Background: Understanding caregiver strain may be crucial to determine which interventions are most needed to mitigate the negative impact of caring for people with multiple sclerosis (MS). The ...Caregiver Strain Index (CSI) is a brief self-assessment tool for measuring the caregivers' perceived level of burden. Limited information is available on the psychometric performance of the CSI in MS. Objective: The objective of this study was to assess the factor structure and construct validity of the CSI in MS. Methods: A multicenter, cross-sectional study in adults with relapsing-remitting and primaryprogressive MS (McDonald 2010 criteria) was conducted. A non-parametric item response theory (IRT) procedure, Mokken analysis, was conducted to assess the dimensional structure of the CSI. A parametric IRT model for dichotomous responses, Rasch model, was conducted to assess item characteristics. Discriminative validity was assessed comparing the distribution of its overall score between people with mild and moderate-severe disability according to the Expanded Disability Status Scale. Results: A total of 72 MS caregivers were studied. The prevalence of a high level of strain was 23.6% (n=17). Internal reliability was high (Cronbach's alpha =0.91). According to Mokken analysis, CSI represented a unidimensional construct of caregiver burden although two of the total 13 items (#1 and #13) could not be assigned to any factor by an automatic item selection procedure. Without these items, the scalability moved from a weak (H. =0.37) to a medium scale (H. =0.44). However, the item characteristic curve of the Rasch model showed a range of appropriate difficulty and the item and person parameters showed good fit (Andersen likelihood ratio test =18.40, df =11; P-value =0.07; all item values for the infit). The CSI score showed a good discriminative validity between the levels of disability of the care recipient. Conclusion: The CSI questionnaire shows appropriate psychometric characteristics being a useful instrument to assess different aspects of burden in MS caregivers in clinical practice. Keywords: caregivers, multiple sclerosis, psychometrics, caregiver burden, strain
Introduction
Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing–remitting multiple sclerosis (RRMS; depending on the local label), ...based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression.
Methods
This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed.
Results
A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (
p
= 0.004) and 29.0 (24.6) at 24 months (
p
= 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14–0.21) from the baseline of 0.42 (95% CI 0.38–0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12–24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not.
Conclusion
Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.
Objectives: To investigate the roles of 2 polymorphisms of the tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) gene, rs1800693 (a common variant) and rs4149584 (a coding ...polymorphism that results in an amino acid substitution-R92Q), as genetic modifiers of multiple sclerosis (MS), and to evaluate their potential functional implications in the disease. Methods: The effects of rs1800693 and rs4149584 on 2 measures of disease severity, age at disease onset and Multiple Sclerosis Severity Score, were analyzed in 2,032 patients with MS. In a subgroup of patients, serum levels of the soluble form of TNF-R1 (sTNF-R1) were measured by ELISA; mRNA expression levels of the full-length TNF-R1 and white triangle up6-TNF-R1 isoform were investigated in peripheral blood mononuclear cells (PBMC) by real-time PCR; cell surface expression of the TNF-R1 was determined in T cells by flow cytometry. Results: For rs4149584, R92Q carriers were younger at disease onset and progressed slower compared to noncarriers. However, no association with disease severity was observed for rs1800693. Serum levels of sTNF-R1 and mRNA expression levels of the full-length receptor were significantly increased in patients with MS carrying the R92Q mutation (p = 0.003 and p = 0.011, respectively), but similarly distributed among rs1800693 genotypes; cell surface TNF-R1 expression in T cells did not differ between rs4149584 and rs1800693 genotypes. The truncated soluble white triangle up6-TNF-R1 isoform was identified in PBMC from patients carrying the risk allele for rs1800693. Conclusions: These findings suggest that both rs1800693 and rs4149584 TNFRSF1A polymorphisms have functional consequences in the TNF-R1.
A series of 18 patients suffering from supraorbital neuralgia have been studied through a seven year period. Appropriate investigations ruled out other headaches.
There was a female (67%) ...preponderance. Mean age at onset was 51.6 years. The mean headache duration was 5.9 years. Five patients had a history of ipsilateral forehead trauma. The main areas of pain were the forehead and orbit. The pain was dull with short sharp or burning exacerbations. The temporal pattern was either remitting (n = 7) or chronic continuous (n = 11). Autonomic accompaniments were generally lacking. Neurological assessment was normal in all but 4 patients who were found to have signs/symptoms of sensory dysfunction in the forehead of the symptomatic side. Trials of different drugs, including migraine and anti-neuralgic drugs, only provided slight relief. Anaesthetic nerve blocks of the supraorbital nerve provided an absolute but transitory relief of pain.
Although aetiology and pathogenesis of supraorbital neuralgia is largely unknown, entrapment of the supraorbital nerve at its outlet and successful decompressive surgery have been previously reported. This and other pathogenic hypotheses are discussed.
This study was aimed determining the effectiveness, tolerance and satisfaction of patients with migraine as regards different triptans, according to the characteristics of their attacks. At the same ...time it sought to establish a predictive model that can be used to recommend one or another, depending on those characteristics.
Retrospective observation-based study conducted in headache units in a number of different centres. Patients included in the study were those with migraine who used the same triptan to treat their attacks. Data concerning preference, effectiveness, speed and tolerance were analysed.
The analysis included 160 patients (88 females), with a mean age of 42.92 years. The most commonly used triptans were eletriptan, almotriptan and rizatriptan. Both patients and doctors reported a high degree of satisfaction (88% and 65%) with the triptan that was used. In the surveys on preference, patients preferred their current triptan to the previous one (83%) or to non-specific drugs. The overall score on a visual analogue scale was above 7 for all the triptans, without any differences from one to another. On analysing the use of a particular triptan depending on the characteristics of the attacks, no statistically significant differences were found.
