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1.  CXCL13 is a Biomarker of Inflammation in Multiple Sclerosis, Neuromyelitis Optica, and Other Neurological Conditions 
CXCXL13, a B-cell chemokine, has been proposed as a biomarker in a variety of conditions, some of which can mimic multiple sclerosis (MS) and can have very high levels. In this case-control study, CSF CXCL13 was elevated in MS, neuromyelitis optica (NMO), and other inflammatory neurological controls compared to noninflammatory controls. Levels did not differentiate disease groups. For all subjects taken together, CSF CXCL13 correlated with CSF WBC, oligoclonal band numbers, CSF protein, EDSS, and neurofilament levels. In subgroup analyses, CSF CXCL13 correlated with CSF WBC in NMO and IgG index in MS. Additionally, serum CXCL13 was elevated in NMO.
doi:10.1177/1352458512473362
PMCID: PMC3959125  PMID: 23322500
Multiple sclerosis; neuromyelitis optica; CXCL13; neuroinflammation; neurofilament; myelin basic protein; biomarker
2.  Role of Magnetic Resonance Imaging, Cerebrospinal Fluid, and Electroencephalogram in Diagnosis of Sporadic Creutzfeldt-Jakob Disease 
Journal of neurology  2012;260(2):498-506.
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia (RPD) that can be difficult to identify ante-mortem, with definitive diagnosis requiring tissue confirmation. We describe the clinical, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and electroencephalogram (EEG) measures of a small cohort of 30 patients evaluated for RPD. Clinical and diagnostic measures were cross-sectionally obtained from 17 sCJD patients (15 definite, 2 probable), 13 non-prion rapidly progressive dementia patients (npRPD), and 18 unimpaired controls. In a subset of patients (9 sCJD and 9 npRPD) diffusion tensor imaging (DTI) measures [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)] were also obtained for the caudate, corpus callosum, posterior limb of the internal capsule, pulvinar, precuneus, and frontal lobe. Differences among groups were assessed by an analysis of variance. Compared to npRPD individuals, sCJD patients had cerebellar dysfunction, significantly higher CSF tau, “positive” CSF 14-3-3, and hyperintensities on diffusion weighted imaging (DWI) that met previously established imaging criteria for sCJD. EEG changes were similar for the two groups. In addition, sCJD patients had significant decreases in DTI measures (MD, AD, RD but not FA) within the caudate and pulvinar compared to either npRPD patients or unimpaired controls. Our results confirm that CSF abnormalities and MRI (especially DWI) can assist in distinguishing sCJD patients from npRPD patients. Future longitudinal studies using multiple measures (including CSF and MRI) are needed for evaluating pathological changes seen in sCJD patients.
doi:10.1007/s00415-012-6664-6
PMCID: PMC3651672  PMID: 22968768
Creutzfeldt-Jakob disease; diffusion magnetic resonance imaging; cerebrospinal fluid
3.  Association of Neuromyelitis Optica With Severe and Intractable Pain 
Archives of neurology  2012;69(11):1482-1487.
Objective
To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS).
Design
Retrospective, cross-sectional cohort study.
Setting
Academic MS center.
Patients
Complete ascertainment of an academic MS center cohort of NMO and an MS comparison sample cohort.
Main Outcome Measures
Current pain was quantified by a 10-point scale and the McGill Pain Questionnaire. Expanded Disability Status Scale score and number of involved spinal cord levels were collected in addition to testing for cognition, fatigue, depression, and quality of life. Number and types of pain medications were tabulated.
Results
Current pain was more common in subjects with NMO (n=29) vs MS (n=66) (86.2% vs 40.9%; P<.001) and more severe on a 10-point scale (5.38 vs 1.85; P <.001). Pain remained more common after controlling for disability and number of spinal cord segments (P=.03). Prescription pain medication was used more frequently in subjects with NMO compared with subjects with MS (75.9% vs 37.8%; P<.001), often requiring more than 1 medication (65.5% vs 15.2%; P<.001). No subject with NMO taking pain medication (22 of 29) rated their current pain as 0 of 10, whereas almost half of those taking pain medication with MS were currently free of pain (0% vs 48%; P=.006).
