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Autosomal recessive cerebellar ataxia type 3 (ARCA3) is a rare inherited disorder caused by mutations in the ANO10 gene. The disease is characterized by slowly progressive spastic ataxia variably associated with motor neuron involvement, epilepsy, and cognitive decline. We performed mutational screening in 80 patients with sporadic or autosomal recessive adult-onset ataxia. We identified 11 ANO10 gene variants in 10 patients from 8 families (10%): 4 mutations were previously described and 7 were novel. Age at onset ranged between 27 and 53 years. All patients presented ataxia, pyramidal signs and cerebellar atrophy at brain MRI. Additional signs were bradykinesia (7/10), mild vertical gaze paresis (5/10), pes cavus (4/10), and sphincteric disturbances (3/10). Six patients, with normal MMSE score, failed several neuropsychological tests rating executive functions. Three patients had giant somatosensory evoked potentials and epileptic spikes in EEG without clinical evidence of seizures. Our observational study indicates a high frequency of ARCA3 disease in sporadic patients with adult-onset cerebellar ataxia. We extended the ANO10 mutational spectrum with the identification of novel gene variants, and further defined the clinical, cognitive, and neurophysiological features in a new cohort of patients. These findings may contribute to the refinement of the complex ARCA3 phenotype and be valuable in clinical management and natural history studies.

Aims: In patients with atrial fibrillation (AF) and indication to Dual Antiplatelet Therapy (DAPT) for Acute Coronary Syndrome (ACS), triple therapy is recommended. However, this issue is still largely debated. Percutaneous Left Atrial Appendage (LAA) occlusion may represent an alternative therapeutic approach in this subset of patients, as it could lead to a reduction in the incidence of bleeding. Nevertheless, due to lack of clinical evidence, this approach does not represent the gold standard treatment for these patients. The objective of this study is to evaluate the safety of percutaneous LAA occlusion in patients with Atrial Fibrillation and indication of concomitant DAPT for ACS. Methods and Results: Fifteen AF-patients with indications to anticoagulant and DAPT after ACS underwent LAA occlusion with Amplatzer Cardiac Plug (ACP) or Amulet ACP (St. Jude) from October 2014 to May 2016. Procedural success was achieved in 14/15 patients, while in 1 patient a clinically non-relevant pericardial effusion was registered before the trans-septal puncture, without implantation of the device. No peri-procedural death, major bleeding and dislocation or thrombi of the device were recorded. During a median follow-up of 182 days (interquartile range [IQR]: 169 to 183 days), one peri-procedural minor bleeding and two non cardiovascular death were described. Conclusions: LAA occlusion represents a relatively safe procedure for patients with atrial fibrillation and the need of DAPT due to ACS. Randomized trials should be designed to evaluate the efficacy and safety of this procedure in this clinical setting.

Objective: Parkinson's disease (PD) is often characterized by altered emotional processing, such as depression and alexithymia. Alexithymic and depressive symptoms may be partially overlapping and the relative independence of these two disorders is strongly debated. Reduced echogenicity of midbrain raphe, evaluated with transcranial sonography (TCS), is a characteristic finding in depression associated with PD. No data are available on brainstem's echogenicity in alexithymic PD patients. We assessed, by means of transcranial sonography, possible differences between PD patient with or without alexithymia and/or depression. Methods: We recruited 22 PD patients among our local cohort of 200 patients referred to our Movement Disorder Center during 2014. All patients were treated with optimal dose of dopaminomimetic (L-DOPA EQ mg 499.7 ± 256.3) and underwent neuropsychological tests including Beck Depression Inventory (BDI) and Toronto Alexithymia Scale-20 (TAS-20). Motor symptoms were assessed with Unified Parkinson's Disease Rating Scale (UPDRS III) and modified Hoehn and Yahr scale (H&Y). TCS was performed, through temporal window, using a color-coded phasedarray ultrasound system (SONOS 7500), to evaluate midbrain raphe (0=absent, 1=discontinuous, 2=continuous). Results: TAS-20 and BDI identified 4 patients with depression without alexithymic symptoms (18.18%), 7 alexithymic patients without depression (31.82%), 5 PD patients with depression and alexithymia (22.73%) and 6 PD patients without any of the two disorders (27.27%). At statistical analysis hypoechogenicity correlated with BDI score and the presence of alexithymia was not significantly correlated with absent or discontinuous raphe. Conclusion: The study evidenced the presence of hypoechogenicity in the midbrain raphe in PD patient with depression. No alteration of midbrain raphe was found in PD patients with alexithymia. These findings suggest that while depression in PD may involve central component of brainstem midline, constituting the basal limbic system, called mesocorticolimbic pathway, alteration in alexithymia does not affect the midbrain. This study provides further evidence that depression and alexithymia are independent affective disorder.

