Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Vagus nerve stimulation for depression: rationale, anatomical and physiological basis of efficacy and future prospects.

Treatment-resistant depression (TRD) is a major public health concern due to its high costs to society. One of the novel approaches for the treatment of depression is the vagus nerve stimulation (VNS). Therapeutic brain stimulation through delivery of pulsed electrical impulses to the left cervical vagus nerve now has established safety and efficacy as an adjunct treatment for medication-resistant epilepsy and has recently been approved as an adjunct long-term treatment for chronic or recurrent depression. There is considerable evidence from both animal and human neurochemical and neuroimaging studies, that the vagus nerve and its stimulation influence limbic and higher cortical brain regions implicated in mood disorders, providing a rationale for its possible role in the treatment of psychiatric disorders. Clinical studies (open-label and comparator with treatment in naturalistic setting) in patients with TRD have produced promising results, especially when the response rates at longer-term (one- and two-year) follow-up time points are considered. Ongoing research efforts will help determine the place of VNS in the armament of therapeutic modalities available for major depression.

Development and initial validation of a screening tool for Parkinson disease surgical candidates.

As there is currently no standardized assessment tool for evaluating Parkinson disease (PD) patients for deep brain stimulation (DBS), the authors developed the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD). Part I of the study was a retrospective analysis of 174 patients presenting for a surgical screening. Part II was a multicenter study to assess the correlation of FLASQ-PD scores. The results of this study suggest that the FLASQ-PD may be a useful triage tool for screening PD patients for DBS surgery.

Radiation and regeneration: behavioral improvement and GDNF expression after Gamma Knife radiosurgery in the 6-OHDA rodent model of hemi-parkinsonism.

BACKGROUND: Recent research has demonstrated that the adult mammalian CNS is capable of regeneration. This regeneration is often initiated as a response to thermal, chemical or mechanical injury. The effects of radiation on the mammalian CNS have also been found to aid in certain regeneration processes. METHOD: In our project we examined the potential therapeutic value of radiation induced regeneration of diseased mammalian rat CNS. Eleven Sprague-Dawley rats with 6-hydroxy-dopamine (6-OHDA) induced hemi-parkinsonism were treated in the Leksell Gamma Knife using a single 4 mm collimator shot targeted to the ipsilateral (parkinsonian) caudate-putamen complex. A maximum dose of 140 Gy was used to create a necrotic lesion. Animals were tested behaviorally using the apomorphine-induced rotational behavior model before and up to 6 months after radiosurgery. Histochemical analysis was performed 2 weeks, 1 month and 4 months after radiosurgery. Histological sections were obtained and immunohistochemistry was performed for glial cell line derived neurotrophic factor (GDNF). FINDINGS: The rotational behavior for 11/11 animals (100%) was found to initially worsen at 2 weeks and 4 weeks after radiosurgery before a statistically highly significant reduction in apomorphine induced rotations was observed at 2, 3, and 4 months after radiosurgery (83% reduction by month four; p < 0.0001). For 2/11 animals the rotational behavior almost disappeared indicating near-abolition of parkinsonian behavior. On histological examination, the lesions were easily identified as areas of necrosis about 4 mm in diameter. The region immediately adjacent to the lesion was found to have highly positive expression of GDNF indicating high activity in dopamine-regenerating processes. INTERPRETATION: In this preliminary study we demonstrated that radiosurgical lesioning with the Gamma Knife into the striatum of hemi-parkinsonian animals resulted in significant behavioral improvement of signs of parkinsonism. Since GDNF expression is tightly linked to the dopaminergic system, we conclude that focused radiation is potentially capable of inducing regeneration of dopaminergic pathways in the adult CNS. Further studies with dose deescalation and molecular biological characterization of the regeneration cascades are necessary to gain access to potential clinical value of our observations.

Gamma knife surgery for treatment of central neurocytomas. Report of four cases.

The authors investigated the use of gamma knife surgery (GKS) in the treatment of central neurocytoma, a usually benign primary brain tumor of the lateral and third ventricles. Four patients with subtotally resected or recurrent central neurocytomas were retrospectively studied. The prescription isodose was 9 to 13 Gy to the 30 to 50% peripheral isodose line. Pre- and postoperative magnetic resonance (MR) images were compared to determine the volume reduction following GKS. Follow-up review included annual MR imaging and clinical evaluation by a neurosurgeon. Follow-up periods ranged from 12 to 99 months. Marked reduction in tumor size was seen in all four patients; the decrease in tumor volume for each was 48%, 72%, 81%, and 77%, respectively, at the last follow-up review. None of the four patients required additional treatment and none experienced a decline in neurological function during the follow-up period. No complications have been noted in any of these patients to date. Even though there have been few observations and follow-up time has been limited, because of the consistency of the response and the lack of observed side effects, GKS may be the treatment of choice for subtotally resected and recurrent central neurocytomas.

Outcomes in patients treated with gamma knife radiosurgery for brain metastases from malignant melanoma.

In order to determine the effectiveness of gamma knife (GK) radiosurgery in patients with malignant melanoma metastases, the authors conducted a prospective multicenter study. Forty-five patients with a total of 96 lesions were treated and followed to measure survival time, tumor control rate, and Karnofsky Performance Scale (KPS) score. The mean survival time was 8.7 months (median 4.2 months), and tumor control was achieved in 86% of lesions. When obtained, the median preoperative KPS of 80 was maintained at a median of 80 post-GK treatment. The authors found GK treatment for metastases of malignant melanoma to be highly effective in controlling tumor growth. Survival rates obtained after GK treatment were found to be superior to historically obtained data concerning external beam radiotherapy follow up. Radiosurgery with the GK can therefore be considered a good primary treatment option for metastatic brain disease of malignant melanoma.

Radiosurgical lesioning of the caudate nucleus as a treatment for parkinsonism: a preliminary report.

In ten patients with parkinsonism a radiosurgical operation with the Gamma Knife was performed in which a small lesion was created in the head of the caudate nucleus bilaterally. Preoperatively, in all cases bradykinesia was the main complaint and in all patients conventional drug treatment no longer resulted in a satisfactory response. After a follow-up period of one month six patients showed clear benefit. There was no complication or side effect that could be related to this form of treatment. Pre- and post-operative testing was performed with the Unified Parkinson Rating Scale and with objective motor tasks. The main improvement seen concerned bradykinesia and rigidity: tremor was ameliorated to a lesser extent. Possible mechanisms underlying the improved motor function are discussed as well as the role of lesioning of the striatum in light of transplantation neurosurgery.

Gamma knife for glioma: selection factors and survival.

PURPOSE: To determine factors associated with survival differences in patients treated with radiosurgery for glioma. METHODS AND MATERIALS: We analyzed 189 patients treated with Gamma Knife radiosurgery for primary or recurrent glioma World Health Organization (WHO) Grades 1-4. CONCLUSION: The median minimum tumor dose was 16 Gy (8-30 Gy) and the median tumor volume was 5.9 cc (1.3-52 cc). Brachytherapy selection criteria were satisfied in 65% of patients. Median follow-up of all surviving patients was 65 weeks after radiosurgery. For primary glioblastoma patients, median survival from the date of pathologic diagnosis was 86 weeks if brachytherapy criteria were satisfied and 40 weeks if they were not (p = 0.01), indicating that selection factors strongly influence survival. Multivariate analysis showed that increased survival was associated with five variables: lower pathologic grade, younger age, increased Karnofsky performance status (KPS), smaller tumor volume, and unifocal tumor. Survival was not found to be significantly related to radiosurgical technical parameters (dose, number of isocenters, prescription isodose percent, inhomogeneity) or extent of preradiosurgery surgery. We developed a hazard ratio model that is independent of the technical details of radiosurgery and applied it to reported radiosurgery and brachytherapy series, demonstrating a significant correlation between survival and hazard ratio. CONCLUSIONS: Survival after radiosurgery for glioma is strongly related to five selection variables. Much of the variation in survival reported in previous series can be attributed to differences in distributions of these variables. These variables should be considered in selecting patients for radiosurgery and in the design of future studies.

Lesion size following Gamma Knife treatment for functional disorders.

In this study we investigated the reproducibility and consistency of the size of radiosurgical lesions produced for functional disorders. The T1 gadolinium-enhanced magnetic resonance (MR) images of 56 patients treated for parkinsonism, pain, or other functional diseases were used to measure 140 lesion sizes at various times after radiosurgical treatment (1-26 months, mean: 11.3 months). Only the 4-mm collimator was used to create the lesions. The maximum dose ranged from 110 to 180 Gy (mean: 145 Gy). In 42 cases (78%), one isocenter was used to create the lesion. Thirteen lesions (20%) were created with two isocenters and in 1 case, three isocenters were used. Lesions were detectable on MR images as early as 30 days after treatment. The maximum lesion volume was reached after 6-12 months and ranged from nondetectable to more than 4,000 mm3. Larger lesion volumes were strongly associated with the use of more than one isocenter. In addition, maximum doses of 160 Gy or more increased the likelihood of producing lesions larger than expected. It is therefore concluded that the use of the Gamma Knife for the treatment of functional disorders is safest when single-isocenter shots with the 4-mm collimator and a maximum dose of less than 160 Gy are used.

Evidence for segregated pain and temperature conduction within the spinothalamic tract.

The lateral spinothalamic tract, located in the anterolateral quadrant of the white matter of the spinal cord, is one of the most important structures in transmitting pain within the central nervous system. It has been known for almost a century that destruction of fibers in this tract results in analgesia contralateral to the lesion. The effectiveness and clinical importance of interruption of the lateral spinothalamic tract has been proven in many studies. Today cordotomies are still a useful neurosurgical treatment modality, especially when pain can no longer be sufficiently controlled by analgesic drugs. Although analgesia on the contralateral side is the desired effect, one must also expect to cause disturbance in temperature sensation when performing a cordotomy. The authors' observations showed that after a cordotomy the dermatome level of analgesia can be variable within certain limits, which is in accordance with the literature. Surprisingly, however, the loss of temperature sensation may differ significantly from the loss of pain sensation. It was also found to be possible to perform a successful cordotomy without altering the sensation of temperature at all. This indicates that pain and temperature sensations may be conducted via separate pathways. Possible mechanisms underlying this phenomenon are discussed.

Stereotactic radiosurgery of skull base meningiomas.

Between April 1992 and March 1994, 48 patients with skull base meningiomas were treated at our department. The age of these patients ranged from 10 to 76 years. The male:female ratio was 1:3. Thirty-seven of these patients had primary open surgery for partial removal and subsequent radiosurgical treatment. In 1 patient a recurrent meningioma after so-called total microsurgical removal was treated radiosurgically. Radiosurgery was performed as a primary treatment in 11 patients. The mean tumor volume was 13.7 cm3 (range: 0.8-82 cm3). These tumor volumes could be covered by mean isodose volumes of 44% (range: 30-70%) and were treated by a mean dose of 15 Gy (range: 8-25 Gy) at the tumor border. One patient underwent radiosurgery with a staged treatment protocol with a 4.6-month interval. In 37 patients, a total of 102 follow-up scans were available. The remaining 11 patients have not been included in the postradiosurgical evaluation, since the observation time was either too short or the patients were lost to follow-up. The mean interval between Gamma Knife treatment and the last follow-up scan was 12 months, with a range from 2.3 to 22.7 months. Follow-up imaging (CT, MRI or both) revealed a decreased volume of the tumor in 9 cases (24%). In 25 cases (68%), tumor progression was stopped, and in 3 cases (8%) increased tumor volumes could be observed (2 patients with malignant meningiomas). In 3 cases marked central tumor necrosis was seen. Neurological follow-up examinations (n = 38 patients) showed a stable neurological status in 74%, ameliorated status in 13% and worsening in 13% of the patients.

Thalamotomy and caudatotomy with the Gamma Knife as a treatment for parkinsonism with a comment on lesion sizes.

Radiosurgery with the Gamma Knife was performed in 12 patients with parkinsonism. In 9 patients small lesions were created in the head of the caudate nucleus bilaterally. Two patients underwent radiosurgical thalamotomy, and 1 patient was treated with caudatotomy and thalamotomy. After a follow-up period of 1-12 months, 9 patients of the caudatotomy group and all patients with thalamotomies showed clear benefit. There was no complication or side effect that could be related to the treatment. Pre- and postoperative testing was performed with the Unified Parkinson Rating Scale and with objective motor tasks. Caudatotomy proved to be an effective treatment for bradykinesia and rigidity, while tremor was ameliorated by thalamotomy. Functional neurosurgery with the Gamma Knife would seem to be a good alternative to open procedures with low morbidity and no mortality. Advantages and drawbacks of radiosurgical techniques for the treatment of parkinsonism are discussed.

Radiosurgery with the first Austrian cobalt-60 Gamma-unit. A one year experience.

During the period of one year, from the 21. 4. 1992 to 21. 4. 1993, a total of 201 radiosurgical sessions on 181 patients were performed with the first Austrian Gamma-unit in Graz. 42% of radiosurgical sessions were undertaken for malignomas, 20% for meningiomas, 11.5% for vascular malformations, 9% for neurinomas, 8.5% for low grade astrocytomas and glomus jugulare tumours, 5% for sellar and suprasellar lesions, and 4% for functional disorders. Dose plan data for all the lesions treated are shown. Clinical and imaging data of the first year which are available for 120 patients (66%) are presented and discussed.

Air embolism with bilateral pneumothorax after a five-meter dive.

After an emergency ascent from very shallow depth, a diver suffered a triad of symptoms after bilateral barotrauma of the lungs: air embolism with subsequent paraparesis, pneumomediastinum, and bilateral pneumothorax. This is the first case of its kind in 20 yr of experience in the hyperbaric center at Graz. The patient was successfully treated by recompression with HBO.

Lesioning of the striatum reverses motor asymmetry in the 6-hydroxydopamine rodent model of parkinsonism.

In the rat several paradigms of grafting of adrenal medulla into the striatum were studied following the induction of a parkinsonian model, using a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Direct autologous grafting of adrenal medulla into the caudate-putamen complex, a radiofrequency lesion of the striatum alone, and a radiofrequency lesion followed by delayed grafting of adrenal medulla were compared by analyzing rotational behavior. Direct grafting of adrenal medulla produced an overall reduction in apomorphine induced turning behavior by 43.5% when compared with controls. Radiofrequency lesioning of the striatum without graft showed the best improvement over control animals with a 92% reduction in the total number of rotations induced by apomorphine. Delayed grafting into the caudate lesion cavity also produced a dramatic reduction in motor asymmetry but did not improve the behavioral outcome over that of the lesion alone. Animals receiving only radiofrequency lesions exhibited a band of increased tyrosine hydroxylase like immunoreactivity bordering the lesion cavity. Graft survival was limited in the non-lesioned animals but appeared enhanced in the animals whose striatum was previously lesioned. Lesion location within the striatum influenced the behavioral outcome. Large reductions in apomorphine-induced rotations could result from small lesions of the dorso-lateral striatum. These findings indicate that selective destruction of the caudate-putamen complex without tissue transplantation produces a dramatic reduction in the motor asymmetry of 6-OHDA treated rats. Suggested explanations for the decrease in induced rotational behavior with radiofrequency lesions include a decrease in the number of striatal dopamine receptors following cell destruction and lesion-induced recovery of host dopaminergic afferents. Striatal damage in critical areas can reverse some of the motor behavior associated with the 6-OHDA model and needs to be considered when evaluating the effects of neural grafting in this model.