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.

Abnormalities of the Descending Inhibitory Nociceptive Pathway in Functional Motor Disorders.

BACKGROUND: Pain is a common disabling non-motor symptom affecting patients with functional motor disorders (FMD). OBJECTIVE: We aimed to explore ascending and descending nociceptive pathways with laser evoked potentials (LEPs) in FMD. METHODS: We studied a "bottom-up and top-down" noxious paradigm applying a conditioned pain modulation (CPM) protocol and recorded N2/P2 amplitude in 21 FMD and 20 controls following stimulation of both right arm and leg at baseline (BS) (bottom-up), during heterotopic noxious conditioning stimulation (HNCS) with ice test (top-down) and post-HNCS. RESULTS: We found a normal ascending pathway, but reduced CPM response (lower reduction of the N2/P2 amplitude) in FMD patients, by stimulating both upper and lower limbs. The N2/P2 amplitude ratio*100 (between the HNCS and BS) was significantly higher in patients with FMD than HC. CONCLUSIONS: Our results suggest that pain in FMD possibly reflects a descending pain inhibitory control impairment, therefore, providing a novel venue to explore the pathophysiology of pain in FMD. © 2024 International Parkinson and Movement Disorder Society.

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.

Defect of the Endogenous Inhibitory Pain System in Idiopathic Restless Legs Syndrome: A Laser Evoked Potentials Study.

BACKGROUND: Restless legs syndrome (RLS) is a complex sensorimotor disorder. Symptoms worsen toward evening and at rest and are temporarily relieved by movement. Symptoms are perceived as painful in up to 45% of cases, and nociception system may be involved. OBJECTIVES: To assess the descending diffuse noxious inhibitory control in RLS patients. METHODS: Twenty-one RLS patients and twenty age and sex-matched healthy controls (HC) underwent a conditioned pain modulation protocol. Cutaneous heat stimuli were delivered via laser evoked potentials (LEPs) on the dorsum of the right hand (UL) and foot (LL). N2 and P2 latencies, N2/P2 amplitude and pain ratings (NRS) were recorded before (baseline), during, and after a heterotopic noxious conditioning stimulation (HNCS) application. The baseline/HNCS ratio was calculated for both UL and LL. RESULTS: N2 and P2 latencies did not vary between groups at each condition and limbs. Both groups showed a physiological N2/P2 amplitude and NRS reduction during the HNCS condition in UL and LL in comparison to baseline and post conditions (all, P < 0.003). Between-groups comparisons revealed a significant lower amplitude reduction in RLS at the N2/P2 amplitude during the HNCS condition only for LL (RLS, 13.6 µV; HC, 10.1 µV; P = 0.004). Such result was confirmed by the significant difference at the ratio (RLS, 69%, HC, 52.5%; P = 0.038). CONCLUSIONS: The lower physiological reduction during the HNCS condition at LL in RLS patients suggests a defect in the endogenous inhibitory pain system. Further studies should clarify the causal link of this finding, also investigating the circadian modulation of this paradigm. © 2023 International Parkinson and Movement Disorder Society.

Guillain-Barré syndrome and COVID-19: A 1-year observational multicenter study.

BACKGROUND AND PURPOSE: Many single cases and small series of Guillain-Barré syndrome (GBS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported during the coronavirus disease 19 (COVID-19) outbreak worldwide. However, the debate regarding the possible role of infection in causing GBS is still ongoing. This multicenter study aimed to evaluate epidemiological and clinical findings of GBS diagnosed during the COVID-19 pandemic in northeastern Italy in order to further investigate the possible association between GBS and COVID-19. METHODS: Guillain-Barré syndrome cases diagnosed in 14 referral hospitals from northern Italy between March 2020 and March 2021 were collected and divided into COVID-19-positive and COVID-19-negative. As a control population, GBS patients diagnosed in the same hospitals from January 2019 to February 2020 were considered. RESULTS: The estimated incidence of GBS in 2020 was 1.41 cases per 100,000 persons/year (95% confidence interval 1.18-1.68) versus 0.89 cases per 100,000 persons/year (95% confidence interval 0.71-1.11) in 2019. The cumulative incidence of GBS increased by 59% in the period March 2020-March 2021 and, most importantly, COVID-19-positive GBS patients represented about 50% of the total GBS cases with most of them occurring during the two first pandemic waves in spring and autumn 2020. COVID-19-negative GBS cases from March 2020 to March 2021 declined by 22% compared to February 2019-February 2020. CONCLUSIONS: Other than showing an increase of GBS in northern Italy in the "COVID-19 era" compared to the previous year, this study emphasizes how GBS cases related to COVID-19 represent a significant part of the total, thus suggesting a relation between COVID-19 and GBS.

Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions.

OBJECTIVE: Single cases and small series of Guillain-Barré syndrome (GBS) have been reported during the SARS-CoV-2 outbreak worldwide. We evaluated incidence and clinical features of GBS in a cohort of patients from two regions of northern Italy with the highest number of patients with COVID-19. METHODS: GBS cases diagnosed in 12 referral hospitals from Lombardy and Veneto in March and April 2020 were retrospectively collected. As a control population, GBS diagnosed in March and April 2019 in the same hospitals were considered. RESULTS: Incidence of GBS in March and April 2020 was 0.202/100 000/month (estimated rate 2.43/100 000/year) vs 0.077/100 000/month (estimated rate 0.93/100 000/year) in the same months of 2019 with a 2.6-fold increase. Estimated incidence of GBS in COVID-19-positive patients was 47.9/100 000 and in the COVID-19-positive hospitalised patients was 236/100 000. COVID-19-positive patients with GBS, when compared with COVID-19-negative subjects, showed lower MRC sum score (26.3±18.3 vs 41.4±14.8, p=0.006), higher frequency of demyelinating subtype (76.6% vs 35.3%, p=0.011), more frequent low blood pressure (50% vs 11.8%, p=0.017) and higher rate of admission to intensive care unit (66.6% vs 17.6%, p=0.002). CONCLUSIONS: This study shows an increased incidence of GBS during the COVID-19 outbreak in northern Italy, supporting a pathogenic link. COVID-19-associated GBS is predominantly demyelinating and seems to be more severe than non-COVID-19 GBS, although it is likely that in some patients the systemic impairment due to COVID-19 might have contributed to the severity of the whole clinical picture.

Very early and early neurophysiological abnormalities in Guillain-Barré syndrome: A 4-year retrospective study.

BACKGROUND AND PURPOSE: In its initial stages, Guillain-Barré syndrome (GBS) is difficult to identify, because diagnostic criteria may not always be fulfilled. With this retrospective study, we wanted to identify the most common electrophysiological abnormalities seen on neurophysiological examination of GBS patients and its variants in the early phases. METHODS: We reviewed the clinical records of patients admitted to our Neurology Unit with a confirmed diagnosis of GBS. The study sample was divided in two subgroups according to whether the neurophysiological examination was performed: within 7 days (very early group) or within 7-15 days (early group). H reflex, F waves, and motor and sensory conduction parameters were judged abnormal if they were outside the normal range for at least two nerves. We evaluated neurophysiological findings in Miller-Fisher syndrome (MFS) separately. RESULTS: The study sample comprised 36 patients. In GBS, the most frequent abnormal neurophysiological parameter was the bilateral absence of the H reflex, followed by F wave abnormalities. Motor conduction parameters were altered in less than 50% of patients, and even less common were sensory nerve action potential reduction and the "sural-sparing" pattern. In MFS, H reflex was absent bilaterally in 100% of patients, followed by a predominant peripheral sensory involvement, whereas motor conduction parameters were frequently normal. CONCLUSIONS: Bilateral absence of the H reflex is the most sensitive parameter in early diagnosis of GBS and its variants.

Feasibility of cerebello-cortical stimulation for intraoperative neurophysiological monitoring of cerebellar mutism.

