Glioma infiltration of the corpus callosum: early signs detected by DTI.

The most frequent primary brain tumors, anaplastic astrocytomas (AA) and glioblastomas (GBM): tend to invasion of the surrounding brain. Histopathological studies found malignant cells in macroscopically unsuspicious brain parenchyma remote from the primary tumor, even affecting the contralateral hemisphere. In early stages, diffuse interneural infiltration with changes of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) is suspected. The purpose of this study was to investigate the value of DTI as a possible instrument of depicting evidence of tumor invasion into the corpus callosum (CC). Preoperatively, 31 patients with high-grade brain tumors (8 AA and 23 GBM) were examined by MRI at 3 T, applying a high-resolution diffusion tensor imaging (DTI) sequence. ADC- and FA-values were analyzed in the tumor-associated area of the CC as identified by fiber tracking, and were compared to matched healthy controls. In (MR-)morphologically normal appearing CC the ADC values were elevated in the tumor patients (n = 22; 0.978 × 10(-3) mm²/s) compared to matched controls (0.917 × 10(-3) mm²/s, p < 0.05), and the corresponding relative FA was reduced (rFA: 88 %, p < 0.01). The effect was pronounced in case of affection of the CC visible on MRI (n = 9; 0.978 × 10(-3) mm²/s, p < 0.05; rFA: 72 %, p < 0.01). Changes in diffusivity and anisotropy in the CC can be interpreted as an indicator of tumor spread into the contralateral hemisphere not visible on conventional MRI.

Comparison of F-18 FET-PET with F-18 FDG-PET for biopsy planning of non-contrast-enhancing gliomas.

OBJECTIVE: The management of non-contrast-enhancing brain tumours largely depends on biopsy, which allows a differentiation of low-grade gliomas (LGG) from high-grade gliomas (HGG). The aim of this study was to compare positron emission tomography using 2-[(18)F]-fluoro-2-deoxy-D: -glucose (FDG-PET) and O-(2-[(18)F]-fluoroethyl)-L: -tyrosine (FET-PET) in terms of providing target regions for biopsies. MATERIALS AND METHODS: Fifteen consecutive patients with newly diagnosed brain tumours (n = 11) or suspected recurrence of a known LGG (n = 4), in whom MRI demonstrated no contrast enhancement, were studied by both FET-PET and FDG-PET. FET-PET, FDG-PET and MRI data were fused, and then transferred to the neurosurgical navigation system, prior to neurosurgical interventions. RESULTS: Histology showed HGG (WHO grade III) in 6/15 and LGG (WHO grade II) in 9/15 patients. FET-PET revealed an increased intratumoural tracer uptake in 8/9 LGG and in 5/6 HGG. FDG-PET depicted hypermetabolic spots in 2/9 LGG and in 4/6 HGG. In 6 patients we observed an increased intratumoural uptake of both tracers. In 4 of them, the area of highest FET accumulation in the tumour corresponded to the focus of increased FDG uptake. CONCLUSIONS: FET-PET appears to be superior to FDG-PET for biopsy planning in non-contrast-enhancing brain tumours. FDG-PET does not provide any additional information in this issue.

123I-IMT SPECT for evaluation of the response to radiation therapy in high grade gliomas: a feasibility study.

Assessing response to radiation therapy in patients with high grade gliomas is needed upon making decisions toward further therapy strategies. Currently used standard imaging tools such as CT and MRI are not sensitive enough to detect early therapy effects. We prospectively investigated if single photon emission computed tomography (SPECT) using radiolabelled amino acid derivate (123)I-methyltyrosine (IMT) would be useful for this aim. 10 patients with histologically proven high grade gliomas, who were candidates for radiation therapy, were enrolled in this investigation. All patients were examined by IMT SPECT before radiation therapy and 4 weeks after the initiation of the hypofractionated application of 40 Gy. Patients were followed up for 39 months; the tumours to background ratios (T/B) for IMT under/before radiation therapy were correlated to survival times. Initially, SPECT depicted an abnormal intratumoural IMT uptake in all patients (mean T/B ratios 1.37-1.87). In four out of 10 patients, the mean T/B ratios decreased by more than 10% under radiation therapy. In six other patients, the BQ decreased by less than 10% or increased. There were no significant correlations between the degree of changes in T/B and survival (r = -0.1, p = 0.973). Serial IMT SPECT measurements allow detection of changes in amino acid accumulation in high-grade gliomas under radiation therapy. However, these changes seem to possess no prognostic value in respect to survival prediction.

Results of chronic subthalamic nucleus stimulation for Parkinson's disease: a 1-year follow-up study.

