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The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of non-invasive stimulation over these networks in 45 patients (AD and bvFTD) who received either anodal (target network: DMN in AD, SN in bvFTD) or cathodal stimulation (target network: SN in AD, DMN in bvFTD). We evaluated changes in clinical, cognitive, functional and structural connectivity, and perfusion measures. In both patient groups, cathodal stimulation was followed by behavioral improvement, whereas anodal stimulation led to cognitive improvement. Neither functional connectivity nor perfusion showed significant effects. A significant interaction between DMN and SN functional connectivity changes and stimulation protocol was reported in AD. These results suggest a protocol-dependent response, whereby the protocols studied show divergent effects on cognitive and clinical measures, along with a divergent modulatory pattern of connectivity in AD.

The energy transition for the industrial sector is not limited to a reduction in energy consumption: the real issue is to combine sustainability with growth, by mixing the two ingredients (the rational energy use and the industrial growth) which are not always compatible. The National Energy and Climate Plan (NECP) and the New Green Deal policies in Italy have the goal to promote an economic development as well as the environment sustainability and social inclusion. RSE1 has investigated the role of the national incentive plan ‘Impresa 4.0’ in Italy (currently ‘Transizione 4.0’, equivalent to ‘Industry 4.0’) as a measure to promote the energy transition, analysing whether and how is it possible to combine economic development with energy efficiency. Originally, it was developed to increase the competitiveness of industrial sector, but, progressively, it was also used to promote energy efficiency and sustainability. A survey was carried out by RSE on about 300 companies that implemented innovation and digitalisation interventions, monitoring the effects and impacts that the ‘4.0 choice’ has determined on energy consumption, on their environmental externalities and, in general, on other costs. Moreover, some case studies were collected, together with a database of ‘Impresa 4.0’ application, which supported technical and economic evaluations. The impact of these measures on energy performance of the companies was estimated from the analysis of actual projects and from interviews and discussions with the operators. In this paper, the results of the survey are presented and the outcomes are analysed in comparison with the Italian manufacturing sector performance, in order to establish the potential of ‘Impresa 4.0’ policies in supporting the decarbonisation process and reaching 2030 environmental targets. This work was financed by the Research Fund for the Italian Electrical System in compliance with the Decree of Minister of Economic Development on 16 April 2018.

The aim of this systematic review and meta-analysis is to examine the efficacy of language training, alone or in combination with non-invasive brain stimulation techniques, designed to improve oral and written naming abilities in Primary Progressive Aphasia (PPA), and to investigate whether gains can be maintained over time and generalize to untrained items. An electronic database search was conducted up to 31st of May 2019. Forty-three articles on language training alone and seven articles on the combined treatment fitted the inclusion criteria for the systematic review. Results indicated that language training, alone or in combination with transcranial direct current stimulation (tDCS), improves oral naming accuracy for trained items in patients with PPA, with a long-term maintenance of the gain over time. Only language training combined with tDCS improves oral naming accuracy for untrained items. Considering written naming abilities, language training combined with tDCS improves performance for both trained and untrained items, immediately after training and at follow-up.

Aging is accompanied by changes in cognitive abilities and a great interest is spreading among researchers about aging impact on social cognition skills, such as the Theory of Mind (ToM). Transcranial direct current stimulation (tDCS) has been used in social cognition studies founding evidence of sex-related different effects on cognitive ToM task in a young people sample. In this randomized, double-blind, sham-controlled study, we applied one active and one sham tDCS session on the medial prefrontal cortex (mPFC) during a cognitive ToM task, including both social (i.e., communicative) and nonsocial (i.e., private) intention attribution conditions, in sixty healthy aging individuals (30 males and 30 females). In half of the participants the anode was positioned over the mPFC, whereas in the other half the cathode was positioned over the mPFC. The results showed that: (i) anodal tDCS over the mPFC led to significant slower reaction times (vs. sham) for social intention attribution task only in female participants; (ii) No effects were found in both females and males during cathodal stimulation. We show for the first time sex-related differences in cognitive ToM abilities in healthy aging, extending previous findings concerning young participants.

