because factors such as activity, psychological stress, or medications can influence the occurrence of genuine tics, the possibility of a functional causation presents an additional diagnostic challenge (18; 79). Moreover, functional tics may be observed along with tics in subjects with Tourette syndrome (122). In a study, a series of 9 patients with functional tics represented 4.9% of 184 patients with different functional movement disorders (18). The mean age of onset was 29.7 years, which represents an older age compared to patients with Tourette syndrome; females are overrepresented in patients with functional tics, compared to organic tics, in which males are the majority of patients. A number of distinctive features are helpful to differentiate functional from organic tics (Table 5), including lack of premonitory sensation, inability to suppress the “tics” at least transitorily, lack of family history of Tourette syndrome, lack of response to dopamine receptor antagonists, and frequent coexistence of other bizarre movements were identified in patients with functional “tics” (18). The lack of the typical rostro-caudal tic distribution seen in patients with Tourette syndrome has also been identified in patients with functional tics (44).
Functional neurologic disorders may also present in the context of Tourette syndrome. Functional movement disorders were identified in 5% out of 201 patients with an organic tic disorder (27). No specific clinical feature was associated with a higher risk of functional movement disorder in patients with organic tic disorder (27).
• More common in women
Functional gait disorders. Various patterns of functional stance and gait disorders have been described. The original term “astasia-abasia,” which literally means “inability to stand and walk” was coined by Paul Blocq to refer to a variety of phenomena affecting gait (155). Functional gait disorders were identified in 39.2% of patients with functional movement disorders, although only 8.5% had an isolated functional gait disorder (ie, without other functional movement disorders) (12). Gait abnormalities have been reported to be significantly more common in a group of elderly patients (mean age 63.5 years) with functional movement disorders, compared to young patients (mean age 35.5 years) with this disorder: 69.7% versus 23.5%, respectively (P< 0.001) (28; 213). In a series of 37 subjects, the observed features included intermittent occurrence of excessively slow or hesitant walking, a delayed disturbance of balance, exaggerated expenditure of effort, awkward postures, sudden buckling of the knees without falls, a “walking on ice” gait pattern, which is characterized by small cautious steps with fixation of the feet at the ankles, and functional “Romber sign” with progressively increased swaying amplitudes (129). Other features include variability throughout the day, collapses, convulsive tremor, and distractibility (95; 232). In addition, a common pitfall for the untrained neurologist may be the often-bizarre gait seen in dystonia and chorea (95). In a study comparing patients with functional movement disorders with and without functional gait disorders, slowness of gait was the most common feature in patients with functional movement disorders combined with a functional gait, whereas knee buckling followed by astasia-abasia were the most common patterns in patients with pure functional gait disorder (11).
The “chair test” has been proposed to help in the diagnosis of functional gait disorders. The test was originally contained in Paul Blocq’s original description of hysterical gait disorders from 1888. The test examines the ability to propel a wheeled chair with the feet while seated normally, but its sensitivity and specificity are unclear. Patients with functional gait disorders usually perform much better when seated in the chair compared to patients with organic gait disorders (156). Effort-associated behaviors (“huffing and puffing”) have been observed in 44% of patients with functional gait disorders and showed a high specificity for the diagnosis of functional gait disorders, despite its low sensitivity (128). Analysis of changes in kinematic patterns through time in patents with functional gait disorders has been proposed as a method to identify patients with functional gait disorders (139).
There is no universal classification for functional gait disorders. One classification considered 7 types of functional gait: (1) ataxic; (2) spastic; (3) weak; (4) antalgic; (5) parkinsonian; (6) hemiparetic; and (7) dystonic (154). Another classification based only in specific signs includes: (1) slow-hesitant gait; (2) astasia-abasia; (3) knee buckling; (4) scissoring; (5) wide based gait; (6) limping; and (7) lower limb dystonia (12). The latter allows classifying patients into more than a single category, as patients with functional gait disorders usually present with more than a single phenomenon.
• More common in women
Functional balance and postural problems. Persistent perceptual postural dizziness (known as PPPD) is a newly coined term to describe patients with functional dizziness and balance problems (174). The condition presents in 10% of patients diagnosed with a primary diagnosis of clinic specialized clinics, and may coexist with organic vestibular disorder; indeed, the disorder is usually triggered by acute dizziness. Other terminology includes phobic postural vertigo, visual vertigo, and chronic subjective dizziness. Patients manifest persistent disequilibrium or nonspinning dizziness provoked by upright posture, active or passive motion, and exposure to complex or moving stimuli (174). These patients usually complain of context-dependent aggravation of their symptoms, such as walking in a supermarket, which leads to avoidance behavior that can be confused with agoraphobia. A functional gait disorder is not uncommon in these cases. A related syndrome named “motorist vestibular disorientation syndrome” manifests with a distorted sense of vehicular tilt while driving with specific speed thresholds (158).
Functional parkinsonism. Functional parkinsonism is observed in between 1.7% and 25% in series of patients with functional movement disorders (116; 125). A prevalence of 0.64 per 100,000 has been estimated in Swiss population (74). These patients usually display a deliberate, slow, and effortful movement instead of the amplitude decrement of bradykinesia observed in Parkinson disease (Table 7) (15; 211). An abnormal (minimal, bizarre, or exaggerated) postural stability testing and tremor of abrupt onset typically involving the dominant hand or starting in 1 leg, with other features of psychogenic tremor are common features of patients with functional parkinsonism (104). Patients with functional parkinsonism usually show Gegenhalten (active resistance to passive movements) instead of the cogwheel rigidity of Parkinson disease. Other features include stuttering or abnormal speech, elaborated and irregular handwriting without micrographia, and bizarre or stiff gait without freezing. Some patients may even develop functional “levodopa-related dyskinesias” with bizarre and incongruous movements instead of chorea or dystonia observed in Parkinson disease (104). Olfactory tests may be normal in functional parkinsonism and are usually abnormal in those with Parkinson disease, which may be helpful in discriminating between the 2 parkinsonian disorders (130).
• Gender distribution is about equal
Functional speech and voice disorders. Functional speech and voice disorders are not uncommon and may coexist with functional movement disorders. They were identified in 16% of patients with various functional motor disorders in a large series (20). Stuttering was the most common speech abnormality (53.3%), followed by speech arrests (13.3%), foreign accent syndrome (6.6%), hypophonia (6.6%), and dysphonia (6.6%), with 13.2% presenting different combinations of the described patterns; no difference in age at onset, gender, and distribution of functional movement disorders were identified in patients with and without functional speech and voice disorders (20). Patients may have a characteristic stutter at the end of words but stuttering at the beginning of words is more common.
