Home treatment against fatigue in multiple sclerosis by a personalized, bilateral whole-body somatosensory cortex stimulation.

BACKGROUND: Fatigue in multiple sclerosis (MS) is a highly invalidating symptom with no pharmacological efficacious therapies, which furthermore present frequent severe side effects. In two previous randomized controlled trials we observed the efficacy of a personalized neuromodulation treatment consisting of a personalized transcranial Direct Current Stimulation (tDCS) for 15 min per day for 5 days (Faremus). METHODS: By this medical-device phase II study, we aimed at assessing the feasibility, acceptance, safety and efficacy of Faremus treatment when applied at patients' home. We considered the efficacy as primary outcome assessed by a reduction of fatigue levels measured by Modified Fatigue Impact Scale (mFIS) scored before and after the treatment. Primary outcome determined the sample size estimate. Individual ad-hoc questionnaires quantified the acceptance, safety and side effects during the treatment. RESULTS: All 15 patients completed the treatment, reporting optimal acceptance and safety on using Faremus at their home without side-effects. The treatment ameliorated fatigue symptoms more than 20% of baseline in 10 out of the 15 patients and of 37% on average, with a corresponding effect size 1.21. CONCLUSIONS: Faremus personalized electroceutical intervention, a 5-days anodal tDCS over the bilateral whole-body somatosensory cortex, is well accepted and can be feasibly, safely, and efficaciously applied at patients' home, offering a comfortable treatment by reducing the need to travel when fatigue-related symptoms hamper the quality of life.

MRI-Guided Regional Personalized Electrical Stimulation in Multisession and Home Treatments.

The shape and position of the electrodes is a key factor for the efficacy of transcranial electrical stimulations (tES). We have recently introduced the Regional Personalized Electrode (RePE), a tES electrode fitting the personal cortical folding, that has been able to differentiate the stimulation of close by regions, in particular the primary sensory (S1) and motor (M1) cortices, and to personalize tES onto such an extended cortical district. However, neuronavigation on individual brain was compulsory for the correct montage. Here, we aimed at developing and testing a neuronavigation-free procedure for easy and quick positioning RePE, enabling multisession RePE-tES at home. We used off-line individual MRI to shape RePE via an ad-hoc computerized procedure, while an ad-hoc developed Adjustable Helmet Frame (AHF) was used to properly position it in multisession treatments, even at home. We used neuronavigation to test the RePE shape and position obtained by the new computerized procedure and the re-positioning obtained via the AHF. Using Finite Element Method (FEM) model, we also estimated the intra-cerebral current distribution induced by transcranial direct current stimulation (tDCS) comparing RePE vs. non-RePE with fixed reference. Additionally, we tested, using FEM, various shapes, and positions of the reference electrode taking into account possible small displacements of RePE, to test feasibility of RePE-tES sessions at home. The new RePE neuronavigation-free positioning relies on brain MRI space distances, and produced a mean displacement of 3.5 ± 0.8 mm, and the re-positioning of 4.8 ± 1.1 mm. Higher electric field in S1 than in M1 was best obtained with the occipital reference electrode, a montage that proved to feature low sensitivity to typical RePE millimetric displacements. Additionally, a new tES accessory was developed to enable repositioning the electrodes over the scalp also at home, with a precision which is acceptable according to the modeling-estimated intracerebral currents. Altogether, we provide here a procedure to simplify and make easily applicable RePE-tDCS, which enables efficacious personalized treatments.

Personalized, bilateral whole-body somatosensory cortex stimulation to relieve fatigue in multiple sclerosis.

BACKGROUND: The patients suffering from multiple sclerosis (MS) often consider fatigue the most debilitating symptom they experience, but conventional medicine currently offers poorly efficacious therapies. OBJECTIVE: We executed a replication study of an innovative approach for relieving MS fatigue. METHODS: According to the sample size estimate, we recruited 10 fatigued MS patients who received 5-day transcranial direct current stimulation (tDCS) in a randomized, double-blind, Sham-controlled, crossover study, with modified Fatigue Impact Scale (mFIS) score reduction at the end of the treatment as primary outcome. A personalized anodal electrode, shaped on the magnetic resonance imaging (MRI)-derived individual cortical folding, targeted the bilateral whole-body primary somatosensory cortex (S1) with an occipital cathode. RESULTS: The amelioration of fatigue symptoms after Real stimulation (40% of baseline) was significantly larger than after Sham stimulation (14%, p = 0.012). Anodal whole body S1 induced a significant fatigue reduction in mildly disabled MS patients when the fatigue-related symptoms severely hampered their quality of life. CONCLUSION: This second result in an independent group of patients supports the idea that neuromodulation interventions that properly select a personalized target might be a suitable non-pharmacological treatment for MS fatigue.

