French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

Automatic Resting Tremor Assessment in Parkinson's Disease Using Smartwatches and Multitask Convolutional Neural Networks.

Resting tremor in Parkinson's disease (PD) is one of the most distinctive motor symptoms. Appropriate symptom monitoring can help to improve management and medical treatments and improve the patients' quality of life. Currently, tremor is evaluated by physical examinations during clinical appointments; however, this method could be subjective and does not represent the full spectrum of the symptom in the patients' daily lives. In recent years, sensor-based systems have been used to obtain objective information about the disease. However, most of these systems require the use of multiple devices, which makes it difficult to use them in an ambulatory setting. This paper presents a novel approach to evaluate the amplitude and constancy of resting tremor using triaxial accelerometers from consumer smartwatches and multitask classification models. These approaches are used to develop a system for an automated and accurate symptom assessment without interfering with the patients' daily lives. Results show a high agreement between the amplitude and constancy measurements obtained from the smartwatch in comparison with those obtained in a clinical assessment. This indicates that consumer smartwatches in combination with multitask convolutional neural networks are suitable for providing accurate and relevant information about tremor in patients in the early stages of the disease, which can contribute to the improvement of PD clinical evaluation, early detection of the disease, and continuous monitoring.

Automatic detection and quantification of hand movements toward development of an objective assessment of tremor and bradykinesia in Parkinson's disease.

BACKGROUND: Classification of parkinsonian symptoms, including tremor and bradykinesia, require the application of validated clinical rating scales which are inherently subjective. In this study, we assessed an objective measure of parkinsonian symptomology using automated analysis of hand gestures. NEW METHOD: We constructed and evaluated a hand and finger motion capture apparatus and analysis pipeline that recorded hand/finger motion of control subjects and patients with Parkinson's disease. The detailed three-dimensional (3D) motion features of each finger joint was extracted by using Discrete Wavelet Transform (DWT). The severity of tremor for each finger joint was quantitated by analyzing the motion changes in the frequency domain on four types of motion from five patients and twenty-two control subjects. RESULTS: The proposed approach could distinguish the behavior of patients with Parkinson's disease and control subjects by analyzing the detailed motion features of their hands/fingers. COMPARISON WITH EXISTING METHODS: Previously established methods to quantitate finger movement dynamics focus on speed and amplitude. In contrast, our approach measures unsupervised motion features, in real-time, using wavelet analysis, of each individual finger joint during active free movement. CONCLUSIONS: The proposed study provides an objective assessment of tremor and bradykinesia in Parkinson's disease. Accordingly, this may help movement disorder clinicians to detect, diagnose and monitor treatment efficacy in Parkinson's disease.

Quantitative assessment of Parkinsonian tremor by using biosensor device.

Parkinson disease (PD) is the second most common neurodegenerative disease which affects population older than 65 years. Tremor represents one of the main symptomatic triads in PD, particularly in rest state.We enrolled 41 idiopathic PD patients, to validate the assessment of tremor symptoms.To be enrolled in the study, patients had to fulfill the movement disorder society clinical diagnostic criteria for PD.We used an innovative home-made, low-cost device, able to quantify the frequency and amplitude of rest tremor and stress conditionOur results confirmed the presence of tremor during muscular effort in a significant number of patients and the influence of emotional stress.We suppose that this new device should be validated in clinical practice as a support of differential diagnosis and therapeutic management of PD patients.

A digital assessment system for evaluating kinetic tremor in essential tremor and Parkinson's disease.

