Morad Nasseri

Evaluation of pseudoprogression in patients with glioblastoma multiforme using dynamic magnetic resonance imaging with ferumoxytol calls RANO criteria into question

BACKGROUND Diagnosis of pseudoprogression in patients with glioblastoma multiforme (GBM) is limited by Response Assessment in Neuro-Oncology (RANO) criteria to 3 months after chemoradiotherapy (CRT). Frequency of pseudoprogression occurring beyond this time limit was determined. Survival comparison was made between pseudoprogression and true progression patients as determined by using perfusion magnetic resonance imaging with ferumoxytol (p-MRI-Fe). METHODS Fifty-six patients with GBM who demonstrated conventional findings concerning for progression of disease post CRT were enrolled in institutional review board-approved MRI protocols. Dynamic susceptibility-weighted contrast-enhanced p-MRI-Fe was used to distinguish true progression from pseudoprogression using relative cerebral blood volume (rCBV) values. rCBV of 1.75 was assigned as the cutoff value. Participants were followed up using RANO criteria, and survival data were analyzed. RESULTS Twenty-seven participants (48.2%) experienced pseudoprogression. Pseudoprogression occurred later than 3 months post CRT in 8 (29.6%) of these 27 participants (ie, 8 [14.3%] of the 56 patients meeting the inclusion criteria). Overall survival was significantly longer in participants with pseudoprogression (35.2 months) compared with those who never experienced pseudoprogression (14.3 months; P < .001). CONCLUSIONS Pseudoprogression presented after 3 months post CRT in a considerable portion of patients with GBM, which raises doubts about the value of the 3-month time limit of the RANO criteria. Accurate rCBV measurement (eg, p-MRI-Fe) is suggested when there are radiographical concerns about progression of disease in GBM patients, regardless of any time limit. Pseudoprogression correlates with significantly better survival outcomes.

Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and PCNSL

Objective: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma. Methods: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol. Results: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3–4.1), and no measurable disease in one case. Conclusions: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA.

Motor cortex stimulation for trigeminal neuropathic or deafferentation pain: an institutional case series experience.

Background: Trigeminal neuropathy is a rare, devastating condition that can be intractable and resistant to treatment. When medical treatment fails, invasive options are limited. Motor cortex stimulation (MCS) is a relatively recent technique introduced to treat central neuropathic pain. The use of MCS to treat trigeminal neuropathic or deafferentation pain is not widespread and clinical data in the medical literature that demonstrate efficacy are limited. Method: We retrospectively reviewed patients with trigeminal neuropathic or trigeminal deafferentation pain who were treated at the Oregon Health & Science University between 2001 and 2008 by 1 neurosurgeon using MCS. Results: Eight of 11 patients (3 male, 8 female) underwent successful permanent implantation of an MCS system. All 8 patients reported initial satisfactory pain control. Three failed to experience continued pain control (6 months of follow-up). Five continued to experience long-term pain control (mean follow-up, 33 months). Average programming sessions were 2.2/year (all 8 patients) and 1.55/year (5 patients who sustained long-term pain control). Patients with anesthesia dolorosa or trigeminal deafferentation pain who had previously undergone ablative trigeminal procedures responded poorly to MCS. We encountered no perioperative complications. Conclusion: MCS is a safe and potentially effective therapy in certain patients with trigeminal neuropathy.

Diagnosis of pseudoprogression using MRI perfusion in patients with glioblastoma multiforme may predict improved survival.

AIMS This retrospective study determined the survival of glioblastoma patients with or without pseudoprogression. METHODS A total of 68 patients were included. Overall survival was compared between patients showing pseudoprogression (in most cases diagnosed using perfusion MRI with ferumoxytol) and in patients without pseudoprogession. MGMT methylation status was also analyzed in the pseudoprogression cases. RESULTS Median survival in 24 (35.3%) patients with pseudoprogression was 34.7 months (95% CI: 20.3-54.1), and 13.4 months (95% CI: 11.1-19.5) in 44 (64.7%) patients without pseudoprogression (p < 0.0001). The longest survival was a median of 54.1 months in patients with combination of pseudoprogression and (MGMT) promoter methylation. CONCLUSION Pseudoprogression is associated with better outcome, especially if concurring with MGMT promoter methylation. Patients never diagnosed with pseudoprogression had poor survival. This study emphasizes the importance of differentiating tumor progression and pseudoprogression using perfusion MRI.

