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1. Albers GW, Thijs VN, Wechsler L, et al. Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol. 2006;60(5):508-517. Observational-Dx 74 consecutive patients Prospective multicenter study to determine whether prespecified baseline MRI profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (OR, 5.4; P=0.039) and an even more favorable response in patients with the Target Mismatch profile (OR, 8.7; P=0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the malignant profile. For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed. 3
2. Davis SM, Donnan GA, Parsons MW, et al. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial. Lancet Neurol. 2008;7(4):299-309. Experimental-Dx 101 patients Prospectively and randomly assign patients to receive alteplase or placebo 36 hours after onset of ischaemic stroke based on mismatch in perfusion-weighted MRI and DWI MRI. Alteplase was nonsignificantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 hours after treatment are warranted. 1
3. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-1587. Experimental-Dx Part 1 – 291 patients; Part 2 – 333 patients Randomized, double-blind trial of IV rtPA for ischemic stroke after recent pilot studies suggested that tPA was beneficial when treatment was begun within 3 hours of the onset of stroke. Part 1-No significant difference between the group given tPA and that given placebo in the percentages of patients with neurologic improvement at 24 hours, although a benefit was observed for the tPA group at three months for all four outcome measures. Part 2 - the long-term clinical benefit of tPA predicted by the results of part 1 was confirmed (global OR for a favorable outcome, 1.7; 95% CI, 1.2-2.6). IV thrombolysis improves patient outcome. 1
4. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999;282(21):2003-2011. Experimental-Dx 180 patients randomized to receive 9 mg of intra-arterial recombinant prourokinase plus heparin (n = 121) or heparin only (n = 59) Randomized controlled multicenter trial to determine the clinical efficacy and safety of intra-arterial recombinant prourokinase in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery occlusion. For the primary analysis, 40% of recombinant prourokinase patients and 25% of control patients had a modified Rankin score of 2 or less (P=.04). Mortality was 25% for the recombinant prourokinase group and 27% for the control group. The recanalization rate was 66% for the recombinant prourokinase group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of recombinant prourokinase patients and 2% of control patients (P=.06). Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with intra-arterial recombinant prourokinase within 6 hours of the onset of acute ischemic stroke caused by middle cerebral artery occlusion significantly improved clinical outcome at 90 days. 1
5. Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score. Stroke. 2009;40(9):2994-3000. Observational-Dx 367 CT angiograms; 3 reviewers Retrospective review of CT angiograms to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. Spot signs identified in 71/367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined, the presence of =3 spot signs, a maximum axial dimension =5 mm, and maximum attenuation =180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation. The spot sign score predicts significant hematoma expansion in primary ICH. If validated in other data sets, it could be used to select patients for early hemostatic therapy. 3
6. Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke. 2010;41(1):54-60. Observational-Dx 573 consecutive patients; 3 reviewers Retrospective study to assess whether the spot sign score can be used to identify primary ICH patients who are at highest risk of in-hospital mortality and poor outcome among survivors at 3-month follow-up. Spot signs identified in 133/573 CT angiograms (23.2%), 11 of which were delayed spot signs (8.3%). The presence of any spot sign increased the risk of in-hospital mortality (55.6%, OR 4.0, 95% CI, 2.6 to 5.9, P<0.0001) and poor outcome among survivors at 3-month follow-up (50.8%, OR 2.5, 95% CI, 1.4 to 4.3, P<0.0014). Spot sign score successfully predicted an escalating risk of both outcome measures. In multivariate analysis, the spot sign score was an independent predictor of in-hospital mortality (OR 1.5, 95% CI, 1.2 to 1.9, P<0.0002) and poor outcome among survivors at 3-month follow-up (OR 1.6, 95% CI, 1.1 to 2.1, P<0.0065). The spot sign score is an independent predictor of in-hospital mortality and poor outcome among survivors in primary ICH. 3
