Neurologic Complications of absence of any systemic symptoms is of both studies are very suggestive of

Tetanus Toxoid related to tetanus toxoid. a specific adverse CNS side effect of

To the Editor.\p=m-\Hollidayand Bauer Case reports are often misleading anticholinergic therapy, it is not cer-
and have caused considerable mis¬ tain that the deficits are clinically
(Archives 1983;40:56-57) described a chief in other vaccine programs.7 Only meaningful in most cases. We suspect
patient in whom polyradiculoneuritis, by prospective epidemiologie studies that they definitely might be in some
and possible myelitis, developed with-
can the risks of immunization be mea¬ patients, especially in those receiving
in hours of immunization with teta-
sured. higher dosages or multiple anticholin¬
nus and diphtheria toxoids, claiming a
cause-and-effect relationship. They
Gerald M. Fenichel, MD ergic drugs. Further experimental
Department of Neurology studies are needed to define fully the
indicated that neurologic complica- Vanderbilt School of Medicine
tions of immunization with combined Nashville, TN 37232 potential severity of this adverse side
effect. Given the age-related declines
tetanus and diphtheria toxoids have 1. Whittle E, Roberton NRC: Transverse in cholinergic functioning,2 it may be
not been reported and concluded that myelitis after diphtheria, tetanus, and polio that older patients, and thus most
tetanus toxoid was probably responsi- immunisation. Br Med J 1977;1:1430-1431.
ble for the adverse reaction. In fact, 2. Ehrengut W: Ueber neurale Komplikation- patients with Parkinson's disease, are
there have been reports of transverse en nach diphterieschutzumpfung oder unipfung- especially susceptible to the effects of
en mit Diphteriertoxoid-mischimpfstoffen. Mon-
myelitis1 and encephalitis2 after atsschr Kinderheilkd 1969;112:331-338.
anticholinergic drugs. However, an¬
other recent study3 has also shown
immunization with diphtheria and 3. Quast U, Hennessen W, Widmark RM:
detrimental effects
tetanus toxoids, but the more impor- Mono- and polyneuritis after tetanus vaccination on memory of
tant issue is whether the tetanus tox- (1970-1977). Dev Biol Stand 1979;43:25-32. anticholinergic therapy in psychiatric
oid immunization in this and other
4. Pollard JD, Selby G: Relapsing neuropathy
due to tetanus toxoid. J Neurol Sci 1978;37:113\x=req-\
patients, thus expanding the range of
reports was responsible for the subse- 125. conditions, ages, and drugs evidencing
5. Jacobs RL, Lowe RS, Lanier BQ: Adverse such effects. It is clear from these
quent neurologic disorder. reactions to tetanus toxoid. JAMA 1982;247:40\x=req-\ various studies that specific memory
The only link between the immuni- 42. effects should be monitored in future
zation and the polyradiculoneuritis 6. Myers MG, Beckman CW, Vosdingh A, et al:
was the temporal relationship. That is Primary immunization with tetanus and diph-
clinical trials of anticholinergic medi¬
theria toxoids: Reaction rates and immunogenic- cations in a wide range of patients and
not a strong link, as it seems unlikely
that a widespread allergic reaction of ity in older children and adults. JAMA treatments, including treatments not
1982;248:2478-2480. directed at the CNS.
the nervous system would develop 7. Fenichel GM: The pertussis vaccine contro- Karl Syndulko, PhD
within hours of immunization in the versy: The danger of case reports. Arch Neurol Wallace W. Tourtellotte, MD, PhD
absence of systemic symptoms. There 1983;40:193-194. Department of Neurology
are rare reports of neuropathy and School of Medicine
cranial neuropathy occurring within University of California
Effect of Anticholinergics on Los Angeles, CA 90024 and
hours of tetanus toxoid immuniza¬ Wadsworth Veterans Administration
Memory in Parkinson's Disease
tion,3 but the cause-and-effect rela¬ Medical Center
tionship in those reports is also To the Editor.\p=m-\Weread with interest Los Angeles
unproved. The clearest evidence of a the recent paper by Sadeh and col- 1. Syndulko K, Gilden ER, Hansch EC, et al:
neurologic complication secondary to leagues (Archives 1982;39:666-667). Decreased verbal memory associated with anti-
tetanus toxoid immunization is the Although they did not refer to our cholinergic treatment in Parkinson's disease
case described by Pollard and Selby.4 study, their results supported our patients. Int J Neurosci 1981;14:61-66.
2. Perry EK, Perry RH, Gibson P, et al: A
Their patient was a 42-year-old man published findings on the effect of cholinergic connection between normal aging
who suffered three episodes of Guil- anticholinergic drugs on memory in and senile dementia in the human hippocampus.
lain-Barré syndrome, each following patients with Parkinson's disease.1 Neurosci Lett 1977;6:85-89.
administration of a tetanus toxoid. We specifically compared the effects 3. Tune LE, Strauss ME, Lew MF, et al: Serum
The episodes were separated by nine levels of anticholinergic drugs and impaired
of therapeutic doses of the anticholin- recent memory in chronic schizophrenic patients.
and five years, and the intervals ergic benztropine mesylate v a place- Am J Psychiatry 1982;139:1460-1462.
between immunization and the onset bo, in a double-blind, crossover study.
of symptoms were three weeks, two We found that administration of In Reply. \p=m-\We regret having been
weeks, and nine days. As Holliday and benztropine for a ten-week period unaware of the study by Dr Syndulka
Bauer pointed out, tetanus toxoid has resulted in a statistically significant and colleagues while we were engaged
an excellent safety record. The imme¬ impairment of delayed recall of verbal in our own. It is satisfying to learn
diate adverse reactions are character¬ material. No significant effects were that other authors have reached con-
ized by local edema and tenderness, found in immediate recall (digit span clusions similar to ours.
fever, and systemic anaphylactoid forward or backward) or performance Although we suggested that our
responses.5·6 Although it is reasonable on Raven's Coloured Progressive findings might have important impli-
to accept the development of Guil- Matrices or the Symbol Digit Modali- cations for patients engaged in occu-
lain-Barré syndrome one to three ties Test. We found no significant pations in which even a mild degree of
weeks after tetanus toxoid immuniza¬ relationship between the adverse memory impairment could be dis-
tion as a possible adverse reaction, memory effect and the positive thera- abling, we agree that these adverse
there is no basis for accepting that peutic effect of the anticholinergic side effects are not always critical for
polyradiculoneuritis occurring within drug on parkinsonian symptoms. the overall functional status of the
hours of immunization and in the Although the experimental findings patient. Indeed, some of our patients

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