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
(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.
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.
PMID: 17701724 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
OBJECTIVE: To describe the clinical presentation, diagnosis, and treatment of myasthenia gravis (MG) while emphasizing the important role of the pharmacist. DATA SOURCES: English-language articles from MEDLINE pertinent to MG study selection and data extraction: All relevant publications addressing MG management were considered, including prospective comparative trials, epidemiological studies, guideline statements, review articles, and editorials. Particular focus occurred on primary literature published after 1976, but limited amount(s) existed. The American Autoimmune Related Diseases Association, Autoimmune Information Network, Inc., Myasthenia Gravis Foundation of America, Inc. (MGFA), National Institute of Neurological Disorders and Stroke, and National Organization for Rare Disorders. DATA SYNTHESIS: MG is an autoimmune disorder involving the neuromuscular junction causing characteristic weakness in voluntary muscle groups. To determine appropriate pharmacotherapy, one must characterize the disease based on the degree of function and region of muscles affected. MGFA established a classification system of the disease in order to assess severity. Contemporary treatments include cholinesterase inhibitors, corticosteroids, immodulating/immunosuppressive therapy, intravenous immune globulin, plasmapheresis, and thymectomy. Because of the lack of double-blind, placebo-controlled, randomized clinical trials, treatments are less evidence-based than many other disease states. Clinicians should be aware of the different treatments and recognize the best treatment for the individual. CONCLUSIONS: The diagnosis and treatment of MG is a therapeutic challenge. Pharmacists play an essential role in the care of these patients by avoiding drugs that exacerbate the disease, promoting optimal pharmacotherapy, monitoring pharmacotherapy, and ensuring compliance with prescribed medications.
PMID: 17658970 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections.
J Child Neurol. 2007 Jun;22(6):741-3
Authors: Ozkinay F, Pehlivan S, Onay H, van den Berg P, Vardar F, Koturoglu G, Aksu G, Unal D, Tekgul H, Can S, Ozkinay C
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.
PMID: 17641261 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
In 2 children, both aged 7 years, multiple sclerosis (MS) was diagnosed. In children, the initial clinical features of MS may vary greatly. The first patient presented with an acute disseminated encephalomyelitis (ADEM), and the other with a hemiparesis on the left side. In both patients, the disease was controlled by prolonged pharmacotherapy, starting with methylprednisolone and followed in the first patient by intravenous infusions of immunoglobulins and in the second patient by beta-interferon.
PMID: 17633977 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Case of severe refractory myasthenia gravis in HUKM.
Med J Malaysia. 2006 Dec;61(5):633-5
Authors: Hamizah R, Norlinah MI, Tan HJ, Soehardy Z, Halim AG, Rohana AG, Hamidon BB, Kong NC, Raymond AA
A 20-year-old girl first notice bilateral ocular muscle weakness in 2001. Two months later, she developed acute muscle paralysis and respiratory failure which required ventilation. Serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation test was positive and consistent with myasthenia gravis (MG). CT scan thorax revealed thymic enlargement and she underwent a video assisted thymectomy (VATS). However, over the next three years, despite maximal doses of various immunosuppressive agents with plasmapheresis and intravenous immunoglobulin, she was admitted with recurrent myasthenic crisis without any obvious precipitant. She was then commenced on mycophenolate mofetil and together with regular plasmapheresis, cyclosporine and prednisolone, her symptoms have finally improved and brought under control.
PMID: 17623968 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study.
Mult Scler. 2007 Nov;13(9):1107-17
Authors: Pöhlau D, Przuntek H, Sailer M, Bethke F, Koehler J, König N, Heesen C, Späth P, Andresen I
In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n=34) and SPMS (n=197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P=0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions.In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P=0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score.In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P=0.028). The difference was significant in PPMS (P=0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P=0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS.
PMID: 17623736 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Antibodies to AChR, MuSK and VGKC in a patient with myasthenia gravis and Morvan's syndrome.
Nat Clin Pract Neurol. 2007 Jul;3(7):405-10
Authors: Díaz-Manera J, Rojas-García R, Gallardo E, Juárez C, Martínez-Domeño A, Martínez-Ramírez S, Dalmau J, Blesa R, Illa I
BACKGROUND: A 46-year-old woman presented to a local hospital with acute respiratory failure and a 2-year progressive history of fatigue, personality changes, increased sweating, dysphagia with substantial weight loss, dysarthria, and intermittent ptosis and diplopia. Neurological examination showed facial weakness, lingual atrophy and bulbar palsy, which necessitated the use of a feeding tube and ventilatory support. Mild limb weakness with severe muscle atrophy and diffuse muscle twitches were observed. The patient had also developed visual hallucinations and persecutory delusions. Her personal and family medical histories were unremarkable. INVESTIGATIONS: Sensory and motor nerve conduction studies, repetitive nerve stimulation, electromyogram, blood-cell counts, general chemistry and metabolic function tests, a CT scan, an [(18)F]fluorodeoxyglucose-PET scan, and tests for serum antibodies to acetylcholine receptors, muscle-specific tyrosine kinase, voltage-gated potassium channels, P/Q-type voltage-gated calcium channels, and paraneoplastic antigens, were carried out. DIAGNOSIS: Myasthenia gravis associated with antibodies to acetylcholine receptor and muscle-specific tyrosine kinase, and Morvan's syndrome associated with antibodies to voltage-gated potassium channels in the absence of thymoma. MANAGEMENT: Combined treatment with prednisone, intravenous immunoglobulin, ciclosporin, and rituximab.