7. Fiebach JB, Schellinger PD, Gass A, et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral hemorrhage: a multicenter study on the validity of stroke imaging. Stroke. 2004;35(2):502-506. Observational-Dx 124 patients Prospective multicenter trial to determine whether stroke MRI is accurate in hyperacute ICH. Images from 62 ICH patients and 62 nonhemorrhagic stroke patients, all imaged within the first 6 hours after symptom onset (mean, 3 hours 18 minutes), and were analyzed. For diagnosis of hemorrhage, CT served as the “gold standard.” Hyperacute ICH causes a characteristic imaging pattern on stroke MRI and is detectable with excellent accuracy. Even raters with limited film-reading experience reached good accuracy. Stroke MRI alone can rule out ICH and demonstrate the underlying pathology in hyperacute stroke. 2
8. Kidwell CS, Chalela JA, Saver JL, et al. Comparison of MRI and CT for detection of acute intracerebral hemorrhage. JAMA. 2004;292(15):1823-1830. Observational-Dx 200 patients; 4 blinded readers Prospective multicenter study to compare the accuracy of MRI and CT for detection of acute ICH in patients presenting with acute focal stroke symptoms. Diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29. Acute hemorrhage, MRI and CT were equivalent (96%). In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic ICH. 2
9. Medina LS. Three-dimensional CT maximum intensity projections of the calvaria: a new approach for diagnosis of craniosynostosis and fractures. AJNR. 2000;21(10):1951-1954. Review/Other-Dx 10 patients To describe the use of calvarial 3D CT maximum intensity projections in children with suspected craniosynostosis and skull fractures. 3D CT maximum intensity projections can depict suture patency, extent of synostosis (ie, complete vs incomplete bone bridging), fracture extent and conspicuity, and 3D calvarial deformity as a single set of projections in children with suspected craniosynostosis or skull fracture. 3D CT maximum intensity projections may provide, in only eight views, all the required information to make the diagnosis of craniosynostosis and calvarial fracture extent in contrast to the combined information of 3D CT shaded surface display and 2D axial CT images (total of 58 views) and complementary skull radiographs. 3D maximum intensity projections can be added to calvarial helical (spiral) CT imaging, adding only 5 minutes of postprocessing time. 4
10. Reuben AD, Watt-Smith SR, Dobson D, Golding SJ. A comparative study of evaluation of radiographs, CT and 3D reformatted CT in facial trauma: what is the role of 3D? Br J Radiol. 2005;78(927):198-201. Observational-Dx 23 patients (7 radiographs, 9 CT studies and 7 cases of 3D reconstruction), 17 trainee maxillofacial surgeons To examine the objective performance of trainee maxillofacial surgeons in their diagnostic evaluation of facial fractures on different imaging techniques, including 3D reformatted CT, and to determine the degree of correlation with their subjective views of the clinical value of each. Overall, surgeons showed more accurate diagnostic reading of radiographs and 3D reformatted images. This was in contrast to their subjective assessment of the clinical value of each modality, which showed a strong preference for 3D over all other techniques and for CT over radiographs. However the perceived benefit of axial CT images over radiographs was not reproduced on objective testing in this group; surgeons appear to perform less well in interpreting CT images than their subjective response to the modality would suggest. 3
11. Brown G, Warren M, Williams JE, Adam EJ, Coles JA. Cranial computed tomography of elderly patients: an evaluation of its use in acute neurological presentations. Age Ageing. 1993;22(4):240-243. Review/Other-Dx 100 consecutive cranial CT scans of patients Retrospective study to assess the use of cranial CT in elderly patients with acute neurological deficits and its influence on patient management. 20 of the patients had treatable lesions (in 6 out of 14 patients with signs atypical of stroke and 7 out of 19 patients with acute confusion). These two groups contained 68% of all treatable lesions found. 44 scans yielded no new diagnostic information; these included all scans for transient ischemic attacks and for progression of stroke. The remaining scans yielded information regarding pathology but did not alter patient management. CT is a valuable first line investigation in elderly patients presenting with signs atypical of stroke and unexplained confusion. 4
12. Yuh WT, Tali ET, Nguyen HD, Simonson TM, Mayr NA, Fisher DJ. The effect of contrast dose, imaging time, and lesion size in the MR detection of intracerebral metastasis. AJNR. 1995;16(2):373-380. Observational-Dx 45 patients; 2 groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg) To evaluate the effect of MR contrast dose vs delayed imaging time on the detection of metastatic brain lesions based on lesion size. Randomized, independent, retrospective blinded review by 4 radiologists was done after the precontrast and postcontrast MR examinations of all patients. There was no difference in the detection rate for lesions >10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions <10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate. In the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose. 2
