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Comments and links for XepolSeptember 2006 - Paper by Dalakas.
June 2006 - Paper by Gonzalez H, Stibrant Sunnerhagen K, Sjoberg I, Kaponides G, Olsson T, Borg K.
March 2006 - Paper by Kaponides G, Gonzalez H, Olsson T, Borg K.
Some Discussion on Immunoglobulin Therapy for PPS
Subject: Role of IVIg in autoimmune, neuroinflammatory...
From: Scout <Scout@SKALLY.NET>
J Neurol. 2006 Sep;253 Suppl 5:v25-v32.
Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative
disorders of the central nervous system: present and future
prospects.
Dalakas MC.
Neuromuscular Diseases Section, NINDS National Institutes of Health,
Building 10, Room 4N248, 10 Center Drive MSC, Bethesda, MD 20892-
1382, USA, dalakasm@ninds.nih.gov.
INTRODUCTION : Although IVIg is highly effective in several
autoimmune neuromuscular disorders (neuropathies, myopathies and
neuromuscular junction disorders), its effectiveness in autoimmune or
neuroinflammatory CNS diseases, with the exception of multiple
sclerosis, has not been explored. Emerging data suggest that IVIg may
have a role not only in certain antibody-mediated CNS diseases but
also in some neurodegenerative disorders associated with
"neuroinflammation" mediated by proinflammatory cytokines.
METHODS : Data from a previously reported controlled study conducted
in patients with stiff person syndrome (SPS) are presented as a
paradigm of a CNS disorder associated with specific autoantibodies
responding to IVIg. Emerging data using IVIg in various
neuroinflammatory and neurodegenerative conditions such as Alzheimers
disease, postpolio syndrome (PPS), fibrotic disorders, chronic
painful conditions and narcoplepsy are summarized.
RESULTS : On the basis of a double-blind placebo-controlled trial
conducted in SPS patients with high anti-GAD antibodies, IVIg was
shown to be effective resulting in improvement of stiffness and
heightened sensitivity scores and increasing the patients' ability to
carry out daily activities. In SPS, IVIg also suppressed the anti-GAD
antibodies titers probably via an anti-idiotypic effect.
A controlled study in patients with PPS, showed reduction in
cytokines in serum and CSF with concomitant improvement in the
patients' strength and ability to carry out their daily activities.
The effect of IVIg in a small number of patients with Alzheimer's
disease was promising by reducing the ADAS-cog scores, suggesting a
reversal of disease progression.
IVIg has been shown to have an effect on tissue fibrosis and in
certain subacute painful conditions by suppressing cytokines that
mediate fibrosis or pain. In another uncontrolled study, IVIg reduced
the number of cataplectic attacks in narcolepsy patients.
CONCLUSIONS : IVIg is effective in anti-GAD-positive patients with
SPS. Whether it is also effective in other GAD-positive CNS disorders
such as epilepsies, cerebellar degenerations or Batten's disease need
to be studied in control trials.
Emerging data suggest that IVIg, by suppressing proinflammatory
cytokines, may exert a beneficial effect in patients with Alzheimer's
disease, postpolio syndrome, chronic pain syndromes, fibrotic
disorders and narcolepsy.
Controlled studies are being planned or conducted to substantiate the
benefit of IVIg in neurodegenerative disorders.
PMID: 16998751 [PubMed - in process]
-----
Subject: Intravenous immunoglobulin for post-polio syndrome...
From: Scout <Scout@SKALLY.NET>
Note: The full text of this paper can be accessed for $30 via
http://linkinghub.elsevier.com/retrieve/pii/S1474-4422(06)70447-1
Lancet Neurol. 2006 Jun;5(6):493-500.
Intravenous immunoglobulin for post-polio syndrome: a randomised
controlled trial.
Gonzalez H, Stibrant Sunnerhagen K, Sjoberg I, Kaponides G, Olsson T,
Borg K.
Division of Rehabilitation Medicine, Department of Clinical Sciences,
Danderyd Hospital, Stockholm, Sweden; Department of Public Health
Sciences, Karolinska Institute, Stockholm, Sweden.
BACKGROUND: Survivors of poliomyelitis often develop increased or new
symptoms decades after the acute infection, known as post-polio
syndrome. Production of proinflammatory cytokines within the CNS
indicates an underlying inflammatory process, accessible for
immunomodulatory treatment. We did a multicentre, randomised, double-
blind, placebo-controlled study of intravenous immunoglobulin in post-
polio syndrome.