Functional chorea. Functional chorea has rarely been described in the medical literature (71). A presentation resembling Huntington chorea has been described in an unaffected member of a family with Huntington disease; the latter diagnosis should be ruled out with a negative DNA test (71). Functional dyskinesia, resembling chorea, have been reported in 3 selected patients treated with deep brain stimulation. The movements were induced or resolved following sham stimulation, supporting a functional etiology (133). Posttraumatic shoulder movements may appear as functional, but electrophysiological testing has not supported such etiology, and further studies are required to define the most common etiology of such movements (159). A functional etiology is an uncommon cause of chorea in children (14).
Functional facial movements. Functional facial spasms are among the most common of the functional cranial movement disorders with several distinguishing features (Table 7) (Yaltho and 104; 110). Functional hemifacial spasms have been observed in between 2.4% and 7.5% of patients referred for evaluation of hemifacial spasm (103; 76; Yaltho and 104). Functional hemifacial spasm represented 9.8% of patients among 184 patients with functional movement disorders (25). The features of functional facial movements have been studied in 61 patients from various centers (67). The most common pattern observed was a sustained, tonic, lateral, and downward protrusion of 1 side of the lower lip with ipsilateral jaw deviation (84.3%); ipsi- or contralateral blepharospasm and excessive platysma contraction occurred in isolation or in combination with fixed lip dystonia in 60.7% of patients. Tonic lip deviation has been recognized as a distinctive feature of functional facial movements (34). Compared with patients with organic hemifacial spasm, those with functional hemifacial spasm are younger and had more frequently tonic muscle contractions, bilateral asynchronous hemifacial involvement, isolated lower facial involvement, downward deviation of the mouth’s angle, and lack of the “other Babinski sign” (ipsilateral elevation of the eyebrow) (23).
• Hemifacial spasm is 1 of the most common features
Functional eye movements. Abnormal eye movement can also be observed in patients with functional movement disorders. In a study of 182 patients with functional movement disorders, abnormal eye movements were identified in 11 patients; the most frequent phenomenology were oculogyric crises (n=7), followed by opsoclonus (n=5) and ocular flutter (n=1) (21). These patients also displayed a myriad of other functional movements. A trend for younger age at onset was observed in patients with functional ocular movements compared to patients without them, otherwise no difference in clinical features was observed in patients with or without functional eye movements (22). Functional eye and eyelid movements may coexist with organic nystagmus and may be provoked with positional maneuvers (146). This may complicate the recognition of functional eye movements in clinical practice, but they should not be ruled out whenever there are signs of organic vestibular dysfunction.
Functional stereotypies. Stereotypies are defined as repetitive, coordinated, seemingly purposeful movements. Stereotypies have been identified in several neurologic conditions and also as part of the phenomenology of functional movements (23b). Stereotypies were observed in 10.3% of patients with functional movements, including orolingual dyskinesia, limb/trunk stereotypies, and respiratory dyskinesia, resembling in many cases tardive dyskinesia. However, patients with functional stereotypies had a younger age at onset, lack of self-biting, uncommon chewing-like movements, isolated lingual dyskinesia, and other functional movements such as tremor compared with patients with tardive dyskinesia in 1 study (23b).
Functional painful legs and moving toes. Painful legs and moving toes syndrome is characterized by the combination of repetitive involuntary toe movements and pain in the feet or legs. The movements can be voluntarily suppressed, disappear during deep sleep, and can be prevented by pressing on the foot or toes (202). Although the disorder has been considered “organic,” few patients with this syndrome suggest a functional or psychogenic etiology due to distractibility, entrainment, and movement frequency similar to voluntary movements (202; 221). A high frequency of restless legs syndrome, assessed by actigraphy, was detected in Czech patients with functional movement disorders compared with controls, suggesting that it may be unrecognized in this group of patients (192).
Functional movements at the extremes of ages. Functional movement disorders have also been described in children and adolescents (72; 191). Functional neurologic disorders in children have an estimated prevalence of 2 to 4 cases per 100,000 (118) and represent 2% to 4% of children presenting to a movement disorders clinic for first evaluation (140). In a meta-analysis of published case-series of functional movement disorders in children, which included 120 patients, tremor was the most common presentation (52.5%), followed by dystonia (43.3%), myoclonus (28.3%), and gait disorders (13.3%), similar to what is observed in adults (15). The diagnosis and therapeutic approach do not differ between children and adults, but the prognosis seems to be better for children (28). Cognitive behavioral therapy, psychotherapy, physiotherapy, and relaxation techniques are the most used therapies in children with functional movement disorders (93). Functional movements are also observed in the elderly. Patients older than 60 years of age represented 21% of cases in a series of 151 patients. The elderly seem to have a higher frequency of functional gait disorders and psychogenic seizures, but a similar frequency of tremor and dystonia compared to younger patients (28).
Mass psychogenic illness. Mass psychogenic illness is a phenomenon occurring in cohesive social groups or families. First registers date back to the Middle Ages in central Europe with the outbreaks of “dancing mania” associated with the Black Plague. The movements were named “chorea sancti viti” or “Saint Vitus dance” after the Christian martyr Saint Vitus, who was invoked to intercede for those affected. Several outbreaks have been registered in recent decades. The phenomenology may include seizures, paralysis, speech/voice disorders, and abnormal movements (15). Most affected individuals are female; 2 conditions are considered necessary to induce the phenomena: (1) a perceived exposure to an illness-causing agent (ie, toxic gas, contagious illness, etc.); (2) observation of other persons developing symptoms (107). However, there is no evidence of particular vulnerable personality that increases the risk to suffer from this phenomenon. Although largely absent from the public discourse, functional neurologic disorders frequently appear in the news incognito, hiding in plain sight (173). Some of these reports, such as the cases of diplomats in Havana, Cuba, have been suggested to represent “mass hysteria,” although this continues to be a source of lively debate (205; 224). The emergence of coronavirus disease 19 (COVID-19), due to SARS-CoV2, has been related to several neurologic manifestations, including movement disorders. A survey in the medical literature yielded 93 new onset movement disorders cases in patients affected with COVID-19 (31). Myoclonus was the most common abnormal movement followed by ataxia and action/postural tremor. Functional movement disorders represented 3.2% of cases. Encephalopathy coexisted with movement disorders in about 40% of cases (31).
Gender differences. Men represent about 30% of all patients with functional movement disorders. A study comparing age at onset and phenomenology differences between women and men with functional movement disorders showed that men had an older age at onset: 40.5 versus 34.1 years (P = 0.026) with an older age at presentation for clinical evaluation. Interestingly, genders were equally represented in patients aged 50 years or older (26). Functional dystonia was more frequent in women than men: 47.5% versus 20.3% (P < 0001); functional gait disorders were more common in men (44% vs. 30%), although they did not reach statistical significance (26). Moreover, an association between sexual abuse and functional movement disorders was observed in women but not in men in another study (OR 4.82; P < 0.0001) (112).
The prognosis of patients with functional movement disorders is usually poor.
Peckham and Hallett have identified a group of prognostic indicators based on a review of the subject and their experience on the evaluation and treatment of patients with functional movement disorders (167). The authors noted the following favorable indicators: short duration of symptoms (less than 1 year); inconsistency of movements; good physical health; positive social life perception; elimination of stressor; patient's perceptions of receiving effective treatment; changed marital status; and, if admitted to hospital, resolution of symptoms on discharge. Poor prognostic factors included the presence of chronic functional symptoms; functional motor symptoms; smoking; suggestibility; pending litigation; dissatisfaction with physician; and older age at onset of symptoms. In a systematic review of 24 studies including patients with functional motor symptoms, 39% of patients were the same or worse at follow-up (range 10% to 90%, n=1134); short duration of symptoms and an acceptable explanation regarding the nature of the disorder were considered important in clinical practice (83). Although gender had no effect on the outcome, other prognostic factors, such as age, comorbid psychiatric disorders, IQ, pending litigation, educational status, and marital status, had variable influence in the outcome between studies (83). In a study of 41 patients with fixed dystonia followed by 7.6 years, 31% had worsened, 46% were the same, and only 23% reported clinical improvement (101). The presence of complex regional pain syndrome predicted a poor score (101). This study suggests that most patients with fixed dystonia have functional motor phenomenon with a particular poor prognosis. In another study, 42 patients were sampled by telephone interview and 90% had persistence of involuntary movements after 3.2 years from diagnosis (69). Patients with functional motor disorders are generally dissatisfied by psychological explanations of their disorder and commonly feel misunderstood and abandoned by health care professionals, making them more prone to iatrogenic harm (149). Moreover, quality of life has been found to be significantly more altered in patients with functional movement disorders than in patients with dystonia, but similar compared with patients with Parkinson disease (84). Higher rates of unemployment are observed in patients with functional neurologic disorders compared with the other conditions (84).
When comparing demographics, mode of onset, comorbid anxiety, depression, pain, and fatigue, no difference was observed among patients with various predominant functional motor manifestations in a study including 160 patients (82). However, physical functioning was worse in patients with a predominant functional gait disorder compared with those with functional tremor or functional myoclonus (82). This finding indicates that certain motor presentations may have a larger impact in quality of life in these patients.
Stress and psychiatric comorbidity. What predisposes individuals to manifest functional disorders in the form of abnormal motor control or involuntary movements is not known. In a study comparing patients with functional movements with those with organic dystonia, the former had a trend to a greater frequency of personality disorders overall, without significant difference when looking to individual personality disorders (41). In a study comparing patients with functional and organic movement disorders, no differences were noted for self-rated measures of depression/anxiety, dissociation, and personality disorders between both groups (216). However, depersonalization was reported in 17 patients with functional movement disorders after the 10-minute Mirror Gazing Test (MGT), suggesting some features of dissociation are more common in these patients than in normal healthy controls (152).
Stress has been deemed important in the pathogenesis of functional movement disorders; however, in a study assessing the role of previous life stress in patients with functional movement disorders, 64 patients with a variety of functional movement disorders were compared to 38 healthy volunteers and 39 patients with focal hand dystonia (119). Patients with functional movement disorders reported higher rates of childhood trauma, greater emotional abuse and neglect, greater fear associated with traumatic events, and greater numbers of traumatic episodes compared to the other groups after controlling for sex and depressive symptoms (119). In a metanalysis of 34 case-control studies including 1405 patients with functional neurologic disorders, emotional neglect in childhood was higher in patients compared to controls: 49% versus 20% (OR: 5.6), as well as sexual abuse, 24% versus 10% (OR: 3.3), and physical abuse, 30% versus 12% (OR: 3.9) (131). Stressful life events in childhood and adulthood were higher in patients, but stressors preceding the onset of the neurologic manifestations were higher in patients compared to controls (OR: 2.8) with stronger association in studies with better methodology (131). It is unclear whether risk factors differ between gender; however, 1 study showed higher self-reported rates of cognitive complaints and functional weakness were reported by men, whereas high rates of past physical/sexual trauma were endorsed by women in a retrospective study of 100 patients with functional neurologic disorders (137). Moreover, in a study assessing the levels of circulating cortisol in 33 patients with clinically definite functional movement disorders and age- and gender-matched controls, no differences in the cortisol levels were observed between groups (136), casting doubts about the role of stress in the pathogenesis of functional movement disorders. Another study demonstrated lower IQ and active coping skills of patients with functional movements compared to normal subjects, but not in patients with organic movement disorders; these lower coping strategies could be the result of having an active disorder (215). In 68% of the patients, comorbid psychiatric diagnoses such as depression, anxiety, bipolar disorder, personality disorders, obsessive compulsive, and eating disorders were identified. An Italian study reported that 10 patients with functional movement disorders had significantly higher levels of anxiety, symptoms related to posttraumatic stress disorder, and perceived stress during the SARS-CoV-2 pandemic compared to controls (153), suggesting an increased vulnerability for stressful situations or life events. Precipitating factors were identified in 80% of patients with functional movement disorders, with injury and infection representing most cases; interestingly, panic attack associated with the precipitating event was identified in 38% of cases (163).
Social influences and modeling. Modeling defined “as the adoption of certain symptoms, behaviors, or motor patterns following the observation of close individuals displaying manifestations” has also been proposed to play a role in the pathogenesis of functional movement disorders (15). In a case-control study of 33 patients with functional movements and 66 age-matched controls, those with functional movements had an OR of 3.9 (P=0.01) of exposure to phenotypically congruent movement disorder mode, mainly when the disease came from friendship, compared to normal controls (168).
Abnormalities in attention, abnormal beliefs, and sense of agency. Three concepts aimed to fit a neurobiological model of functional movement disorders have been proposed: attention, symptom-related beliefs/expectations and sense of agency (51). Attention is proposed as a key feature of functional movement disorders as it is required for the movement to manifest, but when attention is distracted the movement reduces or disappears. Beliefs and expectations are also considered abnormal in these patients. For example, in a study aimed to determine if functional patients tend to “jump into conclusions” more often than other subjects, a group of functional movement disorders patients and controls were presented with 2 jars full of colored beads, 1 with 80% blue and 20% red beads and the other with the inverse proportion of colored beads (162). The jars were hidden, and subjects were presented with a sequence of beads and asked which jar the beads were drawn from. Patients with functional movement disorders made a judgment after significantly fewer draws than controls. In another study, the authors recorded tremor with a wristwatch-like accelerometer during the waking day, comparing patients with essential and functional tremor (164). These recordings were coupled with diaries self-reporting tremor by the participants. Both groups overestimated the amount of time during the day they had tremor; however, patients with psychogenic tremor reported significantly more waking-day tremor than their organic counterparts: 83.5% of the waking day versus 58.0%, despite the fact that patients diagnosed with a functional disorder had tremor only 3.9% of the waking day, compared to 24.8% recorded in those with organic tremor. The loss of sensory attenuation has been correlated with a loss of sense of agency. A reduction in sensory evoked potentials amplitude at the onset of self-paced movements is called sensory attenuation. The loss of sensory attenuation, along with reduction in the intensity of sensory experience when a movement is self-generated, has been associated with loss of sense of agency (132). A study to assess sensory attenuation showed a consistent reduction of this feature in patients with functional movement disorders compared with normal control subjects, contributing to an impaired sense of agency leading to perception of the movements as involuntary (161; 132). Attentional bias has also been detected in patients with functional movement disorders. An experiment where patients and healthy controls were exposed to different types of emotional and neutral faces showed that the former had an attentional bias away from emotional faces, with particular avoidance of sad faces, independently of the presence of alexithymia or mood disorder (135). This was interpreted by the authors as a better perception of general health status by patients suffering functional movements, although patients with functional movement disorders actually report a poor health status.
Abnormalities in somatosensory processing. Abnormalities in sensory or stimulus processing have been reported in patients with functional movement disorders. For example, high temporal discrimination threshold for tactile stimulation is a known feature of generalized and focal organic dystonias. However, this feature has also been found in patients with functional dystonia, but not in matched normal controls, suggesting abnormal processing of somatosensory inputs in both types of dystonia (145), possibly at the level of the supplementary motor area. By using a model for decision-making and sensory processing (the drift diffusion model), the accuracy and reaction time was assessed in patients with functional movement disorders and controls (183). Patients had a pathologically reduced drift that quantifies and qualifies the rate of information accumulation within a sensory task, possibly related to abnormal allocation of attention (183). Patients with fixed dystonia also have abnormal perception of ankle position (203), supporting the evidence of an altered somatosensory processing. Patients with functional dystonia show a dissociation between sensory-discriminative and cognitive-emotional components of pain compared to patients with organic cervical dystonia and normal controls, as pain tolerance was increased in all body regions only in patients with functional dystonia, although pain thresholds were normal in all groups (143). Abnormal sensory processing with tendencies toward low registration, sensory sensitivity, and sensation avoiding was observed in a study of 44 patients with functional neurologic disorders (181). Lifetime anxiety, female gender, and number of current medications, possibly as a proxy of severity, correlated with such abnormal sensory processing (181).
Transcranial magnetic stimulation in patients with functional dystonia has demonstrated altered inhibitory circuits at cortical and spinal levels similar to patients with organic dystonia (60; 07). Furthermore, in 2 patients with functional dystonia who underwent deep brain stimulation as they were thought to have organic dystonia, no differences in intraoperative neurophysiology measures were observed compared with 5 patients with DYT1 mutations and dystonia (179). However, the sensorimotor plasticity measured with a protocol consisting of paired associative stimulation by means of transcranial magnetic stimulation has been reported to be abnormal in organic dystonia, but not in its psychogenic counterpart (178). In another study of 10 patients with complex regional pain syndrome type 1 in the right upper limb associated with fixed dystonia, no differences in sensorimotor plasticity were observed in these patients compared with normal controls (144). Another study demonstrated that primary motor cortex plasticity may change when assessed with transcranial magnetic stimulation coupled with pictures inducing negative emotions; the same changes were not found when positive emotions were induced (114). The authors proposed that negative emotions may alter cortical plasticity and potentially lead to abnormal (functional) movements. Functional MRI studies using an affective task in patients with conversion and movements disorders have demonstrated greater functional connectivity between limbic structures, particularly the amygdala and the right supplementary motor area during emotional versus neutral stimuli, in patients with functional movement disorders compared to controls (226).
Abnormalities in cortical and subcortical activation and connectivity. Studies using positron emission tomography or regional blood flow have compared patients with organic and functional dystonia to normal controls. In such studies, patients with functional dystonia show abnormal increased blood flow in the cerebellum and basal ganglia, with decreased blood flow in the primary motor cortex (186; 09). Increased activation in the right cerebellum has also been registered in patients with functional tremor compared with control (59). The opposite pattern is observed in patients with organic dystonia. This activation pattern suggests an abnormal subcortical function in patients with functional dystonia. Patients with functional dystonia have stimulus-dependent abnormal activation in networks implicated in motor preparation, execution spatial cognition, and attentional control (58). During movement, patients with organic and functional dystonia had an abnormal activation of the right dorsolateral prefrontal cortex, ruling out the possibility that prefrontal abnormalities are a marker of functional disorders. However, it is unclear if this prefrontal activation is part of the abnormalities that provoke dystonia or just a compensatory mechanism aimed to suppress the abnormal movements. In another study of a small group of patients with essential and functional tremor and normal controls, the authors used SPECT at rest and during a tremor-induced motor task (36). Patients with functional tremor showed increased relative cerebral blood flow (rCBF) in the left insula and left inferior frontal gyrus at rest; however, during the motor task, an increased rCBF was observed in the cerebellum with decreased rCBF in the medial prefrontal and anterior cingulated cortex as well as in the anterior regions to the default mode of the brain. An opposite pattern was observed in patients with essential tremor and normal controls. The insula has been implicated in perception of inner body sensations, self-awareness, and self-agency (35). Increased functional connectivity between the bilateral posterior insula, temporoparietal junction, middle cingulate cortex, and putamen has been detected in patients with functional neurologic disorders (47). The anterior insula showed enhanced connectivity with the amygdala, periaqueductal grey matter, and the hypothalamus (47). Linking structures were implicated in self-perception, emotional processing, motor control, and autonomic functions. However, increased connectivity between bilateral amygdala and premotor regions was observed following a 1-week multidisciplinary motor retraining treatment program in 14 patients with functional movement disorders (68). Lower posttreatment severity of functional movement was associated with increased connectivity between the amygdala and ventromedial prefrontal cortex (68).
A model based in the concept of a conditioned pattern of movement established by a previous triggering event proposes that a previously mapped conversion representation may hijack the voluntary action selection system by means of an increased connectivity between the supplementary motor area and limbic structures such as the amygdala, but a lower functional connectivity with bilateral dorsolateral prefrontal cortices (227; 228).
Although functional/functional movements are considered within disorders without an “organic basis” (ie, lack of macroscopic or evident lesions in the nervous system), evidence has pointed to abnormalities in volumetric measurements of the gray matter in these patients. Smaller mean volumes were identified in the basal ganglia and thalamus in 10 women with conversion disorders compared to controls (06), and this has been confirmed by others (148). Furthermore, increases in cortical thickness of the bilateral premotor cortex with a trend towards increased grey matter volume in these regions were observed in patients with functional paresis (08), whereas abnormal right-side cortical atrophy of motor and premotor regions and bilateral cerebellum has been registered in patients with functional nonepileptic seizures (123). Decreased left anterior insular volume was observed in patients with severe functional disorders compared with controls, whereas increased right amygdalar volume was associated with impaired mental health and elevated anxiety (169). Further studies should clarify the meaning of these findings.
The interpretation of all the neurophysiological and anatomical findings is complex, and it is unclear whether they result from suffering chronic, repetitive movement or are the cause of such bizarre movements, and whether improvement of abnormal movements is related to improvement or disappearance of such markers (16). Further research will help to define which are the predisposing, precipitating, and perpetuating factors for functional movement disorders (16).
Functional neurologic disorders have an estimated incidence of 4 to 12 per 100,000 per year with a prevalence of 50 cases per 100,000 in a community registry (33). In a study of 3781 consecutive patients attending to a neurology clinic, 5.4% had a primary diagnosis of a functional neurologic disorder whereas 30% had symptoms that were only partially explained or not explained by the underlying disease (199). Functional or psychological symptoms were identified in 16% of patients in this large cohort from Scotland (199) and represented one third of new neurology outpatients assessed as having symptoms “unexplained by organic disease” (200).
Women are more frequently affected, with about 60% to 75% of cases. In the Columbia-Presbyterian Movement Disorder Clinic functional women outnumbered men 15 to 1 for continuous movements and 5 to 1 for paroxysmal movements (63). However, in patients with functional parkinsonism or myoclonus and young children, the frequency seems to be equal between genders (104; 15). Functional neurologic disorders have a peak incidence between 35 and 50 years of age.
Functional neurologic disorders are identified in about 6% of patients visiting a neurology outpatient clinic (33). This is similar to Charcot’s Tuesday clinic, where 7% of the total population seen during 1 academic year was diagnosed as having hysteria (77). Other authors have reported a frequency between 2.2% and 3.3% of patients seen in a movement disorders clinic (62; 10). However, this proportion may be as high as 20% (91).
No means of prevention are known.
Functional movement disorders may present with any phenomenology closely resembling its organic counterpart. However, the diagnosis of functional movement disorders is not an exclusion one; rather, it is based on positive findings, described in the section of clinical manifestations. Some diagnostic criteria has been developed to diagnose functional movement disorders.
The clinical diagnostic criteria described by Fahn and Williams divides the level of certainty into 4 categories (Table 9). These criteria emphasized the presence of inconsistent or incongruous motor phenomena, plus the presence of somatization and psychiatric disturbances (66). Improvement with placebo, psychotherapy, or surreptitious observation of normal function in patients with continuous functional movements constitutes situations in which the disorder can be regarded as unequivocally functional ("documented" functional movement disorder).
Although psychological factors can be supportive of the diagnosis of movement disorders, their presence alone is not essential for the diagnosis. The DSM-5 criteria for functional (functional) neurologic symptom disorder no longer require the presence of a psychological conflict to make the diagnosis.
(1) Documented: persistent remittance with psychotherapy, or placebo has been demonstrated, which may be helped by physiotherapy, or the patient was seen without the movement disorders when he or she believed to be unobserved
(2) Clinically established: the movement disorder is incongruent with a classical movement disorder or there are inconsistencies in the examination, plus at least 1 of the following; other functional signs, multiple somatizations, or an obvious psychiatric disturbance
(3) Probable: the movement disorder is incongruent or inconsistent with typical movement disorders or there are functional signs multiple somatizations
(4) Possible: the movement disorder is inconsistent/incongruent plus obvious emotional disturbances
Gupta and Lang proposed the following refinement (Table 10) of this earlier classification based on degree of certainty in the diagnosis (88). The refinements proposed by Gupta and Lang incorporate the modern use of electrophysiological techniques and establish a “clinical definite” category.
