Intraventricular Research Articles

Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: a literature review

Acinetobacter baumannii ventriculitis/meningitis due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has become a clinical entity of considerable importance in recent years. A review of the available literature regarding intraventricular (IVT) or intrathecal (ITH) administration of colistin in MDR and XDR A. baumannii ventriculitis/meningitis was conducted and a total of 83 episodes in 81 patients were identified (71 cases in adults and 10 in children and neonates). Colistin was administered via the IVT and ITH route in 52 and 22 cases, respectively, whilst in 7 cases the exact route was not identified. The median dose of local colistin was 125000IU (10mg) with a range of 20000IU (1.6mg) to 500000IU (40mg) in adults, whilst a dose of 2000IU/kg (0.16mg/kg) up to 125000IU (10mg) was used in the paediatric population. The median duration of treatment of IVT/ITH polymyxin E was 18.5 days, whilst the median time to achieve sterilisation of cerebrospinal fluid was 4 days. The rate of successful outcome was 89%, and toxicity related to treatment mainly manifested as reversible chemical ventriculitis/meningitis was reported in nine cases (11%). Nowadays, IVT and ITH colistin represents the last resort treatment of MDR and XDR A. baumannii ventriculitis/meningitis, offering a unique, rather safe and successful mode of therapy.

No Exacerbation of Perihematomal Edema with Intraventricular Tissue Plasminogen Activator in Patients with Spontaneous Intraventricular Hemorrhage

In severe spontaneous intraventricular hemorrhage (IVH), intraventricular (IVR) administration of tissue plasminogen activator (rtPA) clears blood from the ventricles more rapidly than with external ventricular drainage (EVD) alone. However, experimental studies suggest tPA may be neurotoxic in compromised brain tissue and may exacerbate perihematomal edema. We used computerized volumetrics to assess change in intracerebral hemorrhage (ICH), IVH, ventricular, and perihematomal edema (PHE) volumes at 2-4 (T1) and 5-9 (T2) days following diagnostic CT scans (T0) of 24 patients (12 tPA-treated; 12 controls) with IVH requiring EVD. Controls from a hospital registry were matched by IVH and ICH volume to tPA-treated patients who came from a multicenter trial involving 52 patients with IVH. There were no significant differences between matched pairs in admission ICH and IVH volumes. IVR tPA resulted in more rapid clearance of IVH as determined by T2-T0 decrease in median IVH volume (tPA: -18.7 cc, iqr 14.9; control:-6.9 cc, iqr 6.4; P = 0.002). Median ratios of PHE to ICH volume were not significantly different in control versus tPA-treated patients at T1 and T2 [control:tPA = 0.55:0.56 (T1); P = 0.84 and 0.81:0.71 (T2); P = 1.00]. Total ventricular volume was significantly larger in the control group at T2 (mean: 57.57 ± 10.32 vs. tPA: 24.80 ± 2.67 cc; P = 0.01). Bacterial ventriculitis was more frequent in the control group (5 vs. 1 episodes; P = 0.06) as was shunt dependence (4 vs. 0 cases; P = 0.03). For case matched large IVH with small ICH volume, IVR tPA enhances lysis of intraventricular blood clots and has no significant impact on PHE.

Intraventricular antimicrobial therapy in postneurosurgical Gram-negative bacillary meningitis or ventriculitis: A hospital-based retrospective study

Postneurosurgical Gram-negative bacillary meningitis (GNBM) or ventriculitis is a serious issue. Intraventricular (IVT) therapy has been applied; however, its effectiveness remains controversial, and the adverse drug effects are considerable. The demographic data, treatment strategies, and clinical outcomes of patients with postneurosurgical GNBM or ventriculitis were recorded. From 2003 to 2011, data on 127 episodes of infection in 109 patients were collected, and 15 episodes in 14 patients were treated using a sequential combination of intravenous antibiotics and IVT therapy; others received intravenous antibiotics alone. The average age of patients who received a sequential combination with IVT therapy was 48.9 years, and 71.4% of the patients were men. The regimens used for IVT therapies included gentamicin (n = 4), amikacin (n = 7), and colistin (n = 4). After meningitis had been diagnosed, the average period that elapsed before initiation of IVT therapy was 25.4 days, and the average duration of IVT therapy was 13.3 days. The most frequently isolated pathogen from cerebrospinal fluid (CSF) was Acinetobacter baumannii, followed by Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens. The cure rate was 73.3%. Of note, the mean period to sterilize the CSF after appropriate IVT antibiotic treatment was 6.6 days. There were no incidents of seizure or chemical ventriculitis during this IVT therapy. The findings of this study suggest that IVT antibiotic therapy is a useful option in the treatment of postneurosurgical GNBM or ventriculitis, especially for those with a treatment-refractory state.

