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.
We aimed to study the attitude of Italian neurologists in the use of conventional MRI in patients with idiopathic adult-onset focal dystonia. Patients were included in the Italian Dystonia Registry ...by experts working in different Italian centers. MRI was available for 1045 of the 1471 (71%) patients included in the analysis. Using logistic regression analysis, we found that MRI was more likely to be performed in patients with cervical dystonia, spasmodic dysphonia, or non-task-specific upper limb dystonia, whereas it was less likely to be performed in patients with blepharospasm or task-specific upper limb dystonia. We did not find differences in the number of MRIs performed between neurological centers in Northern, Central, and Southern Italy. We conclude that although the diagnosis of idiopathic adult-onset dystonia is mainly based on clinical grounds, many movement disorder experts rely on MRI to confirm a diagnosis of idiopathic dystonia. We suggest that neuroimaging should be used in patients with adult-onset focal dystonia to rule out secondary forms.
Pisa syndrome is a disabling, medication-resistant, postural abnormality that may affect 7–10% of patients with Parkinson's disease. In this study, we sought to assess the efficacy of botulinum toxin ...injections in Parkinson's disease-associated Pisa syndrome using a Magnetic Resonance Imaging-, Ultrasonography-, and Electromyography-guided combined approach.
We conducted a pilot study to evaluate the efficacy of botulinum toxin type-A injection in paraspinal and non-paraspinal axial muscles after a Magnetic Resonance Imaging and ultrasound-guided electromyography evaluation. Inclusion criteria were Pisa syndrome, idiopathic Parkinson's disease, and stable dopaminergic medications. Exclusion criteria were previous treatment with botulinum toxin, history of major spine surgery, and severe orthopedic diseases. As primary endpoint, we measured the rate of patients improving by at least 5° in the lateral trunk flexion 2 months after therapy. Secondary endpoints were the extent of lateral trunk flexion improvement, and changes in PS-associated pain/discomfort, measured by the Visual Analogue Scale.
Out the 15 patients initially enrolled, 13 completed the follow-up assessment, while 2 joined a rehabilitation program and were excluded from the analyses. The rate of responders was 84.6% (n = 11/13), with 40% average reduction in trunk bending. Pain/discomfort improved in all patients, with 52.2% amelioration at the Visual Analogue Scale. The procedure was well tolerated in all cases, without side effects or complications.
A combined imaging and EMG botulinum toxin approach to Pisa syndrome may yield a success rate greater than 80% in Parkinson's disease.
•There is no agreement on how to treat Pisa syndrome with botulinum toxin.•Imaging and electromyography guidance for botulinum injection led to 84% responders.•The mean improvement of the lateral trunk bending obtained after injection was 40%.•The mean improvement of the Pisa-related pain/discomfort after injection was 52.2%.
Natalizumab is a monoclonal antibody highly effective in the treatment of relapsing remitting multiple sclerosis (RRMS) patients. Despite its effectiveness, there are growing concerns regarding the ...risk of progressive multifocal leukoencephalopathy (PML), a brain infection caused by John Cunningham virus (JCV), particularly after 24 doses and in patients who previously received immunosuppressive drugs. Long-term natalizumab treated, immunosuppressive-pretreated, and JCV antibody-positive patients are asked to rediscuss natalizumab continuation or withdrawal after 24 doses. Until now, there has not been a clear strategy that should be followed to avoid PML risk and in parallel reduce clinical and radiological rebound activity. In this review, we analyzed the results of clinical trials and case reports in relation to the following situations: natalizumab continuation, natalizumab discontinuation followed by full therapeutic suspension or switch to other first or second line MS treatments. Quitting all MS treatment after natalizumab increases MS activity occurrence. The results regarding the therapeutic switch are not homogeneous, so at the moment there are no established guidelines regarding natalizumab treatment after 24 administrations; the choice is currently based on the professional experience of the neurologist, and on patients' clinical features and preferences.
