" I have
myasthenia gravis
and have been prescribed a course of treatment with IVIG. Please could you direct me to some research articles on the subject. Thanks, Jenny"
The latest articles are presented below with daily updates. Archived articles with some links to fulltext are presented at the bottom.
BACKGROUND: Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating disease of the peripheral nervous system. Treatment strategies include systemic steroids, immune adsorption, plasmapheresis, and intravenous immunoglobulins. Optic neuritis as an affectation of the central nervous system does not belong to the normal spectrum of neurological symptoms in GBS, which is thought to be restricted to the peripheral nervous system. CASE REPORT: A 55-year-old female patient with unilateral optic neuritis secondary to GBS was referred to our department. Visual acuity was 0.04 in the affected left eye, L. E. and 1.25 in the right eye, R. E. Visual field testing revealed a large centrocecal scotoma. Ophthalmoscopy disclosed a slight oedema of the left optic disc. High-dose steroid treatment based on the diagnosis of optic neuritis secondary to GBS could not improve vision in the patient's left eye. Therefore, a repetitive treatment with high-dose intravenous immunoglobulins (IVIg) was initiated. The patient underwent three treatment cycles - 0.4 g per kg daily for 5 days - with intervals of two weeks between each cycle. Visual acuity and visual field improved gradually after the initiation of the immunoglobulin treatment. At the end of the last treatment course - 7 weeks after the begin of ocular symptoms - visual acuity had recovered to 0.8. A small residual paracentral scotoma resolved completely within the following weeks. Further follow-up examinations revealed a complete recovery of visual acuity to 1.0. Side effects of the immunoglobulin treatment were not observed throughout the treatment period. CONCLUSIONS: Based on the observation that the clinical improvement in our patient coincided with the initiation of the IVIg treatment after steroid treatment had failed, we feel justified in drawing attention to IVIg as a potential treatment option in patients with GBS and involvement of the optic nerve.
PMID: 18260057 [PubMed:- Treatment with IVIG - in process]
BACKGROUND: Myasthenia gravis is an autoimmune disease in which autoantibodies interfere with neuromuscular transmission. As with other autoimmune diseases, people with myasthenia gravis would be expected to benefit from intravenous immunoglobulin (IVIg). OBJECTIVES: The objective of this review was to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease GroupTrials Register (April 2007) and MEDLINE (January 1966 to May 2007) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: We included all randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis. DATA COLLECTION AND ANALYSIS: One review author extracted the data and two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified six randomised controlled trials, all of which investigated short-term benefit. A trial of IVIg compared with placebo including 51 patients provided evidence for the effectiveness of IVIg in myasthenia gravis worsening. A study of 87 participants with exacerbation found no statistically significant difference between immunoglobulin and plasma exchange after two weeks. A study of 12 participants with moderate or severe myasthenia gravis treated in a crossover design trial found no statistically significant difference in the efficacy of immunoglobulin and plasma exchange after four weeks. A study with 15 participants with mild or moderate myasthenia gravis found no statistically significant difference in efficacy of IVIg and placebo after six weeks. A study included 33 participants with moderate exacerbations of myasthenia gravis and showed no statistically significant difference in the efficacy of IVIg and methylprednisolone. The last trial including 173 people with myasthenia gravis exacerbations, showed no superiority of IVIg 1 g/kg on two consecutive days over IVIg 1 g/kg on a single day. AUTHORS' CONCLUSIONS: In exacerbation of myasthenia gravis, one randomised controlled trial of IVIg versus placebo demonstrated the efficacy of IVIg and another did not show a significant difference between IVIg and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of IVIg. A further, but underpowered, trial showed no significant difference between IVIg and oral methylprednisolone.In chronic myasthenia gravis, there is insufficient evidence from randomised trials to determine whether IVIg is efficacious. More research is needed to determine whether IVIg reduces the need for corticosteroids as suggested by two case series.
PMID: 18254004 [PubMed:- Treatment with IVIG - in process]
Redimune((R)) NF Liquid, a ready-to-use, high-concentration intravenous immunoglobulin therapy preparation, is safe and typically well tolerated in the routine clinical management of a broad range of conditions.
Clin Exp Immunol. 2008 Jan 28;
Authors: Piguet D, Tosi C, Lüthi JM, Andresen I, Juge O,
In clinical practice, intravenous immunoglobulin therapy (IVIG) is used in the management of a wide variety of medical conditions. Observational studies examining IVIG use in routine clinical practice are therefore an important means of validating findings from more strictly randomized controlled trials of patients with specific conditions. In this observational study, we examined the tolerability of a high-concentration (12%) ready-to-use liquid IVIG (Redimune(R) NF Liquid) when used in the standard management of a diverse range of conditions (including primary immunodeficiency diseases, neurology conditions, oncology conditions and immune thrombocytopaenic purpura). IVIG regimen and dose were selected by the physician based on the summary of product characteristics. During the study, 193 infusions were administered to 51 patients in 153 infusion cycles (per infusion cycle: one to five infusions; mean dose, 347.6 mg/kg; mean duration, 202.4 min). The mean maximum infusion rate per cycle was 2.9 mg/kg/min, demonstrating that the infusion rate was often higher than that recommended in the summary of product characteristics. Redimune(R) NF Liquid was well tolerated: there were 36 adverse reactions (at least probably associated with IVIG) in 10 patients (19.6% of sample, 0.24 per infusion cycle, 0.19 per infusion). The most common adverse reaction was headache (50% of reactions), followed by chills (13.8%). Most reactions (69%) were mild and there were no serious or unexpected reactions. In conclusion, in routine clinical practice involving patients with many different conditions, Redimune(R) NF Liquid was well tolerated by the majority of patients.
PMID: 18241226 [PubMed:- Treatment with IVIG - as supplied by publisher]
Although polymerase chain reaction (PCR) is a highly sensitive procedure for the diagnosis of enteroviruses, it has never been systemically applied to the treatment of enteroviral encephalitis using intravenous immunoglobulin (IVIg). We conducted a 2-year randomized, controlled comparison of reverse transcription (RT)-PCR of cerebrospinal fluid (CSF) with traditional viral isolation to guide IVIg treatment. Seventy-five patients were enrolled and classified into three groups: one group with clinical manifestations of enteroviral infections and two without. The latter two groups were separated on the basis of whether IVIg treatment was guided by RT-PCR or virus culture assay. CSF specimens from the 18 confirmed cases of enteroviral encephalitis were RT-PCR positive for enterovirus in all but one case. Of the remaining 57 cases of nonenteroviral encephalitis, only 4 were positive for enterovirus RT-PCR. One patient in the group of IVIg treatment guided by viral isolation subsequently displayed a sequel of epilepsy. No patients in the IVIg treatment groups guided by RT-PCR had any neurological sequelae. In conclusion, the use of RT-PCR allowed rapid, sensitive, and specific detection of enteroviral RNA in CSF. When used to guide IVIg treatment, RT-PCR may shorten hospitalization and improve outcomes of patients with enteroviral encephalitis.
PMID: 18219129 [PubMed:- Treatment with IVIG - in process]
Relapsing demyelinating disease affecting both the central and peripheral nervous systems.
