Qiping Yu

Correlates of functional disability in essential tremor

The decision to treat patients with essential tremor (ET) is based primarily on the functional impact of the tremor. Correlates of functional disability, apart from the severity of the tremor itself, have not been studied. The objective of this work was to study correlates of functional disability in ET, and to present data on the extent of functional disability in community‐dwelling ET cases.

Operative techniques and morbidity with subthalamic nucleus deep brain stimulation in 100 consecutive patients with advanced Parkinson’s disease

Objective: Subthalamic nucleus (STN) stimulation for patients with medically refractory Parkinson disease (PD) is expanding. Reported experience has provided some indication of techniques, efficacy, and morbidity, but few centres have reported more than 50 patients. To expand this knowledge, we reviewed our experience with a large series of consecutive patients. Methods: From March 1999 to September 2003, 191 subthalamic stimulator devices (19 unilateral) were implanted in 100 patients with PD at New York Presbyterian Hospital/Columbia University Medical Center. Sixteen patients had undergone a prior surgery for PD (pallidotomy, thalamotomy, or fetal transplant). Microelectrode guided implantations were performed using techniques similar to those described previously. Electrode implantation occurred 1–2 weeks before outpatient pulse generator implantation. Results: Reductions of dyskinesias and off severity/duration were similar to prior published reports. Morbidity included: 7 device infections (3.7%), 1 cerebral infarct, 1 intracerebral haematoma, 1 subdural haematoma, 1 air embolism, 2 wound haematomas requiring drainage (1.0%), 2 skin erosions over implanted hardware (1.0%), 3 periprocedural seizures (1.6%), 6 brain electrode revisions (3.1%), postoperative confusion in 13 patients (6.8%), and 16 battery failures (8.4%). Of the 100 patients, there were no surgical deaths or permanent new neurological deficits. The average hospital stay for all 100 patients was 3.1 days. Conclusion: Subthalamic stimulator implantation in a large consecutive series of patients with PD produced significant clinical improvement without mortality or major neurological morbidity. Morbidity primarily involved device infections and hardware/wound revisions.

Subthalamic nucleus stimulation in advanced Parkinson’s disease: blinded assessments at one year follow up

Objective: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson’s disease. Design: Open label follow up using blinded ratings of videotaped neurological examinations. Patients: 30 patients with advanced Parkinson’s disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. Main outcome measures: Unified Parkinson’s disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. Results: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the “on” and “off” states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%. Conclusions: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.

Validity of spiral analysis in early Parkinson's disease

Spiral analysis is an objective, easy to administer noninvasive test that has been proposed to measure motor dysfunction in Parkinson disease (PD). We compared overall Unified Parkinson Disease Rating Scale Part III scores to selected indices derived from spiral analysis in seventy‐four patients with early PD (mean duration of disease 2.4 ± 1.7 years, mean age 61.5 ± 9.7 years). Of the spiral indices, degree of severity, first order zero crossing, second order smoothness, and mean speed were best correlated with total motor Unified Parkinsons Disease Rating Scale (UPDRS) score (all P < 0.01), and these indices showed a gradient across worsening tertiles of UPDRS (P < 0.05). Spiral indices also correlated with UPDRS ratings for the worst side and worst arm scores as well. The domains of bradykinesia, rigidity, and action tremor were correlated with first order crossing, second order smoothness, and mean speed, where as rest tremor was most highly correlated with degree of severity. This suggests that the spiral analysis may supplement motor assessment in PD, although further analysis of spiral metrics, a larger sample and longitudinal data should be evaluated.

Transcranial magnetic stimulation in ALS: Utility of central motor conduction tests

Objective: To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS). Methods: We prospectively studied 60 patients with ALS subtypes (sporadic ALS, familial ALS, progressive muscular atrophy, and primary lateral sclerosis) using single pulse TMS, recording from abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. We evaluated three measures: 1) TMS motor response threshold to the ADM, 2) central motor conduction time (CMCT), and 3) motor evoked potential amplitude (correcting for peripheral changes). Patients were evaluated at baseline, compared with controls, and followed every 3 months for up to six visits. Changes were analyzed using generalized estimation equations to test linear trends with time. Results: TMS threshold, CMCT, and TMS amplitude correlated (p < 0.05) with clinical upper motor neuron (UMN) signs at baseline and were different (p < 0.05) from normal controls in at least one response. Seventy-eight percent of patients with UMN (41/52) and 50% (4/8) of patients without clinical UMN signs had prolonged CMCT. All three measures revealed significant deterioration over time: TMS amplitude showed the greatest change, decreasing 8% per month; threshold increased 1.8% per month; and CMCT increased by 0.9% per month. Conclusions: Transcranial magnetic stimulation (TMS) findings, particularly TMS amplitude, can objectively discriminate corticospinal tract involvement in amyotrophic lateral sclerosis (ALS) from controls and assess the progression of ALS. While central motor conduction time and response threshold worsen by less than 2% per month, TMS amplitude decrease averages 8% per month, and may be a useful objective marker of disease progression.

Stereotactic posteroventral pallidotomy: Clinical methods and results at 1-year follow up

Twenty consecutive patients with idiopathic Parkinsons disease underwent stereotactic posteroventral pallidotomy. Schwab and England ADL scores in the “off” state were improved by 18% and in the “on” state the scores declined by 2%. Three patients also reported marked improvement in “off” state dystonia. One‐year data are available on 12 patients who underwent evaluations according to the Core Assessment Program for Intracerebral Transplantation protocol preoperatively and at 3, 6, and 12 months after surgery. Significant improvements in Unified Parkinsons Disease Rating Scale sections II and III scores in the “off” state, composite “off” state scores of bradykinesia and rigidity, contralateral tremor in the “off” state, and contralateral dyskinesias were observed. Although there was reduction in the daily levodopa dose, this did not reach statistical significance. Major complications (15%) included hemiparesis (one of 20) and visual field cuts (two of 20); minor complications (45%) included mild cognitive dysfunction (four of 20), reading difficulty not related to visual disturbance (one of 20), and 5–10 lb weight gain (four of 20).

Validation of a portable instrument for assessing tremor severity in epidemiologic field studies.

An important part of epidemiologic and genetic studies of essential tremor (ET) is an assessment of tremor severity. Clinical rating scales are semiquantitative and computerized tremor analysis, available at tertiary medical centers, is not transportable into the field. As part of an epidemiologic study, we modified the Klove‐Matthews Motor Steadiness Battery, collecting objective quantitative data on tremor severity in patients with ET and control subjects.

Clinical and neurophysiological improvement of SGCE myoclonus–dystonia with GPi deep brain stimulation

Myoclonus-dystonia (M-D) is characterized by early onset myoclonus and dystonia. It is thought to be subcortical in origin. Response to oral medications may be incomplete, such that deep brain stimulation (DBS) surgery to the globus pallidum interna (GPi) or ventral intermediate thalamic nucleus (VIM) may be considered. The optimal site is not known. The physiology and surgical response for a 63-year-old woman who underwent GPi DBS for M-D with onset at age 2 and related to a mutation in the epsilon-sarcoglycan gene (SGCE) is described. She showed excellent clinical and neurophysiological improvement of both myoclonus and dystonia, suggesting that modulation by DBS is effective even after long disease duration and only partial response to oral medications.

Digitized spiral analysis is a promising early motor marker for Parkinson Disease

Clinical trials of Parkinson disease (PD) are shaped by the sensitivity of the metrics used to measure dysfunction. While sequential Unified Parkinson Disease Rating Scale (UPDRS) motor scores reflect disease progression [1], objective quantitative motor assessments may be more sensitive in detecting early disease and may supplement the UPDRS. Spiral analysis is a graphonometric method of assessing upper limb kinematics by digitizing and analyzing Archimedean spirals drawn on a digitized graphics tablet [2] that correlates with the motor UPDRS score [3]. It has the advantage of being non-invasive and relatively easy to perform. To test if spiral analysis could detect changes not clinically measurable by UPDRS, we assessed whether spiral analysis could identify abnormalities on the unaffected side in a unique population of early and clinically unilateral PD (i.e. normal motor UPDRS scores on one side of the body).

Spiral analysis—Improved clinical utility with center detection

Spiral analysis is a computerized method that measures human motor performance from handwritten Archimedean spirals. It quantifies normal motor activity, and detects early disease as well as dysfunction in patients with movement disorders. The clinical utility of spiral analysis is based on kinematic and dynamic indices derived from the original spiral trace, which must be detected and transformed into mathematical expressions with great precision. Accurately determining the center of the spiral and reducing spurious low frequency noise caused by center selection error is important to the analysis. Handwritten spirals do not all start at the same point, even when marked on paper, and drawing artifacts are not easily filtered without distortion of the spiral data and corruption of the performance indices. In this report, we describe a method for detecting the optimal spiral center and reducing the unwanted drawing artifacts. To demonstrate overall improvement to spiral analysis, we study the impact of the optimal spiral center detection in different frequency domains separately and find that it notably improves the clinical spiral measurement accuracy in low frequency domains.