Francesca Sperli

EEG source imaging in pediatric epilepsy surgery: a new perspective in presurgical workup.

Summary:  Purpose: Epilepsy is a relatively frequent disease in children, with considerable impact on cognitive and social life. Successful epilepsy surgery depends on unambiguous focus identification and requires a comprehensive presurgical workup, including several neuroimaging techniques [magnetic resonance imaging, positron emission tomography (PET), and single‐photon emission computed tomography (SPECT)]. These may be difficult to apply in younger or developmentally delayed children or both, requiring sedation, and hence, a significant workforce. Modern electric source imaging (ESI) provides accurate epileptic source‐localization information in most patients, with minimal patient discomfort or need for cooperation. The purpose of the present study was to determine the usefulness of ESI in pediatric EEG recordings performed with routine electrode arrays.

Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis.

Background Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. Methodology We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26). Principal Findings Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to “normal” already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month. Conclusions Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies.

Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer's disease: a correlative study

OBJECTIVE To investigate the relationship between the electroencephalographic (EEG) power spectra features obtained by quantitative EEG (qEEG) and the hemodynamic parameters detected by dynamic susceptibility contrast-enhanced MR imaging (DSC MRI) in patients with Alzheimers disease (AD). METHODS Fourteen patients with probable AD and 15 elderly healthy controls were included in the study. All subjects underwent both EEG recording in a rest condition and perfusion MRI. Three EEG scalp areas were defined (anterior, central and posterior) and power spectra values were obtained from each scalp area. Relative values of temporoparietal and sensorimotor regional cerebral blood volume (rCBV) were measured bilaterally and successively averaged to obtain a total perfusion index. The brain atrophy index was calculated and used as a covariate to rCBV. Correlation analysis was performed between EEG variables and hemodynamic-morphological parameters. RESULTS qEEG power spectra of AD patients were characterized by an increase in mean relative power of theta (4-7.75 Hz) associated with a decrease in alpha (8-12.75 Hz) frequency bands with a topographic distribution over the central and posterior EEG scalp regions, when compared with controls; beta (13-31 Hz) frequency band also displayed a significant decrease over the anterior and posterior EEG scalp regions of AD patients with respect to controls. The DSC MRI revealed a bilateral reduction in the temporoparietal and sensorimotor rCBV with respect to controls. Correlation analysis showed that the total level of hypoperfusion selectively correlates with the EEG power spectra in theta and alpha frequency bands distributed over anterior/central and central region, respectively. Within AD patients, the lower the level of hypoperfusion, the higher the content of EEG power spectra in theta frequency band, and the lower the level of hypoperfusion, the lower the content of EEG power spectra in alpha band. CONCLUSIONS The combined qEEG and DSC MRI technology unveiled a selective correlation between neurophysiological and hemodynamical patterns in AD patients. Further investigations will ascertain the relevance of this multi-modal approach in the heterogeneous clinical context of AD.

Contralateral Smile and Laughter, but No Mirth, Induced by Electrical Stimulation of the Cingulate Cortex

Summary:  The cerebral representation of laughter is dissociated. The emotional aspects seem to be processed in the temporal lobe; whereas the motor features apparently rely on the frontal cortex. In a few prior studies of patients in whom laughter was elicited by electrical stimulation (ES), it always was associated with mirth. We report a patient in whom ES in the right cingulate gyrus elicited smile and laughter, but no mirth. At low voltages, smiling was seen first contralaterally and became bilateral with increasing currents. Our observation supports the concept of the motor representation of laughter in the mesial frontal cortex.

Ketotic hyperglycemia and epilepsia partialis continua

Epilepsia partialis continua (EPC) may occur during nonketotic hyperglycemia but has not been described with diabetic ketoacidosis. The authors report a patient with EPC associated with ketotic hyperglycemia. Brain MRI showed two areas of abnormal signal intensity in the left precentral gyrus and in the right cerebellar hemisphere. Hyperglycemia may reduce seizure threshold because of the increase in γ-aminobutyric acid metabolism and may trigger epileptic discharges.

Topiramate: effect on EEG interictal abnormalities and background activity in patients affected by focal epilepsy

PURPOSE To evaluate the effects of topiramate (TPM) on interictal epileptiform abnormalities (IEA) and background activity by means of a computerized EEG analysis, in adult patients affected by focal epilepsy, with or without secondarily generalization, treated with TPM as adjunctive therapy or monotherapy. METHODS Twenty-four patients affected by symptomatic or cryptogenic focal epilepsy underwent long-term video-EEG recording before and after TPM addition (mean dose 175+/-25 mg per day). RESULTS TPM addition induced a significant reduction of both partial and secondarily generalized tonic-clonic (SGTC) seizures; treatment responder patients (seizure reduction > or = 50%) were 19 out of 24 patients (79.1%), of whom 5 were seizure-free. Quantitative analysis of IEA showed a significant decrease in the mean number of spikes/10 min during TPM therapy ( 4.2+/-4.2 versus 2.2+/-4.4; P<0.003 ). The analysis of spatial distribution of interictal spikes showed that such reduction was more evident at the level of the epileptogenic area rather than on the spreading component. Statistical analysis revealed only a significant decrease of mean relative power of alpha band in the EEG spectral content, recorded at rest in a group of 18 out of 24 epileptic patients during TPM therapy. In addition, during TPM treatment we observed a significant reduction in alpha reactivity without any important changes of alpha indexes (peak frequency and median frequency). CONCLUSION These findings suggest that TPM has a strong inhibitory effect on IEA, probably acting on the generating processes, and, if used at low dosage and gradually titrated, seems to have only mild interferences with EEG background activity.

