The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation.

Previous studies from our group indicated a role of SNPs within the innate immunity receptor NOD2/CARD15 as a risk factor for GvHD and treatment-related mortality allogeneic stem cell transplantation from HLA-identical siblings. We now extended these studies to assess the role of NOD2/CARD15 SNPs in 342 unrelated donor transplants. Overall, presence of any SNPs in patients or donor resulted in an increased risk of severe GvHD (25% in wildtype versus 38% in recipients and donors with variants, P= 0.01), which did not translate in increased mortality. When the analysis was broken down to individual SNPs, the presence of a SNP13 in the donor turned out to be the only highly significant risk factor (GvHD III/IV 22% wt, 42% SNP13 donor, P < 0.004; TRM 33% wt versus 59% SNP13 donor, P= 0.01; overall survival 49% wt versus 26% SNP13 donor, P= 0.007). This association was confirmed in multivariate analysis. Analysis of clinical risk factors suggested that this effect was most prominent in patients receiving any form of T cell depletion. Thus our observation indicates that the presence of a defect in innate immunity signalling in donor monocytes and possibly antigen presenting cells is most prominent in patients having additional T cell deficiency.

[FDG-PET-CT based imaging of retropharyngeal lymph nodes with its impact on radiotherapy]. / Die Darstellung retropharyngealer Lymphknoten in der FDG-PET/CT und ihre Bedeutung für die Radiotherapie.

BACKGROUND: In about 20% there is an involvement of the retropharyngeal lymph nodes in patients with locally advanced carcinoma of the hypopharynx and cervical esophagus. A case report should demonstrate the diagnostic and therapeutic impact of FDG-PET/CT in the radiotherapeutic management of a locally advanced carcinoma of the hypopharynx in special consideration of the RPLN. PATIENT AND METHOD: A pretherapeutic FDG-PET/CT was performed with the patient fixed in the radiotherapy mask in order to integrate the anatomic and metabolic information into the radiotherapy planning system by an exact matching of the data. RESULTS: Only the FDG-PET could detect a retropharyngeal lymph node involvement (RPLN) by an intensive glucose utilisation with a consecutive modification of the target volume and dose increase in this region. CONCLUSION: This case report demonstrates that FDG-PET/CT facilitates the imaging of metabolic active and otherwise hardly detectable lymph nodes in locally advanced head and neck cancer with consequences on target volume definition and dose application in radiotherapy.

Papillary microcarcinoma and papillary cancer of the thyroid

AIMS: Major controversies exist regarding the treatment of papillary microcarcinoma of the thyroid (PMC). Prior to 2003 PMC was defined by the WHO as a papillary carcinoma of 1 cm or less in diameter. In 2004 that definition changed, with the new classification requiring that the tumour also must be found incidentally. PATIENTS, METHODS: In this study we reviewed the clinical records of 67 patients with papillary tumours of the thyroid

The prognostic value of anaemia at different treatment times in patients with locally advanced head and neck cancer treated with surgery and postoperative radiotherapy.

AIMS: We report a retrospective mono-institutional analysis of anaemia (< 12 g/dl) at different treatment times (preoperative, postoperative, before radiotherapy and nadir levels during radiotherapy) in head and neck cancer patients treated with surgery and postoperative radiotherapy. The study objective was to determine whether, and at which time points, anaemia had a significant effect on the end points overall survival and local recurrence-free survival (LRFS). MATERIALS AND METHODS: The end points for the statistical analysis in 130 patients were LRFS and overall survival. A univariate analysis (Log-rank test) was carried out on the following variables with potential end point-related impact: gender, T, N, G, American Joint Committee on Cancer (AJCC) stage, tumour site, resection status, overall treatment time (OTT), radiotherapy treatment time (RTT) and preoperative, postoperative, pre-radiotherapy and nadir levels of haemoglobin during radiotherapy. Individual variables with a significant effect (P=0.05) were then subjected to multivariate Cox regression analysis. RESULTS: The median overall survival was 59 months. The univariate analysis showed that AJCC stage (P=0.0268), resection status (P=0.0407), preoperative haemoglobin level (P=0.0087), postoperative haemoglobin level (P=0.0035), RTT (P=0.0042) and OTT (P=0.0343) significantly influenced overall survival. OTT (P=0.0130) and postoperative haemoglobin (P=0.0243) had a significant effect on LRFS. The multivariate Cox regression analysis showed postoperative haemoglobin < 12 g/dl and OTT>100 days to be independent negative prognostic factors for both end points. CONCLUSIONS: Postoperative acute anaemia < 12 g/dl and an OTT>100 days were independent negative prognostic factors for LRFS and overall survival in patients with head and neck cancer treated with surgery and postoperative radiotherapy.

