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The History Caring for a loved one with CJD Getting tested for the CJD Mutation
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ENVIRONMENTALLY-ACQUIRED CJD Environmentally-acquired
cases of CJD are either ‘iatrogenic’ (meaning that they are unknowingly
caused by physicians), or more recently, infectious due to the consumption
of contaminated beef from cattle with BSE.
Fortunately, the number of such cases remains comparatively small,
and measures have been taken to prevent future infections.
Nevertheless, because we did not immediately appreciate the causes of
these acquired infections, and because the period of time elapsing between
infection and illness can be so long, new cases of CJD continue to occur
after longer and longer incubation periods from infections acquired during
the 1970s and 1980’s. Iatrogenic CJD Person-to-person
transmission of CJD was first recognized in 1973 in a patient who 18
months earlier had received a corneal graft from a donor who was only belatedly
discovered to have died of CJD. Stereotactic
EEG electrodes were implicated in two cases of CJD a few years later, and
retrospective studies have identified a handful of cases that most probably
resulted from inadequately sterilized neurosurgical instruments.
Apart from two possible further cases of CJD from corneal grafts, all
other known cases of iatrogenic CJD have been caused by contaminated
pituitary hormones, or contaminated grafts of dura mater (the protective
membrane that surrounds the brain). The current world-wide tally of
iatrogenic CJD from all causes is approximately 250 cases. The
clinical features of iatrogenic disease appear to depend upon the route of
infection. Intracerebral
infections (neurosurgery and corneal grafts via the optic nerve) have
incubation periods of about one and a half years and a clinical presentation
similar to sporadic CJD; cerebral surface infections (dura mater grafts)
have incubation periods ranging from one and a half to 18 years (average, 6
years) and diverse clinical presentations; and peripheral route infections
(pituitary hormones) have an even wider range of incubation periods
(average, 12 years), with prominent incoordination and a course of illness
marked by little if any mental deterioration. Variant CJD (vCJD) The other source of
environmentally acquired CJD, now called ‘variant CJD’ (vCJD) first
appeared in 1994 and has since been occurring at a more or less steady rate
of about 10-20 new cases per year. As
of January 2001 it had been responsible for 93 cases in the United
Kingdom, three cases in France, and one case in the Republic of Ireland.
Strictly speaking, its only association with BSE is that both
diseases are largely confined to Great Britain.
However, epidemiologic, biologic, and molecular biologic evidence has
converged to implicate infection by BSE as the cause of vCJD, and a
consideration of slaughtering practices has revealed numerous ways by which
beef could have become contaminated with tissue from the central nervous
system. Clinically, the most
striking feature of vCJD is the youthfulness of its victims, who range in
age from 14 to 52 years (average, 28 years), and thus clearly separate from
the major 55-75 year age bracket of sporadic disease. The clinical presentation seen in most patients
consists of psychiatric or sensory symptoms, rather than the usual mental-cerebellar-visual
onset of sporadic disease. The illness progresses at a comparatively leisurely pace,
with an average duration of 14 months, and no case dying in less than 7
months. Eventually, most of the
features of sporadic disease appear, including dementia and myoclonus, but
no case has shown a periodic EEG. Because each of these features has also
occurred in cases of sporadic CJD, a definitive diagnosis of vCJD can only
be established at autopsy by the unique microscopic finding of plaques
surrounded by petals of spongiosis (‘daisy’ plaques). Predictions about the
future extent of the outbreak remain shrouded in uncertainty, and
mathematical modeling has produced estimates from a few hundred to more than
a hundred thousand cases, almost all of which would be in residents of Great
Britain. However, BSE has
occurred in much lower incidence in other European countries as a result of
imported livestock protein supplements made from the rendered carcasses of
British cattle, and potentially contaminated British beef continued to be
exported to other (mainly European) countries during the 1980’s when the
BSE epidemic was evolving. The
fact that three cases of vCJD have occurred in French citizens who had never
visited Britain signals the probability that at least a few cases will occur
in other European countries, and perhaps also in long-term visitors to Great
Britain. The implications of
this for iatrogenic transmission of CJD as a result of incubating infections
in apparently healthy people who are undergoing surgery, donating blood, or
being used as sources of organ transplants, continue to create enormous
concern among physicians, scientists, governments, and the general public. Prevention
and therapy
Two approaches are possible for environmentally-acquired disease:
eliminate the sources of infection, and block the routes of invasion from
the periphery of the body to the brain.
As noted, the sources of both iatrogenic and BSE infections have to
the best of our knowledge been either eliminated or reduced to a level that
is too low to be detected. Erecting barricades to the passage of the infectious agent to
the brain has recently shown some promise in experimental models, but
remains imperfect and far from being ready for human clinical trials.
The major problem is that infectivity in these models can be tracked
along at least two, and possibly three different routes to the brain: one
route passes through the spleen and spinal cord, one route passes directly
to the brain via nerves, and a possible third route reaches the brain via
the bloodstream. In
consequence, any effective therapy is going to have to be capable of
blocking all three routes, and will almost certainly require more than one
blocking strategy and more than one drug. Work is going on in several laboratories to develop a screening test
to identify infected individuals before their symptoms begin. If
such a test can be developed, its application in combination with early
preventive drug therapy may finally spell an end to these rare but
ravaging diseases. |
