Abstract

Aim: Complaints about Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (Sativex®; GW Pharma Ltd, Salisbury, UK) in the management of multiple sclerosis spasticity include unpleasant taste and oral mucosal anomalies. This pilot study assessed the use of sugar-free chewing gum and/or a refrigerated bottle of THC:CBD oromucosal spray to mitigate these effects.

Materials & methods: Patients with multiple sclerosis spasticity (n = 52) at six sites in Italy who were receiving THC:CBD oromucosal spray and had associated oral mucosal effects were randomized into Group A (chewing gum; n = 15); Group B (cold bottle; n = 20); and Group C (cold bottle + chewing gum; n = 17).

Results: Taste perception in patients receiving chewing gum ± cold bottle intervention (Groups A and C combined) was significantly (p = 0.0001) improved from baseline to week 4 while maintaining spasticity control.

Conclusion: Patient comfort, satisfaction and treatment adherence may benefit from these interventions.

Keywords: Sativex; THC:CBD; multiple sclerosis; oral cavity complaints; oromucosal spray; spasticity; taste perception.

Abstract

Background: Fingolimod is a modulator of Central and peripheral sphingosine pathways, which is currently approved for treatment of Multiple Sclerosis (MS). In animal models it reduces inflammation, but it is also able to potentiate glutamatergic transmission and synaptic plasticity. We aimed to explore whether Fingolimod is able to modify the clinical expression of new demyelinating lesions with respect to IFNβ-1a in relapsing remitting MS (RRMS) patients suboptimal responders to IFNβ-1a.

Methods: 103 patients with RRMS switching for inefficacy from IFNβ-1a to Fingolimod and treated for at least 12 months were included. Annualised Relapse Rate (ARR), EDSS and the number of new brain and spinal gadolinium enhancing (Gd +) and T2 lesions were retrospectively assessed in the whole group during each treatment period. The likelihood of co-occurrence of new Gd + lesions and clinical relapses during IFNβ-1a and Fingolimod treatment was analysed.

Results: The mean duration of treatment with IFNβ-1a and Fingolimod was 3.14 (SD 1.6) and 3.22 years (SD 1.1) respectively. Significant reduction of ARR (p < .001), total number of Gd + and T2 lesions (p < .001) was found switching from IFNβ-1a to Fingolimod. Gd + lesions occurring during treatment with Fingolimod were more likely to be asymptomatic compared with IFNβ-1a (88% vs 30.9%, p = < .025).

Conclusion: Fingolimod reduces clinical and radiological inflammation in MS. Additionally, it limits the clinical expression of new Gd + lesions, possibly reducing local inflammatory processes and improving brain network plasticity in patients with suboptimal response to IFNβ-1a.

Keywords: Brain plasticity; Fingolimod; INFβ-1a; MRI; Multiple sclerosis; Relapse.

Abstract

In this retrospective, multicenter, real-world study we collected clinical and magnetic resonance imaging (MRI) data of all patients (n = 40) with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab according to a "free-of-charge" protocol available before the drug marketing approval in Italy. Almost all (39/40) started alemtuzumab after discontinuing multiple disease-modifying treatments (DMTs) because of either lack of response or safety concerns. We considered the proportion of alemtuzumab-treated patients who had no evidence of disease activity (NEDA-3) and disability improvement over a 36-month follow-up period. NEDA-3 was defined as absence of relapses, disability worsening, and MRI activity. Disability improvement was defined as a sustained reduction of ≥ 1-point in Expanded Disability Status Scale (EDSS) score. At follow-up, 18 (45%) patients achieved NEDA-3, 30 (75%) were relapse-free, 33 (82.5%) were EDSS worsening-free, and 25 (62.5%) were MRI activity-free. Eleven (27.5%) patients had a sustained disability improvement. We found no predictor for the NEDA-3 status, while the interaction of higher EDSS score by higher number of pre-alemtuzumab relapses was associated with a greater chance of disability improvement (odds ratio 1.10, p = 0.049). Our study provides real-world evidence that alemtuzumab can promote clinical and MRI disease remission, as well as disability improvement, in a significant proportion of patients with RRMS despite prior multiple DMT failures. The drug safety profile was consistent with data available from clinical trials.

Keywords: Alemtuzumab; Multiple sclerosis; Outcome measurement.

Abstract

Introduction Prospective memory is the ability to carry out a delayed intended action, so to maintain and retrieve future plans, goals and activities. Deficits of prospective memory negatively impact on patients and caregivers' everyday living and determine poor adherence to treatment. Since frontal regions are involved in both event- and time-based prospective memory tasks and are impaired in migraine without aura, defects of prospective memory might occur in migraine without aura patients; until now this issue has not been investigated. The aim of the current study was to explore time- versus event-based prospective memory in migraine without aura. Patients and methods Ninty-one consecutive migraine without aura patients and 84 healthy subjects were enrolled in the study. They underwent a standardized measure of prospective memory evaluating both time-based and event-based prospective memory, and the Montreal Cognitive Assessment assessing global cognitive status. Moreover, all participants completed the Beck Depression Inventory-II and a self-administered version of the Apathy Evaluation Scale, to assess severity of depressive symptoms and apathy, respectively. Results Migraine without aura and healthy subjects did not differ on demographic aspects (i.e. age, education and gender). However, individuals with migraine without aura demonstrated impaired prospective memory performance compared to healthy subjects, with a greater impairment demonstrated for the time-based tasks. Within the migraine without aura group, no significant association was found between prospective memory performance and clinical scores, apathy, and depression. Conclusions Individuals with migraine without aura experience particular difficulty executing a future intention; therefore, migraine without aura is associated with dysfunction of prospective memory.

Keywords: Migraine; apathy; cognitive deficit; cognitive dysfunction; depression; prospective memory.

Abstract

Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.

Keywords: Brain reserve; Cognitive deficits; Cognitive impairment; Cognitive reserve; Multiple sclerosis.