13. Rowley HA, Scialfa G, Gao PY, et al. Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide. AJNR Am J Neuroradiol. 2008;29(9):1684-1691. Observational-Dx 138 total patients; 113 patients underwent both examinations To intraindividually compare 0.1-mmol/kg doses of gadobenate dimeglumine with gadodiamide for qualitative and quantitative lesion enhancement. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P<.0001, all readers). Highly significant (P<.0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for contrast-to-noise ratio (increases of 23.3%–34.7% and 42.4%–48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (kappa = 0.47–0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses. Significantly greater diagnostic information and lesion enhancement are achieved on brain MRI with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose. 1
14. Yousry TA, Schmid UD, Jassoy AG, et al. Topography of the cortical motor hand area: prospective study with functional MR imaging and direct motor mapping at surgery. Radiology. 1995;195(1):23-29. Observational-Dx 4 healthy volunteers and 6 patients with tumors Prospective study to localize motor cortex with functional MRI and electrical stimulation and surgery for detection of changes due to central lesions. At functional MRI, circumscribed changes in signal intensity that correlated in time with the task were seen in the central region of the contralateral brain. In the healthy volunteers, the area of change was spotlike and projected into the posterior bank of the precentral gyrus. In 4/6 patients, this area was diffuse and projected into the precentral gyrus. The locations of the cortical hand area as determined with intrasurgical mapping and functional MRI were identical. Identification of the cortical area responsible for motor hand function was similar with functional MRI and with direct stimulation at surgery. A space-occupying lesion can change the cortical representation of motor hand function. 2
15. Melhem ER, Mori S, Mukundan G, Kraut MA, Pomper MG, van Zijl PC. Diffusion tensor MR imaging of the brain and white matter tractography. AJR. 2002;178(1):3-16. Review/Other-Dx N/A To review the tensor theory used to characterize molecular diffusion in white matter and how the tensor elements are measured experimentally using diffusion-sensitive MRI. Also review techniques for acquiring relatively high-resolution diffusion-sensitive MRI and computer-based algorithms that allow the generation of white matter fiber tract maps from the tensor data. Requisites for sound application of diffusion tensor MRI and white matter tractography in central nervous system disease are the establishment of normative anisotropy values and white matter tract maps, and the validation of the normative white matter tract maps on the basis of detailed anatomic knowledge of these tracts. 4
16. Nimsky C, Ganslandt O, Hastreiter P, et al. Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery. Neurosurgery. 2005;56(1):130-137; discussion 138. Observational-Dx 37 patients To investigate the intraoperative displacement of major white matter tracts during glioma resection by comparing preoperative and intraoperative diffusion tensor imaging-based fiber tracking. Maximum white matter tract shifting ranged from –8 to +15 mm (+2.7 +/- 6.0 mm; mean +/- standard deviation); in 29.7%, an inward and in 62.2%, an outward shifting was detected. Comparing preoperative and intraoperative fiber tracking visualizes a marked shifting and deformation of major white matter tracts because of tumor removal. This shifting emphasizes the need for an intraoperative update of navigation systems during resection of deep-seated tumor portions near eloquent brain areas. Fiber tracking is a method not only for preoperative neurosurgical visualization but also for further intraoperative planning. 3
17. Buchpiguel CA, Alavi JB, Alavi A, Kenyon LC. PET versus SPECT in distinguishing radiation necrosis from tumor recurrence in the brain. J Nucl Med. 1995;36(1):159-164. Review/Other-Dx 2 patients Report 201T1-SPECT and FDG-PET findings in patients with suspected tumor recurrence. SPECT and PET imaging were complimentary for distinguishing between tumor recurrence and radiation necrosis. For Patient 1, FDG-PET showed more limitations compared to 201TI SPECT. FDG-PET results on the other hand, were consistent with the final diagnosis and the SPECT image was false positive for tumor recurrence in Patient 2. 4