J Neurol Neurosurg Psychiatry. 2008 Jan 21;
Authors: Zéphir H, Stojkovic T, Latour P, Lacour A, de Seze J, Outteryck O, Maurage CA, Monpeurt C, Chatelet P, Ovelacq E, Vermersch P
BACKGROUND: Clinical and electromyographical findings of chronic inflammatory demyelinating polyradiculopathy (CIDP) are occasionally observed in patients with multiple sclerosis (MS). OBJECTIVE: To define a new inflammatory demyelinating disease unlike MS or CIDP. RESULTS: We report five patients with a demyelinating disease affecting the central nervous system (CNS) and the peripheral nervous system (PNS). Each case presented a relapsing-remitting course in which CNS involvement preceded PNS involvement All patients fulfilled Barkhof's criteria on MRI and the McDonald criteria for MS. Two patients had grey matter lesions with typical white matter changes. No systemic inflammatory disease and no metabolic or inflammatory factor for peripheral neuropathy were found. In all cases electromyography showed a demyelinating peripheral neuropathy without conduction block. Four patients fulfilled the European Federation of Neurological Societies / PNS guideline for chronic demyelinating inflammatory polyradiculopathy and Nicolas et al's criteria for CIDP, one of whom also fulfilled the Ad Hoc Subcommittee criteria for CIDP. Nerve biopsy, performed in two patients, showed histological evidence of CIDP. An improvement of clinical status and neurophysiological parameters was observed in three patients after treatment with either intravenous immunoglobulin (n = 1) or cyclophosphamide (n = 2). CONCLUSION: The CNS and PNS demyelination, the absence of oligoclonal bands, and the peripheral demyelination without conduction block indicate pathogenic mechanisms different from MS and CIDP. The chronology of events suggests an entity unlike that involved in acute demyelinating encephalomyelitis. Immunological reactivity against antigens common to peripheral and central myelin may explain why the demyelinating disease affected both the CNS and the PNS.
PMID: 18208860 [PubMed:- Treatment with IVIG - as supplied by publisher]
A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating polyneuropathy and appear to respond to IVIg.
Rheumatology (Oxford). 2008 Feb;47(2):208-11
Authors: Caro XJ, Winter EF, Dumas AJ
OBJECTIVES: The aetiopathogenesis of the fibromyalgia syndrome (FMS) remains unknown. Recent reports, however, suggest that a subgroup of FMS subjects has an immune-mediated disease. Therefore, our primary objective was to study FMS subjects for evidence of an immune-mediated demyelinating polyneuropathy. Our secondary objective was to determine the effects of treating these FMS subjects with the immune modulator, intravenous immunoglobulin (IVIg). METHODS: Fifty-eight FMS subjects, 26 rheumatic non-FMS subjects and 52 non-rheumatic non-FMS subjects were studied. Subjective measures of paraesthesias, weakness, stocking hypaesthesia, pain, fatigue and stiffness were made. Objective measures of tenderness, proximal muscle strength and electrodiagnostic (EDX) evidence of polyneuropathy and demyelination were also made. Eleven other FMS subjects underwent sural nerve biopsy. RESULTS: Paraesthesias, subjective weakness and stocking hypaesthesia were more common in FMS than in rheumatic non-FMS (P < or = 0.0001). Proximal muscle strength was less in FMS than in rheumatic non-FMS (P < or = 0.0001). EDX demonstrated a distal demyelinating polyneuropathy, suggestive of chronic inflammatory demyelinating polyneuropathy (CIDP), in 33% of FMS subjects. No rheumatic non-FMS subject had polyneuropathy (P = 0.005), or demyelination (P = 0.05). Fifteen FMS/CIDP subjects were subsequently treated with IVIg (400 mg/kg each day for 5 days). Pain (P = 0.01), tenderness (P = 0.001) and strength (P = 0.04) improved significantly. Fatigue and stiffness trended towards improvement. CONCLUSIONS: A significant subset of FMS subjects have clinical and EDX findings suggestive of CIDP. IVIg treatment shows promise in treating this subset. These observations have implications for better understanding and treating some FMS patients.
PMID: 18208823 [PubMed:- Treatment with IVIG - in process]
Reproductive counselling, treatment and course of pregnancy in 73 German MS patients.
Acta Neurol Scand. 2008 Jan 16;
Authors: Hellwig K, Brune N, Haghikia A, Müller T, Schimrigk S, Schwödiauer V, Gold R
Multiple sclerosis (MS) often affects women during the reproductive years of their life. During this period, issues such as choice of immunomodulatory treatment, seeking advice from specialists, relapse-induced steroid application before, during or after pregnancy in combination with breastfeeding gain importance. The objective was to investigate these issues retrospectively using a questionnaire among 73 MS patients with a total of 88 pregnancies. Eighty per cent of the participants consulted their neurologists before and 60% during pregnancy. The annual relapse rate decreased during pregnancy and significantly increased during the first 3 months after delivery. Immunomodulatory treatment was stopped due to desired pregnancy for a mean of 4 years. Fourteen of the MS patients received intravenous immunoglobulin treatment post-natal. Ninety per cent of the study subjects started breastfeeding. However, nearly 30% ablactated, as they received steroids due to a relapse. Weight and height of the full-term children of singleton pregnancies from MS patients were significantly lower compared with the ones of age-matched healthy controls. Our results confirm the known reduced relapse rate during pregnancy, which is followed by an increased relapse rate after delivery. They shed light on the epidemiology of childbirth in patients with MS.
PMID: 18205883 [PubMed:- Treatment with IVIG - as supplied by publisher]
Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2a therapy for chronic hepatitis C virus infection.
World J Gastroenterol. 2008 Jan 14;14(2):318-21
Authors: Khiani V, Kelly T, Shibli A, Jensen D, Mohanty SR
The combination of pegylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP) associated with Peg-IFN-alpha 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection. She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course, neurological findings, an electromyogram (EMG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.
PMID: 18186575 [PubMed:- Treatment with IVIG - in process]
Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial.
Lancet Neurol. 2008 Feb;7(2):136-144
Authors: Hughes RA, Donofrio P, Bril V, Dalakas MC, Deng C, Hanna K, Hartung HP, Latov N, Merkies IS, van Doorn PA,
BACKGROUND: Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP. METHODS: 117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740. FINDINGS: During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension. INTERPRETATION: This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP.
PMID: 18178525 [PubMed:- Treatment with IVIG - as supplied by publisher]
A disease-specific fraction isolated from IVIG is essential for the immunosuppressive effect of IVIG in experimental autoimmune myasthenia gravis.
J Neuroimmunol. 2008 Jan 4;
Authors: Fuchs S, Feferman T, Meidler R, Margalit R, Sicsic C, Wang N, Zhu KY, Brenner T, Laub O, Souroujon MC
Intravenous immunoglobulin (IVIG) treatment is beneficially used in autoimmune disorders including myasthenia gravis (MG) although its mode of action and active components are still not fully identified. In an attempt to isolate from IVIG a disease-specific suppressive fraction, IVIG was passed on columns of IgG from rats with experimental autoimmune MG (EAMG) or from MG patients. These chromatographies resulted in depletion of the suppressive activity of IVIG on rat EAMG whereas the minute amounts of IgG fractions eluted from the EAMG- or MG-specific columns retained the immunosuppressive activity of IVIG. These results demonstrate that a minor disease-specific immunoglobulin fraction present in IVIG is essential for its suppressive activity.
