S L Pullman

Columbia University, New York City, NY, United States

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Publications (70)324.72 Total impact

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    ABSTRACT: Substantia nigra neurons are known to play a key role in normal cognitive processes and disease states. While animal models and neuroimaging studies link dopamine neurons to novelty detection, this has not been demonstrated electrophysiologically in humans. We used single neuron extracellular recordings in awake human subjects undergoing surgery for Parkinson disease to characterize the features and timing of this response in the substantia nigra. We recorded 49 neurons in the substantia nigra. Using an auditory oddball task, we showed that they fired more rapidly following novel sounds than repetitive tones. The response was biphasic with peaks at approximately 250ms, comparable to that described in primate studies, and a second peak at 500ms. This response was primarily driven by slower firing neurons as firing rate was inversely correlated to novelty response. Our data provide human validation of the purported role of dopamine neurons in novelty detection and suggest modifications to proposed models of novelty detection circuitry.
    Brain research 10/2013; · 2.46 Impact Factor
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    ABSTRACT: Orthostatic tremor (OT) was a term first used to describe tremor that occurred in the legs while patients were standing, and which was relieved while patients were walking, seated, or supine.(1) The disorder can be very disabling, and the treatment, which is largely unsuccessful, remains empiric.(2,3) Although there is some evidence of a dopaminergic deficit,(4) the exact circuit responsible for the high frequency, 13-18 Hz tremor that is pathognomonic for this disorder remains unclear. OT is thought to be sporadic rather than familial, which makes the search for a pathophysiologic mechanism particularly challenging. There are only 2 prior case reports of OT in siblings.(5,6) Here we report a third sibling pair, each of whom had clinical and electrophysiologic evidence of OT.
    Neurology 07/2012; 79(3):288-9. · 8.25 Impact Factor
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    ABSTRACT: To compare the phenotype of primary-appearing dystonia due to variant ataxia-telangiectasia (A-T) with that of other dystonia ascertained for genetics research. Movement disorder specialists examined 20 Canadian Mennonite adult probands with primary-appearing dystonia, as well as relatives in 4 families with parent-child transmission of dystonia. We screened for the exon 43 c.6200 C>A (p. A2067D) ATM mutation and mutations in DYT1 and DYT6. Clinical features of the individuals with dystonia who were harboring ATM mutations were compared with those of individuals without mutations. Genetic analysis revealed a homozygous founder mutation in ATM in 13 members from 3 of the families, and no one harbored DYT6 or DYT1 mutations. Dystonia in ATM families mimicked other forms of early-onset primary torsion dystonia, especially DYT6, with prominent cervical, cranial, and brachial involvement. Mean age at onset was markedly younger in the patients with variant A-T (n = 12) than in patients with other dystonia (n = 23), (12 years vs 40 years, p < 0.05). The patients with A-T were remarkable for the absence of notable cerebellar atrophy on MRI, lack of frank ataxia on examination, and absence of ocular telangiectasias at original presentation, as well as the presence of prominent myoclonus-dystonia in 2 patients. Many also developed malignancies. Ataxia and telangiectasias may not be prominent features of patients with variant A-T treated for dystonia in adulthood, and variant A-T may mimic primary torsion dystonia and myoclonus-dystonia.
    Neurology 02/2012; 78(9):649-57. · 8.25 Impact Factor
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    ABSTRACT: 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.
    The Cerebellum 01/2012; · 2.60 Impact Factor
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    Christopher W Hess, Seth L Pullman
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    ABSTRACT: Tremors are among the most common movement disorders. As there can be considerable variability in the manner in which clinicians assess tremor, objective quantitative tools such as electromyography, accelerometry, and computerized, spiral analysis can be very useful in establishing a clinical diagnosis and in research settings. In this review, we discuss the various methods of quantitative tremor analysis and the classification and pathogenesis of tremor. The most common pathologic tremors and an approach to the diagnosis of tremor etiology are described. Pathologic tremors are common, and the diagnosis of underlying etiology is not always straightforward. Computerized quantitative tremor analysis is a valuable adjunct to careful clinical evaluation in distinguishing tremulous diseases from physiologic tremors, and can also help shed light on their pathogenesis.