BACKGROUND: Spiral drawing on papers is a common tremor evaluation tool for diagnosing patients with essential tremor (ET) or Parkinson's disease (PD). No standard drawing methods and parameters that use graphic tablets are yet available for objective evaluation. METHODS: This study established a tremor assessment system for tremor severity by using graphic tablets. Twelve patients with ET and twelve patients with PD were tested to establish system algorithms, and six additional patients were tested with the developed system to evaluate its performance. The patients also performed spiral drawing with three guiding paradigms on a graphic tablet: traced along a given spiral (S1), performed freehand drawing (S2), and traced along a guiding point (S3). Three parameters were calculated to quantify tremor severity: the means of radial difference per radian (|dr/dθ|), the means of radial difference per second (|dr/dt|), and the area under curve (AUC) of the frequency spectrum of the velocity. Each patient's drawing was also evaluated using a visual rating scale (VRS) by experienced physicians. The interrater reliability was examined to identify the most consistent test paradigm. RESULTS: The parameter |dr/dθ| and AUC correlated well with the VRS (R > 0.8) in S1, S2 and S3 tests. The S1 test presented the best interrater reliability (Weighted Kappa coefficient, k = 0.80) among three tests. The Weighted Kappa coefficients are 0.67 and 0.71 in S2 and S3 tests, respectively. CONCLUSIONS: We developed three different guiding paradigms for spiral drawing on a digital graphic tablet for clinical tests. Three parameters were calculated to represent the tremor severity in spiral drawing and used to quantify temporal and spatial characteristics of tremor, and provided good correlation with current clinical assessments. The test "traced along a given spiral" is recommended due to its good interrater reliability.

Tremor Frequency Assessment by iPhone® Applications: Correlation with EMG Analysis.

Tremor frequency analysis is usually performed by EMG studies but accelerometers are progressively being more used. The iPhone® contains an accelerometer and many applications claim to be capable of measuring tremor frequency. We tested three applications in twenty-two patients with a diagnosis of PD, ET and Holmes' tremor. EMG needle assessment as well as accelerometry was performed at the same time. There was very strong correlation (Pearson >0.8, p < 0.001) between the three applications, the EMG needle and the accelerometry. Our data suggests the apps LiftPulse®, iSeismometer® and Studymytremor® are a reliable alternative to the EMG for tremor frequency assessment.

Hilbert-Huang transform based instrumental assessment of intention tremor in multiple sclerosis.

OBJECTIVE: This paper describes a method to extract upper limb intention tremor from gyroscope data, through the Hilbert-Huang transform (HHT), a technique suitable for the study of nonlinear and non-stationary processes. The aims of the study were to: (i) evaluate the method's ability to discriminate between healthy controls and MS subjects; (ii) validate the proposed procedure against clinical tremor scores assigned using Fahn's tremor rating scale (FTRS); and (iii) compare the performance of the HHT-based method with that of linear band-pass filters. APPROACH: HHT was applied on gyroscope data collected on 20 MS subjects and 13 healthy controls (CO) during finger-to-nose tests (FNTs) instrumented with an inertial sensor placed on the hand. The results were compared to those obtained after traditional linear filtering. The tremor amplitude was quantified with instrumental indexes (TIs) and clinical FTRS ratings. MAIN RESULTS: The TIs computed after HHT-based filtering discriminated between CO and MS subjects with clinically-detected intention tremor (MS_T). In particular, TIs were significantly higher in the final part of the movement (TI2) with respect to the first part (TI1), and, for all components (X, Y, Z), MS_T showed a TI2 significantly higher than in CO subjects. Moreover, the HHT detected subtle alterations not visible from clinical ratings, as TI2 (Z-component) was significantly increased in MS subjects without clinically-detected tremor (MS_NT). The method's validity was demonstrated by significant correlations between clinical FTRS scores and TI2 related to X (rs = 0.587, p = 0.006) and Y (rs = 0.682, p < 0.001) components. Contrarily, fewer differences among the groups and no correlation between instrumental and clinical indexes emerged after traditional filtering. SIGNIFICANCE: The present results supported the use of the HHT-based procedure for a fully-automated quantitative and objective measure of intention tremor in MS, which can overcome the limitations of clinical scales and provide supplementary information about this sign.

Determinants of delayed diagnosis in Parkinson's disease.