[Survival with distant metastatic disease in head and neck cancer. A retrospective analysis]. / Uberleben mit hämatogen metastasierten HNO-Tumoren: Eine retrospektive monozentrische Analyse.

QUESTIONS: The objective of this retrospective analysis was to investigate parameters with a potential impact on survival in a collective of 114 patients with distant metastatic disease after head and neck cancer. PATIENTS AND METHODS: The primary endpoint was the survival with distant metastatic disease, the secondary endpoint was overall survival. Primary therapy, local recurrence, second neoplasms, palliative chemotherapy (CHT) and radiotherapy (RT), as well as Karnofsky performance status (KPS) at the time of diagnosis of the metastases were analyzed as potential impact parameters using the log-rank test with subsequent Cox regression analysis. RESULTS: Palliative CHT (P=0.0020) and KPS (P=0.0011) had a significant positive impact on the median survival probability with metastases (8.2 months) using the log-rank test, KPS at the time of diagnosis of metastases remained as an independent prognostic parameter in the Cox regression (P=0.0013). Primary therapy, local tumor control and KPS had a significant positive influence on the median overall survival probability (18.5 months) univariately (P=0.0139, P=0.0106, P= 0.0096) and multivariately (P=0.0123, and P=0.0063, P=0.0197, respectively). CONCLUSIONS: KPS at the time of diagnosis of metastases is an independent prognostic parameter for both endpoints. Lacking evidence for life prolongation, palliative therapies should therefore first and foremost focus on the stabilization of the KPS.

Positron emission tomography findings in obstructive sleep apnea patients with residual sleepiness treated with continuous positive airway pressure.

Despite sufficient continuous positive airway pressure (CPAP) therapy, some patients with the obstructive sleep apnea syndrome (OSAS) still suffer from excessive daytime sleepiness (EDS). In some of them, no cause of the persistence of EDS can be found. Brain damage due to nocturnal hypoxemia is a potential cause for this unclear persistent sleepiness (UPS). This study was done to evaluate this hypothesis. Patients with UPS were identified among the OSAS patients, who came for a CPAP therapy checkup to our sleep laboratory. UPS was recognized when no explanation for persistent EDS could be yielded by standard diagnostic procedures. Out of 167 patients under CPAP therapy 13 had UPS. To investigate the brain morphology, positron emission tomography (PET) scanning with the tracer fluorine-18 fluorodeoxyglucose (FDG), called FDG-PET, were performed in 7 of the UPS patients. Abnormal PET findings were concentrated in frontal area (found in 4 patients). The frontal abnormality seems to distinguish the OSAS patients with UPS from the whole OSAS population, examined in previous studies.