PMID: 18178258 [PubMed:- Treatment with IVIG - as supplied by publisher]
Myasthenia gravis (MG) is an autoimmune disorder resulting from the production of antibodies against acetylcholine receptors leading to the destruction of the postsynaptic membrane at the neuromuscular junction. In the US there are about 18,000 people with MG. Myasthenia gravis crisis (MGC) is defined as any MG exacerbation necessitating mechanical ventilation. Most patients presenting with MGC have an identifiable risk factor. The diagnosis of MGC should be suspected in all patients with respiratory failure, particularly those with unclear etiology. Acute management of MGC requires supportive general and ventilatory therapy and institution of measures to improve the neuromuscular blockade. The latter includes plasma exchange or i.v. immunoglobulin, and removal of the offending trigger. The outcome of patients with MGC has improved significantly and the current mortality rate is about 4 to 8%.
PMID: 18176295 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Long-term Outcomes of Pediatric Ocular Myasthenia Gravis.
Ophthalmology. 2007 Dec 21;
Authors: Ortiz S, Borchert M
PURPOSE: To review the presenting signs, therapeutic interventions, and clinical outcomes of purely ocular myasthenia gravis in a preadolescent population treated primarily with pyridostigmine bromide. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-one consecutive patients younger than 12 years with purely ocular myasthenia gravis at initial presentation. METHODS: The clinical charts were reviewed retrospectively. MAIN OUTCOME MEASURES: Time to generalization, stabilization, or resolution; prism cover test results; and visual acuity. RESULTS: Median age at onset was 26 months. The mean duration of follow-up was 6.5 years (range, 2-15). Presenting signs included ptosis (95%), strabismus (76%), limitation of ductions (17%), and Cogan's lid twitch (76%). The most common form of strabismus was exotropia. Pyridostigmine monotherapy was the initial treatment for all patients. Corticosteroids were added to the therapy for 6 patients. Generalization to systemic disease occurred in 3 patients. Two of those required intravenous immunoglobulin and thymectomy. Complete resolution off of medical therapy occurred in 4 patients. All patients had stabilization of the ocular motor deficits regardless of treatment. Eleven patients were treated for amblyopia; 2 had residual amblyopia. CONCLUSIONS: Ocular myasthenia in preadolescent children generally presents before age 5 and is clinically distinguished from the disease as it affects adults. Although the presenting signs of strabismus, ptosis, and Cogan's lid twitch are common in children or adults, the response to treatment and eventual outcomes differ. Most children can be safely treated with pyridostigmine alone. Generalization to systemic disease occurs at a much lower rate than in adults. Ocular manifestations stabilize in all children and completely resolve in some.
PMID: 18155768 [PubMed:- Treatment with IVIG - as supplied by publisher]
Multiple sclerosis: interferon beta for some serious forms.
Prescrire Int. 2007 Dec;16(92):252-7
Authors:
(1) Multiple sclerosis is a neurological disorder characterised by disseminated inflammatory lesions of the myelin sheath, the white fatty layer that covers the neurons in the brain and spinal column. The clinical repercussions are highly variable, ranging from minor deficits to severe disability and even death. Some patients have exacerbations separated by remissions of varying length, while others experience fairly steady progression of disability. This review article, based on Prescrire's standard in-house methodology, examines treatments proposed to slow the progression of multiple sclerosis. (2) For exacerbations (4 trials, a total of 140 patients), an improvement was noted in 64% of patients treated with intravenous methylprednisolone for 5 days, versus 40% of patients on placebo. (3) Interferon beta is the best-assessed of the disease-modifying drugs. Various marketed interferon beta products have been compared with one another in trials involving more than 1000 patients in total. There are no major differences in effectiveness or adverse effects. The latter are frequent, especially a flu-like syndrome and depression. (4) After a first episode suggestive of multiple sclerosis (3 trials, a total of 1160 patients), 35% of patients treated with interferon beta subsequently developed the disease, versus 50% of patients in the placebo groups. This advantage seemed to persist for at least 8 years. (5) In relapsing-remitting multiple sclerosis (4 trials, a total of 1426 patients), interferon beta prevented about one exacerbation every 2.5 to 3 years but had no clear preventive impact on progression of disability. (6) In secondary progressive multiple sclerosis (5 trials, a total of 3082 patients), interferon beta's effectiveness, if present, was limited to patients who continued to have exacerbations. (7) Natalizumab does not appear to be more effective than interferon beta. It is associated with serious adverse effects, about which only limited information is available. (8) Glatiramer has not been shown to prevent exacerbations or progression of disability. Intravenous immunoglobulin is still being tested in multiple sclerosis. In initially aggressive forms of multiple sclerosis, mitoxantrone has a negative risk-benefit balance (2 trials, 236 patients); it prevents less than one exacerbation during two years of treatment but causes heart failure in 1% to 2% of patients after 10 months of treatment. (9) Patients' anxiety as their disability worsens must not overshadow the fact that there are no treatments available with strong clinical effectiveness, and that all existing treatments carry a risk of serious adverse effects. Pending the arrival of something better, only interferon beta has a favourable risk-benefit balance, and only in selected patients.
PMID: 18092425 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Score-based immunoglobulin G therapy of patients with sepsis: The SBITS study*
Crit Care Med. 2007 Oct 23;
Authors: Werdan K, Pilz G, Bujdoso O, Fraunberger P, Neeser G, Schmieder RE, Viell B, Marget W, Seewald M, Walger P, Stuttmann R, Speichermann N, Peckelsen C, Kurowski V, Osterhues HH, Verner L, Neumann R, Müller-Werdan U,
OBJECTIVE:: Intravenous immunoglobulin as an adjunctive treatment in sepsis was regarded as promising by a Cochrane meta-analysis of smaller trials. In this phase III multicenter trial, we assessed whether intravenous immunoglobulin G (ivIgG) reduced 28-day mortality and improved morbidity in patients with score-defined severe sepsis. DESIGN:: Randomized, double-blind, placebo-controlled, multicenter trial. SETTING:: Twenty-three medical and surgical intensive care units in university centers and large teaching hospitals. PATIENTS:: Patients (n = 653) with score-defined sepsis (sepsis score 12-27) and score-defined sepsis-induced severity of disease (Acute Physiology and Chronic Health Evaluation II score 20-35). INTERVENTIONS:: Patients were assigned to receive either placebo or ivIgG (day 0, 0.6 g/kg body weight; day 1, 0.3 g/kg body weight). MEASUREMENTS AND MAIN RESULTS:: The prospectively defined primary end point was death from any cause after 28 days. Prospectively defined secondary end points were 7-day all-cause mortality, short-term-change in morbidity, and pulmonary function at day 4. Six hundred and fifty-three patients from 23 active centers formed the intention-to-treat group, 624 patients the per-protocol group (placebo group, n = 303; ivIgG group, n = 321). The 28-day mortality rate was 37.3% in the placebo group and 39.3% in the ivIgG group and thus not significantly different (p = .6695). Seven-day mortality was not reduced, and 4-day pulmonary function was not improved. Drug-related adverse events were rare in both groups. Exploratory findings revealed a 3-day shortening of mechanical ventilation in the surviving patients and no effect of ivIgG on plasma levels of interleukin-6 and tumor necrosis factor receptors I and II. CONCLUSIONS:: In patients with score-defined severe sepsis, ivIgG with a total dose of 0.9 g/kg body weight does not reduce mortality.
