OnabotulinumtoxinA in elderly patients with chronic migraine: insights from a real-life European multicenter study.

INTRODUCTION: Although migraine prevalence decreases with aging, some older patients still suffer from chronic migraine (CM). This study aimed to investigate the outcome of OnabotulinumtoxinA (OBT-A) as preventative therapy in elderly CM patients. METHODS: This is a post hoc analysis of real-life prospectively collected data at 16 European headache centers on CM patients treated with OBT-A over the first three treatment cycles (i.e., Cy1-3). We defined: OLD patients aged ≥ 65 years and nonOLD those < 65-year-old. The primary endpoint was the changes in monthly headache days (MHDs) from baseline to Cy 1-3 in OLD compared with nonOLD participants. The secondary endpoints were the responder rate (RR) ≥ 50%, conversion to episodic migraine (EM) and the changes in days with acute medication use (DAMs). RESULTS: In a cohort of 2831 CM patients, 235 were OLD (8.3%, 73.2% females, 69.6 years SD 4.7). MHDs decreased from baseline (24.8 SD 6.2) to Cy-1 (17.5 SD 9.1, p < 0.000001), from Cy-1 to Cy-2 (14.8 SD 9.2, p < 0.0001), and from Cy-2 to Cy-3 (11.9 SD 7.9, p = 0.001). DAMs progressively reduced from baseline (19.2 SD 9.8) to Cy-1 (11.9 SD 8.8, p < 0.00001), to Cy-2 (10.9 SD 8.6, p = 0.012), to Cy-3 (9.6 SD 7.4, p = 0.049). The 50%RR increased from 30.7% (Cy-1) to 34.5% (Cy-2), to 38.7% (Cy-3). The above outcome measures did not differ in OLD compared with nonOLD patients. CONCLUSION: In a population of elderly CM patients with a long history of migraine OBT-A provided a significant benefit, over the first three treatment cycles, as good as in non-old patients.

Emotional processing in RRMS patients: Dissociation between behavioural and neurophysiological response.

BACKGROUNG: Multiple sclerosis (MS) results in a broad range of symptoms, including motor, visual, cognitive, and neuropsychiatric deficits. Some studies, considering affective facial expressions to study emotion processing, demonstrated emotion recognition difficulties in MS patients. OBJECTIVE: We investigated the impact of MS on the emotional-behaviour rating and neurophysiological response (Event Related Potentials-ERP) through a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). METHODS: Twenty patients with diagnosis of Relapsing Remitting MS (RRMS) and 20 Healthy Controls (HC) matched by age, gender and education were enrolled. Each of them, after a neuropsychological assessment, were asked to evaluate arousal and valence of affective visual stimuli. RESULTS: Our results showed higher P300 amplitudes in RRMS patients than HC group for pleasant and unpleasant images. Moreover, RRMS patients showed lower Reaction Time (RT) respect HC in valence rating. No other effect did emerge between groups. CONCLUSION: Our study shows early compensatory cerebral mechanisms in RRMS patients throughout emotional information processing, particularly for unpleasant and pleasant stimuli. We hypothesize that this compensatory cerebral mechanism reduces the behavioural dissimilarity between patients and HC.

Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients with Very Mild Clinical Disability.

Cognitive dysfunction affects 40-65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated. Our results show that 51.1% of MS patients have cognitive dysfunction compared to HC. An impairment of verbal and visual memory, working memory, and executive functions was found in the RRMS group. After subgrouping RRMS by EDSS, group 1 (EDSS ≤ 1.5) showed involvement of verbal memory and executive functions; moreover, group 2 (2 ≤ EDSS ≤ 2.5) patients were also impaired in information processing speed and visual memory. Our results show that utilizing a comprehensive neuropsychological assessment, approximately half of MS patients with very mild physical disability exhibit cognitive impairment with a primary involvement of prefrontal cognitive functions. Detecting impairment of executive functions at an early clinical stage of disease could be useful to promptly enroll MS patients in targeted rehabilitation.

Association between sex, systemic iron variation and probability of Parkinson's disease.

