Tweet
Earlier this summer the FDA put out an alert on the risks of the "liberation" procedure and just last week "another study of cerebrospinal venous abnormalities has failed to confirm a link to multiple sclerosis (MS), this one conducted primarily by imaging specialists rather than neurologists." (http://www.medpagetoday.com/Neurolog...clerosis/34318) This is disappointing, especially because lots of research dollars have been allocated to this potential treatment at the expense of other studies. Below are both the abstract and FDA alert. - Dave
Brain Hemodynamic Changes Associated with Chronic Cerebrospinal Venous Insufficiency Are Not Specific to Multiple Sclerosis and Do Not Increase Its Severity
Francesco G. Garaci, MD, Simone Marziali, MD, Alessandro Meschini, MD, Maria Fornari, MD, Silvia Rossi, MD, Milena Melis, MD, Sebastiano Fabiano, MD, Matteo Stefanini, MD, Giovanni Simonetti, MD, Diego Centonze, MD and Roberto Floris, MD
From the Departments of Diagnostic Imaging (F.G.G., S.M., A.M., M.F., M.M., S.F., M.S., G.S., R.F.) and Neuroscience (S.R., D.C.), University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy; Santa Lucia Foundation/European Center for Brain Research (CERC), Rome, Italy (S.R., D.C.); and IRCCS San Raffaele Pisana, Rome, Italy (F.G.G.).
Abstract
Purpose: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral hemodynamic parameters and to disclose any possible involvement in the pathophysiology of multiple sclerosis (MS).
Materials and Methods: The study was approved by the institutional review board, and written informed consent was obtained from all participants. The diagnosis of CCSVI was assigned by using specific color Doppler ultrasonographic criteria. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time were assessed with dynamic susceptibility contrast material–enhanced magnetic resonance imaging in normal-appearing white matter (NAWM) in 39 patients with MS. Of these, 25 had CCSVI and 14 did not. Twenty-six healthy control subjects were also evaluated, and of these, 14 had CCSVI and 12 did not. Two-way analysis of variance testing was used for statistical analysis, with Bonferroni correction for multiple comparisons. Correlation analysis was performed by calculating Spearman coefficients.
Results: Individuals with CCSVI showed cerebral hemodynamic anomalies, such as decreased CBF and CBV, as compared with individuals without CCSVI, without any delay in mean transit time. No significant interaction between MS and CCSVI was found for any hemodynamic parameters. Furthermore, no correlations were found between CBV and CBF values in NAWM or for severity of disability in patients with MS. The MS group showed prolonged mean transit time in the periventricular NAWM, as compared with the control group, and positive correlation was found between mean transit time values and disability scales in patients with MS.
Conclusion: The data support a role of CCSVI in cerebral hemodynamic changes, such as a decrease of CBV and CBF, regardless of the presence of MS. CCSVI had no effect on neurologic function and disability progression in patients with MS.
FDA issues alert on potential dangers of unproven treatment for multiple sclerosis
The U.S. Food and Drug Administration is alerting health care professionals and patients about injuries and death associated with the use of an experimental procedure sometimes called “liberation therapy” or the “liberation procedure” to treat chronic cerebrospinal venous insufficiency (CCSVI).
Some researchers believe that CCSVI, which is characterized by a narrowing (stenosis) of veins in the neck and chest, may cause multiple sclerosis (MS) or may contribute to the progression of the disease by impairing blood drainage from the brain and upper spinal cord. However, studies exploring a link between MS and CCSVI are inconclusive, and the criteria used to diagnose CCSVI have not been adequately established.
“Because there is no reliable evidence from controlled clinical trials that this procedure is effective in treating MS, FDA encourages rigorously-conducted, properly-targeted research to evaluate the relationship between CCSVI and MS,” said William Maisel, M.D., M.P.H., chief scientist and deputy director for science in the FDA’s Center for Devices and Radiological Health. “Patients are encouraged to discuss the potential risks and benefits of this procedure with a neurologist or other physician who is familiar with MS and CCSVI, including the CCSVI procedures and their outcomes.”
The experimental procedure uses balloon angioplasty devices or stents to widen narrowed veins in the chest and neck. However, the FDA has learned of death, stroke, detachment and migration of the stents, damage to the treated vein, blood clots, cranial nerve damage and abdominal bleeding associated with the experimental procedure. Balloon angioplasty devices and stents have not been approved by the FDA for use in treating CCSVI.
MS is a progressive, immune-mediated disorder of the brain and spinal cord. In MS, the lining around nerve fibers, and often the nerve fibers themselves, in the brain and spinal cord are injured, resulting in significant and disabling neurological symptoms. The underlying cause of MS is not known.
Complications following CCSVI treatment can be reported through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
The FDA also is notifying physicians and clinical investigators who are planning or conducting clinical trials using medical devices to treat CCSVI that they must comply with FDA regulations for investigational devices. Any procedures conducted are considered significant risk clinical studies and require FDA approval, called an investigational device exemption.
In February 2012, the FDA sent a warning letter to a sponsor/investigator who was conducting a clinical study of CCSVI treatment without the necessary approval. The sponsor/investigator voluntarily closed the study.
