Resilience and psychosocial factors in adult with epilepsy: A longitudinal study.

PURPOSE: Resilience is conceptually characterized as a dynamic process encompassing positive adaptation in the context of significant adversity. Our goal was to assess the resilience in people with epilepsy (PWE) and how it impacts longitudinally on psychosocial factors, with a particular focus on the manifestation of stigmatization-related feelings. METHODS: We consecutively enrolled 78 adults PWE (42.5 ± 16.2 years old); among them 36 (46.1 %) were seizure-free. All subjects completed at baseline (T0) the Resilience Scale (RS-14) and questionnaires for the assessment of depressive symptoms, anxiety and quality of life: respectively, Beck Depression Inventory-II (BD-II), Generalized Anxiety Disorder-7 (GAD-7) and QOLIE-31 (Q31). All patients were followed up prospectively and re-evaluated after 6-22 months (T1; mean: 14 ± 8 months; median 14 months); at follow up they also completed the Stigma Scale of Epilepsy (SSE) for the assessment of the stigma associated with epilepsy. We correlated resilience values with all psychosocial scores at T0 and T1. Factors associated with resilient and vulnerable outcomes were identified. Finally, a multiple stepwise regression analysis was applied to identify predictors for resilience and stigma perception. RESULTS: The results showed for the RS-14 score a significant direct correlation with the Q31 (p < 0.001) and an inverse correlation with the depressive and anxiety symptoms at both times (T0 and T1), as evaluated with BDI-II (p < 0.001) and GAD-7 (p < 0.001). Finally, we found a significant inverse correlation between RS-14 at T0 and the levels of stigmatization assessed with SSE at T1 (p =.015). Using a multiple stepwise regression analysis separately for resilience and stigma perception, depressive symptoms turned out as the best predictors for both variables. Finally, considering longitudinal evaluation we did not observe significant changes in depressive and anxious symptoms, despite a significant reduction in the total number of seizures at follow up. CONCLUSIONS: Our study showed that depressive symptoms, anxiety and quality of life were significantly associated with resilience in PwE. Finally, as a novel finding resilience was proved to affect the perception of stigma related to epilepsy more than seizures.

Determinants of medication adherence in people with epilepsy: A multicenter, cross-sectional survey.

OBJECTIVES: Poor medication adherence in people with epilepsy (PwE) increases mortality, hospitalization, and poor quality of life, representing a critical challenge for clinicians. Several demographic, clinical, and neuropsychological factors were singularly found associated with medication adherence in several studies, but the literature lacks a comprehensive study simultaneously assessing all these variables. METHODS: We performed a multicenter and cross-sectional study using online questionnaires with the following clinical scales: Morisky Medication Adherence Scale (MMAS-8), Quality of Life in Epilepsy Inventory 31 (QoLIE-31), Beck Depression Inventory-II (BDI-II), Generalized Anxiety Disorder-7 (GAD-7) and 14-item Resilience scale (RES14) in a population of 200 PwE. We used the ANOVA test and Spearman's correlation to evaluate the relationship between medication adherence and demographic, clinical (seizure frequency, number of anti-seizure medications), and neuropsychological characteristics. We trained separate machine learning models (logistic regression, random forest, support vector machine) to classify patients with medium-high adherence (MMAS-8 ≥ 6) and poor adherence (MMAS-8 < 6) and to identify the main features that influence adherence. RESULTS: Women were more adherent to medication (p-value = 0.035). Morisky Medication Adherence Scale -8 showed a direct correlation with RES14 (p-value = 0.001) and age (p-value = 0.001), while was inversely correlated with BDI-II (p-value = 0.001) and GAD-7 (p-value = 0.001). In our model, the variables mostly predicting treatment adherence were QoLIE-31 subitems, followed by age, resilience, anxiety, years of school, and disease duration. CONCLUSION: Our study confirms that gender, age, and neuropsychological traits are relevant factors in predicting medication adherence to PwE. Furthermore, our data provided the first evidence that machine learning on multidimensional self-report questionnaires could help to develop a decisional support system in outpatient epilepsy clinics.

Resilience predicts and modulates anxiety severity in people with epilepsy.