PMID: 17611489 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Long-term effects of intravenous immunoglobulin in CIDP.
Clin Neurophysiol. 2007 Sep;118(9):1980-4
Authors: Vucic S, Black K, Baldassari LE, Tick Chong PS, Dawson KT, Cros D
OBJECTIVE: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired demyelinating disease of the peripheral nervous system characterized by muscle weakness, areflexia or hyporeflexia, and sensory disturbances. Although short-term efficacy of intravenous immunoglobulin (IVIg) has been demonstrated in randomized-controlled trials, the data pertaining to long-term outcome in CIDP are limited. Consequently, the aim of the present study was to assess the long-term effects of IVIg on neurophysiological parameters in CIDP. METHODS: Neurophysiological records from 11 CIDP patients, treated with IVIg for 12 months, were reviewed. Nerve conduction studies were assessed at baseline, 1-year, and last follow-up. RESULTS: There was a significant reduction in the frequency of conduction blocks (pre-treatment nerve segments affected 61%; last follow-up 39%, P<0.01) and a reduction in ongoing axonal loss (pre-treatment regions with spontaneous activity, 47%; post-treatment 29%, P<0.01) with IVIg treatment. Further, there was significant improvement in sensory nerve conduction studies with IVIg treatment (sensory amplitudes reduced pre-treatment, 90% nerves tested; post-treatment, 62%, P<0.01). CONCLUSIONS: The present study suggests that long-term IVIg maintenance therapy improves neurophysiological parameters in CIDP. However, CIDP patients remain IVIg dependent and new conduction blocks may develop. SIGNIFICANCE: The present study suggests that long-term IVIg maintenance therapy improves neurophysiological parameters in CIDP, possibly by reducing the immune response and thereby fostering nerve healing.
PMID: 17604689 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by a mutation in the Bruton agammaglobulinemia tyrosine kinase gene that results in severe B-cell deficiency. So far, neurological complications of XLA have been primarily related to acute and/or chronic central nervous system enteroviral infections. In the last few years a progressive neurodegenerative syndrome of unknown etiology has been described in XLA patients. We describe and present a video of an XLA patient who developed a fatal dementing, dystonia-Parkinsonism syndrome 14 years into his immune disorder. Physician awareness of this rare syndrome may lead to its better characterization and management.
PMID: 17588239 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[A case of acute hepatitis a complicated by Guillain-Barré syndrome]
Korean J Hepatol. 2007 Jun;13(2):228-33
Authors: Bae YJ, Kim KM, Kim KK, Rho JH, Lee HK, Lee YS, Suh DJ
We report here a case of acute hepatitis A, which was complicated by Guillain-Barré syndrome (GBS). A 32-year old male admitted to our hospital with the symptoms of acute hepatitis and was diagnosed to have acute hepatitis A with positive IgM anti hepatitis A virus antibody. On 9th day after the onset of jaundice, acute progressive, ascending, symmetric motor paralysis were developed and eventually respiratory failure ensued. Cerebrospinal fluid analysis showed albumino-cytologic dissociation and nerve conduction velocity test suggested a polyradiculopathy. He was diagnosed to have GBS and treated with intravenous immunoglobulin and required a ventilatory support. After 90 hospital days, he recovered in ambulatory condition with the aid of crutches. The clinical course, prognosis and the outcome of neuropathic symptoms of GBS following acute hepatitis A were relatively poor in our case.
PMID: 17585196 [PubMed:- Treatment with IVIG - in process]
Anesthetic management of Guillain-Barré syndrome in pregnancy.
J Clin Anesth. 2007 Jun;19(4):299-302
Authors: Kocabas S, Karaman S, Firat V, Bademkiran F
We report the case of a 23-year-old woman who was diagnosed with an axonal type of Guillain-Barré syndrome at 16 weeks' gestation. The patient had severe motor loss but she was treated effectively with intravenous immunoglobulin, and she underwent cesarean delivery with epidural anesthesia at full term.
PMID: 17572328 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Late onset Rasmussen's syndrome: clinical and therapeutic characteristics]
Rev Neurol (Paris). 2007 May;163(5):573-80
Authors: Jaillon-Riviere V, Dupont S, Bertran F, De La Sayette V, Beuvon F, Baulac M, Defer G
Rasmussen's syndrome is a rare inflammatory brain disease characterized by severe intractable epilepsy, and unilateral progressive motor defect associated with controlateral hemispheric atrophy. The disorder usually affects children, although occasional reports of adult-onset Rasmussen's syndrome have been reported. We report her four patients in whom seizures began in adolescence or adulthood with clinical and radiological symptoms suggesting the diagnosis of Rasmussen's syndrome. We compared them with thirty-three cases described in the literature between 1987 and 2004. While adult-onset Rasmussen's syndrome may mimic the early-onset form, symptoms often progress more slowly and the neurological defect is more variable. Occipital lobe involvement appears to be more common than in the childhood form, and some atypical features may be noted such as bilateral hemispheric involvement or a picture of temporal lobe epilepsy or the présence of movement disorders at the beginning of the disease. Surgical hemispheric disconnection that appears the most effective treatment in children to improve seizure control is not indicated in adults for evident functional reasons. Based on recent pathogenic concepts, different medical treatments may be proposed. Large multicentric controlled studies are mandatory to define a clear medical therapeutic strategy in these cases of adult-onset.
