A pancreatic-like ribonuclease is synthesized in rat brain.

The distribution and cell localization of a pancreatic-like ribonuclease (RNAase) in the rat brain has been studied by RNA blot analysis and in situ hybridization using as a probe the cDNA coding for the rat pancreas RNAase, and by immunocytochemistry using an antiserum raised against the rat pancreas RNAase. RNA blot analysis and in situ hybridization experiments have shown that the RNAase mRNA is present in all the cerebral areas investigated and that neurons appeared to be actively expressing RNAase mRNA while glial cells were devoid of hybridization signals. In agreement with these results the immunocytochemical analysis has shown that neurons are specifically immunostained. These experiments demonstrate that a pancreatic-like ribonuclease is synthesized in the neurons of the rat brain.

Environmental stimuli modulate the circadian rhythm of [3H-methyl]thymidine incorporation into brain DNA of male rats.

A circadian rhythm of DNA synthesis is present in most organs of adult mammals, with peak levels (acrophase) generally in the rest period. We have recently reported that in the rat brain the acrophase of the rhythm of thymidine incorporation into DNA occurs on the contrary during the active period. To determine whether the brain waking activity was exerting a modulatory action we measured the circadian rhythm of incorporation in the brain and kidney of young adult male rats housed in conditions of sensory and social enrichment or impoverishment for four days. Biochemical and autoradiographic data show that the brain rhythm persists in the enriched condition, but is abolished in the impoverished condition. On the other hand, the rhythm of incorporation in the kidney is maintained in both conditions. These results suggest that the permanence of the brain oscillation is selectively dependent on the complexity of the sensory and social stimulation.

Gabapentin as add-on therapy in focal epilepsy: a computerized EEG study.

OBJECTIVES: Gabapentin (GBP) possesses a well documented clinical efficacy in those types of focal epilepsy otherwise resistant to conventional antiepileptic drugs (AEDs); on the basis of this, it appears important to investigate the drug effects on the EEG epileptiform and background activity. METHODS: Twenty-five patients with cryptogenic or symptomatic partial epilepsy resistant to conventional AED treatment were included in the study. All patients underwent long-term video-EEG recordings before and after GBP addition (900-1200 mg/day). RESULTS: Quantitative analysis of the interictal EEG paroxysms revealed that GBP had no effect on the rate of occurrence of interictal and ictal EEG abnormalities. GBP was active in delimiting the spatial extent of the interictal spiking activity in those patients who displayed a significant reduction (> or =50%) in seizure occurrence (32% of the patients). EEG background activity recorded under rest condition from 18 out of 25 epileptic patients, before GBP therapy, was characterised by a higher content of the slow spectral components (delta and theta) with respect to control subjects. After GBP addition, the increase of theta relative power was also evident during task performance. CONCLUSIONS: These findings suggest that GBP does not interfere with the generation of interictal EEG spiking while it appears to reduce the susceptibility to seizures concomitantly with a limiting effect on the spiking activity spatial extent. The utilization of GBP in controlling focal seizures is reinforced by the absence of negative influence on cognitive functioning.

Gabapentin-induced modulation of interictal epileptiform activity related to different vigilance levels.

OBJECTIVES: Gabapentin (GBP) is a novel antiepileptic drug (AED), currently used as add-on therapy in patients with partial seizures. Similar to other AEDs, little is known about its effects on nocturnal sleep, despite the strict relationship between sleep and epileptic discharges. The aim of our study was to evaluate the effects of chronic therapy with GBP on both nocturnal sleep and on interictal epileptiform abnormalities (IEA) in relation to the different sleep stages. METHODS: Eighteen patients affected by partial seizures resistant to common AEDs were submitted to nocturnal polygraphic recordings under baseline conditions and after 4 months of add-on GBP treatment. RESULTS: We observed a significant increase in unilateral/focal IEA during light NREM sleep and a significant reduction in bilateral/diffuse IEA during wakefulness after sleep onset (WASO) with respect to the baseline condition. A significant increase in REM sleep and slow wave sleep (SWS) associated with a reduction in the number of awakenings and Stage 1 was also observed after GBP chronic therapy. CONCLUSIONS: GBP therapy improves the sleep pattern of epileptic patients and it seems to modulate the expression of IEA with different effects in relation to the various vigilance levels.

Respiratory disorders during sleep in patients with epilepsy: effect of ventilatory therapy on EEG interictal epileptiform discharges.

OBJECTIVE: Sleep disorders are common and may coexist with a variety of diseases, including epilepsy, with important implications for the clinical management of the latter. Sleep fragmentation and deprivation, and hypoxia associated to sleep disordered breathing (SDB) may contribute to the occurrence of seizures. On the other hand, antiepileptic drugs may worsen SDB by reducing the muscle tone of the upper airways, and increasing the arousal threshold. There is evidence indicating that treatment of the SDB can reduce both frequency and intensity of seizures. This study aimed at further understanding the relationship between SDB and epilepsy, particularly the influence of SDB on epileptogenicity - as evaluated by a quantitative analysis of interictal epileptogenic activity. METHODS: Eight consecutive patients affected by partial epilepsy associated to SDB (OSAS or an association between chronic obstructive pulmonary disease-- COPD - and snoring) underwent two nocturnal polysomnographies (PSG)-- before and after ventilatory therapy with CPAP (in 6 patients with OSAS) or oxygen (in two patients with COPD and snoring). Spiking was quantified during the first sleep cycle in both PSG studies, and spiking rates were calculated both for the entire sleep cycle and for each separate sleep phase (NREM 1, NREM 2, NREM 3-4, REM and wake time after sleep onset - WASO). RESULTS: In all patients, the improvement of the SDB after ventilatory treatment--as demonstrated by a reduction of the respiratory disturbances index (RDI) - was associated to a reduction of spiking rates, both in the entire cycle and in relationship to slow wave sleep. This reduction was particularly marked in patients with higher spiking rates in baseline conditions. CONCLUSION: Our data show that SDB treatment reduces the interictal epileptogenic activity, suggesting that SDB plays a role in increasing epileptogenicity. Further studies will be necessary to clarify the mechanisms whereby this reduction in epileptogenicity occurs, although improved sleep stability seems to play an important role. The presence of an underlying SDB in patients with refractory epilepsy should be investigated.

Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation.

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta 1 and beta 2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

Median nerve somatosensory evoked potentials. Apomorphine-induced transient potentiation of frontal components in Parkinson's disease and in parkinsonism.

Somatosensory evoked potentials (SEPs) to median nerve stimulation have been recorded from parietal and frontal districts in 43 parkinsonians, 17 patients with parkinsonism and 35 healthy controls matched for age and sex. Latency/amplitude characteristics of the parietal P14-N20-P25 and of the frontal P20-N30-P40 wave complexes before and after (10, 20, 30 and 60 min) subcutaneous administration of apomorphine chloride were evaluated in all the 60 patients and in 3 controls. The frontal waves N30 and P40 were either absent or significantly smaller than normal in 31 patients with Parkinson's disease (PD) (72.1%) and in 9 with parkinsonism in baseline records (56.3%). Following apomorphine, the parietal deflections did not significantly vary in amplitude. On the contrary, the frontal complex showed a significant amplitude increase in 27 PD and 8 parkinsonisms (respectively 62.8 and 47.1%); 79.1% of PD and 35.3% of parkinsonisms were improved clinically. Amplitude increase was evident at 10 min after apomorphine, in parallel with clinical improvement, and vanished nearly in coincidence with the end of the clinical effect.

Somatosensory evoked potentials during the ideation and execution of individual finger movements.

Scalp somatosensory evoked potentials (SEPs) were recorded in 10 volunteers after median nerve stimulation, in four experimental conditions of hand movements performance/ideation, and compared with the baseline condition of full relaxation. The experimental conditions were (a) self-improvised hand-finger sequential movements; (b) the same movements according to a read sequence of numbers; (c) mental ideation of finger movements; and (d) passive displacement of fingers in complete relaxation. Latencies and amplitudes of the parietal (N20, P25, N33, and P45) and frontal peaks (P20-22, N30, and P40) were analyzed. Latencies did not vary in any of the paradigms. Among the parietal complexes, only the P25-N33 amplitude was significantly reduced in (a), (b), (c), and (d) and the N20-P25 was reduced in (a) and (d); among frontal waves, N30 and P40 were significantly reduced (20-75%) in (a) and (b). Coronal electrodes showed amplitude decrements maximal at the frontal-rolandic positions contralateral to the stimulated side.

Changes of the EEG paroxysmal pattern during felbamate therapy in Lennox-Gastaut syndrome: a case report.

We report a case of a 43-year old woman with Lennox-Gastaut syndrome who exhibited atypical absence seizures, atonic seizures and generalized toniclonic seizures which were not controlled by antiepileptic drug (AED) treatment. Because of this, felbamate (FBM) (1800 mg per day) was progressively added to the pre-existent therapy. The patient underwent a 24-hour-video-EEG monitoring before and after 4 months of FBM therapy. Analysis of the video-EEG signal recorded during wakefulness revealed the presence of ictal activity represented by repetitive, bilateral, slow spike and wave bursts underlying atypical absence seizures; the ictal activity occurring during non-REM sleep was characterized by runs of bilateral, rapid, high-voltage spikes followed by slow spike and wave complexes corresponding to brief tonic seizures. FBM therapy induced disappearance of the EEG ictal slow, spike and wave complexes leaving rather unaffected the runs of spikes. Computerized analysis of both the EEG background activity and the sleep structure displayed a better organization of the global cerebral rhythms under FBM treatment. Our findings suggest a selective effect of FBM on the ictal atypical spike and wave pattern. The differential effect of FBM on ictal patterns may be a reflection of a different action on the excitatory and inhibitory systems.

Sodium valproate and mental processes in newly referred epileptic patients. A computerized EEG study.

Seventeen epileptic patients suffering from generalized idiopathic epilepsy who underwent antiepileptic treatment with sodium valproate (NaVPA) for the first time were studied. The EEG was recorded at rest with eyes closed (EC), during blocking reaction, fixation and mental arithmetic tasks. The computerized EEG study, performed before and after therapy, utilized spectral analysis; data underwent statistical evaluation including ANOVA and correlation analysis. Before NaVPA therapy, a significant decrease of beta 1 and beta 2 relative power, compared with control subjects, was observed in epileptic patients at rest with EC, whereas fast activity increased during mental tasks. After treatment, no significant variations in fast activity were observed during tasks, with a pattern similar to that observed in the control population. Therefore, considering the effect of NaVPA primarily on fast activity, which reflects rather well preserved mental functioning processes, it is possible to hypothesize that the drug interferes positively with mental activities.

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis.

1. Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures. 2. We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus. 3. In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased. 4. The EEG background activity was not modified by the addition of the drug. 5. Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.

EEG changes induced by vigabatrin monotherapy in focal epilepsy.

The effect of vigabatrin (GVG) monotherapy on EEG interictal abnormalities and on background activity recorded at rest and during mental tasks was studied in 14 patients suffering from focal epilepsy. A long-term EEG monitoring was performed in each patient before and 3 months after the beginning of GVG therapy. Ictal and interictal EEG abnormalities (IEA) were quantified by specific computer programs. Background activity was evaluated by spectral analysis at rest with eyes closed (EC), during blocking reaction (BR) and during fixation of cartoons (FIX). During treatment, IEA was either decreased or unmodified independently from seizure occurrence, which clearly improved in the majority of patients. The only EEG modifications induced by GVG monotherapy were a more pronounced slowing of the background activity at rest with EC and a reduced responsiveness to BR. EEG data suggest a GVG monotherapy induced mild "sedative" action on attentive tasks rather than on cognitive function.