Neurology -- Correspondence for Wollinsky et al., 57 (5) 774-780

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Correspondence published:

Reply to both Letters to the Editor: K Wollinsky, "P J Hulser, F Weber, R Rudel" (14 November 2001)

CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial: Jose Berciano (14 November 2001)

CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial: Paolo L Manfredi (14 November 2001)

Reply to both Letters to the Editor 14 November 2001

K Wollinsky
University of Ulm Ulm Germany,
"P J Hulser, F Weber, R Rudel"
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Re: Reply to both Letters to the Editor

Reinhardt.Rudel{at}medizin.uni-ulm.de K Wollinsky, et al.

As stated in the letter by Dr. Manfredi, and exactly for the reasons given in previous published articles, we started to experiment with CSF filtration (CSFF) in therapy-resistant MS patients having already obtained good results in patients with GBS. [2, 3, 4, 5] Others followed this example. In March 1995, a meeting was held in Linz, Austria, on application of CSFF where several groups reported their results of CSFF in patients with various inflammatory neurologic diseases. Non-peer reviewed short articles were published in German in Neuropsychiatrie {1995;9:82- 111}. Three groups (Allen/Mauer, Austria [6], Haas/Magdeburg, Germany, and our Ulm group) reported their first experiences with MS patients. In six out of 10 selected patients with longstanding MS (EDSS at least 6.5), Haas had found improvement of tremor, spasticity and sensation. [7] We had obtained similar results, and had also, in some patients, seen improvement in visual acuity and clinically assessed strength. [8] Despite these encouraging results, influential German neurologists were not convinced, particularly in view of the arrival of pharmaceutical, non-invasive treatments such as ß-IFN or COP-1 on the market. Thus, we decided to focus first on the completion of the already begun GBS study. [1] Meanwhile, there are still MS patients who do not respond to the established therapies. In the hope that removal of humoral factors causes improvement, a Mayo Clinic group of experts recently performed a randomized trial of plasma exchange in MS patients with promising results. [9] Together with Dr. Manfredi, we hope that on the basis of the results of our GBS study, a number of neurologists will consider a trial of CSFF in such MS patients worthwhile.
We also agree with Dr. Berciano that postforaminal nerve trunk pathology is likely to be beyond the region where CSF filtration can directly act. However, as Feasby and Hartung point out in their Editorial, the clinical pathologic spectrum of GBS also extends to the classical acute inflammatory demyelinating polyneuropathy. [4] Even in the axonal form of GBS "the major burden of pathological changes falls on ventral spinal roots." [5]
Like the majority of experts we accept that the degree of axonal degeneration, be it primary or secondary, is very relevant for the course and outcome of GBS. What is not clear, however, is the question as to whether those distal lesions are of primary or secondary origin. The fact that we found CSF filtration to be an effective treatment might be taken as an indication of a possible influence of the nerve root upon distal lesions. Thus our results with CSF filtration could indeed reduce Dr. Berciano´s concerns.
Treatment of GBS has so far depended on clinical trial and error rather than solid pathologic knowledge. And yet, it has been not only recommended, but applied to the patients´ benefit.
References:
1. Wollinsky KH, Hülser P-J, Brinkmeier H, et al. CSF filtration is an effective treatment of Guillain-Barré syndrome. A randomized clinical trial. Neurology 2001;57:774-780.
2. Asbury AK, Arnason BG, Adams RD. The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine 1969;49:173- 215.
3. Berciano J, García A, Figols J, Muñoz R, Berciano MT, Lafarga M. Perineurium contributes to axonal damage in acute inflammatory demyelinating polyneuropathy. Neurology 2000;55:552-559.
4. Feasby TE, Hartung H-P. Drain the roots. A new treatment for Guillain-Barré syndrome? Neurology 2001;57:753-754.
5. Berciano J, Corea F, Monton F, Calleja J, Figols J, Lafarga M. Axonal form of Guillain-Barré-Syndrome:evidence for macrophage-associated demyelination. Muscle Nerve 1993;16:744-751
6. Allen C, Kepplinger B, Papst H. CSFF (cerebrospinal fluid filtration) bei demyelinisierenden Erkrankungen. Neuropsychiatrie 1995;9:105-109.
7. Haas J, Sailer M, Düzel E, Tendolkar E, Wurster U. Liquorfiltration bei multipler Sklerose: eine experimentelle Therapie. Neuropsychiatrie 1995;9:109-111.
8. Wollinsky KH, Hülser P-J, Brinkmeier H., Mehrkens H-H, Kornhuber HH, Rüdel R. Klinische Erfahrungen mit der CSF-Filtration bei Guillain- Barré Syndrom, chronisch inflammatorischer demylinisierender Polyneuropathie und multipler Sklerose. Neuropsychiatrie 1995;9:95-99.
9. Weinshenker BG, O'Brien PC, Petterson TM et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878-886.

CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial 14 November 2001

Jose Berciano
University Hospital Marques de Valdecilla Santander Spain
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Re: CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial

neuro{at}humv.es Jose Berciano

I read with interest the paper by Wollinsky et al reporting that CSF filtration is an effective treatment of Guillain-Barré syndrome (GBS). [1] According to the authors the rational basis of such CSF filtration is intrathecal elevated concentration of a variety of inflammatory mediators that could be pathogenic by inducing demyelination of the spinal roots. My main concern is whether the clinical picture of GBS could be attributed to selective spinal root dysfunction. In support of this pathophysiology they mention the seminal paper by Asbury et al to state that GBS is a type of multifocal inflammatory process that preferentially affects the ventral roots. [2] They claimed, however, that emphasis on root pathology undoubtedly reflects the fact that at autopsy roots have been taken more frequently than have peripheral nerves. Certainly this is a wise criterion as detailed autopsy studies have shown that inflammatory demyelination is widespread, extending from preforaminal spinal roots to plexuses and more distal nerve trunks. [3] As stated in the accompanying Editorial, such relevant postforaminal nerve trunk pathology is beyond the region where CSF filtration is alleged to act. [4]
It is widely accepted that the degree of axonal degeneration, either primary or secondary, is the most relevant prognostic factor in GBS. Feasby and Hartung comment that a vigorous inflammatory response at the root level could through the generation of secondary axonal degeneration worsen the course and outcome of GBS. [4] It might be inferred from this affirmation that CSF filtration plays a potential role in axonal protection. Although radicular axonal degeneration may to some degree occur in acute inflammatory demyelinating polyneuropathy, there are now both experimental and clinical data demonstrating that the brunt of axonal pathology is localized more distally, namely, in nerves external to the subarachnoid angle where the nerve roots possess epi-perineurium as in the peripheral nerve trunks. [3] Therefore the topography of axonal degeneration is also beyond the region where CSF filtration is alleged to act.
Taking the aforementioned considerations into account, I conclude that there is no pathological background to recommend continuing with CSF filtration in GBS.
References
1. Wollinsky KH, Hülser P-J, Brinkmeier H, et al. CSF filtration is an effective treatment of Guillain-Barré syndrome. A randomized clinical trial. Neurology 2001;57:774-780.
2. Asbury AK, Arnason BG, Adams RD. The inflammatory lesion in idiopathic polyneuritis. Its role in pathogenesis. Medicine 1969;49:173- 215.
3. Berciano J, García A, Figols J, Muñoz R, Berciano MT, Lafarga M. Perineurium contributes to axonal damage in acute inflammatory demyelinating polyneuropathy. Neurology 2000;55:552-559.
4. Feasby TE, Hartung H-P. Drain the roots. A new treatment for Guillain-Barré syndrome? Neurology 2001;57:753-754.

CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial 14 November 2001

Paolo L Manfredi
Memorial Sloan-Kettering Cancer Center New York
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Re: CSF filtration is an effective treatment of Guillain–Barré syndrome: A randomized clinical trial

manfredp{at}mskcc.org Paolo L Manfredi

In 1993, while in my last year of neurology residency, I became intrigued with the idea of treating patients with multiple sclerosis (MS) with removal of CSF from the lumbar cistern, and either replacing it at the same time with saline into the cerebellar cistern or simply waiting for physiologic production to occur. I spoke with my chairman, who as most good chairmen was very busy, prudent and open-minded. He referred me to the MS group of a hospital affiliated with the residency program. My idea was quickly dismissed there to remain only in the background of my mind until I read the recent article on CSF filtration for Guillain-Barré syndrome. The study presented by Wollinsky et al. immediately brought back to my mind the old question. [1] Could CSF filtration improve the clinical manifestations of MS? Ms affects central nervous system myelin, particularly the myelin bathed by CSF. Numerous papers have described humoral and cellular CSF abnormalities in patients with MS [2, 3] and the neural toxicity of their CSF. [4, 5] I certainly regret I did not pursue my question with more conviction but I now have renewed hope that replacing or filtering the CSF of patients with MS will be viewed by experts in the field as feasible and worthwhile of a trial.
References:
1. Wollinsky KH, Hülser P-J, Brinkmeier H, et al. CSF filtration is an effective treatment of Guillain-Barré syndrome. A randomized clinical trial. Neurology 2001;57:774-780.
2. Zerman D, Adam P, Kalistova H, Sobek O, Andel J, Andel M. Cerebrospinal fluid cytologic findings in multiple sclerosis. A comparison between patient subgroups. Cytologica 2001;45:51-59.
3. Olsson T. Multiple sclerosis: Cerebrospinal fluid. Annals of Neurology 1994;36 Suppl:S100-S102.
4. Alcazar A, Regidor I, Masjuan J, Salinas M, Alvarez-Cermeno JC. Axonal damage induced by cerebrospinal fluid from patients with relapsing- remitting multiple sclerosis. Journal of Neuroimmunology 2000;104:58-67.
5. Alcazar A, Regidor I, Masjuan J, Salinas M, Alvarez-Cermeno JC. Induction of apoptosis by cerebrospinal fluid from patients with primary- progressive multiple sclerosis in cultured neurons. Neuroscience Letters 1998;255:75.78.