Motor Improvement and Emotional Stabilization in Patients With Tourette Syndrome After Deep Brain Stimulation of the Ventral Anterior and Ventrolateral Motor Part of the Thalamus.

BACKGROUND: Since its first application in 1999, the potential benefit of deep brain stimulation (DBS) in reducing symptoms of otherwise treatment-refractory Tourette syndrome (TS) has been documented in several publications. However, uncertainty regarding the ideal neural targets remains, and the eventuality of so far undocumented but possible negative long-term effects on personality fuels the debate about the ethical implications of DBS. METHODS: In this prospective open-label trial, eight patients (three female, five male) 19-56 years old with severe and medically intractable TS were treated with high-frequency DBS of the ventral anterior and ventrolateral motor part of the thalamus. To assess the course of TS, its clinical comorbidities, personality parameters, and self-perceived quality of life, patients underwent repeated psychiatric assessments at baseline and 6 and 12 months after DBS onset. RESULTS: Analysis indicated a strongly significant and beneficial effect of DBS on TS symptoms, trait anxiety, quality of life, and global functioning with an apparently low side-effect profile. In addition, presurgical compulsivity, anxiety, emotional dysregulation, and inhibition appeared to be significant predictors of surgery outcome. CONCLUSIONS: Trading off motor effects and desirable side effects against surgery-related risks and negative implications, stimulation of the ventral anterior and ventrolateral motor part of the thalamus seems to be a valuable option when considering DBS for TS.

Stereotactic interstitial brachytherapy for the treatment of oligodendroglial brain tumors.

PURPOSE: We evaluated the treatment of oligodendroglial brain tumors with interstitial brachytherapy (IBT) using (125)iodine seeds ((125)I) and analyzed prognostic factors. PATIENTS AND METHODS: Between January 1991 and December 2010, 63 patients (median age 43.3 years, range 20.8-63.4 years) suffering from oligodendroglial brain tumors were treated with (125)I IBT either as primary, adjuvantly after incomplete resection, or as salvage therapy after tumor recurrence. Possible prognostic factors influencing disease progression and survival were retrospectively investigated. RESULTS: The actuarial 2-, 5-, and 10-year overall and progression-free survival rates after IBT for WHO II tumors were 96.9, 96.9, 89.8 % and 96.9, 93.8, 47.3 %; for WHO III tumors 90.3, 77, 54.9 % and 80.6, 58.4, 45.9 %, respectively. Magnetic resonance imaging demonstrated complete remission in 2 patients, partial remission in 13 patients, stable disease in 17 patients and tumor progression in 31 patients. Median time to progression for WHO II tumors was 87.6 months and for WHO III tumors 27.8 months. Neurological status improved in 10 patients and remained stable in 20 patients, while 9 patients deteriorated. There was no treatment-related mortality. Treatment-related morbidity was transient in 11 patients. WHO II, KPS ≥ 90 %, frontal location, and tumor surface dose > 50 Gy were associated with increased overall survival (p ≤ 0.05). Oligodendroglioma and frontal location were associated with a prolonged progression-free survival (p ≤ 0.05). CONCLUSION: Our study indicates that IBT achieves local control rates comparable to surgery and radio-/chemotherapy treatment, is minimally invasive, and safe. Due to the low rate of side effects, IBT may represent an attractive option as part of a multimodal treatment schedule, being supplementary to microsurgery or as a salvage therapy after chemotherapy and conventional irradiation.

Verbal fluency in essential tremor patients: the effects of deep brain stimulation.

OBJECTIVE: To assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET). METHODS: In 17 ET-patients with thalamic-DBS, Tremor-Rating-Scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i) high-frequency stimulation (HFS), ii) low-frequency stimulation (LFS) and iii) OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated. RESULTS: Tremor was reduced during HFS (MeanTRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (MeanTRS-OFF = 44.4 ± 19.8, P < .001) and to LFS (MeanTRS-10 Hz = 50.0 ± 24.2; P < .001). While performance of Stroop-task and digit-span remained unaffected by stimulation-settings (P > .05), phonemic and semantic VF differed significantly between the three conditions (FPvf = 5.28, FSvf = 3.41, both P < .05). Post-hoc comparisons revealed significant differences for both phonemic and semantic VF between LFS (MeanPvf-10 Hz = 54.6 ± 9.2, MeanSvf-10 Hz = 56.4 ± 7.9) and HFS (MeanPvf-ON = 48.3 ± 11.4, MeanSvf-ON = 51.1 ± 11.0, both P < .05), while DBS-OFF (MeanPvf-OFF = 51.2 ± 9.3, MeanSvf-OFF = 53.6 ± 12.9) and HFS and DBS-OFF and LFS did not differ significantly (P > .05). CONCLUSIONS: HFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor.

OBJECTIVE: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). METHODS: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. RESULTS: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non-current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. CONCLUSION: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.

Intracranial ependymoma: long-term results in a series of 21 patients treated with stereotactic (125)iodine brachytherapy.

BACKGROUND: We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT). METHODS: Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8-70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted (125)Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical resection prior to IBT; in 5 patients, IBT was performed primarily after stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose ranged from 50-65 Gy treating a median tumor volume of 3.6 ml (range, 0.3-11.6 ml). A median follow-up period of 105.3 months (range, 12.7-286.2 months) was evaluated. RESULTS: Actuarial 2-, 5- and 10-years overall- and disease-specific survival rates after IBT were each 90% and 100% at all times for ependymomas WHO I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%, respectively. The neurological status of seven patients improved, while there was no change in 12 and deterioration in 2 patients, respectively. Follow-up MR images disclosed a complete tumor remission in 3, a partial remission in 12 and a stable disease in 6 patients. Treatment-associated morbidity only occurred in a single patient. CONCLUSIONS: This study shows that stereotactic IBT for intracranial ependymomas is safe and can provide a high degree of local tumor control. Due to the low rate of side effects, IBT may evolve into an attractive alternative to microsurgery in ependymomas located in eloquent areas or as a salvage treatment.

11C-Methionine positron emission tomographic imaging of biologic activity of a recurrent glioblastoma treated with stereotaxy-guided laser-induced interstitial thermotherapy.

In patients with recurrent glioblastoma multiforme (GBM), local minimally invasive treatment modalities have gained increasing interest recently because they are associated with fewer side effects than open surgery. For example, local tumor coagulation by laser-induced interstitial thermotherapy (LITT) is such a minimally invasive technique. We monitored the metabolic effects of stereotaxy-guided LITT in a patient with a recurrent GBM using amino acid positron emission tomography (PET). Serial 11C-methyl-L-methionine positron emission tomography (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a hybrid PET/CT system in a patient with recurrent GBM before and after LITT. To monitor the biologic activity of the effects of stereotaxy-guided LITT, a threshold-based volume of interest analysis of the metabolically active tumor volume (MET uptake index of ≥ 1.3) was performed. A continuous decline in metabolically active tumor volume after LITT could be observed. MET-PET seems to be useful for monitoring the short-term therapeutic effects of LITT, especially when patients have been pretreated with a multistep therapeutic regimen. MET-PET seems to be an appropriate tool to monitor and guide experimental LITT regimens and should be studied in a larger patient group to confirm its clinical value.

Essential tremor and tremor in Parkinson's disease are associated with distinct 'tremor clusters' in the ventral thalamus.

Different tremor entities such as Essential Tremor (ET) or tremor in Parkinson's disease (PD) can be ameliorated by the implantation of electrodes in the ventral thalamus for Deep Brain Stimulation (DBS). The exact neural mechanisms underlying this treatment, as well as the specific pathophysiology of the tremor in both diseases to date remain elusive. Since tremor-related local field potentials (LFP) have been shown to cluster with a somatotopic representation in the subthalamic nucleus, we here investigated the neurophysiological correlates of tremor in the ventral thalamus in ET and PD using power and coherence analysis. Local field potentials (LFPs) at different recording depths and surface electromyographic signals (EMGs) from the extensor and flexor muscles of the contralateral forearm were recorded simultaneously in twelve ET and five PD patients. Data analysis revealed individual electrophysiological patterns of LFP-EMG coherence at single and double tremor frequency for each patient. Patterns observed varied in their spatial distribution within the Ventral lateral posterior nucleus of the thalamus (VLp), revealing a specific topography of 'tremor clusters' for PD and ET. The data strongly suggest that within VLp individual tremor-related electrophysiological signatures exist in ET and PD tremor.