PMID: 18090384 [PubMed:- Treatment with IVIG - as supplied by publisher]
[Chronic inflammatory demyelinating polyneuropathies: problem of the long-term therapeutic management]
Rev Neurol (Paris). 2007 Sep;163 Spec No 1:3S90-4
Authors: Camdessanché JP
INTRODUCTION: No guideline is available for the long-term therapeutic management of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). STATE OF THE ART: Efficacy of corticosteroids, intravenous immunoglobulins and plasma exchanges has been shown in trials conducted on short periods. Only experts'recommendations are available for management of patients after initiation of these treatments. For corticosteroids, decrease must be very slow on one or two years. With intravenous immunoglobulins, dose per cure must be diminished and then delay between cures extended. Other immunomodulators or immunosuppressors have been tested in CIDP in case of failure of standard treatment and if treatment dependence appears (cyclophosphamide, cyclosporine, azathioprine, mycophenolate, beta-1a interferon, rituximab, tacrolimus, etc.), but no controlled trials are yet available. Treatment of CIDP in the long term is very complex because this entity brings together very different patients. Thereby, in clinical and electophysiological series of the literature, therapeutic prognostic may depend on the delay between first symptoms and treatment, course of the disease, demyelinating pattern on EMG and development of axonal lesions. PERSPECTIVES/CONCLUSIONS: Progress in the long-term treatment of CIDP depend on best diagnosis of the disease, fundamental research on pathophysiology to propose appropriate chemical molecules, and pursuit of trials with standard treatments on longer period and with others rhythm and way of administration. More recent treatments have to been tested in controlled trials too, in monotherapy or bi-therapy. Global cost in a patient treated for CIDP must be evaluated for each treatment. Multicentric approach of these questions will be recommended because of rarity of CIDP.
PMID: 18087236 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Chronic inflammatory demyelinating polyneuropathy and sarcoidosis: fortuitous association?]
Rev Neurol (Paris). 2007 Sep;163 Spec No 1:3S85-9
Authors: Ducray F, Costedoat-Chalumeau N, Bouhour F, Rousset H, Vial C
We report the case of a 36-year-old-man who first presented two relapses of chronic inflammatory demyelinating polyneuropathy (CIDP) before a diagnosis of sarcoidosis was made. He subsequently presented two combined relapses of CIDP and sarcoidosis. Each time, the outcome was favorable after treatment with intravenous immunglobulins and steroids. The possible relationship between CIDP and sarcoidosis is discussed.
PMID: 18087235 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)]
Rev Neurol (Paris). 2007 Sep;163 Spec No 1:3S68-76
Authors: Uzenot D, Azulay JP, Pouget J
Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.
PMID: 18087233 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous polyclonal human immunoglobulins in multiple sclerosis.
Neurodegener Dis. 2008;5(1):8-15
Authors: Soelberg Sorensen P
Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta-analysis of the four trials has shown that IVIG reduces the relapse rate and, possibly, disease progression. In patients with a first episode of demyelinating disease, IVIG delays the time to the second relapse and thereby to the diagnosis of definite MS. In patients with an acute MS relapse, IVIG as add-on therapy to methylprednisolone does not make remission of symptoms faster or more complete. IVIG does not seem to be of any benefit to chronic visual or motor symptoms in MS. In secondary progressive MS, IVIG has not shown any effect on disease progression, relapses or new magnetic resonance imaging lesions. Experimental studies in the MS model experimental autoimmune encephalomyelitis in rats demonstrate that IVIG has to be administered at the time of induction of a relapse in order to be effective. In conclusion, IVIG can be considered as a second-line treatment to approved therapies for relapsing-remitting MS, but the ideal dosage of IVIG still needs to be determined. In order to be a first-line treatment for MS, the beneficial effect should be confirmed in a large-scale placebo-controlled survey, or in a study comparing the effect with approved therapies for relapsing-remitting MS using appropriate clinical and magnetic resonance imaging outcome measures.
PMID: 18075269 [PubMed:- Treatment with IVIG - in process]
A Role for Interferon-beta in Guillain-Barré Syndrome?
BioDrugs. 2000 Jul;14(1):1-11
Authors: Créange A
Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy that is associated with long-lasting morbidity and a substantial risk of mortality. The 2 reference treatments, plasma exchange and intravenous immunoglobulins (IVIg), do not change the functional prognosis for the most severely ill patients. The pathogenesis of GBS involves humoral and cellular immune dysfunctions that have only recently been characterised. Antibodies to nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity and reversible conduction failure. The cellular immune reaction is associated with increases in pro-inflammatory cytokines [such as tumour necrosis factor-alpha (TNFalpha)] and matrix metalloproteinases (MMPs; e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming growth factor-beta1 (TGFbeta1)]. All the changes favour adhesion to and transmigration across the endothelium of immune cells, a key phenomenon associated with GBS. Recovery from GBS is characterised by the normalisation of these changes. Experimental allergic neuritis (EAN), the experimental model of GBS, has strikingly similar immunological characteristics. The usual treatment options for patients with GBS (plasma exchange and IVIg) mainly target the humoral component of the immune response. Interferon-beta (IFNbeta) is a cellular immunomodulator that inhibits antigen presentation and TNFalpha production and binding, and modulates macrophage properties. IFNbeta increases anti-inflammatory T cell functions and the production of anti-inflammatory cytokines, such as TGFbeta1. IFNbeta has important effects on leukodiapedesis, caused by modulating the expression of cell adhesion molecules and the MMP-9 proteinases. It has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The pathophysiology of patients with GBS, an understanding of IFNbeta properties and results of experimental studies support the investigation of IFNbeta in trials of patients with GBS.
PMID: 18034551 [PubMed:- Treatment with IVIG - in process]
Use of intravenous immunoglobulin in multiple sclerosis.
BioDrugs. 1998 Jun;9(6):465-75
Authors: Achiron A, Barak Y, Sarova-Pinhas I
Intravenous immunoglobulin (IVIg) pooled from healthy human volunteers has a role in several immunomodulating mechanisms which may affect the pathogenesis of multiple sclerosis. Modulation of the disease course by IVIg is achieved both by limiting the inflammatory process and by enhancing remyelination. Clinical evidence of the effects of IVIg in multiple sclerosis is based on the results of several trials demonstrating the beneficial effects of IVIg on the relapse rate and on neurological disability. Brain magnetic resonance imaging studies support the clinical results by showing a decrease in both the disease burden and the appearance of new lesions. Preliminary results have demonstrated an improvement in the parameters of isometric muscle testing, chronic optic neuritis and the prevention of postpartum relapses. However, design and sample size limitations require larger controlled studies to substantiate these reports. Integrating the accumulating experimental data with clinical experience will assist in defining the specific mechanisms by which IVIg suppresses the disease process and clarify the future indications for IVIg treatment in multiple sclerosis.
