scholarly journals Variability of Multiple Sclerosis Spasticity Symptoms in Response to THC:CBD Oromucosal Spray: Tracking Cases through Clinical Scales and Video Recordings

2018 ◽  
Vol 10 (2) ◽  
pp. 169-176
Author(s):  
Peter Flachenecker ◽  
Francesco Saccà ◽  
Carlos Vila
Keyword(s):  
Multiple Sclerosis ◽  
Rating Scale ◽  
Demyelinating Disease ◽  
Numerical Rating Scale ◽  
Individual Variability ◽  
Additional Treatment ◽  
Response To Treatment ◽  
Walk Test ◽  
Modest Improvement ◽  
Clinical Scales

Multiple sclerosis (MS) is an inflammatory and neurodegenerative autoimmune demyelinating disease of the central nervous system. Patients exhibit heterogeneous patterns of disabling symptoms, including spasticity. In the majority of patients with MS spasticity, it and its associated symptoms contribute to disability, interfere with performance of everyday activities, and impair quality of life. Even under treatment with oral antispasticity drugs, about a third of patients continue to experience spasticity of moderate to severe intensity, underscoring the need for additional treatment options. The efficacy of tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray as add-on therapy in patients with refractory MS spasticity has been demonstrated in clinical trials and observational studies. To gain insight into patients’ response to treatment at the individual level, in-depth changes from baseline in various clinical scales and video-assessed parameters were evaluated in patients with resistant MS spasticity before and after 1 month of treatment with THC:CBD oromucosal spray. All 6 patients showed ≥20% improvement in the spasticity Numerical Rating Scale (i.e., were initial responders to treatment), but displayed individual variability in other spasticity-related parameters. Improved Modified Ashworth Scale scores were observed in 5 cases, with a reduction of –2/–3 points in lower limb scores for 1 patient who also showed benefit in terms of a more stable gait but modest improvement in the timed 10-meter walk test (10MWT). Improvement in the 10MWT (or 25-foot walk test) was noted in 4 of the 6 cases. THC:CBD oromucosal spray also improved upper limb function as indicated by faster 9-Hole Peg Test results.

scholarly journals MDR1 Genotypes and Haplotypes Are Closely Associated with Postoperative Fentanyl Consumption in Patients Undergoing Radical Gastrectomy

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Fan Zhang ◽  
Jianbin Tong ◽  
Wenxiang Qing ◽  
Zhonghua Hu ◽  
Jie Hu ◽  
...  
Keyword(s):  
Rating Scale ◽  
Numerical Rating Scale ◽  
Opioid Analgesic ◽  
Individual Variability ◽  
Radical Gastrectomy ◽  
Nucleotide Polymorphisms ◽  
Multidrug Resistance Gene ◽  
Numerical Rating ◽  
Fentanyl Consumption ◽  
The Individual

Fentanyl is a powerful opioid analgesic, and its analgesic effect is greatly different among individuals. This study was aimed at exploring the effects of multidrug resistance gene-1 (MDR1) genetic variation on postoperative fentanyl consumption. A total of 135 patients, who planned to undergo radical gastrectomy with general anesthesia, were studied. The subjects received patient-controlled analgesia (PCA) by intravenous fentanyl within 48 hours after operation and maintained a numerical rating scale (NRS) score ≤ 3 . The consumption and side effects of fentanyl were recorded within 24 hours and 48 hours after the operation. Single nucleotide polymorphisms (SNPs) of all patients with MDR1 1236C>T, 2677G>T/A, and 3435C>T were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or DNA sequence analysis after PCR. There was no difference in postoperative fentanyl consumption among patients having 2677G>T/A and 3435C>T polymorphisms (all P > 0.05 ). MDR1 1236C>T polymorphisms and haplotypes combined by three SNPs, however, significantly affected postoperative fentanyl consumption (all P < 0.05 ). Moreover, 1236TT genotype carriers consumed more fentanyl during 24 hours ( P = 0.038 ) and 48 hours ( P = 0.003 ) postoperatively. The MDR1 TTT haplotype carriers needed more fentanyl compared with the CGC haplotype carriers during the first 48 hours after surgery ( P = 0.017 ). Nausea, vomiting, and dizziness were not found to have significant differences among the above three SNPs and their haplotypes ( P > 0.05 ). MDR1 1236C>T polymorphism and haplotypes were factors contributing to the individual variability in postoperative fentanyl consumption.

Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis

2010 ◽  
Vol 16 (6) ◽  
pp. 707-714 ◽  
Author(s):  
Derick T Wade ◽  
Christine Collin ◽  
Colin Stott ◽  
Paul Duncombe
Keyword(s):  
Multiple Sclerosis ◽  
Odds Ratio ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Meta Analysis ◽  
Treated Group ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Numerical Rating ◽  
Global Impression Of Change

Objective: To determine the efficacy of Sativex (USAN: nabiximols) in the alleviation of spasticity in people with multiple sclerosis. Methods: The results from three randomized, placebo-controlled, double-blind parallel group studies were combined for analysis. Patients: 666 patients with multiple sclerosis and spasticity. Measures: A 0—100 mm Visual Analogue Scale (VAS, transformed to a 0—10 scale) or a 0—10 Numerical Rating Scale (0—10 NRS) was used to measure spasticity. Patients achieving a ≥30% improvement from baseline in their spasticity score were defined as ‘responders’. Global impression of change (GIC) at the end of treatment was also recorded. Results: The patient populations were similar. The adjusted mean change of the numerical rating scale from baseline in the treated group was —1.30 compared with —0.97 for placebo. Using a linear model, the treatment difference was —0.32 (95% CI —0.61, —0.04, p = 0.026). A statistically significant greater proportion of treated patients were responders (odds ratio (OR) = 1.62, 95% CI 1.15, 2.28; p = 0.0073) and treated patients also reported greater improvement: odds ratio 1.67 (95% CI 1.05, 2.65; p = 0.030). High numbers of subjects experienced at least one adverse event, but most were mild to moderate in severity and all drug-related serious adverse events resolved. Conclusion: The meta-analysis demonstrates that nabiximols is well tolerated and reduces spasticity.

scholarly journals Epigenetic research in multiple sclerosis: progress, challenges, and opportunities

2017 ◽  
Vol 49 (9) ◽  
pp. 447-461 ◽  
Author(s):  
Galina Y. Zheleznyakova ◽  
Eliane Piket ◽  
Francesco Marabita ◽  
Majid Pahlevan Kakhki ◽  
Ewoud Ewing ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Sun Exposure ◽  
Response To Treatment ◽  
Variable Response ◽  
Efficient Treatment ◽  
Personalized Care ◽  
Epigenetic Research ◽  
Epigenetic Processes

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis, and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease. Epigenetic processes, such as DNA methylation and histone posttranslational modifications, integrate influences from the genes and the environment to regulate gene expression accordingly. Studying epigenetic modifications, which are stable and reversible, may provide an alternative approach to better understand and manage disease. We here aim to review findings from epigenetic studies in MS and further discuss the challenges and clinical opportunities arising from epigenetic research, many of which apply to other diseases with similar complex etiology. A growing body of evidence supports a role of epigenetic processes in the mechanisms underlying immune pathogenesis and nervous system dysfunction in MS. However, disparities between studies shed light on the need to consider possible confounders and methodological limitations for a better interpretation of the data. Nevertheless, translational use of epigenetics might offer new opportunities in epigenetic-based diagnostics and therapeutic tools for a personalized care of MS patients.

scholarly journals Balancing Early Aggression Against Risk of Progression in Multiple Sclerosis

2015 ◽  
Vol 43 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Pierre Duquette ◽  
Paul S. Giacomini ◽  
Virender Bhan ◽  
Marika Hohol ◽  
Robyn Schecter
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Time Window ◽  
Disease Onset ◽  
Response To Treatment ◽  
Close Monitoring ◽  
Brain Volume Loss ◽  
Risk Of Progression ◽  
The Central Nervous System ◽  
Relapsing Remitting Multiple Sclerosis

AbstractMultiple sclerosis is a chronic demyelinating disease characterized by focal and diffuse inflammation of the central nervous system resulting in significant physical and cognitive disabilities. Disease-modifying therapies targeting the dysfunctional immune response are most effective in the first few years after disease onset, indicating that there is a limited time window for therapy to influence the disease course. No evidence of disease activity is emerging as a new standard for treatment response and may be associated with improved long-term disability outcomes. An aggressive management strategy, including earlier use of more potent immunomodulatory agents and close monitoring of the clinical and radiologic response to treatment, is recommended to minimize early brain volume loss and slow the progression of physical and cognitive impairments in patients with relapsing-remitting multiple sclerosis.

