Cereblon enhancer methylation and IMiD resistance in multiple myeloma.

Cereblon is the direct binding target of the immunomodulatory drugs (IMiDs) that are commonly used to treat multiple myeloma (MM), the second most frequent hematologic malignancy. Patients respond well to initial treatment with IMiDs, but virtually all patients develop drug resistance over time, and the underlying mechanisms are poorly understood. We identified an as yet undescribed DNA hypermethylation in an active intronic CRBN enhancer. Differential hypermethylation in this region was found to be increased in healthy plasma cells, but was more pronounced in IMiD-refractory MM. Methylation significantly correlated with decreased CRBN expression levels. DNA methyltransferase inhibitor (DNTMi) in vitro experiments induced CRBN enhancer demethylation, and sensitizing effects on lenalidomide treatment were observed in 2 MM cell lines. Thus, we provide first evidence that aberrant CRBN DNA methylation is a novel mechanism of IMiD resistance in MM and may predict IMiD response prior to treatment.

Demographics and Etiology for Lower Extremity Amputations-Experiences of an University Orthopaedic Center in Germany.

Background and Objectives: Currently, the worldwide incidence of major amputations in the general population is decreasing whereas the incidence of minor amputations is increasing. The purpose of our study was to analyze whether this trend is reflected among orthopaedic patients treated with lower extremity amputation in our orthopaedic university institution. Materials and Methods: We conducted a single-center retrospective study and included patients referred to our orthopaedic department for lower extremity amputation (LEA) between January 2007 and December 2019. Acquired data were the year of amputation, age, sex, level of amputation and cause of amputation. T test and Chi² test were performed to compare age and amputation rates between males and females; significance was defined as p < 0.05. Linear regression and multivariate logistic regression models were used to test time trends and to calculate probabilities for LEA. Results: A total of 114 amputations of the lower extremity were performed, of which 60.5% were major amputations. The number of major amputations increased over time with a rate of 0.6 amputation/year. Men were significantly more often affected by LEA than women. Age of LEA for men was significantly below the age of LEA for women (men: 54.8 ± 2.8 years, women: 64.9 ± 3.2 years, p = 0.021). Main causes leading to LEA were tumors (28.9%) and implant-associated complications (25.4%). Implant-associated complications and age raised the probability for major amputation, whereas malformation, angiopathies and infections were more likely to cause a minor amputation. Conclusions: Among patients in our orthopaedic institution, etiology of amputations of the lower extremity is multifactorial and differs from other surgical specialties. The number of major amputations has increased continuously over the past years. Age and sex, as well as diagnosis, influence the type and level of amputation.

Analysis of deep grey nuclei susceptibility in early childhood: a quantitative susceptibility mapping and R2* study at 3 Tesla.

PURPOSE: Aging is the most significant determinant for brain iron accumulation in the deep grey matter. Data on brain iron evolution during brain maturation in early childhood are limited. The purpose of this study was to investigate age-related iron deposition in the deep grey matter in children using quantitative susceptibility (QSM) and R2* mapping. METHODS: We evaluated brain MRI scans of 74 children (age 6-154 months, mean 40 months). A multi-echo gradient-echo sequence obtained at 3 Tesla was used for the QSM and R2* calculation. Susceptibility of the pallidum, head of caudate nucleus, and putamen was correlated with age and compared between sexes. RESULTS: Susceptibility changes in all three nuclei correlated with age (correlation coefficients for QSM/R2*: globus pallidus 0.955/0.882, caudate nucleus 0.76/0.65, and putamen 0.643/0.611). During the first 2 years, the R2* values increased more rapidly than the QSM values, indicating a combined effect of iron deposition and myelination, followed by a likely dominating effect of iron deposition. There was no significant gender difference. CONCLUSION: QSM and R2* can monitor myelin maturation processes and iron accumulation in the deep grey nuclei of the brain in early life and may be a promising tool for the detection of deviations of this normal process. Susceptibility in the deep nuclei is almost similar early after birth and increases more quickly in the pallidum. The combined use of QSM and R2* analysis is beneficial.

Sustained response to bevacizumab in a patient with mosaic neurofibromatosis type 2 carrying the NF2:c.784C>T p.(Arg262*) variant.

Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by the growth of schwannomas, especially bilateral vestibular schwannomas (VS), meningiomas, and ependymomas. The anti-VEGF antibody bevacizumab has shown efficacy for VS in some NF2 patients. However, there is limited data on the effect of bevacizumab on non-vestibular tumors, and on the correlation between therapy response and genotype. Here, we report on a 33-year-old patient with bilateral VS, 14 additional intracranial or spinal schwannomas, and a meningioma treated with bevacizumab, off-label in the European Union, for 2 years. The genotype of the patient was determined by mutational analysis of NF2, SMARCB1, and LZTR1 on DNA of multiple tissues. Additionally, we performed volumetric measurements of quantifiable non-vestibular tumors (n = 8) on MRI scans from 5 pre-therapeutic and 2 therapeutic years, and pure-tone audiometry of the non-deaf ear. A heterozygous NM_000268.3(NF2):c.784C>T p.(Arg262*) variant was identified in DNA from 3 schwannomas, but not in leukocyte or oral mucosa DNA, and no rare SMARCB1/LZTR1 variants were detected, establishing the diagnosis of definite NF2 mosaicism. While schwannomas had progressed with a mean annual growth rate of 38% pre-therapeutically, volume stabilization or reduction of all schwannomas along with improvement of pain and neurological deficits, including hearing impairment, were observed under 24 months of bevacizumab. In summary, this is the first report of a sustained response to bevacizumab in a patient shown to carry the frequent mosaic NF2:c.784C>T p.(Arg262*) variant. Our results may be of particular relevance to guide treatment decisions in mosaic NF2 patients harboring this variant.

Primary and secondary gliosarcoma: differences in treatment and outcome.

INTRODUCTION: There are only few studies comparing differences in the outcome of primary versus secondary gliosarcoma. This study aimed to review the outcome and survival of patients with primary or secondary gliosarcoma following surgical resection and adjuvant treatment. The data were also matched with data of patients with primary and secondary glioblastoma (GBM). PATIENTS AND METHODS: Treatment histories of 10 patients with primary gliosarcoma and 10 patients with secondary gliosarcoma were analysed and compared. Additionally, data of 20 patients with primary and 20 patients with secondary GBM were analysed and compared. All patients underwent surgical resection of the tumour in our department. Follow-up data, progression-free survival (PFS), and median overall survival (mOS) were evaluated. RESULTS: The median PFS in patients with primary gliosarcoma was significantly higher than in patients with secondary gliosarcoma (p = 0.037). The 6-month PFS rates were 80.0% in patients with primary and 30.0% in patients with secondary gliosarcoma. Upon recurrence, five patients with primary gliosarcoma and four patients with secondary gliosarcoma underwent repeat surgical resection. The mOS of patients with primary gliosarcoma was significantly higher than that of patients with secondary gliosarcoma (p = 0.031). The percentage of patients surviving at 1-year/2-year follow-up in primary gliosarcoma was 70%/20%, while it was only 10%/10% in secondary gliosarcoma. When PFS and mOS of primary gliosarcoma was compared to primary GBM, there were no statistically differences (p = 0.509; p = 0.435). The PFS and mOS of secondary gliosarcoma and secondary GBM were also comparable (p = 0.290 and p = 0.390). CONCLUSION: Patients with primary gliosarcoma have a higher PFS and mOS compared to those with secondary gliosarcoma. In the case of tumour recurrence, patients with secondary gliosarcoma harbour an unfavourable prognosis with limited further options. The outcome of patients with primary or secondary gliosarcoma is comparable to that of patients with primary or secondary GBM.

Temporal bone primary inverted papilloma - Case Report and review of the literature. / Invertiertes Papillom des Felsenbeins ­ Fallbericht und Literaturübersicht.

Inverted papilloma of middle ear is an extremely rare lesion of the respiratory epithelium that normally occurs in the nasal cavity and paranasal sinuses. So far less than 17 cases were described in literature. A 45-year-old patient was admitted in our Department with hearing loss, otorrhea and pulsing tinnitus on the right ear. The clinical examination showed a granulation tissue on the right eardrum. No tumor formation was seen in the nasal cavity. The MRI showed a tissue formation in the tympanic cavity with an extension in the middle cranial fossa. A mastoidectomy with antrotomy and duraplasty was performed. The histological diagnosis was inverted papilloma of the middle ear. In a second step occurred an eradication of the tumor with a subtotal petrosectomy. The etiology of the inverted papilloma of the middle ear is unknown. Our case is so far the 18nd case described.Our experience has shown that the eradication of the tumor with a subtotal petrosectomy resulted as reasonable procedure. A long-term follow-up is suggested in order to detect possible recurrence or malignant transformation.

Cerebral patterns of neuropsychological disturbances in hepatitis C patients.

Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.

Dimethylarginines in patients with intracerebral hemorrhage: association with outcome, hematoma enlargement, and edema.

BACKGROUND: Asymmetric dimethylarginine (ADMA)--the most potent endogenous NO-synthase inhibitor, has been regarded as mediator of endothelial dysfunction and oxidative stress. Considering experimental data, levels of ADMA and its structural isomer symmetric dimethylarginine (SDMA) might be elevated after intracerebral hemorrhage (ICH) and associated with clinical outcome and secondary brain injury. METHODS: Blood samples from 20 patients with acute ICH were taken at ≤ 24 h and 3 and 7 days after the event. Nine patients had favorable (modified Rankin Scale (mRS) at 90 days 0-2) outcome, and 11 patients unfavorable outcome (mRS 3-6). Patients' serum ADMA, SDMA, and L-arginine levels were determined by high-performance liquid chromatography-tandem mass spectrometry. Levels were compared to those of 30 control subjects without ICH. For further analysis, patients were grouped according to outcome, hematoma and perihematomal edema volumes, occurrence of hematoma enlargement, and cytotoxic edema as measured by computed tomography and serial magnetic resonance imaging. RESULTS: Levels of ADMA--but not SDMA and L-arginine--were elevated in ICH patients compared to controls (binary logistic regression analysis: ADMA ≤ 24 h, p = 0.003; 3 days p = 0.005; 7 days p = 0.004). If patients were grouped according to outcome, dimethylarginines were increased in patients with unfavorable outcome. The binary logistic regression analysis confirmed an association of SDMA levels ≤ 24 h (p = 0.048) and at 3 days (p = 0.028) with unfavorable outcome. ADMA ≤ 24 h was increased in patients with hematoma enlargement (p = 0.003), while SDMA ≤ 24 h was increased in patients with large hematoma (p = 0.029) and perihematomal edema volume (p = 0.023). CONCLUSIONS: Our data demonstrate an association between dimethylarginines and outcome of ICH. However, further studies are needed to confirm this relationship and elucidate the mechanisms behind.

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

Spectroscopic Characterization of Gliosarcomas-Do They Differ From Glioblastomas and Metastases?

OBJECTIVE: To evaluate the spectroscopic pattern of gliosarcomas for differentiation from glioblastomas or metastases. METHODS: H-nuclear magnetic resonance (NMR) spectroscopic intermediate echo time data of 5 patients with histologically proven gliosarcomas were compared with data of 17 metastases and 54 glioblastomas. Specialized H-NMR spectroscopy analysis software was used offline. Lipid and macromolecular resonances between 0.9 ppm and 1.4 ppm were compared besides the main metabolites using the Mann-Whitney U test. RESULTS: Gliosarcomas showed higher lipid and macromolecule resonances and a higher lipid-choline ratio compared with glioblastomas (P < 0.024 and P < 0.036). Glioblastomas showed higher creatine concentrations compared with metastases (P < 0.007) but not compared with gliosarcomas. We found no significant differences between metastases and gliosarcomas. CONCLUSIONS: Gliosarcomas may mimic metastases on H NMR spectroscopy showing high signal intensities from lipid and macromolecule resonances. This tumor type should be suspected if conventional imaging suggests an intra-axial brain neoplasm in combination with high lipids in solid tumor parts.

Description and evaluation of operative deformity correction in calcium-deficiency rickets in Kaduna, northern Nigeria.

PURPOSE: Rickets is a recurrent disease worldwide, especially in countries with limited resources (Nield et al Am Fam Physician 74(4):619-626, 2006; Thacher et al Ann Trop Paediatr 26(1):1-16, 2006). Medical therapy including orally administered calcium substitution is shown to improve a patients clinical symptoms and positively impact bone deformities, especially in the lower extremity. Even though orthopaedic intervention is necessary in a significant percentage of patients, few reports exist about operative deformity correction in patients wtih rickets. METHODS: We describe our concept of operative treatment by single-stage, three-dimensional closing-wedge osteotomies on 45 deformed legs in 27 patients from the rural area of Kaduna, North Nigeria, with calcium-deficiency rickets and evaluate the early results in a 1.5-year follow-up. RESULTS: We found a significant improvement in parameters of quality of life, functionality, clinical and radiological angulation and angles following the definition of Paley et al., with a complication rate of 4 % under 88 osteotomies (Paley et al Orthop Clin North Am 25(3):425-65, 1994). CONCLUSION: The described operative therapy shows to be sufficient and with satisfactory results in correcting rickets-related leg deformities under rural circumstances with low availability of medical resources.

McDonald Criteria 2010 and 2005 Compared: Persistence of High Oligoclonal Band Prevalence Despite Almost Doubled Diagnostic Sensitivity.

The 2010 McDonald criteria were developed to allow a more rapid diagnosis of relapsing-remitting multiple sclerosis (MS) by only one MRI of the brain. Although cerebrospinal fluid (CSF) is not a mandatory part of the latest criteria, the evidence of an intrathecal humoral immunoreaction in the form of oligoclonal bands (OCB) is crucial in the diagnostic workup. To date, the impact of the 2010 McDonald criteria on the prevalence of OCB has not been investigated. We retrospectively evaluated data of 325 patients with a clinical relapse suggestive of demyelination that were treated in a German university hospital between 2010 and 2015. One hundred thirty-six patients (42%) were diagnosed with MS and 189 patients with CIS when the criteria of 2010 were applied. The criteria of 2005 allowed only 70 patients (22%) to be designated as MS. In contrast, the prevalence of OCB was marginal affected in MS patients with 96% for the criteria of 2010 and 98.5% for the criteria of 2005. In conclusion, OCB are prevalent in most MS patients and reflect the chronic inflammatory nature of the disease. We recommend CSF examination to exclude alternative diagnoses and reevaluation of the diagnosis MS in patients with negative OCB.

Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis.

Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis.

Cerebral white matter lesions in patients with cirrhosis - causative for hepatic encephalopathy or bystanders?

BACKGROUND & AIMS: Focal white matter lesions mimicking microvascular lesions were connected to the development of hepatic encephalopathy (HE) in patients with cirrhosis. This study aims to assess the relationship between cerebrovascular risk factors and the prevalence and extent of these lesions in patients with cirrhosis, as well as their impact upon cognitive function. METHODS: 55 cirrhotic patients underwent neurological examination, psychometric testing and magnetic resonance imaging. T2-weighted images were reviewed for white matter lesions by a neuroradiologist and a neurologist, independently. Patients were allocated into three groups: (i) no or <5, (ii) 6-15 and (iii) more than 15 lesions. Allocation was confirmed by a senior neuroradiologist blinded for the clinical data. The patient groups were compared concerning age, underlying liver disease, mortality, MELD Score, history of HE, treatment for HE, cerebrovascular risk factors and psychometric test results. Regression analysis was performed to identify risk factors for the presence and extent of white matter lesions. RESULTS: Patient groups 2 and 3 were older and showed worse results in the psychometric tests than group 1 (P < 0.05). Correlation analyses showed a significant relationship between the number of white matter lesions and the grade of HE (P < 0.001) and cognitive function (P < 0.05), but no interrelationship between the lesions and cerebrovascular risk factors or other factors tested. CONCLUSIONS: Focal white matter lesions in patients with cirrhosis do not represent cerebrovascular small-vessel disease but are related to the pathology of HE. Further studies are needed to clarify the mechanisms behind in detail.

Endoscopic intracranial surgery enhanced by electromagnetic-guided neuronavigation in children.

PURPOSE: Navigated intracranial endoscopy with conventional technique usually requires sharp head fixation. In children, especially in those younger than 1 year of age and in older children with thin skulls due to chronic hydrocephalus, sharp head fixation is not possible. Here, we studied the feasibility, safety, and accuracy of electromagnetic (EM)-navigated endoscopy in a series of children, obviating the need of sharp head fixation. METHODS: Seventeen children (ten boys, seven girls) between 12 days and 16.8 years (mean age 4.3 years; median 14 months) underwent EM-navigated intracranial endoscopic surgery based on 3D MR imaging of the head. Inclusion criteria for the study were intraventricular cysts, arachnoid cysts, aqueduct stenosis for endoscopic third ventriculostomy (ETV) with distorted ventricular anatomy, the need of biopsy in intraventricular tumors, and multiloculated hydrocephalus. A total of 22 endoscopic procedures were performed. Patients were registered for navigation by surface rendering in the supine position. After confirming accuracy, they were repositioned for endoscopic surgery with the head fixed slightly on a horseshoe headholder. EM navigation was performed using a flexible stylet introduced into the working channel of a rigid endoscope. Neuronavigation accuracy was checked for deviations measured in millimeters on screenshots after the referencing procedure and during surgery in the coronal (z = vertical), axial (x = mediolateral), and sagittal (y = anteroposterior) planes. RESULTS: EM-navigated endoscopy was feasible and safe. In all 17 patients, the aim of endoscopic surgery was achieved, except in one case in which a hemorrhage occurred, blurring visibility, and we proceeded with open surgery without complications for the patient. Navigation accuracy for extracranial markers such as the tragus, bregma, and nasion ranged between 1 and 2.5 mm. Accuracy for fixed anatomical structures like the optic nerve or the carotid artery varied between 2 and 4 mm, while there was a broader variance of accuracy at the target point of the cyst itself ranging between 2 and 9 mm. CONCLUSIONS: EM-navigated endoscopy in children is a safe and useful technique enhancing endoscopic intracranial surgery and obviating the need of sharp head fixation. It is a good alternative to the common opto-electric navigation system in this age group.

Electromagnetic navigation-guided surgery in the semi-sitting position for posterior fossa tumours: a safety and feasibility study.

BACKGROUND: Electromagnetic (EM)-guided neuronavigation is an innovative technique and a viable alternative to opto-electric navigation. We have performed a safety and feasibility study using EM-guided neuronavigation for posterior fossa surgery in the semi-sitting position in a selected subset of patients. METHODS: Out of 284 patients with posterior fossa tumours operated upon over a period of 40 months, a subset of 15 patients was thought to possibly benefit from EM navigational guidance and was included in this study. There were six children and nine adults (aged between 8 and 84 years; mean age, 34.6 years) with different neoplasms in the brainstem or close to the midline. All patients had contrast-enhanced three-dimensional (3D) magnetic resonance imaging (MRI) of the head preoperatively. EM-guided navigation was used to identify and preserve the venous sinuses during craniotomy and to determine the trajectory to the lesion using various approaches. Neuronavigation accuracy was repeatedly checked for deviations measured in millimetres on screen shots during surgery before and after dural opening in the coronal (z = vertical), axial (x = mediolateral) and sagittal (y = anteroposterior) plane. RESULTS: Referencing of the patient in the supine position was fast and easy. There was no loss of navigation accuracy after repositioning of the patient in the semi-sitting position (mean, 2.5 mm ± 0.92 mm). Identification of the pathological structure using EM navigation was achieved in all instances. Optimal angulation of the neck was selected individually to permit a comfortable position for the surgeon with full access to the lesion avoiding over-flexion. Deviation of accuracy at the surface of the target lesion ranged between 2.5 and 5.8 mm (mean, 3.9 mm ± 1.1 mm). CONCLUSIONS: EM-guided neuronavigation in the semi-sitting position was safe and technically feasible. It enabled fast and accurate referencing without loss of navigation accuracy despite repositioning of the patient. In contrast to conventional opto-electric neuronavigation there were no line of sight problems.

Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment: case report and review of the literature.

BACKGROUND: Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5% of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. CASE PRESENTATION: A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage IEA disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. CONCLUSION: This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement.

Anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis show distinct patterns of brain glucose metabolism in 18F-fluoro-2-deoxy-d-glucose positron emission tomography.

BACKGROUND: Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. METHODS: The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. RESULTS: Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. CONCLUSIONS: This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.

[Individualized surgical treatment of sarcomas of the extremities]. / Chirurgische Therapieindividualisierung bei Sarkomen der Extremitäten.

Sarcomas of the extremities are rare entities, the treatment of which requires special expertise. Even if the treatment of patients is always interdisciplinary, the surgical R0 resection is the key point of each curatively intended treatment. In addition to resection in sano, the aim is to preserve the extremities and function, so that defect reconstruction after resection plays a decisive role. Due to the heterogeneity of tumors as well as their localization and extent, reconstruction is always an individually adapted treatment. Modular tumor endoprostheses are often used in this context, which can be constructed according to the size of the defect. The transplantation of autologous or allogeneic bone is also frequently used alone or as an additive procedure. Patient-specific (mega)prostheses are used particularly for pelvic tumors. Defect reconstruction using scaffold-based procedures from the field of tissue engineering is being tested as a promising procedure for the future. This article provides an overview of the treatment principles for sarcomas of the extremities and their individual reconstruction options.

Reducing radiation exposure and costs: CT body scout views with an enhanced protocol versus conventional radiography after shunt surgery.

OBJECTIVE: Ventriculoperitoneal shunt implantation has become standard treatment for cerebrospinal fluid diversion, besides endoscopic third ventriculostomy for certain indications. Postoperative X-ray radiography series of skull, chest and abdomen combined with cranial CT are obtained routinely in many institutions to document the shunt position and valve settings in adult patients. Measures to reduce postoperative radiation exposure are needed, however, there is only limited experience with such efforts. Here, we aim to compare routine postoperative cranial CT plus conventional radiography series (retrospective arm) with cranial CT and body scout views only (prospective arm) concerning both diagnostic quality and radiation exposure. PATIENTS AND METHODS: After introduction of an enhanced CT imaging protocol, routine skull and abdomen radiography was no longer obtained after VP shunt surgery. The image studies of 25 patients with routine postoperative cranial CT and conventional radiography (retrospective arm of study) were then compared to 25 patients with postoperative cranial CT and CT body scout views (prospective arm of study). Patient demographics such as age, sex and primary diagnosis were collected. The image quality of conventional radiographic images and computed tomography scout views images were independently analyzed by one neurosurgeon and one neuroradiologist. RESULTS: There were no differences in quality assessments according to three different factors determined by two independent investigators for both groups. There was a statistically significant difference, however, between the conventional radiography series group and the CT body scout view imaging group with regard to radiation exposure. The effective dose estimation calculation yielded a difference of 0.05 mSv (two-tailed t-test, p = 0.044) in favor of CT body scout view imaging. Furthermore, the new enhanced protocol resulted in a reduction of cost and the use of human resources. CONCLUSION: CT body scout view imaging provides sufficient imaging quality to determine shunt positioning and valve settings. With regard to radiation exposure and costs, we suggest that conventional postoperative shunt series may be abandoned.