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Introduction Even if electromyography (EMG) is routinely used to confirm the diagnosis of amyotrophic lateral sclerosis (ALS), few studies have analysed the correlation between electrophysiological parameters and clinical characteristics of ALS. We assessed if the quantification of active denervation (AD) and chronic denervation (CD) provides clinicians with information about phenotype, disease progression and survival in ALS patients. Methods We studied a cohort of 689 ALS patients recording the following parameters: age and site of onset, survival, MRC scale for muscle strength evaluation, burden of upper and lower motor signs as measured with specific scales (PUMNS and LMNS, respectively), ALSFRS-R, progression rate (ΔFS), MITOS and King’s Staging systems (KSS). We performed EMG on 11 muscles, and calculated semiquantitative AD and CD scores for each limb, as well as for the bulbar and spinal regions. Results We found a positive correlation between AD and CD scores with LMNS (respectively p = 4.4 × 10–37 and p = 2.8 × 10–45) and a negative correlation with MRC (respectively p = 4.5 × 10–35 and p = 3.0 × 10–35). Furthermore, patients with higher spinal AD and CD scores had significantly lower ALSFRS-R scores, and higher KSS and MITOS stages. Conversely, only AD was associated to higher ΔFS (p = 1.0 × 10–6) and shorter survival (p = 1.1 × 10–5). Conclusion Our results confirmed that EMG examination represents not only a diagnostic instrument, but also a prognostic tool. In this context, AD seems to be a reliable predictor of disease’s progression and survival while CD better describes functional disability.

Increasing evidence shows that disease spreading in amyotrophic lateral sclerosis (ALS) follows a preferential pattern with more frequent involvement of contiguous regions from the site of symptom onset. Aim of our study is to assess if: 1) burden of upper (UMN) and lower motor neuron (LMN) involvement influences directionality of disease spreading; 2) specific patterns of disease progression are associated with motor and neuropsychological features of different ALS subtypes (classic, bulbar, primary lateral sclerosis, UMN-predominant, progressive muscular atrophy, flail arm, flail leg); 3) specific clinical features may help identify ALS subtypes which remain localized to site of onset for a prolonged time (regionally entrenching ALS, re-ALS). A single-center, retrospective cohort of 913 Italian ALS patients was evaluated to assess correlations between directionality of the disease process after symptom onset and motor/neuropsychological phenotype. All patients underwent an extensive evaluation including the following clinical scales: Penn Upper Motor Neuron Score (PUMNS), MRC scale for muscle strength and Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The most frequent initial spreading pattern was that towards adjacent horizontal regions (77.3%), which occurred preferentially in patients with lower MRC scores (p = 0.038), while vertical diffusion (21.1%) was associated with higher PUMNS (p Our study suggests that motor phenotypes characterized by a predominant UMN involvement are associated with a vertical pattern of disease progression reflecting ipsilateral spreading within the motor cortex while those with predominant LMN involvement display more frequently a horizontal spreading from one side of the spinal cord to the other. These observations raise the hypothesis that one of the mechanisms underlying disease spreading in ALS pathology is represented by diffusion of toxic factors in the neuron microenvironment. Finally, it is possible that in our cohort, re-ALS forms are mainly observed in patients with atypical bulbar phenotypes, characterized by a slowly progressive course and relatively benign prognosis.

We describe 3 cases of solitary sclerosis (SS), a rare condition characterized by a single inflammatory demyelinating lesion in the white matter of the brain or spinal cord. All patients had progressive limb motor impairment (patient 1, 66-year-old female: left spastic hemiparesis; patient 2, 39-year-old male: right spastic hemiparesis; patient 3, 42-year-old female: proximally predominant left upper limb weakness with amyotrophy and fasciculations). In all patients, MRI disclosed a single small T2-hyperintense demyelinating lesion: in the right anterior paramedian upper medulla, in the median-left paramedian anterior lower medulla, and in the left paramedian anterior cervical spinal cord at C4 level, respectively. In patients 1 and 2, transcranial magnetic stimulation (TMS) demonstrated altered motor evoked potentials (MEPs) and increased central motor conduction time (CMCT) in the affected limbs; in patient 3, needle EMG revealed chronic neurogenic changes in C5-C7 muscles of left upper limb. Patients 1 and 2 had normal brain

