American Academy of Neurology Meeting
Posted: Mon Feb 22, 2010 7:16 pm
As noted in another thread, there are several important CCSVI-related presentations planned for the Toronto American Academy of Neurology meeting in April.
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
[P03.128] Hypoperfusion of Brain Parenchyma Is Strongly Associated with the Severity of Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis
Paolo Zamboni, Italy, Eric Menegatti, Ferrera, Italy, Bianca Weinstock-Guttman, Michael G. Dwyer, Claudiu Schirda, Buffalo, NY, Anna Maria Malagoni, Ferrera, NY, Italy, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Christopher Magnano, Buffalo, NY, Ilaria Bartolomei, Bologna, Italy, Fabrizio Salvi, Cesena (FC), Italy, Robert Zivadinov, Buffalo, NY
OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral perfusion in patients with multiple sclerosis (MS). BACKGROUND: CCSVI is a vascular condition described in MS patients, characterized by stenoses of the main extracranial veins with hampered cerebral venous outflow. We hypothesized that the impaired venous outflow contributes to hypoperfusion of brain parenchyma. DESIGN/METHODS: Sixteen consecutive relapsing-remitting MS patients (mean age 36.1yrs, mean disease duration 7.5yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC), were scanned on a GE 3T scanner using dynamic susceptibility contrast enhanced perfusion-weighted imaging (PWI). Cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM), normal appearing (NA) GM, NAWM, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Diagnosis of CCSVI was established based on the venous hemodynamic (VH) Doppler criteria (Zamboni, JNNP, 2009) and the severity was based on fulfilled VH criteria (score 0-5) and VH insufficiency severity score (VHISS) (score 0-16). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between VH criteria and VHISS, and CBF, CBV and MTT in all examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for lower CBF and higher VHISS in the GM, WM, NAGM and NAWM (r= -0.70 to -0.72, p<0.002), and in the thalamus, caudate, putamen, hippocampus, nucleus accumbens (r= -0.6 to -0.72, p<0.008). The correlation coefficients for CBV and MTT were in a range between r= -0.5 to -0.65. No relationship was observed for NC. CONCLUSIONS/RELEVANCE: This study demonstrates that severity of CCSVI is directly associated with hypoperfusion of the brain parenchyma in MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 7:30 AM
Poster Session III: Multiple Sclerosis and Related Diseases: MRI/Technique (7:30 AM-12:00 PM)
[P03.126] Chronic Cerebrospinal Venous Insufficiency and Iron Deposition on Susceptibility-Weighted Imaging in Patients with Multiple Sclerosis
Michael G. Dwyer, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Mark Haacke, Detroit, MI, Erica Menegatti, Ferrara, Italy, Bianca Weinstock-Guttman, Claudiu Schirda, Buffalo, NY, Anna M. Malagoni, Ferrara, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Sara Hussein, Mari Heininen-Brown, Buffalo, NY, Ilaria Bartolomei, Fabrizio Salvi, Ferrera, Italy , Robert Zivadinov, Buffalo, NY
OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and iron deposition in the brain of multiple sclerosis (MS) patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter (DGM) structures and lesions, as measured by susceptibility-weighted imaging (SWI). To preliminarily define the relationship between iron measures and disability outcomes. BACKGROUND: CCSVI is a vascular picture recently described in MS patients that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. DESIGN/METHODS: Sixteen (16) consecutive relapsing-remitting MS patients (mean age 36.17.3 yrs, mean disease duration 7.5 1.9 yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC) were scanned on a GE 3T scanner, by using SWI. Iron concentration was measured in the following DGM structures: thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Iron concentration was also measured in T2, T1, SWI phase and SWI magnitude lesions. Diagnosis of the CCSVI was established based on the previously published VH Doppler criteria (Zamboni, JNNP, 2009). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between higher number of VH criteria and higher iron concentration in T2 (r=0.64, p=0.007) and T1 (r=0.56, p=0.023) lesion volumes. The only DGM structure that correlated significantly with VH criteria was globus pallidus (r=0.58, p=0.019). No relationship was observed for NC. Higher iron concentration in DGM structures was predictive of higher disability status (EDSS) in almost all examined regions. The highest correlations were detected for thalamus (r=0.79, p<0.0001) and red nucleus (r=0.7, p=0.005). CONCLUSIONS/RELEVANCE: The findings from this pilot study suggest that CCSVI may be an important mechanism leading to iron deposition in brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a strong predictor of disability progression in patients with MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 7:30 AM