Mechanisms of regional wall motion abnormalities in contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: In the diagnosis of coronary artery disease (CAD) with Dobutamine Stress Echocardiography (DSE), regional wall motion abnormalities (RWMA) are assumed to indicate a perfusion deficit. METHODS AND RESULTS: For a more particular examination of RWMAs, we compared simultaneous echo-contrast (Optisone)-enhanced DSE (0-40 microg/kg Dobutamine, 16-segment- model) and MiBi-SPECT in a prospective double-blinded study design in 69 non-selected consecutive patients (44 male, 25 female, age 64+/-12 years). Additionally, all patients were examined by coronary-angiography. The prevalence of significant CAD (stenosis >50% lumen diameter) was 52%. DSE had a sensitivity of 78% and a specificity of 66% for the detection of significant CAD with a positive and negative predictive value of 72 and 73%, respectively. Among 28 patients with significant CAD and positive DSE study (true positive), 78% displayed a corresponding perfusion deficit in MiBi-SPECT. Among 11 patients with a positive DSE study but no current significant coronary stenosis (false positive), 82% showed stress-induced RWMAs in the inferior/posterior region, 73% displayed left ventricular hypertrophy, 54% resting-ECG abnormalities and 45% resting-RWMA (3 previous MI, 2 previous CABG surgery). Among 8 patients with negative DSE study but significant coronary stenosis (false negative), 75% had a stenosis of the LCX, 63% displayed resting- WMA, 63% displayed left bundle branch block or ST-segment depression, 50% displayed only peripheral coronary stenosis, and DSE visualization was suboptimal in 38%. CONCLUSION: This prospective study in non-selected patients shows that the majority of RWMAs in DSE are matched to a perfusion deficit detectable by nuclear imaging. Nevertheless, pre-existing cardiac abnormalities may also lead to stress-induced RWMA not associated with a perfusion deficit or mask a perfusion deficit upon DSE. Particularly in patients with LV hypertrophy, resting-RWMA, bundle branch block or ST segment depression, the predictive value of DSE may, therefore, be limited.

[Integration of PACS and HIS into the workflow of a nuclear medicine department. Experience in Regensburg]. / Integration von PACS und KIS in den Workflow einer nuklearmedizinischen Abteilung: Regensburger Erfahrungen.

AIM: The development of new diagnostic techniques and the implementation of a modern quality control management system requires the continuous adaptation of existing data processing tools to the nuclear medicine diagnostic workflow. Furthermore, PACS connected to HIS facilitates and enhances the transfer of data and pictures, and satisfies the legal requirements for data retention as regulated by law. Therefore, the aim of this work is to present the architecture, structure and results of such a system newly installed in a department of nuclear medicine. METHODS: Initially, the nuclear medicine workflow was carefully analyzed and each step was correlated to the corresponding module. The standard SAP R/3 and IS-H/IS-H(*)med based software used for patient administration at the University of Regensburg Hospital was adapted to the needs of the Nuclear Medicine Department. The networking of the imaging systems was done by integration of a PACS. Finally, the PACS was connected to the HIS to allow the attachment of images to the medical report. RESULTS, CONCLUSION: By connecting the HIS to the nuclear medicine PACS, the workflow was significantly improved. The data management sequence starting at the reception desk, continuing through the nuclear medical examination, to the physician's final written and image report is clearly structured. Although high demands exist on technical support and administration the integration of PACS and HIS into the nuclear medicine workflow leads to enhanced efficiency and reduction in hospital costs. Patient and data management are considerably improved in this way.

[Treatment of chronic tinnitus with neuronavigated repetitive Transcranial Magnetic Stimulation (rTMS)]. / Neuronavigierte repetitive transkranielle Magnetstimulation (rTMS). Ein neuartiges Therapieverfahren zur Behandlung des chronischen Tinnitus.

BACKGROUND AND OBJECTIVE: Idiopathic tinnitus is a frequent and debilitating disorder of largely unknown pathophysiology. Focal brain activation in the auditory cortex has recently been demonstrated in chronic tinnitus. Low-frequency rTMS can reduce cortical hyperexcitability. PATIENTS AND METHODS: In 12 patients with chronic tinnitus, fusion of [18F]deoxyglucose-PET and structural MRI (T1, MPRAGE) scans allowed the area of increased metabolic activity in the auditory cortex to be exactly identified; this area was selected as the target for rTMS. A neuronavigational system adapted for TMS positioning enabled the relative positions of the figure-8 coil and the target area to be monitored. Repetitive TMS (110% motor threshold; 1 Hz; 2000 stimuli per day over 5 days) was performed using a placebo-controlled crossover design. A sham coil system was used for the placebo stimulation. Treatment outcome was assessed with a specific tinnitus questionnaire (Goebel and Hiller). RESULTS: In all 12 patients an asymmetrically increased metabolic activation of the gyrus of Heschl was detected. The tinnitus score was significantly improved after 5 days of active rTMS, an effect not seen after placebo stimulation. CONCLUSION: These preliminary results show that neuronavigated rTMS may improve our understanding and treatment of chronic tinnitus.

