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We describe the telemedicine experience of an Italian ALS tertiary Center during COVID-19 pandemic. A total of 144 visits were scheduled between 6th March and 6th April 2020. These mostly consisted of neurological or psychological visits (139, 96.5%). One hundred thirty-nine (96.5%) visits were performed as telemedicine and mostly via phone call (112, 80.6%). Three (2.1%) visits were considered as urgent and maintained as outpatient care. Additionally, patients were still able to telephone, being put through directly to their neurologists. Many requests of contact were addressed at getting information about the scheduled visits or examinations (45, 43.3%). Globally, patients and caregivers were satisfied with the telemedicine service. However, the majority (85, 65.9%) would prefer a face-to-face visit. In conclusion, telemedicine could be considered a good complement to face-to-face care, even after social restrictions have been eased.

Introduction In the brain, the chemokine (C-X3-C motif) receptor 1 (1CX3CR1) gene is expressed only by microglia, where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the 2 common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. Methods The study included 755 ALS patients diagnosed in Piemonte between 2007 and 2012 and 369 age-matched and sex-matched controls, all genotyped with the same chips. Results Neither of the variants was associated with an increased risk of ALS. Patients with the V249I V/V genotype had a 6-month-shorter survival than those with I/I or V/I genotypes (dominant model, P = 0.018). The T280M genotype showed a significant difference among the 3 genotypes (additive model, P = 0.036). Cox multivariable analysis confirmed these findings. Discussion We found that common variants of the CX3CR1 gene influence ALS survival. Our data provide further evidence for the role of neuroinflammation in ALS. Muscle Nerve 57: 212-216, 2018.

Background and purpose: The aim of the study was to evaluate the metabolic correlates of Apolipoprotein E (APOE) genotype in amyotrophic lateral sclerosis (ALS) and to investigate the role of e2 as a risk factor for cognitive impairment. Methods: A total of 159 ALS cases underwent APOE and ALS-related genes analysis, neuropsychological assessment and cerebral 18F-2-fluoro-2-deoxy-Dglucose positron emission tomography. The APOE genotype was regressed against whole brain metabolism as assessed by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography, with age, sex, education, type of onset and C9orf72 status as covariates. Results: Brain metabolism was significantly positively correlated with APOE genotype from e2/e2 to e3/e4 in the left prefrontal [Brodmann area (BA) 10], orbitofrontal (BAs 11, 45, 47) and anterior cingulate (BA 32) cortices. There was a tendency to a relative hypometabolism going towards the e2/e2 extreme. Conclusions: We found a highly significant, relatively lower metabolism in association with the e2 allele in extra-motor areas typically affected in frontotemporal dementia (left prefrontal, orbitofrontal and anterior cingulate cortices), strengthening the finding of a role of e2 as a risk factor for cognitive impairment in ALS. Our data suggested a link between cholesterol homeostasis and neurodegeneration.

ObjectiveIn 2017, the diagnostic criteria for cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (ALSFTD-1) have been modified (ALSFTD-2) with the inclusion of a novel category (ALS with combined cognitive and behavioural impairment, ALScbi) and with changes of operational criteria of the other categories (ALS with cognitive impairment (ALSci), ALS with behavioural impairment (ALSbi) and ALS with frontotemporal dementia (ALS-FTD)). We compared the two sets of criteria to assess the effect of the revised criteria on the cognitive classification of patients with ALS.MethodsTwo cohorts of patients with ALS were included in this study: a population-based cohort including patients identified through the Piemonte/Valle d’Aosta register for ALS in the 2014–2017 period (n=321), and a referral cohort recruited at the Turin ALS centre and at the ALS centre of the Maugeri Institute in Milan in the same period (n=205). Cognitive function was classified in blind by two neuropsychologists expert in ALS.ResultsALSFTD-2 criteria determined a shift of about 15% of patients from their original category to a new one. In both cohorts, about 9% of patients were reclassified to the novel category ALScbi. Among patients previously classified as cognitively normal, 14 (4.3%, population-based cohort) and 19 (9.3%, referral cohort) were reclassified as ALSbi or ALSci. The median survival of the different categories was significantly different with both with sets of criteria.ConclusionsThe new ALSFTD-2 criteria, compared with the old ones, have positive effects on the clinical practice being more sensitive to the early cognitive impairment and having a better prognostic yield.

© 2018 Elsevier Inc., 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.

Objective To assess the prognostic influence of premorbid smoking habits and vascular risk profile on amyotrophic lateral sclerosis (ALS) phenotype and outcome in a population-based cohort of Italian patients. Methods A total of 650 patients with ALS from the Piemonte/Valle d9Aosta Register for ALS, incident in the 2007–2011 period, were recruited. Information about premorbid cigarette smoking habits and chronic obstructive pulmonary disease (COPD) were collected at the time of diagnosis. Results Current smokers had a significantly shorter median survival (1.9 years, IQR 1.2–3.4) compared with former (2.3 years, IQR 1.5–4.2) and never smokers (2.7 years, IQR 1.8–4.6) (p=0.001). Also COPD adversely influenced patients’ prognosis. Both smoking habits and CODP were retained in Cox multivariable model. Conclusions This study has demonstrated in a large population-based cohort of patients with ALS that cigarette smoking is an independent negative prognostic factor for survival, with a dose–response gradient. Its effect is not related to the presence of COPD or to respiratory status at time of diagnosis. The understanding of the mechanisms, either genetic or epigenetic, through which exogenous factors influence disease phenotype is of major importance towards a more focused approach to cure ALS.

Importance Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with a wide spectrum of involvement of cognitive functions. The mechanisms of this heterogeneity are still largely unknown, but genetic variants may account for this variability. Objective To assess the influence of the apolipoprotein E (APOE) andC9ORF72genotypes on cognitive impairment in a population-based series of Italian patients with ALS. Design, Setting, and Participants All 504 patients with ALS living in Piemonte, Italy, diagnosed between January 1, 2009, and December 31, 2013, and identified through the Piemonte and Valle d’Aosta register for ALS, were eligible to participate in the study. Controls were 223 age- and sex-matched individuals identified through the patients’ general practitioners. Data analysis was performed from June 1 to December 31, 2014. Main Outcomes and Measures The presence ofAPOEandC9ORF72genotypes was assessed. Patients were cognitively classified as having ALS with normal cognition, ALS with frontotemporal dementia (FTD), ALS with executive or nonexecutive impairment, and ALS with behavioral impairment. Results Of the 504 patients with incident ALS, 357 (70.8%) were included in the study; 154 were women, 203 were men, they had a mean (SD) age at onset of 64.8 (10.2) years, and 37 of them carried aC9ORF72repeat expansion. Cognitive testing revealed that 184 patients (51.5%) had ALS with normal cognition, 51 (14.3%) had ALS with FTD, 103 (28.9%) had ALS with executive or nonexecutive impairment, and 19 (5.3%) had ALS with behavioral impairment. Distribution ofAPOEhaplotypes did not significantly differ between patients and controls or among patients with different levels of cognitive impairment. According to multivariate logistic regression, the presence ofC9ORF72repeat expansions was the strongest determinant of FTD (odds ratio, 13.08; 95% CI, 4.75-36.02;P Conclusions and Relevance C9ORF72repeat expansions have a primary role in increasing the risk of cognitive impairment in patients with ALS; theAPOEe2 allele, to a lesser extent, also increases the risk of FTD. These study findings highlight the importance of considering the genetic background of patients with ALS when analyzing the putative effect of genetic modifiers.

Objective: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18 F-2-fluoro-2-deoxy-d-glucose-PET ( 18 F-FDG-PET). Methods: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18 F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n = 94), full-blown frontotemporal dementia (ALS-FTD; n = 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n = 37), prevalent behavioral changes (n = 9), or nonclassifiable impairment (n = 10) according to neuropsychological testing. Group comparisons of 18 F-FDG-PET pattern were carried out among the cognitive subgroups. Results: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18 F-FDG uptake differences. Conclusions: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18 F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment.

