Introduction Tremor is among the most common movement disorders and is characterized by rhythmic oscillations of a part of the body around one or more joints. Methods of tremor assessment include simple clinical observation, standardized rating scales, objective clinical assessment of drawn figures, and computerized tremor analysis. A broad overview of tremor, and the relative advantages and disadvantages of tremor assessment methods are discussed below.
As there are different kinds of tremor with numerous underlying causes, the process of tremor classification and evaluation is of critical importance to establish a correct diagnosis and initiate the most appropriate treatment. Classification of tremor Tremor can be most effectively classified based on the circumstances under which it occurs. Rest tremor can be distinguished from other forms of tremor based on its occurrence when the tremoring body part is completely supported against gravity without voluntary muscle contraction, in contrast to action tremor, which occurs with voluntary muscle contraction. Action tremor can be further divided into postural or sustention tremor (occurring while maintaining a posture against gravity) and kinetic tremor (occurring during active movement). Kinetic tremor includes task-specific tremor and tremor that is specific to goal-directed movements ( intention tremor). It can also be associated with situations where there is active muscle contraction against a fixed object ( isometric tremor). While the tremors encountered in clinical practice are usually involuntary, patients can present with psychogenic tremor in isolation or in combination with other neurologic complaints of psychogenic origin, as in psychogenic parkinsonism.
Permissions for industry or clinical use of the MDS-developed rating scales are available. Disease rating scale scores for tremor items were significantly reduced by 60% and function disability measured by the Fahn -Tolosa- Marin rating scale parts A and C in the functional aspects showed significant improvement.
In addition to provoking circumstances, other tremor characteristics have been used to try to classify tremor (such as frequency, amplitude, or distribution). However, such classifications are often problematic as these characteristics can vary greatly within tremor etiologies. Evaluation of tremor Though tremor may be the most quantifiable of all movement disorders, there is currently no universally accepted method of rating or measuring tremor., There can be considerable variability in the manner in which clinicians assess the presence of tremor and its severity. In an attempt to standardize the evaluation of tremor (particularly for clinical research purposes), a number of rating scales have been developed that optimize comparability between studies and patient populations. One of the earlier tremor scales developed that is still in use today is the Fahn–Tolosa–Marin Tremor Rating Scale (TRS).
This 5-point scale rates tremor severity based on tremor amplitude, from 0 (no tremor) to 4 (severe tremor) in each part of the body, and includes assessments of specific abilities and functional disability. A number of other scales have been developed, which include smaller severity gradations or are disease specific., Although tremor scales vary regarding reliability and validity, even the best clinical scale may not be sensitive enough to discern minimal abnormality and subtle changes over time, or objective enough to determine significant responses to therapy. While graphic evidence of tremor activity can be evaluated clinically by examining writing or drawn spirals, these are still interpreted subjectively and are not easily standardized across subjects.
Thus, the objective and quantifiable data analysis afforded by computerized assessment of tremor can be an important tool in research and certain clinical settings. Computerized tremor analysis Because tremors are quasi-sinusoidal movements, they are amenable to quantitative mathematical analysis and modeling with a high degree of fidelity to the clinical picture. To record tremor activity, accelerometry, electromyography (EMG), and other signals (such as force or gyroscopic measurements) are acquired, digitized through an analog-to-digital board and analyzed.
With modern computers and digital signal processing boards, tremors can be analyzed in real time at a high sampling rate or processed off-line. Additional assessments (such as time series analyses) can detect complex synchronization and signal relationships within tremors. Two of the most important characteristics of tremor assessed by tremor analysis are frequency and amplitude. Tremor frequency, or the amount of oscillations per second, is measured in cycles per second (Hz).
If the number of sampled points is N over a period of time T in seconds, then the sampling rate is N/T, the frequency resolution is 1/T Hz and the maximum recordable frequency is N/2T Hz (also known as the Nyquist frequency). Thus, if the highest frequency of concern is 25 Hz (most biological tremors fall in lower frequency ranges), the sampling rate of the recording device must be at least 50 Hz (and preferably several times that) for better signal processing. Low-pass filtering and other techniques can be used to further improve signal-to-noise ratios.
Depending on recording circumstances, tremor frequencies can be reliably calculated to within 0.1 Hz and tremor displacement amplitudes can be determined accurately to less than 0.1 mm. It is important to remember, however, that frequency determination alone is not sufficient for a diagnosis as there is considerable frequency overlap between conditions. While tremors are typically described by their frequency (such as parkinsonian rest tremor ranging from 3 to 6 Hz), patients are usually not greatly bothered by tremor frequency, but rather by the amplitude of their tremor., Therefore, with regard to clinical disability and therapeutic effect, amplitude and other waveform characteristics may be more important. The degree of linear or angular displacement of the limb or body part, or the tremor amplitude, is generally measured in millimeters or degrees.
Tremor amplitude can be accurately assessed using accelerometers or gyroscopes. Miniature accelerometers can be attached to the involved tremulous parts of the body, typically the limbs and occasionally the head, neck, or trunk, and do not interfere with voluntary or involuntary movements. High-powered microcomputers, now capable of recording and analyzing large amounts of data quickly and efficiently, give almost instantaneous displacement from accelerometric signals. Furthermore, such operations can be modified to also filter out low-frequency noise such as unwanted drift or higher frequency electronic interference. Accelerometric or gyroscopic data can be difficult to appreciate clinically because sinusoidal motion is not easily perceived in accelerometric or rotational units; however, with mathematical integration, displacement of the oscillating body part can be derived from these signals. EMG provides additional useful information about the activity of muscles involved in the generation of tremor. EMG activity may be recorded using needle, wire electrodes, or more typically surface electrodes overlying active muscles.
The EMG can provide information about motor unit recruitment and synchronization, and can also elucidate the relationship between involved muscles and tremulous movements, revealing whether antagonist muscles (such as flexors and extensors of the wrist) are working at the same time or alternately to produce tremor. To utilize the EMG most appropriately in tremor analysis, the signal has to be processed by rectification and integration or smoothing to place its frequency profile into the tremor range. The objective and detailed findings of a tremor analysis test are most helpful when the clinical picture is complicated or when clinical signs are subtle.
For example, parkinsonian tremor and essential tremor (ET) can sometimes be difficult to separate clinically, but diagnosis is obviously important to distinguish the appropriate prognosis and treatment., Both conditions occur with increasing age, and both may occur at rest, with postures, or during voluntary movements. EMG-to-movement, side-to-side frequency relationship, EMG topography, reflex responses, tremor amplitude ratios during different clinical tasks, and methods such as time series analyses are ways by which quantified analysis can be diagnostically useful. Computerized tremor analysis can also shed light on the manner in which tremor is perceived and graded by clinician observers.
In evaluating and grading change in tremor severity, the change in tremor amplitude perceived by a clinician is governed by Weber–Fechner laws of psychophysics, in which the size of the discernible change is proportional to the initial tremor amplitude, with a logarithmic relationship between tremor amplitude and perceived change in amplitude, despite the apparent linearity of clinical scales. – A combined study of tremor analysis data from five different laboratories confirmed this non-linear relationship and demonstrated good correlation between computerized tremor analysis and 4- and 5-point tremor rating scales in this context.
In addition to tremor analysis using accelerometry and EMG, tremor can also be evaluated through the quantification of drawn spirals. Representative Quantitative Spiral Analyses for Normal Subjects, Parkinson Disease (PD), and Essential Tremor (ET) Patients Demonstrating Tremor Frequency Spectra and Axis.
Row 1: Original spiral drawings in 10 × 10 cm outlines with two line colors denoting the left and right sides of the spiral. Row 2: The spirals with dimension of time (seconds) in the vertical axis demonstrating temporal executions of the spirals. Row 3: The graphic representations of spiral unraveling where the x-axis = angle (radians) and the y-axis = radius (cm). Row 4: Spectral analyses of spiral tremor frequencies where the x-axis = frequency (Hz) and y-axis = frequency power. Row 5: Tremor axes, when present, illustrating the predominant direction of spiral tremors.
Archimedean spirals drawn on a digitizing tablet can be analyzed in both the x–y plane of the tablet and the z plane of pen pressure perpendicular to the tablet. By mathematically “unraveling” drawn spirals and averaging multiple trials together, tremor characteristics such as frequency, direction, and amplitude can be detected and quantified, as well as an abundance of other variables, including drawing speed and acceleration, loop-to-loop width tightness and variation, and drawing pressure over time. Owing to its portability and ease of data acquisition, which can be analyzed offline, spiral analysis lends itself particularly well to the demonstration and quantification of subtle motor abnormalities in patient cohorts that might not be appreciated using standard clinical rating scales. Tremor pathogenesis Physiologic tremor (PT), like all tremors, is generated and mediated both peripherally and centrally. The peripheral component of PT contributes irregular very low amplitudes and variable (8–12 Hz and higher) oscillations depending on the mass, stiffness, and other properties of the tremoring body part.
It is a passive response caused by disturbances such as cardioballistics, mild physical perturbations, and subtetanic motor unit firing (too few motor units discharge together to result in anything but imperceptible movement or force)., In addition to mechanical factors, short and long loop reflexes influence the peripheral component, although to a lesser degree. Hence, the peripheral component is often termed “mechanical reflex.” If the peripheral component can be detected (which is not always the case), inertial loading (weighting) and other mechanical alterations affect it simply by changing limb physical properties. Inertial loading will decrease the mechanical-reflex frequency component in the same manner as weighting slows down a clock pendulum. However, because of non-linearities in the nervous system (spindle stretch responses, muscle properties changes with length, thixotropy, neural membrane firing characteristics, etc.), inertial loading effects are not simple and must be interpreted cautiously. Furthermore, the mechanical-reflex component is not always detectable. The central component of PT, often referred to as the “central oscillator”, contributes weak 8–12 Hz very low-amplitude movements.
The central oscillator of PT is not greatly affected by inertial loading or other physical manipulations. Motor units are not entrained (discharging in groups) in PT.
When they become entrained, e.g., due to stress, drugs, or cold (as in shivering), PT develops into exaggerated physiologic tremor (EPT). EPT has the same peripheral and central components as PT, but there is greater participation of the stretch reflex and of the 8–12 Hz central oscillator. When EPT becomes clinically symptomatic with posture or movement without provoking factors, it becomes phenomenologically similar to ET and may be difficult to separate from EPT early in its course.
Pathologic tremors such as ET, dystonic tremor (DT), or the tremors of Parkinson disease (PD) result in a variety of tremor frequencies from about 1–25 Hz. They are thought to be generated centrally and usually obfuscate their peripheral components (except in neuropathic tremor). The etiology of tremor in PD is poorly understood, but based on recent magnetoencephalography and imaging studies is thought to involve networks of both cortical and subcortical areas., While traditionally considered a functional monosymptomatic condition, an accumulation of both epidemiologic and pathologic studies have argued that ET may be a neurodegenerative disease with both an increased risk of non-tremulous co-morbidities and structural pathologic changes in the cerebellum. It is generally believed that the tremors in ET have contributions secondary to abnormal oscillatory activity either within the cerebellum or in the olivocerebellothalamic pathway. Rest tremors Rest tremors most often occur in the setting of PD or parkinsonism. PD rest tremors typically start unilaterally and distally as the classic 3–6 Hz “pill-rolling” sinusoidal oscillations, and progress more proximally as they generalize to both sides, though tremor may occasionally start anywhere (such as in the jaw). Early in the disease, tremor amplitude fluctuates significantly with mental or physical demands and thus is often described as intermittent.
Oscillations in wrist extension and flexion, pronation and supination, or finger flexion (producing the pill-rolling quality) can be seen. As with most movement disorders, PD tremor is worsened by stress (which can be useful to bring out tremor during clinical evaluation) and disappears during sleep. Anxiolytics or alcohol can improve symptoms simply by reducing anxiety, which may lead to confusion as ET is specifically responsive to alcohol. A poly-EMG profile of PD rest tremor typically shows alternating (less commonly synchronous) contraction of agonist and antagonist muscles at a frequency of less than 6 Hz with relatively sinusoidal displacement on accelerometric tracings.
Electromyography (EMG) Profile, Movement Analysis, and Frequency Spectrum of Rest Tremor in a Patient with Parkinson Disease (PD). (A) EMG profile. The first four traces represent surface EMG signal from forearm muscles; ECR, extensor carpi radialis; FCR, flexor carpi radialis. The bottom two traces reflect displacement (darker line) derived from accelerometry. Note the relatively sinusoidal tremor displacement in the symptomatic left hand. (B) Frequency spectrum of tremor displacement demonstrating a peak between 4 and 6 Hz in the symptomatic left (gray line) hand, with a trace peak present in the right (black line) hand.
In tremor that is bilateral, tremor frequencies are similar. Some studies have found high coherence between limbs (despite amplitude asymmetry) for brief periods of time, though this is not always observed., While tremor severity does not correlate with the loss of striatal dopamine, and some patients with PD tremor do not improve or even worsen with levodopa, it is generally believed that rest tremors are modulated predominantly centrally by multiple generators within the corticobasal ganglia and corticocerebellar circuitry.
Functional neurosurgical treatments that inhibit pathways through the basal ganglia are thought to work by disrupting these circuits. As ET becomes more severe it may occur at rest; however, this can also sometimes represent coexistent PD or incomplete postural relaxation. ET resting tremor is asymmetric and the frequency relationship between sides is variable. Though less commonly seen in clinical practice, other diseases can produce rest tremors as well, though usually not in isolation. Midbrain (rubral or Holmes) tremor and thalamic tremor are occasional causes of rest tremor. Midbrain tremor is caused by lesions of the cerebellothalamic and nigrostriatal pathways and thus consists of a combination of rest, postural, and kinetic components.
The tremor at rest is of large amplitude and irregular, and commonly involves both proximal and distal muscles at frequencies of 2–5 Hz., Infarction in the midbrain is the most common cause, though tumor, abscess and demyelination are occasionally reported. Thalamic tremor is relatively rare, and causes action and sometimes rest tremor due to lesions most often affecting the ventral lateral posterior nucleus of the thalamus. Though DT and drug-induced tremors are more commonly thought of as action tremors, they can occur at rest, usually along with an action component.
Action tremor in PD Patients with PD can exhibit a variable-onset delayed tremor when holding up an outstretched arm, with a frequency typical of PD rest tremor. This is in contrast with the postural tremor of ET, which has no delay in onset. It is commonly thought of as re-emergent PD rest tremor, though a case of such tremor without rest tremor has been reported. In addition, higher frequency 5–8 Hz lower amplitude action tremors are not uncommon in PD and can be difficult to distinguish from ET.
Single photon emission computed tomography imaging of the dopamine transporter has been approved in the United States of America to help differentiate these entities, and computerized tremor analysis can also be useful in this regard. Electromyography (EMG) Profile, Movement Analysis, and Frequency Spectrum of Postural Tremor in a Patient with Essential Tremor (ET) with Arms Extended. (A) EMG profile. The first four traces represent surface EMG signal from forearm muscles; ECR, extensor carpi radialis; FCR, flexor carpi radialis.
The bottom two traces reflect displacement (darker line) derived from accelerometry (B) Frequency spectrum of tremor displacement demonstrating a broad peak between 4 and 8 Hz in both hands. ET is generally a slowly progressive, clinically monosymptomatic disorder marked by initially low-amplitude tremors (which can increase dramatically as the disease progresses) of mid to high frequency (4–12 Hz that decreases with age) and is most prominent in the hands, though other body parts can be involved. The amplitude of kinetic tremor (which is invariably present) is generally greater than that of postural tremor. A worsening of kinetic tremor as the hand approaches a target (intention tremor) can be seen.
Head tremor (commonly in the horizontal plane) can develop or rarely be present in isolation, and a jaw tremor (in contrast to the lower lip tremor typically associated with PD) can be seen in some cases. Unlike tremor in PD, it is more irregular and more bilaterally symmetric, and it does not occur as a hemibody tremor lateralized to one arm and leg. Cogwheeling is often found secondary to tremor and should not be confused with the rigidity seen in PD patients. The amelioration of tremor with alcohol is common and can help establish the diagnosis, and moderate use of alcohol limited to occasional social settings is usually not discouraged. However, alcohol clearly should not be used in the chronic treatment of ET, and the risk of dependence and abuse in ET has not been completely addressed by formal studies. Cerebellar tremor Cerebellar postural and action tremors are irregular and often of high amplitude, causing severe functional disability. With no rest component, patients may appear normal until they initiate movement or assume a steady posture, and tremor is most pronounced with intention.
Irregular postural tremor of the head and rhythmic postural sway (truncal tremor) may also occur. As with all tremors, the frequency of cerebellar tremor depends upon the part of the body that is affected.
Tremor frequencies range from 3–8 Hz in the upper extremities, around 1–3 Hz in the lower extremities, and 2–4 Hz in the trunk. Injury to the deep cerebellar nuclei and cerebellar outflow tracts are likely involved in tremor production. The benefits of both pharmacologic and surgical treatments have been limited. Orthostatic tremor The term orthostatic tremor (OT) was first used in 1984 and was previously referred to as “shaky leg syndrome”. In this relatively uncommon but distinct disorder, patients find it increasingly difficult to stand still due to sensations variably described as tremor, unsteadiness, and/or pain.
Tasks such as waiting in line or doing dishes become troublesome, and patients find themselves needing to walk in place, continuously shift their weight from one leg to the other, or lean against a wall in order to reduce discomfort. OT may also be associated with muscle cramps, and patients will often describe subjective tremor elsewhere in the body, such as the lips, jaws, or hands. Significant disability and depression with substantial curtailing of activities can occur in severe cases. OT is more common in women, with a mean age of onset in the early sixties, and is generally considered to be sporadic, though associations with various other neurologic disorders have been reported, including ET, PD, cerebellar degeneration, progressive supranuclear palsy, and pontine lesions. – Familial occurrence is uncommon, though EMG-confirmed OT in three brothers has been reported., The diagnosis of OT should be suspected in any patient describing pain or other unpleasant sensations shortly after standing that is relieved by sitting or walking. Auscultation of the gastrocnemius muscles can sometimes reveal a characteristic of barely audible noise akin to the sound of a helicopter. The diagnosis is confirmed by pathognomonic surface EMG recordings revealing rhythmic activation of lower limb muscles at sharply peaked frequencies between 14 and 18 Hz, and sometimes higher.
Electromyography (EMG) Profile and Frequency Spectrum of A Patient with Orthostatic Tremor While Standing. (A) EMG profile. GM, gastrocnemius; Hamst, hamstrings; TA, tibialis anterior; VL, vastus lateralis. (B) Frequency spectra demonstrating a sharp peak at 17.3 Hz in all muscles recorded. (C) Note the high coherence between frequency spectra of the EMG signals in the legs. Frequency spectra consistently show a high degree of coherence between limbs, unlike that in any other form of tremor. The etiology of OT is unclear; while it was initially considered a task-specific tremor, upright body position has been shown to be less important than weight-bearing and the sensation of postural instability, both of which may give rise to the clinical disorder.
It has been demonstrated in all limbs in OT patients with weight bearing and isometric contraction, and high-frequency highly coherent tremor has been produced in normal subjects made to feel unsteady through postural manipulation or galvanic stimulation, suggesting an exaggerated response to postural instability as playing a role. These observations, combined with its demonstration in cranially innervated muscles and the resetting of tremor phase induced with transcranial magnetic stimulation support a supraspinal central generator of the tremor. Treatment of OT is often disappointing, and improvement has been reported mostly with clonazepam, but occasionally with phenobarbital, primidone, or valproate. Improvement with deep brain stimulation (DBS) of the ventrointermediate nucleus (VIM) has also been described.
Dystonic tremor DT occurs in a body part affected by dystonia. It is typically postural or task related, with an irregular or jerky rhythmic low- to mid-frequency tremor secondary to co-contraction of agonist and antagonist muscles. Frequencies range from 1 to 6 Hz during dystonic contractions, with higher frequencies similar to ET seen during voluntary movements. Tremor associated with dystonia (occurring in a clinically non-dystonic body part in a patient with dystonia) can also occur. Characteristic of DT is the null point, a position in which the tremor almost fully abates. It may initially be present during specific action but can generalize to occur with any task. DT of the head or hand can sometimes be confused with ET or PD, and patients with DT have been postulated to account for some of the instances of patients with parkinsonism who have normal dopamine neuroimaging (scans without evidence of dopaminergic deficit (SWEDDs), or scans without evidence of dopaminergic deficit).
Careful evaluation for subtle dystonic posturing and the presence of a null point and/or geste antagoniste (a tactile or proprioceptive sensory trick that reduces the abnormal posture), as well as attention to tremor quality (jerky versus smooth), are helpful in making the correct diagnosis. In patients with head tremor, it is also helpful to remember that the typical head tremor seen in ET rarely occurs in the absence of coexistent hand tremor. Neuropathic tremor Neuropathic tremor is thought to arise secondary to central processing of mistimed and distorted peripheral input that occurs with neuropathic disease. It is usually irregular and distal, and can be asymmetric or relatively symmetric, with frequencies in the upper limbs ranging from 3 to 6 Hz. Demonstrates the distal low frequency tremor that developed subacutely in a patient with sensorimotor neuropathy with demyelinating and axonal features.
Neuropathic tremor can physiologically mimic a number of other tremor disorders, and the most helpful clues to the diagnosis are the coexistence of neuropathic symptoms. It can occur at rest, with posture, or during movement and can develop with multiple neuropathies, such as anti-myelin-associated glycoprotein (anti-MAG) neuropathy.
Most patients with neuropathic tremor are without central nervous system disease, and the tremor subsides with treatment of underlying neuropathy. Beta-blockers and other drugs used in ET have been reported to be helpful for neuropathic tremor, and success with VIM DBS has also been reported. Electromyography (EMG) Profile, Movement Analysis, and Frequency Spectrum of a Patient with Neuropathic Tremor Accompanied by Bilateral Sensory Loss and Weakness. EMG and nerve conduction studies demonstrated sensorimotor neuropathy with both demyelinating and axonal features. Note the distal low-frequency tremor driven primarily by wrist flexors and extensors with little proximal limb involvement. (A) EMG profile. The first six traces represent surface EMG signal from arm muscles.
ECR, extensor carpi radialis; FCR, flexor carpi radialis; Tric, triceps. The bottom two traces reflect displacement (darker line) derived from accelerometry. (B) Frequency spectrum of tremor displacement demonstrating peaks between 4 and 6 Hz. Task-specific tremor Tremor (not associated with abnormal postures or muscle spasm) that occurs predominantly during the execution of a specific (and often skilled) task is considered a task-specific tremor. While the 4–8 Hz tremor of primary writing tremor (PWT) is the most common example of a task-specific tremor, it can be found in musicians, athletes, and other professionals who are highly trained, such as surgeons or dentists. PWT can be sporadic or inherited in an autosomal dominant manner, and its etiology is controversial; it has been proposed to be a variant of DT, ET, and its own distinct entity.
Poly-EMG profiles most commonly show alternating contraction of agonist and antagonist muscles, although various other contraction patterns can be seen as well. Shows co-contraction of agonist and antagonist muscles and excessive muscle activity resulting in 4–5 Hz irregular tremor in a patient with primary writing tremor of 10 years' duration. Electromyography (EMG) Profile, Movement Analysis, and Frequency Spectrum of a Patient with Primary Writing Tremor while Writing with the Dominant Hand. Co-contraction of agonist and antagonist muscles below the deltoid is evident, though alternating contraction of agonist and antagonist muscles may be a more commonly seen pattern.
(A) EMG profile. The first five traces represent surface EMG signal from forearm muscles. ECR, extensor carpi radialis; FCR, flexor carpi radialis. The bottom two traces reflect displacement (darker line) derived from accelerometry (B) Frequency spectrum of tremor displacement demonstrating peaks between 4 and 6 Hz. Drug-induced tremor A wide variety of pharmacologic agents with differing mechanisms of action can cause tremor as a side effect. In general, they are non-progressive, often temporally related to the onset of a medication, and worsen with increasing medication dose.
Drug-induced rest tremor can occur in isolation or as part of drug-induced parkinsonism secondary to the use of antipsychotics, and can be clinically indistinguishable from PD tremor. In addition to neuroleptics, any medication which can cause secondary parkinsonism, such as lithium carbonate, valproate, or serotonin specific reuptake inhibitors, can induce a rest tremor., Many of these medications can cause an action tremor as well. Lithium is a frequent offender, causing tremor at both toxic and therapeutic levels., High blood levels of lithium are not necessary to produce tremor, and no correlation has been found between blood lithium levels and patient complaints of tremor. Non-toxic lithium tremor can occur acutely within the first week of starting therapy, or may develop within weeks or months after starting the medication. Valproate can cause a fine, 6–9 Hz rhythmic postural tremor, similar to the action tremor, which can occur with tricyclic antidepressants, and can mimic ET. Treatment with propranolol can be beneficial. Other tremorogenic medications include anti-arrhythmics, bronchodilators, and chemotherapeutic agents., Drugs of abuse such as alcohol, cocaine, and amphetamines can also cause tremor, due to acute intoxication, chronic use, or withdrawal.
Similar effects can be seen with heavy caffeine use. Psychogenic tremor Psychogenic tremors can occur as a manifestation of an underlying psychiatric disorder such as somatoform or factitious disorder, or can occur in cases of malingering. The diagnosis is based on unusual phenomenology and other diagnostic clues, such as abrupt onset, inconsistencies in tremor pattern and characteristics, spontaneous remissions, response to placebo, and distractibility., Relatively consistent physiologic findings include an increase in tremor amplitude with inertial loading , large fluctuations in frequency and amplitude, co-activation of antagonist muscles at the onset of tremor, and the absence of finger tremors. – Coexistent non-physiologic signs such as weakness or sensory abnormalities and underlying psychopathology can also help to suggest the diagnosis. Because it may be difficult to approach patients with a diagnosis of psychogenic tremor, clinicians are often reluctant to discuss the possibility of psychogenicity.
However, if correctly identified, psychogenic tremor due to a somatoform disorder is potentially curable through a coordinated effort between neurologists and psychiatrists. It is important to remember that the diagnosis of psychogenic tremor can only be made by a neurologist, while the role of the psychiatrist is to explore underlying psychodynamics and the degree of insight, guide psychopharmacologic treatments, and provide the continued psychotherapy critical for improvement. Other types of tremor Some disorders, such as asterixis, epilepsia partialis continua, and rhythmic forms of myoclonus such as palatal myoclonus, are often misinterpreted as tremor. Physiologically, myoclonic EMG bursts do not have gradual rise times and are not sinusoidal, and are separated by discrete periods of muscle silence. Cortical tremor is thought to be a variant of action-induced myoclonus in the setting of cortical myoclonus. It is characterized by distal short duration (generally less than 50 ms) rhythmic irregular bursts on EMG with synchronous activation of agonist and antagonist muscles and alternating periods of near silence.
Peak EMG burst frequency is 9–18 Hz with an associated cortical potential on EEG back-averaging. Funding: This work was supported, in part, by the Parkinson's Disease Foundation. S.L.P is partially supported by NIH grant # NS042859, the Parkinson Disease Foundation, and the Michael J. Fox Foundation.
Financial Disclosures: None. Conflict of Interests: S.L.P serves on the scientific advisory board of Musicians with Dystonia, Dystonia Medical Research Foundation, on the editorial board of Neurological Bulletin, and this journal, Tremor and Other Hyperkinetic Movements. He has a United States Patent 6,454,706 (2002) “System and Method for Clinically Assessing Motor Function.” C.W.H has nothing to disclose.
In a preliminary study, 10 members of TRG simultaneously rated 10 ET patients during the live administration of the TETRAS performance subscale. Excellent inter-rater reliabilities were found for head and upper limb tremor. In another preliminary study, ten members of TRG simultaneously rated three patients with mild, moderate and severe ET and rated the videos of these exams one month later. The correlations between video scores and live exam scores were greater than 0.87 for all items except face (0.67) and voice (0.63) tremor.
We now estimate the inter- and intra-rater reliabilities of the TETRAS performance subscale and the correlation of this subscale with the ADL subscale, using 50 videotaped exams. Methods All studies were performed with the signed written informed consent of the patients and controls, approved by the institutional review board of each institution. Patients with ET and controls with no history of tremor were recruited from the authors’ clinics.
The patients were diagnosed using Tremor Investigation Group criteria. Nine of the authors, all movement disorder specialists, videotaped TETRAS exams of one control and at least four patients. Each specialist was asked to video patients with mild, moderate and severe ET so that the videos were evenly distributed over these levels of severity. The TETRAS ADL and performance subscales were performed during each videotaping.
Fifty videos (44 patients and 6 controls) were compiled in random order to a set of DVDs and mailed to the same specialists and one other. Each specialist rated all 50 videos.
The same videos in different order were rated by the same specialists one to two months after the first rating. Due to omissions in some of the videos, some of the test items could not be scored for every video. Four of the ten video raters had no experience or training in TETRAS, and nearly all video omissions came from these four raters. Nevertheless, all raters scored 31 to 46 videos for each item, except the standing item for which only 19 were scored.
Inter- and intra-rater reliability of the performance subscale were assessed with two-way random effects intraclass correlations (ICC), using an absolute agreement definition. Results The patients (mean 67, range 35–80) and controls (mean 50; range 27–82) had comparable ages, and 27 of 50 participants were men. The average duration of tremor in the 44 patients was 30 years (range 6–72). The distribution of total TETRAS performance scores for the 50 participants was fairly uniform.
The inter- and intra-rater ICCs were greater than 0.85 for all items except face tremor, voice tremor, lower limb tremor and trunk (standing) tremor (see and for details). The six experienced and four inexperienced raters did not differ statistically (repeated measures ANOVA) in their inter- and intra-rater reliabilities for any of the test items, but the biggest differences were for the face, lower extremity and trunk (standing) items.
The raters performed live TETRAS assessments during the videotaping of the 50 TETRAS exams. The Pearson correlation between the total ADL scores and the total performance scores was 0.887 (p. Total ADL and performance scores for the 50 patients and controls Cronbach alpha for the live exams performed during the video tapings was 0.951, and it was 0.968 after removal of the face, lower limb and trunk items. Statistically identical results were obtained when Cronbach alpha was computed using the video ratings of each rater.
The item-to-total score correlations ranged from 0.88 to 0.95 (mean 0.91) for all upper limb items except right upper limb postural tremor with the limb extended forward (0.75). Item-to-total correlations for the head (0.69), face (0.45), voice (0.68), lower limb (0.60) and trunk (0.46) were lower.
