Comprehensive Cardiovascular Management of Myotonic Dystrophy Type 1 Patients: A Report from the Italian Neuro-Cardiology Network.

Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network-"Rete delle Neurocardiologie" (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of myotonic dystrophy type 1 (MD1).

Outcome After Acute Ischemic Stroke Treatment During Covid-19 Outbreak in South-East Tuscany.

BACKGROUND: During Covid-19 pandemic, the Italian National Healthcare Service has faced increasing pressure, especially in Northern Italy. Even in less-affected regions, such as Tuscany, the changes in the healthcare system to prevent Covid-19 spread resulted in difficulty in treating time-dependent disorders like ischemic stroke rapidly. OBJECTIVE: The aim of our study was to assess the outcome after acute ischemic stroke treatments during the Covid-19 spread in comparison with a similar period of the previous year in Siena-Hospital (Hub center in the South-East Tuscany). METHODS: We enrolled all patients admitted to Siena-Hospital for ischemic stroke and submitted them to acute treatments (intravenous and/or mechanical thrombolysis) between February 21st and May 18th, 2020 (study group, n:38) and compared the results with ischemic strokes acutely treated in a similar period in 2019 (control group, n:39). The modified Rankin scale score was assessed at 90 days to evaluate a 3-month clinical outcome. RESULTS: In the study group, the time from symptoms onset to hospital arrival and the door-to-groin puncture time were significantly more prolonged than in the control group. In moderate-severe strokes, the 3-month mortality was significantly higher in the study group (31% vs. 6%; p=0.01), and the number of patients with poor functional outcomes was significantly higher in the study group (73% vs. 44%; p=0.03). CONCLUSION: During the lockdown period due to Covid-19 pandemic, patients with acute ischemic stroke had a worse prognosis. These findings suggest the need to improve the health system organization to guarantee an appropriate treatment during the pandemic, including the patients that are not affected by Covid-19.

Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the natural history and outcomes after treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: This was a multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria recruited through the Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease ßiomarkers International Network from January 2013 to March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, gradient recalled echo-T2*, fluid-suppressed T2-weighted (fluid-attenuated inversion recovery), and T1 postgadolinium contrast-enhanced images acquired on 1.5T MRI, was used at the 3-, 6-, 12-, and 24-month follow-up. Centralized reads of MRIs were performed by investigators blinded to clinical, therapeutic, and time-point information. Main outcomes were survival, clinical and radiologic recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri. RESULTS: The study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri). Their mean age was 72.9 years; 43.4% were female; 37.1% were APOEε4 carriers; 36.3% had a history of Alzheimer disease; and 33.6% had a history of ICH. A history of ICH and the occurrence of new ICH at follow-up were more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%, p < 0.0001 and 19.3% vs 3.6%, p < 0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% confidence interval [CI] 61.6%-78.5%) and 84.1% (95% CI 76.2%-90.6%) clinically recovered within 3 and 12 months, followed by radiologic recovery in 45.1% (95% CI 36.4%-54.8%) and 77.4% (95% CI 67.7%-85.9%), respectively. After clinicoradiologic resolution of the first-ever episode, 38.3% (95% CI 22.9%-59.2%) had at least 1 recurrence within the following 24 months. Recurrence was more likely if IV high-dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering off (hazard ratio 4.68, 95% CI 1.57-13.93; p = 0.006). DISCUSSION: These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in ß-amyloid-driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.

Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort.

BACKGROUND: Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes. OBJECTIVES: To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients. METHODS: A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria. RESULTS: Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age ± SD 65.6 ± 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)]. CONCLUSIONS: Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD.

The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson's disease.

OBJECTIVES: To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson's disease at early stages. METHODS: A total of 385 Parkinson's disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). RESULTS: As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. CONCLUSIONS: Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson's disease may impact disease phenotype.

Appropriateness, safety, and effectiveness of "drip and ship" teleconsultation model in Southeastern Tuscany: a feasibility study.