Clioquinol treatment in familiar early onset of Alzheimer's disease: a case report.

Recently the metal chelator clioquinol (CQ) has been suggested as a possible option for treatment of Alzheimer's disease (AD). We report two patients with early onset of AD [one with a mutant amyloid-precursor-protein (APP) gene] who received long-term treatment with CQ. In both cases focally augmented cerebral glucose metabolism and stabilization but no amelioration of the clinical impression were observed without signs of neurotoxicity. In one case CSF-tau and beta-Amyloid (42/40) concentrations changed during CQ treatment.

Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development.

PURPOSE: During the course of the development of visual prostheses, subretinal stimulation films were implanted in micropigs in order to prove the feasibility of subretinal electrical stimulation with subsequent cortical response. One aim was to demonstrate that epidural recording of visual evoked potentials is possible in the micropig. METHODS: Film-bound stimulation electrode arrays were placed in the subretinal space of micropigs. This enabled the retina to be stimulated subretinally. Since conventional visual evoked potential (VEP) measuring is virtually impossible in the pig from the neurosurgical point of view, epidural recording electrode arrays were positioned over the visual cortex as permanent electrodes. RESULTS: The feasibility of temporary implantation of film-bound stimulation electrode arrays was successfully demonstrated in the micropig model. On stimulation with monopolar voltage pulses (1000 to 3000 mV), reproducible epidural VEP measurements (5 to 10 micronV) were detected. CONCLUSIONS: The feasibility of subretinal stimulation of the retina was demonstrated in a retinal model that is similar to the human retina. This animal model therefore offers a suitable means of studying the tolerability of stimulation situations in the course of visual prosthesis development.

The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.

BACKGROUND: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-Hakola disease, is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts. It is caused by recessively inherited mutations in two genes encoding subunits of a cell membrane-associated receptor complex: TREM2 and DAP12. The clinical course of PLOSL has not been characterized in a series of patients with TREM2 mutations. METHODS: The authors compare neurologic and neuroradiologic follow-up data of six patients carrying TREM2 mutations with PLOSL due to defective DAP12 genes. The authors review the known mutations in these two genes. RESULTS: Mutations in DAP12 and TREM2 result in a uniform disease phenotype. In Finnish and Japanese patients with PLOSL, DAP12 mutations predominate, whereas TREM2 is mutated more frequently elsewhere. CONCLUSIONS: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy should be considered in adult patients under age 50 years with dementia and basal ganglia calcification. Radiographs of ankles and wrists, and DNA test in uncertain cases, confirm the diagnosis.

Cardiovascular risk estimates and risk factors in renal transplant recipients.

Cardiovascular morbidity, including coronary artery disease and left ventricular hypertrophy, and mortality are high in patients following renal transplantation. Cardiovascular disease is thought to be due to traditional (hypertension, hyperlipidemia, diabetes mellitus and smoking) as well as nontraditional cardiovascular risk factors (microinflammation). Furthermore, immunosuppressive drugs, namely, calcineurin inhibitors, sirolimus, and steroids, have been reported to adversely affect cardiovascular risk factors (e.g., hypertension, hyperlipidemia, hyperglycemia). Evidence from comparative trials and from conversion studies suggest that blood pressure, hyperlipidemia, and hyperglycemia after renal transplantation may be differentially affected by the calcineurin inhibitors cyclosporine and tacrolimus. In the European Tacrolimus versus Cyclosporin A Microemulsion Renal Transplantation Study, 557 patients were randomly allocated to therapy with tacrolimus (n = 286) versus cyclosporine (n = 271). In addition, to blood pressure, serum cholesterol, HDL cholesterol, triglycerides, and blood glucose, we estimated the 10-year risk of coronary heart disease (Framingham risk score). Tacrolimus resulted in a significantly lower time-weighted average of serum cholesterol (P < .001), and mean arterial blood pressure (P < .05), but a higher time-weighted average of blood glucose (P < .01) than cyclosporine. Mean 10-year coronary artery disease risk estimate was significantly lower in men treated with tacrolimus, (10.0% versus 13.2%; P < .01) but was unchanged in women (4.7% versus 7.0%). Tacrolimus and cyclosporine microemulsion have compound-specific effects on cardiovascular risk factors that differentially affect the predicted rate of coronary artery disease.

