[Paroxysmal neurogenetic and neurometabolic disorders]. / Trastornos neurogenéticos y neurometabólicos paroxísticos.

AIM: To provide an overview of those neurological disorders that are mainly characterized by a paroxysmal pattern of involvement, and in which a clear genetic or metabolic etiology has been identified. DEVELOPMENT: The term 'paroxysmal' refers to the abrupt onset of clinical manifestations in a relatively stereotyped manner, usually upon exposure to specific triggering factors with an almost complete resolution of such findings between attacks. They are commonly not associated to either a relentless progression or a stepwise deterioration, and the majority of them do not lead to the development of gross neuropathological abnormalities. Although they are difficult to classify due to the heterogeneity of their clinical manifestations and underlying deficits, a neuroaxis-based approach is proposed for practical purposes, for example, from those conditions affecting predominantly cortical grey matter (manifesting mainly with seizures) to those with an almost exclusive muscular and/or neuromuscular pattern of involvement. The majority of them are caused by genetic defects in either transporters or neuronal channels, which can be either ions or neurotransmitters. In recent years, the concept of 'channelopathies' has grown in acceptance in the medical field, although not all of the described disorders are caused by defects in molecular channels. CONCLUSIONS: Despite their individual rarity, as a group, they are important to the neurologist due to the advances that their understanding have provided for the development of the field of neurogenetics and neurosciences in general.

Trastornos neurogenéticos y neurometabólicos paroxísticos / Paroxysmal neurogenetic and neurometabolic disorders

Objetivo. Revisar aquellos trastornos neurológicos caracterizadosprincipalmente por un patrón de afectación paroxístico,y en los cuales se ha identificado una etiología genética o metabólicaclara. Desarrollo. El término ‘paroxístico’ hace referencia alinicio repentino de las manifestaciones clínicas de una manerarelativamente estereotipada, normalmente tras la exposición a unosfactores desencadenantes específicos con la resolución casi total deestos signos entre los episodios. Típicamente no se asocian a unaevolución incesante ni a un deterioro gradual, y la mayoría no conducenal desarrollo de anomalías neuropatológicas importantes.Aunque por la heterogeneidad de las manifestaciones clínicas ydeficiencias subyacentes resultan difíciles de clasificar, por motivosprácticos se propone una aproximación basada en el eje cerebroespinalque permite organizarlas, por ejemplo, desde las patologíasque afectan de modo predominante a la sustancia gris de la cortezacerebral (manifestadas principalmente en forma de crisis) hasta lasque tienen un patrón de afectación casi exclusivamente musculary/o neuromuscular. La mayoría está causada por anomalías genéticasen los transportadores o en los canales neuronales, que puedenser iones o neurotransmisores. En los últimos años, el concepto de‘canalopatías’ ha tenido mayor aceptación en el ámbito médico,aunque no todos los trastornos descritos son causados por defectosen los canales moleculares. Conclusión. A pesar de su poca frecuenciaindividual, como grupo son importantes para el neurólogoporque el conocimiento más profundo logrado ha permitido importantesavances en la neurogenética y las neurociencias en general

Aim. To provide an overview of those neurological disorders that are mainly characterized by a paroxysmalpattern of involvement, and in which a clear genetic or metabolic etiology has been identified. Development. The term‘paroxysmal’ refers to the abrupt onset of clinical manifestations in a relatively stereotyped manner, usually upon exposureto specific triggering factors with an almost complete resolution of such findings between attacks. They are commonly notassociated to either a relentless progression or a stepwise deterioration, and the majority of them do not lead to thedevelopment of gross neuropathological abnormalities. Although they are difficult to classify due to the heterogeneity of theirclinical manifestations and underlying deficits, a neuroaxis-based approach is proposed for practical purposes, for example,from those conditions affecting predominantly cortical grey matter (manifesting mainly with seizures) to those with analmost exclusive muscular and/or neuromuscular pattern of involvement. The majority of them are caused by genetic defectsin either transporters or neuronal channels, which can be either ions or neurotransmitters. In recent years, the concept of‘channelopathies’ has grown in acceptance in the medical field, although not all of the described disorders are caused bydefects in molecular channels. Conclusions. Despite their individual rarity, as a group, they are important to the neurologistdue to the advances that their understanding have provided for the development of the field of neurogenetics and neurosciencesin general

Injections of the NMDA-antagonist D-2-amino-7-phosphonoheptanoic acid (AP-7) into the nucleus accumbens of rats enhance switching between cue-directed behaviours in a swimming test procedure.

The present study explores the behavioural effects of intra-accumbens injections of D-2-amino-7-phosphonoheptanoic acid (AP-7), a selective competitive N-methyl-D-aspartate (NMDA) receptor antagonist, using a swimming test procedure, in which rats were forced to swim for 6 min. The behaviour of the rats was analysed in terms of cue-directed (CDBs) and non-cue-directed behaviours (NCDBs). AP-7 (100-500 ng/0.5 microliter) dose-dependently enhanced the number of switches to CDBs, without affecting the number of switches to NCDBs. Further analysis of the data showed that the number of switches between CDBs was enhanced, while no effect was found on the number of switches from NCDBs to CDBs, from CDBs to NCDBs or between NCDBs. These data suggest that the NMDA-receptor in the nucleus accumbens is involved in the ability to switch between cue-directed behaviours.

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.