Cerebellar Oscillations in Familial and Sporadic Essential Tremor.

Enhanced cerebellar oscillations have recently been identified in essential tremor (ET) patients as a key pathophysiological change. Since ET is considered a heterogeneous group of diseases, we investigated whether cerebellar oscillations differ in ET subtypes (familial vs. sporadic). This study aims to determine cerebellar physiology in familial and sporadic ET. Using surface electroencephalogram, we studied cerebellar physiology in 40 ET cases (n = 22 familial and n = 18 sporadic) and 20 age-matched controls. Both familial and sporadic ET cases had an increase in the intensity of cerebellar oscillations when compared to controls. Interestingly, cerebellar oscillations correlated with tremor severity in familial ET but not in sporadic ET. Our study demonstrated that ET cases have enhanced cerebellar oscillations, and the different relationships between cerebellar oscillations and tremor severity in familial and sporadic ET suggest diverse cerebellar pathophysiology.

Repeated Spiral Drawings in Essential Tremor: a Possible Limb-Based Measure of Motor Learning.

To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects. One hundred and sixty-one ET and 80 age-matched control subjects drew 10 consecutive spirals on a digitizing tablet. Degree of severity (DoS), a weighted, computational score of spiral execution that takes into account spiral shape and line smoothness, previously validated against a clinical rating scale, was calculated in both groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in centimeters, was also calculated. Changes in DoS and Ampl across trials were assessed using linear regression with slope evaluations. Both groups demonstrated improvement in DoS across trials, but with less improvement in the ET group compared to controls. Ampl demonstrated a tendency to worsen across trials in ET subjects. ET subjects demonstrated less improvement than controls when drawing sequential spirals, suggesting a possible motor learning deficit in ET, here captured in an affected limb. DoS improved independently of Ampl, showing that DoS and Ampl are separable motor physiologic components in ET that may be independently mediated.

A Case Series of Isolated Smiling Tremor: What Is the Phenomenology?

BACKGROUND: Five cases of tremor only upon smiling have been reported where no facial tremor is present at rest, when talking, or with full smile. CASES: This report highlights four cases of tremor upon partial smiling, discusses the phenomenology of smiling tremor, and reviews the current literature. Four subjects with lower facial tremor present only upon smiling underwent movement disorders evaluation with video. Tremor frequencies were determined by parsing the video clips into 1-second intervals and averaging the number of oscillations per interval and were determined to be high-frequency 8 to 10 Hz irregular facial tremors with harmonic variations upon moderate effort in all cases. Slight or full-effort smiling did not elicit facial muscle oscillations. Subjects had no other signs of tremor, dystonia, or parkinsonism on examination or in family history. CONCLUSIONS: Tremor upon smiling only, or isolated smiling tremor, is a unique task- and position-specific tremor of the facial musculature.

High width variability during spiral drawing: further evidence of cerebellar dysfunction in essential tremor.

Essential tremor (ET) is among the most prevalent neurological diseases, yet the location of the primary disease substrate continues to be a matter of debate. The presence of intention tremor and mild gait ataxia suggests an underlying abnormality of the cerebellum and/or cerebellar pathways. Uncovering additional signs of cerebellar dysfunction would further substantiate the proposition that ET is a disease of the cerebellar system. We evaluated 145 ET cases and 34 normal controls clinically and by computerized spiral analysis. Spiral analysis is a program that objectively characterizes kinematic and physiologic features of hand-drawn spirals using specific calculated spiral indices that correlate with spiral shape and motor execution. We used the spiral width variability index (SWVI), a measure of loop-to-loop spiral width variation with the influence of tremor removed, as a metric of drawing ataxia. The SWVI was higher in cases than controls (0.91 ± 1.94, median=0.46 vs. 0.40 ± 0.29, median=0.30, p<0.001). Cases with higher SWVI also had greater intention tremor during the finger-nose-finger maneuver, r=0.27, p=0.001), and cases with intention tremor of the head had the highest SWVI (1.57 ± 3.44, median=0.51, p<0.001). There was a modest association between SWVI and number of missteps during tandem gait (r=0.16, p=0.06). The primary anatomical substrate for ET continues to be a matter of speculation, yet these and other clinical data lend support to the notion that there is an underlying abnormality of the cerebellum and/or its pathways.

