Modificazioni fisiopatologiche e cliniche indotte a livello del Sistema Nervoso Centrale dall'Insufficienza Venosa Cerebrospinale Cronica (CCSVI)

BACKGROUND – The description of a new syndrome, the Chronic Cerebrospinal Venous Insufficiency (CCSVI), led us to investigate the relationship between the venous system and Central Nervous System (CNS). In particular, in the last years we have focused on the relationship between CCSVI and Multiple Sclerosis (MS). OBJECTIVES - To evaluate the clinical and pathophysiological changes induced by CCSVI in the CNS, particularly how this syndrome causes iron deposition in the brain parenchyma, the alteration of MRI perfusion, the CSF outflow obstruction and the immune system activation that generates demyelinating lesions. MATERIALS AND METHODS - 102 MS patients (46 RR, 30 SP, 26 PP), and 30 subjects with CNS involvement non MS (15 affected by CIS, 7 people with evidence of RIS, 4 patients with Arnold- Chiari Syndrome and 4 with chronic headache) underwent a combined transcranial and extracranial EchoColorDoppler high-resolution examination (TCCS-ECD) aimed at detecting the prevalence of CCSVI and correlate the venous system involvement with the clinical findings. CCSVI is defined by the presence of at least two out of five parameters of anomalous venous outflow described by Zamboni. Finally we studied the possible correlations between the different hemodynamic patterns and the symptoms of the onset of MS and clinical course; we evaluated the long term clinical outcome of patients with relapsing-remitting MS after PTA treatment. RESULTS -According to the TCCS-ECD criteria, CCSVI is present in 97% of MS patients, in 73% of CIS, in 71% of RIS and even if the cohort is too small to be representative, in 100% of Arnold-Chiari and in 75% of headaches. CCSVI is a syndrome characterized by headache that appears or worse in supine position, sleep disorders, cognitive dysfunctions, chronic fatigue and memory disorders. In a few patients we found extrapyramidal syndrome and normal pressure hydrocephalus. CONCLUSION - MS is strongly associated with CCSVI; endovascular treatment is effective on neurological signs and symptoms of MS although multicenter, double-blind, clinical trial with a larger number of patients will be necessary to confirm this data. Venous neurovascular team is necessary to the care of patients with MS and for better understanding the pathogenesis of MS

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report

<p>Abstract</p> <p>Background</p> <p>Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI).</p> <p>Methods</p> <p>We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities.</p> <p>Results</p> <p>There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (<it>r </it>= -0.70 to -0.71, <it>P </it>< 0.002 and <it>P </it>corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (<it>r </it>= -0.59 to -0.71, <it>P </it>< 0.01 and <it>P </it>corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.</p> <p>Conclusions</p> <p>This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.</p

Diagnostic and Prognostic Value of Conventional Brain MRI in the Clinical Work-Up of Patients with Amyotrophic Lateral Sclerosis

open14noClinical signs of upper motor neuron (UMN) involvement are important in the diagnosis of amyotrophic lateral sclerosis (ALS) though are often difficult to analyze. Many studies using both qualitative and quantitative evaluations have reported abnormal Magnetic Resonance Imaging (MRI) findings at the level of the pyramidal pathway in patients with ALS. Although the most interesting results were obtained by quantitative studies using advanced MR techniques, the qualitative evaluation of MRI images remains the most-used in clinical practice. We evaluated the diagnostic and prognostic contribution of conventional 3T-MRI in the clinical work-up of ALS patients. Two neuroradiologists retrospectively assessed 3T-MRI data of 93 ALS patients and 89 controls. The features of interest were corticospinal tract (CST) T2/FLAIR hyperintensity, motor cortex (MC) T2*/SWI hypointensity, and selective MC atrophy. All MRI features were significantly more prevalent in ALS patients than in controls. The simultaneous presence of CST FLAIR hyperintensity and MC SWI hypointensity was associated with the highest diagnostic accuracy (sensitivity: 70%; specificity: 81%; positive predictive value, PPV: 90%; negative predictive value, NPV: 51%; accuracy: 73%) and a shorter survival (HR: 6.56,p= 0.002). Conventional 3T-MRI can be a feasible tool to detect specific qualitative changes based on UMN involvement and to support clinical diagnosis of ALS. Importantly, CST FLAIR hyperintensity and MC SWI hypointensity are predictors of shorter survival in ALS patients.openRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nullRizzo, Giovanni; Marliani, Anna Federica; Battaglia, Stella; Albini Riccioli, Luca; De Pasqua, Silvia; Vacchiano, Veria; Infante, Rossella; Avoni, Patrizia; Donadio, Vincenzo; Passaretti, Massimiliano; Bartolomei, Ilaria; Salvi, Fabrizio; Liguori, Rocco; On Behalf Of The BoReALS Group, nul