Discussion Our use of performance ratings defined in terms of specific amplitude ranges (cm) resulted in exceptional inter- and intra-rater reliabilities, even for raters without prior experience or training with this scale. However, all raters were experienced movement disorder specialists, and it remains to be determined if raters with less expertise perform as well. Comparable inter-rater reliabilities were found in our earlier preliminary study in which ten TRG members, all developers of TETRAS, simultaneously rated ten ET patients during the live administration of the TETRAS performance subscale.
The TETRAS ADL and performance subscales have obvious content validity for ET, and there is also evidence of strong construct validity. The TETRAS ADL and performance scores are highly correlated, and the TETRAS performance items of upper extremity function correlate strongly with transducer measures of upper limb tremor. – TETRAS was designed specifically for ET and has not been tested in children or other patient populations.
Its metric anchors are too large for small children. TETRAS does not include an assessment of rest tremor because rest tremor is usually not present in ET. Furthermore, distinguishing rest tremor in ET from postural tremor in the presence of incomplete relaxation is difficult and is best avoided when the principal goal is assessment of ET severity rather than the diagnosis or complete characterization of ET in a particular patient. TETRAS is heavily weighted by upper extremity tremor and is arguably not ideal when the principal interest is tremor elsewhere.
The least reliable items of the TETRAS performance subscale were face tremor, lower limb tremor and trunk tremor while standing. This has been the experience with other tremor scales. These items could be deleted with little loss of content validity since the current clinical definition of ET focuses on upper extremity tremor and head tremor. Exclusion of the face, lower limb and trunk (standing) items would reduce the maximum total performance score from 64 to 52. Finally, most of us thought that the anchor “barely perceptible” for grade 1 upper and lower extremity tremor could be improved by adding “. This work was funded by a grant from GlaxoSmithKline.
Financial disclosures for the previous 12 months: Rodger Elble has received consulting fees from the Kinetics Foundation, and he receives research grant support from GlaxoSmithKline, Phytopharm, TEVA, the National Institutes of Health (NINDS), and the Spastic Paralysis Research Foundation of Kiwanis International, Illinois-Eastern Iowa District. Cynthia Comella has received consulting fees from Allergan, Merz, Ipsen, and Nupathe, and she receives research grant support from the Parkinson Disease Foundation, NIH, Dystonia Medical Research Foundation, Allergan, Merz and Ipsen. She receives royalties from Wolters Kluwer, Inc and Cambridge University Press. Stanley Fahn has received consulting fees from AstraZeneca Pharmaceuticals, IMPAX Pharmaceuticals, RJG Foundation, Green Cross Corporation, Civitas, Genervon Laboratories, Intec Pharma, and Merz. He receives grant support from the Parkinson’s Disease Foundation and the Smart Family Foundation. He has received lecture honoraria from the American Academy of Neurology, Columbia University, and Sun Pharmaceuticals India.
He has received editor and author honoraria from Springer for serving as co-editor of Current Neurology and Neurosurgery Report and from Elsevier for co-author of book Principles and Practice of Movement Disorders. Mark Hallett is employed at the NIH. He serves as Chair of the Medical Advisory Board for and receives honoraria and funding for travel from the Neurotoxin Institute. He may accrue revenue on US Patent #6,780,413 B2 (Issued: August 24, 2004): Immunotoxin (MAB-Ricin) for the treatment of focal movement disorders, and US Patent #7,407,478 (Issued: August 5, 2008): Coil for Magnetic Stimulation and methods for using the same (H-coil); in relation to the latter, he has received license fee payments from the NIH (from Brainsway) for licensing of this patent. He received royalties from publishing from Cambridge University Press, Oxford University Press, John Wiley & Sons, Wolters Kluwer, and Elsevier. He has received honoraria for lecturing from Columbia University and the Parkinson and Aging Research Foundation. Hallett's research at the NIH is largely supported by the NIH Intramural Program.
Supplemental research funds came from Ariston Pharmaceutical Company via a Cooperative Research and Development Agreement (CRADA) with NIH for treatment studies of essential tremor, and the Kinetics Foundation, for studies of instrumental methods to monitor Parkinson’s disease, BCN Peptides, S.A., for treatment studies of blepharospasm, and Medtronics, Inc., for studies of deep brain stimulation, via Clinical Trials Agreements (CTA) with NIH. Joseph Jankovic has received research funding from Allergan, Inc; Allon Therapeutics; Ceregene, Inc; Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation; EMD Serono; Huntington’s Disease Society of America; Huntington Study Group; Impax Pharmaceuticals; Ipsen Limited; Lundbeck Inc; Michael J Fox Foundation for Parkinson Research; Medtronic; Merz Pharmaceuticals; National Institutes of Health; National Parkinson Foundation; Neurogen; St. Jude Medical; Teva Pharmaceutical Industries Ltd; University of Rochester; Parkinson Study Group. During the past year Dr.
Jankovic has been compensated for his services as a consultant or an advisory committee member by Allergan, Inc; Auspex Pharmaceuticals, Inc; EMD Serono; Lundbeck Inc; Merz Pharmaceuticals; Michael J Fox Foundation for Parkinson Research; Neurocrine Biosciences; Neurotoxin Institute; Teva Pharmaceutical Industries Ltd. During the past year Dr. Jankovic has served on the following editorial boards: Medlink: Neurology; Expert Review of Neurotherapeutics, Neurology in Clinical Practice; Associate editor of The Botulinum Journal; Therapeutic Advances in Neurological Disorders; Neurotherapeutics; Tremor and Other Hyperkinetic Movements; Journal of Parkinson’s Disease; UpToDate. During the past year Dr.
