Comparison of the Fahn-Tolosa-Marin Clinical Rating Scale and the Essential Tremor Rating Assessment Scale.

BACKGROUND: The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) has been used in large trials for essential tremor (ET), but its anchors for ratings from 0 to 4 of upper limb tremor are probably too low for patients with severe tremor (tremor amplitude >4 cm; grade 4). The Essential Tremor Rating Assessment Scale (TETRAS) is a validated clinical scale designed specifically for the assessment of ET severity. TETRAS has anchors that span a larger range of tremor amplitudes (>20 cm = grade 4), making it more suitable for assessing patients with severe ET. However, there is no direct comparison of these scales in any clinical trial. METHODS: Upper limb postural and kinetic tremor items from both scales were compared using blinded, video-recorded examinations of patients with moderate-to-severe ET who participated in a trial of focused ultrasound thalamotomy. RESULTS: FTM ratings of postural and kinetic tremor correlated strongly with those of TETRAS. However, FTM exhibited a ceiling effect for severe tremor. Rest tremor, exclusive to FTM, correlated poorly with postural and kinetic tremor and had very poor test-retest reliability. In contrast, wing-beating postural tremor, exclusive to TETRAS, exhibited excellent test-retest reliability and a strong correlation with kinetic and limbs-extended-forward postural tremor. Test-retest reliabilities of the other TETRAS and FTM ratings were excellent, and both scales had good sensitivity to treatment effect. CONCLUSIONS: TETRAS has 2 main advantages over FTM in the assessment of tremor severity: (1) the absence of a ceiling effect in patients with severe ET, and (2) the inclusion of wing-beating tremor.

Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson's Disease: A Pilot Randomized Controlled Trial.

OBJECTIVES: To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson's disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. DESIGN: Two-arm, wait-list controlled RCT. SETTINGS: Tertiary care hospital. SUBJECTS: Thirty-two subjects aged 40-75 diagnosed with idiopathic PD within 10 years. INTERVENTIONS: Six-month TC intervention added to usual care (UC) versus UC alone. OUTCOME MEASURES: Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson's Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. RESULTS: Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [-0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. CONCLUSIONS: Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.

Clinical Impact of 123I-Ioflupane SPECT (DaTscan) in a Movement Disorder Center.

BACKGROUND/AIMS: The clinical diagnosis of degenerative forms of parkinsonism is imperfect, with past studies reporting a high rate of misdiagnosis by neurologists and movement disorder specialists, particularly early in the disease course. 123I-ioflupane SPECT (DaTscan) is a diagnostic neuroimaging tool used to distinguish essential tremor from tremor due to degenerative parkinsonisms. The present study expands upon prior studies of the clinical impact of DaTscan imaging in movement disorder centers by assessing quantitative estimates of diagnostic certainty, the impact on subsequent clinical decisions, and the degree to which the asymmetry in the results corresponds to laterality by clinical history and examination. METHODS: In a prospective, observational study of the impact of DaTscan imaging in a movement disorder center over the course of 18 months, 4 specialists completed a questionnaire at the time they ordered imaging and again within 1 month after imaging. RESULTS: Twenty-seven patients underwent DaTscan imaging; the result was normal in 4 cases (14.8%), abnormal in 22 cases (81.4%), and equivocal in 1 case (3.7%). In all cases of a normal result, the post-scan-predicted chance of degenerative parkinsonism decreased compared to the pre-scan prediction (p < 0.05), and in all cases of abnormal scan, the post-scan chance of degenerative parkinsonism increased or remained high (p < 0.0001). Clinical impacts were observed following imaging in a total of 24 patients (88.9%), including changes in medications for 18 patients and psychological impacts for 11 patients. Asymmetric clinical symptoms were corroborated based on the expected asymmetry of dopamine uptake deficits in 57.1% of the cases, were not present in 23.8%, and were opposite of expectations in 19.0% of the scans. CONCLUSION: DaTscan imaging results have an impact on physician's confidence in the diagnosis of parkinsonism and may also have a psychological impact on patients. DaTscan imaging may be a useful adjunct to clinical history and examination in selected patients.

Drooling in Parkinson's disease: A randomized controlled trial of incobotulinum toxin A and meta-analysis of Botulinum toxins.