Objective: To assess the effect of neurobehavioral dysfunction on amyotrophic lateral sclerosis (ALS) survival and on the use of life-prolonging therapies in a population-based setting. Methods: Of the 132 patients diagnosed with ALS in the province of Torino, Italy, between January 1, 2007, and June 30, 2008, 128 participated in the study. Neurobehavioral dysfunction was assessed with the Frontal Systems Behavior Scale (FrSBe), using the Family Rating forms, administered within 4 months from diagnosis. Results: The 128 patients included 71 men and 57 women, with a mean age at onset of 64.7 (SD 11) years. Forty-one patients (32.0%) had a neurobehavioral dysfunction and 9 (7.0%) an isolated dysexecutive behavior. Enteral nutrition (EN) and noninvasive ventilation (NIV) were performed with similar frequencies in patients with and without neurobehavioral dysfunction. Patients with neurobehavioral dysfunction had a significantly shorter survival than those with a normal FrSBe score (median survival, 3.3 vs 4.3 years; p = 0.02). Patients with isolated dysexecutive behavior had a shorter survival than those without neurobehavioral dysfunction (median survival, 2.5 vs 4.5 years; p = 0.03). Patients with neurobehavioral dysfunction had a shorter survival after EN and NIV, while patients with isolated dysexecutive behavior had a shorter survival after NIV but not after EN. The negative effect of comorbid neurobehavioral dysfunction and of isolated dysexecutive behavior on survival persisted under the Cox multivariate model. Conclusions: The presence of neurobehavioral dysfunction or of isolate dysexecutive behavior in ALS at diagnosis is a strong predictor of a poor outcome, partially related to a reduced efficacy of life-prolonging therapies.

Background and purpose: To assess the prevalence and characteristics of pain in an epidemiological series of patients with amyotrophic lateral sclerosis (ALS) compared to population-based controls. Methods: Of the 183 patients with ALS resident in the province of Torino, Italy, 160 accepted to be interviewed. Controls were randomly selected from the lists of general practitioners. Pain was assessed using the Brief Pain Inventory. Results: Patients with ALS reported pain more frequently than controls [91 (56.9%) vs. 53 (33.1%); P = 0.001]. Pain frequency and intensity were correlated with a worse functional score and a longer disease duration. In patients with ALS, pain was more frequently located at the extremities (P = 0.006). Pain interfered with all areas of daily function, but patients reported a greater interference than controls in the domains of enjoyment of life and relation with other people. Sixty-four patients (70.3% of those with pain) and 24 controls (45.3% of those with pain) (P = 0.003) were treated for pain, most frequently with non-steroidal anti-inflammatory drugs. ALS cases were also more frequently prescribed non-opioid analgesics and opioids than controls. Conclusions: Our study indicates that pain is frequent in all stages of ALS, but that it often goes underrecognized and undertreated. It is significantly more frequent in patients with ALS than in population-based controls. Future studies need to clarify the mechanisms of pain in ALS and determine the most effective treatment strategy.

It has been repeatedly shown that religiousness and spirituality have positive effects on quality of life (QoL) and outcome in ALS patients. here are, however, very few data on the impact of religiousness/spirituality on ALS caregivers. We determined the impact of religiousness on caregivers and its correlation with quality of life, depression and anxiety. A total of 75 consecutive ALS patients and their informal caregivers were interviewed using tests evaluating religiousness, depression, anxiety, quality of life and satisfaction with life. Results showed that there was a significant correlation between patients and caregivers' public and total religiousness. Caregivers' private religiousness was related to their age and education level, while their public religiousness was related only to their education level. Caregivers' quality of life was related to their private religiousness and satisfaction with life with their total religiousness. We conclude that religiousness is positively associated with ALS caregivers' quality of life and satisfaction with life, in a measure similar to that observed in ALS patients. Health care professionals caring for ALS patients should consider that the needs of the caregivers include religious/spiritual concerns.

