Open letter by Dr. Franz Schelling to Professor Reeker regarding his “A Swan Song for CCSVI“ commentary.

Nice one again Dr. Franz, thank you very much!!!

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Professor Reekers,

This is an open letter re your commentary “A Swan Song for CCSVI“ (Cardiovasc Intervent Radiol 2014: 37: 287-8) http://link.springer.com/article/10.1007%2Fs00270-013-0833-6.

You declare CCSVI has been shown, scientifically proven, to not exist.

In this vein you discount the observation of many an MS patient’s positive response to balloon dilatation treatments as a never lasting placebo effect.

On the internet you seem accordingly to have found testimonies just 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 a priori 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 reason for the present impasse in CCSVI research.

There exist decidedly more important pieces of evidence on this point 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 time (Kidd D ea. Cortical lesions in MS. Brain 1999; 122: 17-26).

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:

The distribution of MS lesions in the brain follows a specific pattern.

The lesions' form and orientation appears determined by the course of veins (Tan IL ea. MRV of MS. AJNR 2000; 21: 1039-42).

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]“, shelving it under the umbrella notion of a (cryptogenic) inflammatory demyelinating white matter disease.

On neurological wards and in clinical MS research any discrepancy between EAE and MS was soon levelled out in reinterpreting the pathology of MS in diffuse histological terms which turned an aftermath shared by diverse cryptic pathologies into THE injurious event.

By 1965, Charcot’s diagnostic MS triad and any competing MS definition via concrete nervous dysfunctions MS had come to be replaced by simpler and less committal quantitative terms.

The diagnosis of a clinically definite MS now depended on tracing a dissemination [of cryptogenic lesions] in space and time, to be precise in keeping with three temporal cut-off points:

Relapse durations of one day with a relapse interval of one month, respectively a progression of neurodysfunctions over six months became the substratum for diagnosing MS.

Neurodysfunctions of a mere day’s duration do not suffice, however, nor should their progression over half an year be necessary for identifying separate demyelinating events:

Recovering from a demyelinative event is a matter of about three months. In like wise, the need for two relapses 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 does postinfectious acute disseminated encephalomyelitis (ADEM), so also EAE extends in the form of narrow perivenular lesion sleeves quite evenly throughout the cerebral 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, the 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. They next spread out as ovoids, whose series are referred to as strings of beads), tending to flatten out into juxtacortical half-moons upon reaching 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 only known of the work of shock waves of ballistic impacts.

The halo of an isomorphic fibrillary sclerosis spreading beyond the plaques’ border is again hardly to be accounted otherwise than by the spread of subdestructive concussive effects.

The unique co-occurrence of severely desctructive (‘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 favour venous flow reversals during the suprastenotic vein compression of, or hinder a 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 ea’s ballooning of IJV (internal jugular vein) stenoses in MS yet point to the fact that, rather than exspiratory efforts, it are compressions of suprastenotically engorged internal jugular veins that underlie the vein-engendered MS lesions’ surging up in the brain (Schelling F. CCSVI in MS: Weighing the findings. Sang, thrombose, vaisseaux 2012; 24: 394-4-4.

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 (https://docs.google.com/file/d/0B_Ed_wxZvab3clRhVEsybFRLRzQ/edit?pli=1),

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 only paralleled by posttraumatic brain lesions: In both conditions these changes present as Dawson’s finger lesions which arise at Steiner’s wetterwinkel, i.e. the outer angle of the lateral ventricles, and in the undersurface of the corpus callosum of the cerebral hemispheres (literature on request).

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 trial, be it for drug or interventional treatments, on the other hand are treble blinded in the following respects:

Blinded as regards the features that specifically characterize the anatomical pathology of MS;

Blinded for the events which actually underlie the MS specific lesions’ development;

Blinded in view of what is ultimately required for ending the venous damaging of the brain in MS.

Learning to see, and duly appreciate, the crucial differences between EAE and MS is the condition 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.

Sincerely,

Franz Schelling, M.D.