Using computerized spiral analysis to evaluate deep brain stimulation outcomes in Parkinson disease.

OBJECTIVE: To determine whether spiral analysis can monitor the effects of deep brain stimulation (DBS) in Parkinson disease (PD) and provide a window on clinical features that change post-operatively. Clinical evaluation after DBS is subjective and insensitive to small changes. Spiral analysis is a computerized test that quantifies kinematic, dynamic, and spatial aspects of spiral drawing. Validated computational indices are generated and correlate with a range of clinically relevant motor findings. These include measures of overall clinical severity (Severity), bradykinesia and rigidity (Smoothness), amount of tremor (Tremor), irregularity of drawing movements (Variability), and micrographia (Tightness). METHODS: We retrospectively evaluated the effect of subthalamic nucleus (STN) (n = 66) and ventral intermediate thalamus (Vim) (n = 10) DBS on spiral drawing in PD subjects using spiral analysis. Subjects freely drew ten spirals on plain paper with an inking pen on a graphics tablet. Five spiral indices (Severity, Smoothness, Tremor, Variability, Tightness) were calculated and compared pre- and post-operatively using Wilcoxon-rank sum tests, adjusting for multiple comparisons. RESULTS: Severity improved after STN and Vim DBS (p < 0.005). Smoothness (p < 0.01) and Tremor (p < 0.02) both improved after STN and Vim DBS. Variability improved only with Vim DBS. Neither STN nor Vim DBS significantly changed Tightness. CONCLUSIONS: All major spiral indices, except Tightness, improved after DBS. This suggests spiral analysis monitors DBS effects in PD and provides an objective window on relevant clinical features that change post-operatively. It may thus have utilization in clinical trials or investigations into the neural pathways altered by DBS. The lack of change in Tightness supports the notion that DBS does not improve micrographia.

Holmes Tremor due to Artery of Percheron Infarct: Clinical Case and Treatment Using Deep Brain Stimulation of the Vim and ZI Targets.

Background: Holmes tremor (HT) arises from disruption of the cerebellothalamocortical pathways. A lesion can interrupt the projection at any point, resulting in this tremor. We describe a case of HT due to the rare artery of Percheron infarct and its successful treatment using deep brain stimulation. Case report: A 62-year-old woman with a right medial cerebral peduncle and bilateral thalamic stroke developed HT. Ventral intermediate nucleus (Vim) zona incerta (ZI) deep brain stimulation (DBS) surgery was performed, with improvement in her tremor. Discussion: Our case supports the theory that the more caudal ZI target in combination with Vim is beneficial in treating poorly DBS-responsive tremors such as HT.

Neurophysiological features of primary lateral sclerosis.

Primary lateral sclerosis (PLS) is a motor neuron disease characterized by spinobulbar spasticity, absence of progressive lower motor neuron (LMN) dysfunction and marked by a slow functional decline. Electromyography is essential to exclude significant LMN involvement, particularly in the context of distinguishing PLS from amyotrophic lateral sclerosis (ALS), given that the prognosis is substantially better, and respiratory complications are unusual, in PLS. Nevertheless, minor neurogenic changes and occasional fasciculation potentials can be observed in PLS. The most useful technique for the objective assessment of upper motor neuron (UMN) dysfunction is transcranial magnetic stimulation (TMS), which in PLS is characterized by a high cortical threshold and delayed central conduction times. TMS is sensitive to identify cortical dysfunction in PLS and might have potential for monitoring UMN function in longitudinal studies and in clinical trials. The findings of TMS need to be interpreted in the context of the clinical presentation and phenotype, particularly in the differentiation between PLS and ALS. While other neurophysiological techniques have been investigated, studies to date have tended to involve small patient cohorts and as such, their value in distinguishing PLS from ALS remains unclear.

Spiral analysis in Niemann-Pick disease type C.

