Roman A. Klufas

Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence.

Background: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor. Methods: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone. Results: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders. Conclusions: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.

Preoperative Assessment of the Carotid Bifurcation Can Magnetic Resonance Angiography and Duplex Ultrasonography Replace Contrast Arteriography

BACKGROUND AND PURPOSE Noninvasive studies are used with increasing frequency to assess the carotid bifurcation before endarterectomy. Therefore, assessment of their diagnostic accuracies is essential for appropriate patient management. We prospectively evaluate two noninvasive tests, magnetic resonance angiography (MRA) and duplex ultrasonography (DU), as potential replacements for contrast arteriography (CA). METHODS A blinded comparison of three-dimensional time-of-flight (TOF) MRA, two-dimensional TOF MRA, and DU in 176 arteries was performed. CA was used as the standard of comparison. RESULTS Three-dimensional TOF MRA had a sensitivity of 94%, a specificity of 85%, and an accuracy of 88% for the identification of 70% to 99% stenosis; two-dimensional TOF MRA had a sensitivity and specificity that were approximately 10% lower than those of three-dimensional TOF MRA. DU resulted in a sensitivity of 94%, a specificity of 83%, and an accuracy of 86%. Combining data from three-dimensional TOF MRA and DU, allowing for CA only for disparate results, yielded a sensitivity of 100%, a specificity of 91%, and an accuracy of 94% among concordant noninvasive tests, with CA required in 16% of arteries. MRA accurately differentiated 17 carotid occlusions from 16 high-grade (90% to 99%) stenoses, whereas with DU two patent arteries were identified as occluded and one occluded artery was identified as patent. CONCLUSIONS Three-dimensional TOF MRA is the most accurate noninvasive test. Combined use of MRA and DU results in a marked increase in accuracy to a level that obviates the need for CA in a majority of patients.

Best Cases from the AFIP Osmotic Demyelination Syndrome

History A 22-year-old woman with a history of drug abuse was found, by her mother, unconscious and unresponsive at a friend’s house. It was reported that she had a 2-week history of unresponsiveness and vomiting. She was taken to a local hospital by emergency medical services. Upon admission, the patient experienced a generalized tonic-clonic seizure and was intubated for airway protection. She was markedly hyponatremic, her urine toxicology results were negative, and computed tomographic (CT) images of the head were reportedly normal (images unavailable). Her sodium level was rapidly corrected over the course of 11 hours. The initial sodium level was 113 mmol/L. Five hours later it was 124 mmol/L, and 6 hours after that it was 136 mmol/L. For the first few days of hospitalization, the patient remained completely unresponsive. On the 5th day of hospitalization, she began to spontaneously open and close her eyes, but she did not follow commands or track movements. Serial electroencephalograms showed a polymorphic delta rhythm, a finding consistent with severe hypoxic encephalopathy. Magnetic resonance (MR) imaging performed 2 weeks later reportedly showed extensive restricted diffusion throughout the cerebral cortex, thalami, and pons (images unavailable). Her mental status remained unchanged for approximately 2 months, at which time she was transferred to a tertiary care center. Upon admission to the tertiary care center, she was again noted to spontaneously open and close her eyes. Significant findings of neurologic examination were decerebrate posture, bilateral hypertonia in the upper limbs, Babinski reflex on the right side, and normal (downward) plantar reflex on the left.

Research Synthesis: What Is the Diagnostic Performance of Magnetic Resonance Imaging to Discriminate Benign From Malignant Vertebral Compression Fractures? Systematic Review and Meta-analysis