PMID: 18020579 [PubMed:- Treatment with IVIG - in process]
Atypical relapsing course of Kawasaki disease with hemorrhagic serous effusions and hepatic dysfunction.
Indian Pediatr. 2007 Oct;44(10):785-7
Authors: Elizabeth KE, Ahamed MZ, Praveen KS
Kawasaki disease (KD) is a multisystem vasculitis of childhood with cardiac, renal, pulmonary and neurological complications. Hemorrhagic serous effusions, liver dysfunction and relapsing course in spite of treatment are rare. We report an atypical case of KD with a relapsing course, hemorrhagic effusions and hepatic dysfunction, that required two repeated courses of intravenous immunoglobulin (IVIG) and methylprednisolone.
PMID: 17998582 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Abnormality of circulating CD4(+)CD25(+) regulatory T cell in patients with Guillain-Barré syndrome.
J Neuroimmunol. 2007 Dec;192(1-2):206-14
Authors: Chi LJ, Wang HB, Zhang Y, Wang WZ
CD4(+)CD25(+) T regulatory cells (Tregs), a subset of CD4(+) T cells expressing high levels of CD25 and the transcription factor Foxp3, are critical in maintaining immunologic homeostasis and preventing autoimmunity by suppressing self-reactive T cells. Guillain-Barré syndrome (GBS) is thought to be a self-limiting, autoimmune disease of the peripheral nervous system. We hypothesized that altered frequency and/or function of Tregs play a role in the breakdown of immunologic self-tolerance in GBS patients. To characterize Tregs in GBS patients, we used flow cytometry to evaluate peripheral numbers of Tregs, real-time polymerase chain reaction to assay mRNA expression of FOXP3, and coculture to analyze functional suppressive properties of Tregs. The results showed that acute-stage patients with AMAN and AIDP exhibited significantly reduced numbers of peripheral Tregs as compared with healthy donors, but marked improvement was observed in stable-stage patients with GBS after treatment with intravenous immunoglobulin (IVIG), concomitantly with improvement of neuropathic symptoms. On the other hand, GBS-derived Tregs and Tregs from healthy individuals exhibited equal FOXP3-expression of mRNA and their ability of suppressing the proliferation and cytokine secretion of CD4 (+) effector T cells was unimpaired in GBS patients. These results suggest that short-term reduced circulating Tregs may be associated with the pathogenesis of two subtypes of GBS. Reversible number and intact function of Tregs presumably contribute to monophasic self-limiting course in GBS.
PMID: 17997492 [PubMed:- Treatment with IVIG - in process]
Co-infection with Mycoplasma pneumoniae and cytomegalovirus resulting in an acute demyelinating polyneuropathy in a pediatric patient.
Turk J Pediatr. 2007 Jul-Sep;49(3):331-3
Authors: Greco F, Salvo V, Sorge A, Perrini S, Garozzo R, Sorge G
A co-infection with Mycoplasma pneumoniae and cytomegalovirus (CMV) resulting in an acute demyelinating polyneuropathy is reported in an immunocompetent girl. Two months following a respiratory infection, the patient showed a symptomatology consisting of weakness in lower limbs, followed by facial asymmetry and arm weakness. Serum M. pneumoniae antibodies were elevated and active CMV infection was diagnosed by polymerase chain reaction (PCR) performed on cerebrospinal fluid. Treatment with oral clarithromycin, intravenous immunoglobulins and ganciclovir was associated with rapid improvement and complete recovery. It is very probable that clinical findings were secondary to the reactivation of CMV caused by persistent M. pneumoniae infection in the respiratory tract. This may be the first report in the pediatric literature of a co-infection of M. pneumoniae and CMV resulting in peripheral nervous system involvement.
PMID: 17990593 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Myasthenia gravis (MG) is a rare, autoimmune neuromuscular junction disorder. Contemporary prevalence rates approach 1/5,000. MG presents with painless, fluctuating, fatigable weakness involving specific muscle groups. Ocular weakness with asymmetric ptosis and binocular diplopia is the most typical initial presentation, while early or isolated oropharyngeal or limb weakness is less common. The course is variable, and most patients with initial ocular weakness develop bulbar or limb weakness within three years of initial symptom onset. MG results from antibody-mediated, T cell-dependent immunologic attack on the endplate region of the postsynaptic membrane. In patients with fatigable muscle weakness, the diagnosis of MG is supported by: 1. pharmacologic testing with edrophonium chloride that elicits unequivocal improvement in strength; 2. electrophysiologic testing with repetitive nerve stimulation (RNS) studies and/or single-fiber electromyography (SFEMG) that demonstrates a primary postsynaptic neuromuscular junctional disorder; and 3. serologic demonstration of acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) antibodies. Differential diagnosis includes congenital myasthenic syndromes, Lambert Eaton syndrome, botulism, organophosphate intoxication, mitochondrial disorders involving progressive external ophthalmoplegia, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), motor neuron disease, and brainstem ischemia. Treatment must be individualized, and may include symptomatic treatment with cholinesterase inhibitors and immune modulation with corticosteroids, azathioprine, cyclosporine, and mycophenolate mofetil. Rapid, temporary improvement may be achieved for myasthenic crises and exacerbations with plasma exchange (PEX) or intravenous immunoglobulin (IVIg). Owing to improved diagnostic testing, immunotherapy, and intensive care, the contemporary prognosis is favorable with less than five percent mortality and nearly normal life expectancy.
PMID: 17986328 [PubMed:- Treatment with IVIG - in process]
Long-term effect of intravenous immunoglobulin on anti-MuSK antibody-positive myasthenia gravis.
Acta Neurol Scand. 2007 Dec;116(6):406-8
Authors: Shibata-Hamaguchi A, Samuraki M, Furui E, Iwasa K, Yoshikawa H, Hayashi S, Yamada M
Anti-muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) patients show various responses to conventional immunosuppressive treatment and some patients are resistant to these therapies. We report a 50-year-old Japanese man with anti-MuSK antibody-positive MG, who showed no or poor response to various therapies, including plasmapheresis, corticosteroid, and tacrolimus. The patient was then treated with intravenous immunoglobulin (IVIG), and showed a good response that persisted over 20 months. The outcome of this case suggests that IVIG treatment may be an effective therapeutic option for anti-MuSK antibody-positive MG, with a potentially long-term effect.