The observation of neurological patients showing selective impairments for specific conceptual categories contributed in the development of semantic memory theories. Here, we studied two patients (P01, P02), affected, respectively, by the semantic variant of Primary Progressive Aphasia (sv-PPA) and Cortico-Basal Syndrome (CBS). An implicit lexical decision task, including concrete (animals, tools) and abstract (emotions, social, quantity) concepts, was administered to patients and healthy controls.P01 and P02 showed an abolished priming effect for social and quantity-related concepts, respectively. This double dissociation suggests a role of different brain areas in representing specific abstract categories, giving insights for current semantic memory theories.

Background Parkinson’s Disease (PD) with mild cognitive impairment (MCI) (PD-MCI) represents one of the most dreaded complications for patients with PD and is associated with a higher risk of developing dementia. Although transcranial direct current stimulation (tDCS) has been demonstrated to improve motor and non-motor symptoms in PD, to date, no study has investigated the effects of tDCS on Theory of Mind (ToM), i.e., the ability to understand and predict other people’s behaviours, in PD-MCI. Methods In this randomized, double-blind, sham-controlled study, we applied active tDCS over the medial frontal cortex (MFC) to modulate ToM performance in twenty patients with PD-MCI. Twenty matched healthy controls (HC) were also enrolled and were asked to perform the ToM task without receiving tDCS. Results In the patients with PD-MCI, i) ToM performance was worse than that in the HC, ii) ToM abilities were poorer in those with fronto-executive difficulties, and iii) tDCS over the MFC led to significant shortening of latency for ToM tasks. Conclusions We show for the first time that active tDCS over the MFC enhances ToM in patients with PD-MCI, and suggest that non-invasive brain stimulation could be used to ameliorate ToM deficits observed in these patients.

Background: In recent years, emphasis has been placed on cognitive enhancement to stimulate cognitive abilities and prevent functional decline. Considering that traditional face-to-face interventions can be very expensive and are not accessible to all individuals, the need to transfer care from the clinic to the patient's home is evident. In this regard, cognitive tele-enhancement interventions have received increased attention.Aim: The aim of this review was to provide an overview of protocols that apply remotely controlled cognitive training with individualized feedback on performance by the therapist in healthy older adults or participants with subjective memory complaints.Methods: Out of 35 articles assessed for eligibility, eight studies were identified. Of the selected studies, five included cognitively healthy older adults, while three included participants with subjective memory complaints.Results: Most of the reviewed studies showed beneficial effects of cognitive tele-enhancement interventions, reporting improvements in memory, sustained attention, working memory, executive functions, and language abilities. Moreover, reductions in anxiety and depression symptomatology levels, as well as in subjective memory difficulties, were described in some of the studies.Conclusions: Cognitive tele-enhancement treatment could be a good alternative to face-to-face intervention. This literature review highlights the importance of applying preventive cognitive interventions to subjects with initial subjective memory complaints. Remote modalities seem to facilitate the application of such interventions.

Background Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by a gradual, insidious and progressive loss of language abilities, with naming difficulties being an early and persistent impairment common to all three variants. In the absence of effective pharmacological treatments and given the progressive nature of the disorder, in the past few decades, many studies have investigated the effectiveness of language training to minimize the functional impact of word-finding difficulties in daily life. Main body We review language treatments most commonly used in clinical practice among patients with different variants of PPA, with a focus on the enhancement of spoken and written naming abilities. Generalization of gains to the ability to name untrained stimuli or to other language abilities and the maintenance of these results over time are also discussed. Forty-eight studies were included in this literature review, identifying four main types of language treatment: a) lexical retrieval treatment, b) phonological and/or orthographic treatment, c) semantic treatment, and d) a multimodality approach treatment. Overall, language training is able to induce immediate improvements of naming abilities in all variants of PPA. Moreover, despite the large variability among results, generalization and long-term effects can be recorded after the training. The reviewed studies also suggest that one factor that determines the choice of a particular approach is the compromised components of the lexical/semantic processing system. Conclusion The majority of studies have demonstrated improvements of naming abilities following language treatments. Given the progressive nature of PPA, it is essential to apply language treatment in the early stages of the disease.