PURPOSE: Teleconsultation is a consultation between two or more physicians about the diagnostic work-up and therapeutic strategy in the treatment of an individual case by means of modern telematics. 'Drip-and-ship' teleconsultation model consists of the transfer of patients, through telematics stroke networks, with large arteries occlusions from primary to comprehensive stroke centers equipped for endovascular therapy. We retrospectively investigated appropriateness, safety, and effectiveness of 'drip-and-ship' teleconsultation model in a rural area of Tuscany. METHODS: Outcome measures were: door-to-ship time (including door-to-needle time), ratio of number treated/total sent patients, adverse events/mortality during transfer, and mortality and modified Rankin scale at 90 days. Analysis of non-treated patients was also done. RESULTS: Seventy-eight patients were included; 16/78 patients were sent for endovascular therapy alone, and 62/78 for "drip-and-ship"; 12 patients were not treated. Door-to-ship, and door-to-needle times (mean ± SD) were 105 ± 29.8 and 62.5 ± 37.5 min, respectively. The ratio number of treated/total sent patients was 0.85. At 90 days, the global mortality rate was 21%, and 40% of patients showed favorable outcome. The main cause of non-treatment was spontaneous recanalization. CONCLUSIONS: The high value for treated/total sent patients' ratio underlines that "drip-and-ship" teleconsultation model is appropriate and effective, with a few untreated patients. The model is safe, without adverse events during transfer. Taken together, our outcomes are in line with the previous reports. "Drip-and-ship" teleconsultation model is safe and effective in rural areas, allowing good selections and rapid treatments for stroke patients, based on the transfer from the primary to the comprehensive stroke center.

Paraneoplastic movement disorders: phenomenology, diagnosis, and treatment.

Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a heterogeneous group of syndromes encompassing both hyperkinetic and hypokinetic conditions, characterized by acute/sub-acute onset, rapidly progressive evolution, and multifocal localizations with several overlapping features. These movement disorders are immune-mediated, as shown by the rapid onset and by the presence of antineuronal antibodies in biological samples of patients, fundamental for the diagnosis. Antineuronal antibodies could be targeted against intracellular or neuronal surface antigens. Paraneoplastic movement disorders associated with anti-neuronal surface antigens antibodies respond more frequently to immunotherapy. The underlying tumors may be different, according to the clinical presentation, age, and gender of patients. Our search considered articles involving human subjects indexed in PubMed. Abstracts were independently reviewed for eligibility criteria by one author and validated by at least one additional author. In this review, we sought to critically reappraise the clinical features and the pathophysiological mechanisms of paraneoplastic movement disorders, focusing on diagnostic and therapeutic strategies. Our main aim is to make clinicians aware of paraneoplastic movement disorders, and to provide assistance in the early diagnosis and management of these rare but life-threatening conditions.

[The dawn era in the management of acute ischemic stroke and its health policy implications. Should interventional cardiologists be involved?] / La nuova era nel trattamento dell'ictus e le sue implicazioni socio-sanitarie. I cardiologi interventisti dovrebbero essere coinvolti?

Similarly to what happened for myocardial infarction treatment during the two previous decades, ischemic stroke therapy has radically changed in recent years after the encouraging clinical results on the use of mechanical revascularization systems. The ever-increasing use of thrombectomy, which is now the first-choice approach for achieving rapid reperfusion of the ischemic brain, inaugurates a new era in the treatment of ischemic stroke, with important social and healthcare implications and the need for effective integrated stroke networks on a regional basis.Given the high annual rates of stroke and that approximately 35% of strokes are caused by the thrombotic occlusion of a large cerebral vessel, with a treatment window reaching up to 24 h after onset in selected cases, the resources of interventional neuroradiology are not enough to meet treatment needs in terms of performing centers and number of operators. The possibility of using centers already active for the treatment of acute myocardial infarction has therefore been taken into consideration. This article presents objective data to support the validity of this strategy and discusses how to create treatment networks using the interventional skills of cardiologists with the implementation of multidisciplinary functional structures.

Headache secondary to cervical artery dissections: practice pointers.

Cervical artery dissections may present with mild and misleading symptoms such as a headache or cervical pain. In the absence of early diagnosis and therapy, such patients may have a high risk of cerebrovascular events. In order to refine evaluation of cervical artery dissections, we report the experience of a single center, focusing on clinical findings (e.g., headache and pain-related features at onset). From 2012 to 2017, 49 patients with cervical arteries dissections were admitted to our institution; 28 out of 49 patients (57%) presented with a headache or cervical pain, which were evaluated according to the International Classification of Headache Disorders (ICHD-III beta). Item C3a of ICHD-III beta ("pain is severe and continuous for days or longer") was present in all patients symptomatic for a headache. Another common characteristic was the recent onset, with an average (± SD) timing from the onset of a headache to the first neurologic evaluation of 3 (± 2) days (range 1-5). A refined clinical evaluation of patients presenting with a headache at the Emergency Department could improve the early detection and management of patients with cervical artery dissections, in particular when presenting without other associated neurological symptoms.