(1) Documented: remittance with suggestion, physiotherapy, psychotherapy, placebos)
(2a) Clinically established plus inconsistency over time/incongruent with clinical condition and other manifestations (other false signs, multiple somatizations, obvious psychiatric disturbance)
(2b) Clinically established minus other features such as unequivocal clinical features incompatible with organic disease, with no features suggesting another underlying neurologic or psychiatric problem
(3) Clinically definite: the combination of 1, 2a, and 2b
(4) Laboratory-supported definite: electrophysiological evidence proving a functional movement disorder (primarily in cases of functional tremor and functional myoclonus)
In a study aimed to assess the inter-observer diagnostic agreement and clinical certainty judgment by means of the Fahn-Williams and Shill-Gerber criteria, 4 patients with functional movement disorders and 14 with organic movement disorders were presented in video recordings to a group of neurologists, some of them experts in movement disorders; additionally, clinical information was also presented (142). Agreement (kappa) varied between 0.34 and 0.40 (fair) when the raters judged only the videos, but the agreement increased up to 0.74 to 0.81 when historical details of the patients were provided. In a larger study, 60 patients suffering from functional jerks, myoclonus, or tics were rated by 39 international experts using videos, medical history, and neurologic examination (presented on video) (217). Moderate inter-rater agreement (k=0.56) among evaluators was observed with absolute agreement (k=1.0) reached in only 20% of patients, and very good agreement (k=0.75) observed in 72% of cases. The highest agreement was reached for functional tics and the lowest for functional myoclonus. Importantly, the psychiatric evaluation did not contribute to the diagnosis or increased agreement in this study. In another study 60 patients with functional movements were evaluated by 39 movement disorders experts through a stepping process: (1) visual impression; (2) medical history; (3) physical examination on video; (4) the presence of Bereitschaftpotential; and (5) psychiatric evaluation (220). Neurologic examination was the most decisive for diagnosis contribution (in 39.7% of cases) whereas psychiatric evaluation was the least decisive (in 0.5% of cases). More diagnostic switches occurred after addition of medical history (34.5%) (220). In summary, these studies suggest that the diagnosis of functional movements relies mostly on clinical assessments and historical details with little contribution from psychiatric history.
Syndromes of excessive startle, paroxysmal choreoathetosis, dystonia, and tics are especially prone to being regarded as functional. For all of these reasons, it is important to defer a definitive diagnosis until there is convincing evidence.
Functional movement disorders may coexist with genuine movement disorders; this phenomenon has now been estimated in between 10% and 25% of patients referred to a movement disorder clinic (180; 172; 62). There is growing evidence regarding the presence of functional movement disorders in patients with Parkinson disease and Tourette syndrome (165).
Trauma to the central and peripheral nervous system has been associated with a variety of movement disorders (106; 01; 17). Such patients can develop sustained contractions of multiple neck muscles with hypertrophy and continuing pain (86). The contractions of neck muscles in this rare entity of posttraumatic cervical dystonia usually appear quite different from those seen in cervical dystonia. However, its abrupt origin and the preceding mild injury can readily lead to a clinician's conclusion that this problem is rather functional, not organic. Because it does not conform to the usual understanding of dystonia as a basal ganglia disorder, peripheral trauma-induced dystonia will continue to be a diagnostic dilemma for many patients and clinicians (103; 231). Investigations of causalgia demonstrating signs and symptoms of dystonia have also emphasized the diagnostic and management problems presented by this entity, which can affect limbs and other body parts as well as the neck (185; 188; 30). In a review of 713 patients with peripherally induced movement disorders, an overlap with functional movement disorders was identified in 15% (223), although the argument of an organic movement triggered by trauma has been challenged by other authors (94) who argue for a functional cause for those movements, particularly for fixed posttraumatic dystonia. Fahn cautions against considering dystonia to be organic if it begins as a fixed posture (63).
The diagnosis of a functional movement disorder is based on positive clinical findings and should no longer be considered a diagnosis of exclusion. This is important in the initial evaluation at the emergency department in order to avoid unnecessary tests in a time pressure environment (04). Neuroimaging studies such as CT scans or MRI or neurophysiology (EEG, EMG, etc.) can all be used to rule out other neurologic disorders, but the diagnosis of a functional disorder should not be based only in unremarkable studies.
Placebo testing has been used in the evaluations of patients with suspected functional movement disorders in several reports (115; 116; 141). This technique can yield convincing and dramatic results.
Videotaped examination can be used for comparisons of possible functional movement disorders on different occasions. In the setting of a recording for documenting a functional movement disorder, there may be an embellishment of the problem as if the subject regards the recording as an opportunity to validate the disorder. Videotaped examinations conducted by surveillance can sometimes yield answers (121).
In most instances, psychiatric consultation is advisable to extend the therapeutic approach beyond the neurologist's evaluation. Confrontation of patients with an impression of a functional movement should be conducted in a tactful manner. With prior psychiatric consultation and planning as to the patients' needs after making the diagnosis of a functional movement disorder, the occurrence of impulsive or acting-out behaviors may be lessened.
A number of neurophysiology test and functional neuroimaging studies can be used in the diagnostic work-up of patients with functional movement disorders, as described below:
Neurophysiology tests to assess functional tremor. The diagnosis of certain functional movement disorders can be supported with electrophysiological tests. The simultaneous contraction of agonist and antagonist muscles observed in several patients with functional tremor increases the resonance frequency of the joint, making it easier to drive a mechanical system at its resonance frequency and allows a faster frequency of tremor (90). This co-contraction sign in functional tremor can be demonstrated with a tonic discharge of antagonist muscles approximately 300 ms before the onset of tremor burst (212; 46). Measuring the tremor frequency in 2 different body parts is another method to distinguish functional from organic tremor. In the latter, slightly different frequencies are recorded in different body parts, with the notable exception of orthostatic tremor and rare forms of essential tremor (157). Functional tremor usually shows similar frequencies when recorded in different body parts (90). Tremor entrainment and changes in frequency or a sudden stop of tremor (Whack-a-mole sign) with contralateral ballistic movement can also be assessed with electrophysiological studies (90).
In a study assessing the sensitivity and specificity of several neurophysiological tests to differentiate between organic and functional tremor, the authors compared patients with various forms of organic tremor with those affected with functional tremor (190). The assessed tasks included 500-g loading, tapping task performance, entrainment, frequency shifts during tapping, ballistic movements, coherence, and tonic coactivation. Test sensitivity varied between 33% and 77%, whereas specificity varied between 85% and 100%. None of them showed enough sensitivity and specificity to discriminate between organic and functional tremor. However, a summary score (maximum 10 points) had a sensitivity and specificity of 100% when considering 4 or more points. Suggestibility may also be demonstrated in electrophysiologic studies and can be added to differentiate functional from organic movement disorders (184).
