Biomedical subjects

I de las Cuevas

Publications and source records attributed to I de las Cuevas.

5 recordsLinked to original sources

PubMed2005

Ion channels and epilepsy.

The role of voltage-gated and ligand-gated ion channels in epileptogenesis of both genetic and acquired epilepsies, and as targets in the development of new antiepileptic drugs (AEDs) is reviewed. Voltage-gated Na+ channels are essential for action potentials, and their mutations are the substrate for generalised epilepsy with febrile seizures plus and benign familial neonatal infantile seizures; Na+ channel inhibition is the primary mechanism of carbamazepine, phenytoin and lamotrigine, and is a probable mechanism for many other classic and novel AEDs. Voltage-gated K+ channels are essential in the repolarisation and hyperpolarisation that follows paroxysmal depolarisation shifts (PDSs), and their mutations are the substrate for the benign neonatal epilepsy and episodic ataxia type 1; they are new targets for AEDs such as retigabine. Voltage-gated Ca2+ channels are involved in neurotransmitter release, in the sustained depolarisation-phase of PDSs, and in the generation of absence seizures; their mutations are a substrate for juvenile myoclonic epilepsy and the absence-like pattern seen in some mice; the antiabsence effect of ethosuximide is due to the inhibition of thalamic T-type Ca2+ channels. Voltage-gated Cl- channels are implicated in GABA(A) transmission, and mutations in these channels have been described in some families with juvenile myoclonic epilepsies, epilepsy with grand mal seizures on awakening or juvenile absence epilepsy. Hyperpolarisation-activated cation channels have been implicated in spike-wave seizures and in hippocampal epileptiform discharges. The Cl- ionophore of the GABA(A) receptor is responsible for the rapid post-PDS hyperpolarisation, it has been involved in epileptogenesis both in animals and humans, and mutations in these receptors have been found in families with juvenile myoclonic epilepsy or generalised epilepsy with febrile seizures plus; enhancement of GABA(A) inhibitory transmission is the primary mechanism of benzodiazepines and phenobarbital and is a mechanistic approach to the development of novel AEDs such as tiagabine or vigabatrin. Altered GABA(B)-receptor function is implicated in spike-wave seizures. Ionotropic glutamate receptors are implicated in the sustained depolarisation phase of PDS and in epileptogenesis both in animals and humans; felbamate, phenobarbital and topiramate block these receptors, and attenuation of glutamatergic excitatory transmission is another new mechanistic approach. Mutations in the nicotinic acetylcholine receptor are the substrates for the nocturnal frontal lobe epilepsy. The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies.

Action Potentials↗

PubMed2000

[Ion channels and epilepsy].

OBJECTIVE: We review the role of ligand-gated ion channels and voltage-gated ion channels as a substrate for the epileptogenesis and as targets in the development of new antiepileptic drugs. DEVELOPMENT: Voltage-gated calcium channels are involved in the release of neurotransmitters, in the sustained depolarization-phase of paroxysmal depolarisation shifts (PDS), and in the generation of absences; they are also the genetic substrate of generalized tonic-clonic convulsions and absence-like pattern seen in some mice. The voltage-gated potassium channel has been implicated in the hyperpolarization-phase of PDS, it is the genetic substrate of the long QT syndrome, benign neonatal epilepsy, and episodic ataxia/myokymia syndrome, and it is the target of some antiepileptic drugs which activate this channel. The voltage-gated sodium channel is the target of most of the classical and newer antiepileptic drugs; it is also the substrate for generalized epilepsy with febrile seizures plus. The sodium channel of the nicotinic acetylcholine receptor is the substrate for nocturnal frontal lobe epilepsy. The sodium channels of the AMPA and KA glutamate receptors have been proposed as substrate for juvenile absence epilepsy and are a target for new antiepileptic drugs which inhibit it. The calcium channel of the NMDA glutamate receptor has been implicated in the sustained depolarization-phase of PDS and in epileptogenesis after kindling and is a main target for new antiglutamate drugs. The chloride channel of the GABAA receptor is responsible for the rapid hyperpolarization of PDS, it has been involved in epileptogenesis after kindling, it may be the substrate of the Angelman syndrome, and it is activated by many classical and new antiepileptic drugs. CONCLUSION: The knowledge of the role of the ion channels in the epilepsies is allowing the design of new and more specific therapeutic strategies.

Angelman Syndrome↗

PubMed1999

[Epileptic signs of metabolic origin].

INTRODUCTION: It is very difficult to identify metabolic causes of epileptic crises. This is partly because metabolic disorders are not fully understood and partly because the complementary tests required for their identification can be undertaken only in a few laboratories. DEVELOPMENT: We describe the characteristics of the metabolic disorders which may most frequently lead to epileptic crises occurring during the neonatal period, the first year of life, between the ages of one and six years and between six and fifteen years of age. We also emphasize the findings which may help in orientation towards diagnosis of these metabolic disorders, and the complementary tests required for confirmation.

Child↗

PubMed1998

[Diagnostic focus on the child with myoclonic seizures in isolation or associated with other types of seizures].

Myoclonus may be observed in children with mild or severe epileptic syndromes. Both types are seen at characteristic ages, together with other factors: aetiology, family history, hereditary pattern, effect on psychomotor development and EEG-EMG findings. In children with progressive or degenerative encephalopathies and myoclonus, better known as progressive myoclonic epilepsy, there are also specific clinical data, together with biological and genetic markers which permit identification. The most specific clinical characteristics of each of these clinical pictures are described, as are the complementary tests which permit confirmation of these diagnoses.

Adolescent↗

PubMedDate not supplied

[Hereditary neuropathy with liability to pressure palsies in childhood].

INTRODUCTION: The diagnosis of hereditary neuropathy with liability to pressure palsies during childhood is uncommon, since the disorder is still asymptomatic and the clinical features are nonspecific. CLINICAL CASE: We present a case of hereditary neuropathy with liability to pressure palsies in a seven and a half year old girl with deteriorating clinical findings of 'pies cavos', scoliosis, difficulty in walking and torticollis, but without episodes of paralysis. On the electroneurographic (ENG) study numerous anomalies of sensory and motor nerve conduction were seen, especially at sites of nerve trapping, both in the patient and in her mother; genetic study showed deletions of chromosome 17p11.2 in both. CONCLUSIONS: Hereditary neuropathy with liability to pressure palsiesin childhood may follow a course which does not show typical pressure palsies. Therefore the ENG study is very important for detection of the disorder. Torticollis, as well as pies cavos and scoliosis, is frequently seen in neuropaediatric clinics, so the possibility, as in the case reported, that this is part of the clinical spectrum of hereditary neuropathy with liability to pressure palsies should be considered. With diagnostic confirmation on genetic studies, nerve biopsy is not necessary.

Biopsy↗