PMID: 17986100 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Authors: Descloux E, Perpoint T, Ferry T, Lina G, Bes M, Vandenesch F, Mohammedi I, Etienne J
Staphylococcus aureus superantigenic toxins are responsible for menstrual and non-menstrual toxic shock syndrome (TSS). We compared the clinical and biological characteristics of 21 cases of menstrual TSS (MTSS) with 34 cases of non-menstrual TSS (NMTSS) diagnosed in France from December 2003 to June 2006. All 55 S. aureus isolates had been spontaneously referred to the French National Staphylococcal Reference Center, where they were screened for superantigenic toxin gene sequences. Most of the patients had previously been in good health. The most striking differences between MTSS and NMTSS were the higher frequency in NMTSS of neurological disorders (p=0.028), of S. aureus isolation by blood culture (50% versus 0% in MTSS), and the higher mortality rate in NMTSS (22% versus 0% in MTSS). The tst and sea genes were less frequent in isolates causing NMTSS than in those causing MTSS (p<0.001 and 0.051, respectively). Higher mortality was significantly associated with the presence of the sed gene (p=0.041), but when considering NMTSS survivors and non-survivors, no clinical or bacteriological factors predictive of vital outcome were identified. Specific antitoxinic therapy was rarely prescribed, and never in fatal cases. Higher mortality was observed in NMTSS than in MTSS, and no definite factors could explain the higher severity of NMTSS. NMTSS would require more aggressive therapy, comprising systematic rapid wound debridement, antistaphylococcal agents, including an antitoxin antibiotics, and intravenous immunoglobulin.
PMID: 17932694 [PubMed:- Treatment with IVIG - in process]
The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fcgamma receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the development of experimental autoimmune encephalomyelitis (EAE), an accepted animal model for multiple sclerosis (MS). The protection was associated with peripheral increase in CD4+CD25+Foxp3+ regulatory T cell (Treg) numbers and function. The protection was Treg-mediated because IVIg failed to protect against EAE in mice that were depleted of the Treg population. Rather than inducing de novo generation from conventional T cells, IVIg had a direct effect on proliferation of natural Treg. In conclusion, our results highlight a novel mechanism of action of IVIg and provide a rationale to test the use of IVIg as an immunomodulatory tool to enhance Treg in early onset MS and other autoimmune and inflammatory conditions.
PMID: 17932250 [PubMed:- Treatment with IVIG - in process]
Hospital admissions for Guillain-Barré syndrome in the United States, 1993-2004.
Neuroepidemiology. 2007;29(1-2):83-8
Authors: Frenzen PD
BACKGROUND: The hospitalization rate for Guillain-Barré syndrome (GBS) in the USA has recently decreased. This study examined which demographic groups were affected and whether there were any changes in medical care that might explain the decrease. METHODS: Information about hospitalizations for GBS was obtained from the 1993-2004 annual Nationwide Inpatient Sample and used to estimate hospitalization rates and the medical characteristics of hospitalized GBS patients. RESULTS: The GBS hospitalization rate decreased 20.1% (95% CI 18.3-21.9%) between 1993 and 2004. Most groups were affected by the decrease except persons aged 18-44 years. There were several changes in medical care during the period, including a reduction in interhospital transfers and a shift from plasmapheresis to intravenous immunoglobulin (IVIg) therapy. CONCLUSIONS: The reduction in transfers accounted for about one-fourth of the decrease in the GBS hospitalization rate, and may have been related to the shift from plasmapheresis to IVIg therapy. The other causes of the decrease are unknown.
PMID: 17925599 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Surrogate therapeutic outcome measures in patients with myasthenia gravis.
Muscle Nerve. 2008 Feb;37(2):172-6
Authors: Zinman L, Baryshnik D, Bril V
Treatment of acquired myasthenia gravis (MG) with immunotherapies successfully relieves symptoms and improves strength as documented by the Quantitative Myasthenia Gravis Score for disease severity (QMGS). Neuromuscular function, as demonstrated by the surrogate measures of repetitive nerve stimulation (RNS) and single-fiber electromyography (SFEMG), is sensitive for diagnosis and staging disease severity. This study of 51 patients treated with immunomodulation confirmed that RNS and SFEMG are useful to stage disease severity, but found that clinical measures such as the QMGS are more sensitive to change than electrophysiological parameters. The presence of blocking on SFEMG did predict responsiveness to intravenous immunoglobulin (IVIG) treatment, providing clinicians with an objective, reliable, quantitative measure to help determine which patients will benefit from this costly treatment. Muscle Nerve, 2007.
PMID: 17918748 [PubMed:- Treatment with IVIG - in process]
Self-reactivity in the dimeric intravenous immunoglobulin fraction.
Ann N Y Acad Sci. 2007 Sep;1110:681-93
Authors: Schaub A, Wymann S, Heller M, Ghielmetti M, Beleznay Z, Stadler BM, Bolli R, Miescher S
Therapeutic intravenous immunoglobulin (IVIg) preparations contain antibodies reflecting the cumulative antigen experience of the donor population. IVIg contains variable amounts of monomeric and dimeric IgG, but there is little information available on their comparative antibody specificities. We have isolated highly purified fractions of monomeric and dimeric IgG by size-exclusion chromatography. Following treatment of all fractions at pH4, analyses by immunodot and immunocytology on human cell lines showed a preferential recognition of autoantigens in the dimeric IgG fraction. Investigation of the HEp-2 cytoplasmic proteome by 2D-PAGE, Western blot, and subsequent identification of IVIg reactive spots by mass spectrometry (LC-MS/MS) showed that IVIg recognized only a restricted set of the total proteins. Similar experiments showed that more antigens were recognized by the dimeric IgG fraction, especially when the dissociated dimer fraction was used, as compared to its monomeric counterpart. These observations are consistent with idiotype-anti-idiotype masking of auto-specific Abs in the dimeric fraction of IVIg.
PMID: 17911483 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Suppression of experimental autoimmune myasthenia gravis by intravenous immunoglobulin and isolation of a disease-specific IgG fraction.
Ann N Y Acad Sci. 2007 Sep;1110:550-8
Authors: Fuchs S, Feferman T, Zhu KY, Meidler R, Margalit R, Wang N, Laub O, Souroujon MC
Intravenous immunoglobulin (IVIG) administration has been beneficially used for the treatment of a variety of autoimmune diseases including myasthenia gravis (MG). We have demonstrated that IVIG administration in experimental autoimmune MG (EAMG) results in suppression of disease that is accompanied by decreased Th1 cell and B cell proliferation. Chromatography of pooled human immunoglobulins (IVIGs) on immobilized IgG, isolated from rats with EAMG, results in a complete depletion of the suppressive activity of the IVIG. Moreover, the eluate from this EAMG-specific antibody column retains the immunosuppressive activity of IVIG. This study supports the notion that the therapeutic effect of IVIGs is mediated by an antigen-specific anti-immunoglobulin (anti-idiotypic) activity that is essential for its suppressive activity.
PMID: 17911471 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Efficacy of intravenous immunoglobulin in multifocal motor neuropathy.
Ann N Y Acad Sci. 2007 Sep;1110:248-55
Authors: Leger JM, Vargas S, Lievens I
Multifocal motor neuropathy is a distinct entity, whose treatment differs from that of other chronic immune-mediated neuropathies, mainly chronic inflammatory demyelinating polyradiculoneuropathy, and its variant, multifocal acquired demyelinating sensory and motor neuropathy, although they share some electrophysiological characteristics. From the first descriptions, intravenous immunoglobulins (IVIg) have been considered to be the gold standard of treatment for multifocal motor neuropathy. However, if the effectiveness of IVIg has been confirmed by several randomized, double-blind, placebo-controlled trials, only a few patients experience persistent improvement after a single or few courses of therapy, and the long-term efficacy of IVIg in this disease is currently debated. Consequently, there is a need for new therapeutic strategies that focus on the effects and the costs of this therapy over long-term follow-up.
PMID: 17911439 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous immunoglobulin (IVIg) therapy is used increasingly for different immune-mediated diseases, such as the Guillain-Barre syndrome. We report the case of a 55-year-old man who developed a cerebral infarction 2 days after completion of treatment with intravenous immunoglobulin for Guillain-Barre syndrome.
PMID: 17903841 [PubMed:- Treatment with IVIG - in process]
Intravenous immunoglobulin (IVIg) preparations are reportedly effective in inhibiting the relapse of multiple sclerosis (MS), but few reports have investigated the effect of IVIg on dendritic cells (DCs), which are thought to be involved in such relapses. In the system that uses monokines to differentiate DCs from peripheral blood monocytes (Mo-DCs), we investigated the effect of immunoglobulin G (IgG) on these antigen-presenting cells. Using monocytes derived from healthy volunteers, IgG partially inhibited the expression of CD1a, a marker of immature DCs (imDCs), and CD40 and CD80, which are markers associated with T cell activation. In contrast, IgG enhanced the expression of CD83, a marker of mature DCs (mDCs). Furthermore, IgG markedly inhibited the expression of CD49d [very late activation antigen (VLA)-4 alpha4-integrin], the adhesion molecule required for mDCs to cross the blood-brain barrier. We obtained similar results on all the aforementioned cell surface molecules investigated in both healthy controls and MS patients. In addition, IgG treatment of cells from both healthy controls and MS patients inhibited the production of interleukin (IL)-12, a cytokine associated with mDC differentiation, but did not inhibit the production of IL-10. These results suggested the possibility that IgG treatment, apart from its known ability to regulate inflammation, may help to prevent relapses of MS by controlling DC maturation, consequently inhibiting invasion of immune cells into the central nervous system and affecting the cytokine profile.
PMID: 17900307 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Hashimot's encephalopathy-Response to intravenous immunoglobulin.
J Stroke Cerebrovasc Dis. 1998 Jul-Aug;7(4):265-6
Authors: Wirkowski E, Libman RB, Batash M
Background: Hashimoto's encephalopathy is an unusual brain disorder consisting of focal and diffuse cerebral dysfunction that may present in a stroke-like fashion. Treatment has consisted of steroids and immunosuppression. Treatment with a potentially less toxic modality such as intravenous immunoglobulin (IVIG), if found to be effective, might offer an alternative approach to these patients. Case Description: We present an 82-year-old woman who developed headache, changes in mental status, and multifocal neurological deficits. Investigation revealed significantly elevated titers of antithyroid antibodies. Treatment with prednisone and methotrexate was unsuccessful. Treatment with monthly courses of IVIG resulted in marked clinical improvement. Conclusion: Hashimoto's encephalopathy may be more common than is generally recognized. A trial of IVIG should be considered for patients with this devastating condition.
PMID: 17895096 [PubMed:- Treatment with IVIG - in process]
PURPOSE OF REVIEW: To provide clinically useful guidelines in the management of neuropathy associated with monoclonal gammopathy from a review of the most recent literature and our own experience. RECENT FINDINGS: Recent data on neuropathy associated with monoclonal gammopathy come from better descriptions of subgroups, and from new treatment compounds that have shown encouraging results in different entities. SUMMARY: Neuropathies associated with monoclonal gammopathy are relatively rare and most often the neuropathy reveals the monoclonal gammopathy. These conditions require combined neurological and haematological assessments. Their clinical presentations are highly heterogeneous but most have an electrophysiological demyelinating pattern. The main described subgroup is IgM anti-(myelin-associated glycoprotein) neuropathy, which presents as a relatively benign, slowly progressive sensory neuropathy. Nerve biopsy should be considered in patients with progressive and disabling axonal neuropathy. Neuropathies associated with monoclonal gammopathy have various neurological and general outcomes, including life-threatening entities such as light-chain amyloid neuropathy and POEMS syndrome. Treatment choice is wide and depends both on the underlying haematological disorder and severity of the neuropathy. Intravenous immunoglobulin should be assessed in demyelinating monoclonal gammopathy of undetermined significance neuropathy. Malignant haematological disorders should be treated per se. The possibility of a malignant evolution of monoclonal gammopathy of undetermined significance warrants regular haematological monitoring.
PMID: 17885441 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Autoimmune mechanisms are postulated to play a role in the development and progression of dysimmune neuropathies (DN). We investigated the relation between lymphocyte number and marker expression, and disease activity in 20 patients with DN under intravenous immunoglobulins (IVIg) treatment. B- and T-lymphocyte markers were studied by flow cytometry of the expression of CD5, CD25, CD23 and CD38 markers on B cells and of CD3, CD4 and CD8 markers, respectively. These parameters were compared with those obtained from matched healthy volunteers. The proportions of CD38+ B cells were higher in patients compared with those of controls. Proportions of activated CD4+ and CD8+ T cells were comparable in peripheral blood mononuclear cells of patients and controls, but a significant reduction of the absolute numbers of CD3+, CD4+ and CD8+ cells were observed in DN patients. The percentages of CD25+ memory T cells were instead significantly increased in DN patients. Lastly, T-cell reduction and the CD19/CD38 ratio over total B (CD19+) cells directly correlated with a poor response to IVIg therapy. In DN, whereas T-cell number is reduced, activated T and B cells are increased, thus suggesting an intrinsic defect of the immune response.
PMID: 17880569 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease.
Proteomics. 2007 Oct;7(20):3651-60
Authors: Choe L, D'Ascenzo M, Relkin NR, Pappin D, Ross P, Williamson B, Guertin S, Pribil P, Lee KH
An 8-plex version of an isobaric reagent for the quantitation of proteins using shotgun methods is presented. The 8-plex version of the reagent relies on amine-labeling chemistry of peptides similar to 4-plex reagents. MS/MS reporter ions at 113, 114, 115, 116, 117, 118, 119, and 121 m/z are used to quantify protein expression. This technology which was first applied to a test mixture consisting of eight proteins and resulted in accurate quantitation, has the potential to increase throughput of analysis for quantitative shotgun proteomics experiments when compared to 2- and 4-plex methods. The technology was subsequently applied to a longitudinal study of cerebrospinal fluid (CSF) proteins from subjects undergoing intravenous Ig treatment for Alzheimer's disease. Results from this study identify a number of protein expression changes that occur in CSF after 3 and 6 months of treatment compared to a baseline and compared to a drug washout period. A visualization tool was developed for this dataset and is presented. The tool can aid in the identification of key peptides and measurements. One conclusion aided by the visualization tool is that there are differences in considering peptide-based observations versus protein-based observations from quantitative shotgun proteomics studies.
