Elisabetta Sarasso

Brain structural and functional connectivity in Parkinson's disease with freezing of gait

To use a multimodal approach to assess brain structural pathways and resting state (RS) functional connectivity abnormalities in patients with Parkinsons disease and freezing of gait (PD‐FoG).

Brain plasticity in Parkinson’s disease with freezing of gait induced by action observation training

Gait disorders represent a therapeutic challenge in Parkinson’s disease (PD). This study investigated the efficacy of 4-week action observation training (AOT) on disease severity, freezing of gait and motor abilities in PD, and evaluated treatment-related brain functional changes. 25 PD patients with freezing of gait were randomized into two groups: AOT (action observation combined with practicing the observed actions) and “Landscape” (same physical training combined with landscape-videos observation). At baseline and 4-week, patients underwent clinical evaluation and fMRI. Clinical assessment was repeated at 8-week. At 4-week, both groups showed reduced freezing of gait severity, improved walking speed and quality of life. Moreover, AOT was associated with reduced motor disability and improved balance. AOT group showed a sustained positive effect on motor disability, walking speed, balance and quality of life at 8-week, with a trend toward a persisting reduced freezing of gait severity. At 4-week vs. baseline, AOT group showed increased recruitment of fronto-parietal areas during fMRI tasks, while the Landscape group showed a reduced fMRI activity of the left postcentral and inferior parietal gyri and right rolandic operculum and supramarginal gyrus. In AOT group, functional brain changes were associated with clinical improvements at 4-week and predicted clinical evolution at 8-week. AOT has a more lasting effect in improving motor function, gait and quality of life in PD patients relative to physical therapy alone. AOT-related performance gains are associated with an increased recruitment of motor regions and fronto-parietal mirror neuron and attentional control areas.

Action observation training to improve motor function recovery: a systematic review

Following the discovery of Mirror Neuron System (MNS), Action Observation Training (AOT) has become an emerging rehabilitation tool to improve motor functions both in neurologic and orthopedic pathologies.The aim of this study is to present the state of the art on the use of AOT in experimental studies to improve motor function recovery in any disease.The research was performed in PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials (last search July 2015). Randomized controlled trials (RCTs) that analyse efficacy of AOT for recovery of motor functions, regardless of the kind of disease, were retrieved. The validity of the included studies was assessed using the Cochrane Collaboration tool for evaluating risk of bias.Twenty RCTs were eligible. Four studies showed AOT efficacy in improving upper limb functional recovery in participants with chronic stroke, two studies in sub-acute ones and one in acute ones. Six articles suggested its effectiveness on walking performance in chronic stroke individuals, and three of them also suggested an efficacy in improving balance. The use of AOT was also recommended in individuals with Parkinson’s disease to improve autonomy in activities of daily living, to improve spontaneous movement rate of self-paced finger movements and to reduce freezing of gait. Other two studies also indicated that AOT improves upper limb motor function in children with cerebral palsy. The last two studies, showed the efficacy of AOT in improving motor recovery in postsurgical orthopedic participants. Overall methodological quality of the considered studies was medium.The majority of analyzed studies suggest the efficacy of AOT, in addition to conventional physiotherapy, to improve motor function recovery in individuals with neurological and orthopedic diseases. However, the application of AOT is very heterogeneous in terms of diseases and outcome measures assessed, which makes it difficult to reach, to date, any conclusion that might influence clinical practice.

Effects of pharmacological and nonpharmacological treatments on brain functional magnetic resonance imaging in Alzheimer’s disease and mild cognitive impairment: a critical review

BackgroundA growing number of pharmacological and nonpharmacological trials have been performed to test the efficacy of approved or experimental treatments in Alzheimer disease (AD) and mild cognitive impairment (MCI). In this context, functional magnetic resonance imaging (fMRI) may be a good candidate to detect brain changes after a short period of treatment.Main bodyThis critical review aimed to identify and discuss the available studies that have tested the efficacy of pharmacological and nonpharmacological treatments in AD and MCI cases using task-based or resting-state fMRI measures as primary outcomes. A PubMed-based literature search was performed with the use of the three macro-areas: ‘disease’, ‘type of MRI’, and ‘type of treatment’. Each contribution was individually reviewed according to the Cochrane Collaboration’s tool for assessing risk of bias. Study limitations were systematically detected and critically discussed. We selected 34 pharmacological and 13 nonpharmacological articles. According to the Cochrane Collaboration’s tool for assessing risk of bias, 40% of these studies were randomized but only a few described clearly the randomization procedure, 36% declared the blindness of participants and personnel, and only 21% reported the blindness of outcome assessment. In addition, 28% of the studies presented more than 20% drop-outs at short- and/or long-term assessments. Additional common shortcomings of the reviewed works were related to study design, patient selection, sample size, choice of outcome measures, management of drop-out cases, and fMRI methods.ConclusionThere is an urgent need to obtain efficient treatments for AD and MCI. fMRI is powerful enough to detect even subtle changes over a short period of treatment; however, the soundness of methods should be improved to enable meaningful data interpretation.