Psychiatric Comorbidity in Patients Evaluated for Chronic Epilepsy: A Differential Role of the Right Hemisphere?

Introduction: Psychiatric disorders are known to occur frequently in chronic epilepsy. The aim of this study is to investigate the prevalence of psychiatric comorbidity and its relationship to regional cerebral dysfunction in patients admitted to a tertiary epilepsy center for epilepsy surgery. Methods: 217 patients were investigated. A presurgical workup was performed and allowed precise localization of the epileptogenic focus in 156 patients. Sixty-one patients had multifocal or generalized discharges. After 1–3 psychiatric interviews, a psychiatric diagnosis was made (DSM-IV classification). Results: Psychiatric comorbidity was found in 85 patients (39%), more often in those with right or bilateral hemispheric dysfunction (74%, p = 0.04) with no difference between temporal or extratemporal foci location frequency. Additionally, patients with psychiatric disorders were less likely to undergo epilepsy surgery compared to ‘epilepsy-only’ patients (p = 0.003), despite similar good outcome in patients with and without psychiatric comorbidity. Conclusions: Right-sided or bilateral foci seem to represent a risk factor for psychiatric comorbidity in epilepsy, although we did not find any particular association between a psychiatric syndrome and focus localization. Recognition and treatment of psychiatric comorbidity is of major importance since its presence may interfere with patient’s decision making for epilepsy surgery treatment.

No impact of current therapeutic strategies on disease reactivation after natalizumab discontinuation: a comparative analysis of different approaches during the first year of natalizumab discontinuation.

Natalizumab discontinuation induces the recurrence of multiple sclerosis disease activity: currently no therapeutic approach has been found able to abolish disease reactivation.

A methodological reappraisal of non invasive high voltage electrical stimulation of lumbosacral nerve roots.

OBJECTIVE To describe a neurophysiological method to locate the optimal stimulation site (OSS) over the vertebral column, customized to the individual subject, to achieve maximal activation of lumbosacral roots by means of non-invasive high voltage electrical stimulation (HVES). METHODS OSS was located in 30 volunteers by testing different stimulation points of a surface multi-electrode array placed over the dorso-lumbar junction of the vertebral column. The dorso-ventral stimulating montage was used (Troni et al., 1996). Motor responses to root stimulation (rCMAPs) were bilaterally recorded from Vastus Medialis (VM), Tibialis Anterior (TA), Soleus (SL) and Flexor Hallucis Brevis (FHB) muscles. The direct nature of rCMAPs was tested by delivering two maximal stimuli 50 ms apart. RESULTS Except for a few subjects with large girth, maximal rCMAPs could be obtained from all muscles with a stimulating current intensity up to 550 V (1050 mA). Maximal double HVES excluded any reflex component in the recorded rCMAPs. The procedure was well tolerated and no side effects were observed. CONCLUSIONS A single maximal electric shock delivered at the proper vertebral level by means of the dorso-ventral montage is able to safely achieve synchronous, bilateral maximal activation of several roots, from L3 to S1. SIGNIFICANCE Maximal activation of lumbosacral roots at their origin, unattainable with magnetic stimulation, is the essential requirement for direct detection of proximal nerve conduction slowing and block in lower limbs.

Sleep-wake cycle and effects of cabergoline monotherapy in de novo Parkinson's disease patients - An ambulatory polysomnographic study

ObjectiveTo investigatethe sleep-wake cycle and theeffects of cabergoline monotherapyin a homogenous group of de novoParkinson’s Disease (PD) patientswithout confounding comorbidfactors.Design and participantsTwelve de novo patients affected byidiopathic PD underwent twoambulatory polysomnographic (APSG)monitoring sessions. The firstwas performed at baseline, and thesecond recording one-month afterstable treatment with cabergolinemonotherapy. Subjective daytimesleepiness was evaluated by meansof the Epworth Sleepiness Scale.Data obtained in PD patients atbaseline were compared with thoseobtained in 12 age- and sexmatchedhealthy subjects.ResultsDiurnal sleep parameters did notshow significant differencesbetween controls and PD patientsat baseline. In PD patients, nosignificant changes in diurnal sleepwere observed between baselineand cabergoline treatment. Regardingnocturnal sleep, patients atbaseline showed a significantlylower sleep efficiency and a significantlyhigher Wakefulness AfterSleep Onset than controls. Withrespect to baseline, a significantincrease in REM latency and asignificant reduction in REM sleepwere observed during cabergolinetreatment.ConclusionsIn the earlystage of PD, the neurodegenerativeprocess does not seem to be directlyresponsible for daytimesomnolence, but it may be directlyinvolved in the alteration of nocturnalsleep. Cabergoline monotherapydoes not affect daytimesleep propensity and, despite clinicalimprovement, it may have negativeeffects on REM sleep.