Poster Session III: Multiple Sclerosis and Related Diseases: MRI/Technique (7:30 AM-12:00 PM)
[IN7-2.006] Objective Quantification of Cerebrospinal Fluid (CSF) Flow Rate in Cerebral Aqueduct in Patients with Multiple Sclerosis
Claudiu Schirda, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Christopher Magnano, Eric Lindzen, David Wack, Bianca Weinstock-Guttman, Deepa Ramasamy, Ellen Carl, David Hojnacki, Cheryl Kennedy, Michael G. Dwyer, Niels Bergsland, Jennifer L. Cox, Buffalo, NY, Fabrizion Salvi, Ferrera, Italy, Robert Zivadinov, Buffalo, NY
OBJECTIVE: To develop an objective MRI technique for quantifying the cerebrospinal fluid (CSF) flow in Sylvius aqueduct. To apply this technique in a pilot study in multiple sclerosis (MS) patients versus normal controls (NC) and provide further correlates with other MRI specific disease metrics. BACKGROUND: Non-invasive MRI investigation of the CSF dynamics in MS has not been previously reported. DESIGN/METHODS: For consistency and objective quantification of the antegrade (towards 4th ventricle), retrograde (towards 3rd ventricle) and net CSF flow rates, a semi-automated program was developed. The CSF flow quantification technique was validated on a tube phantom, using a power injector which provided a controlled flow rate. 2 NC and 2 MS patients were scanned and rescanned within a week, to test reproducibility. Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched NC were scanned on a GE 3T scanner using a two-dimensional phase-contrast gradient-echo MR technique with high spatial-temporal resolution (in-plane resolution 0.39x.039mm2 and 32 phases, corresponding to a full cardiac cycle) on one 4mm thick slice positioned perpendicular to the Sylvius aqueduct. In addition to CSF flow measures, lesion volume (LV) and atrophy MRI outcomes were calculated. RESULTS: Net CSF flow scan-rescan reproducibility was 10.9%. Net CSF flow rate (stroke volume) was significantly lower in MS patients than in NC (p=0.038). In MS patients, T1-LV was strongly correlated with CSF retrograde (r=0.71, p=0.002) and antegrade flow rates (r=-0.64, p=0.008). T2-LV was also related to CSF flow rate (0.58, p=0.019). Lower net CSF flow rate was related to gray matter (r=-0.63, p=0.009), whole brain and cortical atrophy (p<0.037). CONCLUSIONS/RELEVANCE: CSF flow rate in the Sylvius aqueduct is significantly lower in MS patients than in NC. In MS patients, robust correlations between higher LVs, and advanced atrophy, and altered flow rate measures were found.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 3:30 PM
Poster Session: Integrated Neuroscience: Multiple Sclerosis Imaging (3:30 PM-4:30 PM)
[P06.144] Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD Study). Description of the Design and Interim Results of an Epidemiological Study of the Prevalence of Chronic Cerebrospinal Venous Insufficiency in MS and Related Diseases
Robert Zivadinov, Karen Marr, Murali Ramanathan, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Ralph R. H. B. Benedict, Buffalo, NY, Gary Cutter, Birmingham, AL, Cheryl Kennedy, Makki Elfadil, David Hojnacki, Frederick Munschauer, Justine Reuther, Christina Brooks, Kristin Hunt, Michelle Andrews, Bianca Weinstock-Guttman, Buffalo, NY
OBJECTIVE: To ascertain the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and in normal controls (NC), by using specific proposed Doppler criteria (Zamboni et al, JNNP, 2009). BACKGROUND: CCSVI is a complex vascular condition characterized by anomalies of the main extracranial cerebrospinal (CS) venous routes that interfere with the normal CS venous outflow. This condition was previously associated with clinically definite MS. DESIGN/METHODS: Cross-sectional study that will enroll consecutive 1700 subjects at one MS center including: 1000 adult patients with possible and definite MS (50 clinically isolated syndrome, 50 radiologically isolated syndrome, 500 relapsing-remitting, 300 secondary-progressive, 50 primary-progressive MS and 50 neuromyelitis optica). A comparative group will include 300 OND patients and 