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Christopher R. Honey and Hao Shen

Object. The goal of this study was to compare the effects of short- and long-term immunosuppression induced by cyclosporin with those of immunosuppression induced by a monoclonal antibody against the rat interleukin-2 receptor (anti-CD25 mAb) in rats with xenografts.

Methods. The authors compared the in vivo function and final histological characteristics of fetal mouse mesencephalon xenografts in hemiparkinsonian rats in which immunosuppression was induced by: 1) a short course (2 weeks) of cyclosporin; 2) a long course (8 weeks) of cyclosporin; or 3) a short course of treatment with anti-CD25 mAb. Adult Wistar rats were unilaterally lesioned with 6-hydroxydopamine in their medial forebrain bundle, after which their rotational behavior in response to methamphetamine was quantified. Four groups of 20 rats with rotations numbering greater than six turns per minute received fetal mouse mesencephalon transplants to their dopamine-denervated striatum. Group 1 received no immunosuppression therapy; Group 2 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 2 weeks; Group 3 received daily intraperitoneal injections of 10 mg/kg cyclosporin for 8 weeks; and Group 4 received daily intraperitoneal injections of 1 mg/kg anti-CD25 mAb for 2 weeks. The rats were tested for rotational behavior every 4 weeks and killed after 16 weeks. Surviving xenografts were assessed using immunohistochemical staining for a mouse neuronal marker (Thy-1.2). Sixteen weeks after transplant, there were significantly more surviving xenografts in Groups 3 (p < 0.001) and 4 (p < 0.001) compared with control Group 1 (Fisher's exact test) and significantly better functioning xenografts in Groups 3 (p < 0.01) and 4 (p < 0.05) compared with control Group 1 (contrasts of groups following analysis of variance with Bonferroni correction).

Conclusions. A short course of anti-CD25 mAb—induced immunosuppression was as effective as a long course of cyclosporin-induced immunosuppression in this model.

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Christopher R. Honey, A. Jon Stoessl, Joseph K. C. Tsui, Michael Schulzer and Donald B. Calne

Object. The goal of this study was to determine whether unilateral pallidotomy reduces parkinsonian pain.

Methods. Twenty-one patients suffering from Parkinson's disease (PD) were followed prospectively for 1 year after they had undergone a unilateral pallidotomy to assess the procedure's effect on pain related to PD. Pain unrelated to PD was not studied. Patients scored the level of their PD pain on an ordinal scale (0–10 points) preoperatively and 6 weeks and 1 year postoperatively. The results were analyzed using Wilcoxon's paired-ranks test (with Bonferroni correction) and showed a significant reduction in overall pain scores at 6 weeks (p < 0.001) and 1 year (p = 0.001) following pallidotomy. Various types of PD pain are described and their possible pathophysiological mechanisms are presented.

Conclusions. Unilateral pallidotomy significantly reduces pain attributable to Parkinson's disease.

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Christopher R. Honey, Modestus O. K. Obochi, Hao Shen, Philippe Margaron, Stephen Yip and Julia G. Levy

Object. The goal of this study was to develop a method of reducing neural xenograft rejection by pretreating the graft with photodynamic therapy (PDT).

Methods. Xenograft cell suspensions were prepared from fetal mouse mesencephalon, after which they were incubated for 30 minutes with various concentrations of a photosensitizer, verteporfin for injection, and light exposure. The xenograft cell suspensions were injected into the dopamine-depleted striata of 40 hemiparkinsonian rats assigned to different treatment groups. Four weeks after transplantation, xenograft function (determined by methamphetamine-induced rotation) and survival (determined by immunohistochemical staining for murine neurons) were compared. Group 1 animals (xenografts pretreated with 25 ng/ml verteporfin) and Group 3 animals (no verteporfin pretreatment, but daily administration of cyclosporin A) had significantly better xenograft survival and function compared with control animals (no pretreatment with verteporfin). Group 2 animals (xenografts pretreated with 250 ng/ml verteporfin) had no significant improvement.

Conclusions. This work demonstrates improved neural xenograft survival and function when using pretransplant PDT of the graft in a rodent model. The potential benefits of this new therapy are its convenience (one pretransplant treatment) and its compatibility with host immunosuppression.

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Caglar Berk and Christopher R. Honey

✓ Isolated head tremor is rare, but can be disabling. The authors' experience with the treatment of limb tremor due to essential tremor led them to consider using bilateral thalamic deep brain stimulation (DBS) in two patients presenting only with disabling head tremor.

