Interstitial brachytherapy using stereotactic implanted (125)iodine seeds for recurrent medulloblastoma.

AIMS: To evaluate the efficacy of interstitial brachytherapy using (125)iodine ((125)I) seeds for the treatment of recurrent multimodal treated medulloblastoma. MATERIALS AND METHODS: Between September 1989 and August 2009, 12 patients (female:male=3:9, median age 19 years, range 7-55 years) with 23 recurrent medulloblastomas underwent interstitial brachytherapy using (125)I seeds. Before brachytherapy, all patients underwent microsurgical resection; six patients underwent a combined adjuvant treatment consisting of craniospinal irradiation and chemotherapy; three received craniospinal irradiation alone and two received chemotherapy alone. One patient was treated by surgery alone. The median tumour volume was 4.9ml (range 0.4-44.2ml), the median tumour surface dose 50Gy (range 32-50Gy) and the median implantation time 42 days (range 42-90 days). A median follow-up of 26 months was available (range 5-116 months). RESULTS: After brachytherapy, nine of 23 tumours (39%) presented a complete remission, nine (39%) a partial remission and five (22%) stable disease on magnetic resonance images. The neurological status improved in six patients and remained unchanged in four. Two patients deteriorated: one developed spinal metastasis and another a treatment-related adverse radiation effect. Ten patients died due to disseminated disease despite local tumour control. The median survival after treatment was 15 months (range 5-68 months). CONCLUSIONS: Our results show a good response of recurrent medulloblastoma after interstitial brachytherapy. High rates of tumour remission were yielded with low rates of treatment-related morbidity. Thus, (125)I seed brachytherapy should be considered as a treatment option for recurrent medulloblastoma.

Clinical effectiveness of unilateral deep brain stimulation in Tourette syndrome.

Dysfunctional basal ganglia loops are thought to underlie the clinical picture of Tourette syndrome (TS). By altering dopaminergic activity in the affected neural structures, bilateral deep brain stimulation is assumed to have a modulatory effect on dopamine transmission resulting in an amelioration of tics. While the majority of published case reports deals with the application of bilateral stimulation, the present study aims at informing about the high effectiveness of unilateral stimulation of pallidal and nigral thalamic territories in TS. Potential implications and gains of the unilateral approach are discussed.

[The prevalence of bilateral malignant uveal melanoma]. / Zur Häufigkeit bilateraler maligner Melanome der Aderhaut.

BACKGROUND: Malignant melanoma of the choroid is the most common ocular primary malignancy, but is still a rare tumour. The occurrence of bilateral uveal melanoma is exceedingly rare. The probability of any one individual developing bilateral melanoma is estimated to be 1 to 50 million. MATERIALS AND METHODS: A retrospective search of the photo database of patients between 1970 and 2006 with uveal melanoma was performed. RESULTS: Four patients with bilateral melanoma were identified. The case reports of the two females and two males are presented. CONCLUSIONS: In summary, bilateral primary uveal melanoma seems to occur more frequently than expected. The estimated probability for patients with unilateral primary uveal melanoma of developing bilateral melanoma is 0.2 %. In single cases the interval between the occurrence of the second melanoma can be more than 30 years. In patients with a history of malignant melanoma of the choroid it is important to carefully observe the other eye life-long.

Neurosurgical pain therapy with epidural spinal cord stimulation (SCS).

Neurosurgical therapy for intractable pain with epidural implantable electrodes has become a widely used and efficient alternative when conservative or less invasive therapies are no longer effective. A complete interdisciplinary work-up is required before considering a patient as a candidate for a spinal cord stimulation (SCS) device. In more than 1300 patients we implanted an SCS device in our clinic; more than 52% reported a significant (>50%) long-term improvement for more than 3 years and a significant reduction in their analgesic drugs. Although placement of the electrode and implantation of the stimulator are technically easy to perform, they do carry a risk of potentially debilitating complications such as meningitis or component migration. Hence. SCS therapy should only be performed in specialized centers. In peripheral vascular disease (PVD) and angina, the initial results are very promising, but the long-term efficacy has to be proven by multicenter studies.

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.

Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson's disease: measuring the on- and off-conditions with FDG-PET.

In order to compare the effects of high-frequency stimulation of the subthalamic nucleus (STN-DBS) and a levodopa-challenge on cerebral metabolic activity, we conducted PET scans with [(18)F]2-fluoro-2-deoxyglucose (FDG) in the drug- and stimulation- on- and off-condition in a single patient suffering from advanced PD. Our data revealed evidence for improved thalamocortical processing released from inhibition by overactive basal ganglia output nuclei in both on-conditions. While levodopa also led to a reduction of lentiform hyperactivity, effective STN stimulation seemed to interfere with distinct cerebellar and limbic circuits.

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinson's disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. METHODS: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinson's disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. RESULTS: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US dollars 20,810, EURO 20,410, GB pounds 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7+/-21.8 (US dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Effects of pallidal deep brain stimulation and levodopa treatment on reaction-time performance in Parkinson's disease.

Basal ganglia-thalamocortical circuits play an important role in movement preparation and execution. Tracer, single-cell, and lesion studies in monkeys suggest the existence of topologically segregated motor and nonmotor basal ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of the posteroventrolateral globus pallidus internus (GPi) in patients with Parkinson's disease to elucidate the function of the GPi in human sensorimotor behavior. This question was investigated by comparing the influence of DBS on patients' performance in various reaction-time tasks that differed with respect to cognitive but not motor requirements. As a main result, DBS improved performance on the different tasks independently of the complexity of the involved cognitive processing functions. Furthermore, the observed effects did not depend on the modality of the processed information. These results suggest that the functional state of the posteroventrolateral GPi selectively affects the motor stage in simple sensorimotor acts, because this stage was the only stage involved in all investigated tasks. In addition to DBS, we manipulated the levodopa medication state of the PD patients. In contrast to DBS, levodopa effects on reaction times were less consistent. Levodopa improved reaction times in choice reaction tasks significantly, while affecting reaction times in a simple reaction task to a lesser extent. Error analysis revealed that the medication-dependent reaction-time improvement in the choice reaction tasks was accompanied by an increase in errors, suggesting a shift of the speed-accuracy criteria of the patients. A similar pattern of results was not observed for the DBS effects. Taken together, our data are in agreement with recent findings in monkeys that indicate a topological organization of the GPi in which motor functions are localized in posterolateral regions apart from cognitive regions. Furthermore, our data show a way to uncover the subcortical-cortical circuitry serving human sensorimotor behavior.

Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson's disease.

Bilateral high-frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age-matched healthy subjects served as controls. The non-random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation-induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non-significant increases in both step length and cadence contributed.

Deep brain stimulation of the internal pallidum did not improve chorea in a patient with neuro-acanthocytosis.

We report the failure of bilateral globus pallidus internus deep brain stimulation to improve chorea in a patient with chorea-acanthocytosis. Prior to this surgery the patient had experienced a striking but short lived amelioration of symptoms with clozapine therapy.

Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease.

We report here the results of an open prospective study in 9 patients suffering from severe Parkinson's disease with on/off fluctuations and restricted off-period mobility, who underwent bilateral implantation of stimulating electrodes in the internal pallidum. At 3-month follow-up, the total Unified Parkinson's Disease Rating Scale (UPDRS) motor score in the medication-off state was reduced from 54.1+/-14.8 to 23.9+/-11.7 (44.2%) when stimulation was turned on. Comparison of UPDRS subscores revealed significant improvements for tremor, rigidity, bradykinesia, gait and posture, and dyskinesias. The results of the clinical scoring could be confirmed by significant changes in the quantitative assessment of hand function and walking. Bilateral pallidal stimulation reduced the amount and severity of on/off fluctuations. Additional follow-up at 6 months (n=6), 9 months (n=6), and 12 months (n=4) did not show a decline in effectiveness of stimulation. There was no permanent morbidity associated with the procedure. A subtle reduction of verbal fluency, which was not evident to the patients, was the only cognitive side effect of the procedure in neuropsychological testing. Chronic bilateral high-frequency stimulation of the internal pallidum seems to be a neurologically safe and highly effective treatment for "off" symptoms, dyskinesias, and motor fluctuations in advanced stages of Parkinson's disease.

Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson's disease.

In the past, stereotactic surgery was a regular treatment for prominent unilateral tremor in Parkinson's disease (PD), but follow-up studies were usually short-term and always unblinded. We examined 17 PD patients in long-term follow-up (mean, 10.9 years after surgery) and used videotapes and the Unified Parkinson's Disease Rating Scale to blindly compare tremor ipsilateral and contralateral to the side of surgery. Since the patients were specifically selected for stereotactic surgery because of asymmetric tremor, and the surgical side chosen was contralateral to the predominant tremor, a sign of long-term efficacy would be current postoperative reversal of tremor side predominance. Upper extremity tremor was significantly better contralateral to the surgery compared with the ipsilateral side. We conclude that stereotactic surgery improved the absolute magnitude of tremor or ameliorated its rate of progression. Since asymmetric bradykinesia and dyskinesia were not a prerequisite for the choice of surgical side, we cannot make any conclusion about long-term impact of surgery on these features.

Computerized optimization of 125I implants in brain tumors.

A computer program for treatment planning for the interstitial radiotherapy of brain tumors with 125I stereotactic implants is presented. To minimize brain traumatization only 1-3 catheters loaded with several seeds are implanted. It is possible to position the catheters very accurately due to CT guided stereotactic techniques. Precise treatment planning is necessary because of the high dose gradient of the radiation field. Two planning methods are available: conventional planning with interactive optimization of source configurations and an automatic optimization procedure. The goal of optimization is to identify source parameters (catheter positions and seed activities) for which a prescribed dose at the target surface is approximated as closely as possible.

Neurosurgical treatment of cancer pain.

Neurosurgical pain operations in carcinoma patients should always be considered when conservative treatment methods fail or pain relief can be attained only at the cost of undesired side effects. The therapeutic spectrum of neurosurgery has been appreciably extended in recent years. Due to the introduction of percutaneous surgery methods, the operations have become less burdensome, so that carcinoma patients who were formerly regarded as inoperable can also be given neurosurgical pain treatment. The advances in neurophysiology have led to a better understanding of pain mechanisms, in consequence of which the various possibilities of treatment can be employed more specifically with prospects of better treatment results. The spectrum of neurosurgical treatment extends from destructive measures (rhizotomies, cordotomies, thalamotomies, neurolytics) via intrathecal administration of morphine-like substances to the augmentative nondestructive neurostimulation techniques. Despite the advances in conservative therapy of cancer pain, in many cases, a neurosurgical procedure is most efficacious in controlling carcinoma pain.

Chronic electrical stimulation of the thalamic unspecific activating system in a patient with coma due to midbrain and upper brain stem infarction.

Chronic intermittent bipolar electrical stimulation of the left nucleus reticulatus polaris thalami was performed in a patient in a state of subcoma due to ischaemic infarction of wide medial parts of the midbrain, mainly the tegmentum, and the right-sided mediobasal parts of the forebrain. Stimulation immediately resulted in autonomic reactions and behavioural arousal reactions during the periods of stimulation. Longterm effect consisted of a rise in the level of clinical responsiveness for a period of seven weeks. A preexistent severe pneumonia disappeared completely after one week of stimulation and returned after seven weeks. The results are discussed on the basis of the pathoanatomical findings and of the physiological functions of the damaged as well as of the stimulated areas.