Robert Zivadinov

University at Buffalo, State University of New York

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Bianca Weinstock‐Guttman

University at Buffalo, State University of New York

394

Michael G. Dwyer

University at Buffalo, State University of New York

393

Niels Bergsland

University at Buffalo, State University of New York

366

Dejan Jakimovski

University at Buffalo, State University of New York

211

Ralph H. B. Benedict

University at Buffalo, State University of New York

157

Murali Ramanathan

University at Buffalo, State University of New York

148

Jesper Hagemeier

University at Buffalo, State University of New York

145

Deepa P. Ramasamy

University at Buffalo, State University of New York

143

Ellen Carl

Roswell Park Comprehensive Cancer Center

Ferdinand Schweser

University at Buffalo, State University of New York

Cooperative Institutions

University at Buffalo, State University of New York

415

Jacobs Institute

148

Buffalo Psychiatric Center

128

University of Melbourne

Harvard University

The Royal Melbourne Hospital

Johns Hopkins University

University College London

Monash University

University of California, San Francisco

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Subcortical and Cortical Gray Matter Atrophy in a Large Sample of Patients with Clinically Isolated Syndrome and Early Relapsing-Remitting Multiple Sclerosis

American Journal of Neuroradiology (2012)

Niels Bergsland Dana Horáková Michael G. Dwyer Ondřej Doležal Zdeněk Seidl

BACKGROUND AND PURPOSE:

Recent studies have shown that selective regional, but not global, GM atrophy occurs from clinical onset to conversion to clinically definite MS. Our aim was to investigate the difference in the extent of SDGM and cortical atrophy in a large sample of patients with CIS and early RRMS and to explore the relationship between SDGM and cortical atrophy and other MR imaging and clinical outcomes.

MATERIALS AND METHODS:

Two hundred twelve patients with CIS recruited at the first clinical event (mean age, 29.3 years; median EDSS, 1.5; median disease duration, 3 months) and 177 patients with early RRMS (mean age, 30.7 years; median EDSS, 2.0; median disease duration, 47 months) were imaged on a 1.5T scanner by using a high-resolution 3D T1 spoiled gradient-recalled sequence. Volumetric data for SDGM structures were obtained by using FSL FIRST, while whole-brain, GM, white matter, cortical, and lateral ventricle volumes were estimated by using SIENAX software. Comparisons between the groups were adjusted for age and sex.

RESULTS:

Patients with early RRMS showed significantly lower SDGM but not cortical volumes compared with patients with CIS. The most apparent SDGM differences were evident in the caudate and thalamus (P < .0001), total SDGM (P = .0001), and globus pallidus (P = .01). Patients with CIS with a median T2 lesion volume >4.49 mL showed lower total SDGM, caudate, thalamus (P < .001), globus pallidus (P = .007), hippocampus (P = .004), and putamen (P = .01) volumes and higher lateral ventricle volume (P = .001) than those with a median T2 lesion volume <4.49 mL. Decreased thalamic volume showed the most consistent relationship with MR imaging outcomes (P < .0001) in patients with CIS.

CONCLUSIONS:

Significant SDGM, but not cortical, atrophy develops during the first 4 years of the RRMS. GM atrophy is relevant for disease progression from the earliest clinical stages.

Clinically isolated syndrome

Putamen

Caudate nucleus

10.3174/ajnr.a3086

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Citations (150)

Iron Deposition on SWI Filtered Phase in the Subcortical Deep Gray Matter of Clinically Isolated Syndrome Patients May Precede Structure-Specific Atrophy (P03.032)

Neurology (2012)

Jesper Hagemeier B. Weinstock‐Guttman Niels Bergsland Mari Heininen‐Brown Ellen Carl

Susceptibility Weighted Imaging

Gray (unit)

10.1212/wnl.78.1_meetingabstracts.p03.032

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Citations (1)

A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes

Journal of NeuroVirology (2013)

David B. Clifford Avindra Nath Paola Cinque Bruce J. Brew Robert Zivadinov

Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.

JC Virus

Clinical endpoint

10.1007/s13365-013-0173-y

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Citations (152)

IRONMAP: Iron Network Mapping and Analysis Protocol for Detecting Over-Time Brain Iron Abnormalities in Neurological Disease.

arXiv (Cornell University) (2025)

Jack A. Reeves Fahad Salman Michael G. Dwyer Niels Bergsland Sarah F. Muldoon

Pathologically altered iron levels, detected using iron-sensitive MRI techniques such as quantitative susceptibility mapping (QSM), are observed in neurological disorders such as multiple sclerosis (MS) and may play a crucial role in disease pathophysiology. However, brain iron changes occur slowly, even in neurological diseases, and can be influenced by physiological factors such as diet. Therefore, novel analysis methods are needed to improve sensitivity to disease-related iron changes as compared to conventional region-based analysis methods. This study introduces IRONMAP, Iron Network Mapping and Analysis Protocol, which is a novel network-based analysis method to evaluate over-time changes in magnetic susceptibility. With this novel methodology, we analyzed short-term (<1 year) longitudinal QSM data from a cohort of individuals with MS (pwMS) and healthy controls (HCs) and assessed disease-related network patterns, comparing the new approach to a conventional per-region rate-of-change method. IRONMAP analysis was able to detect over-time, MS-related brain iron abnormalities that were undetectable using the rate-of-change approach. IRONMAP was applicable on the per-subject level, improving binary classification of pwMS vs HCs compared to rate-of-change data alone (areas under the curve: 0.773 vs 0.636, p = 0.024). Further analysis revealed that the observed IRONMAP-derived HC network structure closely aligned with simulated networks based on healthy aging-related susceptibility data, suggesting that disruptions in normal aging-related iron changes may contribute to the network differences seen in pwMS. IRONMAP is generalizable to any neurological disease, including Alzheimer's disease and Parkinson's disease, and may allow for study of brain iron abnormalities over shorter timeframes than previously possible.

Quantitative Susceptibility Mapping

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HLA genotypes and disease severity assessed by magnetic resonance imaging findings in patients with multiple sclerosis

Journal of Neurology (2003)

Robert Zivadinov Laura Uxa T Zacchi Davide Nasuelli Maja Ukmar

Neuroradiology

10.1007/s00415-003-0164-7

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Citations (42)

Ventricular enlargement and mild cognitive impairment in early Parkinson's disease

Movement Disorders (2010)

Turi O. Dalaker Robert Zivadinov Deepa P. Ramasamy Mona K. Beyer Guido Alves

Mild cognitive impairment (MCI) may predict future development of dementia in Parkinson's disease (PD). We aimed to examine the extent of subcortical brain atrophy in patients with early PD with and without MCI compared to normal controls (NC). Participating in a population-based study were 43 early, drug-naïve PD patients and 41 NC. Eleven patients were classified with MCI (MCI PD) and 32 patients without (non-MCI PD). Volumetric segmentation of 3D-T1 weighted brain MRI was performed using FreeSurfer. Groups were compared applying MANCOVA corrected for total intracranial volume, age, and sex. Results showed that left inferior lateral ventricle and third ventricle volumes were significantly larger in MCI PD than in non-MCI PD and NC. Fourth ventricular size in MCI PD was significantly different from NC and highly correlated with memory performance in MCI PD patients. This suggests that cognitive dysfunction in early PD may be associated with ventricular enlargement. © 2010 Movement Disorder Society

10.1002/mds.23443

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Citations (62)

Assessing Abnormal Iron Content in the Deep Gray Matter of Patients with Multiple Sclerosis versus Healthy Controls

American Journal of Neuroradiology (2011)

Charbel Habib M. Liu N. Bawany James Garbern Ines Krumbein

BACKGROUND AND PURPOSE:

It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the THA. In this study, we used SWI to quantify iron content in patients with MS and healthy volunteers.

MATERIALS AND METHODS:

Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and THA structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep GM structures. Each structure was separated into 2 regions: a low-iron-content region and a high-iron-content region. The average phase, the percentage area, and the total phase of the high-iron-content region were evaluated. A weighting was also assigned to each subject depending on the level of iron content and its deviation from the normal range.

RESULTS:

A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor >3 SDs from the normal mean (P < .05). The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content.

CONCLUSIONS:

Iron-weighting factors in the basal ganglia, THA, and the midbrain appeared to be abnormal in roughly two-thirds of patients with MS as measured by SWI.

Relapsing remitting

Susceptibility Weighted Imaging

10.3174/ajnr.a2773

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Citations (52)

Internal jugular vein cross-sectional area and cerebrospinal fluid pulsatility in the aqueduct of Sylvius

CB Beggs Christopher Magnano Pavel Belov Jacqueline Krawiecki DP Ramasamy

1 Centre for Infection Control and Biophysics, University of Bradford, Richmond Road, Bradford BD7 1DP, UK; 2 Buffalo Neuroimaging Analysis Center, Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, 100 High St., Buffalo, NY 14203, NY, USA; 3 MRI Clinical Translational Research Center, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

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Quantitative diffusion weighted imaging measures in patients with multiple sclerosis

NeuroImage (2007)

Eleonora Tavazzi Michael G. Dwyer Bianca Weinstock‐Guttman Jordan Lema Stefano Bastianello

Diffusion imaging

10.1016/j.neuroimage.2007.03.056

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Citations (50)

Neuromyelitis optica immunoglobulins as a marker of disease activity and response to therapy in patients with neuromyelitis optica

Multiple Sclerosis Journal (2008)

Bianca Weinstock‐Guttman Curtis Miller EA Yeh M. Stosic Margaret Umhauer

Objective To determine whether neuromyelitis optica (NMO) immunoglobulin (IgG) antibody status in NMO/Devic’s disease patients followed prospectively is persistent or can change relative to the clinical status and/or response to therapy. Design A cross-sectional group of patients with NMO, relapsing extensive longitudinal transverse myelitis (RLETM) or optico-spinal multiple sclerosis (OSMS) were evaluated for the presence of NMO IgG antibodies. Repeated evaluation was made in all NMO/RLETM patients and in a subgroup of OSMS patients. Setting Baird Multiple Sclerosis Center, Buffalo, New York, an academic multiple sclerosis center. Results Out of a consecutive cohort of 38 patients evaluated for the presence of NMO IgG, 12 had NMO and 26 had OSMS. Five of the 12 NMO/RLETM patients were NMO IgG positive at the time of their initial evaluation. Four of these patients were repeatedly tested for NMO IgG: two of these became negative and two remained positive. One patient who was initially negative became positive during an acute event and again became negative during the stable disease phase following treatment. A positive test result was associated with active disease, whereas a negative NMO IgG result was consistently found in stable, long-term treated patients. None of the OSMS patients were positive for NMO IgG even during acute attacks. Conclusions NMO IgG antibodies are associated with active NMO/RLETM. A well-controlled stable disease usually under effective immunosuppressive therapy can transform the NMO IgG to a negative status. Repeated NMO IgG testing should be considered as a useful biological marker for monitoring NMO/RLETM disease and or response to therapy.

Neuromyelitis Optica

10.1177/1352458508092811

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Citations (38)