Neurophysiology tests to assess functional dystonia. In patients with dystonia, the lack of co-contractions of agonist and antagonist muscles can be a clue of functionality in some cases (90). The blink reflex recovery cycle, a mean to measure the excitability of brainstem interneurons, is usually disinhibited in patients with organic dystonia, but does not differ between patients with functional blepharospasm and normal controls (189). There is no other reliable way to distinguish functional from organic dystonia by neurophysiology. A retrospective study assessed the neuronal firing patterns at the thalamic ventral oral posterior nucleus in patients with organic and functional dystonia who underwent pallidotomy (113). The authors found no differences in firing rates and thalamic reorganization between both types of dystonia; however, coherence between electromyograms from different muscles and signal-to-noise ratio was abnormal only in those with organic dystonia.
Neurophysiology tests to assess functional myoclonus. Functional myoclonus can also be approached with neurophysiological tests. When myoclonus is of cortical origin (a fragment of epilepsy), the EMG burst lasts between 30 and 50 ms. This short-lasting potential is rarely recorded in other forms of myoclonus, including those of functional origin. However, long-lasting myoclonus (> 100 ms) may be observed in some types of organic myoclonus and in functional myoclonus. The Bereitschaftspotential, also known as premotor or readiness potential, is a slow-rising negativity 1 to 2 seconds before the EMG indicates activation of the premotor cortex, particularly the supplementary motor area in preparation for an intended movement (91), and is usually recorded in patients with functional myoclonus. The Bereitschaftspotential has been considered as proxy for voluntary movements; however, the presence of this motor potential by itself does not indicate “voluntariness.” Indeed, the appearance of this potential in patients that perceive their movements as involuntary as in functional myoclonus is 1 of the main arguments against associated “voluntariness” (90). The frequency of the Bereitschaftspotential has been investigated in patients with functional jerks and other movement disorders. The Bereitschaftspotential was present in 25 of 29 (86%) patients with functional jerks and in 6 of 14 (43%) patients with Tourette syndrome (219). Those with functional movements had a significantly higher proportion of early Bereitschaftspotential (deflection ≤ 1000 ms before movement onset) compared to patients with Tourette syndrome. Although the presence of a Bereitschaftspotential showed a low specificity and sensitivity for the diagnosis of functional jerks, 68% and 26%, respectively, this test may help to differentiate between organic and functional jerks. In a series of 64 patients with propriospinal myoclonus, the Bereitschaftspotential was recorded in 86.1% of patients, whereas an incongruent electromyographic pattern was observed in 84.6% of study subjects (54). Interestingly, the combination of Bereitschaftspotential with incongruent polymyographic pattern suggested that 50% of patients with a clinical diagnosis of organic propriospinal myoclonus were indeed of functional origin (54). The physiological correlate of reflex myoclonus is called the C-reflex, which indicates the hyperexcitability of 1 of several long-latency reflex pathways. These pathways have shorter latencies than the fastest voluntary pathways of about 40 to 50 ms. In functional reflex myoclonus the latencies are similar to, but never faster than, the fastest voluntary reaction time of 100 ms (90). Unfortunately, none of these neurophysiology tests have high diagnostic accuracy for the diagnosis of functional myoclonus.
Functional imaging. Functional imaging is usually reserved for research purposes. However, in a case of suspected functional parkinsonism, imaging with [18F]-fluorodopa (FDOPA) positron emission tomography or dopamine transporter (DAT) scan can provide valuable information to differentiate organic from functional parkinsonism, as the former usually displays dopaminergic denervation in the basal ganglia (176). However, the clinician should be aware that between 10% and 15% of patients with Parkinson disease may have scans without evidence of dopaminergic deficit (SWEDDs). Some of these patients may eventually have abnormal DAT scans, whereas others are considered to have other disorders not associated to dopaminergic denervation such as dystonic tremor (104).
The attitudes and opinions of physicians treating patients with functional movement disorders have been assessed by a survey to members of the International Parkinson and Movement Disorder Society. Results from the most recent survey showed that the likelihood of ordering neurologic investigations prior to delivering a diagnosis was 47%, whereas 27% of responders stated that they would communicate the diagnosis without additional tests; the majority of responders envisioned their role as diagnostic providers and management coordinators (124).
The treatment of functional movement disorders has proven to be extremely challenging. These patients frequently suffer morbidity related to unnecessary, costly, and potentially dangerous diagnostic, pharmacological, and surgical interventions. The approach to these patients should be done by a multidisciplinary team. General principles for the treatment of functional motor disorder are presented in Table 11. Effective communication of the diagnosis, emphasizing the positive ways the diagnosis was made, is 1 of the first steps before treatment is recommended (50).
• Diagnosis should be clearly communicated to the patient, family, and caregivers
• Approach the patient as a multidisciplinary team
• The physician should show a positive attitude towards the diagnosis, avoid judging the patient
• Emphasize the positive way the diagnosis was made and not by exclusion
• Ensure that the patient understand the potential reversibility of the disorder and lack of brain damage
• Explore the potential stressors and contribution of psychiatric comorbidity
• Involve the family and caregivers in the understanding and treatment of the disorder
• Discourage excessive attention to abnormal movements
Pharmacological treatment. Therapies based on a pharmacological approach are not supported by current evidence. Except for patients with fixed dystonia and complex regional pain syndrome, where the use of intrathecal baclofen has given great results in some studies, most pharmacological treatments usually fail in patients with functional movements. Treatment with intrathecal baclofen is frequently associated with complication (222). Botulinum toxin can be used in patients with functional dystonia, although it did not provide any additional benefit in a short trial combined with cognitive behavioral therapy (225). The use of antidepressants has provided benefit in a subset of patients, particularly in those affected by depression; however, these medications have not been demonstrated to systematically improve functional movement disorders (229).
Some authors have advocated the use of placebos for these patients (182). Placebos can be used to confirm the diagnosis; for example, a robust clinical improvement to carbidopa (without levodopa) supports the diagnosis of functional parkinsonism (104). Placebos may induce changes in the prefrontal cortex, and these changes may predict a positive response to the placebo (100). Positron emission tomography studies have shown brain release of dopamine with placebos, which may stimulate the reward mechanisms (42). Some authors have pointed out that placebos are ethically justifiable, particularly when the nature of the treatment is revealed to the patient, considering that functional movement disorders are frequently disabling and have a poor prognosis in many patients (182; 108). Unfortunately, the long-term benefit of placebos in patients with functional disorders is unknown.