Transcranial Direct Current Stimulation (tDCS) has become an increasingly promising tool for understanding the relationship between brain and behavior. The purpose of this study was to investigate whether the magnitude of sex- and age-related tDCS effects previously found in the medial prefrontal cortex (mPFC) during a Theory of Mind (ToM) task correlates with social cognition performance, in particular, we explored whether different patterns of activity would be detected in high- and low-performing participants. For this, young and elderly, male and female participants were categorized as a low- or high-performer according to their score on the Reading the Mind in the Eyes task. Furthermore, we explored whether sex- and age-related effects associated with active tDCS on the mPFC were related to cognitive functioning. We observed the following results: (i) elderly participants experience a significant decline in ToM performance compared to young participants, (ii) low-performing elderly females report slowing of reaction time when anodal tDCS is applied over the mPFC during a ToM task, and (iii) low-performing elderly females are characterized by lower scores in executive control functions, verbal fluency and verbal short-term memory. The relationship between tDCS results and cognitive functioning is discussed in light of the neuroscientific literature on sex- and age-related differences.

Objectives Episodic memory is impaired in amnestic mild cognitive impairment (aMCI), which is posited as a potential prodromal form of Alzheimer’s disease. Reactivated existing memories become sensitive to modification during reconsolidation. There is evidence that the lateral prefrontal cortex (PFC) plays causal role in episodic memory reconsolidation. Transcranial direct current stimulation (tDCS) applied to the PFC after a contextual reminder enhanced episodic memory performance up to 1 month, conceivably through reconsolidation, in older adults with subjective memory complaints, a condition that may represent a “pre-mild cognitive impairment” stage. The aim of this pilot study was to test the effect of PFC-tDCS (anode over left lateral PFC, cathode over right supraorbital area) after a contextual reminder on episodic memory in older adults with aMCI. Method Older adults with aMCI learned a list of words. Twenty-four hours later, tDCS (Active or Sham) was applied after a contextual reminder. Memory retrieval (free recall and recognition) was tested 48 hrs and 1 month after the learning session. Results Active tDCS enhanced recognition memory relative to Sham stimulation. Discussion Modulating reconsolidation with PFC-tDCS might be a novel intervention to enhance episodic memories in aMCI.

Language assessment has a critical role in the clinical diagnosis of neurodegenerative diseases, in particular, in the case of Primary Progressive Aphasia (PPA). The current diagnostic criteria (Gorno-Tempini et al., 2011) identify three main variants on the basis of clinical features and patterns of brain atrophy. Widely accepted tools to diagnose, clinically classify, and follow up the heterogeneous language profiles of PPA are still lacking. In this study, we develop a screening battery, composed of nine tests (picture naming, word and sentence comprehension, word and sentence repetition, reading, semantic association, writing and picture description), following the recommendations of current diagnostic guidelines and taking into account recent research on the topic. All tasks were developed with consideration of the psycholinguistic factors that can affect performance, with the aim of achieving sensitivity to the language deficit to which each task was relevant, and to allow identification of the selective characteristic impairments of each PPA variant. Normative data on 134 Italian subjects pooled across homogeneous subgroups for age, sex, and education are reported. Although further work is still needed, this battery represents a first step towards a concise multilingual standard language examination, a fast and simple tool to help clinicians and researchers in the diagnosis of PPA.

Episodic memory shows the largest degree of age-related memory decline. There is evidence that consolidation, the process that stabilizes memories after encoding, is reduced in older adults. Previous studies have shown that transcranial direct current stimulation (tDCS) applied during intentional encoding or immediately after a contextual reminder enhanced delayed episodic memory performance, suggesting a potential interaction between tDCS and consolidation or reconsolidation processes. The present randomized, double-blind, sham-controlled study addressed the question whether tDCS applied immediately after verbal encoding enhances episodic memory recall through consolidation in healthy older adults. Twenty-eight participants received tDCS (Active or Sham) over the prefrontal cortex (anode over the left dorsolateral prefrontal cortex and cathode over the contralateral supraorbital region), a brain region contributing to episodic memory function. Verbal recall was tested two days and one month later. The results showed that recall performance at one month was enhanced in the Active tDCS group relative to the Sham group. These findings suggest that tDCS applied off-line immediately after encoding over the prefrontal cortex interacts with the processes promoting consolidation of episodic memories in healthy older adults. Targeting consolidation by means of tDCS might be a novel strategy for reducing episodic memory decline.

