Diagnosis Of Central Nervous System Research Articles

Leveraging the interplay of nanotechnology and neuroscience: Designing new avenues for treating central nervous system disorders.

Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuroinflammation, brain dysfunction, psychiatric conditions, brain cancer, and nerve injury provide insights into the potential of nanomedicine. We also highlight nanotechnology-enabled neuroscience techniques such as electrophysiology and intracellular sampling to improve our understanding of the brain and its components. With nanotechnology integrally involved in the advancement of basic neuroscience and the development of novel treatments, combined diagnostic and therapeutic applications have begun to emerge. Nanotheranostics for the brain, able to achieve single-cell resolution, will hasten the rate in which we can diagnose, monitor, and treat diseases. Taken together, the recent advances highlighted in this review demonstrate the prospect for significant improvements to clinical diagnosis and treatment of a vast array of neurological diseases. However, it is apparent that a strong dialogue between the nanoscience and neuroscience communities will be critical for the development of successful nanotherapeutics that move to the clinic, benefit patients, and address unmet needs in CNS disorders.

Clinical presentation, treatment, and outcomes of patients with central nervous system involvement in extranodal natural killer/T-cell lymphoma

Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is a rare type of Non-Hodgkin’s lymphoma which rarely metastasizes to the central nervous system (CNS). Ten of 60 patients (16.7%) with ENKTCL followed at Memorial Sloan Kettering Cancer Center (MSKCC) were diagnosed with CNS involvement between 1995 and 2016. Eight patients had systemic disease at the time of CNS diagnosis; one patient never developed systemic disease and another was in remission at the time of CNS relapse. Median overall survival was 3.8 months; at time of this report 9 patients have died and one who underwent autologous stem cell transplant (ASCT) is alive 27 months after CNS diagnosis. Five patients achieved a complete response in the CNS; one is still alive, one died of systemic disease, and three died of infection. CNS ENKTCL portends a grim prognosis, with no standard treatment. Prospective study on ASCT and immunotherapy in CNS ENKTCL is warranted.

Factors influencing the documentation of fertility-related discussions for adolescents and young adults with cancer.

A cancer diagnosis and treatment may have significant implications for a young patient's future fertility. Documentation of fertility-related discussions and actions is crucial to providing the best follow-up care, which may occur for many years post-treatment. This study examined the rate of medical record documentation of fertility-related discussions and fertility preservation (FP) procedures for adolescents and young adults (AYAs) with cancer in Australia. A retrospective review of medical records for 941 patients in all six Australian states. Patients were identified through population-based cancer registries (four states) and hospital admission lists (two states). Trained data collectors extracted information from medical records using a comprehensive data collection survey. Records were reviewed for AYA patients (aged 15-24 years at diagnosis), diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, central nervous system (CNS) tumours, soft tissue sarcomas (STS), primary bone cancer or Ewing's family tumours between 2007 and 2012. 47.2% of patients had a documented fertility discussion and 35.9% had a documented FP procedure. Fertility-related documentation was less likely for female patients, those with a CNS or STS diagnosis and those receiving high-risk treatments. In multivariable models, adult hospitals with an AYA focus were more likely to document fertility discussions (odds ratio[OR] = 1.60; 95%CI = 1.08-2.37) and FP procedures (OR = 1.74; 95%CI = 1.17-2.57) than adult hospitals with no AYA services. These data provide the first national, population-based estimates of fertility documentation for AYA cancer patients in Australia. Documentation of fertility-related discussions was poor, with higher rates observed in hospitals with greater experience of treating AYA patients.

Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathologic analysis of 71 cases

Objective: As solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) share the same molecular genetics features, the 2016 WHO classification of central nervous system (CNS) tumors had created the combined term SFT/HPC and assigns three grades. This study aims to investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of CNS SFT/HPC. Methods: Seventy-one cases of CNS SFT and HPC were retrospectively reclassified and studied. Histopathological, immunohistochemical and imaging features were analyzed. The follow-up data were analyzed. Results: There were 37 male and 34 female patients. The median age was 48 years (range, 3-77 years). Twelve cases (17%) were WHO grade Ⅰ, 26 (37%) were WHO grade Ⅱ and 33 (46%) were WHO grade Ⅲ. Microscopically the tumor could show traditional SFT phenotype, HPC phenotype or mixed phenotype. Immunochemically, 97%(69/71) were positive for STAT6, with 96%(66/69)showing diffuse strong staining. Approximately 90% were diffusely positive for bcl-2, CD99 and vimentin. The expression rate of CD34 decreased with increasing tumor grade, and the mean expression rate was 78%. SSTR2a was variably expressed in 10% (7/71) of cases including one case showing strong cytoplasmic staining. A few cases expressed EMA, CD57 and S-100 focally. The Ki-67 index ranged from 1% to 50%. Thirty four patients were followed up for 8-130 months; 12 patients(35%)had recurrences, and two (6%) had liver metastases. Conclusions: CNS SFT/HPC is relatively uncommon. There was significant morphological overlap or transition between different grades. STAT6 is a specific marker for the diagnosis of this tumor. Surgical resection is the preferred treatment. WHO grade Ⅱ and Ⅲ SFT/HPC show rates of local recurrence and systemic metastasis, with liver being the most common site of extracranial metastasis.

Vasculitis in the Central Nervous System.

Central nervous system (CNS) vasculitides are a heterogeneous group of disorders characterized by an inflammatory cell infiltration and necrosis of blood vessel walls in the brain, spinal cord, and the meninges. The CNS complications are likely to be fatal without judicious use of immunosuppression; thus, early diagnosis may prevent from damage and disability. This chapter updates our knowledge on CNS vasculitis-related immunological mechanisms, neurological complications, diagnosis, and management.

Central Nervous System Involvement at the Time of Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with a Poor Outcome in Patients with Acute Myeloid Leukemia.

Recent reports suggested that central nervous system (CNS) involvement (CNS+) in patients with acute myeloid leukemia (AML) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not an independent predictor of survival after allo-HSCT. However, these studies did not analyze minimal residual disease in the CNS at the time of allo-HSCT. We evaluated the effect of residual CNS+ on the transplant outcomes of 214 AML patients in a single institution. Twenty-one (10%) patients were diagnosed with CNS+ prior to allo-HSCT. Of these, 13 patients had CNS disease at the time of allo-HSCT. The patients in CNS+ AML remission at the time of allo-HSCT had better overall survival (OS) than the patients who were not in remission (2-year OS: 55% vs. 7.7%, p=0.0001). In multivariate analyses, CNS+ at the time of allo-HSCT (hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.05-3.59; p=0.04), age over 50years at the time of allo-HSCT, and non-complete remission disease status in bone marrow at the time of allo-HSCT were independent adverse factors for OS. However, a prior history of CNS+ before allo-HSCT did not independently affect OS (HR, 1.27; 95% CI 0.53-2.07; p=0.6). Early diagnosis and eradication of CNS+ at the time of allo-HSCT may be necessary to improve the outcome for patients with CNS+ AML.

Méningite lymphocytaire chez une patiente lupique révélant un lymphome cérébral primitif : une association rare

IntroductionWe report an unusual observation of central nervous system (CNS) lymphoma in a 60-year-old woman with systemic lupus erythematosus and fatal outcome. ObservationThe patient had systemic erythematosus lupus for 7 years, treated with mycophenolate mofetil and developed lymphocytic meningitis in 2015 associated to the presence of EBV in the cerebrospinal fluid and a necrotic vermis’ lesion. Diagnosis of large B-cell lymphoma was histologically confirmed from stereotaxic biopsy, shortly before she died from neurological complications. ConclusionEven though the current association is unusual, lymphocytic meningitis with hypoglycorrachia in patients with systemic lupus erythematosus may reveal CNS lymphoma and diagnosis confirmation requires stereotaxic biopsy in order not to delay specific therapeutic management.

