No evidence of JC virus reactivation in natalizumab treated multiple sclerosis patients: an 18 month follow-up study.

Background And Aim: Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MS patients treated with natalizumab over 18 months, and followed by a thorough monitoring programme.

Methods: 42 patients (F/M: 24/18, mean age 34.

Magnetic resonance evidence of cerebellar cortical pathology in multiple sclerosis.

Background: Although neuropathological observations suggest that cerebellar cortex is a major site of demyelination in multiple sclerosis (MS), only a few MRI studies on cerebellar cortical pathology in MS are available.

Objective: To analyse cerebellar cortical volume (CCV) and leucocortical lesions (CL) in MS, and their impact on clinical disability.

Methods: The authors studied 125 patients divided into 38 Clinical Isolated Syndrome (CIS), 35 relapsing remitting multiple sclerosis (RRMS), 27 secondary progressive multiple sclerosis (SPMS) and 25 primary progressive multiple sclerosis, and 32 normal controls (NC).

Cyclophosphamide as second-line therapy in multiple sclerosis: benefits and risks.

Cyclophosphamide (Cy) is an alkylating agent used over the past 40 years to halt rapidly progressive forms of multiple sclerosis (MS). High doses of Cy produce marked immunosuppression and an anti-inflammatory immune deviation. Cy is most effective in young patients, with very active MS (frequent relapses, rapid accumulation of disability, and gad+ lesions on brain MRI).

Severe relapses after the first infusion of natalizumab in active relapsing-remitting multiple sclerosis.

We describe three patients suffering from a very active form of relapsing-remitting multiple sclerosis (MS), who experienced severe disease worsening, associated with a marked increase in brain inflammation, a few days after the first administration of natalizumab. In line with preclinical studies, our observations suggest that natalizumab, when administered during active disease phases, may worsen disease evolution possibly by modifying the regulatory network in the brain. We suggest that relapsing-remitting MS patients having had a recent relapse should be treated with natalizumab only after achieving complete clinical and radiological remission.

Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis.

Background: Neuropsychological deficits in patients with multiple sclerosis (MS) have been shown to be associated with the major pathological substrates of the disease, ie, inflammatory demyelination and neurodegeneration. Double inversion recovery sequences allow cortical lesions (CLs) to be detected in the brain of patients with MS. Modern postprocessing techniques allow cortical atrophy to be assessed reliably.

Cyclophosphamide-based combination therapies for autoimmunity.

Immunomodulatory agent (IMA)-unresponsive multiple sclerosis (MS) can quickly evolve to a dramatic and irreversible disability. Treating these patients with appropriate immunosuppressive therapies can be a chance to arrest disease activity and progression. Cyclophosphamide (Cyc)-based intense immunosuppression has been successfully used to treat rapidly deteriorating, IMA-refractory MS patients.

Morphology and evolution of cortical lesions in multiple sclerosis. A longitudinal MRI study.

Cortical lesions (CLs) can be detected in the majority of patients with established multiple sclerosis (MS), but little is known about their evolution over time. This study was performed to investigate the short-term MRI evolution of CLs, with the ultimate aim to achieve a better in vivo understanding of their nature. Seven hundred and sixty-eight CLs from 107 MS patients (76 with relapsing-remitting [RR] and 31 with secondary progressive [SP] MS) were followed with brain MR examinations, including a double inversion recovery (DIR) sequence, every 6 months for 1 year.

Extensive cortical inflammation is associated with epilepsy in multiple sclerosis.

Introduction: Epilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR.

Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis.

Background: A significant inflammatory pathologic disorder in the cortex of patients with multiple sclerosis (MS) has been demonstrated by ex vivo studies.

Objective: To determine the frequency, time of appearance, and clinical relevance of intracortical lesions (ICLs) in MS in vivo.

Design: Double inversion recovery sequence study.

The safety profile of cyclophosphamide in multiple sclerosis therapy.

Cyclophosphamide (Cyc) is an alkylating agent used to treat malignancies and autoimmune diseases, such as lupus nephritis, rheumatoid arthritis and immune-mediated neuropathies. Over the past 40 years, Cyc has also been applied to treat multiple sclerosis (MS) and the effective stabilisation of rapidly progressive forms of MS has been demonstrated in several studies. Cyc has a dose-dependent bimodal effect on the immune system.

Cortical atrophy is relevant in multiple sclerosis at clinical onset.

Introduction: Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated.

Methods: 115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI.

Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells.

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects, the underlying mechanisms of which remain unclear. In the current study, we questioned whether CBD modulates activation of mast cells, key players in inflammation. By using the rat basophilic leukemia mast cell line (RBL-2H3), we demonstrate that CBD (3-10 muM) augments beta-hexosaminidase release, a marker of cell activation, from antigen-stimulated and unstimulated cells via a mechanism, which is not mediated by G(i)/G(o) protein-coupled receptors but rather is associated with a robust rise in intracellular calcium ([Ca(2+)](i)) levels sensitive to clotrimazole and nitrendipine (10-30 muM).

Longitudinal analysis of immune cell phenotypes in early stage multiple sclerosis: distinctive patterns characterize MRI-active patients.

To investigate whether peripheral immune abnormalities are associated with brain inflammation in multiple sclerosis, and whether differences in MRI activity are paralleled by changes in leukocyte composition, we conducted a prospective longitudinal study in patients at their clinical onset. Twenty patients presenting a first inflammatory event in the central nervous system suggestive of multiple sclerosis underwent, every 45 days for one year, immunophenotyping of 98 blood cell subsets together with brain MRI and clinical evaluation. Six patients showed intense MRI activity, six patients did not display MRI activity, while the remaining 8 patients had low (i.

HPLC electrochemical detection of trace amines in human plasma and platelets and expression of mRNA transcripts of trace amine receptors in circulating leukocytes.

We evaluated, using a multi-channel electrochemical HPLC system, whether trace amines are detectable in plasma and platelets of healthy control subjects. To this end, levels of tyramine, octopamine and synephrine were assessed in samples obtained from eight males and eight females, age matched and free from drugs. In plasma, octopamine was detectable in all subjects, synephrine in 15 and tyramine in six out of 16 subjects.