Glutamate quantification in patients with supratentorial gliomas using chemical shift imaging.

This study aimed to evaluate and validate chemical shift imaging (CSI) for in vivo glutamate (Glu) quantification in patients with supratentorial gliomas. If validated, CSI could become an extremely useful tool to investigate metabolic dysfunction of Glu in excitotoxic neuropathologies. Quantitative CSI estimates of Glu concentrations were compared with known concentrations of Glu in aqueous phantom solutions. Forty-one patients with known or likely supratentorial gliomas underwent preoperative CSI. The spectra obtained were analyzed for Glu concentrations and Glu to creatine (Cr) ratios. These in vivo measurements were correlated against ex vivo Glu content quantified by high performance liquid chromatography (HPLC) measured in 65 resected brain tumor and peritumoral brain specimens. For the phantom solutions the CSI estimates of Glu concentration and the Glu/Cr ratios were highly correlated with known Glu concentration (r² = 0.95, p = 0.002, and r² = 0.97, p < 0.0001, respectively). There was a modest, but statistically significant, correlation between the ex vivo measured Glu and in vivo spectroscopic Glu concentration (r² = 0.22, p = 0.04) and ratios of Glu to Cr (r² = 0.30, p = 0.002). Quantitative measurement of Glu content is feasible in patients with supratentorial gliomas using CSI. The in vitro and in vivo results suggest that this has the potential to be a reliable quantitative imaging assay for brain tumor patients. This may have wide clinical research applications in a number of neurological disorders where Glu excitotoxicity and metabolic dysfunction are known to play a role in pathogenesis, including tumor associated epilepsy, epilepsy, stroke and neurotrauma.

Neuro-Oncology and Radiogenomics: Time to Integrate?

Radiogenomics aims to predict genetic markers based on imaging features. The critical importance of molecular markers in the diagnosis and management of intracranial gliomas has led to a rapid growth in radiogenomics research, with progressively increasing complexity. Despite the advances in the techniques being examined, there has been little translation into the clinical domain. This has resulted in a growing disconnect between cutting-edge research and assimilation into clinical practice, though the fundamental goal is for these techniques to improve patient care. The goal of this review, therefore, is to discuss possible clinical scenarios in which the addition of radiogenomics may aid patient management. This includes facilitating patient counseling, determining optimal patient management when complete molecular characterization is not possible, reclassifying tumors, and overcoming some of the limitations of histologic assessment. The review also discusses considerations for selecting relevant radiogenomic features based on the clinical setting.

In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs.

TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients.

Use of tissue plasminogen activator in the treatment of shunt blockage secondary to intraventricular haemorrhage.

A 51-year-old woman with a history of idiopathic aqueduct stenosis, treated initially with insertion of a ventriculo peritoneal shunt, presented to our institution with shunt dysfunction. She had previously undergone multiple shunt revisions for shunt infection, shunt blockage and low-pressure symptoms, most recently with conversion to a ventriculo atrial (VA) shunt. Her VA shunt was again revised, with replacement of the ventricular catheter, however surgery was complicated by a large intraventricular haemorrhage (IVH) requiring placement of an external ventricular drain (EVD). Prior to eventual removal of her EVD it was determined that the VA shunt had blocked as a result of the IVH. Subsequently alteplase, a recombinant tissue plasminogen activator (tPA), was administered into the shunt reservoir, resulting in successful return of shunt function, therefore avoiding the need for further shunt revision. This is the first description of the use of tPA to unblock a shunt obstructed by blood.

MRI grading versus histology: predicting survival of World Health Organization grade II-IV astrocytomas.

BACKGROUND AND PURPOSE: Histologic grading of intracranial astrocytomas is affected by sampling error and substantial inter- and intraobserver variability. We proposed that incorporating MR imaging into grading will predict patient survival more accurately than histopathology alone. MATERIALS AND METHODS: Patients with a new diagnosis of World Health Organization grades II-IV astrocytoma or mixed oligoastrocytoma diagnosed between September 2007 and December 2010 were identified. Two hundred forty-five patients met the inclusion criteria. Preoperative MRIs were independently reviewed by 2 readers blinded to the histologic grade, and an MR imaging grade was given. The MR imaging and histopathologic grades were compared with patient survival. RESULTS: Patients with grade II or III astrocytomas on histology but evidence of necrosis on MR imaging (consistent with a grade IV tumor) had significantly worse survival than patients with the same histology but no evidence of necrosis on MR imaging (P = .002 for grade II histology and P = .029 for grade III). Their survival was not significantly different from that in patients with grade IV tumors on histology (P = .164 and P = .385, respectively); this outcome suggests that all or most are likely to have truly been grade IV tumors. MR imaging evidence of necrosis was less frequent in grade II and III oligoastrocytomas, preventing adequate subgroup analysis. CONCLUSIONS: MR imaging can improve grading of intracranial astrocytomas by identifying patients suspected of being undergraded by histology, with high interobserver agreement. This finding has the potential to optimize patient management, for example, by encouraging more aggressive treatment earlier in the patient's course.

Parents' versus physicians' values for clinical outcomes in young febrile children.

OBJECTIVE: To compare how parents and physicians value potential clinical outcomes in young children who have a fever but no focus of bacterial infection. METHODS: Cross-sectional study of 100 parents of well children aged 3 to 24 months, 61 parents of febrile children aged 3 to 24 months, and 56 attending staff physicians working in a children's hospital emergency department. A pretested visual analog scale was used to assess values on a 0-to-1 scale (where 0 is the value of the worst possible outcome, and 1 is the value for the best) for 22 scenarios, grouped in three categories according to severity. Based on the three or four common attributes comprising the scenarios in a given group, each respondent's value function was estimated statistically based on multiattribute utility theory. RESULTS: For outcomes in group 1 (rapidly resolving viral infection with one or more diagnostic tests), no significant group differences were observed. For outcomes in groups 2 (acute infections without long-term sequelae) and 3 (long-term sequelae of urinary tract infection or bacterial meningitis), parents of well children and parents of febrile children had values that were similar to each other but significantly lower than physicians' values for pneumonia with delayed diagnosis, false-positive diagnosis of urinary tract infection, viral meningitis, and unilateral hearing loss. For bacterial meningitis with or without delay, however, the reverse pattern was observed; physicians' values were lower than parents'. In arriving at their judgment for group 2 and 3 scenarios, parents gave significantly greater weight to attributes involving the pain and discomfort of diagnostic tests and to diagnostic error, whereas physicians gave significantly greater weight to attributes involving both short- and long-term morbidity and long-term worry and inconvenience. Parents were significantly more likely to be risk-seeking in the way they weighted the attributes comprising group 2 and 3 scenarios than physicians, ie, they were more willing to risk rare but severe morbidity to avoid the short-term adverse effects of testing. CONCLUSIONS: Parents and physicians show fundamental value differences concerning diagnostic testing, diagnostic error, and short- and long-term morbidity; these differences have important implications for diagnostic decision making in the young febrile child.

Role of the complete blood count in detecting occult focal bacterial infection in the young febrile child.

Previous studies of the value of the complete blood count (CBC) in distinguishing viral from bacterial infection in young febrile children have failed to exclude children with clinically evident bacterial infection and thus have inflated the positive predictive value of the test for occult focal infection. We prospectively studied 2492 children 3-24 months of age who presented to a children's hospital emergency department between March 1989 and August 1990 with fever (> or = 38.0 degrees C) of acute (< or = 4 days) onset but no evident bacterial focus of infection, 433 (17.4%) of whom received a CBC. We also carried out an 8-year retrospective analysis to estimate prior, or pre-test, probabilities (prevalences) and examine CBC results for rare occult bacterial infections (meningitis, osteomyelitis, and septic arthritis). Estimated prior probabilities for the four most common categories of infection that can be diagnosed at the initial visit were: non-pneumonitic viral infection, 88.6% in boys and 86.0% in girls; pneumonia, 8.5% in both sexes; urinary tract infection (UTI), 3.0% in boys and 5.5% in girls; and bacterial meningitis, 0.0066% in both sexes. The likelihood (sensitivity) of a total white blood cell (WBC) count > or = 15,000/mm3 was 25.5, 64.5, 62.5, and 50.0% for viral infection, pneumonia, UTI, and meningitis, respectively. Among children with a high total white blood cell count, neither a total polymorphonuclear count > or = 10,000/mm3 nor a band count > or = 500/mm3 was associated with significantly elevated likelihoods for occult pneumonia or UTI, a finding confirmed by multiple logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcutaneous carbon dioxide measurement after craniotomy in spontaneously breathing patients.

OBJECTIVE: The purpose of this study was to determine the incidence of postoperative hypercarbia in patients undergoing intracranial neurosurgery. Postoperative hypercarbia is a well-recognized cause of postoperative morbidity. METHODS: Sixty-four patients undergoing craniotomy were monitored in the first 36 postoperative hours using transcutaneous CO2 monitoring. We collected and analyzed demographic data, complete medical histories and examinations, and details of surgery, anesthesia, and postoperative progress. The accuracy of the transcutaneous CO2 monitoring was evaluated by comparison with arterial blood gas CO2. INSTRUMENTATION: The "TINA" TCM3 Transcutaneous CO2 Monitor (Radiometer, Copenhagen, Denmark) was used. RESULTS: Thirty-nine patients (61%) developed no hypercarbia. Nineteen patients (30%) developed mild to moderate hypercarbia (46-59 mm Hg) and six patients (9%) developed severe hypercarbia (60 mm Hg or greater). Statistically significant differences were observed between the severely hypercarbic group and the other two groups combined, as follows: a higher incidence of preoperative and postoperative seizures, a lower average postoperative Glasgow Coma Scale score, a higher incidence of reintubation and ventilation, and a higher degree of intraoperative brain disturbance. Analysis of transcutaneous CO2 measurements and time-matched arterial blood gas CO2 measurements revealed an acceptable accuracy of the transcutaneous method. CONCLUSION: this study demonstrates that, in routine neurosurgical practice, a subgroup of patients are at risk of developing postoperative hypercarbia, which may be more common than is generally recognized and will not usually be detected by routine postoperative monitoring. Transcutaneous CO2 monitoring is a useful technique that may impact management decisions.

Surgery for cerebral arteriovenous malformation: risks related to lenticulostriate arterial supply.

The aim of this study was to compare complications of surgery in arteriovenous malformations (AVMs) supplied by the middle cerebral artery (MCA) with and without a lenticulostriate arterial contribution. Ninety-two consecutive surgical resections of AVMs with an angiographically demonstrated MCA supply were performed between January 1989 and July 1996. Ten of these cases had a significant lenticulostriate arterial contribution. The cases were graded according to the Spetzler-Martin classification. There were no deaths and 4.3% of cases developed new major neurological deficit by the 3-month follow-up examination. All cases had angiographically confirmed obliteration of the AVM. There were no complications in 16 patients with Spetzler-Martin Grade I AVMs, one case of complications in 40 patients with Grade II AVMs, eight cases of complications in 26 patients with Grade III AVMs, and seven cases of complications in 10 patients with Grade IV and V AVMs. The supply of blood from lenticulostriate branches was associated with complications in eight of the 10 cases. The effect of the presence of a lenticulostriate arterial supply was most apparent in cases of Grade III AVMs: complications were experienced in three of 20 patients whose AVMs were not supplied by the arteries and in five of six patients whose AVMs were fed by the lenticulostriate arteries. This difference is significant (p < 0.0001). The conclusions drawn from this study are that for Grade III AVMs, the presence of a lenticulostriate arterial supply can be considered a factor predictive of an increased risk of surgical complications.

