Rule Out (R/O) Vasculitis

When imaging patients for vasculitis, the goals are: (1) to determine if there is evidence of acute or subacute cerebral injury and (2) to assess the contour of the major intracranial arteries. An additional but still experimental goal is (3) to determine if there are areas of altered perfusion that suggest active small vessel disease. Standard MR images and diffusion‐weighted imaging are used to detect and determine the age of parenchymal lesions. The 3‐D TOF MRA helps evaluate the large and medium vessels. Perfusion‐weighted imaging may detect regions of altered relative blood flow and blood volume. This unit contains a basic protocol for the evaluation of stable patients as well as an alternative protocol for unstable patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145238/1/cpmia0106.pd

Rule Out (R/O) Intracranial Aneurysm

When imaging patients for intracranial aneurysm, the goals are: (1) to assess the contour of the intracranial arteries, particularly in he regions of the ACOM (anterior communicating artery), PCOM (posterior communicating artery), ICA (internal carotid artery) bifurcation, MCA (middle cerebral artery) trifurcation, basilar tip, and PICA (posterior inferior cerebellar artery); (2) to assess the anatomy of the Circle of Willis and direction of flow, and; (3) to determine if there is evidence of a recent subarachnoid bleed. This unit describes a that can be used for standard imaging of aneurysm in stable patients. An is described for situations when there is concern for vasospasm and infarction.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145398/1/cpmia0102.pd

Cerebral Infarct/Intracranial Cerebrovascular Disease

Imaging goals for intracranial cerebral vascular disease are (1) to assess the degree of parenchymal injury and identify intraparenchymal hemorrhage; (2) to determine if there are areas of altered perfusion that may be at risk for future injury; and (3) to assess the intracranial arteries (patency as well as direction of flow). This unit describes a that can be used to evaluate stable patients with acute, subacute, or chronic cerebrovascular symptoms. An is also given for cases of hyperacute strokes or cerebrovascular symptoms in an unstable patient.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145276/1/cpmia0101.pd

Evaluating effects of normobaric oxygen therapy in acute stroke with MRI-based predictive models

<p>Abstract</p> <p>Background</p> <p>Voxel-based algorithms using acute multiparametric-MRI data have been shown to accurately predict tissue outcome after stroke. We explored the potential of MRI-based predictive algorithms to objectively assess the effects of normobaric oxygen therapy (NBO), an investigational stroke treatment, using data from a pilot study of NBO in acute stroke.</p> <p>Methods</p> <p>The pilot study of NBO enrolled 11 patients randomized to NBO administered for 8 hours, and 8 Control patients who received room-air. Serial MRIs were obtained at admission, during gas therapy, post-therapy, and pre-discharge. Diffusion/perfusion MRI data acquired at admission (pre-therapy) was used in generalized linear models to predict the risk of lesion growth at subsequent time points for both treatment scenarios: NBO or Control.</p> <p>Results</p> <p>Lesion volume sizes 'during NBO therapy' predicted by Control-models were significantly larger (P = 0.007) than those predicted by NBO models, suggesting that ischemic lesion growth is attenuated during NBO treatment. No significant difference was found between the predicted lesion volumes at later time-points. NBO-treated patients, despite showing larger lesion volumes on Control-models than NBO-models, tended to have reduced lesion growth.</p> <p>Conclusions</p> <p>This study shows that NBO has therapeutic potential in acute ischemic stroke, and demonstrates the feasibility of using MRI-based algorithms to evaluate novel treatments in early-phase clinical trials.</p

Model Ziegler-Natta α-Olefin Polymerization Catalysts Derived from [{(η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}(PMe_3)Sc(µ_2-H)]_2 and [{(η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}Sc(µ_2-CH_2CH_2CH_3)]_2. Synthesis, Structures, and Kinetic and Equilibrium Investigations of the Catalytically Active Species in Solution