To compare serum levels of the astrocyte biomarker glial fibrillary acidic protein (GFAP) in patients with amyotrophic lateral sclerosis (ALS) and neurologically healthy controls and to analyze the relations between serum GFAP (sGFAP) and phenotype in ALS.We studied 114 ALS patients and 38 controls. sGFAP was quantified with single molecule array (Simoa) technology.In both ALS patients and controls, sGFAP moderately correlated with age. ALS patients had higher sGFAP levels compared to controls, but this yielded a weak discriminative performance (AUC = 0.6198). In ALS, sGFAP was not associated with most of the motor phenotypic features, including site of onset, functional status, disease progression rate, disease stage, and indices of upper (UMN) and lower motor neuron (LMN) impairment. However, sGFAP negatively correlated with cognitive scores regarding ALS-nonspecific functions, particularly memory (r = -0.2082) and tended to be higher in ALS patients with eye movement abnormalities (p = 0.0628). sGFAP also correlated with polysomnographic indices of oxygen desaturation (ODI; r = 0.2639) and apnea-hypopnea (AHI; r = 0.2858). In a multivariate analysis, sGFAP was negatively associated with survival (HR = 1.005). Relevantly, we found a negative correlation between sGFAP and estimated glomerular filtration rate (eGFR; r = -0.3500).Our work provides neurochemical evidence of astrocyte involvement in ALS pathophysiology and particularly in the development of extra-motor manifestations (namely, cognitive - memory - impairment) and respiratory dysfunction. The negative correlation between sGFAP and eGFR has practical relevance and should not be disregarded in future investigations.

We aimed to study the attitude of Italian neurologists in the use of conventional MRI in patients with idiopathic adult-onset focal dystonia. Patients were included in the Italian Dystonia Registry by experts working in different Italian centers. MRI was available for 1045 of the 1471 (71%) patients included in the analysis. Using logistic regression analysis, we found that MRI was more likely to be performed in patients with cervical dystonia, spasmodic dysphonia, or non-task-specific upper limb dystonia, whereas it was less likely to be performed in patients with blepharospasm or task-specific upper limb dystonia. We did not find differences in the number of MRIs performed between neurological centers in Northern, Central, and Southern Italy. We conclude that although the diagnosis of idiopathic adult-onset dystonia is mainly based on clinical grounds, many movement disorder experts rely on MRI to confirm a diagnosis of idiopathic dystonia. We suggest that neuroimaging should be used in patients with adult-onset focal dystonia to rule out secondary forms.

Background The differentiation of functional dystonia from idiopathic dystonia may be clinically challenging. Objective To identify clinical features suggestive of functional dystonia to guide physicians to distinguish functional dystonia from idiopathic dystonia. Methods Patient data were extracted from the Italian Registry of Functional Motor Disorders and the Italian Registry of Adult Dystonia. Patients with functional and idiopathic dystonia were followed up at the same clinical sites, and they were similar in age and sex. Results We identified 113 patients with functional dystonia and 125 with idiopathic dystonia. Sudden onset of dystonia, evidence of fixed dystonia, and acute peripheral trauma before dystonia onset were more frequent in the functional dystonia group. No study variable alone achieved satisfactory sensitivity and specificity, whereas a combination of variables yielded 85% sensitivity and 98% specificity. A diagnostic algorithm was developed to reduce the risk of misclassifying functional dystonia. Conclusion Our findings extend the current diagnostic approach to functional dystonia by showing that clinical information about symptom onset, fixed dystonia, and history of peripheral trauma may provide key clues in the diagnosis of functional dystonia.

Primary lateral sclerosis (PLS) is a rare degenerative disease of upper motor neurons (UMNs) manifesting with progressive spasticity. Disease progression is definitely slower than in amyotrophic lateral sclerosis (ALS). Clinical distinction between PLS and ALS can be challenging, as the UMN-dominant form of ALS may sometimes not manifest lower motor neuron (LMN) signs for a long time after symptom onset.1 Therefore, traditional PLS diagnostic criteria allowed diagnosis only after 3 or 4 years of documented absence of LMN signs,2 which poses a psychological burden on patients, hinders correct clinical management and prevents enrolment in clinical trials. In order to overcome these issues, new diagnostic criteria have been recently formulated, shortening the time required for a diagnosis of probable PLS to 2 years.1 Diagnostic uncertainties in PLS are complicated by the lack of specific neurochemical biomarkers. Whereas cerebrospinal fluid (CSF) neurofilament levels are clearly increased in ALS, making them a well-established ALS biomarker reflecting axonal degeneration, few studies reported lower increases in PLS3; a similar pattern was observed for the putative ALS microglial biomarker chitotriosidase (Chit1).4 Here we measured phosphorylated neurofilament heavy chain (pNFH) and Chit1 in the CSF of patients with PLS, ALS and non-neurodegenerative neurological conditions, focusing on the ability of each biomarker to distinguish PLS from controls and from ALS. ### Patients In this retrospective study we included those 10 patients (5 men, 5 women) from our consecutive PLS series (n=52) whose CSF was stored in our biobank. They all fulfilled—at the time of sampling or on later evaluations—the recently published diagnostic criteria for definite (n=9) or probable (n=1) PLS.1 Patients with ALS and neurological controls (NCs) were selected randomly from our biobank to form two cohorts with sex and age distributions similar to PLS. Patients with ALS (n=28; 16 men, 12 women) fulfilled …