18. Rock JP, Hearshen D, Scarpace L, et al. Correlations between magnetic resonance spectroscopy and image-guided histopathology, with special attention to radiation necrosis. Neurosurgery. 2002;51(4):912-919; discussion 919-920. Observational-Dx 27 patients To determine the value of 1H MRSI in guiding the clinical management of untreated patients. Metabolite ratios derived on the basis of 1H MRSI spectral patterns do allow reliable differential diagnostic statements to be made when the tissues are composed of either pure tumor or pure necrosis, but the spectral patterns are less definitive when tissues composed of varying degrees of mixed tumor and necrosis are examined. 3
19. Kim YJ, Chang KH, Song IC, et al. Brain abscess and necrotic or cystic brain tumor: discrimination with signal intensity on diffusion-weighted MR imaging. AJR. 1998;171(6):1487-1490. Observational-Dx 9 total patients; 5 consecutive patients with proven brain abscesses and 4 patients with proven cystic or necrotic brain tumors Prospective study to determine the differences in signal intensity between brain abscesses and necrotic or cystic tumors on DWI MRI. Brain abscesses demonstrated marked hyperintense signal on DWI. Necrotic or cystic brain tumors revealed hypointense signal in all 4 patients. 3
20. Leuthardt EC, Wippold FJ, 2nd, Oswood MC, Rich KM. Diffusion-weighted MR imaging in the preoperative assessment of brain abscesses. Surg Neurol. 2002;58(6):395-402; discussion 402. Review/Other-Dx 5 patients Retrospective study to examine the ability of DWI to strongly suggest brain abscess. Restricted water diffusion, as indicated by hyperintensity on DWI and low apparent diffusion coefficient, in ring-enhancing lesions assists in differentiating brain abscess from necrotic tumor. 4
21. Younis RT, Anand VK, Davidson B. The role of computed tomography and magnetic resonance imaging in patients with sinusitis with complications. Laryngoscope. 2002;112(2):224-229. Observational-Dx 82 adult and pediatric patients Retrospective review comparing the role of CT with MRI in patients with sinusitis with complications. For patients with orbital complications, the diagnostic accuracy was 82% for clinical assessment compared with 91% for CT. For patients with intracranial complications, meningitis was common diagnosis and MRI was more accurate (97%) in determining diagnoses than CT (87%) or clinical findings (82%). 3
22. Lerner DN, Choi SS, Zalzal GH, Johnson DL. Intracranial complications of sinusitis in childhood. Ann Otol Rhinol Laryngol. 1995;104(4 Pt 1):288-293. Review/Other-Dx 443 children; 14 presented with intracranial extension of the infection and abscess formation To retrospectively review intracranial complications of sinusitis in childhood. Risk of developing an intracranial abscess secondary to sinusitis was 3%. Management of patients included surgical drainage of the infected sinuses and intracranial surgical exploration. Cranialization and exenteration of the frontal sinus proved to be effective single-stage procedures. While not indicated in all patients, these procedures eliminated the sinus as a source of continued or potential infection and obviated the need for a second obliterative procedure. Combined antimicrobial therapy and surgical drainage should be the management protocol. 4
23. Singh B, Van Dellen J, Ramjettan S, Maharaj TJ. Sinogenic intracranial complications. J Laryngol Otol. 1995;109(10):945-950. Review/Other-Dx 219 total patients To analyze clinical and therapeutic aspects of intracranial complications of sinusitis. 35 deaths (16%) occurred. The highest mortality rate was recorded in patients with meningitis (45%) followed by brain abscess (19%) and subdural empyema (11%). Despite CT and early antibiotics, mortality remains significant. 4
24. Remy C, Grand S, Lai ES, et al. 1H MRS of human brain abscesses in vivo and in vitro. Magn Reson Med. 1995;34(4):508-514. Review/Other-Dx 5 patients To identify specific resonance lines in the contents of abscesses in vivo and in vitro. In addition to resonance lines from compounds (lactate, alanine and lipids) often found in the spectra from intracranial tumors, resonance lines were detected from a number of markers of infectious involvement (acetate, succinate, and various amino acids). Results suggest that 1H MRSI in vivo might contribute in establishing noninvasively a differential diagnosis between brain abscess and tumor. 4
25. Chang L, Miller BL, McBride D, et al. Brain lesions in patients with AIDS: H-1 MR spectroscopy. Radiology. 1995;197(2):525-531. Observational-Dx 26 men with 35 AIDS-related brain lesions To evaluate the role of proton 1H MRS in the differential diagnosis of focal brain lesions in AIDS patients. 1H MRS findings showed significantly different biochemical profiles for each diagnostic group (P = .0001) with regard to N-acetyl compounds, total creatine pool, choline-containing compounds, myoinositol, and lactate. 1H MRS alone helped correctly diagnose 94% (84% with jackknifed classification) of the brain lesions, without overlap between toxoplasmosis and lymphoma. 1H MRS is a sensitive and potentially specific noninvasive adjunctive method for differential diagnosis of focal brain lesions in AIDS. 3
