Cervical dysplasia in a patient with multiple sclerosis treated with natalizumab

We describe one report of a cervical dysplasia in a patient receiving natalizumab for multiple sclerosis. Other cases were identified in the WHO's global individual case safety report database, VigiBase^®. These data underline the importance of monitoring HPV infection in patients with MS treated with natalizumab.     

Use of natalizumab in multiple sclerosis: current perspectives

ABSTRACT

Introduction: Natalizumab is an efficacious monoclonal antibody approved for use in relapsing-remitting multiple sclerosis (RRMS). Multiple studies have demonstrated reduced relapse rate, decreased disability progression and prolonged disease-free intervals with natalizumab use. However, natalizumab is associated with an increased risk of progressive multifocal leukoencephalopathy (PML), thus restricting its widespread use with populations at high risk for developing PML. Recently, the effect of natalizumab in secondary-progressive (SPMS) population has been explored.

Areas covered: This review highlights the pathophysiology behind disease progression in MS and summarizes various attributes of natalizumab including: its pharmacological properties and global economic impact, results of clinical efficacy studies, its role in SPMS, pregnancy and its adverse events profile including PML and discontinuation protocols.

Expert opinion: Despite an established role in reducing RRMS disease activity, natalizumab has found limited use in SPMS due to insufficient evidence of efficacy. Current disease-modifying therapies exert modest overall benefit in SPMS owing to its complex pathophysiology, higher prevalence of comorbidities and increased PML risk with age and lack of reliable outcome measures. Finding more appropriate MRI and clinical outcome measures is quintessential for designing future randomized trials and possibly exploring primary neuroprotective agents for treating SPMS.     

Negative impact of episodic migraine on a university population: quality of life, functional impairment, and comorbid psychiatric symptoms

(Headache 2011;51:581‐589) Background.— Migraine is associated with significant negative impact, including reduced quality of life, impaired functioning, and comorbid psychiatric disorders. However, the impact of migraine on university students is understudied, despite their high prevalence of migraine and psychiatric disorders and their frequent use in research studies. Objectives.— The aim of this cross‐sectional study was to evaluate the impact of migraine among college students on quality of life, functional impairment, and comorbid psychiatric symptoms. Methods.— Three hundred and ninety‐one students (76.73% female, mean age = 19.43 ± 2.80 years) completed well‐validated measures of migraine and migraine‐related disability, quality of life, and comorbid psychiatric symptoms. They also quantified impairment in school attendance and home functioning and reported the number of medical visits during the preceding 3 months. Results.— One hundred and one (25.83%) met conservative screening criteria for episodic migraine; their mean score on the Migraine Disability Assessment Questionnaire was 9.98 ± 12.10. Compared to those not screening positive for migraine, the migraine‐positive group reported reduced quality of life on 5 of 6 domains, as well as a higher frequency of missed school days (2.74 vs 1.36), impaired functioning at home (2.84 vs 1.21 days), and medical visits (1.86 vs 0.95). They also reported more symptoms of both depression and anxiety than controls, although differences in functional impairment remained after controlling for these comorbid psychiatric symptoms. These differences were highly statistically significant and corroborated by evidence of clinically significant impairment; the corresponding effect sizes were modest but non‐trivial. Conclusions.— Episodic migraine is associated with negative impact in numerous domains among university students. These findings replicate and extend those of studies on other samples and have implications for future research studies with this population.     

Effectiveness of interferon beta treatment in relapsing-remitting multiple sclerosis: an Italian cohort study

RATIONALE, AIMS AND OBJECTIVES: Randomized clinical trials (RCTs) have provided evidence for the efficacy of interferon beta (IFNbeta) in the treatment of relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to evaluate the effectiveness of IFNbeta treatment in clinical practice. METHODS: This was a national, multicentre, observational study of patients with confirmed RRMS. Demographic, clinical and therapeutic data were retrospectively collected for each patient enrolled in the study. RESULTS: The study cohort consisted of 427 patients exposed to and 245 never exposed to IFNbeta treatment during the study period (for a total 2297 patient-years of follow-up). Among the exposed patients, 215 were initially untreated and then began IFNbeta later in the follow-up period; 137 of these patients were exposed to IFNbeta for more than 2 years. In these patients, IFNbeta treatment reduced the mean relapse rate by 24.2%[95% confidence interval (CI): 5.8-42.5%]. For 640 of the 672 patients enrolled in the study, it was possible to calculate the area under the disability/time curve compared to that present at baseline. A total of 117 (18.3%) patients displayed disability progression. Adjustment of the disability progression rates for potential confounders and/or for propensity scores by Poisson regression model resulted in relative risks for patients exposed to IFNbeta treatment compared to those never exposed to IFNbeta of 0.87 (95% CI: 0.56-1.34) after an exposure of < or = 2 years, and of 0.35 (95% CI: 0.21-0.60) after an exposure of >2 years. CONCLUSIONS: These findings suggest that the evidence from RCTs on the treatment of RRMS with IFNbeta has been effectively translated into routine clinical practice.     

