Neurology -- Correspondence for Kuwabara et al., 63 (3) 529-533

Correspondence published:

Does Campylobacter jejuni infection elicit "demyelinating" Guillain–Barré syndrome?: José Berciano, Isabel Illa, Hospital "Santa Creu i Sant Pau", Barcelona, Spain (4 October 2004)

Reply to Berciano et al: Satoshi Kuwabara, Nobuhiro Yuki (4 October 2004)

Does Campylobacter jejuni infection elicit "demyelinating" Guillain–Barré syndrome? 4 October 2004

José Berciano,
University Hospital
Avda. Valdecilla, s/n, 39008 Santander, Spain,
Isabel Illa, Hospital "Santa Creu i Sant Pau", Barcelona, Spain
Send Correspondence to journal:
Re: Does Campylobacter jejuni infection elicit "demyelinating" Guillain–Barré syndrome?

jaberciano{at}humv.es José Berciano, et al.

We read with interest the article by Kuwabara et al. [1] Their series includes 159 consecutive patients with Guillain-Barré syndrome (GBS). There was evidence of recent C. jejuni infection in 22 patients, 16 of them being electrophysiologically classified as acute motor axonal neuropathy (AMAN), 5 as AIDP, and the remaining 1 as unclassified. Since these AIDP patients showed transient slowing of nerve conduction mimicking demyelination, the authors concluded that C. jejuni infection does not appear to elicit AIDP.
We reported a patient aged 67 years with fulminant GBS who died 18 days after onset. [2] One week before admission, he had had an upper respiratory infection. Three serial electrophysiological examinations revealed universal nerve inexcitability. Using reported techniques [3], both IgM and IgG anti-C. jejuni antibodies were detected at 1/40 serum dilution (positive as of 1/10); stool culture for C. jejuni was not done. There were no increased titers of IgM or IgG antiganglioside antibodies (GM1, asialo-GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b and GQ1b). Autopsy showed extensive inflammatory demyelination of spinal roots and a variable combination of axonal degeneration and demyelination in peripheral nerve trunks including femoral, median, ulnar and sural nerves. This is a prototypic example of a severe GBS case combining primary demyelination and axonal degeneration secondary to inflammation.
One outstanding pathological finding was radicular paranodal demyelination (see figure 2C). We argued that this finding concurred with the suggestion that an immune reaction to C. jejuni could mediate antibody- and complement-mediated reactions directed to target epitopes in the paranodal region and periaxonal space, recruiting macrophages and ultimately leading to fiber degeneration. [2]
Unlike China and Japan where AMAN predominates, epidemiological surveys have demonstrated that in Europe that AIDP is the most prevalent form of GBS, axonal variants representing around 6% of cases. [4] In another study conducted in Britain, C. jejuni infection was associated with both AIDP and AMAN. [5] As stated by Kuwabara et al [1], host susceptibility factors could account for differences between Eastern and Western countries.
References
1. Kubawara S, Ogawara K, Misawa S, et al. Does Campylobacter jejuni infection elicit “demyelinating” Guillain-Barré syndrome? Neurology 2004; 63: 529-533.
2. Berciano J, Figols J, García A, et al. Fulminant Guillain-Barré syndrome with universal inexcitability of peripheral nerves: a clinicopathological study. Muscle Nerve 1997; 20: 846-857.
3. Illa I, Ortiz N, Gallard E, Juarez C, Grau JM, Dalakas MC. Acute axonal Guillain-Barré syndrome with IgG antibodies against motor axons following parental gangliosides. Ann Neurol 1995; 38: 218-224.
4. Sedano MJ, Calleja J, Canga E, Berciano J. Guillain-Barré syndrome in Cantabria, Spain. An epidemiological and clinical study. Acta Neurol Scand 1994; 89: 287-292.
5. Rees JH, Gregson NA, Hughes RAC. Anti-ganglioside GM1 antibodies in Guillain-Barré syndrome and their relationship to Campylobacter jejuni infection. Ann Neurol 1995; 38: 809-816.

Reply to Berciano et al 4 October 2004

Satoshi Kuwabara,
Department of Neurology, Chiba University School of Medicine
1-8-1, Inohana, Chuo-ku, Chiba, 260-8670, Japan,
Nobuhiro Yuki
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Re: Reply to Berciano et al

kuwabara-s{at}faculty.chiba-u.jp Satoshi Kuwabara, et al.

We thank Berciano et al for their interest in our paper, which suggests that Campylobacter jejuni infection is not likely to elicit the demyelinating form Guillain-Barre syndrome--acute inflammatory demyelinating polyneuropathy (AIDP)--in Japan. [1]
Dr. Berciano et al reported a case of severe Guillain-Barre syndrome with serologic evidence of recent C. jejuni infection, and autopsy showed pathology of AIDP. We agree with the comment that primary severe demyelination and secondary axonal degeneration were responsible for inexcitable nerves in that patient. However, we think that only positive serology for anti-C. jejuni assay is not sufficient evidence for preceding C. jejuni infection. There are no standards for serologic testing for this bacterium with regard to antigens and cut-off values for the positivity, and actually, the sensitivity and specificity of serologic assays varies considerably among laboratories. [2]
The specificity of our assay is 88%, and in combination with a clinical history of a definite diarrheal illness in our study, the strict criteria could reduce the false-positive cases. Moreover, 91% of our 22 anti-C. jejuni-positive patients were anti- ganglioside positive. In the case reported by Dr. Berciano et al, an antecedent event was upper respiratory infection, anti-ganglioside antibodies were negative, and stool culture was not done. It is unlikely that his patient suffered C. jejuni infection.
References
1) Does Campylobacter jejuni infection elicit demyelinating Guillain- Barre syndrome? Neurology 2004;63:529-533.
2) Koga M, Ang CW, Yuki N, et al. Comparative study on preceding Campylobacter jejuni infection in Guillain-Barre syndrome between Japan and Netherlands. J Neurol Neurosurg Psychiatry 2001;70:693-695.