Biomedical subjects

T Granata

Publications and source records attributed to T Granata.

34 records · Page 2Linked to original sources

PubMed1997

Lamotrigine plasma concentrations in children and adults: influence of age and associated therapy.

The effects of age and concomitant treatment on plasma lamotrigine (LTG) concentration/dose (C/D) ratios were retrospectively evaluated on 482 consecutive routine LTG determinations from 106 chronically-treated patients with epilepsy (40 children and adolescents aged younger than 16 years, and 66 adults aged 17 to 62 years). A linear dose/level relationship was observed in individual patients but not in the cumulative analysis, which failed to show any correlation between the administered LTG dose and plasma concentrations. In the adult group, there were no correlations between the administered LTG dose and plasma concentrations. Associated antiepileptic therapy affected the LTG concentration/dose ratio, which was significantly higher in the patients receiving valproic acid (3.4 +/- 2.0, n = 23) and significantly lower in those treated with enzyme-inducing antiepileptic drugs (0.6 +/- 0.5, n = 57) than in the patients receiving valproic acid in combination with enzyme-inducing antiepileptic drugs, ethosuximide, vigabatrin, or clobazam (1.9 +/- 1.6, n = 26). The LTG C/D ratios significantly increased with increasing plasma valproic acid concentrations, and significantly decreased with increasing phenytoin concentrations. The effect of enzyme-inducing antiepileptic drugs increased with the number of associated drugs. A clear age effect was demonstrated in the homogeneously treated subgroups, in all of which adults had higher C/D ratios than children.

Adolescent↗

PubMed1997

Periventricular nodular heterotopia: epileptogenic findings.

PURPOSE: We studied 17 patients with periventricular nodular heterotopia (PNH) to further investigate the electroclinical pictures and semiology of the associated seizures. METHODS: PNH was diagnosed by means of magnetic resonance imaging (MRI). The patients' clinical and familial histories were carefully analyzed, and their electroclinical features and course of epilepsy followed for periods ranging from 10 months to 22 years. The electroclinical data were compared with those of previously reported PNH cases. RESULTS: The patients were subdivided into those with bilateral (7) and unilateral (10) PNH. The former were mainly characterized by structural abnormalities in the posterior cerebral fossa and multiple seizure types; the latter were characterized by the paratrigonal location of the malformation and, frequently, by elementary seizures with a visual or auditory onset. Focal seizures were drug resistant in most cases. The interictal EEG abnormalities were always focal and consistent with the location of the PNH. A previously unreported photic driving of posterior background activity was observed in all patients and was always consistent with the PNH location. CONCLUSIONS: Our present findings and previously reported data show that bilateral and unilateral PNH cases are different in their morphological and electroclinical features and may be determined by different etiologies. The female predominance, frequent familial occurrence, and positive family history for epilepsy suggest that genetic factors may be involved in the genesis of bilateral and symmetrical PNH, whereas the presence of prenatal risk factors and its location in the watershed paratrigonal area suggest that vascular mechanisms may determine unilateral PNH.

Adolescent↗

PubMed1997

Familial schizencephaly associated with EMX2 mutation.

We describe two brothers aged 8 and 10 affected by severe bilateral schizencephaly, carrying an identical point mutation of the homeobox gene EMX2. Both children had severe neurologic deficits and mental retardation, although they differed in the anatomic extent of the brain malformation and in the severity of the clinical picture. The present findings, together with the reported cases of schizencephaly associated with EMX2 mutations, support the hypothesis that, at least in some cases, schizencephalies are determined by deleterious mutations of this homeobox gene. The different morphoclinical pictures suggest that, besides the EMX2 mutation, other factors are relevant in determining the severity of the brain malformation and clinical picture.

Brain↗

PubMed1996

Neuronal migration disorders and epilepsy: a morphological analysis of three surgically treated patients.

Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.

Brain↗

PubMed1996

Schizencephaly: neuroradiologic and epileptologic findings.

PURPOSE: Nine patients affected by schizencephaly were analyzed, and the epileptologic findings prospectively studied, to define the relations between the anatomic brain malformations and clinical outcome. METHODS: The schizencephaly was diagnosed by means of magnetic resonance imaging (eight cases) or computed tomography (one case). The clinical histories of all the patients were analyzed, and a psychometric evaluation was made. The electroclinical features and course of epilepsy in the six patients with epilepsy were prospectively followed up for a period ranging from 3 to 14 years. RESULTS: The patients were divided into those who were unilaterally (six) and those bilaterally (three) affected. The former were characterized by mild neurologic deficits and late-onset epilepsy; their epileptologic features were consistent in terms of age of onset, seizure semiology, the absence of secondary generalization, and resistance to antiepileptic treatment. The patients with bilateral schizencephaly associated with other brain malformations were characterized by severe neurologic deficits but were only rarely affected by epilepsy, which was always completely controlled by antiepileptic treatment. CONCLUSIONS: Our data show that the extent of anatomic malformation is strictly related to the severity of motor and mental impairment but not to the presence or severity of epilepsy. The absence of prenatal risk factors for brain damage in our series, previously described familial cases of schizencephaly, and the recent report of mutations in homeobox gene EMX2 associated with cases of schizencephaly all indicate that genetic factors may play a key role in the pathogenesis of this brain malformation.