Functional MRI in Atypical Parkinsonisms

The present chapter reports the current knowledge on the use of functional MRI (fMRI) in patients with atypical parkinsonisms, including Multiple System Atrophy, Corticobasal Syndrome and Progressive Supranuclear Palsy syndrome. Both resting state functional connectivity and task-based brain activity abnormalities are reported in atypical parkinsonisms relative to healthy controls and Parkinsons disease patients. Functional alterations were observed earlier than structural damage and may help to make early diagnosis. The chapter also examines the few longitudinal evidence on fMRI changes in patients with these conditions. The potential use of fMRI techniques in aiding the differential diagnosis, accurately measuring disease progression and assessing the effectiveness of therapeutic interventions is discussed.

Are there two different forms of functional dystonia? A multimodal brain structural MRI study

This study assessed brain structural alterations in two diverse clinical forms of functional (psychogenic) dystonia (FD) – the typical fixed dystonia (FixFD) phenotype and the “mobile” dystonia (MobFD) phenotype, which has been recently described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43 healthy controls were recruited. All subjects underwent 3D T1-weighted and diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness, volumes of gray matter (GM) structures, and white matter (WM) tract integrity were assessed. Normal cortical thickness in both FD patient groups compared with age-matched healthy controls were found. When compared with FixFD, MobFD patients showed cortical thinning of the left orbitofrontal cortex, and medial and lateral parietal and cingulate regions bilaterally. Additionally, compared with controls, MobFD patients showed reduced volumes of the left nucleus accumbens, putamen, thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared with both controls and MobFD cases, FixFD patients showed a severe disruption of WM architecture along the corpus callous, corticospinal tract, anterior thalamic radiations, and major long-range tracts bilaterally. This study showed different MRI patterns in two variants of FD. MobFD had alterations in GM structures crucial for sensorimotor processing, emotional, and cognitive control. On the other hand, FixFD patients were characterized by a global WM disconnection affecting main sensorimotor and emotional control circuits. These findings may have important implications in understanding the neural substrates underlying different phenotypic FD expression levels.

Mirror therapy for an adult with central post-stroke pain: a case report

BackgroundTreatment of central post-stroke pain (CPSP) after a thalamic-capsular stroke is generally based on pharmacological approach as it is low responsive to physiotherapy. In this case report, the use of mirror therapy (MT) for the reduction of CPSP in a subject after a stroke involving thalamus is presented.Case presentationFive years after a right lenticular-capsular thalamic stroke, despite a good recovery of voluntary movement that guaranteed independence in daily life activities, a 50-year-old woman presented with mild weakness and spasticity, an important sensory loss and a burning pain in the left upper limb. MT for reducing arm pain was administered in 45-min sessions, five days a week, for two consecutive weeks. MT consisted in performing symmetrical movements of both forearms and hands while watching the image of the sound limb reflected by a parasagittal mirror superimposed to the affected limb. Pain severity was assessed using visual analogue scale (VAS) before and after the intervention and at one-year follow-up. After the two weeks of MT, the patient demonstrated 4.5 points reduction in VAS pain score of the hand at rest and 3.9 points during a maximal squeeze left hand contraction. At one-year follow-up, pain reduction was maintained and also extended to the shoulder.ConclusionThis case report shows the successful application of a motor training with a sensory confounding condition (MT) in reducing CPSP in a patient with a chronic thalamic stroke.

DIAGNOSTIC UTILITY OF FDG-PET TO CONFIRM A CLINICAL SUSPICION OF AMYOTROPHIC LATERAL SCLEROSIS

that AD family history (FH) changes the association between VL poly-T length and cognitive decline in cognitively normal middle-aged and aged adults across the AD spectrum. Thus, we examined TOMM40 poly-T genotype, FH, and their interaction on changes in medial temporal lobe (MTL) gray matter (GM) and glucose metabolism across time. Methods:Longitudinal linear mixed modeling assessed FH and TOMM40 main effects and interactions, among non-APOE4’s, for subsets of 913 middle-aged subjects from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) over 7-10 years and 334 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) over 3 years. FreeSurfer was used to derive mean MTL volume and cortical thickness (CT). Arterial spin labeling (ASL) in WRAP and fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in ADNI were used to gauge MTL glucose metabolism. Results: Significant TOMM40 x FH interactions indicated that TOMM40 VL’s who were FHand FH+ respectively showed robust step-wise protective or detrimental effects for GM, ASL, and FDG-PET. Figure 1 and Figure 2 illustrate this association in MTL volume for WRAP and MTL CT for ADNI. Figure 3 illustrates this association for MTL versus global cerebral blood flow in WRAP, with comparable associations seen for FDG-PET in ADNI. Conclusions: Findings in both late middle-aged and aged cohorts suggest that FH strongly modulates the association of TOMM40 VL genotype over time on regional brain volume and glucose metabolism indices. These results extend previous findings on cognitive decline and may clarify discrepancies in the TOMM40 ‘523 poly-T literature.