Molecular cytogenetic characterization of inv dup del(8p) in a fetus associated with ventriculomegaly, hypoplastic left heart, polyhydramnios and intestinal obstruction

ObjectiveTo present molecular cytogenetic characterization of inv dup del(8p) in a fetus with congenital malformations. Materials and MethodsA 19-year-old, primigravid woman underwent cord blood sampling at 31 weeks of gestation because of prenatal ultrasound findings of polyhydramnios, intestinal obstruction, right ventriculomegaly, and hypoplastic left heart. Preterm precipitous labor and delivery occurred at 32 weeks of gestation. Array comparative genomic hybridization (aCGH), conventional cytogenetic analysis and metaphase fluorescence in situ hybridization (FISH) were applied on cord blood lymphocytes. aCGH was also applied on the umbilical cord. Conventional cytogenetic analysis was applied on parental bloods. ResultsaCGH detected an 11.35 Mb deletion in 8p23.3-p23.1 encompassing SOX7 and GATA4, and a 31.99 Mb duplication in 8p23.1-p11.1 in the fetus. Metaphase FISH confirmed inv dup del(8p). The fetus had a karyotype of 46,XX,der(8)del(8)(p23.1) inv dup(8) (p11.1p23.1). Parental karyotypes were normal. A malformed fetus was delivered with facial dysmorphism. ConclusionFetuses with inv dup del(8p) may present central nervous system (CNS) abnormality and congenital heart defect on prenatal ultrasound. Prenatal diagnosis of concomitant CNS and cardiac abnormalities should include a differential diagnosis of chromosome 8p inverted duplication deletion syndrome.

Antibody biomarkers in CNS demyelinating diseases - a long and winding road.

Over several decades, studies sought potential markers to diagnose and to predict the clinical course of central nervous system (CNS) demyelinating disorders, especially in multiple sclerosis, acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. Reliable biomarkers would ensure correct diagnoses, determine future disease evolvements, stratify patients for appropriate treatments and monitor disease activity and treatment effects - in summary, meet the longing for personalized medicine in these diseases. Out of a plethora of potential biomarker candidates antibodies have turned (again) into the scientific focus, due to pivotal immunological and neuropathological findings in the past 20 years. A major breakthrough and stimulus for further research was the identification of anti-aquaporin-4 antibodies in neuromyelitis optica. Various other myelin and non-myelin antigens were investigated in detail for diagnostic and prognostic purposes, such as antibodies to myelin oligodendrocyte glycoprotein or to the potassium channel KIR4.1. Further, the use of biopharmaceutical treatments in multiple sclerosis led to intense research activities to identify anti-treatment neutralizing antibodies and their clinical consequences. This review briefly summarizes the current knowledge on antibodies in the diagnosis, prognosis, disease and treatment monitoring of CNS demyelinating disorders.

Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study.

PURPOSEContrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood–brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight.MATERIALS AND METHODSProspective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology.RESULTSOf the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%).CONCLUSIONGadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.

Platinum sensitivity and CD133 expression as risk and prognostic predictors of central nervous system metastases in patients with epithelial ovarian cancer.

BackgroundTo characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC).MethodsA retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases.ResultsAmong 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases.ConclusionsThese data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.

Type of tumour, gender and time since diagnosis affect differently health-related quality of life in adolescent survivors.

Research findings about health-related quality of life (HRQoL) of childhood cancer survivors are mixed and the features which could modulate these results have not been investigated rigorously. This research aims to improve the knowledge on these topics. Thus, HRQoL between central nervous system (CNST) and non-central nervous system (non-CNST) adolescent cancer survivors was compared. The influence of selected factors (gender and years since diagnosis) on HRQoL was also analysed. In a cross-sectional design, 78 survivors (12-20 years) who were ≥ 1 year free of oncological treatment answered the self-reported version of the KIDSCREEN-52. HRQoL mean scores of CNST survivors were lower in comparison with non-CNST in physical well-being and social support and peers dimensions. Furthermore, female gender was also related to lower HRQoL scores for both types of tumours in physical well-being and autonomy dimensions. Additionally, scores on psychological well-being, social support and peers, parent relations and home life and school environment dimensions decrease with length of time from diagnosis. Therefore, diagnosis of CNST and gender were related to lower HRQoL among survivors in some dimensions, whereas time from diagnosis was related to impaired HRQoL in other features. These results can help to design tailored interventions and psychosocial guidelines to follow-up survivors.

