Casey H. Halpern, MD

All Publications

• Laser interstitial thermal therapy (LITT): Seizure outcomes for refractory mesial temporal lobe epilepsy. Epilepsy & behavior : E&B Le, S., Ho, A. L., Fisher, R. S., Miller, K. J., Henderson, J. M., Grant, G. A., Meador, K. J., Halpern, C. H. 2018; 89: 37–41

  Abstract

  BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive alternative with less cognitive risks compared with traditional surgery for focal drug-resistant epilepsy.OBJECTIVE: We describe seizure outcomes and complications after LITT in our cohort with intractable mesial temporal lobe epilepsy (MTLE).MATERIAL AND METHODS: We prospectively tracked Stanford's MTLE cases treated with LITT from October 2014 to October 2017. Primary endpoints were seizure outcomes by (1) Engel classification and (2) reduction in baseline seizure frequency. Secondary outcomes were postablation complications.RESULTS: A total of 30 patients underwent selective amygdalohippocampotomy via LITT. Mesial temporal sclerosis (MTS) was present in 23/30 (77%) patients. Median follow-up was 18 ± 12 months (range: 6-44 months). Almost all 28/29 (97%) patients had >50% reduction, and 22/29 (76%) patients had >90% reduction in seizure frequency. Engel Class I outcome was achieved in 18/29 (62%) patients; with complete seizure freedom in 9/29 (31%) patients (Engel Class IA). Three (10%) patients have had only focal aware seizures (Engel Class 1B). Seizures only occurred with medication withdrawal in 6/29 (21%) patients (Engel Class ID). Class II was achieved by 6/29 (21%) and Class III by 5/29 (17%) patients. Complications included perioperative seizures in 10/29 (34%) and nonseizure complaints in 6/29 (21%) patients. Three (10%) patients had neurological deficits including one permanent superior quadrantanopsia, one transient trochlear, and one transient oculomotor nerve palsy.CONCLUSIONS: Overall, Engel Class I outcome was achieved in 62% of patients with MTLE, and 97% of patients achieved >50% seizure frequency reduction. Complications were largely temporary, though there was one persistent visual field deficit. Laser ablation is well-tolerated and offers marked seizure reduction for the majority of patients.

  View details for DOI 10.1016/j.yebeh.2018.09.040

  View details for PubMedID 30384097

• Deep Brain Stimulation for Chronic Cluster Headache: A Review. Neuromodulation : journal of the International Neuromodulation Society Vyas, D. B., Ho, A. L., Dadey, D. Y., Pendharkar, A. V., Sussman, E. S., Cowan, R., Halpern, C. H. 2018

  Abstract

  OBJECTIVES: Cluster headaches are a set of episodic and chronic pain syndromes that are sources of significant morbidity for patients. The standard of care for cluster headaches remains medication therapy, however a minority of patients will remain refractory to treatment despite changes to dosage and therapeutic combinations. In these patients, functional neuromodulation using Deep Brain Stimulation (DBS) presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.MATERIAL AND METHODS: We review the literature on chronic cluster headache, including the growing number of DBS case reports and series that describe the alleviation of pain in a majority of patients through conventional or endoventricular targeting of the posterior hypothalamus and ventral tegmental area, with a minimal side effect profile.RESULTS: In this review, the history and outcomes of DBS use for medication-refractory cluster headaches are examined, with discussion on future directions for improving this novel treatment modality and providing efficacious, longer-lasting pain relief in headache patients.CONCLUSION: In patients with chronic cluster headache, functional neuromodulation using DBS presents the opportunity to alleviate the significant pain that is experienced by targeting the neurophysiological substrates that mediate pain.

  View details for DOI 10.1111/ner.12869

  View details for PubMedID 30303584

• Robot-guided pediatric stereoelectroencephalography: single-institution experience. Journal of neurosurgery. Pediatrics Ho, A. L., Muftuoglu, Y., Pendharkar, A. V., Sussman, E. S., Porter, B. E., Halpern, C. H., Grant, G. A. 2018: 1–8

  Abstract

  OBJECTIVE Stereoelectroencephalography (SEEG) has increased in popularity for localization of epileptogenic zones in drug-resistant epilepsy because safety, accuracy, and efficacy have been well established in both adult and pediatric populations. Development of robot-guidance technology has greatly enhanced the efficiency of this procedure, without sacrificing safety or precision. To date there have been very limited reports of the use of this new technology in children. The authors present their initial experience using the ROSA platform for robot-guided SEEG in a pediatric population. METHODS Between February 2016 and October 2017, 20 consecutive patients underwent robot-guided SEEG with the ROSA robotic guidance platform as part of ongoing seizure localization and workup for medically refractory epilepsy of several different etiologies. Medical and surgical history, imaging and trajectory plans, as well as operative records were analyzed retrospectively for surgical accuracy, efficiency, safety, and epilepsy outcomes. RESULTS A total of 222 leads were placed in 20 patients, with an average of 11.1 leads per patient. The mean total case time (± SD) was 297.95 (± 52.96) minutes and the mean operating time per lead was 10.98 minutes/lead, with improvements in total (33.36 minutes/lead vs 21.76 minutes/lead) and operative (13.84 minutes/lead vs 7.06 minutes/lead) case times/lead over the course of the study. The mean radial error was 1.75 (± 0.94 mm). Clinically useful data were obtained from SEEG in 95% of cases, and epilepsy surgery was indicated and performed in 95% of patients. In patients who underwent definitive epilepsy surgery with at least a 3-month follow-up, 50% achieved an Engel class I result (seizure freedom). There were no postoperative complications associated with SEEG placement and monitoring. CONCLUSIONS In this study, the authors demonstrate that rapid adoption of robot-guided SEEG is possible even at a SEEG-naive institution, with minimal learning curve. Use of robot guidance for SEEG can lead to significantly decreased operating times while maintaining safety, the overall goals of identification of epileptogenic zones, and improved epilepsy outcomes.

  View details for DOI 10.3171/2018.5.PEDS17718

  View details for PubMedID 30117789

• The nucleus accumbens and alcoholism: a target for deep brain stimulation NEUROSURGICAL FOCUS Ho, A. L., Salib, A. N., Pendharkar, A., Sussman, E. S., Giardino, W. J., Halpern, C. H. 2018; 45 (2): E12

  Abstract

  Alcohol use disorder (AUD) is a difficult to treat condition with a significant global public health and cost burden. The nucleus accumbens (NAc) has been implicated in AUD and identified as an ideal target for deep brain stimulation (DBS). There are promising preclinical animal studies of DBS for alcohol consumption as well as some initial human clinical studies that have shown some promise at reducing alcohol-related cravings and, in some instances, achieving long-term abstinence. In this review, the authors discuss the evidence and concepts supporting the role of the NAc in AUD, summarize the findings from published NAc DBS studies in animal models and humans, and consider the challenges and propose future directions for neuromodulation of the NAc for the treatment of AUD.

  View details for DOI 10.3171/2018.5.FOCUS18157

  View details for Web of Science ID 000440488900012

  View details for PubMedID 30064314

• Validity and Reliability of a Virtual Reality Game in Evaluating the Projected Frontal Plane Knee Angle When Landing From a Drop Vertical Jump. Journal of sport rehabilitation Mills, K., Idris, A., Pham, T., Porte, J., Wiggins, M., Kavakli, M. 2018: 1–5

  Abstract

  OBJECTIVES: To determine the validity and reliability of the peak frontal plane knee angle evaluated by a virtual reality (VR) netball game when landing from a drop vertical jump.STUDY DESIGN: Laboratory.METHODS: Forty participants performed 3 drop vertical jumps evaluated by 3-dimensional motion analysis and 3 drop vertical jumps evaluated by the VR game. Limits of agreement for the peak projected frontal plane knee angle and peak knee abduction were determined. Participants were given a consensus category of "above threshold" or "below threshold" based on a prespecified threshold angle of 9° during landing. Classification agreement was determined using kappa coefficient, and accuracy was determined using specificity and sensitivity. Ten participants returned 1 week later to determine intrarater reliability, standard error of the measure, and typical error.RESULTS: The mean difference in detected frontal plane knee angle was 3.39° (95% confidence interval [CI], 1.03° to 5.74°). Limits of agreement were -10.27° (95% CI, -14.36° to -6.19°) to 17.05° (95% CI, 12.97° to 21.14°). Substantial agreement, specificity, and sensitivity were observed for the threshold classification (kappa=.66; 95% CI, .42 to .88; specificity=0.96; 95% CI, 0.78 to 1.0; and sensitivity=0.75; 95% CI, 0.43 to 0.95). The game exhibited acceptable reliability over time (intraclass correlation coefficient, ICC3,1=.844), and error was approximately 2°.CONCLUSION: The VR game reliably evaluated a projected frontal plane knee angle. Although the knee angle detected by the VR game is strongly related to peak knee abduction, the accuracy of detecting the exact angle was limited. A threshold approach may be a more accurate approach for gaming technology to evaluate frontal plane knee angles when landing from a jump.

  View details for DOI 10.1123/jsr.2017-0264

  View details for PubMedID 29252092

• Frameless stereotactic dual lead placement through single burr hole: A technical report. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Cartmell, S. C., Miller, K. J., Ho, A. L., Halpern, C. H. 2018

  Abstract

  Deep Brain Stimulation (DBS) surgery is a neurosurgical procedure involving the placement of stimulatory leads in subcortical structures. Rarely, DBS requires placement of dual ipsilateral leads. Previously, techniques for placing dual ipsilateral leads through a single burr hole were reported using a traditional stereotactic frame. Here, we demonstrate that dual ipsilateral leads can be safely and effectively placed through a single burr hole using a frameless stereotactic DBS system (NexFrame) with only simple modifications to existing equipment.

  View details for DOI 10.1016/j.jocn.2018.06.053

  View details for PubMedID 30007524

• Cognitive safety of intracranial electrodes for epilepsy. Epilepsia Meador, K. J., Halpern, C. H., Hermann, B. P. 2018; 59 (6): 1132–37

  Abstract

  Two recent articles in Epilepsia have raised concerns about adverse cognitive effects associated with intracranial electrode implantation. However, both studies have important limitations, and their results contrast with studies that report no adverse cognitive effects of intracranial electrodes for diagnosis or neurostimulation in epilepsy. Furthermore, no data are provided on the relative safety of depth electrodes implanted along the longitudinal axis of the hippocampus vs other electrode locations or types of electrodes. Instituting changes in the use of depth electrodes based solely on these 2 studies is not clinically indicated. Further research is needed.

  View details for DOI 10.1111/epi.14197

  View details for PubMedID 29771452

• Neuromodulatory Treatments for Alcohol Use Disorder: A Review. Brain sciences Salib, A. N., Ho, A. L., Sussman, E. S., Pendharkar, A. V., Halpern, C. H. 2018; 8 (6)

  Abstract

  Alcohol use disorder (AUD) is a prevalent condition characterized by chronic alcohol-seeking behaviors and has become a significant economic burden with global ramifications on public health. While numerous treatment options are available for AUD, many are unable to sustain long-term sobriety. The nucleus accumbens (NAcc) upholds an integral role in mediating reward behavior and has been implicated as a potential target for deep brain stimulation (DBS) in the context of AUD. DBS is empirically thought to disrupt pathological neuronal synchrony, a hallmark of binge behavior. Pre-clinical animal models and pilot human clinical studies utilizing DBS for the treatment of AUD have shown promise for reducing alcohol-related cravings and prolonging abstinence. In this review, we outline the various interventions available for AUD, and the translational potential DBS has to modulate functionality of the NAcc as a treatment for AUD.

  View details for DOI 10.3390/brainsci8060095

  View details for PubMedID 29843426

• Improved operative efficiency using a real-time MRI-guided stereotactic platform for laser amygdalohippocampotomy JOURNAL OF NEUROSURGERY Ho, A. L., Sussman, E. S., Pendharkar, A. V., Le, S., Mantovani, A., Keebaugh, A. C., Drover, D. R., Grant, G. A., Wintermark, M., Halpern, C. H. 2018; 128 (4): 1165–72

  Abstract

  OBJECTIVE MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive method for thermal destruction of benign or malignant tissue that has been used for selective amygdalohippocampal ablation for the treatment of temporal lobe epilepsy. The authors report their initial experience adopting a real-time MRI-guided stereotactic platform that allows for completion of the entire procedure in the MRI suite. METHODS Between October 2014 and May 2016, 17 patients with mesial temporal sclerosis were selected by a multidisciplinary epilepsy board to undergo a selective amygdalohippocampal ablation for temporal lobe epilepsy using MRgLITT. The first 9 patients underwent standard laser ablation in 2 phases (operating room [OR] and MRI suite), whereas the next 8 patients underwent laser ablation entirely in the MRI suite with the ClearPoint platform. A checklist specific to the real-time MRI-guided laser amydalohippocampal ablation was developed and used for each case. For both cohorts, clinical and operative information, including average case times and accuracy data, was collected and analyzed. RESULTS There was a learning curve associated with using this real-time MRI-guided system. However, operative times decreased in a linear fashion, as did total anesthesia time. In fact, the total mean patient procedure time was less in the MRI cohort (362.8 ± 86.6 minutes) than in the OR cohort (456.9 ± 80.7 minutes). The mean anesthesia time was significantly shorter in the MRI cohort (327.2 ± 79.9 minutes) than in the OR cohort (435.8 ± 78.4 minutes, p = 0.02). CONCLUSIONS The real-time MRI platform for MRgLITT can be adopted in an expedient manner. Completion of MRgLITT entirely in the MRI suite may lead to significant advantages in procedural times.

  View details for DOI 10.3171/2017.1.JNS162046

  View details for Web of Science ID 000429045500258

  View details for PubMedID 28665249

• Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man. Proceedings of the National Academy of Sciences of the United States of America Wu, H., Miller, K. J., Blumenfeld, Z., Williams, N. R., Ravikumar, V. K., Lee, K. E., Kakusa, B., Sacchet, M. D., Wintermark, M., Christoffel, D. J., Rutt, B. K., Bronte-Stewart, H., Knutson, B., Malenka, R. C., Halpern, C. H. 2018; 115 (1): 192–97

  Abstract

  Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

  View details for DOI 10.1073/pnas.1712214114

  View details for PubMedID 29255043

  View details for PubMedCentralID PMC5776799

• Hair sparing does not compromise real-time magnetic resonance imaging guided stereotactic laser fiber placement for temporal lobe epilepsy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Singh, S., Kumar, K. K., Rabon, M. J., Dolce, D., Halpern, C. H. 2018; 52: 71–73

  Abstract

  Pre-operative scalp shaving is conventionally thought to simplify postoperative cranial wound care, lower the rate of wound infections, and ease optimal incision localization. Over the past few decades, some neurosurgeons have refrained from scalp shaving in order to improve patient satisfaction with brain surgery. However, this hair-sparing approach has not yet been explored in the growing field of magnetic resonance-guided laser interstitial thermal therapy (MRgLITT). This study investigated the initial impact of a no-shave technique on post-operative wound infection rate as well as on entry and target accuracy in MRgLITT for mesial temporal epilepsy. Eighteen patients selected by the Stanford Comprehensive Epilepsy Program between November 2015 and August 2017 were included in the study. All patients underwent functional selective amygdalohippocampotomies using MRgLITT entirely within a diagnostic MRI suite. No hair was removed and no additional precautions were taken for hair or scalp care. Otherwise, routine protocols for surgical preparations and wound closure were followed. The study was performed under approval from Stanford University's Internal Review Board (IRB-37830). No post-operative wound infections or erosions occurred for any patient. The mean entry point error was 2.87 ± 1.3 mm and the mean target error was 1.0 ± 0.9 mm. There have been no other complications associated with this hair-sparing approach. The study's results suggest that hair sparing in MRgLITT surgery for temporal epilepsy does not increase the risk of wound complications or compromise accuracy. This preferred cosmetic approach may thus appeal to epilepsy patients considering such interventions.

  View details for DOI 10.1016/j.jocn.2018.03.022

  View details for PubMedID 29602604

• Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. NeuroImage. Clinical Tian, Q., Wintermark, M., Jeffrey Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K. B., McNab, J. A. 2018; 19: 572–80

  Abstract

  Purpose: To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methods: Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.Results: The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = -0.929, -0.75, -0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = -0.719, -0.976, -0.707, -0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).Conclusion: Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

  View details for DOI 10.1016/j.nicl.2018.05.010

  View details for PubMedID 29984165

• Letter: Electric Beats Open New Frontiers for Deep Brain Stimulation NEUROSURGERY Halpern, C. H., Miller, K. J., Wu, H., Tass, P. A. 2018; 82 (1): E19–E20

  View details for DOI 10.1093/neuros/nyx482

  View details for Web of Science ID 000424223500008

• Novel application of virtual reality in patient engagement for deep brain stimulation: A pilot study. Brain stimulation Collins, M. K., Ding, V. Y., Ball, R. L., Dolce, D. L., Henderson, J. M., Halpern, C. H. 2018

  View details for DOI 10.1016/j.brs.2018.03.012

  View details for PubMedID 29631869

• Awake versus asleep deep brain stimulation for Parkinson's disease: a critical comparison and meta-analysis. Journal of neurology, neurosurgery, and psychiatry Ho, A. L., Ali, R., Connolly, I. D., Henderson, J. M., Dhall, R., Stein, S. C., Halpern, C. H. 2017

  Abstract

  No definitive comparative studies of the efficacy of 'awake' deep brain stimulation (DBS) for Parkinson's disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques.We conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up. There were 145 studies, 16 of which were under general anaesthesia. Data were pooled using an inverse-variance weighted, random effects meta-analytic model for observational data.There was no significant difference in mean target error between local and general anaesthesia, but there was a significantly less mean number of DBS lead passes with general anaesthesia (p=0.006). There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia (p<0.001). There were no significant differences in Unified Parkinson's Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, p=0.022).Our meta-analysis demonstrates that while DBS under general anaesthesia may lead to lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS or prefer the asleep alternative.

  View details for DOI 10.1136/jnnp-2016-314500

  View details for PubMedID 28250028

• Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network NATURE NEUROSCIENCE Polepalli, J. S., Wu, H., Goswami, D., Halpern, C. H., Sudhof, T. C., Malenka, R. C. 2017; 20 (2): 219-229

  Abstract

  Hippocampal network activity is generated by a complex interplay between excitatory pyramidal cells and inhibitory interneurons. Although much is known about the molecular properties of excitatory synapses on pyramidal cells, comparatively little is known about excitatory synapses on interneurons. Here we show that conditional deletion of the postsynaptic cell adhesion molecule neuroligin-3 in parvalbumin interneurons causes a decrease in NMDA-receptor-mediated postsynaptic currents and an increase in presynaptic glutamate release probability by selectively impairing the inhibition of glutamate release by presynaptic Group III metabotropic glutamate receptors. As a result, the neuroligin-3 deletion altered network activity by reducing gamma oscillations and sharp wave ripples, changes associated with a decrease in extinction of contextual fear memories. These results demonstrate that neuroligin-3 specifies the properties of excitatory synapses on parvalbumin-containing interneurons by a retrograde trans-synaptic mechanism and suggest a molecular pathway whereby neuroligin-3 mutations contribute to neuropsychiatric disorders.

  View details for DOI 10.1038/nn.4471

  View details for Web of Science ID 000393271000016

  View details for PubMedID 28067903

  View details for PubMedCentralID PMC5272845

• Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. Journal of magnetic resonance imaging : JMRI Federau, C., Goubran, M., Rosenberg, J., Henderson, J., Halpern, C. H., Santini, V., Wintermark, M., Butts Pauly, K., Ghanouni, P. 2017

  Abstract

  Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor.To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor.Retrospective.Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T.T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T.An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year.Statistical significance was assessed using the Wilcoxon two-tailed rank test.The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure.In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS.1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

  View details for DOI 10.1002/jmri.25878

  View details for PubMedID 29076274

• Laser interstitial thermal therapy for the treatment of epilepsy: evidence to date NEUROPSYCHIATRIC DISEASE AND TREATMENT Shukla, N. D., Ho, A. L., Pendharkar, A. V., Sussman, E. S., Halpern, C. H. 2017; 13: 2469–75

  Abstract

  Medically intractable epilepsy is associated with increased morbidity and mortality. For those with focal epilepsy and correlated electrophysiological or radiographic features, open surgical resection can achieve high rates of seizure control, but can be associated with neurologic deficits and cognitive effects. Recent innovations have allowed for more minimally invasive methods of surgical seizure control such as magnetic resonance-guided laser interstitial therapy (MRgLITT). MRgLITT achieves the goal of ablating seizure foci while preserving neuropsycho-logical function and offering real-time feedback and monitoring of tissue ablation. This review summarizes the utilization of MRgLITT for mesial temporal lobe epilepsy and other seizure disorders. Overall, the efficacy of MRgLITT is comparable to that of open surgery and offers a less invasive approach in patients with significantly less morbidity.

  View details for DOI 10.2147/NDT.S139544

  View details for Web of Science ID 000411676000001

  View details for PubMedID 29026310

  View details for PubMedCentralID PMC5627747

• Vocal Tremor: Novel Therapeutic Target for Deep Brain Stimulation. Brain sciences Ravikumar, V. K., Ho, A. L., Parker, J. J., Erickson-DiRenzo, E., Halpern, C. H. 2016; 6 (4)

  Abstract

  Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT). Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life. Traditional EVT treatments have demonstrated limited success in long-term management of symptoms. However, voice tremor has been noted to decrease in patients receiving deep brain stimulation (DBS) with the targeting of thalamic nuclei. In this study, we describe our multidisciplinary procedure for awake, frameless DBS with optimal stimulation targets as well as acoustic analysis and laryngoscopic assessment to quantify tremor reduction. Finally, we investigate the most recent clinical evidence regarding the procedure.

  View details for PubMedID 27735866

  View details for PubMedCentralID PMC5187562

• Predicting variation in subject thermal response during transcranial magnetic resonance guided focused ultrasound surgery: Comparison in seventeen subject datasets. Medical physics Vyas, U., Ghanouni, P., Halpern, C. H., Elias, J., Pauly, K. B. 2016; 43 (9): 5170-?

  Abstract

  In transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) treatments, the acoustic and spatial heterogeneity of the skull cause reflection, absorption, and scattering of the acoustic beams. These effects depend on skull-specific parameters and can lead to patient-specific thermal responses to the same transducer power. In this work, the authors develop a simulation tool to help predict these different experimental responses using 3D heterogeneous tissue models based on the subject CT images. The authors then validate and compare the predicted skull efficiencies to an experimental metric based on the subject thermal responses during tcMRgFUS treatments in a dataset of seventeen human subjects.Seventeen human head CT scans were used to create tissue acoustic models, simulating the effects of reflection, absorption, and scattering of the acoustic beam as it propagates through a heterogeneous skull. The hybrid angular spectrum technique was used to model the acoustic beam propagation of the InSightec ExAblate 4000 head transducer for each subject, yielding maps of the specific absorption rate (SAR). The simulation assumed the transducer was geometrically focused to the thalamus of each subject, and the focal SAR at the target was used as a measure of the simulated skull efficiency. Experimental skull efficiency for each subject was calculated using the thermal temperature maps from the tcMRgFUS treatments. Axial temperature images (with no artifacts) were reconstructed with a single baseline, corrected using a referenceless algorithm. The experimental skull efficiency was calculated by dividing the reconstructed temperature rise 8.8 s after sonication by the applied acoustic power.The simulated skull efficiency using individual-specific heterogeneous models predicts well (R(2) = 0.84) the experimental energy efficiency.This paper presents a simulation model to predict the variation in thermal responses measured in clinical ctMRGFYS treatments while being computationally feasible.

