Long-Term Tumor Control Following Targeted Alpha Therapy (TAT) of Low-Grade Gliomas (LGGs): A New Treatment Paradigm?

The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [213Bi]Bi/[225Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [90Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule-catheter system. The activity used for radiolabeling was 2-2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG.

Does Functional Imaging Play a Role in Pre-Operative Diagnosis of Brain Tumours?

Although there is a large variability in the neural organization of language function between individuals, there is an ongoing debate about functional imaging as a standard procedure in the preoperative setting of brain tumors. Brain mapping of the language centers differs from individual to individual in multilingual patients and changes in its architecture may occur as a result of neuroplasticity induced by a mass lesion. This article discusses the role of functional imaging in the preoperative setting.

The Role of Endonasal Endoscopic Skull Base Repair in Posttraumatic Tension Pneumocephalus.

OBJECTIVES: Information about the endonasal endoscopic approach (EEA) for the management of posttraumatic tension pneumocephalus (PTTP) remains scarce. Concomitant rhinoliquorrhea and posttraumatic hydrocephalus (PTH) can complicate the clinical course. METHODS: The authors systematically reviewed pertinent articles published between 1961 and December 2020 and identified 6 patients with PTTP treated by EEA in 5 reports. Additionally, the authors share their institutional experience including a seventh patient, where an EEA resolved a recurrent PTTP without rhinoliquorrhea. RESULTS: Seven PTTP cases in which EEA was used as part of the treatment regime were included in this review. All cases presented with a defect in the anterior skull base, and 3 of them had concomitant rhinoliquorrhea. A transcranial approach was performed in 6/7 cases before EEA was considered to treat PTTP. In 4/7 cases, the PTTP resolved after the first intent; in 2/ 7 cases a second repair was necessary because of recurrent PTTP, 1 with and 1 without rhinoliquorrhea, and 1/7 case because of recurrent rhinoliquorrhea only. Overall, PTTP treated by EEA resolved with a mean radiological resolution time of 69 days (range 23-150 days), with no late recurrences. Only 1 patient developed a cerebrospinal fluid diversion infection probably related to a first incomplete EEA skull base defects repair. A permanent cerebrospinal fluid diversion was necessary in 3/7 cases. CONCLUSIONS: Endonasal endoscopic approach repair of air conduits is a safe and efficacious second-line approach after failed transcranial approaches for symptomatic PTTP. However, the strength of recommendation for EEA remains low until further evidence is presented.

Differentiation of rare brain tumors through unsupervised machine learning: Clinical significance of in-depth methylation and copy number profiling illustrated through an unusual case of IDH wildtype glioblastoma.

Methylation profiling has become a mainstay in brain tumor diagnostics since the introduction of the first publicly available classification tool by the German Cancer Research Center in 2017. We demonstrate the capability of this system through an example of a rare case of IDH wildtype glioblastoma diagnosed in a patient previously treated for T-cell acute lymphoblastic leukemia. Our novel in-house diagnostic tool EpiDiP provided hints arguing against a radiation-induced tumor, identified a novel recurrent genetic aberration, and thus informed about a potential therapeutic target.

Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of IL-8 (-251T/A) and IL-6 (-174G/C) and the risk of oral cancer (OC). METHODS: PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg's and Egger's tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results. RESULTS: Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between IL-8 (-251T/A) polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 (p = 0.78), 0.86 (p = 0.55), 0.78 (p = 0.37), 0.83 (p = 0.45), and 1.10 (p = 0.34), respectively. The pooled ORs IL-6 (-174G/C) polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 (p = 0.87), 1.17 (p = 0.82), 1.44 (p = 0.38), 1.28 (p = 0.61), and 0.96 (p = 0.93), respectively. There was no association between IL-8 (-251T/A) polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of IL-6 (-174G/C) polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association. CONCLUSIONS: The meta-analysis confirmed that there was no association between the polymorphisms of IL-6 (-174G/C) and IL-8 (-251T/A) and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of IL-6 (-174G/C) and the risk OC.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Non-invasive neural stem cells become invasive in vitro by combined FGF2 and BMP4 signaling.