In Severe Mental Disorders (SMDs) the most important cognitive deficits involve the Executive Functions (EFs). In this study we examined the association between EFs and aggressive behaviour in outpatients with SMDs. We included a total of 247 outpatients divided into two groups: 'cases', patients with a history of violence (N=126) and 'non-violent' (N=121). We compared their EFs score and then categorized the participants into four groups (Pathological Non-Violent comparison group; Non-Pathological Non-Violent comparison group; Pathological Violent cases and Non-Pathological Violent cases), based on the scores of a subtest assessing processing speed (i.e., Symbol-coding task) of the Brief Assessment of Cognition in Schizophrenia (BACS). We followed the 4 groups during a 1-year follow-up (FU) monitoring violent behaviour with the Modified Overt Aggression Scale (MOAS). According to the classification based on the BACS-Symbol Coding Task we found no statistically significant differences between subgroups in MOAS scores. We only found that the trend curve for PV was almost consistently over the other group curves in the MOAS 'aggression against people'. Our results suggested a worse performance in the violent compared to non-violent group in EFs. Despite this evidence, the score on the processing speed task was not associated with aggressive behaviour during FU.

A progressive speech/language disorder, such as the non fluent/agrammatic variant of primary progressive aphasia and progressive apraxia of speech, can be due to neuropathologically verified Progressive Supranuclear Palsy (PSP). The prevalence of linguistic deficits and the linguistic profile in PSP patients who present primarily with a movement disorder is unknown. In the present study, we investigated speech and language performance in a sample of clinically diagnosed PSP patients using a comprehensive language battery, including, besides traditional language tests, a detailed analysis of connected speech (picture description task assessing 26 linguistic features). The aim was to identify the most affected linguistic levels in seventeen PSP with a movement disorder presentation, compared to 21 patients with Parkinson's disease and 27 healthy controls. Machine learning methods were used to detect the most relevant language tests and linguistic features characterizing the language profile of PSP patients. Our results indicate that even non-clinically aphasic PSP patients have subtle language deficits, in particular involving the lexical-semantic and discourse levels. Patients with the Richardson's syndrome showed a lower performance in the word comprehension task with respect to the other PSP phenotypes with predominant frontal presentation, parkinsonism and progressive gait freezing. The present findings support the usefulness of a detailed language assessment in all patients in the PSP spectrum.

Background: We evaluated the psychometric proprieties of the Screening for Aphasia in NeuroDegeneration (SAND) battery in Italian primary progressive aphasia (PPA) and movement disorder (MD) patients. Methods: The sample included 30 consecutive PPA and 45 MD patients who completed the SAND battery together with a clinical interview and a neurological/neuropsychological examination and 130 healthy controls (HC). Results: The SAND battery showed good internal consistency and good convergent and divergent validity. receiver operating characteristic analysis revealed an area under the curve of 0.978 for PPA versus HC and of 0.786 for PPA versus MD. A cutoff ≥3 gave a sensitivity of 0.933% and a specificity of 0.946% for discriminating PPA versus HC, whereas a cutoff ≥5 gave a sensitivity of 0.767% and a specificity of 0.667% for discriminating PPA versus MD. Conclusion: These results indicate that the SAND battery is an adequate, reliable, and valid diagnostic tool for PPA.

Background A number of non-motor symptoms occurs in Parkinson Disease (PD), cognitive decline and mood disturbances representing the most prevalent. Recent studies reported that cognitive training could potentially help to attenuate cognitive deficits in patients with PD and several researches demonstrated a beneficial effect of active transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex (anode over left dorsolateral prefrontal cortex, cathode over right supraorbital area) on cognitive deficits and mood disturbances. Objective To investigate the effects of active tDCS combined with computerized cognitive training on cognition and mood disturbances in PD patients. Methods Twenty-two patients with PD were assigned to either active tDCS plus computerized cognitive training (CCT) or sham tDCS plus CCT groups. Each patient underwent two weeks' treatment of daily application of tDCS for 25 minutes during CCT focalized on functions related with prefrontal cortex. Each patient was evaluated at baseline, after treatment and at 3-month follow-up. Results A significant reduction of depressive symptoms was observed in the active tDCS group from baseline to post-treatment assessment and from baseline to 3-month follow-up. An improvement in cognitive performances, referring more specifically to language, attentional and executive functions, was observed in both groups post-treatment and at follow-up. However, phonemic verbal fluency showed significant greater changes from baseline in the active tDCS group. Conclusions We concluded that cognitive training along with active tDCS is a useful combined approach in the management of mood and cognitive dysfunctions in PD.

