Marco Turatti

Assessment of outcome predictors in first-episode acute myelitis: a retrospective study of 53 cases.

OBJECTIVE To identify predictors of short- and long-term outcomes in acute myelitis (AM). DESIGN First episodes of AM were retrospectively identified in a single institution. Information regarding demographics, clinical status, laboratory workup, magnetic resonance imaging of the spine and brain, and electrophysiological assessment was collected. Tau, 14-3-3 protein, and cystatin C levels were assessed de novo in stored cerebrospinal fluid samples. SETTING A neurological department database. Patients Fifty-three patients with a first episode of AM. MAIN OUTCOME MEASURES The prognostic value of all variables was analyzed for the following outcomes: recovery from the initial event, symptom recurrence, conversion to multiple sclerosis (MS), and long-term disability. RESULTS Median follow-up was 6.2 years. Six patients (11%) remained monophasic; 5 (9%) developed recurrent myelitis; and 42 (79%) underwent conversion to MS. Sensory level absence, no sphincter involvement, abnormal magnetic resonance imaging findings in the brain, spinal cord lesions shorter than 3 vertebral segments, and abnormal somatosensory evoked potentials predicted MS conversion. Fifteen of 32 patients with pyramidal dysfunction at onset (47%) and 17 of 43 with relapses during follow-up (40%) had significant disability at the last visit compared with 2 of 21 patients without pyramidal manifestations (10%) and none of the patients without exacerbations (P = .006 and P = .02, respectively). In 11 patients with exacerbations, we observed a significant correlation between cerebrospinal fluid levels of cystatin C and the degree of neurological disability at the last visit (Spearman rho = 0.69; P = .03). CONCLUSIONS For patients with first-episode AM, the conversion rate to MS is high. Motor dysfunction at onset and relapse occurrence are associated with worse outcome. Cerebrospinal fluid levels of cystatin C may prove useful for predicting the prognosis of such patients.

Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS), a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-β1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management.

Prevalence of multiple sclerosis in Verona, Italy: an epidemiological and genetic study

Recent multiple sclerosis (MS) prevalence studies classify Italy as a high‐risk area without intra‐regional latitude effect.

Benign course of tumour-like multiple sclerosis. Report of five cases and literature review.

BACKGROUND Multiple sclerosis (MS) with initial neuroradiological features suggestive of brain tumour (tumour-like MS) may represent a challenging diagnosis. METHODS Among the patients seen at the MS centre of our Institution between 2000 and 2010, we identified cases presenting with a large (diameter>2 cm), well-defined lesion, suggestive of brain tumour on initial brain magnetic resonance imaging (MRI). Only patients with at least 10 years follow-up were included. RESULTS Five young women with MS who presented with a tumour-like lesion on initial brain MRI are described. All cases presented with sudden-onset neurological deficits due to a single large brain lesion compatible with neoplasm at MRI. Two cases underwent brain stereotactic biopsy, both misdiagnosed as astrocytoma. However, the subsequent clinical and MRI follow-up was consistent with MS in all cases. Unnecessary surgery and radiotherapy were responsible for disability in two cases. In three cases, the course of the disease remains benign after more than 13 years from symptoms onset. CONCLUSIONS Our report of clinical, radiological and pathological features of five tumour-like MS cases confirms that it is mandatory to consider a demyelinating process in the differential diagnosis of tumour-like brain lesions. Many tumour-like MS cases may have a favourable long term prognosis.

Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.

Primary progressive multiple sclerosis: current therapeutic strategies and future perspectives

ABSTRACT Introduction: Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system with heterogeneous features. Primary progressive (PP) MS is a rare disease subtype characterized by continuous disability worsening from onset. No disease-modifying therapy is currently approved for PP MS due to the negative or inconsistent results of clinical trials conducted on a wide range of interventions, which are reviewed in the present paper. Areas covered: The features and results of randomized trials of disease-modifying treatments for PP MS are discussed, including immunosuppressants, immunomodulators, monoclonal antibodies, and putative neuroprotective agents. Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. Other emerging treatment strategies include cell metabolism modulation and inflammatory pathways inhibition, which are being investigated in several ongoing phase II and III placebo-controlled trials. Future PP MS trials will need to systematically include efficacy endpoints other than physical disability alone, such as cognition, quality of life, advanced MRI measures and molecular biomarkers.

Clinical and biomarker assessment of demyelinating events suggesting multiple sclerosis

Initial demyelinating event (IDE) diagnosis and prognosis are not straightforward.

Guillain-Barré syndrome after short-course efalizumab treatment.

Efalizumab (Raptiva , Serono, London, UK) is a humanized recombinant monoclonal antibody against the CD11a subunit of lymphocyte function-associated antigen-1 (LFA-1). Efalizumab inhibits LFA-1 from binding to the endothelial adhesion protein intercellular adhesion molecule-1 (ICAM-1). LFA-1 is presented by activated T-cells while ICAM-1 is over-expressed by endothelial cells and keratinocytes in the psoriatic plaque. Therefore, efalizumab prevents adhesion and extravasation of activated T-cells. Efalizumab is indicated for moderate-to-severe chronic plaque psoriasis, unresponsive or intolerant to other therapies. In February 2009, the European Medicines Agency recommended the suspension of its marketing authorisation because of safety concerns including the occurrence of progressive multifocal leukoencephalopathy (PML) [2]. After several alerts by the US Food and Drug Administration, efalizumab was voluntarily removed from the US market [2]. Other efalizumab serious side effects include Guillain-Barré syndrome (GBS), [7] transverse myelitis, meningoencephalitis, sepsis and cerebral lupus-like syndrome. Principally, side effects took place after longduration treatment. Here we report the case of a patient who developed GBS after a short-course efalizumab treatment. A 40-year-old man developed rapidly progressive symmetrical limb weakness with numbness and paresthesia. Past history showed a diagnosis of plaque psoriasis, treated with efalizumab on a weekly basis (1 mg/kg/week) for 7 weeks. The last dose was administered 4 days before symptoms onset. Recent history was negative for infections, vaccination, or surgery. Examination showed ataxic gait, distal limb symmetrical weakness and hypoareflexia. Neurography showed signs of demyelinating polyneuropathy (prolonged distal latencies, reduced nerve conduction velocity and absent or prolonged F-waves). Cerebrospinal fluid (CSF) examination revealed albumino-cytological dissociation with increased proteins (91 mg/dl) and normal white cell count. A diagnosis of acquired demyelinating neuropathy, namely GBS, was made. Treatment with efalizumab was immediately discontinued. The patient was treated with intravenous immunoglobulin (0.4 g/kg daily for 5 days). He rapidly improved with full recovery after 10 days. GBS is a common and severe cause of acute neuromuscular paralysis. Molecular mimicry and cross-reactive immune response play a central role in its pathogenesis, but GBS and related disorders have been reported to occur with a variety of drugs and biologic therapies [5]. Although spontaneous etiology cannot be excluded, the present patient satisfied the proposed criteria to suspect druginduced illness [3]. GBS was temporally associated with efalizumab treatment. Likely, alternative explanations were ruled out because of no exposure to other agents and the extensive work-up that excluded antecedent or latent infection [6]. The symptoms rapidly ameliorated after efalizumab discontinuation. Biological plausibility was supported by the observations that (1) efalizumab may cause increase of CD4? and CD8? naive and memory circulating T-cells and lymphocyte monoclonal expansion M. Turatti S. Tamburin (&) M. L. Praitano Department of Neurological and Visual Sciences, University of Verona, Piazzale Scuro 10, 37100 Verona, Italy e-mail: stefano.tamburin@univr.it; s_tamburin@yahoo.com

Benign multiple sclerosis: physical and cognitive impairment follow distinct evolutions.

Benign multiple sclerosis (BMS) definitions rely on physical disability level but do not account sufficiently for cognitive impairment which, however, is not rare.

A case of acute fulminant multiple sclerosis treated with alemtuzumab

We describe the case of a woman who came to our attention for acute onset and very rapidly worsening left hemiplegia, vision loss and cognitive impairment. MRI, laboratory and clinical investigations were highly suggestive of an active inflammatory demyelinating disease. Following exclusion of other possible etiologies, a diagnosis of Marburgs variant multiple sclerosis was made. After repeated high-dose steroids and plasma-exchange, the patient was treated with a first course of alemtuzumab followed by improvement of the clinical and MRI picture. This is the first reported case of Marburg type multiple sclerosis treated with alemtuzumab.