Nabiximols discontinuation rate in a large population of patients with multiple sclerosis: a 18-month multicentre study.

Introduction: Delta-δ-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray is used as an add-on therapy option for moderate to severe multiple sclerosis (MS) spasticity resistant to other medications. Aims of this study were to provide real-life data on long-term clinical outcomes in a large population of Italian patients treated with THC:CBD and to evaluate predictors of THC:CBD therapy continuation.

Materials And Methods: This prospective observational multicentre Italian study screened all patients with MS consecutively included in the Agenzia Italiana del Farmaco e-registry at the start of THC:CBD treatment (baseline), after 4 weeks (T1), 12±3 weeks (T2), 24±3 weeks (T3), 48±3 weeks (T4) and 72±3 weeks (T5) from baseline.

A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

Background: Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors.

Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying a high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma.

Methods: Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas.

Clinical, laboratory features, and prognostic factors in adult acute transverse myelitis: an Italian multicenter study.

Objectives: We compared the clinical, laboratory, and radiological features of different subgroups of acute transverse myelitis (ATM) diagnosed according to the criteria established by the Transverse Myelitis Consortium Working Group (TMCWG) as well as of non-inflammatory acute transverse myelopathies (NIATM) to identify possible short- and long-term prognostic factors.

Methods: A multicenter and retrospective study comprising 110 patients with ATM and 15 NIATM admitted to five Italian neurological units between January 2010 and December 2014 was carried out.

Results: A significantly higher frequency of isolated sensory disturbances at onset in ATM than in NIATM patients (chi-square = 14.

Association of circulating anti-CD64 IgM levels with favourable long-term clinical outcomes in multiple sclerosis patients.

Circulating levels of IgM anti-CD64, an immunosuppressive antibody recently identified in long-term stable multiple sclerosis (MS) patients, were found to fluctuate over time in MS patients. Antibody-positive patients showed a significantly lower annualized relapse rate value as well as reached sustained disability worsening and had a relapse in a significantly longer median time than those without antibody. Disease-modifying therapies (DMTs) only were the covariate influencing both the relapse occurrence and the disability accrual.

Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients.

There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [occludin (OCLN), claudin-5 (CLN-5) and zonula occludens-1 (ZO-1)] levels, sphingosine-1 phosphate 1 (S1P) receptor expression on circulating leukocyte populations as well as in vitro PBMC migration were longitudinally assessed in 20 MS patients under 12-months fingolimod treatment and correlated with clinical and magnetic resonance imaging (MRI) parameters. After 12 months of treatment, a significant reduction of mean relapse rate as well as number of active lesions at MRI was found.

Longitudinal quantitative assessment of macula during therapy with fingolimod in relapsing-remitting multiple sclerosis.

Purpose: Fingolimod is the first oral drug approved for treatment of relapsing-remitting multiple sclerosis (RR-MS), and it has potential macular side effects. Despite the qualitative evidence of macular oedema under treatment, longitudinal quantitative assessment is lacking. To address this issue, we measured macular volume and central foveal thickness in a cohort of MS patients on fingolimod over 12 months of treatment.

Nimodipine confers clinical improvement in two models of experimental autoimmune encephalomyelitis.

Multiple sclerosis is characterised by inflammatory neurodegeneration, with axonal injury and neuronal cell death occurring in parallel to demyelination. Regarding the molecular mechanisms responsible for demyelination and axonopathy, energy failure, aberrant expression of ion channels and excitotoxicity have been suggested to lead to Ca overload and subsequent activation of calcium-dependent damage pathways. Thus, the inhibition of Ca influx by pharmacological modulation of Ca channels may represent a novel neuroprotective strategy in the treatment of secondary axonopathy.

Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.

COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines.

No evidence for an effect on brain atrophy rate of atorvastatin add-on to interferon β1b therapy in relapsing-remitting multiple sclerosis (the ARIANNA study).

Background: A previous phase 2 trial has suggested that statins might delay brain atrophy in secondary progressive multiple sclerosis.

Objectives: The objective of this study was to evaluate the effect of atorvastatin add-on therapy on cerebral atrophy in relapsing-remitting multiple sclerosis.

Methods: This randomised, placebo-controlled study compared atorvastatin 40 mg or placebo add-on therapy to interferon β1b for 24 months.

Meaningful improvement in walking performance after Botulinum neurotoxin A (BoNT-A) in chronic spastic patients.

Background: Botulinum neurotoxin A (BoNT-A) may reduce lower limb spasticity but its role in improving walking ability remains to be established.

Objective: To investigate the efficacy of simultaneous BoNT-A injections into several targeted spastic muscles of different joints on gait speed and on functional gains in gait performance in chronic stroke and MS patients.

Methods: Twenty patients affected by stroke or multiple sclerosis were tested before, one and three months after BoNT-A administration.

Expression of Tight Junction and Drug Efflux Transporter Proteins in an in vitro Model of Human Blood-Brain Barrier.