Adolescent↗

PubMed1995

Linguistic development in a patient with Landau-Kleffner syndrome: a nine-year follow-up.

A longitudinal linguistic analysis of aphasic disorder in a 15-year-old boy affected by Landau-Kleffner syndrome followed since the age of 6 is reported. The phonological, morphosyntactic and lexical levels of verbal deficits have been evaluated by means of collected samples of spontaneous language and a battery of linguistic tests. The clinical course has fluctuated with improvement and worsening of aphasia and epilepsy; at the end of the follow-up the boy was seizure-free and a medium-degree disturbance in language production and comprehension was present. The results of the linguistic evaluation suggest that the aphasic disturbance was related to a deficiency in phonological decoding which leads to phonological, morphosyntactic and lexical disturbances. A temporal relationship between the electroclinical picture and the aphasia has been observed: the persistent improvement in linguistic performances took place only after the disappearance of the seizures and of the EEG epileptic anomalies during sleep.

Adolescent↗

PubMed1994

Band heterotopia: correlation of outcome with magnetic resonance imaging parameters.

The "band heterotopia" or "double cortex" is a brain anomaly that is presumed to result from a premature arrest of neuronal migration. Patients with this anomaly are reported to have a variable clinical course that has been, heretofore, unpredictable. The clinical records and magnetic resonance (MR) imaging studies of 27 patients with band heterotopia were retrospectively reviewed in an attempt to determine whether imaging findings are useful in predicting clinical outcome of affected patients. Statistical analyses revealed the following correlations: (1) severity of T2 prolongation in the brain with motor delay (p = 0.03); (2) degree of ventricular enlargement with the age of seizure onset (p = 0.04), and with development and intelligence (p = 0.04); (3) severity of pachygyria with the age of seizure onset (p = 0.01), seizure type (p = 0.03), and an abnormal neurologic examination (p = 0.002); (4) parietal involvement with delayed speech development (p = 0.05); (5) occipital involvement with age of seizure onset (p = 0.006); (6) age of seizure onset with development and intelligence (p = 0.03) and with an abnormal neurologic examination (p = 0.04); and (7) severity of the pachygyria and thickness of band with development of symptomatic generalized epilepsy (p = 0.002 and p = 0.02, respectively) and Lennox-Gastaut syndrome (p = 0.002 and p = 0.01, respectively).

Brain Diseases↗

PubMed1994

Double cortex syndrome: electroclinical study of three cases.

We describe three female patients (aged 10, 11 and 21 years) with a Magnetic Resonance appearance of band heterotopia, a diffuse neuronal migration disorder, also known as double cortex syndrome. The clinical picture was characterized by the association of epilepsy and mental retardation in all three cases, as has been previously described in patients with double cortex syndrome. The epileptic syndrome (Lennox-Gastaut syndrome in one case, and symptomatic partial epilepsy in the other two), the response to medical treatment, and the severity of mental retardation were markedly different in the three patients. No clear-cut relationship was found between the clinical picture and the severity of the neuronal migration disorder, as revealed by magnetic resonance imaging. In the three cases, EEG shares some common features: multifocal epileptic activity with frequent bilateral diffusion, and high-amplitude anterior fast activity, intermingled in two patients with bursts of repetitive spikes.

Adult↗

PubMed1993

Lamotrigine in resistant childhood epilepsy.

Fourteen children (6 M, 8 F) suffering from refractory epilepsy received LTG as add-on therapy. LTG was administered twice daily at dosages increasing up to 2 mg/kg/day (for patients taking VPA) or to 10 mg/kg/day for patients taking AEDs that induce hepatic metabolism. The drug was withdrawn for side effects in 3 cases (rash: two cases, hirsutism: one), because of increased seizure frequency in 2 cases and because of unchanged seizure frequency in one. One patient died from acute respiratory failure, after repeated respiratory tract infections. A decrease in seizure frequency after one year of treatment with LTG was observed in 6 of the 7 patients who completed the study. The median total seizure frequency decreased from 10.7 +/- 7.3 to 3.8 +/- 4.6 seizures per day. At the end of the study, seizure frequency had decreased by more than 50% in 2 patients, by more than 75% in 2 patients, and 2 patients were seizure-free; in the remaining patient seizure frequency was unchanged. The best results were obtained with plasma LTG concentrations ranging from 0.5 to 5.4 micrograms/ml; no further improvement was observed at higher LTG concentrations.

Adolescent↗

PubMed1992

Changes in unbound and total valproic acid concentrations after replacement of carbamazepine with oxcarbazepine.

Total and free valproic acid (VPA) concentrations were measured in patients switched from a combined VPA and carbamazepine (CBZ) to a combined VPA and oxcarbazepine (OXC) therapy, both administered in individualized daily doses. Four young epileptic patients (13-17 years old) were studied for a 12-week period, total and free VPA concentrations being analyzed just before and 4 h after the morning dose, at the end of VPA and CBZ therapy, and 2 and 10 weeks after CBZ was replaced by OXC. The expected increase in the level/dose (L/D) ratio of total VPA observed at the end of the study was preceded by a clear-cut increase in the L/D ratio of free VPA, which led to VPA-related side effects and required the retitration of VPA daily doses.