    Tremor and other hyperkinetic movements (New York, N.Y.). 01/2012; 2.
  • Neurology 10/2011; 77(15):e88-92. · 8.25 Impact Factor
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    Parkinsonism & Related Disorders 03/2010; 16(3):233-4. · 3.27 Impact Factor
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    ABSTRACT: 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.
    Clinical neurology and neurosurgery 11/2009; 112(2):149-52. · 1.30 Impact Factor
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    ABSTRACT: 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/s2, 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. © 2009 Movement Disorder Society
    Movement Disorders 10/2009; 24(13):1984 - 1990. · 4.56 Impact Factor
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    ABSTRACT: 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.
    Journal of Clinical Neuroscience 04/2009; 16(6):771-8; discussion 779. · 1.25 Impact Factor
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    ABSTRACT: To investigate transcranial magnetic stimulation (TMS) measures as clinical correlates and longitudinal markers of amyotrophic lateral sclerosis (ALS). 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. 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. 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.
    Neurology 03/2009; 72(6):498-504. · 8.25 Impact Factor
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    ABSTRACT: 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.
    Supplements to Clinical neurophysiology 01/2009; 60:153-62.
  • The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 10/2008; 35(4):513-5. · 1.33 Impact Factor
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    ABSTRACT: 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.
    Journal of Neuroscience Methods 07/2008; 171(2):264-70. · 2.11 Impact Factor
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    Anna M Conti, Seth Pullman, Steven J Frucht
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    ABSTRACT: 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.
    Movement Disorders 05/2008; 23(10):1398-406. · 4.56 Impact Factor
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    ABSTRACT: 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. © 2007 Movement Disorder Society
    Movement Disorders 03/2008; 23(4):531 - 537. · 4.56 Impact Factor
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    M M Kurtis, A G Floyd, Q P Yu, S L Pullman
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    ABSTRACT: Involuntary up-going toe can be a disabling consequence of dystonia or spasticity. In this study, we treated eight patients with botulinum toxin (BTx) in the extensor hallucis longus (EHL) and applied objective and subjective outcome measures to determine treatment efficacy. Using 100% higher doses than generally reported, patients noted 62+/-20% mean benefit and scores on a modified Fahn-Marsden Dystonia Scale decreased significantly by 1.8+/-0.6 (p=0.010). High doses (up to 160 BTx A units) into the EHL were safe and dosage correlated highly and significantly with treatment efficacy (rho=0.859, p=0.006).
    Journal of the Neurological Sciences 02/2008; 264(1-2):118-20. · 2.24 Impact Factor
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    ABSTRACT: To provide the first descriptive analysis of upper limb motor physiology in Niemann-Pick Type C disease (NP-C). Fifteen patients with confirmed NP-C underwent motor physiology testing using accelerometry and surface EMG (sEMG). Tremor amplitude and frequency were quantified using accelerometry, and sEMG was examined for abnormal patterns consistent with various movement disorders. Forty-seven percent of patients had postural tremor in the upper limbs, generally bilateral, with frequencies ranging from 0.3 to 3 Hz, and an average amplitude of 1.20+/-0.98 mm. Eighty-seven percent of patients had bilateral action tremor with frequencies ranging from 2.0 to 3.7 Hz, and an average amplitude of 5.25+/-3.76 mm. sEMG revealed long but variable duration, variable amplitude muscle burst discharges during action in some patients, as well as short high frequency irregularly timed bursts in others. Accelerometric findings correlated with the clinical findings were most consistent with cerebellar outflow tremors. sEMG revealed a mix of dystonic, myoclonic and choreiform movements. These quantitative methods may serve as ancillary measures of disease pathophysiology, markers of change over time, and methods to evaluate efficacy, and side effects, of new treatments as they are developed.
    Clinical Neurophysiology 06/2007; 118(5):1010-8. · 3.14 Impact Factor