A procedure aimed to support designers in achieving structural improvements to reduce the seismic vulnerability of an electrical network is presented. This method based on the use of ASK4ELP software (Assessment of Seismic Risk for Electric Power Grids) allows minimising the costs of the actions needed in order to reach the required level of reliability, as defined by two different indexes of damage, namely the loss of transmitted power and the number of customers excluded from the service. An updating plan for the reinforcement of a power transmission grid includes the identification of its critical nodes, of the electromechanical components to be strengthened and of the related reinforcement level. In this paper, it is shown how the vulnerability assessment carried out with ASK4ELP can help in finding the optimal solution to these tasks, increasing the effectiveness-to-costs ratio. Three different empirical criteria for the individuation of the critical nodes are evaluated and the simulation of a signif...

Seismic vulnerability assessment of electric power grids is not an easy task and has to be supported via efficient computational tools. The ASK4ELP software package has recently undergone an extensive upgrading and testing. The flexibility and computing efficiency have been improved; moreover, several features have been added, including a new graphical interface, the computation of vulnerability expressed as probability of exceeding given damage levels in an assigned time and a tool for evaluating the vulnerability reduction interventions on a cost-effectiveness basis. In this article, a brief description of the software and its most significant features will be given, as well as the results of an extensive study performed on a large representative part of the Italian electric network will be shown. This network includes more than 500 substations, operating at different voltages and located next to one of the largest and most seismic areas of the Italian peninsula. Operational and ultimate limit states ar...

Recently, atypical bovine pestiviruses (BVDV-3) have been identified in batches of contaminated foetal calf serum (FCS) and in naturally infected cattle. During routine screening of FCS by conventional panpestivirus PCR assay, one batch showed traces of pestivirus nucleic acids, and the contaminating virus was typed as BVDV-3-like. Phylogenetic analysis based on three genome regions (5′UTR, Npro and E2) showed that this strain, named IZSPLV_To, clusters in a separate clade with CH_KaHo/cont, a cell culture contaminant detected in Switzerland. This study is the first report of the detection in Italy of a FCS batch contaminated with BVDV-3 and adds more evidence that atypical pestiviruses represent a serious cause for concern in cell culture laboratories, with potential repercussions on BVD control and vaccine biosafety. Our findings suggest that the BE/B2 primers may be able to detect BVDV-3 in a panpestivirus assay, but testing of a larger number of strains is required.

A survey was performed to find in the literature theoretical models suitable to the description of the triaxial creep behaviour of plain concrete at high stresses. The considered models are based on the theory of elasto-viscoplasticity with damage and are mainly addressed to the domain of geotechnics. Application of these models to the simulation of experiments turned out to be satisfactory on the whole, although several features of the creep behaviour of the material are not reproduced. The suggestions given by this preliminary work will be taken into account in the development of a future model specifically conceived for concrete.

Background The Home or Hospital in Heart Failure Study (HHH) is a European Community funded trial (QLGA-CT-2001-02424) which compares usual care of heart failure (HF) with three home-based interventions in a multicenter, multicountry (Italy, Poland and UK), randomized controlled clinical trial. Home telemonitoring (HT) of clinical parameters represents a potential alternative (or addition) to traditional home care models. Nocturnal respiratory disorders (periodic breathing, sleep apnea) are very common in HF, and are associated with increased morbidity and mortality. We developed an integrated HT system for monitoring of both vital signs and respiration. All measurements were patient-managed. This paper describes the architecture of this system, and assesses its feasibility. Methods and results 461 clinically stable patients were randomized first to usual vs home-monitored care; the latter were further randomized to 3 strategies. Over a 12-month follow-up 2 of these 3 groups (195 patients, age: 60±11 years, NYHA class II–III: 97%, LVEF 28±7%) underwent self-administered home monitoring of vital signs (weekly — 12 parameters using an interactive voice response system) and respiration (monthly — 24-hour recording). Data were transmitted over conventional telephone lines; 81% of actually practicable vital signs measurements were completed by the patients (range: 75% (PL)–93% (UK)), as well as 92% of practicable respiratory recordings (range: 85% (PL)–99% (UK)). 87% of nighttime recordings were eligible for the study (good quality signals for ≥2.5 h). Conclusions This study, the largest so far, demonstrates that self-managed home telemonitoring of both vital signs and respiration is feasible in HF patients, with surprisingly high compliance. We found an excellent rate of acceptable nocturnal respiratory recordings, which are those with the greatest clinical relevance.