A 65-year-old man, who was diagnosed with Pompe disease when he was 50 years, developed memory loss and urinary urgency. His medical history showed severe left hip arthrosis with osteonecrosis which caused intense pain and functional limitations. The patient was also affected by chronic obstructive pulmonary disease, benign prostatic hyperplasia, and hyperamylasemia. Examination revealed a lack of strength in the deltoid muscles (bilateral F = 3), biceps brachii muscles (bilateral F = 4.5), gluteus maximus muscles (bilateral F = 4.5), bilateral iliopsoas muscles (F = 4), and tibialis anterior muscles (bilateral F = 4), hyperlordosis, right winged scapula, anserine gait, which was only possible with unilateral support, and an inability to completely abduct the arms. No extrapyramidal signs were observed except for postural instability, which might also be compatible with the weakness of pelvic muscles. The patient underwent psychometric tests which revealed Mini-Mental-State-Examination score equal to 24 (adequate to age and schooling) and short memory loss. Brain MRI showed increased dimension of ventricular system with reduced subarachnoid cavities and periventricular hyperintensity, supporting normal pressure hydrocephalus and, moreover, atrophy of the A Case of Normal Pressure Hydrocephalus in Adult-Onset Pompe Disease

Objectives Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1–3 repeats (1–3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1–3 DRA. Setting Italy. Participants 66 index cases and 33 relatives carrying 1–3 DRA. Outcomes The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. Results No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1–3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. Conclusions The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity.

Based on the 7-year experience of the Italian Clinical Network for FSHD, we revised the FSHD clinical form to describe, in a harmonized manner, the phenotypic spectrum observed in FSHD. The new Comprehensive Clinical Evaluation Form (CCEF) defines various clinical categories by the combination of different features. The inter-rater reproducibility of the CCEF was assessed between two examiners using kappa statistics by evaluating 56 subjects carrying the molecular marker used for FSHD diagnosis. The CCEF classifies: (1) subjects presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1–A3), (2) subjects with muscle weakness limited to scapular girdle or facial muscles (category B subcategories B1, B2), (3) asymptomatic/healthy subjects (category C, subcategories C1, C2), (4) subjects with myopathic phenotype presenting clinical features not consistent with FSHD canonical phenotype (D, subcategories D1, D2). The inter-rater reliability study showed an excellent concordance of the final four CCEF categories with a κ equal to 0.90; 95 % CI (0.71; 0.97). Absolute agreement was observed for categories C and D, an excellent agreement for categories A [κ = 0.88; 95 % CI (0.75; 1.00)], and a good agreement for categories B [κ = 0.79; 95 % CI (0.57; 1.00)]. The CCEF supports the harmonized phenotypic classification of patients and families. The categories outlined by the CCEF may assist diagnosis, genetic counseling and natural history studies. Furthermore, the CCEF categories could support selection of patients in randomized clinical trials. This precise categorization might also promote the search of genetic factor(s) contributing to the phenotypic spectrum of disease. Electronic supplementary material The online version of this article (doi:10.1007/s00415-016-8123-2) contains supplementary material, which is available to authorized users.

During the past few years, a new and attractive approach--transcatheter aortic valve implantation (TAVI)--has been developed for patients who are symptomatic of aortic stenosis and, due to the high expected operative risk, would not be otherwise treated. Unfortunately, TAVI can result in endocarditis of the percutaneously implanted valve that may present atypically and cause delays in diagnosis and treatment. Herein, the case is described of a 79-year-old female affected by endocarditis on aortic valve percutaneously implanted caused by Enterococcus faecium, complicated by iatrogenic pancytopenia and subacute disseminated intravascular coagulation, that proved fatal at six months after TAVI. During the past few years, a new and attractive approach--transcatheter aortic valve implantation (TAVI)--has been developed for patients who are symptomatic of aortic stenosis and, due to the high expected operative risk, would not be otherwise treated. Unfortunately, TAVI can result in endocarditis of the percutaneously implanted valve that may present atypically and cause delays in diagnosis and treatment. Herein, the case is described of a 79-year-old female affected by endocarditis on aortic valve percutaneously implanted caused by Enterococcus faecium, complicated by iatrogenic pancytopenia and subacute disseminated intravascular coagulation, that proved fatal at six months after TAVI.