  View details for DOI 10.1118/1.4955436

  View details for PubMedID 27587047

• A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. New England journal of medicine Elias, W. J., Lipsman, N., Ondo, W. G., Ghanouni, P., Kim, Y. G., Lee, W., Schwartz, M., Hynynen, K., Lozano, A. M., Shah, B. B., Huss, D., Dallapiazza, R. F., Gwinn, R., Witt, J., Ro, S., Eisenberg, H. M., Fishman, P. S., Gandhi, D., Halpern, C. H., Chuang, R., Butts Pauly, K., Tierney, T. S., Hayes, M. T., Cosgrove, G. R., Yamaguchi, T., Abe, K., Taira, T., Chang, J. W. 2016; 375 (8): 730-739

  Abstract

  Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

  View details for DOI 10.1056/NEJMoa1600159

  View details for PubMedID 27557301

• Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences CELL Ye, L., Allen, W. E., Thompson, K. R., Tian, Q., Hsueh, B., Ramakrishnan, C., Wang, A., Jennings, J. H., Adhikari, A., Halpern, C. H., Witten, I. B., Barth, A. L., Luo, L., McNab, J. A., Deisseroth, K. 2016; 165 (7): 1776-1788

  Abstract

  A major challenge in understanding the cellular diversity of the brain has been linking activity during behavior with standard cellular typology. For example, it has not been possible to determine whether principal neurons in prefrontal cortex active during distinct experiences represent separable cell types, and it is not known whether these differentially active cells exert distinct causal influences on behavior. Here, we develop quantitative hydrogel-based technologies to connect activity in cells reporting on behavioral experience with measures for both brain-wide wiring and molecular phenotype. We find that positive and negative-valence experiences in prefrontal cortex are represented by cell populations that differ in their causal impact on behavior, long-range wiring, and gene expression profiles, with the major discriminant being expression of the adaptation-linked gene NPAS4. These findings illuminate cellular logic of prefrontal cortex information processing and natural adaptive behavior and may point the way to cell-type-specific understanding and treatment of disease-associated states.

  View details for DOI 10.1016/j.cell.2016.05.010

  View details for Web of Science ID 000378062000026

  View details for PubMedID 27238022

• Long-term quality of life after posterior cervical foraminotomy for radiculopathy. Clinical neurology and neurosurgery Faught, R. W., Church, E. W., Halpern, C. H., Balmuri, U., Attiah, M. A., Stein, S. C., Dante, S. J., Welch, W. C., Simeone, F. A. 2016; 142: 22-25

  Abstract

  Cervical radiculopathy may cause symptoms and loss of function that can lead to a significant reduction in health related quality of life (HRQOL). As part of a comprehensive review of long-term outcomes, we examined HRQOL in a large cohort of patients undergoing posterior cervical foraminotomy (FOR) for radiculopathy.338 patients who underwent FOR between 1990 and 2009 participated in a telephone interview designed to measure symptomatic and functional improvements following surgery. We also administered the EQ-5D, a standardized tool for assessing HRQOL. We analyzed this data for associations between patient and treatment characteristics, improvements in symptoms and function, and HRQOL as measured by the EQ-5D.Mean follow-up was 10.0 years. The average EQ-5D at follow-up was 0.81±0.18, and improvements in pain, weakness and function as well as ability to return to work correlated with improved EQ-5D score (p<0.0001). There was no correlation between length of follow-up and EQ-5D score (p=0.980). Additionally, there was no difference between mean EQ-5D score for soft disc versus osteophyte pathology (0.84 versus 0.81, p=0.21).These data provide evidence that FOR for cervical radiculopathy is associated with improved HRQOL at long-term follow-up. The lack of correlation between length of follow-up and HRQOL suggests that FOR is a durable treatment option. Moreover, FOR is associated with improved HRQOL whether radiculopathy is due to soft disc or osteophyte pathology.

  View details for DOI 10.1016/j.clineuro.2016.01.013

  View details for PubMedID 26802616

• Long-term quality of life after posterior cervical foraminotomy for radiculopathy CLINICAL NEUROLOGY AND NEUROSURGERY Faught, R. W., Church, E. W., Halpern, C. H., Balmuri, U., Attiah, M. A., Stein, S. C., Dante, S. J., Welch, W. C., Simeone, F. A. 2016; 142: 22-25

  Abstract

  Cervical radiculopathy may cause symptoms and loss of function that can lead to a significant reduction in health related quality of life (HRQOL). As part of a comprehensive review of long-term outcomes, we examined HRQOL in a large cohort of patients undergoing posterior cervical foraminotomy (FOR) for radiculopathy.338 patients who underwent FOR between 1990 and 2009 participated in a telephone interview designed to measure symptomatic and functional improvements following surgery. We also administered the EQ-5D, a standardized tool for assessing HRQOL. We analyzed this data for associations between patient and treatment characteristics, improvements in symptoms and function, and HRQOL as measured by the EQ-5D.Mean follow-up was 10.0 years. The average EQ-5D at follow-up was 0.81±0.18, and improvements in pain, weakness and function as well as ability to return to work correlated with improved EQ-5D score (p<0.0001). There was no correlation between length of follow-up and EQ-5D score (p=0.980). Additionally, there was no difference between mean EQ-5D score for soft disc versus osteophyte pathology (0.84 versus 0.81, p=0.21).These data provide evidence that FOR for cervical radiculopathy is associated with improved HRQOL at long-term follow-up. The lack of correlation between length of follow-up and HRQOL suggests that FOR is a durable treatment option. Moreover, FOR is associated with improved HRQOL whether radiculopathy is due to soft disc or osteophyte pathology.

  View details for DOI 10.1016/j.clineuro.2016.01.013

  View details for Web of Science ID 000372677400004

• Responsive Direct Brain Stimulation for Epilepsy. Neurosurgery clinics of North America Morrell, M. J., Halpern, C. 2016; 27 (1): 111-121

  View details for DOI 10.1016/j.nec.2015.08.012

  View details for PubMedID 26615113

• Stereotactic Bony Trajectory Preservation for Responsive Neurostimulator Lead Placement Following Depth EEG Recording. Cure¯us Miller, K., Halpern, C. H. 2016; 8 (3)

  Abstract

  Responsive neurostimulation (RNS) is rapidly gaining traction as a therapy for medically refractory epilepsy. Depth electrode placement for stimulation of a deep seizure focus may be indicated after the focus has been electrophysiologically localized using depth electroencephalography (depth EEG). We describe a simple technique whereby the bony trajectories created during initial stereotactic placement of depth EEG electrodes are preserved and reused for RNS with depth electrodes. This technique may help to improve targeting and maximize surgical efficiency.

  View details for DOI 10.7759/cureus.549

  View details for PubMedID 27158578

• Stereotactic laser ablation of the splenium for intractable epilepsy. Epilepsy & behavior case reports Ho, A. L., Miller, K. J., Cartmell, S., Inoyama, K., Fisher, R. S., Halpern, C. H. 2016; 5: 23-26

  Abstract

  Partial or complete corpus callosotomies have been applied, traditionally via open surgical or radiosurgical approaches, for the treatment of epilepsy in patients with multifocal tonic, atonic, or myoclonic seizures. Minimally invasive methods, such as MRI-guided laser interstitial thermal ablation (MTLA), are being employed to functionally remove or ablate seizure foci in the treatment of epilepsy. This therapy can achieve effectiveness similar to that of traditional resection, but with reduced morbidity compared with open surgery. Here, we present a patient with a history of prior partial corpus callosotomy who continued to suffer from medically refractory epilepsy with bisynchronous onset. We report on the utilization of laser ablation of the splenium in this patient to achieve full corpus callosotomy. Adequate ablation of the splenial remnant was confirmed by postoperative MRI imaging, and at four-month follow-up, the patient's seizure frequency had dropped more than 50%. This is the first reported instance of laser ablation of the splenium to achieve full corpus callosotomy following a previous unsuccessful anterior callosotomy in a patient with intractable generalized epilepsy.

  View details for DOI 10.1016/j.ebcr.2015.12.003

  View details for PubMedID 26955518

  View details for PubMedCentralID PMC4761694

• Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology. Neurosurgical focus Ho, A. L., Erickson-DiRenzo, E., Pendharkar, A. V., Sung, C., Halpern, C. H. 2015; 38 (6): E6-?

  Abstract

  Tremulous voice is a characteristic feature of a multitude of movement disorders, but when it occurs in individuals diagnosed with essential tremor, it is referred to as essential vocal tremor (EVT). For individuals with EVT, their tremulous voice is associated with significant social embarrassment and in severe cases may result in the discontinuation of employment and hobbies. Management of EVT is extremely difficult, and current behavioral and medical interventions for vocal tremor result in suboptimal outcomes. Deep brain stimulation (DBS) has been proposed as a potential therapeutic avenue for EVT, but few studies can be identified that have systematically examined improvements in EVT following DBS. The authors describe a case of awake bilateral DBS targeting the ventral intermediate nucleus for a patient suffering from severe voice and arm tremor. They also present their comprehensive, multidisciplinary methodology for definitive treatment of EVT via DBS. To the authors' knowledge, this is the first time comprehensive intraoperative voice evaluation has been used to guide microelectrode/stimulator placement, as well as the first time that standard pre- and post-DBS assessments have been conducted, demonstrating the efficacy of this tailored DBS approach.

  View details for DOI 10.3171/2015.3.FOCUS1537

  View details for PubMedID 26030706

• Deep brain stimulation for vocal tremor: a comprehensive, multidisciplinary methodology NEUROSURGICAL FOCUS Ho, A. L., Erickson-DiRenzo, E., Pendharkar, A. V., Sung, C., Halpern, C. H. 2015; 38 (6)

  View details for DOI 10.3171/2015.3.FOCUS1537

  View details for Web of Science ID 000355539900006

  View details for PubMedID 26030706

• Deep brain stimulation for obesity: rationale and approach to trial design NEUROSURGICAL FOCUS Ho, A. L., Sussman, E. S., Pendharkar, A. V., Azagury, D. E., Bohon, C., Halpern, C. H. 2015; 38 (6)

  Abstract

  Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

  View details for DOI 10.3171/2015.3.FOCUS1538

  View details for Web of Science ID 000355539900008

  View details for PubMedID 26030708

• Deep brain stimulation for obesity: rationale and approach to trial design. Neurosurgical focus Ho, A. L., Sussman, E. S., Pendharkar, A. V., Azagury, D. E., Bohon, C., Halpern, C. H. 2015; 38 (6): E8-?

  Abstract

  Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity.

  View details for DOI 10.3171/2015.3.FOCUS1538

  View details for PubMedID 26030708

• Deep brain stimulation for Alzheimer disease: a decision and cost-effectiveness analysis JOURNAL OF NEUROLOGY Mirsaeedi-Farahani, K., Halpern, C. H., Baltuch, G. H., Wolk, D. A., Stein, S. C. 2015; 262 (5): 1191-1197

  Abstract

  Alzheimer disease (AD) is characterized by impairments in memory function. Standard AD treatment provides marginal improvements in this domain. Recent reports, however, suggested that deep brain stimulation (DBS) may result in improved memory. Given significant equipment costs and health expenses required for DBS surgery, we determine clinical and economic thresholds required for it to be as effective as standard AD treatment. Literature review yielded annual AD progression probabilities, health-related quality of life (QoL), and costs by AD stage. Our 5-year decision analysis model compared cumulative QoL in quality-adjusted life years (QALYs) and costs of standard therapy to theoretical DBS treatment of various success rates, using known complication rates and QoL data. The base case was a patient with mild-stage AD. DBS success was defined as regression to and maintenance of minimal stage AD, which was defined as midway between mild and no dementia, for the first year, and continuation of the natural course of AD for the remaining 4 years. Compared to standard treatment alone, DBS for mild-stage AD requires a success rate of 3% to overcome effects of possible surgical complications on QoL. If DBS can be delivered with success rates above 20% ($200 K/QALY) or 74% ($50 K/QALY) for mild AD, it can be considered cost-effective. Above a success rate of 80%, DBS treatment is both clinically more effective and more cost-effective than standard treatment. Our findings demonstrate that clinical and economic thresholds required for DBS to be cost-effective for AD are relatively low.