Patients with Increased Non-Ceruloplasmin Copper Appear a Distinct Sub-Group of Alzheimer's Disease: A Neuroimaging Study.

BACKGROUND: Meta-analyses show that copper non-bound to ceruloplasmin (non-Cp Cu, also known as 'free' copper) in serum is higher in a percentage of Alzheimer's disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp Cu cut-off sustains the existence of a copper AD metabolic subtype. OBJECTIVE: In order to find evidence of the existence of a detectable metabolic subtype of AD associated to copper abnormalities, we explore the hypothesis of a neuroimaging pattern heterogeneity in an homogenous and well characterized AD population classified in two groups by the stratification of patients on the basis non-Cp Cu cut-off. METHOD: We assessed levels of copper, ceruloplasmin, non-Cp Cu, cerebrospinal levels of total Tau protein (h-tau), Thr 181 phosphorylated tau protein (P-tau) and ß-amyloid 1-42, and APOE4 genotype in 66 AD patients and compared neuroimaging indices of a visual rating scale of cerebral atrophy and neurovascular burden in AD patients stratified in 'Normal' and 'High' non-Cp Cu groups. RESULTS: The stratification for non-Cp Cu originated AD groups which did not differ for medial temporal lobe atrophy, periventricular hyperintensities, deeper hyperintensities (including frontal, parietooccipital and temporal white matter hyperintensities), infratentorial hyperintensities indices, while they differed for global atrophy. More specifically, AD patients within the high non-Cp Cu group had a less severe burden of global atrophy (p=0.042). CONCLUSION: This neuroimaging heterogeneity between AD groups is suggestive of the existence of a copper metabolic subtype of AD; non-Cp Cu appears a good marker of this copper AD.

The Role of White Matter Damage in the Risk of Periprocedural Diffusion-Weighted Lesions after Carotid Artery Stenting.

BACKGROUND: White matter hyperintensities (WMH) are a common finding in aged individuals affected by carotid artery disease and are a risk factor for first-ever and recurrent stroke. We investigated if white matter damage increases the risk of brain microembolism during carotid artery stenting (CAS), as evaluated by the appearance of new areas of restricted diffusion on diffusion-weighted images (DWI). METHODS: We evaluated 47 patients with severe internal carotid artery (ICA) stenosis undergoing CAS, comparing preprocedural clinical, ultrasound and radiological characteristics. WMH volume was computed on FLAIR images before CAS. After CAS, the DWI scan was looked over for areas of restricted diffusion (DWI lesions). A first univariate analysis was adopted to compare groups according to the occurrence of DWI lesions. Then, the variable DWI lesion was modelled by means of a logistic regression model. RESULTS: Seventeen patients developed at least 1 DWI lesion after CAS. Compared with non-DWI, DWI patients were more commonly treated in the left ICA (p = 0.007) and had a more severe WMH damage (p = 0.027). Indeed, the risk of a DWI lesion was higher in left versus right stenosis (OR = 9.0, 95% CI 1.9-42.7, p = 0.005) and increased for each log-unit of WMH lesion load (OR = 7.05, 95% CI 1.07-46.49, p = 0.042). A WMH lesion load of at least 5.25 cm3 had a 50% probability of occurrence of a new DWI lesion. CONCLUSIONS: Treated side and preexisting white matter damage are risk conditions for brain microembolism during CAS. This should be taken into account to optimize severe carotid artery disease management.

Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue.