The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis

Background: Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-β-1b decreases the formation of CELs. However, the ability of IFN-β-1b to reduce the size of CELs arising during therapy has not been extensively investigated. Methods: Thirty patients with relapsing-remitting (RR) MS were followed for a 3-month pre-therapy phase then for a 6-month therapy phase during which treatment with IFN-β-1b at a dosage of 250 μg subcutaneously injected every other day was employed. Each patient underwent monthly clinical and MRI examinations. For all patients, CELs were identified on postcontrast T1-weighted MRIs. CEL number, size, and volume were computed using Medx software. Results: The average number and total lesion volume of CELs visible during the therapy phase were significantly lower than the number and total lesion volume of CELs observed in the pre-therapy phase. However, there was no significant reduction between pre-therapy and therapy phases in the mean size of individual lesions arising during the respective phases. Conclusions: Since size of CELs has been related to severity of tissue damage, the lack of size decrease during therapy suggested a limited therapeutic effect of IFN-β-1b if a blood–brain barrier breakdown has occurred.     

Migraine versus multiple sclerosis

A headache associated with focal neurological signs and symptoms is always a clinical dilemma.     

Chronic myeloid leukaemia in two multiple sclerosis patients on interferon beta-1a

Haematological problems are commonly associated with use of beta-interferon in multiple sclerosis (MS) patients. However these problems are usually benign and are reversible when the drug is stopped. We describe two patients, with the diagnosis of MS, who developed leucocytosis. Cytogenetic studies showed the presence of the Philadelphia chromosome in all the cells analysed, confirming the diagnosis of chronic myeloid leukaemia (CML). The first patient currently on imatimib mesylate and interferon beta-1a is asymptomatic. For the second patient, interferon beta-1a was withdrawn after suspicion of CML.     

The association of brainstem lesions with migraine-like headache: an imaging study of multiple sclerosis

OBJECTIVE: To determine if the prevalence of migraine-like headache in patients with multiple sclerosis (MS) is associated with plaques in the brainstem or in other locations. BACKGROUND: There is increasing evidence to suggest that periaqueductal gray matter (PAG) plays a role in the pathophysiology of migraine headache. There are a few clinical case studies and some experimental evidence in support of this observation. METHODS: The study population of patients with demyelinating disease was identified by accessing the Department of Radiology magnetic resonance imaging (MRI) database accumulated between the years of December 1992 and June 2002. A total of 4369 MRI scan reports were available for review from that time period. Out of this, 1533 studies were reported to have possible demyelinating lesions. Medical records of these patients were reviewed to confirm the diagnosis of MS and also to document the headache complaints, if any. Two hundred and seventy-seven patients were identified with definite MS. A questionnaire was mailed to these patients to obtain additional details regarding MS and headache. The questionnaire response rate was 61% (169 of 277). This data were added to the information previously obtained from the medical records. The MRI films of each patient were examined, documenting location of the plaque, rather than the actual number. MRI and clinical data were kept separate until the final analysis. The International Headache Society criteria were used to classify headache types. RESULTS: There were 207 female and 70 male patients available for analysis. Sixty-six percent (182 of 277) of patients were diagnosed with remitting-relapsing MS, 17% (47 of 277) with primary progressive MS, and 17% (48 of 277) with secondary progressive MS. Overall, 55.6% (154 of 277) of patients had a complaint of headache. Of these patients, 61.7% (95 of 154) met criteria for migraine-like headache, 25.3% (39 of 154) met criteria for tension-type headache, and 13% (20 of 154) had features of migraine and tension-type headache. MS patients with a plaque within the midbrain/periaqueductal gray matter areas had a four-fold increase in migraine-like headaches (odds ratio 3.91, 95% confidence interval 2.01 to 7.32; P < .0001), a 2.5-fold increase in tension-type headaches (odds ratio 2.58, 95% confidence interval 1.13 to 5.85; P= .02), and a 2.7-fold increase in combination of migraine and tension-type headaches (odds ratio 2.77, 95% confidence interval 0.98 to 7.82; P= .05) when compared to MS patients without a midbrain/periaqueductal gray matter lesion. Although not statistically significant, MS patients with three or more lesion locations were found to be approximately two times more likely to have migraine-like headaches compared to MS patients with 0 to 2 locations (3 to 5: odds ratio 2.47, 95% confidence interval 0.90 to 6.84; 6 to 8 locations: 1.82, 0.64 to 5.17; > or =9 locations: 2.41, 0.63 to 9.13). A linear trend was also observed between numbers of lesion locations and migraine-like headaches (P= .02). CONCLUSION: The results of this study indicate that the presence of a midbrain plaque in patients with MS is associated with an increased likelihood of headache with migraine characteristics. (Headache 2005;45:670-677).     

Recent developments in interferon-based therapies for multiple sclerosis

Introduction: Multiple sclerosis (MS) is a chronic and disabling immune-mediated disease of the central nervous system. Beta-interferons are the first approved and still the most widely used first-line disease-modifying treatment in MS.

Areas covered: Here we focus on recent developments in pharmacology and delivery systems of beta-interferons, and discuss their place within current state of the art therapeutic approaches. We briefly review the clinical trials for classical and PEGylated formulations, emphasizing effectiveness, safety concerns, and tolerability. The mechanisms of action of IFN-β in view of MS pathogenesis are also debated.

Expert opinion: Though only modestly efficient in reducing the annualized relapse rate, beta-interferons remain a valid first-line option due to their good long-term safety profile and cost-efficacy. Moreover, they are endogenous class II cytokines essential for mounting an effective antiviral response, and they may interact with putative MS triggering factors such as Epstein-Barr virus infection and human endogenous retroviruses. Recent improvements in formulations, delivery devices and drug regimens tackle the tolerability and adherence issues frequently seen with these drugs, and scientific advances may offer means for a better selection of patients. Although a well-established immunomodulatory treatment, beta-interferons have not said their last word in the management of MS.     

Frequency of Chronic Headaches in Japanese Patients With Multiple Sclerosis: With Special Reference to Opticospinal and Common Forms of Multiple Sclerosis

Background.— Headache is common in Western patients with multiple sclerosis (MS), but its frequency has not been reported in Asian patients. In Asians, the opticospinal form of MS, showing similar characteristics to relapsing neuromyelitis optica in Westerners, is regarded as a different subtype from conventional MS. Objectives.— The aim of this study was to clarify the frequency of primary and chronic secondary headaches in Japanese patients with MS and the factors associated with the emergence of such headaches. Methods.— We investigated 127 consecutive patients with clinically definite MS. Frequencies of primary and chronic secondary headaches were compared according to clinical subtype, administration of interferon beta, and anti‐aquaporin‐4 antibody status. Results.— The frequency of patients with primary and chronic secondary headaches at the time of interview was 64/127 (50.4%); the frequency of migraine was 26/127 (20.4%) and that of tension‐type headache was 38/127 (29.9%). The frequencies of patients with primary and chronic secondary headaches and migraine without aura after the onset of MS were higher in patients undergoing interferon beta therapy than in those not on the therapy (42.4% vs 23.4%, P < .05 and 15.1% vs 4.3%, P = .05, respectively). There were no significant differences in the frequency of primary and chronic secondary headaches based on clinical subtype of MS. However, among patients not receiving interferon beta, the occurrence of migraine with aura after the onset of MS was significantly higher in patients with anti‐aquaporin‐4 antibody than in patients without the antibody (13.3% vs 0.0%, P < .05). Conclusions.— In Japanese patients with MS, the frequency of primary and chronic secondary headaches, especially migraine, was higher than in the general Japanese population. Administration of interferon beta was related to a higher frequency of primary and chronic secondary headaches, especially migraine without aura, irrespective of clinical subtype of MS.     

MS and me: exploring the impact of multiple sclerosis on perceptions of self

Purpose: The aim of this qualitative study was to explore the impact of multiple sclerosis (MS) on perceptions of self as well as the emotional, social and practical implications of any self-reported changes. Method: Twelve participants were interviewed and interpretative phenomenological analysis used to analyse the data. Participants were recruited from a MS hospital clinic in the north-west of England. Results: Four themes were identified although for reasons of space and novelty three were discussed, (i) ‘my body didn’t belong to me’: the changing relationship to body, (ii) ‘I miss the way I feel about myself’: the changing relationship to self and (iii) ‘let’s just try and live with it’: incorporating yet separating MS from self. Conclusions: The onset of MS was seen to impact upon self yet impact did not necessarily equate with a loss of self but rather a changed self. Self-related changes did, however, carry the potential to impact negatively upon a person’s mood and psychological functioning and consequently, clinicians are encouraged to consider issues relating to self as standard.

Implications for Rehabilitation

• The onset of MS does not automatically bring into question a person’s sense of self. Rather, it is the degree to which symptoms impact upon a person’s ability to fulfil roles integral to their pre-MS self, that appear to have the greatest re-defining impact.

• Symptoms that threaten perceptions of self are more likely to contribute to emotional problems such as depression and anxiety.

• Clinicians can support people to maintain a positive sense of self by assessing which symptoms affect them most and, where possible, helping them reconnect with valued interests, roles and activities, albeit in an adapted fashion.

     

Glatiramer acetate versus interferon beta-1a for subcutaneous administration: Comparison of outcomes among multiple sclerosis patients

INTRODUCTION: We compared the outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (GA) (Copaxone(R), Teva Pharmaceutical Industries, Israel) or interferon beta-1a for subcutaneous administration (IFN beta-1a-SC) (Rebif(R), Merck Serono, Switzerland). METHODS: Data were obtained from i3's Lab Rx Database from July 2001 to June 2006. We established an 'intent-to-treat' (ITT) cohort (n=845) of patients diagnosed with MS who began therapy on either GA (n=542) or IFN beta-1a-SC (n=303) and had continuous insurance coverage from 6 months before to 24 months after the date they began taking the medication. We also created a 'continuous use' (CU) cohort (n=410) of individuals who, in addition to the criteria listed above, used either GA or IFN beta-1a-SC within 28 days of the end of the 2-year-post period. Using multivariate regressions, we examined both the 2-year total direct medical costs and the likelihood of relapse associated with the use of these two MS medications. We defined relapse as either being hospitalised with a diagnosis of MS, or being diagnosed with MS during an outpatient visit and then prescribed steroids within a 7-day period. All regressions controlled a wide range of factors that have potentially affected outcomes. RESULTS: In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (5.92% versus 10.89%; P=0.0305), as well as significantly lower 2-year total medical costs (US$41,786 versus US$49,030; P=0.0002). In the CU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (1.94% versus 9.09%; P=0.0049) and significantly lower total medical costs (US$45,213 versus US$57,311; P<0.0001). CONCLUSIONS: Results indicate that, compared with the use of IFN beta-1a-SC, use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs. In addition, these results are more pronounced among patients defined as continuous users.     

影像组学在多发性硬化中的研究进展

多发性硬化（MS）是自身特异性免疫介导的中枢神经系统脱髓鞘疾病,是青壮年人群最常见的致残性神经系统疾病之一,精准诊断、及时治疗对改善患者长期预后至关重要。影像组学是新兴的精准影像分析技术,能从影像大数据中提取高通量影像特征从而进行定量分析,近年来已逐渐应用于分析MS的病理损伤、诊断、鉴别诊断及预后预测等多个方面。本文就影像组学在MS的研究进展进行综述。     

Update on Disease-Modifying Treatments for Multiple Sclerosis

PurposeThe purpose of this review is to discuss the selection and use of disease- modifying treatments for patients with relapsing forms of multiple sclerosis (MS).MethodsPubMed was searched (1966–2014) using the terms multiple sclerosis, treatment, interferon, glatiramer acetate, dimethyl fumarate, fingolimod, teriflunomide, natalizumab, rituximab, and alemtuzumab.FindingsMS is a chronic neurological disorder that can cause a substantial degree of disability. Because of its usual onset in young adults, patients may require treatment for several decades. Currently available agents include platform injectable therapies, newer oral agents, and second-line monoclonal antibody treatments. Treatment decisions have become more complex with the introduction of new approaches, and a major goal is to balance perceived efficacy and tolerability in a specific patient with the relative impact of disease activity and adverse events on quality of life. Here the options for disease-modifying treatments for relapsing forms of MS are reviewed, and current and future challenges are discussed.ImplicationsAn evidence-based approach can be used for the selection of disease-modifying treatments based on disease phenotype and severity, adverse events, and perceived efficacy.     

中国北方人群多发性硬化的临床与MRI特点研究

目的回顾性分析中国北方人群MS的临床特点与MRI影像表现。方法回顾性分析117例MS患者临床资料,分为视神经脊髓组(OSMS)42例和经典多发性硬化组(CMS)75例。比较2组患者临床特点、MRI表现和EDSS评分。结果OSMS患者脑脊液中白细胞数量显著高于CSM患者(P0.05)。MRI显示2组脊髓病灶数量差异有统计学意义(P0.05)。MRI显示CMS脊髓病灶为沿着脊髓长轴分布,且脊髓肿胀。OSMS脊髓呈萎缩状态。5年EDSS评分显示OSMS显著高于CMS(P0.05)。1~5年OSMS复发率明显高于CMS患者。结论 OSMS发病率高于西方患者。     

Suicidal thinking in multiple sclerosis

Purpose.?Studies demonstrate that suicidal ideation ((SI)) is greater in persons with multiple sclerosis ((MS)) than in the general population. SI may offer some MS patients a mechanism for feeling in control of their lives, in the face of a daunting, unpredictable disease. In this study, we determined what specific mental constructs or perceptual themes occur for MS patients experiencing SI, while also examining the construct of ‘control’ as a central theme.

Methods.?Individual interviews ((N == 16)) were audiotaped, transcribed and qualitatively analysed by two independent raters to test for key themes in MS patients reporting SI.

Results. In relation to SI, eight key themes were identified by both raters as having been expressed in interviews: perceived loss of control, increased family tension, loneliness, hopelessness and frustration, physical and psychological impact of MS, loss of perceived masculinity or femininity, regaining control and failure to achieve desired or expected role functioning. We created a model to explain the emergence of these themes as they contribute to SI among patients with MS. All participants indicated that perceived loss of control elicited thoughts of suicide.

Conclusion.?Perceived loss of control appears to be a major disease related burden associated with SI in MS patients.     

A comparison of written materials vs. materials and counselling for women with sexual dysfunction and multiple sclerosis

Aim. Evaluate whether symptoms of vaginal dryness, low libido, less intense or delayed orgasm could be improved in women with multiple sclerosis who took part in an education or education plus counselling programme. Background. Sexual dysfunction, a prevalent symptom in women with multiple sclerosis, can negatively affect quality‐of‐life. Methods. Women attending a large multiple sclerosis clinic were invited and 62 were randomized into one of two groups. Group 1 received written materials on primary, secondary and tertiary sexual dysfunction in multiple sclerosis as well as additional resources (books, websites, list of local psychologists specializing in sexual counselling). Group 2 received the same written materials as well as three counselling sessions from the clinic nurse, the latter two by telephone. The primary outcome measures were the expanded disability status scale and the multiple sclerosis intimacy and sexuality questionnaire‐19. Repeated‐measures analysis of variance was used to evaluate sexual dysfunction score over time and to compare two groups. Results. At baseline, total expanded disability status scale scores were not correlated with primary, secondary or tertiary sexual dysfunction. Total multiple sclerosis intimacy and sexuality questionnaire‐19 score was correlated with use of anti‐cholinergic medications [r (54) = 0·28, P < 0·05], but no other medications, alcohol or tobacco use. Both groups had equivalent and significant reductions in primary sexual dysfunction [F (1) = 14·79, P < 0·001] postintervention. There was a trend towards an interaction effect for tertiary sexual dysfunction [F (1) = 2·88, P = 0·096], in the direction of group 2 (education and counselling). Subjectively, women welcomed the opportunity to discuss sexual concerns and noted that the written information allowed a framework for initiating discussion with their spouses. Conclusion. Relatively straightforward interventions provided by a clinic nurse may help women cope with the symptoms of sexual dysfunction associated with multiple sclerosis. Women who do not benefit from basic interventions could then be referred to an expert sexual dysfunction practitioner. Relevance to clinical practice. Women with multiple sclerosis experience many disease‐related physical and emotional challenges of which sexuality is only one. Sensitivity to sexual dysfunction and being willing to approach the topic is appreciated by women with multiple sclerosis. Nurses do not require in‐depth expertise to offer some basic suggestions which may significantly improve life quality and assist the woman with multiple sclerosis to talk about or cope with sexuality issues.     

多发性硬化脑脊液变化特点

目的　探讨MS的脑脊液特点 ,为MS提供可靠的有价值的诊断资料。方法　采用临床病例分析统计方法 ,归纳、分析MS患者的CSF资料。结果　脑脊液外观正常 ;压力大多正常 ,少数有轻度升高 ;蛋白正常或轻度升高 ,以免疫球蛋白升高为主 ;白细胞数正常或轻度升高 ,以大淋巴细胞和激活淋巴细胞增多为主。结论　在临床资料的基础上 ,再结合脑脊液检查则有助于MS的诊断和鉴别诊断。