INTRODUCTION: Botulinum toxins are a therapeutic option for drooling in Parkinson's Disease (PD). The aims of this study were to: 1. evaluate the efficacy of incobotulinum toxin A for drooling in PD. 2. Perform a meta-analysis of studies of Botulinum toxins for drooling in PD. METHODS: 1. Primary study: Randomized, double blind, placebo controlled, cross over trial. Incobotulinum toxin (100 units) or saline was injected into the parotid (20 units) and submandibular (30 units) glands. Subjects returned monthly for three evaluations after each injection. Outcome measures were saliva weight and Drooling Frequency and Severity Scale. 2. Systematic review of literature, followed by inverse variance meta-analyses using random effects models. RESULTS: 1. Primary Study: Nine of 10 subjects completed both arms. There was no significant change in the primary outcome of saliva weight one month after injection in the treatment period compared to placebo period (mean difference, gm ± SD: -0.194 ± 0.61, range: -1.28 to 0.97, 95% CI -0.71 to 0.32). Secondary outcomes also did not change. 2. Meta-analysis of six studies demonstrated significant benefit of Botulinum toxin on functional outcomes (effect size, Cohen's d: -1.32, CI -1.86 to -0.78). The other studies used a higher dose of Botulinum toxin A into the parotid glands. CONCLUSIONS: This study did not demonstrate efficacy of incobotulinum toxin A for drooling in PD, but lacked precision to exclude moderate benefit. The parotid/submandibular dose-ratio may have influenced results. Studies evaluating higher doses of incobotulinum toxin A into the parotid glands may be useful.

Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action Tremor.

BACKGROUND: Resting tremor is common in Parkinson's disease (PD), but up to 47% of PD patients have action tremor, which is sometimes resistant to medications. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus or subthalamic nucleus (STN) is effective for medication-refractory tremor in PD, though it remains unclear whether STN DBS is as effective as VIM DBS for postural/action tremor related to PD. METHODS: We carried out a single-center retrospective review of patients with medication-refractory resting, postural, and action PD tremor, treated with either VIM or STN DBS between August 2004 and March 2014. We assessed the degree of improvement using items 20 and 21 of the Unified Parkinson's Disease Rating Scale (UPDRS) motor scale and examined the proportion of patients achieving tremor arrest. RESULTS: A total of 18 patients were analyzed, 10 treated with STN and eight treated with VIM, with similar off-medication motor UPDRS scores. There was no significant difference in improvement in tremor scores or in the proportion of patients experiencing tremor arrest between the two stimulation sites. Overall, 56% and 72% of patients experienced complete absence of postural/action tremor and resting tremor, respectively, at last follow-up. DISCUSSION: This study demonstrated excellent outcomes on both resting and postural/action tremor after either VIM or STN DBS. Resting tremor improved to a greater degree than postural/action tremor in both groups. These results suggest that a large randomized controlled trial is needed to show a superior effect of one target on PD tremor.

Phonemic verbal fluency decline after subthalamic nucleus deep brain stimulation does not depend on number of microelectrode recordings or lead tip placement.

BACKGROUND: Evidence suggests that both motor improvement and decline in verbal fluency in Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) may be attributed to a lead implantation effect. OBJECTIVE: We investigated whether the number of microelectrode recording (MER) passes influenced either motor UPDRS scores just prior to stimulation initiation at 4 weeks or decline in verbal fluency 6-24 months after surgery. METHODS: We retrospectively analyzed 50 PD patients who underwent bilateral STN DBS. Off medication UPDRS III motor scores were obtained before surgery and before stimulation was initiated. Neuropsychological testing was completed pre- and post-operatively in 28 patients at a mean of 377 days. Coordinates of lead tip and active stimulation site were calculated. RESULTS: There was no improvement in off-medication UPDRS III motor scores at a mean 33.9 days following surgery, with mean change of 0.04 ± 10.48 (p = 0.98). There was no correlation between the number of MER passes and change in individual UPDRS motor score (r = -0.0001, p = 1.0). We observed significant decline in phonemic verbal fluency by 16% (p = 0.003) but it was not correlated with number of left hemisphere (r = -0.15, p = 0.46), or total number of passes (r = -0.02, p = 0.94) or coordinates of the lead tip or active stimulation site. There was a trend toward correlation with age (r = 0.38, p = 0.07). CONCLUSIONS: Significant decline in phonemic verbal fluency did not correlate with surgical passes nor with location of the lead tip or active stimulation site. These data suggest that age may influence verbal fluency decline more than surgical technique.

The current state and needs of north american movement disorders fellowship programs.

Background. Movement disorders fellowships are an important source of future clinician-specialists and clinician-scientists for the field. Scant published information exists on the number and characteristics of North American movement disorders fellowship training programs. Methods. A 31-item internet-based survey was formulated and distributed to academic movement disorders listed in the American Academy of Neurology (AAN) directory as having a movement disorders fellowship and to all National Parkinson Foundation Centers of Excellence and Care Centers in North America. Results. There was a 77% response rate among academic movement disorders centers. Broad similarities in clinical training were identified. The two most important rated missions of maintaining a movement disorders fellowship were contributions to scholarly activities and to fulfilling a critical need for specialists. Almost a quarter of fellowship programs did not offer a fellowship slot during the most recent academic year. Fellowship directors cited a wide variety of funding sources, but their top concern was lack of available funding for fellowship programs. Conclusions. North American movement disorders fellowship training programs currently offer similar methods of clinical training and education. Lack of funding was the most important obstacle to maintaining fellowship programs and should be made a priority for discussion in the field.