BACKGROUND: Anxiety is one of the most relevant psychiatric comorbidities in people with epilepsy (PwE). The role of resilience (RES) in the development of anxiety is not well understood. We purposed to better characterize RES impact on anxiety severity in PwE. MATERIALS AND METHODS: One hundred and seventy-six PwE underwent online surveys including a collection of socio-demographic, seizure-related, and psychological variables. PwE were grouped according to the data collected; anxiety levels were compared through non-parametric statistics. Hierarchical regression analysis (HRA) and logistic regression were performed to characterize RES contribute in predicting the presence and the severity of anxiety. Mediation/moderation analysis was performed to evaluate causal effects among RES, depression, and anxiety. RESULTS: Anxiety did not differ according to socio-demographic and seizure-related variables, exemption for the presence of drug-related adverse effects. Depression, RES, and sleep quality provided the major contribute on anxiety variance. The addiction of RES level in HRA and logistic regression provided a significant increase of R-squared value (p-value = 0.02) and of area under the curve (p-value = 0.03), respectively. RES modulated depression/anxiety relationship (p-value < 0.001), whereas depression did not mediate RES/anxiety correlation (p-value = 0.68). CONCLUSIONS: We demonstrated that RES is a significant independent predictor of anxiety in PwE and is able to modulate depression impact on anxiety. Moreover, we confirmed the relevance of depression and sleep quality on anxiety severity.

Quantitative measures of the resting EEG in stroke: a systematic review on clinical correlation and prognostic value.

OBJECT: Quantitative electroencephalography (qEEG) has shown promising results as a predictor of clinical impairment in stroke. We systematically reviewed published papers that focus on qEEG metrics in the resting EEG of patients with mono-hemispheric stroke, to summarize current knowledge and pave the way for future research. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the literature for papers that fitted our inclusion criteria. Rayyan QCRR was used to allow deduplication and collaborative blinded paper review. Due to multiple outcomes and non-homogeneous literature, a scoping review approach was used to address the topic. RESULTS: Or initial search (PubMed, Embase, Google scholar) yielded 3200 papers. After proper screening, we selected 71 papers that fitted our inclusion criteria and we developed a scoping review thar describes the current state of the art of qEEG in stroke. Notably, among selected papers 53 (74.3%) focused on spectral power; 11 (15.7%) focused on symmetry indexes, 17 (24.3%) on connectivity metrics, while 5 (7.1%) were about other metrics (e.g. detrended fluctuation analysis). Moreover, 42 (58.6%) studies were performed with standard 19 electrodes EEG caps and only a minority used high-definition EEG. CONCLUSIONS: We systematically assessed major findings on qEEG and stroke, evidencing strengths and potential pitfalls of this promising branch of research.

The Italian technical/administrative recommendations for telemedicine in clinical neurophysiology.

Recent advances in technology, information technology, Internet networks, and, more recently, fiber optics in industrialized countries allow the exchange of a huge amount of data, in real time, across the globe. The acquisition of increasingly sophisticated technologies has made it possible to develop telemedicine, by which the specialist's evaluation can be carried out on the patient even remotely. In Italy, this very useful tool, although possible from a technological and information technology point of view, has not been developed because of the lack of clear and univocal rules and of major administrative obstacles related to the Italian Public Health System. To promote telemedicine implementation in Italy, the Italian Society of Clinical Neurophysiology and the Italian Society of Telemedicine together with the National Centre for Telemedicine and New Assistive Technologies of the Italian Higher Institute of Health prepared these inter-society recommendations. Because of potential forensic value of these recommendations, they were prepared considering the current regulations and the General Data Protection Regulation and will provide the basis for a Consensus Conference planned to discuss and prepare National Telemedicine Guidelines.

Familiarity for famous faces and names is not equally subtended by the right and left temporal poles. Evidence from an rTMS study.

The aims of the present experiment was to investigate: (a) if transient disruption of neural activity in the right (RTP) or left temporal pole (LTP) can interfere with the development of a familiarity feeling to the presentation of faces/written names of famous/unknown people; and (b) if this interference specifically affects the familiarity for faces after inhibition of the RTP and for names after inhibition of the LTP. Twenty healthy volunteers took part in the study. Repetitive transcranial magnetic stimulation (rTMS) was administered online; it disrupted the neural activity of the right or left TP in concomitance with the presentation of each face and name whose familiarity had to be assessed. Furthermore, in a control group, each participant was submitted to a single experimental session in which rTMS was delivered to the vertex in association with the presentation of faces and written names. Since previous rTMS studies have shown that the temporary inactivation of the right and left TP influences the response latencies, but not the number of correct responses, in this study we took into account both the number of correct responses obtained in different experimental conditions and the corresponding response latencies. A three-way factorial ANOVA carried out on the Response Scores showed only a general effect of the Type of Stimuli, due to better performances on names than on faces. This greater familiarity of names is consistent with previous data reported in the literature. In the three-way factorial ANOVA carried out on the Latency Scores, post-hoc analyses showed an increased latency of responses to faces after right stimulation in Latency Total, Latency on Correct responses and Latency on Unfamiliar faces. None of these results were obtained in the control group. These data suggest that rTMS at the level of the RTP preferentially affects the development of familiarity feelings to the presentation of faces of famous people.