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain.

Background Acute peripheral trauma is a controversial risk factor for idiopathic dystonia. Materials and methods We retrospectively analyzed data from the Italian Dystonia Registry regarding the occurrence of acute peripheral trauma severe enough to require medical attention in 1382 patients with adult-onset idiopathic dystonia and 200 patients with acquired adult-onset dystonia. Results Patients with idiopathic and acquired dystonia showed a similar burden of peripheral trauma in terms of the number of patients who experienced trauma (115/1382 vs. 12/200, p = 0.3) and the overall number of injuries (145 for the 1382 idiopathic patients and 14 for the 200 patients with secondary dystonia, p = 0.2). Most traumas occurred before the onset of idiopathic or secondary dystonia but only a minority of such injuries (14 in the idiopathic group, 2 in the acquired group, p = 0.6) affected the same body part as that affected by dystonia. In the idiopathic group, the elapsed time between trauma and dystonia onset was 8.1 ± 9.2 years; only six of the 145 traumas (4.1%) experienced by 5/1382 idiopathic patients (0.36%) occurred one year or less before dystonia onset; in the acquired dystonia group, the two patients experienced prior trauma to the dystonic body part 5 and 6 years before dystonia development. Discussion and conclusion Our data suggest that the contribution of peripheral acute trauma to idiopathic dystonia is negligible, if anything, and likely involves only a small subset of patients.

Objective: Angiogenin (ANG) is a pro-angiogenic and neurotrophic factor with an important role in stress-induced injury, by promoting neovascularization and neuronal survival. Identification of loss-of-function mutations and evidence of beneficial effect of ANG administration in transgenic SOD1G93A mice have linked ANG to the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), stimulating interest in considering circulating ANG levels as an ALS disease biomarker although robust evidence is still lacking. Aim of our study was to assess differences of ANG levels in the cerebrospinal fluid (CSF) of a large cohort of patients with ALS and frontotemporal dementia (FTD) compared to controls and to explore correlations between ANG content and disease-related clinical variables. Methods: ANG levels were measured in CSF samples using a commercially available ELISA kit in 88 patients affected with ALS and/or FTD and 46 unrelated individuals (control group). Results: ANG levels didn’t differ significantly between cases and controls. Patients with FTD or ALS-FTD showed significantly increased CSF concentration of ANG compared to ALS patients without dementia and controls in a multivariate regression model (p found in ALS/FTD patients between ANG levels and clinical parameters, including age, presence of C9orf72 repeat expansion, body mass index (BMI). Conclusions: our findings highlight a role of ANG as CSF biomarker useful to identify ALS patients with concurrent FTD and suggest that it should be further explored as potential biomarker for FTD.

We report on a family with occipital horn syndrome (OHS) diagnosed in the proband's late fifties. A novel ATP7A pathogenic variant (c.4222A > T, p.(Lys1408*)), representing the first nonsense variant and the second late truncation causing OHS rather than classic Menkes disease, was found to segregate in the family. The predicted maintenance of transmembrane domains is consistent with a residual protein activity, which may explain the mild clinical presentation.

Objective: Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous p ...

