Multiple Sclerosis Exacerbations Research Articles

Spotlight on the May 31 Issue

Clinical relapses of 1866 patients and gadolinium-enhanced (Gd+) lesions of 341 patients were analyzed over an 8-month period. This paper provides evidence that when you stop Tysabri in patients with multiple sclerosis, clinical and MRI activity gradually returns to pre-study baseline activity over 3–4 months. See p. 1858; Editorial, p. 1854 Several studies have shown that stressful life events are associated with an increased risk of multiple sclerosis (MS) exacerbations. This study found, in two cohorts of female nurses, that there was no increased risk of MS in those with severe stress at home, severe physical abuse during childhood …

Acute Multiple Sclerosis Lesion: Conversion of Restricted Diffusion Due to Vasogenic Edema

It is widely accepted that acute demyelinating plaques in patients with multiple sclerosis (MS) demonstrate increased apparent diffusion coefficient (ADC) and increased diffusion weighted imaging (DWI) signals on MRI. These imaging characteristics in acute MS lesions have been postulated to be due to peripheral vasogenic edema that typically increases the ADC. This assumption is commonly used to differentiate stroke from MS lesions since acute and subacute stroke lesions demonstrate increased DWI signal with reduced ADC due to acute cytotoxic edema. We report a case of active relapsing-remitting MS with two new symptomatic contrast-enhancing lesions. The lesions had reduced diffusion on the ADC map in the early acute phase of MS exacerbation. The reduced ADC signal was subsequently "converted" to increased ADC signal that coincided with the development of profound peripheral vasogenic edema seen on T2-weighted images. To our knowledge, this is the first serial MRI study describing decreased ADC signal in the early acute phase of contrast-enhancing MS lesion. The implications of decreased diffusion in the acute phase of MS lesions for the disease pathogenesis are discussed.

Introduction: Enhancing Mobility in Multiple Sclerosis

Mobility limitations, which affect the majority of individuals living with multiple sclerosis (MS), are frequently addressed by clinicians and researchers, as they are at the heart of patients' (and families') concerns at the time of diagnosis and throughout the course of the disease. Ambulation, one of the key components of mobility, is routinely assessed through patient report, direct observation, and standardized tests and scales to monitor the progression of MS and the efficacy of disease-modifying therapies. Mobility-related issues can be a major source of frustration for patients, families, and health-care providers given the progressive nature of the disease, its heterogeneity, and its unpredictability. However, the recent growth in the body of evidence for the assessment and management of mobility restrictions, and in the spectrum of interventions available, brings renewed energy and hope.

Relapse risk in patients with multiple sclerosis after H1N1 vaccination, with or without seasonal influenza vaccination

The safety of vaccination in multiple sclerosis (MS) raises concern, particularly the relapse risk post-vaccination. With the recent H1N1 pandemic, people with chronic diseases, including neurological conditions such as MS, were prioritised for vaccination. Two questions therefore arise in this context: whether vaccination increases the relapse rate, and whether the relapse is more severe postvaccination. Seasonal influenza immunisation does not increase the risk of MS exacerbation; a systematic review found no increased risk of early (3–4 weeks post-vaccination) or late (4–6 months) exacerbations [1]. Likewise, influenza vaccination resulted in no relative increase in disease-activity to controls based on new Gd-enhancing lesions on MRI [2, 3]. The evidence is less clear-cut regarding the pandemic influenza H1N1 vaccine and relapse risk. Reports from the 1970s suggested an increased risk of Guillan-Barre and MS-like syndromes following this vaccine [4], although formal controlled trials did not. Two placebo controlled studies involving 88 and 127 MS patients, reported similar frequency of MS relapses in the H1N1 and placebo-vaccinated groups [5, 6] (12 vs. 14% and 3 vs. 6.5%, respectively). In our acute weekly relapse clinic, we recorded data from 30 consecutive patients between 11/2009 and 01/2010. During this period in the UK, all MS patients were actively offered H1N1 vaccination [7]. Relapse onset date, and H1N1/seasonal influenza vaccination status (with administration date where appropriate) were recorded. The expanded disability status scale (EDSS), multiple sclerosis impact scale (MSIS-29 v 2.0), and use of corticosteroid treatment were also documented. Eighteen (60%) of patients received either/both vaccination prior to relapse onset, leaving 40% not vaccinated (Table 1). Neither the relapse severity (EDSS/MSIS-29 v 2.0) nor the numbers receiving corticosteroid treatment were significantly different (Table 1). The association between relapse rate and vaccination in a relapse clinic can be evaluated using a case-crossover design; as in a previous report of different vaccinations in MS relapse clinics [8]. This method compares vaccine exposure in a specified risk period immediately preceding the relapse to that in several prior control periods of equal duration, thus quantifying the relative relapse risk in the specified post-vaccination period. Using a similar analysis in our 30 patients, 15 received H1N1 vaccination (Fig. 1a, flow chart); of whom 10

