вход по аккаунту


Campylobacter jejuni and Guillain-Barr syndrome.

код для вставкиСкачать
tron respiratory chain are without doubt more accurate for
the assessment of mitochondrial function as long as the patient’s age is carefully considered in these functional studies
C2-41. Nevertheless, ragged-red fibers, although not specific,
are generally accepted as good indicators of mitochondrial
damage 151.
All our patients underwent conventional manual muscle
testing evaluation in 16 muscle groups at the same time as
myometric recording. To better standardize and compare
groups, statistics were offered on the results obtained with
the myometer in only one muscle [l]. In any case, our 6
asymptomatic patients with ragged-red fibers in muscle tissue
had normal muscle strength in both upper and lower limbs.
Serum creatine kinase was normal or minimally raised, and
the percentage of ragged-red fibers (as indicated in our article) was similar to that found in the remaining symptomatic
patients. Unfortunately, electromyography was not routinely
performed in our patients. We are not familiar with the observation of Chariot and colleagues regarding the selective
clinical involvement of lower limbs in zidovudine-related myopathy, but this is an interesting observation.
As we say in our article, we do not know why some patients with ragged-red fibers are not weak, nor do we know
the real cause of weakness in human immunodeficiency virus
type 1-infected subjects treated with zidovudine. The recent
report of Chariot and colleagues 161 throws some light on
these issues. The crucial role of zidovudine in clinical symptoms that Mhiri and co-workers {7]from the same group
claim, apart from “other possible factors” that we suggest,
seems difficult to sustain with the currently available data. In
their published work, not all patients improved after withdrawal of zidovudine and, furthermore, others were o n steroids. Zidovudine-related myopathy is yet to be fully understood.
Muscle Research Unit
Hospital Clinic Prmkial
080.36 Barcelona, Spain
1. Grau JM, MasanCs F, Pedro1 E, et al. Human immunodeficiency
virus type 1 infection and myoparhy: clinical relevance of zidovudine therapy. Ann Neurol 1993;34:206-211
2 . Muller-Hacker J. Cytochrome c oxidase deficient fibres in the
limb muscle and diaphragm of man without muscular disease: an
age-related alteration.J Neurol Sci 1990;loO: 14-21
3. Trounce I, Byrne E, Marzulci S. Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in ageing.
Lancet 1989;1:637-639
4. Cardellach F, Galofre J, Cuss6 R, Urbano-Mirquez A. Decline
in skeletal muscle mitochondrial respiratory chain function with
ageing. Lancet 1989;2:44-45
5. Olson W, Engel WK, Walsh GO, Einaugler R. Oculocraniosomatic neuromusculardisease with “ragged-red”fibers: histochemical and ultrastructural changes in limb muscles of a group of
patients with idiopathic progressive external ophthalmoplegia
Arch Neurol 1972;26:193-211
6. Chariot P, Monnet I, Gherardi R. Cytochromec oxidase reactions
improves histopathological assessment of zidovudine myopachy.
Ann Neurol 1993;34:561-565
7. Mhiri C, Baudrimont M, Bonne G, et al. Zidovudine myopathy:
a distinctive disorder associated with mitochondrial dysfunction.
Ann Neurol 1991;29:606-614
Annals of Neurology
Vol 35
No 2
February 1994
Cdmpylobdcter jejzmi and
Guillain-Bar6 Syndrome
J. H. Rees and R. A. C . Hughes
Campylobacterjejuni infection is the commonest illness preceding Guillain-Barrt syndrome (GBS) although the exact
relationship between the two is not clearly understood. We
read with interest the reports of Enders and colleagues [ 1}
and Vriesendorp and co-workers [2], who have presented
serological data on 38 and 58 GBS patients, respectively.
Neither study confirmed previous reports of the occurrence
of more severe disease with predominant axonal degeneration and a poorer prognosis in patients with both C . jejuni
infection and anti-glycocon jugate antibodies. This discrepancy may be partly due to the relative lack of specificity
of enzyme-linked immunosorbent assays (ELISAs) against C.
jejuni. In addition patients with stool culture-positive C. j e juni infection d o not always mount an antibody response (as
shown by Enders and colleagues [l] 1, so purely serological
analysis may lead to an underestimate of the true numbers
of infected patients.