  View details for DOI 10.1007/s00415-015-7688-5

  View details for Web of Science ID 000354950500011

  View details for PubMedID 25740662

• Deep Brain Stimulation for Obesity. Cureus Ho, A. L., Sussman, E. S., Zhang, M., Pendharkar, A. V., Azagury, D. E., Bohon, C., Halpern, C. H. 2015; 7 (3)

  Abstract

  Obesity is now the third leading cause of preventable death in the US, accounting for 216,000 deaths annually and nearly 100 billion dollars in health care costs. Despite advancements in bariatric surgery, substantial weight regain and recurrence of the associated metabolic syndrome still occurs in almost 20-35% of patients over the long-term, necessitating the development of novel therapies. Our continually expanding knowledge of the neuroanatomic and neuropsychiatric underpinnings of obesity has led to increased interest in neuromodulation as a new treatment for obesity refractory to current medical, behavioral, and surgical therapies. Recent clinical trials of deep brain stimulation (DBS) in chronic cluster headache, Alzheimer's disease, and depression and obsessive-compulsive disorder have demonstrated the safety and efficacy of targeting the hypothalamus and reward circuitry of the brain with electrical stimulation, and thus provide the basis for a neuromodulatory approach to treatment-refractory obesity. In this study, we review the literature implicating these targets for DBS in the neural circuitry of obesity. We will also briefly review ethical considerations for such an intervention, and discuss genetic secondary-obesity syndromes that may also benefit from DBS. In short, we hope to provide the scientific foundation to justify trials of DBS for the treatment of obesity targeting these specific regions of the brain.

  View details for DOI 10.7759/cureus.259

  View details for PubMedID 26180683

  View details for PubMedCentralID PMC4494510

• Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report. Cureus Ho, A. L., Choudhri, O., Sung, C. K., DiRenzo, E. E., Halpern, C. H. 2015; 7 (3)

  Abstract

  Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS).

  View details for DOI 10.7759/cureus.256

  View details for PubMedID 26180680

• Brief Pain Inventory-Facial minimum clinically important difference JOURNAL OF NEUROSURGERY Sandhu, S. K., Halpern, C. H., Vakhshori, V., Mirsaeedi-Farahani, K., Farrar, J. T., Lee, J. Y. 2015; 122 (1): 180-190

  Abstract

  Neurosurgeons are frequently the primary physicians measuring pain relief in patients with trigeminal neuralgia (TN). Unfortunately, the measurement of pain can be complex. The Brief Pain Inventory-Facial (BPI-Facial) is a reliable and validated multidimensional tool that consists of 18 questions. It measures 3 domains of pain: 1) pain intensity (worst and average pain intensity), 2) interference with general activities of daily living (ADL), and 3) face-specific pain interference. The objective of this paper is to determine the patient-reported minimum clinically important difference (MCID) using the BPI-Facial.The authors conducted a retrospective study of 234 patients with TN seen in a single neurosurgeon's office. Patients completed baseline and 1-month follow-up BPI-Facial questionnaires. The MCID was calculated using an anchor-based approach in which the defined anchor was the 7-point patient global impression of change (PGIC). Two statistical methods were employed: mean change score and optimal cutoff point.Using the mean change score method, the investigators calculated the MCID for the 3 domains of the BPIFacial: 44% and 30% improvement in pain intensity at its worst and average, respectively, 54% improvement in interference with general ADL, and 63% improvement in interference with facial ADL. Using the optimal cutoff point method, they also calculated the MCID for the 3 domains of the BPI-Facial: 57% and 28% improvement in pain intensity at its worst and average, respectively, 75% improvement in interference with general ADL, and 62% improvement in interference with facial ADL.The BPI-Facial is a multidimensional pain scale that measures 3 domains of pain. Although 2 statistical methods were used to calculate the MCID, the optimal cutoff point method was the superior one because it used data from the majority of subjects included in this study. A 57% improvement in pain intensity at its worst and a 28% improvement in pain intensity at its average were the MCIDs for patients with facial pain. A greater improvement was needed to achieve the MCID for interference with general and facial ADL. A 75% improvement in interference with general ADL and a 62% improvement in interference with facial ADL were needed to achieve an MCID. While pain intensity is easier to measure, pain's interference with ADL may be more important for patient outcomes when designing or evaluating interventions in the field of TN. The BPI-Facial is a useful instrument to measure changes in multidimensional aspects of pain in patients with TN.

  View details for DOI 10.3171/2014.8.JNS132547

  View details for Web of Science ID 000346947600026

  View details for PubMedID 25361481

• A step-wise approach to deep brain stimulation in mice ACTA NEUROCHIRURGICA Halpern, C. H., Attiah, M. A., Tekriwal, A., Baltuch, G. H. 2014; 156 (8): 1515-1521

  Abstract

  Studies of deep brain stimulation (DBS) in mice are rare due to their small size, agility, aversion to handling, and high anxiety compared to larger species. Studying DBS modulation of neural circuitry in murine models of human behavior may ensure safety, guide stimulatory parameters for clinical trials in humans, and inform a long-eluded mechanism.Stereotactic deep brain electrode implantation in a mouse is performed. Mechanical etching of the skull with a high-speed drill is used with placement of cyanoacrylate glue and molding of dental acrylate to affix the electrode in place. Stimulation experiments are conducted in the home cage after a habituation period. After testing is complete, electrode placement is verified in fixed tissue.Electrodes can be safely and accurately implanted in mice for DBS experimentation. Previous findings demonstrated accuracy in placement within the nucleus accumbens shell of 93 % [14]. In this study, there were no hardware malfunctions that required interrupting experimentation.Stereotactic DBS studies may be safely and effectively performed in mice to investigate neuropsychiatric disorders. In addition, examining the biochemical and molecular mechanisms underlying these disorders may be facilitated by widely available transgenic mouse lines and the Cre-Lox recombination system.

  View details for DOI 10.1007/s00701-014-2062-4

  View details for Web of Science ID 000339724900014

  View details for PubMedID 24687810

• Cervical laminoforaminotomy for radiculopathy: Symptomatic and functional outcomes in a large cohort with long-term follow-up. Surgical neurology international Church, E. W., Halpern, C. H., Faught, R. W., Balmuri, U., Attiah, M. A., Hayden, S., Kerr, M., Maloney-Wilensky, E., Bynum, J., Dante, S. J., Welch, W. C., Simeone, F. A. 2014; 5: S536-43

  Abstract

  The efficacy and safety of cervical laminoforaminotomy (FOR) in the treatment of cervical radiculopathy has been demonstrated in several series with follow-up less than a decade. However, there is little data analyzing the relative effectiveness of FOR for radiculopathy due to soft disc versus osteophyte disease. In the present study, we review our experience with FOR in a single-center cohort, with long-term follow-up.We examined the charts of patients who underwent 1085 FORs between 1990 and 2009. A cohort of these patients participated in a telephone interview designed to assess improvement in symptoms and function.A total of 338 interviews were completed with a mean follow-up of 10 years. Approximately 90% of interviewees reported improved pain, weakness, or function following FOR. Ninety-three percent of patients were able to return to work after FOR. The overall complication rate was 3.3%, and the rate of recurrent radiculopathy requiring surgery was 6.2%. Soft disc subtypes compared to osteophyte disease by operative report were associated with improved symptoms (P < 0.05). The operative report of these pathologic subtypes was associated with the preoperative magnetic resonance imaging (MRI) interpretation (P < 0.001).These results suggest that FOR is a highly effective surgical treatment for cervical radiculopathy with a low incidence of complications. Radiculopathy due to soft disc subtypes may be associated with a better prognosis compared to osteophyte disease, although osteophyte disease remains an excellent indication for FOR.

  View details for DOI 10.4103/2152-7806.148029

  View details for PubMedID 25593773

  View details for PubMedCentralID PMC4287901

• Ethical considerations in deep brain stimulation for psychiatric illness JOURNAL OF CLINICAL NEUROSCIENCE Grant, R. A., Halpern, C. H., Baltuch, G. H., O'Reardon, J. P., Caplan, A. 2014; 21 (1): 1-5

  Abstract

  Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation.

  View details for DOI 10.1016/j.jocn.2013.04.004

  View details for Web of Science ID 000330149900001

  View details for PubMedID 24055023

• Amelioration of Binge Eating by Nucleus Accumbens Shell Deep Brain Stimulation in Mice Involves D2 Receptor Modulation JOURNAL OF NEUROSCIENCE Halpern, C. H., Tekriwal, A., Santollo, J., Keating, J. G., Wolf, J. A., Daniels, D., Bale, T. L. 2013; 33 (17): 7122-?

  Abstract

  Hedonic overconsumption contributing to obesity involves altered activation within the mesolimbic dopamine system. Dysregulation of dopamine signaling in the nucleus accumbens shell (NAS) has been implicated in reward-seeking behaviors, such as binge eating, which contributes to treatment resistance in obesity (Wise, 2012). Direct modulation of the NAS with deep brain stimulation (DBS), a surgical procedure currently under investigation in humans for the treatment of major depression, obsessive-compulsive disorder, and addiction, may also be effective in ameliorating binge eating. Therefore, we examined the ability of DBS of the NAS to block this behavior in mice. c-Fos immunoreactivity was assessed as a marker of DBS-mediated neuronal activation. NAS DBS was found to reduce binge eating and increased c-Fos levels in this region. DBS of the dorsal striatum had no influence on this behavior, demonstrating anatomical specificity for this effect. The dopamine D2 receptor antagonist, raclopride, attenuated the action of DBS, whereas the D1 receptor antagonist, SCH-23390, was ineffective, suggesting that dopamine signaling involving D2 receptors underlies the effect of NAS DBS. To determine the potential translational relevance to the obese state, chronic NAS DBS was also examined in diet-induced obese mice and was found to acutely reduce caloric intake and induce weight loss. Together, these findings support the involvement of the mesolimbic dopamine pathways in the hedonic mechanisms contributing to obesity, and the efficacy of NAS DBS to modulate this system.