RATIONALE: We recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments. OBJECTIVE: The present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas. METHOD: Two separate groups of fatigued MS patients were given a 5-day tDCS treatments targeting, respectively, the whole body somatosensory areas (S1wb) and the hand sensorimotor areas (SM1hand). The study had a double blind, sham-controlled, randomized, cross-over (Real vs. Sham) design. Before and after each treatment, we measured fatigue levels (by the modified fatigue impact scale, mFIS), motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and somatosensory evoked potentials (SEPs) in response to median nerve stimulation. We took MEPs and SEPs as measures of the excitability of the primary motor area (M1) and the primary somatosensory area (S1), respectively. RESULTS: The Real S1wb treatment produced a 27% reduction of the mFIS baseline level, while the SM1hand treatment showed no difference between Real and Sham stimulations. M1 excitability increased on average 6% of the baseline in the S1wb group and 40% in the SM1hand group. Observed SEP changes were not significant and we found no association between M1 excitability changes and mFIS decrease. CONCLUSION: The tDCS treatment was more effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area. Changes in S1 and M1 excitability did not correlate with symptoms amelioration. SIGNIFICANCE: The neuromodulation treatment that proved effective against MS fatigue induced only minor variations of the motor cortex excitability, not enough to explain the beneficial effects of the intervention.

Cortical ischemic lesion burden measured by DIR is related to carotid artery disease severity.

BACKGROUND: Over time, exposure to cerebrovascular risk factors and carotid artery disease may cause multiple asymptomatic brain cortical and subcortical microinfarcts, which are commonly found at brain autopsy. So far, lack of convenient neuroimaging tools limited the investigation of grey matter ischemic damage in vivo. We applied the Double Inversion Recovery (DIR) sequence to explore the impact of carotid artery disease on intracortical ischemic lesion load in vivo, taking into account the impact of demographic characteristics and vascular risk factors. METHODS: DIR was acquired in 62 patients with common cerebrovascular risk factors stratified in three groups according to carotid artery disease severity. Intracortical lesions scored on DIR (DIRlns) were classified by vascular territory, lobe and hemisphere. White matter hyperintensities (WMHs) volume was also quantified on Fluid Attenuated Inversion Recovery sequence (FLAIR). RESULTS: Among demographic characteristics and cerebrovascular risk variables explored, General Linear Model indicated that age and carotid artery disease were significantly associated to DIRlns. After correcting for age, DIRlns load was found to be significantly dependent on carotid artery stenosis severity (F(2, 58) = 5.56, p = 0.006). A linear positive correlation between DIRlns and WMHs was found after correcting for age (p = 0.003). CONCLUSIONS: Carotid disease severity is associated with DIRlns accrual. Microembolism and impaired cerebral hemodynamics may act as physiopathological mechanisms underlying cortical ischemic damage. The role of other factors, such as small vessel disease and the possible interaction with carotid disease, remains to be further explored.

Sella turcica atypical teratoid/rhabdoid tumor complicated with lung metastasis in an adult female.

Here we present the case of a 60-year-old woman with a rare sellar region atypical teratoid/rhabdoid tumor (AT/RT), complicated by lung metastasis and treated with neurosurgery, radiotherapy, and chemotherapy. The patient had recurrent headache associated with left cavernous sinus syndrome after a previous endonasal transsphenoidal resection for a presumptive pituitary macroadenoma. Pituitary magnetic resonance imaging showed a tumor regrowth in the original location with a haemorrhagic component involving the left cavernous sinus. A near complete transsphenoidal resection of the sellar mass was performed followed by 3 months of stereotactic radiotherapy. Because of a worsening of the general clinical conditions, respiratory failure, and asthenia, the patient underwent a contrast enhanced computer tomography of the whole body which showed the presence of lung metastasis. The histopathological diagnosis on samples from pituitary and lung tissues was AT/RT. The patient survived 30 months after diagnosis regardless chemotherapy. In the adult, the AT/RT should be considered as a possible rare, aggressive, and malignant neoplasm localized in the sella turcica.

Diffusion-weighted lesions after carotid artery stenting are associated with cognitive impairment.

The effect of carotid artery stenting (CAS) on cognitive function is still debated. Cerebral microembolism, detectable by post-procedural diffusion-weighted imaging (DWI) lesions, has been suggested to predispose to cognitive decline. Our study aimed at evaluating the effect of CAS on cognitive profile focusing on the potential role of cerebral microembolic lesions, taking into consideration the impact of factors potentially influencing cognitive status (demographic features, vascular risk profile, neuropsychological evaluation at baseline and magnetic resonance (MR) markers of brain structural damage). Thirty-seven patients with severe carotid artery stenosis were enrolled. Neurological assessment, neuropsychological evaluation and brain MR were performed the day before CAS (E0). Brain MR with DWI was repeated the day after CAS (E1), while neuropsychological evaluation was done after a 14-month median period (E2). Volumes of both white matter hyperintensities and whole brain were estimated at E0 on axial MR FLAIR and T1w-SE sequences, respectively. Unadjusted ANOVA analysis showed a significant CAS*DWI interaction for MMSE (F=7.154(32), p=.012). After adjusting for factors potentially influencing cognitive status CAS*DWI interaction was confirmed for MMSE (F=7.092(13), p=.020). Patients with DWI lesions showed a mean E2-E0 MMSE reduction of -3.1, while group without DWI lesions showed a mean E2-E0 MMSE of +1.1. Our study showed that peri-procedural brain microembolic load impacts negatively on cognitive functions, independently from the influence of patients-related variables.

Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease.

The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.

Antioxidant status and APOE genotype as susceptibility factors for neurodegeneration in Alzheimer's disease and vascular dementia.

Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the ε4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes. To address this issue, we evaluated the effects of antioxidant status and APOE genotype on neurodegeneration in patients with dementia of the Alzheimer type (AD), with vascular dementia (VaD), and in elderly healthy controls. Eighty-two AD, 42 VaD patients, and 26 healthy controls were recruited and underwent medial temporal lobe atrophy (MTA) assessment, white matter hyperintensities rating (WMH), serum total antioxidant status assaying (TAS), and APOE genotyping. A logistic regression algorithm applied to our data revealed that a 0.01 mmol/L decrease of TAS concentration increased the probability of MTA by 24% (p=0.038) and that carriers of the APOE ε4 allele showed higher WMH scores (p=0.018), confirming that small variations in antioxidant systems homeostasis are associated with relevant modifications of disease risk. Furthermore, in individuals with analogous TAS values, the presence of the ε4 allele increased the predicted probability of having MTA. These outcomes further sustain the interaction of oxidative stress and APOE genotype to neurodegeneration.

Thalamocortical sensorimotor circuit in multiple sclerosis: an integrated structural and electrophysiological assessment.

Demyelination and axonal damage are pathologic hallmarks of multiple sclerosis (MS), leading to loss of neuronal synchronization, functional disconnection amongst brain relays, and clinical sequelae. To investigate these properties, the primary component of the sensorimotor network was analyzed in mildly disabled Relapsing-Remitting MS patients without sensory symptoms at the time of the investigation. By magnetoencephalography (MEG), the recruitment pattern within the primary sensory (S1) and motor (M1) areas was estimated through the morphology of the early components of somatosensory evoked magnetic fields (SEFs), after evaluating the S1 responsiveness to sensory inputs from the contralateral arm. In each hemisphere, network recruitment properties were correlated with ispilateral thalamus volume, estimated by morphometric techniques upon high-resolution 3D structural magnetic resonance images (MRI). S1 activation was preserved, whereas SEF morphology was strikingly distorted in MS patients, marking a disruption of primary somatosensory network patterning. An unbalance of S1-M1 dynamic recruitment was documented and correlated with the thalamic volume reduction in the left hemisphere. These findings support the model of MS as a disconnection syndrome, with major susceptibility to damage experienced by nodes belonging to more frequently recruited and highly specialized networks.

Ceruloplasmin/Transferrin ratio changes in Alzheimer's disease.

The link between iron and Alzheimer's disease (AD) has been mainly investigated with a focus on the local accumulation of this metal in specific areas of the brain that are critical for AD. In the present study, we have instead looked at systemic variations of markers of iron metabolism. We measured serum levels of iron, ceruloplasmin, and transferrin and calculated the transferrin saturation and the ceruloplasmin to transferrin ratio (Cp/Tf). Cp/Tf and transferrin saturation increased in AD patients. Cp/Tf ratios also correlated positively with peroxide levels and negatively with serum iron concentrations. Elevated values of ceruloplasmin, peroxides, and Cp/Tf inversely correlated with MMSE scores. Isolated medial temporal lobe atrophy positively correlated with Cp/Tf and negatively with serum iron. All these findings indicate that the local iron accumulation found in brain areas critical for AD should be viewed in the frame of iron systemic alterations.

Ceruloplasmin/Transferrin system is related to clinical status in acute stroke.

