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1.
Article in English | MEDLINE | ID: mdl-38708124

ABSTRACT

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales. Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™. Physician-reported measures (TETRAS Performance Item 4 and TETRAS ADL total) and patient-reported QoL measures (generic EuroQol-5 Dimension 5 Level [EQ-5D-5 L] and ET-specific Quality of Life in Essential Tremor Questionnaire (QUEST)) were assessed with bivariate and multivariable analyses. Sensitivity analyses were also conducted. Results: The bivariate association between TETRAS Performance Item 4 score and TETRAS ADL total score was high (Pearson r = 0.761, P < 0.001). The bivariate associations between TETRAS Performance Item 4 score and EQ-5D-5 L index score (r = -0.410, P < 0.001) and between TETRAS ADL total score and EQ-5D-5 L index score (r = -0.543, P < 0.001) were moderate. The bivariate associations between TETRAS Performance Item 4 score and QUEST total score (r = 0.457, P < 0.001), and between TETRAS ADL total score and QUEST total score (r = 0.630, P < 0.001) were also moderate. These associations were unaltered by the inclusion of covariates. Discussion: This study showed that greater tremor severity (TETRAS Performance Item 4) was positively correlated with ADL impairment (TETRAS ADL) and negatively associated with QoL (EQ-5D-5 L and QUEST). TETRAS Performance Item 4 score is a robust predictor of TETRAS ADL total score, and TETRAS Performance Item 4 and TETRAS ADL total scores were robust predictors of the 2 QoL scales. The results demonstrate the value of TETRAS scores as valid endpoints for future clinical trials. Highlights: This real-world study assessed TETRAS scores as predictors of impaired QoL in ET. TETRAS Performance Item 4 and ADL were associated with EQ-5D-5 L and QUEST. TETRAS scores may serve as valid endpoints for future clinical trials.


Subject(s)
Activities of Daily Living , Essential Tremor , Quality of Life , Humans , Essential Tremor/physiopathology , Essential Tremor/psychology , Female , Male , Cross-Sectional Studies , Aged , Middle Aged , Aged, 80 and over , Severity of Illness Index
2.
Article in English | MEDLINE | ID: mdl-38765931

ABSTRACT

Background: The Essential Tremor Rating Assessment Scale (TETRAS) is a popular scale for essential tremor (ET), but its activities of daily living (ADL) and performance (P) subscales are based on a structured interview and physical exam. No patient-reported outcome (PRO) scale for ET has been developed according to US regulatory guidelines. Objective: Develop and validate a TETRAS PRO subscale. Methods: Fourteen items, rated 0-4, were derived from TETRAS ADL and structured cognitive interviews of 18 ET patients. Convergent validity analyses of TETRAS PRO versus TETRAS ADL, TETRAS-P, and the Quality of Life in Essential Tremor Questionnaire (QUEST) were computed for 67 adults with ET or ET plus. Test-retest reliability was computed at intervals of 1 and 30 days. The influence of mood (Hospital Anxiety and Depression Scale, HADS) and coping behaviors (Essen Coping Questionnaire, ECQ) was examined with multiple linear regression. Results: TETRAS PRO was strongly correlated (r > 0.7) with TETRAS ADL, TETRAS-P, and QUEST and exhibited good to excellent reliability (Cronbach alpha 95%CI = 0.853-0.926; 30-day test-retest intraclass correlation 95%CI = 0.814-0.921). The 30-day estimate of minimum detectable change (MDC) was 6.6 (95%CI 5.2-8.0). TETRAS-P (rsemipartial = 0.607), HADS depression (rsemipartial = 0.384), and the coping strategy of information seeking and exchange of experiences (rsemipartial = 0.176) contributed statistically to TETRAS PRO in a multiple linear regression (R2 = 0.67). Conclusions: TETRAS PRO is a valid and reliable scale that is influenced strongly by tremor severity, moderately by mood (depression), and minimally by coping skills. The MDC for TETRAS PRO is probably sufficient to detect clinically important change.


Subject(s)
Activities of Daily Living , Essential Tremor , Patient Reported Outcome Measures , Humans , Essential Tremor/physiopathology , Essential Tremor/psychology , Essential Tremor/diagnosis , Female , Male , Middle Aged , Aged , Reproducibility of Results , Aged, 80 and over , Quality of Life , Adult , Surveys and Questionnaires
3.
Mov Disord ; 39(4): 733-738, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38357797

ABSTRACT

BACKGROUND: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABAA receptors. OBJECTIVE: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET). METHODS: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days. The primary endpoint was change from baseline in The Essential Tremor Rating Assessment Scale-Performance Subscale (TETRAS-PS) Item 4 (upper-limb tremor) at day 29 with SAGE-324/BIIB124 versus placebo. RESULTS: Between May 2020 and February 2021, 69 U.S. participants were randomly assigned to receive SAGE-324/BIIB124 (n = 34) or placebo (n = 35). There was a significant reduction from baseline in TETRAS-PS Item 4 at day 29 with SAGE-324/BIIB124 versus placebo (least squares mean [standard error]: -2.31 [0.401] vs. -1.24 [0.349], P = 0.0491). The most common treatment-emergent adverse events included somnolence, dizziness, fatigue, and balance disorder. CONCLUSION: These results support further development of SAGE-324/BIIB124 for potential ET treatment. © 2024 Sage Therapeutics, Inc and The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Essential Tremor , Humans , Essential Tremor/drug therapy , Male , Middle Aged , Female , Aged , Double-Blind Method , Adult , Aged, 80 and over , Young Adult , Adolescent , Treatment Outcome
4.
J Clin Neurol ; 18(2): 127-139, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35274833

ABSTRACT

Essential tremor (ET) plus is a new tremor classification that was introduced in 2018 by a task force of the International Parkinson and Movement Disorder Society. Patients with ET plus meet the criteria for ET but have one or more additional systemic or neurologic signs of uncertain significance or relevance to tremor ("soft signs"). Soft signs are not sufficient to diagnose another tremor syndrome or movement disorder, and soft signs in ET plus are known to have poor interrater reliability and low diagnostic sensitivity and specificity. Therefore, the clinical significance of ET plus must be interpreted probabilistically when judging whether a patient is more likely to have ET or a combined tremor syndrome, such as dystonic tremor. Such a probabilistic interpretation is possible with Bayesian analysis. This review presents a Bayesian analysis of ET plus in patients suspected of having ET versus a dystonic tremor syndrome, which is the most common differential diagnosis in patients referred for ET. Bayesian analysis of soft signs provides an estimate of the probability that a patient with possible ET is more likely to have an alternative diagnosis. ET plus is a distinct tremor classification and should not be viewed as a subtype of ET. ET plus covers a more-comprehensive phenotyping of people with possible ET, and the clinical interpretation of ET plus is enhanced with Bayesian analysis of associated soft signs.

5.
J Neurol Sci ; 435: 120202, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35220111

ABSTRACT

The purpose of this review is to characterize and compare validated clinical rating scales and transducers that are used in the clinical assessment of tremor disorders. Tremor is an involuntary oscillatory movement of a body part. Tremor can be characterized in terms of amplitude and frequency of oscillation, and these kinematic properties vary randomly and with activities of daily living. Clinical rating scales are most useful when performing a comprehensive assessment of tremor severity (amplitude), anatomical distribution, activation conditions, and impact on activities of daily living and quality of life. Motion transducers are often used in conjunction with surface electromyography to discern properties of tremor that are important diagnostically. Motion transducers are needed for an accurate determination of tremor frequency and for precise quantification of changes in amplitude and frequency over time. The precision and accuracy of motion transducers exceed that of all clinical rating scales. However, these advantages of transducers are mitigated by the considerable within-subject random variability in tremor amplitude, such that the smallest detectable statistically significant change in tremor amplitude is comparable for scales and transducers. Comprehensive anatomical and behavioral assessment of tremor with transducers is not clinically feasible. Transducers and scales are presently viewed as complementary methods of quantifying tremor amplitude. Transducer measures are logarithmically related to clinical ratings, as predicted by the Weber-Fechner law of psychophysics. This relationship must be considered when interpreting change in clinical ratings, produced by disease or treatment. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.