  View details for DOI 10.1523/JNEUROSCI.3237-12.2013

  View details for Web of Science ID 000318419300002

  View details for PubMedID 23616522

• Deep brain stimulation and obesity RESPONSE JOURNAL OF NEUROSURGERY Halpern, C. H., Wolf, J. A., Jaggi, J. L., Grady, M. S., Baltuch, G. H. 2013; 118 (2): 487-487

  View details for DOI 10.3171/2009.8.JNS091131

  View details for Web of Science ID 000313937900049

• Deep brain stimulation of the nucleus accumbens for the treatment of addiction ADDICTION REVIEWS Mueller, U. J., Voges, J., Steiner, J., Galazky, I., Heinze, H., Moeller, M., Pisapia, J., Halpern, C., Caplan, A., Bogerts, B., Kuhn, J. 2013; 1282: 119-128

  View details for DOI 10.1111/j.1749-6632.2012.06834.x

  View details for Web of Science ID 000324841500009

• Can Broad-Range 16S Ribosomal Ribonucleic Acid Gene Polymerase Chain Reactions Improve the Diagnosis of Bacterial Meningitis? A Systematic Review and Meta-analysis ANNALS OF EMERGENCY MEDICINE Srinivasan, L., Pisapia, J. M., Shah, S. S., Halpern, C. H., Harris, M. C. 2012; 60 (5): 609-620

  Abstract

  We aim to evaluate the accuracy of the broad-range 16S polymerase chain reaction test in the diagnosis of bacterial meningitis through a systematic review and meta-analysis.We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry, using the Medical Subject Headings terms "polymerase chain reaction," "RNA, ribosomal, 16S," and "bacterial meningitis." For our primary analysis, we examined the 16S polymerase chain reaction in culture-proven bacterial meningitis. In ancillary observations, we included studies of culture-negative presumed bacterial meningitis, in which there was high clinical suspicion for bacterial meningitis despite negative cerebrospinal fluid culture results. We extracted information necessary to calculate sensitivity and specificity and used bivariate hierarchic modeling meta-analysis methods to obtain pooled statistics. We also estimated potential sources of error and bias such as between-study heterogeneity and publication bias.Fourteen of 299 studies met inclusion criteria for culture-proven bacterial meningitis; 448 (16.1%) of 2,780 subjects had positive cerebrospinal fluid culture results. Pooled analysis demonstrated a sensitivity of 92% (95% confidence interval [CI] 75% to 98%), specificity of 94% (95% CI 90% to 97%), positive likelihood ratio of 16.26 (95% CI 9.07 to 29.14), and negative likelihood ratio of 0.09 (95% CI 0.03 to 0.28) for culture-proven bacterial meningitis. The polymerase chain reaction test result was also positive in 30% of cases of culture-negative presumed bacterial meningitis. There was significant heterogeneity between studies.This meta-analysis supports the role of 16S ribosomal ribonucleic acid polymerase chain reaction as a diagnostic tool in bacterial meningitis. With further refinements in technology, the polymerase chain reaction test has the potential to become a useful adjunct in the diagnosis of bacterial meningitis in the emergency department.

  View details for DOI 10.1016/j.annemergmed.2012.05.040

  View details for Web of Science ID 000310928800013

  View details for PubMedID 22883680

• Pediatric indications for deep brain stimulation CHILDS NERVOUS SYSTEM Difrancesco, M. F., Halpern, C. H., Hurtig, H. H., Baltuch, G. H., Heuer, G. G. 2012; 28 (10): 1701-1714

  Abstract

  Based on the success of deep brain stimulation (DBS) in the treatment of adult disorders, it is reasonable to assume that the application of DBS in the pediatric population is an emerging area worthy of study. The purpose of this paper is to outline the current movement disorder indications for DBS in the pediatric population, and to describe areas of investigation, including possible medically refractory psychiatric indications.We performed a structured review of the English language literature from 1990 to 2011 related to studies of DBS in pediatrics using Medline and PubMed search results.Twenty-four reports of DBS in the pediatric population were found. Based on published data on the use of DBS for pediatric indications, there is a spectrum of clinical evidence for the use of DBS to treat different disorders. Dystonia, a disease associated with a low rate of remission and significant disability, is routinely treated with DBS and is currently the most promising pediatric application of DBS. We caution the application of DBS to conditions associated with a high remission rate later in adulthood, like obsessive-compulsive disorder and Tourette's syndrome. Moreover, epilepsy and obesity are currently being investigated as indications for DBS in the adult population; however, both are associated with significant morbidity in pediatrics.While currently dystonia is the most promising application of DBS in the pediatric population, multiple conditions currently being investigated in adults also afflict children and adolescents, and thus warrant further research.

  View details for DOI 10.1007/s00381-012-1861-2

  View details for Web of Science ID 000309131400007

  View details for PubMedID 22828866

• Durability of Roux-en-Y Gastric Bypass Surgery A Meta-Regression Study ANNALS OF SURGERY Attiah, M. A., Halpern, C. H., Balmuri, U., Vinai, P., Mehta, S., Baltuch, G. H., Williams, N. N., Wadden, T. A., Stein, S. C. 2012; 256 (2): 251-254

  Abstract

  The present meta-regression pools data from reports of long-term follow-up (>2 years) to assess durability of the efficacy associated with Roux-en-Y gastric bypass (RYGB) surgery.Medline and PubMed searches for articles pertaining to long-term weight loss after RYGB surgery were performed.Various studies have consistently shown short-term (<2 years) efficacy of RYGB surgery for morbid obesity, corroborated by meta-analytic techniques. Relatively few studies have assessed efficacy over longer periods of time. This is the first meta-analysis to analyze long-term effects of RYGB surgery on weight loss.Twenty-two reports with a total of 4206 patient cases were included. Sixteen of the 22 studies had multiple follow-up times, ranging from 2 to 12.3 years (mean: 3.6 years). An inverse variance weighted model and meta-regression were used to generate the pooled percent mean excess weight loss (EWL) and the durability of EWL over time, respectively.Meta-regression did not reveal any significant change in EWL over time. Pooled mean EWL was 66.5%, and there was no significant association between EWL and length of follow-up.Pooling data from multiple studies meta-analytically revealed that weight loss after RYGB is maintained over the long-term. Further investigation would be necessary to ascertain similar durability in comorbidity reduction after RYGB surgery.

  View details for DOI 10.1097/SLA.0b013e3182565712

  View details for Web of Science ID 000306372500010

  View details for PubMedID 22584693

• Error Reduction with Routine Checklist Use during Deep Brain Stimulation Surgery STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Kramer, D. R., Halpern, C. H., Connolly, P. J., Jaggi, J. L., Baltuch, G. H. 2012; 90 (4): 255-259

  Abstract

  The use of checklists to reduce error rates in procedural literature has led our group to employ this strategy during deep brain stimulation (DBS) surgery.We sought to examine the improvement in the number of errors made during DBS surgery after long-term use of a checklist.Our checklist has been used for all DBS cases at our institution since the beginning of this study's enrollment in 2008. The number of cases in which errors were detected after 1 year of routine use (group B, n = 11) was compared in one cohort of DBS subjects to that of an earlier cohort of patients (group A, n = 17), which underwent DBS exactly 1 year prior.Eleven of the 14 cases where major errors were detected occurred in group A; 6 of the 9 cases where only minor errors were detected were also in group A; of the patients without any error, all 5 were in group B. We found a significant difference in these proportions between group A and group B [χ(2)(2) = 9.73; p < 0.008].After 1 year of checklist use, the total number of major and minor errors made was reduced, indicating an improvement in error rate after long-term routine incorporation of this checklist.

  View details for DOI 10.1159/000338091

  View details for Web of Science ID 000307936100006

  View details for PubMedID 22699928

• Implications for programming strategy of the location of the active contact in subthalamic nucleus deep brain stimulation JOURNAL OF CLINICAL NEUROSCIENCE Connolly, P. J., Halpern, C. H., Baltuch, G. H., Danish, S. F., Jaggi, J. L. 2012; 19 (7): 1029-1031

  Abstract

  We aimed to determine whether our targeting method for the subthalamic nucleus (STN) in Parkinson's disease informs the initial programming sequence. We evaluated 100 STN-lead pairs from 50 patients who underwent bilateral STN-deep brain stimulation operations. All patients had at least one year of follow-up. In each patient, we measured coordinates of the STN borders and determined the center from special T2-weighted MRI. We then measured the postoperative location of the lead tip by MRI registered to preoperative images. Finally, we determined the mode and active contact(s). Programming was monopolar 71% of the time. A total of 52% of left and 72% of right STN active contacts were located posterolateral to the STN center. In z, only 14% of the active contact(s) were >1mm below the STN center. Contacts 1 or 2 were active 90% of the time. The consistent location of active contacts suggests that initial programming began with contact 1 or 2.

  View details for DOI 10.1016/j.jocn.2011.12.002

  View details for Web of Science ID 000311323800023

  View details for PubMedID 22551587

• Self-administered preoperative antiseptic wash to prevent postoperative infection after deep brain stimulation AMERICAN JOURNAL OF INFECTION CONTROL Halpern, C. H., Mitchell, G. W., Paul, A., Kramer, D. R., McGill, K. R., Buonacuore, D., Kerr, M., Jaggi, J. L., Stern, J. J., Baltuch, G. H. 2012; 40 (5): 431-433

  Abstract

  Prevention of surgical site infections is critical in deep brain stimulation (DBS). In the present study, we tested the ability of a self-administered preoperative alcohol-based (70% ethyl alcohol) preparation to reduce the rate of postoperative infection after DBS surgery.This Institutional Review Board-approved retrospective review was conducted at our institution between January 2005 and October 2007 (mean follow-up, 23 months). The participants comprised a consecutive sample of 172 patients with movement disorders who underwent DBS surgery at our institution. Starting in January 2007, all patients were required to use the alcohol-based preparation. These patients (n = 48) were instructed to self-administer the wash on the night before surgery and the morning of surgery. Before this time, no self-administered wash was used (n = 122).There was no difference in preoperative skin cleansing between the 2 groups, and all patients received intravenous antibiotics immediately before and after surgery for 24 hours. We compared the rate of postoperative infection in the 2 groups and reviewed other possible factors underlying infection. We found 11 cases of infection (6.47%), all in the group without the preoperative antiseptic wash. The infection rate was 9.02% in the group without the preoperative wash and 0 in the group with the preoperative wash (P < .029). There was no difference between the 2 groups in terms of mean age, duration of operative procedure, or number of microelectrode tracts attempted.Our results support the incorporation of this self-administered antiseptic wash into our standard antiseptic protocol for patients undergoing DBS surgery.

  View details for DOI 10.1016/j.ajic.2011.06.005

  View details for Web of Science ID 000304378300009

  View details for PubMedID 21890239

• Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma NEURO-ONCOLOGY Tykocinski, E. S., Grant, R. A., Kapoor, G. S., Krejza, J., Bohman, L., Gocke, T. A., Chawla, S., Halpern, C. H., Lopinto, J., Melhem, E. R., O'Rourke, D. M. 2012; 14 (5): 613-623

  Abstract

  Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.

  View details for DOI 10.1093/neuonc/nos073

  View details for Web of Science ID 000303334500009

  View details for PubMedID 22492960

• Deep Brain Stimulation of the Nucleus Accumbens Attenuates Binge Eating in Mice 67th Annual Meeting of the Society-of-Biological-Psychiatry Halpern, C. ELSEVIER SCIENCE INC. 2012: 304S–304S

  View details for Web of Science ID 000302466001276

• Sex Differences in Deep Brain Stimulation Amelioration of Binge Eating 67th Annual Meeting of the Society-of-Biological-Psychiatry Siegel, C. M., Halpern, C. H., Bale, T. ELSEVIER SCIENCE INC. 2012: 306S–306S

  View details for Web of Science ID 000302466001284

• Deep brain stimulation compared with methadone maintenance for the treatment of heroin dependence: a threshold and cost-effectiveness analysis ADDICTION Stephen, J. H., Halpern, C. H., Barrios, C. J., Balmuri, U., Pisapia, J. M., Wolf, J. A., Kampman, K. M., Baltuch, G. H., Caplan, A. L., Stein, S. C. 2012; 107 (3): 624-634

  Abstract

  To determine the success threshold at which a theoretical course of deep brain stimulation (DBS) would provide the same quality of life (QoL) and cost-effectiveness for heroin dependence as methadone maintenance treatment (MMT).We constructed a decision analysis model to calculate QoL after 6 months of MMT and compared it to a theoretical course of DBS. We also performed a cost-effectiveness analysis using societal costs of heroin dependence, MMT and DBS.Systematic literature review and meta-analysis.Patients (n = 1191) from 15 trials administering 6 months of MMT and patients (n = 2937) from 45 trials of DBS for movement disorders.Data on QoL before and after MMT, retention in MMT at 6 months, as well as complications of DBS and their impact on QoL in movement disorders.We found a QoL of 0.633 (perfect health = 1) in heroin addicts initiating MMT. Sixty-six per cent of patients completed MMT, but only 47% of them had opiate-free urine samples, resulting in an average QoL of 0.7148 (0.3574 quality-adjusted life years (QALYs) over 6 months). A trial of DBS is less expensive ($81,000) than untreated (or relapsed) heroin dependence ($100,000), but more expensive than MMT ($58,000). A theoretical course of DBS would need a success rate of 36.5% to match MMT, but a success rate of 49% to be cost-effective.The success rate, defined as the percentage of patients remaining heroin-free after 6 months of treatment, at which deep brain stimulation would be similarly cost-effective in treating opiate addiction to methadone maintenance treatment, is estimated at 49%.

  View details for DOI 10.1111/j.1360-0443.2011.03656.x

  View details for Web of Science ID 000299997000022

  View details for PubMedID 21919988

• The Effect of Intraventricular Trajectory on Brain Shift in Deep Brain Stimulation STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Kramer, D. R., Halpern, C. H., Danish, S. F., Jaggi, J. L., Baltuch, G. H. 2012; 90 (1): 20-24

  Abstract

  Brain shift during deep brain stimulation (DBS) surgery may compromise target localization. Loss of cerebrospinal fluid is believed to be the underlying mechanism, thus an intraventricular trajectory during DBS surgery may be associated with increased shift, in addition to other complications, such as intraventricular hemorrhage.We set out to assess the effect of traversing the lateral ventricle on brain shift during DBS surgery.We performed a retrospective review of 65 pre- and postoperative MR images of patients who underwent bilateral subthalamic nucleus deep brain stimulator placement to treat advanced Parkinson's disease. Patients were separated into two groups: Group A (intraventricular trajectory, n = 46) and Group B (no intraventricular trajectory, n = 19). In these patients, we compared pre- and postoperative frame coordinates of the red nucleus (RN).Group B demonstrated significantly more posterior shift of the center of the RN (1.40 ± 1.32 mm) than Group A (0.64 ± 1.76 mm; p < 0.02). We found no increase in incidence of intraventricular hemorrhage or the number of microelectrode trajectory attempts.Intraventricular trajectories during DBS surgery do not appear to compromise safety or targeting accuracy.

  View details for DOI 10.1159/000332056

  View details for Web of Science ID 000300204600005

  View details for PubMedID 22190056

• Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management ACTA NEUROCHIRURGICA Halpern, C. H., Torres, N., Hurtig, H. I., Wolf, J. A., Stephen, J., Oh, M. Y., Williams, N. N., Dichter, M. A., Jaggi, J. L., Caplan, A. L., Kampman, K. M., Wadden, T. A., Whiting, D. M., Baltuch, G. H. 2011; 153 (12): 2293-2306

  Abstract

  The indications for deep brain stimulation (DBS) are expanding, and the feasibility and efficacy of this surgical procedure in various neurologic and neuropsychiatric disorders continue to be tested. This review attempts to provide background and rationale for applying this therapeutic option to obesity and addiction. We review neural targets currently under clinical investigation for DBS—the hypothalamus and nucleus accumbens—in conditions such as cluster headache and obsessive-compulsive disorder. These brain regions have also been strongly implicated in obesity and addiction. These disorders are frequently refractory, with very high rates of weight regain or relapse, respectively, despite the best available treatments.We performed a structured literature review of the animal studies of DBS, which revealed attenuation of food intake, increased metabolism, or decreased drug seeking. We also review the available radiologic evidence in humans, implicating the hypothalamus and nucleus in obesity and addiction.The available evidence of the promise of DBS in these conditions combined with significant medical need, support pursuing pilot studies and clinical trials of DBS in order to decrease the risk of dietary and drug relapse.Well-designed pilot studies and clinical trials enrolling carefully selected patients with obesity or addiction should be initiated.

  View details for DOI 10.1007/s00701-011-1166-3

  View details for Web of Science ID 000297159700001

  View details for PubMedID 21976235

• Carpal tunnel syndrome secondary to an osteophyte of the trapezium JOURNAL OF CLINICAL NEUROSCIENCE Mascitelli, J. R., Halpern, C. H., Dolinskas, C. A., Zager, E. L., Welch, W. C. 2011; 18 (11): 1558-1559

  Abstract

  We report a 42-year-old man with a rare carpal tunnel syndrome (CTS) secondary to an osteophyte of the trapezium. The patient presented with a 3-year history of CTS, consisting of progressive pain and paresthesias in his right hand, positive Tinel and Phalen signs, and an electrodiagnostic study demonstrating median nerve compression at the wrist. The procedure was an open carpal tunnel release. Intraoperatively, a bony protuberance was found beneath the transverse carpal ligament (TCL), resulting in compression of the median nerve. The median nerve was decompressed and the patient's symptoms resolved postoperatively. Surgical pathology revealed bony fragments, and a postoperative CT scan was supportive of an osteophytic remnant protruding from the trapezium. Carpal bone osteophytes are rarely reported causes of CTS.

  View details for DOI 10.1016/j.jocn.2011.03.011

  View details for Web of Science ID 000296402800034

  View details for PubMedID 21868228

• Re: Halpern CH, Milby AH, Wensheng G, et al. Clearance of the cervical spine in clinically nonevaluable trauma patients. Spine 2010; 35:1721-8. RESPONSE SPINE Halpern, C. H., Schuster, J. M., Stein, S. C., Milby, A. H. 2011; 36 (14): 1167-1168

  View details for DOI 10.1097/BRS.0b013e3182222c98

  View details for Web of Science ID 000291245100028

• Re: Halpern CH, Milby AH, Wensheng G, et al. Clearance of the cervical spine in clinically nonevaluable trauma patients. Spine 2010; 35: 1721-8 SPINE Halpern, C. H., Stein, S. C., Milby, A. H. 2011; 36 (14): 1165-1166

  View details for DOI 10.1097/BRS.0b013e31821d2e8e

  View details for Web of Science ID 000291245100026

• Longevity Analysis of Currently Available Deep Brain Stimulation Devices STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Halpern, C. H., McGill, K. R., Baltuch, G. H., Jaggi, J. L. 2011; 89 (1): 1-5

  Abstract

  There continues to be debate about the surgical technique, electrophysiology, and hardware used in deep brain stimulation (DBS), despite its widespread use in medically intractable Parkinson's disease and essential tremor. This article is the first, to our knowledge, to compare the longevity of the available internal pulse generators (IPGs) of DBS (Kinetra and Soletra, Medtronics).We compared the elapsed time from the initial surgery to the first replacement of IPGs in patients with bilateral Soletra IPGs to those with the unilateral Kinetra IPG and analyzed the various stimulation parameters of each device.The battery life of the Soletra system was significantly longer than that of the Kinetra and also allowed for higher voltages, longer use of monopolar mode, and a greater number of electrode contacts.Our findings support superior battery life and a greater capacity for titration to symptom control with bilateral Soletra IPGs.

  View details for DOI 10.1159/000321710

  View details for Web of Science ID 000287320700001

  View details for PubMedID 21124046

• Clearance of the Cervical Spine in Clinically Unevaluable Trauma Patients SPINE Halpern, C. H., Milby, A. H., Guo, W., Schuster, J. M., Gracias, V. H., Stein, S. C. 2010; 35 (18): 1721-1728

  Abstract

  Meta-analytic costeffectiveness analysis.Our goal was to compare the results of different management strategies for trauma patients in whom the cervical spine was not clinically evaluable due to impaired consciousness, endotracheal intubation, or painful distracting injuries.We performed a structured literature review related to cervical spine trauma, radiographic clearance techniques (plain radiography, flexion/extension, CT, and MRI), and complications associated with semirigid collar use.Meta-analytic techniques were used to pool data from multiple sources to calculate pooled mean estimates of sensitivities and specificities of imaging techniques for cervical spinal clearance, rates of complications from various clearance strategies and from empirical use of semirigid collars. A decision analysis model was used to compare outcomes and costs among these strategies.Slightly more than 7.5% of patients who are clinically unevaluable have cervical spine injuries, and 42% of these injuries are associated with spinal instability. Sensitivity of plain radiography or fluoroscopy for spinal clearance was 57% (95% CI: 57%-60%). Sensitivities for CT and MRI alone were 83% (82%-84%) and 87% (84%-89%), respectively. Complications associated with collar use ranged from 1.3% (2 days) to 7.1% (10 days) but were usually minor and short-lived. Quadriplegia resulting from spinal instability missed by a clearance test had enormous impacts on longevity, quality of life, and costs. These impacts overshadowed the effects of prolonged collar application, even when the incidence of quadriplegia was extremely low.As currently used, neuroimaging studies for cervical spinal clearance in clinically unevaluable patients are not cost-effective compared with empirical immobilization in a semirigid collar.

  View details for DOI 10.1097/BRS.0b013e3181e9acb2

  View details for Web of Science ID 000281277700009

  View details for PubMedID 21374896

• Best surgical practices: a stepwise approach to the University of Pennsylvania deep brain stimulation protocol NEUROSURGICAL FOCUS Kramer, D. R., Halpern, C. H., Buonacore, D. L., McGill, K. R., Hurtig, H. I., Jaggi, J. L., Baltuch, G. H. 2010; 29 (2)

  Abstract

  Deep brain stimulation (DBS) is the treatment of choice for otherwise healthy patients with advanced Parkinson disease who are suffering from disabling dyskinesias and motor fluctuations related to dopaminergic therapy. As DBS is an elective procedure, it is essential to minimize the risk of morbidity. Further, precision in targeting deep brain structures is critical to optimize efficacy in controlling motor features. The authors have already established an operational checklist in an effort to minimize errors made during DBS surgery. Here, they set out to standardize a strict, step-by-step approach to the DBS surgery used at their institution, including preoperative evaluation, the day of surgery, and the postoperative course. They provide careful instruction on Leksell frame assembly and placement as well as the determination of indirect coordinates derived from MR images used to target deep brain structures. Detailed descriptions of the operative procedure are provided, outlining placement of the stereotactic arc as well as determination of the appropriate bur hole location, lead placement using electrophysiology, and placement of the internal pulse generator. The authors also include their approach to preventing postoperative morbidity. They believe that a strategic, step-by-step approach to DBS surgery combined with a standardized checklist will help to minimize operating room mistakes that can compromise targeting and increase the risk of complication.

  View details for DOI 10.3171/2010.4.FOCUS10103

  View details for Web of Science ID 000283802400004

  View details for PubMedID 20672920

• Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study NEUROSURGICAL FOCUS Pisapia, J. M., Halpern, C. H., Williams, N. N., Wadden, T. A., Baltuch, G. H., Stein, S. C. 2010; 29 (2)

  Abstract

  Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries.Medline searches were performed for studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was considered successful if postoperative excess weight loss exceeded 45% at 1-year follow-up. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no surgical treatment. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used.Fifteen studies involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies involving 2937 cases treated with DBS were included. The operative successes were 0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB. Sensitivity analysis revealed utility of surgical complications in LRYGB, probability of surgical complications in DBS, and success rate of DBS as having the greatest influence on outcomes. At no values did LAGB result in superior outcomes compared with other treatments.Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity.