BACKGROUND: Cerebellar mutism can occur in a third of children undergoing cerebellar resections. Recent evidence proposes it may arise from uni- or bilateral damage of cerebellar efferents to the cortex along the cerebello-dento-thalamo-cortical pathway. At present, no neurophysiological procedure is available to monitor this pathway intraoperatively. Here, we specifically aimed at filling this gap. METHODS: We assessed 10 patients undergoing posterior fossa surgery using a conditioning-test stimulus paradigm. Electrical conditioning stimuli (cStim) were delivered to the exposed cerebellar cortex at interstimulus intervals (ISIs) of 8-24 ms prior to transcranial electric stimulation of the motor cortex, which served as test stimulus (tStim). The variation of motor-evoked potentials (MEP) to cStim + tStim compared with tStim alone was taken as a measure of cerebello-cortical connectivity. RESULTS: cStim alone did not produce any MEP. cStim preceding tStim produced a significant inhibition at 8 ms (p < 0.0001) compared with other ISIs when applied to the lobules IV-V-VI in the anterior cerebellum and the lobule VIIB in the posterior cerebellum. Mixed effects of decrease and increase in MEP amplitude were observed in these areas for longer ISIs. CONCLUSIONS: The inhibition exerted by cStim at 8 ms on the motor cortex excitability is likely to be the product of activity along the cerebello-dento-thalamo-cortical pathway. We show that monitoring efferent cerebellar pathways to the motor cortex is feasible in intraoperative settings. This study has promising implications for pediatric posterior fossa surgery with the aim to preserve the cerebello-cortical pathways and thus prevent cerebellar mutism.

Effects of safinamide on pain in Parkinson's disease with motor fluctuations: an exploratory study.

Pain is a common and disabling non-motor symptom (NMS) of Parkinson's disease (PD), which occurs through the course of the disease, often unrecognized and undertreated. For this study, we evaluated the efficacy and safety of safinamide to reduce pain in PD patients with motor fluctuations. A total of 13 PD patients with pain receiving safinamide (Xadago®, 100 mg/daily) were prospectively evaluated for 12 weeks. The primary outcome measures were changes in the total score of the King's Pain Scale for Parkinson's Disease (KPPS), Brief Pain Inventory (BPI) Intensity and Interference, and the Numeric Rating Scale (NRS). Secondary outcomes were the proportion of pain responders, changes in the Clinical Global Impression of Change (CGI), the Parkinson's disease Quality of Life 39 (PDQ39), the Unified Parkinson's Disease Rating Scale parts III and IV (UPDRS III and IV), and laser-evoked potentials (LEPs). LEPs were used to assess potential changes in the central processing of nociceptive inputs. The safety profile was evaluated based on the occurrence of treatment-emergent side effects and the dropout rate. After 12 weeks of add-on safinamide therapy, a significant improvement was noted in the primary (KPPS, BPI Intensity and interference, and NRS) and the secondary outcomes (UPDRS III, IV, CGI, and PDQ39). No significant changes in LEP complexes were observed. All patients completed the study and no treatment-emergent side effects were reported. Our preliminary findings suggest that safinamide 100 mg/day may be effective for the management of pain in PD patients with motor fluctuations and is safe. Further randomized controlled trials are needed to confirm its efficacy.

Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.

Intra-operative neurophysiological mapping and monitoring during brain tumour surgery in children: an update.

INTRODUCTION: Over the past decade, the reluctance to operate in eloquent brain areas has been reconsidered in the light of the advent of new peri-operative functional neuroimaging techniques and new evidence from neuro-oncology. To maximise tumour resection while minimising morbidity should be the goal of brain surgery in children as much as it is in adults, and preservation of brain functions is critical in the light of the increased survival and the expectations in terms of quality of life. DISCUSSION: Intra-operative neurophysiology is the gold standard to localise and preserve brain functions during surgery and is increasingly used in paediatric neurosurgery. Yet, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation, and some technical aspects need to be tailored for its use in children, especially in infants. This paper will review the most recent advances in the field of intra-operative neurophysiology (ION) techniques during brain surgery, focussing on those aspects that are relevant to the paediatric neurosurgery practice.

Antidromic sensory nerve conduction study of the digital branches of the medial plantar nerve: a novel method to detect early diabetic sensory axonal polyneuropathy.

INTRODUCTION: Distal sensory neuropathy is the most common form of diabetic neuropathy. We developed a novel antidromic technique for assessment of distal nerve function for early diagnosis of diabetic neuropathy. METHODS: Diabetic and control groups underwent standard and more distal sensory nerve conduction studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital branches of the medial plantar nerve were recorded with our method after stimulation at the sole and recording from digits I and II. RESULTS: Comparison between controls and diabetics showed a statistically significant difference in mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs was obtained with our technique than with either conventional or more distal NCS in all patients. CONCLUSIONS: As compared with clinical evaluation and other NCS, our antidromic stimulation was the most sensitive method to detect abnormal sensory nerve conduction in symptomatic and asymptomatic diabetic patients.