Interendothelial cell tight junctions (TJs) proteins contribute to maintain the structural and functional integrity of the blood-brain barrier (BBB) and several efflux transporters regulate transport of compounds across BBB. A unique double compartment-model of the BBB, consisting of cerebral endothelial cells isolated from cryopreserved human glial tumors, alone and in the presence of human astroglial cells derived from the same tissue preparation was established. Endothelial cell viability and transendothelial electrical resistance (TEER) were measured in this model and three representative TJ proteins - occludin (OCLN), zonula occludens-1 (ZO-1) and claudin-5 (CLN-5) - as well as several drug efflux transporters - P-glycoprotein (P-gp), multidrug resistance protein-1 and 2 (MRP-1 and MRP-2), organic anion-transporting polypeptide-1 and 3 (oatp1 and oatp3) were analyzed at both the protein and gene transcript level.

Successful response of non-recovering Ramsay Hunt syndrome to intravenous high dose methylprednisolone.

Ramsay Hunt syndrome (RHS) is a frequent cause of facial palsy. It is a consequence of the infection of geniculate ganglion by herpes zoster or herpes simplex virus. In the lack of randomized controlled trials, RHS is empirically treated by a combination therapy of antiviral agents and steroids given orally.

Symptomatic cranial neuralgias in multiple sclerosis: clinical features and treatment.

In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of neuropathic pain. Neuralgias are characterised by paroxysmal painful attacks of electric shock-like sensation, occurring spontaneously or evoked by innocuous stimuli in specific trigger areas.

Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study.

Objective: To assess longitudinally cognitive functioning in relapsing-remitting multiple sclerosis (RRMS) patients and its relationship with clinical and MRI variables.

Methods: Early RRMS patients and matched healthy controls were assessed in parallel in three testing sessions over 3 years, using the Rao's Brief Repeatable Battery of Neuropsychological Tests. Patients also underwent an MRI analysis of T2-weighted lesion volume (T2LV), number of gadolinium-enhanced lesions and whole brain atrophy.

Transient supranuclear paresis of the abduction in viral encephalitis of the brainstem.

The supranuclear paresis of the abducens system, also known as posterior internuclear ophthalmoplegia of abduction, is a very rare disorder clinically characterized by unilateral or bilateral abduction paresis sometimes associated with nystagmus of the contralateral adducting eye, slowing of abduction saccades, and intact horizontal vestibulo-ocular reflex. Here, we report a 35-year-old woman who presented transient left side abduction deficit in conjunction, as the only symptom of self-limited viral encephalitis of the brainstem. Brain MRI including DWI and ADC maps showed an area of abnormal signal intensity in the mid-right ponto-mesencephalic junction.

Reliability, practice effects, and change indices for Rao's Brief Repeatable Battery.

The role of cognitive impairment in multiple sclerosis is now widely recognized. However, there is a dearth of research on variability and practice effects of neuropsychological measures when repeated over time. The objective was to assess reliability and practice effects for Rao's Brief Repeatable Battery of neurophysiological tests and the Stroop Test, and to provide data for correction for variability and practice effects in serial assessments.

Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis.

The interaction between the immune and nervous systems can be both detrimental and beneficial. Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune demyelination that histologically and clinically mimics multiple sclerosis (MS). Myelin-reactive T cells produce and release brain-derived neurotrophic factor (BDNF) directly in the central nervous system, which stimulates tissue repair after traumatic injury.

Impairment of vertical saccades from an acute pontine lesion in multiple sclerosis.

A 62-year-old woman with relapsing-remitting multiple sclerosis suddenly complained of diplopia associated with bilateral adduction impairment, nystagmus of the abducting eye bilaterally, and sparing of abduction, convergence, and vertical eye movements, consistent with bilateral internuclear ophthalmoplegia. Within 1 week, she had developed a complete horizontal gaze paralysis even with the oculocephalic maneuver. Vertical saccades were slow and convergence was preserved.

Higher expression of BDNF receptor gp145trkB is associated with lower apoptosis intensity in T cell lines in multiple sclerosis.

Conflicting data exist on expression of gp145trkB, the high affinity receptor for brain-derived neurotrophic factor (BDNF), on peripheral blood immunocompetent cells in multiple sclerosis (MS). We analyzed expression of gp145trkB by western blotting and flow cytometry in myelin basic protein (MBP)- and ovalbumin (OVA)-T cell lines prepared from 12 patients with relapsing-remitting MS and 12 normal healthy subjects (NHS) and correlated it with activation-induced apoptosis. We found a higher percentage of gp145trkB-expressing MBP-T cells in MS patients than in NHS (p=0.

Clinical-radiologic heterogeneity of occipital neuralgiform pain as multiple sclerosis relapse.

Occipital neuralgia may be related to traumatic, compressive, or inflammatory injury to the occipital nerve or C2 radicular level and cervical spinal cord lesions. We report a series of 3 patients with definite relapsing-remitting multiple sclerosis (MS) who experienced sudden occipital neuralgiform pain with or without diminished sensation in the cervical region and associated with magnetic resonance imaging (MRI) evidence of a new active or new T2-weighted demyelinating C2 cervical lesion. We suggest that sudden paroxysmal occipital pain may signal relapse of MS and cervical MRI with gadolinium should be considered; these patients show good clinical response to high-dose intravenous corticosteroids.