In this selected group of patients, triptans are a treatment that patients claim to be very satisfied with. Although there are no overall differences in the scores among different triptans, the fact that certain triptans are used more by patients after previous experiences with others suggests that they are more effective. We did not find any parameter that predicts the use of a particular triptan.
SUNCT is probably a distinct syndrome, although it shares some common features with cluster headache (CH): male sex preponderance, clustering of attacks, unilaterality of headache without sideshift, ...pain of non-pulsating type with its maximum in the periocular area, ipsilateral autonomic phenomena (e.g. conjunctival injection, lacrimation, rhinorrhea, increased forehead sweating), systemic blood pressure increment with heart rate decrement, blood flow velocity decrement in the middle cerebral artery, and hyperventilation. In spite of these similarities, SUNCT syndrome differs clearly from CH as regards a number of clinical variables, such as duration, intensity, frequency, and nocturnal preponderance of attacks. The two syndromes also differ markedly as regards precipitation of attacks, the usual age at onset, and efficacy of various treatment alternatives. Laboratory investigations have disclosed differences as regards presence or absence of Horner-like picture and possibily also the respiratory sinus arrhythmia pattern. All in all, these differences seem sufficiently ponderous to make it likely that SUNCT syndrome and CH differ essentially. SUNCT seems to be a "neuralgiform" headache, but different from trigeminal neuralgia.PUBLICATION ABSTRACT
Attacks of chronic paroxysmal hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5‐HT1‐like receptors, has proven effective in the treatment of ...cluster headache attacks. There are clear clinical similarities between chronic paroxysmal hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether chronic paroxysmal hemicrania also responds similarly to sumatriptan. Since hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with chronic paroxysmal hemicrania and 7 patients (5 women and 2 men) with hemicrania continua. In chronic paroxysmal hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 ± 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 ± 20 minutes). In none of the patients did the mean duration of the “test attack” decrease as compared to the attacks antedating the test attach (25 ± 11 minutes and 19 ± 9 minutes, respectively) (P=0.027, Wilcoxon). In 2 patients with chronic paroxysmal hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks.
There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in hemicrania continua (P=0.04, Wilcoxon). There was no clear, ie, clinically meaningful, reduction in visual analog scale values in any particular patient with hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in chronic paroxysmal hemicrania, but may have a partial efficacy in hemicrania continua. However, the latter effect is clinically unimportant This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in chronic paroxysmal hemicrania clearly and markedly strengthens the nonalignment concept in regard to chronic paroxysmal hemicrania and cluster headache.
We report the coexistence of both chronic paroxysmal hemicrania (CPH) and trigeminal neuralgia (tic douloureux) in a female patient. The clinical features combined to make a configuration of CPH-tic ...syndrome. The two components of the syndrome appeared synchronously in the same orbital region—first branch of the trigeminal nerve—with a latency of several years after the onset of isolated tic attacks of the second and third trigeminal divisions. The concurrence of both types of pain in the same symptomatic area may have some significance for pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1 tic.
BackgroundLamotrigine has been suggested as possibly effective for preventing migraine aura. ObjectiveTo describe our experience with a series of patients with disturbing migraine aura treated with ...lamotrigine. MethodsThe members of the Headache Group of the Spanish Society of Neurology were sent an ad hoc questionnaire to collect patients treated with lamotrigine due to disturbing migraine aura. The main outcome parameter ('response') was a >50% reduction in the mean frequency of migraine auras at 3 to 6 months of treatment. ResultsA total of 47 patients had been treated with lamotrigine due to severe migraine aura. Three could not complete the protocol as a result of developing skin rashes. Thirty (68%) patients responded. These were 21 females and 9 males whose ages ranged from 19 to 71 years. Eight suffered from migraine with 'prolonged' aura, 8 typical aura with migraine headache (but had frequent episodes including speech symptoms), 6 basilar-type migraine, 6 typical aura without headache, and 2 hemiplegic migraine. Fifteen had been previously treated, without response, with other preventatives. The mean monthly frequency of migraine auras in these 30 patients changed from 4.2 (range: 1 to 15) to 0.7 (range: 0 to 6). Response was considered as excellent (>75% reduction) in 21 cases (70% of responders). Auras reappeared in 2 months in 9 out of 13 patients where lamotrigine was stopped, and ceased as soon as this drug was reintroduced. ConclusionsLamotrigine should be considered in clinical practice for the preventive treatment of selected patients with disturbing migraine auras. Lamotrigine seems worthy of a controlled trial as prophylaxis of migraine aura.
Greater occipital nerve (GON), supraorbital nerve (SON), and minor occipital nerve (MON) blockades-in this sequence-were carried out on the symptomatic side in patients with chronic paroxysmal ...hemicrania (CPH) (no = 6) and hemicrania continua (HC) (no = 7). Prior to the blockade, indomethacin was discontinued for a sufficiently long time (24 h) to allow a constant flow of attacks/constant pain. The local anaesthetic agent used was lidocaine. The blockades were invariably negative in CPH. In HC, the GON and MON blockades generally had no positive influence. The pattern as regards SON blockades was slightly different, in that the pre-test average VAS-value of 7.3 decreased to 4.6 (p < 0.05, Student's t-test, and p = 0.065 Wilcoxon) and-on an individual basis-decreased in 4 out of 7 patients. GON/MON blockades will help distinguish CPH/HC from cervicogenic headache. SON blockade will have to be carried out in a good-sized series of HC patients in order to establish more concrete evidence of the putative effect in HC. SON blockades may eventually also aid in the distinction between HC and supraorbital nerve neuralgia (where the blockade effect generally seems to be complete).