PMID: 17880003 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
We describe relapse of chronic inflammatory demyelinating polyneuropathy in a patient who had been in remission for 5 years after treatment with autologous stem cell transplantation. Before the transplant, he needed higher doses of immunosuppressive treatment than are now necessary to maintain his improved condition. He now receives intravenous immunoglobulins at monthly intervals.
PMID: 17878198 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Immunoglobulins and physiopathology: actual indications]
Rev Med Interne. 2007 May;28 Spec No. 1:11-7
Authors: Mouthon L, Guilpain P
Intravenous Immunoglobulin (IVIg) are therapeutic preparations of normal human IgG that are obtained from pools of plasma from healthy blood donors. IVIg can be used at high dose as an immunomodulatory agent in a large number of autoimmune and/or systemic inflammatory diseases, particularly in hematologic or neurologic diseases. Mechanisms of action of IVIg are multiple and intricate. The development of new therapeutic trials in association with analyses of mechanisms of action should help to define new indications of IVIg therapy.
PMID: 17768833 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Initially used for the treatment of immunodeficiencies, intravenous immunoglobulin (IVIg) has increasingly been used as an immunomodulatory agent in immune thrombocytopenic purpura, autoimmune neuropathies, systemic lupus erythematosus, myasthenia gravis, Guillain-Barré syndrome, and Kawasaki disease. Although IVIg benefits have been reported in many autoimmune and systemic inflammatory diseases, its mechanisms of immunomodulation are not fully understood and probably involve Fc-dependent and/or F(ab')(2)-dependent mutually non-exclusive effects. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg.
PMID: 17765663 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
A retrospective study of 120 cases of acute polyradiculoneuropathy hospitalized in the National Institute of Neurology, since 1974. We analysed the clinical and neurophysiological pictures, the course of the disease and the prognosis. All ages and sex were affected. The mean age of onset was 34 years. There were a predominance of male 2.5:1. Weakness, particularly of the lower limbs, was the initial complaint of patients. A rise in the level of cerebro-spinal fluid protein in the absence of pleiocytosis was found in 80% of patients. Electrophysiological data showed most frequent sensory motor demyelinating polyradiculo-neuropathies (60%). Conduction blocks were found in 90% of cases. The last 6 years, gammaglobulin (0.4g/kg per day for 5 days) was given for the first days of the disease and has been shown to improve the vital and functional prognosis.
PMID: 17722794 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Immune responses to myelin proteins in Guillain-Barre syndrome.
J Neurol Neurosurg Psychiatry. 2007 Aug 23;
Authors: Makowska A, Pritchard J, Sanvito L, Gregson N, Peakman M, Hayday A, Hughes R
BACKGROUND: Potential target autoantigens in the demyelinating form of Guillain-Barré Syndrome (GBS) include the myelin proteins PMP22, P0 and P2. METHODS: We investigated immunoreactivity to P0, P2 and PMP22 proteins in 37 GBS patients and 32 healthy controls. RESULTS: Antibodies to PMP22 or P0 peptides were detected at presentation in only 5 out of 37 patients. In ELISPOT assays, blood mononuclear cells from 15 out of 24 GBS patients but none of the control subjects produced interleukin-10 (IL-10) in response to peptides from proteins P0, P2 or PMP22 (p = 0.0003). The cells from only two patients produced interferongamma (IFNgamma).The cells from 11 GBS patients had increased IL-10 responses to peptides representing sequences from the extracellular domains of PMP22 before intravenous immunoglobulin (IVIg) treatment (p = 0.006). The cells from 11 GBS patients, including seven who responded to the extracellular domains of PMP22, had increased IL-10 responses to the intracellular domain of P0 before (p = 0.005) and those from 9 patients after they had been treated with IVIg (p = 0.01). CONCLUSIONS: Antibodies to P0 and PMP22 protein peptides do occur in GBS but are uncommon. Circulating mononuclear cell IFNgamma responses to P0 and PMP22 myelin proteins are rare but IL-10 responses occur significantly more often than in normal subjects. They might be part of a harmful pathogenetic process or represent a regulatory response.
PMID: 17717020 [PubMed:- Treatment with IVIG - as supplied by publisher]
Chronic inflammatory demyelinating polyneuropathy associated with intestinal tuberculosis.
J Microbiol Immunol Infect. 2007 Aug;40(4):377-80
Authors: Chong VH, Joseph TP, Telisinghe PU, Jalihal A
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an increasingly common but under-recognized neurological disorder. It is immune mediated, and usually has a relapsing and remitting course. However, the initial presentation may be rapid. It can be associated with significant morbidity and mortality, particularly if there is a delay in diagnosis and treatment. It has been associated with both infective and non-infective etiologies. We present a case of CIDP associated with ileocecal tuberculosis (TB), presenting with progressive motor weakness and significant weight loss. The patient's symptoms improved to some extent with intravenous immunoglobulin and steroid, but improved significantly after being started on anti-TB therapy. However, his symptoms relapsed when he stopped his anti-TB treatment prematurely whilst continuing the immunosuppressive therapy. Upon resuming the anti-TB therapy, he made a good recovery. CIDP associated with TB has only been reported once. Our case highlights the need to consider TB in patients with neurological disorders.
PMID: 17712474 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Authors: Garssen MP, van Koningsveld R, van Doorn PA, Merkies IS, Scheltens-de Boer M, van Leusden JA, van Schaik IN, Linssen WH, Visscher F, Boon AM, Faber CG, Meulstee J, Prick MJ, van den Berg LH, Franssen H, Hiel JA, van den Bergh PY, Sindic CJ
PMID: 17702789 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous immunoglobulin therapy for neuromuscular disorders.
Semin Neurol. 2007 Sep;27(4):340-6
Authors: Ross MA
Treatment of specific immune-mediated neuromuscular disorders involves consideration of many factors including severity of illness, concurrent medical problems, supportive therapies, and immune-modulating therapies. Many immune-modulating therapies are available, including steroids, an increasing number of immunosuppressive drugs, plasmapheresis, and intravenous immunoglobulin (IVIG). Deciding on which immune-modulating therapy involves selecting from those with proven efficacy for a specific disorder and global considerations of which therapies are most appropriate for an individual patient's circumstances. IVIG has become a commonly used therapy as it is well tolerated, easily administered, and is often efficacious with a relatively rapid action. IVIG has become a first-line therapy for several immune-mediated demyelinating polyneuropathies and may play a role in treating exacerbations of myasthenia gravis and selected chronic treatment-refractory cases of Lambert-Eaton myasthenic syndrome, dermatomyositis, and polymyositis.
PMID: 17701871 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Guillain-Barré syndrome associated with scrub typhus.
Scand J Infect Dis. 2007;39(9):826-8
Authors: Lee SH, Jung SI, Park KH, Choi SM, Park MS, Kim BC, Kim MK, Cho KH
We report a 42-y-old female with Guillain-Barré syndrome (GBS) who presented with scrub typhus for a duration of 2 weeks. Subsequently, ascending paralysis and facial diplegia developed. GBS was confirmed with nerve conduction studies and cerebrospinal fluid examinations. After administration of intravenous immunoglobulin, symptoms gradually disappeared.