To resolve this issue, we are conducting a case control
study of patients with GBS in South East England specifically
looking for evidence of recent C. jejuni infection by stool
cultures as well as serology using a standard ELISA technique. To date, we have successfully isolated C. jejuni from
the stools of 4 of 36 (11%)patients compared with 1 of 49
(2%) controls. Only 2 of these 4 (50%;)patients showed
a significant antibody response. Furthermore, there were 5
additional patients who had strong serological evidence of
recent infection, bringing the number of C. jejuni infected
patients to 9 ( 2 5 % ) . Eight of these 9 patients had experienced diarrhea as an antecedent illness compared with 3 of
27 (11%) C. jejuni-negative patients ( p < 0.001). Five
( 5 5 7 6 ) had a pure motor syndrome, 3 (33%) showed clear
electrophysiological evidence of axonal degeneration, and 7
(78%) had one or more antibodies to glycoconjugates, IgG
anti-ganglioside GM1 being the commonest (6 of 9).
W e believe, therefore, that even with these small numbers
there is a strong association between antecedent C . jrjuni
infection and the development of a pure motor syndrome,
often characterized electrophysiologically by the presence of
axonal degeneration either alone or in combination with demyelination. Furthermore, in accordance with the findings of
Walsh and associates f3] and Gregson and co-workers 141,
the combination of recent C . jejuni infection and positive
anti-ganglioside GM1 antibodies heralds a poor prognosis as
4 of 5 such patients in our series have not made good recoveries. W e agree therefore with Griffin and Ho [5] that further work is required to elucidate the immunopathogenesis
of this intriguing association by detailed analysis of C. ,&mi
isolates from GBS patients and, to that end, have begun
work on extracting the lipopolysaccharide fraction from the
bacterial cell membrane of these strains.
Department of Neurology
UMDS, Guyk Hospital
London S E l 9RT, UK
1. Enders U, Karch H, Toyka KV, et al. The spectrum of immune
responses to Campylubacterjejuni and glycoconjugates in GuilhnBarrC syndrome and in other neuroimmunological disorders. Ann
Neurol 199334:136- 144
2. Vriesendorp FJ, Mishu B, Blaser MJ, Koski CL. Serum antibodies
to GML, G D l b , peripheral nerve myelin, and Campyhbartev jejuni in patients with Guillain-Barrt syndrome and controls: correlation and prognosis. Ann Neurol 1993;34:130-135
3. Walsh PS, Cronin M, Koblar S, et al. Association between glycocon jugate antibodies and Campylubartev infection in patients with
Guillain-Barre syndrome. J Neuroimmunol 1991;34:43-5 1
4. Gregson NA, Koblar S, Hughes RAC. Antibodies to gangliosides
in Guillain-BarrCsyndrome: specificity and relationslp to clinical
features. Q J Med 1993;86:111-1 17
5. Griffin JW, Ho TW-H. The Guihn-Barre syndrome ar 75: the
Campylobarter connection. Ann Neurol 1993;34:125-127
F. J. Vriesendorp, B. Mishu, M. J. Blaser, and C. L. Koski
In response to the letter of Rees and Hughes we have the
following comments:
In our study of 58 Guillain-Barre (GBS) patients we did
confirm the association of poor prognosis for recovery with
Campylobacterjejuni infection, since the only 3 patients who
did not walk by 1 year all had serologic evidence of preceding
C. jejuni infection. Antibodies to gangliosides were not found
in these 3 patients and all GBS patients with antibodies to
gangliosides had good recovery El]. In contrast, Rees and
Hughes report poor recovery in association with both preceding C. jejuni infection and antibodies to gangliosides (predominantly IgG antibodies to GM1). The difference between
the results of the two studies may be due to the small number
of GBS patients with poor recovery or to differences in test
In our study, serological evidence of antecedent C. jejuni
infection was considered as positive if an optical density ratio
of 2 was obtained by enzyme-linked immunosorbent assay
by two different isotypes. We used this threshold since it
corresponded with a test specificity of 97% in a series of
patients with culture-proven C.jejuni infection {2]. It is possible that the incidence of C. jejuni infection was underestimated. An increase in C. jejani incidence could potentially
increase the number of patients with antibodies both to C.