Abstract P6-11-09: Impact of tumor subtype on clinical features, treatment, and clinical outcomes among breast cancer patients with central nervous system disease

Abstract Background: Breast cancer is the second most common cancer associated with brain metastases. For some patients, central nervous system (CNS) progression is the primary clinical problem, and the optimal management of these patients remains a challenge. In this study we examined the differences in clinical characteristics, the features of CNS-directed therapy, and outcomes among breast cancer patients with brain metastases according to tumor subtype. Methods: A retrospective series of 214 breast cancer patients with brain metastases treated at the Dana-Farber Cancer Institute from 1999-2011 was identified. Tumor subtype was classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). Descriptive analysis was performed; Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used to compare clinical characteristics, CNS-directed therapy features, and outcomes between groups. Results: Median follow-up time since CNS progression was 8 months (0-117). Median age at CNS diagnosis was 52 years (30-82). Tumor subtype distribution was as following: 35% HR+, 36% HER2+, and 29% triple negative. Table 1 represents the clinical characteristics, CNS-directed therapy features, and outcomes according to tumor subtypes. More patients with triple negative disease (32%) had CNS involvement at presentation of metastatic disease. 8% of HER2+ patients had CNS as the only site of disease. A higher proportion of patients with HER2+ disease received more than one modality of CNS directed treatment as initial therapy. These patients also received more lines of CNS-directed therapy during the entire course of their disease. The median survival time after CNS progression differed by subtype; patients with HER2+ disease had the longest median survival times. Conclusions: Tumor subtype appears to impact clinical presentation, type and number of CNS-directed therapies, and survival among patients with breast cancer with brain metastases. Table 1 Tumor subtype HR+ (n = 74, 35%)HER2+ (n = 78, 36%)Triple negative (n = 62, 29%)P-valueBreakdown of treatment periods 0.2011999-200334%45%29% 2004-200628%17%31% 2007-201138%38%40% Clinical features at CNS disease presentationCNS disease at presentation of metastatic disease,%1522320.052Only site of metastatic disease,%181 Time from metastatic disease until CNS disease (median, min-max; months)16 (0-113)12 (0-65)6 (0-60)&amp;lt;0.001Type of CNS disease,% 0.004Brain only849589 Leptomeningeal disease only040 Brain and leptomeningeal disease16111 Number of CNS lesions,% 0.4141202921 2-3151413 4+625666 Unknown300 CNS-directed therapy1st CNS-directed therapy,% 0.126Surgery553 Whole brain radiotherapy725660 SRS896 Experimental drug135 More than one modality directed to CNS82721 Never received a CNS-directed therapy505 CNS-directed therapy (first and subsequent treatments combined),% Surgery113360.003SRS154421&amp;lt;0.001Whole brain radiotherapy8788850.866Intrathecal therapy114150.085Systemic therapy3215&amp;lt;0.001Number of CNS-directed treatments (median, min-max)1 (0-6)2 (1-9)1 (0-5)&amp;lt;0.001Clinical outcomesSurvival times (median, min-max; months)6 (0-83)22 (1-117)4 (0-110)&amp;lt;0.001Events,%9697980.016 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-09.

Abstract P6-11-12: CNS metastases in breast cancer: A comparison report

Abstract Background: Breast cancer is one of the most common causes of central nervous system (CNS) metastases, with 25-34% of patients experiencing brain metastases. Typically, CNS metastasis is associated with a dismal survival largely due to the inability of chemotherapeutic and biologic agents to cross the blood-brain barrier. In the last 5 to 7 years the management of CNS metastases utilizing targeted therapies, stereotactic radiation, and craniotomy have all shown to improve survival. We reviewed and analyzed data for CNS metastastic breast cancer treated at City of Hope (COH), a tertiary cancer center in California, in two cohorts between 2000-2005 and 2006-2011 to compare their survival. Methods/Results: A retrospective, comparative, correlational chart review was performed. Data from 172 women diagnosed with CNS metastases between 2000 and 2011 at COH, was evaluated. There were 47 patients in 2000-2005 and 125 patients in 2006-2011. The sample consisted of Caucasians (49.7%), Hispanics (26.1%), Asians (16.8%), and African Americans (7.4%). The median age at CNS diagnosis was 53 years old (24-87). Of these patients 38.2% were Her2neu positive, 30.6% ER/PR positive, and 21.4% triple negative (TN). In this cohort, the median survival for all patients with brain metastases is 5 months (0.03-85.6 months). The survival with brain metastasis among Her2neu positive, TN, and ER/PR positive is significantly different (8 months, 2.5 months, and, 5.3 months, respectively, p&amp;lt;0.0295). Limited sample size prevented the relatively substantial difference in patients with with Her2+ versus Her2- from reaching significance (median survival 8months vs 3.8 months respectively, p&amp;lt;0.0939). The median survival for patients diagnosed and treated in 2006-2011 is statistically significantly worse than those in 2000-20005 (4.4 months and 7 months, respectively, p = 0.0042). Most patients received treatment for brain metastases with one or more therapies, including whole brain radiation, stereotactic radiation, craniotomy, and intrathecal chemotherapy. Most of the patients who received chemotherapy, craniotomy, and/or stereotactic radiation were in the 2006-2011 group (100%, 82.5%, and 72.6%, respectively).There was also a shift in the incidence of patients with TN, her2neu positive, and ER/PR positive disease in the 2006-2011 as compared to 2000-2005 (24% vs 14.6%, p&amp;lt;0.004; 40% vs 31.3%, p&amp;lt;0.000; 31.2% vs 29.2%, p 0.033, respectively). Conclusion: The results of our study showed that despite the new therapies there was no change in survival for brain metastasis in breast cancer. In this single institution report, this may be in part due to an increase number of patients with TN and Her2neu positive CNS disease, better data collection, or due to better systemic control. We also noted an increase in the number of patients with brain metastases, which may be attributed to the increase in the number of patients presenting with metastatic breast cancer at COH for consideration of investigational therapies. Further studies aimed to determine why there is a shift in the tumor biology, as well as, to characterize risk factors for development of CNS disease and to develop new treatment strategies are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-12.

The incidence of secondary central nervous system involvement in patients with non-Hodgkin’s lymphoma as detected by 18F-FDG PET/CT

Secondary central nervous system (CNS) involvement is a devastating and usually fatal complication of non-Hodgkin's lymphoma (NHL). We aimed to evaluate the incidence of secondary CNS involvement and the value of (18)F-FDG PET/computed tomography (CT) imaging in the detection of secondary CNS involvement in patients with NHL. A total of 123 immunocompetent patients (58 men, 65 women; mean age: 56.5±19.2) with biopsy-proven NHL who underwent (18)F-FDG PET/CT for primary staging (n=68) and restaging (n=55) of recurrent disease were reviewed retrospectively. Those with secondary CNS involvement as diagnosed on PET/CT were identified. CNS involvement was confirmed by MRI and cerebrospinal fluid cytology. The clinical Ann Arbor stages of the patient population were as follows: stage I - 10 patients; stage II - 44 patients; stage III - 32 patients, and stage IV - 37 patients. PET/CT detected CNS involvement in six patients. The ages of patients with CNS disease ranged from 23 to 68 (mean: 47.2) years. Three patients presented with CNS involvement associated with systemic disease manifestation at initial diagnosis; one patient had isolated CNS relapse and two had relapsed systemic NHL with progression to CNS involvement. Relapse interval was 8-12 months following initial diagnosis. The types of CNS involvement in patients were as follows: parenchymal (n=2), leptomeningeal (n=2), both parenchymal and leptomeningeal (n=1), and pituitary gland involvement (n=1), which is an uncommon manifestation. Median duration of survival was 2.5 months after the diagnosis of CNS involvement. The incidence of secondary CNS involvement was 4.4% at initial diagnosis and 5.4% among patients with relapse of lymphoma in our study. PET/CT is a sensitive, objective, and valuable method for the diagnosis of secondary CNS involvement in patients with NHL. In addition, pituitary gland involvement, as a very rare manifestation of secondary CNS lymphoma, has been shown.

Pica Causing Neurocysticercosis in Pregnancy Presenting as Eclampsia: A Report of Two Cases

Eclampsia of pregnancy is a multi system disorder,which is commonly suspected whenever a woman presents with the clinical picture of elevated B.P. and convulsions. Neurocysticercosis is a common parasitic infestation of the central nervous system (CNS) caused by the pork tapeworm (Taenia solium) and is common in India [1]. The patient presents with focal seizures, with or without loss of consciousness and has been proved to be as common amongst vegetarian probably to improper washing and incomplete cooking of vegetables. The CNS diagnosis of cerebral cysticercosis is clinched by: The typical CT findings of enhancing ring or nodular lesions ranging from 5 to 20 mm in diameter, in any part of the brain. There may be a punctate, eccentric, high density structure suggestive of scolex, seen in 44 % of cases. MRI shows characteristic hypointense ring with a hyperintense or isointense centre [2]. Pica is an eating disorder defined as the persistent eating of non-nutritive substances practiced in many societies in India during pregnancy. Geophagia, or ingestion of soil, clay etc. may lead to parasitic infestations. Two cases of Neurocysticercosis in pregnancy caused by pica which were initially treated as cases of Eclampsia are presented. Case 1: A 25 years old vegetarian woman in the 28th week of gestation was admitted with generalised tonic–clonic convulsions, bilateral pedal oedema and a BP of 140/90. Fundus examination showed papilloedema and CT scan revealed multiple ring enhancing lesions surrounded by hypo-intensity due to perifocal oedema. There was a single lesion at the pontomedullary junction and one in the cerebellum. The lesions were hyper-intense on T2WI and hypo-intense on T1WI. The lesions showed eccentric nodules (Fig. 1). Fig. 1 CT scan Case 2: A 22 years old woman in her 27th week of gestation presented with left sided simple focal seizures. Her BP was 136/94 and MRI of the head revealed a single ring lesion in the right parietal lobe with an eccentric nodule. There was perifocal oedema on T2WI, and the lesion was hypo-intense on T1WI (Fig. 2). Fig. 2 CT scan These two women initially diagnosed and treated as cases of Eclampsia were given Albendazole therapy with anticonvulsants after diagnosis (Fig. 3). Fig. 3 MRI Conclusion Neurocysticercosis should be considered as a possibility in pregnant women who present with signs of raised intracranial pressure like papilledema, as in the first case and/or focal seizures as in the second case. Hypertension may be secondary to convulsions, due to neurocysticercosis MRI scanning should be carried out in suspected cases as it is a safe procedure during pregnancy.

Central Nervous System (CNS) Involvement with Multiple Myeloma (MM) – Longterm Survival Can Be Achieved with Radiation, Intrathecal (IT) Chemotherapy, and Immunomodulatory Agents (IMiDs),

Abstract 3983 Introduction:CNS involvement with MM is uncommon, estimated at 1% of patients (pts)(Fassas 2002). CNS myeloma has a reportedly dismal prognosis with median survival of only 2 months (mos) from CNS diagnosis (Nieuwenhuizen 2007). These data derive primarily from small case reports predating the use of novel agents such as the IMiDs and bortezomib. We reviewed our institutional experience with 37 CNS myeloma pts, many treated with novel agents, specifically aiming to identify longterm survivors and their disease/treatment characteristics. Methods:From 1999 to 2010, all pts with CNS MM identified by CSF plasmacytosis and/or leptomeningeal/dural disease on imaging at our institution were reviewed. Pt demographics, disease characteristics, treatments, and survival were retrospectively reviewed from charts, pharmacy records, and a myeloma database. Survival was calculated from time of CNS disease to progression (time to progression; TTP) or death (overall survival; OS). Survival analyses were performed using the Kaplan Meier method (SPSS v17.0). Results:Patient and disease characteristics:Of 758 pts diagnosed with MM at our institution over the 20 year period, 37 pts developed CNS disease (incidence 4.9%). Median age of the 37 CNS pts was 54 years (range 36–70), 51% male. A predominance of light chain subtype was noted: light chains only 32%, IgG 30%, IgA 24%, other 13%. CNS involvement was present at MM diagnosis in 9 pts (24%); at relapse in 28 pts (76%). In the relapsed pts, median number of prior therapies was 2(1–5). Median time from MM diagnosis to CNS presentation was 19.1 mos (range 4.4 weeks–11 years). Cranial nerve involvement (diplopia, facial numbness, visual blurring) was present in 24 of 37 pts (65%). Other common symptoms were headache, cognitive impairment, seizures. Fifteen pts (40%) had plasma cell leukemia (PCL) at CNS presentation. Symptomatic involvement of the orbits (11 pts; 30%) and spinal dura/epidura (17 pts; 46%) was common. Plasmacytomas of the skull adjacent to dura were seen in 65% of cases, suggesting contiguous spread. Leptomeningeal/dural enhancement or thickening on MRI was visualized in 54%, whereas parenchymal brain involvement was rare (5%). CSF plasmacytosis was reported in 24 of 34 pts tested (70%). Treatment and survival:Most pts (30/37 pts; 81%) received intrathecal (IT) chemotherapy (hydrocortisone, methotrexate, and/or cytarabine) with rapid clearance of plasma cells from CSF. Radiation was administered in 28 pts (10 craniospinal, 8 cranial only, 8 spinal only). Ten pts (30%) presented with localized CNS disease and did not require immediate systemic therapy. Various systemic therapies were used: IMiDs 16(43%), cisplatin-based (DPACE) 9(24%), bortezomib 7(19%), alkylators 5(13%), dexamethasone (DEX) alone 4(10.8%), autotransplant 1(2.7%). Consistent with the literature, median TTP from onset of CNS disease for all pts was short at 3.1 mos (95% CI 8.2–18.9). At median follow-up of 24.2 mos, median OS from CNS disease was only 4.3 mos (95% CI 3.1–5.5). However, 7 pts had prolonged survival after onset of CNS disease: 13.2, 16.1, 17.1, 34.3, 35.6, and 69.5 mos. There were no uniform laboratory or clinical features to these 7 longterm survivors. Although 2 of these pts had stable systemic disease at time of CNS onset, 3 had PCL, 5 had aggressive bone/soft tissue plasmacytomas. Three longterm survivors presented with CNS disease at time of MM diagnosis, 4 at relapse. Though all 7 underwent radiation, 6 of 7 pts received repeated IT chemotherapy (4 received maintenance IT chemotherapy every 1–2 mos), and 5 of 7 pts received thalidomide as TD (thalidomide, DEX), CTD (cyclophosphamide, thalidomide, DEX) or DTPACE (DEX, thalidomide, cisplatin, adriamycin, cyclophosphamide, etoposide). Conclusion:Although CNS disease is considered an aggressive complication of MM, in our review of 37 pts, one of the largest single-institution reports of CNS myeloma in the literature, clinical presentation and outcomes are heterogeneous. The high rate of PCL and skull-based plasmacytomas suggest that both hematogenous and contiguous spread from bone can occur. With our experience, longterm survival can be achieved with cranial/spinal irradiation, multi-dosing IT chemotherapy, and oral thalidomide, previously reported to cross the blood-brain barrier. This triple modality approach, using DPACE with or without thalidomide, is being further evaluated at our institution. Disclosures:Chen:Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria.

Excessive daytime sleepiness and sleep-disordered breathing disturbances in survivors of childhood central nervous system tumors.

Improvements in treatment and management for pediatric central nervous system (CNS) tumors have increased survival rates, allowing clinicians to focus on long-term sequelae, including sleep disorders. The objective of this study was to describe a series of CNS tumor survivors who had sleep evaluations that included polysomnography (PSG) with attention to sleep disorder in relation to the tumor site. We report on 31 patients who had retrievable reports including an overnight PSG; 17 also underwent multiple sleep latency tests (MSLT) to characterize their sleepiness. Mean age at tumor diagnosis was 7.4 years, mean age at sleep referral 14.3 years, and a mean time between tumor diagnosis and sleep referral of 6.9 years. The most common tumor location was the suprasellar region, the most common reason for sleep referral was excessive daytime sleepiness (EDS), and the most common sleep diagnosis was obstructive sleep apnea (n = 14) followed by central sleep apnea (n = 4), hypersomnia due to medical condition (n = 4), and narcolepsy (n = 3). Twenty-six of the 31 subjects were obese/overweight, and among those with the concurrent complaint of EDS, the mean sleep latency on MSLT was 3.16 minutes, consistent with excessive sleepiness. Suprasellar region tumor survivors who are obese or overweight are more likely to have complaints of EDS and are at greater risk of sleep-disordered breathing. Sleep-related symptoms may not be recognized and referral initiated until years after CNS diagnosis. A periodic and thorough sleep history should be taken when caring for CNS tumor survivors.

Central Nervous System Metastases in Patients with HER2-Positive Metastatic Breast Cancer: Incidence, Treatment, and Survival in Patients from registHER

registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.

Frequency and cause of disagreements in imaging diagnosis in children with ventriculomegaly diagnosed prenatally

To assess the frequency and cause of variability in diagnosis on cranial sonography and magnetic resonance imaging (MRI) in children referred following prenatal diagnosis of ventriculomegaly. Between 19 September 2003 and 16 March 2007, 119 infants with ultrasound and/or MRI studies performed within 13 months (median, 6 days) after birth, following prenatal referral for ventriculomegaly, were studied prospectively. There were 97 infants with ultrasound results and 53 with MRI, including 31 with both. Three sonologists and three pediatric neuroradiologists interpreted the postnatal ultrasound and MRI findings, blinded to prenatal diagnosis, and a final consensus diagnosis or group of diagnoses was obtained. Ventricular sizes as well as types of and reasons for any disagreement in diagnosis were recorded. Disagreements on a per patient basis were categorized as being major when they crossed diagnostic categories and had the potential to change patient counseling. Postnatal and prenatal diagnoses were compared. There was prospective agreement on 42/97 (43%) ultrasound and on 9/53 (17%) MRI readings. Prospective consensus was more likely when the number of central nervous system (CNS) anomalies was lower (P < 0.001 and P = 0.002 for ultrasound and MRI, respectively). In 24/55 (44%) ultrasound and 11/44 (25%) MRI examinations with disagreement in diagnosis, there was disagreement concerning the presence of ventriculomegaly. In 22/97 (23%) ultrasound studies and 22/53 (42%) MRI studies the disagreements were potentially important. Reasons for discrepancies in the reporting of major findings included errors of observation as well as modality differences in depiction of abnormalities. In comparing prenatal with postnatal diagnoses, there were 11/97 (11%) ultrasound and 27/53 (51%) MRI examinations with newly detected major findings, the most common being migrational abnormalities, callosal dysgenesis/destruction and interval development of hemorrhage. Variability in postnatal CNS diagnosis is common after a prenatal diagnosis of ventriculomegaly. This is due in part to a lack of standardization in the definition of postnatal ventriculomegaly.