The scandium hydride complex [(Cp*SiNR)(PMe_3)Sc(µ-H)]_2 (1), ((Cp*SiNR) = ((η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}) is prepared by hydrogenation of (Cp*SiNR)ScCH(SiMe_3)_2 in the presence of trimethylphosphine. The hydride complex is a catalyst precursor for the polymerization of α-olefins, yielding atactic products of low molecular weight (M, = 3000-7000). GC/MS analysis of volatile, oligomeric products revealed that all scandium centers are active during the polymerization. Selectivity for head-to-tail insertion is high (>99%) and for the tetramer, pentamer, and hexamer formed during propene polymerization, the maximum theoretical numbers of head-to-tail stereoisomers are observed by capillary GC. The stoichiometric reaction between 1 and 2 equiv of ethylene produces the unusual ethylene-bridged dimer [(Cp*SiNR)(PMe_3)Sc]_2(µ,η^2,η^2-C_2H_4) (2) and an equivalent of ethane, whereas the same reaction with propene affords the phosphine-free, alkyl-bridged scandium dimer [(Cp*S~NR)Sc]_2(µ-CH_2CH_2CH_3)_2 (3). The absence of coordinating phosphine allows the latter complex to function as a more active olefin polymerization catalyst precursor. 1 reacts with styrene to form a unique double-insertion product arising from sequential 1,2- and 2,1-styrene insertion. The structure of the catalytic intermediate in solution was determined by low-temperature ^(13)C-NMR studies of the model complexes (Cp*SiNR)(P(^(13)CH_3)_3]ScCH_2CH(CH_3)CHCH_2CH_2CH_3 and (Cp*SiNR)(PMe_3)Sc^(13)CH_2CHCH(^(13)CH_3)_2. One phosphine-bound species is observed in equilibrium with only one phosphine-free species. The symmetry properties of the latter indicate that it is a monomeric, hence 12-electron, scandium alkyl complex. Semiquantitative treatment of equilibrium concentration data supports this conclusion

Model Ziegler-Natta α-Olefin Polymerization Catalysts Derived from [{(η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}(PMe_3)Sc(µ_2-H)]_2 and [{(η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}Sc(µ_2-CH_2CH_2CH_3)]_2. Synthesis, Structures, and Kinetic and Equilibrium Investigations of the Catalytically Active Species in Solution

The scandium hydride complex [(Cp*SiNR)(PMe_3)Sc(µ-H)]_2 (1), ((Cp*SiNR) = ((η^5-C_5Me_4)SiMe_2(η^1-NCMe_3)}) is prepared by hydrogenation of (Cp*SiNR)ScCH(SiMe_3)_2 in the presence of trimethylphosphine. The hydride complex is a catalyst precursor for the polymerization of α-olefins, yielding atactic products of low molecular weight (M, = 3000-7000). GC/MS analysis of volatile, oligomeric products revealed that all scandium centers are active during the polymerization. Selectivity for head-to-tail insertion is high (>99%) and for the tetramer, pentamer, and hexamer formed during propene polymerization, the maximum theoretical numbers of head-to-tail stereoisomers are observed by capillary GC. The stoichiometric reaction between 1 and 2 equiv of ethylene produces the unusual ethylene-bridged dimer [(Cp*SiNR)(PMe_3)Sc]_2(µ,η^2,η^2-C_2H_4) (2) and an equivalent of ethane, whereas the same reaction with propene affords the phosphine-free, alkyl-bridged scandium dimer [(Cp*S~NR)Sc]_2(µ-CH_2CH_2CH_3)_2 (3). The absence of coordinating phosphine allows the latter complex to function as a more active olefin polymerization catalyst precursor. 1 reacts with styrene to form a unique double-insertion product arising from sequential 1,2- and 2,1-styrene insertion. The structure of the catalytic intermediate in solution was determined by low-temperature ^(13)C-NMR studies of the model complexes (Cp*SiNR)(P(^(13)CH_3)_3]ScCH_2CH(CH_3)CHCH_2CH_2CH_3 and (Cp*SiNR)(PMe_3)Sc^(13)CH_2CHCH(^(13)CH_3)_2. One phosphine-bound species is observed in equilibrium with only one phosphine-free species. The symmetry properties of the latter indicate that it is a monomeric, hence 12-electron, scandium alkyl complex. Semiquantitative treatment of equilibrium concentration data supports this conclusion

