Barbara Poletti

Genetics of familial Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a late onset, rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. About 10% of all ALS cases are familial (FALS), and constitute a clinically and genetically heterogeneous entity. To date, FALS has been linked to mutations in 10 different genes and to four additional chromosomal loci. Research on FALS genetics, and in particular the discoveries of mutations in the SOD1, TARDBP, and FUS genes, has provided essential information toward the understanding of the pathogenesis of ALS in general. This review presents a tentative classification of all FALS-associated genes identified so far.

Validating the neuro vr-based virtual version of the multiple errands test: Preliminary results

The purpose of this study was to establish ecological validity and initial construct validity of the virtual reality version of the Multiple Errands Test based on NeuroVR software as an assessment tool for executive functions. In particular, the Multiple Errands Test is an assessment of executive functions in daily life which consists of tasks that abide by certain rules and is performed in a shopping mall-like setting where there are items to be bought and information to be obtained. The study population included three groups: post-stroke participants (n = 9), healthy young participants (n = 10), and healthy older participants (n = 10). The general purpose of the study was investigated through the following specific objectives: (1) to examine the relationships between the performance of three groups of participants in the Virtual Multiple Errands Test (VMET) and in the traditional neuropsychological tests employed to assess executive functions; and (2) to compare the performance of post-stroke participants to those of healthy young and older controls in the Virtual Multiple Errands Test and in the traditional neuropsychological tests employed to assess executive functions. Correlations between Virtual Multiple Errands Test variables and some traditional executive functions measures provide preliminary support for the ecological and construct validity of the VMET; further performance obtained at the Virtual Multiple Errands Test provided a distinction between the clinical and healthy population, and between the two age control groups. These results suggest a possible future application of such an ecological approach for cognitive assessment and rehabilitation of stroke patients and elderly population with age-related cognitive decline.

The use of P300-based BCIs in amyotrophic lateral sclerosis: from augmentative and alternative communication to cognitive assessment

The use of augmentative and alternative communication (AAC) tools in patients with amyotrophic lateral sclerosis (ALS), as effective means to compensate for the progressive loss of verbal and gestural communication, has been deeply investigated in the recent literature. The development of advanced AAC systems, such as eye‐tracking (ET) and brain‐computer interface (BCI) devices, allowed to bypass the important motor difficulties present in ALS patients. In particular, BCIs could be used in moderate to severe stages of the disease, since they do not require preserved ocular‐motor ability, which is necessary for ET applications. Furthermore, some studies have proved the reliability of BCIs, regardless of the severity of the disease and the level of physical decline. However, the use of BCI in ALS patients still shows some limitations, related to both technical and neuropsychological issues. In particular, a range of cognitive deficits in most ALS patients have been observed. At the moment, no effective verbal‐motor free measures are available for the evaluation of ALS patients’ cognitive integrity; BCIs could offer a new possibility to administer cognitive tasks without the need of verbal or motor responses, as highlighted by preliminary studies in this field. In this review, we outline the essential features of BCIs systems, considering advantages and challenges of these tools with regard to ALS patients and the main applications developed in this field. We then outline the main findings with regard to cognitive deficits observed in ALS and some preliminary attempts to evaluate them by means of BCIs. The definition of specific cognitive profiles could help to draw flexible approaches tailored on patients’ needs. It could improve BCIs efficacy and reduce patients’ efforts. Finally, we handle the open question, represented by the use of BCIs with totally locked in patients, who seem unable to reliably learn to use such tool.

Aripiprazole in the treatment of Huntington’s disease: a case series

Objectives: The aim of the study was to describe the effects of aripiprazole, a new atypical antipsychotic drug that acts as a partial dopamine agonist on motor, behavioral and cognitive functions in patients with genetically confirmed Huntington’s disease (HD). Methods and results: Three HD patients were evaluated for Unified Huntington Disease Rating Scale part I and II and Beck Depression Inventory at baseline, after two months and one-year treatment. Aripiprazole effectively controlled involuntary movements and psychiatric symptoms, with effects on cognitive functions. Conclusions: Our case reports suggest that aripiprazole is well tolerated, remarkably improving some of the motor and behavioral symptoms in patients affected by HD. Randomized, controlled, long-term studies are warranted.

Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD)

There is increasing clinical, imaging and neurophatological evidence that amyotrophic lateral sclerosis (ALS) represents a multisystem neurodegenerative disease. Neurodegeneration is not restricted to motor neurons, but also includes parts of the brain other than the motor cortex, especially the prefrontal and/or anterior temporal lobe, that contribute to the clinical syndrome. In some cases an evident dementia that resembles frontotemporal degeneration (FTD) was observed. It is now suggested that ALS and FTD are closely related conditions with overlapping clinical, pathological, radiological, and genetic characteristics. The presence of a frontal dementia in ALS has also crucial practical consequences for management of the patients, whose disorder requires critical life decisions for enteral nutrition and respiratory complications. It is our intent to provide a brief overview of the relationships between ALS and FTD.