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study, Sox2-positive NSCs from the E14.5 rat cortex were found to be non-invasive and showed only limited migration in vitro. By contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR (Ngfr) at the plasma membrane after exposure to FGF2 and BMP4. FGF2 and BMP4 together upregulated the expression of Msx1, Snail1, Snail2, Ngfr, which are all found in neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), but not in forebrain stem cells. Invasive cells downregulated the expression of Olig2, Sox10, Egfr, Pdgfra, Gsh1/Gsx1 and Gsh2/Gsx2. Migrating and invasive NSCs had elevated expression of mRNA encoding Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3. On the basis of the strongest upregulation in invasion-induced NSCs, we defined a group of five key invasion-related genes: Ngfr, Sparc, Snail1, Pdpn and Tnc. These genes were co-expressed and upregulated in seven samples of glioblastoma multiforme (GBM) compared with normal human brain controls. Induction of invasion and migration led to low expression of differentiation markers and repressed proliferation in NSCs. Our results indicate that normal forebrain stem cells have the inherent ability to adopt a glioma-like invasiveness. The results provide a novel in vitro system to study stem cell invasion and a novel glioma invasion model: tumoral abuse of the developmental dorsoventral identity regulation.

A better surgical resectability of WHO grade II gliomas is independent of favorable molecular markers.

A higher extent of resection (EOR) in WHO grade II gliomas (GIIG) is correlated with longer survival. However, the molecular markers also feature prognostic relevance. Here, we examined whether maximal EOR was related to the genetic profile. We retrospectively investigated the predictive value of 1p19q, IDH1, 53 expression and Ki67 index for the EOR in 200 consecutive GIIGs (2007-2013). Data were modeled in a linear model. The analysis was performed with two statistical methods (arcsin-sqrt and Beta-regression model with logit link). There was no deletion 1p19q in 118 cases, codeletion 1p19q (57 cases), single deletion 1p (4 cases) or19q (16 cases). 155 patients had a mutation of IDH1. p53 was graded in 4 degrees (0:92 cases, 1:52 cases, 2:31 cases, 3:8 cases). Mean Ki67 index was 5.2 % (range 1-20 %). Mean preoperative tumor volume was 60.8 cm(3) (range 3.3-250 cm(3)) and mean EOR was 0.917 (range 0.574-1). The statistical analysis was significant for a lower EOR in patients with codeletion 1p19q (OR 0.738, p = 0.0463) and with a single deletion 19q (OR 0.641, p = 0.0168). There was no significant correlation between IDH1 or p53 and the EOR. Higher Ki67 was marginally associated with higher EOR (p = 0.0603). The study demonstrates in a large cohort of GIIG that a higher EOR is not attributable to favorable genetic markers. This original result supports maximal surgical resection as an important therapeutic factor per se to optimize prognosis, independently of the molecular pattern.

Radiolabeled Somatostatin Receptor Antagonist Versus Agonist for Peptide Receptor Radionuclide Therapy in Patients with Therapy-Resistant Meningioma: PROMENADE Phase 0 Study.

Our primary aim was to compare the therapeutic index (tumor-to-bone marrow and tumor-to-kidney absorbed-dose ratios) of the new radiolabeled somatostatin receptor antagonist [177Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [177Lu]Lu-DOTATOC in the same patients with progressive, standard therapy-refractory meningioma. Methods: In this prospective, single-center, open-label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [177Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m2 × body surface area) of [177Lu]Lu-DOTA-JR11 at an interval of 10 ± 1 wk. In total, 1 [177Lu]Lu-DOTATOC and 2-3 [177Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor-to-organ absorbed-dose ratios (3-dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [177Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [177Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3-5.3 Gy) for [177Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [177Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed-dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor-to-kidney absorbed-dose ratio with [177Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [177Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [177Lu]Lu-DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [177Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [177Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [177Lu]Lu-DOTA-JR11 are warranted in meningioma patients.

Effects of two types of exercise training on psychological well-being, sleep and physical fitness in patients with high-grade glioma (WHO III and IV).

