Identifying MS on MR images: A matter of clinical agreements — or of morphological expertise?
MR imaging markers of multiple sclerosis: Of interest, valuable, in themselves? Or just under certain clinical circumstances?
MR imaging persists in making amazing advances, offering opportunities for identifying MS which await their due appreciation.
This relates to the following:
After having been invoked as the gold standard for identifying MS for one and a half centuries, the series of intriguing, graphically illustrated post mortem observations that made MS a distinct pathological entity has fallen into oblivion.
This happened with the adoption of the assumption that a certain timing of cryptic neurological dysfunctions is capable of indicating a specific (histo-)pathological entity.
An assumption that appears questionable for three reasons.
(1) It is rather speculative to assume certain periods of neuronal dysfunctions were a reliable indicator of definite histopathological changes.
(2) A pathology set apart by such trivial phenomena as inflammation and demyelination can hardly be said to be adequately characterized.
(3) The claim MS was the result of the work of an unidentified autoimmune agent relies on no more than its persistent assertion by clinical authorities.
Clinging to such untouchable tenets will neither contribute to perceiving the findings which are peculiar to MS, nor elucidate the physical reasons for their development.
It rather obviates any attempt at integrating MS specific post mortem and in vivo imaging findings in terms of a concrete pathological entity.
Limited to tracing disturbed neuronal (re-)activities, even the most experienced neurologist can’t make the radiologists’ and pathologists’ morphological expertise a matter of secondary importance.
Monitoring the course of neurological dysfunctions will never disclose the ways and directions in which the underlying lesions progress, let alone reveal the underlying activities.
What can be expected to elucidate the condition’s nature and cause(s) is focusing on the observations exclusively made in MS.
Not quite sure about this? Please google ‘Franz Schelling’ or contemplate the pictorial evidence presented at www.ms-info.net.
Minding the venous MR imaging markers of cerebral MS?
Original naked-eye observations
Post mortems show the pathology of multiple sclerosis (MS) in unmatched detail. For one and a half centuries, therefore, autopsy findings were the gold standard for identifying MS.
A plaque, exactly depicted by Charcot in June 1866, shows the lesion’s relationhip to (proximal parts of) ventricular roof veins. Its forming the archetype of cerebral MS is as unquestionable as Carswell and Cruveilhier’s having first illustrated pontine and spinal MS.
In 1884 Charcot showed another, no less specifically characterized MS lesion: A plaque projected up into the corpus callosum in a distinctive series of waves, and this from below.
A grand, in fact unique, synopsis of the diverse lesion patterns being typical of cerebral MS surfaced in a book of Gabriel Steiner, in 1931.
Steiner traced ovoid lesion ‘splashes’ radiating, at times in series, in a peripheral direction. Lined up on the central vessel of a lesion cone projected from a ventricle-based plaque. Part of the ovoids connected to more central lesions via perivascular sleeves or ‘stalks’. Others were found to impact on the cerebral cortex, or end flattened out against its border.
Lumsden later referred to the serial lesions as a ‘string of beads’. The ovoids molded against the cortical border having before been singled out, by Fog, as ‘semilunar plaques’.
According to Steiner, white and grey matter are similarly involved: Compact lesions appear punched out from the cerebral cortex from the outside, at times impacting — another peculiarity of cerebral MS — in a ‘sausage-shape’ upon neighbouring gyri. Emerging from an axis taking its course in the pia mater. The pia having been removed, the axis’ nature remained an enigma.
Forty-one years later, Lumsden showed the cross-section of a lesion cut out, in two half circles, of opposing gyri. The damage was referred to as ‘kissing plaques’.
The two halves of this lesion centered on a vein.
MS was also found to affect the brain’s only pure grey matter structure, the retina, by infiltrations encompassing veins. Rucker’s 1945 discovery of this ‘periphlebitis retinae’ opened up a first, scarcely exploited, opportunity to observe MS lesions over time.
Overwhelming strides towards a better understanding of the process of MS were made by examining three serially sectioned brains. This was towards 1937 and 1964.
The 3D-reconstructions of Putnam and Adler’s findings revealed strange lesion configurations. And even more grotesque dilations, distortions and gnarled looks of the lesions’ veins. Which, in the end, dwindled away.
Complementary to this, Fog pictured a smoothly and massively distended lesion vein — fed by small, inconspicuous branches. This fact was left without comment. Fog yet wondered why the brain lesions’ development in dependence on certain ‘parent veins’ had never been pointed out before.
