By
Charles M. Poser MD FRCP
Neurological complications of immunizations have been recorded
in the medical literature for many years, yet many physicians
fail to recognize their clinical manifestations and identify
their etiology. This is due in part to their rarity, and to
the well-publicized, overriding public health benefits that
make these complications easily overlooked. Yet they can be
devastating despite the fact that early treatment is often
successful.
A great deal of knowledge regarding their pathogenesis has
accumulated over the years based on the existence of excellent
animal models of the human disease, acute disseminated encephalomyelitis,
the commonest neurological manifestation of an adverse immune
response to vaccines. Experimental allergic encephalomyelitis
and neuritis faithfully reproduce the pathologic alterations
of the nervous system that may complicate immunizations.
Adverse reactions involving the nervous system from a wide
variety of immunizations result from the same pathogenetic
mechanism. They may affect any and all parts of the central
and peripheral nervous systems. With rare exceptions, e.g.
rubella immunization, the nature of the vaccine does not seem
to influence the nature of the response.
Thus the nervous system ailments include many different clinical
forms, ranging from the classic acute disseminated encephalomyelitis
to aseptic meningoencephalitis. In rare instances, in the
case of live viruses, e.g. polio and smallpox, an actual infection
by the virus itself may ensue. Many different vaccinations
involving many different sites in the nervous system have
been reported. This is particularly true of vaccines commonly
used in children against measles, varicella and rubella.
The pathogenetic mechanism is as follows: the primary effect
of the hyperergic (immune) reaction is on the small blood
vessels of the nervous system, usually capillaries, but occasionally
involving arterioles and venules; in exceptional circumstances,
even major arteries such as the carotid may be affected. The
vasculopathy may cause vessel obstruction and ischemia, a
stroke. Rupture of the vessel wall results in hemorrhage.
More commonly, however, there is alteration of the blood-brain
barrier, exsudation of water and edema (swelling) of nervous
tissue. 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 known
as acute hemorrhagic leukoencephalopathy, which despite its
awesome appearance is usually responsive to vigorous treatment.
The extent of pathological involvement of nervous tissue
also varies greatly, as seen in vaccination against measles,
mumps and varicella. In infants, brain swelling, also known
as congestive edematous encephalopathy, may be the only complication,
a condition that often responds dramatically to treatment
with corticosteroids. It occurs most commonly in vaccination
against smallpox.
The diagnosis of acute disseminated encephalomyelitis, the
commonest complication of vaccinations in both children and
adult, has been aided by magnetic resonance imaging (MRI).
The pictures are reasonably characteristic, yet, unfortunately,
despite many published descriptions, these images are not
always correctly interpreted, and are often misread as those
of multiple sclerosis.
There is also some confusion in terminology: "encephalitis"
and "meningoencephalitis" refer to actual invasion
of the brain by a virus, while "encephalopathy"
is a generic term that simply describes a pathological condition
of the brain; "encephalomyelitis" refers to an "allergic"
or immune reaction of the nervous system. It is the latter
term that should be generally used for the nervous system
complications of vaccinations.
The official publications that commented on the ill effects
of the 1976 swine-flu (A-New Jersey 76) vaccination campaign
illustrate the problems that arise when there is need to extrapolate
scientific data to judicial considerations. The report stating
that the Landry-Guillain-Barré syndrome (LGBS) was
the only "real" complication of the swine-flu vaccine
passed over published reports to the contrary. The statement
that there had been underreporting of complications was simply
ignored. The accepted view is that if an adverse reaction
does not reach the magical figure of 5 percent, it does not
exist.
The reverence accorded to statistical analyses overlooks
the value of anecdotal reports in constructing valid medical
hypotheses; this is despite the warnings by respected epidemiologists
that such studies can never deny the existence of a cause-and-effect
relationship. This is illustrated by the report of nervous
system complications following vaccination against hepatitis
B. Another problem arose from the decision to limit the "acceptable"
time period of onset after immunization, which ignored a number
of reports of well-documented delayed reactions.
In the last few years a new mantra has emerged to the effect
that all published results such as proposed new treatments,
must meet the test of being "evidence-based," which
means that they must be derived from statistically verified
data. Thus calculations of probabilities, also known as educated
guesses, will take precedence over clinical, pathological,
radiological or experimental data. Close examination of some
specific situations will reveal the flaws of this concept.
There is no way of predicting who will have an adverse reaction
to vaccination. The individual’s susceptibility is determined
by the genetic background and previous immunological history.
We are constantly exposed to a wide variety of viral antigens
that cause our immune system to develop antibodies against
them. The phenomenon of molecular mimicry explains why some
people’s immune system will mistakenly respond to the
measles antigen, for instance, in the vaccine because some
of its amino acid groupings, its epitopes, are the same as
those in the protein of a previously encountered viral antigen.
This is why there was an unexpected preponderance of people
in 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 also
germane 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 the
vaccines’ constituents.
Physicians often neglect to ask about previous vaccinations
when confronted with puzzling neurological illness. Most of
them appear to have been convinced that immunizations are
completely harmless. Many also believe that such reactions
must occur within one month from vaccination, and therefore
do not inquire about immunizations in previous months.
Because of the expense of testing drugs, vaccines and other
medical products, the pharmaceutical industry has assumed
an increasingly important role in the conduct of therapeutic
trials and post-marketing surveillance. This is both understandable
and often beneficial. On the downside, however, is the appearance
of conflict of interest when the analyses of the results are
carried out by the pharmaceutical firm itself, or the government
agency charged with guarding the safety of the product.
Dr. Poser is visiting professor of neurology,
Department of Neurology, Harvard Medical School, Boston, and
is senior neurologist with Beth Israel Deaconess Med Center
in Boston.
[Copyright 2003 by the author. First printed
in Mealey's Litigation Report, Thimerosal & Vaccines,
Volume 1, Issue #10, April 2003]
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