Objective This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). Methods Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. Results Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories “Not-ALS”, “Definite”, and “Probable”, and poorest for “Possible” and “Probable Laboratory-supported”. Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of “Probable Laboratory-supported” patients by AC. However, AC was significantly more effective in classifying patients as “ALS” versus “Not-ALS” (p Conclusions Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the “Probable Laboratory-supported” category. Significance The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Previous studies have associated single-nucleotide polymorphisms (SNPs) in the gene encoding the detoxifying enzyme paraoxonase 1 (PON1) to the risk of sporadic ALS. Here, we aimed to assess the role of the coding rs662 (Q192R) SNP as a modifier of ALS phenotype. We genotyped a cohort of 409 patients diagnosed with ALS at our Center between 2002 and 2009 (269 males and 140 females; mean age at onset, 58.3 ± 37.5 years). We found PON1 to be a disease modifier gene in ALS, with the minor allele G associated both with bulbar onset (30.9% vs. 24.6%, p = 0.013) and independently with reduced survival (OR = 1.38, p = 0.012) under a dominant model. No association was found with gender or age at onset. As this SNP is known to modify the detoxifying activity of paraxonase 1 with respect to different substrates as well as other activities of the protein, we hypothesize that the identified association might reflect specific motor neuron vulnerability to certain exogenous toxic substances metabolized less efficiently by the 192R alloenzyme, or to detrimental endogenous pathophysiological processes such as oxidative stress. Further exploration of this possible metabolic susceptibility could deepen our knowledge of ALS pathomechanisms.

© 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

Objectives. Diabetic neuropathy is the most common complication of diabetes. The idea of alterations in energy metabolism in diabetes is emerging. The biogenic antioxidant R(+)-thioctic acid has been successfully used in the treatment of diabetic polyneuropathic (DPN) patients. Methods. The effects of R(+)-thioctic acid (1 tablet, 1.6 g) administration were evaluated in 12 DPN patients at baseline and at 15, 30, 60, and 120 administration days throughout the assessment of oxidative stress (OxS); ROS production rate by electron paramagnetic resonance (EPR) technique; and oxidative damage biomarkers (thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC)), electroneurography (ENG) and visual analogue scale. Results. Supplementation induced significant changes (p<0.05) at 30 and 60 days. ROS production rate up to −16%; TBARS (−31%), PC (−38%), and TAC up to +48%. Motor nerve conduction velocity in SPE and ulnar nerves (+22% and +16%) and sensor conduction velocity in sural and median nerves (+22% and +5%). Patients reported a general wellness sensation improvement (+35%) at 30 days: lower limb pain sensation (−40%) and upper limbs (−23%). Conclusion. The results strongly indicate that an increased antioxidant capacity plays an important role in OxS, nerve conduction velocity, pain, and general wellness improvement. Nevertheless, the effects of the antioxidant compound were found positive up to 60 days. Then, a hormesis effect was observed. Novelty of the research would be a challenge for investigators to carefully address issues, including dose range factors, appropriate administration time, and targeting population to counteract possible “boomerang effects.” The great number of monitored parameters would firmly stress these conclusions.

Objective Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1‐transgenic animal models. Pyrimethamine produces dose‐dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). Methods A multicenter (5 sites), open‐label, 9‐month‐duration, dose‐ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale–Revised, and McGill Quality of Life Single‐Item Scale were measured at screening, visit 6, and visit 9. Results We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p

Objectives To study inter- and intra-rater agreement on diagnostic criteria for amyotrophic lateral sclerosis (ALS). Methods Four-hundred-and-two patients referred for ALS were classified according to the revised El Escorial criteria (EEC) and the Awaji criteria (AwC) independently by eight experienced physicians from seven different countries. Intra-rater agreement was further assessed from 352 of the cases, which were interpreted twice by the same physician. Clinical and electrophysiological data were presented in standardised forms. Results Two-by-two Kappa coefficients among the eight physicians varied from 0.15 to 0.75 (mean 0.40) for EEC and from 0.18 to 0.80 (mean 0.43) for AwC. Kappa coefficients for intra-rater agreement varied from 0.08 to 0.81 (mean 0.56) for EEC and from 0.18 to 0.85 (mean 0.67) for AwC. Disagreement was seen on all diagnostic categories, most pronounced for “probable lab-supported” and “possible”. There were no differences between EEC and AwC. Discussion The large variation on EEC and AwC may be due to the complexity of the criteria including the definition of four body regions, interpretation and significance of clinical findings of upper or lower motor neuron signs, significance of findings being rostral or caudal to each other, and interpretation of detailed electrophysiological findings as evidence of acute or chronic denervation. Conclusions The large variation in interpretation of both EEC and AwC may be considered unacceptable for criteria used to include patients in research studies. Significance Variability on interpretation of diagnostic criteria for ALS should be considered in the assessment of scientific studies. Initiatives to develop more reproducible diagnostic criteria for ALS are needed.