26. Ernst TM, Chang L, Witt MD, et al. Cerebral toxoplasmosis and lymphoma in AIDS: perfusion MR imaging experience in 13 patients. Radiology. 1998;208(3):663-669. Observational-Dx 13 patients Prospective study to evaluate perfusion MRI characteristics of cerebral toxoplasmosis and lymphoma in patients with AIDS. The regional cerebral blood volume was decreased (44% +/- 24 [standard deviation] of regional cerebral blood volume in the contralateral regions) throughout the toxoplasmosis lesions and in the surrounding edema of both lesion types, whereas all active lymphomas displayed areas of increased regional cerebral blood volume (258% +/- 99). These differences were significant (P<.005). Reduced regional cerebral blood volume in toxoplasmosis lesions is probably due to a lack of vasculature within the abscess; increased regional cerebral blood volume in lymphomas is probably due to hypervascularity in foci of active tumor growth; and decreased regional cerebral blood volume in the edema is probably due to vasoconstriction associated with increased interstitial pressure. Perfusion MRI is a rapid, noninvasive tool that may allow differentiation between cerebral lymphoma and toxoplasmosis in patients with AIDS. 3
27. Narayanan S, Fu L, Pioro E, et al. Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions. Ann Neurol. 1997;41(3):385-391. Review/Other-Dx 28 patients MRI and MRS were performed on patients with multiple sclerosis and lesion distribution images generated for each patient to compare images from different patients on a voxel-by-voxel basis. Spatial distribution of lesions in the transformed MRI did not differ significantly between the relapsing and the progressive disease groups. Neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2-weighted lesion probability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. Diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis. 4
28. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338(5):278-285. Review/Other-Dx 15 total patients; 11 patients with multiple sclerosis and 4 subjects without brain disease To conduct pathological studies of brain tissues to define the changes in axons in patients with multiple sclerosis. Transected axons per cubic millimeter of tissue averaged 11,236 in active lesions, 3,138 at the hypocellular edges of chronic active lesions, 875 in the hypocellular centers of chronic active lesions, and less than 1 in normal-appearing white matter from the control brains. Transected axons are common in the lesions of multiple sclerosis, and axonal transection may be the pathologic correlate of the irreversible neurologic impairment in this disease. 4
29. Rudick RA, Cohen JA, Weinstock-Guttman B, Kinkel RP, Ransohoff RM. Management of multiple sclerosis. N Engl J Med. 1997;337(22):1604-1611. Review/Other-Dx N/A Review article on management of multiple sclerosis. Article gives an overview of state of the art and future directions for research. 4
30. Arnason BG, Toscas A, Dayal A, Qu Z, Noronha A. Role of interferons in demyelinating diseases. J Neural Transm Suppl. 1997;49:117-123. Review/Other-Dx N/A To review role of interferons in demyelinating diseases. Interferon beta-1b reduces the frequency of major multiple sclerosis attacks by 50%. Serial MRI over the course of the clinical trial that led to approval of the agent revealed a significant lessening both in disease activity and in accumulating burden of disease in interferon beta-1b-treated patients compared to placebo-treated controls. 4
31. Arnason BG. Interferon beta in multiple sclerosis. Clin Immunol Immunopathol. 1996;81(1):1-11. Review/Other-Dx N/A To determine the effects of interferon beta-1b for multiple sclerosis. The immunomodulatory actions of interferon beta-1b acting in concert would be expected to attenuate delayed-type hypersensitivity responses and exert a beneficial effect in multiple sclerosis, as is found. 4
32. Lublin FD, Whitaker JN, Eidelman BH, Miller AE, Arnason BG, Burks JS. Management of patients receiving interferon beta-1b for multiple sclerosis: report of a consensus conference. Neurology. 1996;46(1):12-18. Review/Other-Dx N/A Report of a consensus conference on management of patients receiving interferon beta-1b for multiple sclerosis. Interferon beta-1b is effective in reducing the progression of total disease burden as seen on MRI in patients with multiple sclerosis. Its use is relatively straightforward and generally does not require alteration in the symptomatic treatment of multiple sclerosis. Patient education and support remain the mainstays of maintaining compliance through the early phases of therapy. 4
