MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.

Following the discovery of glial fibrillary acidic protein (GFAP) mutations as the causative factor of Alexander disease (AxD), new case reports have recently increased, prompting a more detailed comprehension of the clinical features of the three disease subtypes (infantile, juvenile and adult). While the clinical pattern of the infantile form has been substantially confirmed, the late-onset subtypes (i.e., juvenile and adult), once considered rare manifestations of AxD, have displayed a wider clinical spectrum. Our aim was to evaluate the clinical phenotype of the adult and juvenile forms by reviewing the previously reported cases. Data were collected from previously published reports on 112 subjects affected by neuropathologically or genetically proven adult and juvenile Alexander disease. Although the late-onset forms of AxD show a wide clinical variability, a common pattern emerges from comparing previously reported cases, characterized by pseudo-bulbar signs, ataxia, and spasticity, associated with atrophy of the medulla and upper cervical cord on neuroimaging. Late-onset AxD cases can no longer be considered as rare manifestations of the disease. The clinical pattern usually reflects the topographic localization of the lesions, with adult cases displaying a predominant infratentorial localization of the lesions. Juvenile cases show clinical and radiological features which are intermediate between adult and infantile forms.

turchEtti 34 , donatella bonaiuti 35 on behalf of italian consensus conference on robotics in neurorehabilitation (cicEronE)1 irccs centro neurolesi bonino-pulejo, Messina, italy; 2 department of Medicine and rehabilitation, polyclinic of Monza, Monzabrianza, italy; 3 spinal cord unit and intensive rehabilitation Medicine, ausl piacenza, Villanova sull'arda and castel san Giovanni, piacenza, italy; 4 Gait and Motion analysis laboratory opa sol et salus, torre pedrera, rimini, italy; 5 department of Experimental and clinical Medicine università politecnica delle Marche (uniVpM), ancona, italy; 6 spinal cord unit, department of rehabilitation Medicine, Gervasutta hospital, udine, italy; 7 azienda sanitaria universitaria friuli centrale (asu-fc), udine, italy; 8 neuromotor and rehabilitation department, laM-Motion analysis laboratory, ausl-irccs reggio Emilia, reggio Emilia, italy; 9 rehabilitation therapeutic center, tramutola, potenza, italy; 10 irccs a. Gemelli university polyclinic foundation, rome, italy; 11 section of neurorehabilitation, department of translational research and new technologies in Medicine and surgery, university of pisa, pisa, italy; 12 Montecatone rehabilitation institute, imola, bologna, italy; 13 unit of neurophysiopathology, ics Maugeri, Montescano institute, pavia, italy; 14 centro protesi Vigorso di budrio, istituto nazionale assicurazione infortuni sul lavoro (inail),

Pathogenic, dominant, de novo missense mutations in the glial fibrillary acidic protein (GFAP) have been found in the three subtypes of infantile, juvenile and adult Alexander disease. Here we describe four members of an Italian family (32 to 66-yearsold, 2 women and 2 men) affected by adult Alexander disease, the least common and the most clinically variable form. Direct sequencing of all coding regions of the GFAP gene, neurological examination and brain MRI were performed. Two novel missense mutations were found involving two very close codons, c.[988C > G, 994G > A], leading to p.[Arg330Gly, Glu332Lys]. Clinically, two members exhibited pseudo-bulbar signs, gait ataxia and spasticity, one showed a severe cranial sensory symptomatology, and one subject was asymptomatic.Medulla and cervical cord atrophy was present in all of them on MRI. Although adult Alexander disease shows a wide clinical variability, a more frequent pattern can be identified characterized by bulbar or pseudo-bulbar signs, gait ataxia, and spasticity, and including on MRI medulla and cervical cord atrophy. Our findings also confirm that the clinical spectrum of adult Alexander disease includes cases without overt neurological involvement and with minimal brain MRI alterations.

INTRODUCTION: There is growing evidence on the efficacy of gait robotic rehabilitation in patients with multiple sclerosis (MS), but most of the studies have focused on gait parameters. Moreover, clear indications on the clinical use of robotics still lack. as part of the cicEroNE italian consensus on robotic rehabilitation, the aim of this systematic review was to investigate the existing evidence concerning the role of lower limb robotic rehabilitation in improving functional recovery in patients with Ms. EVidENcE acQuisitioN: We searched for and systematically reviewed evidence-based studies on gait robotic rehabilitation in Ms, between January 1 st , 2010 and december 31 st , 2020, in the following databases: cochrane library, pEdro, pubMed and Google scholar. the study quality was assessed by the 16-item assessment of multiple systematic reviews 2 (aMstar 2) and the 10-item pEdro scale for the other research studies. EVidENcE syNthEsis: after an accurate screening, only 17 papers were included in the review, and most of them (13 rct) had a level ii evidence. Most of the studies used the Lokomat as a grounded robotic device, two investigated the efficacy of end-effectors and two powered exoskeletons. Generally speaking, robotic treatment has beneficial effects on gait speed, endurance and balance with comparable outcomes to those of conventional treatments. however, in more severe patients (Edss >6), robotics leads to better functional outcomes. Notably, after gait training with robotics (especially when coupled to virtual reality) Ms patients also reach better non-motor outcomes, including spasticity, fatigue, pain, psychological well-being and quality of life. unfortunately, no clinical indications emerge on the treatment protocols. CONCLUSIONS: The present comprehensive systematic review highlights the potential beneficial role on functional outcomes of the lower limb robotic devices in people with Ms. future studies are warranted to evaluate the role of robotics not only for walking and balance outcomes, but also for other gait-training-related benefits, to identify appropriate outcome measures related to a specific subgroup of MS subjects' disease severity.(Cite this article as: calabrò rs, cassio a, Mazzoli d, andrenelli E, bizzarini E, campanini i, et al.; italian consensus conference on robotics in Neurorehabilitation (cicEroNE). What does evidence tell us about the use of gait robotic devices in patients with multiple sclerosis? a comprehensive systematic review on functional outcomes and clinical recommendations.