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Biomedical subjects

Catherine Chiron

Publications and source records attributed to Catherine Chiron.

8 recordsLinked to original sources
PubMed2003

Topiramate: efficacy and tolerability in children according to epilepsy syndromes.

To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in children less than 12 years of age with refractory epilepsy, according to epilepsy syndromes, we conducted an open, prospective, pragmatic and multicenter study in France. Efficacy was assessed, especially according to epilepsy syndromes, as well as tolerability. We included 207 children (41 of whom were less than 4 years of age). TPM was effective (responders with >50% decrease in seizure frequency) in 50% of 128 patients with partial epilepsy, and in 44% of 79 patients with generalized epilepsy. In case of generalized epilepsy, responders more frequently had generalized symptomatic epilepsy, severe myoclonic epilepsy and myoclono-astatic epilepsy, whereas response rate was mild in both infantile spasms and Lennox-Gastaut syndrome (LGS). Improvement was well maintained in all patients during the treatment period (median 5.6 months). Seizure frequency/severity increased (worsening) in 13% of patients with partial epilepsy and 17% with generalized epilepsy (particularly in those with infantile spasms), and resulted in withdrawal of TPM for 8%. The most frequently reported adverse events were moderate neurobehavioral and gastrointestinal disorders. Adverse events led to withdrawal of TPM from 13.5% of patients. Children less than 4 years of age had particularly good tolerability. Results confirm that TPM is effective and well tolerated in children under 12 years of age in a broad range of epilepsy syndromes, including refractory partial epilepsy, and symptomatic and myoclonic generalized epilepsy. Use of TPM should be considered in children under 4 years of age, and slow and progressive titration is important.

Anticonvulsants↗
PubMed2003

Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro.

PURPOSE: We developed a new in vitro preparation of immature rats, in which intact corticohippocampal formations (CHFs) depleted in magnesium ions become progressively epileptic. The better to characterize this model, we examined the effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice. METHODS: Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact CHFs of P7-8 rats, and extracellular recordings were performed in the hippocampus and neocortex. AEDs were applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Their ability to prevent or to delay the next ILE was examined. RESULTS: Valproic acid and benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam prevent the occurrence of seizures. In contrast, usual concentrations of carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In addition, LTG and CBZ aggravate seizures in one third of the cases. CONCLUSIONS: This intact in vitro preparation in immature animals appears to be quite resistant to most AEDs. Blockade of seizures was achieved with drugs acting mainly at the gamma-aminobutyric acid (GABA)A-receptor site but not with those that increase the amount of GABA. Drugs with a broad spectrum of activity are efficient but not those preferentially used in partial seizures or absences. We suggest that this preparation may correspond to a model of epilepsy with generalized convulsive seizures and could be helpful to develop new AEDs for refractory infantile epilepsies.

Age Factors↗
PubMed2002

Drug therapy for West's syndrome.

West's syndrome resists most of the standard anticonvulsants. It may respond, however, to steroids or to some of the newer drugs like vigabatrin.

Anticonvulsants↗
PubMed2002

Characteristics of epilepsy in focal cortical dysplasia in infancy.

To describe the poorly known characteristics of epilepsy during infancy in focal cortical dysplasia (FCD), one of the most frequent cause of infantile epilepsy. All 28 patients with FCD referred to two specialized centres were retrospectively studied regarding seizure characteristics, psychomotor evaluation, and response to medical and surgical treatment. All patients presented with early partial seizures. Semiology, but not the age of onset, depended on the topography of the dysplasia, with abnormal eye movements in all cases of posterior FCD. Eleven patients also developed infantile spasms (IS), mainly asymmetrical. IS were easily controlled with Vigabatrin or ACTH, but no partial seizures could be medically controlled except in one patient. All patients except one had abnormal neuropsychological findings. Fifteen patients had surgery, eight became seizure free, and seven were significantly improved regarding psychomotor development. Very early and refractory partial seizures, but easily controlled IS are the main characteristics of FCD in infancy. Only the focal ictal semiology may help differentiate the localization of FCD. Its intrinsic epileptogenicity could sustain this clinical pattern. Since the chances for medical control and normal neurodevelopment are poor, surgical treatment should be considered early in infants with FCD.

Age Factors↗
PubMed2002

Is refractory epilepsy preventable?

About a third of the patients diagnosed with epilepsy will not be fully controlled with antiepileptic drugs (AEDs), and many of them will have frequent and disabling seizures. These patients will undergo multiple drug trials, most often without complete seizure remission. Moreover, refractory epilepsy is associated with increased morbidity (from seizures and medications), social isolation, unemployment, and overall reduced quality of life. There is evidence that refractory epilepsy can be a progressive disorder, which, if controlled early, might never develop into a full syndrome with all of its associated sequelae. The difficulty lies in identifying at an early stage patients who are likely to progress to intractability. No currently known markers enable clinicians to make this identification with confidence. Advances in pharmacogenomics and our understanding of pharmacologic responsiveness in epilepsy may change this situation. Even now, we are able to identify many patients with a poor prognosis earlier than before, particularly in the pediatric population, in which syndromic classification may provide an approach to predict intractability. The early initiation of aggressive therapy may improve outcome and overall quality of life.

Disease Progression↗
PubMed2002

Late plasticity for language in a child's non-dominant hemisphere: a pre- and post-surgery fMRI study.

The ability of the right hemisphere to sustain the acquisition or the recovery of language after extensive damage to the left hemisphere has been essentially related to the age at the time of injury. Better language abilities are acquired when the insult occurs in early childhood (perinatal insults) compared with later occurrence. However, while previous studies have described the neuropsychological pattern of language development in typical cases, the neural bases of such plasticity remain unexplored. Non-invasive functional MRI (fMRI) is a unique tool to assess the neural correlates of brain plasticity through repeated studies, but the technique has not been widely used in children because of methodological limitations. Plasticity of language was studied in a boy who developed intractable epilepsy related to Rasmussen's syndrome of the left hemisphere at age 5 years 6 months, after normal language acquisition. The first fMRI study at age 6 years 10 months showed left lateralization of language networks during a word fluency task. After left hemispherotomy at age 9 years, the child experienced profound aphasia and alexia, with rapid recovery of receptive language but slower and incomplete recovery of expressive language and reading. Postoperative fMRI at age 10 years 6 months showed a shift of language-related networks to the right during expressive and receptive tasks. Right activation was seen mainly in regions that could not be detected preoperatively, but mirrored those previously found in the left hemisphere (inferior frontal, temporal and parietal cortex), suggesting reorganization in a pre-existing bilateral network. In addition, neuropsychological data of this case support the hypothesis of innately more bilateral distribution of receptive than expressive language. This first serial fMRI study illustrates the great plasticity of the child's brain and the ability of the right hemisphere to take over some expressive language functions, even at a relatively late age. It also suggests a limit for removal of the dominant hemisphere beyond the age of 6 years, a classical limit for the critical period of language acquisition.

Brain↗
PubMed2002

Computer-aided intrapatient comparison of brain SPECT images: the gray-level normalization issue applied to children with epilepsy.

UNLABELLED: A tool was developed for automated intrapatient comparison of brain SPECT images, with specific emphasis on gray-level normalization. METHODS: Ictal and interictal (99m)Tc-ethyl cysteinate dimer SPECT images were acquired for 6 children with partial epilepsy (age range, 2-10 y). For each patient, 3-dimensional rigid geometric ictal-to-interictal image registration optimizing different classic criteria (correlation coefficient, ratio uniformity) in a multiscale translation-rotation 6-parameter space was first performed. Gray-level normalization was then performed with different methods, using a 1- or 2-parameter linear model. In the 1-parameter case, the scaling factor was equal to the interictal-to-ictal ratio of the maximum, mean, or median values calculated within different reference volumes (whole brain or cerebellum) or obtained by linear regression between ictal and interictal counts in the brain or by maximizing a robust criterion, the number of deterministic sign changes in the subtraction images. In the 2-parameter case, the scaling factor and additive constant were estimated using these last 2 methods. For each patient, registration validity and normalization plausibility were assessed by considering the correlation scatterplot together with the different normalization lines and by comparing interictal and registered normalized ictal images using a twin display (with isocontours) in the 3 orthogonal planes. Three-dimensional volumes of interest could be selected on coupled interictal-subtraction images for further focused numeric comparison. RESULTS: After a satisfactory and stable geometric registration with both criteria, the different normalization methods led to similar subtraction images for 5 of 6 patients, except the maxima ratio, which gave noticeably different results in 2 patients. For the remaining patient, with highly dissimilar ictal-interictal images, the maxima ratio normalization was obviously wrong and the other 1-parameter methods probably better depicted the data than did the 2-parameter methods. CONCLUSION: When comparing intrapatient brain SPECT images, one should be aware of the potential impact of the gray-level normalization method on clinical interpretation. For ictal-interictal images, simple robust scaling should be recommended. In particular, image maximum should generally not be considered a valid reference, and no additive constant is needed in the linear gray-level normalization model.

Brain↗