Infections of cerebrospinal fluid diversion devices in adults: The role of intraventricular antimicrobial therapy

The precise role for intraventricular (IVT) antimicrobials in combination with systemic antibiotics in management of cerebrospinal fluid (CSF) diversion device-associated infections is uncertain. We evaluated our current practice, comparing dual therapy against systemic antimicrobials alone. All adult patients with at least two consecutive CSF isolates who were treated for CSF diversion device-related infection over a 5-year period (2005-2010) were identified retrospectively. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were analysed. Forty-eight patients were identified - 25 received IVT and systemic antibiotics (group A), and 23 systemic antibiotics alone (group B). Clinical features were similar between groups, as were causative organisms. CSF leucocyte counts differed slightly (A>B, p=0.067) but no laboratory parameters differed significantly. Infected devices were generally revised (A=92%, B=91%). Mean times to CSF sterilisation and normalisation of CSF microscopy were significantly shorter for group A (p<0.05 and p<0.005 respectively), as was duration of hospital stay (p<0.002) and required length of systemic antimicrobial therapy (p<0.001). Our findings indicate that IVT antibiotics enhance clinical and microbiological recovery and should therefore be considered for patients with CSF infection associated with a CSF diversion device. We recommend further evaluation of this approach in a prospective, randomised, controlled trial.

Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Vancomycin in Adults

Central nervous system infections requiring treatment with intraventricular (IVT) vancomycin are becoming increasingly common with advent of intracranial devices and increasing prevalence of multi-drug resistant and nosocomial organisms. Administering vancomycin via IVT route bypasses the blood-brain barrier to allow localized and controlled delivery directly to the desired site of action, achieving high concentrations for more reliable bactericidal action. This article systematically reviews current literature on IVT vancomycin in adults, compiles current knowledge, and integrates available evidence to serve as a practical reference.Medline (1946-July 2012), Embase (1974-July 2012), and International Pharmaceutical Abstracts (1970-July 2012) were searched using terms vancomycin, intraventricular, shunt infection, cerebrospinal fluid, and intraventriculitis. Seventeen articles were included in this review. Indications for IVT vancomycin included meningitis unresponsive to intravenous antibiotics, ventriculitis, and intracranial device infections. No serious adverse effects following IVT vancomycin have been reported. Dosages reported in literature ranged from 0.075-50 mg/day, with the most evidence for dosages of 5 to 20 mg/day. Duration of therapy most commonly ranged from 7 to 21 days. Therapeutic drug monitoring was reported in 11 studies, with CSF vancomycin levels varying widely from 1.1 to 812.6 mg/L, without clear relationships between CSF levels and efficacy or toxicity. Using IVT vancomycin to treat meningitis, ventriculitis, and CNS device-associated infections appears safe and effective based on current evidence. Optimal regimens are still unclear, and dosing of IVT vancomycin requires intricate consideration of patient specific factors and their impact on CNS pathophysiology. Higher-quality clinical trials are necessary to characterize the disposition of vancomycin within CNS, and to determine models for various pathophysiological conditions to facilitate better understanding of effects on pharmacokinetic and pharmacodynamic parameters.

Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) associated with "responsive" malignancies.

2015 Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent + CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had + CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13+, 30+, 33+, and 180+ wks. 4 pts (24%) lived &gt; 95 wks. Of 11 w/ baseline + CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear = 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.

Abstract 3443: No Exacerbation of Perihematomal Edema or Ventricular Volume with Intraventricular Tissue Plasminogen Activator in Patients with Spontaneous Intraventricular Hemorrhage

Introduction: In severe spontaneous intraventricular hemorrhage (IVH), intraventricular (IVR) administration of tissue plasminogen activator (tPA) results in more rapid clearing of blood from the ventricles than with external ventricular drainage (EVD) alone. However, experimental studies suggest tPA may be neurotoxic in compromised brain tissue and may exacerbate perihematomal edema. Methods: We used computerized volumetrics to assess change in intracerebral hemorrhage (ICH), IVH, ventricular and peri-ICH edema (PHE) volumes at 2-5 (T1) and 5-9 (T2) days following diagnostic CT scans (T0) of 20 patients (10 tPA treated; 10 controls) with IVH requiring EVD. Control patients from a hospital database treated with EVD alone were matched by IVH and ICH volume to tPA-treated patients. Treated patients came from two multicenter trials involving 100 patients with IVH, and spontaneous ICH volume &lt;30cc and received a median of 4 doses (range 1-8) of tPA. Results: There were no significant differences between matched pairs in terms of age, admission Glasgow Coma Score, Graeb IVH score, PHE volume, total ventricular volume, or ICH volume. Median IVH volume was larger in the tPA-treated group (26.2 cc iqr10.2 vs. 23.1 cc iqr9.2; P=0.02). IVR tPA resulted in more rapid clearance of IVH as determined by T2-T0 decrease in Graeb score and median IVH volume (tPA: -18.7 (10.8) cc; control:-7.6 (3.2) cc; P=0.005). Ratios of PHE to ICH volume were non-significantly higher in control vs. tPA treated patients at T1 and T2 [control:tPA = 0.82:0.77 (T1);P=0.44 and 0.64:0.56 (T2);P=0.48]. Total ventricular volume was significantly larger in the control group at T2 (median: 41.7 (36.9) cc vs. tPA: 24.5 (11.9) cc; P=0.02) and cumulative median cerebrospinal fluid drainage was non-significantly higher (control: 1079 (463) cc vs. tPA: 639 (428) cc; P=0.08). Ventriculitis was more frequent in the control group (4 vs. 2 episodes; P=0.08) as was shunt dependence (4 vs. 0 cases; P=0.04). Conclusions: For case matched large IVH with small ICH volume, IVR tPA enhances lysis of intraventricular blood clots, accelerates resolution of post-hemorrhagic hydrocephalus and has no significant impact on perihematomal edema.

İleri derecede erken doğmuş yenidoğanların düzeltilmiş 1-3 yaşlarındaki nörogelişimsel ve psikiyatrik değerlendirmesi

Aim: To assess the neurodevelopmental and psychiatric outcomes of very preterm vs preterm infants at 1 3 years of corrected age Material and Method: Between years 2005 2008 premature infants followed up in the NICU designated as Group 1 lt;32 wks;n=36 were evaluated in comparison to Group 2 33 37wks; n=56 with the approval of Ethics Committee TUTFEK 2008 083 in terms of neurodevelopmental and psychiatric development by using Denver developmental screening test the brief infant toddler social emotional assessment childcare provider version Mothers rsquo; psychiatric symptoms were assessed by the brief symptom inventory Socioeconomic status was determined by using SES scale t test or Mann Whitney U tests chi square and Spearman tests were used for statistical analysis Results: In Group 1 paternal education level and psychodevelopmental score was lower than group 2 abnormal outcome in Denver developmental test was more frequent Psychiatric problem score was higher in boys whereas psychodevelopmental score was higher in girls Psychosocial developmental score was lower in those infants with intraventricular hemorrhage and this score showed positive correlation with Denver developmental test results There was no difference between the two groups in terms of brief symptom inventory Conclusions: Although very preterm infants more frequently showed abnormal neuropsychological development they were not significantly different with regard to psychiatric problems Girls were more advantegous than boys in terms of psychodevelopment We conclude that these findings should be validated by larger and further studies Turk Arch Ped 2011; 46: 280 5

A Systematic Review on the Use of Intrathecal Rituximab in CNS Lymphoma

Abstract 4987 Introduction:Central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL) is a rare but serious complication with a high mortality rate and few effective therapeutic options. Rituximab is an anti-CD20 monoclonal antibody that is administered systemically in combination with chemotherapy, but can also be given intrathecally. When administered intrathecally (IT), rituximab achieves more predictable and higher cerebrospinal fluid (CSF) concentrations compared to its intravenous administration, however the efficacy and safety of IT rituximab are unknown (Rubenstein et al., J Clin Oncol 2007). We recently treated a 52 year old woman for a CNS relapse of diffuse large B-cell lymphoma (DLBCL) using a combination of IT rituximab, cytarabine, methotrexate and hydrocortisone, as well as craniospinal radiation. After initial improvement, she developed subacute combined degeneration (SCD) of the spinal cord. This prompted the present systematic review of the literature in order to explore the efficacy and safety of administering rituximab directly into the CSF for the treatment of CNS involvement by NHL. Methods:We identified all relevant citations in MEDLINE/EMBASE/CINAHL/BIOSIS Previews from their date of inception to June 20th, 2011. Prospective studies, case reports and case series reporting on intrathecal or intraventricular (via ommaya-reservoir) use of rituximab in relapsed primary (PCNSL) or secondary CNS-lymphoma were included. All articles citing the included articles, as well as the reference lists of included articles were reviewed to ensure capture of all relevant studies. In some cases, authors were contacted to gather additional information. Two authors independently evaluated study eligibility. Disagreements were resolved by consensus and agreement was assessed using the kappa statistic. All non-human studies were excluded. Due to the nature of the studies, a meta-analysis was not performed. Results:The search strategy identified 148 potential reports published between 2002–2011 of which 22 were included (3 prospective trials, 2 phase-I trials, 2 case-series and 15 case reports). The kappa value for inter-author agreement was 0.881. A total of 74 patients, aged 4–84 years old (Mean age 48), with PCNSL (28%) or secondary CNS-Lymphoma (ALL 14%, DLBCL 8%, Burkitt’s 4%, Mantle Cell Lymphoma 5%, Post-transplant lymphoproliferative disorder 4%, Unknown histology 37%), received 1 to 22 doses of 10–50mg of intrathecal (43%) or intraventricular (IVT) rituximab, either alone or in combination with other therapies. At a mean follow-up of 43 weeks (Range 2–178), 34% of patients were in complete remission and 28% showed a partial response. Patients having both leptomeningeal and parenchymal involvement of CNS lymphoma were the most likely to have progression of disease with IT/IVT rituximab (44%), as compared to those with isolated disease in the leptomeninges (29%) or parenchyma (33%). Fifty percent of patients with isolated disease in the leptomeningeal compartment showed complete remission with IVT/IT rituximab therapy. Fatigue, nausea/vomiting and paresthesias were the most commonly reported side effects. In one series, seven patients developed arachnoiditis. There was a single case of Hepatitis B virus reactivation in a patient with parenchymal PCNSL. In addition, our patient developed symptoms and findings consistent with SCD and in whom a relation between SCD and rituximab could not be ruled out. Conclusion:In case series and reports, IT rituximab appears to be a safe and modestly effective therapy when used in conjunction with other salvage therapies for the management of refractory CNS-lymphoma. The overall proportion of complications appears to be reasonably low. To our knowledge, our patient is the first case of SCD reported in a patient who received IT rituximab. Further studies with a particular emphasis on safety are needed before widespread use can be recommended. Disclosures:Off Label Use: Systematic literature review on the use of intrathecal rituximab for CNS lymphoma (off-label use). Lazo-Langner:Leo Pharma: Honoraria; Pfizer Inc.: Honoraria.

Çok düşük doğum ağırlıklı erken doğmuş bebeklerin nörogelişimsel sorunları ve nörolojik hastalığa etki eden etmenlerin araştırılması

Aim: To evaluate neurodevelopmental outcome of premature infants born with a gestational age less than 32 weeks and or very low birth weight lt;1500gr at the adjusted age of three years Material and Method: nbsp; In this study neurodevelopmental characteristics Denver II Developmental screening Test DDST II nbsp; and neurological sequelaes Amiel Tison were examined retrospectively Results: Seventeen hundred infants were evaluated at a mean age of 35 8 plusmn;2 3 months 27 2 nbsp; There were 57 female and 60 male patients and mean birth weight and gestational age were 1271 22 09 gr and 31 2 1 weeks respectively nbsp; Most important acute morbidities included respiratory distress syndrome nbsp; nbsp; RDS nbsp; 21 nbsp; bronchopulmonary dysplasia BPD 8 nbsp; severe retinopathy of prematurity nbsp; ROP nbsp; 5 nbsp; sepsis nbsp; 21 severe intraventricular hemorrhage IVH nbsp; 7 and an Apgar score of lt;6 24 nbsp; 9 4 nbsp; of the patients had major neurological sequelae; ten cases had cerebral palsy five had hydrocephalus and two had blindness Denver II Developmental Screening Test was abnormal in 23 nbsp; cases Conclusions: Our neurodevelopmental assessment results were similar to the literature One of the most important risk factors in neurodevelopmental retardation was transport Turk Arch Ped 2011; 46: 199 206

Case studies of patients receiving intraventricular topotecan for treatment of neoplastic meningitis.

e12540 Background: As cancer patients experience longer survival times, the leptomeningies increasingly play host to metastatic disease from a variety of primary sources. The disease is known as lymphomatous meningitis, or carcinomatous meningitis, depending on the site of origin of the tumor. Generically, the disease can be called neoplastic meningitis (NM) or leptomeningeal metastasis. Sadly, NM frequently results in neurological and functional devastation in afflicted patients. Research into effective and well tolerated treatments is on the rise as the incidence of NM increases. Intrathecal and intraventricular (IVt) chemotherapy via an implanted ventricular reservoir is often administered in order to circumvent the blood-brain-barrier and blood-CSF-barrier, and to provide direct contact of drug with tumor cells. The use of IVt topotecan in the treatment of NM results in progression-free survival outcomes similar to other IVt chemotherapies, while being particularly well tolerated by most patients. Methods: We present case studies from 5 patients who received IVt topotecan for NM. Primary tumors in these patients were as follows: 2 patients with primary breast cancer, 1 patient with multiple myeloma, 1 patient with medulloblastoma and 1 patient with melanoma. Results: In this series of patients, 5 months was the minimum length of treatment with IVt topotecan and maximum length of treatment was 10 months. One patient continues to receive treatment after 7 months. One patient experienced fatigue which was well controlled with dexamethasone. One patient consistently experienced nausea the day after treatment which was well controlled with compazine. There were no other adverse effects. Reasons for stopping treatment were as follows. One patient had progressive systemic disease, 2 patients experienced progression of NM, 1 patient stopped due to progressive neurological and physical decline, one patient continues treatment at this time. Conclusions: Overall, we find IVt topotecan a well tolerated and viable treatment for patients with NM originating from a variety of primary malignancies. No significant financial relationships to disclose.

Efficacy of human adipose tissue-derived stem cells in cardiac muscle repair in an experimental acute myocardial infarction model using nude rats (Crl:NIH-Fox1RNU)

This study was designed to compare the efficacy of intraventricular (IV), intramyocardial (IM) or combined IV and IM injections of human adipose tissue-derived stem cells (hADSCs) administered either immediately, 5, or 10 days after induction of acute myocardial infarction (AMI) in a nude rat model. Acute myocardial infarction was induced in 99, adult (250–350 g BW), male nude rats strain Crl:NIH-Fox1RNU. Rats received either no cells (group I, n = 15) or 2 million, hADSCs as follows: group II (n = 19) IV injection immediately after AMI; group III (n = 18) IV injection 5 days after AMI; group IV (n = 15) IV injection 5 days and IM injection 10 days after AMI; group V (n = 17) IV injection immediately after AMI and IM injection 10 days after AMI and group VI (n = 15) IM injection 10 days after AMI. Tissue sections from hearts were studied using H&E and immunohistochemistry. In the control group, there was a tendency toward granulation tissue formation, active phagocytosis, and variable angiogenesis when evaluated at 10 days, early fibrosis when evaluated at 30 days, and established fibrosis when evaluated at 60 days. However, hADSC-treated groups showed a tendency toward cardiomyocyte regeneration and prominent angiogenesis when evaluated at 10 days and smaller infarction size when evaluated at 30 and 60 days. The present study showed a significantly decreased amount of scar tissue following myocardial infarction and enhanced regenerative capacity of myocardial cells following a single, intraventricular injection of 2 million hADSCs immediately after AMI.

Intraventricular meningiomas: radiological findings and clinical features in 12 patients

Purpose To characterize the computed tomography (CT) and magnetic resonance (MR) imaging findings and clinical features of intraventricular (IV) meningiomas. Materials and methods CT ( n=8) and MR ( n=12) images and medical records of 12 patients (five men and seven women; mean age, 36 years; range, 14–68 years) with pathologically proven IV meningiomas were retrospectively reviewed. Particular attention was put on the size and shape of the mass; internal architecture such as necrosis or calcification within the tumor; peritumoral edema; associated hydrocephalus and clinical features such as symptoms, treatment, and prognosis. Results There were five of benign, three of atypical, and four of malignant subtype. All lesions were located in the lateral ventricle ranging in maximum diameters from 4.0 to 7.3 cm (mean, 5.4 cm). All tumors had lobulated shape. Five (71%, 5/7) of the atypical and malignant IV meningiomas, but just two (40%, 2/5) benign IV meningiomas, had irregular lobulation. The tumors were isointense ( n=7) or hypointense ( n=5) to gray matter on T1-weighted images, whereas isointense ( n=9) or hyperintense ( n=3) on T2-weighted images. On gadolinium-enhanced T1-weighted images, homogeneous enhancement was seen in five lesions, and heterogeneous enhancement was seen in seven lesions, Most patients ( n=10) had associated localized hydrocephalus due to ventricular entrapment. Intratumoral necrosis was seen in two cases (17%, 2/12), all of these were malignant subtype. In two cases of atypical and malignant subtypes, recurrences were found during the follow-up period after surgical resection. Conclusion More than half ( n=7, 58%) of the IV meningiomas were of atypical ( n=3) or malignant ( n=4) subtype. IV meningiomas tend to have a lobulated shape, especially irregular lobulation, and intratumoral necrosis was frequently seen in the atypical or malignant subtypes.

Migrating intraventricular cysticercosis: magnetic resonance imaging findings

Dr. Emerson L. Gasparetto – Rua Lopes Trovao 88 / 1702B 24110-071 Niteroi RJ Brasil. Neurocysticercosis (NCC) is the most common parasitic infestation affecting the central nervous system (CNS). It is frequent cause of seizures and hydrocephalus in adults from endemic regions, including Brazil. Brain parenchymal involvement occurs in 60 to 92% of patients with NCC, but intraventricular (IV) lesions are seen in only 7 to 20% of cases. Although NCC is usually self-limited by the life cycle of the parasite, intraventricular involvement is often more difficult to manage due to obstruction of cerebrospinal fluid (CSF) pathways and ependymal inflammation. Intraventricular neurocysticercosis (IVNCC) can produce mechanical obstruction of CSF flow anywhere in the ventricular system, resulting in hydrocephalus or focal neurological deficits. The symptoms can also result from ependymal inflammation associated with cyst degeneration, or from diffuse meningitis causing communicating hydrocephalus. The intraventricular cysts may circulate freely throughout the CSF pathways or become attached to the ependyma anywhere in the ventricles, but their predilection is for the occipital horn of the lateral and fourth ventricles. Although the obstruction of the CSF flow is a common cause of symptoms in patients with IVNCC, reports demonstrating the migrating cysts causing hydrocephalus are extremely rare. We report a case of intraventricular neurocysticercosis presenting with hydrocephalus due to third ventricle obstruction secondary to migrating cysticercus.

Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis

The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr-5 weeks posttransplant. Using FACS analysis, both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient. In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks. This transparent adult zebrafish serves as the ideal combination of both sensitivity and resolution for in vivo stem cell analyses.

A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt®) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study

Cytarabine liposome injection (DepoCyt), a sterile suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine. The objective of this study was to determine the pharmacokinetics (PK) of cytarabine after intrathecal administration of 50 mg encapsulated cytarabine (DepoCy) in patients with neoplastic meningitis up to 336 h (14 days) after dosing. This was an open-label study wherein two 50-mg doses of DepoCyt were administered 14 days apart via the intraventricular (IVT) route or by lumbar puncture (LP). Cerebrospinal fluid (CSF) samples were collected from eight adult patients at various times up to 14 days after each dose. Plasma samples were also collected within the same time period. CSF samples were analyzed for unencapsulated (free) and encapsulated cytarabine and the cytarabine metabolite, ara-U. Plasma samples were analyzed for free cytarabine and ara-U. The limit of detection was 0.003 microg/mL cytarabine and 0.016 microg/ml for ara-U. The concentration of free and encapsulated cytarabine in the ventricular and lumbar CSF ranged from 0.01 to 1500 microg/mL and were detectable up to 14 days post-dosing. Free cytarabine concentrations in plasma were only sporadically detectable. CSF and plasma concentrations of ara-U were low in all samples. The administration of intrathecal encapsulation cytarabine prolongs sustained tumor exposure to cytotoxic concentrations of cytarabine (>0.02 microg/ml) with a slow continuous release of cytarabine from the DepoFoam particles, so drug exposure is prolonged over time, resulting in lower peak cytarabine levels and a longer duration of exposure compared with standard cytarabine (Ara-C).

Remote myocardium gene expression after 30 and 120 min of ischaemia in the rat

The aim of the present study was to investigate how early the onset of ischaemia-induced changes in gene expression is in remote myocardium, and whether these changes would be different for left and right ventricles. Wistar rats (n=27) were randomly assigned to left coronary artery (LCA) ligation for 30 or 120 min and sham groups. Evans Blue infusion revealed antero-apical left ventricle (LV) and left intraventricular (IV) septal ischaemia (35.5+/-0.6% of LV mass). LCA ligation induced transient LV systolic dysfunction and sustained biventricular slowing of relaxation. Regarding mRNA levels, type B natriuretic peptide (BNP) was upregulated in the LV at 30 (+370+/-191%) and 120 min (+221+/-112%), whilst in the right ventricle (RV) this was only significant at 120 min (+128+/-39%). Hipoxia-inducible factor 1alpha and interleukin 6 overexpression positively correlated with BNP. Inducible NO synthase upregulation was present in both ventricles at 120 min (LV, +327+/-195%; RV, +311+/-122%), but only in the RV at 30 min (+256+/-88%). Insulin-like growth factor 1 increased in both ventricles at 30 (RV, +59+/-18%; LV, +567+/-192%) and 120 min (RV, +69+/-33%; LV, +120+/-24%). Prepro-endothelin-1 was upregulated in the RV at 120 min (+77+/-25%). Ca2+-handling proteins were selectively changed in the LV at 120 min (sarcoplasmic reticulum Ca2+ ATPase, 53+/-7%; phospholamban, +31+/-4%; Na+-Ca2+ exchanger, 31+/-6%), while Na+-H+ exchanger was altered only in the RV (-79+/-5%, 30 min; +155+/-70%, 120 min). Tumour necrosis factor-alpha and angiotensin converting enzyme were not significantly altered. A very rapid modulation of remote myocardium gene expression takes place during myocardial ischaemia, involving not only the LV but also the RV. These changes are different in the two ventricles and in the same direction as those observed in heart failure.

Aktuelle klinische Aspekte der bakteriellen Meningitis

Zu den wichtigsten zerebralen Komplikationen der bakteriellen (eitrigen) Meningitis gehoren: generalisiertes Hirnodem, zerebrovaskulare arterielle oder venose Komplikationen und Hydrozephalus. Diese Komplikationen konnen zu einem Anstieg des intrakraniellen Drucks fuhren. Bei schweren, komplizierten klinischen Verlaufen der bakteriellen Meningitis werden zusatzlich zu den Antibiotika verschiedene adjuvante Therapiemasnahmen eingesetzt, z. B. intravenose Gabe von hyperosmolaren Substanzen (Mannit) und externe intraventrikulare Liquordrainage. Wenn im Kernspintomogramm eine septische Sinusoder kortikale Venenthrombose nachweisbar ist, sollte die Dosisadaptierte intravenose Heparintherapie erwogen werden. Die kurzlich publizierten Daten einer prospektiven, randomisierten, multizentrischen Doppelblindstudie bei Erwachsenen mit bakterieller Meningitis zeigten einen gunstigen Effekt einer intravenosen Dexamethasontherapie im Vergleich zu Placebo bei Patienten mit Pneumokokkenmeningitis. Aufgrund dieser Studie wird die Gabe von Dexamethason bei erwachsenen Patienten mit V. a. bakterielle Meningitis (d. h. klinischer Verdacht plus truber Liquor, Nachweis von Bakterien im Liquor in der Gramfarbung oder einer Liquorpleozytose von >1000/μl) empfohlen.

Intraventricular Vancomycin In Pediatric Patients With Cerebrospinal Fluid Shunt Infections

TO DETERMINE: 1) the range and magnitude of vancomycin trough cerebrospinal fluid (CSF) concentrations following intraventricular (IVT) vancomycin; 2) any correlation between patient demographic and CSF vancomycin concentrations; and 3) eradication and complications rates following IVT vancomycin. Medical records of pediatric patients with shunt infection who received IVT vancomycin during a 12 month period were reviewed. Demographic, microbiological data, IVT/intravenous (IV) vancomycin dosing, concomitant antibiotics, CSF and serum vancomycin concentrations, and CSF drainage output were recorded. Seventeen patients ages 4 months to 17 years were hospitalized for shunt infection. Staphylococcus epidermidis (n=12) was the predominant organism. Sixteen patients received 10 mg, and one patient received 5 mg of IVT vancomycin for 3-23 days. All but one received concurrent IV vancomycin. The mean maximum trough CSF vancomycin concentration noted for 16 patients who recieved 10 mg of IVT vancomycin was 18.4±21.8 μg/mL (range: between 0.4 to 187.3 μg/mL). All four adolescents ≥25 kg had CSF vancomycin concentrations ≤5 μg/mL, three of four infants/children between 10.1 and 24.9 kg had trough CSF vancomycin concentrations between 10-20 μg/mL, and five of nine infants <10 kg had CSF concentrations >20 μg/mL. All organisms were successfully eradicated. One patient developed chronic eosinophilia presumed related to elevated CSF vancomycin concentrations (187 μg/mL). CONCLUSIONS #ENTITYSTARTX02013;: The combination of IVT and IV vancomycin effectively eradicated CSF shunt infections. CSF vancomycin concentrations are highly variable and poorly correlated with age and CSF output. Following a 10 mg IVT vancomycin dose, CSF concentrations appear to be lower in older children and elevated in infants/young children. One infant experienced a complication related to an elevated CSF vancomycin concentration; hence, therapy must be individualized, using CSF trough vancomycin concentrations.

Mechanisms in T-wave alternans caused by intraventricular block

It is recognized that 2:1 intraventricular (IV) block can result in T-wave alternans but is usually assumed that it would also affect QRS waveform. Block in a local region is not, however, varied activation sequence of the same muscle mass because the blocked region is not activated and is not part of the mass that is activated in cycles without block. Also, the block region may have electrocardiogram (ECG) effects when its state differs from other regions. In view of those considerations, the ECG effects of IV block were evaluated by using a computer model of excitation and recovery. ECGs were calculated from differences between the excited state and various degrees of recovery. Results provided evidence that boundaries associated with regions of block rather than regions having varied activation sequence were the major factors in T-wave alternans caused by IV block. Effects of the boundaries included cancellation of the effects of IV block on QRS complexes. Findings suggest that IV block cannot be excluded as a mechanism of T-wave alternans in the absence of QRS alternans.