Psychotherapy. Limited evidence supports the role of psychotherapy for these patients (99), and cognitive-behavior therapy has proven beneficial for some functional neurologic disorders (99). Disorder-adapted cognitive behavioral therapy seems useful for patients with functional movement disorders. Cognitive behavioral therapy is a structured, time-limited therapy that helps patients identify how thinking affects emotional states and specific behaviors. A small study that evaluated patients with functional tremor treated with cognitive behavioral therapy using pre- and post-therapeutic functional MRI showed increased activation of the anterior cingulate/paracingulate cortex at baseline with decreased activation following cognitive behavioral therapy (61). Patients with severe depression at baseline had the more significant change posttreatment, suggesting a contribution of the mood disorder. Other techniques include cognitive behavioral therapy-oriented self-management and interdisciplinary psychodynamic interpersonal therapy and psychodynamic psychotherapy (117). Besides movements, depression and anxiety may improve with appropriate psychotherapy (117). In a retrospective study of 30 patients with functional movements, 60% improved with psychodynamic psychotherapy, although predictors for such response have not been readily identified (194). Some authors have suggested, based on their experience, that showing the patient their physical signs or symptoms, such as the Hoover sign in the case of leg paralysis or the effect of “entrainment” in functional tremor, may help them to understand the accuracy of the diagnosis, and that this is made positively and not by exclusion, and the potential for symptom reversibility with secondary improvement of symptoms (201; 204).
Hypnosis has been used in the management of patients with spasmodic torticollis thought to be of functional origin (40). However, hypnosis has not proved consistent usefulness to treat patients with functional movement disorders and has been largely abandoned.
Physical therapy. Physical therapy is currently considered 1 of the therapies with most evidence regarding effectiveness. A combination with psychotherapeutic modalities provides the best success for physical therapy. The objective of motor rehabilitation is to help patients to establish normal control of movements, progressively introducing more complex movements (56). In a study with a 1-week intensive rehabilitation program based on the concept of motor reprogramming was provided to patients with functional movement disorders (37). At follow-up (median 25 months), 60.4% of patients had markedly improved or had a complete remission of their symptoms, compared to 21.9% of controls (P< 0.001). Benefit has also been reported with a supervised 12-week program of low- to medium-intensity walking (39). In another study aimed at “retraining” tremor frequency, 10 patients with functional tremor were evaluated; 6 of these patients maintained benefit for up to 6 months (57). In a study of 47 patients undergoing a 5-day physiotherapy focused on education and movement retraining with long-term self-management, 65% of patients rated their symptoms as “very much improved” or “much improved” at the end of treatment, and this reduced to 55% at 3 months; the improvement was in physical and gait domains, but not in mental health (150).
Studies assessing the impact of physiotherapy in patients with functional movement disorders have shown improvement in the cortical wave responses related to pre-cued imperative stimulus requiring a quick motor response (207), suggesting that physiotherapy is associated with faster reaction time and improvement in attention bias in patients with functional movement disorders.
A multidisciplinary approach is desirable for patients with functional movement disorders; however, not all members of the health team may be trained to treat these patients. For example, a study assessing the knowledge and attitudes of physiotherapists toward patients with functional movement disorders in the United Kingdom showed that these professionals were only moderately interested in these patients (ranking 6 out of 10 neurologic conditions), and reported having a poor self-judged knowledge of these disorders, poor support by the referring physician, and inadequate service structures to help these patients (53). However, in a study where patients received daily physical, occupational, speech therapy, and psychotherapy, an improvement was observed in 87% of cases after 1 week and it was sustained in 70% of cases at 6-month follow up by means of the CGI (102). Another study showed improvement after 5-week multidisciplinary training (170). Combining physiotherapy with telemedicine sessions can improve general health, vitality, social function, and mental health in these patients (43). The results of a randomized trial including 264 patients with functional movement disorders will elucidate the effect of specialist versus community physiotherapy with a follow-up at 6 and 12 months in the near future (151). An inpatient multidisciplinary rehabilitation program including motor retraining, psychotherapy, and psychotropic medication was used in 17 patients with functional movement disorders (97). A 93% improvement in the abnormal movements was observed at discharge, whereas at 1 year, 54% maintained some improvement by neurologist rating and 77% by patient rating (97).
Neurostimulation. Transcranial magnetic stimulation has been used to treat functional movement disorders (38). In a study of 24 patients with a variety of functional movements and a median evolution time of 2.8 years, transcranial magnetic stimulation using low frequency (0.25 Hz) was delivered on the motor cortex contralateral to the symptoms, with a stimulation intensity sufficient to cause a motor response (81). Seventy-five percent of patients had an improvement of 50% or more in their symptoms, with one third of them having complete resolution of their symptoms. Improvement was observed immediately after the session. At the last follow-up (after a median of 19.8 months), 71% of patients felt improved. Furthermore, in another study using repetitive transcranial magnetic stimulation in the premotor cortex combined with strong suggestion to suppress functional movement disorders, this combined therapy improved physical quality of life, but a reduction in psychological quality of life was observed (193). Repetitive transcranial magnetic stimulation over the premotor cortex at 1 Hz showed improvement in a case of lower limb functional (psychogenic) myoclonus (147). However, transcranial magnetic stimulation did not show efficacy for upper limb functional paresis (138). The efficacy of large-field repetitive transcranial magnetic stimulation has also been evaluated in patients with functional symptoms, showing a dramatic response with 1 or several sessions of 60 stimuli with circular coils (160). Although the mechanism for improvement is unknown, it may be related to suggestion, placebo effect, or cognitive-behavioral effect, but is unlikely to be related to modulation of cortical activity as this is short-lived (175); another study showed no difference between contralateral cortical and ipsilateral spinal root magnetic stimulation (80). Transcranial magnetic stimulation seems to be a promising for treatment of functional movement disorders, but it needs confirmation in large randomized trials with a placebo arm.
Transcutaneous electrical nerve stimulation has proved useful to modulate sensory and motor transmission within the central nervous system. In a study of 19 patients with functional movement disorders treated with transcutaneous electrical nerve stimulation, 5 patients had a robust improvement (> 50%); some improvement was observed in 4 patients, and no improvement in 10 patients (73). Patients with a shorter course had a better outcome.
Jose Fidel Baizabal-Carvallo MD
Dr. Baizabal-Carvallo of University of Guanajuato, Mexico has no relevant financial relationships to disclose.See Profile
Robert Fekete MD
Dr. Fekete of New York Medical College received consultation fees from Acadia, Acorda, Adamas, Amneal/Impax, Kyowa Kirin, Lundbeck, Neurocrine, and Teva.See Profile
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