The early and accurate diagnosis of Parkinson's disease (PD) is the first step towards optimal patient management. The aim of this study was to investigate the major determinants of delayed diagnosis in PD. We recruited a population-representative cohort of 239 newly-diagnosed PD patients who underwent clinical and neuropsychological evaluation. Non-parametric methods were used to define the factors associated with diagnostic delay. The median time from motor symptom onset to primary care physician (PCP) presentation was considerably longer than the time from PCP presentation to PD diagnosis (11 vs. 1 months). Male sex and presenting motor phenotype were independently associated with delayed PCP presentation on Cox regression analysis. Patients presenting with gait disturbance experienced the longest delay, whilst those presenting with tremor had the shortest. In summary, male sex and presenting motor phenotype are key determinants of delayed diagnosis in PD.

Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications.

Assessment of mitochondrial respiratory chain function in hyperphenylalaninaemia.

Phenylketonuria (PKU) is an autosomal recessive disorder resulting in neurological and intellectual disability when untreated. However, even in treated patients there may be residual neurological impairment such as tremor. It has been suggested that the hyperphenylalaninaemia in patients with PKU reduces complex I (NADH:ubiquinone reductase) activity of the mitochondrial respiratory chain (MRC) and/or biosynthesis of coenzyme Q(10) (CoQ(10)), which acts as an electron carrier in the MRC, leading to impaired energy metabolism in the brain of patients with PKU and hence the neurological pathology. The aim of this study was to elucidate the mechanism of phenylalanine (Phe) toxicity on the MRC. We compared mean plasma and blood-spot Phe and mononuclear CoQ(10) levels in 17 patients with PKU and a tremor compared to 22 patients without tremor. Human 1321N1 astrocytoma cells were exposed to hyperphenylalaninaemia by the addition of 300 or 900 micromol/L of Phe to the cell culture medium. Following 96 h of culture we measured complex I and citrate synthase activities and CoQ(10) level. Results showed no significant difference in Phe or CoQ(10) levels in patients with tremor compared to those without tremor. Further, hyperphenylalaninaemia did not cause a significant reduction in complex I activity or CoQ(10) biosynthesis, even when taking into account the mitochondrial enrichment of the cell samples by expressing complex I and CoQ(10) as a ratio to citrate synthase. In conclusion, the results of this study suggest that hyperphenylalaninaemia does not contribute to the pathophysiology of PKU by causing a decrease in MRC complex I activity and/or CoQ(10) biosynthesis.

Clinically deployable Kinesia technology for automated tremor assessment.

The objective was to design, build, and assess Kinesia, a wireless system for automated assessment of Parkinson's disease (PD) tremor. The current standard in evaluating PD is the Unified Parkinson's Disease Rating Scale (UPDRS), a qualitative ranking system typically completed during an office visit. Kinesia integrates accelerometers and gyroscopes in a compact patient-worn unit to capture kinematic movement disorder features. Objectively quantifying PD manifestations with increased time resolution should aid in evaluating efficacy of treatment protocols and improve patient management. In this study, PD subjects performed the tremor subset of the UPDRS motor section while wearing Kinesia. Quantitative kinematic features were processed and highly correlated to clinician scores for rest tremor (r(2) = 0.89), postural tremor (r(2) = 0.90), and kinetic tremor (r(2) = 0.69). The quantitative features were used to develop a mathematical model that predicted tremor severity scores for new data with low errors. Finally, PD subjects indicated high clinical acceptance.

Assessment of rest tremor in Parkinson's disease.

BACKGROUND AND PURPOSE: Rest tremor is the most frequent sign of Parkinson's disease (PD) after bradykinesia, occurring with various severity in about 75% of patients. An objective assessment of rest tremor is difficult. The aim of the study was to analyze rest tremor in PD with the three-dimensional gauging system CMS 10; more specifically, the impact of levodopa treatment on rest tremor, the influence of clinical factors, and the correlation between rest tremor and clinical scales were assessed. MATERIAL AND METHODS: Ninety-five patients with PD (mean age 67.6 years) and 30 healthy people in a control group (mean age 59.3 years) were examined. Clinical scales (UPDRS, Hoehn and Yahr, Schwab and England, as well as Webster scale) were used to assess severity of PD. The assessment of rest tremor was performed within the more and less affected upper limb with the three-dimensional gauging system CMS 10 (Zebris GmbH) before and 1-2 hours after levodopa intake. Frequency (Hz), amplitude (deg), velocity (deg/ms) and acceleration (deg/s2) of the tremor were evaluated. Results were compared with averaged results for left and right upper limb in the control group. RESULTS: The method used in this study objectively showed asymmetry in rest tremor. After levodopa intake, all evaluated parameters of rest tremor were decreased (mainly the amplitude and frequency, and to a lesser degree, velocity and acceleration). The motor part of UPDRS showed the best correlation with rest tremor. CONCLUSIONS: The three-dimensional measuring system CMS 10 is useful in the objective assessment of rest tremor in PD. Rest tremor in PD is under the influence of PD form, the intake of levodopa dose, the amount of levodopa, gender and level of education.