Optimal Brain MRI Protocol for New Neurological Complaint

Background/Purpose Patients with neurologic complaints are imaged with MRI protocols that may include many pulse sequences. It has not been documented which sequences are essential. We assessed the diagnostic accuracy of a limited number of sequences in patients with new neurologic complaints. Methods: 996 consecutive brain MRI studies from patients with new neurological complaints were divided into 2 groups. In group 1, reviewers used a 3-sequence set that included sagittal T1-weighted, axial T2-weighted fluid-attenuated inversion recovery, and axial diffusion-weighted images. Subsequently, another group of studies were reviewed using axial susceptibility-weighted images in addition to the 3 sequences. The reference standard was the study's official report. Discrepancies between the limited sequence review and the reference standard including Level I findings (that may require immediate change in patient management) were identified. Results: There were 84 major findings in 497 studies in group 1 with 21 not identified in the limited sequence evaluations: 12 enhancing lesions and 3 vascular abnormalities identified on MR angiography. The 3-sequence set did not reveal microhemorrhagic foci in 15 of 19 studies. There were 117 major findings in 499 studies in group 2 with 19 not identified on the 4-sequence set: 17 enhancing lesions and 2 vascular lesions identified on angiography. All 87 Level I findings were identified using limited sequence (56 acute infarcts, 16 hemorrhages, and 15 mass lesions). Conclusion: A 4-pulse sequence brain MRI study is sufficient to evaluate patients with a new neurological complaint except when contrast or angiography is indicated

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Predictors of functional outcome vary by the hemisphere of involvement in major ischemic stroke treated with intra-arterial therapy: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Conflicting data exists regarding the effect of hemispheric lateralization on acute ischemic stroke outcome. Some of this variability may be related to heterogeneous study populations, particularly with respect to the level of arterial occlusion. Furthermore, little is known about the relationship between stroke lateralization and predictors of outcome. The purpose of this study was to characterize the impact of stroke lateralization on both functional outcome and its predictors in a well-defined population of anterior circulation proximal artery occlusions treated with IAT.</p> <p>Methods</p> <p>Thirty-five consecutive left- and 35 consecutive right-sided stroke patients with intracranial ICA and/or MCA occlusions who underwent IAT were retrospectively analyzed. Ischemic change on pre-treatment imaging was quantified. Reperfusion success was graded using the Mori scale. Good outcome at three months was defined as an mRS ≤ 2. Left- and right-sided strokes were compared for outcome and its predictors.</p> <p>Result</p> <p>Of 70 patients with median NIHSS score of 18 (IQR, 14-21), 19 (27.1%) had a good outcome. There were 21 terminal ICA and 49 MCA occlusions. There was no difference in the rate of good outcomes between left- (n = 9) and right-sided (n = 10) strokes (p = 0.99). There were no significant differences in occlusion level, age, ischemic change on initial imaging and degree of reperfusion between left- and right-sided strokes. Left-sided strokes had higher baseline NIHSS scores (p = 0.02) and lower admission SBP (p = 0.009). Independent predictors of outcome for left-sided strokes were NIHSS (p = 0.0002) and reperfusion (p = 0.006), and for right-sided strokes were age (p = 0.002) and reperfusion (p = 0.003). In univariate analysis, pre-treatment ischemic change on NCCT was associated with outcome only for left-sided strokes (p = 0.05).</p> <p>Conclusions</p> <p>In anterior circulation proximal artery occlusions treated with IAT, hemispheric lateralization influences the clinical and imaging predictors of outcome. Most notably, NIHSS predicts outcome only for the left-sided strokes in this population. This finding has important implications for outcome prediction in the acute setting and indicates a need for stroke severity scales more sensitive to right hemispheric deficits.</p