Aristotle's illusion reveals interdigit functional somatosensory alterations in focal hand dystonia.

In focal hand dystonia, the cortical somatosensory representation of the fingers is abnormal, with overlapping receptive fields and reduced interdigit separation. These abnormalities are associated with deficits in sensory perception, as previously demonstrated by applying tactile stimuli to one finger at a time. What is still unknown is whether the sensory deficits can be observed when tactile perception involves more than one finger. To address this issue, we applied 'Aristotle's illusion' to 15 patients with focal hand dystonia, 15 patients with dystonia not affecting the hand (blepharospasm and cervical dystonia) and 15 healthy control subjects. In this illusion, one object touching the contact point of two crossed fingertips is perceived as two objects by a blindfolded subject. The same object placed between two parallel fingertips is correctly perceived as one. The illusory doubling sensation is because of the fact that the contact point between the crossed fingers consists of non-adjacent and functionally unrelated skin regions, which usually send sensory signals to separate spots in the somatosensory cortex. In our study, participants were touched by one sphere between the second-third digits, the second-fourth digits and the fourth-fifth digits of both hands, either in crossed or in parallel position, and had to refer whether they felt one or two stimuli. The percentage of 'two stimuli' responses was an index of the illusory doubling. Both healthy control subjects and dystonic patients presented Aristotle's illusion when the fingers were crossed. However, patients with focal hand dystonia presented a significant reduction of the illusion when the sphere was placed between the crossed fourth and fifth digits of the affected hand. This reduction correlated with the severity of motor disease at the fingers. Similar findings were not observed in non-hand dystonia and control groups. The reduction of Aristotle's illusion in non-affected fingers and its preservation in affected fingers suggests dissociation between the abnormal processing of sensory signals and the motor impairment. Based on previous evidence showing that the sensory signals coming from the fourth digit determine lower activation in the somatosensory cortex than those coming from the fifth digit, we suggest that in the crossed position, the tactile information conveyed by the fifth digit prevailed over the fourth digit, thus resulting in the perception of one stimulus. The reduction of the illusory doubling perception, therefore, may represent the functional correlate of the different level of activation between the fourth and the fifth digit in the somatosensory cortex.

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.

Intraoperative Neurophysiological Monitoring in Tethered Cord Syndrome Surgery: Predictive Values and Clinical Outcome.

INTRODUCTION: "Tethered cord syndrome" (TCS) refers to a congenital abnormality associated with neurological signs and symptoms. The aim of surgery is to prevent or arrest their progression. This study reports a retrospective case series of tethered cord syndrome surgeries, supported by intraoperative neurophysiological monitoring. METHODS: The case series comprises 50 surgeries for tethered cord syndrome in which multimodal intraoperative neurophysiological monitoring was performed using motor evoked potentials (transcranial motor evoked potentials [TcMEPs]), tibial nerve somatosensory evoked potentials (TNSEPs), and pudendal-anal reflex (PAR). The intraoperative neurophysiological monitoring results are reported and correlated with clinical outcomes. RESULTS: Sensitivity, specificity, and negative predictive value were high for TcMEPs and TNSEPs, while PAR exhibited low sensitivity and positive predictive value but high specificity and negative predictive value. Fisher's exact test revealed a significant correlation between changes in TcMEPs, TNSEPs, and clinical outcome ( P < 0.000 and P = 0.049 respectively), but no correlation was detected between PAR and urinary/anal function ( P = 0.497). CONCLUSIONS: While TcMEPs and TNSEPs were found to be reliable intraoperative neurophysiological monitoring parameters during tethered cord syndrome surgery, PAR had low sensitivity and positive predictive value probably because the reflex is not directly related to bladder function and because its multisynaptic pathway may be sensitive to anesthetics. New onset muscle weakness and sensory deficits were related to postoperative changes in TcMEPs and TNSEPs, whereas changes in PAR did not predict bladder/urinary impairment. Urinary deficits may be predicted and prevented with other neurophysiological techniques, such as the bladder-anal reflex.

Intraoperative neurophysiology in tethered cord surgery: techniques and results.

