EEG Resting-State Functional Networks in Amnestic Mild Cognitive Impairment.

Background. Alzheimer's cognitive-behavioral syndrome is the result of impaired connectivity between nerve cells, due to misfolded proteins, which accumulate and disrupt specific brain networks. Electroencephalography, because of its excellent temporal resolution, is an optimal approach for assessing the communication between functionally related brain regions. Objective. To detect and compare EEG resting-state networks (RSNs) in patients with amnesic mild cognitive impairment (aMCI), and healthy elderly (HE). Methods. We recruited 125 aMCI patients and 70 healthy elderly subjects. One hundred and twenty seconds of artifact-free EEG data were selected and compared between patients with aMCI and HE. We applied standard low-resolution brain electromagnetic tomography (sLORETA)-independent component analysis (ICA) to assess resting-state networks. Each network consisted of a set of images, one for each frequency (delta, theta, alpha1/2, beta1/2). Results. The functional ICA analysis revealed 17 networks common to groups. The statistical procedure demonstrated that aMCI used some networks differently than HE. The most relevant findings were as follows. Amnesic-MCI had: i) increased delta/beta activity in the superior frontal gyrus and decreased alpha1 activity in the paracentral lobule (ie, default mode network); ii) greater delta/theta/alpha/beta in the superior frontal gyrus (i.e, attention network); iii) lower alpha in the left superior parietal lobe, as well as a lower delta/theta and beta, respectively in post-central, and in superior frontal gyrus(ie, attention network). Conclusions. Our study confirms sLORETA-ICA method is effective in detecting functional resting-state networks, as well as between-groups connectivity differences. The findings provide support to the Alzheimer's network disconnection hypothesis.

Robot-assisted adrenalectomy: a technical option for the surgeon?

BACKGROUND: The robotic approach is an interesting option for overcoming the limitations of laparoscopic adrenalectomy. We aimed to report our technique and outcomes of robot-assisted adrenalectomy (RAA). METHODS: From November 2000 to February 2010, all consecutive patients who underwent a RAA by the same surgeon were prospectively entered into a dedicated database. The data were reviewed retrospectively. RESULTS: During the study period, 21 right (50%), 20 left (47.6%) and 1 bilateral (2.4%) RAA were performed. Mean lesion size was 5.5 cm (max. 10 cm). Mean operative time was 118 ± 46 min and median blood loss was 27 ml. There were no conversions. The postoperative morbidity rate was 2.4%; mortality rate, 2.4%; median hospital stay, 4 days. CONCLUSIONS: RAA achieves good short-term outcomes and could be considered a valid option for the treatment of adrenal masses, with the potential to expand the limits of minimally invasive surgery.

Auditory event-related potentials in subcortical vascular cognitive impairment and in Alzheimer's disease.

BACKGROUND: Few studies exist on ERPs and patients with subcortical vascular cognitive impairment (SVCI). This latter is a quite homogeneous subtype of vascular dementia whose cognitive profile is quite different from that of Alzheimer disease (AD). AIMS: The present study aims at comparing the ERPs profile both in patients with SVCI and in patients with AD. SUBJECTS AND METHODS: ERPs and psychometric tests were collected from 39 healthy elderly controls, 51 patients with SVCI and 43 patients with AD. Subjects mentally count high pitched target tones that were randomly intermixed with low pitched frequent tones. We measured ERPs latencies (N1, P2, N2 and P3), and interpeak latencies (N1-P3, N1-P2, N1-N2). RESULTS: Grand averaged potentials in SVCI showed a significant increase of P3 latency. AD patients showed a prolongation of N1, P2, N2, P3 latencies. As far as interpeak latencies are concerned, SVCI patients showed a significant prolongation of N1-P3, AD patients had a significant increase of N1-N2, and N1-P3 intervals. When all patients were considered as a single group, correlation of neuropsychological tests scores showed a significant negative relationship between P300 latency and, respectively, Mini Mental Status Examination, auditive and visual span forward. In both groups, ERPs latency sensitivity, was low, whilst specificity values were quite high. CONCLUSIONS: Our finding suggest that these two dementing diseases have different electrophysiologic features that may be related to their specific underlying pathogenetic mechanism; in particular, we hypothesise that, differently from AD, P300 latency prolongation characterizes the early stage of SVCI. So, this ERPs approach could be helpful to detect early alterations of the attentional/working-memory functions in patients with subcortical ischaemic vascular disease.