Initial treatment of Parkinson's disease: an update.

OPINION STATEMENT: This is an update to an article published in this journal in 2006, which covered the initial treatment of Parkinson's disease (PD). In this update, we review new research into symptomatic treatments, potential disease modifying ("neuroprotective") agents, and evidence-based reviews of current treatment. We discuss the usage of the MAO-B inhibitors, including the controversy surrounding the possible neuroprotective effects of rasagiline. Usage of extended release formulations of pramipexole and ropinirole, as well as the transdermal dopamine agonist rotigotine, are reviewed. Side effects of the dopamine agonists are discussed, including the cardiac side effects of ergot-derived dopamine agonists, and the impulse control disorders associated with the dopamine agonists. The use of zonisamide as an agent for PD tremor is reviewed. We touch on the clinical research into the benefits of exercise in PD, and briefly review some of the current studies for new formulations of levodopa and other medications and treatments with novel mechanisms of action.

Loss of benefit in VIM thalamic deep brain stimulation (DBS) for essential tremor (ET): how prevalent is it?

Ventralis intermedius (Vim) thalamic deep brain stimulation for medication-refractory essential tremor (ET) has been shown to significantly improve severity of limb tremor in several large case series with significant reduction in objective motor scores. A variable proportion of patients experience decline in benefit over time, however, most studies have not been designed to describe the phenomenon of waning benefit in terms that are helpful for patient counseling. In this retrospective single center study, we define waning benefit as a phenomenon that occurs after patients begin to require reprogramming visits to optimize DBS benefit on tremor. We employed a survival analysis with time to escape (TTE) as a quantitative measure of time elapsed between implantation and the need for subsequent reprogramming. In our cohort of ET patients operated on with Vim DBS from 1994 to 2009, among 45 subjects who met inclusion criteria, 73% reported waning benefit at some point during a mean follow-up period of 56 months (range 12-152 months). The mean TTE from implantation date was 18 months (range 3-75 months). We conclude that loss of benefit over time from Vim DBS for ET is more prevalent than previously published estimates have indicated and should be discussed during patient counseling regarding durability of expected benefit. In addition, this data suggests that a disease-based explanation rather than technical factors are more likely to explain the decline in benefit.

Reliability of a new scale for essential tremor.

BACKGROUND: The objective of this study was to determine the reliability of a new scale for the clinical assessment of essential tremor. The Essential Tremor Rating Assessment Scale contains 9 performance items that rate action tremor in the head, face, voice, limbs, and trunk from 0 to 4 in half-point intervals. Head and limb tremor ratings are defined by specific amplitude ranges in centimeters. METHODS: Videos of 44 patients and 6 controls were rated by 10 specialists on 2 occasions 1-2 months apart. Inter- and intrarater reliability was assessed with a 2-way random-effects intraclass correlation, using an absolute agreement definition. RESULTS: Inter- and intrarater intraclass correlations for head and upper-limb tremor ranged from 0.86 to 0.96, and intraclass correlations for total score were 0.94 and 0.96. The intraclass correlations for voice, face, trunk, and leg were less robust. CONCLUSIONS: This scale is an exceptionally reliable tool for the clinical assessment of essential tremor.

Psychogenic facial movement disorders: clinical features and associated conditions.

The facial phenotype of psychogenic movement disorders has not been fully characterized. Seven tertiary-referral movement disorders centers using a standardized data collection on a computerized database performed a retrospective chart review of psychogenic movement disorders involving the face. Patients with organic forms of facial dystonia or any medical or neurological disorder known to affect facial muscles were excluded. Sixty-one patients fulfilled the inclusion criteria for psychogenic facial movement disorders (91.8% females; age: 37.0 ± 11.3 years). Phasic or tonic muscular spasms resembling dystonia were documented in all patients most commonly involving the lips (60.7%), followed by eyelids (50.8%), perinasal region (16.4%), and forehead (9.8%). The most common pattern consisted of tonic, sustained, lateral, and/or downward protrusion of one side of the lower lip with ipsilateral jaw deviation (84.3%). Ipsi- or contralateral blepharospasm and excessive platysma contraction occurred in isolation or combined with fixed lip dystonia (60.7%). Spasms were reported as painful in 24.6% of cases. Symptom onset was abrupt in most cases (80.3%), with at least 1 precipitating psychological stress or trauma identified in 57.4%. Associated body regions involved included upper limbs (29.5%), neck (16.4%), lower limbs (16.4%), and trunk (4.9%). There were fluctuations in severity and spontaneous exacerbations and remissions (60%). Prevalent comorbidities included depression (38.0%) and tension headache (26.4%). Fixed jaw and/or lip deviation is a characteristic pattern of psychogenic facial movement disorders, occurring in isolation or in combination with other psychogenic movement disorders or other psychogenic features.