PMID: 17571025 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Chronic inflammatory demyelinating polyneuropathy in a diabetic patient: deterioration after intravenous immunoglobulins treatment and favorable response to steroid treatment.
Acta Neurol Belg. 2007 Mar;107(1):14-7
Authors: Pedersen K, Pandolfo M, Mavroudakis N
The authors report the case of a 54-year old type-2 diabetic female patient with a Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). She progressively developed distal hypoesthesia and tetraparesis. She deteriorated after two courses of intravenous immunoglobulins (IVIG) administration and became rapidly wheelchair bound. After one month of steroid treatment, the patient was walking alone. This case raises the question whether IVIG is to be considered as first line treatment for diabetes associated CIDP.
PMID: 17569228 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Myasthenic crisis: guidelines for prevention and treatment.
J Neurol Sci. 2007 Oct 15;261(1-2):127-33
Authors: Jani-Acsadi A, Lisak RP
Management of myasthenic crisis (MC) requires admission of the patient into a neurological intensive care unit and timely institution of an efficient and safe treatment. Despite the growing clinical experience with disease modifying immunotherapy there is no clinical consensus regarding the use of plasma exchange or high dose immunoglobulin treatment in an ICU setting. The choice of treatment modalities seem to rely mostly on institutional preferences primarily due to a lack of well-designed clinical trials comparing currently available therapeutic options. In our experience and based on a review of recent literature we advocate the use of plasma exchange (PE) as a primary modality in the acute care setting, supported by other immunomodulatory medications such as corticosteroids. Pharmacological management cannot substitute for adequate intensive care management of the respiratory and bulbar insufficiency associated with MC. Every effort should be done to prevent myasthenic exacerbation/crisis and to develop a maintenance management that leads to effective prevention.
PMID: 17544450 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Opsoclonus-myoclonus syndrome associated with Mycoplasma pneumoniae infection]
Arch Pediatr. 2007 Aug;14(8):1003-6
Authors: Chemli J, Ketata S, Dalhoumi A, Ajmi H, Hassayoun S, Fodha I, Boujaafar N, Harbi A
Mycoplasma pneumoniae infection is associated with various manifestations involving the central nervous system but it has never been reported as a potential aetiology of opsoclonus-myoclonus syndrome (OMS) in children. OBSERVATION: We report on a case in a 4-year-old girl who presented neurological manifestations compatible with an OMS, after a respiratory tract disease. Aetiological investigations revealed M. pneumoniae infection as specific IgM were present in the serum (Elisa). Evolution after corticosteroid, intravenous immunoglobulins and macrolide therapy was favourable as clinical symptoms disappeared. After a 12-month follow-up, the patient has no neurological sequela. CONCLUSION: M. pneumoniae infection should be added to the list of causes to be screened in OMS. Its pathophysiology remains unknown but may involve a dysimmune postinfectious mechanism.
PMID: 17543509 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Therapeutic options in autoimmune myasthenia gravis.
Autoimmun Rev. 2007 Jun;6(6):373-8
Authors: García-Carrasco M, Escárcega RO, Fuentes-Alexandro S, Riebeling C, Cervera R
Autoimmune myasthenia gravis (MG) is associated with circulating antibodies to AChR, modification of the synaptic cleft, and destruction of the postsynaptic neuromuscular membrane. The hallmark is fluctuating muscular weakness and fatigability of muscles on sustained repeated activity. Various drugs and invasive procedures have been used in the treatment of MG including acetylcholinesterase inhibitors, corticosteroids, azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, etanercept, intravenous immunoglobulin, plasma exchange and thymectomy. We review the role of each of these drugs and invasive procedures in MG. Although current treatment is highly successful and mortality is almost nil, further trials are required to identify the most suitable treatments for different subgroups of MG patients. In addition, safer and more potent drugs are required as most current drugs have major side effects due to immunosuppression. Therefore, the goal of novel therapies should be increased specificity of the immune-directed agents.
PMID: 17537383 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Pharmacoeconomics of therapy for Guillain-Barré syndrome: plasma exchange and intravenous immunoglobulin.
J Clin Neurosci. 2007 Jul;14(7):625-9
Authors: Tsai CP, Wang KC, Liu CY, Sheng WY, Lee TC
Guillain-Barré syndrome (GBS) is an acute neuropathy and a clinical syndrome that includes a number of pathological and electrophysiological subtypes. Intravenous immunoglobulin (IVIG) and plasma exchange (PE) are both equally efficacious for the treatment of GBS; however, the cost of IVIG may be lower for both the patient and the healthcare system. To compare the pharmacoeconomics of PE and IVIG in GBS, a retrospective study was done from 1999 to 2004, which included a total of 24 patients with GBS who were admitted to Taipei Veterans General Hospital. This showed that except for the costs of the drugs used in IVIG, treatment of GBS with IVIG was more cost-effective (p=0.057) than that with PE in total length of hospitalization and the cost of procedures and hospitalization. The study also showed that the total costs were higher for patients on ventilators than those not requiring ventilators (p=0.008, t-test) and the length of hospitalization showed a very strong linear relationship to total costs (Pearson correlation coefficient=0.907). The regression analysis showed that each additional day of hospitalization increased the hospitalization costs by an average of 5599 New Taiwan Dollars (NT) (US$1.00=NT$33.50 in 2005).
PMID: 17532498 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Chronic inflammatory demyelinating polyradiculoneuropathy presenting as cauda equina syndrome in a diabetic.