300 adult age- and sex-matched NC. Fifty pediatric patients (<18 yrs) with acquired demyelinating diseases (MS and acute disseminated encephalomyelitis) and 50 pediatric NC will be assessed. All participants will undergo clinical examination and a Doppler scan of the head and neck. All MS patients and a subcohort of NC and OND will undergo an MRI of the brain. A consecutive subgroup (MS, NC and OND) will have also an MRI of the veins of the neck to corroborate the Doppler diagnosis of CCSVI. The Doppler, and MRI evaluators are blinded to the subject status. The prevalence and severity of venous hemodynamic abnormalities identified in the different groups will be analyzed. Data will be unblinded at three predetermined time-points based on the number of subjects enrolled: at 500, 1000 and 1700 subjects respectively. RESULTS: As of 1 Nov 2009, 473 subjects signed informed consent. The initial interim analysis following the first 500 subjects is scheduled for December 2009. CONCLUSIONS/RELEVANCE: The interim results of the first 500 enrolled subjects will be presented.
Category - MS and Related Diseases - Clinical Science
Thursday, April 15, 2010 3:00 PM
Poster Session VI: Multiple Sclerosis and Related Diseases: Clinical Trials (3:00 PM-7:30 PM)
The embargo for all abstracts to be presented at the 59th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.
[P03.128] Hypoperfusion of Brain Parenchyma Is Strongly Associated with the Severity of Chronic Cerebrospinal Venous Insufficiency in Patients with Multiple Sclerosis
Paolo Zamboni, Italy, Eric Menegatti, Ferrera, Italy, Bianca Weinstock-Guttman, Michael G. Dwyer, Claudiu Schirda, Buffalo, NY, Anna Maria Malagoni, Ferrera, NY, Italy, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Christopher Magnano, Buffalo, NY, Ilaria Bartolomei, Bologna, Italy, Fabrizio Salvi, Cesena (FC), Italy, Robert Zivadinov, Buffalo, NY
OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral perfusion in patients with multiple sclerosis (MS). BACKGROUND: CCSVI is a vascular condition described in MS patients, characterized by stenoses of the main extracranial veins with hampered cerebral venous outflow. We hypothesized that the impaired venous outflow contributes to hypoperfusion of brain parenchyma. DESIGN/METHODS: Sixteen consecutive relapsing-remitting MS patients (mean age 36.1yrs, mean disease duration 7.5yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC), were scanned on a GE 3T scanner using dynamic susceptibility contrast enhanced perfusion-weighted imaging (PWI). Cerebral blood flow (CBF), blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM), normal appearing (NA) GM, NAWM, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Diagnosis of CCSVI was established based on the venous hemodynamic (VH) Doppler criteria (Zamboni, JNNP, 2009) and the severity was based on fulfilled VH criteria (score 0-5) and VH insufficiency severity score (VHISS) (score 0-16). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between VH criteria and VHISS, and CBF, CBV and MTT in all examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for lower CBF and higher VHISS in the GM, WM, NAGM and NAWM (r= -0.70 to -0.72, p<0.002), and in the thalamus, caudate, putamen, hippocampus, nucleus accumbens (r= -0.6 to -0.72, p<0.008). The correlation coefficients for CBV and MTT were in a range between r= -0.5 to -0.65. No relationship was observed for NC. CONCLUSIONS/RELEVANCE: This study demonstrates that severity of CCSVI is directly associated with hypoperfusion of the brain parenchyma in MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 7:30 AM
Poster Session III: Multiple Sclerosis and Related Diseases: MRI/Technique (7:30 AM-12:00 PM)
[P03.126] Chronic Cerebrospinal Venous Insufficiency and Iron Deposition on Susceptibility-Weighted Imaging in Patients with Multiple Sclerosis
Michael G. Dwyer, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Mark Haacke, Detroit, MI, Erica Menegatti, Ferrara, Italy, Bianca Weinstock-Guttman, Claudiu Schirda, Buffalo, NY, Anna M. Malagoni, Ferrara, David Hojnacki, Cheryl Kennedy, Ellen Carl, Niels Bergsland, Sara Hussein, Mari Heininen-Brown, Buffalo, NY, Ilaria Bartolomei, Fabrizio Salvi, Ferrera, Italy , Robert Zivadinov, Buffalo, NY