He explained this oversight was due to the eccentric way the lesions spread off their vein, the unpredictable divergences between the axis of the lesion and the axis of its vein. A conclusion he buttressed with countless illustrations.
Steiner also noted: The MS lesions’ advance off their vessels shows an striking independence of the vessel’s course.
But he is best commemorated for revealing this fact: The area from which MS lesions preferentially, the earliest, and predominantly emerge is formed by the long bow of the lateral ventricular angle (including the posterior horn) — the domain being immortalized as “Steiner’s wetterwinkel”.
Colin Adams’ masterpiece “A Colour Atlas of Multiple Sclerosis” (Wolfe, London 1989/Mosby, St.Louis, MO 1991) eventually discloses breathtaking details about what takes place in the walls of the lesion veins themselves. At times, before any tissue damage is manifest.
All sorts of extravasations, including hemorrhages, are seen. Involving, emerging from, also remarkably large veins. Some vein walls are more or less severely disintegrated, others massively broadened by a partly multilayered, progressing vein wall hyalinosis. Some veins prove ruptured, one appears even torn to shreds (pp 188–194).
A picture that looks quite different from the microvessel exudations and ring bleedings seen in leucoencephalitis (p. 41). But reminds instead, quite amazingly, of the vascular and perivascular changes observed in arterial hypertension.
Is clinical MS research oblivious to these facts?
MR scans: Ancillary adjuncts to the monitoring of neurological dysfunctions?
The clinical understanding of MS relies on the tacit assumption:
Monitoring of the course of neurological dysfunctions over time enables to the identification of the nature of the underlying pathological processes … provided the dysfunctions’ cause remains unexplained.
Agreed on criteria for making dysfunction-times based MS diagnoses were promulgated to indicate a not further specified kind of inflammatory demyelination.
Conceded a certain delay, the postulated kind of inflammatory demyelination was, in the meantime, exemplified.
Who provided the prime example of the kind of inflammation that underlies MS was Eduard Rindfleisch in 1863. This was in the autopsy of a male victim of tabes dorsalis.
The autopsy gave no evidence of a luetic posterior tract degeneration. Instead, millet to pea-sized vessel-centered foci of an unspecified, supposedly persistent or recurrent process of inflammation were spread throughout the white matter of the forebrain and the anterior tracts of the spinal cord (Rindfleisch E. Histologisches Detail zu der grauen Degeneration von Gehirn und Rueckenmark. Arch path Anat Physiol klin Med 1863;26:474–83).
The idea of an MS-specific kind of demyelination, on the other hand, has its origin in two passages of Jean-Martin Charcot’s second lecture on MS, given on December 3rd 1868, (M. Charcot. Histologie de la sclerose en plaques. Gaz hopitaux 1868;141:554–5,557–8,566).
Focusing on the spinal cord, Charcot presented a slide showing demyelinated axons pervading the center of a scarred, but not otherwise characterized lesion. He emphatically declared: “The persistence of a certain number of axons amidst extremely scarred ‘parts’ appears to be proper to multiple sclerosis.” In making this declaration the culmination of his comment on the slide.
Nothing is yet known on the source of the specimen or any of its further properties.
What the countless references to this lecture are, besides not mentioning is this: Charcot concluded the presentation with the note: The nerve fiber’s decay in MS looks exactly the same as after the transection of a nerve tract.
The claim MS was a process of inflammatory demyelination is ultimately backed but by the expertise of clinical authorities. Their intuition seems in urgent need of being supported by convincing pieces of evidence.
Neuroimaging in MS: Reports blur essential facts
In MRI reports on patients suspected of ‘having MS’, it is now common usage to refer to lesions as foci of demyelination (excepting, at times, persistent ‘black holes’).
This irrespective of the impossibility of differentiating zones of edema and/or gliosis from zones of demyelination on routine scans.
Veins are further preferentially referred to as ‘vessels’, or otherwise venules, and this irrespective of their actual size. At spatial resolutions at which no venule of even the largest caliber can possibly be made out.
The reasons for these terminological adaptations and corrections in the sense of clinical doctrine have remained unfathomed to this very day.
Venous MR imaging markers: What prevents their diagnostic value from being recognized?
About two decades ago, the term ‘Dawson’s fingers’ (Lumsden’s name for Steiner’s ventricle-based lesion cones) found entrance into MRI reports. In the attempt at characterizing the periventricular lesion spread in the cerebral hemispheres.
