Tango classes in people with Multiple Sclerosis (PwMS): Impact on motor and non-motor functions.

BACKGROUND: While music-based therapy (MBT) has been shown to improve motor and non-motor features in multiple sclerosis (MS), benefits of tango have never been assessed. OBJECTIVE: To evaluate the benefits of tango classes on quality of life (QoL), mood, fatigue, gait, balance, perception of cognitive disorder and sexuality in people with MS. METHODS: 7 participants (age 41.14 ± 14.27 years, disease duration 14.14 ± 7.6 years) and respective partners undertook one-hour weekly classes for 20 weeks. Participants had early-stage MS (EDSS<3.5). They were assessed for mood (ZUNG rating scale; Beck Depression Inventory -II); balance (Berg Balance Test; Tinetti scale), cognition (MS Neuropsychological Screening Questionnaire), SD (Multiple Sclerosis Intimacy and Sexuality Questionnaire), fatigue (Fatigue Severity Scale) and QoL (36-Item Short Form Survey). RESULTS: Group comparison of pre-post change scores showed a general improvement in all the outcome measures, which was significant in mood, SD, cognition and QoL. DISCUSSIONS AND CONCLUSION: Tango classes provides benefits to pwMS, especially on non-motor symptoms. Follow-up assessment is required to confirm the durability of these effects.

Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family.

BACKGROUND: SPG18 is caused by mutations in the endoplasmic reticulum lipid raft associated 2 (ERLIN2) gene. Autosomal recessive (AR) mutations are usually associated with complicated hereditary spastic paraplegia (HSP), while autosomal dominant (AD) mutations use to cause pure SPG18. AIM: To define the variegate clinical spectrum of the SPG18 and to evaluate a dominant negative effect of erlin2 (encoded by ERLIN2) on oligomerization as causing differences between AR and AD phenotypes. METHODS: In a four-generation pedigree with an AD pattern, a spastic paraplegia multigene panel test was performed. Oligomerization of erlin2 was analyzed with velocity gradient assay in fibroblasts of the proband and healthy subjects. RESULTS: Despite the common p.V168M mutation identified in ERLIN2, a phenoconversion to amyotrophic lateral sclerosis (ALS) was observed in the second generation, pure HSP in the third generation, and a complicated form with psychomotor delay and epilepsy in the fourth generation. Erlin2 oligomerization was found to be normal. DISCUSSION: We report the first AD SPG18 family with a complicated phenotype, and we ruled out a dominant negative effect of V168M on erlin2 oligomerization. Therefore, our data do not support the hypothesis of a relationship between the mode of inheritance and the phenotype, but confirm the multifaceted nature of SPG18 on both genetic and clinical point of view. Clinicians should be aware of the importance of conducting an in-depth clinical evaluation to unmask all the possible manifestations associated to an only apparently pure SPG18 phenotype. We confirm the genotype-phenotype correlation between V168M and ALS emphasizing the value of close follow-up.

Does sex influence the natural history of idiopathic adult-onset dystonia?

BACKGROUND: Several 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. OBJECTIVE: To provide accurate information on the relationship between sex differences, motor phenomenology, dystonia-associated features and the natural history of IAOD. METHODS: Data of 1701 patients with IAOD from the Italian Dystonia Registry were analysed. RESULTS: Women 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. CONCLUSIONS: Our 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.

Oromandibular dystonia: from onset to spread a multicenter italian study.

BACKGROUND: Detailed information about the epidemiological and phenomenological differences among the aetiological subtypes of oromandibular dystonia (OMD) is lacking. Moreover, the OMD tendency to spread to other body sites has never been investigated. AIM: To compare the main demographic and clinical features of OMD in different aetiological groups and assess the risk of spread. MATERIALS AND METHODS: We retrospectively analysed data from patients contained in the Italian Dystonia Registry. The risk of spread was assessed by Kaplan Meyer curves and Cox regression analysis. RESULTS: The study included 273 patients (175 women) aged 55.7 years (SD 12.7) at OMD onset. Female predominance was observed. Idiopathic dystonia was diagnosed in 241 patients, acquired dystonia in 22. In 50/273 patients, dystonia started in the oromandibular region (focal OMD onset); in 96/273 patients the onset involved the oromandibular region and a neighbouring body site (segmental/multifocal OMD onset); and in 127/273 patients OMD was a site of spread from another body region. Sensory trick (ST) and positive family history predominated in the idiopathic group. No dystonia spread was detected in the acquired group, whereas spread mostly occurred within the first five years of history in 34% of the focal OMD onset idiopathic patients. Cox regression analysis revealed ST as a significant predictor of spread (HR, 12.1; 95% CI, 2.5 - 18.8; P = 0.002). CONCLUSION: This large study provides novel information about the clinical phenomenology of idiopathic and acquired OMD. We pointed out a possible role of oestrogens in favouring dystonia development. Moreover, we described for the first time the association between ST and dystonia spread, revealing possible common pathophysiological mechanisms. Our findings may be suggested as a referral point for future pathophysiological and therapeutic studies on OMD.

Does thyroid diseases contribute to the natural history of idiopathic adult-onset dystonia? Data from the Italian Dystonia Registry.

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.

The long-term response to botulinum toxin injections in patients with blepharospasm undergoing upper eyelid surgery.

BACKGROUND: Upper eyelid surgery (UES) is a therapeutical strategy used for those patients affected by blepharospasm (BSP) who either do not respond or experience a gradual decrease in responsiveness to botulinum toxin (BoNT) injections. Nevertheless, most of them need to restart with BoNT despite the intervention. AIM: To evaluate the long-term post-surgical response to BoNT in patients with BSP and to identify predictive factors associated to treatment outcome. METHODS: We collected data of 60 BS patients, divided into two groups - blepharoplasty YES (8) and NO (52), collecting demographic - age, sex - and clinical data -disease duration, duration of the treatment with BoNT. Respective responses to injections - evaluated through the differences of both Jancovic Rating Scale and the Blepharospasm Disability Index pre and post BoNT (delta JRS and delta BSDI) just before their periodic three-month injection and after 1 month from it - were compared. Finally, clinical and demographics variables were included in multivariate regression and correlation analyses to assess their impact on the long-term response to injections. RESULTS: Patients who underwent UES had significantly lower delta at both scales, showing a poorer outcome after BoNT treatment. No variable was found to be associated with the response. DISCUSSION: Our data seem to suggest that surgery does not improve response to BoNT injections on the long run. As such, UES could be considered as an efficacious treatment in BSP just if evaluated soon after its performing. Long-term BSP management seems still difficult to be performed adequately and new therapeutical approaches are still needed.