OBJECTIVE: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and iron deposition in the brain of multiple sclerosis (MS) patients by correlating venous hemodynamic (VH) parameters and iron concentration in deep-gray matter (DGM) structures and lesions, as measured by susceptibility-weighted imaging (SWI). To preliminarily define the relationship between iron measures and disability outcomes. BACKGROUND: CCSVI is a vascular picture recently described in MS patients that is characterized by stenoses affecting the main extracranial venous outflow pathways and by a high rate of cerebral venous reflux that may lead to increased iron deposition in the brain. DESIGN/METHODS: Sixteen (16) consecutive relapsing-remitting MS patients (mean age 36.17.3 yrs, mean disease duration 7.5 1.9 yrs and median EDSS 2.5) and 8 age- and sex-matched normal controls (NC) were scanned on a GE 3T scanner, by using SWI. Iron concentration was measured in the following DGM structures: thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. Iron concentration was also measured in T2, T1, SWI phase and SWI magnitude lesions. Diagnosis of the CCSVI was established based on the previously published VH Doppler criteria (Zamboni, JNNP, 2009). RESULTS: All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4, median VHISS=9) and none of the NC. There was a significant association between higher number of VH criteria and higher iron concentration in T2 (r=0.64, p=0.007) and T1 (r=0.56, p=0.023) lesion volumes. The only DGM structure that correlated significantly with VH criteria was globus pallidus (r=0.58, p=0.019). No relationship was observed for NC. Higher iron concentration in DGM structures was predictive of higher disability status (EDSS) in almost all examined regions. The highest correlations were detected for thalamus (r=0.79, p<0.0001) and red nucleus (r=0.7, p=0.005). CONCLUSIONS/RELEVANCE: The findings from this pilot study suggest that CCSVI may be an important mechanism leading to iron deposition in brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a strong predictor of disability progression in patients with MS. Supported by: Hillarescere Foundation and Buffalo Neuroimaging Analysis Center.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 7:30 AM
Poster Session III: Multiple Sclerosis and Related Diseases: MRI/Technique (7:30 AM-12:00 PM)
[IN7-2.006] Objective Quantification of Cerebrospinal Fluid (CSF) Flow Rate in Cerebral Aqueduct in Patients with Multiple Sclerosis
Claudiu Schirda, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Christopher Magnano, Eric Lindzen, David Wack, Bianca Weinstock-Guttman, Deepa Ramasamy, Ellen Carl, David Hojnacki, Cheryl Kennedy, Michael G. Dwyer, Niels Bergsland, Jennifer L. Cox, Buffalo, NY, Fabrizion Salvi, Ferrera, Italy, Robert Zivadinov, Buffalo, NY
OBJECTIVE: To develop an objective MRI technique for quantifying the cerebrospinal fluid (CSF) flow in Sylvius aqueduct. To apply this technique in a pilot study in multiple sclerosis (MS) patients versus normal controls (NC) and provide further correlates with other MRI specific disease metrics. BACKGROUND: Non-invasive MRI investigation of the CSF dynamics in MS has not been previously reported. DESIGN/METHODS: For consistency and objective quantification of the antegrade (towards 4th ventricle), retrograde (towards 3rd ventricle) and net CSF flow rates, a semi-automated program was developed. The CSF flow quantification technique was validated on a tube phantom, using a power injector which provided a controlled flow rate. 2 NC and 2 MS patients were scanned and rescanned within a week, to test reproducibility. Sixteen (16) consecutive relapsing-remitting MS patients and 8 age- and sex-matched NC were scanned on a GE 3T scanner using a two-dimensional phase-contrast gradient-echo MR technique with high spatial-temporal resolution (in-plane resolution 0.39x.039mm2 and 32 phases, corresponding to a full cardiac cycle) on one 4mm thick slice positioned perpendicular to the Sylvius aqueduct. In addition to CSF flow measures, lesion volume (LV) and atrophy MRI outcomes were calculated. RESULTS: Net CSF flow scan-rescan reproducibility was 10.9%. Net CSF flow rate (stroke volume) was significantly lower in MS patients than in NC (p=0.038). In MS patients, T1-LV was strongly correlated with CSF retrograde (r=0.71, p=0.002) and antegrade flow rates (r=-0.64, p=0.008). T2-LV was also related to CSF flow rate (0.58, p=0.019). Lower net CSF flow rate was related to gray matter (r=-0.63, p=0.009), whole brain and cortical atrophy (p<0.037). CONCLUSIONS/RELEVANCE: CSF flow rate in the Sylvius aqueduct is significantly lower in MS patients than in NC. In MS patients, robust correlations between higher LVs, and advanced atrophy, and altered flow rate measures were found.
