Age-related changes of cortical excitability in subjects with sleep-enhanced centrotemporal spikes: a somatosensory evoked potential study.

Middle-latency somatosensory evoked potentials (SEPs) of particularly large amplitude (giant) have been reported in subjects with benign childhood epilepsy with centrotemporal spikes (BECT) and in normal children, which usually show significant age-related changes. However, the mechanisms by which age modifies the appearance of centrotemporal spikes and giant SEPs in these children, are not known. The characteristics of SEPs were studied in a group of 18 subjects (10 males and 8 females, aged 7.1-17.2 years) with sleep-enhanced centrotemporal spikes, with or without BECT and the results were compared with those obtained from a group of age-matched normal controls. Giant SEPs were recorded in 6 subjects and, in 3 of these, EEG spikes evoked by hand tapping were obtained also. No subjects with giant SEPs were found in subjects older than 12 years, and an age-related decrease in amplitude of giant SEPs as this age approached was observed. Moreover, at repeated SEP recordings, a clear trend towards a more important reduction in amplitude of giant SEPs over the temporal and parietal than over the central regions was evident. The study of EEG spikes evoked by hand tapping showed a striking similarity between the averaged evoked spikes and the main negative component of giant SEPs. It was also possible to observe that the spike negative peak recorded over the central areas always preceded the same component recorded over the parietal and temporal areas by 5-15 ms. Our study seems to support the idea that giant SEPs in subjects with centrotemporal spikes are generated by a complex mechanism different from that at the basis of the normal N60 component of SEPs; they also show peculiar age-related modifications which can be interpreted in terms of maturational changes of brain excitability/inhibition and probably constitute a tool for monitoring the clinical course of BECT, when present.

Sleep in subjects with autistic disorder: a neurophysiological and psychological study.

Polysomnography (EOG, EEG, EMG) was carried out in 17 male children and adolescents with autistic disorder, in seven patients with mental retardation and fragile X syndrome, and in five age- and sex-matched normal male subjects. Density of rapid eye movements was not significantly different in the three groups of subjects; however, some sleep parameters such as time in bed, sleep period time, and total sleep time were significantly lower in subjects with autistic disorder than in normal controls; moreover, patients with autistic disorder showed values of sleep period time, first REM latency and percent (%) sleep stage 1 lower than those of patients with fragile X syndrome with mental retardation. Density of muscle twitches was significantly higher in patients with autistic disorder than in normal controls. In contrast only minor differences were observed between patients with autistic disorder and those with fragile X syndrome with mental retardation. Furthermore, some psychoeducational profile-revised items such as perception and eye-hand coordination, showed significant correlation with some sleep parameters (time in bed, sleep latency, stage shifts, first REM latency and wakefulness after sleep onset). Childhood Autism Rating Scale (CARS) scores to visual response and non-verbal communication showed significant correlation with some tonic sleep parameters, such as sleep period time, wakefulness after sleep onset, and total sleep time. Relating to people and activity level items were found to be significantly correlated with rapid eye movement density. Our results suggest the existence of a sleep pattern in autistic patients different from that observed in subjects with mental retardation and from that of normal controls. In addition, these findings indicate that sleep parameters in these patients are correlated with some psychological indices generally used for the diagnosis of autistic disorder; for this reason, polysomnographies might be useful in the comprehension of the neurophysiological mechanisms underlying this condition.

Skin pathology findings in a cohort of 1500 adult and elderly subjects.