Cardiovascular impairment in a patient with acute myelitis.

STUDY DESIGN: Case report. OBJECTIVE: to report and discuss the development of sudden symptomatic sinus bradycardia in a 35-year-old woman with acute myelitis. CASE REPORT: A 35-year-old woman presented rapidly progressive weakness and hypoesthesia in the left hemibody. Five days after symptom onset, she developed symptomatic sinus bradycardia up to 30 b.p.m. Bradycardia was completely resolved ∼36 h after its onset. RESULTS: Cervical spine magnetic resonance imaging showed a focal T2-hyperintense intramedullary lesion at C2 level, with moderate cord swelling. The lesion involved bilaterally dorsal funiculi, and left lateral and ventral funiculi. Cardiac I-123 metaiodobenzylguanidine (MIBG) scintigraphy showed a decreased cardiac MIBG uptake suggesting sympathetic denervation. CONCLUSION: The most likely explanation for bradycardia in our patient is the myelitis-related disruption of descending vasomotor pathways, resulting in sympathetic hypoactivity. Our case extends the spectrum of the clinical presentations of cervical myelitis and emphasizes the importance of careful cardiac monitoring in acute phase of cervical myelitis.

Whole-body computed tomography as first-line imaging procedure to exclude cancer in patients with neurological suspicion of paraneoplastic syndromes: shall clinical practice adhere to recommendations?

INTRODUCTION: To assess the efficacy of whole-body computed tomography (WB-CT) as imaging procedure to exclude cancer in patients with neurological symptoms and signs at clinical onset. METHODS: A retrospective observational study was designed to identify consecutive WB-CT requested by the Neurology Unit with a suspicion of an underlying tumor potentially linked to a paraneoplastic neurological syndrome (PNS) between January 2019 and February 2022. The following data were collected: diagnosis at admission and at discharge, the presence of onconeural antibodies, the scans dose length product (DLP), the estimated effective dose (ED), the total estimated time requested; the PNS-Care-Score was retrospectively calculated only in subjects with available antibodies. RESULTS: The total number of patients included was 158. In 13/158 (positive group) a malignant or locally aggressive neoplasm was found while in 145/158 no malignant lesions were found on the WB-CT. Among the positive group, in 7/13 onconeural antibodies were diagnosed, resulting negative in all cases and the most frequent tumor was lung cancer (30.8%). PNS-Care-Score was of 6-7 in 2/7 (probable PNS) and in no case the PNS-Care-Score was ≥8 (definite PNS). The mean DLP for all the scans was 2798 ± 952 mGy cm (average estimated ED of 42 ± 14 mSv). The total estimated time requested for all scans was 11,060 min. CONCLUSION: If a PNS is suspected, we encourage the prescription of unenhanced chest CT and/or abdomen/testis/female pelvis ultrasound and/or mammography based on clinical picture. The WB-CT using a single portal phase would be appropriate as a second-line technique while magnetic resonance imaging might be indicated for the exclusion of nervous system diseases. IMPLICATIONS FOR PRACTICE: Our suggestion results in saving in terms of radiation exposure, financial resources and time.

Somatosensory input in the context of transcranial magnetic stimulation coupled with electroencephalography: An evidence-based overview.

The transcranial evoked potential (TEP) is a powerful technique to investigate brain dynamics, but some methodological issues limit its interpretation. A possible contamination of the TEP by electroencephalographic (EEG) responses evoked by the somatosensory input generated by transcranial magnetic stimulation (TMS) has been postulated; nonetheless, a characterization of these responses is lacking. The aim of this work was to review current evidence about possible somatosensory evoked potentials (SEP) induced by sources of somatosensory input in the craniofacial region. Among these, only contraction of craniofacial muscle and stimulation of free cutaneous nerve endings may be able to induce EEG responses, but direct evidence is lacking due to experimental difficulties in isolating these inputs. Notably, EEG evoked activity in this context is represented by a N100/P200 complex, reflecting a saliency-related multimodal response, rather than specific activation of the primary somatosensory cortex. Strategies to minimize or remove these responses by EEG processing still yield uncertain results; therefore, data inspection is of paramount importance to judge a possible contamination of the TEP by multimodal potentials caused by somatosensory input.

Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation.

Transcranial direct current stimulation (tDCS) can produce a lasting polarity-specific modulation of cortical excitability in the brain, and it is increasingly used in experimental and clinical settings. Recent studies suggest that the after-effects of tDCS are related to molecular mechanisms of activity-dependent synaptic plasticity. Here we investigated the effect of DCS on the induction of one of the most studied N-methyl-d-aspartate receptor-dependent forms of long-term potentiation (LTP) of synaptic activity at CA3-CA1 synapses in the hippocampus. We show that DCS applied to rat brain slices determines a modulation of LTP that is increased by anodal and reduced by cathodal DCS. Immediate early genes, such as c-fos and zif268 (egr1/NGFI-A/krox24), are rapidly induced following neuronal activation, and a specific role of zif268 in the induction and maintenance of LTP has been demonstrated. We found that both anodal and cathodal DCS produce a marked subregion-specific increase in the expression of zif268 protein in the cornus ammonis (CA) region, whereas the same protocols of stimulation produce a less pronounced increase in c-fos protein expression in the CA and in dentate gyrus regions of the hippocampus. Brain-derived neurotrophic factor expression was also investigated, and it was found to be reduced in cathodal-stimulated slices. The present data demonstrate that it is possible to modulate LTP by using DCS and provide the rationale for the use of DCS in neurological diseases to promote the adaptive and suppress the maladaptive forms of brain plasticity.

The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex.

Weak cathodal transcranial direct current stimulation (tDCS) of the human hand area modulates corticospinal excitability with a suppression of motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). The changes in excitability persist beyond the time of stimulation if tDCS is given for several minutes and can remain stable for an hour or more. The aim of present study was to evaluate whether a long-lasting suppression of cortical excitability could be induced by prolonged cathodal tDCS (20 min of stimulation). We also explored the impact of brain-derived neurotrophic factor (BDNF) gene polymorphisms, on tDCS after-effects. Cortical excitability to single and paired-pulse TMS was evaluated both for the stimulated and contralateral hemisphere, before and up to 24 h after 20 min of cathodal tDCS. We evaluated threshold and amplitude of MEPs, short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). tDCS produced a pronounced suppression of MEP amplitude that was still significant at 3 h after the end of stimulation. The BDNF genotype had not influence on tDCS after-effects. Thresholds for MEPs, SICI and ICF were not affected. No significant effect was observed in the contralateral hemisphere. Twenty minutes of cathodal tDCS is capable of inducing a long-lasting suppression of the excitability of the human motor cortex.

EEG spectral exponent as a synthetic index for the longitudinal assessment of stroke recovery.

OBJECTIVE: Quantitative Electroencephalography (qEEG) can capture changes in brain activity following stroke. qEEG metrics traditionally focus on oscillatory activity, however recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. We assessed neurophysiological alterations and recovery after mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD). METHODS: Eighteen patients (n = 18) with mild to moderate mono-hemispheric Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n = 16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients. RESULTS: At T0, stroke patients showed significantly more negative SE values than HC (p = 0.003), reflecting broad-band EEG slowing. Most important, in patients SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1. This SE renormalization significantly correlated with National Institute of Health Stroke Scale (NIHSS) improvement (R = 0.63, p = 0.005). CONCLUSIONS: SE is a reliable readout of the neurophysiological and clinical alterations occurring after an ischaemic cortical lesion. SIGNIFICANCE: SE promise to be a robust method to monitor and predict patients' functional outcome.

Vagal nerve stimulation cycles alter EEG connectivity in drug-resistant epileptic patients: A study with graph theory metrics.

OBJECTIVE: Vagal Nerve Stimulation (VNS) is an effective treatment for Drug-Resistant (DR) epilepsy. Albeit the corroborated effectiveness of VNS, little is known about how VNS works. We aim to leverage quantitative Electroencephalography (qEEG) to study how the brain responds to VNS cycles. METHODS: Eighteen subjects with DR epilepsy were enrolled in our study. 64-channel EEG was recorded during VNS stimulation. Periods of stimulation (VNS), preceding (preVNS) and following stimulation (postVNS) were identified via an electrode placed on the stimulator. We used qEEG analysis to assess changes in spectral and network activity that characterize these conditions. Graph theory metrics were used to calculate differences in network connectivity. RESULTS: No differences were found in spectral activity between preVNS, VNS, and postVNS. Graph theory showed consistent changes in network organization expressed by Small World Index (SWI), Betweenness Centrality (BtwC), and Global Efficiency (gE). These changes were most significant in the slow EEG bands. CONCLUSIONS: In DR epilepsy, VNS has a significant effect on brain network activity, as assessed by EEG connectivity, acting on widespread network distribution rather than band-power. SIGNIFICANCE: Our findings support the hypothesis that VNS acts on epilepsy by influencing diffuse network connectivity in the brain.

Modulation of motor cortex neuronal networks by rTMS: comparison of local and remote effects of six different protocols of stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human motor cortex can produce long-lasting changes in the excitability of excitatory and inhibitory neuronal networks. The effects of rTMS depend critically on stimulus frequency. The aim of our present study was to compare the effects of different rTMS protocols. We compared the aftereffects of 6 different rTMS protocols [paired associative stimulation at interstimulus intervals of 25 (PAS(25)) and 10 ms (PAS(10)); theta burst stimulation delivered as continuous (cTBS) or intermittent delivery pattern (iTBS); 1- and 5-Hz rTMS] on the excitability of stimulated and contralateral motor cortex in 10 healthy subjects. A pronounced increase of cortical excitability, evaluated by measuring the amplitude of motor evoked potentials (MEPs), was produced by iTBS (+56%) and PAS(25) (+45%). Five-hertz rTMS did not produce a significant increase of MEPs. A pronounced decrease of cortical excitability was produced by PAS(10) (-31%), cTBS (-29%), and 1-Hz rTMS (-20%). Short-interval intracortical inhibition was suppressed by PAS(10). Cortical silent period duration was increased by 1-Hz stimulation. No significant effect was observed in the contralateral hemisphere. Head-to-head comparison of the different protocols enabled us to identify the most effective paradigms for modulating the excitatory and inhibitory circuits activated by TMS.

Neurophysiological evaluation of the pedunculopontine nucleus in humans.

The pedunculopontine nucleus (PPTg) is constituted by a heterogeneous cluster of neurons located in caudal mesencephalic tegmentum which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. It has been investigated as potential deep brain stimulation (DBS) target for treating Parkinson's disease (PD) symptoms. Neurophysiological studies conducted in humans using DBS electrodes for exploring functional properties of PPTg in vivo, reviewed in this paper, demonstrated that the functional connections between PPTg and cortex, basal ganglia, brainstem network involved in sleep/wake control, and spinal cord can be explored in vivo and provided useful insights about the physiology of this nucleus and pathophysiology of PD.

Contrast transoesophageal echocardiography remains superior to contrast-enhanced cardiac magnetic resonance imaging for the diagnosis of patent foramen ovale.

AIMS: In 30-40% of patients with acute ischaemic stroke, the cause remains undefined (cryptogenic stroke). Contrast transoesophageal echocardiography (TEE) is considered the gold standard for patent foramen ovale (PFO) detection. Recently, however, cardiac magnetic resonance (CMR) has also been applied to detect PFO. In this study, we compared the diagnostic value of CMR and TEE in detecting PFO in a group of patients with apparently cryptogenic stroke. METHODS AND RESULTS: Twenty-five patients (age 50 ± 13 years, 16 males) with apparently cryptogenic ischaemic stroke underwent contrast-enhanced TEE and contrast CMR for detection of possible PFO. Both imaging studies were performed during Valsalva manoeuvre. PFO grading results were assessed visually both for TEE and for CMR, according to the entity of contrast passage in the left atrium (grade 0 = no PFO; grades 1, 2, and 3 = mild, medium, and wide PFO, respectively). TEE detected PFO in 16 patients (64%). Contrast-enhanced CMR identified a PFO in 7 (44%) of these patients. TEE showed a grade 1 PFO in five patients, a grade 2 PFO in eight patients, and a grade 3 PFO in three patients. Of these patients, CMR failed to identify PFO in all five patients with a grade 1 PFO, in one patient with a grade 2 PFO, and one patient with grade 3 PFO according to TEE. None of the nine patients without PFO at TEE was shown to have a PFO at CMR. When compared with TEE, the present methodology of CMR had a sensitivity of 50%, specificity of 100%, negative predictive value of 31%, and a positive predictive value of 100%. CONCLUSION: Our data suggest that TEE is the cornerstone imaging diagnostic test to detect and characterize PFO in patients with ischaemic stroke, and is shown to be better compared with the current CMR sequences.

