HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Correspondence to:

BRIEF COMMUNICATIONS: S. Nishino, T. Kanbayashi, N. Fujiki, M. Uchino, B. Ripley, M. Watanabe, G. J. Lammers, H. Ishiguro, S. Shoji, Y. Nishida, S. Overeem, I. Toyoshima, Y. Yoshida, T. Shimizu, S. Taheri, and E. Mignot CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies Neurology 2003; 61: 823-825 [Abstract] [Full text] [PDF]

Correspondence: Submit a response to this article

Correspondence published:

CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies

Christian R. Baumann, Claudio L. Bassetti   (29 December 2003)

Reply to Baumann

Seiji Nishino, MD, PhD, T. Kanbayashi, N. Fujiki, M. Uchino, B. Ripley, M. Watanabe, G.J. Lammers, H. Ishiguro, S. Shoji, Y. Nishida, S. Overeem, Y. Yoshida, S. Taheri, T. Shimizu, E. Mignot   (29 December 2003)

CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies 29 December 2003
Christian R. Baumann, Neurology Department, University Hospital Zurich Frauenklinikstrasse 26, 8091 Zurich, Switzerland, Claudio L. Bassetti Send Correspondence to journal: Re: CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies christian.baumann{at}usz.ch Christian R. Baumann, et al.	Nishino et al reported low/undetectable cerebrospinal fluid (CSF) hypocretin-1 levels in 18 of 28 patients (64%) with Guillain-Barre syndrome (GBS) and in 5 of 12 patients (42%) with Miller-Fisher syndrome (MFS). [1] All GBS patients with undetectable hypocretin levels (n=7) were Japanese. The authors reported an association between decreased CNS hypocretin levels and rapid disease progression/involvement of upper CNS levels. Sleep-wake disturbances were not observed in the majority of hypocretin-deficient GBS patients. We determined CSF hypocretin-1 levels in 12 caucasian patients (four women and eight men with a mean age 44 years) with GBS (n=11) and MFS (n=1). Disease progression was rapid (onset to peak symptomatology in <10 days) in eight patients. Upper extremities', respiratory, or cranial nerve functions were impaired in eight GBS patients. Antecedent infections were reported by nine patients. Five patients received IV immunoglobulin treatment. CSF was obtained by lumbar puncture (carried out before beginning of treatment in four of five patients). Determination of CSF hypocretin levels in a control group (n=20, mean level 497 pg/ml) allowed the calculation of low levels (<320 pg/ml). Hypocretin-1 values were normal in 9 of 11 GBS patients and in the MFS patient. The mean level (475 pg/ml) did not differ significantly from the control group's mean level. However, two patients had moderately decreased hypocretin levels (224 and 254 pg/ml), undetectable levels were not observed. CSF cell count ranged from 0 to 20, protein levels from 0.60- 6.99 g/l (normal: 0.15-0.45). Anti-ganglioside antibodies were positive in two of six patients. Immunological testing revealed increased titers of antinucleotide antibodies in four patients and monoclonal gammopathy in one patient. There was no correlation between low hypocretin-1 levels and age, gender, rapidity of progression, involvement of upper CNS levels, CSF protein levels, antiganglioside antibodies, or immunological markers. It should be noted that the patients with low levels had the highest CSF cell counts (14 and then 20 cells). None of the patients reported sleep-wake disturbances. We could not confirm the finding of low/undetectable CSF hypocretin-1 levels in a significant portion of patients with GBS. We hypothesize that the difference in ethnic origin of the recruited patients (Japanese patients [1] vs. our 12 caucasian patients) and thus possible different pathophysiological pathways in GBS might be responsible for the discrepancy. References 1.) Nishino S, Kanbayashi T, Fujiki N et al. CSF hypocretin levels in Guillain–Barré syndrome and other inflammatory neuropathies. Neurology 2003; 61: 823-825.
Reply to Baumann 29 December 2003