Study Design. This study is a research synthesis of the published literature evaluating the performance of magnetic resonance imaging (MRI) for differentiation of malignant from benign vertebral compression fractures (VCFs). Objective. Perform a systematic review and meta-analysis to summarize and combine the published data on MRI for discriminating malignant from benign VCFs. Summary of Background Data. The differentiation between benign and malignant VCFs in the spine is a challenging problem confronting spine practitioners. Methods. MEDLINE, EMBASE, and other databases were searched by 2 independent reviewers to identify studies that reported the performance of MRI for discriminating malignant from benign VCF. Included studies were assessed for described MRI features and study quality. The sensitivity, specificity, and diagnostic odds ratio (OR) of each feature were pooled with a random-effects model weighted by the inverse of the variance of each individual estimate. Results. A total of 31 studies with 1685 subjects met the selection criteria. All the studies focused on describing specific features rather than overall diagnostic performance. Signal intensity ratio on opposed phase (chemical shift) imaging 0.8 or more (OR = 164), apparent diffusion coefficient on echo planar diffusion-weighted images 1.5 × 10–3 mm2/s or less with b value 500 s/mm2 (OR = 130), presence of other noncharacteristic vertebral lesions (OR = 55), presence of paraspinal mass (OR = 33), involvement of posterior element (OR = 28), involvement of pedicle (OR = 24), complete replacement of normal bone marrow in VCF (OR = 19), presence of epidural mass (OR = 13), and diffuse convexity of posterior vertebral border (OR = 10) were associated with malignant VCFs, whereas coexisting healed benign VCF (OR = 0.006), presence of “fluid sign” (OR = 0.08), presence of focal posterior vertebral border convexity/retropulsion (OR = 0.08), and band-like shape of abnormal signal (OR = 0.07) were associated with benign VCFs. Conclusion. Several specific MRI features using signal intensity characteristics, morphological characteristics, quantitative techniques, and findings at other levels can be useful for distinguishing benign from malignant VCFs and can serve as inputs for a prediction model. Observer performance reliability has not been adequately assessed.

Comparison of Four Prediction Models to Discriminate Benign From Malignant Vertebral Compression Fractures According to MRI Feature Analysis

OBJECTIVE The purpose of this study was to identify a set of significant predictors, predominantly based on MRI features and limited demographic data, for differentiating benign from malignant vertebral compression fractures (VCFs) and to compare the diagnostic value of four different types of prediction models. MATERIALS AND METHODS The cohort included 101 subjects (mean age, 64 years; range, 22-89 years; 39.6% were men) with 128 VCFs, 84 (65.6%) of which were proven to be malignant by biopsy or follow-up imaging. A set of 36 predictors (34 MRI features, age, and sex) was acquired for each VCF retrospectively. RESULTS Univariate analysis and initial variable screening selected 14 moderately significant predictors. All four model types performed similarly in overall discrimination power. The median area under the curve for each model type was 0.872 for logistic regression, 0.781 for classification tree, 0.760 for support vector machine, and 0.730 for neural network, but no significant difference was found between any two model types by Student t test. Five predictors for the logistic regression model were statistically significant (p < 0.01). Focal paraspinal mass and depositlike appearance of pedicle involvement were positively correlated with VCF malignancy. Age, other compression deformities without bone marrow edema, and intravertebral fluid collection or fluid signal were negatively correlated with VCF malignancy. CONCLUSION It is possible to estimate the malignancy risk of VCF by using a small number of MRI features and patient age. The diagnostic performance of models selected by logistic regression, support vector machine, neural network, and classification tree was similar.

Neuroimaging in Closed Head Injury.

Closed head injury can be associated with significant neurologic dysfunction. Neuroimaging in this condition consists of conventional techniques such as computed tomography (CT) and magnetic resonance imaging (MR), and functional imaging studies such as single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Whereas CT and MR are sufficient to show the acute concomitants of head trauma such as extra-axial hematomas, contusions, and shear injury, functional brain imaging has been shown to play an important role in management of victims of closed head injury, particularly in the chronic stages. Detection of changes in regional cerebral blood flow associated with brain injury have been found to correlate better with neurological status and prognosis than abnormalities seen by CT or MRI.

Diffuse cauda equina enhancement in a middle aged male with Susac syndrome and symptomatic cauda equina syndrome

Susac syndrome is a rare neurologic disorder first described by Susac et al. in 1979. Clinically, Susac syndrome consists of a triad including encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. All three components of the triad usually do not present at the same time, thus delaying time to diagnosis. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum. Intracranial leptomeningeal enhancement may be seen, however, cauda equina involvement has not been described to our knowledge. We present a case of Susac syndrome in a middle-aged male with symptoms of cauda equina syndrome, and spinal MRI showing diffuse enhancement of the nerve roots of the cauda equina.

Cauda equina involvement in Susac's syndrome.

Susacs syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susacs syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susacs syndrome. This case is important not only because it expands the clinical features of Susacs syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.