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    ABSTRACT: To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS. We prospectively studied 64 patients with ALS and its subsets using clinical measures, proton MR spectroscopic imaging ((1)H MRSI), diffusion tensor imaging, transcranial magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and every 3 months for 15 months and compared them with control subjects. (1)H MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration were markedly reduced in ALS (p = 0.009) and all UMN syndromes combined (ALS, familial ALS [fALS], and primary lateral sclerosis; p = 0.03) vs control values. Central motor conduction time to the tibialis anterior was prolonged in ALS (p < 0.0005) and combined UMN syndromes (p = 0.001). MUNE was lower in ALS (p < 0.0005) and all LMN syndromes combined (ALS, fALS, and progressive muscular atrophy; p = 0.001) vs controls. All objective markers correlated well with the ALS Functional Rating Scale-Revised, finger and foot tapping, and strength testing, suggesting these markers related to disease activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging markers changed more slowly and did not significantly differ from baseline. (1)H MR spectroscopic imaging measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration and ratio of NAA to creatine, central motor conduction time to the tibialis anterior, and motor unit number estimation significantly differed between ALS, its subsets, and control subjects, suggesting they have potential to provide insight into the pathobiology of these disorders.
    Neurology 04/2007; 68(17):1402-10. · 8.25 Impact Factor
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    ABSTRACT: Patients with medically refractory Parkinson's disease (PD) obtain significant clinical benefit from subthalamic nucleus (STN) stimulation. The degree to which a successful outcome relates to the anatomic location of the stimulating electrode has not yet been clearly established. Many studies have attempted to correlate the clinical result with the electrode location using postoperative magnetic resonance imaging (MRI) and there have been a few that used autopsy-determined locations. In this report, we describe long-term clinical follow-up in a patient with autopsy-determined electrode tip anatomic location. A 67-year-old patient with a 27-year history of idiopathic PD complicated by disabling motor fluctuations and dopaminergic dyskinesias underwent bilateral STN deep brain stimulation (DBS). He was prospectively followed in a long-term clinical protocol until his death 40 months after electrode placement. Postoperative magnetic resonance (MR) imaging and postmortem studies of this patient's brain were performed to localize DBS tip locations. STN stimulation produced improvement of the patient's motor fluctuations, dyskinesias and clinical motor performance, especially appendicular tremors, rigidity and bradykinesia. MRI showed the electrode tips to be within 2 mm of the intended target. Postmortem brain analysis identified the right DBS tip location at the dorsomedial edge of the STN, with the left electrode in the vicinity (but not within) the STN. Chronic DBS elicited minor reactive changes were confined to the immediate vicinity of the electrode tracks. The pathological analysis demonstrated numerous cortical Lewy bodies and degenerative encephalopathy, establishing the diagnosis of transitional type diffuse Lewy body disease (DLBD) rather than simple PD. This patient obtained clinical benefit from STN stimulation typical of that seen for most PD patients. Both the MR analysis and the autopsy demonstrated electrode placement at or outside the boundaries of the STN, suggesting that that clinical efficacy may not depend on electrode location within the central region of the STN.
    Clinical neuropathology 01/2007; 26(6):267-75. · 1.34 Impact Factor

Publication Stats

2k Citations
324.72 Total Impact Points

Institutions

  • 1994–2012
    • Columbia University
      • • College of Physicians and Surgeons
      • • Department of Neurology
      • • Center for Neurobiology and Behavior
      New York City, NY, United States
  • 2009
    • Weill Cornell Medical College
      New York City, New York, United States
    • University of Minnesota Twin Cities
      • Department of Neurosurgery
      Minneapolis, MN, United States
  • 1991–2009
    • CUNY Graduate Center
      New York City, New York, United States
  • 2005–2008
    • Barrow Neurological Institute
      • Department of Neurology
      Phoenix, AZ, United States
    • Devry College of New York, USA
      New York City, New York, United States
  • 2004
    • New York Presbyterian Hospital
      New York City, New York, United States
    • Rush University Medical Center
      • Department of Neurological Sciences
      Chicago, IL, United States
  • 2000
    • American Academy of Neurology
      Saint Paul, Minnesota, United States
  • 1999
    • University of Cincinnati
      • Department of Neurology
      Cincinnati, OH, United States