Spiral analysis is a computerized method of analyzing upper limb motor physiology through the quantification of spiral drawing. The objective of this study was to determine whether spirals drawn by patients with Niemann-Pick disease type C (NPC) could be distinguished from those of controls, and to physiologically characterize movement abnormalities in NPC. Spiral data consisting of position, pressure, and time were collected from 14 NPC patients and 14 age-matched controls, and were analyzed by the Mann-Whitney U test. NPC spirals were characterized by: lower speed (2.67 vs. 9.56 cm/s, P < 0.001) and acceleration (0.10 vs. 2.04 cm/s(2), P < 0.001), higher loop width variability (0.88 vs. 0.28, P < 0.001), tremor (5/10 vs. 0/10 trials in the dominant hand, P < 0.001), and poor overall spiral rating (2.53 vs. 0.70, P < 0.005). NPC spirals also exhibited sustained drawing pressure profiles that were abnormally invariant with time. Other features, such as the tightness of loop widths, were normal. Our findings reveal that differing aspects of tremor, Parkinsonism, ataxia, and dystonia are quantifiable in NPC patients.

Motor unit number estimation (MUNE) in diseases of the motor neuron: utility and comparative analysis in a multimodal biomarker study.

We prospectively studied 64 patients with motor neuron disease (amyotrophic lateral sclerosis (ALS), familial ALS (fALS), progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS)) using multiple point stimulation motor unit number estimation (MUNE), transcranial magnetic stimulation (TMS), proton magnetic resonance spectroscopic imaging (1H MRSI), diffusion tensor imaging (MRDTI), and clinical measures at baseline and every 3 months thereafter for 15 months. Substantial differences in MUNE were noted among the motor neuron disease subgroups (P = 0.0005) and mean values for each motor neuron disease subgroup were significantly lower vs. controls (ALS = 76, fALS = 80, PMA = 29, and PLS = 174) vs. the normal control average (267). MUNE correlated well with % FVC (r = 0.32; P = 0.01), manual muscle testing (r = 0.52; P < 0.0005), grip strength (r = 0.34; P = 0.007), and pinch strength (r = 0.49; P < 0.0005). Overall, MUNE showed the greatest significant change over time of any measure, clinical or otherwise, tested in this study (-2.35 linear trend % change per month, mean). MUNE clearly delineates lower motor neuron dysfunction, strongly correlates with important clinical functions (such as strength and respiration) and is a highly sensitive marker of disease progression over time. These features make MUNE an important tool for both the study of the pathophysiology of the motor neuron diseases, as well as an important measure for incorporation into future clinical trials.

Typical variations of subthalamic electrode location do not predict limb motor function improvement in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for patients with medically refractory Parkinson's disease (PD). The degree to which the anatomic location of the DBS electrode tip determines the improvement of contralateral limb movement function has not been defined. This retrospective study was performed to address this issue. Forty-two DBS electrode tips in 21 bilaterally implanted patients were localized on postoperative MRI. The postoperative and preoperative planning MRIs were merged with the Stealth FrameLink 4.0 stereotactic planning workstation (Medtronic Inc., Minneapolis, MN, USA) to determine the DBS tip coordinates. Stimulation settings were postoperatively optimized for maximal clinical effect. Patients were videotaped 1 year postoperatively and assessed by a movement disorder neurologist blinded to electrode tip locations. The nine limb-related components of the Unified PD Rating Scale Part III were tabulated to obtain a limb score, and the electrode tip locations associated with the 15 least and 15 greatest limb scores were evaluated. Two-tailed t-tests revealed no significant difference in electrode tip location between the two groups in three-dimensional distance (p=0.759), lateral-medial (x) axis (p=0.983), anterior-posterior (y) axis (p=0.949) or superior-inferior (z) axis (p=0.894) from the intended anatomical target. The range of difference in tip location and limb scores was extensive. Our results suggest that anatomic targeting alone may provide the same clinical efficacy as is achieved by "fine-tuning" DBS placement with microelectrode recording to a specific target.

A novel exaggerated "spino-bulbo-spinal like" reflex of lower brainstem origin.

BACKGROUND: Many different oligosynaptic reflexes are known to originate in the lower brainstem which share phenomenological and neurophysiological similarities. OBJECTIVE: To evaluate and discuss the differences and aberrancies among these reflexes, which are hard to discern clinically using neurophysiological investigations with the help of a case report. METHODS: We describe the clinical and neurophysiological assessment of a young man who had a childhood history of opsoclonus-myoclonus syndrome with residual mild ataxia and myoclonic jerks in the distal extremities presenting with subacute onset total body jerks sensitive to sound and touch (in a limited dermatomal distribution), refractory to medications. RESULTS: Based on clinical characteristics and insights gained from neurophysiological testing we could identify a novel reflex of caudal brainstem origin. CONCLUSIONS: The reflex described is likely an exaggerated normal reflex, likely triggered by a dolichoectatic vertebral arterial compression and shares characteristics of different reflexes known to originate in caudal brainstem, which subserve distinctive roles in human postural control.

