Functional Tremor Research Articles

Diagnosis and Treatment of Functional (Psychogenic) Parkinsonism.

Functional (psychogenic) parkinsonism (FP) is recognized by the mandatory combination of marked slowness without progressive decrement on repetitive manual tasks and variable resistance against passive movements in the absence of cogwheel rigidity. Other functional phenotypes, such as functional tremor and functional gait impairment, may coexist. Although neither necessary nor sufficient for the diagnosis of FP, supportive historical clues include the sudden onset of symptoms and absent or nonphysiologic response to levodopa. In selected cases where examination features remain insufficient to render a clinically definite FP diagnosis, normal dopaminergic transporter imaging (DAT scan) confirms "laboratory supported" FP. The management of FP begins with diagnostic debriefing, as the full acceptance of the diagnosis is critical in ensuring patient involvement in individualized psychoeducation, psychotherapy, and physical and occupational therapy.

Intra-tester reliability of three-dimensional kinematics in obese children and adolescents

Functional tremor is the commonest reported functional movement disorder. A confident clinical diagnosis of functional tremor is often possible based on the following “positive” criteria: a sudden tremor onset, unusual disease course, often with fluctuations or remissions, distractibility of the tremor if attention is removed from the affected body part, tremor entrainment, tremor variability, and a coactivation sign. Many patients show excessive exhaustion during examination. Other somatizations may be revealed in the medical history and patients may show additional functional neurologic symptoms and signs. In cases where the clinical diagnosis remains challenging, providing a “laboratory-supported” level of certainty aids an early positive diagnosis. In rare cases, in which the distinction from Parkinson's disease is difficult, dopamine transporter single-photon emission computed tomography (DAT-SPECT) can be indicated.

A Functional Parkinsonian Tremor in a Pediatric Patient.

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How typical are ‘typical’ tremor characteristics? Sensitivity and specificity of five tremor phenomena

IntroductionDistinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five ‘typical’ tremor phenomena. MethodsRetrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on ‘typical’ characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (FT)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the ‘typical’ group was compared to the whole group. ResultsMost patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FT, whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity. ConclusionIn this study, we retrospectively determined sensitivity and specificity for five ‘typical’ tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders.

Validation of "laboratory-supported" criteria for functional (psychogenic) tremor.

In a small group of patients, we have previously shown that a combination of electrophysiological tests was able to distinguish functional (psychogenic) tremor and organic tremor with excellent sensitivity and specificity. This study aims to validate an electrophysiological test battery as a tool to diagnose patients with functional tremor with a "laboratory-supported" level of certainty. For this prospective data collection study, we recruited 38 new patients with functional tremor (mean age 37.9 ± 24.5 years; mean disease duration 5.9 ± 9.0 years) and 73 new patients with organic tremor (mean age 55.4 ± 25.4 years; mean disease duration 15.8 ± 17.7 years). Tremor was recorded at rest, posture (with and without loading), action, while performing tapping tasks (1, 3, and 5 Hz), and while performing ballistic movements with the less-affected hand. Electrophysiological tests were performed by raters blinded to the clinical diagnosis. We calculated a sum score for all performed tests (maximum of 10 points) and used a previously suggested cut-off score of 3 points for a diagnosis of laboratory-supported functional tremor. We demonstrated good interrater reliability and test-retest reliability. Patients with functional tremor had a higher average score on the test battery when compared with patients with organic tremor (3.6 ± 1.4 points vs 1.0 ± 0.8 points; P < .001), and the predefined cut-off score for laboratory-supported functional tremor yielded a test sensitivity of 89.5% and a specificity of 95.9%. We now propose this test battery as the basis of laboratory-supported criteria for the diagnosis of functional tremor, and we encourage its use in clinical and research practice.

Chapter 19 - Functional tremor

Functional tremor is the commonest reported functional movement disorder. A confident clinical diagnosis of functional tremor is often possible based on the following "positive" criteria: a sudden tremor onset, unusual disease course, often with fluctuations or remissions, distractibility of the tremor if attention is removed from the affected body part, tremor entrainment, tremor variability, and a coactivation sign. Many patients show excessive exhaustion during examination. Other somatizations may be revealed in the medical history and patients may show additional functional neurologic symptoms and signs. In cases where the clinical diagnosis remains challenging, providing a "laboratory-supported" level of certainty aids an early positive diagnosis. In rare cases, in which the distinction from Parkinson's disease is difficult, dopamine transporter single-photon emission computed tomography (DAT-SPECT) can be indicated.