Conclusions
Neuromyelitis optica is frequently associated with severe pain that appears insufficiently controlled by pharmacologic interventions. Future studies should evaluate the efficacy of a multidisciplinary and multimodal approach to pain management.
doi:10.1001/archneurol.2012.768
PMCID: PMC3561507  PMID: 22926050
4.  Rituximab-Associated Progressive Multifocal Leukoencephalopathy in Rheumatoid Arthritis 
Archives of neurology  2011;68(9):1156-1164.
Objective
To describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab.
Design
Case study.
Setting
Clinical care for patients with rheumatologic diseases. Most were referred to academic centers for care after diagnosis (Washington University, St Louis, Missouri; Karolinska Insitute, Stockholm, Sweden; and Royal Melbourne Hospital, Melbourne, Australia) while one was cared for in a neurology practice in Dallas, Texas, with consultation by an academic neurovirologist from the University of Colorado in Denver.
Patients
Four patients developing PML in the setting of rituximab therapy for RA.
Intervention
Rituximab therapy.
Main Outcome Measures
Clinical and pathological observations.
Results
Four patients from an estimated population of 129 000 exposed to rituximab therapy for RA are reported in whom PML developed after administration of this drug. All were women older than 50 years, commonly with Sjögren syndrome and a history of treatment for joint disease ranging from 3 to 14 years. One case had no prior biologic and minimal immunosuppressive therapy. Progressive multifocal leukoencephalopathy presented as a progressive neurological disorder, with diagnosis confirmed by detection of JC virus DNA in the cerebrospinal fluid or brain biopsy specimen. Two patients died in less than 1 year from PML diagnosis, while 2 remain alive after treatment withdrawal. Magnetic resonance scans and tissue evaluation confirmed the frequent development of inflammatory PML during the course of the disease.
Conclusion
These cases suggest an increased risk, about 1 case per 25 000 individuals, of PML in patients with RA being treated with rituximab. Inflammatory PML may occur in this setting even while CD20 counts remain low.
doi:10.1001/archneurol.2011.103
PMCID: PMC3428054  PMID: 21555606
5.  The immuno-pathophysiology of multiple sclerosis 
Neurologic clinics  2011;29(2):257-278.
doi:10.1016/j.ncl.2010.12.009
PMCID: PMC3080042  PMID: 21439440
multiple sclerosis; neuro-immunology; demyelination; pathogenesis
6.  PATHOGENICITY OF SEVERE ACUTE RESPIRATORY CORONAVIRUS DELETION MUTANTS IN hACE-2 TRANSGENIC MICE 
Virology  2008;376(2):379-389.
Recombinant severe acute respiratory virus (SARS-CoV) variants lacking the group specific genes 6, 7a, 7b, 8a, 8b and 9b (rSARS-CoV-Δ[6-9b]), the structural gene E (rSARS-CoV-ΔE), and a combination of both sets of genes (rSARS-CoV-Δ[E,6-9b]) have been generated. All these viruses were rescued in monkey (Vero E6) cells and were also infectious for human (Huh-7, Huh7.5.1 and CaCo-2) cell lines and for transgenic (Tg) mice expressing the SARS-CoV receptor human angiotensin converting enzyme-2 (hACE-2), indicating that none of these proteins is essential for the viral cycle. Furthermore, in Vero E6 cells, all the viruses showed the formation of particles with the same morphology as the wt virus, indicating that these proteins do not have a high impact in the final morphology of the virions. Nevertheless, in the absence of E protein, release of virus particles efficacy was reduced. Viruses lacking E protein grew about 100-fold lower than the wt virus in lungs of Tg infected mice but did not grow in the brains of the same animals, in contrast to the rSARS-CoV-Δ[6-9b] virus, which grew almost as well as the wt in both tissues. Viruses lacking E protein were highly attenuated in the highly sensitive hACE-2 Tg mice, in contrast to the minimal rSARS-CoV-Δ[6-9b] and wt viruses. These data indicate that E gene might be a virulence factor influencing replication level, tissue tropism and pathogenicity of SARS-CoV, suggesting that ΔE attenuated viruses are promising vaccine candidates.
doi:10.1016/j.virol.2008.03.005
PMCID: PMC2810402  PMID: 18452964
7.  A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters▿  
Journal of Virology  2008;82(15):7721-7724.
The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.
doi:10.1128/JVI.00304-08
PMCID: PMC2493341  PMID: 18463152

Results 1-7 (7)