Unilateral isolated hypoglossal nerve palsy (IHNP) is a condition (1–7) usually symptomatic of a pathology of the skull base (6,8). In rare cases, IHNP remains of unknown aetiology and is classifie...

Importance This study reports the long-term epidemiologic trends of amyotrophic lateral sclerosis (ALS) based on a prospective register. Objective To examine the 20-year epidemiologic trends of ALS in the Piemonte and Valle d’Aosta regions of Italy. Design, Setting, and Participants The Piemonte and Valle d’Aosta Register for ALS (PARALS) is an epidemiologic prospective register that covers 2 Italian regions (population of 4 476 931 inhabitants according to the 2011 census) from January 1, 1995, through December 31, 2014. Case ascertainment is based on multiple sources (neurologic departments, hospital discharge archives, and mortality records). Incidence rates are age and sex standardized for the Italian population of the 2011 census. Age-period-cohort (APC) analysis was performed using a Poisson regression model. Main Outcomes and Measures The primary study outcomes were long-term incidence and prevalence rates of ALS using a prospective design and their determinants. Results During the study period, a total of 2702 patients (mean [SD] age at onset, 65.7 [11.1] years; 1246 [46.1%] female and 1456 [53.9%] male) received a diagnosis of ALS between 1995 and 2014, corresponding to a crude annual incidence rate of 3.03 per 100 000 population (95% CI, 2.85-3.23) and an adjusted incidence rate of 2.78 per 100 000 population (95% CI, 2.57-2.96). The age-adjusted incidence rate increased in the 2 decades of the study (1995-2004: 2.66; 95% CI, 2.50-2.83; 2005-2014: 2.89; 95% CI, 2.71-3.07; P = .04), mostly in women. The adjusted rate ratio of men to women decreased from 1.27:1 (1995-2004) to 1.17:1 (2005-2014). The analysis of deviance for the APC regression models indicated that the drift variable is relevant in explaining the variation of ALS incidence rates over time in the overall population (change in deviance, 4.6553; P = .03) and in women (change in deviance, 3.8821; P = .05) but not in men (change in deviance, 0.77215; P = .38). A total of 479 patients with ALS were alive and had not undergone tracheostomy at the prevalence day (December 31, 2014), corresponding to a crude prevalence rate of 10.54 per 100 000 population (95% CI, 9.64-11.52). Conclusions and Relevance During the 1995 to 2014 period, the crude and adjusted incidences of ALS increased in Piemonte and Valle d’Aosta, mostly in women. The APC model revealed that the increase of ALS incidence is attributable to a birth cohort effect in women, with a peak in the 1930 cohort. The different increase of ALS incidence in men and women points to an effect of exogenous factors with a differential effect on the 2 sexes, acting on a genetic background.

Amyotrophic lateral sclerosis causes upper and lower motor neurons degeneration. Respiratory failure usually leads to death within three years. ALS is considered a complex disease, involving geneti...

The frequency of SOD1 mutations differs among populations: in Italy they account for 13.6% of familial ALS and 0.7% of sporadic cases. We describe an apparently sporadic Italian ALS patient, carrying a novel p.E121G heterozygous missense mutation of SOD1, with a 14-year disease course and a prevalent lower motor neuron phenotype, which are not uncommon among SOD1 mutations carriers. To our knowledge, no other mutation of codon 121 of SOD1 has ever been reported. Three in silico models suggest a deleterious effect of the p.E121G mutation. Nevertheless, further studies are necessary to confirm its pathogenic role and to evaluate eventual genotype-phenotype correlations.

