Behavioral & Cognitive Disorders
Nov. 14, 2023
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This topic reviews functional neurologic disorder, Munchausen syndrome, Munchausen syndrome by proxy, and Ganser syndrome. These neurobehavioral disorders are related by their (1) resemblance to other, more familiar neurologic disorders; (2) lack of established biomarkers (eg, specific structural lesions on brain imaging studies, seizure waveforms on EEGs); and (3) aggravation of symptoms or those reported by a caregiver from the patient’s or caregiver’s attention to the disorder. However, the features and causes for these disorders are very different from each other and are reviewed. This topic also reviews several widespread manifestations of functional neurologic disorder, including Havana syndrome, mass psychogenic illness that is disseminated by social media, and postvaccination functional neurologic disorder, in particular following the COVID disease vaccination. For functional neurologic disorder, new biomarkers are being intensively investigated.
• Functional neurologic disorders are commonly encountered in general neurologic practices and, hence, knowing their manifestations and treatment is crucial for clinical care.
• The disturbance is involuntary, and yet at the same time it can be intermittently improved by the patient, depending on the patient’s reducing attention to the deficits.
• Although it can be improved intermittently by the patient, the disturbance is generally disabling unless expert professional care intervenes.
• There is no consistent association between functional neurologic disorders and either posttraumatic emotional stress, psychiatric disease, or sexual abuse.
• Although most forms of functional neurologic disorder are relatively benign, Munchausen syndrome by proxy (the intentional false reporting of illness by caregivers of dependent individuals) demands rapid intervention.
• Forms of Munchausen syndrome that involve self-inflicted tissue injury can have distinctive pathological findings.
"Hysteria" was the original term for fluctuating and disabling neurologic disorders in alert sufferers, which were attributed from classical times to a "wandering uterus" because of their predominance in women (302). Offray de La Mettrie, for example, published in 1738 an account of episodic catalepsy (waxy immobility of the limbs) in a woman that he attributed to hysteria arising from amenorrhea (289). Eighteenth century treatments for hysteria were radical and untested, including bloodletting, beatings, diet, fresh air, and writing (179).
Broca’s 1861 seminal and replicated discovery that aphasia follows from focal lesion in the brain as found on autopsy, more often in the left cerebral hemisphere, inspired subsequent neuroscientists to trace other neurobehavioral disorders to their respective specific brain regions (see the MedLink article, “Nonprogressive aphasia”). Broca’s contemporary neuroscientist Briquet related functional neurologic disorders of both women and men also to cerebral disease, but in contrast to aphasia, these disorders did not leave visible lesions at autopsy (65). Nonetheless, Briquet relocalized functional neurologic disorders from the uterus to the brain. Reynolds published in 1869 a prescient overview of functional movement or sensory disorders that appeared to be based on an ideological fixation and were amenable to compassionate behavioral retraining (217). In 1888 Blocq comprehensively described a case series of the acute inability to stand and walk despite full motor control of the legs while the patients were supine, which he termed “astasia-abasia,” a term that continues today (195). Although he doubted that the disturbance had a purely psychologic etiology, his pathophysiologic hypothesis—that marked emotional distress can aggravate cerebral inhibition over spinal walking mechanisms—is remarkably similar to current pathophysiologic hypotheses for functional disturbances. Late in his career, Charcot opined that functional disorders emanated from focal disturbances of the nervous system, but which did not affect a specific part of the body. Therefore, Charcot hypothesized that functional neurologic disorder did not seem to result from a consistent structural central nervous system lesion. Instead, he postulated that functional neurologic disorder may emerge from an anatomically “dynamic” lesion, for which extant neurologic examination techniques could not identify (107).
Near the end of the 19th century, Freud (who trained as a neurologist under Charcot and observed his demonstrations of hysteria in his patients) hypothesized that an unconscious and involuntary cognitive process called “conversion” caused functional neurologic disorders (47; 95). In this model, emotionally conflicting memories of young life abuse or other upsetting personal experiences are involuntarily repressed and “converted” to severe somatic involuntary disturbances. Although no experimental evidence for this process was adduced for this nonfalsifiable model, this concept became firmly established and continues today in contemporary medical care (56). Commonly, functional neurologic disorder is called “conversion disorder,” including in present-day medical diagnostic classifications for clinical billing.
A surge of interest in functional neurologic disorders came with World War I, when European soldiers returned from combat with a variety of fluctuating neurologic deficits without traumatic brain injury (128; 159). These post-combat disorders were considered to be neurologic, even though their precise etiologies were unclear. However, the neurologic interest in the causes, physiologic basis, and treatment of functional disorders became overshadowed, for the most part, by the successful outcomes of the psychoanalysis that was developed by Freud (65). Over the 20th century, the lack of rigorous empirical evidence for unconscious repression led to a return of interest to the neurophysiological basis of functional disorders, beginning in the 1960s, and continues to the present.
A wide variety of synonyms for these disorders have been used up to the present, which hampers understanding. These terms include hysteria, conversion disorder, medically unexplained disorder, shell shock, combat neurosis, psychogenic neurologic disorder, and pseudoseizure. Edwards and Bhatia emphatically recommended the term “functional neurologic disorder” on the grounds that patients find this less objectionable than rival terms (263; 77), which helps to emphasize the reversibility of the disorder (216; 257). PubMed shows a continually increasing adoption of this term since 2005.
"Somatization disorder" or "Briquet syndrome" is a variant of functional disorder in which diverse bodily complaints (eg, fatigue, insomnia, irritable bowel) occur without resembling specific neurologic disorders and without objective physiologic evidence (137; 257). "Malingering" is the fully aware simulation of a medical disorder (frequently neurologic) for personal gain, particularly for money, material goods, or improved access to specific privileges (eg, transfer from jail). "Factitious disorder" is the willful simulation of a medical disorder without clear financial or opportunistic gain (22). Instead, sufferers have a need for an enhanced feeling of control or attention. "Munchausen syndrome" is a variant of factitious disorder (often with diverse complaints), in which the patient undergoes frequent clinic or hospital evaluation, sometimes resulting in invasive, even injurious, testing or treatment. The term was coined by Asher (11), who thought that the wide meanderings of afflicted patients from clinic to clinic and their elaborate health histories resembled the fantastic travels regaled by a fictitious character depicted by Raspe in 1785, Baron Munchausen (200). (This individual was likely inspired by the real Baron Münchhausen; consequently, German spellings of this disorder also appear.) "Munchausen syndrome by proxy" refers to a caregiver's bearing false evidence of medical illness in another individual who is incompetent to represent himself (a child, in most cases described thus far) (178). Ganser syndrome involves the inconsistent confabulation of knowledge of facts (98).
Functional neurologic disorder is a form of automatic-voluntary dissociation (see separate topic in MedLink Neurology). Functional neurologic disorder is the generic term for the inconsistent neurologic symptoms that disable everyday life activities and upset the patient, and the symptoms are peculiarly aggravated by the patient’s attention to them. Some individuals have one symptom; in others, a wide variety may occur. Functional symptoms may also evolve in their quality or severity or spontaneously recede. The functional neurologic disorders can affect nearly any widely recognized neurologic function. Unlike many traditional neurologic disorders, functional neurologic disorders are not consistently associated with objective biomarkers on standard instrumented assessments (eg, structural damage evident on brain MRI, epileptic waveforms on EEG). In addition, traditional neurologic disorders are considered either to be unaffected or not improved by attention. This latter tenet, however, has not been rigorously or critically examined, and numerous examples of contradictory evidence are found in Parkinson disease (see below), dystonia, and stroke (167). An emerging interest is in the placebo or nocebo responses to treatments of Parkinson disease and other common neurologic disorders (237; 90; 297). In addition, persons with either Parkinson disease or stroke overestimate the daily frequency of their motor deficits (204; 286). These characteristics could prompt reconsidering consistency of classical symptoms in traditional neurologic disorders in relation to self-directed attention.
Common features of functional neurologic disorders include the patients’ limited awareness that their attention to their symptoms can aggravate their severity, lack a sense of self-agency, limited awareness of intact neurologic control for the specific symptom, and perceived great effort when attempting to control their symptoms (81; 272). Patients view their disorders as stressful and disabling. In contrast, la belle indifference, or the lack of concern for the neurologic symptom, does not occur in the majority of patients with functional disorder and is not a specific finding (260).
Often functional neurologic disorder is preceded by an abrupt physical event in the preceding three months, most often physical injury, infection, or traditional acute neurologic illnesses (eg, facial neuritis, migraine, brachial neuritis) (203). Therefore, physical triggers may be key to the onset of many forms of functional neurologic disorder. However, functional symptoms can also develop in progressively degenerative neurologic disorders, particularly in Parkinson disease (296). This observation also emphasizes that functional neurologic disorder can co-occur with traditional neurologic disorder, eg, functional epilepsy occurring with apparently self-uncontrollable epilepsy associated with epileptiform waves on EEG (223).
In an emerging form of functional neurologic disorder, case reports are appearing of functional movement disorder or functional seizures following vaccination for the COVID illness (51; 80; 86). The author of this topic himself has treated two adults with functional movement disorder after the COVID vaccination and a third following the mumps vaccination. Consequently, the common factor may be the planned (though limited) soft tissue injury, rather than the content of the vaccine itself. A great concern is that as these reports become widespread, skepticism of the COVID illness vaccination may increase. It is consequently highly important for general practitioners to become alert to the possibility of postvaccination functional neurologic disorder and refer for appropriate management immediately.
The prevalence of functional neurologic disorders has been estimated to be 1% to 15% of all presentations at neurologic clinics (293; 02; 55). Pediatric manifestations are relatively uncommon, especially before the age of 8 years (198); however, they may account for up to 15% of patients who are seen in pediatric neurologic clinics (89). In one epidemiologic study of 405 patients with functional neurologic disorder, the leading manifestations were pain, negative motor symptoms (eg, astasia, paresis), vertigo, seizures (which can include hyperactive motor phenomena such as clonic movements), and somatosensory disturbances (158).
Espay and colleagues categorize the diverse manifestations of functional neurologic disorders according to either the part of the body involved or behavioral characteristics (81). These major categories are reviewed below.
Functional movement disorder affects predominantly one or more limbs while not occurring during walking. Functional paresis has an incidence of 4 in 100,000 (262). In contrast, functional parkinsonism (tremor, generalized weakness, rigidity) is much more rare (151). Among functional dyskinesias, action tremor is most common, followed by resting tremor, dystonia, bradykinesia, and myoclonus (119). Functional palatal tremor has occasionally been observed. However, as noted above, functional movement disorders may co-occur with traditional neurologic disorders. Parkinson disease as diagnosed by Hoehn and Yahr diagnostic criteria, or abnormal 123I-ioflupane SPECT scanning (DATscan evaluation) consistent with Parkinson disease, was preceded by functional movement disorder in 26% of patients (296). Therefore, functional movement disorder may be an inherent part of Parkinson disease in the same way that rapid eye movement sleep behavior disorder may be an inherent behavioral part of Parkinson disease. Moreover, functional movement disorder may follow deep brain stimulator implantation for refractory parkinsonism (46). These authors suggested that functional movement disorder resulted from the patients’ unmet expectations for improved movement control. However, the report did not consider the alternative that direct brain injury that followed deep brain stimulator placement itself may have directly caused the functional movement disorder.
The classical involuntary motor symptoms of Parkinson disease can improve with environmental modifications and therapeutic suggestions, and it can be aggravated by attention to symptoms, which may be regarded also as forms of functional movement disorder. Thus, freezing of gait can be aggravated by attention to walking and improved by distraction to high-contrast visual stimuli (193); gait speed can be increased by marching to an auditory metronome (273); rest tremor, rigidity, and bradykinesia can be reduced by placebo (108; 18); and various adverse effects can also follow placebo treatment in drug studies (the nocebo effect), including aggravated dyskinesias (253). The latter may result from patients’ having been informed of potential adverse effects, as required by the ethics of human drug research, despite their having received biologically inert medication.
The functional movement disorders include nonhyperkinetic disorders, including functional limb paresis that resembles poststroke changes and functional dystonia, which can involve sustained muscular contraction. In orthopedic surgery practices, the “clenched fist” or the “psycho-flexed fist” can occur. In contrast to many hyperkinetic functional movement disorders, the functionally maintained flexion can develop gradually. In many instances, functional flexed limbs can lead to soft tissue changes over lengthy periods, including reversible maceration, atrophy, contracture, swelling, and joint dislocation (244; 96; 87; 251; 301; 277). These disorders can reveal their functional character by symptom improvement with testing the passive range of motion during general anesthesia and following counseling.
A special subcategory of functional movement disorder is the task-specific disruption of either hand or mouth control in individuals who require precise motor control for these parts of their bodies for their professions. This disorder develops gradually following years of prolonged, extreme practice and is aggravated by strong concentration and anxiety. For golfers, this disturbance is called “yips” (174). For gymnasts, it has been called the “twisties” (105). For deer hunters, “buck fever” can occur when aiming a rifle toward wildlife, which can include temporarily impaired vision and hearing as well as loss of motor control and can occur in novices (48). Musicians can endure “performance dystonia” (224). Less famous individuals may suffer from “writer’s cramp” (239). One notable exception was the case report of unilateral athetosis specific to using a spoon for self-feeding in a 30-year-old woman, which lasted for at least three years (248). Other than mild writer’s cramp, the woman had no other complaints and no abnormality for using other handheld implements. At present the literature on performance-specific dystonia does not attribute such disturbances to functional movement disorder, but the rationale for differentiating between these two kinds of disturbances has not been specified.
Axial functional neurologic disorder affects the body’s core. This most often appears as gait disorder. A common subtype is astasia-abasia (from the Greek for inability to stand and walk). Astasia-abasia involves very unstable and marked lower extremity incoordination during walking, but with normal leg control in other contexts, for example, when asking the patient to walk backwards or move in bed. This category also includes abnormal posture, such as functional camptocormia, (ie, variable marked forward flexion of the trunk) (245).
A variant of axial functional neurologic disorder is total-body immobility that is incurred immediately following sexual assault (171; 186). The persistence or recurrence of this condition, termed “tonic immobility,” are not understood, and indeed this phenomenon is little evaluated in any respect.
Oculomotor functional disorder is most often observed as convergence spasm (132). In this disorder, the patient looks medially with one eye (ie, cross-eyed), even when attempting to look at a distant object. The functional aspect of this disorder can be revealed by normal eye movements during optokinetic stimulation. Other oculomotor disorders include functional nystagmus, oscillopsia, and blepharospasm.
Functional sensory disorder can affect nearly any of the traditional special senses. Some of the more common presentations include functional visual field deficits, including tunnel vision (the visual field deficit on perimetry that changes in relation to the distance of the object that is being viewed) (81). A classic presentation is splitting the dermatome when applying a vibrating tuning fork to the forehead midline. Seldom discussed in this regard is Morgellons syndrome, also termed delusional parasitosis, in which patients complain of the sensation of crawling arthropods on or under their skin, and even the assertion that alien fibers are protruding through their skin, despite normal tissue demonstrated on professional examination (143). In contrast to these preceding disorders, diagnosing functional auditory disorders, in contrast with other auditory disorders, has not been well developed (15). However, functional perception of tones without clear source has been recognized in incidents of mass psychogenic illness and is described below (19).
To a greater extent than functional auditory disorder, functional disequilibrium disorders have been recognized. The disorder termed persistent postural perceptual dizziness, or PPPD, has been recognized (81). This involves fluctuating dizziness that is aggravated by looking at complex or moving visual patterns, and often following inner ear disease (72). A similar disorder is mal de debarquement syndrome (French for sickness from exiting a boat), a persisting perception of rhythmic bobbing of the body, without actual movement, which can follow travel by boat or train (225). This may result from excessive stimulation of the ordinary vestibulo-ocular reflex during sea travel.
Functional cognitive disorder involves the patient’s complaint of intermittent cognitive impairment (most often memory loss), yet with generally normal performance on standard cognitive assessments. However, some cognitive test abnormalities are consistently found, including slowed cognitive processing speed and working memory (272). In addition, patients with functional amnesia have a “reversed temporal gradient,” ie, with better recall of recent rather than remote events, which is opposite to the progressive memory loss that typifies neurodegenerative diseases such as Alzheimer disease (114). A striking variety of functional cognitive disorder is fugue, which involves inconsistent disruption of autobiographical knowledge, along with wandering from home for extended periods, unaccountably. In some instances, patients temporarily fail to recognize family members, nor recall their own identities.
Ganser syndrome may be a special form of functional cognitive disorder (described below), except that such patients do not complain of the disorder.
Functional seizure disorder is more often termed psychogenic nonepileptic seizures or PNES. Functional seizure is the most common of paroxysmal functional disorders; functional syncope or drop attack also can occur (120). Functional seizure involves abrupt, episodic stereotyped movements and interruption of awareness, without epileptic waveforms on EEG (10). Eye closure is common and characteristic (62). Because functional seizure can occur spontaneously without evident self-attention, this may question whether such nonepileptic seizures should be regarded as a form of functional neurologic disorder.
Mass psychogenic illness (MPI) is the currently preferred term for what was formerly called mass hysteria or mass sociogenic illness. Mass psychogenic illness (MPI) is distinguished from the other functional disorders by their being contagious. MPI has been extensively documented over the centuries (84). Mass psychogenic illness occurs among individuals who are grouped in close settings, including school and the workplace (20). The symptoms that have been reported include tics, perceived low-frequency sounds, vertigo, syncope, headache, tachypnea, tremor, astasia-abasia, disinhibited emotion, and inattention (21). Although many reports of mass psychogenic illness have involved populations that may be considered to be not well educated (children, people from developing countries), a notorious and controversial incident involved half of the American embassy staff in Havana, Cuba between 2016 and 2017 involving auditory disorders, imbalance, and headache (19). In the initial report, now commonly termed as Havana syndrome, the authors excluded mass psychogenic illness but did not adduce a convincing alternate explanation, and they did not appear to be familiar with how functional neurologic disorders can present (267; 39).
A new surge in mass psychogenic illness since 2019 is occurring as social media is becoming more widely used. In particular, young women and teenage girls are prone to functional movement disorders following observing charismatic women (“influencers”) on TikTok or YouTube who demonstrate what they refer to as tics (124; 196; 187). Highly unusual in the history of research on mass psychogenic illness is that this variant is precipitated by exposure to electronic kinematic visual media without the afflicted persons sharing physical space with other similar individuals. In the largest study thus far of diagnosed “functional” tics (involving 294 individuals), this movement disorder overwhelmingly occurred in girls and largely followed observing internet media (170). The prognosis is favorable: peak severity is at one month, then decline; spontaneous remission occurs in 20%. Although medications are not efficacious, psychological care can benefit.
Dissociative identity disorder deserves special mention. In this controversial illness, formerly termed multiple personality disorder, for the most part the symptoms do not involve neurologic deficits, but rather the presentation of entire “personalities,” ie, a coherent array of habits and emotional patterns that characterize a distinct “identity” that is different from the patient’s original personality (44). The core personality is often unaware, or incompletely aware, of the other personalities, extending to amnesia of the experiences of the other personalities, thus overlapping functional cognitive disorder (described above). Dissociative identity disorder shares etiology with functional neurologic disorder in that it appears to be a response to severe stress. Moreover, dissociative identity disorder can include objective neurologic changes, including personality-specific suppressed visual evoked potentials (265), nystagmus (32), EEG (35), and cerebral perfusion patterns (231).
Whereas functional neurologic disorder involves primarily one symptom, the complaints in somatization disorder (or Briquet syndrome) involve multiple, typically autonomic neurologic dysfunctions and do not suggest well-defined neurologic or other medical disorders. Examples of such complaints include nonfocal abdominal pain, nonspecific chest pain, dysuria, backache, erectile dysfunction, food intolerance, and fatigue (137).
Factitious disorder is the fabrication of illness within oneself for gaining personal attention rather than monetary or material gain. An unmet need to feel in control may be responsible for some instances. Neurologic illnesses that may be feigned include meningoencephalitis, epilepsy, loss of consciousness, visual loss, speech disorder, limb paresis (22), unilateral neglect during clock-drawing (136), quadriplegia (87), or irregular breathing (288). Personality disturbances can attend factitious disorder, including aggressivity, impaired impulse control, suicidal threats, and self-destructive behavior. A history of aliases and changing of hospitals or physicians may occur. Factitious disorder may be triggered in children by a sudden change in lifestyle or other psychosocial trauma (75).
Factitious disorder associated with repeated hospitalization, particularly when the patient presents to a multitude of medical centers, qualifies as Munchausen syndrome (11). Pseudologia fantastica is a characteristic finding (ie, excessive lying without delusion) (201; 138). Not uncommonly, such patients endure repeated invasive procedures for diagnosis or treatment, to no avail. Munchausen syndrome has been reported to present as complex regional pain syndrome (formerly termed reflex sympathetic dystrophy) (60), hemiplegia (37), status epilepticus (230; 61), neurogenic bladder (117), paraparesis (155; 144), meningitis (166), metabolic encephalopathy (266), or syncope (271).
In contrast from factitious disorder, malingering is the fabrication of symptoms to obtain personally favorable changes in environmental conditions such as employment or finances (97).
Munchausen syndrome by proxy is the fabrication of medical complaints in a dependent individual by another, usually by a mother for her underage child (178). The behavior allows the caregiver to have the social attention or improved feeling of importance that he or she feels otherwise not to be able to obtain, while also placing the child's health in peril. This is child abuse. A 9% mortality rate has been identified from literature review (222). The dependent undergoes needless evaluation that can be invasive, loses time from school or other activities necessary for maturation, suffers psychologic trauma from chronically being in a sick role, and may be harmed by unnecessary medication. To achieve the deception, the caregiver must have detailed medical knowledge. Nonneurologic manifestations of Munchausen syndrome by proxy may include applying iodine to the dependent’s skin to simulate jaundice and adding menstrual blood to the dependent’s urine to suggest hematuria (17). Unfortunately, the diagnosis has been carelessly applied in the medical literature, extending to instances where the mother has sincere but mistaken beliefs concerning disease in the child (255).
The most common neurologic manifestation of Munchausen syndrome by proxy is alleged epileptic seizures because serious medical action may be prompted simply by false eyewitness testimony rather than from physical evidence or abnormal clinical exam. In a variation of Munchausen syndrome by proxy, a lawsuit in the United States has alleged that a pediatric neurologist fabricated the diagnosis of epilepsy in several hundred of his underage patients, with concomitant needless prescription of antiepileptic medications and implantation of seizure-control devices, to reap profits for himself and his hospital (78). Other neurologic manifestations can include apnea, loss of consciousness, and in one instance, myalgic encephalomyelitis (161). In contrast to the usual victim being a child, however, several case reports have indicated abuse of adults (243; 111), often involving covert poisoning by the caregiver. In one of these cases, a 71-year-old man had recurrent stupor for two decades that was reversed by intravenous flumazenil. The clinicians had become convinced that the patient had a strange disorder that released an endogenous benzodiazepine, until they discovered that the patient’s wife had confessed to surreptitiously intoxicating him (as well as her mother) with lorazepam. The investigators themselves confessed to having easily been misled by a beguiling, but ultimately false, hypothesis.
As with Munchausen syndrome by proxy, patients with Ganser syndrome do not originate complaints about their abnormal findings. The disorder involves the tetrad of recurrent obviously incorrect answers to questions despite intact speech comprehension (eg, 1 + 1 = “4; ” how many legs does a duck have? = “8”), impaired arousal, functional somatic findings (eg, nonphysiologic distribution of somatosensory loss), and hallucinations (98). The first sign – incorrect answers (vorbeigehen [“passing over”] in Ganser’s terminology) – gives the appearance of the simulation of dementia or psychosis, and has been frequently used to diagnose Ganser syndrome even in the absence of the other original features. The four features may variably coexist from patient to patient (242), which raises the question for whether Ganser syndrome describes a genuine symptom complex. When inappropriate answers to questions appear prominently in illness without all of the other diagnostic features, clinicians either loosely diagnose “Ganser syndrome” (205) or more properly report “Ganser symptom” (183). Consistent with other functional neurologic disorders, Ganser syndrome may abruptly resolve with psychotherapeutic intervention (66). However, in other instances the symptoms may persist for months despite therapeutic interventions (183) or the absence of obvious gain (67), which challenges the impression that the confabulatory answers strictly result from an intention to simulate neurologic illness. Indeed, such responses considerably resemble behaviors encountered in a wide variety of cerebral disorders. Furthermore, Ganser syndrome is frequently associated with brain injury and in one instance followed an extensive cerebral infarction (295). Consequently, confabulated responses to questions cannot by themselves indicate whether the disorder is functional.
Because diverse factors may be responsible for functional illnesses, a simple statement concerning prognosis is not possible. Furthermore, research studies have used (and probably continue to use) inconsistent methods for diagnosing functional disorders (182), thus, confounding metaanalysis at this point.
Functional movement disorders may endure for years and disrupt daily living activities and employment (254; 102). Only about one half of patients with functional tremor or paresis improve, generally in response to eliminating stressors and cultivating the patient’s trust in the physician (127; 102). Prognosis for improvement from functional dystonia is poor, but combined psychotherapy and physical therapy may be efficacious in some instances and, therefore, should be tried (232). Functional movement disorders are also costly, with an estimated annual cost of care exceeding $100 billion in the United States (06).
Functional seizures are likely to recur in patients with depression, personality disorders, a history of chronic abuse, or abnormal MRI findings (131). Approximately 30% of patients with functional seizures have no recurrence. Functional seizures may occur in pregnant women. One study has reported that some continue taking antiepileptic medication, despite having been admonished otherwise, or present to emergency rooms with nonepileptic seizures and receive intravenous anticonvulsants. Thus, they risk avoidable harm to the fetus (71). It may be difficult to dissuade such patients from taking medications, due to heightened anxiety among family members who note increased seizure frequency when off the medication.
The presentation of functional hemiparesis or other stroke deficits becomes potentially dangerous if emergency medical personnel are unable to recognize the functional source of symptoms and fibrinolytic therapy is administered (eg, rtPA). However, research has shown no harm from fibrinolytics given to persons presenting with acute stroke symptoms with unremarkable neuroimaging, including persons later diagnosed with functional stroke (59).
Functional tics associated with watching tics on electronic media have shown a 20% spontaneous resolution rate (170).
Munchausen syndrome by proxy is associated with a fatality rate of from 9% to 30% for involved children (17).
A 43-year-old man presented to the hospital complaining of increasingly frequent seizures over the past few days. He reported seizure disorder for the preceding 25 years following thoracic surgery for a chest wound. He was new to the hospital and did not supply medical records but indicated he had been evaluated at multiple other hospitals throughout the United States for his seizures. He reported that phenytoin caused him to have urticaria, and valproic acid had been only temporarily helpful. Concurrent carbamazepine and gabapentin that was started one month earlier when the patient had been away on vacation seemed to have reduced the seizure frequency to one per day until the present admission.
The seizure disorder had begun while he was in the military service. He felt frustrated trying to obtain a pension through the Department of Veterans Affairs because one doctor had alleged that the seizures may have originated prior to his military service, due to an undocumented history of unexplained loss of consciousness during adolescence. He was upset with most other medical institutions' evaluations, and he felt that clinicians either had considered the seizures to be psychologic or had despaired with treating him due to lack of improvement.