Pineal parenchymal tumors. Management with interstitial iodine-125 radiosurgery.

PURPOSE: To evaluate the efficacy of interstitial radiosurgery (IRS) for pineal parenchymal tumors (PPTs). PATIENTS AND METHODS: 18 consecutively admitted patients (twelve male and six female, age range 6-68 years, median age 34 years) with PPTs (eight pineocytomas, ten malignant PPTs) were treated at the authors' institution with IRS using stereotactically guided iodine-125 seed implantation ((125)I-IRS) as either primary or salvage therapy. The cumulative tumor surface dose ranged from 40 to 64 Gy. Adjuvant radiotherapy of the whole brain or the craniospine was done in patients with grade III and grade IV PPT. The median follow-up period was 57.4 months (range 6-134 months). RESULTS: Overall actuarial 5- and 8-year survival rates after IRS were 100% and 86% for pineocytomas, and the overall actuarial 5-year survival rate was 78% for high-grade PPTs. Follow-up magnetic resonance imaging showed complete remission in 72% (13/18) and partial remission in 28% (5/18) of the cases. One patient developed an out-of-field relapse 4 years after partial remission of a pineocytoma, which had already been treated with IRS. There was no treatment-related mortality. Treatment-related morbidity occurred in two patients only. CONCLUSION: This study indicates that stereotactic (125)I-IRS for the management of PPTs is quite efficient and safe. Due to the low rate of side effects, IRS may develop into an attractive alternative to microsurgery in de novo diagnosed pineocytomas. In malignant PPTs, IRS may be routinely applied in a multimodality treatment schedule supplementary to conventional irradiation.

Combined x-ray and magnetic resonance imaging facility: application to image-guided stereotactic and functional neurosurgery.

OBJECTIVE: To assess the feasibility of a hybrid imaging setup combining x-ray and magnetic resonance imaging (MRI) in the setting of both stereotactic and functional neurosurgery. METHODS: A combined x-ray and MRI scanning facility with a trolley system for a fast patient transfer between both modalities was installed in a neurosurgical setting. A registration algorithm for fusion of MRI scans and x-ray images was derived for augmentation of fluoroscopic x-ray projection images with MRI scan data, such as anatomic structures and planned probe trajectories. Phantom measurements were obtained between both modalities for estimation of registration accuracy. Practical application of our system in stereotactic and functional neurosurgery was tested in brachytherapy, deep brain stimulation, and motor cortex stimulation. RESULTS: Phantom measurements yielded a mean spatial deviation of 0.7 +/- 0.3 mm with a maximum deviation of 1.1 mm for MRI scans versus x-rays. Augmentation of x-ray images with MRI scan data allowed intraoperative verification of the planned trajectory and target in three types of neurosurgical procedures: positioning iodine seeds in brachytherapy in one case with cerebellar metastasis, placement of electrodes for deep brain stimulation in two cases of advanced Parkinson's disease, and placement of an epidural grid for motor cortex stimulation in two cases of intractable pain. CONCLUSION: Combined x-ray and MRI-guided stereotactic and functional neurosurgery is feasible. Augmentation of x-ray projection images with MRI scan data, such as planned probe trajectories and MRI scan segmented anatomic structures may be beneficial for probe guidance in stereotactic and functional neurosurgery.

Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease.

This article deals with technical aspects of intraoperative functional magnetic resonance imaging (fMRI) for monitoring the effect of deep brain stimulation (DBS) in a patient with Parkinson's disease. Under motor activation, therapeutic high-frequency stimulation of the subthalamic nucleus was accompanied by an activation decrease in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. Furthermore, an activation increase in the contralateral basal ganglia and insula region were detected. These findings demonstrate that fMRI constitutes a promising clinical application for investigating brain activity changes induced by DBS.