OBJECTIVE: Iron homeostasis appears altered in Parkinson's disease (PD). Recent genetic studies and meta-analyses have produced heterogeneous and inconclusive results. In order to verify the possible role of iron status in PD, we have screened some of the main metal gene variants, evaluated their effects on iron systemic status, and checked for possible interactions with PD. MATERIALS AND METHODS: In 92 PD patients and 112 healthy controls, we screened the D544E and R793H variants of the ceruloplasmin gene (CP), the P589S variant of the transferrin gene (TF), and the H63D and C282Y variants of the HFE gene, encoding for homologous proteins, respectively. Furthermore, we analyzed serum concentrations of iron, copper and their related proteins. RESULTS: The genetic investigation revealed no significant differences in allelic and genotype distributions between patients and controls. Two different multivariable forward stepwise logistic models showed that, when the effect of sex is considered, an increase of the probability of having PD is associated with low iron concentration and Tf-saturation. CONCLUSIONS: This study provides new evidence of the involvement of iron metabolism in PD pathogenesis and reveals a biological effect of sex.

Effects of hemochromatosis and transferrin gene mutations on peripheral iron dyshomeostasis in mild cognitive impairment and Alzheimer's and Parkinson's diseases.

Deregulation of iron metabolism has been observed in patients with neurodegenerative diseases. We have carried out a molecular analysis investigating the interaction between iron specific gene variants [transferrin (TF, P589S), hemochromatosis (HFE) C282Y and (H63D)], iron biochemical variables [iron, Tf, ceruloplasmin (Cp), Cp:Tf ratio and % of Tf saturation (% Tf-sat)] and apolipoprotein E (APOE) gene variants in 139 Alzheimer's disease (AD), 27 Mild Cognitive Impairment (MCI), 78 Parkinson's disease (PD) patients and 139 healthy controls to investigate mechanisms of iron regulation or toxicity. No difference in genetic variant distributions between patients and controls was found in our Italian sample, but the stratification for the APOEε4 allele revealed that among the APOEε4 carriers was higher the frequency of those carriers of at least a mutated TF P589S allele. Decreased Tf in both AD and MCI and increased Cp:Tf ratio in AD vs. controls were detected. A multinomial logistic regression model revealed that increased iron and Cp:Tf ratio and being man instead of woman increased the risk of having PD, that increased values of Cp:Tf ratio corresponded to a 4-fold increase of the relative risk of having MCI, while higher Cp levels were protective for PD and MCI. Our study has some limitations: the small size of the samples, one ethnic group considered, the rarity of some alleles which prevent the statistical power of some genetic analysis. Even though they need confirmation in larger cohorts, our data suggest the hypothesis that deregulation of iron metabolism, in addition to other factors, has some effect on the PD disease risk.

A contralesional EEG power increase mediated by interhemispheric disconnection provides negative prognosis in acute stroke.

BACKGROUND AND PURPOSE: Despite similar clinical onset, recovery from stroke can be largely variable. We searched for electrophysiological prognostic indices, believing that they can guide future neuromodulation treatments boosting clinical recovery. METHODS: 19-channels resting electroencephalogram (EEG) was collected in 42 patients after 4-10 days (t0) from a unilateral ischemic stroke in the middle cerebral artery (MCA) territory and 20 controls. National Health Institute Stroke Scale (NIHSS) was collected at t0 and 6 months later (t1). Standard spectral band powers and interhemispheric coherences between homologous MCA regions were calculated in both hemispheres. RESULTS: Total spectral, delta and theta band powers were higher bilaterally in patients than in controls and directly correlated with NIHSSt0 in both hemispheres. A linear regression model including each EEG patient's variable differing from those of controls and correlating with effective recovery [ER = (NIHSSt0-NIHSSt1)/(NIHSSt0-NIHSS in healthy conditions)] showed contralesional delta power as the only valid predictor of ER. A further regression model including also NIHSSt0 confirmed that contralesional delta power can add prognostic information to acute clinical impairment. Contralesional delta activity increase was best explained, in addition to the increasing ipsilesional delta activity, by a reduction of interhemispheric functional coupling--which did not explain a significantly portion of effective recovery variability by itself. CONCLUSIONS: Contralesional EEG delta activity retains relevant negative prognostic information in acute stroke patients. Present results point to the interhemispheric interplay as a decisive target in setting up enriched rehabilitations.

