Iatrogenic Disease

Pathogenesis and Pathophysiology. Iatrogenic disease poses no difficulty in regard to pathogenesis; when the infectious agent is accidentally introduced into the body, whether directly into the nervous system or by peripheral routes, the seed is sown for its replication and spread, and the disease eventually appears when infectivity and neuropathology have reached a high enough level. The length of the incubation period between the infecting event and the onset of symptomatic disease ranges from about 2 years in cases in which infection is introduced directly into the brain, to an average of nearly 15 years in those who are inoculated subcutaneously (and some incubation periods are as long as 20 to 30 years).

Epidemiology. Iatrogenic disease, which is fortunately still rare but is increasing every year, is the only category of these diseases that may be said to lend itself to the kind of traditional detective work practiced by field epidemiologists. The first case was recognized in the early 1970s in a U.S. recipient of a corneal graft from a patient who was later discovered to have died from CJDy ; soon afterward, two cases occurred in Swiss patients who had undergone stereotactic electroencephalography with needles that had been previously used in a patient with CJD. y A few years later, retrospective analysis of a series of British neurosurgical cases revealed that three of the patients had probably been infected by surgical instruments contaminated in an earlier operation on a CJD patient. y These few reports constituted the totality of iatrogenic disease until the past decade, when separate outbreaks of disease were traced to contaminated batches of pituitary hormones and dura mater grafts obtained from human cadavers.y , y There are currently nearly 200 recognized cases of iatrogenic disease from all causes, and a few cases of CJD in patients treated with growth hormone continue to appear each year, with increasingly longer incubation periods between the cessation of cadaveric hormone therapy in 1985 and the onset of CJD (... Table. ...43-3 ).

Clinical Features and Associated Disorders. Iatrogenic disease syndromes are significantly influenced by

TABLE 43-3 -- IATROGENIC CREUTZFELDT-JAKOB DISEASE

Mode of Infection

Number of Patients

Agent Entry into Brain

Mean Ineubation Period (range)

Clinical Presentation

Corneal transplant

2

Optie nerve

17 mo (1B, 18)

Dementia/cerebellar

Stereotaetie EEG

2

Intra-eerebral

18 mo (1B, 20)

Dementia/eerebellar

Neurosurgery

4

Intra-eerebral

20 mo (15-28)

Visual, dementia/eerebellar

Dura mater graft

B8

Cerebral surfaee

S 5 yr (1.5-1B)

Cerebellar (visual, dementia)

Gonadotrophin

4

Hematogenous

13 yr* (12-1B)

Cerebellar

Growth hormone

103

Hematogenous

12 yr* (5-30)

Cerebellar

* Calculated from mid-point of therapy to onset of CJD.

different routes of infection. 33] Introduction of the infectious agent into the brain parenchyma, directly or via the optic nerve, produces an illness that is in all respects similar to sporadic CJD. Introduction of the agent into the brain by a peripheral route of infection (hormone therapy) produces a distinctively different illness that begins with ataxia and even in its later stages may not include significant mental deterioration; this syndrome is strongly reminiscent of kuru, which was also acquired through peripheral routes of infection. Application of the agent to the brain surface through dura mater grafts produces an illness with intermediate characteristics, comprising either prominent cerebellar/visual or demential features. The duration of illness is unrelated to the route of infection, and the disease runs a course similar to that of sporadic CJD.

Evaluation. Periodic EEG activity has been seen in about half of all patients, and the CSF tests positive for the "14-3-3" proteins in most patients in whom it has been examined; this positive result was especially important in some of the earlier hormone-treated cases, when the link between hormone contamination and CJD was still tenuous.

Management, Treatment, and Prevention. Good nursing care and attention to symptomatic relief of movement disorders remain the only palliative measures available for these unfortunate victims of our own mistakes. The prevention of future episodes of iatrogenic disease is therefore an object of increasingly close scrutiny by physicians, research scientists, and government regulatory agencies alike.

In the past, neurosurgical instruments were subjected to the standard 15 to 30 minutes of steam autoclaving at 131° C; EEG needles were disinfected with benzene, ethanol, and formaldehyde vapor; cadaveric pituitary tissue extracts were sequentially passed through glacial acetic acid, acetone, and dilute NaOH; and dura mater grafts were irradiated. We know now that none of these procedures can be fully guaranteed to inactivate the infectious agent. y y [sel y

Therefore, the time and temperature requirement for steam autoclaving of neurosurgical instruments has been raised to 1 hour at 134° C, stereotactic EEG needles are discarded after each use, and pituitary hormones are made with recombinant technology rather than from cadaveric sources. Dura mater grafts are exposed to high (1N) concentrations of NaOH or avoided in favor of synthetic membrane patches. Renewed attention is being paid to other potential sources of infection from human-to-human transfers of tissue, tissue extracts, and blood or plasma derivatives; donors at higher than usual risk of CJD such as growth hormone recipients or members of CJD families are screened out, and chemical or filtration processing steps are being devised to eliminate any potential contamination of biological products.

PreviousNext

Unraveling Alzheimers Disease

Unraveling Alzheimers Disease

I leave absolutely nothing out! Everything that I learned about Alzheimer’s I share with you. This is the most comprehensive report on Alzheimer’s you will ever read. No stone is left unturned in this comprehensive report.

Get My Free Ebook


Post a comment