Rodger J. Elble

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results

We present a clinimetric assessment of the Movement Disorder Society (MDS)‐sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS‐UPDRS). The MDS‐UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS‐UPDRS has four parts, namely, I: Non‐motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item‐specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS‐UPDRS (65 items) to 877 English speaking (78% non‐Latino Caucasian) patients with Parkinsons disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS‐UPDRS showed high internal consistency (Cronbachs alpha = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS‐UPDRS for rating PD.

CENTRAL MECHANISMS OF TREMOR

Physiologic and pathologic tremors are mechanistically classified into two broad groups: (1) those produced by oscillation in sensorimotor loops, so-called mechanical-reflex tremors, and (2) those produced by the oscillatory properties of central neuronal networks. This review provides a contemporary perspective of tremor pathophysiology while acknowledging that no form of tremor is understood completely. Indeed, the origin of oscillation in most forms of tremor is undefined, and in many instances the underlying pathology is unknown.

Practice Parameter: Therapies for essential tremor Report of the Quality Standards Subcommittee of the American Academy of Neurology

Background: Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. Methods: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August 2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. Results and Conclusions: Propranolol and primidone reduce limb tremor (Level A). Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective in reducing limb tremor (Level B). Limited studies suggest that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness, hoarseness, and swallowing difficulties may occur in the treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure carries a small risk of major complications. Some adverse events from DBS may resolve with time or with adjustment of stimulator settings. There is insufficient evidence regarding the surgical treatment of head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional prospective, double-blind, placebo-controlled trials are needed to better determine the efficacy and side effects of pharmacologic and surgical treatments of ET.

Stride-dependent changes in gait of older people.

SummaryInfrared computerized stroboscopic photometry was used to measure the kinematic profile of walking of 20 young adults and 20 neurologically healthy elderly people. Compared with the young adults, the elderly exhibited 17–20% reductions in the velocity of gait and length of stride. The elderly also exhibited comparable reductions in the maximum toe-floor clearance, arm swing, and rotations of the hips and knees, but these alterations in gait were attributable to the reduction in stride length, which may have non-neurological causes. The influence of reduced gait velocity and stride length on the other characteristics of walking must be considered when evaluating the pattern of walking in elderly people.

Physiologic and essential tremor

We studied physiologic and essential hand tremor using inertial loading; hand acceleration and forearm EMG data were analyzed by auto- and cross-spectral analysis. Early essential tremor was qualitatively similar to the 8- to 12-Hz component of physiologic tremor, suggesting that this tremor component is a forme fruste of essential tremor. Advanced essential tremor had a frequency of 4 to 8 Hz. Patients with tremor frequencies in both ranges were observed in each of 10 families. In antagonistic forearm muscles, both synchronous and alternating tremor bursts were observed in 11 of 44 patients. Essential tremor should not be classified solely on the basis of frequency or EMG pattern.

Treatment of patients with essential tremor

Essential tremor is a common movement disorder. Tremor severity and handicap vary widely, but most patients with essential tremor do not receive a diagnosis and hence are never treated. Furthermore, many patients abandon treatment because of side-effects or poor efficacy. A newly developed algorithm, based on the logarithmic relation between tremor amplitude and clinical tremor ratings, can be used to compare the magnitude of effect of available treatments. Drugs with established efficacy (propranolol and primidone) produce a mean tremor reduction of about 50%. Deep brain stimulation (DBS) in the thalamic nucleus ventrointermedius or neighbouring subthalamic structures reduces tremor by about 90%. However, no controlled trials of DBS have been done, and the best target is still uncertain. Better drugs are needed, and controlled trials are required to determine the safety and efficacy of DBS in the nucleus ventrointermedius and neighbouring subthalamic structures.