Neurologic examination was normal. During the present hospitalization, he suffered multiple daily seizures, up to four per hour. Seizures consisted of tonic posturing of one of the upper extremities, followed by total body stiffening, lordosis, unresponsiveness to verbal stimulation, diaphoresis, and low amplitude axial contractions, for as long as 15 minutes. The patient was tachypneic during these episodes, with slight facial reddening. The contractions occurred with an irregular rhythm and sometimes were interrupted by a few seconds' suspension of movement before restarting. During these episodes, pupillary responses were preserved to light, and plantar responses could not be elicited. Vital signs recorded during the seizures indicated only mildly elevated blood pressure. The patient claimed to be amnestic for these episodes. Even prolonged seizures were followed a few minutes later by purposeful activity such as postural adjustments in bed, reaching for water, and coherent conversation. Intravenous lorazepam and diazepam did not reliably terminate these episodes. The patient was electively intubated and given continuous intravenous midazolam for two days, which produced profound sedation. EEG during this time was unremarkable apart from intermittent theta and delta rhythm during light sleep that was thought to be possibly due to benzodiazepine treatment. Extubation and withdrawal of the midazolam were followed by resumption of the seizures.
His gabapentin was continued at 1500 mg/day, the carbamazepine was raised to 1000 mg/day, and valproic acid was restarted at 1500 mg/day. Nonetheless, seizure character, frequency, and duration did not change, despite technically "therapeutic" serum levels of the latter two drugs. Brain MRI scan, arterial blood gases, complete blood count, and serum electrolyte and hepatic enzyme levels were all normal.
He underwent three days of continuous video-EEG monitoring. Review of the video recordings and simultaneous EEG by two neurologists identified multiple seizures but no abnormal EEG activity. The consultant neurologist conferred at length with the patient and his fiancée and said that he had "nonepileptic seizures" whose basis could not be explained. The patient worried that he would be considered psychotic, but the neurologist reassured him that this was not so. The couple was pleased to review several video tape recordings of the seizures, in which the neurologist indicated the normal EEG. The patient was advised to continue present oral medication because the fiancée felt that the episodes had become less violent. The neurologist indicated that he would have office visits with the patient several times a year and might reduce the medications if there were no overall worsening. The neurologist indicated that because vital signs and EEG were unremarkable during these episodes, emergency treatment was not needed for these seizures. The couple left the hospital satisfied with the attention of a qualified clinician who had taken a serious interest in the patient's problems.
Comment. The patient's history of evaluation at multiple medical centers and 25 years of uncontrolled generalized seizures with normal neurologic findings suggested functional seizures. This was supported by normal brain imaging, extended EEG recording, and observations of prolonged but irregular convulsive movements that were interspersed by rest periods and followed by rapid resumption of environmental interaction. Although the origin for these seizures was unclear, they may have been reinforced by the patient's failure to obtain a military pension. Because doctors had told him he had a psychologic disorder or had failed to maintain clinical follow-up, there was no chance for therapeutic success. Confidence in the neurology consultant was established through careful attention to the patient's complaints, frank discussion and review of the EEG findings, and avoiding diagnosing psychopathology or referral to a psychiatrist. Although there was no orthodox indication for antiepileptic medication, there appeared to be no short-term harm from its continuation. More important, the neurology consultant established clinical rapport, which so far had been lacking, through assuring regular follow-up and sincere interest in the patient's problems. This foundation is essential before exploring medication tapering and psychosocial stresses and to avoid the patient's possibly turning to unqualified clinicians for help.
Although structural MRI in functional neurologic disorders have reported significant structural changes, they have not been consistent and were identified only at the group level. Thus, increased cortical grey matter was observed in patients with functional seizures (left insula, bilateral medial frontal areas, left supplementary motor area, right superior temporal gyrus, motor cortex) and functional hemiparesis (bilateral premotor cortices) (13; 220; 141; 177). In contrast, decreased cortical grey matter was reported in functional seizure (right motor area, bilateral cerebellum, bilateral precentral), functional motor disorder (left anterior cingulate cortex), and dissociative identity disorder (insula, anterior cingulate, parietal, temporal, and orbitofrontal cortices) (13; 145; 207; 213). Therefore, at present no signature structural brain MRI finding characterizes functional neurologic disorders.
According to a comprehensive review of the literature, there is no preponderant involvement of one side of the body or the other (259). Thus, these reports do not point to a characteristic focal structural brain finding that is associated with functional neurologic disorders.
The etiology, if there can be only one, for functional neurologic disorders is highly controversial and unresolved. The past century of thought about functional neurologic disorder centered on the hypothetical mechanism of “conversion” that was purported by Freud and Breuer (47; 95). According to this hypothesis, repressed psychological distress is ameliorated by subconscious conversion to an involuntary bodily symptom. There is, however, no scientific evidence for this process, and indeed, the hypothesis is untestable (56).
A major difficulty with positing a single pathophysiological etiology is that among all patients with functional neurologic disorders, there are many exceptions to “rules” or patterns that have been recognized. Thus, for example, psychiatric disorder has been invoked as a precondition for functional neurologic disorders because this is common among the patients. However, many patients do not have psychiatric complaints (279). Similarly, psychiatric disorder is common in stroke, Parkinson disease, multiple system atrophy, dystonia, and epilepsy (91; 157; 180; 300), but it has not been apparent that psychiatric disorder causes these neurologic disorders. The absence of distinct biomarkers in functional neurologic disorders that are available on clinically ordered brain MRI scan or EEG is also true for many other neurologic disorders, such as Parkinson disease, essential tremor, dystonia, amblyopia, and migraine.
Functional neurologic disorder is frequently preceded either immediately or within a few weeks by either emotional or physical trauma. Seldom recognized, but pertinent, is that functional disorders can appear in other animals following emotional or physical trauma (07; 118; 227; 134). These reports involved reversible neurologic changes that were not associated with neuroanatomical changes. A related response to threat to survival is “learned helplessness”—sudden immobility—in laboratory animals (235). Clinical studies in recent years have reported tonic immobility in victims of sexual assault that resembled learned helplessness (171; 186). “Resignation syndrome” has been recognized in recent years in children who are refugees from war-torn countries and whose applications for asylum have not been resolved (226). This disorder involves persisting minimal interaction with the environment, requiring total care by families. For unclear reasons, it has been concentrated in Sweden.
An insight by Kretschmer was that the recourse by various vertebrates to hyperactivity or feigning death as an instinctive antipredator mechanism could be the basis for diverse functional neurologic disorders in humans in response to perceived threat (142). This idea has been resurrected by Cretton and colleagues (64).
A comprehensive literature review by Edwards and colleagues suggests that for certain individuals, a traumatic event, either psychological or physical, markedly disrupts the patient’s predictions or anticipation for the quality of the external or internal world following the patient’s actions (76). Such a distorted prediction of sensory experience may thus apply to functional blindness, anesthesia, or pain. Furthermore, the altered expectation for sensory input may pertain to kinesthesis as well, and thus, cause patients to anticipate that part of their body will have either degraded kinesthesis (the situation following paralysis) or fluctuating kinesthesis (eg, following tremor, dystonia, or tonic seizures). According to the “Bayesian” hypothesis as termed by Edwards and colleagues, the patient may then unconsciously adjust limb movement to match prediction, and thus resolve a perceptual mismatch. Support for this comes from the observation that patients with idiopathic unilateral facial paresis (Bell palsy) may also show ipsilateral limb hemiparesis (133), even though the peripheral locus of injury is physiologically incompatible with hemiparesis. Keane suspected that hemiparesis with Bell palsy arises because patients assume that they have a stroke, and so ipsilateral weakness is to be expected. Keane reported that such patients’ hemiparesis can be resolved simply with counseling. In everyday life, involuntary adjustment of perceptual gain may occur when, for example, we “ignore” pain from an injury when we have to focus on escaping danger. As another example, we may become so preoccupied in our thoughts as to fail to recognize familiar passersby who technically happen within visual field. On the other hand, Edwards and colleagues cite experimental evidence that ordinary perception of a mildly noxious stimulus may be aggravated by a preceding aversive stimulus (76). Hence, the revision of perceptual gain may not be all that unusual. In the case of functional illness, however, such resetting is greater, enduring, and difficult to voluntarily reset.
A difficulty with the Bayesian hypothesis is that it posits that the pathologic voluntary action results from a recurrent cycle of mismatched sensory input and abnormal expectation. This process is beyond experimental validation; thus, the hypothesis is not testable. Moreover, unexplained is why some functional neurologic symptoms involve just one part of the body, rather than enveloping the entire body or a specific sensory system such as vision. It is not clear, for example, why a distorted prediction by the patient may involve only one arm or leg with functional tremor or paresis, while sparing the other side of the body. In addition, Edwards and colleagues predicted that functional movement disorder patients will have abnormal somatic sensation (76). Contrary to the hypothesis, patients with functional neurologic disorder are not exceptional in their sensory experiences when compared to healthy individuals or individuals afflicted by other neurologic disorders (219; 276).
As noted above, physical trauma can precipitate functional neurologic disorder, including following the COVID illness vaccination (described under the “Clinical manifestations” section). A possible mechanism involves the release of proinflammatory cytokines after physical injury. The clue comes from the release of cytokines (inflammatory kinds of protein that are widely released in the body by macrophages and helper T cells after neural injury) early in complex regional pain syndrome (CRPS) (299; 36). Complex regional pain syndrome, in turn, often involves functional movement disorder (232; 234; 282; 135). Consequently, proinflammatory cytokines may be instrumental to the onset of functional neurologic disorder, at least following limb tissue injury. Further research will be needed to determine how cytokines may elicit variable limb motor control, for example, by inducing neuroplastic changes in brain or spinal cord sensorimotor structure directly connected to the specific limb.
Of note is that individuals who are homozygous for the catechol-O-methyltransferase gene (Val158Met) have heightened somatosensory perceptions (291). Such individuals may be prone to complex regional pain syndrome and functional neurologic disorder following physical injury, though at this stage this can only be speculative. Familial functional movement disorder has been reported, which further supports a genetic basis (252).
Marshall and colleagues evaluated a patient with functional hemiparesis following unspecified trauma (169). Attempted movement of the hemiparetic limb was associated with increased metabolic activity of the contralateral orbitofrontal and anterior cingulate areas, which are thought to be involved with motor inhibition. The affective response to painful stimuli can be modulated by hypnotic suggestion. This response has been associated with altered activity of the anterior cingulate area in human volunteers (212). Patients with functional hemiparesis, regardless of symptom laterality, may show decreased activity in the left dorsolateral prefrontal cortex on PET scanning during voluntary movements (250). The failure by such patients to activate motor-related frontal cortical areas while observing a moving hand (unlike healthy individuals) suggests a deficit of motor imagery (50). Another study has reported decreased thalamic and caudate nucleus metabolism contralateral to the side of functional hemiparesis, which resolved when the hemiparesis resolved (285). This observation may be related to the structural imaging finding of bilateral thalamic atrophy in chronic functional hemiparesis (12; 190). In contrast, functional limb paresis has been found to be associated with hypertrophy of the premotor cortices, which may reflect the effects of increased motor inhibitory activity (13).
Similarly, reduced contralateral somatosensory cortical activity to peripheral tactile stimulation was demonstrated on fMRI in patients with unilateral functional somatosensory loss (104). In contrast, cortical activity in the deficient areas occurred when the patients underwent bilateral tactile stimulation; the authors speculate that this was because the patients were distracted from maintaining inhibited awareness of stimulation on the affected side. It was suggested from this evidence that the frontal cortex may activate the nucleus reticularis of the thalamus, which secondarily inhibits primary somatosensory cortex processing in individuals with functional somatosensory loss (116).
Increased metabolic activity in frontal and subcortical areas may appear in patients with suspected functional hemianopia, which suggests a focal cerebral inhibitory process in functional visual loss similar to that postulated for functional somatosensory loss (292). An interesting case report indicated psychic blindness associated with specific personalities in dissociative personality disorder. Visual evoked responses were absent only in the personalities that were blind (287). The authors suggested that strong, “top-down” cerebral inhibition (perhaps mediated by the thalamus) could have this remarkable neurophysiological effect. Similarly, healthy subjects can become experimentally trained to forget emotionally upsetting scenes (70). Such forgetfulness is associated with right inferior frontal increased metabolism, coupled with decreased metabolism in memory-associated and vision-associated brain areas. A related case report of a woman with selective loss of autobiographical memories from childhood demonstrated different areas of brain activity on fMRI when well-recalled episodes were probed compared to poorly recalled episodes (42). Combined, these results suggest that circumstances that lead to psychologic repression (either of memories, voluntary movements, or sensations) involve direct participation of inhibitory brain areas.
A case report of functional aphonia demonstrated sustained resolution following repetitive transcranial magnetic stimulation to the right motor cortex, whereas such stimulation to the left hemisphere had been previously unsuccessful (58). This finding, which deserves confirmation, suggests that interhemispheric inhibition may be a feature of functional disorders.
A case report identified astasia-abasia along with diffuse, continuous limb tremor two months after temporal lobectomy for refractory epilepsy (09). Although the patient’s motor disorder dissipated following intensive psychotherapy, which suggested a psychological basis for the disturbance, of note was that the investigators did not identify any psychologic stressors, but did find that the patient also appeared depressed post-surgery. The depression also reduced with psychotherapy. A wide variety of somatic disorders as well as depression have been reported to follow temporal lobectomy (188; 93; 163). Therefore, temporal lobectomy may elicit neurophysiologic changes that can give rise both to affective disorders and to behavioral changes suggesting functional disorder, but without the stressors that have usually been associated with the latter. The favorable responsiveness of an apparently neurophysiologic disturbance to psychotherapy is unsurprising, in view of the similar neurophysiologic changes that can be demonstrated to follow either successful psychotherapy or pharmacotherapy for obsessive-compulsive disease (233). This provides evidence that successful psychotherapy can directly change brain physiology.
Increased functional connectivity on fMRI evaluations has been observed between emotionally related brain areas and motor-associated areas in persons with either functional dyskinesias, gait disturbances, or seizures (284; 280). These results suggest, in contrast to the inhibitory mechanisms above, a vulnerability to excessive activation of motor areas by emotional stimuli. Consequently, it is presently unclear whether a unitary hypothesis regarding regional cerebral activation patterns and functional neurologic disorders can be advanced.
Munchausen syndrome is not generally associated with tissue changes. In an exceptional instance, a woman who had repeatedly covertly self-administered intravenous insulin had developed reactive Langerhans cell hypertrophy in her pancreas (nesidioblastosis), which was found on partial pancreatectomy, and initially led to the diagnosis of noninsulinoma pancreatogenous hypoglycemia syndrome (270). Repeated hypoglycemia led to reassessment, which led to discovering that the patient had harbored ampules of insulin. In another form of tissue damage, self-inflicted (or inflicted on a dependent individual) skin lesions generally have irregular borders and occur symmetrically on the body (40).
The frequency of functional neurologic disorders has been estimated to be 1% to 15% of all presentations of neurologic diagnoses (293; 02; 55). There is a substantial predilection of functional neurologic disorders for women (158; 57; 223). Peak incidence tends to be in young adulthood, and there is a high association with anxiety disorders and depression (158; 199; 03; 34). Nonetheless, psychosocial stressors are not invariably identified in persons with functional neurologic disorders, whereas preceding physical trauma is frequently identified (203).
Although the functional neurologic disorders resemble highly deleterious medical illnesses, examination for which should routinely be conducted in the work-up, functional neurologic disorder should not be considered a diagnosis of exclusion (74; 256). Instead, the well-trained and insightful clinician should be highly suspicious of such disease in the presentation of attentionally-modifiable disorder or of a disorder that superficially resembles conventional neurologic disease but that shows markedly atypical characteristics (eg, astasia-abasia, concentric visual field loss that changes visual angle when testing with stimuli at different distances from the patient). A history of psychiatric disturbance or concurrent personality disorder raises the suspicion for functional disorder, but these do not by themselves rule out structural, physiologic, or infectious pathologic processes, nor do they conversely rule in functional neurologic illness.
The following can be considered only an incomplete overview of conditions that may be confused with functional disorders because new examples are published frequently.
Functional neurologic disorder is suggested in part by the variability of the symptoms, particularly for impairments that are chronic, such as paralysis or visual loss. Nonetheless, the clinician must recall that "traditional" neurologic disorders, even if chronic and "stable," may also have variable presentations. Thus, for example, the comprehension deficit in aphasia may vary in relation to how often the patient is tested: it is usually at its best on initial evaluation and then worsens, suggesting vulnerability to fat (31). Tremor (as in Parkinson disease or essential tremor) typically abates during sleep and, thus, is clearly influenced by the extent of conscious arousal. Moreover, tremor can be dampened through voluntary reaching. A remarkable instance of voluntary, nonfunctional palatal tremor has been described (33). Postanoxic action myoclonus and Parkinsonian tremor may be aggravated by anxiety and may be abate when the individual is emotionally calm (221; 08). Tics may be voluntarily suppressed, but only for a limited period (140). Fatigue, intoxication, medication effects, or systemic infection may aggravate nearly any central nervous system disorder. Such disturbances are distinguished from functional disorders by their adherence to a replicable association with toxic agents, fatigue, or sleep deprivation. In contrast, functional disorders fluctuate over several seconds to minutes and sometimes in relation to who is observing (including the patient himself) or if the patient is aware of being observed.
Primary progressive aphasia is a dementing illness that involves gradual, irreversible impairment in language, with comparative retention of other cognitive functions. This may be mistaken for functional neurologic disorder but can be recognized by abnormal brain SPECT imaging (208). Acute aphasia due to neurosyphilis has been mistaken for functional illness, due to the absence of corroborative CT scan abnormalities (43).
Complex regional pain syndrome is a controversial disorder that was formerly termed either “reflex sympathetic dystrophy,” “shoulder-hand syndrome,” “Sudeck dystrophy,” or “algodystrophy.” It is frequently mistaken for malingering. In this disorder, a usually catastrophic physiologic event (traumatic limb injury, spinal cord injury, stroke, myocardial infarction, or extensive burns) precipitates severe pain in a limb, sometimes associated with focal autonomic changes (altered perspiration, hair growth, skin color, or edema) and in late stages with focal osteomalacia. In a strange alternation of cause and effect, one case of complex regional pain syndrome included unilateral leg edema and was apparently triggered by acute severe emotional distress (110), rather than the behavioral change occurring in response to somatic illness. Afflicted individuals, particularly children, may manifest "incongruent pain," ie, cheerful affect and lack of protective measures, despite maintaining that the pain is severe. It is unfortunate that for such a frequently incapacitating illness, consistent objective laboratory test findings have not been identified. The disorder responds to the combination of physical therapy and behavioral therapy, which best should be provided by hospitalization with the care of a multidisciplinary team (241). However, in one case, the present topic’s author has found substantial pain reduction following implantation of a spinal cord stimulator. Although the present author’s perspective that complex regional pain syndrome is not itself a form of functional neurologic disorder, it should be noted that complex regional pain syndrome often includes functional movement disorder, ie, varying involuntary movements in relation to self-attention (232; 234; 282; 135).
A wide variety of perceptual disorders associated with brain injury may show a "covert" recognition of stimuli under special circumstances, despite the overt denial of awareness. The existence of intact but unconscious processing is indicated by autonomic changes (altered heart rate, respiration, skin conductance, pupillary size, etc.) for certain stimuli (eg, familiar faces or voices), despite overt denial. This has been termed "guilty knowledge" due to the similarity to the autonomic signs of criminality during polygraphy in legal investigations (23). Nonautonomic behaviors may also signify retained sensory processing despite an overt failure of recognition. Disorders with dissociations between conscious and unconscious sensory processing include prosopagnosia (impaired face recognition) (23), cortical deafness (79), visual agnosia (184), acquired alexia (inability to read meaningfully), in which patients may still have intact lexical decision (eg, intact ability to categorize uncomprehended words) (63), and unilateral neglect, where stimulus size may affect bisection judgments despite unawareness of peripheral stimulus extent (168). Such findings demonstrate that overt disability may coexist with covert ability, due to the failure of intact cognitive processes to attain conscious awareness following certain forms of brain injury. These disturbances are almost invariably associated with focal structural brain lesions.
Contrary to what one might expect, patients with functional seizures only rarely have coexisting epilepsy (27; 181). Because functional seizures occur only sporadically, they can be difficult to distinguish from epileptic seizures, particularly if functional seizures are associated with interictal spike discharges on EEG (a normal finding in some healthy individuals). However, it is noteworthy that the occurrence of objective brain abnormalities (epileptiform potentials on EEG, structural brain MRI abnormalities) has been found in as many as 22% of persons with functional seizures (215). Persons with functional seizures also have higher resting serum cortisol levels than do healthy control subjects (16). The average time to diagnosis of functional seizures may be 7 years due to this difficulty (214). Epileptic seizures reportedly may be aborted by passive painful dorsiflexion of the palm (54). Consequently, the cessation of seizures immediately following specific environmental stimuli cannot by itself imply a functional disorder.
Complex partial seizures originating from the frontal lobe may result in convulsive episodes not characteristic of generalized seizures, but suggesting functional seizures, including kicking, complex arm movements, tongue protrusion, and pelvic thrusting (294; 130; 103). Conscious interaction with the environment is possible with frontal lobe seizures (122). The diagnosis of epileptic seizures is benefited by noting the stereotypical features of the phenomena, supplemented by EEG. However, scalp EEG may be insensitive to these seizures, which, therefore, may require depth electrodes instead. The retention of consciousness in generalized seizures has been occasionally reported (26). Therefore, the retention of consciousness during seizures does not by itself imply functional disorder.
A variety of functional seizures occur, which likely reflects their diverse etiologies (148). These paroxysmal disturbances may include panic attacks, intense anxiety, dissociation, episodic dyscontrol, and other psychiatric disorders that can be confused with epileptic seizures due to their associated autonomic alterations (04). Comprehensive psychiatric evaluation is best to diagnose these disorders.
However, a few etiologies for functional seizures have also been recognized. Strokes, particularly involving the brainstem, may provoke convulsive movements without ictal EEG changes (228). The disorder is rarely seen and its mechanism is not understood. Neuroglycopenia secondary to pancreatic insulinomas may present with nonepileptic attacks that include confusion, lethargy, complex actions (eg, fidgeting, shouting, falling), limb or whole body shaking, amnesia, incontinence, autonomic hyperactivity, and prolonged postepisode confusion. EEG abnormalities typical of seizures are absent, although slowing may appear. The onset is insidious in midlife, with a female preponderance. The condition is easily mistaken for other neuropsychiatric disorders (24; 112). It can be diagnosed by the pattern of absent response to antiepileptic medication, attacks during fasting, concurrent hypoglycemia, and resolution with glucagon. Excision of the tumor resolves the illness.
Increasing attention has been drawn to the diagnostic confusion that can attend antibody-mediated epilepsies, in particular, NMDA-receptor (or NMDAR) encephalitis. In the latter disorder, there is a frequent occurrence of bizarre, rapidly fluctuating behavioral disturbances that may include paranoia, delusions, hallucinations, suicidality, and apparent seizures, despite generally unremarkable standard structural brain imaging and video EEG recording. The predominant occurrence of such findings in young women, which in many cases is associated with an ovarian teratoma, may lead to the mistaken impression of functional seizures (146; 53). When a teratoma is present, the disorder often markedly improves with surgical removal of the tumor and immunosuppressant medication.
Confabulatory responses to questions raise the possibility of Ganser syndrome and, thus, possible functional dementia. Functional illness should be suspected when the illness onset is abrupt and without identifiable physiologic causes and if sources for secondary gain can be identified. On the other hand, confabulatory responses in the setting of brain injury or without accompanying features of psychosis suggest either serious structural brain injury or schizophrenia.
Psychiatric delusion may cause somatic injury without demonstrating a contributing structural or physiologic etiology. In one instance, a young woman chronically kept her left hand in a tight fist, causing edema, contracture, and cellulitis (251). The patient believed that her hand held treasure and did not want anyone else to have it.
Opposite to functional neurologic disorder is anosognosia, the unawareness of neurologic deficit (eg, hemiparesis, amnesia, aphasia) (14). A classic example of anosognosia is Anton syndrome, the denial of blindness (94). Although a psychologic defense mechanism is plausible in certain cases following cerebral injury, the associated cognitive deficits suggest that such lack of awareness more often results from defective cognitive functions essential for self-monitoring (175). Acute brain injury may rarely be associated with denial of intact ability (eg, vision) (115). Such “inverse anosognosia” is more often observed in functional neurologic disorders, a distinction being that persons who are afflicted with functional neurologic disorders are emotionally disturbed by their deficits, in contrast to the denial of intact visual ability in structural brain damage.
Functional neurologic disorder may occur with or without concurrent other neurologic disorder. Consequently, diagnosing traditional neurologic disorder (eg, stroke, Parkinson disorder) does not assure excluding functional neurologic disorder.
Although there is a high co-occurrence of psychiatric disorder in persons with functional neurologic disorder, the majority of persons with functional disorder do not have mood disorder (279). Consequently, the clinician should not assume that persons with functional neurologic disorder have mood disorder, but instead should inquire of them directly.
In a small study of functional neurologic disorder, about half of patients had hypermobile Ehlers-Danlos Syndrome and hypermobile spectrum disorders, in other words, they’re double-jointed (192). About 40% of patients with functional movement disorder have restless legs syndrome as well (236). In another small sample, the incidence of irritable bowel syndrome was twice (36%) in persons with functional movement disorder than in control subjects (261). There, thus, appears to be an emerging literature that implies widespread bodily disorder beyond the central nervous system. Emerging evidence is also suggesting that functional neurologic disorder involves elevated inflammatory blood biomarkers (238; 278; 202).
At present there is no gold standard diagnostic method for functional movement disorder (139). Three leading methods of diagnosis are in use: (1) variants of the Fahn and Williams criteria (85); (2) the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), approach (05); or (3) clinician-determined. Similarly, there is no consensus of diagnostic criteria for functional seizures (113). The lack of consensus on diagnostic criteria hampers research progress on assessment and management.
As with any complaints of bodily disorder or functional disability, or the observation of behavioral changes that suggest specific neurologic disorders (eg, seizures), patients should undergo the usually indicated workups, unless the patient has been recognized by staff to have presented frequently with the same complaints without objectively confirmed abnormal biomarkers (eg, lesions on brain MRI, epileptiform waves on EEG). In such instances, the reliability of previous workups should be reviewed before deciding that the illness is functional. Otherwise, the suspicion of functional disorder should not preclude a conventional medical workup because functional disorder does not in itself exclude concurrent medically treatable disorders. The failure to identify structural brain lesion in a neurologic disorder should not lead to suspecting functional disturbance if the presenting complaint is consistent (73). It should be noted that a growing body of literature has identified “MRI-negative” stroke on standard MRI in as many as one third of patients with suspected stroke (164), which may indicate crucial limits to routine neuroimaging for acute brain illness. Conversely, abnormal brain imaging findings or other objective findings are not inconsistent with functional disorder (88). In addition, severe medical problems may directly follow functional disorders, such as chronic muscle atrophy in functional quadriplegia (87) and recurrent severe head injury in functional falls (283). Functional fixed dystonia of the hand, resulting in chronically maintained clenching of the fist (“clenched-fist syndrome” or “psycho-flexed hand”), may lead to local swelling and other chronic soft tissue changes (251; 301). Essentially, the clinician must decide whether objective study results are consistent with the presenting complaint for the purpose of directing management.
In the clinic or hospital, functional neurologic disorder should be diagnosed when noting the patient’s complaint of a persisting neurologic symptom that disrupts everyday activities, and which varies with self-attention. Supportive findings include variability of neurologic signs during history taking and formal examination. The specific conditions that elicit or aggravate symptoms should be tested, for example, during formal neurologic motor limb or oculomotor assessment. In addition, techniques that may distract the patient from the symptoms could be administered to determine whether the symptoms can ameliorate. For example, after noting that formal limb power or coordination testing may aggravate tremor or paresis, the patient’s limb control should be reassessed when asking the patient to perform naturalistic, whole-body maneuvers without drawing attention to the particular part of the body. This can include asking the patient to transfer between a chair or wheelchair to the examination bed, or to walk backwards.
Another common feature, of secondary importance, is the patient’s unawareness or diminished awareness of periods of normalcy (204). This can be demonstrated during clinical examination, including examining the patient with distracting methods as referred to above. This should be used to show to the patient that the condition is intermittent and reversible.
On the other hand, the clinician’s failure to change the symptoms or signs during examination should raise the possibility of an alternative, nonfunctional diagnosis.
Functional neurologic disorder may be suggested by a history of frequent changes in the involvement of medical practitioners, particularly when workups failed to identify the disorder, or if historical details are vague. Multiple surgical scars may suggest Munchausen syndrome (11). Fluctuation of a deficient function, such as limb use or vision, suggests functional disorder (216; 257). Paroxysmal disorders (eg, epilepsy) that appear to be triggered by suggestion or particular social settings also increase suspicion. Similar concerns apply to malingering or factitious disorder (22). The suspicion for factitious disorder should be raised in patients who present themselves for diagnostic workup despite a longstanding history of repeated invasive diagnostic measures (as evidenced by multiple surgical scars). A history of using aliases also should alert suspicion for factitious disorder.
Although studies have indicated a high incidence of history of sexual abuse in persons with functional neurologic disorders (281; 229), Stone and colleagues advise deferring inquiry for sexual abuse to an expert in this area because of the considerable amount of skillful evaluation and discussion that would be needed (257).
A large number of clinical neurologic tests may improve diagnosing functional neurologic disorders, specific to the presenting complaint. Stone and colleagues offer a brief overview of these tests and their degree of reliability (258). The following provides some considerations with diagnosing specific functional neurologic phenomena.
Nonparoxysmal functional disorders are suggested by fluctuating manifestations during examination. Nonetheless, tremors that are commonly thought not have a functional etiology may also diminish with distraction (172). This observation suggests that conventional tremor may in fact have a functional basis. Variable muscle recruitment during contractions or irregular intervals from stimulus to jerk onset are consistent with functional myoclonus or functional startle (274). Dystonia accompanied by pain and variable presentation suggests functional neurologic disorder (151). In a large study, 37% of patients with fixed-hand dystonia (most of whom were women) fulfilled diagnostic criteria for functional etiology (232). This was considered by the authors to be underestimated, owing to the presumed difficulty with distracting the patient from maintaining the fixed posture of the limb.
The occurrence of asynchronous rhythmic oscillations in different parts of the body (eyes, neck) can be self-induced through practice (156) and, therefore, does not exclude functional tremor or nystagmus. In contrast, entrainment is a well-recognized and reliable sign for unilateral functional upper limb tremor (82). After recognizing the characteristic frequency of the functional tremor, the patient is asked to copy the examiner’s demonstrated tremor with the other hand and at a frequency different from the functional tremor. Entrainment is demonstrated if the functional hand becomes synchronized with the copied tremor.
In functional seizures that resemble complex partial seizures, the patient’s recall of events during the ictus is usually better than in complex partial seizures (25). However, it is unclear whether this observation can be reliably used on a case-by-case basis, unless patients who manifest complex partial seizure signs demonstrate considerable recall of ictal events. To evaluate functional seizures, routine EEG may be misleading because some seizures (particularly those that emanate from the medial temporal lobe) may be difficult to detect through scalp electrodes.
Furthermore, as is well known among clinicians, the interictal EEG may be normal in epileptic seizure disorder. On the other hand, the provocation of seizures through suggestion, particularly during EEG-video monitoring, suggests functional seizure disorder in the absence of characteristic spike-wave discharges during the ictus. Although provocation has classically been performed through intravenous saline injection (informing the patient that he may develop a limited seizure following injection) (160), this is ethically objectionable because it requires the clinician to mislead the patient (ie, a saline injection is unlikely to provoke so great an electrochemical alteration in salt balance as to risk seizures). Accordingly, Benbadis and colleagues recommend using noninvasive measures that are already known to induce seizures in epileptic patients with reduced seizure threshold, such as photic stimulation or hyperventilation. The patient is told that such maneuvers can trigger an attack, and the EEG examination is intended to evaluate this possibility. This approach is reported to be as sensitive as intravenous saline (28). However, the response to provocation may not accurately reflect the characteristics of the seizures that actually appear in the patient (100), and so one must be careful with this technique. The foregoing concerns notwithstanding, intravenous saline was found by one research group to be the only way to establish a diagnosis in 32% of their patients considered to have functional seizures (218).
Weeping at the end of episodes suggests nonepileptic functional seizures (30). This can be fairly reliably found on EEG-video monitoring. Bergen and Ristanovic encountered 10 patients in 4 years who wept following functional seizures. In contrast, crying induced by epileptic seizures is rare. Eye closure during seizures is remarkably reliable at distinguishing functional seizures (where eye closure is continuously present) from epileptic seizures (where eye opening usually occurs) (62).
Assessing the relative change in heart rate from resting baseline can reliably distinguish epileptic seizures from functional seizures, whether convulsive or not. Functional seizures cause minimal change in heart rate (at most 7%), whereas epileptic seizures increase the heart rate by at least 17% (on average) (197).
During tilt-table testing, individuals who are considered to have functional syncope are highly likely to close their eyes on the onset of apparent syncope, in marked contrast to persons who have cardiovascular syncope (269).
Commonly seen in functional coma are normal vital signs, toxicology, complete blood count, and serum electrolytes, with normal tendon, pupillary, and vestibulo-ocular reflexes, normal muscular tone, and flexor plantar responses. In true coma the patient does not prevent his hand from striking his face when it is released from grasp above the face. In contrast, in functional coma (or mildly impaired arousal), the patient’s hand misses the face when released from above. In the presence of such findings, cerebral neuroimaging is unlikely to be necessary. Ice-water caloric vestibular testing (after ascertaining integrity of the tympanic membrane) may induce nausea so severe as to provoke well-integrated limb or postural movements or arousal. Similar defensive maneuvers may follow presentation of concentrated ammonia ("smelling salts") to the nose. Failure to demonstrate integrated responses to noxious environmental stimuli should prompt evaluation with EEG to rule out nonconvulsive status epilepticus.
Assessing functional visual disorders must be tailored to the presenting symptom. Helpful tests for evaluating functional visual loss include observing the patient's pupillary and facial responses to silently presenting a mirror. Functional blindness patients often attend the clinic wearing sunglasses, which may be a useful sign (29). Blink to visual threat may signify integrity of visual awareness (as long as one prevents corneal stimulation through gusts of air). However, the absent blink to threat does not strictly imply visual loss but may be due to inattention (69). It is conceivable that patients who anticipate testing methods for functional visual loss may willfully prevent reflexive eye movements such as blink to threat. Further recommendations for assessment are available (41). Automated assessment of visual fields unfortunately does not distinguish between functional and structural visual disorders (246). Similarly, visual evoked responses can be episodically inhibited in dissociative personality disorder in individuals with personality-dependent visual loss, which suggests that this technique is not reliable when evaluating suspected mechanisms of visual loss (287).
Functional hemianesthesia may be suspected when the application of a vibrating tuning fork to the forehead is not felt past the midline (136; 106).
Functional hemiparesis of the lower extremities has been traditionally diagnosed through examining for the Hoover sign, which applies distraction away from the paretic limb (121). This is tested by having the patient supine in bed or the examination table while the examiner places both hands beneath the patient's heels. When asked to force the feet down (essentially, hip extension), only one leg moves. Then the examiner tests leg elevation in the nonparetic side while keeping the hand beneath the paretic heel. In true hemiparesis, upward mobility of the nonparetic leg causes no forceful movement of the paretic limb. In functional hemiparesis, in contrast, the "paretic" leg will move down forcefully, to stabilize the upward movement of the other leg (264). Although useful, this sign is subjective and, thus, may be difficult to assess reliably. This difficulty may be overcome through using strain gauges attached to the lower extremities and even the upper extremities and calculating the ratio of voluntary activation versus involuntary activation (through mobilizing the opposite limb) (303). Although more objective, this measure is elaborate and, thus, unlikely to become popular. It should also be noted that concurrent pain with leg movement may confound interpreting the test, the test’s reliability has not been assessed, and test performance among individuals with defined neurologic disease (eg, multiple sclerosis) has not been evaluated (264).
In contrast to the Hoover sign, a reportedly more reliable test is to assess whether there is voluntary stabilization of the “paretic” leg while the unimpaired leg is actively abducted against the examiner’s resistance (249). In nonfunctional hemiparesis, the paretic limb hyperabducts when the opposite leg abducts against resistance. In functional hemiparesis, the unimpaired leg hyperadducts when the “paretic” leg is required to abduct against resistance. Blinded study is needed to confirm the validity of this method.
The suspicion of functional paraparesis may be confirmed with the Spinal Injuries Center (SIC) test (298). In this test, patients who demonstrate inability to elevate their legs have their knees passively flexed while they are recumbent. The examiner gently removes contact. The maintenance of flexed posture is a positive test and has a reported 100% sensitivity and 98% specificity.
Unilateral functional sensorimotor deficit (resembling stroke) may be associated with increased N140 component of the event-related potential following somatic stimulation on the affected side (165). This asymmetry reverses following therapeutic hypnotic suggestion.
Functional paraplegia is frequently accompanied by dense sensory loss that does not respect dermatomal boundaries but rather the "underwear line" (257). Lower extremity tendon reflexes, cremasteric reflexes, plantar responses, anal sphincter tone, and limb muscle tone are usually normal. Case studies demonstrate that normal motor evoked potentials support the diagnosis of functional paraplegia (209). Integrity of muscle tone (and, hence, some degree of voluntary muscle control) may be demonstrated by flexing the hip and knee while the patient is supine and noting whether the leg slowly falls to one side, if at all. The clinician may surreptitiously monitor for subtle postural adjustments of the lower extremities while pretending to attend to the patient's upper body. Monitoring during sleep (eg, by direct observation, video monitoring, or accelerometry) can disclose lower extremity movements that are asynchronous with upper extremity movements and, hence, not reflexive (154). If the patient is not medically astute, then the clinician may purposefully mislead the patient by claiming that the flexor response to plantar stimulation was evidence for a slight reversal of the paralyzing illness, and further improvement is expected to follow. The clinician may also mislead the patient into believing that the pin sensory level has slowly been retreating. Further improvement may follow over several minutes to an hour, particularly if the patient is given serious attention and is encouraged to believe that slow but steady improvement often occurs in such illnesses.
The science of statistics can help uncover factitious amnesia. Subjects with true amnesia should have about a 50/50 chance of recalling whether individual test stimuli were present on a 20-item list they have been shown. In contrast, subjects with malingered amnesia, who are naive to the principles of probability, may fail to recall items correctly at greater than 50% probability (45), thereby indicating covert recognition of list items.
Munchausen syndrome by proxy may be suspected for unexplained pediatric illnesses in which a parent (usually a mother) shows obsessive concern with the illness and is medically astute while developing close social relationships with clinical staff. Frequently, the father is unaware of the child's disorder and may not accompany the child to the clinic (17). Confirmation of the fabrication of the illness in hospitalized children may be obtained through surreptitious video recording. However, the legality of this measure may vary with the jurisdiction serving the particular hospital, and so legal counsel is needed when entertaining this approach. If a clinical program adopts this approach, a well-defined plan for taking action to protect the child must be in place (255). Careful monitoring of the child's visitors, objects taken to the child or left in the room with the child may aid in the diagnosis. Monitoring of physiologic functions such as respiration may also assist.
Patients with functional neurologic disorders commonly refuse psychiatric referral because they do not believe that they have a psychological disturbance (131). However, some studies have found that counseling can benefit functional seizures (240; 01). This can include providing video feedback to the patient of his functional seizures or video demonstration of intact leg movements during sleep to patients with functional paraplegia (126).
Hypnosis, which was first applied in the late 19th century (38), may be therapeutically successful in the hands of a skillful practitioner, at least when motor disturbances occur (185). Praise given by clinicians or therapists for functional gains, however small, can help to accelerate recovery while allowing the patient to maintain dignity (68). Frank discussion of the diagnosis by itself can reduce attacks in a minority of persons with functional seizures (176).
In contrast, psychiatric disturbances that are acknowledged by functional patients, such as depression or anxiety, should be treated according to the standard of care, which may include psychiatric or psychologic referral. The psychotropic medication venlafaxine has been associated with reduced nonepileptic seizures in patients who have coexisting affective disorders (210). Similarly, sertraline has benefited functional seizures (149). At present, however, prospective therapeutic trials to evaluate specific interventions are few and strongly deserve increased undertaking (101).
In general, respectful encouragement for a positive prognosis can benefit, as well as indicate, that the thoroughly conducted workup has suggested that there is no life-threatening disorder. Reassurance while conveying sincere interest in the patient's welfare will prove valuable (216; 206; 262). Rather than conveying a lack of understanding, the clinician should provide a positive diagnosis that the person has a “functional neurologic disorder.” The terms "hysteria" and "malingering" should not be used (247). Patients must never be told that they are "faking" the disorder, or they will almost surely seek medical treatment elsewhere, including from unqualified and potentially harmful practitioners, or they may bring legal action. Although hospitalized patients with functional disorder may provoke resentment among staff, the clinician must always maintain a calm, professional, respectful attitude and be in charge. Avoid describing patients as "manipulative" because this amounts to admitting the clinician's failure to maintain control of a vexing clinical presentation and can induce hospital staff not to act in the best interests of the patient's long-term health. The clinician above all needs to be a team leader to maintain a coherent staff approach to the patient. Private meetings with hospital or clinic staff, conducted with complete respect for the patient and acknowledgment that functional presentations are common experiences, may help to unify the staff approach and maintain an empathetic attitude.
Clinical trials preliminarily suggests that cognitive behavioral therapy (CBT) is efficacious for functional disorders (150; 109; 262). The approach includes relaxation training and teaching patients to control their illness, rather than being passive. Combining sertraline with cognitive behavioral therapy may considerably reduce functional seizures than cognitive behavioral therapy by itself (147). Inpatient treatment with cognitive behavioral therapy, for functional paresis at least, may be more efficacious than outpatient treatment (173). When diagnosing functional seizure distresses patients, extended empathic therapy and support are advisable (275).
Physical therapy for functional restricted bodily movement has been reported to have enduring benefit (189). The therapeutic process included establishing rapport with the patient. It is conceivable that such intervention undoubtedly is a form of psychotherapy itself, in providing to the patient reassurance, empathy, feedback, and encouragement. In similar manner, compassionate visual training exercises applied over weeks to months can improve functional blindness (92).
A clinical trial of the Movement Retraining, or MoRe method, obtained outstanding improvement for functional movement disorder (125). This method involved a 5-day hospital admission (after having failed outpatient therapy), providing daily symptom-oriented physical or occupational therapy, with daily assessments and management by a staff psychologist, including elements of cognitive behavioral therapy. At the end of treatment, 87% of the patients improved on the patient-rated Clinical Global Impression Scale.
In contrast, an outpatient clinical trial that used only cognitive behavioral therapy, and which required patients being told that they had a psychologic disorder, resulted only in a 50% success rate (194). Preliminarily, this finding suggests that implying a psychologic disorder to the patient undermines the patient’s confidence with improvement and should not be used. In a comparable study of outpatient cognitive behavioral therapy combined with physical therapy, the success rate was only 34% (162). This result suggests that treatment outcomes would be more successful when given as a compact inpatient program, as shown above by the MoRe program.
In a small outpatient cognitive behavioral therapy trial for unilateral functional tremor, tremor reduction occurred in 73% of the patients at 12 weeks (83). In contrast to the other cognitive behavioral therapy trials, however, there was no indication for whether the patients’ self-reported clinical global impression had changed.
A preliminary report of virtual reality exposure training indicates feasibility (49). In this approach, patients view themselves as cartoon depictures of themselves, or “avatars,” while they are encouraged to comply with various video-based motoric gaming. Further results are pending.
A limitation for comparing these trials of either cognitive behavioral therapy, physical therapy, or both for functional movement disorder is the inconsistency of outcome measures. In addition, the field for managing functional neurologic disorder lacks outcome measures that are more specific for the particular symptom, in particular with regard to the impact of such therapy upon everyday self-care abilities in the community.
One case report observed resolution of functional itch with topiramate, which suggests a potential role for pharmacologic treatments for functional diseases (52).
An exciting development is the application of repetitive transcranial magnetic stimulation (TMS) to motor-associated cortex in individuals with functional disorders. A chance observation led to finding an 89% success rate with this form of treatment for various forms of functional paresis (57). Successful outcomes have also been described following TMS for functional aphonia and functional movement disorders (58; 99). Nonetheless, a review of studies to date found considerable inconsistency in results and the absence of placebo control interventions (211).
The basis for such improvement is unknown. Chastan and colleagues suggested that patients with functional paresis may be helped by observing their involuntary limb contractions that are induced by stimulation. However, this would not explain improvement for active, dyskinetic movement disorders. Instead, the improvement of interhemispheric inhibition than can follow TMS may possibly be responsible (153). Such treatment already has been shown to have ample success for depression that is refractory to medication (290). Thus, it may also be possible that functional disturbances may improve following TMS, secondary to improving an underlying emotional disorder. One may expect to observe further exciting developments in this line of investigation.
The diagnosis of Munchausen syndrome by proxy requires assembling involved clinical staff and legal counsel to review evidence supporting the diagnosis and then contacting a child protection agency for the child's safety and removal. Such steps must be undertaken without informing the responsible caregiver first (17). Advice or leadership from clinicians with expertise in diagnosing and intervening in the condition is recommended (255). Psychiatric evaluation of the caregiver may be required and may involve a court order.
Thus far, there is limited research on the retention of treatment improvements for appreciably long periods for functional neurologic disorder. Repetitive transcranial magnetic stimulation to the brain has led to a sustained reduction of functional tremor as much as 12 months subsequently, unlike patients who underwent sham treatment (268).
Physical therapy combined with physical retraining has demonstrated, and 69% retained gains at 6-month follow-up (125). Comparable findings were obtained in the management of functional gait disorder (129). Replication trials are needed. A similar, 5-day inpatient program of physical therapy but without cognitive behavioral therapy obtained an impressive 72% improvement at 6 months’ follow-up on a clinical global impression scale (191). Entrainment treatment (in which unilateral functional tremor is trained to match an imposed, different tremor in the opposite arm) was efficacious in 60% of participants at 6-month follow-up, though relapses were also noted (82). Four to 6 days of psychotherapy led to improved symptom control in persons with either functional movement disorder or functional seizures (123). Replication trials are needed.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Victor W Mark MD
Dr. Mark of the University of Alabama at Birmingham has no relevant financial relationships to disclose.See Profile
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