METHODS: 142 patients at four university clinics were randomly
assigned infusion of either 90 g in total of intravenous
immunoglobulin (n=73) or placebo (n=69) during 3 consecutive days,
repeated after 3 months.
Seven patients were withdrawn from the study. Thus, 135 patients were
assessed per protocol. Primary endpoints were muscle strength in a
selected study muscle and quality of life as measured with the SF-36
questionnaire (SF-36 PCS). Secondary endpoints were 6-minute walk
test (6MWT), timed up and go (TUG), muscle strength in muscles not
chosen as the study muscle, physical activity scale of the elderly
(PASE), visual analogue scale (VAS) for pain, multidimensional
fatigue inventory (MFI-20), balance, and sleep quality. Outcome tests
were done immediately before the first infusion and 3 months after
the second infusion. This study is registered with , number
NCT00160082.
FINDINGS: Compared with baseline, median muscle strength differed by
8.3% between patients receiving intravenous immunoglobulin and
placebo, in favour of the treatment group (p=0.029). SF-36 PCS did
not differ significantly between the groups after treatment
(p=0.321). Differences in the subscale vitality score (p=0.042) and
PASE (p=0.018) favoured the active treatment group. MFI-20, TUG,
muscle strength in the muscles not chosen as the study muscle, 6MWT,
balance, and sleep quality did not differ between groups.
For the whole study population there was no significant change in
pain, as determined by VAS. Nevertheless, patients who reported pain
at the study start improved in the intervention group but not in the
placebo group (p=0.037). Intravenous immunoglobulin was well
tolerated.
INTERPRETATION: Intravenous immunoglobulin could be a supportive
treatment option for subgroups of patients with post-polio syndrome.
Further studies on responding subgroups, long-term effects, and
dosing schedules are needed.
PMID: 16713921 [PubMed - in process]
Subject: Effect of intravenous
immunoglobulin in patients with (PPS)
From: Scout <Scout@SKALLY.NET>
NOTE: Full text of paper can be
obtained for a fee via:
http://shurl.net/zI
J Rehabil Med. 2006 Mar;38(2):138-40.
Effect of intravenous immunoglobulin
in patients with post-polio
syndrome - an uncontrolled pilot
study.
Kaponides Md G, Gonzalez Md H, Olsson
Md Phd T, Borg Md Phd K.
>From the Departments of Public
Health Sciences, Division of
Rehabilitation Medicine, Stockholm,
Sweden.
Objective: To analyse changes in
muscle strength, physical
performance and quality of life
during intravenous immunoglobulin
(IVIg) treatment in patients with
post-polio syndrome.
Design:
Open clinical trial.
Patients:
A total of 14 patients (6 women, 8
men; mean age 57 years, range 43-
67 years) were included in the study.
Intervention:
Treatment with 90 g IVIg (30 g daily
for 3 days).
Main outcome:
Muscle strength, measured with
dynamic dynamometry, muscle function,
by means of performing the 6-minute
walk test, and quality of life,
analysed by means of the SF-36
questionnaire, were performed before
and after treatment.
Results:
For quality of life there was a
statistically significant improvement
for all but one of the 8 multi-item
scales of SF-36 when comparing
data before and after treatment with
IVIg. The multi-item scale most
improved was Vitality. There was no
significant increase in muscle
strength and physical performance.
Conclusion:
Data indicate that IVIg may have a
clinically relevant effect, with
an improvement in quality of life.
The effect may be due to a
decrease in an inflammatory process
in the central nervous system,
which earlier has been reported in
patients with past-polio syndrome
after IVIg treatment.
Since a possible placebo effect
cannot be ruled out, a randomized
controlled study is needed.
PMID: 16546773
[PubMed - in process]
-----
Subject: Some Discussion on Immunoglobulin Therapy for PPS
From Post-Polio Health International
Intravenous Immunoglobulin Treatment for Improving Muscle Strength
http://www.post-polio.org/ipn/PPHsp06p7.pdf
Recent Experience Using Immunoglobulin to Treat Post-Polio Syndrome
http://www.post-polio.org/ipn/PPHsum06p4-5.pdf
--
From: Ron
I read the article from Post-Polio Health about Immunoglobulin
treatment for PPS with interest. They report an 8.6% improvement on
average in muscle strength with people with PPS. I find this to be an
impressive statistic. They also report that a course of Immunoglobulin
treatment would be an infusion once a day for 3-5 days at the cost of
about $10,000 a course. My question, assuming that this research is
successfully replicated, is how long does a course of this treatment
last? How often will it be required to, at the least, arrest the
continual deterioration of muscle mass?