Treatment of Parkinson disease: a 64-year-old man with motor complications of advanced Parkinson disease.

In early stages, Parkinson disease typically begins with asymmetric or unilateral motor symptoms due to combinations of mild bradykinesia, rigidity, and tremor. In most cases, with progression, signs of more generalized bradykinesia appear, which include facial masking, reduced voice volume, and slowing of activities of daily living. In more advanced Parkinson disease, other disabling manifestations may follow, such as impaired balance, gait freezing, falls, speech disturbance, and cognitive impairment. Levodopa is the most effective medical treatment for Parkinson disease. However, motor complications uniquely related to levodopa treatment may emerge that may be difficult to manage. These include fluctuating levodopa responses and involuntary movements and postures known as dyskinesia and dystonia. Medication adjustments are usually effective, but in some cases surgical intervention with deep brain stimulation becomes necessary to alleviate motor complications. The case of Mr L, a man with an 11-year history of Parkinson disease, illustrates these emerging motor complications and the manner in which they may be managed both medically and surgically.

Singing in groups for Parkinson's disease (SING-PD): a pilot study of group singing therapy for PD-related voice/speech disorders.

Parkinson's disease related speech and voice impairment have significant impact on quality of life measures. LSVT(®)LOUD voice and speech therapy (Lee Silverman Voice Therapy) has demonstrated scientific efficacy and clinical effectiveness, but musically based voice and speech therapy has been underexplored as a potentially useful method of rehabilitation. We undertook a pilot, open-label study of a group-based singing intervention, consisting of twelve 90-min weekly sessions led by a voice and speech therapist/singing instructor. The primary outcome measure of vocal loudness as measured by sound pressure level (SPL) at 50 cm during connected speech was not significantly different one week after the intervention or at 13 weeks after the intervention. A number of secondary measures reflecting pitch range, phonation time and maximum loudness also were unchanged. Voice related quality of life (VRQOL) and voice handicap index (VHI) also were unchanged. This study suggests that a group singing therapy intervention at this intensity and frequency does not result in significant improvement in objective and subject-rated measures of voice and speech impairment.

Survey of U.S. neurologists' attitudes towards deep brain stimulation for Parkinson's disease.

OBJECTIVES: Deep brain stimulation (DBS) for Parkinson's disease (PD) was approved by the Food and Drug Administration in 2002 and has demonstrated clinical benefit in advanced PD. Our aim was to assess attitudes of U.S. neurologists towards the role of DBS in management of advanced PD. MATERIALS AND METHODS: We sent a 40-item Internet-based survey assessing opinions regarding the role of medical and surgical therapies in managing PD to 7722 neurologists in the American Medical Association Physician MasterFile data base. RESULTS: The response rate was low (4.2%). In total, 78 of the 298 (26%) responders self-identified as movement disorders specialists. Specialists and non-specialists had differences on a number of medical strategies used to manage PD. There were no statistically significant differences in reasons for or against referring patients for DBS, except for the number of non-specialists who agreed with referring a patient who had a "poor or absent response to levodopa" (71% vs. 16%, p < 0.001). Both groups indicated a need for more information concerning appropriate indications for DBS, adverse effects of surgery, and postoperative programming. CONCLUSIONS: Movement disorders specialists and non-specialists were in general agreement towards the beneficial role of DBS in management of advanced PD except for whether to refer patients with poor or absent response to levodopa.

Sustained dyskinesias following elective cessation and reactivation of chronic subthalamic nucleus deep brain stimulation for a surgical procedure.

OBJECTIVES: Subthalamic nucleus deep brain stimulation (STN DBS) is effective for treatment of levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Medical or surgical procedures requiring electrocautery may require inactivation of the pulse generators to avoid damage to the lead or extension wire or possible reprogramming of the stimulators. This generally causes only mild and temporary disability. We report a patient with previously well-controlled dyskinesias who had severe and prolonged dyskinesias following reactivation of deep brain stimulation (DBS) following an orthopedic procedure. MATERIALS AND METHODS: Retrospective chart review. RESULTS: The patient underwent two orthopedic procedures, each requiring inactivation of DBS. After reactivation of DBS, the patient experienced severe dyskinesias that ultimately required sedation and ventilation to control large-amplitude dyskinesias. CONCLUSIONS: Clinicians caring for PD patients treated with STN DBS should be aware of the possible reappearance of severe dyskinesias arising from routine inactivation and reactivation of pulse generators for medical or surgical procedures.