Exacerbation history is associated with medication and appointment adherence in MS

Disease-modifying treatments are designed to prevent exacerbations in multiple sclerosis (MS). To date, few studies have examined the relationship between disease activity and treatment adherence in MS. The primary aim of this study was to examine the association between disease activity (e.g., annualized relapse rates), medication adherence, and appointment adherence in relapsing-remitting MS. Retrospective exacerbation and appointment data were collected and used to predict prospective medication adherence. Results indicated that patients with higher annualized relapse rates missed fewer doses of medication and were less likely to miss appointments. Conversely, patients with relatively stable disease were more likely to demonstrate poor medication adherence and poor appointment adherence. Patients who missed more appointments also missed more doses of their disease modifying medication. Future studies may wish to examine clinical methods designed to improve immunotherapy adherence among patients who are in relatively symptom-free stages of relapsing-remitting MS.

Neuroantigen-specific CD8+ regulatory T-cell function is deficient during acute exacerbation of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). MS is thought to be T-cell-mediated, with prior research predominantly focusing on CD4+ T-cells. There is a high prevalence of CNS-specific CD8+ T-cell responses in MS patients and healthy subjects. However, the role of neuroantigen-specific CD8+ T-cells in MS is poorly understood, with the prevalent notion that these may represent pathogenic T-cells. We show here that healthy subjects and MS patients demonstrate similar magnitudes of CD8+ and CD4+ T-cell responses to various antigenic stimuli. Interestingly, CD8+ T-cells specific for CNS autoantigens, but not those specific for control foreign antigens, exhibit immune regulatory ability, suppressing proliferation of CD4+CD25− T-cells when stimulated by their cognate antigen. While CD8+ T-cell-mediated immune suppression is similar between healthy subjects and clinically quiescent treatment-naïve MS patients, it is significantly deficient during acute exacerbation of MS. Of note, the recovery of neuroantigen-specific CD8+ T-cell suppression correlates with disease recovery post-relapse. These studies reveal a novel immune suppressor function for neuroantigen-specific CD8+ T-cells that is clinically relevant in the maintenance of peripheral tolerance and the intrinsic regulation of MS immune pathology.

Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations

Background: Staphylococcus aureus may produce superantigens that can non-specifically activate CD4+ cells to potentially target the myelin basic protein. Objective: This study examined the association between individuals with multiple sclerosis (MS) and colonization with S. aureus harbouring superantigens. Methods: Nasal swabs were collected from non-MS subjects and patients with MS who had not experienced a relapse in the past six months (MS stable group) and who had suffered a relapse within 30 days of study recruitment (MS exacerbation group). S. aureus was isolated from the anterior nares of participants following standard procedures and staphylococcal superantigen genes (sea, seb, and tsst-1) were detected using standard laboratory PCR techniques. Results: The study enrolled 204 patients, 80 in the non-MS and MS stable groups and 44 patients in the MS exacerbation group. Overall, 27.0% of patients were colonized with S. aureus with no significant differences identified between study groups. Amongst individuals colonized with S. aureus, the prevalence of sea was significantly greater in the MS exacerbation versus non-MS study group (p < 0.05; odds ratio 7.9; 95% confidence interval 1.2–49.5). Conclusions: The ability to rapidly screen patients for the presence of S. aureus producing sea may serve as a useful marker of a potential MS exacerbation.