Subject(s)
Essential Tremor , Tremor , Activities of Daily Living , Biomechanical Phenomena , Humans , Quality of Life , Tremor/diagnosis
6.
Clin Neurophysiol ; 136: 93-129, 2022 04.
Article in English | MEDLINE | ID: mdl-35149267

ABSTRACT

The various forms of tremor are now classified in two axes: clinical characteristics (axis 1) and etiology (axis 2). Electrophysiology is an extension of the clinical exam. Electrophysiologic tests are diagnostic of physiologic tremor, primary orthostatic tremor, and functional tremor, but they are valuable in the clinical characterization of all forms of tremor. Electrophysiology will likely play an increasing role in axis 1 tremor classification because many features of tremor are not reliably assessed by clinical examination alone. In particular, electrophysiology may be needed to distinguish tremor from tremor mimics, assess tremor frequency, assess tremor rhythmicity or regularity, distinguish mechanical-reflex oscillation from central neurogenic oscillation, determine if tremors in different body parts, muscles, or brain regions are strongly correlated, document tremor suppression or entrainment by voluntary movements of contralateral body parts, and document the effects of voluntary movement on rest tremor. In addition, electrophysiologic brain mapping has been crucial in our understanding of tremor pathophysiology. The electrophysiologic methods of tremor analysis are reviewed in the context of physiologic tremor and pathologic tremors, with a focus on clinical characterization and pathophysiology. Electrophysiology is instrumental in elucidating tremor mechanisms, and the pathophysiology of the different forms of tremor is summarized in this review.


Subject(s)
Essential Tremor , Tremor , Brain , Brain Mapping/adverse effects , Essential Tremor/diagnosis , Humans
7.
Dystonia ; 12022.
Article in English | MEDLINE | ID: mdl-37101941

ABSTRACT

Introduction: A common view is that head tremor (HT) in cervical dystonia (CD) decreases when the head assumes an unopposed dystonic posture and increases when the head is held at midline. However, this has not been examined with objective measures in a large, multicenter cohort. Methods: For 80 participants with CD and HT, we analyzed videos from examination segments in which participants were instructed to 1) let their head drift to its most comfortable position (null point) and then 2) hold their head straight at midline. We used our previously developed Computational Motor Objective Rater (CMOR) to quantify changes in severity, amplitude, and frequency between the two postures. Results: Although up to 9% of participants had exacerbated HT in midline, across the whole cohort, paired t-tests reveal no significant changes in overall severity (t = -0.23, p = 0.81), amplitude (t = -0.80, p = 0.43), and frequency (t = 1.48, p = 0.14) between the two postures. Conclusions: When instructed to first let their head drift to its null point and then to hold their head straight at midline, most patient's changes in HT were below the thresholds one would expect from the sensitivity of clinical rating scales. Counter to common clinical impression, CMOR objectively showed that HT does not consistently increase at midline posture in comparison to the null posture.

8.
Front Neurol ; 11: 586606, 2020.
Article in English | MEDLINE | ID: mdl-33101188

ABSTRACT

A task force of the International Parkinson and Movement Disorder Society (MDS) recently published a tremor classification scheme that is based on the nosologic principle of two primary axes for classifying an illness: clinical manifestations (Axis 1) and etiology (Axis 2). An Axis 1 clinical syndrome is a recurring group of clinical symptoms, signs (physical findings), and possibly laboratory results that suggests the presence of at least one underlying Axis 2 etiology. Syndromes must be defined and used consistently to be of value in finding specific etiologies and effective treatments. The MDS task force concluded that essential tremor is a common neurological syndrome that has never been defined consistently by clinicians and researchers. The MDS task force defined essential tremor as a syndrome of bilateral upper limb action tremor of at least 3 years duration, with or without tremor in other locations (e.g., head, voice, or lower limbs), in the absence of other neurological signs (e.g., dystonia, parkinsonism, myoclonus, ataxia, peripheral neuropathy, and cognitive impairment). Deviations from this definition should not be labeled as essential tremor. Patients with additional questionably-abnormal signs or with signs of uncertain relevance to tremor are classified as essential tremor plus. The MDS classification scheme encourages a thorough unbiased phenotyping of patients with tremor, with no assumptions of etiology, pathology, pathophysiology, or relationship to other neurological disorders. The etiologies, pathology, and clinical course of essential tremor are too heterogeneous for this syndrome to be viewed as a disease or a family of diseases.

