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Biomedical subjects

P Curatolo

Publications and source records attributed to P Curatolo.

At least 19 recordsLinked to original sources
PubMed2006

Oxcarbazepine and atypical evolution of benign idiopathic focal epilepsy of childhood.

Patients that have benign epilepsy with centrotemporal spikes (BECTS) may occasionally experience an atypical development in their course when treated with drugs such as carbamazepine. Three patients with electroclinical patterns consistent with BECTS showed seizure exacerbation during oxacarbazepine (OXC) therapy. Two manifested atypical absences, neuropsychological disturbances, and generalized spike-and-wave discharges in their electroencephalograms (EEGs) that became continuous during sleep. The third patient showed, during OXC therapy, more frequent partial motor seizures which ended with ictal vomiting and post-ictal obnubilation. EEGs recorded during sleep showed discontinuous paroxysmal activity in the right centrotemporal area. Symptoms were reversed following discontinuation of the OXC therapy. Although electroclinical findings were consistent with a BECTS diagnosis, all patients had some atypical features. Our observations show that BECTS patients, in particular those presenting with atypical findings, might be at risk for developing paradoxical reactions to OXC therapy. We suggest that OXC should be included in the list of drugs that may cause electroclinical deterioration in these patients.

Carbamazepine↗
PubMed2004

Convulsive disorder and genetic polymorphism. Association of idiopathic generalized epilepsy with haptoglobin polymorphism.

Haptoglobin is a polymorphic protein that is well known for its hemoglobin (Hb)-binding property. The protein shows gross differences in molecular size among genotypes, resulting in different degrees of diffusion in central nervous system tissue. Since the breakdown of erythrocytes in the intracerebral fluid results in Hb-mediated free OH radical formation, lipid peroxidation, and increased neuronal excitability, a differential diffusion of haptoglobin phenotypes in the intracerebral fluid might result in a different degree of protection from oxidative damage. We have studied two samples of children with idiopathic generalized epilepsy from two different Italian populations. In both samples the haptoglobin *1/*1 genotype is much less represented in epileptic children than in controls. These observations suggest that subjects carrying the Hp*1/*1 genotype, that has the lowest molecular size and diffuses more readily in the interstitial cerebral fluid, are more protected against idiopathic generalized epilepsy than those with other haptoglobin genotypes.

Adult↗
PubMed2003

Cortical dysplasia, temporal atrophy, mental retardation, dysmorphic facies, and partial epilepsy: an EEG and dynamic susceptibility contrast (DSC) MRI study in a new possible genetic syndrome.

We report the case of a 24-year-old female with partial epilepsy, mental retardation, and dysmorphic facies. In EEG, a high spiking rate (HSR) was evident with abnormalities in the right frontal region. Morphological MRI showed a left temporo-mesial sclerosis and a cortical dysplasia localized in the right frontal cortex. Dynamic susceptibility contrast (DSC) MRI showed hyperperfusion in right frontal region and hypoperfusion in left fronto-temporal region. Left fronto-temporal hypoperfusion is consistent with temporo-mesial sclerosis. Right frontal hyperperfusion is related to the cortical dysplasia area with HSR. HSR may resemble both electroencephalographic and perfusional ictal pattern. DSC MRI is useful in the evaluation of regions involved in the genesis of ictal and interictal epileptiform activity. Furthermore, we hypothesize that our patient would be affected by a new possible genetic syndrome.

Adult↗
PubMed2003

GABA(A) receptor active steroids are altered in epilepsy patients with tuberous sclerosis.

BACKGROUND: The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-amino-butyric acid (GABA)(A) receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility. OBJECTIVE: To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis. METHODS: Plasma concentrations of the enantiomers 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method. RESULTS: In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects. CONCLUSIONS: The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.

Adolescent↗
PubMed2001

Autism: evidence of association with adenosine deaminase genetic polymorphism.

Reduced adenosine deaminase (ADA) activity has been reported in sera of autistic children relative to controls. Additionally, the Asn allele of the ADA Asp8Asn polymorphism has been associated with reduced enzymatic activity. Therefore, we studied this polymorphism in autistic children and controls from two Italian populations. We observed a significantly elevated frequency of the low-activity Asn allele in the total sample of autistic cases relative to controls (P < 0.00001), and in both study populations (P < 0.001 and P < 0.025). We suggest that this putative genotype-dependent reduction in ADA activity may be a risk factor for the development of autism.

Adenosine Deaminase↗
PubMed2001

Vigabatrin for tuberous sclerosis complex.