Impulse control disorders in advanced Parkinson's disease with dyskinesia: The ALTHEA study.

BACKGROUND: Impulse control disorders and dyskinesia are common and disabling complications of dopaminergic treatment in Parkinson's disease. They may coexist and are possibly related. The objectives of this study were to assess the frequency and severity of impulse control disorders in Parkinson's disease patients with dyskinesia. METHODS: The ALTHEA study enrolled 251 Parkinson's disease patients with various degrees of dyskinesia severity from 11 movement disorders centers in Italy. Each patient underwent a comprehensive assessment including Unified Dyskinesia Rating Scale and the Questionnaire for Impulsive Compulsive Disorders in Parkinson Disease-Rating Scale. RESULTS: There was an overall 55% frequency of impulse control disorder and related behaviors (36% were clinically significant). The positive patients were younger at disease diagnosis and onset and had higher Unified Dyskinesia Rating Scale historical and total score (P = 0.001 and P = 0.02, respectively, vs negative). There was an increased frequency of clinically significant impulse control disorders in patients with severe dyskinesia (P = 0.013), a positive correlation between the questionnaire total score and dopamine agonist dose (P = 0.018), and a trend with levodopa dose. CONCLUSIONS: More than half of Parkinson's disease patients with dyskinesia have impulse control disorders and related behaviors, which are frequently clinically significant. Dopaminergic therapy total dose is associated with their severity. Clinicians should carefully assess patients with maladaptive behaviors and dyskinesia because they do not properly evaluate their motor and nonmotor status. © 2017 International Parkinson and Movement Disorder Society.

Head trauma and Parkinson's disease: results from an Italian case-control study.

We evaluated the possible association between head trauma and Parkinson's disease (PD). The FRAGAMP (Fattori di Rischio Ambientali e Genetici Associati alla Malattia di Parkinson) study is a large Italian multicenter case-control study carried out to evaluate the possible role of environmental and genetic factors in PD. Cases and controls were enrolled from six movement disorders centers located in the Central-Southern Italy. A standardized questionnaire was administered to record demographic, epidemiological, and clinical data. Positive history of head trauma was considered only if the head trauma preceded the onset of PD. All cases and controls underwent a standard neurological examination. Adjusted ORs and 95% CI were estimated using multivariate analysis (logistic regression). Four hundred ninety-two PD patients (292 men and 200 women) and 459 controls (160 men and 299 women) were enrolled in the study. A positive history for head trauma was reported by 106 (21.5%) PD patients and by 62 (13.5%) healthy controls. Multivariate analysis (OR adjusted by age, sex, family history, coffee smoking, and alcohol consumption) showed a significant positive association between PD and head trauma with an adjusted OR of 1.50 (95%CI 1.04-2.17; p value 0.03). In agreement with literature data, our study supports the positive association between head trauma and PD.

Percutaneous transbiliary biopsy.

Percutaneous drainage of the bile ducts is an established procedure for malignant obstructions, in which a histological diagnosis is often not obtained. We describe the biopsy technique of obstructive lesions through biliary drainage access, using a 7F endoscopic biopsy forceps, widely available; some are even reusable. This technique applies to lesions of the hepatic ducts, of the common hepatic duct and of all extension of the common bile duct. RESUMO A drenagem percutânea das vias biliares é um procedimento estabelecido para obstruções malignas, nos quais, muitas vezes, não se consegue um diagnóstico histológico. Descrevemos a técnica de biópsia da lesão obstrutiva através do acesso de drenagem biliar, utilizando um fórcipe de biópsia endoscópica 7F, amplamente disponível e alguns reutilizáveis. Esta técnica aplica-se a lesões dos ductos hepáticos, do hepático comum e de toda extensão do colédoco.

Treatment Strategies in Early Parkinson's Disease.

The clinicians' approach to the treatment of early Parkinson's disease (PD) should take into account numerous aspects, including how to inform a patient upon diagnosis and the critical decision of what therapy to adopt and when to start it. The treatment of the motor disorder associated with early PD needs to consider several crucial factors, such as age at onset, comorbidities, and the patient's functional requirements, and cannot be summarized in a simple formula. In younger patients (i.e., before the age of 70) and in those without high functional requirements, treatment is usually initiated with dopamine agonists and/or monoamine oxidase-B enzyme inhibitors (MAO-B I). By contrast, in older patients, or in those with high functional requirements, low doses of levodopa are generally used when treatment is started. In younger patients, levodopa should be added to dopamine agonists and/or MAO-B I, as required by disease progression, whereas in older patients, when response to levodopa alone is not satisfactory, dopamine agonists or catechol-O-methyltransferase inhibitors may subsequently be added.