BACKGROUND: Deep brain stimulation (DBS) has been established as an alternative approach for the treatment of advanced Parkinson's disease (PD). Recently, the subthalamic nucleus (STN) has been identified as the optimal target for DBS. METHODS: Thirty-eight patients have undergone surgery for advanced PD since 1996. They include 12 females and 26 males with a mean age of 55.6 years. The mean stage on the Hoehn and Yahr Scale was 3.5 (off condition). Electrodes (Medtronic DBS 31389) were stereotactically implanted into the STN bilaterally. Targeting was performed using computerized tomography (CT) scans and ventriculography (VG). After 4 days of external stimulation, permanent neurostimulators were implanted. Patients were evaluated preoperatively and 1, 6, and 12 months postoperatively. Evaluations were performed in defined on and off states using the Unified Parkinson's Disease Rating Scale (UPDRS) as well as the Hoehn and Yahr Scale, the dyskinesia scale, and the Activities of Daily Living (ADL) Scale. RESULTS: Significant improvement of all motor symptoms was found in all patients (UPDRS motor score 32/48 preoperatively versus 15/30 at 12-month follow-up, p < 0.001). Daily off-times were reduced by 35%. Dyskinesias also improved markedly (UPDRS IV: 3.2/3.1 [on/off] vs. 0.9/1.3 at 12 months follow-up). Postoperative L-dopa medication was adjusted (mean reduction: 53%). Complications occurred in two patients (5%) who developed infections, leading to system removal. Systems were replaced after 6 months. Two patients (5%) had a permanent worsening of a previously known depressive state and developed progressive dementia. CONCLUSIONS: TN stimulation is a relatively safe procedure for treating advanced PD. The possibility of readjusting the stimulation parameters postoperatively improves the therapeutic outcome and reduces side effects in comparison to ablative methods.

Deep brain stimulation of the globus pallidus internus (GPI) for torsion dystonia--a report of two cases.

Generalized dystonia is known as a type of movement disorder in which pharmacotherapeutic options are very limited. Deep Brain Stimulation (DBS) is well established for Parkinson's disease (PD) and tremor dominant movement disorders. We report on two cases of generalized dystonia which were successfully treated by chronic high frequency stimulation in the Globus pallidus internus (GPI). Two 26 and 27 years old males suffered from severe torsion dystonia and multisegmental dystonia of the lower limbs. Case 1 is a familiar type of dystonia (DYT1 positive). The onset of symptoms in both cases was at age 7. The complaints were initially treated with orally administered benzodiazepines, anticholinergic drugs, later by baclofen and L-DOPA. However there was no response. Case 2 was a patient with a history of left side dominated dystonia since the age of 8. It was first diagnosed as a psychogenic movement disorder. Prior to surgery he was treated with L-DOPA, anticholinergics, Baclofen without any effect. There was only a limited effect on high doses of diazepam. The patient is DYT1 negative. The target point was on both sides the GPI. Intraoperative computerized tomography (CT) and ventriculography (VG) were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode position. Surgery was performed under analgosedation. Two weeks after surgery we first observed a relief of symptoms in both cases. A significant reduction in the Burke-Fahn-Marsden-Dystonia Movement Rating Scale was observed at the 6 month follow-up (case 1: 95%, case 2: 80%). In case 1 a slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The medication was continuously reduced. At the 24 month follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (mean 3.5 V, 400 microseconds, 145 Hz).

Differences in immune cell invasion into the cerebrospinal fluid and brain parenchyma during cerebral infusion of interleukin-1beta.

Cytokine-mediated inflammatory cell recruitment into the brain is a critical step in the response to diverse insults, including infection, trauma, and stroke. Hence, continous intra-cerebroventricular infusion of interleukin (IL)-1beta leads to an impressive cell invasion into the cerebrospinal fluid, as well as the brain parenchyma. Neither tumor necrosis factor-alpha nor IL-6 induced any significant cell invasion at all. However, the diverse immune cells (granulocytes, monocytes/macrophages) showed a different time course of invasion. Moreover, there was an association between the number of infiltrating immune cells and the infused IL-1 concentration. By analyzing intra-brain immune events, we demonstrated a time- and dose-dependent induction of intercellular adhesion molecule (ICAM)-1, whereas there were no differences for P-selectin, vascular cell adhesion molecule (VCAM)-1, and monocyte-chemotractant protein (MCP)-1, comparing vehicle and IL-1-infused animals. In conclusion, we assume IL-1beta to be a key cytokine for the granulocyte and monocyte recruitment into the central nervous system after various insults. However, granulocytes anticipate monocyte invasion.

Mutational analysis of INI1 in sporadic human brain tumors.

The INI1/SMARCB1/hSNF5 gene on chromosome 22 is frequently mutated in rhabdoid tumors. An association of INI1 mutations with allelic losses on chromosome 22 supports a classical tumor suppressor mechanism. Several brain tumor entities including astrocytomas, glioblastomas and ependymomas are characterized by allelic losses on chromosome 22. In the present study we examined a series of 200 brain tumors by Single-strand conformation polymorphism analysis and direct sequencing for point mutations in INI1. In addition, all tumors were analyzed for homozygous deletions spanning both exons 3 and 8 of INI1. No mutations or homozygous deletions were detected in astrocytomas, glioblastomas, oligodendroglial tumors, neurinomas or medulloblastomas. However, a point mutation could be identified in the single case of plexus carcinoma. Our data suggest that INI1 mutations are involved in the pathogenesis of plexus carcinoma; however, INI1 alterations are not a frequent event in the majority of brain tumor entities.