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. ET cases and age-matched control subjects were ascertained from a tertiary referral center at Columbia-Presbyterian Medical Center and a community in northern Manhattan, N.Y. Subjects underwent a 2.5-hour evaluation, including a tremor disability questionnaire, a videotaped tremor examination rated by a neurologist, a performance-based test of function, quantitative computerized tremor analysis, the Hamilton Anxiety Rating Scale, and the depression module of the Structured Clinical Interview for DSM-IV. Seventy-six (85.4%) of 89 cases reported disability on > or =1 item on the disability questionnaire. In multivariate linear regression analyses, current major depression, Hamilton Anxiety Rating Scale score, age, and tremor severity were independently correlated with performance-based test scores. Twenty-seven (73.0%) of 37 community cases reported disability on > or =1 (mean = 8.4) item on the questionnaire, and 25 (67.6%) demonstrated moderate or greater difficulty on > or =1 (mean = 4.2) task in a performance-based test. Depression, anxiety, and age, independent of the severity of tremor, were associated with greater functional disability in ET, so that these factors must be considered when assessing the impact of new treatments in ET. Among a group of community-dwelling cases, approximately three-quarters reported disability, suggesting that the number of individuals who might receive some benefit from advances in the treatment of ET is probably a great deal larger than previously thought.

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A valid performance-based test was developed to objectively assess functional capacity in patients with ET. This test would be useful in therapeutic trials, where it would provide an objective means to quantify the functional impact of tremor.

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 Parkinson's 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.

Orthostatic tremor (OT) is a condition described as high-frequency tremors predominantly in the legs and trunk, which are present not only in the standing position but also during isometric contraction of the limb muscles. This report is one of the largest OT series describing clinical and neurophysiologic findings in 26 subjects with OT. The main findings included 13.0 to 18.6 Hz leg tremors while standing with varied patterns of phase relationships between the antagonists of the ipsilateral leg and between the homologous muscles of the contralateral leg, short latency tremor onset upon standing with abrupt cessation after sitting, coexistence of tremors in the cranial structures and the arms, and sense of unsteadiness without actual falls. Although the oscillator of OT is most likely located in the brainstem, cerebral cortex, basal ganglia, and cerebellum may also be involved in its pathogenesis.

SUMMARY Majewski Osteodysplastic Primordial Dwarfism type II (MOPDII) is caused by mutations in the centrosome gene pericentrin (PCNT) which lead to severe pre- and post-natal growth retardation[1]. As in MOPDII patients, disruption of pericentrin (Pcnt) in mice caused a number of abnormalities including microcephaly, aberrant hemodynamics analyzed by in utero echocardiography and cardiovascular anomalies; the latter being associated with mortality, as in the human condition[1]. To identify the mechanisms underlying these defects, we tested for changes in cell and molecular function. All Pcnt−/− mouse tissues and cells examined showed spindle misorientation. This mouse phenotype was associated with misdirected ventricular septal growth in the heart, decreased proliferative symmetric divisions in brain neural progenitors and increased misoriented divisions in fibroblasts; the same phenotype was seen in fibroblasts from three MOPDII individuals. Misoriented spindles were associated with disrupted astral microtubules and near complete loss of a unique set of centrosome proteins from spindle poles (ninein, Cep215, centriolin). All these proteins appear to be crucial for microtubule anchoring and all interacted with Pcnt, suggesting that Pcnt serves as a molecular scaffold for this functionally-linked set of spindle pole proteins. Importantly, Pcnt disruption had no detectable effect on localization of proteins involved in the cortical polarity pathway (NuMA, p150glued, aPKC). Not only do these data reveal a spindle-pole-localized complex for spindle orientation, but they identify key spindle symmetry proteins involved in the pathogenesis of MOPDII.

Object Deep brain stimulation (DBS) of the subthalamic nucleus (STN) performed using intraoperative microelectrode recording (MER) to adjust electrode placement has become a widely used treatment for patients with advanced Parkinson disease (PD). Few studies have been conducted to examine the location of implanted electrodes relative to the intended target, and even fewer have been undertaken to investigate the degree to which variations in the location of these electrodes impacts their clinical efficacy. This study was performed to examine these issues. Methods The authors located 52 bilaterally implanted DBS electrode tips on postoperative magnetic resonance (MR) images obtained in 26 consecutive patients. Postoperative and preoperative planning MR images were merged to determine the DBS electrode tip coordinates relative to the midcommissural point. Surgical records listed the intended target coordinates for each DBS electrode tip. Clinical outcome assessment included the Unified PD Rating Scale (UPDRS) motor score at 1 year, standardized questionnaires, and routine follow-up visits. The mean difference between electrode tip location and intended target for all 52 electrodes was less than 2 mm in all axes. Only one electrode was farther than 3 mm from the intended target, and this was the only electrode that had to be replaced due to lack of clinical efficacy (lack of tremor suppression); its reimplantation 4 mm more medially provided excellent tremor control. High correlation coefficients indicate that the MR imaging analysis accurately determined the anatomical location of the electrode tips. Blinded videotape reviews of UPDRS motor scores comparing effects of stimulation in patients who were “on” and “off” medication identified subgroups in whom there was minimal and maximal stimulation response. Patients in these subgroups had no differences between the MR imaging–determined actual electrode tip location and its intended location. Similarly, improvements of dyskinesias and severity of symptoms encountered during the wearing-off period for the drug did not correlate with variations of electrode tip location. Conclusions The findings in this study lead the authors to suggest that a DBS electrode placed anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the STN (based on stereotactic atlas coordinates) provides similar clinical efficacy. Future studies may be warranted to evaluate prospectively the degree to which MER modification of the anatomically and/or image-determined target improves clinical efficacy of DBS electrodes.

IMPORTANCE Recent evidence supports the presence of macular damage (within 8°of the central field) to retinal ganglion cells and associated central visual field (VF) defects in glaucoma, even in early stages. Despite this, to our knowledge, the association of 10-2 VF damage with vision-related quality of life (QOL) has not been well studied.OBJECTIVE To determine the association between QOL and visual function as measured by 24-2 and 10-2 VFs in patients with primary open-angle glaucoma and to test the hypothesis that patients with vision-related QOL disproportionate to their 24-2 VF status may exhibit 10-2 damage overlooked by the 24-2 test. DESIGN, SETTING, AND PARTICIPANTSIn this cross-sectional analysis of observational cohort study data taken from a tertiary care specialty practice, 113 patients with glaucoma with the entire range of 24-2 VF damage completed the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).