Low-power inversion recovery MRI preserves brain tissue contrast for patients with Parkinson disease with deep brain stimulators.

BACKGROUND AND PURPOSE: Fast spin-echo short τ inversion recovery sequences have been very useful for MR imaging-guided deep brain stimulation procedures in Parkinson disease. However, high-quality fast spin-echo imaging deposits significant heat, exceeding FDA-approved limits when patients already have undergone deep brain stimulation and need a second one or a routine brain MR imaging for neurologic indications. We have developed a STIR sequence with an ultra-low specific absorption rate that meets hardware limitations and produces adequate tissue contrast in cortical and subcortical brain tissues for deep brain stimulation recipients. MATERIALS AND METHODS: Thirteen patients with medically refractory Parkinson disease who qualified for deep brain stimulation were imaged at 1.5T with a fast spin-echo short τ inversion recovery sequence modified to meet conditional MR imaging hardware and specific absorption rate restrictions. Tissue contrast-to-noise ratios and implant localization were objectively and subjectively compared by 2 neuroradiologists, and image quality for surgical planning was assessed by a neurosurgeon for high and low specific absorption rate images. RESULTS: The mean contrast-to-noise ratio for cerebral tissues without including the contrast-to-noise ratio for ventricular fluid was 35 and 31 for high and low specific absorption rate images. Subjective ratings for low specific absorption rate tissue contrast in 77% of patients were identical to (and in a few cases higher than) those of high specific absorption rate contrast, while the neurosurgical coordinates for fusing the stereotactic atlas with low specific absorption rate MR imaging were equivalent to those of the high specific absorption rate for 69% of patients. CONCLUSIONS: Patients with Parkinson disease who have already had a deep brain stimulation face a risk of neural injury if routine, high specific absorption rate MR imaging is performed. Our modified fast spin-echo short τ inversion recovery sequence conforms to very conservative radiofrequency safety limits, while it maintains high tissue contrast for presurgical planning, postsurgical assessment, and radiologic evaluations with greater confidence for radiofrequency safety.

Sixty hertz pallidal deep brain stimulation for primary torsion dystonia.

OBJECTIVE: To evaluate the safety and efficacy of 60 Hz deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 15 consecutive patients with primary dystonia. METHODS: We conducted a retrospective analysis of clinic charts relative to 15 consecutive patients with medically refractory primary dystonia who underwent stereotactic implantation of DBS leads within the GPi. Twelve had the DYT1 gene mutation. Frame-based MRI and intraoperative microelectrode recording were employed for targeting. All patients were treated exclusively with stimulation at 60 Hz from therapy outset. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) served as the primary measure of symptom severity at baseline and 1, 3, 6, and 12 months after treatment. RESULTS: All patients tolerated DBS treatment well and showed a progressive median improvement of their BFMDRS motor subscores from 38% at 1 month to 89% at 1 year (p < 0.001, Wilcoxon rank sum test). The disability subscores were similarly improved. The clinical response to DBS allowed seven patients to completely discontinue their medications; six additional patients had reduced their medications by at least 50%. Surgical complications were limited to two superficial infections, which were treated successfully. CONCLUSIONS: Stimulation of the internal globus pallidus at 60 Hz is safe and effective for treating medically refractory primary dystonia.

Deep brain stimulation for torsion dystonia.

Deep brain stimulation (DBS) at the globus pallidus pars internus (GPi) is an effective treatment for some patients with medically refractory torsion dystonia. In this chapter we review the classification and treatment of torsion dystonia including the current indications for DBS surgery. Details of the DBS procedure and programming of the DBS devices are discussed. Pallidal DBS is most effective in patients with primary generalized dystonia. Children and adolescents possessing the DYT1 gene mutation may respond best of all. Patients with cervical dystonia may also improve with pallidal DBS but definitive clinical evidence is lacking. As a group, patients with secondary dystonias respond less well to DBS than do patients with primary dystonia; however, patients with dystonia secondary to anoxic brain injury who have grossly intact basal ganglia anatomy, and patients with tardive dystonia may represent secondary dystonia subtypes for whom pallidal DBS is a viable option.