One patient exhibited no peripheral tremor and the other displayed only a slight upper-limb tremor. Both patients underwent placement of units that apply simultaneous bilateral thalamic DBS. Surgical targets were verified by using intraoperative macrostimulation, and the stimulators were implanted during the same surgery. Patients were videotaped preoperatively and at 2, 4, 6, and 9 months postoperatively during periods in which the stimulators were turned on and off. Videotapes were randomized and rated for resting, postural, and action tremors according to the Fahn clinical rating scale for tremor. Because this scale is not designed for head tremor, the patients were also evaluated on the basis of a functional scale that reflected their quality of life and the amount of disability caused by head tremor.

Both patients experienced no tremor after their stimulators were turned on and properly adjusted at the 6th postoperative week. The patients were followed for a total of 9 months and results remained stable throughout this period. No complications were encountered.

Bilateral thalamic DBS appears to be an effective and safe treatment for isolated head tremor in patients with essential tremor. The authors present a scale for the functional assessment of head tremor.

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Ravikant S. Palur, Caglar Berk, Michael Schulzer and Christopher R. Honey

Object. There is an active debate regarding whether pallidotomy should be performed using macroelectrode stimulation or the more sophisticated and expensive method of microelectrode recording. No prospective, randomized trial results have answered this question, although personnel at many centers claim one method is superior. In their metaanalysis the authors reviewed published reports of both methods to determine if there is a significant difference in clinical outcomes or complication rates associated with these methods.

Methods. A metaanalysis was performed with data from reports on the use of unilateral pallidotomy in patients with Parkinson disease (PD) that were published between 1992 and 2000. A Medline search was conducted for the key word “pallidotomy” and additional studies were added following a review of the references. Only those studies dealing with unilateral procedures performed in patients with PD were included. Papers were excluded if they described a cohort smaller than 10 patients or a follow-up period shorter than 3 months or included cases that previously had been reported. The primary end points for outcome were the percentages of improvement in dyskinesias and in motor scores determined by the Unified PD Rating Scale (UPDRS). Complications were categorized as mortality, intracranial hemorrhage, visual deficit, speech deficit, cognitive decline, weakness, and other.

There were no significant differences between the two methods with respect to improvements in dyskinesias (p = 0.66) or UPDRS motor scores (p = 0.62). Microelectrode recording was associated with a significantly higher (p = 0.012) intracranial hemorrhage rate (1.3 ± 0.4%), compared with macroelectrode stimulation (0.25 ± 0.2%).

Conclusions. In reports of patients with PD who underwent unilateral pallidotomy, operations that included microelectrode recording were associated with a small, but significantly higher rate of symptomatic intracranial hemorrhage; however, there was no difference in postoperative reduction of dyskinesia or bradykinesia compared with operations that included macroelectrode stimulation.

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Caglar Berk, Jason Carr, Marci Sinden, Jeff Martzke and Christopher R. Honey

Object. In several studies a significant reduction in tremor after thalamic deep brain stimulation (DBS) has been reported among patients with multiple sclerosis (MS). It has not been determined if this results in an improved quality of life. In this study the authors prospectively evaluated the effects of thalamic DBS on tremor and quality of life.

Methods. Videotapes of the patients' tremor were made preoperatively and 2 and 12 months postoperatively, and tremor was scored by a neurologist blinded to the treatment. Patients were tested pre- and postoperatively to measure any changes in their reported ability to perform selected activities of daily living and in their health-related quality of life. Patients were asked to complete a questionnaire about their satisfaction with the surgery. Postoperative changes were examined using paired t-tests.

There were significant reductions in postural, action, and overall tremor at 2 and 12 months postoperatively. The patients' reported ability to feed themselves was significantly improved 2 months after surgery (p = 0.01). There were short-term trends toward improvement in reported dressing ability, personal hygiene, and writing. There were no significant changes in the SF-36 subscales or total score.

Conclusions. In this cohort of patients with MS who suffered from tremor, thalamic DBS significantly improved their tremor and ability to feed themselves. Patient satisfaction with the procedure, however, was variable. Preoperative patient education about what functions might (and might not) be improved is crucial to avoid unrealistic expectations. Our results indicate that younger patients with MS tremor who had a shorter disease duration and no superimposed ataxia benefited most from this surgery.

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Ming-Chieh Sun, Christopher R. Honey, Caglar Berk, Norman L. M. Wong and Joseph K. C. Tsui

Object. Aquaporin-4 (AQP4) plays a significant role in the regulation of brain water homeostasis. In this study the authors investigated the regulation of AQP4 following a focal cortical contusion injury in rats.