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

2020 ◽  
Vol 91 (9) ◽  
pp. 914-920
Author(s):  
Clara Grazia Chisari ◽  
Claudio Solaro ◽  
Pasquale Annunziata ◽  
Roberto Bergamaschi ◽  
Assunta Bianco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Large Population ◽  
Real Life ◽  
Discontinuation Rate ◽  
Real Life Data ◽  
Numerical Rating ◽  
Therapy Option

IntroductionDelta-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 methodsThis 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.ResultsA total of 1845 patients were recruited from 32 MS Italian centres. At T1, 1502 (81.4%) of patients reached a Numerical Rating Scale (NRS) improvement of ≥20%, with an NRS reduction of 26.9% at T1 and of 34.4% at T5. At T5, 725 patients (48.3% of 1502) discontinued treatment with highest discontinuation rate at T2 and T3. Daily number of puffs was generally stable through the observation period. The multivariate analysis showed that higher NRS scores at baseline (OR 2.28, 95% CI 1.15 to 6.36, p<0.01) and higher differences of NRS between T0 and T1 (OR 2.11, 95% CI 1.08 to 8.26, p<0.05) were associated with an increased probability to continue therapy after 18 months.DiscussionTHC:CBD effects were sustained for 18 months with a relatively stable number of puffs per day. About 50% of patients abandoned THC:CBD therapy for loss of efficacy or adverse events.

A comparison of the effects of reflexology and relaxation on pain in women with multiple sclerosis

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Fatemeh Nazari ◽  
Mozhgan Soheili ◽  
SayedMohsen Hosseini ◽  
Vahid Shaygannejad
Keyword(s):  
Multiple Sclerosis ◽  
Pain Intensity ◽  
Repeated Measures ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Statistical Tests ◽  
Control Group ◽  
Minimization Method ◽  
Significant Difference ◽  
And Control

Abstract: Pain is a common and significant symptom in many individuals with multiple sclerosis (MS). The presence and severity of pain in individuals with MS has also been shown to be associated with higher levels of depression, functional impairment, and fatigue. It is common for MS patients and their caregivers to worry about narcotic addiction in the management of chronic pain. Therefore, this study aimed to determine and compare the effects of reflexology and relaxation on pain in women suffering from MS.: This study was a single-blind randomized clinical trial performed on 75 patients with MS referred to the MS Clinic of Ayatollah Kashani Hospital (Isfahan, Iran). After simple non-random sampling, using the minimization method, participants were randomly assigned to the three groups of reflexology, relaxation, and control. In the experimental groups, foot reflexology and relaxation interventions (Jacobson and Benson) were performed within 4 weeks, twice a week for 40 min. The control group received routine care and medical treatment as directed by a doctor. Data were collected using the Numerical Rating Scale before, immediately after, and 2 months after interventions in all three groups. Data analysis was performed using SPSS version 18 and descriptive and inferential statistical tests.: Findings obtained from analysis of variance (ANOVA) showed no significant differences between mean pain intensity scores in the three groups preintervention and 2 months after interventions (p > 0.05). However, this difference was statistically significant immediately after the study (p < 0.05). Findings obtained from repeated measures ANOVA showed that the severity of pain significantly differed during different times in reflexology and relaxation (p < 0.05); however, this difference was not significant in the control group (p > 0.05). Furthermore, Fisher’s least significant difference (LSD) revealed a significantly higher reduction in pain intensity scores in the reflexology group after the intervention, compared with the two other groups, but showed no significant differences between relaxation and control groups. There were no significant differences between the three groups 2 months after the interventions (p > 0.05).: The results showed that both interventions are effective on relieving pain in women with MS; however, it appears that the effect of reflexology on pain reduction is greater than that of relaxation. Hence, these two methods can be recommended as effective techniques.