BACKGROUND AND PURPOSE: In acute stroke, Iron (Fe) may amplify reperfusion injury by catalyzing the conversion of superoxide and hydrogen peroxide into highly reactive radicals. Transferrin (Tf) is the main protein regulating Fe homeostasis, whereas Ceruplasmin (CP) is a circulating ferroxidase enzyme able to oxidize ferrous ions to less toxic ferric forms. This study aims at investigating whether CP, Copper (Cu), Tf, and Fe play a role in the pathophysiology of acute stroke. METHODS: We enrolled 35 acute stroke patients and 44 controls. All patients underwent: neurological examination assessed by National Institutes of Health Stroke Scale (NIHSS), ultrasound evaluation of carotid atherosclerosis, brain MRI to quantify ischemic lesion volume and measurement of serum levels of CP, Cu, Tf, Fe, hydro-peroxides, and Total plasmatic antioxidant capacity. RESULTS: In patients, NIHSS scores were associated with Tf (r=-0.48, P=0.004), hydro-peroxides (r=0.34, P=0.046), CP (r=0.43, P=0.012), and lesion volume (r=0.50, P=0.004). Lesion volume was inversely associated with Tf (r=-0.44, P=0.012). CP and hydro-peroxides were also largely related (r=0.81, P<0.001). The model multiple R was 0.57, resulting in a 32.5% of explained NIHSS variance with Tf accounting for 23.4% and CP for 9.1%. CONCLUSIONS: CP and Tf levels are representative of clinical status in acute stroke patients. Our findings suggest a protective role of Tf in acute stroke and a possible ambivalent role of CP.

Neuronal functionality assessed by magnetoencephalography is related to oxidative stress system in acute ischemic stroke.

The hypoxic brain damage induced by stroke is followed by an ischemia-reperfusion injury modulated by oxidative stress. Magnetoencephalographic (MEG) recording of rest and evoked cortical activities is a sensitive method to analyse functional changes following the acute ischemic damage. We aimed at investigating whether MEG signals are related to oxidative stress compounds in acute stroke. Eighteen stroke patients and 20 controls were enrolled. All subjects underwent MEG assessment to record background activity and somatosensory evoked responses (M20 and M30) of rolandic regions, neurological examination assessed by National Institute of Health Stroke Scale (NIHSS) and plasmatic measurement of copper, iron, zinc, ceruloplasmin, transferrin, total peroxides and Total Anti-Oxidant Status. Magnetic Resonance was performed to estimate the lesion site and volume. Delta power and M20 equivalent current dipole (ECD) strength in the affected hemisphere (AH) correlated with NIHSS scores (respectively, rho=.692, p=.006 and rho=-.627, p=.012) and taken together explained 67% of NIHSS variability (p=.004). Higher transferrin and lower peroxides levels correlated with better clinical status (respectively, rho=-.600, p=.014 and rho=.599, p=.011). Transferrin also correlated with AH M20 ECD strength (rho=.638 p=.014) and inversely with AH delta power (rho=-.646 p=.023) and the lesion volume, especially in cortico-subcortical stroke (p=.037). Our findings strengthen MEG reliability in honing the evaluation of neuronal damage in acute ischemic stroke also demonstrating an association between the MEG parameters most representing the clinical status and the oxidative stress compounds. Our results meet at a possible protective role of transferrin in limiting the oxidative damage in acute stroke.

Intra-cortical connectivity in multiple sclerosis: a neurophysiological approach.

Multiple sclerosis is an autoimmune disease predominantly affecting the white matter of the CNS, causing--among functional sequelae-cortico--cortical partial or total disconnection. Since functional connectivity linking cerebral regions is reliably reflected by synchronization of their neuronal firing, in this study an electrophysiological parameter measured by magnetoencephalography was used to quantify an intra-cortical connectivity (ICC) index focused on the primary somatosensory cortical areas (S1). Twenty-one patients affected by mild (Extended Disability Scale Score, median 1,5) relapsing-remitting (RR) multiple sclerosis in the remitting phase without clinically evident sensory impairment were evaluated. Three dimensional MRI was used to quantify the lesion load, discriminating black hole and non-black hole portions, normalized by individual brain volumes. When matched with a control population, multiple sclerosis patients showed a reduced ICC combined with the complete loss of the finger-dependent functional specialization in S1 cortex of the dominant hemisphere. No association was found between ICC impairment and disease duration, or prolongation of the central sensory conduction time, presence of spinal cord lesions and ongoing disease modifying therapy. The ICC index slightly correlated with the lesion load. A local index of ICC in a circumscribed brain primary area was altered in mildly disabled RR-multiple sclerosis patients, also in absence of any impairment of central sensory conduction. In conclusion, the diffuse damage influencing the multi-nodal network subtending complex cerebral functions also affects intrinsic cortical connectivity. The S1 ICC index is proposed as a highly sensitive and simple-to-test functional measure for the evaluation of intra-cortical synchronization mechanisms in RR-multiple sclerosis.

