SVILUPPO E VALIDAZIONE DI PROTOCOLLI AD IMPEDENZA MIOGRAFICA PER LO STUDIO DELLA ARCHITETTURA MUSCOLARE NELLE PATOLOGIE NEUROMUSCOLARI

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Assessing  Skeletal Muscle Architecture and neuromuscular disease with multifrequency electrical impedance myography.

Electrical impedance myography (EIM) is a new non-invasive technique for the evaluation of neuromuscular disease that relies upon the application and measurement of high-frequency, low-intensity electrical current.

EIM assesses disease-induced changes to muscle’s normal composition and architecture, including myocyte atrophy and loss, edema, reinnervation, and the deposition of endomysial connective tissue and fat.

With application of single-frequency electrical current, EIM can be used to help grade the severity of neuromuscular disease. Assessing electrical impedance across a spectrum of applied frequencies and with current flow at multiple orientations relative to the major muscle fiber direction can provide a more complete picture of muscle condition.

EIM holds the promise of serving as an indicator of disease status, thus being useful in clinical trials work and in monitoring effectiveness of treatment in individual patients; ultimately, it may also find diagnostic application.

Ongoing efforts have been focused on obtaining a deeper understanding of the basic mechanisms of impedance change, studying EIM in a variety of clinical contexts, and further refining the methods of EIM data acquisition and analysis

PROGETTAZIONE E  VALIDAZIONE DI PROTOCOLLI BASATO ESERCIZI A  PEDANA VIBRANTE SU SOGGETTI CON PATOLOGIA DI PARKINSON E SCLEROSI MULTIPLA

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The effects of whole-body-vibration exercises (mechanical oscillations)in
Parkinson´s disease and multiple sclerosis

Parkinson’s disease (PD) is a complex, progressive and disabling neurodegenerative disorder marked by progressive loss of nigrostriatal dopaminergic neurons which is related to a continuous impairment of motor functions.

As pharmacological treatments (L-Dopa, Dopamin Agonists) are lowly effective with
respect to postural disturbance, and furthermore they lose effectiveness with disease progression potent nonpharmacologic therapies, are of crucial importance for the management of impairments.

Approximately 400,000 people in the EU suffer from multiple sclerosis, a disease of the spinal cord, brain and nervous system that affects motor control, vision, cognitive function and emotions.

There is no cure for multiple sclerosis, though various drug and physical therapies may help to decrease symptoms.

Besides traditional types of exercise, like strength or endurance training, passive exercise, whole body vibration was found having positive influence on PD and MS motor symptoms.

 As the use of the oscillating platforms is very inexpensive and positive clinical findings have been noticed with the use of whole body vibration in patients with PD, and MS it is suggested to implement the studies involving the application of the exercises with whole body vibration in oscillating platforms to manage the patients with PD.

STUDIO DEGLI EFFETTI DELLA TOSSINA BOTULINICA IN DISORDINI MOTORI, DISTONIA,SPASTICITA'

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Study of the selectivity of botulinum toxins (BoNT-A and BoNT-C) for muscle fiber type units and their kinetics diffusion by exo-endocytosis: electro and impedence myography evaluation, biochemical pathway analysis and possible clinical implication in Spasticity, Dystonia, and Related Motor Disorders

Design implementation and clinical validation of 2D high-density electrode arrays (2DHDEMGs),with a bi-dimensional grid of 128 electrodes (8x16 with 10 mm interelectrode distance) positioned on the muscle suitable for recording EMGsurface signals (array processing) from different types of muscles and analysis of innervation zone (IZ).

The knowledge of innervation zone position (IZ) of muscles is crucial to injection the product (BoNTs) in specific sites of muscle to have more efficacy and less side effects .

Analyze the effect of blockade of nerve activity, induced by Botulinum Neurotoxin type A (BoNT/A), that promotes the expression of the slow isoform of myosin heavy chain (MyHC) in contrast with other neuromuscular inactivity models; and correlate the MyHC isoform switch with the muscle fiber denervation by BoNTs to better understand this phenomenon and to investigate if botulinum neurotoxins block preferentially some motor units rather than others.

Study of diffusion of different Botulinum neurotoxin (BoNT-A and BoNT-C) formulations injected in the mouse model using an highly sensitive test based on Neural Cell Adhesion Molecule (N-CAM) expression in muscle.

STUDIO DEGLI EFFETTI DI ESERCIZIO RIABILITATIVO ASSISTITO AD ALTA INTENSITA' IN PAZIENTI PARKINSON

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Study of different types of exercises (randomized controlled trials) of FORCED EXERCISE (mechanically assisted) in order to minimize the negative effects of the PD on motor and functional performance

Forced Exercise (FE), is a  relatively new approach to exercise in human patients with PD. FE, is defined operationally as a mode of aerobic exercise in which exercise rate is augmented mechanically to assist the participant in achieving and maintaining an exercise rate that is greater than their preferred voluntary rate of exercise. It is important to note that during FE, the participant is contributing actively to the exercise; they are not being moved through the motion passively.