Percutaneous transbiliary biopsy / Biópsia percutânea transbiliar

ABSTRACT Percutaneous drainage of the bile ducts is an established procedure for malignant obstructions, in which a histological diagnosis is often not obtained. We describe the biopsy technique of obstructive lesions through biliary drainage access, using a 7F endoscopic biopsy forceps, widely available; some are even reusable. This technique applies to lesions of the hepatic ducts, of the common hepatic duct and of all extension of the common bile duct.

RESUMO A drenagem percutânea das vias biliares é um procedimento estabelecido para obstruções malignas, nos quais, muitas vezes, não se consegue um diagnóstico histológico. Descrevemos a técnica de biópsia da lesão obstrutiva através do acesso de drenagem biliar, utilizando um fórcipe de biópsia endoscópica 7F, amplamente disponível e alguns reutilizáveis. Esta técnica aplica-se a lesões dos ductos hepáticos, do hepático comum e de toda extensão do colédoco.

Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson's disease.

It is unclear whether patients with different clinical phenotypes of Parkinson's disease (PD) differ in their risk of developing levodopa-induced dyskinesia. We evaluated the possible association between clinical phenotypes and risk of levodopa-induced dyskinesia in PD patients using a case-control design. The FRAGAMP study is a large Italian multicenter study. Patients affected by PD diagnosed according to the Gelb's criteria were enrolled and underwent a face-to-face interview. Clinical scales were used to evaluate motor and cognitive impairment. Presence of dyskinesia was assessed by the item 32 of the UPDRS section IV. On the basis of the most prominent motor symptoms at onset PD, patients were classified as tremor-dominant, akinetic-rigid, or mixed type. 485 PD patients (292 men; mean age 65.6 ± 9.8) were enrolled in the study of whom 128 (26.4 %) presented levodopa-induced dyskinesia. Of the 485 patients, 311 (64.1 %) were classified as tremor-dominant, 104 (21.4 %) as Akinetic-Rigid and 70 (14.4 %) as mixed type. Multivariate logistic regression analysis showed a significant negative association between tremor-dominant phenotype and levodopa-induced dyskinesia (adjusted OR 0.48; 95 % CI 0.23-1.00; p value 0.05). When analysis was stratified by age at onset a stronger negative association was found among the late onset (>50 years) PD patients (OR 0.28; 95 % CI 0.11-0.70; p value 0.007) while no association was found among patients with an early onset. Our findings support the hypothesis that the occurrence of resting tremor as an initial manifestation of PD may predict a lower probability of developing levodopa-induced dyskinesia.

Pisa syndrome in Parkinson disease: An observational multicenter Italian study.

OBJECTIVE: To estimate the prevalence of Pisa syndrome (PS) in patients with Parkinson disease (PD) and to assess the association between PS and demographic and clinical variables. METHODS: In this multicenter cross-sectional study, consecutive outpatients with PD attending 21 movement disorders Italian tertiary centers were enrolled and underwent standardized clinical evaluation. PS was defined as trunk lateral deviation ≥10°. Patients with PD were compared according to the presence of PS for several demographic and clinical variables. RESULTS: Among 1,631 enrolled patients with PD, PS was detected in 143 patients (8.8%, 95% confidence interval 7.4%-10.3%). Patients with PS were older, had lower body mass index, longer disease duration, higher disease stages, and poorer quality of life. Falls were more frequent in the PS group as well as occurrence of "veering gait" (i.e., the progressive deviation toward one side when patient walked forward and backward with eyes closed). Patients with PS received higher daily levodopa equivalent daily dose and were more likely to be treated with combination of levodopa and dopamine agonists. Osteoporosis and arthrosis were significantly the most frequent associated medical conditions in patients with PS. Multiple explanatory variable logistic regression models confirmed the association of PS with the following variables: Hoehn and Yahr stage, ongoing combined treatment with levodopa and dopamine agonist, associated medical conditions, and presence of veering gait. CONCLUSIONS: Our results suggest that PS is a relatively frequent and often disabling complication in PD, especially in the advanced disease stages. The association is dependent on a number of potentially relevant demographic and clinical variables.