| Commonly used Immunoherapy
in Neurology |
| Steroid |
| Oral regimen |
Prednisone |
Dexamethaxone |
| Commonly used dose |
1 mg/kg |
4 to 16 mg /day. |
| Advantages |
shorter half life,
may eventually taper to alternate day dose when used for long term |
less
mineralocorticoid effect |
| Biological half-life |
8 hours (8 to 24
hours) |
32 hours (32 to 72
hours) |
| Bio-equivalence (determined by
relative equivalence & biological half-life) |
40 mg |
1 mg |
|
Usual dose of IV Steroid
 | 500 to 1000 mg of methyl prednisolone daily for 3
to 5 days. |
| P saline and administered over
2 to 4 hours. |
|
| Intravenous Immunoglobulin (IVIg) |
| IVIg is prepared from pooled blood from healthy donors. |
| Contains >IgG and small amounts of other immunoglobulins and
other proteins. |
| IVIg is preferred for
 | Chronic inflammatory demyelinating polyneuropathy (CIDPN) |
| Multifocal motor neuropathy with conduction block (MMN) |
|
| Both IVIg & plasmapharesis are similarly effective in Guillain Barre
syndrome. |
| Treatment efficacy with IVIG in the remainder of the diseases remains
unproven. |
|
| Reduce the auto aggressive effect of macrophages. |
| Can also down-regulate cytokine production and neutralize proinflammatory
cytokines. |
| Appears to promote remyelination following demyelination in rodents due
to Theiler's murine encephalomyelitis virus. |
|
| Usual dose |
| Studies of neurologic diseases use a variety of doses and protocols |
| Usual dosing: 400 mg/kg IV daily for 3-5 days plus booster doses every 1
to 2 months as needed. |
|
| Neurologic Diseases in which IVIg is effective |
Multiple sclerosis (MS)
| Randomized placebo-controlled trial of monthly IVIg in
relapsing-remitting MS (Fazekas et al 1997)
| 150 patients randomly assigned to IVIg 0.15-0.20g/kg body weight monthly
or placebo for 2 years. |
| Beneficial effect:
 | on disability - measured by change in EDSS score from
first to last study visit |
| on annual relapse rate |
| The effect of treatment on sustained progression of disability was not
reported. |
|
| Serial MRI scans not performed during that study. |
|
| Randomized, double-blind, cross-over trial of IVIg 1 gram/kg daily or
placebo on 2 consecutive days every month during two 6-month treatment periods (Sorensen
et al 1998).
| Fewer enhancing MRI lesions observed per patient per scan during IVIg
treatment. |
| More IVIg recipients were exacerbation free. |
| Total number of exacerbations & change in total
T2-weighted MRI lesions load during the IVIg and placebo periods were similar. |
| Significantly more IVIg recipients experienced headaches, nausea and
urticarial rashes. 11 of 26 patients experienced eczema
during treatment. |
| One patient developed hepatitis C. |
|
|
Guillain-Barre (GB) syndrome
| Inhibition or neutralization of anti-neuronal antibodies with IVIg might
be an appealing treatment option for GBS. |
| Controlled randomized studies have shown treatment effect with IVIg in
Guillain Barre syndrome (Van der Meche 1992, Bril et al 1996). |
| Isolated case reports suggest some GB patients may experience relapses
during or shortly after treatment with IVIg (Castro 1993). |
| Data from a recent multinational study indicate IVIg and PE are equally
effective yet combined treatment does not improve outcome beyond that seen with either
drug alone (Plasma exchange/Sandoglobulin Guillain-Barre study group 1995). |
| Glucocorticosteroids are not effective (Hughes 1978, Guillain-Barre
syndrome steroid group 1993). |
| The Dutch GB study group reports patients with CMV and c.
Jejuni-associated GB experience greater benefit from IVIg than PE (Visser et al 1996). It
is noteworthy that these patients have less favorable prognoses than the group of GB
patients overall. |
|
CIDPN
| Double-blind, placebo-controlled, cross-over study demonstrated
improvement in 63% of treated vs. 17% of placebo recipients (Hahn 1996). |
| Patients benefiting most were those with recent onset (< 1 year) or
recent exacerbation. Patients with chronic progressive CIDNP 9/19 experienced sustained
benefit with a single course of IVIg. |
| In contrast, in patients with relapsing CIDPN, treatment effects were
less sustained lasting approximately 6 weeks (vs 2-4 weeks with PE) before retreatment was
required at patient-specific intervals. |
|
| Diseases in which IVIg may be effective |
| Multifocal motor neuropathy with conduction block (MMN)
| The benefit of IVIg in MMN appears limited to newly developing deficits
and may not affect long term prognosis (Elliott 1994) implying the need for additional
immunotherapy for long-term management. |
|
| Dermatomyositis (DM)
| Some patients with DM who do not respond to steroid treatment may respond
transiently to IVIg (Dalakas et al 1993). It remains undetermined whether
glucocorticosteroids or IVIg is the preferred initial treatment for DM. |
|
| Lambert-Eaton syndrome
| A single study demonstrates short term benefits with IVIg therapy.
Treatment benefits occurred in conjunction with a reduction in levels of antibodies
directed against voltage-gated calcium channels (Bain et al 1996). |
|
| Other diseases have been treated with IVIg: some success but not in
controlled or blinded studies.
| myasthenia gravis (Edan 1994) |
| paraneoplastic syndromes (Phyphanich et al 1996) |
| MS (Achiron 1994, 1995, Francis 1994, Schuller 1983) |
| Miscellaneous neuropathies (Leger et al 1996, Dalakas 1993) |
| Adrenoleukodystrophy (Cappa et al 1994) |
|
|
| Adverse effects of IVIg |
| Adverse reactions are dose related |
| Headaches, nausea and skin rashes are most commonly experienced during or
shortly after IVIg infusions. |
| Excema is particularly problematic with doses of 1 gram/kg. |
| More serious adverse reactions includes
| anaphylaxis in IgA deficient
patients (Buckely 1991) |
| acute renal failure (Tan et al 1993) |
| aseptic meningitis (Sekul
et al 1994) |
| cerebral thrombosis (Dalakas 1994) |
| reversible cerebral vasospasm (Voltz 1996) |
| transmission of hepatitis C (Schiff 1994) |
|
| The cost of IVIg approximates $1200 for a 70 kg person at a dose of >
4mg/kg. This cost is similar to that for plasma exchange in the USA. |
|
| References: |
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