9.
Mov Disord ; 35(10): 1796-1801, 2020 10.
Article in English | MEDLINE | ID: mdl-32562441

ABSTRACT

BACKGROUND: Limited tools are available for the assessment of orthostatic tremor severity and disability. OBJECTIVES: To develop and validate a self-administered orthostatic tremor scale. METHODS: After expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews. Clinimetric evaluations included assessing content validity, internal consistency, measurement error and reliability, construct validity, and concurrent validity anchored on the examiner's Clinical Global Impression score. RESULTS: Eleven items ranked on a Likert scale from 0 (no disability/severity) to 5 (maximal disability/severity) were evaluated in 54 orthostatic tremor patients (16 men and 38 women; mean age: 69.17 ± 9.64 years; disease duration: 13.83 ± 11.24 years) to probe severity and disability over the preceding 1-week period. The 11-item scale showed good internal consistency (Cronbach's alpha = 0.863) and acceptable (>0.40) item-to-total correlation. However, one item was removed at the final Delphi panel because of significant floor effect, poor item-to-total correlation, and poor factor-loading, leaving the scale with 10 items (10-item Orthostatic Tremor Severity and Disability Scale). Test-retest reliability at 2 weeks was excellent (two-way random intraclass correlation coefficient > 0.90), and the individual item test-retest reliability showed good agreement, with a threshold weighted kappa >0.60 for all items. Exploratory factor analyses revealed a parsimonious two-factor construct accounting for 57.7% of the scale's variance. The 10-item Orthostatic Tremor Severity and Disability Scale scores correlated with the CGI. CONCLUSIONS: The self-administered 10-item Orthostatic Tremor Severity and Disability Scale scale is valid and reliable for capturing orthostatic tremor-related severity and disability. © 2020 International Parkinson and Movement Disorder Society.


Subject(s)
Disability Evaluation , Tremor , Aged , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Psychometrics , Reproducibility of Results , Surveys and Questionnaires , Tremor/diagnosis
10.
Mov Disord Clin Pract ; 7(4): 399-404, 2020 May.
Article in English | MEDLINE | ID: mdl-32373656

ABSTRACT

BACKGROUND: Perampanel is a noncompetitive antagonist of alpha-amino-3-hydroxy-5-methylisoxazole propionic acid glutamate receptors suggested to modulate tremor. OBJECTIVES: To assess the efficacy and tolerability of perampanel for essential tremor. METHODS: This was a double-blind, placebo-controlled, randomized, cross-over trial involving 26 patients titrated to 8 mg/day or a lower maximally tolerated dose as monotherapy or adjunct to antitremor medication. Tremor was assessed at the beginning and end of each 14-week treatment arm. The primary endpoint was change in the videotaped performance subscale of The Essential Tremor Rating Assessment Scale, scored by a blinded rater. Secondary endpoints included change in The Essential Tremor Rating Assessment Scale Activity of Daily Living and Quality of Life in Essential Tremor and Subject Global Impression of Change subscales. RESULTS: Data are available for 15 and 11 participants who completed placebo and perampanel arms, respectively. Perampanel was superior to placebo on the primary endpoint (P = 0.028), Activity of Daily Living (P = 0.009), and Subject Global Impression of Change (P = 0.016), but not Quality of Life (p = 0.48). Video scores were rated >50% improved in 3/11 on perampanel and 0/15 on placebo. Adverse events were more likely on perampanel (especially at >4 mg/day) than on placebo, leading to withdrawal (36% vs. 10%) and dose reduction (41% vs. 15%). Adverse events more common with perampanel included imbalance/falls (50% vs. 10%), dizziness (36% vs. 10%), and irritability (27% vs. 5%). CONCLUSIONS: These findings suggest that perampanel exerts efficacy for some persons with essential tremor, but this population appears prone to adverse events.

11.
Cerebellum Ataxias ; 7: 3, 2020.
Article in English | MEDLINE | ID: mdl-32082592

ABSTRACT

BACKGROUND: The syndrome of oculopalatal tremor is a known consequence of lesions in the dentate-olivary pathway. Hypertrophic degeneration of the inferior olive is a recognized pathological correlate of these lesions and hypothesized to cause tremorogenic olivary hypersynchrony. However, oculopalatal tremor also occurs in Alexander disease, which produces severe inferior olive degeneration without intervening hypertrophy. METHODS: Serial clinical, imaging, video-oculography and kinematic tremor recording of a patient with oculopalatal and limb tremor. CASE STUDY: We report an unusual presentation of oculopalatal tremor and right upper extremity myorhythmia following sequential right dorsolateral and left anteromedial medullary infarcts directly involving both inferior olives. As in adult Alexander disease, our patient did not have hypertrophic olivary degeneration during 10 years of follow-up. CONCLUSION: Contemporary theories have emphasized the role of cerebellar maladaptation in "shaping" oscillations generated elsewhere, the inferior olive in particular. Our patient and published Alexander disease cases illustrate that oculopalatal tremor can occur in the absence of hypertrophic olivary degeneration. Therefore, cerebellar maladaptation to any form of olivary damage may be the critical pathophysiology in producing oculopalatal tremor.

13.
Cerebellum ; 18(6): 1036-1063, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31124049

ABSTRACT

Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied. To overcome these obstacles, animal models can provide an important means to look into human tremor disorders. In this manuscript, we will discuss the use of different species of animals (mice, rats, fruit flies, pigs, and monkeys) to model human tremor disorders. Several ways to manipulate the brain circuitry and physiology in these animal models (pharmacology, genetics, and lesioning) will also be discussed. Finally, we will discuss how these animal models can help us to gain knowledge of the pathophysiology of human tremor disorders, which could serve as a platform towards developing novel therapies for tremor.


Subject(s)
Brain/diagnostic imaging , Consensus , Expert Testimony , Models, Animal , Nerve Net/diagnostic imaging , Tremor/diagnostic imaging , Animals , Brain/physiopathology , Drosophila , Expert Testimony/standards , Haplorhini , Mice , Nerve Net/physiopathology , Rats , Swine , Tremor/physiopathology
14.
Expert Rev Neurother ; 18(4): 303-321, 2018 04.
Article in English | MEDLINE | ID: mdl-29475371

ABSTRACT

INTRODUCTION: Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishing severe tremor that is refractory to available pharmacotherapies. Surgical methods are raspidly improving and are the subject of this review. Areas covered: A PubMed search on 18 January 2018 using the query essential tremor AND surgery produced 839 abstracts. 379 papers were selected for review of the methods, efficacy, safety and expense of stereotactic deep brain stimulation (DBS), stereotactic radiosurgery (SRS), focused ultrasound (FUS) ablation, and radiofrequency ablation of the cerebellothalamocortical pathway. Expert commentary: DBS and SRS, FUS and radiofrequency ablations are capable of reducing upper extremity tremor by more than 80% and are far more effective than any available drug. The main research questions at this time are: 1) the relative safety, efficacy, and expense of DBS, SRS, and FUS performed unilaterally and bilaterally; 2) the relative safety and efficacy of thalamic versus subthalamic targeting; 3) the relative safety and efficacy of atlas-based versus direct imaging tractography-based anatomical targeting; and 4) the need for intraoperative microelectrode recordings and macroelectrode stimulation in awake patients to identify the optimum anatomical target. Randomized controlled trials are needed.


Subject(s)
Deep Brain Stimulation/methods , Essential Tremor/surgery , High-Intensity Focused Ultrasound Ablation/methods , Neurosurgical Procedures/methods , Radiofrequency Ablation/methods , Radiosurgery/methods , Humans
15.
Article in English | MEDLINE | ID: mdl-31637097