Essential tremor — Neurodegenerative or nondegenerative disease towards a working definition of ET

Essential tremor (ET) is a syndrome of tremor in posture and movement, but recent studies have revealed additional cerebellar motor disturbances, cognitive disturbances, personality changes, hearing loss, and olfactory deficits. Even dementia and shortened life expectancy were found in one cohort. Recent postmortem studies have found limited Lewy body pathology in some patients and Purkinje cell loss with torpedoes and Bergmann gliosis in others. These findings have led to the hypothesis that ET is a syndrome produced by at least two neurodegenerative diseases with more widespread clinical consequences than previously appreciated. We review the evidence for and against this hypothesis and conclude that studies purporting to support this hypothesis have failed to control for age‐associated comorbidities, depression, medications, and other confounding factors. We propose the alternative hypothesis that abnormal neuronal oscillation is the fundamental abnormality in ET, and the well‐documented cerebellar signs and symptoms, the controversial non‐motor signs, and even the cerebellar pathology of ET could be caused by this oscillation. A major problem for many studies is the lack of a diagnostic gold standard. Lacking such a standard, we propose a subclassification of ET into three categories: hereditary ET, sporadic ET, and senile ET, which we believe will help researchers resolve many of the controversies in this field.

Assessment of interrater and intrarater reliability of the Fahn–Tolosa–Marin Tremor Rating Scale in essential tremor

The purpose of this study was to evaluate interrater and intrarater reliability of the Fahn–Tolosa–Marin Tremor Rating Scale (TRS) in essential tremor (ET). Proper treatment of ET is contingent upon correct assessment of the severity, loss of function, and disability related to tremor. Videotape recordings of 17 subjects with ET evaluated with the TRS were produced and sent to 59 raters. Once the raters returned the videotape and completed the score sheet, they were mailed a second tape with the same recordings presented in a different order. In the interrater reliability evaluation, modified Kappa statistics for seven tremor type composites ranged from 0.10 to 0.65 in the first videotape and 0.17 to 0.62 in the second videotape. Interrater reliabilities were greater for Part A items (magnitude of tremor in different body parts) than for Part B items (tremor in writing and drawings) of the TRS. The average Spearman correlation was 0.87, indicating very good consistency between the two videotapes, but correlations for Part A were somewhat better than for Part B. It is best when the same rater performs repeated measures of tremor on a patient, particularly when judging tremor in handwriting and drawings. Training of raters on use of the TRS would help standardize judgement.

Evidence-based guideline update: Treatment of essential tremor Report of the Quality Standards Subcommittee of the American Academy of Neurology

Background: This evidence-based guideline is an update of the 2005 American Academy of Neurology practice parameter on the treatment of essential tremor (ET). Methods: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 2004 and April 2010. Results and Recommendations: Conclusions and recommendations for the use of propranolol, primidone (Level A, established as effective); alprazolam, atenolol, gabapentin (monotherapy), sotalol, topiramate (Level B, probably effective); nadolol, nimodipine, clonazepam, botulinum toxin A, deep brain stimulation, thalamotomy (Level C, possibly effective); and gamma knife thalamotomy (Level U, insufficient evidence) are unchanged from the previous guideline. Changes to conclusions and recommendations from the previous guideline include the following: 1) levetiracetam and 3,4-diaminopyridine probably do not reduce limb tremor in ET and should not be considered (Level B); 2) flunarizine possibly has no effect in treating limb tremor in ET and may not be considered (Level C); and 3) there is insufficient evidence to support or refute the use of pregabalin, zonisamide, or clozapine as treatment for ET (Level U).

Topiramate in essential tremor A double-blind, placebo-controlled trial

Background: Essential tremor is most prevalent and most disabling in older patients. Additional therapies are required for patients with an inadequate response or intolerable side effects. In small trials, topiramate appeared to be beneficial in essential tremor. Methods: In this multicenter, double-blind, placebo-controlled, parallel-design trial, patients with moderate to severe essential tremor of the upper limbs were randomized to 24 weeks of treatment with placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct to one antitremor medication. The primary efficacy variable was the final visit tremor score based on the Fahn–Tolosa–Marin Tremor Rating Scale (TRS). Results: The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100). The final visit score (last observation carried forward) was lower in the topiramate group than with placebo (p < 0.001). Mean percentage improvement in overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and 16% with placebo (p < 0.001). Topiramate was associated with greater improvement in function and disability (p = 0.001). A between-group difference (p < 0.001) was observed at the first on-treatment visit at 4 weeks when the target topiramate dose was 100 mg/day (mean achieved dose, 62 ± 9 mg/day). The most common treatment-limiting adverse events in topiramate-treated patients were paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate patients and 9.5% of placebo patients. Conclusions: Topiramate was effective in the treatment of moderate to severe essential tremor. Tremor reduction was accompanied by functional improvements, such as in motor tasks, writing, and speaking.