Seiji Nishino, MD, PhD, Associate Professor, Psychiatry and Behavioral Sciences, Stanford University 701B Welch Road, RM 142, Palo Alto, CA 94304, T. Kanbayashi, N. Fujiki, M. Uchino, B. Ripley, M. Watanabe, G.J. Lammers, H. Ishiguro, S. Shoji, Y. Nishida, S. Overeem, Y. Yoshida, S. Taheri, T. Shimizu, E. Mignot Send Correspondence to journal: Re: Reply to Baumann nishino{at}stanford.edu Seiji Nishino, MD, PhD, et al.	Baumann reported that none of 11 Caucasian Guillain-Barre syndrome (GBS) subjects (with impaired upper extremities, respiratory or cranial nerve functions) had undetectably-low CSF hypocretin-1 levels, and only 2 of the 11 showed moderately reduced CSF hypocretin-1 levels (47% and 53% of the mean level of controls). We believe that Baumann's findings are noteworthy. We measured CSF hypocretin levels in 40 healthy controls, and CSF levels were not reduced in any of these controls to the same degree (363.2±16.3 pg/ml, range 222-653 pg/ml). [1] Considering the acute onset of the disease, the reduced CSF hypocretin level in these two GBS subjects is likely to reflect the disease process. Nevertheless, we agree that there is a discrepancy in the portion of GBS patients who had low CSF hypocretin levels, and also to the degree of reduction observed between Baumann's and our studies. Our experiment was retrospective and the CSF samples used were previously collected from multiple sites. Only five were obtained from Caucasian patients. The majority of CSF samples (23 out of 28) were from hospitals located in the northern (Akita University), central (Tsukuba University) and southern (Kumamoto University) parts of Japan. Undetectably low CSF hypopocretin-1 levels in GBS were observed in patients from both northern and southern areas (moderately reduced hypocretin-1 levels were from all three areas). In some GBS subjects, undetectable CSF hypocretin levels were observed repeatedly during the course of the disease, thus the finding was consistent. Griffin et al. suggested that GBS in northern China (acute motor axonal neuropathy[AMAN] associated with Campylobacter) is a different disease than GBS seen in western countries. [2,3] A previous postmortem study suggested that axonal involvement is more frequent among Japanese patients than in the Caucasian population. [4] Furthermore, antibodies to GM1 and Gal NAc-GD1a, often associated with AMAN in northern China, are also high in Japanese GBS. [5] Thus, it is possible that GBS in Japan also has features that distinguish it from GBS in western countries. Our seven undetectable CSF hypocretin GBS cases exhibited severe and rapid onset with frequent respiratory involvement which may suggest a link between AMAN and hypocretin deficiency. However, four out of seven undetectable cases also exhibited sensory impairments. There was also no association between anti GM1 and Gal NAc-GD1a antibodies and low hypocretin levels. In addition, we did not observe any findings suggesting a special link with Campylobacter infection. Therefore, low CSF hypocretin levels and the issue of GBS subsets is unclear. Hypocretin deficiency in the brain, as observed in hypocretin-deficient narcolepsy, has not yet been confirmed in GBS subjects with low CSF hypocretin-1 levels. For these reasons, we consider future studies regarding the mechanism of low CSF hypocretin levels in a subset of GBS subjects to be important. References 1. Mignot E, Lammers GJ, Ripley B et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol 2002;59:1553-1562. 2. Griffin JW, Li CY, Ho TW et al. Guillain-Barre syndrome in northern China. The spectrum of neuropathological changes in clinically defined cases. Brain 1995;118 ( Pt 3):577-595. 3. Ho TW, Mishu B, Li CY, et al. Guillain-Barre syndrome in northern China. Relationship to Campylobacter jejuni infection and anti- glycolipid antibodies. Brain 1995;118 ( Pt 3):597-605. 4. Sobue G, Li M, Terao S, et al. Axonal pathology in Japanese Guillain-Barre syndrome: a study of 15 autopsied cases. Neurology 1997;48:1694-1700. 5. Yuki N, Ho TW, Tagawa Y, et al. Autoantibodies to GM1b and GalNAc-GD1a: relationship to Campylobacter jejuni infection and acute motor axonal neuropathy in China. J Neurol Sci 1999;164:134-138.