The hand that has forgotten its cunning--lessons from musicians' hand dystonia.

Focal task-specific dystonia of the musicians' hand (FTSDmh) is an occupational movement disorder that affects instrumental musicians and often derails careers. There has been speculation on the role of intense practice or the specific technical demands of various instruments as triggers for the development of FTSDmh. In this study, we review the clinical features of all published cases (899 patients) and 61 previously unpublished cases of FTSDmh. Our primary goals were to search for patterns in the clinical phenotype, and to discern if specific instrumental technical demands might be related to the development of dystonia. Symptoms of FTSDmh began at a mean age 35.7 years (SD = 10.6), with an overwhelming male predominance (M:F = 4.1:1). The right hand was preferentially affected in keyboard and plucked string players (77%), and the left hand in bowed string players (68%). Flexion movements were the most common dystonic movement in each instrument class, and fingers 3, 4, and 5, either in isolation or combination, were most frequently involved. The clinical implications of these findings and their possible relationship to the pathophysiology of focal task-specific dystonia are explored.

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 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.

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.

Objective predictors of 'early tolerance' to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients.

OBJECTIVE: To identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit 'early tolerance' to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS). METHODS: Identification of comparative characteristics of defined cases of 'early tolerance' versus patients with sustained satisfactory response treated with Vim DBS surgery for medically-refractory ET, based on retrospective chart review by a clinician blinded to the findings of computerized spiral analysis. RESULTS: Statistically significant differences in two spiral analysis indices, SWVI and DoS, were found in the dominant upper limbs of patients who developed 'early tolerance', whereas the clinical characteristics were not significantly different. CONCLUSION: Objective measurements of upper limb kinematics using graphonomic tests like spiral analysis should be considered in the pre-operative evaluation for DBS, especially in the setting of moderate-severe predominantly action and proximal postural tremors. SIGNIFICANCE: Ours is the first investigation looking into the pre-operative clinical and objective physiologic characteristics of the patients who develop 'early tolerance' to Vim DBS for the treatment of essential tremor. The study has significant implications for pre-operative evaluation and potential surgical target selection for the treatment of tremors.

Transient, Isolated Head Tremor in "Unaffected" Individuals: Is Essential Tremor an Even More Prevalent Disease Than We Suppose?

Background: Mild and transient head tremor may sometimes be observed in otherwise tremor-free relatives of essential tremor (ET) cases, although its prevalence is unclear. A diagnostic question is whether this transient, isolated head tremor, often observed as no more than a wobble, is an early manifestation of ET or whether it is a normal finding. A direct comparison with controls is needed. Methods: Two hundred and forty-one first-degree relatives of ET cases (FD-ET) and 77 spousal controls (Co) were enrolled in a study of ET. Each underwent a detailed evaluation that included a tremor history and videotaped neurological examination. None of the enrollees reported tremor, had a prior diagnosis of ET, or had significant tremor on screening spirals. All videotaped examinations were initially reviewed by a movement disorder neurologist blinded to subject type, and among those with head tremor on examination, co-reviewed by two additional movement disorders neurologists. Results: Twenty-six (10.8, 95% Confidence interval [CI] = 7.5-15.3%) of 241 FD-ET vs. 2 (2.6, 95% CI = 0.7-9.0%) of 77 Co had isolated, transient head tremor (odds ratio = 4.54, 95% CI = 1.05-19.57, p = 0.04). No enrollee had significant upper extremity tremor and none met inclusion criteria for ET based on the presence of upper extremity tremor. With one exception, head tremor occurred during or after phonation. It was always transient (generally a single back and forth wobble) and rare (observed briefly on one or two occasions during the videotaped examination) and had a faster frequency, lower amplitude and a different quality than voluntary head shaking. Conclusion: The basis for the observed isolated head tremor is unknown, but it could be an early feature of ET in ET families.Indeed, one-in-ten otherwise unaffected first-degree relatives of ET cases exhibited such tremor. To a far lesser extent it was also observed in "unaffected" controls. In both, it is likely a sign of early, emerging, undiagnosed ET, although follow-up studies are needed to confirm this. If it were ET, it would indicate that the prevalence of ET may be considerably higher than previously suspected.