J Neurol Sci. 2007 Sep 15;260(1-2):267-70
Authors: Lai WW, Ubogu EE
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may occur in association with diabetes mellitus (DM). We report a case of a poorly controlled diabetic patient who presented with rapid onset of bilateral lower extremity weakness and sensory loss associated with sacral and posterior thigh paresthesias and urinary and bowel incontinence, indicative of cauda equina syndrome (CES). Subsequent evaluation was consistent with CIDP. Monthly infusions with intravenous immunoglobulins (IVIg) with strict glycemic control using insulin resulted in remarkable clinical and electrophysiological recovery. This case report describes a rare presentation of CIDP and emphasizes the importance of early utility of electrodiagnostic (EDX) studies in the clinical evaluation of diabetic patients presenting with rapidly progressive lower extremity weakness and sensory loss associated with diminished reflexes.
PMID: 17521674 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
How intravenous immunoglobulin is used in clinical practice: audits of two Sydney teaching hospitals.
Intern Med J. 2007 May;37(5):308-14
Authors: Lin MW, Kirkpatrick PE, Riminton DS
BACKGROUND: The clinical demand for i.v. immunoglobulin (IVIg) continues to increase in Australia for reasons that are not clear. IVIg is distributed for approved indications according to Australian Health Ministers' Advisory Council 2000 guidelines that are currently under review. IVIg may also be purchased by hospitals for uses not covered by these indications on an individual patient use basis. These audits were developed to examine current hospital practice in IVIg use. METHODS: Six-month prospective audits of all IVIg use were conducted at two teaching hospitals in Sydney (Concord and Royal Prince Alfred Hospitals). Medical files and dispensing records were examined and compared with current guidelines. RESULTS: One hundred and sixty-five recipients received 24,251 g of IVIg (mean total use 147 g/patient) for 36 distinct diagnoses, with 5.5% mortality. Drug committees supplied 1580 g of IVIg (6.5% of total product issued) to 12 recipients (7.3% of total recipients). The clinical specialties of immunology, haematology and neurology accounted for 92.9% of IVIg use, with 51.8% of overall use for replacement indications. Forty-two patients (25.5%) received IVIg for non-category 1 indications (4718 g, 19.5% of total product). Patients receiving IVIg for category 1 disorders had a 94.4% compliance with the guideline prerequisites where data were sufficient for assessment. DISCUSSION: Our findings show a greater than expected proportion of non-category 1 IVIg use and substantial contributions from drug committees. Careful case selection within category 1 indications is evident in the high level of compliance with qualifying criteria. Current distribution procedures do not enable capture of outcome data to inform guideline revisions. CONCLUSION: These audits emphasize the requirement for updated National Clinical Practice Guidelines, improved approval procedures, consensus statements in the specialties of immunology, haematology and neurology and clarification of the role of drug committees.
PMID: 17504278 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
We report a patient who developed overlapping symptoms of ophthalmoplegia and oropharyngeal palsy after Campylobacter jejuni infection. A 15-year-old man had diarrhea and fever, and developed dysarthria, diplopia and ptosis two weeks later. He did not show ataxia, weakness or abnormal tendon reflexes in the extremities during the clinical course. In the acute phase of the disease, we found significant elevation of anti-GQlb and anti-GTla IgG antibodies in the serum, and high-dose intravenous immunoglobulin therapy remarkably ameliorated the symptoms. Our patient was atypical of Fisher syndrome or pharyngeal-cervical-brachial (PCB) weakness, and this is the first case of multiple cranial neuropathy associated with C. jejuni infection.
PMID: 17491339 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Classifications and treatment responses in chronic immune-mediated demyelinating polyneuropathy.
Neurology. 2007 May 8;68(19):1622-9
Authors: Tackenberg B, Lünemann JD, Steinbrecher A, Rothenfusser-Korber E, Sailer M, Brück W, Schock S, Zschenderlein R, Zipp F, Sommer N
BACKGROUND: Chronic immune-mediated demyelinating polyneuropathy (CIP) represents a heterogeneous pool of motor, sensory, sensorimotor, symmetric, or asymmetric syndromes. OBJECTIVE: To evaluate published diagnostic classifications and characterize predictors of treatment response. METHODS: One hundred two of 158 patients with a working diagnosis of CIP were included and clinically characterized because they had electrophysiologic and/or histologic evidence of demyelination. The biostatistical profile of patients with symmetric clinical manifestation was analyzed using three proposed classifications (American Academy of Neurology [AAN] criteria, modified AAN criteria, European Federation of Neurological Societies/Peripheral Nerve Society [EFNS/PNS] criteria). Treatment responses to IV immunoglobulins (IVIg) and their positive predictors were investigated. RESULTS: Sensitivities (0.52 [AAN] vs 0.83 [modified AAN] vs 0.95 [EFNS/PNS]) and negative predictive values (0.68 vs 0.85 vs 0.92) differed markedly, whereas specificities (0.94 vs 0.90 vs 0.96) and positive predictive values (0.89 vs 0.89 vs 0.97) were similar. In CIP patients treated with IVIg, a positive response was found in 62 of 76 (82%). Patients with a monophasic or relapsing-remitting course or a more than twofold CSF protein increase had the highest probability to respond to IVIg, most evident when using the modified AAN criteria. CONCLUSIONS: The European Federation of Neurological Societies/Peripheral Nerve Society criteria for chronic inflammatory demyelinating polyneuropathy improve treatment of patients with chronic immune-mediated demyelinating polyneuropathy, particularly with respect to diagnostic issues. To predict IV immunoglobulin treatment response, the modified American Academy of Neurology criteria are the most valuable classification provided an increased CSF protein level.