The effects of FE on motor and behavioral function using the 6-OHDA or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD has been studied extensively. [Fisher BE, Petzinger GM, Nixon K, et al. Exercise-induced behavioral recovery and neuroplasticity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse basal ganglia. J. Neurosci. Res. 2004; 77(3):378–90,; Zigmond MJ. Triggering endogenous neuroprotective mechanisms in Parkinson's disease: studies with a cellular model. J. Neural Transm. Suppl. 2006; (70):439–42;Zigmond MJ, Cameron JL, Leak RK, et al. Triggering endogenous neuroprotective processes through exercise in models of dopamine deficiency. Parkinsonism Relat. Disord. 2009; 15(Suppl 3):S42–5.] A typical FE paradigm is motorized treadmill running that requires the animal to maintain a running velocity that is greater than its preferred running velocity.

STUDIO DEGLI EFFETTI DI UNA SUPPLEMENTAZIONE DI AMINOACIDI ARRICCHITI CON LEUCINA IN PAZIENTI CON SCLEROSI LATERALE AMIOTROFICA

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Effect of branched-chain amino acid (BCAA) supplementation enriched  of leucine (LEU)in amyotrophic lateral sclerosis patients

A prospective randomized double-blind study was performed with 12 male PALS,        ( ranging between 44 and 63 y.o.) divided into two groups: the treatment group (T) received BCAA supplementation (80 mg/kg bodyweight/day with ratio leucine/isoleucine/valine of 6/1/1), whereas the control group (C) received placebo (similar enriched flavours) .

ALS patients meeting El Escorial criteria for defined disease, either with bulbar or appendicular onset, regularly assisted in the Clinic, were included in the study. Patients with nasogastric tube or gastrostomy, on assisted mechanical ventilation and without intervening neurological illnesses. Body weight (kg) and height (m) were assessed ,Body mass index (BMI - kg/m2) and midarm circumference (MAC - cm), were determined;

The tricipital (TSF), skinfolds were measured using the scientific Lange branded (0.1mm-accuracy adipometer) midarm muscle circumference (MAMC), arm muscle area (AMA) and arm fat area (AFA) were obtained from MAC and TSF according to Heymsfield et al. The percentage of weight loss (%WL) was determined based upon the usual and the actually measured weight of the patient. BIA was performed by measuring the bioimpedances at 50 kHz and FFM was calculated by using TSF and Desport equation.

We determined the serum levels of albumin, pre-albumin, creatine-kinase (CK), creatine, urea, glucose, aspartate transferase (AST), alanine transferase (ALT), total lymphocyte count, platelets, sodium and potassium for each patient. All measurements were taken before (baseline), every 4 months (mid-points) and at the end of the trial (end – point) .

STUDIO DELLA ANALISI BIOIMPEDENZIOMETRICA SEGMENTALE E CORRELAZIONE CON SPESA ENERGETICA A RIPOSO IN PAZIENTI CON SCLEROSI LATERALE AMIOTROFICA

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Correlation among Forced Vital Capacity (FVC), Resting Energy            Expenditure (REE) and segmental trunk Bioelectrical Impedance Analysis (stBIA) in ALS patients for predicting clinical disease progression: a preliminary study

In als  patients (mean age ± SD: 52.1 ± 11.5 yrs; 7 M; 5 F) with definite ALS, neurologic deficit was quantified by manual muscular testing of all extremities and the neck as defined by the Medical Research Council.

All patients were stable in pharmacological medication (50 mg riluzole twice a day); no patient received any steroid drug treatment. FVC was measured with a pneumotachograph system (Medical Graphics, St Paul): findings were expressed in relation to a theoretical calculated index value.

Indirect calorimetry was performed with a VO2000 (Medical Graphics, St Paul) that was calibrated each morning before the measurements were made. Measurements were accepted if the results were at a stable plateau for ≥ 20 min.

The measured REE (mREE) was compared with REE obtained from a control population volunteers and with REE calculated (cREE) by using the Harris-Benedict equations. In stBIA, (50 kHz) the 4 source electrodes and the combination of 8 detecting electrodes used in this study allowed to separate the trunk into 5 parts and determine the Z of each part. All PALS were tested each 6 months: in such a preliminary work a 24-month period was analyzed.

UTILIZZO DELLA MIOGRAFIA ULTRASONOGRAFICA NELLA SCLEROSI LATERALE AMIOTROFICA

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QUANTITATIVE MUSCLE ULTRASONOGRAPHY IN AMYOTROPHIC LATERAL SCLEROSIS

In this study, we examined whether quantitative muscle ultrasonography can detect structural muscle changes in early-stage amyotrophic lateral sclerosis (ALS).

Bilateral transverse scans were made of five muscles or muscle groups (sternocleidomastoid, biceps brachii/brachialis, forearm flexor group, quadriceps femoris and anterior tibialis muscles) in  patients with ALS.

 Quantitative analysis revealed a significant increase in echo intensity in all muscles and a decrease in muscle thickness of the biceps brachii, forearm flexors and quadriceps femoris on both sides.

Fasciculations were easy to detect in multiple muscles of all screened patients except one.

Quantification of muscle thickness and echo intensity provides a sensitive and specific objective method to discriminate between neuromuscular and non-neuromuscular disease.

We conclude that quantitative ultrasonography can be used to detect muscle changes caused by ALS in an early phase of the disease