Inter-hemispheric coupling changes associate with motor improvements after robotic stroke rehabilitation.

PURPOSE: In the chronic phase of stroke brain plasticity plays a crucial role for further motor control improvements. This study aims to assess the brain plastic reorganizations and their association with clinical progresses induced by a robot-aided rehabilitation program in chronic stroke patients. METHODS: 7 stroke patients with an upper limb motor impairment in chronic phase underwent a multi-modal evaluation before starting and at the end of a 12-week upper-limb neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and performance indices of hand movement performance (isometric pinch monitored through a visual feedback) were collected. Cerebral reorganizations were characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional and contralesional resting state properties investigating both bipolar derivations overlying the middle cerebral artery territory and the primary somatosensory sources (S1) obtained through the Functional Source Separation (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh) at rest were measured and correlated with clinical and hand control robot-induced improvements. RESULTS: After the robotic rehabilitation we found an improvement of FMAS scores and hand motor control performance and changes of brain connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement of motor performance correlated with the modulation of the interhemispheric S1 coherence in the high beta band (24-33 Hz). CONCLUSIONS: Recently it has been shown that an upper limb robot-based rehabilitation improves motor performance in stroke patients. We confirm this potential and demonstrate that a robot-aided rehabilitation program induces brain reorganizations. Specifically, interhemispheric connectivity between primary somatosensory areas got closer to a 'physiological level' in parallel with the acquisition of more accurate hand control.

Primary headache and epilepsy: a multicenter cross-sectional study.

The prevalence and characteristics of interictal headache, epilepsy and headache/epilepsy comorbidity were assessed in 858 women and 309 men aged 18-81 years from headache and epilepsy centers in Italy. The research hypothesis was that comorbidity among patients with either disorder would be expected to be higher than in the general population. Interictal headache was diagnosed in 675 cases (migraine 482; tension-type headache 168; other types 25), epilepsy in 336 (partial 171; generalized 165) and comorbidity in 156 (1.6% from headache centers; 30.0% from epilepsy centers). Patients with epilepsy, headache and comorbidity differed in a number of demographic and clinical aspects. However, for both headache and epilepsy, a family history of the same clinical condition was equally prevalent in patients with and without comorbidity. These findings do not support the purported association between headache and epilepsy.

Systemic lupus erythematosus patients with and without neuropsychiatric manifestations: a neck and transcranial duplex sonography study.

Neuropsychiatric manifestations are not rarely associated with systemic lupus erythematosus (SLE). Magnetic resonance angiography and positron emission tomography can provide excellent images of cerebral perfusion and metabolism whereas information is still lacking on a possible diagnostic role of ultrasound. In this study we aim to assess whether duplex sonography of neck and intracranial vessels may be useful in distinguishing patients with and without neuropsychiatric SLE (NPSLE). Neck and transcranial duplex sonography was performed by a single operator on 33 women affected by SLE (mean age +/- SD: 47.69+/-8.17 years) and on 15 healthy control subjects. Nineteen patients presented NPSLE. Pulsatility and resistivity indices (PI and RI) were automatically calculated by the ultrasound instrument in internal carotid (ICA) and middle cerebral artery (MCA), on both sides, according to standard methods. No significant haemodynamic differences were found in mean and median PI and RI values of ICA and MCA comparing SLE with NPSLE patients and with healthy control subjects. No correlation was found between MCA and ICA parameters in the same group of patients. Duplex sonography of cerebral vessels is unable to distinguish SLE and NPSLE patients. Heterogeneity of causes in the pathogenesis of NPSLE and the different vascular adaptation of cerebral macrocirculation as opposed to cerebral microcirculation may represent possible reasons that explain the inability of ultrasound to differentiate SLE patients from NPSLE patients.

An unusual cause of dementia: essential diagnostic elements of corticobasal degeneration-a case report and review of the literature.