  View details for DOI 10.3171/2010.5.FOCUS10109

  View details for Web of Science ID 000283802400016

  View details for PubMedID 20672917

• Intracerebral microdialysis during deep brain stimulation surgery JOURNAL OF NEUROSCIENCE METHODS Kilpatrick, M., Church, E., Danish, S., Stiefel, M., Jaggi, J., Halpern, C., Kerr, M., Maloney, E., Robinson, M., Lucki, I., Krizman-Grenda, E., Baltuch, G. 2010; 190 (1): 106-111

  Abstract

  This report describes the use of microdialysis in conjunction with deep brain stimulation (DBS) surgery to assess extracellular levels of neurotransmitters within the human basal ganglia (BG). Electrical stimulation of the subthalamic nucleus (STN) is an efficacious treatment for advanced Parkinson's disease, yet the mechanisms of STN DBS remain poorly understood. Measurement of neurotransmitter levels within the BG may provide insight into mechanisms of DBS, but such an approach presents technical challenges.After microelectrode recordings confirmed location of STN, a custom microdialysis guide cannula was inserted. A CMA (Stockholm, Sweden) microdialysis probe was then positioned to the same depth as the microrecording electrode in STN or 2mm inferiorly to record in the substantia nigra. The catheter was perfused at a rate of 2.0 microL/min with a sterile mock CSF solution and samples of extracellular fluid were collected at regular intervals. Dialysate samples were analyzed using high-pressure liquid chromatography (HPLC) detection procedures for quantitation of glutamate, gamma-aminobutyric acid (GABA), and dopamine.Levels of neurotransmitters were reliably identified in dialysate samples using HPLC. By monitoring concentrations of glutamate, GABA and dopamine, we were able to demonstrate what seemed to be a steady state baseline within approximately 30 min.Microdialysis during DBS surgery is a feasible method for assessing levels of glutamate, GABA and dopamine within the human BG. Obtaining a steady state baseline of neurotransmitter levels appears feasible, thus making future studies of intraoperative microdialysis during DBS meaningful.

  View details for DOI 10.1016/j.jneumeth.2010.04.013

  View details for Web of Science ID 000279888800015

  View details for PubMedID 20416339

• Deep brain stimulation in the treatment of refractory epilepsy: Update on current data and future directions NEUROBIOLOGY OF DISEASE Lega, B. C., Halpern, C. H., Jaggi, J. L., Baltuch, G. H. 2010; 38 (3): 354-360

  Abstract

  Deep brain stimulation for epilepsy has garnered attention from epileptologists due to its well-documented success in treating movement disorders and the low morbidity associated with the implantation of electrodes. Given the large proportion of patients who fail medical therapy and are not candidates for surgical amelioration, as well as the suboptimal seizure control offered by vagus nerve stimulation, the search for appropriate brain structures to serve as targets for deep brain stimulation has generated a useful body of evidence to serve as the basis for larger investigations. Early results of the SANTE trial should lay the foundation for widespread implementation of DBS for epilepsy targeting the anterior thalamic nucleus. Other targets also offer promise, including the caudate nucleus, the subthalamic nucleus, the cerebellum, the centromedian nucleus of the thalamus, and the hippocampus. This paper reviews the logic which underlies these potential targets and recapitulates the current data from limited human trials supporting each one. It also provides a succinct overview of the surgical procedure used for electrode implantation.

  View details for DOI 10.1016/j.nbd.2009.07.007

  View details for Web of Science ID 000277648200005

  View details for PubMedID 19631750

• SUBCUTANEOUS HEPARIN FOR PROPHYLAXIS OF VENOUS THROMBOEMBOLISM IN DEEP BRAIN STIMULATION SURGERY: EVIDENCE FROM A DECISION ANALYSIS NEUROSURGERY Bauman, J. A., Church, E., Halpern, C. H., Danish, S. F., Zaghloul, K. A., Jaggi, J. L., Stein, S. C., Baltuch, G. H. 2009; 65 (2): 276-280

  Abstract

  The addition of subcutaneous heparin (SQH) to mechanical prophylaxis for venous thromboembolism (VTE) involves a balance between the benefit of greater protection from VTE and the added risk of intracranial hemorrhage. There is evidence that the hemorrhage risk outweighs the benefits for patients undergoing craniotomy. We investigated the safety of SQH in patients undergoing deep brain stimulation (DBS) surgery.A retrospective analysis was performed of all patients with movement disorders (n = 254) undergoing DBS surgery at our institution from 2003 to 2007. Before September 2005, none of the patients undergoing DBS received SQH (non-SQH group) (n = 121). Thereafter, all patients were administered SQH perioperatively (SQH group) (n = 133). All patients wore graduated compression stockings and pneumatic compression boots postoperatively in bed. A postoperative brain magnetic resonance imaging scan was obtained on the day of surgery.Five (3.8%) of 133 SQH patients and 1 (0.8%) of 121 non-SQH patients developed asymptomatic intracranial hemorrhage. None of the SQH patients developed clinically significant VTE, whereas 3 (2.5%) non-SQH patients developed VTE (1 deep venous thrombosis, 2 pulmonary embolisms). Using a decision-analysis model, we have shown that the use of SQH plus mechanical prophylaxis together yielded outcomes at least as good as mechanical prophylaxis alone.Our findings suggest that SQH for VTE prophylaxis in patients with movement disorders undergoing DBS surgery is safe. SQH protects against VTE in this patient population and merits further investigation.

  View details for DOI 10.1227/01.NEU.0000348297.92052.E0

  View details for Web of Science ID 000268523200013

  View details for PubMedID 19625905

• Cognition of the following bilateral deep brain stimulation surgery subthalamic nucleus for Parkinson's disease INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Halpern, C. H., Rick, J. H., Danish, S. F., Grossman, M., Baltuch, G. H. 2009; 24 (5): 443-451

  Abstract

  Parkinson's disease (PD) is a neurodegenerative disorder characterized by significant motor dysfunction and various non-motor disturbances, including cognitive alterations. Deep brain stimulation (DBS) is an increasingly utilized therapeutic option for patients with PD that yields remarkable success in alleviating disabling motor symptoms. DBS has additionally been associated with changes in cognition, yet the evidence is not consistent across studies. The following review sought to provide a clearer understanding of the various cognitive sequelae of bilateral subthalamic nucleus (STN) DBS while taking into account corresponding neuroanatomy and potential confounding variables.A literature search was performed using the following inclusion criteria: (1) at least five subjects followed for a mean of at least 3 months after surgery; (2) pre- and postoperative cognitive data using at least one standardized measure; (3) adequate report of study results using means and standard deviations.Two recent meta-analyses found mild post-operative impairments in verbal learning and executive function in patients who underwent DBS surgery. However, studies have revealed improved working memory and psychomotor speed in the 'on' vs 'off' stimulation state. A deficit in language may be a consequence of the surgical procedure.While cognitive decline has been observed in some domains, our review of the data suggests that STN DBS is a worthwhile and safe method to treat PD.

  View details for DOI 10.1002/gps.2149

  View details for Web of Science ID 000265996500002

  View details for PubMedID 19016252

• Vagus Nerve Stimulation in the Treatment of Refractory Epilepsy 4th Workshop on New Horizons in the Development of Antiepileptic Drugs Milby, A. H., Halpern, C. H., Baltuch, G. H. SPRINGER. 2009: 228–37

  Abstract

  Many patients with epilepsy suffer from persistent seizures despite maximal anti-epileptic drug therapy. Chronic, intermittent vagus nerve stimulation has been proven to be an effective option for many patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, vagus nerve stimulation, as an adjunct to medical therapy, may result in significant improvements in quality of life. Vagus nerve stimulation is generally well-tolerated, as device implantation is associated with a low rate of perioperative complications, and the majority of side effects are stimulation-dependent and thus reversible.

  View details for Web of Science ID 000264659900003

  View details for PubMedID 19332314

• Prevalence of cervical spinal injury in trauma NEUROSURGICAL FOCUS Milby, A. H., Halpern, C. H., Guo, W., Stein, S. C. 2008; 25 (5)

  Abstract

  Diagnosis of cervical spinal injury (CSI) is an essential aspect of the trauma evaluation. This task is especially difficult in patients who are not clinically able to be evaluated (unevaluable) because of distracting painful injuries, intoxication, or concomitant head injury. For this population, the appropriate use of advanced imaging techniques for cervical spinal clearance remains undetermined. This study was undertaken to estimate the prevalence of unstable CSI, particularly among patients in whom clinical evaluation is impossible or unreliable.Estimates of the prevalence of CSI in populations consisting of all trauma patients, alert patients only, and clinically unevaluable patients only were determined by variance-weighted pooling of data from 65 publications (281,864 patients) that met criteria for review.The overall prevalence of CSI among all trauma patients was 3.7%. The prevalence of CSI in alert patients was 2.8%, whereas unevaluable patients were at increased risk of CSI with a prevalence of 7.7% (p = 0.007). Overall, 41.9% of all CSI cases were considered to exhibit instability.Trauma patients who are clinically unevaluable have a higher prevalence of CSI than alert patients. Knowledge of the prevalence and risk of such injuries may help establish an evidence-based approach to the detection and management of clinically occult CSI.

  View details for DOI 10.3171/FOC.2008.25.11.E10

  View details for Web of Science ID 000260566600010

  View details for PubMedID 18980470

• Deep brain stimulation in the treatment of obesity JOURNAL OF NEUROSURGERY Halpern, C. H., Wolf, J. A., Bale, T. L., Stunkard, A. J., Danish, S. F., Grossman, M., Jaggi, J. L., Grady, M. S., Baltuch, G. H. 2008; 109 (4): 625-634

  Abstract

  Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

  View details for DOI 10.3171/JNS/2008/109/10/0625

  View details for Web of Science ID 000259549100006

  View details for PubMedID 18826348

• Gene-environment contributions to the development of infant vagal reactivity: The interaction of dopamine and maternal sensitivity CHILD DEVELOPMENT Propper, C., Moore, G. A., Mills-Koonce, W. R., Halpern, C. T., Hill-Soderlund, A. L., Calkins, S. D., Carbone, M. A., Cox, M. 2008; 79 (5): 1377-1394

  Abstract

  This study investigated dopamine receptor genes (DRD2 and DRD4) and maternal sensitivity as predictors of infant respiratory sinus arrhythmia (RSA) and RSA reactivity, purported indices of vagal tone and vagal regulation, in a challenge task at 3, 6, and 12 months in 173 infant-mother dyads. Hierarchical linear modeling (HLM) revealed that at 3 and 6 months, RSA withdrawal in response to maternal separation was greater (suggesting expected physiological regulation) in infants without the DRD2 risk allele than those with the risk allele. At 12 months, infants with the risk allele who were also exposed to maternal sensitivity showed levels of RSA withdrawal comparable to infants who were not at genetic risk. Findings demonstrate the importance of developmental analysis of gene-environment interaction.

  View details for Web of Science ID 000259270200011

  View details for PubMedID 18826531

• Traumatic coagulopathy: The effect of brain injury 56th Annual Meeting of the Congress-of-Neurological-Surgeons Halpern, C. H., Reilly, P. M., Turtz, A. R., Stein, S. C. MARY ANN LIEBERT, INC. 2008: 997–1001

  Abstract

  Traumatic coagulopathy has several possible mechanisms. In traumatic brain injury (TBI), the principal process involves the release of tissue factor (TF). There is no agreement how common this mechanism is following general trauma. Furthermore, when TF-induced coagulopathy occurs, it is unknown whether the source of TF (TBI or extracranial trauma) influences the course of coagulopathy. We undertook this investigation to address both questions. The temporal course of prothrombin times (PTs) were recorded in a group (n = 441) with isolated TBI (head Abbreviated Injury Scale [AIS] >or= 3, non-head AIS < 3) and a group (n = 101) with extracranial trauma (non-TBI; non-head AIS >or= 3; head AIS < 3). Data were arranged according to preset time intervals after injury. The PT values in both groups were elevated and not significantly different for the first 12 h after trauma. Values then fell to normal in TBI patients, but remained elevated in non-TBI injury. Traumatic coagulopathy can be explained at least in part by TF release into the general circulation with activation of the coagulation cascade in both TBI and non-TBI. We hypothesize that the different time courses of coagulopathy represented by PT values in these populations were due to reconstitution of the blood-brain barrier, although further investigation is warranted. Peripheral hematologic studies may not reflect persistent coagulopathy in cerebral circulation.

  View details for DOI 10.1089/neu.2008.0548

  View details for Web of Science ID 000258895700005

  View details for PubMedID 18687038

• Deep brain stimulation for epilepsy NEUROTHERAPEUTICS Halpern, C. H., Samadani, U., Litt, B., Jaggi, J. L., Baltuch, G. H. 2008; 5 (1): 59-67

  Abstract

  Many patients who suffer from medically refractory epilepsy are not candidates for resective brain surgery. Success of deep brain stimulation (DBS) in relieving a significant number of symptoms of various movement disorders paved the way for investigations into this modality for epilepsy. Open-label and small blinded trials have provided promising evidence for the use of DBS in refractory seizures, and the first randomized control trial of DBS of the anterior thalamic nucleus is currently underway. There are multiple potential targets, because many neural regions have been implicated in seizure propagation. Thus, it is difficult as yet to make any definitive judgments about the efficacy of DBS for seizure control. Future study is necessary to identify a patient population for whom this technique would be indicated, the most efficacious target, and optimal stimulation parameters.

  View details for Web of Science ID 000252532300007

  View details for PubMedID 18164484

• Vagus nerve stimulation for epilepsy and depression NEUROTHERAPEUTICS Milby, A. H., Halpern, C. H., Baltuch, G. H. 2008; 5 (1): 75-85

  Abstract

  Many patients with epilepsy suffer from persistent seizures despite maximal antiepileptic drug (AED) therapy. Chronic, intermittent vagus nerve stimulation (VNS) has proven to be a safe, effective option for patients suffering from refractory seizures who are not candidates for surgical resection. Although only a small minority of patients will be entirely seizure-free, VNS as an adjunct to medical therapy does appear to provide a significant amount of improvement in quality of life. Reports of antidepressant effects independent of seizure control, along with the use of multiple AEDs in the treatment of depression, has led to the investigation of VNS as a potential adjunctive treatment for major depressive disorder. Both the number of severely depressed patients refractory to available pharmacologic options and the need for repeated treatments and significant side effects associated with electroconvulsive therapy have heightened the interest in VNS for this patient population. Pilot studies of VNS for depression have shown impressive response rates; however, the effect appears to be gradual in onset, as demonstrated by the lack of a favorable response in a short-term, randomized controlled study. Investigation is thus needed to establish the potential role of VNS as an adjunctive treatment for severe depression.

  View details for Web of Science ID 000252532300009

  View details for PubMedID 18164486

• Brain shift during deep brain stimulation surgery for Parkinson's disease STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Halpern, C. H., Danish, S. F., Baltuch, G. H., Jaggi, J. L. 2008; 86 (1): 37-43

  Abstract

  Brain shift may occur during deep brain stimulation (DBS) surgery, which may affect the position of subcortical structures, compromising target localization.We retrospectively evaluated pre- and postoperative magnetic resonance imaging in 50 Parkinson's disease patients who underwent bilateral subthalamic nucleus (STN) DBS. Patients were separated into two groups: group A - those with <2 mm cortical displacement (66 leads) and group B - those with >or=2 mm cortical displacement (34 leads). Pre and post-op coordinates of anterior (AC) and posterior commissures (PC), as well as the boundaries of red nucleus (RN) were compared.AC-PC shortening due to posterior displacement of AC correlated with cortical displacement (p < 0.02) and was significantly greater in group B (0.41 +/- 0.68 mm) than A (0.04 +/- 0.76 mm; p < 0.005). Posterior shift of AC and RN's center positively correlated (p < 0.0001). Shift appeared to impact the number of microelectrode tracks made to optimize STN targeting. AC-PC shortening also correlated with age (p < 0.003) and duration of surgery (p < 0.04).Subcortical structures shift during DBS surgery. This shift appears to be gravity-dependent since structures only shifted posteriorly, and patients were primarily in the supine position. Posterior shift of RN may indicate STN displacement. Such positional change may compromise target localization, requiring multiple microelectrode adjustments. This may provide indirect justification for the necessity of microelectrode recordings during DBS surgery.

  View details for DOI 10.1159/000108587

  View details for Web of Science ID 000251662700004

  View details for PubMedID 17881887

• Perfusion-weighted imaging identifies MR surrogates of malignant glioma molecular subtypes 12th Annual Meeting of the Society-for-Neuro-Oncology Whitmore, R., Halpern, C., Kapoor, G., Wolf, R., Woo, J., Baccon, J., Chawla, S., Oleage, L., Lopinto, J., Plaum, J., Melhem, E., O'Rourke, D. OXFORD UNIV PRESS INC. 2007: 577–78

  View details for Web of Science ID 000249999100418

• Dissociable numerosity and executive components of quantifier knowledge Troiani, V., Peelle, J. E., Halpern, C., Clark, R., Grossman, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2007: 12–13

  View details for DOI 10.1016/j.bandl.2007.07.006

  View details for Web of Science ID 000250660100004

• Too much to count on: Impaired very small numbers in corticobasal degeneration BRAIN AND COGNITION Halpern, C., Clark, R., Moore, P., Cross, K., Grossman, M. 2007; 64 (2): 144-149

  Abstract

  Patients with corticobasal degeneration (CBD) have calculation impairments. This study examined whether impaired number knowledge depends on verbal mediation. We focused particularly on knowledge of very small numbers, where there is a precise relationship between a cardinality and its number concept, but little hypothesized role for verbal mediation. We evaluated accuracy and reaction time (RT) for matching dot arrays and Arabic numerals involving smaller (2-4) and larger (5-9) cardinalities in non-aphasic patients with CBD (n=16), frontotemporal dementia (FTD; n=23), and healthy controls (n=15). CBD were less accurate and slowed at judging smaller Arabic numeral-dot array stimuli compared to FTD patients and controls. Moreover, only CBD showed longer RTs judging successively larger number-dot array pairs among the smaller cardinalities. Difficulty judging very small numbers is impaired in CBD, suggesting degraded representation of precise number knowledge that does not depend on language functioning.

  View details for DOI 10.1016/j.bandc.2007.01.006

  View details for Web of Science ID 000248255500004

  View details for PubMedID 17397978

  View details for PubMedCentralID PMC1986671

• Deep brain stimulation in neurologic disorders PARKINSONISM & RELATED DISORDERS Halpern, C., Hurtig, H., Jaggi, J., Grossman, M., Won, M., Baltuch, G. 2007; 13 (1): 1-16

  Abstract

  Deep brain stimulation (DBS) is an effective surgical therapy for well-selected patients with medically intractable Parkinson's disease (PD) and essential tremor (ET). The purpose of this review is to describe the success of DBS in these two disorders and its promising application in dystonia, Tourette Syndrome (TS) and epilepsy. In the last 10 years, numerous short- and intermediate-term outcome studies have demonstrated significant relief to patients with PD and ET. A few long-term follow-up studies have also reported sustained benefits. When successful, DBS greatly reduces most of parkinsonian motor symptoms and drug-induced dyskinesia, and it frequently improves patients' ability to perform activities of daily living with less encumbrance from motor fluctuations. Quality of life is enhanced and many patients are able to significantly reduce the amount of antiparkinsonian medications required to still get good pharmacological benefit. Overall, adverse effects associated with DBS tend to be transient, although device-related and other postoperative complications do occur. DBS should be considered the surgical procedure of choice for patients who meet strict criteria with medically intractable PD, ET and selected cases of dystonia.

  View details for DOI 10.1016/j.parkreldis.2006.03.001

  View details for Web of Science ID 000244408400001

  View details for PubMedID 17141550

• Verbal mediation of number knowledge: Evidence from semantic dementia and corticobasal degeneration BRAIN AND COGNITION Halpern, C., Clark, R., Moore, P., Antani, S., Colcher, A., Grossman, M. 2004; 56 (1): 107-115

  Abstract

  Patients with corticobasal degeneration (CBD) appear to have impaired number knowledge. We examined the nature of their number deficit while we tested the hypothesis that comprehension of larger numbers depends in part on verbal mediation. We evaluated magnitude judgments and performance on number conservation measures rooted in Piagetian theory in nonaphasic patients with CBD (n=13) and patients with a fluent form of progressive aphasia known as semantic dementia (SD; n=15). We manipulated the numbers of the arrays and the visual-spatial properties of the stimuli being compared during magnitude judgments and Piagetian conservation measures. CBD patients were consistently impaired judging the magnitudes of larger numbers (4-9), while they had minimal difficulty with smaller numbers (magnitudes < or = 3). By comparison, SD patients performed all measures of number knowledge at a ceiling level regardless of number magnitude. Neither patient group was significantly impacted by manipulations of the spatial properties of the stimuli. CBD patients' impairment with larger numbers despite minimal aphasia, and SD patients' intact performance despite an aphasia, challenge the proposal that understanding larger numbers depends on verbal mediation.

  View details for DOI 10.1016/j.bandc.2004.07.001

  View details for Web of Science ID 000224313600013

  View details for PubMedID 15380881

• Dissociation of numbers and objects in corticobasal degeneration and semantic dementia NEUROLOGY Halpern, C. H., Glosser, G., Clark, R., Gee, J., Moore, P., Dennis, K., McMillan, C., Colcher, A., Grossman, M. 2004; 62 (7): 1163-1169

  Abstract

  Semantic memory is thought to consist of category-specific representations of knowledge that may be selectively compromised in patients with neurodegenerative diseases, but this has been difficult to demonstrate reliably across object categories.The authors evaluated performance on several simple measures requiring number representations (including addition and magnitude judgments of single digits), and on a task that requires object representations (an object naming task) in patients with corticobasal degeneration (CBD; n = 13) and semantic dementia (SD; n = 15). They also examined regional cortical atrophy using voxel-based morphometric analyses of high resolution structural MRI in subgroups of five CBD patients and three SD patients.CBD patients were consistently more impaired on simple addition and magnitude judgment tasks requiring number representations compared to object representations. Impaired performance with numbers in CBD was associated with cortical atrophy in right parietal cortex. By comparison, SD patients demonstrated a greater impairment on a naming task requiring object representations relative to their performance on measures involving number representations. This was associated with left anterior temporal cortical atrophy.The cognitive and neuroanatomic dissociations between CBD and SD are consistent with the hypothesis that number and object representations constitute distinct domains in semantic memory, and these domains appear to be associated with distinct neural substrates.

  View details for Web of Science ID 000220769300022

  View details for PubMedID 15079017

• Calculation impairment in neurodegenerative diseases JOURNAL OF THE NEUROLOGICAL SCIENCES Halpern, C., McMillan, C., Moore, P., Dennis, K., Grossman, M. 2003; 208 (1-2): 31-38

  Abstract

  We examined oral calculation in patients with corticobasal degeneration (CBD; N=17), frontotemporal dementia (FTD; N=17), and Alzheimer's disease (AD; N=20), as well as 17 healthy seniors matched for age and education. Our calculation model involves at least three components: numerosity, combinatorial processes, and executive resources such as working memory. We assessed addition, subtraction, multiplication, and division involving small numbers (small, single-digit answers) and large numbers (larger, single- and double-digit answers). We also assessed dot counting for small numbers (2-5) and large numbers (6-9), as well as a measure of working memory. All patient groups differed from healthy seniors in oral calculation. CBD (36% correct) and FTD (65% correct) demonstrated a significant overall impairment in oral calculation relative to AD (76% correct). CBD (66% correct) had more difficulty counting dots overall relative to AD (94% correct) and FTD (86% correct), consistent with our hypothesis that the calculation deficit in CBD is due in large part to a numerosity deficit. FTD had more difficulty relative to AD in their performance of reverse digit span, consistent with our hypothesis that FTD patients' executive resource limitation contributes to their pattern of calculation impairment.

  View details for DOI 10.1016/S0022-510X(02)00416-1

  View details for Web of Science ID 000181923400005

  View details for PubMedID 12639722