Utvikling av ny behandling for multippel sklerose

Current first line treatment for multiple sclerosis is only moderately effective and is associated with frequent and disturbing side effects. We here describe opportunities and challenges related to drugs under development. Non-systematic search in PubMed and congress abstracts. Monoclonal antibodies (e.g. natalizumab, alemtuzumab, rituximnab and dacklizumab) and oral agents (e.g. fingolimod and cladribine) target molecules or cells which are important in the immunopathogenesis of multiple sclerosis. These agents seem to have a considerable effect on relapsing-remitting multiple sclerosis, but may also be associated with serious side effects. Natalizumab is licensed as second line treatment for relapsing-remitting multiple sclerosis, and also as first line treatment in especially serious cases. Cladribine and fingolimod may be available in Norway in 2011. Treatment of exacerbations in multiple sclerosis is changing. Indication for the drugs under development is not yet clear.

Restless Legs Syndrome Presenting as an Acute Exacerbation of Multiple Sclerosis

Restless legs syndrome is common in patients with multiple sclerosis but has not been reported as occurring due to an acute, inflammatory, demyelinating attack. Restless legs syndrome is known to be related to low brain iron levels. Multiple sclerosis has been associated with the abnormal accumulation of iron in the chronic, progressive phase of axonal degeneration. Iron deficiency may play a role in demyelination. This suggests that restless legs syndrome may be caused by the inflammatory, demyelinating component of multiple sclerosis rather than axonal degeneration. The author presents a case of self-limited restless legs syndrome occurring as an acute attack of multiple sclerosis, supporting the notion that inflammatory demyelination is the underlying pathophysiology of restless legs syndrome in multiple sclerosis.

Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis

BackgroundA poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures.Methodology/Principal FindingsFifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31–175) at week 0 to 380 nmol/L (151–535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naïve and memory) CD4+ Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P = 0.143). An increased proportion of IL-10+ CD4+ T cells was found after supplementation (P = 0.021). Additionally, a decrease of the ratio between IFN-γ+ and IL-4+ CD4+ T cells was observed (P = 0.035).Conclusion/SignificanceTwelve week supplementation of high dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.Trial RegistrationClinicaltrials.gov NCT00940719

Interferon‐β inhibits toll‐like receptor 9 processing in multiple sclerosis

Viral infections have been implicated in the pathogenesis of multiple sclerosis (MS). Plasmacytoid dendritic cells (pDCs) are present in peripheral blood, cerebrospinal fluid, and brain lesions of MS patients. pDCs sense viral DNA via Toll-like receptor 9 (TLR9), which has to be cleaved from the N-terminal to become functional (TLR9 processing). pDCs activated with TLR9 agonists promote T-helper type 1 (Th1)/T-helper type 17 (Th17) responses. In the animal model of MS, TLR9 agonists can induce disease. We hypothesized that pDCs are inhibited by disease-modifying therapy such as interferon (IFN)-β, consequently decreasing the frequency of MS attacks. We separated pDCs from healthy subjects and patients diagnosed with relapsing-remitting MS and clinically isolated syndrome. Cytokine secretion by pDCs activated with TLR9 agonists was measured by enzyme-linked immunosorbent assay and multianalyte profiling. TLR9 gene and protein expression was studied by DNA microarrays and western blot. In untreated patients, pDCs activated with TLR9 agonists produced increased levels of IFN-α, a Th1-promoting cytokine, as compared to healthy subjects. In IFN-β-treated patients, activated pDCs had decreased ability to produce both IFN-α and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α as compared to untreated patients. pDCs separated from IFN-β-treated patients had significantly reduced levels of the processed TLR9 protein but normal levels of the full-length TLR9 protein and TLR9 gene expression as compared to untreated patients. This finding represents a novel immunomodulatory mechanism of IFN-β: inhibition of TLR9 processing. This results in decreased activation of pDCs by viral pathogens and, thus, may affect the frequency of MS exacerbations.

IFNβ-1b may severely exacerbate Japanese optic-spinal MS in neuromyelitis optica spectrum

Interferon-β-1b (IFNβ-1b) has been used to prevent exacerbation of relapsing-remitting multiple sclerosis (RRMS) including optic-spinal multiple sclerosis (OSMS) in Japan. We encountered 2 patients with OSMS with unexpectedly severe exacerbation soon after the initiation of IFNβ-1b therapy. The experience urged us to retrospectively review the patients with RRMS who had been treated with IFNβ-1b to identify similar cases. At neurologic departments of 9 hospitals, the medical records of 56 patients with RRMS were reviewed to identify those who showed severe exacerbation soon after the initiation of IFNβ-1b therapy. Of 56 patients with RRMS, we identified 7 who experienced severe exacerbation (exacerbation with increased scores of Expanded Disability Status Scale ≧7.0) within 90 days of the initiation of IFNβ-1b therapy. In all 7 patients, the exacerbations after the initiation of IFNβ-1b therapy were more severe than those experienced by the individual patients before the use of IFNβ-1b, and seemed to have occurred unexpectedly in a short time after the initiation of INFβ-1b therapy. A retrospective analysis revealed that all 7 patients had antibodies toward aquaporin 4, and the clinical features of all 7 patients after the exacerbation were consistent with those of neuromyelitis optica (NMO) spectrum. Our study suggests that IFNβ-1b may trigger severe exacerbation in patients with the NMO spectrum. In INFβ-1b therapy, cases in NMO spectrum should be carefully excluded.

Mediterranean Weather Conditions and Exacerbations of Multiple Sclerosis

Background: Previous studies provide increasing support for the impact of environmental factors on disease incidence and activity in multiple sclerosis (MS). Objectives: The purpose of this research was to assess the relationship between the incidence of MS relapses and weather conditions in Israel. Methods: Clinical data, including occurrence of relapses in 235 patients, during 3 consecutive years (2001–2003) were assessed against the general daily meteorological variables. Initially, the relationship between the relapses and their mode of distribution was evaluated. Second, the relationship between the number of relapses on a specific date and the meteorological variables was assessed. Third, the tendency to seasonality in the occurrence of relapses was examined. Results: No significant correlation was found between the number of relapses and a specific season, month or day. Moreover, no clear relationship was found between certain meteorological variables or a combination of variables and the frequency of the relapses. Conclusion: The meteorological parameters studied were not found to have a significant impact on the occurrence of relapses in this group of patients. These findings raise questions regarding the clinical significance of the impact of weather conditions, at least in the context of the Mediterranean climate, on the disease course of patients with MS.

Pharmacological Management of Pain in Patients with Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating, autoimmune disease of the CNS. There are currently a number of disease-modifying medications for MS that modulate or suppress the immune system; however, these medications do not directly relieve MS symptoms, which include visual deficits, gait problems, sensory deficits, weakness, tremor, spasticity and pain, among others. Pain is a common symptom in MS which has recently been estimated to be experienced by more than 40% of patients. Nociceptive pain occurs as an appropriate physiological response transmitted to a conscious level when nociceptors in bone, muscle or any body tissue are activated, warning the organism of tissue damage. Neuropathic pain is initiated as a direct consequence of a lesion or disease affecting the somatosensory system, with no physiological advantage. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease, and may be associated with other symptoms. Central neuropathic pain has been reported to be among the most common pain syndromes in MS. It is described as constant, often spontaneous, burning occurring more frequently in the lower limbs. Treatment typically includes tricyclic antidepressants and antiepileptic medications, although studies have been conducted in relatively small samples and optimal dosing has not been confirmed. Cannabinoids have been among the few treatments studied in well designed, randomized, placebo-controlled trials for central neuropathic pain. In the largest of these trials, which included 630 subjects, a 15-week comparison between Delta9-tetrahydrocannabinol and placebo was performed. More patients receiving active treatment perceived an improvement in pain than those receiving placebo, although approximately 20% of subjects reported worsening of pain while on active treatment. Trigeminal neuralgia, while affecting less than 5% of patients with MS, is the most studied pain syndrome. The pain can be extreme and is typically treated with carbamazepine, although adverse effects can mimic an MS exacerbation. Painful topic spasms occur in approximately 11% of the MS population and are treated with antispasticity medications such as baclofen and benzodiazepines. Gabapentin has also demonstrated efficacy, but all studies have included small sample sizes. In general, evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS, which should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS.

P01-313 - Psychotic exacerbations in a patient with multiple sclerosis

ObjectiveThere is retrospective evidence of a correlation between psychosis in multiple sclerosis (MS) however comorbidity of Psychosis in MS patients is a less frequent condition and the treatment of this condition seems to be hard and complex.Case32 years old, male patient with MS had psychotic symptoms simultaneously with exacerbations of MS symptoms for three times in three years.The first psychiatric episode was one year after he had the diagnosis of MS due to episodes of difficulty in walking and determination of demyelination plagues by MRI. Irritability, delusions of jealousness and persecutions, agitation, drug refusal were occurred simultaneously with the exacerbated symptoms of MS as right sided hemiparesia. He had been hospitalized and treated with olanzapine and high dose of corticosteroids. After this first episode he had two simultaneous episodes of psychosis with similar symptoms to previous one and exacerbations of MS with more severe symptoms as additional urinary incontinence. He was treated with olanzapine and corticosteroids in all episodes. The psychotic symptoms were remitted and the symptoms of MS were improved partially.ConclusionPsychosis is not a prominent feature of MS, occurring in 5% of cases. The relationship between lesions of the central nervous system and psychiatric illness has not been established yet. Some reports have implicated the contribution of acute demyelination to psychosis. In this case the simultaneous episodes of MS symptoms and psychosis suggest a common etiology. Prospective studies are required both about the common etiology and treatment.

Immunization in Patients With Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and some axonal damage. An overactive or dysfunctional immune response to self-antigen is believed to be the pathogenic mechanism and therefore the treatment of MS often involves immunosuppressive therapy. Because of altered immune function in patients with MS, questions arise about risk of infections in this population and the safety and efficacy of common immunizations. The risk of MS exacerbation with common infections and safety and efficacy of immunization are reviewed along with the available guidelines for use of vaccines in patients with MS.

Multiple sclerosis and pregnancy

Epilepsy and multiple sclerosis (MS) are the 2 most common neurologic disorders affecting women of childbearing age. As many as 25,000 women with epilepsy (WWE) give birth annually.1 While similar national estimates for birth prevalence in women with MS (WWMS) are not available, with the average age at MS onset at 30 years, around one fifth of women with MS will bear children after onset of the disease.2 This presents an important opportunity for neurologists caring for these women to provide transparent, evidence-based information to both inquiring patients and to referring physicians who may be providing concurrent care. In planning pregnancy, these women will want to know both the impact of a potential pregnancy on the neurologic disease (e.g., seizure frequency, MS exacerbation), as well as the impact of the disease on pregnancy and birth outcomes. For epilepsy, an extensive amount of useful information on both issues was recently published in a series of evidence-based guidelines in Neurology ®.3,4 There is also substantial information on the short-term impact of pregnancy on MS: the exacerbation rate is reduced during the second and third trimester and increased during the first 3 months following delivery, resulting in no net change in relapse rates over the entire pregnancy year (9 months gestation + 3 months postpartum).5 In addition, exclusive breastfeeding has been recently reported to dramatically reduce the postpartum …

The effect of war stress on multiple sclerosis exacerbations and radiological disease activity

Objective The relationship between stressful life events and multiple sclerosis (MS) exacerbations or radiological disease activity is at best controversial. The aim of this study is to examine the relationship between exposure to war-related events incurred during the July 2006 Israeli–Lebanese war and clinical relapses and MRI disease activity among Lebanese MS patients. Methods We studied a group of 216 patients with clinically definite relapsing remitting MS (RRMS), on whom clinical data was available for the war period and for the preceding and following year(s). The number of relapses was determined during the war period and during similar periods over a 3-year span. All patients with brain MRI during the war period had their scans reviewed for evidence of disease activity as defined by the presence of gadolinium enhancing (Gd+) lesions. A group of patients with brain MRI performed outside the war period was used for comparison. Results The total number of relapses during the war period ( n = 23) was significantly higher than during non-war periods (mean = 8.4, SD = 0.86) ( p = 0.006). Of the 18 patients with brain MRI during the war, 5/7 with relapses and 1/11 without relapses had Gd+ lesions ( p = 0.013). More patients had Gd+ lesions during the war period (33%) compared to controls (13%) ( p = 0.075). Interpretation Our study shows that exposure to war-related events is likely to lead to an increase in both clinical relapses and MRI disease activity in patients with MS.

Impfen und Multiple Sklerose

Vaccinations to prevent communicable diseases are, like in other chronic diseases, of special importance in patients with multiple sclerosis (MS). Various bacterial and viral infections have been shown to induce relapses of MS. Reports of possible adverse effects of vaccinations on the course of multiple sclerosis have led patients and treating physicians to exercise caution in the use of vaccines. A number of vaccines have been studied with respect to the risk in MS patients. Some vaccines, for example against yellow fever, are not indicated in MS due to the risk of MS exacerbation. In contrast, tetanus or hepatitis B vaccines do not represent a risk for manifestation or disease progression of MS. Before and during immunomodulatory therapy of MS special attention should be given to adequate protection against vaccine preventable diseases.This paper reviews the indications and specific side effects of vaccinations in MS patients. Additionally, issues of vaccination under immunomodulatory therapy of MS are discussed.

IVIG for Refractory Clostridium difficile Colitis in an Immunosuppressed Patient

Purpose: Background: Clostridium difficile-associated diarrhea (CDAD) is increasing in incidence and severity, with recent outbreaks due to more virulent strains.1 Metronidazole is still considered the first-line therapy, with oral Vancomycin reserved for severe cases.2 CDAD is, however, becoming increasingly refractory to these two therapies. Intravenous immunoglobulin (IVIG) has been reported as an alternative treatment for refractory cases in several case reports and three uncontrolled studies.3 Case Report: A 56 year-old female with a history of multiple sclerosis (MS) presented with sudden bilateral lower extremity weakness, bloody diarrhea, and diffuse abdominal pain. Home medications included monthly Natalizumab and a recent 7 day course of Ciprofloxacin. She was diagnosed with CDAD by positive stool toxin and treated with Metronidazole 500 mg orally three times daily. She also received intravenous Methylprednisolone 1 gram daily for 5 days for MS exacerbation. The diarrhea initially improved, but became increasingly severe and associated with abdominal pain and distention one week after initiating Metronidazole therapy. Oral Vancomycin was added to the regimen, but the patient failed to improve. Stool toxin remained positive at 10 days. Leukocyte count remained persistently high at 35.000-40.000/dl. Abdominal computerized tomography revealed diffuse colonic wall thickening and ileus. On day 11, the patient was transferred to the intensive care unit. Vancomycin enemas were considered, but the patient could not tolerate them due to profuse diarrhea. Serum levels of total IgG, and of IgG1, IgG2, and IgG4 were low. The patient was administered two doses of IVIG 400 mg/kg on days 13 and 14. She had a significant clinical improvement after the IVIG and colectomy was thereby avoided. Discussion: Patients with severe CDAD may have a defective humoral response to toxin A as suggested by finding lower levels of IgG antitoxin A antibodies in these patients4,5. Correction of hypogammaglobulinemia by IVIG administration in the post-transplant period has been shown to decrease the incidence of CDAD6. The currently reported patient was on Natalizumab maintenance therapy, and received high-dose steroids synchronous with treatment for CDAD. Both factors are associated with CDAD development and relapse7,8. She failed both Metronidazole and oral Vancomycin therapy, but improved promptly with administration of IVIG. Colectomy was thereby averted. IVIG therapy may be considered as salvage therapy in immunosuppressed patients with refractory CDAD, especially if they have hypogammaglobulinemia.