Natalizumab is a humanized monoclonal antibody highly effective in relapsing-remitting multiple sclerosis (MS). Important concerns about its safety have been pointed out mainly because of the risk of ...progressive multifocal leukoencephalopathy (PML), caused by the opportunistic John-Cunningham virus (JCV). Areas covered: This review analyzes all the safety aspects related to the use and safety of natalizumab in MS patients. Other than PML, post-marketing, safety red-flags have been reported, as liver or haematological serious adverse events. Pregnancy evidences will be pointed out. The risk of PML depends on: concomitant or previous immunosuppression, exposure duration, anti-JCV antibody level. In natalizumab-related PML the average survival is 77%; prognostic features and information for the earliest identification of PML have been identified to maximally reduce its incidence, mortality and morbidity. Expert opinion: Natalizumab is a highly effective drug for MS patients but its safety issues represent a relevant limitation and impose strict clinical surveillance of treated patients. Some post-marketing safety red-flags have been pointed out, with higher attention to severe liver failures and limphoma cases. If PML and its consequences are considered the most relevant issues, a continuous surveillance must be maintained also regarding other possible SAEs like liver diseases and malignancies.
The three interferon beta preparations approved for treatment of relapsing-remitting multiple sclerosis (MS) differ in dose and frequency of administration. Interferon beta-1a 30 μg is administered ...once a week, interferon beta-1a 22 μg or 44 μg is given three times a week, and interferon beta-1b 250 μg is administered on alternate days. No clinical study directly comparing the different regimens has been published. The INCOMIN study was designed to compare the clinical and magnetic resonance imaging (MRI) benefits of on-alternate-day interferon beta-1b 250 μg with once-weekly interferon beta-1a 30 μg.
INCOMIN was a 2-year, prospective, randomised, multicentre study. 188 patients with relapsing-remitting MS were assigned to interferon beta-1b (n=96) or interferon beta-1a (n=92). Primary outcome measures were the proportion of patients free from relapses and that of patients free from new proton density/T2 lesions at MRI assessment. Several secondary outcome measures were also assessed. Analysis was by intention to treat.
Over 2 years, 49 (51%) individuals administered interferon beta-1b remained relapse-free compared with 33 (36%) given interferon beta-1a (relative risk of relapse 0·76; 95% Cl 0·59–0·9; p=0·03); and 42 (55%) compared with 19 (26%), respectively, remained free from new T2 lesions at MRI (relative risk of new T2 lesion 0·6; 0·45–0·8; p·0<0003). In both groups, the differences between the two treatments increased during the second year. There were also significant differences in favour of interferon beta-1b in most of the secondary outcome measures, including delay of confirmed disease progression.
High-dose interferon beta-1b administered every other day is more effective than interferon beta-1a given once a week.
BackgroundSeveral earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, ...sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread.ObjectiveTo provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD.MethodsData of 1701 patients with IAOD from the Italian Dystonia Registry were analysed.ResultsWomen predominated over men in blepharospasm, oromandibular, laryngeal and cervical dystonia; the sex ratio was reversed in task-specific upper limb dystonia; and no clear sex difference emerged in non-task-specific upper limb dystonia and lower limb dystonia. This pattern was present at disease onset and the last examination. Women and men did not significantly differ for several dystonia-associated features and tendency to spread. In women and men, the absolute number of individuals who developed dystonia tended to increase from 20 to 60 years and then declined. However, when we stratified by site of dystonia onset, different patterns of female-to-male ratio over time could be observed in the various forms of dystonia.ConclusionsOur findings provide novel evidence on sex as a key mediator of IAOD phenotype at disease onset. Age-related sexual dimorphism may result from the varying exposures to specific age-related and sex-related environmental risk factors interacting in a complex manner with biological factors such as hormonal sex factors.
A few earlier observations and recent controlled studies pointed to the possible contribution of thyroid diseases in idiopathic adult-onset dystonia (IAOD). The aim of this study was to investigate ...the association between thyroid status and clinical characteristics of IAOD, focusing on dystonia localization, spread, and associated features such as tremors and sensory tricks. Patients were identified from those included in the Italian Dystonia Registry, a multicentre dataset of patients with adult-onset dystonia. The study population included 1518 IAOD patients. Patients with hypothyroidism and hyperthyroidism were compared with those without any thyroid disease. In the 1518 IAOD patients, 167 patients (11%; 95% CI 9.5–12.6%) were diagnosed with hypothyroidism and 42 (2.8%; 95% CI 1.99–3.74) with hyperthyroidism. The three groups were comparable in age at dystonia onset, but there were more women than men in the groups with thyroid disease. Analysing the anatomical distribution of dystonia, more patients with blepharospasm were present in the hyperthyroidism group, but the difference did not reach statistical significance after the Bonferroni correction. The remaining dystonia-affected body sites were similarly distributed in the three groups, as did dystonia-associated features and spread. Our findings provided novel information indicating that the high rate of thyroid diseases is not specific for any specific dystonia subpopulation and does not appear to influence the natural history of the disease.
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