A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy

Fabrizio Salvi, Ilaria Bartolomei, Angelo Lorusso, and Elena Barbarossa are with the Department of Neuroscience, Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy -- Michael H. Smolensky is with the Department of Biomedical Engineering, the University of Texas at Austin, USA -- Ann Maria Malagoni, Paolo Zamboni, and Roberto Manfredini are with the Vascular Diseases Center, University of Ferrara, Italy -- Roberto Manfredini is with the Department of Internal Medicine, Hospital of the Delta, Azienda Unità Sanitaria Locale, Ferrara, Italy and the Department of Clinical and Experimental Medicine, Clinica Medica and Vascular Diseases Center, University of Ferrara, ItalyBackground: Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables. Results: We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011). Conclusions: In this Italian setting we found a biphasic pattern, peaks in spring and autumn, in severe MS relapses requiring medical consultation by doctors of the MS specialty center apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.Biomedical [email protected]

Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Città e territori di democrazia. Una riflessione su politiche urbane e pratiche dal basso, su tramando ed evoluzione dell’urbanistica

The connection between the forms of power exercise and those of space must be under continuous observation. In a co-evolutionary ecosystem, where local societies transform (and transform themselves with) the environments in which they live, a perturbation in the ways of living and producing eventually also perturbs forms of governance, and vice versa. In this process of becoming and con-being, the condition for safeguarding democracy is the protection of what we define here as democratic cities and territories, of which we have collectively attempted to circumscribe the meaning, character and limits. Whether they are real or utopian expressions, an observation or a desire; whether there are models for implementing them; whether there are parameters that identify their democratic nature; whether an aesthetic characterises them: we attempt to answer these questions in this issue of the journal ‘in_bo’. In the first section of this issue, the analysis of the condition of permeability of democratic institutions by mercantile powers provided the means to understand whether planning is still able to produce imaginaries, elaborate models, support - symbolically and practically - the elaboration of ‘landscapes of rootedness’. Urbanism once again becomes the promoter of projects with a broad social and environmental spectrum when it is supported by a nomos derived from collective discernment. The second section of the booklet is dedicated to this complex topic, bringing together examples of micro-political alternatives to the capitalist development model and anthropocentric conception. The third section welcomes a reflection that calls into question the legacy and vocabulary of town planning, as well as its renewal. Numerous thematic threads bind the contributions: whether the urban planning toolbox knows how to absorb the acceleration of the changes taking place, whether it knows how to orientate its evolution, whether it has coined a language capable of representing the fluidity of the present time; whether the hybridisation between plan technique and digital technique generates virtuous progress.La connessione tra le forme di esercizio del potere e quelle dello spazio va posta sotto continua osservazione. In un ecosistema coevolutivo, dove le società locali trasformano (e si trasformano con) gli ambienti in cui esse vivono, un perturbamento nelle modalità dell’abitare e del produrre finisce per perturbare anche le forme di governo, e viceversa. In questo moto di divenire e con-divenire, condizione di salvaguardia della democrazia è la tutela di ciò che qui chiamiamo città e territori democratici, dei quali abbiamo collettivamente tentato di circoscrivere senso, caratteri, limiti. Se essi siano espressioni reali o utopiche, constatazione o desiderio; se esistano modelli per attuarli; se esistano parametri che ne identificano la democraticità; se un’estetica li contraddistingue: a tali interrogativi cerchiamo di dare risposta nel presente numero della rivista in_bo. Nella prima sezione del presente fascicolo, l’analisi della condizione di permeabilità delle istituzioni democratiche da parte dei poteri mercantili ha fornito i mezzi per comprendere se la pianificazione sia tuttora in grado di produrre immaginari, elaborare modelli, sostenere – simbolicamente e praticamente – l’elaborazione di paesaggi di radicamento.  L’urbanistica torna a farsi promotrice di progetti ad ampio spettro sociale e ambientale allorquando essa sia sostenuta da un nomos derivante dal discernimento collettivo. A questo complesso argomento è dedicata la seconda sezione del fascicolo, che raggruppa esempi di micropolitiche alternative al modello di sviluppo capitalistico e alla concezione antropocentrica. La terza sezione accoglie una riflessione che chiama in causa il tramando e il lessico dell’urbanistica, nonché il suo rinnovo. Numerosi fili tematici ne legano i contributi: se lo strumentario urbanistico sappia assorbire l’accelerazione dei cambiamenti in atto, se sappia orientarne l’evoluzione, se abbia coniato un linguaggio capace di rappresentare la fluidità del tempo presente; se l’ibridazione tra tecnica del piano e tecnica digitale generi progressi virtuosi