scholarly journals Chemokine Receptors as Biomarkers in Multiple Sclerosis

2006 ◽  
Vol 22 (4) ◽  
pp. 227-233 ◽  
Author(s):  
Robert J. Fox ◽  
Pia Kivisäkk ◽  
Jar-Chi Lee ◽  
Barbara Tucky ◽  
Claudia Lucchinetti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chemokine Receptors ◽  
Individual Variability ◽  
Response To Treatment ◽  
Considerable Variability ◽  
Set Point ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Peripheral Leukocytes ◽  
Over Time

Leukocyte infiltrates characterize tissue inflammation and are thought to be integral in the pathogenesis of multiple sclerosis (MS). This attribute underlines the importance of understanding mechanisms of leukocyte migration. Chemokines are secreted proteins which govern leukocyte trafficking into targeted organs. Chemokine receptors (CKR) are differentially expressed on leukocytes and their modulation is a potential target for MS disease modifying therapies. Chemokines and their receptors are also potential biomarkers of both disease activity and response to treatment. We describe the fluctuations in CKR expression on peripheral leukocytes in a group of MS patients followed longitudinally for up to 36 months. We observed little fluctuation in CKR expression within each patient over time, despite considerable variability in CKR expression between patients. These observations suggest that individual patients have a CKR set point, and this set point varies from one patient to another. Evaluation of chemokines or chemokine receptors as biomarkers in MS will need to account for this individual variability in CKR expression.

scholarly journals Rethinking pain threshold as a zone of uncertainty

2019 ◽  
Author(s):  
Victoria J Madden ◽  
Peter R Kamerman ◽  
Mark J Catley ◽  
Valeria Bellan ◽  
Leslie N Russek ◽  
...  
Keyword(s):  
Stimulus Intensity ◽  
Pain Threshold ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Individual Variability ◽  
Stimulus Response ◽  
Stable Relationship ◽  
Painful Events ◽  
The Individual ◽  
Actual Response

AbstractBackgroundThe pain threshold is traditionally conceptualised as a boundary that lies between painful and non-painful events, suggesting a reasonably stable relationship between stimulus and response. In two previous experiments, participants received laser stimuli of various intensities and rated each stimulus on the Sensation and Pain Rating Scale (SPARS), which includes ranges for rating painful and non-painful events and clearly defines the presumed boundary between them. In the second experiment, participants also provided ratings on the conventional 0-100 Numerical Rating Scale for pain (NRS) and a new rating scale for non-painful events. Those data showed the SPARS to have a curvilinear stimulus-response relationship, reflecting that several different intensities may be rated as painful and non-painful in different trials. This suggests that participants were uncertain about painfulness over a range of intensities and calls into question the idea of a boundary between non-painful and painful events. The current study aimed to determine the number of different stimulus intensities across which each participant provided ‘painful’ and ‘non-painful’ reports in different trials.MethodsWe undertook novel exploratory analyses on data from the aforementioned two experiments (n = 19, 11 female, 18-31 years old; n = 7, 5 female, 21-30 years old). We used the binomial test to formally determine the width of this ‘zone of uncertainty’ about painfulness, using ratings on the SPARS and the comparator scales, and data visualisation to assess whether trial-to-trial change in stimulus intensity influences ratings.ResultsWe found that the width of the zone of uncertainty varied notably between individuals and that the zone was non-continuous for most participants. Plots of group-level data concealed the inter-individual variability apparent in the individual plots, but still showed a wide zone of uncertainty on both the SPARS and the NRS, but a narrow zone on the scale for non-painful events. There was no evidence that trial-to-trial change in stimulus intensity influenced ratings.ConclusionsThe variability revealed by this study has important design implications for experiments that include initial calibration of repeatedly delivered stimuli. The variability also stands to inflate the size of sample that is required for adequate statistical powering of experiments, and provides rationale for the use of statistical approaches that account for individual variability in studies of pain. Finally, the high variability implies that, if experimental stimuli are to be used in clinical phenotyping, many trials may be required to obtain results that represent a single patient’s actual response profile.

scholarly journals Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Marie D’hooghe ◽  
Barbara Willekens ◽  
Valerie Delvaux ◽  
Miguel D’haeseleer ◽  
Daniel Guillaume ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Average Dose ◽  
Patient Reported ◽  
Numerical Rating ◽  
Vas Scores ◽  
Effectiveness Assessment ◽  
Eq Vas ◽  
Term Data

Abstract Background This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. Methods Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. Results Mean 0–10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks’ range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. Conclusions More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.

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