Enhanced human brain associative plasticity in Costello syndrome.

Costello syndrome (CS) is a rare multiple congenital anomaly disorder which is caused by germline mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homologue (HRAS) proto-oncogene. Experimental data suggest perturbing effects of the mutated protein on the functional and structural organization of networks of cerebral cortex and on the activity-dependent strengthening of synaptic transmission known as long term potentiation (LTP). In five patients with molecularly proven diagnosis of CS and in a group of 13 age-matched control subjects we investigated activity-dependent synaptic plasticity. To this end, we used a paired associative stimulation (PAS) protocol, in which left ulnar nerve stimuli were followed by transcranial magnetic stimulation (TMS) pulses to right cortical hand area, and recorded motor evoked potentials (MEPs) by single pulse TMS from left first dorsal interosseus (FDI) muscle before and after PAS. In 4 out of 5 CS patients and in a subgroup of nine control subjects we also evaluated the time course and the topographical specificity of PAS after-effects. In these two subgroups, MEPs were measured before, immediately after and 30 min after PAS in the left FDI and left abductor pollicis brevis (APB). While the PAS protocol led to a 65% increase of the FDI MEP amplitude in controls, the LTP-like phenomenon was significantly more pronounced in CS patients, with motor responses increased by 230%. In addition, CS patients showed a similar MEP increase in both muscles while control subjects showed a slight increase in APB and only immediately after PAS. We hypothesize that the extremely enhanced PAS after-effects could be due to the influence of HRAS activity on the susceptibility of synapses to undergo LTP.

Associative motor cortex plasticity: direct evidence in humans.

Previous studies have shown that paired associative stimulation (PAS) protocol, in which peripheral nerve stimuli are followed by transcranial magnetic stimulation (TMS) of the motor cortex at intervals that produce an approximately synchronous activation of cortical networks, enhances the amplitude of motor evoked potentials (MEPs) evoked by cortical stimulation. Indirect data support the hypothesis that the enhancement of MEPs produced by PAS involves long-term potentiation like changes in cortical synapses. The aim of present paper was to investigate the central nervous system level at which PAS produces its effects. We recorded corticospinal descending volleys evoked by single pulse TMS of the motor cortex before and after PAS in 4 conscious subjects who had an electrode implanted in the cervical epidural space for the control of pain. The descending volleys evoked by TMS represent postsynaptic activity of corticospinal neurones that can provide indirect information about the effectiveness of synaptic inputs to these neurones. PAS significantly enhanced the amplitude of later descending waves, whereas the earliest descending wave was not significantly modified by PAS. The present results show that PAS may increase the amplitude of later corticospinal volleys, consistent with a cortical origin of the effect of PAS.

Standardizing the intensity of upper limb treatment in rehabilitation medicine.

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.

Does exposure to extremely low frequency magnetic fields produce functional changes in human brain?

Behavioral and neurophysiological changes have been reported after exposure to extremely low frequency magnetic fields (ELF-MF) both in animals and in humans. The physiological bases of these effects are still poorly understood. In vitro studies analyzed the effect of ELF-MF applied in pulsed mode (PEMFs) on neuronal cultures showing an increase in excitatory neurotransmission. Using transcranial brain stimulation, we studied noninvasively the effect of PEMFs on several measures of cortical excitability in 22 healthy volunteers, in 14 of the subjects we also evaluated the effects of sham field exposure. After 45 min of PEMF exposure, intracortical facilitation produced by paired pulse brain stimulation was significantly enhanced with an increase of about 20%, while other parameters of cortical excitability remained unchanged. Sham field exposure produced no effects. The increase in paired-pulse facilitation, a physiological parameter related to cortical glutamatergic activity, suggests that PEMFs exposure may produce an enhancement in cortical excitatory neurotransmission. This study suggests that PEMFs may produce functional changes in human brain.