[The therapeutic impact of (18)F-FDG whole body PET. A radiooncologist's view]. / Der Einfluss der (18)F-FDG-Ganzkörper-PET auf das therapeutische Management onkologischer Patienten aus strahlentherapeutischer Sicht.

AIMS: An explorative analysis of the diagnostic as well as therapeutic impact of (18)F-FDG whole body PET on patients with various tumours in the setting of an university hospital radiation therapy was performed. PATIENTS AND METHODS: 222 FDG PET investigations (148 initial stagings, 74 restagings) in 176 patients with diverse tumour entities (37 lung carcinoma, 15 gastrointestinal tumours, 38 head and neck cancer, 30 lymphoma, 37 breast cancer, 19 sarcoma and 16 other carcinomas) were done. All PET scans were evaluated in an interdisciplinary approach and consecutively confirmed by other imaging modalities or biopsy. Unconfirmed PET findings were ignored. Proportions of verified PET findings, additional diagnostic information (diagnostic impact) and changes of the therapeutic concept intended and documented before PET with special emphasis on radiooncological decisions (therapeutic impact) were analysed. RESULTS: 195/222 (88%) FDG-PET findings were verified, 104/222 (47%) FDG-PET scans yielded additional diagnostic information (38 distant, 30 additional metastasis, 11 local recurrencies, 10 primary tumours and 15 residual tumours after chemoptherapy). The results of 75/222 (34%) scans induced changes in cancer therapy and those of 58/222 (26%) scans induced modifications of radiotherapeutic treatment plan (esp. target volumes). CONCLUSION: (18)F-FDG whole body PET is a valuable diagnostic tool for therapy planning in radiooncology with a high impact on therapeutic decisions in initial staging as well as in restaging. Especially in a curative setting it should be used for definition of target volumes.

Implantation of stimulation electrodes in the subretinal space to demonstrate cortical responses in Yucatan minipig in the course of visual prosthesis development.

PURPOSE: During the course of the development of visual prostheses, subretinal stimulation films were implanted in micropigs in order to prove the feasibility of subretinal electrical stimulation with subsequent cortical response. One aim was to demonstrate that epidural recording of visual evoked potentials is possible in the micropig. METHODS: Film-bound stimulation electrode arrays were placed in the subretinal space of micropigs. This enabled the retina to be stimulated subretinally. Since conventional visual evoked potential (VEP) measuring is virtually impossible in the pig from the neurosurgical point of view, epidural recording electrode arrays were positioned over the visual cortex as permanent electrodes. RESULTS: The feasibility of temporary implantation of film-bound stimulation electrode arrays was successfully demonstrated in the micropig model. On stimulation with monopolar voltage pulses (1000 to 3000 mV), reproducible epidural VEP measurements (5 to 10 micronV) were detected. CONCLUSIONS: The feasibility of subretinal stimulation of the retina was demonstrated in a retinal model that is similar to the human retina. This animal model therefore offers a suitable means of studying the tolerability of stimulation situations in the course of visual prosthesis development.

Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells.

CX+/CX- and Colo+/Colo- tumor sublines with stable heat shock protein 70 (Hsp70) high and low membrane expression were generated by fluorescence activated cell sorting of the parental human colon (CX2) and pancreas (Colo357) carcinoma cell lines, using an Hsp70-specific antibody. Two-parameter flow cytometry revealed that Hsp70 colocalizes with Bag-4, also termed silencer of death domain, not only in the cytosol but also on the plasma membrane. After nonlethal gamma-irradiation, the percentage of membrane-positive cells and the protein density of Hsp70 and Bag-4 were found to be strongly upregulated in carcinoma sublines with initially low expression levels (CX-, Colo-). Membrane expression of Hsp70 was also elevated in Bag-4 overexpressing HeLa cervix carcinoma cells when compared to neo-transfected cells. In response to gamma-irradiation, neo-transfected HeLa cells behaved like Hsp70/Bag-4 low-expressing CX- and Colo-, and Bag-4-transfected HeLa cells like Hsp70/Bag-4 high-expressing carcinoma sublines CX+ and Colo+. Immunoprecipitation studies further confirmed colocalization of Hsp70 and Bag-4 but also point to an association of Hsp70 and Hsp40 on the plasma membrane of CX+ and Colo+ cells; on CX- and Colo- tumor sublines, Hsp40 was detectable in the absence of Hsp70 and Bag-4. Other co-chaperones including Hsp60 and Hsp90 were neither found on the cell surface of CX+/CX-, Colo+/Colo- nor on HeLa neo-/HeLa Bag-4-transfected tumor cells. Functionally, Hsp70/Bag-4 and Hsp70/Hsp40 membrane-positive tumor cells appeared to be better protected against radiation-induced effects, including G2/M arrest and growth inhibition, on the one hand. On the other hand, membrane-bound Hsp70, but neither Bag-4 nor Hsp40, served as a recognition site for the cytolytic attack mediated by natural killer cells.

Vocal stability in functional dysphonic versus healthy voices at different times of voice loading.

Functional (nonorganic) dysphonia is often characterized by vocal instability. The purpose of the prospective study was to examine whether there is a difference in vocal instability of functional dysphonic voices compared with healthy ones, this means whether electroglottographic perturbation values differ (1) between healthy and dysphonic voices and (2) between two subgroups of the dysphponic voices (hypertonic and hypotonic dysphonic voices). Twenty-three patients with hypertonic functional dysphonia, 9 with hypotonic functional dysphonia and 31 healthy nonsmokers, were each examined electroglottographically before (Ex 1), immediately after (Ex 2), and 1 hour after (Ex 3) voice loading. Perturbations of frequency, amplitude, quasi-open-quotient, and contact-index were calculated from the EGG signal. At all three times of examination, hypertonic dysphonic voices showed higher perturbations than healthy voices, and they had higher perturbations than hypotonic dysphonic voices before and 1 hour after voice loading. Hypotonic dysphonic voices showed higher perturbations than healthy voices only 1 hour after voice loading. Voice loading induced different reactions in dysphonic voices: Some voices showed increased perturbations, and others exhibited normal or even decreased perturbation immediately after voice loading. Examination of electroglottographic-derived perturbations immediately after voice loading seems not to be useful. Differentiation of hypertonic and hypotonic dysphonic voices was possible with an estimated sensitivity of 88.9% and a specificity of 87.0% by using the sum of the amplitude-perturbation and the quasi-open-quotient-perturbation measured before voice loading.

Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease.

[18F]FDG positron emission tomography (PET) scans of 14 patients comprising the clinical prototypes of dementias that are considered to be associated with frontotemporal lobar degeneration (FTLD) were compared to a population of 15 patients with early onset Alzheimer's disease (EOAD). The FTLD group included patients with frontotemporal dementia (FTD), semantic dementia (SD), and primary progressive aphasia (PPA). A voxel to voxel group comparison identified metabolic impairment in the bilateral ventromedial frontal area, the left anterior insula, and inferior frontal cortex, and indicated the right middle temporal gyrus to exhibit increased activity in FTLD compared to EOAD patients. All identified cortical structures are considered to be critically involved in neuropsychological features associated with FTLD (altered social behavior, aphasia) and EOAD (impaired linguistic and visuo-constructive abilities). In conjunction with recent insights from neuropathologic investigations, these results implicate that the a priori heterogeneous prototypes of FTLD (FTD, SD, PPA) may share more common ground than previously assumed, and therefore would become distinguishable as an entire group from EOAD.

Intraventricular cytarabine in a case of idiopathic hypertrophic pachymeningitis.

Idiopathic hypertrophic chronic pachymeningitis (IHCP) is characterised by inflammatory fibrotic thickening of the dura mater. Long term management is controversial. A 28 year old man with craniospinal IHCP and prominent lymphocytic meningitis is reported. Cerebrospinal fluid and histological examination suggested a CD4+ T cell driven process and B cell stimulation. After surgical, tuberculostatic, and immunosuppressive treatment failed to control the progressive meningeal hypertrophy, causing severe headache and neurological disability, the disease process eventually abated with intraventricular cytarabine treatment.