Delayed intracranial hypertension after cranial vault remodeling for nonsyndromic single-suture synostosis

OBJECT Delayed intracranial hypertension may occur after cranial vault remodeling for synostosis and may result in visual loss and developmental delay. Delayed intracranial hypertension is relatively common in children with syndromic, multisuture synostosis, but the incidence is poorly defined in children with single-suture nonsyndromic synostosis. This study evaluates the frequency of reoperation for delayed intracranial hypertension after single-suture synostosis repair. METHODS Patients who had undergone cranial vault remodeling for nonsyndromic single-suture synostosis and were treated at a single tertiary pediatric hospital between July 2000 and December 2010 were analyzed for the occurrence of delayed intracranial hypertension and reoperation for cranial vault remodeling. RESULTS Eighty-one patients with clinical follow-up of at least 3 years were analyzed from a total of 156 consecutive patients. The average patient age at the initial operation was 9.1 months. Five (6.2%) of 81 patients presented with delayed clinical and ophthalmological signs and symptoms of intracranial hypertension following initial cranial vault reconstruction, confirmed indirectly in each case by CT findings and directly by intracranial pressure monitoring. These 5 patients underwent repeat cranial vault reconstruction. CONCLUSIONS Calvarial growth restriction and intracranial hypertension occur sporadically following primary cranial vault reconstruction for single-suture nonsyndromic cranial synostosis. In this series, delayed intracranial hypertension occurred only in male patients who underwent primary repair of isolated sagittal synostoses at an age less than or equal to 5 months.

Incidence of Pneumocystis jirovecii pneumonia after temozolomide for CNS malignancies without prophylaxis

AIMS Prophylaxis against Pneumocystis jiroveci pneumonia (PJP) is currently recommended for patients receiving chemoradiation with temozolomide for newly diagnosed glioblastoma multiforme. At our institution, PJP prophylaxis during temozolomide treatment has not been routinely given because of the paucity of supporting data. We investigated the rate of PJP infections in our patients. PATIENTS & METHODS We conducted a retrospective chart review of 240 brain tumor patients treated between 1999 and 2012 with temozolomide and no PJP prophylaxis, 127 of which received concurrent chemoradiation. RESULTS One in 240 patients (0.4%; 95% CI: 0.01-2.00; median total dose: 7375 mg/m(2); interquartile range: 1300) were diagnosed with PJP. CONCLUSION There was a <1% rate of PJP for brain tumor patients treated with temozolomide until progression without PJP prophylaxis.

Blood-Tumor Barrier Normalization Effects on Cytotoxic Drug Delivery to Brain Tumors

The blood-brain barrier (BBB) restricts delivery of anti-cancer drugs to brain tumors, but the leaky neovasculature of the blood-tumor barrier (BTB) permits systemically delivered cytotoxic agents to reach the tumor. Anti-angiogenic therapies such as bevacizumab (BEV) have been shown to “normalize” brain tumor vasculature,1 but the impact on chemotherapy delivery remains unclear.2 The goal of this study was to use magnetic resonance imaging (MRI) to investigate the consequences of BTB normalization, via BEV, on temozolomide (TMZ) chemotherapy. Non-invasive MRI techniques were used to track the transport of a chemotherapy surrogate, a low molecular contrast agent (Gd-DTPA), in an intracerebrally implanted human glioma. MRI-derived Gd-DTPA concentration curves were fit to a transvascular exchange model to measure vascular permeability changes and were used to quantify initial area under the gadolinium curve (IAUGC) over the course of treatment.Copyright