BACKGROUND: There is evidence that regular exercise training has the potential to improve psychological well-being among cancer survivors. However, limited findings are available for individuals with high-grade glioma (HGG; WHO grade III and IV) after neurosurgery and undergoing radiochemotherapy. Given this, endurance and strengths training were employed to investigate their impact on symptoms of depression, feelings of stress and anxiety, fatigue, insomnia, and physical fitness, compared to an active control condition. METHODS: A total of 29 patients (M = 52.07, SD = 12.45, 55.2% women) participated in this randomized controlled trial (RCT). After neurosurgical treatment and during adjuvant radiotherapy and chemotherapy or combined radiochemotherapy, patients were randomly assigned to the following conditions: Endurance training (n = 10); strengths training (n = 11); active control condition (n = 8). At baseline, three weeks and six weeks later at the end of the study physical fitness was objectively measured with a 6-min walk test (6MWT) and a handgrip test. Participants completed a series of questionnaires covering sociodemographic information, symptoms of depression, stress, anxiety, fatigue, and insomnia. Further, experts rated participants' severity of symptoms of depression. RESULTS: Over time and compared to the strengths and active control condition, self-rated symptoms of depression, state and trait anxiety, stress and insomnia decreased in the endurance condition. Over time and compared to the endurance and active control condition, no changes on symptoms of depression, anxiety, stress, or insomnia were observed in the strengths condition. Over time and compared to the endurance and strengths condition, symptoms of depression (self-ratings), stress, insomnia and fatigue decreased in the active control condition. Fatigue increased in both exercising conditions. Over time and irrespective from the study condition, physical fitness did neither improve nor decrease. CONCLUSIONS: The pattern of results suggests that endurance training and an active control condition improved dimensions of depression, stress, and anxiety, while mere strengths training appeared to neither improve, nor decrease dimensions of psychological functioning. Further, exercise interventions did not change physical fitness, but increased fatigue. Overall, endurance training and an active control condition appeared to favorably impact on psychological well-being among patients with high-grade glioma after neurosurgery and undergoing radiochemotherapy.

High Precision Bone Cutting by Er: YAG Lasers Might Minimize the Invasiveness of Navigated Brain Biopsies.

Biopsies of brain tissue are sampled and examined to establish a diagnosis and to plan further treatment, e.g. for brain tumors. The neurosurgical procedure of sampling brain tissue for histologic examination is still a relatively invasive procedure that carries several disadvantages. The "proof of concept"-objective of this study is to answer the question if laser technology might be a potential tool to make brain biopsies less invasive, faster and safer. Laser technology might carry the opportunity to miniaturize the necessary burr hole and also to angulate the burr hole much more tangential in relation to the bone surface in order to take biopsies from brain regions that are usually only difficult and hazardous to access. We examined if it is possible to miniaturize the hole in the skull bone to such a high extent that potentially the laser-created canal itself may guide the biopsy needle with sufficient accuracy. The 2-dimensional, i.e. radial tolerance of the tip of biopsy needles inserted in these canals was measured under defined lateral loads which mimic mechanical forces applied by a surgeon. The canals through the skull bones were planned in angles of 90° (perpendicular) and 45° relative to the bone surface. We created a total of 33 holes with an Er : YAG laser in human skull bones. We could demonstrate that the achievable radial tolerance concerning the guidance of a biopsy needle by a laser created bone canal is within the range of the actual accuracy of a usual navigated device if the canal is at least 4 mm in length. Lateral mechanical loads applied to the biopsy needle had only minor impact on the measurable radial tolerance. Furthermore, in contrast to mechanical drilling systems, laser technology enables the creation of bone canals in pointed angles to the skull bone surface. The latter opens the perspective to sample biopsies in brain areas that are usually not or only hazardous to access.

Fitness-to-drive for glioblastoma patients: Guidance from the Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM).

OBJECTIVE: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess "fitness-to-drive" of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess "fitness-to-drive" of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS: Consensus on minimum requirements for a "fitness-to-drive" programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm "fitness-to-drive" for glioblastoma patients after initial tumour-directed therapy. The proposed "fitness-to-drive" assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting "fitness-to-drive" and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P--results from a phase I study.

Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevant.

An Unusual Bump on the Head: Intracranial and Extracranial Cytokeratin-Positive Interstitial Reticular Cell Tumor.

BACKGROUND: We describe a cytokeratin positive interstitial reticulum cell tumor (CPIRCT) as the cause of a large and defacing scalp tumor. Clinically these tumors manifest as progressive, painless swelling. Treatment usually consists of surgery with or without irradiation; chemotherapy is applied in metastatic disease. CASE DESCRIPTION: A patient was referred after attempted removal of a large bump on the head. The tumor was initially noted about 12 months earlier. Assuming a benign lipoma, resection without prior imaging was attempted. During surgery, the underlying bone was found to be profoundly destroyed. Cranial magnetic resonance imaging revealed a large mass with an extracranial and intracranial component. Subsequent extensive resection finally led to the diagnosis of CPIRCT. CONCLUSIONS: Most CPIRCTs manifest as progressive palpable or visible masses. Radical excision is usually the mainstay of treatment, although there is no generally accepted treatment strategy. A needle biopsy might not be diagnostic and can complicate future curative surgery. Especially in fast-growing lesions, imaging studies should be considered before surgery. Their potential recurrence and metastatic spread render CPIRCTs an interdisciplinary challenge and highlight the need for long-term follow-up.