Chapter 6 - Neurophysiologic studies of functional neurologic disorders

Functional neurologic disorders are largely genuine and represent conversion disorders, where the dysfunction is unconscious, but there are some that are factitious, where the abnormality is feigned and conscious. Malingering, which can have the same manifestations, is similarly feigned, but not considered a genuine disease. There are no good methods for differentiating these three entities at the present time. Physiologic studies of functional weakness and sensory loss reveal normal functioning of primary motor and sensory cortex, but abnormalities of premotor cortex and association cortices. This suggests a top-down influence creating the dysfunction. Studies of functional tremor and myoclonus show that these disorders utilize normal voluntary motor structures to produce the involuntary movements, again suggesting a higher-level abnormality. Agency is abnormal and studies shows that dysfunction of the temporoparietal junction may be a correlate. The limbic system is overactive and might initiate involuntary movements, but the mechanism for this is not known. The limbic system would then be the source of top-down dysfunction. It can be speculated that the involuntary movements are involuntary due to lack of proper feedforward signaling.

Functional disorders

Functional disorders in neurology: Changing a negative to a positiveFunctional symptoms and disorders (also called psychogenic, non-organic and conversion disorders) are a common cause of distress and disability and account for around 1 in 6 new referrals to the neurology clinic. In the last 10-15 advances in understanding, diagnosis and treatment of patients with functional disorders have changed the clinical landscape1. These are turning traditionally negative views in to a more positive approach which brings these disorders back within standard neurological practice.In this lecture I will discuss: 1) The importance of making the diagnosis, not on psychosocial grounds or as a diagnosis of exclusion, but using positive diagnostic clinical signs, such as Hoover’s sign of functional leg weakness or the entrainment test of functional tremor; 2) The central role of the neurologist in providing explanation, information (for example www.neurosymptoms.org), and triage of treatment (with some practical examples); 3) Increasing recognition of the evidence base for physiotherapy2 as well as psychological therapy3; 4) Changes in the model that we use to think about the mechanism and aetiology of these problems which now incorporate biological as well as psychological factors4.1. Stone, J. & Carson, A. Functional Neurologic Disorders. Continuum. 21, 818–837 (2015).2. Nielsen, G. et al. Physiotherapy for functional motor disorders. JNNP (2015). doi:10.1136/jnnp-2014-3092553. Goldstein, L. H. et al. Cognitive-behavioral therapy for psychogenic nonepileptic seizures: A pilot RCT. Neurology 74, 1986–1994 (2010).4. Edwards, M. J., et al A Bayesian account of ‘hysteria’. Brain 135, 3495–512 (2012). Functional disorders in neurology: Changing a negative to a positive Functional symptoms and disorders (also called psychogenic, non-organic and conversion disorders) are a common cause of distress and disability and account for around 1 in 6 new referrals to the neurology clinic. In the last 10-15 advances in understanding, diagnosis and treatment of patients with functional disorders have changed the clinical landscape1. These are turning traditionally negative views in to a more positive approach which brings these disorders back within standard neurological practice. In this lecture I will discuss: 1) The importance of making the diagnosis, not on psychosocial grounds or as a diagnosis of exclusion, but using positive diagnostic clinical signs, such as Hoover’s sign of functional leg weakness or the entrainment test of functional tremor; 2) The central role of the neurologist in providing explanation, information (for example www.neurosymptoms.org), and triage of treatment (with some practical examples); 3) Increasing recognition of the evidence base for physiotherapy2 as well as psychological therapy3; 4) Changes in the model that we use to think about the mechanism and aetiology of these problems which now incorporate biological as well as psychological factors4. 1. Stone, J. & Carson, A. Functional Neurologic Disorders. Continuum. 21, 818–837 (2015). 2. Nielsen, G. et al. Physiotherapy for functional motor disorders. JNNP (2015). doi:10.1136/jnnp-2014-309255 3. Goldstein, L. H. et al. Cognitive-behavioral therapy for psychogenic nonepileptic seizures: A pilot RCT. Neurology 74, 1986–1994 (2010). 4. Edwards, M. J., et al A Bayesian account of ‘hysteria’. Brain 135, 3495–512 (2012).

Therapeutic advances in tremor.