Intraoperative microelectrode recording equipment: what features are necessary?

Intraoperative neurophysiologic methods for localizing targets deep in the brain require the use of specialized monitoring and recording equipment, including stimulators, neurophysiologic recording devices, and image manipulation tools. When using microelectrode recording devices there are some specifications that are more important than others, such as signal-to-noise ratios and amplifier impedance. As more companies develop tools to be used in the operating room, the end users have more choices. Some of the more important specifications are discussed and a comparison is made of the five major brands on the market today.

Contemporary psychosurgery and a look to the future.

OBJECT: Despite a long and controversial history, psychosurgery has persisted as a modern treatment option for some severe, medically intractable psychiatric disorders. The goal of this study was to review the current state of psychosurgery. METHODS: In this review, the definition of psychosurgery, patient selection criteria, and anatomical and physiological rationales for cingulotomy, subcaudate tractotomy, anterior capsulotomy, and limbic leukotomy are discussed. The historical developments, modern procedures, and results of these four contemporary psychosurgical procedures are also reviewed. Examples of recent advances in neuroscience indicating a future role for neurosurgical intervention for psychiatric disease are also mentioned. CONCLUSIONS: A thorough understanding of contemporary psychosurgery will help neurosurgeons and other physicians face the ethical, social, and technical challenges that are sure to lie ahead as modern science continues to unlock the secrets of the mind and brain.

Surgical options in Parkinson's disease.

Surgical treatments for Parkinson's disease (PD) have again become important adjuncts of care in these patients. We have learned much from the thousands of lesions performed historically, and are now advancing the entire field of movement disorder surgery to new levels of sophistication and understanding. The last 5 years have seen more precise and reliable lesioning and the arrival of multiple sites of intervention afforded by recent developments in deep brain stimulators. Because patients typically derive significant benefit in their quality of life from these procedures, while undergoing little risk, the surgical options should be carefully considered for selected PD patients.

Microelectrode recording during posteroventral pallidotomy: impact on target selection and complications.

OBJECTIVE: To assess the practical usefulness of single-cell microelectrode recording (MER) when performing posteroventral pallidotomy. METHODS: A retrospective comparison of the initial, magnetic resonance imaging-derived coordinates of the pallidotomy target to the final, MER-refined lesion coordinates in 132 consecutive pallidotomies was conducted. The time required to perform the procedure and the surgical complications are reported. RESULTS: MER led to targeting changes in 98% of the cases. In 12%, the MER-refined target was more than 4 mm from the original, image-guided site, which is a targeting error that could adversely affect outcome. Although all components of targeting were affected by MER, laterality and depth were impacted most. The ventral border of the globus pallidus pars interna was located within 1 mm of the magnetic resonance imaging-selected target in only 40% of the cases. On average, only 2.2 MER trajectories were required to perform pallidotomy. During the last 3 years of our study, 85% of the procedures were performed with one or two trajectories. The mean operating time of the operations performed during the last 3 years was 2 hours and 12 minutes. The incidence of intracerebral hemorrhage in our series (1.5%) was no higher than that reported for other large series of stereotactic procedures. No patient suffered an optic tract injury. CONCLUSION: MER provides important targeting information for performing pallidotomy. In particular, the micrometric delineation of the ventral border of the globus pallidus pars interna permits safe lesioning of the posteroventral region of the globus pallidus pars interna with little risk of visual field deficit. These data can be obtained efficiently and without increased surgical risk.

Targeting for thalamic deep brain stimulator implantation without computer guidance: assessment of targeting accuracy.

