MCI a verosimile fenotipo FTD: un caso clinico ad esordio tardivo

Una paziente di 75 anni, giungeva in visita geriatrica nel settembre 2013, lamentando sintomatologia ansiosa ingravescente, perdita d\u2019interessi e paure per situazioni non conosciute, esordite dal 2011. In anamnesi si rilevavano una familiarit\ue0 per demenza (ad esordio tardivo) e un episodio di depressione reattiva alla morte del padre. Le scale di valutazione funzionale mostravano una completa preservazione dell\u2019autonomia (ADL 6/6, IADL 8/8), i test cognitivi di screening erano nella norma (MMSE 30/30, CDT 4/5), mentre si obiettivava una deflessione del tono dell'umore (GDS 14/30). Venivano effettuati: test neuropsicologici conclusivi per MCI non amnesico a dominio singolo dis-esecutivo, TC encefalo (lieve ampliamento dei corni frontali dei ventricoli laterali e lieve vasculopatia), RMN encefalo (iniziale atrofia corticale, lieve vasculopatia), PET cerebri (moderato ipometabolismo glucidico corticale bilaterale pre-frontale), genotipizzazione dell\u2019ApoE (e3/e3) e del gene C9ORF72 (assenza di ripetizioni), dosaggio della progranulina (nella norma). Si poneva diagnosi preliminare di MCI in sospetta FTD. La sintomatologia ansioso-depressiva della paziente, risultata resistente a numerose terapie (bromazepam, alprazolam, sertralina, escitalopram, levosulpiride), migliorava con l\u2019introduzione di paroxetina. \ua0 La diagnosi clinica di MCI FTD \ue8 molto complessa, in quanto i sintomi d\u2019esordio sono spesso sovrapponibili a quelli riscontrati in varie patologie psichiatriche. I test neuropsicologici sono fondamentali per una diagnosi precoce, le prove che valutano le funzioni esecutive frontali e/o il linguaggio, possono essere infatti alterate sin dagli stadi precoci. La RMN encefalo permette di escludere patologie organiche che potrebbero essere la causa dei disturbi lamentati dai pazienti (es. tumori o esiti ischemici in sede frontale) e avvalora la diagnosi di FTD nel caso in cui si evidenzi un\u2019atrofia focale dei lobi frontali e/o temporali. Tuttavia, negli stadi iniziali della malattia tale reperto non \ue8 sempre rilevabile, pertanto per supportare la diagnosi si utilizza la PET che pu\uf2 evidenziare un ipometabolismo glucidico in sede fronto-temporale anche quando il parenchima cerebrale \ue8 ancora volumetricamente integro. Ad oggi non esiste un trattamento farmacologico in grado di impedire o di rallentare la progressione di questa patologia neurodegenerativa. La terapia \ue8 pertanto volta al controllo dei disturbi comportamentali e si avvale principalmente degli inibitori selettivi del reuptake della serotonina (SSRI), in quanto nella FTD vi \ue8 una riduzione della concentrazione di serotonina a livello dei circuiti frontali sottocorticali. La diagnosi precoce di FTD \ue8 di fondamentale importanza perch\ue9 consente un approccio terapeutico in grado di migliorare la qualit\ue0 di vita dei pazienti e dei familiari

Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Do not forget lupus anticoagulant in the era of antiphospholipid antibodies

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Acute renal failure mimicking haemolytic uraemic syndrome in a patient with factor V Leiden mutation and essential thrombocytemia

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Failure of the war to the knife against antiphospholipid antibodies by conventional immunosuppressive therapy in systemic lupus erythematosus

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Forum on: The role of recombinant factor VIII in children with severe haemophilia A

The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970-1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first-choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on-demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti-FVIII alloantibodies, whereas other treatment-related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti-FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first-choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long-lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report

Factor V Arg506-->Gln mutation in patients with antiphospholipid antibodies

Antiphospholipid antibodies (APA) have thought to be implicated in the pathogenesis of both arterial and venous thrombosis. Because of heterogeneity of APA, direct evidence of their involvement in a thrombotic event is not yet available. Development of thrombosis in the antiphospholipid antibody syndrome (APS) may occur because of the presence of additional risk factors. Here we have analysed 60 patients with APA for the presence of the Arg506-->Gln mutation in factor V. Among them 26 suffered from deep venous thrombosis, 13 from arterial thrombosis and 21 had no history of arterial or venous thrombosis. In the first group four patients were found to be heterozygous and one homozygous for the factor V Arg506-->Gln mutation. None of the patients with the factor V mutation was found in the second and third group. The incidence of factor V mutation was significantly elevated in the group of patients with venous thrombosis. These data suggest that in patients with antiphospholipid antibodies the factor V Arg506-->Gln mutation may play a major role in the occurrence of venous thrombosi