Vigabatrin (VGB) was found to be an effective anti-epileptic drug to reduce infantile spasms in about 50% of patients and it has been found most effective in infantile spasms due to tuberous sclerosis (TSC) in which up to 95% of infants had complete cessation of their spasms. VGB was synthesized to enhance inhibitory gamma-aminobutyric acidergic (GABAergic) transmission by elevating GABA levels via irreversible inhibition of GABA transaminase. The mechanism underlying the particular efficacy of VGB in TSC is still unknown. However, its efficacy suggests that epileptogenesis in TSC may be related to an impairment of GABAergic transmission. VGB should be considered as the first line monotheraphy for the treatment of infantile spasms in infants with confirmed diagnosis of TSC. The efficacy of VGB treatment can be assessed in less than 10 days, but usually a few days treatment with a dose of about 100 mg/kg/day stops infantile spasms. The cessation of the spasms is associated with a marked improvement of behaviour and mental development. Unfortunately, it has become clear that the use of VGB is associated with a late appearance of visual-field defects in up to 50% of patients. Currently the minimum duration and doses of VGB treatment that can produce side effects are unknown. The feasibility of using short treatment periods (2-3 months) should be investigated.

Anticonvulsants↗
PubMed2001

Infantile spasms in tuberous sclerosis complex.

The high incidence of infantile spasms (IS) and hypsarrhythmia in tuberous sclerosis complex (TSC) has long been emphasized but it is now clear that infants with TSC show clinical and EEG differences from those with classical West syndrome. Seizures at onset are mainly characterized by partial motor seizures and IS. Subtle partial seizures may be present in the early neonatal period and may precede the onset of IS. Visual recording techniques have led to significant progress in the classification of seizures associated with TSC, demonstrating that they have a focal or multifocal origin in the vast majority of cases. In most cases, an awake interictal EEG shows focal or independent multifocal spike and slow-wave activity at onset and later a pseudo-hypsarrhythmic pattern. Ictal EEG starts with focal spikes originating from the posterotemporal, or occipital regions followed by a generalized irregular slow transient and an abrupt diffuse flattening. Although the pathophysiological mechanisms responsible for the coexistence of partial seizures and IS are still unclear, IS associated with TSC may be the result of a rapid secondary generalization. The presence of IS due to TSC is strongly predicted by the cortical tuber count, while the age of onset of seizures and the age of occurrence of EEG foci depend on the localization of cortical tubers with an earlier expression of the parieto-occipital than of the frontal regions. Early recognition of these distinctive features appears worthwhile for therapeutic and prognostic implications. Despite the efficacy of vigabatrin the prognosis of IS is generally poor. Studies using combined topographic mapping of EEG, magnetic resonance imaging and positron emission tomography may provide new strategies for selecting candidates suitable for surgery.

Electroencephalography↗
PubMed2001

Neurologic aspects of adenylosuccinate lyase deficiency.

Adenylosuccinate lyase deficiency is an autosomal-recessive disorder of the purine de novo synthesis pathway, diagnosed up to now in approximately 40 patients. The clinical presentation is characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features. Neonatal seizures and a severe infantile epileptic encephalopathy are often the first manifestations of this disorder. The existence of genetic heterogeneity for the adenylosuccinate lyase defect could account for variability of the clinical presentation. Deficiency of purine nucleotides, impairment of energy metabolism, and toxic effects are potential mechanisms of cerebral damage. Laboratory investigations show the presence in urine and cerebrospinal fluid of succinylpurines, which are normally undetectable. Currently, no effective treatment is available for adenylosuccinate lyase deficiency. A search for this disorder should be included in the screening program of children with unexplained neonatal seizures or severe infantile epileptic encephalopathy.

Adenylosuccinate Lyase↗
PubMed2001

Prenatal and perinatal determinants of neonatal seizures occurring in the first week of life.

To evaluate prenatal and perinatal risk factors for early neonatal seizures, we conducted a case-control study including 100 newborns with neonatal seizures in the first week of life and 204 controls randomly selected from a list of healthy newborns born in the same hospital during the study period. Generalized tonic seizures were the most common seizures observed (29%), although the majority of newborns (71%) experienced more than one type of seizure. The most frequent presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%). A history of epilepsy in first-degree relatives was found only for cases. Neonatal seizures were found to be associated with maternal disease in the 2 years before pregnancy, mother's weight gain > 14 kg during pregnancy, placental pathology, preeclampsia, low birthweight, low gestational age, and jaundice in the first 3 days of life. The need for cardiopulmonary resuscitation was found only for cases (37%). The causal pathways for neonatal seizures often begin before birth, and some of the factors identified may be preventable.

Asphyxia Neonatorum↗
PubMed2000

Diffuse polymicrogyria associated with congenital hydrocephalus, craniosynostosis, severe mental retardation, and minor facial and genital anomalies.

We report an infant boy with an apparently new malformation syndrome. The major anomalies showed by the patient include diffuse polymicrogyria, congenital hydrocephalus, craniosynostosis with severe scaphocephaly, severe mental retardation, intractable epilepsy, and minor facial and genital anomalies. Our review of the literature and two computerized dysmorphology databases found some papers reporting polymicrogyria or lissencephaly associated with craniosynostosis or hydrocephalus. None of the reported patients had a phenotype similar to that of our patient.

Abnormalities, Multiple↗
PubMed1999

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 Down's 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.

Adolescent↗
PubMed1999

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

OBJECTIVE: Autism 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. METHODS: Fourteen 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. RESULTS: The 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. CONCLUSIONS: To our knowledge this is the first electrophysiological evidence of a deficit in auditory information processing and automatic memory in TSC patients with autistic behaviour.

Auditory Perception↗
PubMed1999

Differing risk factors for cerebral palsy in the presence of mental retardation and epilepsy.

Whether the combined diagnosis of cerebral palsy with mental retardation or with mental retardation and epilepsy reflects more severe manifestations of the spectrum of cerebral palsy, or whether these conditions reflect overlapping outcomes related to different exposure, remains an open question. At two centers, in Rome and Conegliano, Italy, 51 children with combined cerebral palsy, mental retardation, and epilepsy, 31 children with both cerebral palsy and mental retardation, and 48 with cerebral palsy alone were identified and examined, and their mothers interviewed. The triple diagnosis group was significantly more likely than the other two groups to have a history of neonatal convulsions and a history of epilepsy in first-degree relatives, but less likely to have a mother's age at delivery greater than 33 years, a birthweight less than 1500 g, or gestational age less than 32 weeks. The dual diagnosis group was more likely than the other two groups to have maternal education of less than 8 years. These data suggest the possibility of different etiopathogenetic pathways for various presentations of cerebral palsy.

Adolescent↗
PubMed1999

Seizures in Chiari I malformation: a clinical and electroencephalographic study.

Seven subjects with Chiari I malformations and seizures (four males, three females; age range 11 years, 7 months to 36 years; mean, 22.28 +/- 7.58 years; median, 21) were identified in four different centers from among a group of 10 patients. Our aim was to analyze clinical and electroencephalographic characteristics of seizures in this etiologically homogeneous group of patients. Most of the seizures were of the complex partial type, and paroxysmal abnormalities were mainly localized over the frontal and temporal regions. The course of the epilepsy was rather benign, with complete control of seizures in four patients and an important reduction in frequency in the remaining three subjects. Other cortical alterations are not usually associated with the typical abnormalities of the posterior fossa in Chiari I malformation; thus, it is possible to hypothesize that cerebral microdysgenesis or, alternatively, a cerebellar dysfunction could underlie epileptogenesis in these patients.

Adolescent↗
PubMed1998

Magnetic source imaging and reactivity to rhythmical stimulation in tuberous sclerosis.

The present study combined functional magnetoencephalography (MEG) and anatomical magnetic resonance imaging (MRI) information in three patients affected by tuberous sclerosis and partial epilepsy. MEG recordings were performed during both spontaneous and visual evoked activity. The former showed a large variety of complexes whose spatial and temporal distribution suggested different neuronal populations acting simultaneously in the same focal district. When these data were integrated with MRI images (magnetic source imaging, MSI) there was agreement in the definition of tubers and extension of the epileptogenic area. Furthermore, cortical reactivity to rhythmical stimulation was studied with trains of visual stimuli according to a recently proposed frequency responsiveness procedure (FRP). As compared to normal controls, a large 6 Hz activity was observed during the pause after a non-resonant stimulation. This altered resonance property may indicate a disturbed primary sensory processing notwithstanding a preserved associated processing. These results show that neuronal malfunctioning in tuberous sclerosis complex patients may not be restricted to the area of cortical tubers, but can also affect functionally correlated regions.

Adolescent↗
PubMed1998

Changes in cerebral blood flow velocities during childhood absence seizures.

A simultaneous recording of mean flow velocity in the right middle cerebral artery by transcranial Doppler ultrasonography and electroencephalographic activity was performed in 5 children with multiple daily typical absence seizures. Twenty-eight absence episodes were recorded. Mean flow velocity increased gradually a few seconds before the clinical and electroencephalographic manifestations of each seizure and reached the maximum values (range of increase: 25.5-42.8% with respect to baseline) within 2-3 seconds from their onset. This increase was then followed by a fast reduction in flow velocity, with the lowest levels (range of decrease: 30.8-44.0% with respect to baseline) recorded within 4-6 seconds from the end of each absence seizure. These findings suggest that changes in cerebral blood flow and activity are quite complex during absence seizures and that they do not fully correlate with clinical and electroencephalographic manifestations.

Analysis of Variance↗