jejuni and gangliosides. However, in our series of GBS patients, using even less stringent criteria, neither the already
noted association of poor recovery with antibodies to C. j e juni nor the lack of such an association with antibodies to
gangliosides changed. To us this discrepancy suggests that
severity could reflect an as yet undefined factor that may
include the T-cell response, cytokines, or even endotoxin.
W e agree with both Rees and Hughes and Griffin and H o
that despite some differences in the reported study results
of the various investigators, the association of antecedent C.
jejuni infection and GBS may form a fruitful area of further
research into the basic mechanisms of the disease.
Department of Neurology
Unive&ty of Texas Health Science Center
Houston, T X 77030
1. Vriesendorp g,Mishu B, Blaser MJ, Koski CL. Serum antibodies
to GM1, GDlb, peripheral nerve myelin, and Campylubacter jejuni in patients with Guillain-Barre syndrome and controls: correlation and prognosis. Ann Neurol 1993;34:130-135
2. Mishu B, Ilyas AA, Koski CL, et al. Serologic evidence of preceding Cam~ylohucterjejuni infection in patienrs with Guillain-Bar6
syndrome. Ann Int Med 1993;118:9447-953
Uwe Enders, MD, Helge Karch, PhD,
Klaus V. Toyka, MD, Jiirgen Heesemann, MD,
and Hans-Peter Hartung, MD
W e appreciate the comments of Drs Rees and Hughes. We
agree that western blot analysis is more specific than enzymelinked imrnunosorbent assay in demonstrating a humoral immune response to Campylobarter.jejuni and hence we applied
this technique [I). Since submission of our manuscript we
have had the opportunity to examine sera from 13 additional
Guillain-Barre (GBS) patients, bringing the total number to
51. W e detected C . jejani-specific IgA antibodies in 18 of
those 5 1 (355%) and IgG antibodies in 27 of these 51 (53%)
GBS patients.
W e agree that performing stool cultures is important to
provide evidence of recent C . jejuni infection in GBS patients and greatly look forward to the results of the ongoing
prospective case control study being undertaken in South
East England. However, it shouid be pointed out that, at least
in a proportion of cases, C. jejuni may already have been
eliminated from the gastrointestinal tract by the time these
patients present with GBS 12,31.Thus, with the techniques
presently available one still has to rely in large part on serological means to prove a preceding C. jejuni infection.
Finally we would like to report that to date we have successfully isolated C . jejuni from the stools of 4 of 26 (15%)
patients available for study early in the disease. Two of these
4 (50%)patients had IgA and JgG antibody responses t o C.
jejmi. Interestingly, serotyping revealed that in 4 of 4
(100%) culture-positive GBS patients the pathogen recovered was C. jejuni Lior 11. This is the serovar that was predominantly associated with GBS in our series, while uncomplicated enteritis in most cases was due to C. jejuni Lior type
4 [11.
Department of Neurology and Depurtment of Hygiene
and Microbiology
Julius-Maximilians- Uniuersitat
Josef-Schneider-Strusse1 I
0-97080 Wurzburg, Germany
1, Enders u, Karch H, Toyka Kv, et d.The spectrum of immune
responses to Canipylobacterjejurii and glycoconjugates in GuillainB u r t syndrome and in ocher neuroimmunological disorders. Ann
Neurol 1993;%:136-144
2. Blaser MJ, Reller LB. Campyiobacter enteritis. N Engl J &fed
3. Cover TL, Blaser MJ. The pathobiology of campylobacter infections in humans. Annu Rev Med 1989;40:269-285
Annals of Neurology
Vol 35
No 2 February 1994 249
Без категории
Размер файла
256 Кб
barry, syndrome, guillain, jejuni, campylobacter
Пожаловаться на содержимое документа