ABSTRACT

Tremor rating scales are the standard method for assessing tremor severity and clinical change due to treatment or disease progression. However, ratings and their changes are difficult to interpret without knowing the relationship between ratings and tremor amplitude (displacement or angular rotation), and the computation of percentage change in ratings relative to baseline is misleading because of the ordinal nature of these scales. For example, a reduction in tremor from rating 2 to rating 1 (0-4 scale) should not be interpreted as a 50% reduction in tremor amplitude, nor should a reduction in rating 4 to rating 3 be interpreted as a 25% reduction in tremor. Studies from several laboratories have found a logarithmic relationship between tremor ratings R and tremor amplitude T, measured with a motion transducer: logT  =  α·R + ß, where α ≈ 0.5, ß ≈ -2, and log is base 10. This relationship is consistent with the Weber-Fechner law of psychophysics, and from this equation, the fractional change in tremor amplitude for a given change in clinical ratings is derived: (Tf-Ti)/Ti=10α(Rf-(Ri)-1, where the subscripts i and f refer to the initial and final values. For a 0-4 scale and α  =  0.5, a 1-point reduction in tremor ratings is roughly a 68% reduction in tremor amplitude, regardless of the baseline tremor rating (e.g., 2 or 4). Similarly, a 2-point reduction is roughly a 90% reduction in tremor amplitude. These Weber-Fechner equations should be used in clinical trials for computing and interpreting change in tremor, assessed with clinical ratings.


Subject(s)
Clinical Trials as Topic/standards , Outcome Assessment, Health Care/standards , Psychophysics/standards , Severity of Illness Index , Tremor/diagnosis , Tremor/physiopathology , Humans
16.
Mov Disord ; 33(1): 75-87, 2018 01.
Article in English | MEDLINE | ID: mdl-29193359

ABSTRACT

BACKGROUND: Consensus criteria for classifying tremor disorders were published by the International Parkinson and Movement Disorder Society in 1998. Subsequent advances with regard to essential tremor, tremor associated with dystonia, and other monosymptomatic and indeterminate tremors make a significant revision necessary. OBJECTIVES: Convene an international panel of experienced investigators to review the definition and classification of tremor. METHODS: Computerized MEDLINE searches in January 2013 and 2015 were conducted using a combination of text words and MeSH terms: "tremor", "tremor disorders", "essential tremor", "dystonic tremor", and "classification" limited to human studies. Agreement was obtained using consensus development methodology during four in-person meetings, two teleconferences, and numerous manuscript reviews. RESULTS: Tremor is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: Axis 1-clinical characteristics, including historical features (age at onset, family history, and temporal evolution), tremor characteristics (body distribution, activation condition), associated signs (systemic, neurological), and laboratory tests (electrophysiology, imaging); and Axis 2-etiology (acquired, genetic, or idiopathic). Tremor syndromes, consisting of either isolated tremor or tremor combined with other clinical features, are defined within Axis 1. This classification scheme retains the currently accepted tremor syndromes, including essential tremor, and provides a framework for defining new syndromes. CONCLUSIONS: This approach should be particularly useful in elucidating isolated tremor syndromes and syndromes consisting of tremor and other signs of uncertain significance. Consistently defined Axis 1 syndromes are needed to facilitate the elucidation of specific etiologies in Axis 2. © 2017 International Parkinson and Movement Disorder Society.


Subject(s)
Consensus , International Cooperation , Societies, Medical/standards , Tremor/classification , Tremor/diagnosis , Humans , MEDLINE/statistics & numerical data
17.
J Clin Mov Disord ; 4: 15, 2017.
Article in English | MEDLINE | ID: mdl-29051824

ABSTRACT

BACKGROUND: Pure akinesia with gait freezing is a rare syndrome with few autopsied cases. Severe freezing of gait occurs in the absence of bradykinesia and rigidity. Most autopsies have revealed progressive supranuclear palsy. We report the clinical and postmortem findings of two patients with pure akinesia with gait freezing, provide video recordings of these patients, and review the literature describing similar cases. We also discuss bradykinesia, hypokinesia and akinesia in the context of this clinical syndrome. CASE PRESENTATION: Two patients with the syndrome of pure akinesia with gait freezing were examined by the same movement disorder specialist at least annually for 9 and 18 years. Both patients initially exhibited freezing, tachyphemia, micrographia and festination without bradykinesia and rigidity. Both autopsies revealed characteristic tau pathology of progressive supranuclear palsy, with nearly total neuronal loss and gliosis in the subthalamus and severe neuronal loss and gliosis in the globus pallidus and substantia nigra. Previously published postmortem studies revealed that most patients with this syndrome had progressive supranuclear palsy or pallidonigroluysian atrophy. CONCLUSIONS: Pallidonigroluysian degeneration produces freezing and festination in the absence of generalized slowing (bradykinesia). Freezing and festination are commonly regarded as features of akinesia. Akinesia literally means absence of movement, and akinesia is commonly viewed as an extreme of bradykinesia. The pure akinesia with gait freezing phenotype illustrates that bradykinesia and akinesia should be viewed as separate phenomena.

