High dose intravenous immune globulins and plasma exchange in Guillain-Barré Syndrome

We report the effects of treatment with plasma-exchange (PE) and intravenous immune globulins (IVIg) in 36 out of 50 patients with Guillain-Barré syndrome (GBS) recruited by an incidence study in the Emilia-Romagna region of Italy. Comparison of the patients treated with PE and IVIg showed no significant differences in terms of effectiveness in improving the clinical course of GBS: at one month, respectively 11.1% and 25% had recovered, and 55.5% and 58.3% had improved by at least one grade. These results are in agreement with those of the Dutch GBS trial. No relapses were observed in either group. Moreover, our results showed no difference in clinical outcome at 1 and 3 months between the patients receiving only one therapy and those receiving two; a second cycle of therapy did not seem to improve the clinical course of the disease significantly. We conclude that PE and IVIg are both safe and effective therapies for GBS.     

IVIg in idiopathic autoimmune neuropathies: analysis in the light of the latest results

High-dose intravenous immunoglobulin (IVIg) is effective in the treatment of idiopathic autoimmune neuropathies including Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor neuropathy (MMN), representing a useful option or, as in MMN, the gold standard for their treatment. In GBS, two randomised, controlled trials (RCT) showed that IVIg is at least as effective as plasma exchange (PE). IVIg may however be preferred due to its low number of contraindications and complications and the fact that it can be administered at any time, in any department, including patients with contraindications to PE, or in intensive care units. In CIDP, at least four RCTs have demonstrated the efficacy of IVIg in over 60% of CIDP patients, while two additional RCTs have shown a comparable effect to steroids and PE as initial treatment. As with PE, the effects of IVIg usually last a few weeks meaning that the majority of patients require periodic maintenance infusions. The lower cost and easier administration of oral steroids compared to IVIg may be partly compensated by the safer long-term profile of IVIg over steroids. In MMN, almost 80% of patients improve with IVIg, the efficacy of which has been confirmed by four RCTs, making of IVIg the first-choice therapy in MMN, for which steroids and PE are ineffective or even detrimental. Also in these patients, IVIg induces a rapid improvement that usually lasts only a few weeks and has to be maintained with periodic IVIg infusions for long periods of time, if not indefinitely.     

PLASMA EXCHANGE VERSUS IMMUNOGLOBULIN INFUSION THERAPY IN MYASTENIC CRISIS. REPORT OF SIX CASES

The clinical effectiveness of plasma exchange (PE) and intravenous immunoglobulin infusion (IVIg) were compared in six patients during myastenic crisis. Five subjects had autoimmune myastenia and one myastenia-like syndrome. Neurological examination showed low values of myastenic muscle score. The initial treatment was infusion of IVIg 0.4 gr/Kg/day for 5 days, but despite therapy, progressive dyspnea and worsening muscular weakness appeared. After a variable delay from the last IG infusion (from 2 to 12 days) patients underwent PE treatment (Dideco Vivacell 798DE System) for 8 days, receiving a daily, single-volume exchange with 5% albumin replacement. After the fourth–fifth exchange, the patient weakness improved. Because PE started from 2 to 12 days after the last IVIg infusion, the therapeutic effect of PE did not depend on a delayed IVIg action. A spontaneous recovery also appears unlikely, because all the patients had severe, progressive neurological symptoms that proved insensitive to anticholinesterase drugs. A possible reason why IVIg proved ineffective is that the various immunoglobulin preparations differed in the proportion of specific antibody and therefore did not sufficiently counteract the patient's autoantibodies. In agreement with this hypothesis, others have recently described a remarkable post-exchange response to IVIgs in a different dysimmune syndrome. PE was effective because it directly washed the autoantibodies off.
In conclusion, these findings lend support to the use of PE as first-choice treatment in patients in myastenic crisis. Infusion of IgIV should be given only when PE is unavailable or contraindicated and supportive therapy alone proves inadequate.     

