Association study of autistic disorder and chromosome 16p.
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Adolescent↗
Biomedical subjects
Maurizio Elia
Publications and source records attributed to Maurizio Elia.
No evidence of GABRG2 mutations in severe myoclonic epilepsy of infancy.
Severe myoclonic epilepsy of infancy (SMEI) has been long suspected to have a genetic origin. Recently mutations in the gene encoding a voltage-gated alpha-1 sodium channel subunit-SCN1A-have been identified as a common cause of SMEI. Moreover, a mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor-GABRG2-has been described in a GEFS+ family with a member affected by SMEI. In order to further investigate the role of GABRG2 in the pathogenesis of SMEI, we have screened for mutations 53 SMEI patients who resulted negative for SCN1A mutations. Mutational screening of GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. Twenty-nine variant chromatograms were identified corresponding to seven different nucleotide variants. None of them leads to an amino acid change or obvious protein dysfunction. No difference in allele frequency was observed for the SMEI patients compared to a control population indicating that these variants are not involved in SMEI. Our study demonstrates that GABRG2 is not a commonly involved in the etiology of SMEI and suggests that other and yet unidentified genes are involved in the syndrome
Alleles↗
Nonlinear EEG analysis during sleep in premature and full-term newborns.
OBJECTIVE: Recently it has been shown that the adult sleep EEG is mostly determined by high-dimensional, linear dynamics with the exception of the A phase of the cyclic alternating pattern which displays more synchronized nonlinear dynamics. It is not known how these two different types of brain dynamics develop in early life; for this reason the aim of this study was that to extend the nonlinear analysis to the EEG during sleep recorded in premature and full-term newborns. METHODS: EEG epochs were chosen from a total of 24 polygraphic recordings from 14 babies (9 males and 5 females) aged between 33 weeks 3 days and 4 months conceptional age. All subjects were neurologically normal and showed normal psychomotor development at follow-up. A total of 243 artifact-free epochs was chosen during active sleep (AS, 74 total epochs), quiet sleep (QS, 76 total epochs) and indeterminate sleep (IS, 93 total epochs). The dynamic properties of the EEG were assessed by means of the nonlinear cross prediction test which uses 3 different 'model' time series in order to predict nonlinearly the original data set (Pred, Ama, and Tir). Pred is a measure of the predictability of the time series, and Ama and Tir are measures of asymmetry, indicating nonlinear structure. RESULTS: Our results show that the structure of sleep EEG in newborns is significantly different from that of adults, it cannot be distinguished from that of high-dimensional noise in the majority of epochs, and shows a tendency to become nonlinear in nature, mostly during QS, in a small percentage of the epochs analyzed. CONCLUSIONS: These findings can be interpreted as the effect of immature synaptic interconnections between neurons in the newborn brain.
Aging↗
The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects.
OBJECTIVE: In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two automatic components of the auditory event-related potentials (ERPs): the mismatch negativity (MMN)--a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced--and the novelty-related P3a which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli. METHODS: Ten male subjects, mean age 12.3 years (SD 4.95), affected by autism and mental retardation were admitted to this study. All patients were also mentally retarded. Ten normal male subjects, mean age 12.2 years (SD 3.94), were used as controls. Auditory evoked potentials were recorded from 19 scalp electrodes (10-20 system), and stimuli were presented in sequences consisting of 2000 tones (70 dB, ISI=800 ms). Three types of stimuli were presented: (1) standard stimuli (1000 Hz tones, 80% of total stimuli), (2) deviant stimuli (1300 Hz tones, 10% of total stimuli), and (3) novel stimuli (complex and non-monotonal, 10% of total stimuli). To quantify the MMN, the evoked response to the standard tones was subtracted from the corresponding deviant stimulus response and its amplitude and latency at peak were measured over Fz, Cz and Pz; similarly, the P3a component of the ERP was obtained by subtracting the response to the standard tone from that to the novel stimuli and its amplitude and latency at peak were measured over Fz, Cz and Pz. Also, the amplitude and latency at peak for the N1 component of the auditory evoked potential obtained with the standard stimuli were measured over Fz, Cz and Pz. The correlation between age and MMN and P3a amplitude was also analyzed. RESULTS: N1 showed significantly shorter latencies in the autistic groups. MMN elicited by deviant stimuli, but not that elicited by novel stimuli, was found to be significantly larger in autistic children than in normal controls. P3a showed higher amplitude in autistic subjects than in normal controls during childhood; the opposite was observed during young adulthood. DISCUSSION: Our findings indicate that significant changes in ERPs can also be seen in non-cooperative individuals with autism and mental retardation, which might be different from the changes already reported for high-functioning autistic subjects and deserve further insight. These changes show developmental modifications that should be taken into consideration when analyzing data from autistic subjects.
Acoustic Stimulation↗
Peripheral markers of the gamma-aminobutyric acid (GABA)ergic system in Angelman's syndrome.
It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three gamma-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls.
Adolescent↗
Two-loci ADA haplotypes in autistic disorder.
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Adenosine Deaminase↗
Non-linear EEG measures during sleep: effects of the different sleep stages and cyclic alternating pattern.
The objective of this work was to study the non-linear aspects of sleep EEG, taking into account the different sleep stages and the peculiar organization of its phasic events in ordered sequences (CAP) by applying a series of new non-linear measures (non-linear cross prediction or NLCP), which appear more reliable for the detection and characterization of non-linear structures in experimental data than the commonly used correlation dimension. Eight healthy subjects aged 18-20 years participated in this study. Polysomnography was performed in all subjects; signals were sampled at 128 Hz and stored on hard disk. The C3 or C4 derivation was used for all the subsequent computational steps, which were performed on EEG epochs (4096 data points) selected from sleep stage 2 (S2) and slow-wave sleep (SWS), in both CAP and non-CAP (NCAP) conditions. Also, epochs from sleep stage 1 (S1), REM and wakefulness preceding sleep were recorded. The dynamic properties of the EEG were assessed by means of the non-linear cross-prediction test, which uses three different 'model' time series in order to predict non-linearly the original data set (Pred, Ama, and Tir). Pred is a measure of the predictability of the time series, and Ama and Tir are measures of asymmetry, indicating non-linear structure. The non-linear measures applied in this study indicate that sleep EEG tends to show non-linear structure only during CAP periods, both during S2 and SWS. Moreover, during CAP periods, non-linearity can only be detected during the phase A1 subtypes (and partially A2) of CAP. The A3 phases show characteristics of non-stationarity and bear some resemblance to wakefulness. Based on the results of this study, sleep might be considered as a dynamically evolving sequence of different states of the EEG, which we could track by detecting non-linearity, mostly in association with CAP. Our results clearly show that detectable non-linearity in the EEG is closely related to the occurrence of the phase A of CAP.
Adolescent↗
Heart rate variability during sleep in children with partial epilepsy.
Alterations in autonomic control of cardiac activity in epileptic patients have been reported by several studies in the past, and both ictal and interictal modifications of heart rate regulation have been described. Alterations of autonomic control of cardiac activity can play an important role in sudden unexplained death in patients with epilepsy (SUDEP). However, the presence of specific changes in heart rate variability (HRV) during sleep, not correlated with seizures, has not been assessed in children with epilepsy; for this reason, we evaluated features of cardiac autonomic function during sleep without ictal epileptiform electroencephalogram (EEG) activity in a group of children with partial epilepsy. Eleven patients (five males and six females; mean age 11.5 years, SD: 3.65 years) affected by partial epilepsy were admitted to this study; 11 normal subjects (five males and six females; mean age 12.9 years, SD: 2.72 years) served as a control group. All subjects slept in the laboratory for two consecutive nights. The data were analyzed during the second night. Sleep was polygraphically recorded [including one electrocardiography (ECG) channel] and signals were digitally stored. A series of 5-min ECG epochs were chosen from each sleep stage, during periods without evident ictal epileptiform activity in the EEG. Electrocardiography signals were analyzed for automatic detection of R-waves and, subsequently, a series of time- and frequency-domain measures were calculated. Epileptic subjects tended to show an overall lower HRV in both time- and frequency-domain parameters, principally during rapid eye movement (REM) sleep and, to a lesser extent, during sleep stage 2. Among the different bands, this decrease was most evident for the high-frequency band (HF) absolute power. For this reason, the ratio between the low-frequency band (LF) and HF was always higher in epileptic patients than in normal controls and the difference was statistically significant during sleep stages 3 and/or 4 and REM sleep. Our results indicate that during sleep, a particular condition of basal modification in autonomic characteristics occurs (mostly during REM sleep) in partial epilepsy patients. This finding might represent an important factor contributing to the complex mechanism of SUDEP which takes place most often during sleep and supports the need of studying HRV specifically during this state in subjects with seizures.
Anticonvulsants↗
Mild generalized epilepsy and developmental disorder associated with large inv dup(15).
PURPOSE: Several studies attempted to clarify the genotype-phenotype correlations in patients with inverted duplication of chromosome 15 [inv dup(15)], which is usually characterized by severe mental retardation and epilepsy in individuals with large duplications including the Prader-Willi/Angelman region. We report two patients with inv dup(15) who, in spite of a large duplication, had a mild phenotype including adult-onset epilepsy. This report may help to define the milder spectrum of the syndrome. METHODS: A 25-year-old girl with mild mental retardation had a 6-year history of absence seizures, with occasional head drop. Interictal EEG revealed diffuse spike-wave complexes. Epilepsy was well controlled by a combination of lamotrigine (LTG) and valproate (VPA). The other patient, a 27-year-old man with mild mental retardation, had a 5-year history of rare generalized tonic-clonic seizure during sleep, and frequent episodes of unresponsiveness, which appeared to be atypical absence seizures on video-EEG recordings. A combination of VPA and LTG led to a remarkable improvement, although no complete control. RESULTS: Molecular analysis revealed a large inv dup15 in both patients. CONCLUSIONS: The discrepancy between the mild phenotype and the severe chromosomal abnormality detected in these two patients further supports the notion that the site of breakpoint might be contributory to the inv dup(15) phenotype. Inv dup(15) should be considered in atypical cases of generalized epilepsy of adult onset without clear-cut etiology.
Adult↗