Margaret F. Turk

Thalamic stimulation for the treatment of midline tremors in essential tremor patients

Article abstract The authors prospectively collected unblinded data from 27 consecutive patients following thalamic stimulation. A significant reduction of midline tremor was achieved after unilateral surgery, but a staged contralateral surgery had an additional effect. A subgroup analysis showed significant beneficial effects for head, voice, tongue, and face tremor. The most frequent reversible side effects were disequilibrium, dysarthria, and paresthesias. We observed more pulse generator adjustments for speech problems in the bilaterally implanted group.

Magnetic Resonance Imaging and Deep Brain Stimulation

OBJECTIVE To determine whether cranial magnetic resonance imaging (MRI) is associated with deep brain stimulation (DBS) lead displacement or program interference. METHODS In vitro and in vivo studies were performed with the Itrel II implantable pulse generator (IPG) (Model 7424; Medtronic, Minneapolis, MN), Medtronic 3387 and 3389 leads, and a 1.5-T GE Horizon LX scanner (General Electric, Milwaukee, WI). In the in vivo study, two MRI volumetric data sets were compared for each of five patients undergoing staged, bilateral, DBS electrode placement in the thalamic or subthalamic nucleus. The data sets were acquired shortly after the initial implantation and during stereotactic planning for the second implantation (1-8 mo between acquisitions). An additional thalamotomy-treated patient was included as a control patient. Volumetric data were analyzed in a blinded manner, using AnalyzeAVW 3.0 software (Biomedical Imaging Resource, Mayo Clinic, Rochester, MN), to determine lead movement. In the in vitro study, the IPG and leads were positioned in the magnetic field in various configurations and were systematically assessed for movement. RESULTS In vivo, the majority of measured deviations (88%) were within the standard error of measurement (1.4 mm). The maximal measured deviation was 3 mm (2% occurrence). Excellent tremor control with stimulation was demonstrated, which did not change after MRI. In vitro, the DBS leads demonstrated no deflection when introduced into the magnetic field. Similarly, no changes in IPG battery strength, lead impedance, or program settings were observed. CONCLUSION MRI was not associated with significant DBS electrode movement or changes in clinical responses. Other IPG models and components and MRI scanners should be evaluated, to develop specific guidelines for MRI among individuals with implanted DBS systems.

Reliability of reported age at onset for Parkinson's disease

An individuals age at onset of Parkinson disease (PD) can be collected through a variety of sources, including medical records, family report, and clinical observation. The most common source of PD age at onset information in the research setting is family‐report, which is then typically used to classify a subject as juvenile, young, or late age at onset. The reliability of the family‐reported age at onset of PD has not been rigorously examined. The present study used data from individuals diagnosed with PD to evaluate the reliability of age at onset information by comparing data obtained from three sources: 1) the subjects medical records, 2) a Family History Questionnaire, and 3) a Subject History Questionnaire. Among the 149 subjects with data for all three age at onset sources, the estimated reliability was R = 0.94. Similar reliability was observed when the sample was stratified based on gender, age at examination, disease duration, first symptom of PD, and years of education. The three measures of age at onset of PD show excellent agreement, strengthening confidence in the reliability of the reported age of clinical onset for PD.

Mutations in LRRK2 other than G2019S are rare in a north-American based sample of familial Parkinson's didease

A total of 956 individuals with Parkinsons disease (PD) from 430 multiplex PD pedigrees were screened for 12 previously reported, pathogenic LRRK2 mutations: R793M, L1114L, I1371V, R1441C, R1441G, R1441H, Y1699C, M1869T, I2012T, I2020T, G2385R, and IVS31 +3G>A. Previous screening identified the LRRK2 G2019S mutation in 5% of our families. Only 1 of the 12 newly screened mutations, R1441C, was detected in a single family in our patient cohort. These results indicate that, although the G2019S mutation remains the most common mutation identified in familial PD patients, other mutations in LRRK2 are infrequent.

