•OnabotA treatment has beneficial effects on psychiatric comorbidities in CM and MOH.•ICDs occur with a prevalence of 30% and decrease after OnabotA treatment.•Anxiety symptoms significantly decrease ...after OnabotA treatment.
Chronic migraine (CM) with medication overuse headache (MOH) is one of the most common and disabling chronic headache disorders associated with both frequencies of use of medication and behavioral alterations, including psychopathology and psychological drug dependence. Several previous studies on large patient samples have demonstrated the efficacy of Onabotulinum toxin A (OnabotA) on physical symptomatology treatment of headache, but effects on behavioral alterations remain still debate. Our study investigated the effects of OnabotA on psychiatric comorbidities and on quality of life of patients with CM and MOH that failed on traditional therapies. OnabotA was injected, according to the PREEMPT paradigm, 40 patients with CM and MOH and data on headache-related impairment, before and after the OnabotA injections were collected from the patient’s headache diaries. Data on depressive, anxiety symptomatology and impulse control disorders also were collected by means of self-report scales and a semi-structured interview. After six months, patients with CM and MOH showed a significant decrease in monthly headache attacks (from 19.3 ± 5.9 to 11.8 ± 8.5, p = 0.003), monthly headache days (from 23 ± 8.9 to 11.1 ± 6.2, p = 0.001), numbers of analgesics used per month (from 18.2 ± 6.3 to 8.5 ± 4.7, p < 0.0001). The anxiety symptomatology (p ≤ 0.003) and impulse control disorders (from 30% to 10%), but not depressive symptomatology (p = 0.81), were significantly reduced from throughout the study. The treatment with OnabotA proved beneficial effects on anxiety symptomatology and on impulse control disorders in our clinical practice with CM and MOH and further studies should shed light in larger patient samples on long-term behavioural effects.
We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 ...(COVID-19) outbreak.
The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period).
Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 (95% CI, 0.71-0.80
<0.001); intracerebral hemorrhages decreased from 400 to 322 (hospitalization RR, 0.81 95% CI, 0.69-0.93;
=0.004), and transient ischemic attacks decreased from 322 to 196 (hospitalization RR, 0.61 95% CI, 0.51-0.73;
<0.001). Hospitalizations decreased in Northern, Central, and Southern Italy. Intravenous thrombolyses decreased from 531 (22.1%) in 2019 to 345 in 2020 (19.1%; RR, 0.86 95% CI, 0.75-0.99;
=0.032), while primary endovascular procedures increased in Northern Italy (RR, 1.61 95% CI, 1.13-2.32;
=0.008). We found no correlation (
=0.517) between the hospitalization RRs for all strokes or transient ischemic attack and COVID-19 incidence in the different areas.
Hospitalizations for stroke or transient ischemic attacks across Italy were reduced during the worst period of the COVID-19 outbreak. Intravenous thrombolytic treatments also decreased, while endovascular treatments remained unchanged and even increased in the area of maximum expression of the outbreak. Limited hospitalization of the less severe patients and delays in hospital admission, due to overcharge of the emergency system by COVID-19 patients, may explain these data.
Oral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.
We identified all patients with ...relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).
The eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).
The effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.
Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. ...Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis.
Several studies have supported the efficacy of complementary and alternative medicine approaches (physical, behavioral and nutraceutical therapies) in the treatment of headache disorders. ...Nutraceutical treatment consists of taking vitamins, supplements (magnesium, riboflavin, coenzyme Q10, and alpha lipoic acid) and herbal preparations (feverfew and butterbur), and its usage is frequently determined by dissatisfaction with conventional medical therapies. There is a growing body of research on nutraceutical use for migraine prophylaxis. This brief overview provides information about the potential efficacy and side effects of various nutraceutical products summarizing randomized controlled trials of some of the most commonly used non-pharmacological treatments for the prophylaxis and treatment of migraine, including magnesium, coenzyme Q10, riboflavin (vitamin B
2
), petasites, and feverfew.
•Apathy is frequent in MS and associated with more severe executive dysfunctions.•Higher level of apathy at baseline predicts the cognitive decline at 4-year follow-up.•Apathy represents an early ...neurobehavioral marker of the dysexecutive syndrome in MS.•Apathy may be considered a potential target of interventions for delaying clinical decline in MS.
Cognitive dysfunctions are highly prevalent in multiple sclerosis (MS) and negatively impact occupational and social functioning.
In the present longitudinal study, we aimed at modeling cognitive changes and at assessing whether apathy could be a predictor of cognitive decline in MS.
We assessed 67 people with MS at two-time points (baseline, T0; 4-year follow-up, T1), by means of several clinical, behavioural, and cognitive measures. We used a delta approach to measure cognitive decline during the follow-up period. We applied a mixed factorial design and a linear regression model to explore factors associated with cognitive changes over time.