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. We describe the case of a patient with a rapidly progressive form of ALS characterized by both upper and lower motor neuron impairment, no early bulbar signs and severe pain in all four extremities. The patient had a heterozygous c.271G > A mutation in SOD1, leading to an amino acids substitution of asparagine to aspartate at position 90 of the protein chain (p.D90N). Our report confirms that ALS patients with D90 codon heterozygous mutations may be associated with rapid progression and a prominent pain syndrome.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving upper and lower motor neurons. Up to 50 % of ALS cases have cognitive and/or behavioral impairment falling into the spectrum of frontotemporal dementia (FTD) [1]. Approximately 10 % of cases are familial (FALS), while the others are considered sporadic, as their occurrence seems to be random throughout the population. Recently, a GGGGCC hexanucleotide repeat expansion in the first intron of c9orf72 gene on chromosome 9p21 has been related to familial and sporadic cases with ALS, ALS-FTD, or FTD. [2–4]. We describe a 52-year-old man carrying the GGGGCC expansion in the c9orf72 gene. At 50, he developed muscle weakness and wasting at the right hand. Soon after he developed intrusive thoughts of urine loss, not supported by clinical evidence. After a pantoclastic episode characterized by aggressiveness towards objects and auditory hallucinations due to an obsessive impulse to urinary stimuli, he was admitted to our hospital. He had muscle weakness and atrophy of upper limbs (predominantly right) and spasticity of upper and lower limbs, hyperactive deep tendon reflexes, hyperactive jaw jerk, and fasciculations at limbs and trunk muscles. Bulbar and respiratory muscles were spared. Needle EMG showed a diffuse pattern of chronic and active denervation, with normal nerve conduction studies. Motor-evoked potentials demonstrated increased central motor conduction time. Psychiatric evaluation was consistent with obsessive–compulsive disorder (OCD) with predominantly Obsessional Thoughts or Rumination (ICD-10 code F42.0), with psychotic manifestations. The patient’s father died at 42 years old from spinal amyotrophic lateral sclerosis (ALS); he had no cognitive or behavioral impairment. The patient’s sister and a paternal uncle had a depressive disorder. The patient was found to carry a hexanucleotide repeat expansion in c9orf72 gene ([50 repeats); no other mutations of major ALS-FTD related genes were found. Magnetic resonance imaging (MRI) revealed bilateral reduction of fractional anisotropy along the corticospinal tract (predominantly right). Brain positron emission tomography (PET) with FDG presented reduced hypometabolism in the motor cortex bilaterally, in the fronto-mesial cortex bilaterally between the anterior and the middle cingulate gyrus (predominantly right) and in the postero-lateral occipital cortex bilaterally (Fig. 1). The neuropsychological assessment was consistent with a diagnosis of behavioral FTD, associated to OCD, hallucinations, and depressive mood disorder. In the following months, the patient developed dysarthria, dysphagia, tongue atrophy with fasciculations, lower limb weakness and hypotrophy, and worsening of spasticity at the upper and lower limbs. A. Calvo (&) C. Moglia A. Canosa A. Ilardi E. Bersano D. Bertuzzo A. Chio Department of Neuroscience, University of Turin, via Cherasco 15, 10126 Turin, Italy e-mail: andreacalvo@hotmail.com

Background Different amyotrophic lateral sclerosis (ALS) phenotypes have been recognised, marked by a varying involvement of spinal and bulbar upper and lower motor neurons. However, the differential characteristics of these phenotypes are still largely unknown. Objective To define the epidemiology and outcome of ALS phenotypes in a population based setting. Methods All ALS cases incident in two Italian regions were prospectively collected from 1995 to 2004 in an epidemiological register. Cases were classified according to established ALS phenotypes: classic, bulbar, flail arm, flail leg, pyramidal, respiratory, pure lower motor neuron (PLMN) and pure upper motor neuron (PUMN). Results ALS phenotype were determined in 1332 out of 1351 incident patients (98.6%). Classic and bulbar phenotypes had similar mean annual incidence rates. Gender specific incidence rates showed a male preponderance in respiratory, flail arm, classic and PLMN phenotypes; in all other phenotypes, men and women had similar incidence rates. Age at onset was significantly lower in pyramidal, PLMN and PUMN phenotypes and higher in the bulbar phenotype. The best outcomes were observed in PUMN, pyramidal, PLMN and flail arm phenotypes and the worst in respiratory and bulbar phenotypes. Conclusions Our epidemiological findings suggest that ALS phenotypes carry distinctive and easily distinguishable clinical and prognostic characteristics, strongly related to a complex interplay between gender and age. The categorisation of ALS patients according to more homogenous clinical groups is relevant in identifying biological markers for ALS and should be considered for the design of clinical trials.

Monomelic amyotrophy (MA) is a variant of motor neuron disease (MND), characterized by muscle weakness and atrophy restricted to one limb. We describe the case of a 56-year-old Italian patient who developed a segmental muscular atrophy limited to the lower left limb. After 11 years of clinical stability he developed progressive spread of the disease to all limbs and to bulbar and respiratory muscles. The patient died from respiratory failure 15 years after disease onset. This case demonstrates that monomelic amyotrophy may rarely evolve to a diffuse fatal MND, even after more than a decade of clinical stability. Our findings support the idea that MA is part of the clinical continuum of MND.

Recently hyperlipidemia was reported to be related to a significantly better outcome in amyotrophic lateral sclerosis (ALS). To investigate this, we evaluated the status of blood lipids in a large Italian series of patients with ALS, and assessed the effect of hyperlipidemia on patients' survival.The study population included 658 patients with ALS consecutively observed in 2 Italian ALS centers between 2000 and 2006. They were compared to a series of 658 healthy subjects, matched by age and gender.The mean levels of total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and the LDL/HDL ratio were similar in patients with ALS and controls. Total cholesterol, HDL, triglyceride, and LDL/HDL ratio levels showed a significant decrease in patients with forced vital capacity70% compared to those with FVCor=90%. For each level of ALS-FRS, poorer respiratory function was related to a lower LDL/HDL ratio. Univariate survival analysis did not find any significant effect of LDL/HDL ratio on survival, either when comparing patients with ratiosor=2.99 vs2.99 or patients in the first quartile of LDL/HDL ratio (or=1.67) vs those in the fourth quartile (2.79). No dose-response was found for LDL/HDL ratio subdividing patients into 5 quintiles.Our findings do not support the observation that patients with amyotrophic lateral sclerosis have hyperlipidemia or that hyperlipidemia in this population is related to longer survival. However, some evidence emerged that respiratory impairment, but not a worse clinical status or a lower body mass index, is related to a decrease in blood lipids and LDL/HDL ratio.

Objective: To describe a patient with a double pathogenetic mutation of C9ORF72 and TARDBP genes. Background Several genes have been found to be related to ALS; however, patients carrying two different pathogenetic genetic mutations have never been described. Design/Methods: We are performing a study of genetic determinants of familial ALS in Italy. All patients undergo mutational analysis for SOD1, FUS and TARDBP and OPTN . Repeat primer PCR to screen the presence of the hexanucleotide expansion in the first intron of C9ORF72 is performed. Results: The index case was a year-old man who at 43 developed bulbar-onset ALS with behavioural frontemporal dementia (FTD) occurring one year later. He deceased 34 months after the onset of ALS. He carried both a A382T missense mutation of the TARDBP gene and a hexanucleotide repeat expansion of C9ORF72 gene. His father, who also had a hexanucleotide repeat expansion of C9ORF72 gene, developed spinal onset ALS at 64, and behavioural FTD two years later. He deceased 78 months after the onset of ALS. His mother developed spinal onset ALS at 69 and a mild FTD six months later. She deceased at 73. She carried a A382T missense mutation of the TARDBP gene. The proband9s brother developed ALS at 33 and deceased 75 months after the onset of ALS, without cognitive impairment. No DNA is available of this patients. Conclusions: The proband had two mutations pathogenetic for ALS and FTD, one ( TARDBP ) transmitted from the maternal line, and the other ( C9ORF72 ) from the paternal line. He developed ALS with FTD at 43 years, much earlier than his parents, and had a more severe clinical course. The presence of two pathogenetic mutations in this patients indicates that multiple genetic factors should be considered in pathogenesis of ALS and are likely to modify the clinical course of the disease. Disclosure: Dr. Calvo has nothing to disclose. Dr. Borghero has nothing to disclose. Dr. Cannas has nothing to disclose. Dr. Marrosu has received personal compensation for activities with Biogen Idec and Merck Serono. Dr. Marrosu has received personal compensation in an editorial capacity for Neurological Sciences. Dr. Marrosu has received research support from Serono Foundation, Biogen Idec, Schering Italy, and Sanofi Aventis. Dr. Murru has nothing to disclose. Dr. Floris has nothing to disclose. Dr. Traynor has received personal compensation in an editorial capacity for the journal Neurology. Dr. Renton has nothing to disclose. Dr. Moglia has nothing to disclose. Dr. Canosa has nothing to disclose. Dr. Ilardi has nothing to disclose. Dr. Cammarosano has nothing to disclose. Dr. Brunetti has nothing to disclose. Dr. Ossola has nothing to disclose. Dr. Restagno has nothing to disclose. Dr. Chio has nothing to disclose.