Although tremor is a highly prevalent movement disorder, progress in this field is limited because of the poor understanding of many of the underlying conditions. This review summarizes recent treatment attempts since 2013. For essential tremor, recent innovations are phase I or II studies of Octanol, several clinically relevant refinements for deep brain stimulation, and the development of the new magnetic resonance imaging guided focused ultrasound technique. Further new invasive and noninvasive electrical and magnetic stimulation techniques have been tested for essential tremor and parkinsonian tremor. For multiple sclerosis tremor, some open-label observations have shown positive results (natalizumab, dalfampridine, levetiracetam), whereas controlled trials using cannabinoids have been negative. Functional tremor has shown a positive response to retrainment. Neuroprosthetic devices have been tested in a variety of tremor conditions. Several promising medical and surgical treatment trials are underway and will be completed shortly.

An Update on Functional (Psychogenic) Tremor

Functional tremor accounts for at least 50% of patients with functional movement disorders. The diagnostic work-up of these patients can be challenging. It is a multistep process based on patients’ history and clinical criteria finally providing a ‘positive’ diagnosis. Variability of the tremor over the disease course and during clinical examination is characteristic. Patients often show increased attention toward the tremulous body part and distractability of the tremor once attention is drawn away. Sometimes distractability becomes obvious during history taking or neurological examination, in others certain distraction tasks are needed. If uncertainty remains, ancillary investigations such as electrophysiological tests may be helpful. Recent studies suggested that a loss of sense of control of ones actions may help to explain why patients with functional tremor report that they do not experience the abnormal movement as voluntary. Treatment has to be placed in a multidisciplinary team involving neurologists, psychiatrists, physiotherapists and psychologists.

Usefulness of intermuscular coherence and cumulant analysis in the diagnosis of postural tremor

ObjectiveTo investigate the potential value of two advanced EMG measures as additional diagnostic measures in the polymyographic assessment of postural upper-limb tremor. MethodsWe investigated coherence as a measure of dependency between two EMG signals, and cumulant analysis to reveal patterns of synchronicity in EMG activity in muscle pairs. Eighty datasets were analyzed retrospectively, obtained from four groups: essential tremor (ET), Parkinson’s disease (PD), enhanced physiological tremor (EPT), and functional tremor (FT). ResultsIntermuscular coherence was highest in the PD group (0.58), intermediate in FT (0.43) and ET (0.40), and weakest in EPT (0.16) (p=0.002). EPT patients could be distinguished by low coherence: coherence <0.18 in the wrist+elbow extensors differentiates EPT in this sample with a sensitivity of 86% and specificity of 84%.Cumulant analysis showed predominantly alternating activity between wrist and elbow extensor in ET patients, while a more synchronous pattern was predominant in PD, EPT and FT (p=0.008). EMG activity in wrist and elbow flexors tended to be more synchronous in PD (p=0.059). ConclusionOur results suggest that coherence and cumulant analysis may be of additional value in the diagnostic work-up of postural tremor. SignificanceThese additional measures may be helpful in diagnosing difficult tremor cases.

Correction: Tactile and Proprioceptive Temporal Discrimination Are Impaired in Functional Tremor

Correction: Tactile and Proprioceptive Temporal Discrimination Are Impaired in Functional Tremor

Increased variability in spiral drawing in patients with functional (psychogenic) tremor

Increased variability is a characteristic clinical and physiologic feature of functional (psychogenic) tremor. In this study, we use computerized spiral analysis to show that the variability of a motor task is a quantifiable characteristic of functional tremor. We compare functional tremor patients to phenomenologically similar dystonic tremor patients and to normal controls. We used the spiral severity score, a measure that does not incorporate spiral tightness, as a marker of spiral drawing performance, and inter-spiral tightness variability (based on the 25–75%ile range in tightness across ten spirals) to evaluate the effects of functional tremor on drawing spirals. The spirals of 74 participants: 22 functional tremor, 21 dystonic tremor, and 31 normal controls were analyzed. Spiral severity was higher in both tremor groups compared to controls, but did not differentiate them. Inter-spiral variability, however, was higher in the functional tremor group compared to both other groups. Thus, spiral analysis captures variability of a motor task and may be used as an objective test for functional tremor. The effect of functional tremor in other motor tasks should be investigated.

Tactile and proprioceptive temporal discrimination are impaired in functional tremor.

Background and MethodsIn order to obtain further information on the pathophysiology of functional tremor, we assessed tactile discrimination threshold and proprioceptive temporal discrimination motor threshold values in 11 patients with functional tremor, 11 age- and sex-matched patients with essential tremor and 13 healthy controls.ResultsTactile discrimination threshold in both the right and left side was significantly higher in patients with functional tremor than in the other groups. Proprioceptive temporal discrimination threshold for both right and left side was significantly higher in patients with functional and essential tremor than in healthy controls. No significant correlation between discrimination thresholds and duration or severity of tremor was found.ConclusionsTemporal processing of tactile and proprioceptive stimuli is impaired in patients with functional tremor. The mechanisms underlying this impaired somatosensory processing and possible ways to apply these findings clinically merit further research.