Digitized spiral analysis may be a potential biomarker for brachial dystonia.

INTRODUCTION: Objective measures for detection and quantification of dystonic movements may guide both diagnosis and clinical monitoring. Digitized spiral analysis is a non-invasive method used to assess upper limb motor control in movement disorders and may have utility in dystonia. We aimed to determine if digitized spiral analysis can distinguish dystonia subjects from controls, and evaluated correlation with a validated clinical rating scale. METHODS: Kinematic, dynamic, and spatial attributes of Archimedean spirals drawn with an inking pen on a digitizing tablet were compared for participants with brachial dystonia and either Tor1A (DYT1) (n = 15) or THAP1 (DYT6) mutations (n = 12) and age and gender matched controls (n = 27) using Receiver Operator Characteristics (ROC) analysis. Spiral indices including an overall degree of severity (DoS) were also calculated and correlated with clinical severity ratings as measured by the Burke-Fahn-Marsden scale. RESULTS: Dystonia spirals had significantly higher severity scores as well as higher measures of spiral irregularity compared to controls. ROC analysis demonstrated that the DoS score had good discriminative ability to distinguish dystonia spirals from controls, with an Area Under the Curve (AUC) of 0.87. Measures of spiral irregularity correlated with validated clinical rates of dystonia severity in the analyzed arm, with one particular index, Residue of Theta vs R, showing the highest correlation (r = 0.55, p = 0.005). CONCLUSION: Digitized spiral analysis may be a promising non-invasive method to objectively quantify brachial dystonia. It may also be a useful way to monitor subtle changes in dystonia severity over time not captured with current clinical rating scales.

Tremor amplitude is logarithmically related to 4- and 5-point tremor rating scales.

Tremor rating scales (TRSs) are used commonly in the clinical assessment of tremor, but the relationship of a TRS to actual tremor amplitude has never been quantified. Consequently, the resolution of these scales is unknown, and the clinical significance of a 1-point change in TRS is uncertain. We therefore sought to determine the change in tremor amplitude that corresponds to a 1-point change in a typical 5-point TRS. Data from five laboratories were analysed, and 928 patients with various types of hand tremor were studied. Hand tremor was quantified with a graphics tablet in three different labs, an accelerometer in three labs and a mechanical-linkage device in one lab. Tremor in writing, drawing, horizontal posture, rest and finger-nose testing was graded using a variety of TRSs. The relationship between TRS scores and tremor amplitude was computed for each task and laboratory. A logarithmic relationship between a 5-point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in all five labs, despite widely varying rating scales and transducer methodology. Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441 for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor, 0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha = 0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are 0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS represents a substantial change in tremor amplitude. Knowledge of the relationship between TRS and precise measures of tremor is useful in interpreting the clinical significance of changes in TRS produced by disease or therapy.

Computerized spiral analysis using the iPad.

BACKGROUND: Digital analysis of writing and drawing has become a valuable research and clinical tool for the study of upper limb motor dysfunction in patients with essential tremor, Parkinson's disease, dystonia, and related disorders. We developed a validated method of computerized spiral analysis of hand-drawn Archimedean spirals that provides insight into movement dynamics beyond subjective visual assessment using a Wacom graphics tablet. While the Wacom tablet method provides robust data, more widely available mobile technology platforms exist. NEW METHOD: We introduce a novel adaptation of the Wacom-based method for the collection of hand-drawn kinematic data using an Apple iPad. This iPad-based system is stand-alone, easy-to-use, can capture drawing data with either a finger or capacitive stylus, is precise, and potentially ubiquitous. RESULTS: The iPad-based system acquires position and time data that is fully compatible with our original spiral analysis program. All of the important indices including degree of severity, speed, presence of tremor, tremor amplitude, tremor frequency, variability of pressure, and tightness are calculated from the digital spiral data, which the application is able to transmit. COMPARISON WITH EXISTING METHOD: While the iPad method is limited by current touch screen technology, it does collect data with acceptable congruence compared to the current Wacom-based method while providing the advantages of accessibility and ease of use. CONCLUSIONS: The iPad is capable of capturing precise digital spiral data for analysis of motor dysfunction while also providing a convenient, easy-to-use modality in clinics and potentially at home.

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.