Corticobasal degeneration (CBD) is an uncommon, sporadic, neurodegenerative disorder of mid- to late-adult life. We describe a further example of the pathologic heterogeneity of this condition. A 71-year-old woman initially presented dysarthria, clumsiness, progressive asymmetric bradykinesia, and rigidity in left arm. Rigidity gradually involved ipsilateral leg; postural instability with falls, blepharospasm, and dysphagia subsequently developed. She has been previously diagnosed as unresponsive Parkinson's Disease. At our clinical examination, she presented left upper-arm-fixed-dystonia, spasticity in left lower limb and pyramidal signs (Babinski and Hoffmann). Brain MRI showed asymmetric cortical atrophy in the right frontotemporal cortex. Neuropsychological examination showed an impairment in visuospatial functioning, frontal-executive dysfunction, and hemineglect. This case demonstrates that association of asymmetrical focal cortical and subcortical features remains the clinical hallmark of this condition. There are no absolute markers for the clinical diagnosis that is complicated by the variability of presentation involving also cognitive symptoms that are reviewed in the paper. Despite the difficulty of diagnosing CBD, somatosensory evoked potentials, motor evoked potentials, long latency reflexes, and correlations between results on electroencephalography (EEG) and electromyography (EMG) provide further support for a CBD diagnosis. These techniques are also used to identify neurophysiological correlates of the neurological signs of the disease.

Association of reversed Robin Hood syndrome with risk of stroke recurrence.

BACKGROUND: Reversed Robin Hood syndrome (RRHS) has recently been identified as one of the mechanisms of early neurologic deterioration in acute ischemic stroke (AIS) patients related to arterial blood flow steal from ischemic to nonaffected brain. We sought to investigate the association of RRHS with risk of stroke recurrence in a single-center cohort study. METHODS: Consecutive patients with AIS or TIA affecting the anterior circulation were prospectively evaluated with serial NIH Stroke Scale assessments and bilateral transcranial Doppler monitoring with breath-holding test. RRHS was defined according to previously validated criteria. RESULTS: A total of 360 patients (51% women, mean age 62 ± 15 years) had an ischemic stroke (81%) or TIA (19%) in the anterior circulation, and 30 (8%) of them had RRHS. During a mean follow-up period of 6 months (range 1-24), a total of 16 (4%) recurrent strokes (15 ischemic and 1 hemorrhagic) were documented. The cumulative recurrence rate was higher in patients with RRHS (19%; 95% confidence interval [CI] 1-37) compared to the rest (15%; 95% CI 0-30; p = 0.022 by log-rank test). All recurrent strokes in patients with RRHS were cerebral infarcts that occurred in the ipsilateral to the index event anterior circulation vascular territory. After adjusting for demographic characteristics, vascular risk factors, and secondary prevention therapies, RRHS was independently associated with a higher stroke recurrence risk (hazard ratio 7.31; 95% CI 2.12-25.22; p = 0.002). CONCLUSIONS: Patients with AIS and RRHS appear to have a higher risk of recurrent strokes that are of ischemic origin and occur in the same arterial territory distribution to the index event. Further independent validation of this association is required in a multicenter setting.

High frequency repetitive transcranial magnetic stimulation decreases cerebral vasomotor reactivity.

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR). METHODS: Twenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before (T(0)) and within 10 min (T(1)) following rTMS. Four subjects underwent further VMR evaluations at 2 (T(2)), 5 (T(3)) and 24 h (T(4)) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial. RESULTS: Following real rTMS on M1 (p=0.002) and calcarine cortex (p<0.001) VMR decreased with respect to T(0) in both hemispheres, while no change was observed after sham rTMS (p>0.6). VMR tended to remain lower than T(0) until T(3.) Cerebral VMR decreased independently of the stimulated side also in the patients' group. CONCLUSIONS: High frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics. SIGNIFICANCE: The effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients.

Cerebral hemodynamics and cognitive performance in patients with asymptomatic carotid stenosis.