Candida endocrinopathy syndrome with membranoproliferative glomerulonephritis: demonstration of glomerular candida antigen.

A boy who had the Candida endocrinopathy syndrome, consisting of mucocutaneous candidiasis, hypoparathyroidism and hypoadrenocorticism, also had hypocomplementemic membranoproliferative glomerulonephritis. A renal biopsy at age 16 showed lobular glomerulonephritis with chronic interstitial inflammation. Glomerular and focal tubular deposition of IgG and C3, but not C4, were seen by immunofluorescence microscopy. Electron microscopy revealed dense intramembranous deposits in glomerular, tubular and Bowman's capsul basement membranes. C. albicans antigenic material was detected in the glomeruli by immunofluorescence microscopy using an FITC-labelled rabbit antiserum to the patient's organism. These fidings suggest that chronic C. albicans infection led to an immune complex form of nephritis. Clinical and laboratory evidence of resolution of his nephritis and return to normal serum levels of C3 followed prolonged antifungal therapy.

Red cell membrane phospholipid abnormalities in the hemolytic uremic syndrome.

Eight patients with the hemolytic uremic syndrome had depression of percentage of red cell phosphatidyl ethanolamine content. Five patients also had subnormal plasma tocopherol levels. In addition all patients had significant increases in total plasma lipids which could contribute to peroxidative damage. The association of depressed red cell phosphatidyl ethanolamine and plasma tocopherol levels is suggestive of peroxidative damage, and may contribute to the hemolysis in this syndrome.

Friedreich's ataxia with nephrotic syndrome and convulsive disorder: clinical and neurophysiological studies with renal and nerve biopsies and an autopsy.

In a sibship of four, Friedreich's ataxia and minimal lesion nephrotic syndrome occurred in two siblings, a third sibling had Friedreich's ataxia, but no evidence of nephrotic syndrome; the fourth sibling had neither condition. The chance of Freidreich's ataxia and minimal lesion nephrotic syndrome occurring in two siblings is small, and suggested a common immunological abnormality. High dose prednisone and antimetabolites given for the nephrotic syndrome did not appear to affect the course of Friedreich's ataxia. The two siblings with Friedrich's ataxia and nephrotic syndrome developed epilepsy at age 15 years. All three children with Friedreich's ataxia had abnormal electroencephalograms (EEGs). These epileptiform EEG abnormalities were probably inherited from the mother, who had spike wave epilepsy. The neurologic deficits of Friedreich's ataxia, in turn, may have allowed the EEG trait to be expressed as a seizure disorder. The progressive ataxia and epileptic, sometimes myoclonic, seizures in these patients and the dentate nucleus changes in the autopsied patient were consistent with the diagnosis of dyssynergia cerebellaris myoclonica. This suggested that the latter disorder may represent a coincidence of two genetic entities: Friedreich's ataxia and spike wave epilepsy.

Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3.

A 4-year-old boy had hemolytic uremic syndrome (HUS) associated with depression of serum C3 level, a B-hemolytic streptococcal throat infection, and an elevated level of antistreptolysin O titer. In addition to the characteristic histologic changes associated with this syndrome, substantial infiltration of polymorphonuclear leukocytes and nodular deposits of C3 globulin were seen in the glomeruli of the first biopsy specimen. Two months after clinical remission, he had a recurrence of hemolytic anemia, thrombocytopenia, and acute renal failure. The serum C3 concentration had decreased again, and serum C3NeF was detected in the serum. The typical changes associated with HUS were still present on electron microscopy. Bilateral nephrectomy and renal transplantation were done because of the development of uncontrollable severe hypertension and increasing azotemia. This patient had three manifestations of HUS, but because of several differences, such as hypocomplementemia, serum C3NeF, a recurrence, and persistent glomerular deposits of C3 globulin, he appears to have had a different form of the syndrome.

Metastatic atypical meningioma: case report and review of the literature.

Extracranial metastasis of an intracranial meningioma is rare. We discuss the clinical, radiological and histopathological presentation of an elderly man with pulmonary metastases from a recurrent meningioma of atypical histology, and review the literature pertaining to this phenomenon.

Surgical management of dural arteriovenous malformations of the cranium.

Ten patients undergoing surgical treatment of dural arteriovenous malformations of the cranium between June 1992 and June 1995 are presented. Indications for surgery were prevention of intracranial haemorrhage in eight cases and palliation of neurological deficits in two cases. The aim of surgery was attempted complete cure when considered technically feasible. Six patients underwent aggressive surgical resection in an ablation attempt and four underwent leptomeningeal venous disconnection only. In those undergoing aggressive surgical resection, one patient died, one was rendered disabled and angiographic cure was achieved in four without mishap. In those undergoing leptomeningeal venous disconnection, there was no mortality or morbidity but angiographic cure was achieved in only one of four patients. As a result of our experience our policy has changed. When the indications for surgery are to palliate leptomeningeal venous hypertension or as prophylaxis against future haemorrhage, interruption of the involved leptomeningeal venous drainage in the subarachnoid space without attempted cure is now the sole aim of surgery. The surgical technique employed should be based on the pathophysiological disturbance requiring correction rather than the resectability of the lesion.

Intracranial haemorrhage associated with anomalous venous drainage.

Two patients presented following small posterior fossa intraparenchymal haemorrhages from which they fully recovered. In one case this was a repeat haemorrhage. Both patients had sustained this haemorrhage within the bed of anomalous venous drainage. Angiography suggested that in both cases the anastomosis of the anomalous draining vein with the dural sinus was stenosed. These cases support the concept that anomalous venous drainage can be associated with intraparenchymal haemorrhage unassociated with cavernous malformation, that a compromised venous drainage may be the cause for such haemorrhage and that surgical resection of 'venous angiomas' is inappropriate.

Radiation safety and protection of neonates in radiological examinations.

Radiation reduction methods in neonatal radiographic examinations are discussed. Studies performed on radiation exposures to the neonates, scattered radiation level, exposure to the nursery personnel, effectiveness of the various shielding methods, uniformity of the x-ray field, heel effect, and skin exposure estimation are described. In summary, recommendations for exposure reduction based on our experimental findings as well as on the ALARA concept of radiation safety are provided.

Socio-demographic factors and their impact on the number of resections for patients with recurrent glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour. Having a second or subsequent operation at recurrence may be a positive prognostic factor for survival. Recent studies suggest that socio-demographic variables may influence survival, raising the question whether surgical care differs based on these variables. We examined the relationship between selected socio-demographic variables and the number of repeat operations undergone by patients with recurrent GBM. Data from all patients diagnosed with GBM between 2001 and 2011 was obtained from a clinical database maintained across two institutions (one public, one private). The clinical and socio-demographic factors for patients who received one operation were compared to those who had two or more operations, using chi-squared analyses to determine statistical differences between groups. Socioeconomic status was measured using the Index of Relative Socioeconomic Advantage and Disadvantage scores. Of 553 patients, 449 (81%) had one operation and 104 (19%) had ≥2 operations. Patients who had ≥2 operations were significantly younger (median 55 years versus 64 years, p<0.001), less likely to have multifocal (p=0.043) or bilateral (p=0.037) disease and more likely to have initial macroscopic resection (p=0.006), than those who had only one operation. Socioeconomic status did not significantly differ between the groups (p=0.31). Similarly, there was no significant difference between the number of operations in patients from regional versus city residence and public versus private hospital. This is reassuring as it suggests similar surgical management options are available for patients regardless of socio-demographic background.