BACKGROUND: No extensive studies are available in the literature on the eventual skin pathology induced by neurologic or systemic diseases in elderly individuals. Other factors, such as health and hygiene, socioeconomic status, and climate can also play an important role. METHODS: Fifteen-hundred subjects (886 women and 614 men; mean age, 67.8 years; range, 39-90 years) were admitted to the Department of Geriatrics at the Oasi Institute between 1992 and 1997; all these subjects were carefully evaluated from a dermatologic point of view. Each subject underwent specialist examinations, routine blood analyses, thoracic X-rays, cerebral computerized tomography (CT) scan, and magnetic resonance imaging (MRI) when appropriate. A group of subjects without significant neurologic or systemic disease, comprising 116 women and 60 men (mean age, 64.5 years; range, range, 40-90 years), was selected and used as a normal control group. Subsequently, our attention was focused on the eventual presence of the following neurologic diseases: Alzheimer-type dementia, vascular dementia, mixed-type dementia, subcortical dementia, Parkinson's disease, vascular brain disease, hemiplegia, etc. Thus, different subgroups were formed on the basis of such diagnostic categories and the frequency of skin pathology in each subgroup was evaluated. RESULTS: Of the 1500 subjects, 1439 stated that they had never been affected by dermatologic disease. No statistically significant difference in frequency of skin pathology was found between normal controls and the different patient subgroups. Unsuspected and singular dermatoses were found, however, such as paraneoplastic syndromes, idiopathic tripe palms, white fibrous papulosis of the neck as an expression of photoaging, conditions induced by former popular traditions of Sicilian culture (anetoderma secondary to the application of Hirudo medicinalis and erythema ab igne), pigmented dermatoses never described before in Italy (prurigo pigmentosa and friction amyloidosis), and nail abnormalities (atypical half-and-half nail, and dyschromic nail changes in multiple system atrophy and in hemiplegia). CONCLUSIONS: The dermatologic screening performed in 1500 patients revealed several unexpected diagnoses and some original observations. Some rare dermatoses were described and certain hypotheses were suggested to explain the peculiar dyschromic changes of the fingernails in multiple system atrophy, the atypical cases of half-and-half nail, and the so-called idiopathic tripe palms associated with psoriasis.

Heart rate variability and apnea during sleep in Down's syndrome.

Autonomic system dysfunction has been reported to occur frequently in patients with Down's syndrome (DS) and is constituted mainly by an imbalance between the sympathetic and vagal systems. The analysis of heart rate variability (HRV) during sleep is a quantitative reliable method for studying such a mechanism, but it has not yet been extensively and adequately applied in DS. In this study, HRV during sleep was evaluated in seven DS patients and in six normal controls, by also controlling for the presence of sleep apnea or arousal. The main results were an increased sympathetic function (low-frequency component of HRV) and a decreased vagal activity (high-frequency component of HRV) in DS with respect to normal controls, during apnea-free periods. Moreover, the presence of apnea, in DS, induced a further significant increase in low-frequency and very low-frequency components of HRV during sleep Stage 2. This study provides additional evidence of a brainstem dysfunctioning in DS, responsible for the abnormal imbalance between the sympathetic and vagal systems and confirms the brainstem involvement already suggested in the literature in order to explain brainstem-auditory evoked potential abnormalities and central sleep apnea in these patients.

Familial cortical tremor, epilepsy, and mental retardation: a distinct clinical entity?

OBJECTIVE: To describe a European family with cortical tremor, epilepsy, and mental retardation, the pedigree of which indicates an autosomal dominant inheritance of the disease. DESIGN: Clinical, laboratory, neurophysiological, and neuroimaging data were studied. SETTING: Institute for research on mental retardation. PATIENTS: Two siblings (aged 25 and 28 years) and their 49-year-old mother had postural and action tremor, seizures, and mental retardation. Only tremor was present in the maternal grandmother (aged 68 years). The electroencephalogram showed diffuse spike-and-wave complexes and/or posterior spikes, and a photoparoxysmal response in the 4 subjects. The typical electrophysiologic features of cortical reflex myoclonus, such as giant somatosensory evoked potentials, enhancement of the C-reflex, and jerk-locked premyoclonus spikes, were found in all patients. CONCLUSION: This syndrome may represent a specific form of familial cortical tremor with a benign form of epilepsy and a new genetic model of cortical hyperexcitability inherited with an autosomal dominant mechanism.

Correlation dimension of EEG slow-wave activity during sleep in children and young adults.

In a recent work, the calculation of the correlation dimension (CD) of the profiles of EEG slow-wave activity during sleep in 7 young subjects, allowed us to conclude that sleep-regulation might be considered a deterministic non-linear process with an average dimension above 3. In this paper we report the results of the calculation of the CD of EEG slow-wave activity in 20 normal subjects (children and young adults) who slept in the laboratory for 3 consecutive nights. The results confirm that it is possible to calculate the CD in most normal profiles (33 out of 40) and to discriminate between chaos and noise. The lower limit of CD was found as ranging between approximately 2.5 and 4.5, it did not show significant changes across consecutive nights in the same subject and did not seem to change significantly with age in children and young adults.

Respiratory patterns during sleep in Down's syndrome:importance of central apnoeas.

Obstructive sleep apnoea episodes have been reported repeatedly in Down's syndrome (DS) patients as a consequence of the presence of predisposing malformations or intercurrent pathology of the upper airways. There are no data on respiratory patterns of uncomplicated Down's syndrome subjects. In order to evaluate the eventual effects of central nervous system (CNS) impairment on respiration in DS, we studied the respiratory patterns during sleep of a group of 10 DS subjects, aged 8.6-32.2 y, without relevant upper airway pathology. In order to control the possible effects of sleep structure and mental retardation on the results obtained, we compared the findings in DS with those obtained from a group formed by subjects affected by fragile X syndrome (six males and one female, aged 10.0-15.42 y) another genetically determined type of mental retardation. Sleep structure was similar in both groups; however, DS subjects showed significantly higher indices of central sleep apnoea and of oxygen desaturation than fragile X patients (P < 0.005). As far as DS individuals were considered, a significant preponderance of central, as opposed to obstructive, sleep apnoeas was found (89.4% vs. 9.4%, respectively; 1.2% were mixed) which showed a significant age-related increase. Central respiratory pauses were mostly preceded by sighs, which occurred more frequently during sleep stages 1 and REM, and were often organized in long sequences of periodic-like breathing. During REM sleep, they were less frequently preceded by sighs and by body movements than during NREM sleep. Obstructive sleep apnoeas occurred more often during REM sleep and were more rarely preceded by sighs or by body movements. Both central and obstructive apnoeas induced significant oxygen desaturation in 50-69.6%. Sleep structure was not significantly modified by apnoeas and oxygen desaturation. We hypothesize that the increase in central sleep apnoeas is related to a dysfunction of the central respiratory control at a brainstem level in DS.

A new family with periventricular nodular heterotopia and peculiar dysmorphic features. A probable X-linked dominant trait.

OBJECTIVE: To describe 3 sisters with brain periventricular heterotopia and peculiar dysmorphic features as a probable X-linked dominant trait. DESIGN: Clinical, laboratory, neurophysiological, and brain imaging data were studied. SETTING: Research institute for mental retardation. PATIENTS: The 3 sisters had mental retardation, drug-resistant epilepsy, gray matter heterotopia, and peculiar malformations (low nasal bridge, upslanting palpebral fissures, palpebral edema, attached hypoplastic earlobes, thickened calvaria, rectal fibrovascular polyps, urinary tract anomalies, and increased foot length). The patients were 35, 30, and 25 years old and belonged to a sibship of 6, born of nonconsanguineous healthy parents. CONCLUSION: The 3 patients constitute a well-defined clinical entity not previously described of a probable X-linked dominant nature.

Chaotic behavior of EEG slow-wave activity during sleep.

The study of the dynamics of non-linear systems allows the evaluation of the correlation dimension which, in turn, provides an estimate of the number of variables needed to model the process. In such a view, the correlation dimension was calculated for the profiles of the EEG slow-wave activity during sleep obtained from 7 young normal controls and in their corresponding artificial stochastic signals. It was possible to evaluate the complexity of all the real profiles which exhibited an average dimension of 3.76 (SD 0.331), but not that of the artificial control ones. This allows us to conclude that sleep regulation might be considered as a deterministic non-linear process and that the already proposed two-process model of sleep regulation needs to include additional variables with non-linear interactions.

Saethre-Chotzen syndrome: a clinical, EEG and neuroradiological study.

Saethre-Chotzen syndrome is a form of acrocephalosyndactyly with autosomal dominant inheritance, characterized by craniosynostosis, facial asymmetry, palpebral ptosis, deviated nasal septum, partial cutaneous syndactyly, and various skeletal abnormalities. We studied in detail the neurological, EEG, and neuroradiological features of a group of 11 (6 male, 5 female) patients with Saethre-Chotzen syndrome. Four subjects were affected by seizures; they had paroxysmal EEG abnormalities, and gross neuroimaging revealed destructive brain lesions or malformations. Our findings suggest that CNS involvement in Saethre-Chotzen syndrome might be more severe than previously reported and support the wider use of neurophysiological and neuroimaging techniques in the study of children with this syndrome.

Spike morphology in PTZ-induced generalized and cobalt-induced partial experimental epilepsy.

Interictal epileptiform EEG activity was recorded in 10 rats with pentylenetetrazol-induced generalized seizures and in 10 rats with cobalt-induced partial epilepsy. Thirty spikes were averaged for each rat, and morphological parameters of the average waveform (such as amplitude, duration, and 1st derivative of the rising and falling spike deflections, and sharpness at peak) were measured. Pentylenetetrazol rats showed significantly higher and longer spikes than cobalt animals with a faster 1st derivative of both deflections; sharpness at peak was also higher in this group. The second spike deflection was higher and longer than the first in both groups of animals. The conclusion is that morphological spike parameters, when studied in groups of animals not treated with antiepileptic drugs, show significant differences between different experimental groups, probably reflecting a different cortical involvement and/or different epileptogenic mechanisms. The study of spike morphology can be extended to human epilepsy if etiopathogenetically homogeneous and untreated groups of patients are considered.

Scalp topographic mapping of middle-latency somatosensory evoked potentials in normal aging and dementia.

Middle-latency somatosensory evoked potentials (MLSEPs) were recorded in four groups of subjects: 13 normal young controls (mean age, 17.9 years). 11 normal elderly (mean age, 66.9 years), 11 patients with dementia of Alzheimer's type (DAT: mean age, 70.5), and four with vascular dementia (mean age, 79.3). MLSEPs in normal elderly showed an increase in the latency of P22, N30, P45, N60, and P100, and in the amplitude of N60. DAT patients also presented such changes; however, the increase in the amplitude of N60 was much more evident than that found in normal aging and was accompanied by a significant increase in amplitude of P45. Patients with vascular dementia tended to show longer latencies and larger amplitudes than the other groups. The increase in amplitude of P45 and N60 in MLSEPs seems to be characteristically associated with normal aging and the development of dementia. It is suggested that the mechanism of such functional changes might be correlated with the structural and neurochemical changes accompanying neuronal loss in these conditions.

Age-and height-dependent changes of amplitude and latency of somatosensory evoked potentials in children and young adults with Down's syndrome.

Middle-latency somatosensory evoked potentials (MLSEPs) were recorded from 19 scalp electrodes in 34 patients with Down's syndrome (DS) aged 7.4 to 35.7 years and in 16 normal control subjects aged 6.4 to 34.4 years. DS patients showed an increase in amplitude of P22, P45, and N60. P100 latency was significantly shortened. After normalization for height of subjects, N20 and N60 latencies were significantly longer in the patient group than in control subjects. On the other hand, it was possible to observe in both groups a significant trend for MLSEP amplitudes to decrease with age during the age period considered in this work. This study further confirms that the pattern of increase in amplitude of MLSEP components observed in DS is a finding peculiar of this syndrome and is not correlated with early aging processes.