Introduction The revised El Escorial Criteria (rEEC) from 2000 and their amendment, the Awaji Criteria (AC) from 2008, are widely used diagnostic criteria for amyotrophic lateral sclerosis (ALS) and their sensitivity and specificity have been evaluated in several studies, however, reproducibility among different raters has not been studied. This study was undertaken to assess inter-rater agreement on rEEC and AC. Methods Eight experienced physicians from seven different countries independently classified 399 patients referred for ALS according to the rEEC and the AC. Clinical and electrophysiological data were presented in standardised forms. Agreement was evaluated by Kappa coefficients. Diagnostic sensitivity and specificity were calculated from the majority diagnosis of the eight physicians for 349 cases with follow-up data. Results Kappa coefficients differed among the diagnostic categories for rEEC (“Definite”: 0.50, CI:0.39–0.60, “Probable”: 0.36, CI:0.31–0.41, “Probable Laboratory Supported”: 0.25,CI:0.18–0.34, “Possible”: 0.14, CI:0.09–0.20, and “Not-ALS”: 0.59, CI:0.51–0.65) as well as for AC (“Definite”: 0.44, CI:0.37–0.51, “Probable”: 0.34, CI:0.29–0.39, “Possible”: 0.33, CI:0.26–0.40, and “Not-ALS”: 0.65, CI:0.58–0.72). The only significant difference in agreement between rEEC and AC was for the category “Possible”. A large fraction of cases classified as “Probable” using the rEEC were upgraded to “Definite” using the AC, however, many cases classified as “Probable Laboratory Supported” by rEEC were downgraded to “Possible” by the AC. Sensitivity for “Definite/Probable” versus “Possible/Not-ALS” did not differ between rEEC (0.64, CI:0.58–0.69) and AC (0.63, CI:0.58–0.69). Similarly, there was no difference in specificity between rEEC (0.91, CI:0.74–0.98) and AC (0.85, CI:0.67–0.94). Conclusion There is a large inter-rater variation on rEEC and AC most pronounced for the “Probable Laboratory Supported” and “Possible” categories. The sensitivity was rather low compared to other studies and was not significantly increased using AC, probably due to omission of the “Probable Laboratory Supported” category. However, in trials including patients with possible disease AC may be advantageous. Inter-rater variation may be due to (1) a high complexity of the rEEC, which is also inherited in the AC, including definition of four body regions, interpretation of clinical findings (upper/lower motor neuron signs), significance of rostral/caudal signs, and significance of EMG findings (acute/chronic signs), and (2) the need to apply rEEC together with AC. However, pre-study training and quality control at individual laboratories may reduce variation and improve sensitivity and specificity. The results indicate that there is a need for initiatives to develop more simple and reproducible criteria.

Telepresence teaching is a very useful complementary means of allowing university teaching whenever there is a lack of local resources. To be effective it requires a user friendly environment for both teachers and learners. The experience of the Technical University of Milan in delivering telepresence courses for more than four years has promoted investigation and development of effective teleteaching equipment. The paper suggests a teleteaching standard and presents the equipment being developed at Politecnico di Milano. A layered equipment architecture has been introduced while users requirements and available technologies are intertwined to identify equipment functional specifications. Modular equipment as a Teacher Tracker, a Laser Beam Mouse, a Student Pointer and a Multiplexed Videocodec are among the designed and prototype equipment. The activity indicates the possibility of applying well established technologies in teleteaching systems by promoting University laboratories where user requirements and a large spectrum of technologies are investigated to anticipate useful products whenever market specifications are not yet established.

Breast reconstruction tissue expander-based is the most common technique used for reconstruction after radical mastectomy for cancer. Breast reconstruction with fat grafting (FAT transfer) is a technique widely used in current practice. 62-year-old woman has been subjected to mastecmia and subsequent reconstructive surgery of the breast expander based, retaining the expander for 10 months. After 3–4 weeks from placement of the breast implant, developed a sub-rhythmic spasm of chest muscles during standing. This spasm is persisted even after the removal of the prosthesis a year later and without any pain. She had never been subjected to chemotherapy or radiotherapy. Electromyography showed unintentional electrical activity sub-rhythmic burst with 200–250 ms, frequency 2 Hz. We have also studied the brachial plexus nerve and breastplate with magnetic resonance imaging (DTI sequences) and ultrasound of the breast region. The patient was subjected to infiltration under electromyography and ultrasound guidance of pectoralis major muscle with onabotulinumtoxinA with cramp reduction/interruption. Chest cramps is not due to nerve compression trauma implants pectoral mammal, but it should be due to the irritative activity of the graft on the pectoral nerve. In fact the spasm started after the placement of the graft.

