multiple sclerosis pediatrician muco-ciliar barrier defect astrocytes Domenico Fiore bordetella marijuana virus neurology ebv bmc mpo
Dr. Domenico Fiore: multiple  sclerosis Dr. Domenico FIORE
V.le Madonna delle Grazie, 17
I-35028 Piove di Sacco (Padova - Italy)
MULTIPLE SCLEROSIS: DIAGNOSIS - THERAPY - PROPHYLAXIS
40th National Congress of H.N.S.
(Hospital Neurologists, Neurosurgeons and Neuroradiologists Society)
Otranto (Italy), 31 May - 1.2.3. June 2000

I have been carrying on my research on Bordetella (BB) and Multiple Sclerosis (MS) and, confirming "negative" all the healthy controls I had examined earlier and seeing that out of 3875 healthy subjects, from 5 Italian regions, in young people from 17 to 19 years of age, antipertussis toxins IgG were absent in the 95% of the cases, I have studied the following groups of MS patients:

1° group
For 72 not selected patients, I asked for the sample’s and cut-off optic density (O.D.) in E.L.I.S.A. to the Laboratory and found:

  • anti-BB IgG positive in 40 cases = 55%
  • anti-BB IgM positive in 7 cases = 9,72%
  • both IgG and IgM positive in 11 cases = 12,27%
  • IgG and IgM negative in 14 cases = 19,45%.
  • Total: 58 positive patients out of 72 = 80,55%.
2° group
By searching in E.L.I.S.A. for the antibodies of the acute phase of the pertussis infection, the anti-Filamentous Hemoagglutinin (FHA) and the anti-Pertussis Toxins (PT), the Laboratory, in accordance with the interpretative scheme enclosed in the diagnostic kit, speaks about "absence of infection and of immunity" ("negative") or attests a "taking place or very recent infection". With this method I studied 40 chronic-evolutive MS patients: 4 patients resulted "negative" (10%); for 36 patients (90%) the Laboratory attested a "taking place or very recent infection".

3° group
By searching in E.L.I.S.A. for both anti-FHA and anti-PT antibodies, which prove the BB-infection in S-phase (first generation BB, virulent, provided with fimbriae with adhesins, producers of all toxins), and total anti-BB IgG and IgM, I studied 92 MS patients not selected for clinic form and pharmacological treatment they were administered. In 63 out of 92 (68,48%), the Laboratory found that "the infection was taking place ". 29 out of 92 (31,52%) did not have antibodies of the acute phase, but in 24 out of these 29 (the 26,10% of the total) there were IgM at little inferior levels than those of IgG, therefore manifestative of a chronic infection from R-phase BB (second generation BB which have lost virulence, fimbriae and main wall toxins). Total: in the 94,57% of 92 MS patients, not selected according to their clinic form and present therapeutic treatment, the presence of an infection from B-Pertussis has been demonstrated.

We may affirm that, while the first infection from BB provokes pertussis in children, the reinfection in an adult with muco-ciliar barrier defect causes MS. The clinic forms of this disease depend on the relationship between BB and Host: a just protracted survival of BB on the mucosae takes to an attack (remittent MS); the stable colonization of mucosae by BB produces chronic-evolutive MS. BB toxins, come into circulation, with preexisting and/or newformed  specific antibodies form immune circulating complexes (ICC). These ICC (the antibodies which compose them are not neutralizing and the FHA toxins carry the adhesins at their extremity, molecules of the vasal endotheliums) precipitate at the level of the small cerebral vessels, damaging the haemato-encephalic barrier and the perivenous nervous tissue (MS attack).
MS is a toxo-infective disease from barrier defect; the environmental factor, sine qua non, is a defect of the muco-ciliar barrier, a primary or secondary defect (acute diseases of the first respiratory tract; chronic rhino-sinusitis. Its pathogenesis is the classical one from a precipitation of immune circulating complexes; in subjects with astrocytes which produce 2° class HLA antigens (second individual factor), half-delayed transitory basophil hypersensitivity of Jones and Mote may arise.

SEROLOGIC DIAGNOSIS
The pathognomonic diagnosis of MS and of its clinic forms requires:

  • the research of anti-FHA and anti-PT IgA and IgG;
  • the research in E.L.I.S.A. of total anti-BB IgG and IgM (the method of Complement Fixation is little sensitive: there are false negatives at the presence of ICC, IgA, and endotoxins).
The quantity of IgG and IgM present in the serum to examine is calculated in spectrophotometric unities (absorbance values or extinction values = VE) with the formula  [VE = (patient’s O.D. / cut-off O.D.) x 10]; the sample’s and the cut-off  O.D. (serocalibrator, enclosed in the diagnostic kit) of both immunoglobulinic classes must be specified and, as far as pertussis is concerned, VE < 9 are considered "negative".
In MS we find:
  • positive IgG and IgM at  VE <= 3 in the R-R forms, remittent;
  • in C-E forms (chronic-evolutive):
    1. a) positive IgG and IgM;
    2. b) only IgG positive;
    3. c) only IgG positive, but IgM exceed 4 VE unities;
    4. d) both immunoglobulin classes negative, but IgM level is very close to IgG level.
The presence of IgM is not coherent with a normal secondary immune response, in which, as a rule, only IgG are produced; in an adult, the anti-BB IgM express the peculiar response to the protracted stimulation from pertussis lipopolisaccharide: they demonstrate the stable colonization of mucosae by Bordetella, that is C-E MS. When the toxinic stimulus ceases, IgG are still being produced for some years, IgM for 4-5 months. Anti-FHA and anti-PT IgA drop to O.D. <=  0,30 within 7-8 months; only after this period, the Laboratory will attest the "absence of infection". But, after 4 months of Eritrocina, to confirm the mucosae’s reclamation, IgG will be unvaried or increased (the ones that before were absorbed into ICC become measurable, too) and IgM will get back to normal (VE <= 3).

THERAPY
The specific etiologic MS therapy consists of a protracted administration of Erythromycin to reclaim the rhino-sinusalis mucosa from B-Pertussis. Obviously, the antibiotic treatment will arrest the disease evolution and it will not make consolidated lesions regress; therefore, the more precociously it is started, the more effective it is. Erythromycin has no contraindications or important side effects (see below), so that it can be used also during pregnancy. At the beginning of the treatment there may be an aggravation of the neurologic symptomatology caused by the onset of a Jarisch-Erxheimer reaction: the bacterial lysis entails an increase of toxemia, an increase of ICC containing pertussis toxins, a precipitation of these complexes to the level of small cerebral vessels, and a seeming renewal of MS disease. This reaction may arise even 20-40 days after the beginning of the antibiotic treatment; but the new lesions will regress completely by adding some cortisone bolus, as it were a real attack. In the presence of chronic rhino-sinusitis (very frequent and very often ignored) Thiamphenicol by nasal aerosol may be associated to macrolide by os (15-20 days). Beta-lactam antibiotics are contraindicated, as they ease the transformation of BB into R-forms and into spheroplasts.

PROPHYLAXIS OF RELAPSES
In all cases, due to the great spreading of Bordetella, there may be a reinfection; only in the patient under antibiotic treatment, the reinfective bacterial charge will not root; the quantity of toxins will be small and will not recur; the patient may have a rekindling of the disease, but the new lesions, this time too, will completely regress with a few days of cortisone treatment. Keeping in mind that, with few well-known exceptions, erythromycin can be associated to all medicines in the market at present, in MS we will adopt the protocol which, in subjects allergic to penicillin, is practiced all over the world for the prophylaxis of rheumatic disease: erythromycin will be administered for a long time, for at least 5 years from the latest attack. The precocious etiologic serodiagnosis and the specific antibiotic treatment (erythromycin) will allow to arrest the course of the disease before the arising of the dramatic disability, which still strikes many MS patients.


Bibliography
  1. Please have a look at all my contributions to SNO Congresses from 1990 to 1999.
  2. Vierucci A. e Altri: Le vaccinazioni in Pediatria.. 1993. 203.
  3. Mandel-Douglas-Bennet: Malattie infettive ad eziologia batterica. Churchill Livingstone - Momento Medico. 1999. 49-50.
  4. Harrison: Principi di Medicina Interna. McGraw-Hill Italia. Milano 1005. 1198.
Index    Top page
Dr. Domenico Fiore ©1990-2000 All rights reserved - Duplications is forbidden without prior Author's written consent