The ‘cock’s comb contour’ of a series of Dawson’s fingers rising from the lateral ventricles — comparable to Charcot’s corpus callosum lesion of 1884 — was thereby noted as being ‘virtually pathognomonic’, as not having been found anywhere except in MS (Heckl RW. Multiple Sklerose. Thieme, Stuttgart 1994, p. 166).
Reports on the central-vessel or central-vein sign of cerebral MS further motivated repeated references to Fog’s pertinent post mortem observations.
Some imperceptible obstacle nonetheless prevents from conceding this fact:
Charcot, Steiner, Putnam & Adler, Fog, Lumsden, and Adams’ graphical morphological lesion characterizations have to be considered as the touchstone for the identification of a lesion of MS.
Serial MRIs: mere monitoring of disease progression?
The decisive advantage of MRI is its potential to disclose, in serial studies, (1) the structures along which, (2) the directions in which, and (3) the speed at which the process of cerebral MS advances — and this, ideally, before there accrue damages which cannot be repaired.
Even in abstaining from a delineation of lesion veins, time-lapse movies which illustrate the brain lesion dynamics with the best achievable temporal resolution offer quite a deal of insight into what happens in MS. Causing, at times, amazement at what is seen in the absence of any clinical changes.
Such studies led to the following realizations:
(1) In a given patient different lesions appear to develop largely independent of each other. As do the durations of their T2 activities and gadolinium enhancements, each varying widely (Cotton F ea. MRI contrast uptake in new lesions in RR MS followed at weekly intervals. Neurology 2003;60:640–6).
(2) A disproportionally greater amount of recovery was observed for larger lesions (Meier DS ea. MRI intensity modeling of damage and repair in MS. AJNR 2007;28:1956–63).
Unfortunately, it seems not to have been examined how far this finding was actually due to the larger lesions’ more peripheral location.
In watching the time-lapse movie somewhat more closely, a number of other telling observations can be made:
Anybody who knows the divergencies in the course of periventricular veins and arteries will immediately perceive: The lesions have emerged, sort of erupted from, along tributaries respectively in the vascular territory of the inner cerebral veins.
As the process of MS is known to be, as a rule, the most active along the lateral ventricle’s outer edge (Steiner’s wetterwinkel), the movie’s two upper cines are of special interest.
Ventricle-based lesions (Dawson’s fingers) projecting intermittently off, and subsequently receding to, the ventricular border are clearly evident.
On the cine on the right separate lesion developments are seen to do so in precise synchrony. First, along the ventricular triangle on the left (the picture’s right) side and, quickly thereafter, off the frontal horn and ventricular triangle on opposite sides.
The fleeting mass effects of the largest, most peripheral lesions manifests in the irregularly projecting haloes of peri-lesional edema. It may be responsible for the lack of a coincidence of particularly large lesion eruptions.
Behind the right posterior horn, a giant lesion’s mass effects directly impact on the dynamics of a nearby Dawson’s finger formation.
These few comments may show: Delving more deeply into the treasure trove of information provided by weekly to monthly MRI series in MS has its rewards — even if none of the given cine’s lesion-flare ups had become clinically manifest.
Waiting for confirmation are equally the more recent observations of a dilation of inner cerebral and plaque-veins in flaring up lesions, which contrasts with the reduction of these veins’ caliber during remissions (Zeng C ea. Cerebral vein changes in RR MS demonstrated by 3D enhanced T2*w angiography at 3T. Eur Radiol 2013;23:869–78)
Over and above this, MRI’s potential of elucidating the bizarre traits of the MS-lesions vein-relationships (Oeztoprak B ea. The effect of venous anatomy on the morphology of MS lesions: an SWI study. Clinical Radiology 2016;xxx:1–9) won’t be quickly exhausted.
Static and dynamic MRI (plus MRV) appear poised to unlock the mysteries surrounding MS. And to dispel any misconception shrouding the condition’s nature.
In reviewing cines of the lesions’ developments one thing is immediately evident: These damages can’t have been brought about, as is habitually assumed, by a merging of Rindfleisch’s haphazardly scattered microvascular foci of the size of a millet to pea.
Old pathologists described the lesions as ‘punched out’. Early MRI jargon as ‘bumpy’. A recent paper even as ‘single-hit lesions’ .
These expressions’ dynamic connotation, or overtone, must not be missed.
As shouldn’t the vein-related ventricle-based changes’ spread in a direction opposite to the local blood flow.
Reaching its acme in a fireworks display of outbursts of peripheral lesions.
Urging to locate their momentum’s source.