PMID: 17485651 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Miller Fisher syndrome: a case with pattern of pure sensory polyneuropathy concomitant with anti-GQ1B antibody.
Turk J Pediatr. 2007 Jan-Mar;49(1):109-12
Authors: Akinci G, Polat M, Tosun A, Serdaroğlu G, Gökben S, Tekgül H
Miller Fisher syndrome is characterized by the acute onset of ophthalmoplegia, ataxia, and areflexia. Anti-GQ1b antibodies are useful markers for the differential diagnosis of Miller Fisher syndrome. We describe the case of a seven-year-old male who presented with a four-day history of diplopia and ophthalmoplegia following a febrile flu-like illness with sore throat. On examination he was found to have ataxia, areflexia and ophthalmoplegia, and a diagnosis of Miller Fisher syndrome was made after the exclusion of other conditions and concomitant with electrophysiological findings on electromyography. Although this disorder has a rare incidence, it should still be considered in the differential diagnosis in our country.
PMID: 17479657 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Treatment of neurodegenerative CNS disease in Langerhans cell histiocytosis with a combination of intravenous immunoglobulin and chemotherapy.
Pediatr Blood Cancer. 2008 Feb;50(2):308-11
Authors: Imashuku S, Okazaki NA, Nakayama M, Fujita N, Fukuyama T, Koike K, Minato T, Kobayashi R, Morimoto A,
BACKGROUND: In rare cases, patients with Langerhans cell histiocytosis (LCH) develop neurodegenerative CNS disease (ND-CNS-LCH). Management of ND-CNS-LCH has not been established. METHODS: We treated five pediatric patients with a combination of intravenous immunoglobulin (IVIG) and chemotherapy (steroid +/- vinblastine +/- 6-mercaptopurine +/- methotrexate). Prior to the therapy, three of the five patients had cerebellar ataxia while the remaining two had abnormal MRI findings without apparent neurological deficits. IVIG was given monthly or twice monthly at the dosage of 250-400 mg/kg/dose. RESULTS: The four patients administered more than 23 doses of IVIG and chemotherapy remained in a stable condition and did not show significant progression signs in neurological deficits or brain MRI findings during the 30-month follow-up period (median; range: 19+ to 38+) following the initiation of therapy for ND-CNS-LCH. CONCLUSION: The IVIG-containing treatment may be promising for ND-CNS-LCH; however, its effectiveness remains to be further tested in more patients as well as in a randomized trial.
PMID: 17458874 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Anecdotal reports of acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) with cytomegalovirus (CMV) suggested as the etiological agent have been described in transplant recipients with poor prognosis. We describe a 48-year-old man, a cadaveric renal allograft recipient on cyclosporine, mycophenolate mofetil and prednisolone, who developed febrile illness with unexplained anemia followed by progressive weakness of the upper and lower limbs. He was diagnosed as a case of Guillain-Barré syndrome (GBS). His CMV serology was positive by polymerase chain reaction (PCR). We treated him with both gancyclovir and intravenous immunoglobulins within a week of the onset of GBS and observed rapid recovery. Thus, search for CMV is warranted in transplant patients presenting with GBS, as early initiation of treatment with gancyclovir and immunoglobulins can help expedite recovery.
PMID: 17450421 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous immunoglobulin in MS: promise or failure?
J Neurol Sci. 2007 Aug 15;259(1-2):61-6
Authors: Fazekas F, Strasser-Fuchs S, Hommes OR
There is an established role for intravenous immunoglobulin (IVIG) in the treatment of certain neurologic autoimmune disorders which affect the peripheral nervous system and a variety of immunomodulatory properties of IVIG have been proposed. This prompted an intense research into the efficacy of IVIG in central nervous system autoimmune disorders and until now several well-controlled clinical trials have been performed in different stages and phenotypes of multiple sclerosis (MS). The results were mixed. Speculations that IVIG might be able to reverse fixed neurologic deficits from MS could not be confirmed. Adding IVIG to the conventional treatment of MS relapses with high-dose IVMP also did not provide any additional benefits. Similarly, trials failed to establish a role for IVIG in the treatment of secondary or primary progressive MS. Most consistent beneficial results with a reduction of relapse rates and a slowing of disability have been obtained in relapsing-remitting MS including clinically isolated syndromes although a most recent study did not confirm a reduction of disease activity based on clinical and MRI findings. Trial results also suggest that IVIG might serve to suppress an increased recurrence of relapses immediately after delivery. Consequently, IVIG treatment may be considered as second line option for these indications although there is still uncertainty regarding the actual mechanism(s) of action and optimal dosage of this treatment.
PMID: 17449063 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Slowly progressive distal muscular atrophy of the bilateral upper limbs (O'Sullivan-McLeod syndrome) partially alleviated by intravenous immunoglobulin therapy.
Intern Med. 2007;46(8):515-8
Authors: Kawano Y, Nagara Y, Murai H, Kikuchi H, Ohyagi Y, Kira J
We report a case of O'Sullivan-McLeod syndrome in a 59-year-old man, who had experienced slowly progressive weakening of both hands since he was 20 years of age. Mild hyperIgEemia and eosinophilia were present. Nerve conduction studies revealed reduced F wave-evoked frequencies for the median and ulnar nerves. Intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg/day was given for 5 days. After IVIG, the muscle weakness of the distal upper extremities improved together with increased F wave-evoked frequencies. These effects lasted for a few months. These observations suggest that immune-mediated neural damage partially contributes to O'Sullivan-McLeod syndrome.
PMID: 17443046 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Efficacy of various intravenous immunoglobulin therapy protocols in autoimmune and chronic inflammatory disorders.
Ann Pharmacother. 2007 May;41(5):812-23
Authors: Gürcan HM, Ahmed AR
OBJECTIVE: To determine the efficacy of various intravenous immunoglobulin (IVIG) protocols used in the treatment of autoimmune and chronic inflammatory disorders. DATA SOURCES: Literature retrieval was accessed through MEDLINE (November 1984-March 2007) and a search was conducted using the term intravenous immunoglobulin. References cited in the selected articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria for studies were (1) English language, (2) randomized controlled trials, (3) defined protocols, (4) a minimum of 15 patients, and (5) objective criteria provided to assess clinical outcomes and course. DATA SYNTHESIS: The therapeutic efficacy of IVIG therapy is well established, and defined protocols exist for treatment of Kawasaki disease, immune thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and autoimmune mucocutaneous blistering diseases. In the absence of a defined protocol, studies have demonstrated that IVIG therapy is effective in the treatment of myasthenia gravis, dermatomyositis, stiff person syndrome, antineutrophil cytoplasmic antibody positive systemic vasculitides, Graves' ophthalmopathy, and certain forms of systemic lupus erythematosus. It might also be of benefit in some patients with relapsing-remitting multiple sclerosis. The outcomes are variable in these studies. In toxic epidermal necrolysis and Stevens-Johnson syndrome, use of IVIG has dramatically influenced clinical response and reduced mortality. CONCLUSIONS: The cumulative evidence suggests that the clinical outcomes observed are significantly influenced by the use of a defined protocol. There is a need for multicenter trials approved by the Food and Drug Administration to better define the role of IVIG in many disease states. Such studies would be able to establish the indications for use, optimal dose, frequency of infusions, duration of therapy, and need for gradual withdrawal versus sudden cessation. Defined protocols resulting from the study of a large cohort of patients often convince insurance companies to create policies that provide access to IVIG therapy.
PMID: 17440006 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Clinical analysis of paraneoplastic encephalitis associated with ovarian teratoma.
J Neurooncol. 2007 Sep;84(3):287-92
Authors: Tonomura Y, Kataoka H, Hara Y, Takamure M, Naba I, Kitauti T, Saito K, Ueno S
BACKGROUND: Recently, paraneoplastic encephalitis associated with ovarian teratoma has been described and related to an autoantibody. METHODS: We describe four patients with ovarian teratoma-associated encephalitis (OTE) and compared their clinical pictures with those of 17 previously reported patients with OTE. RESULTS: Clinically, OTE was characterized by the development of acute prominent psychiatric symptoms (20 of 21 patients), seizures (15 of 21 patients), and central hypoventilation (13 of 21 patients). Our patients had hypersalivation (three patients) and cardiac conduction problems (all patients); hypothermia was present in one patient. The mean time from the onset of OTE to tumor diagnosis was 19.6+/-22.1 weeks. Ventilatory support was required for 54.9+/-25.4 days on average. The white blood cell count in cerebrospinal fluid was 55.1+/-61.2/mm3. Twelve patients showed abnormalities on cranial MRI, involving areas such as the temporal regions (seven patients) or brainstem (four patients). In addition to tumor resection, 17 patients received some type of immunotherapy: 17 patients received corticosteroids, 10 received intravenous immunoglobulins, two received cyclophosphamide, seven received plasma exchange. Eighteen patients with OTE had neurological improvement, including 11 with full recovery. CONCLUSIONS: OTE presents with cardiac conduction problems and hypersalivation in addition to psychiatric symptoms, seizures, and central hypoventilation.
PMID: 17431543 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
The spectrum of neuromyelitis optica: a case of NMO with extensive brain stem involvement.
Neurol Res. 2007 Jan;29(1):32-5
Authors: Vendrame M, Azizi SA
Neuromyelitis optica (NMO), regarded as a distinct clinical entity from multiple sclerosis (MS), is generally characterized by demyelinating lesions involving optic nerves and spinal cord with sparing of the brain. We report a case with initial clinical, radiological and serological features consistent with NMO, but with concomitant extensively clinical and radiological involvement of the brain stem. Although there are well defined criteria for NMO that restricts the lesions to optic nerves and spinal cord, the case presented here and the review of literature support the idea that NMO may present as a spectrum of clinical and radiological entities rather than the confining clinical criteria that has been hitherto applied.
PMID: 17427272 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Determination of pain and response to methylprednisolone in Guillain-Barré syndrome.
J Neurol. 2007 Oct;254(10):1318-22
Authors: Ruts L, van Koningsveld R, Jacobs BC, van Doorn PA
Pain can be a serious problem in patients with Guillain-Barré syndrome (GBS). Different pain symptoms and the effect of methylprednisolone on pain are evaluated. METHODS : GBS patients were recruited from a randomized placebo-controlled study comparing intravenous immunoglobulin (IVIg) + methylprednisolone (500 mg for 5 days) versus IVIg + placebo. Presence and severity of pain were prospectively scored at randomization and after 4 weeks. Efficacy of methylprednisolone was evaluated using endpoints: percentage of patients with pain and percentage of patients improving in pain-severity level. Medical records of the subgroup of patients treated in the Erasmus MC were screened retrospectively for different pain symptoms and course. Pain was scored at different time intervals: within 4 weeks before randomization and 0-2, 2-4, 4-24, 24-52 weeks after randomization. RESULTS : 123 (55%) of 223 patients had pain at randomization. In 70%, pain already started before onset of weakness. Methylprednisolone did not show a positive effect on the presence and reduction of pain. In the subgroup of 39 patients, backache (33%), interscapular (28%), muscle (24%), radicular pain (18%) and painful par-/dysaesthesiae (18%) were most frequently present within the period of 4 weeks before randomization. Twenty-six percent had extreme pain 0-2 weeks after randomization. Most symptoms of pain decreased after this period, but painful par-/dysaesthesiae and muscle pain often remained present during at least 6 months. CONCLUSIONS : Pain frequently occurs, often starts before onset of weakness and may cause severe complaints. Especially painful par-/dysaesthesiae and muscle pain may persist for months. Methylprednisolone seems to have no significant effect on the presence and intensity of pain.
PMID: 17426908 [PubMed:- Treatment with IVIG - in process]
Postoperative delayed respiratory failure caused by Guillain-Barré syndrome--a case report.
Acta Anaesthesiol Taiwan. 2007 Mar;45(1):43-6
Authors: Kuok CH, Tsai PS, Hsu YW, Ko YP, Huang CJ, Chen CC
Postoperative respiratory failure caused by Guillain-Barré syndrome (GBS) is a rare complication after general anesthesia. We report a GBS patient who after receiving an operation for polycystic liver disease under general anesthesia developed weakness of upper and lower extremities on the 3rd postoperative day, with decreased deep tendon reflex, which ultimately evolved into respiratory failure. Slurred speech and bilateral ptosis were also noted. All these manifested an acute peripheral polyneuropathy combined with bulbar involvement. According to the clinical picture, CSF examination and results of nerve conduction tests, Guillain-Barré syndrome was diagnosed. Plasmapheresis was immediately arranged and her motor weakness problem was soon improved after treatment. No neurological sequelae were found two months after discharge. Postoperative muscle weakness is usually caused by residual effects of anesthetic agents or surgical complications. But it may sometimes be related to some rare neurological diseases. To prompt an accurate diagnosis of Guillain-Barré syndrome is important because it can help forestall fatal complications. In addition, the prognosis will be encouraging with early treatment.
PMID: 17424759 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Intravenous immunoglobulin therapy for Miller Fisher syndrome.
Neurology. 2007 Apr 3;68(14):1144-6
Authors: Mori M, Kuwabara S, Fukutake T, Hattori T
We analyzed clinical recovery of 92 patients with Miller Fisher syndrome who had been treated with IV immunoglobulin (IVIg; n = 28), plasmapheresis (n = 23), and no immune treatment (n = 41). IVIg slightly hastened the amelioration of ophthalmoplegia and ataxia, but the times of the disappearances of those symptoms were similar among three groups. In Miller Fisher syndrome, IVIg and plasmapheresis seem not to have influenced patients' outcomes, presumably because of good natural recovery.
PMID: 17404197 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
The classic paraneoplastic neurological syndromes include Lambert-Eaton myasthenic syndrome, limbic encephalitis, sensory neuronopathy, intestinal pseudo-obstruction, subacute cerebellar degeneration, encephalomyelitis, and dermatomyositis. Approximately ten onconeural antibodies that recognize cancer and the nervous system have been described in paraneoplastic neurological syndromes. These antibodies appear to be important diagnostic tools, even though they may not always be present. Deciding whether a given neurological picture is definitely or possibly paraneoplastic depends on the clinical syndrome, any association with onconeural antibodies, and the time elapsed between onset of neurological symptoms and the discovery of the cancer. Diagnosis of a classic paraneoplastic neurological syndrome or the discovery of onconeural antibodies mandates an active and persistent search for cancer, using new techniques such as fluorodeoxyglucose positron emission tomography. In patients with one of these syndromes, the best treatment of the neurological disease is often the diagnosis and early treatment of the cancer.
PMID: 17399944 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Guidelines on the use of intravenous immune globulin for neurologic conditions.
Transfus Med Rev. 2007 Apr;21(2 Suppl 1):S57-107
Authors: Feasby T, Banwell B, Benstead T, Bril V, Brouwers M, Freedman M, Hahn A, Hume H, Freedman J, Pi D, Wadsworth L
Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for neurologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 22 neurologic conditions and formulate recommendations on IVIG use for each. A panel of 6 clinical experts, one expert in practice guideline development and 4 representatives from the NAC met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 2 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and, where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to neurologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Recommendations for use of IVIG were made for 14 conditions, including acute disseminated encephalomyelitis, chronic inflammatory demyelinating polyneuropathy, dermatomyositis, diabetic neuropathy, Guillain-Barré syndrome, Lambert-Eaton myasthenic syndrome, multifocal motor neuropathy, multiple sclerosis, myasthenia gravis, opsoclonus-myoclonus, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, polymyositis, Rasmussen's encephalitis, and stiff person syndrome; IVIG was not recommended for 8 conditions including adrenoleukodystrophy, amyotropic lateral sclerosis, autism, critical illness polyneuropathy, inclusion body, myositis, intractable childhood epilepsy, paraproteinemic neuropathy (IgM variant), and POEMS syndrome. Development and dissemination of evidence-based clinical practice guidelines may help to facilitate appropriate use of IVIG.
PMID: 17397768 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Rituximab in chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus.
J Neurol Sci. 2007 May 15;256(1-2):100-2
Authors: Münch C, Anagnostou P, Meyer R, Haas J
The authors report a 57-year-old patient with chronic inflammatory demyelinating polyneuropathy (CIDP) associated with diabetes mellitus (DM) who was treated successfully with rituximab. The B lymphocyte suppression using rituximab was followed 4 weeks later by neurological improvement and a stable disease course of over 10 months. We suggest that rituximab may be a treatment option in CIDP increasingly less responsive to intravenous immunoglobulin, particularly in patients with concurrent DM.
PMID: 17382963 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
Use of immunoglobulin in severe childhood Guillain-Barré syndrome.
Acta Neurol Scand. 2007 Apr;115(4):289-93
Authors: Ortiz-Corredor F, Peña-Preciado M
OBJECTIVES: To compare the clinical results in children with Guillain-Barré syndrome (GBS) admitted to the intensive care unit. Patients treated with intravenous immunoglobulin (IVIg) were compared with patients admitted before the immunoglobulin treatment was introduced. DESIGN: Study of historical cohorts. Methods - The outcome of the children who did not receive IVIg before 1993 was compared with those children who received immunoglobulin treatment from this year until 2002. The days of ventilatory support and the time it took to reach state III on the GBS disability scale were used as measures of outcome. Age, muscular strength, cranial nerve palsy and the electrophysiological classification were the independent variables. RESULTS: In all, 48 of 96 children were classified - 18 patients as axonal motor acute neuropathy (AMAN) and 30 patients as axonal inflammatory demyelinating polyneuropathy (AIDP). For both groups the analysis showed similar results behavior when comparing the outcome of patients with or without immunoglobulin treatment. A high proportion of patients with unexcitable nerves was found in the group with immunoglobulin treatment. Quadriplegia and the presence of unexcitable motor nerves were associated with a longer period of recovery. CONCLUSION: Immunoglobulin did not change the history of the illness as far as the time of ventilatory support in AMAN and AIDP groups is concerned and the time to reach state III on the GBS disability scale.
PMID: 17376129 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
A case of Miller Fisher syndrome with anti GQ1b in Thailand.
J Med Assoc Thai. 2007 Feb;90(2):391-3
Authors: Sawanyawisuth K, Tiamkao S, Jitpimolmard S, Vincent A
Miller-Fisher syndrome (MFS) is a rare variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ataxia, ophthalmoplegia, and areflexia. The incidence rate in Thailand has not been established but it occurred approximately 1-5% that of GBS. Here, the authors report a Thai patient diagnosed as MFS that had a positive test of antibodies against the ganglioside GQ1b. These antibodies have diagnostic and pathogenic importance to MFS because of high sensitivity and specificity. All other investigations, such as cerebrospinal fluid analysis, electrophysiological studies, and imaging studies had no significant abnormalities. The patient was successfully treated with intravenous immunoglobulin and fully recovered within one month. After eighteen months follow-up, he is still healthy and has had no recurrent symptoms.
PMID: 17375649 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
[Facial diplejia: a regional variant of Guillain-Barré syndrome]
An Med Interna. 2007 Jan;24(1):24-6
Authors: Piñol Ripoll G, Larrodé Pellicer P, de la Puerta González-Miró I, Tejero Juste C, Iñiguez Martínez C, Santos Lasaosa S, Mostacero Miguel E
Facial palsy is a uncommon clinical manifestation that it can be caused by different etiologies.We show a patient with a chronic periodontal disease who presented a sudden facial palsy, initially in left-face but it becomes bilateral quickly. In few days he associated paresthesias in his right arm and hyporreflexia. These clinical findings with albumin-cytological dissociation, they had allowed to establish the diagnosis of regional variant of Guillain-Barré Syndrome (SGB). Facial diplejia is an idiopathic manifestation in 25% of patients, and this is the most common cause. However, facial diplejia can be secondary to many etiologies as SGB. The affectation of facial nerve associated to other motor symptoms in SGB is frequent, but it is not frequent the presentation as facial diplejia alone. In conclusion, it is necessary a high clinical suspicion to do a lumbar punction (PL) and MRI to reject neoplasic pathologies and to obtain a diagnosis and an adequate treatment.
PMID: 17373865 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]
IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial.
Neurology. 2007 Mar 13;68(11):837-41
Authors: Zinman L, Ng E, Bril V
OBJECTIVE: We aimed to determine the effectiveness of IV immunoglobulin (IVIG) in the treatment of patients with myasthenia gravis (MG) and worsening weakness in a randomized, placebo-controlled, masked study. METHODS: Fifty-one patients with worsening weakness due to MG were randomized to infusion with 2 g/kg of IVIG or an equivalent volume of IV dextrose 5% in water. The Quantitative Myasthenia Gravis (QMG) Score for Disease Severity, a validated clinical composite scale, was calculated by a masked observer at baseline and days 14 and 28. RESULTS: In IVIG-treated patients, a clinically meaningful improvement in QMG Score for Disease Severity was observed at day 14 and persisted at day 28. The greatest improvement occurred in patients with more severe disease as defined by a QMG Score for Disease Severity greater than 10.5. CONCLUSION: This study provides level 1 evidence for the effectiveness of IV immunoglobulin in patients with worsening weakness due to myasthenia gravis.
PMID: 17353471 [PubMed:- Treatment with IVIG - indexed for MEDLINE:- Treatment with IVIG]