Gian Luigi Gigli

Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy.

We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci. Forty patients were studied prospectively. Spikes were assessed for rates, field, and appearance of new foci. Final localization was determined by surgery, electrocorticography, and seizure onset. Comparison of interictal EEG foci with final localization was made. In 39 patients, slow-wave sleep activated spiking compared with wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4. Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred. New foci appeared in non-rapid eye movement sleep in 53% of patients. Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep. All REM foci were unilateral. Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep.

Non-invasive evaluation of input-output characteristics of sensorimotor cerebral areas in healthy humans

The topography of scalp SEPs to mixed and sensory median nerve (MN) and to musculocutaneous nerve stimulation was examined in 20 healthy subjects through multichannel (12-36) recording in a 50 msec post-stimulus epoch. MN-SEPs in both frontal leads were characterized by an N18, P20, N24, P28 complex showing maximal amplitude at contralateral parasagittal sites. This was sometimes partly obscured by a wide wave N30 having a fixed latency, but a steep amplitude gradient moving toward the scalp vertex. A P40 component followed, having longer peak latencies, moving the recording sites from contralateral medial parietal toward the vertex and frontal ipsilateral positions. MN-SEPs in contralateral parietal leads contained a widespread N20 with a maximum source posterior to the Cz-ear line. The following P25 enveloped two subcomponents - early and late P25 - having different distributions. The late P25 showed a maximum - coincident with that of wave N20 - which was localized more posteriorly than that of the early P25. An inconstant wave N33 with progressively longer peak latencies from sagittal toward lateral positions was then recorded. MN-SEPs in contralateral central positions showed a well-localized P22 wave in which both the parietal early P25 and the frontal P20 were vanishing. Common or separate generators for frontal, central and parietal SEPs were discriminated by evaluating the influence of stimulus rate and intensity, as well as of general anesthesia and transient CBF deficits, investigated in 7 patients undergoing carotid endarterectomy. Unifocal anodal threshold shocks were separately delivered to each of the scalp electrodes and motor action potentials were recorded from the target muscle in order to delineate the scalp representation of the motor strip for the upper limb and, consequently, to monitor, through SEP tracings, the short-latency sensory input to the motor cortex for hand and shoulder muscles. This was characterized by a boundary zone separating the parietal N20-early P25 complex, from the fronto-central N18-P22 one. This zone had an oblique direction strongly resembling that of the central sulcus.

Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects

We compared sleep parameters in mentally retarded infantile autism (MRIA) and mentally retarded Downs syndrome (MRDS) by means of polysomnography, evaluating traditional analysis with particular attention to the phasic components in each disorder. Data were compared with those obtained in normal subjects matched for age and sex. Mental age, Intellectual Quotient and the Childhood Autism Rating Scale were performed to obtain an estimation of the neuropsychological deficit. Abnormalities of phasic components of sleep and the presence of REM sleep components into non-REM sleep were observed in both MRIA and MRDS even if in different ways. In fact, MRDS subjects presented a reduction of REM sleep percentage and R index (number of high frequency REMs against number of low frequency REMs) and this was positively correlated to a low IQ. Unlike MRDS subjects, MRIA subjects did not show any parallelism between intellectual abilities and REM sleep deficit. In addition, the presence of undifferentiated sleep in autistic subjects implies a maturational deficit that is still present in adulthood. Finally, a high R index in MRIA was observed. This finding, which is not present in MRDS, could represent an estimation of the disorganized arrival of information caused by a dyscontrol or a reduction of inhibitor pathway. With reference to sleep mechanisms, our results suggest that the cognitive deficit in MRIA may differ from that of MRDS subjects. A maturational deficit of CNS with a dysfunction of brainstem monoaminergic neurons could represent the underlying mechanism.

Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: changes after treatment with controlled-release carbamazepine

Summary: Purpose: To define sleep disturbances in patients with temporal lobe epilepsy (TLE) and explore the association between carbamazepine (CBZ) therapy, sleep, and daytime somnolence.

Sleep organization pattern as a prognostic marker at the subacute stage of post-traumatic coma

OBJECTIVES The aim of this study is to identify the predictive indexes for post-traumatic coma prognosis, which is important to better direct acute and subacute treatments and rehabilitation efforts. The pattern of sleep organization is a potential prognostic marker, but its role has not been established yet in the context of modern critical care. In the present study, we used a new protocol to evaluate the prognostic value of the different levels of sleep-wake organization recorded at the subacute stage of post-traumatic coma. METHODS Twenty-four head-injured comatose patients were monitored with 24h polysomnographic recordings. The predictivity of the different levels of sleep-wake organization on polysomnography was compared with other possible prognostic indexes (i.e. neuroradiological findings, age and Glasgow Coma Scores (GCS)). Main outcome measures were survival and the degree of disability after recovery from coma. RESULTS The presence of organized sleep patterns, but not GCS, was highly predictive of better outcome (odds ratio=10.78, P=0.01), even after correction for potentially confounding variables with multivariate analysis. CONCLUSIONS Our study demonstrates that the sleep-wake organization pattern based on 24h polysomnographic recordings at the subacute stages of post-traumatic coma is a reliable prognostic marker, both for survival and for functional recovery.

Poststroke Late Seizures and Their Role in Rehabilitation of Inpatients

Summary: Purpose: This study was designed to (a) identify the prevalence of poststroke late seizures in a population of patients admitted to rehabilitation of neurologic sequelae of their first stroke, (b) recognize reliable prognostic factors associated with the occurrence of poststroke late seizures, and (c) evaluate the impact of seizures on the results of rehabilitation treatment.

Drugs with anticholinergic properties as a risk factor for cognitive impairment in elderly people: a population-based study.

Prevention of drug-related problems is a key issue in the aged. Anticholinergic (ACH) drugs are a biologically plausible and potentially modifiable risk factor for cognitive impairment. Therefore, we intended to evaluate the association between ACH drugs and cognitive impairment. Our study comprised 750 subjects aged 65 years or older. Cognitive impairment was evaluated using Mini-Mental State Examination and Global Deterioration Scale. Patients were classified into ACH-drug users and non-ACH-drug users. Those using ACH drugs (20.1%) were more likely to have cognitive impairment than those using non-ACH drugs (odds ratio, 3.18; 95% confidence interval, 1.93-5.23; P < 0.001); this association remained significant even after adjusting for potential confounding variables (odds ratio, 2.30; 95% confidence interval, 1.19-4.45). Our data suggest that ACH drug intake should be regarded a potentially modifiable risk factor for cognitive impairment in the elderly.

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.

Sensory gating deficit assessed by P50/Pb middle latency event related potential in Alzheimer's disease.

Summary: Sensory gating is defined as the brain’s ability to inhibit repetitive and irrelevant incoming sensory stimuli and is supposed to be related to cholinergic transmission. Indeed, Alzheimer’s disease (AD) is characterized by a cholinergic deficit that is believed to be involved in cerebral cortex hyperexcitability and short latency afferent inhibition deficit. Therefore, a sensory gating deficit may be supposed present in AD within the frame of cortex hyperexcitability and loss of cortex modulation of sensory inputs. The authors investigated whether a sensory gating deficit may be present in AD and whether this deficit may be related to the presence of neuropsychiatric symptoms (NPS) and reversed by donepezil treatment. Sensory gating was evaluated using a paired-stimulus auditory P50 event-related potential paradigm. Eighteen drug-naïve probable AD patients (mean age 76.1 years; SD 5.6 years; 13 females and 5 males) and 15 healthy elderly controls (mean age 74.2 years; SD 5.4 years; 10 females and 5 males) were recruited. Sensory gating was evaluated in AD patients before starting therapy and after 1 and 3 months of donepezil treatment. Auditory P50 sensory gating was impaired in AD patients but no correlation was found between gating deficit and NPS. Moreover, AD patients displayed increased P50 amplitude when compared with healthy elderly subjects. Donepezil treatment did not improve P50 sensory gating in AD patients but decreased P50 amplitude. Patients with AD displayed an augmented P50 amplitude, in accordance with previous studies, suggesting increased cortex excitability. Donepezil does not affect P50 sensory gating but reduces P50 amplitude. Donepezil may induce P50 amplitude reduction by means of enhanced dopamine release. Indeed, it has been demonstrated that donepezil induces dopamine release “in vitro.” The findings suggest that AD patients have a sensory gating impairment but the link with both NPS and the cholinergic deficit is doubtful.

Effects of Seizures, Kindling, and Carbamazepine on Sleep Organization in Cats

Summary: We studied the relationships between epilepsy, sleep, and anticonvulsant drugs in kindled cats. No sleep alteration was present at midkindling. When the animals became fully kindled, a reduction in REM sleep percentage and the number of entries into REM sleep were observed compared to baseline. In addition, with further seizures, an increase in the percentage of wake‐fulness appeared, accompanied by a further reduction in the number of entries into REM sleep. It therefore seems that there is a progressive disruption of sleep, dependent on the increasing number of tonic‐clonic generalized seizures. After a seizure‐free interval, REM sleep and wake‐fulness returned to baseline values. A reduction in the percentage of stage II compared to baseline was found and remained as a long‐term effect of the kindling process. Acute administration of carbamazepine (CBZ) reduced the REM sleep percentage. This effect, paralleled by a reduction in the number of entries into REM sleep, was evident both at baseline and when the animals were fully kindled. After a large number of seizures, however, CBZ administration did not cause a further reduction in the already low percentage of REM sleep. Results are discussed with reference to previous literature. We propose a hypothesis of competition between seizure and REM sleep in the elimination of epileptogenic and hypnogenic factors.