Objective: To assess the recognition of facial expression of primary and social emotions and to correlate it with depressive and behavioural symptoms. Background Facial expressions play an important role in communication processes. Previous studies have indicated that ALS patients have disturbances in emotional perception and memory. Understanding social abilities in ALS patients is therefore a focus for further consideration and concern about the disease and patients management. Design/Methods: A group of 43 consecutive ALS patients and 54 controls were tested to evaluate their ability to recognize facial expressions of basic and social emotions. Further questionnaires were administered to the patients group in order to assess behavioural changes, mood and quality of life. Results: In recognizing facial expressions ALS patients made significantly more errors than healthy controls. Considering the 6 basic emotions, 12 patients and only 2 controls showed performances above the cut-off score. Similarly, patients made more errors than controls in the social emotion test. Bulbar onset or the presence of bulbar signs at the time of the evaluation was not correlated to the error recognition rate of basic and social facial expression. The error rate was not correlated to the patients physical status. We also found a statistically significant correlation between the facial recognition of basic emotions and neurobehavioral symptoms with a higher number of errors corresponding to a higher FrSBe score. Conclusions: Our findings suggest that patients with ALS show a different pattern of recognition in facial expression when compared to healthy adults. Emotional recognition deficits may occur in ALS, particularly with emotional facial expressions, and can arise independently from depressive symptoms. In our series the recognition of facial basic emotions seems to be correlated with the presence of behavioural changes of the frontotemporal type supporting the presence of a diminished social competence. Disclosure: Dr. Moglia has nothing to disclose. Dr. Calvo has nothing to disclose. Dr. Ilardi has nothing to disclose. Dr. Canosa has nothing to disclose. Dr. Cammarosano has nothing to disclose. Dr. Bersano has nothing to disclose. Dr. Bertuzzo has nothing to disclose. Dr. Manera has nothing to disclose. Dr. Moglia has nothing to disclose. Dr. Casale has nothing to disclose. Dr. Montuschi has nothing to disclose. Dr. Chio has nothing to disclose.

To evaluate information preferences and information seeking behaviour in ALS patients and caregivers. Sixty ALS patients and caregivers couples were interviewed using a structured questionnaire about the content of diagnosis communication and their information seeking behaviour. The patients (35 men and 25 women) had a mean age of 63.4 years (SD 9.5). The caregivers (21 men and 39 women) had a mean age of 53.3 years (SD 14.9). The overall satisfaction with bad news communication and the impression that the physician had understood their feelings were higher amongst patients. Both parties indicated that the most important aspects to be informed were current researches, disease-modifying therapies and ALS outcome. Approximately 55% of patients and 83.3% of caregivers searched for information from sources outside the healthcare system. The most frequently checked source was internet, although its reliability was rated low. The caring neurologist should better attune the content of communication to patients' and caregivers' preferences, trying to understand what they want to know and encouraging them to make precise questions. Health professionals should be aware that ALS patients and caregivers often use internet to obtain information and should help them to better sort-out and interpret the news they found.