The authors assess the accuracy of targeting nucleus ventralis intermedius (Vim) with fast spin echo inversion recovery (FSE/IR) magnetic resonance imaging (MRI) in 18 successful deep brain stimulator (DBS) implants for medically refractory tremor. FSE/IR-MRI-derived coordinates are compared to the final coordinates employed for DBS lead placement, selected with intraoperative neurophysiology. The authors conclude that FSE/IR MRI is sufficiently reliable to serve as the sole means of anatomically targeting Vim for DBS lead placement. An independent computer workstation is not required for accurate targeting; however, intraoperative neurophysiology remains essential.

Cost-effective screening for cerebral aneurysms.

The advent of accurate, noninvasive angiography has raised hopes that premorbid screening for cerebral aneurysm will soon be possible. This article discusses the medical and economic issues which will determine the appropriate conditions for, and cost-effectiveness of, large-scale aneurysm screening.

Pallidotomy technique and results: the New York University experience.

The authors relate the New York University experience with 171 pallidotomies performed on 160 consecutive patients over a 6-year period. Details of their patient selection criteria, operative technique, preliminary clinical results, and surgical complications are reported. They conclude that unilateral posteroventral pallidotomy is a safe and effective treatment for a subset of Parkinson's disease patients who suffer with rigidity, bradykinesia, tremor, and L-dopa-induced dyskinesia. Patients with Parkinson's Plus syndromes can be definitively identified with positron emission tomography and do not improve with pallidotomy. The routine performance of bilateral pallidotomy remains controversial.

Preoperative indicators of clinical outcome following stereotaxic pallidotomy.

We assessed the utility of preoperative clinical assessment and functional brain imaging with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in predicting the clinical outcome of stereotaxic pallidotomy for the treatment of advanced Parkinson's disease (PD). Twenty-two PD patients undergoing posteroventral pallidotomy were assessed preoperatively with the Core Assessment Program for Intracerebral Transplantation (CAPIT) ratings measured on and off levodopa; quantitative FDG/PET was also performed before surgery. Preoperative clinical and metabolic measurements were correlated with changes in off-state CAPIT ratings determined 3 months after surgery. Clinical outcome following pallidotomy was also correlated with intraoperative measures of spontaneous pallidal single-unit activity as well as postoperative MRI measurements of lesion volume and location. We found that unilateral pallidotomy resulted in variable clinical improvement in off-state CAPIT scores for the contralateral limbs (mean change 30.9 +/- 15.5%). Postoperative MRI revealed that pallidotomy lesions were comparable in location and volume across the patients. Clinical outcome following surgery correlated significantly with preoperative measures of CAPIT score change with levodopa administration (r = 0.60, p < 0.005) and with preoperative FDG/PET measurements of lentiform glucose metabolism (r = 0.71, p < 0.0005). Operative outcome did not correlate with intraoperative measures of spontaneous pallidal neuronal firing rate. We conclude that preoperative measurements of lentiform glucose metabolism and levodopa responsiveness may be useful indicators of motor improvement following pallidotomy. Both preoperative quantitative measures, either singly or in combination, may be helpful in selecting optimal candidates for surgery.

Metabolic correlates of pallidal neuronal activity in Parkinson's disease.

We have used [18F]fluorodeoxyglucose and PET to identify specific metabolic covariance patterns associated with Parkinson's disease and related disorders previously. Nonetheless, the physiological correlates of these abnormal patterns are unknown. In this study we used PET to measure resting state glucose metabolism in 42 awake unmedicated Parkinson's disease patients prior to unilateral stereotaxic pallidotomy for relief of symptoms. Spontaneous single unit activity of the internal segment of the globus pallidus (GPi) was recorded intraoperatively in the same patients under identical conditions. The first 24 patients (Group A) were scanned on an intermediate resolution tomograph (full width at half maximum, 8 mm); the subsequent 18 patients (Group B) were scanned on a higher resolution tomograph (full width half maximum, 4.2 mm). We found significant positive correlations between GPi firing rates and thalamic glucose metabolism in both patient groups (Group A: r = 0.41, P < 0.05; Group B: r = 0.69, P < 0.005). In Group B, pixel-based analysis disclosed a significant focus of physiological-metabolic correlation involving the ventral thalamus and the GPi (statistical parametric map: P < 0.05, corrected). Regional covariance analysis demonstrated that internal pallidal neuronal activity correlated significantly (r = 0.65, P < 0.005) with the expression of a unique network characterized by covarying pallidothalamic and brainstem metabolic activity. Our findings suggest that the variability in pallidal neuronal firing rates in Parkinson's disease patients is associated with individual differences in the metabolic activity of efferent projection systems.