OBJECTIVE: The aim of this study was to investigate whether the presence of severe internal carotid artery stenosis may be associated with different cognitive performance in relation to the side of the stenosis and its hemodynamic consequences. METHODS: Eighty-three patients with asymptomatic severe unilateral internal carotid stenosis were included. A neuropsychological investigation including Verbal Fluency using phonemic and category access, Coloured Progressive Matrices, and Complex Figure Test Copy was performed. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler ultrasonography using the breath-holding index (BHI). Thirty healthy subjects comparable for demographic characteristics and vascular risk profile served as controls. Subjects with carotid stenosis were classified into two groups: preserved CVR (BHI > or =0.69), 48 patients (25 with left and 23 with right stenosis); and impaired CVR (BHI <0.69), 35 patients (19 with left and 16 with right stenosis). RESULTS: Subjects with left stenosis and reduced CVR had significantly lower performances at phonemic verbal fluency with respect to controls and the other groups of stenosis. In subjects with right stenosis and reduced CVR, scores obtained in Coloured Progressive Matrices and in Complex Figure Test Copy were significantly lower with respect to the other groups. CONCLUSIONS: These results suggest that an alteration of cerebrovascular reactivity may be responsible for reduction in some cognitive abilities involving the function of the hemisphere ipsilateral to carotid stenosis. Such findings may be of interest for providing a more comprehensive indication to surgical treatment in subgroups of subjects with asymptomatic carotid stenosis.

Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease.

BACKGROUND: Serum copper not bound to ceruloplasmin ("free") appears slightly elevated in patients with Alzheimer disease (AD). We explored whether a deregulation of the free copper pool can predict AD clinical worsening. METHODS: We assessed levels of copper, iron, zinc, transferrin, ceruloplasmin, peroxides, total antioxidant capacity, free copper, and apolipoprotein E genotype in 81 patients with mild or moderate AD, mean age 74.4, SD = 7.4 years, clinically followed up after 1 year. The association among biologic variables under study and Mini-Mental State Examination (MMSE) (primary outcome), activities of daily living (ADL), and instrumental activities of daily living (IADL) (secondary outcomes) performed at study entry and after 1 year were analyzed by multiple regression. RESULTS: Free copper predicted the annual change in MMSE, adjusted for the baseline MMSE by means of a linear regression model: it raised the explained variance from 2.4% (with only sex, age, and education) to 8.5% (p = 0.026). When the annual change in MMSE was divided into < 3 or > or = 3 points, free copper was the only predictor of a more severe decline (predicted probability of MMSE worsening 23%: odds ratio = 1.23; 95% confidence interval = 1.03-1.47; p = 0.022). Hyperlipidemic patients with higher levels of free copper seemed more prone to worse cognitive impairment. Free copper at baseline correlated with the ADL and IADL clinical scales scores at 1 year. CONCLUSIONS: These results show an association between copper deregulation and unfavorable evolution of cognitive function in Alzheimer disease. Further research is needed to establish whether copper is an independent risk factor for cognitive decline.

Functional transcranial Doppler assessment of cerebral blood flow velocities changes during attention tasks.

BACKGROUND AND PURPOSE: Aim of our study was to evaluate cerebral hemodynamic changes during performance of attention tasks and to correlate them with reaction time (RT) and percentage of right answers. METHODS: Mean flow velocity (MFV) in middle cerebral arteries was monitored in 30 subjects by transcranial Doppler during tonic alertness, phasic alertness, focused and divided attention tasks. RESULTS: Mean flow velocity increase was significantly higher during divided attention with respect to other tasks (P < .001). MFV increase was higher in the right than in the left side (P < .001). Asymmetry during attention tasks resulted significantly higher than that observed in tonic alertness condition. RT was increased during focused attention tasks (P < .001 vs. both alert tasks), with further increase during divided attention tasks (P < .001 vs. focused attention task). RT was inversely related to MFV increase only during tonic alertness (P = 0.012 for left side; P = 0.008 for right side). During the divided attention tasks, an association was found between MFV increase and correct answers (r = 0.39, P = 0.033). CONCLUSIONS: These data show a relationship between RT, correct answers and changes in blood flow velocity and suggest that this method of cerebral blood flow investigation could be a useful approach during assessment of patients with attention deficit.

Increased cerebral vasomotor reactivity in migraine with aura: an autoregulation disorder? A transcranial Doppler and near-infrared spectroscopy study.