Among Persons With Multiple Sclerosis (MS), Objective Sleep, Psychological Functioning, and Higher Physical Activity Scores Remained Stable Over 2 Years-Results From a Small Study Under Naturalistic Conditions.

Background: Persons with multiple sclerosis (PwMS) are at increased risk to report poor sleep patterns and lower physical activity indices. To date, data on longitudinal objectively sleep assessment is missing. In the present study, we investigated the pattern of objective sleep and subjective physical activity indices over a period of 13.5 months, under naturalistic conditions. Method: 13.5 months after their first assessment, a total of 16 PwMS (mean age = 49.13 median EDSS score: 5; 11 females) were reassessed on their objective sleep via portable sleep-electroencephalogram (EEG-) devices, along with their subjective sleep patterns (symptoms of insomnia, restless legs syndrome (RLS), and sleep-disordered breathing), physical activity indices, psychological functioning (symptoms of depression, fatigue, daytime sleepiness), and MS-related information (fatigue, EDSS; disease-modifying treatments). While the baseline assessment was performed in a rehabilitation center, the follow-up assessment took place at participants' naturalistic and familiar setting. Results: Statistically, symptoms of depression and fatigue, subjective sleep, and physical activity levels did neither increase, nor decrease over time, although descriptively, both moderate and vigorous physical activity levels decreased, and fatigue and subjective insomnia increased. Time awake after sleep onset statistically significantly decreased, while light sleep duration increased by trend. Conclusions: Among a smaller sample of PwMS, objective sleep in their naturalistic setting remained fairly stable over a mean time lapse of 13.5 months after clinic discharge. Physical activity levels descriptively decreased. The present results are of clinical and practical importance for treatment counseling: PwMS can be reassured that their sleep quality does not deteriorate, once they have left a rehabilitation center. Further, they should be encouraged to keeping their physical activity levels as stable as possible.

Intradural spinal metastasis of renal cell cancer. Report of a case and review of 26 published cases.

Metastatic disease in the intradural compartment of the spine is a rare manifestation of cancer. We report the case of an 82-year-old patient with an intradural, extramedullary metastasis of renal cell carcinoma in the cervical spine. A literature search for intradural spinal metastases of renal cell carcinoma yielded a total of 26 further cases. 18 patients had sporadic renal cell carcinoma, and 9 patients had von Hippel-Lindau disease (VHL) in which the metastases of the renal cell carcinoma were embedded within spinal haemangioblastomas. Patients presented with paresis, back pain, altered sensation or, less frequently, bladder dysfunction. Intradural spinal metastases were diagnosed at an earlier age in VHL patients than in sporadic cases (mean 43 +/- 5 years vs. 60 +/- 14.5 years). The metastasis was surgically removed in 81% of patients. Pain improved in all patients, paresis in 90%, hypaesthesia in 38% and bladder dysfunction in 50%. Death occurred as a result of systemic cancer progression. 93% of patients in the sporadic renal cell cancer group died within 1.5 years, whereas two thirds of the VHL patients were alive after 2 years.

Long-Term Results of Targeted Low-Grade Glioma Treatment with 213Bi-DOTA-[Thi8,Met(O2)11]-Substance P.

The aim was to evaluate long-term effectiveness, functional outcome, and side effects of targeted α radiotherapy as an alternative treatment for low-grade gliomas (LGGs) in eloquent brain areas. Five patients with gliomas World Health Organization (WHO) II-IV were treated with tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-213Bi substance P. In this study, the LGG patients' (WHO II) clinical and radiological long-term outcome was examined. Ten years after treatment with DOTA-213Bi substance P, both LGG patients are still alive without evidence for tumor recurrence and without new functional deficits. Targeted α radiotherapy of LGG might have the potential of long-term tumor control, due to the short tissue range of α particles especially for eloquently located LGG.