INTRODUCTION: Intraoperative neurophysiologic monitoring (IOM) is nowadays extensively used to minimize neurological morbidity in tethered cord surgery. Our goal is to describe and discuss the standard IOM techniques used during these surgical procedures and to summarize our clinical experience using a multimodal IOM approach. MATERIAL AND METHODS: Neurophysiological mapping of the conus-cauda is performed through direct stimulation of these structures and bilateral recording from segmental target muscles. While mapping identifies ambiguous neural structures, their functional integrity during surgery can be assessed by monitoring techniques only, such as somatosensory evoked potentials (SEPs), transcranial motor-evoked potentials (MEPs) from the limb muscles and anal sphincters, and the bulbocavernosus reflex (BCR). RESULTS: Between 2002 and 2012, we performed 48 surgical procedures in 47 patients with a tethered cord secondary to a variety of spinal dysraphisms. The monitorability rate was 84 % for SEPs, 97 % for limb muscle MEPs, 74 % for the anal sphincter MEPs, and 59 % for the BCR. In all patients but one, SEP, MEP, and BCR remained stable during surgery. Postoperatively, two out of 47 patients presented a significant-though transient-neurological worsening. In six patients, an unexpected muscle response was evoked by stimulating tissue macroscopically considered as not functional. CONCLUSIONS: Mapping techniques allow identifying and sparing functional neural tissue and vice versa to cut nonfunctional structures that may contribute to cord tethering. Monitoring techniques, MEP and BCR in particular, improve the reliability of intraoperative neurophysiology, though these may require a higher degree of neuromonitoring expertise. IOM minimizes neurological morbidity in tethered cord surgery.

Intraoperative cortical mapping of visuospatial functions in parietal low-grade tumors: changing perspectives of neurophysiological mapping.

OBJECT: The aim of this study was to explore the feasibility of intraoperative visuospatial mapping with the same criteria currently used to define essential language areas. METHODS: The authors compared surgical procedures in 2 patients with similar tumors (Grade II oligodendroglioma in the right parietal lobe) undergoing awake, image-assisted surgery for lesion removal with intraoperative neurophysiological monitoring. The line bisection task was used in both patients but with different criteria. RESULTS: In the first case, the authors respected any area, even within the tumor, where significant interference was found (a stimulation-induced error in 2 of 3 applications defined an essential area). In the second case, they removed 1 essential area located in the tumor and recorded an uneventful clinical response soon thereafter. They continued to monitor the patient without stimulation and stopped the resection when the patient was close to the criteria valid for defining spatial neglect. The signs of spatial neglect were present for 3 days postoperatively and then cleared spontaneously. Subtotal tumor removal was achieved in both cases. CONCLUSIONS: Evidence in the present study reveals that areas for visuospatial functions cannot be assessed with the same criteria used for language functions, since essential areas located in the tumor can be safely removed.

Do cerebrovascular risk factors impact the clinical expression of idiopathic isolated adult-onset dystonia?

BACKGROUND: Although acquired dystonia may develop following ischaemic/haemorrhagic stroke, the relationship between cerebrovascular disease and idiopathic dystonia has been poorly investigated. This cross sectional study aimed at evaluating the impact of cerebrovascular risk factors on the clinical expression of idiopathic adult onset dystonia (IAOD), with reference to dystonia localization and dystonia-associated features. METHODS: Data were obtained from the Italian Dystonia Registry. Patients with IAOD were stratified into two groups according to the presence of diabetes mellitus and/or arterial hypertension and/or dyslipidemia and/or heart disease. The two groups were compared for demographic features, dystonia phenotype, and dystonia-associated features (sensory trick, tremor, eye symptoms in blepharospasm, and neck pain in cervical dystonia). RESULTS: A total of 1108 patients participated into the study. Patients who reported one cerebrovascular factor or more (n = 555) had higher age and longer disease duration than patients who did not. On multivariable logistic regression analysis, blepharospasm was the only localization, and sensory trick was the only dystonia-associated feature that was significantly associated with cerebrovascular risk factors. Linear regression analysis showed that the strength of the association between cerebrovascular factors and blepharospasm/sensory trick increased with increasing the number of cerebrovascular factors per patient. CONCLUSIONS: Results of the present study showed that cerebrovascular risk factors may be associated with specific features of IAOD that is development of blepharospasm and sensory trick. Further studies are needed to better understand the meaning and the mechanisms underlying this association.