33. Ertl-Wagner BB, Reith W, Sartor K. Low field-low cost: can low-field magnetic resonance systems replace high-field magnetic resonance systems in the diagnostic assessment of multiple sclerosis patients? Eur Radiol. 2001;11(8):1490-1494. Observational-Dx 20 patients; 2 independent observers Prospective assessment of differences in imaging quality between low- and high-field MRI in multiple sclerosis patients. Lower number of white matter lesions could be identified in low-field MRI both on T1- and on T2-weighted images (T2: high field 700, low field 481; T1: high field 253, low field 177). 114 enhancing lesions were discerned in the high-field MRI as opposed to 45 enhancing lesions in low-field MRI. Blood-brain barrier disruption was identified in 11/20 patients in the high-field MRI, but in 4/20 patients in low-field MRI. 2
34. Goodkin DE. MS clinical trial design for the future. Mult Scler. 1996;1(6):393-399. Review/Other-Dx N/A To identify optimal designs for evaluating alternatives for managing multiple sclerosis. It appears that T1 weighted gadolinium + activity and change in T2 weighted lesion burden will be most useful as outcomes in patients who recently have experienced frequent relapses. It is anticipated that improved composite outcomes and more powerful statistical methods will facilitate improved predictive validity for MRI techniques. 4
35. Tubridy N, Ader HJ, Barkhof F, Thompson AJ, Miller DH. Exploratory treatment trials in multiple sclerosis using MRI: sample size calculations for relapsing-remitting and secondary progressive subgroups using placebo controlled parallel groups. J Neurol Neurosurg Psychiatry. 1998;64(1):50-55. Observational-Dx 59 total patients; 31 relapsing-remitting and 28 secondary progressive Serial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting and secondary progressive multiple sclerosis. For pilot trials, sample size calculations for the relapsing-remitting subgroup are based on the data from small numbers of patients and separate calculations for the secondary progressive subgroup have not been performed. This study considers these issues. The sample sizes required for relapsing-remitting patients were comparable with previous smaller studies. Larger sample sizes were needed for the secondary progressive group, but the extra run in scan resulted in a reduction in both groups. 3
36. Paty DW, Li DK. Interferon beta-lb is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. 1993 [classical article]. Neurology. 2001;57(12 Suppl 5):S10-15. Experimental-Dx 327 patients had MRI analysis Yearly MRI analyses were performed on patients in a multicenter, randomized, double blind, and placebo-controlled trial of interferon beta-1b. Baseline MRI characteristics were the same in all treatment groups. 52 patients had frequent MRIs (one every 6 weeks) for analysis of disease activity. There was a significant reduction in disease activity as measured by numbers of active scans (median 80% reduction, P=0.0082) and appearance of new lesions. In addition, there was an equally significant reduction in MRI detected burden of disease in the treatment as compared with placebo groups (mean group difference of 23%, P=0.001). 1
37. Simon JH, Jacobs LD, Campion M, et al. Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol. 1998;43(1):79-87. Experimental-Dx 301 patients To provide further detail of the MR-based data, including additional analyses based on T2 lesions, the interrelationships between MR measures and correlations between MR and clinical outcome measures. The data was based on The Multiple Sclerosis Collaborative Research Group trial, which was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a in relapsing forms of multiple sclerosis. Treatment with interferon beta-1a resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and interferon beta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and interferon beta-1a patients were 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Correlations between MRI and clinical measures at baseline and throughout the study were in general poor. 1
38. Simon JH. Contrast-enhanced MR imaging in the evaluation of treatment response and prediction of outcome in multiple sclerosis. J Magn Reson Imaging. 1997;7(1):29-37. Review/Other-Dx N/A Review emphasizes: (a) recent developments in the use of contrast-enhanced MRI as a measure of disease in patient groups and individuals and (b) its emerging role in evaluating new therapies. MRI is becoming important in the evaluation of multiple sclerosis based on its sensitivity to acute, often subclinical events in the brain and because it provides a basis for measuring the accumulation of disease over time. Contrast-enhanced MRI in particular evaluates disease at the fundamental level of events affecting the blood-brain barrier. 4
39. Thorpe JW, Kidd D, Moseley IF, et al. Serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Neurology. 1996;46(2):373-378. Observational-Dx 10 patients To examine serial gadolinium-enhanced MRI of the brain and spinal cord in early relapsing-remitting multiple sclerosis. Monthly gadolinium-enhanced brain and spinal cord MRI scans were performed over 1 year in patients with relapsing-remitting multiple sclerosis. 6 of the patients had a total of 11 clinical relapses, 8 of which involved the spinal cord. Only one active brain lesion was symptomatic compared with 6 spinal cord lesions. Overall, one-third of new spinal cord lesions were symptomatic, and three-quarters of clinical spinal cord relapses were associated with a new MRI lesion in a location appropriate to the symptoms. There was a strong association between the spinal cord and brain MRI activity. Study concludes that, in relapsing-remitting multiple sclerosis, imaging of the brain alone will detect 90% of active lesions; spinal cord MRI using current technology will therefore provide only modest gains in treatment trials in which lesion activity is the primary outcome measure. 3
40. Silver NC, Good CD, Barker GJ, et al. Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging. Brain. 1997;120 ( Pt 7):1149-1161. Observational-Dx 50 patients A prospective study of three potential methods for further improving sensitivity of contrast enhanced MRI; the use of 0.3 mmol/kg (triple dose) Gd-DTPA, magnetization transfer contrast imaging and the introduction of a delay between contrast-medium injection and imaging. The use of gadolinium contrast-media in MRI studies increases both the reliability and sensitivity of detecting active lesions in multiple sclerosis. Study concludes that for relapsing-remitting and secondary progressive multiple sclerosis, the combination of triple-dose Gd-DTPA and delayed magnetization transfer imaging more than doubles the sensitivity to contrast-enhancing lesions. 2
41. Filippi M, Campi A, Martinelli V, Colombo B, Scotti G, Comi G. Brain and spinal cord MR in benign multiple sclerosis: a follow-up study. J Neurol Sci. 1996;143(1-2):143-149. Observational-Dx 19 patients Prospective study in which a clinical and MR longitudinal study were performed in patients with benign multiple sclerosis to achieve a better definition of the nature of disability in multiple sclerosis. Study suggests that patients with benign multiple sclerosis have two different patterns of disease evolution; one characterized by very low clinical and MRI activities, the other in which the lack of disabling symptomatology might be related to factors like site, size and nature of lesions. It also indicates that in patients with benign multiple sclerosis and high MR lesion loads the risk of developing a secondary progressive form of the disease is still present even after many years after onset. 3
42. van Waesberghe JH, Castelijns JA, Roser W, et al. Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium in the MR detection of multiple sclerosis lesions. AJNR. 1997;18(7):1279-1285. Observational-Dx 21 patients (16 with relapsing-remitting disease and 5 with secondary-progressive disease) To compare the efficacy of single-dose gadolinium with magnetization transfer contrast with that of triple-dose gadolinium in detecting enhancing multiple sclerosis lesions. All images were evaluated in a blinded fashion and scored in random order by two readers. 81% more enhancing lesions and 49% more active MR examinations were detected when a triple dose of gadolinium was used as compared with a single dose. With triple-dose gadolinium, contrast ratios and areas of enhancement increased by 10% and 33%, respectively. Delayed imaging increased the size of the lesion by 11% on single-dose magnetization transfer contrast images and by 18% on triple-dose images. Triple-dose gadolinium is more effective (higher sensitivity and interobserver agreement) than single-dose gadolinium in combination with magnetization transfer contrast in detecting enhancing multiple sclerosis lesions. 1
43. Narayana PA, Doyle TJ, Lai D, Wolinsky JS. Serial proton magnetic resonance spectroscopic imaging, contrast-enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis. Ann Neurol. 1998;43(1):56-71. Observational-Dx 25 patients Retrospective study in which MRSI, contrast-enhanced MRI, and lesion volumetric studies were performed on multiple sclerosis patients. Metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Transient changes in N-acetylaspartate levels were sometimes found in acute plaques and indicate that a reduced N-acetylaspartate level does not necessarily imply axonal loss. An inverse correlation between the average N-acetylaspartate within the spectroscopic volume and the total lesion volume in the whole brain was observed, suggesting that N-acetylaspartate can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of enhancement and MRI-defined lesions were observed in 4 patients, suggesting that demyelination can occur independent of perivenous inflammatory changes. 2