Adolescent↗

PubMed1992

Malformations in offspring of 305 epileptic women: a prospective study.

This paper deals with malformations detected in 26 of 315 newborns of 305 epileptic mothers followed prospectively. In 3 more cases, malformations were detected in utero and therapeutic abortion was performed. Two hundred and seven women were on monotherapy, 102 on polytherapy and 9 were not treated. In total, malformations overall incidence was 9.1%. Minor anomalies were detected in 42 newborns (13.3%). A higher rate of malformations and minor anomalies was found among offspring of mothers treated with valproic acid (VPA). In the VPA group, mothers of malformed babies had higher plasma levels in the first trimester than mothers of babies without malformations. The need for accurate prenatal diagnostic studies in pregnant women with epilepsy is stressed.

Abnormalities, Drug-Induced↗

PubMed1992

Intrauterine growth in the offspring of epileptic mothers.

The present paper concerns the fetal growth of 315 newborns of epileptic mothers prospectively followed from the beginning of pregnancy. In comparison with Italian standards, neonatal weight, length and head circumference at birth were below the 10th percentile in respectively 15.7%, 1.1% and 19.2% of the newborns. Weight at birth was above the 90th percentile in 8 cases. Observed frequencies were significantly higher than expected frequencies for both weight and head circumference. The percentage of newborns with a small head circumference increased significantly according to the number of drugs taken by the mother during the first three months of pregnancy: 7.1% with no drug, 16.8% with one drug, 23.6% with two drugs and 50% with three drugs. A statistically significant correlation was found between gestational age-adjusted head circumference and drug-level scores during the first trimester. Head circumferences below the 10th percentile were fewer among newborns treated with CBZ than among newborns treated with either PB or VPA.

Anticonvulsants↗

PubMed1990

Grazing in a turbulent environment: energy dissipation, encounter rates, and efficacy of feeding currents in Centropages hamatus.

The creation of feeding currents by calanoid copepods increases encounter rates of copepods with their food and provides and advantage in dilute nutritional environments. Small-scale turbulence has also been hypothesized to increase the encounter rate between planktonic predators and their food. Centropages hamatus was exposed to turbulent and nonturbulent environments at two prey concentrations to quantify the influence of turbulence on feeding current efficacy. Turbulent energy dissipation rates used in the experiment were in the range of 0.05-0.15 cm2. sec-3. In the nonturbulent environments, feeding currents increased the encounter rates of C. hamatus 3-5 times that of control encounter areas. In turbulent environments, encounter rates were not increased by feeding currents, yet C. hamatus continued to create feeding currents. Energetic calculations indicate a tradeoff in the value of turbulence to a copepod feeding on phytoplankton. While turbulence is probably beneficial at low food concentrations, it may be deleterious at high food concentrations.

Journal Article↗

PubMedDate not supplied

Burst suppression and impairment of neocortical ontogenesis: electroclinical and neuropathologic findings in two infants with early myoclonic encephalopathy.

We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. The neurons have been interpreted as abnormally persisting interstitial cells in 2.5-month-old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst-suppression phenomena.

Brain↗

PubMedDate not supplied

Comparative pharmacokinetic study of chewable and conventional carbamazepine in children.

Fifteen children (7 boys and 8 girls) with generalized tonic-clonic seizures (GTCS) and partial seizures with elementary or complex symptomatology, treated with carbamazepine (CBZ) alone (n = 7) or in combination with either phenobarbital (PB, n = 6) or clobazam (CLB, n = 2) given for at least 3 months at stable individualized doses and regimens, entered an open, within-patient, change-over study of consecutive periods, each lasting 2 weeks. During period 1, conventional CBZ was given; during period 2, a chewable CBZ formulation was substituted for conventional CBZ and given at the same total daily dosage with the same schedule as in period 1. Blood samples for measuring plasma concentration of both total CBZ and CBZ-10,11 epoxide (CBZ-E) were taken on the last day of each period. No significant difference between the two periods was noted in the mean +/- SD of Cmax, Css mean, and area under the curve (AUC) of total CBZ and CBZ-E. The two different CBZ formulations, administered at the same total daily dosage, can be considered bioequivalent.

Administration, Oral↗

PubMedDate not supplied

A number of schizencephaly patients including 2 brothers are heterozygous for germline mutations in the homeobox gene EMX2.

We report here that some patients affected by schizencephaly are heterozygous for mutations in EMX2, a homeobox gene implicated in the patterning of the developing forebrain. Schizencephaly is a very rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. Large portions of these may be absent and replaced by cerebrospinal fluid. We previously reported the presence of EMX2 mutations in 7 out of 8 sporadic cases of schizencephaly. We now extend this analysis to 10 additional patients, including 2 brothers. Six patients were found to be heterozygous for de novo mutations in EMX2. In particular, the 2 brothers show the same mutation affecting the splicing of the first intron, while this mutation is absent in their parents and in the 2 unaffected siblings.

Base Sequence↗