Failure of the vascular hypothesis of multiple sclerosis in a rat model of chronic cerebrospinal venous insufficiency (original) (raw)
Related papers
Chronic cerebrospinal venous insufficiency and venous stenoses in multiple sclerosis
Acta Neurologica Scandinavica, 2012
Methods. Sixteen (16) consecutive relapsing-remitting MS patients and 8 age-and sex-matched healthy controls (HC) were scanned on a GE 3T scanner, using SWI. Results. All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC. In MS patients, the higher iron concentration in the pulvinar nucleus of the thalamus, thalamus, globus pallidus, and hippocampus was related to a higher number of VH criteria (P<0.05). There was also a significant association between a higher number of VH criteria and higher iron concentration of overlapping T2 (r=-0.64, P=0.007) and T1 (r=-0.56, P=0.023) phase lesions. Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume. Conclusion. The findings from this pilot study suggest that CCSVI may be an important mechanism related to iron deposition in the brain parenchyma of MS patients. In turn, iron deposition, as measured by SWI, is a modest-to-strong predictor of disability progression, lesion volume accumulation and atrophy development in patients with MS. [Int Angiol 2010;29:158-75]
Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis
Neurological Sciences, 2011
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.
Chronic cerebrospinal venous insufficiency and multiple sclerosis
Annals of Neurology, 2010
A chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI), is claimed to be a pathologic phenomenon exclusively seen in multiple sclerosis (MS). This has invigorated the causal debate of MS and generated immense interest in the patient and scientific communities. A potential shift in the treatment paradigm of MS involving endovascular balloon angioplasty or venous stent placement has been proposed as well as conducted in small patient series. In some cases, it may have resulted in serious injury. In this Point of View, we discuss the recent investigations that led to the description of CCSVI as well as the conceptual and technical shortcomings that challenge the potential relationship of this phenomenon to MS. The need for conducting carefully designed and rigorously controlled studies to investigate CCVSI has been recognized by the scientific bodies engaged in MS research. Several scientific endeavors examining the presence of CCSVI in MS are being undertaken. At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena. ANN NEUROL 2010;67:286 -290 R ecently, the topic of chronic cerebrospinal venous insufficiency (CCSVI) and its potential relationship to multiple sclerosis (MS) has generated tremendous interest in the news media, spilling over to the patient and scientific communities. Described as a state of chronic impaired venous drainage from the central nervous system (CNS), the emergence of CCSVI with respect to MS is based on the work done by Zamboni and colleagues. 1 This was followed by a small open-label study conducted to study the effect of endovascular angioplasty in MS patients with CCSVI. 2 Prompted by this series of events, this Point of View will review available information on CCSVI, its potential relationship to MS pathology, and what further research needs to be undertaken while keeping patient safety foremost.
International Journal of Current Research and Review
Background: Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system presumed to be of autoimmune nature. This MRI based study was done to see iron deposition in deep subcortical nuclei and look for any abnormalities in extracranial venous drainage system and to look for any correlation with clinical parameters. Material and Methods: This case control study was done in a single large north Indian institute and had two groups of 25 cases each. One group being of consecutive MS patients and another of other neurological disease (OND). The two groups were age and sex matched. Both the groups underwent Magnetic Resonance Venography (MRV) of neck vessels and azygous system and cross sectional areas of internal jugular veins, azygous veins were measured. Iron stores in deep grey matter nuclei were quantified with Susceptibility weighted Imaging (SWI) studies. Results: The predefined cross sectional areas of internal jugular veins (IJV) and azygous veins were comparable. On comparing the flows of right and left IJVs, there was a clear dominance of right side in both MS and OND groups. We found more iron in all the nuclei in MS group compared to OND group. But statistically significant difference between the two groups was seen in bilateral pulvinar thalami and red nuclei, right putamen, right caudate nucleus and left substantia nigra. The absence of any difference in anatomical parameters in two groups goes against any vascular hypothesis of iron deposition in deep subcortical nuclei. The iron deposition may be an epiphenomenon of underlying disease rather than having to do something with etiopathogenesis.
Comment on “no evidence of chronic cerebrospinal venous insufficiency at multiple sclerosis onset”
Annals of Neurology, 2011
Objective: An impaired cerebrospinal venous drainage, defined as chronic cerebrospinal venous insufficiency (CCSVI), has been recently hypothesized to be the possible cause of multiple sclerosis (MS). We investigated this hypothesis by studying the occurrence of CCSVI in clinically isolated syndromes (CISs) suggestive of MS. Methods: Fifty consecutive patients presenting with a CIS and evidence of dissemination in space of the inflammatory lesions (ie, possible MS [pMS]) underwent a detailed diagnostic workup, including extracranial and transcranial venous echo-color Doppler sonography (ECDS-TCDS). Those with CCSVI underwent selective venography. Fifty healthy subjects (HCs) age-matched and gender-matched with pMS patients (HC1); 60 patients with transient global amnesia (TGA); and 60 healthy subjects age-matched and gender-matched with TGA patients (HC2) constituted the control groups and underwent ECDS-TCDS. Results: Mean age of pMS patients was 33.0 6 8.5 years (range, 14-50); 35 (70%) were female (female:male ratio, 2.3). TCDS was normal in all pMS patients. One or more abnormal ECDS findings were observed in 26 of 50 (52.0%) pMS patients, in 35 of 110 (31Á8%) HCs (HC1þHC2), and in 41 of 60 (68.3%) TGA patients. Eight (16%) pMS patients fulfilled the diagnosis of CCSVI. Selective phlebography performed in 7 of these patients (1 denied consent) did not show venous anomalies. Interpretation: Our findings do not support a cause-effect relationship between CCSVI and pMS. Further studies are warranted to clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS. FIGURE 3: (A) ECDS in pMS patient in the supine position: IJV stenosis with septum. (B) Venography in the same patient, supine position: no lumen irregularities. (C) Venography, 45-degree tilt: normal drainage. ECDS 5 extracranial echo-color Doppler sonography; IJV 5 internal jugular vein; pMS 5 possible MS. ANNALS of Neurology 96 Volume 69, No. 1