Gabapentin in the treatment of hemifacial spasm.

OBJECTIVES: To evaluate the efficacy of gabapentin in the treatment of hemifacial spasm. MATERIAL AND METHODS: Twenty-three patients with hemifacial spasm not suitable for surgery or therapy with botulinum toxin were treated with gabapentin. The main efficacy parameter was the percentage of spasm reduction. RESULTS: A clinically significant reduction of spasms was obtained by 16 patients. CONCLUSION: Gabapentin was effective and safe in reducing hemifacial spasm in 16 out 23 (69.6%) patients.

Auditory event-related potentials (P300) in epileptic patients.

Auditory event-related potentials (AERPs) were recorded during an auditory oddball paradigm in 108 epileptics and in 32 healthy controls. P300 latency varied in relationship with age only in controls. Symptomatic epileptics had significantly prolonged P300 mean latency compared to those without detectable brain lesion(s) on MR scan. Moreover, these latter patients were compared on the basis of epilepsy duration, type of seizure, seizure frequency and antiepileptic treatment; the application of a multiple regression model showed a significant relationship between P300 latency prolongation and epilepsy duration, seizure frequency and polytherapy.

Multievoked potentials in type I diabetic patients: one year follow-up study.

A neurophysiological (SEP, VEP) follow-up study was carried out in 30 diabetic patients with type I diabetes mellitus of ten or more years duration. This in order to investigate whether one year of improved glucoregulation may influence the progression of central damage. In our series, patients showed a significant decrement of HbA1C levels (p < 0.05) in the one-year follow-up. In the same period the frequency of SEP and VEP abnormalities varied from 10/30 (33%) to 16/30 (53%) and from 8/30 (26%) to 5/30 (16%) respectively. This finding would suggest that prevailing glycaemic control would be a major determinant for the outcome of VEP measurements. SEP alterations, in contrast, tend to progress in a 12 months period despite a considerable improvement in glycaemic control. However, by dividing patients in two groups according mean one year HbA1C less than 8% and more than 8%, the latter group only showed a significant increasing of absolute latencies of each median and tibial SEP components. Our results suggest that VEP abnormalities are still reversible in diabetic patients with improved metabolic control. The acquired abnormalities of somatosensory pathways persist longer, but a strict glycaemic control may influence and retard the progression of central conduction involvement.

Evoked potential study and radiological findings in patients with systemic lupus erythematosus.

We performed clinical, radiological (MRI) and neurophysiological (NCV, SEPs, and BAEPs) investigations in 36 unselected patients affected by Systemic Lupus Erythematosus (SLE). Fifteen patients (42%) presented clear neurological events and were considered as definite neuropsychiatric lupus (NPLE); 21 (58%) presented minor subjective complaints or no neurological problems referable to SLE and were considered as no-NPLE. Twenty-three patients (64%) showed neurophysiological abnormalities: 21 (58%) presented central abnormal neurophysiological measurements (including SEP and BAEP values), while 17 (47%) has slowed peripheral nerve conduction. Twenty-six out of 36 patients executed brain MRI examination. High intensity spots (HIS) in deep or subcortical white matter were the most common abnormalities and were present in 19 of the 26 patients (73%). We found that the incidence of neurophysiological and radiological abnormalities did not significantly differ in neurologically symptomatic and asymptomatic patients. Central nervous system impairment evidenced by abnormal N13-20 interpeak intervals (p = 0.05) and HIS (p = 0.01) findings was significantly associated with the presence of cutaneous vasculitis; while peripheral nerve involvement was significantly more frequent in patients with renal failure (p = 0.006).

Pancreatic cancer and tumor markers: role of the newly identified CAR-3 antigen.

BACKGROUND AND AIM: The aim of this study is to assess the clinical usefulness of the serum assay for CAR-3 in the diagnosis and follow-up of pancreatic cancer. MATERIALS AND METHODS: Serum levels of tumor markers (CAR-3, Ca 19.9, Ca 195 and CEA) were measured in a total of 238 patients with various diseases of the gastrointestinal (GI) tract, including 61 pancreatic cancers. Cut-off levels were calculated on the basis of a non-parametric estimate of 90% specificity. After surgery, patients with pancreatic cancer underwent a combined serological and radiological (CT-scan) follow-up. RESULTS: At the cut-off level of 6.15 U/L, the sensitivity of CAR-3 was 62.3% (CA 19.9: 77%; Ca 195: 75.4%; CEA: 24.5%). In the differential diagnosis between pancreatic cancer and other GI diseases, significant differences were found. No association was discovered either between serum level of tumor markers and tumor stage or between short- and long-term survivors. In the follow-up, CT-scan was superior to serologic tests (sensitivity: 94.2%). Among tumor markers, CAR-3 achieved a sensitivity of 62.5% (Ca 19.9: 83.3%; Ca 195: 75%). DISCUSSION: CAR-3 is shed in the circulating stream in a much lower proportion of cases than that observed for antigen expression at immunohistochemistry. During the follow-up CT-scan was the most accurate diagnostic tool. However, the meagre therapeutical options for recurrent pancreatic cancer, do not justify such an aggressive follow-up. CONCLUSIONS: Ca 19.9 remains the tumor marker of choice for either the pre-operative work-up or the post-surgical follow-up of patients with pancreatic cancer.

Electrophysiological and iontophoretic aspects of the habenular influence on hippocampal neurones.

In previous experimental studies, carried out on cats, we demonstrated that electrical stimulation of lateral habenula (LH) at 0.5-3.0 Hz or 5-20 Hz had a double effect (low frequency-excitation; high frequency-inhibition) on the spontaneous firing rate of single hippocampal neurones. Our results, in agreement with similar case studies, allowed us to hypothesise that in the habenular modulation of the hippocampus the raphe nucleus is probably involved. In fact, all the effects of LH stimulation were antagonised by the iontophoretic intrahippocampal application of methysergide. In the present series of experiments, performed on rats, it was possible to demonstrate that LH stimulation at 1-10 Hz causes an excitation of a progressively major number of hippocampal neurones depending upon the increase of frequency stimulation. The absence of habenulo-induced effects after a iontophoretic application of methysergide on single hippocampal units suggests the involvement of the raphe nucleus. Furthermore, in consideration of recent anatomical evidences demonstrating an excitatory projection between LH and raphe nucleus, intraraphal N-methyl-D-aspartate (NMDA) application, performed through a Hamilton microsyringe, induces an inhibitory effect. All the results suggest that in the raphe context it is possible to hypothesise the presence of an intrinsic interneurone, directly activated by the excitatory projection arising from the LH; this interneurone is likely inhibitory on the serotonergic raphe-hippocampus efferent neurone. This functional organization is responsible for the effect of LH stimulation at different frequencies as well as for the effects of intraraphal NMDA application.

Anticonvulsant activity of the noradrenergic locus coeruleus system: role of beta mediation.

Many experimental observations have demonstrated the modulatory role exerted by several neural structures and neurotransmitters on spontaneous and paroxysmal bioelectric activity of the hippocampus. Recently, the control exerted by locus coeruleus (LC) and its noradrenergic (NA) efferent pathway on different experimental models of epilepsy (e.g. cortical cobalt chronic epilepsy, amygdaloid and hippocampal kindling) was emphasised. On this basis, a series of experiments was performed to elucidate the functional role of LC-NA system on the hippocampal penicillin (PCN) focus and the type of adrenergic receptor involved. The experiments were carried out on 25 rats in which an epileptiform hippocampal focus was obtained through intrahippocampal PCN administration (100-200 I.U.). In these conditions, LC, ipsilateral to PCN hippocampal focus, was stimulated before and after intraperitoneal (i.p.) administration of a beta-adrenergic receptor antagonist propranolol (2 mg/kg). Results showed a significant reduction of hippocampal spiking frequency during LC stimulation; after i.p. propranolol injection, LC stimulation, at the same parameters, failed to induce any sort of modification of PCN hippocampal spiking frequency. Furthermore, intrahippocampal application of a beta-selective agonist 2-fluoro-noradrenaline (2-FNA) mimics the inhibitory effects of LC stimulation. All data suggest that the LC-NA system is able to induce a net reduction of hippocampal epileptiform focus and the inhibitory NA control involves the activation of adrenergic beta receptors.

Bilateral reciprocal organisation in man: focus on IA interneurone.

The H reflex of flexor carpi radialis and radial-induced reciprocal inhibition were recorded in normal subjects during conditioning stimulation of the contralateral median or radial nerves. It was found that stimulation of the contralateral median nerve enhanced the degree of reciprocal inhibition exerted by the radial nerve on the median nerve, while contralateral radial nerve stimulation reduced the reciprocal inhibition exerted by the extensor on the flexor. In two subjects in which a pure extensor H reflex was recorded specular features were observed following contralateral median and radial stimulation. These findings are considered to be the electrophysiological manifestation of contralateral modulation of reciprocal inhibition, which is likely to act at the level of the IA interneurone.

Accumbens-caudate-septal circuit as a system for hippocampal regulation: involvement of a GABAergic neurotransmission.

Hippocampal-based epileptiform activity may reach the basal ganglia via the nucleus accumbens. Previous data suggested that caudate nucleus is able to influence hippocampal epilepsy, probably sending a projection to the septum. In order to test the hypothesis of a retrograde activation of accumbens-caudate pathway in hippocampal regulation, we electrically stimulated both caudate nucleus and nucleus accumbens and studied modifications of hippocampal EEG in the feline focal epilepsy model. We also performed bilateral electrolytic lesion of nucleus accumbens and repeated caudate stimulation. Results showed that nucleus accumbens stimulation was ineffective in modifying hippocampal epilepsy; on the contrary, caudate stimulation caused a statistically significant decrease of hippocampal spike frequency and amplitude. On the other hand, in accumbens-lesioned animals caudate activation consistently reduced hippocampal epilepsy to a significant degree. As the caudate nucleus influences hippocampal activity and the septum may constitute a relay station of this functional relation, a possibility was tested concerning a GABAergic mediation. To this end, after a stable caudate-induced effect was reached, an intraseptal microinjection of picrotoxin (GABA receptor antagonist) was made and caudate stimulation repeated at the same parameters. Such a study showed that after intraseptal picrotoxin, caudate stimulation failed to elicit any type of modification of hippocampal activity. Experimental findings support the notion that the striatal modulation on hippocampus is mediated by an anterograde rather than a retrograde pathway, and underline the possibility of a GABAergic caudate-septal influence.

Evidence of a contralateral motor influence on reciprocal inhibition in man.

The role of contralateral movement on both H reflex and reciprocal inhibition was studied. In normal men H reflex was induced by median nerve stimulation. Reciprocal inhibition was achieved through stimulation of the antagonist radial nerve. On this basis the effects of contralateral arm movement were analyzed. Furthermore the putative influence of exteroceptive origin was also verified by means of digit stimulation. Results showed that contralateral arm movement did not affect H reflex amplitude; on the contrary, it was able to enhance reciprocal inhibition induced by extensors on flexors. Study of cutaneous afferents demonstrated that contralateral digit stimulation failed to elicit modifications on both H reflex and reciprocal inhibition. On the other hand, ipsilateral digit stimulation lowered H reflex amplitude and increased the degree of reciprocal inhibition. Experimental findings underline the possibility that an informational array reaches the contralateral IA interneuron: therefore a mutual (bilateral) interaction among IA interneurones may accordingly be hypothesised.

Electrophysiological and microiontophoretic analysis of the habenulo-hippocampal circuit.

In the cat, the effects of lateral habenula stimulation, at different ranges of frequency, on hippocampal units were studied. Habenular stimulation at low frequency excited, while at high frequency inhibited the greater part of hippocampal units. Moreover, in order to clarify the possible pathway involved in the habenulo-hippocampal circuit, the effects of iontophoretic acetylcholine and serotonin on hippocampal units were compared with those of habenular stimulation. Iontophoretic acetylcholine induced both excitatory and inhibitory responses while serotonin induced only inhibitory responses. Iontophoretic atropine blocked the effects of acetylcholine ejection but did not antagonize stimulation effects; ion-tophoretic methysergide induced an increase of basal firing of hippocampal units and antagonized both serotonin and habenular stimulation inhibition. The results suggest an influence of lateral habenula to the hippocampus which does not appear to be cholinergically-mediated. A possible involvement of the raphe as a relay station in the habenulo-hippocampal pathway is discussed.

Dopaminergic control of feline hippocampal epilepsy: a nigro hippocampal pathway.

Substantia nigra is a mesencephalic structure inserted along several circuits which appear to play a key role in epilepsy. In previous researches we postulated that substantia nigra pars compacta (SNpc) may be the site of a precise control of hippocampal epilepsy while substantia nigra pars reticulata (SNpr) may exert a modulation of both neocortical epilepsy and spreading of hyperactivity toward a motor target. In order to better understand mechanisms subserving nigral action in feline hippocampal epilepsy we electrically stimulated SNpc (dopaminergic), before and after sulpiride (dopamine receptor-antagonist) intravenous injection. Furthermore we compared hippocampal epileptiform activity prior to and after apomorphine (dopamine receptor-agonist) intrahippocampal injection as well as prior to and after SNpc electrolytic destruction. Results showed that SNpc is able to regulate hippocampal epilepsy. This effect is selectively antagonized by sulpiride while apomorphine exerts, synergically with SNpc stimulation, inhibitory effects. On the contrary SNpc lesions induces a significant enhancement of hippocampal epileptiform spikes. Experimental findings suggest that SNpc represents a strategic region for the control of hippocampal excitability and that this regulation appears to be dopaminergic in nature.

A feature of caudate control of focal hippocampal epilepsy: evidence for an anterograde pathway.

Previous experimental evidences showed that the caudate nucleus has a modulatory effect on hippocampal epilepsy. The caudate's regulating action might reach the hippocampus either via the septal region or, retrogradely, via the accumbens nucleus. In order to obtain new data about the pathway involved in caudate hippocampal influence the spreading of abnormal activity towards the nucleus accumbens was studied. Furthermore the effects of caudate stimulation in animals with electrolytic lesions of the nucleus accumbens were analyzed. It was observed that abnormal penicillin-induced activity spreaded from the hippocampus to the nucleus accumbens in about 30 minutes. In animals with and without lesions of nucleus accumbens, caudate stimulation brought about a significant decrease in the frequency and amplitude of hippocampal activity. The results suggest that the nucleus accumbens is reached by the spreading of hippocampal epilepsy but does not participate in the control exerted by the caudate nucleus on the hippocampus. Thus the caudate-induced inhibition takes place through an anterograde caudate-hippocampal circuit, while at the same time excluding retrograde activation by way of a caudate-accumbens-hippocampal pathway.

[Neurophysiologic study of the influence of the habenula on the hippocampus: electroencephalographic aspects]. / Studio neurofisiologico dell'influenza abenulare sull'ippocampo: aspetti elettroencefalografici.

The habenula, an epithalamic structure considered as a part of the limbic system, is able to control interictal activity of the hippocampus. Its influence seems to be facilitatory and to have the raphé as a relay station. Habenular action might putatively be ascribed to activation of the serotonergic system.