Gabrielle Rudolf

Vigabatrin, the GABA-transaminase inhibitor, damages cone photoreceptors in rats.

Epileptic patients experienced an irreversible loss of their peripheral visual field upon treatment with vigabatrin (gamma‐vinyl GABA), an inhibitor of the GABA degrading enzyme, GABA transaminase. Subsequently, central visual function was reported to also be irreversibly altered. This visual loss is associated with a decrease in the electroretinogram measurement localizing the deficit to the retina. To investigate its cellular origin, we treated rats daily with vigabatrin for 45 days. Two days after arresting this treatment, rats exhibited an irreversible decrease in the photopic electroretinogram, the flicker response, and the oscillatory potentials. These functional alterations were associated with a peripheral disorganization of the outer retina. However, photoreceptor damage was not limited to these disorganized areas, but cone inner and outer segments were severely injured in more central areas and their numbers were irreversibly decreased by 17 to 20%. Ultrastructural examination of the retina confirmed the presence of major photoreceptor damages, which were further supported by terminal deoxynucleotidyltransferase–mediated dUTP nick end labeling (TUNEL) and caspase‐3 activation both indicative of photoreceptor apoptosis. This study suggests that the visual field loss in vigabatrin‐treated epileptic patients may result from a sequence of events starting from cone cell injury to a more severe disorganization of the photoreceptor layer.

Polygenic Control of Idiopathic Generalized Epilepsy Phenotypes in the Genetic Absence Rats from Strasbourg (GAERS)

Summary:u2003 Purpose: Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike‐and‐wave discharges (SWDs) on electroencephalographic recordings, concomitant with behavioral arrest. The GAERS (genetic absence rats from Strasbourg) strain, a well‐characterized inbred model for idiopathic generalized epilepsy, spontaneously develops EEG paroxysms that resemble those of typical absence seizures. The purpose of this study was to investigate the genetic control of SWD variables by using a combination of genetic analyses and electrophysiological measurements in an experimental cross derived from GAERS and Brown Norway (BN) rats.

Cerebral correlates of hemispheric lateralization during a pitch discrimination task: an ERP study in dichotic situation.

OBJECTIVEnElectrophysiological correlates of perceptual asymmetry for dichotic pitch discrimination were investigated in 12 right-handed volunteers, whose dichotic listening performances attested the classical right ear advantage in a verbal discrimination task.nnnMETHODSnEvent related potentials (ERPs), elicited by dichotic and binaural pairs of tones applied in a classical oddball paradigm including right ear targets, left ear targets and binaural targets (5% occurrence each) were recorded from medial and lateral scalp locations. Latencies and baseline to peak amplitudes were measured for P1, N1, P2, N2 and P3 components.nnnRESULTSnERPs recorded in response to dichotic (compared with binaural) target pairs, exhibited delayed latencies for N2 and P3, correlated with prolonged RTs, probably linked to greater difficulty in identification of the target. They also displayed enhanced N1 and P2 voltages, which may reflect the simultaneous activation of two different populations of neurons in the auditory cortical areas. We observed specific lateralization effects for pitch discrimination with a left ear advantage on latency of early components.nnnCONCLUSIONSnTogether with amplitude asymmetries in the N2 component, the findings bring strong electrophysiological support to Kimuras structural model for dichotic perceptions with a right hemisphere prevalence in a pitch discrimination task.

Electrophysiological evidence of persisting unilateral auditory cortex dysfunction in the late outcome of Landau and Kleffner syndrome.