Intravenous immunoglobulin reduces serum tumor necrosis factor alpha in patients with Guillain-Barre syndrome

BACKGROUND: Tumor necrosis factor a TNF-alpha has a possible role in the pathogenesis of the Guillain-Barre syndrome (GBS). AIMS: To study the effect of intravenous immunoglobulin (IVIg) on serum TNF-alpha concentrations in patients with GBS. MATERIAL AND METHODS: The effect of IVIg on TNF-alpha was evaluated in 36 patients with GBS. Serum TNF-alpha concentration was measured by enzyme-linked immunosorbent assay (ELISA). The sera of 22 (61%) patients with GBS showed elevated concentrations of TNF-alpha (35-182 pg/ml) and these sera were individually incubated in vitro with IVIg (0.25 mg/ml) at 37 degrees C for 24 hours. RESULTS: The serum TNF-alpha concentrations in the 22 GBS patients with elevated levels showed a steady decline (60.34-19.78 pg/ml) following incubation with IVIg. These 22 patients also received IVIg therapy, and serum TNF-alpha concentrations showed a significant decline (65.5-9.75 pg/ml) at the end of the therapy. At the time of discharge from the hospital, there was a positive correlation between neurological recovery and decline in TNF-alpha concentrations in these 22 GBS patients. CONCLUSIONS: The results of this study indicate that elevated levels of TNF-alpha occur in a proportion of patients with GBS and in these patients elevated serum TNF-alpha levels decline with IVIg therapy.     

Autoimmune neuropathies: diagnosis, treatment, and recent topics

Here, we have reviewed the clinical patterns, diagnostic paradigms, etiopathogenesis, and therapeutic strategies of autoimmune neuropathies such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and IgM paraproteinemic neuropathy. Antiganglioside antibodies are frequently present in the serum samples obtained during the acutephase of GBS and Miller Fisher syndrome (MFS), a subtype of GBS. Recently, we found that some patients with GBS and MFS have serum antibodies against antigenic epitopes formed by 2 different gangliosides (ganglioside complex). The antibodies against GD1a/GD1b and/or GD1b/GT1b complexes are associated with severe disability and a requirement for mechanical ventilation. Anti-GM1/GalNAc-GD1a antibodies are found to be associated with pure motor GBS with frequent conduction blocks. In GBS, corticosteroids given alone do not significantly hasten the recovery or affect the long-term treatment outcome. Intravenous immunoglobulin therapy (IVIg) or plasma exchange (PE) is equally effective. Combined treatment with corticosteroids and IVIg may be a promising therapy for GBS. On the basis of the EFNS/PNS guidelines, we describe the treatment of chronic autoimmune neuropathies such as CIDP, MMN, and IgM paraproteinemic neuropathy. In treating CIDP, corticosteroids, IVIg, and plasma exchange are equally effective. In MMN, IVIg is the first-choice therapy; corticosteroids and PE are ineffective or even detrimental. IgM paraproteinemic neuropathies are known to be intractable, and these patients often have anti-myelin-associated glycoprotein antibodies and may respond to immunosuppressive and immunomodulatory therapies. However, the potential therapeutic benefits should be balanced against their possible side effects and usual slow disease progression.     

I.v. immunoglobulin reduces circulating proinflammatory cytokines in Guillain-Barré syndrome.

BACKGROUND: Treatment with human i.v. immunoglobulin (IVIg) modifies the course of Guillain-Barré syndrome (GBS), but its specific mode of action is unknown. Cellular interactions mediated through the release of cytokines play a role in the pathogenesis of GBS and may be regulated by IVIg therapy. OBJECTIVE: To delineate possible immunoregulatory mechanisms of IVIg in patients with GBS. METHODS: Circulating levels of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, were assayed in 21 patients with GBS before and serially after IVIg therapy. Comparisons were made with serum concentration of the anti-inflammatory cytokines, soluble TNF-alpha receptor and IL-10. Serial measurements were also performed in 12 untreated patients with relatively mild disease and 7 patients treated by plasma exchange. RESULTS: Circulating levels of TNF-alpha and IL-1beta decreased after treatment with IVIg but remained relatively high in untreated patients and in those treated by plasma exchange. Clinical improvement in patients treated with IVIg was associated with a reduction in unbound TNF-alpha during the acute phase of the illness. Circulating levels of anti-inflammatory cytokines were not affected by IVIg treatment. CONCLUSION: Data presented here suggest a novel mechanism of action of IVIg that involves selective modulation of circulating proinflammatory cytokines.     