Tremor retrainment as therapeutic strategy in psychogenic (functional) tremor

Entrainment, the change or elimination of tremor as patients perform a voluntary rhythmical movement by the unaffected limb, is a key diagnostic hallmark of psychogenic tremor. To evaluate the feasibility of using entrainment as a bedside therapeutic strategy ('retrainment') in patients with psychogenic tremor. Ten patients with psychogenic tremor (5 women, mean age, 53.6±12.8 years; mean disease duration 4.3±2.7 years) were asked to participate in a pilot proof-of-concept study aimed at "retraining" their tremor frequency. Retrainment was facilitated by tactile and auditory external cueing and real-time visual feedback on a computer screen. The primary outcome measure was the Tremor subscale of the Rating Scale for Psychogenic Movement Disorders. Tremor improved from 22.2±13.39 to 4.3±5.51 (p=0.0019) at the end of retrainment. The benefits were maintained for at least 1 week and up to 6 months in 6 patients, with relapses occurring in 4 patients between 2 weeks and 6 months. Three subjects achieved tremor freedom. Tremor retrainment may be an effective short-term treatment strategy in psychogenic tremor. Although blinded evaluations are not feasible, future studies should examine the long-term benefits of tremor retrainment as adjunctive to psychotherapy or specialized physical therapy.

The treatment of tremor.

Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various etiological subtypes of tremor are recognized, with essential tremor (ET) and Parkinsonian tremor being the most common. Here we review the current literature on tremor treatment regarding ET and head and voice tremor, as well as dystonic tremor, orthostatic tremor, tremor due to multiple sclerosis (MS) or lesions in the brainstem or thalamus, neuropathic tremor, and functional (psychogenic) tremor, and summarize main findings. Most studies are available for ET and only few studies specifically focused on other tremor forms. Controlled trials outside ET are rare and hence most of the recommendations are based on a low level of evidence. For ET, propranolol and primidone are considered drugs of first choice with a mean effect size of approximately 50 % tremor reduction. The efficacy of topiramate is also supported by a large double-blind placebo-controlled trial, while other drugs have less supporting evidence. With a mean effect size of about 90 % deep brain stimulation in the nucleus ventralis intermedius or the subthalamic nucleus may be the most potent treatment; however, there are no controlled trials and it is reserved for severely affected patients. Dystonic limb tremor may respond to anticholinergics. Botulinum toxin improves head and voice tremor. Gabapentin and clonazepam are often recommended for orthostatic tremor. MS tremor responds only poorly to drug treatment. For patients with severe MS tremor, thalamic deep brain stimulation has been recommended. Patients with functional tremor may benefit from antidepressants and are best be treated in a multidisciplinary setting. Several tremor syndromes can already be treated with success. But new drugs specifically designed for tremor treatment are needed. ET is most likely covering different entities and their delineation may also improve treatment. Modern study designs and long-term studies are needed.

THE ENTRAINMENT TEST IN TREMOR ASSESSMENT: INFLUENCE OF HISTORICAL FACTORS AND CLINICAL METHODOLOGY

ObjectiveDiagnosing functional tremors is challenging, usually relying solely on history and examination. However, it has been suggested that clinicians may disregard the outcome of observational tests; basing diagnoses on history...

How to use the entrainment test in the diagnosis of functional tremor

Functional (psychogenic) tremor is the commonest functional movement disorder.1 As with other functional neurological symptoms, a key diagnostic component is to search for positive physical signs.1 ,2 A key positive...

The tremor network targeted by successful VIM deep brain stimulation in humans

Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation. We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites. VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation. Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities.

Glutethimide Treatment of Disabling Action Tremor in Patients With Multiple Sclerosis and Traumatic Brain Injury

Glutethimide has been used to control essential tremor. Its efficacy in the treatment of disabling cerebellar and rubral tremor was assessed in an open study of six patients with multiple sclerosis and two patients with traumatic brain injury. Functional and quantitative tremor severity was assessed before treatment and 7 to 14 days after a stable dose was achieved. Six of eight patients exhibited visible functional benefit from treatment with glutethimide; abstract testing results correlated well with functional status in most cases. Four patients chose to continue to receive medication. Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated.