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In this paper, we present, with particular focus on the adopted processing and identification chain and protocol-related solutions, a whole self-paced brain-computer interface system based on a 4-class steady-state visual evoked potentials (SSVEPs) paradigm. The proposed system incorporates an automated spatial filtering technique centred on the common spatial patterns (CSPs) method, an autoscaled and effective signal features extraction which is used for providing an unsupervised biofeedback, and a robust self-paced classifier based on the discriminant analysis theory. The adopted operating protocol is structured in a screening, training, and testing phase aimed at collecting user-specific information regarding best stimulation frequencies, optimal sources identification, and overall system processing chain calibration in only a few minutes. The system, validated on 11 healthy/pathologic subjects, has proven to be reliable in terms of achievable communication speed (up to 70 bit/min) and very robust to false positive identifications.

Background: Hereditary spastic paraplegia (HSP) with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterised by slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the gene associated with the major locus involved, encodes spatacsin, a protein of unknown function. Methods: Different types of mutations were identified in patients with the complex form of HSP (cHSP) including TCC. We screened a series of 45 index patients with different types of cHSP with (n = 10) and without (n = 35) TCC. Results: Ten mutations, of which five are novel, were detected in seven patients. Of importance, three out of seven mutated patients present with cHSP without TCC. Among the novel mutations identified, we characterised a large intragenic rearrangement deleting 2.6 kb of the SPG11 gene. The rearrangement is due to non-allelic homologous recombination between Alu sequences flanking the breakpoints. Conclusions: These findings expand the mutation spectrum of SPG11 and suggest that SPG11 mutations may occur more frequently in familial than sporadic forms of cHSP without TCC. This helps to define further clinical and molecular criteria for a correct diagnosis of the SPG11 related form of cHSP. In addition, the intragenic deletion detected here, and the mechanism involved, both provide clues to address the issue of SPG11 missing mutant alleles previously reported.

Mutations in the SPG7 gene encoding a mitochondrial protein termed paraplegin, are responsible for a recessive form of hereditary spastic paraparesis. Only few studies have so far been performed in large groups of hereditary spastic paraplegia (HSP) patients to determine the frequency of SPG7 mutations. Here, we report the result of a mutation screening conducted in a large cohort of 135 Italian HSP patients with the identification of six novel point mutations and one large intragenic deletion. Sequence analysis of the deletion breakpoint, together with secondary structure predictions of the deleted region, indicate that a complex rearrangement, likely caused by extensive secondary structure formation mediated by the short interspersed nuclear element (SINE) retrotransposons, is responsible for the deletion event. Biochemical studies performed on fibroblasts from three mutant patients revealed mild and heterogeneous mitochondrial dysfunctions that would exclude a specific association of a complex I defect with the pathology at the fibroblast level. Overall, our data confirm that SPG7 point mutations are rare causes of HSP, in both sporadic and familial forms, while underlying the puzzling and intriguing aspects of histological and biochemical consequences of paraplegin loss.

We investigated the gait pattern of 21 patients with Duchenne muscular dystrophy (DMD), compared to 10 healthy controls through 3D Gait Analysis. An overall observation of gait pattern in our DMD patients when compared to controls confirmed the data previously reported for small dystrophic groups. An excessive anterior tilt of pelvis and abnormal knee pattern in loading response phase were found. Since during the swing phase the DMD foot is too plantarflexed, patients adopt a higher flexion and abduction of the hip in order to advance the swinging limb. Velocity and cadence of DMD patients resulted similar to those calculated for healthy subjects, whereas stride length was reduced and step width was increased. We then divided the DMD patients in to two subgroups (treated with steroids and untreated), and we observed that the only statistically significant differences between the two groups in Gait Analysis parameters were found for the maximum of ankle power. 3D Gait Analysis gives objective and quantitative information about the gait pattern and the deviations due to muscular situation of DMD subjects; being our study a single moment evaluation, it is otherwise unable to unravel changes only detectable through serial analysis during the time course of the disease and, if any, due to the treatment.

Results from several studies suggest that the process of language acquisition may be altered in patients suffering from Duchenne Muscular Dystrophy. In this study, a group of 8 male participants with Duchenne Muscular Dystrophy ( M age = 16 yr., SD = 4.7) underwent an extensive neuropsychological and language assessment. They also performed a discourse production task. Results showed mild mental retardation associated with a specific deficit in Verbal rather than Performance IQ. At the linguistic assessment, 7 of 8 participants showed moderate to severe difficulties on oral language processing with particularly impaired morphosyntactic competence.

Patients with hereditary spastic paraplegia (HSP) often resemble patients with mild spastic diplegia (SD), although their motor limitations differ. The aim of this study was to analyse quantitatively the gait of HSP and SD subjects in order to define the gait pattern in HSP and the differences between the two conditions. Fifteen subjects with HSP, 40 patients with SD and 20 healthy subjects underwent gait analysis (GA). The spatio-temporal and kinematic parameters at the proximal joints were found to be similar in HSP and SD, whereas the most significant differences were found at the knee and ankle joints. Both groups displayed a tendency for knee hyperextension in the midstance phase, but the duration of this hyperextension was longer in the HSP patients. This study shows that GA complements traditional clinical evaluations, making it possible to distinguish, clearly, between motor ability in HSP and in SD patients; the duration of the knee hyperextension during midstance was found to discriminate between the two gait patterns.

The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly affected in visual attention and short-term memory processing. At the linguistic assessment, neither receptive (word comprehension) nor expressive (naming tasks and fluency) lexical abilities were impaired. However, their narratives were qualitatively inferior with respect to those produced by a group of typically developing children. Their speech samples were characterized by the presence of fewer verbs and complete sentences. It is suggested that the reduced production of complete sentences is due to a selective problem in verb argument structure generation. Since the lack of dystrophin is assumed to produce effects on the maturation of the cerebellum, whose involvement has been recently suggested in verb and syntactic processing, these findings may lend indirect support to the hypothesis of a cerebellar-cortical circuit specialized in verb and sentence production.

Non progressive cognitive impairment and increased rates psychosocial disorders, ADHD and Autism are reported in DMD patients. Through structured and validated questionnaire (Wechsler scales or Griffiths developmental scale, CBCL, Youth Self Report, Strengths and Difficulties Questionnaire, ADOS and DAWBA) we explored the possible role of cognitive impairment on the neuropsychiatric comorbidity in 32 boys with DMD (4–18 years). Our preliminary analysis shows a mean Full Intelligence Quotient of the whole group of 83.90 ± 16.68, lower in the patients with deletions in the distal portion of the gene (78.28 ± 16.72) than in the ones with proximal deletions (88.52 ± 15.62), with a very high frequency of Autism (about 20%) particularly in children with lower IQ level, and a high frequency of internalizing problems at CBCL, in boys with FIQ within the normal range, suggesting a role of cognitive capabilities in DMD children psychopathology.

every foot joint during gait. For this reason a FE model was created and a validated using a dummy model. Patients/materials and methods: Gait analysis in one patient was done with a Vicon MX System and 6 cameras, one AMTI Force plate and one EMED SF pressure measurement platform. The “GaitLowerExtremity” model from the ANYBODY Repository AMMRV1.4.1 and ANYBODY Version 5.1 was used to determine the muscle forces of the lower leg during gait. The muscle forces from the ANYBODY model, the regional reaction forces from the EMED SF platform and the 3D kinematics were used to build up the FE-model. A “standard foot model” was created from a CT scan of one healthy foot. This model was imported in ANSYS Workbench V.14.0 and scaled according to the patient’s standard X-rays. The bony segments were linked by revolute joints. This model was validated by measuring the intra-articular forces at the ankle joint in a dummy model constructed by aluminium and computing the FE Model using data for both analysis from the same patient at 50% stance phase (Figs. 1 and 2). Results: Validation of the FE model shows a good correlation of the measured data in the dummy model and the computed data at the ankle joint in the FE model. Only the moments in z direction (vertical to the floor) showed a difference of 19%. All other differences were in a range between 2 and 8%. Discussion and conclusions: For the dynamic validation of the FEmodel the load during one representative step inmid stancewas applied on the dummymodel. The results of the dummymodel and the FE calculation correlated well. Only the moments in z direction at the ankle joint differed between FE Model and dummy model. The reason is not understood yet and is further analyzed.

Mitochondrial encephalomyopathies (ME) are a multisystemic group of diseases characterized by a wide range of biochemical and genetic mitochondrial defects with a variable mode of inheritance. We studied the neuropsychological profile, magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) data in a group of ME patients in order to look for common or specific cognitive defects and a possible correlation with related brain areas. Three main cognitive areas were assessed: general intelligence, memory functions and visuo-perceptual skills. Our sample included 16 ME patients (nine males, seven females) aged 25-68 years (mean age 45.2, SD 13.0). No sign of mental deterioration was found in the group of elderly subjects. Despite subjects showing no global cognitive impairment they scored lower in nonverbal versus verbal tasks. Visuo-spatial skills and short-term memory were selectively impaired. There was no correlation between neuropsychological results and age, illness duration, age of onset, clinical phenotypes, genetic mitochondrial alterations and pharmacological therapy. The most frequent SPECT pattern observed was the hypoperfusion of temporal lobes, with a direct localization in the temporal cortex and with prevalent mesial involvement. The neuropsychological profile and SPECT imaging revealed similarities with focal defects.

We have investigated 59 Becker muscular dystrophy patients, representing 56 independent mutations, to test the hypothesis of predictability of muscle dystrophin expression and clinical phenotype based on location of dystrophin gene mutations. Partial intragenic deletions and duplications account for 82% of the independent mutations, of which 76.7% were deletions and 5.3% duplications. Mutations in which boundaries could be defined, were of in-frame type (35 out of 37, 94.6%, with two exceptions. Eighty-two percent of mutations were located at the distal part of the rod domain (exons 45-60), 9% at domain I (promoter through exon 9) and 9% at proximal and central parts of domain II. Domain I deleted patients tended to have a worse clinical phenotype, with earlier presentation, faster progression rate and lower dystrophin expression, while distal rod domain deleted patients showed a more classic Becker muscular dystrophy phenotype. Between these two groups, only the differences in the immunohistochemical patterns of dystrophin expression and disease progression rate were statistically significant. Partial clinical and biochemical heterogeneity was observed in the distal domain II patient group, due to the presence of few patients covering the extremities of clinical severity. Two asymptomatic patients had deletions located in the central (exons 41-44) and distal parts (exons 50-53) of the rod domain. Severe myalgia and cramps were often reported as early onset symptoms (18 out of 59): no correlation was found between this symptomatology and the location of the mutation. Relative levels of muscle dystrophin correlated with immunohistochemical patterns of subsarcolemma staining. Dystrophin levels (as estimated by 30 kDa antibody immuno-reactivity) correlated with age of reaching a moderate degree of muscle involvement as well as with delay in reaching that stage, a parameter of disease progression rate. Our data confirm that different Becker muscular dystrophy gene in-frame mutations have different effects on dystrophin expression and clinical severity, indicating several functional roles of the dystrophin domains.

Cognitive function and dystrophin gene mutations were investigated in 50 DMD patients (mean age 11.1 yr; range 3.5-20.3). General intelligence assessment showed 31% of patients with Wechsler full intelligence quotient (FIQ) lower than 75 (normal values: 100 +/- 14), and only 24% with appropriate FIQ level. Modal distribution of Wechsler verbal, performance, and FIQs, and Raven IQs was normal. Verbal IQ was more affected than performance IQ (PIQ) only in the younger group of subjects. Low PIQ correlated with the presence of macroglossia, detected in 13 out of 50 patients. Impairment of productive language was of non-dysphasic nature and correlated with defects of short-term memory, which was also affected in non-verbal skills. DMD patients shared the same spectrum of neuropsychological defects, regardless of whether they were or were not mentally retarded. The proportion of patients with dystrophin gene deletions was 64%. No statistically significant correlations were found between genetic data and psychometric assessment. Finally, (18F)-fluorodeoxyglucose positron emission tomography studies demonstrated cerebellar hypometabolism in all the DMD patients examined and variable involvement of associative cortical areas. These findings suggest a possible role of the cerebral and cerebellar hypometabolism in the cognitive impairment of DMD.

Objective: The aims of this study are to quantify the movement limitation of upper limbs in hemiplegic children with traumatic brain injury (TBI) by using a clinical-functional scale and upper limb kinematics and to evaluate the effectiveness of constraint-induced movement therapy (CIMT) on upper limbs. Design: Pre-post study. Setting: Clinical rehabilitation research laboratory. Participants: Ten children with TBI. Main Outcome Measures: The participants were evaluated by clinical examinations (Gross Motor Function Measure, Besta scale, Quality of Upper Extremities Skills Test, and Manual Ability Classification System) and 3D kinematic movement analysis of the upper limb before the CIMT program (pretest: 0.7 years after the injury) and at the end of the program (posttest: 10 weeks later). Results: After the CIMT, most of the clinical measures improved significantly. Some significant improvements were present in terms of kinematics, in particular, in the movement duration and the velocity of movement execution of both tasks; the index of curvature and the average jerk improved, respectively, during reaching and hand-to-mouth task, while the adjusting sway parameter decreased during the 2 movements. Significant improvements were found in upper limb joint excursion after the rehabilitative programme too. Conclusions: Our results suggest that the CIMT program can improve movement efficiency and upper limb function in children after TBI. The integration of the clinical outcomes and upper limb kinematics revealed to be crucial in detecting the effects of the CIMT programme. Keywords: children, CIMT, kinematics, rehabilitation, traumatic brain injury, upper limbs

Patients affected by hereditary spastic paraplegia (HSP) are generally characterised by delay in walking and increased spasticity on the lower extremities with general weakness (prevalence between 2.0 and 9.6/100000) [1]. They often resemble patients who have a mild form of spastic diplegia (SD) secondary to cerebral palsy as for deambulation. Unlike SD, which gait pattern has been investigated and quantified deeply with gait analysis (GA), in literature analysis of gait strategy of HSP patients was limited to clinical examination; only one study was conducted using GA in HSP during walking on treadmill [1]. The main objective of this study is the identification and the quantification of gait pattern of HSP in order to define its features and the differences between HSP and SD gait strategy, with kinematic and kinetic indices.

We attempted to quantify the effects of isolated femoral derotation osteotomies using clinical evaluation and gait analysis (kinematics and kinetics) in patients with cerebral palsy (CP). Twelve children with CP were evaluated before and 10 months after isolated femoral derotation osteotomy, and 15 healthy children were evaluated as controls. There were significant improvements on clinical examination. A better position of the hip and ankle in the transverse plane was evident and significant changes occurred in terms of hip and ankle kinetics after surgery. Improvements in kinematics and hip and ankle power are very important biomechanically. The correction of lever arm dysfunction and more physiological hip and ankle power generation result in an improvement in terms of energy consumption, leading to a more functional and economic gait pattern.