Methods. Thirty-three adult male Wistar rats received a focal cortical contusion of the parietal cortex. An additional nine rats underwent a craniectomy, but no trauma was inflicted (sham injury). Animals were killed 1, 4, and 24 hours later. The rat brains were examined for water content by comparing the wet and dry weights of each hemisphere. Aquaporin-4 messenger (m)RNA was measured by reverse transcription—polymerase chain reaction. A ratio of AQP4 mRNA expression in the lesioned hemisphere compared with that in the contralateral control hemisphere was calculated for each animal at the injury site (parietal cortex) and at sites adjacent to (occipital cortex) and distant from the injury (frontal pole cortex).

Brain edema was significantly increased at the injury site. The expression of AQP4 mRNA was significantly increased at the injury site, significantly decreased adjacent to the injury site, and not significantly different at a site distant from the injury. The magnitude of AQP4 mRNA upregulation at the injured parietal cortex correlated with the degree of downregulation in the adjacent occipital cortex.

Conclusions. Data from this study demonstrate that an upregulation of AQP4 occurs at the site of traumatic brain injury and that a downregulation of this molecule occurs adjacent to the site of injury. Understanding the physiology of AQP4 and its regulation following brain injury may allow for the development of novel treatments for cerebral edema that accompanies head injury.

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Jason A. R. Carr, Christopher R. Honey, Marci Sinden, Anthony G. Phillips and Jeffrey S. Martzke

Object. The aim of this study was to examine neuropsychological outcome from unilateral posteroventral pallidotomy (PVP) in Parkinson disease while controlling for confounding factors such as test practice and disease progression.

Methods. Participants underwent baseline and 2-month follow-up assessments of cognition, quality of life, mood, and motor functioning. The surgery group (22 patients) underwent PVP (15 left, seven right) after baseline assessment. The waitlist group (14 patients) underwent PVP after follow up. At follow up, the left PVP group exhibited a decline on verbal measures of learning, fluency, working memory, and speeded color naming. The incidence of significant decline on these measures after left PVP ranged from 50 to 86%. The right PVP group did not exhibit a significant cognitive decline, but fluency did decline in 71% of patients who underwent right PVP. Participants who underwent PVP reported better bodily pain and social functioning at follow up than participants in the waitlist group. Improved bodily pain was evident for 62% of the surgery group, and social functioning improved for 19%. Surgery did not alter reported physical functioning or mood. Dyskinesia improved after surgery, but there were no improvements in “on-state” manual dexterity or handwriting.

Conclusions. Most patients who underwent left PVP exhibited declines in learning, fluency, working memory, and speeded color naming. Accounting for retesting effects altered the magnitude of these declines by up to one quarter of a standard deviation, but did not increase the breadth of postsurgical neuropsychological decline beyond that typically reported in the literature. It was found that PVP improved dyskinesia, bodily pain, and social functioning, but did not lead to improvement on other objective and self-reported measures of motor functioning.

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Sebastião Gusmão, Marcelo Oliveira, Uedson Tazinaffo and Christopher R. Honey

✓ The authors describe a new procedure for percutaneous trigeminal radiofrequency rhizotomy. Computerized tomography fluoroscopy is used for guidance of the rhizotomy needle insertion through the foramen ovale. Ten patients were treated using this method, and in each case the target was reached with a single puncture. The potential benefits of this method are presented.

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Rodrigo Mercado, Tomasz Mandat, G. R. Wayne Moore, David Li, Alex MacKay and Christopher R. Honey


Surgery for tremor targets the ventrolateral nuclei of the thalamus. An initial radiological estimation of this target can be further refined through intraoperative physiological confirmation. Direct visualization of these nuclei has not yet been described. The improved signal-to-noise ratio associated with 3-tesla (3T) magnetic resonance (MR) imaging makes increased spatial resolution possible, which may aid in the identification of subtle morphological features. This study was conducted to describe the anatomy of the nuclei and fiber projections within the ventral thalamus by using 3T MR imaging.


Using a commercially available 3T MR unit, the authors obtained images of a formalin-fixed, paraffin-embedded brain. Slices with a 2-mm thickness and 0.2-mm gap were obtained parallel to the anterior commissure–posterior commissure (AC–PC) line. The brain was then sectioned through the cerebral hemispheres to obtain tissue slices encompassing the same levels. Adjacent 10-μm paraffin sections from the middle of each level were stained with Luxol fast blue and cresyl violet. The MR image and histological sections at the level of the AC–PC line were then compared in detail. In a separate study, the human thalamus was scanned in vivo using 3T and 1.5T MR imaging for anatomical comparison.


The anatomy of the nuclei and fiber projections within the ventrolateral thalamus in humans can be described using 3T MR imaging. The findings were reproducible in vivo with 3T but not 1.5T MR imaging. Additional studies are needed to confirm the accuracy of this observation for clinical purposes.