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.

OBJECTIVE: To explore the effect of treatment after botulinum toxin type A combined with treatments for the spastic foot. DESIGN: Single-blind, randomized trial, with 3-month follow-up. SUBJECTS: Twenty-three chronic hemiplegic adult patients with spastic equinus foot. METHODS: Following botulinum toxin type A injection at the medial and lateral gastrocnemius, patients were assigned randomly to 3 groups, and treated with taping, electrical stimulation or stretching. They were evaluated before treatment (t0), and at 10 (t1), 20 (t2) and 90 (t3) days after treatment. Outcome measures were: Modified Ashworth Scale; passive range of motion at the ankle; measurement of muscle action potential at the gastrocnemius medialis; and measurement of maximum ankle dorsiflexion angle in stance using gait analysis. RESULTS: The group treated with electrical stimulation performed better at t1 on the Modified Ashworth Scale. The taping and electrical stimulation groups performed better in all outcome measures at t3. The taping group performed better mainly for maximum ankle dorsiflexion angle in stance. The stretching group showed a less durable result, with some worsening at the t3 evaluation compared with the assessment performed before treatment. CONCLUSIONS: This pilot study indicates that combining botulinum toxin type A administration for the ankle plantar flexors with taping and electrical stimulation might be beneficial.

Fatigue is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005). Significantly higher parietal lobe (P< 0.05), internal capsule (P< 0.05), and periventricular trigone (P< 0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.

The repeatability of initial value and rate of change of mean spectral frequency (MNF), average rectified values (ARV) and muscle fiber conduction velocity (CV) was investigated in the dominant biceps brachii of ten normal subjects during sustained isometric voluntary contractions. Four levels of contraction were studied: 10%, 30%, 50% and 70% of the maximal voluntary contraction level (MVC). Each contraction was repeated three times in each of three different days for a total of nine contractions/level/subject and 90 contractions per level across the ten subjects. Repeatability was investigated using the Intraclass Correlation Coefficient (ICC) and the standard error of the mean (SEM) of the estimates for each subject. Contrary to observations in other muscles, CV estimates appeared to be very repeatable both within and between subjects. CV showed a small but significant increase when contraction force increased from 10% to 50% MVC but no change for further increase of force. As force increased, MNF showed a slight decrease possibly related to a wider spreading of the CV values. The rate of time decrement of MNF and CV increased with the level of contraction. The normalized decrement (% of initial value per second) was in general higher for MNF than for CV and was more repeatable between subjects at 10% MVC than at 70% MVC. A final observation is that a resting time of 5 minutes may not be sufficient after a contraction at 50% or 70% MVC.

Telepresence teaching is a very useful mean of allowing university teaching whenever there is a lack of local resources. To be effective it requires a user friendly environment for both teachers and learners. The experience of the technical University of Milan in delivering telepresence courses has promoted investigation and development of effective teleteaching equipment. A layered equipment architecture has been introduced while users requirements and available technologies are intertwined to identify equipment functional specifications. Modular equipment as a Teacher Tracker, a Laser Beam Mouse, a Student Pointer and a Multiplexed Videocodec are among the designed and prototyped equipment. The activity indicates the possibility of applying well established technologies in teleteaching systems by promoting University laboratories where user requirements and a large spectrum of technologies are investigated to anticipate useful products whenever markets specifications are not yet established.

The tarsal tunnel syndrome (TTS) is an entrapment of the posterior tibial nerve at the ankle, which, like carpal tunnel syndrome, improves with surgery but needs an instrumental diagnosis to exclude other diseases. This study was performed to evaluate the diagnostic value of nerve conduction tests proposed for the diagnosis of TTS. Of the 13 patients who were investigated 12 had secondary unilateral and 1 idiopathic bilateral TTS. One or more neurophysiologic parameters were abnormal in all cases. The diagnostic value of each neurophysiologic parameter was calculated by comparing conduction on the affected side with conduction on the healthy side of each patient with TTS. The accuracies of the sensory nerve action potential and mixed nerve action potential, both after stimulation of the plantar nerves, were almost the same, with sensory nerve action potentials more sensitive and less specific and mixed nerve action potentials less sensitive and more specific. Because from the clinical point of view we must be more afraid of false-positive results, the mixed nerve action potential is recommended for presurgical diagnosis of TTS. Coexistence of mixed nerve and sensory nerve action potential abnormalities, especially if asymmetric, are highly indicative of TTS.