Category - MS and Related Diseases - Clinical Science
Wednesday, April 14, 2010 3:30 PM
Poster Session: Integrated Neuroscience: Multiple Sclerosis Imaging (3:30 PM-4:30 PM)
[P06.144] Combined Transcranial and Extracranial Venous Doppler Evaluation (CTEVD Study). Description of the Design and Interim Results of an Epidemiological Study of the Prevalence of Chronic Cerebrospinal Venous Insufficiency in MS and Related Diseases
Robert Zivadinov, Karen Marr, Murali Ramanathan, Buffalo, NY, Paolo Zamboni, Ferrera, Italy, Ralph R. H. B. Benedict, Buffalo, NY, Gary Cutter, Birmingham, AL, Cheryl Kennedy, Makki Elfadil, David Hojnacki, Frederick Munschauer, Justine Reuther, Christina Brooks, Kristin Hunt, Michelle Andrews, Bianca Weinstock-Guttman, Buffalo, NY
OBJECTIVE: To ascertain the prevalence of chronic cerebrospinal venous insufficiency (CCSVI) in a large cohort of patients with multiple sclerosis (MS), patients with other neurological diseases (OND) and in normal controls (NC), by using specific proposed Doppler criteria (Zamboni et al, JNNP, 2009). BACKGROUND: CCSVI is a complex vascular condition characterized by anomalies of the main extracranial cerebrospinal (CS) venous routes that interfere with the normal CS venous outflow. This condition was previously associated with clinically definite MS. DESIGN/METHODS: Cross-sectional study that will enroll consecutive 1700 subjects at one MS center including: 1000 adult patients with possible and definite MS (50 clinically isolated syndrome, 50 radiologically isolated syndrome, 500 relapsing-remitting, 300 secondary-progressive, 50 primary-progressive MS and 50 neuromyelitis optica). A comparative group will include 300 OND patients and 300 adult age- and sex-matched NC. Fifty pediatric patients (<18 yrs) with acquired demyelinating diseases (MS and acute disseminated encephalomyelitis) and 50 pediatric NC will be assessed. All participants will undergo clinical examination and a Doppler scan of the head and neck. All MS patients and a subcohort of NC and OND will undergo an MRI of the brain. A consecutive subgroup (MS, NC and OND) will have also an MRI of the veins of the neck to corroborate the Doppler diagnosis of CCSVI. The Doppler, and MRI evaluators are blinded to the subject status. The prevalence and severity of venous hemodynamic abnormalities identified in the different groups will be analyzed. Data will be unblinded at three predetermined time-points based on the number of subjects enrolled: at 500, 1000 and 1700 subjects respectively. RESULTS: As of 1 Nov 2009, 473 subjects signed informed consent. The initial interim analysis following the first 500 subjects is scheduled for December 2009. CONCLUSIONS/RELEVANCE: The interim results of the first 500 enrolled subjects will be presented.
Category - MS and Related Diseases - Clinical Science
Thursday, April 15, 2010 3:00 PM
Poster Session VI: Multiple Sclerosis and Related Diseases: Clinical Trials (3:00 PM-7:30 PM)