A nationwide retrospective analysis on the effect of immune therapies in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Background and purpose: The guidelines for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) therapy suggest to use immunoglobulins (IVIg) and steroid as first‐line therapies. Patients who do not respond to one of the two drugs should be switched to the other drug. We collected therapeutic outcome data in patients followed at 11 centres in order to document the clinical practice in Italy. Methods: Clinical and electrophysiological data of patients with CIDP were entered into a central database. The clinical outcome (Rankin Scale) and drug side effects (SE) for first‐ and second‐line therapies were recorded. Results: A total of 267 patients were included. The percentage of responders (R) to first‐line therapy [steroid or IVIg or plasma exchange (PE)] was 69%; this number increased to 81% when patients who switched to different therapies were included. Overall, the percentage of R to IVIg was similar to R to steroids (P = 0.07) and higher than R to PE (P < 0.001). Of the main therapies, PE frequently caused SE (19%), followed by steroids (12.5%) and IVIg (4%). Conclusions: Switching between traditional therapies increases the number of responder patients. IVIg was confirmed to be a therapy with low SE.     

Plasma exchange and intravenous immunoglobulins: mechanism of action in immune-mediated neuropathies

Immune-mediated neuropathies are a heterogeneous group of peripheral nerve disorders, which are classified by time course, clinical pattern, affected nerves and pathological features. Plasma exchange (PE) and intravenous immunoglobulins (IVIg) are mainstays in the treatment of immune-mediated neuropathies. Of all treatments currently used, IVIg has probably the widest application range in immune-mediated neuropathies and efficacy has been well documented in several randomized controlled trials for Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP). Beneficial effects of IVIg have also been proven for multifocal motor neuropathy (MMN). Likewise, PE is an established treatment for GBS and CIDP, whereas it is considered to be ineffective in MMN. Different mechanisms of action are sought to be responsible for the immunemodulatory effect of PE and IVIg in autoimmune disorders. Some of those might be important for immune-mediated neuropathies, while others are probably negligible. The aim of this review is to summarize the recent advances in elucidating disease-specific mechanisms of actions of PE and IVIg in the treatment of immune-mediated neuropathies.     

Intravenous immunoglobulin therapy for Guillain-Barré syndrome with IgG anti-GM1 antibody

To compare the effects of intravenous immunoglobulin (IVIg) therapy and plasmapheresis for the IgG anti-GM1-positive subtype of Guillain-Barré syndrome (GBS), clinical and electrophysiological recoveries were analyzed in 24 patients treated with IVIg (n = 10) or plasmapheresis (n = 14). At entry, there were no significant differences between the two patient groups in age, sex, clinical severity (Hughes grade), sum scores of distally evoked amplitudes of compound muscle action potentials (CMAPs), and frequency of Campylobacter jejuni infection. The patients treated with IVIg had significantly lower Hughes grade scores 1, 3, and 6 months after onset (P = 0.03), and a higher probability to regain independent locomotion at 6 months [P(logrank) = 0.044]. In the IVIg group, markedly rapid recovery (improvement by two or more Hughes grade scores within 4 weeks) was more frequent (6 of 10 vs. 3 of 14, P = 0. 03), and delayed recovery (unable to walk independently at 6 months) was less frequent (0 of 10 vs. 4 of 14, P = 0.06). CMAP sum score at 6 months tended to be greater for the IVIg group (P = 0.07). For the IgG anti-GM1-positive subgroup of GBS patients, IVIg therapy may be a more efficacious treatment than plasmapheresis.     

Statin therapy and small fibre neuropathy: a serial electrophysiological study

Since plasma exchange (PE) and intravenous immunoglobulin (IVIg) have been widely used in treatment for Guillain–Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by IVIg, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/IVIg and the outlasting inflammatory response in peripheral nerves.