A novel computer-based technique for the assessment of tremor in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease and the diagnosis of its idiopathic form remains challenging. The diagnosis of idiopathic form is based on clinical features which can have poor sensitivity with about 25% of patients diagnosed as having the disease actually having other conditions. In this study we assess the suitability and clinical value of a low cost computer-based system as an aid to diagnosis of PD, in particular the presence of tremor. All participants (12 patients and 10 controls) performed a shape-tracing task using a graphic tablet attached to a laptop. To assess the presence of tremors in the collected data, a statistical spectral analysis of the moment-to-moment fluctuations in the position signal of the output from the digitising tablet was performed. This allowed the comparison of power spectrums obtained from the control and patient responses respectively. A peak in log power between the 5 Hz & 6 Hz can clearly be identified in the patient's spectrum and is indicative of Parkinson's related tremor and no similar peak could be seen in the control's spectrum, suggesting this type of sequential task and automated data analysis may be useful in the diagnosis of tremor.

Pramipexole in the treatment of Parkinson's disease: new developments.

The nonergot dopamine agonist pramipexole is an efficient and safe drug for the treatment of Parkinson's disease. Clinicians may favor pramipexole over other dopamine agonists because of its suggested higher tolerability with respect to peripheral dopaminergic side effects. Importantly, nonergot dopamine agonists such as pramipexole may not cause restrictive valvular heart disease and may therefore represent the first choice in patients with valvular lesions under treatment with ergot dopamine agonists. However, particular caution has to be exercised in younger Parkinson's disease patients with a shorter disease duration regarding the occurrence of sudden onset of sleep. In light of cost-effectiveness and quality-of-life issues, its final significance for the initial treatment of patients with early Parkinson's disease remains to be determined.

A portable hand-held device for quantifying and standardizing tremor assessment.

We describe the results of a hand-held device for quantifying tremor in the upper extremity. The specific aims of the study were to evaluate: (1) the reliability of the device to record tremor frequency and amplitude; (2) the relationship between observer ratings of tremor severity and spectral power derived from the instrument; (3) the effects of limb posture on tremor properties recorded by the instrument; and (4) whether scores from the instrument can discriminate types of tremor with sufficient accuracy to be of diagnostic value. Results from 242 subjects with tremor showed significant effects of limb posture on tremor frequency detected by the device which could not be revealed using traditional observer severity ratings. Subjects with tremor associated with idiopathic Parkinson's disease were distinguished from patients with drug-induced parkinsonian tremor with 83% accuracy. These and other findings on instrument validity demonstrate that tremor assessment can be performed using standard quantitative procedures which overcome many of the limitations inherent in subjective observer ratings. The portability of this instrument, referred to as the Tremorometer, makes it a useful tool for multi-site collaborative studies in community settings.

Motor signs during the course of Alzheimer disease.

BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. OBJECTIVE: To describe the progression and identify predictors of individual MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

Costs of thalamic deep brain stimulation for movement disorders in patients with multiple sclerosis.