Ron
--
From: "Brenda"
Ron,
More detailed information about the study is at www.post-polio.org,
in the spring 2006 edition, vol. 22, no. 2. The information you read
is in the summer 2006, vol. 22, no. 3 article. A variation of this
article was also in the Polio Outreach of Washington spring 2006. In
this article it states "We next developed a multi-center
placebo-controlled study, double-blinded in 135 post-polio patients.
(In the former study we used 90 grams of IvIg; 30 grams daily for 3
days.) In this study we used 30 grams for 3 days, repeated twice. We
noted an increase in muscle strength of 4.3% in the post-polio
patients. In the placebo group, muscle strength was decreased by
5.7%. The natural course of decrease in strength was 5.7% in one-half
year."
Based on the above "30 grams a day for 3 days, repeated twice," this
is a total of 9 days of 30 grams of immunoglobulin. The timeframe of
the study is one-half year, the above 4.3% increase in muscle
strength is over a one-half year timeframe. I would assume that the
treatment would need to be repeated every 6 months.
It would be nice to find a clinical trial in America using
immunoglobulin treatment for post-polio.
Brenda
--
Subject: From Dr. Borg about IVIG
From: Post-Polio Health International <director@POST-POLIO.ORG>
PHI received this response about IVIG from Dr. Borg, Professor and
Chair, Karolinska Institutet, Div of Rehabilitation Medicine, Danderyd
Hospital, Stockholm.
We have preliminary results from follow-up studies showing that the
cytokine levels in the cerebrospinal fluid is significantly decreased
one year after the treatment. There is a statistical improvement of
quality of life 2 years after the treatment. For the individual, the
effect may last from 6 weeks to several years.
--
Subject: Re: From Dr. Borg about IVIG
From: EDWARD BOLLENBACH <edward.bollenbach@SNET.NET>
<snip>
The second thing, which I think may have profound importance to those of
us with PPS is that proinflammatory cytokines, like Tumor Necrosis
Factor alpha, and several interferons also present, damage tissue. If
Spinal tissue is damaged over 20 or so years and then if the culprit
cytokines are removed with IVig how long will it take to realize
improvement? Will there be resprouting over a long time? Are there
enough living myofibrils (muslce fibers or cells) to make a big
difference? All of these questions remain unanswered.
The other thing, which has tangential relation to Borg, is that Insulin
like Growth Factor-1 was tried early on to see if it would stimulate
resprouting as it does in the normal spine. In PPS subjects these
experiments were dissappointing. As little as billionths of a gram of
Tumor Necrosis Factor in the cord will change the conformation of the
IGF receptors on motor neurons so that no Insulin like Growth Factor
will be taken up. Those who have undergone Borg/ Gonzalez treatment need
to then try IGF but I haven't seen anything of this anywhere. Researchers???
Eddie
--
From: Rick
The Borg paper stated that the research finding had a p valuse of
0.029. While I agree with the statement "any p value less than 0.05 is
significant", note that most studies that return really meaningful
results have p values of 0.01 or less and most usually less. The p
value from Borg's data is almost 0.03. I only mention this to note that
the increase in muscle strength following the use of IV immunoglobulin
statistically is not that great.
Consider this in light of the possibility of side effects from this
therapy including the possibility of HIV if the source of the
immunoglobulin is human and not recombinant. And keep in mind that the
median increase in muscle strength is only 8.3%. Seems like a lot of
downside risk for a minimal potential upside benefit.
Just my thoughts on this.
--
Subject: Re: From Dr. Borg about IVIG
From: EDWARD BOLLENBACH <edward.bollenbach@SNET.NET>
Rick (MDK) wrote:
POST-POLIO-MED@LISTSERV.ICORS.ORG
The Borg paper stated that the research finding had a p valuse of
0.029. While I agree with the statement "any p value less than 0.05 is
significant", note that most studies that return really meaningful
results have p values of 0.01 or less and most usually less.
From http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat4.section.7663