The FDA will continue to monitor reports of adverse events associated with “liberation therapy” or the “liberation procedure” and keep the public informed as new safety information becomes available.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
http://www.fda.gov/NewsEvents/Newsro.../ucm303538.htm
Brain Hemodynamic Changes Associated with Chronic Cerebrospinal Venous Insufficiency Are Not Specific to Multiple Sclerosis and Do Not Increase Its Severity
Francesco G. Garaci, MD, Simone Marziali, MD, Alessandro Meschini, MD, Maria Fornari, MD, Silvia Rossi, MD, Milena Melis, MD, Sebastiano Fabiano, MD, Matteo Stefanini, MD, Giovanni Simonetti, MD, Diego Centonze, MD and Roberto Floris, MD
From the Departments of Diagnostic Imaging (F.G.G., S.M., A.M., M.F., M.M., S.F., M.S., G.S., R.F.) and Neuroscience (S.R., D.C.), University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy; Santa Lucia Foundation/European Center for Brain Research (CERC), Rome, Italy (S.R., D.C.); and IRCCS San Raffaele Pisana, Rome, Italy (F.G.G.).
Abstract
Purpose: To investigate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and cerebral hemodynamic parameters and to disclose any possible involvement in the pathophysiology of multiple sclerosis (MS).
Materials and Methods: The study was approved by the institutional review board, and written informed consent was obtained from all participants. The diagnosis of CCSVI was assigned by using specific color Doppler ultrasonographic criteria. Cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time were assessed with dynamic susceptibility contrast material–enhanced magnetic resonance imaging in normal-appearing white matter (NAWM) in 39 patients with MS. Of these, 25 had CCSVI and 14 did not. Twenty-six healthy control subjects were also evaluated, and of these, 14 had CCSVI and 12 did not. Two-way analysis of variance testing was used for statistical analysis, with Bonferroni correction for multiple comparisons. Correlation analysis was performed by calculating Spearman coefficients.
Results: Individuals with CCSVI showed cerebral hemodynamic anomalies, such as decreased CBF and CBV, as compared with individuals without CCSVI, without any delay in mean transit time. No significant interaction between MS and CCSVI was found for any hemodynamic parameters. Furthermore, no correlations were found between CBV and CBF values in NAWM or for severity of disability in patients with MS. The MS group showed prolonged mean transit time in the periventricular NAWM, as compared with the control group, and positive correlation was found between mean transit time values and disability scales in patients with MS.
Conclusion: The data support a role of CCSVI in cerebral hemodynamic changes, such as a decrease of CBV and CBF, regardless of the presence of MS. CCSVI had no effect on neurologic function and disability progression in patients with MS.
FDA issues alert on potential dangers of unproven treatment for multiple sclerosis
The U.S. Food and Drug Administration is alerting health care professionals and patients about injuries and death associated with the use of an experimental procedure sometimes called “liberation therapy” or the “liberation procedure” to treat chronic cerebrospinal venous insufficiency (CCSVI).
Some researchers believe that CCSVI, which is characterized by a narrowing (stenosis) of veins in the neck and chest, may cause multiple sclerosis (MS) or may contribute to the progression of the disease by impairing blood drainage from the brain and upper spinal cord. However, studies exploring a link between MS and CCSVI are inconclusive, and the criteria used to diagnose CCSVI have not been adequately established.
“Because there is no reliable evidence from controlled clinical trials that this procedure is effective in treating MS, FDA encourages rigorously-conducted, properly-targeted research to evaluate the relationship between CCSVI and MS,” said William Maisel, M.D., M.P.H., chief scientist and deputy director for science in the FDA’s Center for Devices and Radiological Health. “Patients are encouraged to discuss the potential risks and benefits of this procedure with a neurologist or other physician who is familiar with MS and CCSVI, including the CCSVI procedures and their outcomes.”
The experimental procedure uses balloon angioplasty devices or stents to widen narrowed veins in the chest and neck. However, the FDA has learned of death, stroke, detachment and migration of the stents, damage to the treated vein, blood clots, cranial nerve damage and abdominal bleeding associated with the experimental procedure. Balloon angioplasty devices and stents have not been approved by the FDA for use in treating CCSVI.
MS is a progressive, immune-mediated disorder of the brain and spinal cord. In MS, the lining around nerve fibers, and often the nerve fibers themselves, in the brain and spinal cord are injured, resulting in significant and disabling neurological symptoms. The underlying cause of MS is not known.
Complications following CCSVI treatment can be reported through MedWatch, the FDA Safety Information and Adverse Event Reporting program.
The FDA also is notifying physicians and clinical investigators who are planning or conducting clinical trials using medical devices to treat CCSVI that they must comply with FDA regulations for investigational devices. Any procedures conducted are considered significant risk clinical studies and require FDA approval, called an investigational device exemption.
In February 2012, the FDA sent a warning letter to a sponsor/investigator who was conducting a clinical study of CCSVI treatment without the necessary approval. The sponsor/investigator voluntarily closed the study.
The FDA will continue to monitor reports of adverse events associated with “liberation therapy” or the “liberation procedure” and keep the public informed as new safety information becomes available.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
http://www.fda.gov/NewsEvents/Newsro.../ucm303538.htm