A commentary to the article: Reekers J. A swan song for CCSVI. Cardiovasc Intervent Radiol 2014;37:287-8.
Franz Schelling, MD
Gaissau, Austria
dr.franz.schelling@gmail.com
Open letter
Professor Jim Reekers,
My emails to you seem not to have provoked any reaction.
Please find below an attempt to render the open letter re your commentary A swan song for CCSVI1 a little more concrete.
You declared that CCSVI has been shown, scientifically proven, to not exist. And that the observations of positive responses to its balloon dilatation treatments were just a never lasting placebo effect.
All that the internet could show to you were testimonies by disappointed MS patients.
What, however, were they disappointed by?
Failed, or abortive exams for CCSVI? Denied, or unsuccessful interventions? Unreasonably high expectations, or treatment complications?
Most importantly, however, how could, or why did you find no access to all the accounts of persistent, at times bewildering benefits following interventions for CCSVI?
Why is there a call for double blinded trials on a CCSVI that is said not to exist, and found it on an impenetrable clinical MS entity that lacks in any concrete marker for its identification?
Ought we not focus instead on what is known about the MS lesions’ relationship to the venous pathways which the CCSVI findings relate to?
The usual reduction of CCSVI to an appealing abbreviation for the narrowing of the (internal) jugular vein, evident already from your introduction, is one of the reasons for the present impasse in CCSVI research.
There exist decidedly more important pieces of evidence on our topic than your statement that some early MS lesions are located around a vein is willing to admit.
It was actually with the participation of your Institute of Radiology at Amsterdam that the damaging of the cortical grey matter on the part of venous trunks and branches was made evident in MS for the first time2 and it was your very institute that first revealed in vivo, in seventeen patients with MS, two facts disclosed until then only in general and in separate post mortem specimens:
i) the distribution of MS lesions in the brain follows a specific pattern;
ii) the lesions’ form and orientation appears determined by the course of veins.3
The unparalleled nature of these features of MS has been pointed out by numerous observers without ever being granted due attention in clinical MS research.
Instead, in WW ii, there occurred a fatal shift in the way clinical neurology understands MS: Its distinctive anatomical pathology came to be equated and ultimately displaced by findings made in an animal model created for unraveling immunization encephalomyelitis: experimental allergic encephalomyelitis or EAE.
Clinical jargon soon referred to MS simply as Enc[ephalomyelitis] diss[eminata].
In forgetting about all its well documented venous and scarring findings, Charcot’s multilocular sclerosis had thus become an inflammatory myelin/white matter disease whose brain lesions originated in venules and not in veins.
As in other ill-understood disease processes, declaring observed inflammatory/immunological reactions as primary, spontaneous, idiopathic, and sufficed for turning them into injurious events.
On the other hand, by 1965, Charcot’s diagnostic MS triad and any competing MS definition via concrete nervous dysfunctions had come to be replaced by less committal numeric terms.
The diagnosis of a clinically definite MS now depended on tracing a dissemination (of as indefinite as unexplainable lesions) in space and time, to be precise in keeping with three temporal cut-off points:
i) relapse durations of one day with a relapse interval of one month, respectively a progression of neurodysfunctions over six months became the substratum, the only concrete data to rely on in making a diagnosis, i.e. tracing the demyelinating episodes of MS;
ii) neurodysfunctions of a mere day’s duration cannot suffice, however, nor should their progression over half a year be necessary for identifying these demyelinative events: the repair of an area of demyelination takes about three months.
In likewise, the need for two relapses, demyelinating episodes, to be separated by a month so as to prove MS is bound to remain inscrutable.
What about the much invoked EAE MS analogy?
As post-infectious/immunization ADEM (acute disseminated encephalomyelitis) does in man, so also the animal MS of EAE extends in the form of narrow perivenular lesion sleeves quite evenly throughout the brain, in particular its white matter.
The sleeves are 0,1 to 1,0 mm in diameter and often interspersed with punctate ring-bleedings. In converging towards the lateral ventricles, they may merge to form wider, unevenly outlined lesion pools.
Reaching far larger dimensions, plaques of human MS proper erupt from subependymal veins. In lining and rising from the lateral ventricles, they form the Dawson’s fingers of Steiner’s wetterwinkel. Plaques which spread farther out resemble ovoids whose lining up on a medullary vein reminds of a string of beads. Ultimately, the plaques tend to flatten out into juxtacortical half-moons once they reach the cortical border.
The lesions expand from acutely or chronically injured veins, and do so via succeeding, more or less eccentric hits. Most plaques attain sizes which are out of any proportion to the size of their vessel of origin.
Such ranges of a destructive efficacy are known of the work of shock waves of ballistic impacts. And so the pattern of the haloes of the isomorphic fibrillary sclerosis surpassing the plaque borders is hardly to be accounted otherwise than by the spread of sub-destructive concussive effects.
The unique co-occurrence of severely destructive (black-holes on MRI) besides demyelinated and shadow plaques (subject of neuroradiological UBO, i.e. unidentified bright object counts) finds it explanation by local impacts of differing severity.
All these changes, readily evident on longitudinal MRI studies, are to be physically accounted for by retrograde venous pressure surges and the momentum of abrupt venous flow reversals alone.
For such venous bores to come about, engorged, compliant lengths of the venous pathways involved must be abruptly compressed, and this in the presence of some hindrance to the compressed blood’s momentary escape, be it infra- trans- or intracranially, in other than cerebral veins and eventually to the heart.
In the presence of incompetent valves, any sufficiently strong expiratory effort or abrupt trunk compression suffices for driving blood back via the internal jugular vein: CCSVI criterion 1.
CCSVI criteria 3 to 5 indicate circumstances that either favor venous flow reversals during the suprastenotic vein compression of, or hinder contralateral collateral reflux drainage via, the internal jugular vein itself.
It is CCSVI criterion 2, however, that illustrates the decisive injurious event, the venous flow reversals in the brain. Unfortunately this widely neglected parameter has as yet not been evaluated round the clock in everyday’s life and needs to be further improved in its sensitivity.
In 1981 varicose dilations of the transition of the sigmoid sinus into the jugular vein seen in cranial radiographs of nearly a hundred patients with MS led to my conjecturing that the retrograde venous damaging of the brain seen in MS might be ended in shunting an incompetent confluence of sinuses or doing a valvuloplasty or even ligature high up in the involved internal jugular veins.
The benefits of Zamboni et al.’s ballooning of IJV (internal jugular vein) stenosis in MS yet point to the fact that, rather than expiratory efforts, it are compressions of suprastenotically engorged internal jugular veins that underlie the vein-engendered MS lesions’ surging up in the brain.4
As for the cerebral veins being thereby specifically involved, all the pertinent literature, from Charcot’s lesion sketches of 1866 to the latest ESWAN MRIs, has consistently shown that it is the internal cerebral veins and branches which are primarily at risk.
The retrograde overburdening, even rupturing of these veins and their adjacent tissues structures seen in MS is paralleled by a special variant of TBI (traumatic brain injury) alone: Both conditions present with Dawson’s finger lesions arising from Steiner’s wetterwinkel, the outer angle of the lateral ventricles, and in the undersurface of the corpus callosum.
These facts are already evident in comparing a few pertinent observations made in MS5,6 with such made in traumatic brain injury.7,8
A comparison of the respiratory, exertional and accidental peak pressures in the venous pathways that relate to cerebral MS lesions with such that do not ought thus to reveal the prime cause of cerebral MS. Prominent and exclusive connections of straight and lateral/occipito-marginal sinus appear thereby of special relevance.
Clinical MS trials, be it for drug or interventional treatments, on the other hand are treble blinded in the following respects:
i) blinded as regards the features that specifically characterize the anatomical pathology of MS;
ii) blinded for the events which actually underlie the MS specific lesions’ development;
iii) blinded in view of what is ultimately required for ending the venous damaging of the brain in MS.
Learning to see, and duly appreciate, how different EAE and MS - respectively how close the parallels between MS and certain forms of TBI - actually are the condition sine qua non for understanding MS.
Without understanding the processes which the MS specific venous damages are caused by, it is simply impossible to arrive at a sound evaluation of the different findings of CCSVI and thereby to prepare predictable cures of MS.
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