Outcome prediction in acute monohemispheric stroke via magnetoencephalography.

BACKGROUND: Following an ischemic stroke a highly variable clinical outcome is commonly evident despite similar onset symptoms as well as lesion characteristics. The aim of this study was to identify indexes providing early prediction of functional recovery, in addition to clinical severity and lesion dimension at onset of stroke. METHODS: In 32 patients, magnetoencephalographic (MEG) parameters collected in the acute phase (<10 days from symptoms onset, T0) from affected (AH) and unaffected (UH) hemispheres at rest and evoked by sensory stimuli were evaluated in association with the clinical outcome in a stabilized phase (T1, median 7.8 months) classified with three levels: worsening, partial and full recovery. RESULTS: Multiple multinomial logistic regression indicated AH gamma and UH delta band powers able to prognosticate clinical outcome at T1. After inclusion in this analysis, lesion volume had the strongest predictive ability, and UH delta band power remained as a predictive factor with a measurable cut-off, maximizing both sensitivity and specificity of the prediction: a patient with UH delta below cut-off would recover to some extent; a patient with UH delta above cut-off would have a probability of about 70% to worsen. CONCLUSIONS: MEG UH delta and AH gamma band powers were found to provide useful information about long-term outcome prognosis. Only the increase of delta band activity in the unaffected hemisphere contains information about the outcome in addition to the lesion volume.

Brain sensorimotor hand area functionality in acute stroke: insights from magnetoencephalography.

An understanding of the functional readjustments that the brain undergoes during the early days after a stroke would give us a major insight into how and how much neurons are capable to react to an insult. Thirty-two patients affected by an acute monohemispheric ischemic stroke were enrolled in the study. Magnetoencephalography was used to record the somatosensory-evoked fields (SEF) generated in response to median nerve stimulation. Latency, strength, and position of the related early cortical components (M20 and M30) were studied both separately within each hemisphere, and in terms of interhemispheric differences. Interhemispheric cross-correlations among SEF waveshapes in the two hemispheres were also investigated. Overall, except for some source displacement possibly induced by the perilesional edema, results did not demonstrate any unusual neural recruitment. The severity of the clinical picture was found related to the sources' strengths (both as absolute values and as interhemispheric differences), to excessive interhemispheric differences in SEF waveshapes and in the M30 latencies. Signs of an enhanced excitability were present in the affected hemisphere (AH) following a cortical lesion, usually in combination with preserved hand functionality. An enhanced excitability of the unaffected hemisphere (UH) was paired with larger lesions with cortical involvement; signs compatible with an abnormal transcallosal transmission and intracortical function of inhibitory GABAergic interneurons in the AH were found subtending UH enhancement. Spared responsiveness from Brodmann's area (BA) 2 and posterior parietal areas despite an altered response from BA 3b was found in six patients, combined to high hand functionality. Present results in acute phase increase the knowledge of the mechanisms governing brain adaptation/reaction capabilities, for future efforts to establish therapeutic and rehabilitative procedures.

Copper perturbation in 2 monozygotic twins discordant for degree of cognitive impairment.

BACKGROUND: Recent evidence indicates that peripheral tissue markers can provide information regarding changes affecting cellular metabolism in Alzheimer disease (AD). We previously reported that serum copper levels can discriminate subjects with AD from normal control subjects (with 60% sensitivity and 95% specificity) and from patients with vascular dementia (with 63% sensitivity and 85% specificity). OBJECTIVE: To study the correlation between AD and serum levels of transition metals and markers of peripheral oxidative stress. DESIGN: Case study. SETTING: General hospital inpatient wards and outpatient clinics. Patients A pair of elderly monozygotic female twins discordant for AD. MAIN OUTCOME MEASURES: Biochemical analyses of peripheral-blood transition metals and indicators of oxidative stress and neurologic and neuropsychological assessments of clinical status for presence of cognitive impairment and AD. RESULTS: Serum copper and total peroxide levels were both 44% higher in the twin with greater cognitive impairment and a diagnosis of AD. CONCLUSIONS: The cases reported support the hypothesis of a major involvement of copper and oxidative abnormalities in AD.