OBJECTIVESnIn the late outcome of Landau and Kleffner syndrome (LKS), a childhood-acquired epileptic aphasia, most patients show after complete recovery of epilepsy a permanent one-ear extinction on dichotic listening tests contralateral to the temporal cortex previously affected by the epileptic focus. The pathophysiological significance of this dichotic extinction is not yet understood. It may be a consequence of a permanent dysfunction in the auditory system due to epileptic activity during the maturing period of the auditory system. Evoked potentials were used to check this hypothesis and to localize the level of the dysfunction along the auditory pathways.nnnMETHODSnEarly, middle latency and late auditory evoked potentials were recorded in 5 right-handed children having recovered from LKS. They were compared with those of 5 control children paired for age and gender.nnnRESULTSnIn all 5 LKS patients, early and middle latency auditory evoked potentials were normal. But the amplitude of N1c (arising from associative auditory areas) was strongly reduced at temporal electrodes contralateral to the extinguished ear, whereas latency and amplitude of N1b (related to primary auditory areas) were in the normal range.nnnCONCLUSIONSnUnilateral voltage reduction of late auditory evoked potentials over the temporal areas previously involved by epileptic discharges suggests a permanent dysfunction in the associative auditory cortex, the behavioral expression of which is the unilateral dichotic extinction.

Dichotic listening performances in the follow-up of Landau and Kleffner syndrome

Abstract In the follow-up study of 4 children with acquired epileptic aphasia or Landau and Kleffner syndrome, dichotic listening studies evidenced a unilateral ear extinction. In the four cases, the dichotic extinction was contralateral to the temporal cortex involved in the generation of epileptic discharges during the active period of epilepsy. This pattern of dichotic performances persisted several years after the complete recovery from epilepsy and EEG normalization. The long-lasting dichotic extinction revealed a permanent dysfunction in the temporal auditory system that may be a consequence of the presence of an active epileptogenic focus during the critical period of functional differentiation of the temporal cortex.

Pentylenetetrazol-induced status epilepticus up-regulates the expression of glucose transporter mRNAs but not proteins in the immature rat brain

Prolonged pentylenetetrazol (PTZ)-induced seizures increase cerebral energy demands in a region-specific manner. During PTZ seizures, cerebral glucose utilization increases over control levels in all brain regions at 10 days while 21-day-old rats exhibit increases, decreases or no change. To explore the effects of such acute changes in metabolic demand on the expression of glucose transporter proteins mediating glucose delivery to brain, we studied the consequences of PTZ seizures on GLUT1 and GLUT3 mRNAs and proteins between 1 and 72 h after seizure induction. At both ages, seizures induced a rapid up-regulation of GLUT1 and GLUT3 mRNAs which was prominent at 1 and 4 h, and was greater at 10 than at 21 days. By 24 h and 72 h, the levels of the mRNAs of the two transporter returned to control levels or were slightly down-regulated. The levels of GLUT1 and GLUT3 proteins were not affected by the seizures and only scattered decreases in GLUT3 protein were recorded, mainly in midbrain-brainstem areas. These data show that acute pentylenetetrazol seizures induce a rapid up-regulation of the GLUT1 and GLUT3 mRNAs, but do not result in measurable increases in protein levels, suggesting translational regulation.

Pathophysiological aspects of Landau-Kleffner syndrome: from the active epileptic phase to recovery.

Publisher Summary In their original description of the syndrome of “acquired aphasia with convulsive disorder,” Landau and Kleffner (1957) suggested “that persistent convulsive discharges in brain tissue largely concerned with linguistic communication result in the functional ablation of these areas for normal linguistic behavior.” In further case studies, the observation of continuous epileptic discharges in electroencephalograms (EEGs) recorded during sleep agreed with this early suggestion. Although several group studies emphasized the almost parallel fluctuation of aphasic disorders and EEG abnormalities, the causal relationship between epileptiform EEG discharges and the language defect remains a matter of debate. Another subject of discussion concerns the outcome of aphasia after recovery of epilepsy that typically occurs at the beginning of adolescence. In the Landau-Kleffner syndrome (LKS), the prognosis of aphasia varies in a manner opposite that observed after structural lesions of the left hemisphere. To further elucidate the pathophysiological basis of aphasia and its poor outcome in LKS, this chapter reexamines five clinical studies of LKS with particular emphasis on electrophysiological and metabolic findings and their relationship to neuropsychological deficits. The data presented and discussed covers a follow-up period extending for each case from the active period to the late recovery phase of epilepsy lasting from 7 to 15 years. The chapter summarizes the clinical histories and neuropsychological findings gathered during the period when the children were aphasic and epileptic and after recovery and focuses on the experimental data supporting focal or regional cerebral dysfunction underlying this particular acquired childhood aphasia.