ByCharles M. Poser MD FRCP
Neurological complications of immunizations have been recordedin the medical literature for many years, yet many physiciansfail to recognize their clinical manifestations and identifytheir etiology. This is due in part to their rarity, and tothe well-publicized, overriding public health benefits thatmake these complications easily overlooked. Yet they can bedevastating despite the fact that early treatment is oftensuccessful.
A great deal of knowledge regarding their pathogenesis hasaccumulated over the years based on the existence of excellentanimal models of the human disease, acute disseminated encephalomyelitis,the commonest neurological manifestation of an adverse immuneresponse to vaccines. Experimental allergic encephalomyelitisand neuritis faithfully reproduce the pathologic alterationsof the nervous system that may complicate immunizations.
Adverse reactions involving the nervous system from a widevariety of immunizations result from the same pathogeneticmechanism. They may affect any and all parts of the centraland peripheral nervous systems. With rare exceptions, e.g.rubella immunization, the nature of the vaccine does not seemto influence the nature of the response.
Thus the nervous system ailments include many different clinicalforms, ranging from the classic acute disseminated encephalomyelitisto aseptic meningoencephalitis. In rare instances, in thecase of live viruses, e.g. polio and smallpox, an actual infectionby the virus itself may ensue. Many different vaccinationsinvolving many different sites in the nervous system havebeen reported. This is particularly true of vaccines commonlyused in children against measles, varicella and rubella.
The pathogenetic mechanism is as follows: the primary effectof the hyperergic (immune) reaction is on the small bloodvessels of the nervous system, usually capillaries, but occasionallyinvolving arterioles and venules; in exceptional circumstances,even major arteries such as the carotid may be affected. Thevasculopathy may cause vessel obstruction and ischemia, astroke. Rupture of the vessel wall results in hemorrhage.
More commonly, however, there is alteration of the blood-brainbarrier, exsudation of water and edema (swelling) of nervoustissue. Inflammation and disorganization of the myelin lamellae(layers) and destruction of myelin may ensue but are not obligatory.In some cases, there is sufficient red blood cell diapedesis(migration through the vessel wall) to produce what is knownas acute hemorrhagic leukoencephalopathy, which despite itsawesome appearance is usually responsive to vigorous treatment.
The extent of pathological involvement of nervous tissuealso varies greatly, as seen in vaccination against measles,mumps and varicella. In infants, brain swelling, also knownas congestive edematous encephalopathy, may be the only complication,a condition that often responds dramatically to treatmentwith corticosteroids. It occurs most commonly in vaccinationagainst smallpox.
The diagnosis of acute disseminated encephalomyelitis, thecommonest complication of vaccinations in both children andadult, has been aided by magnetic resonance imaging (MRI).The pictures are reasonably characteristic, yet, unfortunately,despite many published descriptions, these images are notalways correctly interpreted, and are often misread as thoseof multiple sclerosis.
There is also some confusion in terminology: "encephalitis"and "meningoencephalitis" refer to actual invasionof the brain by a virus, while "encephalopathy"is a generic term that simply describes a pathological conditionof the brain; "encephalomyelitis" refers to an "allergic"or immune reaction of the nervous system. It is the latterterm that should be generally used for the nervous systemcomplications of vaccinations.
The official publications that commented on the ill effectsof the 1976 swine-flu (A-New Jersey 76) vaccination campaignillustrate the problems that arise when there is need to extrapolatescientific data to judicial considerations. The report statingthat the Landry-Guillain-Barré syndrome (LGBS) wasthe only "real" complication of the swine-flu vaccinepassed over published reports to the contrary. The statementthat there had been underreporting of complications was simplyignored. The accepted view is that if an adverse reactiondoes not reach the magical figure of 5 percent, it does notexist.
The reverence accorded to statistical analyses overlooksthe value of anecdotal reports in constructing valid medicalhypotheses; this is despite the warnings by respected epidemiologiststhat such studies can never deny the existence of a cause-and-effectrelationship. This is illustrated by the report of nervoussystem complications following vaccination against hepatitisB. Another problem arose from the decision to limit the "acceptable"time period of onset after immunization, which ignored a numberof reports of well-documented delayed reactions.
In the last few years a new mantra has emerged to the effectthat all published results such as proposed new treatments,must meet the test of being "evidence-based," whichmeans that they must be derived from statistically verifieddata. Thus calculations of probabilities, also known as educatedguesses, will take precedence over clinical, pathological,radiological or experimental data. Close examination of somespecific situations will reveal the flaws of this concept.
There is no way of predicting who will have an adverse reactionto vaccination. The individual’s susceptibility is determinedby the genetic background and previous immunological history.We are constantly exposed to a wide variety of viral antigensthat cause our immune system to develop antibodies againstthem. The phenomenon of molecular mimicry explains why somepeople’s immune system will mistakenly respond to themeasles antigen, for instance, in the vaccine because someof its amino acid groupings, its epitopes, are the same asthose in the protein of a previously encountered viral antigen.
This is why there was an unexpected preponderance of peoplein their 50s and 60s who developed LGBS after swine-flu vaccination,because they might have been exposed to the "Asian flu"caused by a somewhat similar virus in the 1920s. It is alsogermane to point out that vaccines contain a number of substances,many of them as antigenic as the one for which they were designed.Preservatives may also contribute to the adverse side effects.It is extremely difficult to distinguish the effects of thevaccines’ constituents.
Physicians often neglect to ask about previous vaccinationswhen confronted with puzzling neurological illness. Most ofthem appear to have been convinced that immunizations arecompletely harmless. Many also believe that such reactionsmust occur within one month from vaccination, and thereforedo not inquire about immunizations in previous months.
Because of the expense of testing drugs, vaccines and othermedical products, the pharmaceutical industry has assumedan increasingly important role in the conduct of therapeutictrials and post-marketing surveillance. This is both understandableand often beneficial. On the downside, however, is the appearanceof conflict of interest when the analyses of the results arecarried out by the pharmaceutical firm itself, or the governmentagency charged with guarding the safety of the product.
Dr. Poser is visiting professor of neurology,Department of Neurology, Harvard Medical School, Boston, andis senior neurologist with Beth Israel Deaconess Med Centerin Boston.
[Copyright 2003 by the author. First printedin Mealey's Litigation Report, Thimerosal & Vaccines,Volume 1, Issue #10, April 2003]