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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.

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.

Somatoform Disorders (SFMD) were recently described in Parkinson Disease (PD) and Dementia with Lewy Bodies (DLB). The present paper updates the observations in our cohort of patients and further details clinical phenomenology. Of 3178 patients consecutively referred to our Institutions from 1999, 1572 subjects had neurodegenerative diseases and 1718 psychiatric disorders. After 2-9 years of follow up, 488 patients were labelled as PD, 415 as Alzheimer Disease, 162 as DLB, 48 as Progressive Supranuclear Palsy, 48 as Multiple System Atrophy and 49 as Fronto-Temporal Dementia. The frequency of SFMD (DSM-IV-TR criteria) was determined in each diagnostic category by direct observation of SFMD symptoms, psychiatric interviews, SCL 90Rss, collection of previous general practitioners and hospital charts. The frequency of SFMD was considerably higher in DLB (29 patients, 18%) and PD (37 patients, 7.5%) than in any other group (0-2%). The frequency of SFMD in psychiatric patients was 2%. SFMD in PD and DLB were characterised by motor and non-motor patterns and were often accompanied by catatonic signs consisting of posturing stereotypies and negativism (55%). SFMD symptoms preceded PD motor signs by 6 months-5 years in 92% of the 29 DLB and 37 PD patients and in 70% SFMD were recurrent at follow-up. In 93% of these patients, hypochondria was a preceding or concomitant background.

Paradoxical kinesia (PK) is the sudden resolution of a previously stabilized akinesia in an advanced idiopathic Parkinson’s disease (IPD) patient facing an immediate threat. We are reporting the effect of PK, as a consequence of a life threatening event (earthquake), in a group of 14 patients with parkinsonism and dementia in Hoehn/Yahr (H/Y) stage 3–5. All the patients presented an extraordinary motor response during the earthquake that has recently stricken the Italian city of L’Aquila. All of them were able to safely escape unaided and, in some cases, to assist their families, despite they suffered before from severe night time akinesia and gait difficulties with postural instability requiring assistance. In five patients, the improvement of motor disabilities, particularly of freezing, lasted for 2–5 months.