Withdrawal of mechanical ventilation in amyotrophic lateral sclerosis patients: a multicenter Italian survey

Background: Law 219/2017 was approved in Italy in December 2017, after a years-long debate on the autonomy of healthcare choices. This Law, for the first time in Italian legislation, guarantees the patient's right to request for withdrawal of life-sustaining treatments, including mechanical ventilation (MV). Objective: To investigate the current status of MV withdrawal in amyotrophic lateral sclerosis (ALS) patients in Italy and to assess the impact of Law 219/2017 on this practice. Methods: We conducted a Web-based survey, addressed to Italian neurologists with expertise in ALS care, and members of the Motor Neuron Disease Study Group of the Italian Society of Neurology. Results: Out of 40 ALS Italian centers, 34 (85.0%) responded to the survey. Law 219/2017 was followed by an increasing trend in MV withdrawals, and a significant increase of neurologists involved in this procedure (p 0.004). However, variations across Italian ALS centers were observed, regarding the inconsistent involvement of community health services and palliative care (PC) services, and the intervention and composition of the multidisciplinary team. Conclusions: Law 219/2017 has had a positive impact on the practice of MV withdrawal in ALS patients in Italy. The recent growing public attention on end-of-life care choices, along with the cultural and social changes in Italy, requires further regulatory frameworks that strengthen tools for self-determination, increased investment of resources in community and PC health services, and practical recommendations and guidelines for health workers involved

Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiomyopathy. The identification of patients with HCM is sometimes still a challenge. Moreover, the pathophysiology of the disease is complex because of left ventricular hyper-contractile state, diastolic dysfunction, ischemia and obstruction which can be coexistent in the same patient. In this review, we discuss the current and emerging echocardiographic methodology that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM

Pseudobulbar affect (PBA) in an incident ALS cohort: results from the Apulia registry (SLAP).

International audienceThe aim of this study is to investigate the frequency and the clinical correlations of pseudobulbar affect (PBA) in a population-based incident cohort of ALS patients. Incident ALS cases, diagnosed in 2011 and 2012, according to El Escorial criteria were enrolled from a prospective population-based registry in Apulia, Southern Italy. Neurological status was assessed using a standard neurological examination and the revised ALS Functional Rating Scale (ALSFRSr). The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate the presence and severity of PBA. Total scores range from 7 to 35. A score ≥13 was used to identify the presence of PBA. One-hundred thirty-two sporadic incident ALS cases were enrolled. Median disease duration was 20 months (range 2-143), median onset-diagnosis interval (ODI) 12 months (range 2-131), median ALSFRSr at baseline 36/48 (range 2-47) and median ALSFRSr bulbar sub-score 10/12 (range 0-12). Neurological examination revealed presence of PBA in 34/132 patients (26%). Pathological CNS-LS score was found in 45/132 patients (34%). Median total CNS-LS score was 9/35 (range 7-29). The subgroup with pathological CNS-LS was characterized by a short disease duration from symptom onset, ODI, time to diffusion to a second region, time to generalization and ALSFRSr bulbar sub-score, bulbar onset, "definite" diagnostic category, bulbar upper motor-neuron involvement and presence of PBA at neurological examination. In population-based setting, one-third of ALS patients present PBA at diagnosis. The presence of PBA is associated with bulbar UMN involvement and markers of a more severe phenotype

La Rocca di Monfalcone

[This corrects the article DOI: 10.3389/fnmol.2018.00288.]. Erratum for Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis. [Front Mol Neurosci. 2018

Verbal Learning Abilities in ALS Patients (P01.109)

Objective: to study the neurocognitive dysfunctions spectrum in ALS. Background neurocognitive impairment involves mainly executive dysfunction (1). On the other hand, is not clear if memory is involved primary (2). Design/Methods: fifty-five consecutive ALS patients referred to Motor NeuronCenter, Department of Neurology, University of Bari. The diagnosis was based on El Escorial criteria (Brooks, 1994). Seventy healthy age-matched control were recruited. We examined the memory abilities through the Rey's Auditory Verbal Learning Test (RAVLT): free recall in five trials, immediate and delayed recall, verbal learning, verbal forgetting, primary and recency effect score. All subjects completed also the following neuropsychological battery: Mini Mental State Examination (MMSE), Frontal Assessment Battery (FAB): Digit span forward (DSF); Digit span backward (DSB); Attentional Matrices (AM); Verbal Fluency Test (VFT); Stroop Test (ST); Raven's Colored Matrices (RCM). Results: we enrolled 33 men and 22 women in ALS group (age 59.7±9.7; educational level 9.6±4.1 yrs; disease duration at baseline 30.9±32.1 months; ALSFRS-r 37.8±6.2; FVC 92.5±22.7; MMT 8.1±1.3). Compared with controls, ALS patients performed worse on the recall immediate (p=.007). The recency and primary effect was less evident in ALS than control group (p=.018; p=.004). Moreover, the ALS group performed worse on short-term memory (DSF, p=.005), working memory (DSB, p=.000), verbal fluency (VFT, p=.000), flexibility (RCM, p=.025) and general cognitive abilities (MMSE, p=.001; FAB, p=.009). The different indices of RAVLT showed a significant correlation with all executive measures in ALS group. Conclusions: ALS patients present impairment of both executive and memory dysfunctions. The executive dysfunctions are primary involved with failure of elaborative encoding and strategic retrieval processing, as a consequence of verbal learning identified by free recall, recency and primary effect scores. On the other hand, storage processes, a main component of memory, are intact

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease

[Real-time multiplane echocardiography. Current applications, limits and perspectives]

Echocardiography is the most commonly used imaging technique in current clinical cardiology practice and is usually performed using a monoplane approach. In recent years new matrix-array transducers have become available that allow the real-time simultaneous display of two or more echocardiographic scanning planes from the same acoustic window. This multiplane approach is particularly interesting as it may reduce, during the examination, the number of probe movements and consequently facilitate image acquisition. In some clinical applications, moreover, the multiplane approach improves both accuracy and reproducibility of echocardiography. This review evaluates the state of the art of multiplane echocardiography and discusses possible clinical applications, advantages and limitations of this technique

Respiratory function in a large cohort of treatment-naïve adult spinal muscular atrophy patients: a cross-sectional study

: Due to poor data in literature, we aimed to investigate the respiratory function in a large cohort of naïve Italian adult (≥18 years) SMA patients in a multi-centric cross-sectional study. The following respiratory parameters were considered: forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and need for non-invasive ventilation (NIV). We included 145 treatment-naïve adult patients (SMA2=18, SMA3=125; SMA4=2), 58 females (40 %), with median age at evaluation of 37 years (range 18-72). Fifty-six (37 %) and 41 (31 %) patients had abnormal (<80 %) values of FVC and FEV1, respectively. Fourteen (14 %) patients needed NIV, started at median age of 21 (range 4-68). Motor function, measured by Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module as well as SMA2, loss of walking ability, surgery for scoliosis, use of NIV, and cough assisting device (CAD) were all significantly associated to lower FVC and FEV1 values, while no association with age at baseline, disease duration, gender or 6 min walking test was observed, except for a correlation between FVC and age in SMA3 walkers (p < 0.05). In conclusion, respiratory function in adult SMA patients is relatively frequently impaired, substantially stable, and significantly correlated with motor function and disease severity

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3

Objective: To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA). Methods: Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6). Results: We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18-72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14. Conclusions: Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear