Antonella Cerquiglini

An Investigation of Sleep Characteristics, EEG Abnormalities and Epilepsy in Developmentally Regressed and Non-regressed Children with Autism

This study investigated sleep of children with autism and developmental regression and the possible relationship with epilepsy and epileptiform abnormalities. Participants were 104 children with autism (70 non-regressed, 34 regressed) and 162 typically developing children (TD). Results suggested that the regressed group had higher incidence of circadian rhythm disorders than non-regressed children. The regressed group showed higher Children’s Sleep Habits Questionnaire Bedtime Resistance, Sleep Onset Delay, Sleep Duration and Night-Wakings scores. Epilepsy and frequent epileptiform EEG abnormalities were more frequent in regressed children. Past sleep disorders and a history of developmental regression were significantly associated with sleep disorders. This study is an initial step in better understanding sleep problems in regressed children with autism, further studies are necessary to better investigate these aspects.

Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing.

OBJECTIVEnAutism is a frequent manifestation of tuberous sclerosis complex (TSC) being reported in up to 60% of the patients. Its presence is in association with cortical and subcortical lesions involving the temporal lobes. This study was designed to shed light on the functional mechanisms linking anatomical lesions of TSC and behavioural phenotype by investigating scalp recorded event related potentials to auditory stimuli.nnnMETHODSnFourteen children with TSC, seven of which fulfilled the DSM IV criteria for autistic disorder were selected for this study. All of the subjects underwent high resolution MRI, EEG, brainstem auditory evoked potentials, cognitive and behavioural evaluation. Electrical evoked responses to two different pitches, presented with different probability (80% 1000 Hz, 20% 1500 Hz) were recorded from 21 scalp electrodes in the autistic and non-autistic subgroups, to assess central auditory processing and automatic memory.nnnRESULTSnThe first component of the long latency auditory response (N1) had a significantly prolonged latency with lower amplitude in all of the patients with autistic behaviour who, contrary to non-autistics had MRI lesions involving one or both temporal lobes. A mismatch negativity was detected in all subjects and had a longer latency in subjects with autistic behaviour.nnnCONCLUSIONSnTo our knowledge this is the first electrophysiological evidence of a deficit in auditory information processing and automatic memory in TSC patients with autistic behaviour.

Spike-induced interference in auditory sensory processing in Landau-Kleffner syndrome.

OBJECTIVESnLandau-Kleffner Syndrome (LKS) is an epileptic syndrome characterised by a deficit in language comprehension and production, paroxysmal epileptiform activity in the posterior temporal leads, and by the inconsistent presence of epileptic fits. Its interest lies in the fact that it stands as a model for the study of interference of epileptiform activity on cognitive function, although the pathophysiology of the decline in language skills that follows its onset has not yet been clarified.nnnMETHODSnWe have recorded spike-triggered auditory evoked responses in a group of 6 children with LKS, to investigate whether the occurrence of individual EEG paroxysms is able per se to induce a decline in the response of the auditory cortex.nnnRESULTSnResults have indicated that left hemisphere spikes are associated with a greater reduction in amplitude and an increase in latency of the NI, than spikes occurring in the right hemisphere. No stable change in the evoked response has been detected outside of the EEG paroxysm.nnnCONCLUSIONSnWe postulate EEG interictal activity is able to induce impairment in processing auditory information and that this may play a role in the pathogenesis of language deficit in LKS.

Frontal Lobe Epilepsy Associated With Tuberous Sclerosis: Electroencephalographic-Magnetic Resonance Image Fusioning

We studied the topographic relationships between cortical and subcortical lesions shown on magnetic resonance images (MRI) and sources of epileptiform activity in a series of nine children with intractable epilepsy and tuberous sclerosis complex. Although video-electroencephalographic (EEG) monitoring was suggestive of a frontal seizure onset, interictal EEG was, in seven of nine cases, in the form of apparently bisynchronous discharges. In all cases, the use of a short time lag estimation procedure based on a nonlinear correlation function between surface recorded EEG signals allowed the detection of a lateralized onset of EEG paroxysmal activity. Furthermore, a computerized method based on a source localization EEG-MRI image fusioning procedure, has revealed a topographic concordance between well-defmed frontal cortical lesions shown on MRI and site of onset of paroxysmal discharges. Lennox-like EEG patterns frequently reported in children with tuberous sclerosis complex could be the result of the tendency of frontal tubers to induce secondary bilateral synchrony, with implications in the medical and eventually surgical management of the often drug-resistant associated seizures. (J Child Neurol 1998;13:33-38).

Sleep in children with autism with and without autistic regression

The purpose of the present investigation was to characterize and compare traditional sleep architecture and non‐rapid eye movement (NREM) sleep microstructure in a well‐defined cohort of children with regressive and non‐regressive autism, and in typically developing children (TD). We hypothesized that children with regressive autism would demonstrate a greater degree of sleep disruption either at a macrostructural or microstructural level and a more problematic sleep as reported by parents. Twenty‐two children with non‐regressive autism, 18 with regressive autism without comorbid pathologies and 12 with TD, aged 5–10u2003years, underwent standard overnight multi‐channel polysomnographic evaluation. Parents completed a structured questionnaire (Childrens’ Sleep Habits Questionnaire—CSHQ). The initial hypothesis, that regressed children have more disrupted sleep, was supported by our findings that they scored significantly higher on CSHQ, particularly on bedtime resistance, sleep onset delay, sleep duration and night wakings CSHQ subdomains than non‐regressed peers, and both scored more than typically developing controls. Regressive subjects had significantly less efficient sleep, less total sleep time, prolonged sleep latency, prolonged REM latency and more time awake after sleep onset than non‐regressive children and the TD group. Regressive children showed lower cyclic alternating pattern (CAP) rates and A1 index in light sleep than non‐regressive and TD children. Our findings suggest that, even though no particular differences in sleep architecture were found between the two groups of children with autism, those who experienced regression showed more sleep disorders and a disruption of sleep either from a macro‐ or from a microstructural viewpoint.

Neurophysiology of CSWS-associated cognitive dysfunction

The phenomenon of continuous spikes and waves during slow‐wave sleep (CSWS) is associated with a number of epileptic syndromes, which share a behavioral phenotype characterized by deterioration of cognitive, behavioral, or sensorimotor functions. Available evidence seems to suggest that spike‐wave activity is a result of a complex interaction between cortical and subcortical inhibitory networks and can “per se” produce a transient loss of underlying cortical functions. Syndromes like Landau‐Kleffner syndrome, CSWS, and phenomena such as negative myoclonus could share in common—at least at the neurophysiological level—some similarities. Differences in behavioral phenotypes could be explained in term of maturational and genetic differences, as well as by the functional specificity of the involved areas.

Tuberous sclerosis: relationships between topographic mapping of EEG, VEPs and MRI findings.

A group of 10 patients suffering from tuberous sclerosis (TS) and epilepsy was studied by means of topographic mapping of EEG and visual evoked potentials. The localizing ability of the technique was compared to the topography of hyperintense T2-dependent areas seen on magnetic resonance images (MRI). Data were collected from 19 electrodes, free from interictal EEG transients and artifacts, spectral analysis was performed using the FFT algorithm and color maps were produced by specialized equipment. Data were analyzed with respect to the presence of interhemispheric asymmetries and significant differences with age-matched normal controls. The topography of slow frequency components was the best clue for localization, with a concordance between imaging and spectral EEG data in 76% of the lesions detected by MRI. In 7 patients topographic mapping revealed spectral abnormalities in areas where MRI was not able to detect morphological lesions. These abnormalities were characterized by an increased delta (5 patients), theta (4 patients), or lowered ipsilateral alpha (1 patient) power. Although full agreement between imaging and electrophysiological data was not observed, we believe that in patients with TS the study of EEG rhythm activity can add valuable information to the visual inspection of the tracings.

An educational campaign about epilepsy among Italian primary school teachers. 2. The results of a focused training program

A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of dont know answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.

Brain Mechanisms of Altered Consciousness in Generalised Seizures

In spite of the inherent difficulties in achieving a biologically meaningful definition of consciousness, recent neurophysiological studies are starting to provide some insight in fundamental mechanisms associated with impaired consciousness in neurological disorders. Generalised seizures are associated with disruption of the default state network, a functional network of discrete brain areas, which include the fronto-parietal cortices. Subcortical contribution through activation of thalamocortical structures, as well as striate nuclei are also crucial to produce impaired consciousness in generalised seizures.

Magnetoencephalography in the study of epilepsy and consciousness

The neural bases of altered consciousness in patients with epilepsy during seizures and at rest have raised significant interest in the last decade. This exponential growth has been supported by the parallel development of techniques and methods to investigate brain function noninvasively with unprecedented spatial and temporal resolution. In this article, we review the contribution of magnetoencephalography to deconvolve the bioelectrical changes associated with impaired consciousness during seizures. We use data collected from a patient with refractory absence seizures to discuss how spike-wave discharges are associated with perturbations in optimal connectivity within and between brain regions and discuss indirect evidence to suggest that this phenomenon might explain the cognitive deficits experienced during prolonged 3/s spike-wave discharges.