8.6 Perivenous syndrome

First, all sons and daughters, take your father out to dinner on Sunday.

Happy Father's Day!

We will now touch upon the "perivenous syndrome". Perhaps the best explanation is that in Prof Philip James's " Hyperbaric oxygenation in fluid microembolism", Neurol Res, 29(2): 156-161(6), 2007:

[Abstract] "...Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid..."

Having already gone over the principle and practice of NMR, now a quick review of the current treatment of multiple sclerosis (MS):

MS, despites years of research, still does not have an agreed upon etiology. Since the principal symptom is inflammation, treatments thus far have targeted it by using anti-inflammatories. For acute relapses, patients with relapse-remitting MS are treated with steroids usually intravenous methylprednisolone (IVMP). For longer-term maintenance, there are the interferons, IFN1a and INF1b, that can block immune factors known as class II MHC molecules. With this treatment, the T cells can no longer breach the blood-brain barrier to cause cerebral damages.

The search for a better alternative to interferons culminated in 2004 when natalizumab, a monoclonal antibody, was approved for MS treatment. However, shortly after, reports of a rare progressive multifocal leukoencephalopathy (PML) surfaced. This new drug was withdrawn from the market in Feb, 2005. And after extensive reviews, in June, 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. The benefits of natalizumab, either by itself or in conjunction with IFNa1 seem to outweigh the risks according to several 2006 reports. So MS patients actually do have treatment choices and many are well-managed by their neurologists.

Of course, there are always other drugs being developed and tested, for example, the immunosuppressants, the statins, estrogen, even the cannabinoids. Also being tested are stem-cell implants and plasmapheresis. Preliminary results are somewhat mixed in most if not all cases.

Most intriguing, however, is the hyperbaric oxygen treatment (HBOT) of MS. In fact, the efficacy of HBOT has been reported in as early as 1983 (for details, see: Fischer BH et al. Hyperbaric oxygen in the treatment of multiple sclerosis; a randomised placebo-controlled double-blind trial. New Eng J Med 1983;308:181-186).

Because of the venous leakage that causes inflammation in the surrounding area, the treatment principle is to provide the repairing process the best environment before sclerosis sets in. And one of the major environmental factors is indeed oxygen. Logically, then HBOT should be employed urgently as it it the best way of delivering oxygen.

Treating early stage MS is now possible with the advent of MRI and MRS (and eventually, the 4-dimensional NMR spectroscopy). To firmly establish HBOT as the treatment of choice, large-scale double-blind studies based on MR technology must be conducted. The focus will be on the level of lactate, the 1.35-ppm resonance [note: its chemical shift is pH-dependent], th index of anaerobic glucose metabolism.

In fact, all eye doctors should be on the lookout for patients with early MS - pay more attention to a complaint of diplopia for one thing, and do take retrobulbar pains seriously. A judicious referral for MRI scan is mandatory. The treatment choices also must be presented and explained to the patients.

Ideally, those microemboli that cause focal ischemia in MS in the first place should be definitely identified and the method for their removal developed. Something for the near future, perhaps.

Lest we forget: many devastating ocular diseases are ischemic in nature, for example, primary open-angle glaucoma, age-related macular degeneration, and diabetic retinopathy. Is there a role for HBOT in the treatment of these diseases? You tell me.