Nonwalking response to fampridine in patients with multiple sclerosis in a real-world setting.

OBJECTIVES: Mobility impairments constitute a long-term burden in patients with multiple sclerosis (MS). Currently there is evidence that the drug fampridine may improve nonwalking symptoms in MS patients. The main objective of this study is to analyze whether participants showing a beneficial walking response to fampridine, also show a positive response in nonwalking assessments in a real-world clinical setting. METHODS: Subjects enrolled were part of a study analyzing gait parameters, for which response to treatment with fampridine was monitored after a period of 2 weeks. Neurologists then decided whether patients were responders to fampridine (RF) according to their global impression of patients' gait improvement. As nonwalking outcomes, we included the nine-hole peg test (9-HPT), the EuroQoL five dimensions questionnaire (EQ-5D) for quality of life, The Würzburger Fatigue Inventory for MS (WEIMuS), the Center for Epidemiologic Studies depression scale (CES-D), and the Paced Auditory Serial Addition Test (PASAT). Minimal clinically important difference (MCID) was evaluated for each test. RESULTS: A total of 189 participants were included: 122 were women (64.55%), with a mean age of 53.55 (±10.83). RFs showed significant improvement in all of the nonwalking outcomes (p < 0.05), except for a nonsignificant improvement in nondominant upper limb function and PASAT; the largest score improvement was seen in the physical and cognitive sections of the WEIMuS (25.69% and 29.81%, respectively, p < 0.001). CONCLUSION: We provide evidence that physician's global judgement of walking improvement is a reliable measure for determining response to fampridine in nonwalking parameters, with fatigue showing the greatest score improvement after 2 weeks.

Fampridine response in MS patients with gait impairment in a real-world setting: Need for new response criteria?

OBJECTIVE: The primary objective of this real-world study was to describe the response to fampridine and changes of gait parameters in multiple sclerosis (MS) patients' walking disability (Expanded Disability Status Scale (EDSS): 4-7) after treatment with fampridine for 2 weeks as recommended by the European Medicines Agency (EMA) and compare it with the overall physician's judgement. METHODS: A total of 211 adult MS patients were analyzed using a multimodal gait assessment including the timed 25-foot walk test (T25FW), 2-minute walking test (2-MWT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), the GAITRite electronic walkway system, and the patients' clinical global impression (CGI). Multimodal gait assessment was compared with the clinician's impression of overall improvement after 2 weeks. RESULTS: In total, 189 subjects were included, of which 133 (70.37%) were responders to fampridine (RF), according to physician's judgement. Looking at independent multimodal gait assessment, RFs showed improvement of 12.60% in the T25FW, 19.25% in the 2-MWT, 21.12% in the MSWS-12, and 6.54% in their Functional Ambulation Profile (FAP) score. The combination of the T25FW and the MSWS-12 would offer the best sensitivity and specificity for determining response to fampridine according to both neurologists' and patients' classification. CONCLUSION: This study provides new information on the use of fampridine in a real-world setting with a large patient sample on the potential benefit of using more definitive responder criteria to fampridine for the clinical setting.

Evaluation of heart involvement in calpainopathy (LGMD2A) using cardiovascular magnetic resonance.

INTRODUCTION: Cardiac dysfunction occurs in several forms of limb girdle muscular dystrophy (LGMD). The aim of this study was to investigate cardiac involvement in calpainopathy (LGMD2A). METHODS: Cardiovascular evaluation was performed in 10 patients with genetically verified LGMD2A by echocardiography, 3 Tesla - cardiovascular magnetic resonance, 24-h electrocardiography recordings with heart rate variability (HRV) analysis, and 24-h blood pressure recordings. RESULTS: No patient with calpainopathy showed impairment of left or right ventricular function. One patient had a small amount (2% of left ventricle mass) of late gadolinium enhancement. HRV analysis revealed no significant difference compared with external reference data. CONCLUSIONS: The main finding of this study is the lack of cardiac involvement in patients with calpainopathy. Cardiac involvement was not found, even in individuals with advanced age and greater disease severity. Furthermore, we did not observe an overall reduction of cardiac autonomic regulation in calpainopathy.

Accumulation and therapeutic modulation of 6-sulfo LacNAc(+) dendritic cells in multiple sclerosis.

OBJECTIVE: To examine the potential role of 6-sulfo LacNAc(+) (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS). METHODS: We determined the presence of slanDCs in demyelinated brain lesions and CSF samples of patients with MS. In addition, we explored the impact of methylprednisolone, interferon-ß, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-ß modulates important proinflammatory capabilities of slanDCs. RESULTS: SlanDCs accumulate in highly inflammatory brain lesions and are present in the majority of CSF samples of patients with MS. Short-term methylprednisolone administration reduces the percentage of slanDCs in blood of patients with MS and the proportion of tumor necrosis factor-α- or CD150-expressing slanDCs. Long-term interferon-ß treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-ß inhibits the secretion of proinflammatory cytokines by slanDCs and their capacity to promote proliferation and differentiation of T cells. CONCLUSION: Accumulation of slanDCs in highly inflammatory brain lesions and their presence in CSF indicate that slanDCs may play an important role in the immunopathogenesis of MS. The reduction of blood-circulating slanDCs and the inhibition of their proinflammatory properties by methylprednisolone and interferon-ß may contribute to the therapeutic efficiency of these drugs in patients with MS.

Neuroborreliosis during natalizumab treatment in multiple sclerosis.

We present a case of acute neuroborreliosis in the setting of long-term treatment with natalizumab. A 33-year-old man was diagnosed with relapsing-remitting multiple sclerosis (MS) in 1999. Following failure of various immunomodulatory treatments including interferon and immunoglobulin, he was treated with mitoxantrone from May 2000 to August 2004. Due to persistently high disease activity, he was also treated with cyclophosphamide (December 2005-April 2006) and then azathioprine (April-June 2006), which were both discontinued due to adverse effects. After the patient scored 6.5 on the Expanded Disability Status Scale and had 2 relapses in 2006, we initiated natalizumab therapy (300 mg monthly, starting September 2006). The patient improved significantly in ambulation and the relapse rate slowed as well.

Multiple sclerosis documentation system (MSDS): moving from documentation to management of MS patients.

The long disease duration of multiple sclerosis and the increasing therapeutic options require a individualized therapeutic approach which should be carefully documented over years of observation. To switch from MS documentation to an innovative MS management, new computer- and internet-based tools could be implemented as we could demonstrate with the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and management of visit schedules and mandatory examinations via defined study modules by integration of data input from various sources (patients, attending physicians and MS nurses). It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information can be collected via interactive touch screens. Specific modules allow the management of highly efficacious treatments as natalizumab or fingolimod. MSDS can be used to transfer the documented data to databases as, e.g. the registry of the German MS society or REGIMS. MSDS has already been implemented successfully in clinical practice and is currently being evaluated in a multicenter setting. High-quality management and documentation are crucial for improvements in clinical practice and research work.

Reliability of brain CT evaluation by stroke neurologists in telemedicine.

OBJECTIVE: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke. METHODS: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κ(w)) statistic was used to determine the interobserver agreement for ASPECTS. RESULTS: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κ(w) = 0.62; 95% confidence interval 0.54-0.71). CONCLUSIONS: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Use and acceptance of electronic communication by patients with multiple sclerosis: a multicenter questionnaire study.

BACKGROUND: The number of multiple sclerosis (MS) information websites, online communities, and Web-based health education programs has been increasing. However, MS patients' willingness to use new ways of communication, such as websites, mobile phone application, short message service, or email with their physician, remains unknown. OBJECTIVES: We designed a questionnaire to evaluate the a priori use of electronic communication methods by MS patients and to assess their acceptance of such tools for communication with their health care providers. METHODS: We received complete data from 586 MS patients aged between 17 and 73 years. Respondents were surveyed in outpatient clinics across Germany using a novel paper-and-pencil questionnaire. In addition to demographics, the survey items queried frequency of use of, familiarity with, and comfort with using computers, websites, email, and mobile phones. RESULTS: About 90% of all MS patients used a personal computer (534/586) and the Internet (527/586) at least once a week, 87.0% (510/586) communicated by email, and 85.6% (488/570) communicated by mobile phone. When asked about their comfort with using electronic communication methods for communication with health care providers, 20.5% (120/586) accepted communication by mobile Internet application or short message service via mobile phone, 41.0% (240/586) by websites, 54.3% (318/586) by email service, and 67.8% (397/586) by at least one type of electronic communication. The level of a priori use was the best predictor for the acceptance of electronic communication with health care providers. Patients who reported already searching online for health information (odds ratio 2.4, P < .001) and who had already communicated with a physician through a website (odds ratio 3.3, P = .03) reported higher acceptance for Web-based communication. Patients who already scheduled appointments with their mobile phones (odds ratio 2.1, P = .002) were more likely to accept the use of mobile phone applications or short message service for communicating with their physician. CONCLUSIONS: The majority of MS patients seen at specialist centers already use modern communication technology regularly. New forms of electronic communication appear to have high levels of acceptance for exchanging information about MS between patients and health care providers. Such methods should be integrated into eHealth services such as electronic health records and patient relationship management systems.