Botulinum toxin for the management of spasticity in multiple sclerosis: the Italian botulinum toxin network study.

BACKGROUND: Botulinum toxin (BT) is an effective and safe treatment for spasticity, with limited evidence in multiple sclerosis (MS). We aim to describe the use of BT for the management of MS spasticity in the clinical practice, its combination with other anti-spastic treatments in MS and possible MS clinical correlates. METHODS: This is a multicentre cross-sectional observational study including 386 MS patients, receiving BT for spasticity in 19 Italian centres (age 53.6 ± 10.9 years; female 228 (59.1%); disease duration 18.7 ± 9.2 years; baseline Expanded Disability Status Scale (EDSS) 6.5 (2.0-9.0)). RESULTS: BT was used for improving mobility (n = 170), functioning in activities of daily living (n = 56), pain (n = 56), posturing-hygiene (n = 63) and daily assistance (n = 41). BT formulations were AbobotulinumtoxinA (n = 138), OnabotulinumtoxinA (n = 133) and IncobotulinumtoxinA (n = 115). After conversion to unified dose units, higher BT dose was associated with higher EDSS (Coeff = 0.591; p < 0.001), higher modified Ashworth scale (Coeff = 0.796; p < 0.001) and non-ambulatory patients (Coeff = 209.382; p = 0.006). Lower BT dose was used in younger patients (Coeff = - 1.746; p = 0.009), with relapsing-remitting MS (Coeff = - 60.371; p = 0.012). BT dose was higher in patients with previous BT injections (Coeff = 5.167; p = 0.001), and with concomitant treatments (Coeff = 43.576; p = 0.022). Three patients (0.7%) reported on post-injection temporary asthenia/weakness (n = 2) and hypophonia (n = 1). CONCLUSION: BT was used for spasticity and its consequences from the early stages of MS, without significant adverse effects. MS-specific goals and injection characteristics can be used to refer MS patients to BT treatment, to decide for the strategy of BT injections and to guide the design of future clinical trials and observational studies.

Determinants of botulinum toxin discontinuation in multiple sclerosis: a retrospective study.

The purpose of the present study was to investigate the long-term persistence to treatment with botulinum toxin type A (BoNT-A) for multiple sclerosis (MS)-related spasticity and the determinants of BoNT-A discontinuation in daily clinical setting. We retrospectively collected data of patients who started BoNT-A injections and underwent regular follow-up visits. Determinants of BoNT-A discontinuation were explored in a time-to-event Cox regression analysis which included as independent variables a large set of demographic and clinical characteristics. A total of 185 patients started BoNT-A injections from 2002 to 2014 and were followed up to September 2016. Of them, data on 121 were considered in our analysis. At follow-up, 53 (44%) patients were still on treatment and 68 (56%) patients discontinued BoNT-A after a median time of 1.2 years [interval 6 months to 7.4 years]. The reasons for discontinuation were loss of efficacy (n = 45), logistic problems or barriers to reach the structure (n = 16), and adverse events (n = 7). The absence of caregiver (hazard ratio = 1.69, p = 0.03) and lack of regular rehabilitation (hazard ratio = 1.78, p = 0.02) were two independent predictors for BoNT-A discontinuation. Our study confirms the beneficial effect of combining BoNT-A injections with rehabilitation and highlights the crucial role of caregivers for achieving better long-term outcomes in people with MS suffering from spasticity.

The impact of extended release dopamine agonists on prescribing patterns for therapy of early Parkinson's disease: an observational study.

BACKGROUND: Dopamine agonists (DA) are the first-choice drug for treatment of the early stage of Parkinson's disease (PD) in subjects younger than 70 years. Recently, a number of third generation DA have been marketed, including transdermal patch of rotigotine and extended release oral formulation of ropinirole and pramipexole.We investigated the impact of third generation DA on management of the early stage of PD in an outpatient service for Movement Disorders in Italy. METHODS: Two 12-month observation periods were selected (January - December, 2007, and January - December, 2011) as representative for prescription of immediate and extended release formulations of DA respectively. Within each period, PD patients were divided into subgroups according to age (<65 years; 65-75 years; >75 years) or functional requirement (high; moderate; low). For each period, the number of subjects receiving monotherapy with DA, monotherapy with levodopa (LD), or combined DA/LD therapy and the relative doses were calculated. The severity of parkinsonian motor symptoms was calculated by means of the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The frequency and severity of side-effects leading to discontinuation or reduction of DA drugs at each time point were also calculated. RESULTS: We found a significant reduction of daily LD dose (both as mono- and combined therapy) between the second and the first observation period. There was also a significant increase of monotherapy with DA and corresponding reduction of monotherapy with LD in patients aged 65-75 years, as well as in PD patients with moderate functional requirements. A significant reduction of frequency of side-effects was measured with extended release DA as compared to immediate release formulations. There were no significant differences of the UPDRS-III scores between the 2 observation periods in any subgroup. CONCLUSIONS: Our results suggest that extended release DA might optimize therapeutic management of the early stages of PD even in patients older than 70 years of age.

Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system.

BACKGROUND AND OBJECTIVES: The most frequently mechanism underlying sudden cardiac death in myotonic dystrophy type 1 (DM1) is bradyarrhythmias due to cardiac conduction abnormalities. However the risk of ventricular tachyarrhythmias remains a concern in clinical management as well as in its determinant. We therefore assessed autonomic nervous system activity aiming to disclose differences in the QT variability index (QTVI)-a marker of temporal myocardial repolarization lability-between DM1 patients and healthy controls. We also investigated the possible differences within DM1 patients by subdividing them according either to the presence of first degree atrioventricular block (1st AVB) or to the cytosine-thymine-guanine (CTG) repeat expansion size. METHODS: Sixty-two DM1 patients and 20 healthy subjects underwent neurological and cardiological examinations, the latter including ECG, echocardiography and 24-hour Holter monitoring. All underwent a 5-minute ECG recording to assess heart rate variability power spectral components, and the QTVI values. RESULTS: Power spectral data, namely total power, low frequency power and high frequency power, were lower, whereas QTVI values were higher in DM1 patients than in controls (p<.0001). Higher QTVI values were found in DM1 subgroups with 1st AVB (p=.009) and more than 500 CTG repeat (p=.014) with respect to DM1 patients without 1st AVB and CTG<500. Spectral data did not significantly differ. At multivariable analysis, QTVI and age were independently associated with PR interval and CTG repeat. CONCLUSIONS: The increased values of QTVI argue in favour of an important heart involvement extending beyond the conduction system. Whether QTVI could be useful in predicting clinical course of DM1 clearly requires larger prospective studies.

Hypogonadism in DM1 and its relationship to erectile dysfunction.

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

Intrathecal anti-CD20 antibody: an effective and safe treatment for leptomeningeal lymphoma.

A patient with relapsed B cell non-Hodgkin lymphoma (NHL) infiltrating the Central nervous system (CNS) and resistant to chemotherapy was treated with intrathecal Rituximab (IT RTX), administered weekly for eight weeks at increasing doses, from 10 to 40 mg. After the second administration the patient showed significant clinical improvement and Cerebro spinal fluid (CSF) clearance of lymphomatous cells. A MRI scan performed after 30 days from the start of therapy showed full regression of lymphomatous infiltration. This report confirms the efficacy and safety of IT RTX in the treatment of CNS B-cell NHL.