Background: Hereditary hemochromatosis is a recessive disorder characterized by iron accumulation in parenchymal cells, followed by organ damage and failure. The disorder is mainly attributable to the C282Y and H63D mutations in the HFE gene, but additional mutations in the HFE, transferrin receptor 2 (TfR2), and hepcidin genes have been reported. The copresence of mutations in different genes may explain the phenotypic heterogeneity of the disorder and its variable penetrance. Methods: We used denaturing HPLC (DHPLC) for rapid DNA scanning of the HFE (exons 2, 3, and 4), hepcidin, and TfR2 (exons 2, 4 and 6) genes in a cohort of 657 individuals with altered indicators of iron status. Results: DHPLC identification of C282Y and H63D HFE alleles was in perfect agreement with the restriction endonuclease assay. Fourteen DNA samples were heterozygous for the HFE S65C mutation. In addition, we found novel mutations: two in HFE (R66C in exon 2 and R224G in exon 4), one in the hepcidin gene (G71D), and one in TfR2 (V22I), plus several intronic or silent substitutions. Six of the seven individuals with hepcidin or TfR2 coding mutations carried also HFE C282Y or S65C mutations. Conclusion: DHPLC is an efficient method for mutational screening for the genes involved in hereditary hemochromatosis and for the study of their copresence.

Background. Mitoxantrone is an anthracenedione derivative with cytostatic and immunomodulatory activity, which is licensed for worsening multiple sclerosis (MS), an autoimmune central nervous system disease. The occurrence of acute promyelocytic leukaemia (APL) following mitoxantrone therapy in MS has been sporadically reported, but its actual incidence and clinical outcome need further definition Aims and Methods. Among 1050 patients with a diagnosis of MS followed at our Institution since 1985, the clinical records of those receiving mitoxantrone were reviewed, in order to clarify the incidence of secondary APL as well as its clinical characteristics and outcome. Results. Since 1990, 98 patients affected by MS were treated with mitoxantrone, in most cases as third-line treatment after corticosteroids and interferon therapy. Four patients (M/F: 1/4) developed APL. Median age at presentation was 57.5 year (range 47–59), significantly higher than that of unselected MS patients. APL developed a median of 55.5 months (range 3766 mo) after the first course of mitoxantrone. The median total dose of mitoxantrone was 149 mg (range 35–234 mg), delivered over a median of 7 courses (3–13). The cumulative number of years of follow-up after the start of mitoxantrone was 690. Therefore the risk of developing APL in this cohort was 5.8‰. All but one patients were classified as low-risk APL according to the GIMEMA/PETHEMA scoring system, the fourth being intermediate-risk. Morphology was FAB M3v in 1 case, and classic in the remaining. Typical chromosomal translocation t(15;17) was observed in all patients as well as PML/RAR-α molecular rearrangement, of bcr1 type in all. Flt-3 mutation was always absent. Given the treatment-related pathogenesis of APL, a modification of the AIDA2000 treatment program was used, with a reduced dose of idarubicin during induction in 2 patients. The second consolidation course with mitoxantrone was avoided by repeating the first course twice. Complete hematologic and cytogenetic remission was obtained after induction in all patients. Two patients are receiving consolidation. Molecular response was documented after consolidation in the other two patients. Both of them relapsed. The first had molecular relapse after 4 months; he was treated with ATRA and Ara-C and obtained a second molecular remission, lasting 50+ months. The second patient showed a morphological relapse after 5 months. She was treated with arsenic trioxide obtaining a second complete morphologic and molecular remission, but relapsed 1 month after autologous peripheral stem cell transplantation given for consolidation. She is currently on reinduction therapy with arsenic trioxide, 26 months after diagnosis. Conclusions. APL is a rare hematological disease, but its incidence among mitoxantrone-treated MS patients is significantly increased, like in patients with malignant diseases treated with mitoxantrone. Age is a major risk factor for the development of mitoxantrone-related APL. Analysis of further potential risk-factor is ongoing. The clinical outcome of this subset of patients seems worse than in de-novo APL. The use of anthracyclines as part of the treatment program needs further evaluation.