Effect of high-dose intravenous immunoglobulin on amyotrophic lateral sclerosis and multifocal motor neuropathy
M. C. Dalakas, D. P. Stein, C. Otero, E. Sekul, E. J. Cupler and S. McCrosky
Neuromuscular Diseases Section, National Institutes of Health, Bethesda, Md.
OBJECTIVE: To determine if high-dose intravenous immunoglobulin therapy is
effective in improving muscle strength or in arresting the pace of disease
progression in patients with rapidly progressive amyotrophic lateral
sclerosis. DESIGN: An open-label pilot study of intravenous infusions of
high-dose immunoglobulin administered once a month for 3 months in nine
patients with classic amyotrophic lateral sclerosis. Selected patients had
a rapidly progressive course with signs of worsening noticeably evident
every 6 weeks prior to therapy. A patient with multifocal motor neuropathy
with conduction block that presented as a lower motor neuron syndrome was
concurrently treated to document the efficacy of the same preparation of
immunoglobulin in a potentially treatable disease that simulates lower
motor neuron syndrome. The efficacy of high-dose intravenous immunoglobulin
infusions was assessed by objective measurement of maximum voluntary
isometric contraction in all muscle groups of two limbs before and after
therapy. SETTING: The Clinical Center of the National Institutes of Health,
Bethesda, Md. RESULTS: All patients with amyotrophic lateral sclerosis
worsened during the study. By the end of the third month, their mean total
muscle scores (megascores) had declined by 71.2 points, from a mean of
369.7 (range, 200 to 605) to 298.5 (range, 130 to 552) points. The pace of
progression did not change during the 4-month observation period. In
contrast, the patient with multifocal motor neuropathy responded to
intravenous immunoglobulin therapy and increased his megascores by 146
points after 3 months. The GM1 antibody titers were normal in all the
patients. CONCLUSIONS: High-dose intravenous immunoglobulin, a
prohibitively expensive drug, has no apparent therapeutic role in improving
the symptoms or arresting the pace of progression in patients with
amyotrophic lateral sclerosis. In contrast, multifocal motor neuropathy is
an immunopathologically different disease that responds to intravenous
immunoglobulin therapy.