Jankovic has received royalties from the following publishers: Elsevier and Wiley-Blackwell. Jorge Juncos has research support from Chelsea, Covance and the National Institutes of Health. Peter LeWitt has received lecture fees from Chelsea, Lundbeck, and Novartis, consulting fees from Depomed, ExpressScripts, Knopp Biosciences, Glaxo SmithKline, Impax, Intec, Ipsen, NeuroDerm, Merck, Noven Pharmaceuticals, Orient Pharma, Tercica, Teva, UCB, and XenoPort; and clinical research grant support (for clinical trials and other research) from Adamas, Addex, Biotie, Great Lakes Neurotechnologies, The Michael J.
Fox Foundation for Parkinson’s Research, Merz, Neurologix, and Novartis, Phytopharm, and UCB. He serves with compensation as editor-in-chief of Clinical Neuropharmacology and as an uncompensated editorial board member for Translational Neuroscience and Journal of Neural Transmission. Kelly Lyons has received consulting fees from St Jude Medical and Teva Neuroscience.
She has received royalties from Informa Healthcare and Oxford University Press. William Ondo has received speaker fees from GSK, Teva, Allergan, Ipsen, Lundbeck, Avanir, and Merz. Rajesh Pahwa received personal compensation from Teva Neuroscience, Merck Serono, Novartis, Medtronic, GE Healthcare, Impax, Ceregene, Noven, Adamas, St. Jude Medical for consulting.
Pahwa has received personal compensation from Informa Healthcare for being Co-Editor of the International Journal of Neuroscience. Pahwa has received research support as PI of clinical trials sponsored by Novartis, Impax, Merck Serono, BI, Schering, Adamas, Biotie, Phytopharm, Allon, Acadia, Xenoport, GlaxoSmithKline and NINDS. Kapil Sethi is a consultant for Abbott, Synosia and Veloxis. He has part time employment as a Senior Medical Expert Merz Pharmaceuticals. He is a speaker for Teva, Ipsen and Merz and receives research support from the National Institutes of Health, National Parkinson Foundation, Impax, Acadia, Synosia, Adamas, BI Pharmaceuticals, and Teva.
He has provided expert testimony for welding defense and metoclopramide litigation. He owns stock in Elan Pharma.
Natividad Stover receives research grant support from GSK, Allergan, NINDS, Biotie, EMD Serono, Impax Laboratories and Teva. Daniel Tarsy has received grant support from Phytopharm PLC and Michael J.
Fox, patient education grants from Allergan, UCB, Teva, and Ipsen, unrestricted grants for fellowship support from Allergan and Teva, personal compensation as a consultant for Neurocrine Biosciences and Genzyme, royalties from UpToDate and Springer, foundation support from National Parkinson Foundation, and honoraria from the Movement Disorders Society. Claudia Testa received research support from the Huntington Society of Canada (principal investigator), as well as the Tremor Research Group, HighQ Foundation, and Huntington Study Group (site principal investigator subcontracts). Huntington Study Group subcontract sponsors were NIH/NINDS or Medivation. She was a co-investigator on NIH/NCRR 2R24RR018827-05A1 and NIH/NIA P50 AG025688. She received Emory institutional support via NIH PHS UL1 RR025008 and NIH PHS M01-RR00039.
She received an honorarium from Virginia Commonwealth University, Department of Neurology. Ron Tintner received personal compensation from BI Pharmaceuticals for speaking, Allergan for speaking and Advisory Board, and Merz Pharmaceuticals for Advisory Board. Theresa Zesiewicz has received speaker fees from Teva, UCB Pharma, and General Electric. Watts has received honoraria for serving on the International Parkinson Disease Scientific Advisory Board of UCB Pharma. Author roles: 1) Research project: A. Conception, B.
Organization, C. Execution; 2) Statistical Analysis: A. Execution, C. Review and Critique; 3) Manuscript: A.
Writing of the first draft, B. Review and Critique. Contributor Information Rodger Elble, Southern Illinois University School of Medicine, Springfield IL. Cynthia Comella, Rush University Medical Center, Chicago IL. Stanley Fahn, Columbia University Medical Center, New York NY. Mark Hallett, National Institute of Neurological Disorders and Stroke, Bethesda MD. Joseph Jankovic, Baylor College of Medicine, Houston TX.
Juncos, Emory University, Atlanta GA. Peter LeWitt, Henry Ford Health Systems, Bloomfield MI. Kelly Lyons, University of Kansas Medical Center, Kansas City KS.
William Ondo, University of Texas Health Science Center, Houston TX. Rajesh Pahwa, University of Kansas Medical Center, Kansas City KS. Kapil Sethi, Georgia Health Sciences University, Augusta GA. Natividad Stover, University of Alabama at Birmingham, Birmingham, AL. Daniel Tarsy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA.
Claudia Testa, Virginia Commonwealth University, Richmond, VA. Ron Tintner, The Methodist Hospital, Houston TX. Ray Watts, University of Alabama at Birmingham, Birmingham, AL.
Theresa Zesiewicz, University of South Florida, Tampa FL.