Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS.

Objective: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS).

Methods: The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II).

Results: Both treatments prevented T2-hyperintense lesion volume increases from baseline.

Correlation of the VEMP score, ambulation and upper extremity function in clinically isolated syndrome.

Objective: To investigate the correlation of the vestibular evoked myogenic potential (VEMP) score with Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test (PASAT) and EDSS in patients with multiple sclerosis (MS).

Methods: This prospective, cross sectional study included 52 patients with clinically isolated syndrome (CIS). Cervical VEMP (cVEMP) and ocular VEMP (oVEMP), analyzed in the form of the cVEMP, oVEMP and VEMP scores, T25FW, 9HPT, PASAT and Expanded Disability Status Scale (EDSS) were performed.

Should MS be treated by escalation or induction therapy?

MS is a chronic, increasingly disabling disease whose long-term outcomes determine the key social, medical and economic impact of this disease. Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are prescribed to delay disease progression and to protect a patient's functional capability. The concepts of escalation and induction immunotherapy in MS represent different therapeutic strategies for the treatment of MS.

Retinal nerve fiber thickness and MRI white matter abnormalities in healthy relatives of multiple sclerosis patients.

Objectives: To compare retinal nerve fiber (RNFL) thickness and conventional and non-conventional MRI characteristics of healthy controls (HCs) from the general population (non-fHC) to healthy relatives of multiple sclerosis (MS) patients (fHC).

Methods: Sixty-eight (68) HCs underwent optical coherence tomography (OCT) and 3T MRI examination. Subjects were classified based on whether or not there was a family history of MS.

Acute disseminated encephalomyelitis associated with hepatitis B virus reinfection--consequence or coincidence?

Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis. ADEM typically occurs as a post-infectious phenomenon, and usually presents a monophasic episode, but also includes recurrent and multiphasic forms. We report a case of ADEM associated with hepatitis B virus (HBV) reinfection.

Challenges in multiple sclerosis; how to define occurence of progression.

The challenges in MS are related to number of controversies in various aspects of disease but the relationship between relapses and disability progression, or aspects of MS as an inflammatory and/or neurodegenerative disease are extremely important because of its implications on prognosis and therapy of MS. MS was classically regarded as white matter inflammatory disease, while disability progression, brain and spinal cord atrophy were regarded as a consequence of global inflammation of NAWM and secondary involvement of grey matter. More recent histopathology studies, but also new, modern MRI techniques changed this view in MS as a prominent grey and white matter disease.

Alemtuzumab-related thyroid dysfunction in a phase 2 trial of patients with relapsing-remitting multiple sclerosis.

Context: Alemtuzumab, an anti-CD52 monoclonal antibody, increased the risk of thyroid dysfunction in CAMMS223, a phase 2 trial in relapsing-remitting multiple sclerosis.

Objective: The objective of the study was a detailed description of thyroid dysfunction in CAMMS223.

Design: Relapsing-remitting multiple sclerosis patients (n=334) were randomized 1:1:1 to 44 μg sc interferon-β-1a (SC IFNB-1a, Rebif) or annual courses of 12 or 24 mg iv alemtuzumab.

Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.

Background: The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of first-line alemtuzumab compared with interferon beta 1a in a phase 3 trial.

Methods: In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-50 years with previously untreated relapsing-remitting multiple sclerosis.

Early-onset ataxia with progressive external ophthalmoplegia associated with POLG mutation: autosomal recessive mitochondrial ataxic syndrome or SANDO?

Autosomal recessive ataxias caused by mutations of the polymerase γ (POLG) gene make an important group of progressive ataxias accompanied by a diverse spectrum of neurological disorders. Because the clinical picture can be quite miscellaneous, it is challenging to assort patients to any of the currently described syndromes; therefore, to provide such a patient with a conclusive diagnosis can be challenging for the neurologist. A typical magnetic resonance imaging finding is probably the most useful landmark in the diagnostic process, which will steer the clinician toward POLG gene testing.

Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial.

Objective: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon β-1a (IFNβ-1a) through extended follow-up (up to 60 months from baseline).

Methods: Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNβ-1a).

Diagnostic approach of patients with longitudinally extensive transverse myelitis.

The aim of this study is to present a diagnostic and therapeutic approach in patients with LETM. In a period between June 2008 and June 2010, all patients who fulfilled criteria for LETM were included in the study. All patients underwent a standardized protocol of investigations presented in this paper.

Sporadic CJD in a patient with relaplsing-remitting multiple sclerosis on an immunomodulatory treatment.

Creutzfeld-Jacob disease (CJD) is a degenerative, invariably fatal brain disorder. Multiple sclerosis (MS) is a chronic, potentially disabling, immune-mediated inflammatory demyelinating disease of the central nervous system. Here, we report a 50-year-old woman who, two years after the diagnosis of relapsing remitting MS, developed altered consciousness, dystonic posture of the left hand and myoclonic jerks.

Spinal cord tumor versus transverse myelitis.

Background Context: Longitudinally extensive transverse myelitis (LETM) is one of the defining features of neuromyelitis optica (NMO). Despite the well-established criteria, clinical and paraclinical features, the disease is often misdiagnosed and erroneously treated.

Purpose: We report on a case of LETM in a patient with spatially limited NMO spectrum disorder that was misdiagnosed as spinal cord tumor and underwent spinal cord biopsy.

Central positioning upbeat nystagmus and vertigo due to pontine stroke.

We present a female patient with central positioning nystagmus and vertigo (c-PPV) due to a pontine stroke. To our knowledge this is the first report of central upbeat positioning nystagmus caused by pontine lacunar stroke. This report, together with those published previously, supports the existence of a crossing ventral tegmental tract in humans.

Alemtuzumab versus interferon β-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes.

Background: Alemtuzumab is a humanised monoclonal antibody that depletes lymphocytes, causing long-term immunomodulation. In a 3-year, rater-blinded phase 2 study (the CAMMS223 study) in patients with relapsing-remitting multiple sclerosis (RRMS), alemtuzumab reduced relapse rate and the risk of sustained accumulation of disability compared with subcutaneous interferon beta-1a, and the mean expanded disability status scale (EDSS) score of the alemtuzumab cohort improved compared with baseline. Adverse events included infusion-associated reactions, predominantly mild to moderate infections, thyroid disorders, and immune thrombocytopenia.

Downbeat nystagmus, ataxia and spastic tetraparesis due to coeliac disease.

A 25-year-old female presented to a university neurology clinic with a 1-month history of progressive ataxia, downbeat nystagmus and spastic tetraparesis. Personal history revealed polyarthralgias and weight loss. Family history was negative.

A case of lichen ruber planus in a patient with familial multiple sclerosis.

Multiple sclerosis and lichen ruber planus are clinically and histologically distinct complex disorders of putative autoimmune aetiology that are fairly commonly observed in isolation but rarely found in combination. Only two previous reports have described lichen skin disorders in association with multiple sclerosis. The present report describes the case of a 51-year-old Caucasian woman exhibiting both familial multiple sclerosis and lichen ruber planus.

Genes associated with multiple sclerosis: 15 and counting.

Evaluation of: The International Multiple Sclerosis Genetics Consortium (IMSGC). IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci. Genes Immun.

Treatment of steroid unresponsive relapse with plasma exchange in aggressive multiple sclerosis.

The options for treating steroid unresponsive relapses in relapsing remitting multiple sclerosis (RRMS) are modest. We present a small series of patients with an aggressive course of RRMS whose steroid unresponsive relapses were treated with plasma exchange. In the period from January 2007 until February 2009 we identified four patients with steroid unresponsive relapses.

Genomics in multiple sclerosis.

Multiple sclerosis (MS) is chronic, inflammatory disease of the central nervous system that mainly affects young adults and is characterized with dissemination of demyelinating lesions in time and space. It is well known that MS is very heterogeneous disease, so biomarkers that would reliably determine disease course, outcome or treatment response in early stages of the disease (preferentially clinically isolated syndrome) are desperately needed. Genome-wide expression analysis represents the profile of all genes in a certain tissue or cell population in a certain time point.