A sad truth of life is that we are often unappreciative of important things until they are lost. Our most precious asset is our intact nervous system. To experience its impairment, hopefully only transiently, provides all of us with a healthy respect for the importance of its integrity.

Our brains, spinal cords, and spinal nerves are protected externally by the armor of the skull and spinal column and internally by the meninges. The thick dura mater also serves to protect the inner structures. The thin and delicate pia mater and arachnoid membranes exist to nourish and support neural tissue. Cerebrospinal fluid is created in the spinal subarachnoid space and flows over the surface of the brain where it is reabsorbed into our circulatory systems. The subarachnoid space is a very delicate and fragile structure. A more pristine ecological environment does not exist in our body. This fragility allows only a slight tolerance for insult. The subarachnoid space is the true "salum sactorum" of the human body.

Despite this observation the subarachnoid space is a medical roadway occasionally traveled for the purpose of spinal anesthesia, myelography, intra-thecal catheters for drug infusion, etc. The sensitivity of the subarachnoid space to foreign body substances was well demonstrated by an epidemic of permanent paralysis relating to spinal anesthesia in the United States in the 1950s. This was before the advent of disposable syringes and needles. It was subsequently determined that the etiology of these disastrous complications was the presence of minute particles of simple detergent remaining in the syringes after cleaning. Even today the medical insurance rates relating to performance of spinal anesthesia remain high because of this experience. What have we learned from this experience? Actually not much.

The sanctity of the subarachnoid space has been severely tested in the 20th century. The desire to radiographically outline this area of the body for diagnostic purposes led to the introduction of air myelography by Dandy in 1919. This was subsequently followed by the introduction of thorium dioxide (Thorotrast) which, unlike air, provided excellent x-ray images. Thorium’s major liability turned out to be its radioactivity and long half-life. The risks associated with its use did not become evident until many years had passed. It was only when clinicians began to investigate the epidemic of resulting malignant brain and spinal cord tumors that the connection was made and Thorotrast ceased to be used.

Lipiodol replaced Thorotrast as a myelographic agent in the 1920s. This oil based chemical was, however, recognized as being highly neurotoxic soon afterwards. This discovery was vividly pointed out by neurosurgeon Eric Oldberg in a 1940 editorial referencing Lipiodol:

"Anyone who has had perforce to dig about in the soggy mess which is the cauda equina of some unfortunate in whom five or ten cubic centimeters of lipiodol had been optimistically injected a year or two previously will understand this statement. Not only is the original disease still present, but a chronic, adhesive, chemical inflammation of the caudal roots has been engrafted upon it."

The desire to find a more acceptable alternative to Lipiodol led, in the 1940s, to the introduction of the oil-ester based chemical iophendylate (Pantopaque, Myodil). "With the assurance from the initial experimental studies that it was "safe" Steinhausen and associates, in 1942, advocated the routine use of iophendylate for spinal myelography. In truth iophendylate was never shown to be "safe" in experimental animals. The neurotoxicity of iophendylate turned out to be only slightly less than Lipiodol. It took a period of almost 50 years and about 5 million iophendylate myelograms before this fact even began to enter into the medical profession’s awareness of the issue. Even as we approach the end of the millenium there still exists scant understanding or general knowledge regarding this subject. This has been due, in large part, to a failure in releasing known adverse animal experimental data.

Early concerns regarding iophendylate were expressed, however, in some medical communities throughout the world. This was particularly so in Sweden where the quest to develop water-soluble alternatives to iophendylate was initiated in the late 1940s. As opposed to the toxic effects of the oil based chemicals the side-effects of the water soluble alternatives tended to be immediate, and were, at first, quite drastic. Today’s non-ionic water soluble myelographic agents represent a major advance in decreasing patient risk.

Due to the development of high resolution non-invasive MRI scanning there is now a much reduced need for myelography. When water-soluble dyes are used appropriately their risk is low and the benefit to the patient can be high. When they are used inappropriately (wrong agent, wrong concentration, etc.) they continue to have the potential of being highly toxic to the tissues of the nervous system. The unknown factor in all cases of introducing a foreign body substances into the subarachnoid space is the nature of any given individual’s auto immune response to it. Examples of this phenomenon abound in medicine. Most are familiar, as with the anaphylactic potential of penicillin and more are now becoming aware of the allergic potential of other common substances including household cleaners, latex, etc.

The adverse sequela relating to the introduction of foreign body substances into the body’s "salum sactorum" remains a game of chance for the patient. When the reactions are of an acute nature (i.e. the wrong concentration of a water-soluble contrast agent) the resulting nerve injury can be similar, in clinical signs and symptoms, to those resulting from the body’s exposure to environmental nerve gas or the ingestion of neurotoxins. The picture is often that of transient, or permanent, neurologic dysfunction and/or incapacitation. The present lack of information and general education regarding these issues is appalling. It means that there is a lack of informed consent for the patient and also precludes the possibility of patient pre-treatment with medications which can be effective in preventing the serious known potential adverse side-effects.

Today the most serious example of the dumping of toxic chemicals into the subarachnoid space relates to the widely unappreciated serious complications of inadvertently depositing the steroid preparations Depo-medrol or Depo-medrone during the common practice of epidural steroid injection intended to relieve back pain. Many cases of incapacitating adhesive arachnoiditis have now been observed as a result of this.

While there remain patients who still require the placement of foreign body substances into their subarachnoid spaces for diagnostic and therapeutic purposes this is something which clearly needs to become obsolete in the future. If only some of the energetic activism presently occupying the world’s attention on environmental issues could be directed to concerns regarding the ecological sanctity of the subarachnoid space.

P.S.
The title of Dr. Oldberg’s 1940s editorial was:

"A PLEA FOR RESPECT FOR THE TISSUES OF THE CENTRAL NERVOUS SYSTEM"

Charles V. Burton, M.D.
March 13, 1999
Minneapolis, Minnesota