Migraine with aura (MA) is associated with changes in cerebral blood flow (CBF), whereas the role of cerebral autoregulation is uncertain. This study aimed to evaluate basal CBF, cerebral blood volume (CBV) and vasomotor reactivity (VMR) in MA patients. Twenty-one controls and 16 MA patients (eight with side predominance) underwent simultaneous examination of flow velocity in the middle cerebral arteries by transcranial Doppler (TCD) and of near-infrared spectroscopy (NIRS) parameters [oxygen haemoglobin saturation: oxygen%, and total haemoglobin content (THC)] at rest and after hypercapnia. Cerebral VMR, THC and oxygen% increases were significantly greater on the predominant compared with the non-predominant migraine side, with both sides of patients without side predominance and with controls. These findings suggest altered autoregulation in MA patients, possibly secondary to impaired cerebrovascular autonomic control. Simultaneous TCD and NIRS investigation could represent a non-invasive approach to evaluate cerebral haemodynamics at the cortical and subcortical level.

Plasma levels of nitric oxide and stroke outcome.

Production of reactive oxygen species after cerebral blood flow disruption may enhance tissue damage through multiple molecular pathways. Changes in nitric oxide (NO) metabolism and oxidative stress status were investigated in 47 patients with ischemic stroke by measuring plasma nitric oxide (NO) and peroxynitrite (ONOO(-)) levels.A correlation was sought between these two parameters and i) baseline stroke severity based on the National Institute of Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS changes from entry (T(0)) to 30 days after symptom onset (T(1)). The control group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels of ONOO(-) (arbitrary fluorescence number +/- SD) were significantly higher in patients (7.70 +/- 1.71 vs 5.35 +/- 0.69, p < 0.001), whereas mean NO levels (nmol/mg protein) were significantly higher in controls (115.40 +/- 12.40 vs. 51.10 +/- 12.50, p < 0.001). Plasma ONOO(-) was significantly higher among patients with non-lacunar stroke (8.48 +/- 1.50 vs. 6.95 +/- 1.58 in those with lacunar stroke; p = 0.001), whereas NO levels were significantly higher among lacunar stroke patients (60.00 +/- 7.86, vs. 41.77 +/- 9.29 in patients with nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that changes in NO metabolism may be considered as markers of brain injury in patients with ischemic stroke. Further work is needed to establish whether the amount of biochemical changes related to oxidative stress may influence outcome in these patients.

Neuroimaging experimental studies on brain plasticity in recovery from stroke.

Topographical cortical organization of sensorimotor area has been shown to be highly plastic, altering his configuration in response to training in different tasks in healthy controls and neurological patients. The term ''brain plasticity'' encompasses all possible mechanisms of neuronal reorganization: recruitment of pathways that are functionally homologous to, but anatomically distinct from, the damaged ones (eg, non-pyramidal corticospinal pathways), synaptogenesis, dendritic arborisation and reinforcement of existing but functionally silent synaptic connections (particularly at the periphery of core lesion). The study of neuroplasticity has clearly shown the ability of the developing brain--and of the adult and ageing brain--to be shaped by environmental inputs both under normal conditions (ie, learning) and after a lesion. Neuronal aggregates adjacent, or distant to a lesion in the sensorimotor area can progressively adopt the function of the injured area. Imaging studies indicate that recovery of motor function after a lesion (i.e. stroke) is associated with a progressive change of activation patterns in specific brain structures. Transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) can detect reshaping of sensorimotor areas; they have a high temporal resolution but have several limitations. TMS can only provide bidimensional scalp maps and MEG depicts three-dimensional spatial characteristics of virtual neural generators obtained by use of a mathematical model of the head and brain. However, the use of objective methods that assess brain reactivity to a physical stimulus (i.e., TMS) or to a sensory input (ie, electrical stimulation to hand and fingers) can integrate information from self-paced motor tasks, because the resolution of abnormal activation over time could be secondary to recovery. Functional MRI (fMRI) and positron emission tomography (PET), on their own, have insufficient time resolution to follow the hierarchical activation of relays within a neural network; however, because of their excellent spatial resolution, they can integrate the findings of TMS and MEG. An integrated approach constitutes, at present, the best way to assess the brain plasticity both under normal conditions and after a lesion.