The diagnosis of Amyotrophic Lateral Sclerosis in 2010

The diagnosis of Amyotrophic lateral sclerosis (ALS) remains in 2010 clinical with neurophysiological support in absence of specific biomarker(s). The disease is diverse in its presentation, cause, and progression. Treatable mimic syndromes must be excluded before the diagnosis is ascribed: ALS and its variants are recognized by neurologists, but 10% of patients are misdiagnosed. Delays in diagnosis are common. Less than 10% of cases are familial and associated with several interactive genes. The onset of ALS predates development of the clinical symptoms by an unknown interval which may extend several years. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and family, a positive care plan are pre-requisites for the good clinical management of ALS patients.

The validation of the Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS)

Abstract This study presents the Italian validation of the recently developed Edinburgh Cognitive and Behavioural ALS Screen (ECAS), a short screen for cognitive/behavioural alterations in patients with amyotrophic lateral sclerosis (ALS). We evaluated the psychometric properties of the ECAS Italian version in terms of reliability and convergent validity for both cognitive and behavioural features. Furthermore, we investigated the relationship with affective and clinical variables, in addition to ECAS usability and patients’ insight into cognitive/behaviour changes. Finally, correlations between genetic and cognitive/behavioural data were analysed. We recruited 107 patients with ALS. Normative data were collected on 248 healthy subjects. Participants were administered the ECAS and two standard cognitive screening tools (FAB, MoCA), two psychological questionnaires (BDI, STAI/Y) and an ad hoc usability questionnaire. The FBI was also carried out with caregivers. Results showed that the ECAS Italian version discriminated well between patients and controls. The most prevalent deficit occurred in executive functions and fluency. Correlations were observed between the ECAS and standard cognitive screening tools and between the ECAS carer interview and the FBI, supporting its full convergent validity. In conclusion, the ECAS Italian version provides clinicians with a rapid, feasible and sensitive tool, useful to identify different profiles of cognitive-behavioural impairment in ALS.

Implementation of the Multiple Errands Test in a NeuroVR supermarket: A possible approach

Our goal was to develop a tool for the assessment of executive functions by customizing a virtual reality (VR) version of the Multiple Errands Test (MET) [Shallice & Burgess, 1991; Fortin et al., 2003]. The MET is an assessment of executive functions in daily life which consists of tasks that abide by certain rules. It is performed in an actual shopping mall-like setting where there are items to be bought and information to be obtained. The specific goal of this study was to conduct a pilot study using the virtual version of MET (VMET) with both control subjects and patients with cognitive impairment derived from stroke.

Validation of a Neuro Virtual Reality-based version of the Multiple Errands Test for the assessment of executive functions.

The purpose of this study was to establish ecological validity and initial construct validity of the Virtual Reality (VR) version of the Multiple Errands Test (MET) (Shallice & Burgess, 1991; Fortin et al., 2003) based on the NeuroVR software as an assessment tool for executive functions. In particular, the MET is an assessment of executive functions in daily life, which consists of tasks that abide by certain rules and is performed in a shopping mall-like setting where items need to be bought and information needs to be obtained. The study population included three groups: post-stroke participants (n = 5), healthy, young participants (n = 5), and healthy, older participants (n = 5). Specific objectives were (1) to examine the relationships between the performance of three groups of participants in the Virtual Multiple Errands Test (VMET) and at the traditional neuropsychological tests employed to assess executive functions and (2) to compare the performance of post-stroke participants to those of healthy, young controls and older controls in the VMET and at the traditional neuropsychological tests employed to assess executive functions.

Dysgraphia in patients with primary lateral sclerosis: a speech-based rehearsal deficit?

The present study aims to demonstrate that errors when writing are more common than expected in patients affected by primary lateral sclerosis (PLS) with severe dysarthria or complete mutism, independent of spasticity. Sixteen patients meeting Pringle’s et al. [34] criteria for PLS underwent standard neuropsychological tasks and evaluation of writing. We assessed writing abilities in spelling through dictation in which a set of words, non-words and short phrases were presented orally and by composing words using a set of preformed letters. Finally, a written copying task was performed with the same words. Relative to controls, PLS patients made a greater number of spelling errors in all writing conditions, but not in copy task. The error types included: omissions, transpositions, insertions and letter substitutions. These were equally distributed on the writing task and the composition of words with a set of preformed letters. This pattern of performance is consistent with a spelling impairment. The results are consistent with the concept that written production is critically dependent on the subvocal articulatory mechanism of rehearsal, perhaps at the level of retaining the sequence of graphemes in a graphemic buffer. In PLS patients a disturbance in rehearsal opportunity may affect the correct sequencing/assembly of an orthographic representation in the written process.