Unilateral pallidotomy for Parkinson's disease: speech, motor, and neuropsychological outcome measurements

We studied the effects of unilateral medial pallidotomy in the first 57 consecutive Parkinsons disease (PD) patients undergoing this MRI/electrophysiologically guided procedure at our institution, obtaining qualitative and quantitative measures of speech, motor function, activities of daily living, and neuropsychological functioning at 3 and 12months post-operatively. Speech intelligibility was typically preserved, declining mildly in one-third of patients post-operatively. Pallidotomy significantly improved motor function similarly in patients >/=65 or <65years (n=20). Cognitive abilities generally remained stable following surgery; however, performance on measures of letter fluency and semantic fluency declined in patients with left pallidotomies. We conclude that in our series mild deterioration in speech may occur with unilateral pallidotomy in patients otherwise responsive to this treatment.

Efficacy of levodopa therapy on motor function after posteroventral pallidotomy for Parkinson's disease

To the Editor: We read with interest the article by Uitti et al. on the efficacy of levodopa therapy on motor function in 41 patients with complicated PD submitted to microelectrode-guided pallidotomy.1 The authors found no significant change in the latency, duration, or magnitude of clinical response after administration of an acute challenge of levodopa. However, it is difficult to understand how the magnitude of the clinical response remained unchanged after surgery. This pharmacologic parameter is defined as the difference between basal “off ” and best “on” Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores. Many reports confirm that pallidotomy provides marked contralateral amelioration of parkinsonian symptoms, and after surgery patients reported less recognizable “on-off ” fluctuations. Current ideas about the pathophysiologic basis of motor fluctuations suggest that the magnitude of the motor response is the key factor in the development of the wearing-off phenomenon.2 The improvement in motor fluctuations after pallidotomy is most likely due to a reduction in the magnitude of the motor response as a result of reduced severity of the parkinsonian signs and symptoms in the operated side. Indeed, Uitti et al. noted that the mean motor “off ” score after pallidotomy was improved by 10 points (48.7 versus 38.6). The best motor “on” score was also improved, although to a lesser degree (24.6 versus 20.1). Despite this improvement in both scores, the magnitude of the motor response should be reduced after surgery because the degree of improvement in the “off ” score is bigger than that obtained in the best “on” score. Other groups, despite methodologic differences, have found a significant reduction in the magnitude and an increase in the duration of the clinical benefit after acute levodopa and apomorphine challenges.3-5 We evaluated six patients with PD who underwent pallidotomy. The magnitude was reduced by 30% and the duration of either levodopa or apomorphine effect was 40% longer.6 Merello et al. recently reported similar results although they did not specifically evaluate the magnitude of the response.5 More recently, we have extended our results to a group of 14 patients submitted to deep brain stimulation of the subthalamic nucleus or internal globus pallidus, obtaining similar results, although the changes were more pronounced in these patients, probably because of the bilateral nature of the surgical intervention.7 In our experience, pallidotomy and deep brain stimulation shift the pharmacologic response profile to a pattern more characteristic of less advanced parkinsonian patients. These changes may account for the “disappearance” or lack of perception of motor fluctuations leading to a less difficult drug management.

Correlation of outcome to neurosurgical lesions: confirmation of a new method using data after microelectrode-guided pallidotomy.

The purpose of this study was the development of a new method to correlate functional surgery with outcome measures. Lesions following microelectrode guided globus pallidus internus (GPi) pallidotomy for Parkinsons disease are presented to demonstrate this new method in regard to clinical outcome. A clinical series of 26 patients with extensive neurological and neuropsychological data were studied. Three-month postoperative MRI lesion borders at the AC–PC plane were scaled to a standard size, and the lesions were stored in a virtual array with a cell size of one voxel. The average outcome measure for each voxel is presented graphically. Unified Parkinsons disease rating scale (UPDRS) motor scores improved more with posterolateral and centrally located GPi lesions than with anteromedial lesions. A correlation of lesion location to outcome was also visible for subscales of the UPDRS. The distributions were similar for the left and right sides, as well as for ipsi- and contralateral measurements. In general, verbal fluency decreased after lesioning the dominant hemisphere, and posterolateral lesions caused less impairment. This method enables associative analyses between brain area and outcome down to the size of a few voxels. This may be particularly helpful for planning and validating neurosurgical targets for various disorders.