Efficacy of bilateral pallidotomy.

Unilateral pallidotomy is a safe and effective treatment for medically refractory bradykinetic Parkinson's disease, especially in those patients with levodopa-induced dyskinesia and severe on-off fluctuations. The efficacy of bilateral pallidotomy is less certain. The authors completed 11 of 12 attempted bilateral pallidotomies among 150 patients undergoing pallidotomy at New York University. In all but one patient, the pallidotomies were separated by at least 9 months. Patients were selected for bilateral pallidotomy if they exhibited bilateral rigidity, bradykinesia, or levodopa-induced dyskinesia prior to treatment or if they exhibited disease progression contralateral to their previously treated side. The Unified Parkinson's Disease Rating Scale (UPDRS) and timed upper-extremity tasks of the Core Assessment Protocol for Intracerebral Transplantation (CAPIT) were administered to all 12 patients in the "off" state (12 hours without receiving medications) preoperatively and again at 6 and 12 months after each procedure. The median UPDRS and contralateral CAPIT scores improved 60% following the initial procedure (p = 0.008, Wilcoxon rank sums test). The second pallidotomy generated only an additional 10% improvement in the UPDRS and CAPIT scores ipsilateral to the original procedure (p = 0.05). Worsened speech was observed in two cases. In the 12th case, total speech arrest was noted during test stimulation. Speech returned within minutes after stimulation was halted. Lesioning was not performed. These results indicate that bilateral pallidotomy has a narrow therapeutic window. Motor improvement ipsilateral to the first lesion leaves little room for further improvement from the second lesion and the risk of speech deficit is greatly enhanced. Chronic pallidal stimulation contralateral to a previously successful pallidotomy may prove to be a safer alternative for the subset of patients who require bilateral procedures.

Selection criteria for unilateral posteroventral pallidotomy.

In an attempt to refine the indications for posteroventral pallidotomy (PVP) the authors instituted strict selection criteria which are based on the experience gained from the first 60 pallidotomy patients treated at their institution. In addition to clinical evaluation, all pallidotomy candidates undergo neuropsychological testing and 18F-fluoro-deoxyglucose utilization positron emission tomography (FDG/PET). The data from which these criteria were developed are presented as are early clinical results. The authors demonstrate that these criteria enhance the efficacy of the procedure by assuring therapeutic response and reducing the incidence of post-operative dementia. Their indications and contraindications for pallidotomy are discussed.

Pallidal targeting with the COMPASS system.

The authors describe their initial experience with the new pallidotomy targeting software for the COMPASS system. As COMPASS permits window and contrast settings to be changed at any time, multiple imaging modalities can be employed for targeting. This feature allowed the incorporation of fast-spin echo/inversion recovery (FSE/IR) magnetic resonance images (MRI) into the planning protocol. COMPASS has now been employed for 33 consecutive pallidotomies over the last year (July 96-June 97). A statistically significant reduction in the number of microelectrode recording trajectories required to physiologically localize sensorimotor globus pallidus interna (GPi) is noted in these cases as compared to the 41 cases performed in the previous year with a different computer planning system. The authors conclude that the COMPASS system accurately and efficiently targets the internal pallidum when FSE/IR MRI is employed. Nevertheless, pallidotomy should not be performed without neurophysiological localization.

Electrical stimulation of the globus pallidus preceding stereotactic posteroventral pallidotomy.

Physiological methods such as microelectrode recording of neuronal activity and electrical stimulation of target structures can improve the safety and efficacy of certain stereotactic surgeries. The globus pallidus (GP) was electrically stimulated in 136 patients with Parkinson's disease prior to unilateral posteroventral pallidotomy to identify functional areas and prevent deficits. We found that electrical stimulation of the GP elicited two principal responses: contractions of the contralateral hand and flashing lights. The mean voltage that evoked motor responses was 4.3 V (range 1.7-9.0 V), while higher intensity was necessary to elicit visual responses (mean 6.8 V; range 3.5-9.9 V). Contralateral tremor, speech impairment, paresthesias, and warm sensations were also elicited.

Stereotactic ventrolateral thalamotomy: is ventriculography necessary?

In the computed tomography/magnetic resonance imaging (CT/MRI) era, the need for ventriculography to perform ventrolateral thalamotomy accurately has been debated. We retrospectively compared CT/MRI-derived coordinates for ventrolateral thalamotomy with the final lesion coordinates that were determined by ventriculography and microelectrode recording in 74 thalamotomies performed from 1984 to 1994. The median three-dimensional distance between the CT/MRI-derived loci and the ventriculography/microelectrode loci was 4.7 mm (range, 1.0-11.7 mm). The techniques correlated least along the Y axis (median, -0.3 mm; range, -8.2 to 8.0 mm). Correlation along the X axis was most consistent (median, 0.5 mm; range, -4.2 to 5.0 mm). Since 1990, the CT/MRI-derived coordinates have been generated by a multimodality correlative imaging technique (MCIT). A comparison of thalamotomies performed with and without the MCIT revealed a significant improvement in the correlation of CT/MRI- and ventriculography/microelectrode-derived coordinates when the MCIT was employed. The greatest improvement was noted along the Y axis where the median absolute difference was reduced from 4.0 to 1.8 mm (P = 0.0001). The result was a statistically significant reduction in the median three-dimensional distance from 5.6 to 3.7 mm (P = 0.0007). The authors conclude that thalamotomies can be safely and effectively performed without ventriculography when the MCIT is employed and supported by neurophysiological monitoring.

Colony stimulating factor-1 expression in human glioma.

Colony stimulating factor 1 (CSF-1) is a functionally versatile, circulating homodimeric growth factor that stimulates the survival, proliferation, and differentiation of mononuclear phagocytic cells, the differentiation of osteoclast progenitor cells and that regulates cells of the female reproductive tract. CSF-1 is also expressed in the central nervous system where it may regulate the differentiation and activation of microglia. The diverse forms of CSF-1 are all encoded by a single gene. Alternative posttranscriptional splicing and posttranslational cleavage determines whether CSF-1 will be produced as a secreted proteoglycan, secreted glycoprotein, or as a cell-surface glycoprotein that may be involved in cell-cell interactions. CSF-1 is expressed in glioblastoma cell-lines, normal human astrocytes, and in operative specimens of human glioma. The CSF-1 receptor, encoded by the c-fms proto-oncogene, is also expressed in human gliomas. We conclude that coexpression of CSF-1 and its receptor in some human gliomas hints at a possible autocrine or paracrine growth stimulatory role for CSF-1; however, its function in the mammalian CNS remains to be elucidated.

A primary encephalocele culture yields a pure population of human astrocytes.

In order to develop a reliable source of human astrocytes for in vitro studies, we established a primary explant culture of a human encephalocele. This culture yielded a population of cells which were karyotypically normal, morphologically resembled astrocytes, expressed glial fibrillary acid protein, and responded mitogenically to exogenous growth factors. We conclude that white matter derived from human encephaloceles can be used to generate pure populations of normal astrocytes.