From Dr. Haacke:
A Brief History of the Early Venous Vascular Observations in MS
This section will be developing over time as we review the past and sometimes almost ancient literature related to MS. According to Putnam (1) who discussed vascular abnormalities in MS in 1936, the first observations related to abnormal vasculature or effects related to the vasculature appeared in Cruveilhier (2) in 1839, more than 170 years ago who compared areas of sclerosis with the results of embolism. Rindfleisch (3) noted in 1863 an engorged vessel in the center of a plaque and in the same year Charcot (4) described vascular obstruction in MS. These observations would be noted again and again over the next 135 years. What was missing was the advent of imaging as a tool to investigate the vascular system in three dimensions, something that ultrasound takes a step toward as used by Zamboni and more recently the use of magnetic resonance imaging in the study of cerebro-spinal vascular insufficiency or CCSVI.
But Putnam didn't stop there. With an ingenious idea, he proceeded to study the effects of obstructed venous flow in the cerebral veins of dogs. These animals developed a number of abnormalities many of them similar to encephalitis or multiple sclerosis. His comment at the end of his paper was as follows (5): "The later stages (up to ten months) of the lesions consist of plaques of demyelinization with practically complete preservation of the axis-cylinders and with dense fibrous gliosis confined to the white matter. The similarity between such lesions and many of those seen in cases of multiple sclerosis in man is so striking that the conclusion appears almost inevitable that venular obstruction is the essential immediate antecedent fo the formation of typical sclerotic plaques." Despite the wonderful immunological advances in the last 75 years, how can we ignore the early work that so clearly demonstrates the role of the venous system in MS? The precocious work of these early researchers today finds its laurels in the current extracranial obstructions proposed by and seen by Zamboni (6) and now others.
There are more intriguing connections as one reads these old papers. Venous blood is more prone to clot. And these micro-thrombi may rapidly disappear and so become unobservable. An increase in capillary density also seems to develop and this may well describe the "capillary recruitment for venous drainage hypothesis proposed by Haacke". In this hypothesis, the obstructed flow leads to endothelial damage (7) and iron build up (8) and the need to increase the outflow capacity in the venous system. The brain then recruits capillaries to become veins and these in turn are also damaged leading to further iron deposition. If this is the case, then the iron build up should take place backward along the venous drainage system, which appears to be the case (9).
The story continues with a reference to Borst who founded a theory on the occurrence of vascular obstruction where he mentions the process of significant narrowing to the point of complete obliteration, hyaline transformation, etc. Perivacular hemorrhages were also frequently described by many authors. Borst (10) also mentions the presence of pigments. Others describe the combination of all three: congestion, perivascular hemorrhage and pigments (possibly hemosiderin or iron related) in encephalitis post measles (11). Many noticed venous engorgement and one study showed that thrombi were visualized in nine of seventeen MS cases and all three encephalomyelitis cases.
(1) Putnam (1939). Evidences of vascular occlusion in multiple sclerosis and encephalomyelitis.
(2) Cruveilhier (1839).
(3) Rindfleisch (1863). Histologisches detail zu der grauen degeneration von gehirn und rueckenmark. Arch. Path. Anat. Physiol. Klin. Med. 26: 474.
(4) Charcot (1863).
(5) Putnam (1935). Studies in multiple sclerosis: encephalitis and sclerotic plaques produced by venular obstruction. Archives of Neurology and Psychiatry. 33: 929-940.
(6) Zamboni (2009). Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 80:392-399.
(7) Adams 1987. Periventricular lesions in MS. Neuropathol Appl Neurobiol. 13: 141.
(8) Singh and Zamboni (2009). Anomalous venous blood flow and iron deposition in multiple sclerosis Anomalous venous blood flow and iron deposition. JCBF 1-12.
(9) Haacke et al. Evidence of an increase in basal ganglia and thalamic iron content in multiple sclerosis and its vascular implications: An initial analysis with susceptibility weighted imaging. Submitted to Intern. Angiology.
(10) Borst Anatomica 9, 67, 1903 Die multiple sklerose des zentranervovensystems.
(11) F. Wohlwill. Ueber encephalomyelitis. Neurol and Psychiat, 112: 20, 1928.