Reviews on Recent Clinical Trials (Online)
Volume 7, Number 2, May 2012
Editorial
New Avenues of Research on Multiple Sclerosis from the Perspective of Chronic Cerebrospinal Venous Insufficiency Paradigm
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Multiple sclerosis (MS) is a chronic and debilitating neurological disease characterized by multifocal areas of inflammation, demyelination and neurodegeneration within the brain and spinal cord. At its core MS is still a big enigma and it seems that there is clearly a gap in our knowledge about this disease [1,2]. It is hoped that the discovery of venous lesions associated with MS, the so-called chronic cerebrospinal venous insufficiency (CCSVI) [3,4] will--at least partially--fill that gap.
Although it is widely accepted that MS is an autoimmune disorder, which means that the disease is caused by autoimmune attack against nervous tissue antigens, therapeutic strategies that are based on this autoimmune concept fall short of success in the long-run and cannot protect the patients from the accumulation of disability [5-8]. Over the last century alternative causes of MS were discussed, including infectious, environmental, genetic, epigenetic and --importantly--vascular factors. Vascular model of MS has recently been revived by Italian vascular surgeon, Paolo Zamboni. His group demonstrated that majority of MS patients present with obstructive vascular abnormalities in the main veins draining the central nervous system: the internal jugular veins and the azygous vein. Zamboni’s venous paradigm claims for significant role of these venous blockages in neurological pathophysiology [9-11]. The idea that MS may be contributable to vascular disorders is not new and stretches much back in time then the Zamboni’s discovery [12]. It actually has its roots in the first description of MS by Charcot who depicted plaques characterized by vasocentric localization [13]. However, prior to CCSVI hypothesis, MS has not been suggested to result from impaired venous outflow.
It should be emphasized that this new venous model of MS is not necessarily contrary to its currently ruling autoimmune paradigm. The heterogeneity of MS and a relative lack of response to immunomodulatory treatments leads to the hypothesis that the autoimmune and venous disorders may represent two sides of the same coin, with MS being a disease triggered and exacerbated by immune and vascular [14], and possibly also other mechanisms.
The research on venous aspects of MS is still at its infancy and at present most of the questions and uncertainties related to this topic remain unanswered. This hot-topic issue of the Reviews on Recent Clinical Trials is aimed at presenting a theoretical framework for further research on this intriguing problem.
First article in this issue, paper by Haacke et al., gives historical overview of potential vascular background of MS and other neurodegenerative diseases [15]. Besides, the Authors discuss the role for magnetic resonance imaging of the brains affected by impaired venous outflows in the validation of this new model of MS. In the other paper by this team Feng et al., using novel MR imaging protocols, demonstrate a reduced blood flow through the IJVs in the MS population with stenotic veins compared to those without stenoses and healthy controls [16]. It should be mentioned that--thus far-- a routine MR imaging protocol was not very successful in diagnosing outflow disturbances in the IJVs [17,18]. This paper, on the contrary, shows that magnetic resonance can be a powerful diagnostic tool in this venous territory, on condition that a proper imaging technique is applied.
Then, the reader of this hot-topic issue can learn from the next two reviews how the vascular lesions may be related to neurological pathology. Most of the mainstream scientists rigorously contest venous MS hypothesis, claiming that: firstly, venous occlusion of a vein draining the brain cannot compromise outflow from this organ, since collaterals can easily compensate such a blockage, and secondly, even if such a blockage were significantly impairing outflow, an abnormal circulation cannot meaningfully influence normal functioning of the central nervous system [18-20]. Yet, these opinions are not necessarily correct. In the review by Zaniewski et al. it is explained why, from the physical point of view and respecting the basic laws governing the fluid mechanics, blockages in the internal jugular veins cannot be easily compensated by collateral venous network [21]. The other review by Simka addresses the challenging question of whether venous insufficiency may contribute to tissue damage found in the settings of MS [22]. Several possible pathomechanisms that may be capable of triggering MS-associated disorders in a case of compromised venous outflow are debated. Although current evidence supporting these suggested mechanisms is rather slim, this paper shows new avenues for research in this area.
An accumulating body of evidence shows that the most frequent vascular abnormally found in MS patients is the stenotic valve of the internal jugular vein [3,11]. Other vascular lesions and malformations found in MS patients are far less common.
Such a valve seems to impair significantly cerebral outflow [23]. Moreover, these stenotic jugular valves are usually seen in combination with collapsed middle and upper parts of jugular vein, resulting in even more increased flow resistance. In the paper by Al-Omari et al. a wide spectrum of differently malformed jugular valves is presented [24]. This paper, based on personal experience of the Authors, enables a better understanding of flow abnormalities triggered by such pathological valves. In addition, it is hoped that future imaging protocols for the assessment of jugular valves (such as Doppler sonography and MR venography) [25] may benefit from this review, even if clinical meaning of flow reduction incurred by such over-competent valves remains to be established.
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Marian Simka
(Guest Editor)
Department of Vascular & Endovascular Surgery,
Euromedic Specialist Clinics, Katowice,
Poland
Source: http://www.benthamdirect.org/pages/b_viewarticle.php
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