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.

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.

Movement disorders following mechanical thrombectomy resulting in ischemic lesions of the basal ganglia: An emerging clinical entity.

BACKGROUND AND PURPOSE: Post-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). METHODS: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. RESULTS: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. CONCLUSION: Post-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge.

Social cognition in Parkinson's disease and functional movement disorders.

INTRODUCTION: Functional movement disorders (FMD) can overlap with Parkinson's disease (PD), and distinguishing between the two clinical conditions can be complex. Framing social cognition (theory of mind) (TOM) disorder, attention deficit, and psychodynamic features of FMD and PD may improve diagnosis. METHODS: Subjects with FMD and PD and healthy controls (HC) were administered tasks assessing TOM abilities and attention. The psychodynamic hypothesis of conversion disorder was explored by a questionnaire assessing dissociative symptoms. A comprehensive battery of neuropsychological tasks was also administered to FMD and PD. RESULTS: Although both FMD and PD scored lower than HC on all TOM tests, significant correlations between TOM and neuropsychological tasks were found only in PD but not in FMD. Only PD showed a reduction in attentional control. Dissociative symptoms occurred only in FMD. DISCUSSION: Cognitive-affective disturbances are real in FMD, whereas they are largely dependent on cognitive impairment in PD. Attentional control is preserved in FMD compared to PD, consistent with the hypothesis that overload of voluntary attentional orientation may be at the basis of the onset of functional motor symptoms. On a psychodynamic level, the confirmation of dissociative symptoms in FMD supports the conversion disorder hypothesis. CONCLUSION: FMD and PD can be distinguished on an affective and cognitive level. At the same time, however, the objective difficulty often encountered in distinguishing between the two pathologies draws attention to how blurred the boundary between 'organic' and 'functional' can be.

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.

Intraoperative microelectrode recording during asleep deep brain stimulation of subthalamic nucleus for Parkinson Disease. A case series with systematic review of the literature.

The use of microelectrode recording (MER) during deep brain stimulation (DBS) for Parkinson Disease is controversial. Furthermore, in asleep DBS anesthesia can impair the ability to record single-cell electric activity.The purpose of this study was to describe our surgical and anesthesiologic protocol for MER assessment during asleep subthalamic nucleus (STN) DBS and to put our findings in the context of a systematic review of the literature. Sixty-three STN electrodes were implanted in 32 patients under general anesthesia. A frameless technique using O-Arm scanning was adopted in all cases. Total intravenous anesthesia, monitored with bispectral index, was administered using a target controlled infusion of both propofol and remifentanil. A systematic review of the literature with metanalysis on MER in asleep vs awake STN DBS for Parkinson Disease was performed. In our series, MER could be reliably recorded in all cases, impacting profoundly on electrode positioning: the final position was located within 2 mm from the planned target only in 42.9% cases. Depth modification > 2 mm was necessary in 21 cases (33.3%), while in 15 cases (23.8%) a different track was used. At 1-year follow-up we observed a significant reduction in LEDD, UPDRS Part III score off-medications, and UPDRS Part III score on medications, as compared to baseline. The systematic review of the literature yielded 23 papers; adding the cases here reported, overall 1258 asleep DBS cases using MER are described. This technique was safe and effective: metanalysis showed similar, if not better, outcome of asleep vs awake patients operated using MER. MER are a useful and reliable tool during asleep STN DBS, leading to a fine tuning of electrode position in the majority of cases. Collaboration between neurosurgeon, neurophysiologist and neuroanesthesiologist is crucial, since slight modifications of sedation level can impact profoundly on MER reliability.

Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease.

INTRODUCTION: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood. Here we aimed at reporting the results of a large PD population screening with dried blood spot tests for GD. METHODS: We measured GCase activity and GlcSph levels in 1344 PD patients with dried blood spot tests, and performed GBA1 genetic sequencing. RESULTS: While the GCase activity was reduced in GBA1-PD carriers compared to wild type PD, GlcSph was increased in GBA1-PD compared to GBA1-controls, regardless of the underlying type of GBA1 variant. 13.6 % and 0.4 % of PD patients had mono- or biallelic GBA1 mutations respectively. GCase deficiency, lipid accumulation and clinical manifestations of GD was detected in five PD patients with biallelic GBA1 mutations, of whom four had a risk combined with a GD causing variant. CONCLUSIONS: GlcSph appearing higher in PD may represent a reliable biomarker of the disease and deserves to be further investigated. This study highlights the importance of screening PD patients for possible underlying GD, which is a treatable condition that should not be missed. We diagnosed GD cases carrying a "risk" variant in one allele, which is an unprecedented finding deserving further investigation.