18.
Article in English | MEDLINE | ID: mdl-28966878

ABSTRACT

BACKGROUND: Drawing Archimedes spirals is a popular and valid method of assessing action tremor in the upper limbs. We performed the first blinded comparison of Fahn-Tolosa-Marín (FTM) ratings and tablet measures of essential tremor to determine if a digitizing tablet is better than 0-4 ratings in detecting changes in essential tremor that exceed random variability in tremor amplitude. METHODS: The large and small spirals of FTM were drawn with each hand on two consecutive days by 14 men and four women (age 60±8.7 years [mean±SD]) with mild to severe essential tremor. The drawings were simultaneously digitized with a digitizing tablet. Tremor in each digitized drawing was computed with spectral analysis in an independent laboratory, blinded to the clinical ratings. The mean peak-to-peak tremor displacement (cm) in the four spirals and mean FTM ratings were compared statistically. RESULTS: Test-retest intraclass correlations (ICCs) (two-way random single measures, absolute agreement) were excellent for the FTM ratings (ICC 0.90, 95% CI 0.76-0.96) and tablet (ICC 0.97, 95% CI 0.91-0.99). Log10 tremor amplitude (T) and FTM were strongly correlated (logT=αFTM + ß, α≈0.6, ß≈-1.27, r=0.94). The minimum detectable change for the tablet and FTM were 51% and 67% of the initial assessment. DISCUSSION: Digitizing tablets are much more precise than clinical ratings, but this advantage is mitigated by the natural variability in tremor. Nevertheless, the digitizing tablet is a robust method of quantifying tremor that can be used in lieu of or in combination with clinical ratings.


Subject(s)
Computers, Handheld , Diagnosis, Computer-Assisted , Essential Tremor/diagnosis , Motor Skills , Double-Blind Method , Essential Tremor/physiopathology , Female , Humans , Linear Models , Male , Middle Aged , Reproducibility of Results
20.
Mov Disord Clin Pract ; 4(2): 205-211, 2017.
Article in English | MEDLINE | ID: mdl-30363428

ABSTRACT

BACKGROUND: Accelerometers and gyroscopes are used commonly in the assessment of hand tremor, but their validity in the assessment of head tremor has not been studied. We hypothesized that gyroscopy would be superior to accelerometry because head tremor is rotational motion, and gyroscopes record rotational motion, free of gravitational artifact. We also hypothesized a strong logarithmic relationship between 0 to 4-point tremor ratings and the transducer measures of tremor amplitude, similar to those previously reported for hand tremor. METHODS: Head tremor was recorded for 1 minute in each of the five head positions used in the Essential Tremor Rating Assessment Scale, using a triaxial accelerometer and triaxial gyroscope mounted at the vertex of the head. Mean and maximum 3-second burst displacement tremor and rotation tremor were computed by spectral analysis. The minimum detectable change for the transducers was estimated using the residual mean squared error from repeated-measures analysis of variance. RESULTS: Tremor displacement and rotation (T) were logarithmically related to tremor ratings (tremor rating score; TRS): log(T) = α TRS + ß, where α ≈ 0.47 for displacement and ≈0.64 for rotation, and ß ≈ -1.8 and -1.4. Tremor ratings correlated more strongly with gyroscopy (r = 0.83-0.87) than with accelerometry (r = 0.71-0.75). Minimum detectable change (percent reduction) was approximately 66% of the baseline geometric mean. CONCLUSIONS: Gyroscopic transducers are superior to accelerometry for assessment of head tremor. Both measures of head tremor are logarithmically related to tremor ratings. The minimum detectable change of the transducer measures is comparable to those previously reported for hand tremor.

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