A higher level of apathy at baseline predicted the progressive cognitive decline at follow-up, whereas a higher level of depression did not. Among demographic and clinical characteristics, only low education level was significantly associated with cognitive decline over time. Interestingly, participants with persistent apathy (diagnosis of apathy at T0 and T1, A+A+) and those who developed apathy (A-A+) showed poorer inhibitory control and a larger decline in executive functioning during the 4-year follow-up than participants who had never received the diagnosis of apathy (A-A-).
Apathy represents an early marker of cognitive decline in MS. These findings have important clinical and prognostic implications.
Background and purpose
A rapid response to preventive therapy is of pivotal importance in severely disabled patients with chronic migraine (CM) and diverse preventive treatment failures. This ...prospective, observational, multicenter real‐life study aimed at investigating the effectiveness of galcanezumab in the first 3 months of treatment of CM patients at 14 Italian headache centers.
Methods
All consecutive adult patients with CM diagnosis with the clinical indication for galcanezumab were considered. We collected patients' baseline characteristics, monthly headache days, monthly painkiller intake, migraine clinical characteristics, and disability scale scores during a 1‐month run‐in period (baseline) and the first 3 months of therapy. Possible predictive factors of treatment were considered.
Results
A total of 156 patients (82.4% female, aged 47.3 ± 12.3 years) were enrolled. The 65 (41.7%) patients with a consecutive ≥50% response rate (RR) in the 3 months of therapy presented a lower body mass index (p = 0.004) and more frequently presented unilateral migraine pain (p = 0.002) and good response to triptans (p = 0.003). Persistent conversion from CM to episodic migraine was observed in 55.8% (87/156) of patients. They more frequently presented a good response to triptans (p = 0.003) and unilateral pain (p = 0.046). At baseline, 131 of 156 (83.9%) patients presented medication overuse (MO). Of these, 61.8% (81/131) no longer displayed MO consistently during the 3 months. These patients were more frequently responders to triptans (p = 0.002) and less frequently suffered from gastrointestinal comorbidity (p = 0.007).
Conclusions
Unilateral pain, good response to triptans, and normal weight may be associated with a persistent positive response in the first 3 months of therapy with galcanezumab in CM patients.
Rapid response to preventive therapy and its possible predictive factors are fundamental in patients with chronic migraine (CM). In our study, galcanezumab reduced monthly headache days by at least 50% from baseline in >50% of our real‐life CM patients after the first month, in about two thirds after 3 months, and in >40% during all 3 months of treatment. More than 60% of subjects discontinued medication overuse (MO) during all 3 months of treatment. Unilateral pain, good response to triptans, normal weight, and MO at baseline appeared to be associated with a positive response.
Multiple Sclerosis is more common in women than men and females have more relapses than men. In a large international cohort we have evaluated the effect of gender on disability accumulation and ...disease progression to determine if male MS patients have a worse clinical outcome than females.
Using the MSBase Registry, data from 15,826 MS patients from 25 countries was analysed. Changes in the severity of MS (EDSS) were compared between sexes using a repeated measures analysis in generalised linear mixed models. Kaplan-Meier analysis was used to test for sex difference in the time to reach EDSS milestones 3 and 6 and the secondary progressive MS.
In relapse onset MS patients (n = 14,453), males progressed significantly faster in their EDSS than females (0.133 vs 0.112 per year, P<0.001,). Females had a reduced risk of secondary progressive MS (HR (95% CI) = 0.77 (0.67 to 0.90) P = 0.001). In primary progressive MS (n = 1,373), there was a significant increase in EDSS over time in males and females (P<0.001) but there was no significant sex effect on the annualized rate of EDSS change.
Among registrants of MSBase, male relapse-onset patients accumulate disability faster than female patients. In contrast, the rate of disability accumulation between male and female patients with primary progressive MS is similar.
Background: Neuropsychiatric symptoms are common in multiple sclerosis (MS). Among these, apathy is relatively frequent but its relationships with cognitive dysfunctions have been poorly ...investigated. Objective: To explore cognitive correlates of apathy with or without depression ("pure apathy") in MS patients. Material and Method: Nondemented MS patients (n = 125), consecutively referred to the Multiple Sclerosis Center of Moscati Hospital, in Avellino, Italy, underwent the Apathy Evaluation Scale Self-Rated (AES-S), the Hamilton Depression Rating Scale (HDRS), and a comprehensive neuropsychological battery. Results: According to cut-off scores of AES-S (≥36), of HDRS (≥15) and criteria for diagnosis of apathy and major depression, the sample was divided into 4 subgroups: 49 patients without apathy or depression (A−D−), 20 patients with "pure" apathy (A+D−), 29 patients with depression only (A−D+), and 27 patients with apathy and depression (A+D+). Cognitive performance significantly differed in the 4 groups: in particular MS patients with apathy (A+D− and A+D+) performed significantly worse on executive tasks than patients without apathy, whereas patients with "pure" apathy (A+D−) performed significantly worse than patients without apathy only on executive tasks tapping cognitive control abilities. Conclusions: We found a significant relationship between apathy and dysexecutive defects in MS, consistent with the hypothesis that dysfunctions of prefrontal cortico-subcortical circuits contribute to specific neuropsychiatric syndromes in MS patients.