Several studies have shown that thalamic deep brain stimulation (DBS) reduces tremor and improves hand performance in patients with multiple sclerosis (MS). The purpose of this paper is to describe the cost implications of DBS in MS patients and to highlight postoperative medical requirements that can be associated with this therapy. In a prospective study of thalamic DBS in MS patients the mean equipment costs were pounds 4769 (median pounds 7010, Medtronic, 1998 prices); mean neurosurgical inpatient costs per operated patient (n = 15) were pounds 4848 (range pounds 1982-8920, median pounds 5110); and mean in-patient postoperative rehabilitation cost pounds 4602 (range pounds 0-32,225, median pounds 1783). In addition there were transport and follow up costs. Mean neurosurgical inpatient stay following stereotactic DBS implantation was 15 days (median 12 days); and mean inpatient, postoperative rehabilitation stay 54 days (median 25 days). Although there were significant improvements in hand function and tremor reduction at 12 months postoperation, the level of patient performance in activities of daily living, their perception of their handicap and ipse facto the amount of home support required were unchanged from preoperative levels. This study has highlighted significant unforeseen medical requirements and costs that can occur in MS patients who have thalamic DBS surgery.

HIV-related movement disorders: epidemiology, pathogenesis and management.

Clinically relevant movement disorders are identified in 3% of patients with HIV infection seen at tertiary referral centres. In the same setting, prospective follow-up shows that 50% of patients with AIDS develop tremor, parkinsonism or other extrapyramidal features. Hemiballism-hemichorea and tremor are the most common hyperkinesias seen in patients who are HIV positive, but other movement disorders diagnosed in these patients include dystonia, chorea, myoclonus, tics, paroxysmal dyskinesias and parkinsonism. Patients with movement disorders usually present with other clinical features such as peripheral neuropathy, seizures, myelopathy and dementia. In the vast majority of patients, hyperkinesias result from lesions caused by opportunistic infections, particularly toxoplasmosis, which damage the basal ganglia connections. On the other hand, parkinsonism and tremor can result from dopaminergic dysfunction resulting from HIV itself or the use of antidopaminergic drugs. The management of patients who are HIV positive who present with movement disorders involves recognition and treatment of opportunistic infections, symptomatic treatment of the movement disorder and the use of highly active antiretroviral therapy (HAART). The most effective treatment of cerebral toxoplasmosis in patients with HIV infection is the combination of sulfadiazine and pyrimethamine. Symptomatic treatment of the movement disorder is often disappointing: hemiballism improves with antipsychotics, but tremor, parkinsonism and other phenomena usually fail to respond to available therapies. Preliminary data suggest that HAART may be helpful in the symptomatic control as well as prevention of movement disorders in patients who are HIV positive.

A cross-over clinical and electromyographic assessment of treatment for parkinsonian tremor.

BACKGROUND: Whether dopaminergic and anticholinergic drugs exert influence on parkinsonian rest and postural tremor is a subject of debate. Different types of tremor may be influenced differently by the drugs. The aim of this study was to reevaluate the differential effects of levodopa and anticholinergic drugs on parkinsonian tremor in different limb positions and on different types of postural tremor. METHODS: Thirty-eight patients with parkinsonian resting tremor and postural tremor were included in this study. Patients were divided into two groups according to the electromyographic pattern of the postural tremor. We found fast synchronous postural tremor (>7 Hz) in 16 patients, and slow alternating postural tremor in 22 patients. The tremor was scored clinically in each limb position using the Webster Tremor Scale. Surface electromyographic recordings from the most involved limb in all positions were also performed. The patients were randomly assigned to levodopa (one 250/50-mg tablet), or to biperiden (one 3-mg tablet). Tremor was assessed by clinical and electromyographic examinations at base line 1h following ingestion of the drug. The subjective tremor improvement was also assessed. RESULTS: We found that levodopa had a good effect on the amplitude of the resting tremor, while the effect of biperiden was weaker. Both levodopa and biperiden has less effect on postural tremor. However, levodopa's effect was better than that of biperiden. Levodopa and biperiden had better effect on slow alternating postural tremor than on fast synchronous postural tremor. They had no effect on kinetic and intention tremors. CONCLUSIONS: Levodopa and anticholinergic drugs have differing effects on both resting and postural tremor Also, the different categories of postural tremor respond differently to treatment. The mechanisms underlying resting parkinsonian tremor may be different from those underlying postural, kinetic and intention tremor. Moreover, the mechanisms underlying different types of postural tremor may be different.