Treatment of status epilepticus in children.

Status epilepticus (SE) is a condition characterised by frequent and prolonged epileptic seizures which frequently develop in the immature brain. Fever, metabolic disorders and subtherapeutic concentrations of antiepileptic drugs are the most common factors precipitating SE in children. Progressive neuronal damage occurs if convulsive SE persists for more than 30 minutes, with neurological, epileptic and cognitive sequelae. Unfortunately, the immature brain is more predisposed to SE and its sequelae than the mature brain. SE may be categorised as convulsive, nonconvulsive or neonatal according to its responsiveness to antiepileptic drugs. Regardless of category, the main objective in the treatment of SE is to abort the seizures and treat the inciting condition. Treatment includes: (i) monitoring of hydration, electrolyte balance, and cardiocirculatory and pulmonary functions; and (ii) rapid intravenous administration of specific antiepileptic drugs. Benzodiazepines (usually diazepam, lorazepam or midazolam) are the most effective agents for the initial treatment of convulsive and nonconvulsive SE. In particular, midazolam infusion is an effective and well tolerated therapeutic approach for the management of childhood SE, including refractory SE. Phenytoin remains an excellent agent because of its long duration of action, but it is not active in nonconvulsive SE. Fosphenytoin, a phenytoin prodrug, represents a significant advance in the treatment of children with convulsive SE. Intravenous phenytoin and intramuscular phenobarbital (phenobarbitone) are generally used in neonatal SE; other agents are rarely used.

Neuropsychological disorders related to interictal epileptic discharges during sleep in benign epilepsy of childhood with centrotemporal or Rolandic spikes.

Nine children (five males, four females; age range 6 years 1 month to 11 years 1 month) affected by benign epilepsy of childhood with centrotemporal or Rolandic spikes (BECRS) with EEG evidence of marked activation of interictal epileptic discharges (IEDs) during sleep, and nine unaffected control children matched for age, sex, and socioeconomic status, were enrolled in a prospective study. At the time of detection of IED activation during sleep, patients showed a mean Full-Scale IQ score within the normal range, but significantly below that of control participants; neuropsychological assessment revealed disorders in visuospatial short-term memory (Corsi's Block Tapping Test), attention, and cognitive flexibility (Trail Making Test and Stroop Color-Word Test), picture naming, and fluency (Benton's Naming Test and Word Fluency), visuoperceptual skill (Ghent-Poppelreuter and Street Gestalt Completion Tests) and visuomotor coordination (Bender Test). After detection of IED activation during sleep, children were followed up for 2 years. At the time of IED remission (T1), neuropsychological re-evaluation showed a notable increase in IQ score and a significant improvement (t-test: p<0.007) in visuomotor coordination, non-verbal short-term memory, sustained attention and mental flexibility, picture naming, and visual-perceptual performance. At T1, patients' performance did not differ from the controls (Mann-Whitney U test).

Modulation of sleep interictal epileptiform discharges in partial epilepsy of childhood.

OBJECTIVE: NREM sleep increases the Interictal Epileptic Discharges (IEDs) in the majority of children affected by partial epilepsy (both symptomatic or cryptogenetic). Experimental data revealed that the normal sleep oscillations, leading to the appearance of spindles and delta waves on the surface EEG during NREM sleep, might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (slow wave activity, SWA, 0,5-4,5 Hz) and sigma activity (SA, 12.0-16.0 Hz) and can be used to assess the relationship between SA, SWA and IEDs during sleep. DESIGN AND METHODS: We have performed overnight continuous EEG-polysomnographic studies in 7 patients (mean age 7.2+/-1.3). The temporal series of SWA and SA were obtained from a spike-free derivation lead. The IEDs count was performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significant higher correlation between IEDs and SA with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between SA and IEDs. CONCLUSIONS: Our data suggest that the neural mechanisms involved in the generation of sleep spindles facilitate the IEDs production in childhood partial epilepsies at least in those strongly activated by sleep.

Relationship of sleep interictal epileptiform discharges to sigma activity (12-16 Hz) in benign epilepsy of childhood with rolandic spikes.

OBJECTIVE: The activation of interictal epileptic discharges (IEDs) by NREM sleep is a well-known phenomenon in benign epilepsy of childhood with rolandic spikes (BECRS). The activating properties of NREM sleep on IEDs have been attributed to increased synchronization within thalamocortical neurons. During NREM sleep two synchronizing mechanisms lead to the appearance of spindles and delta waves on the EEG. Spectral analysis technique is a suitable method that can be used to quantitatively describe the dynamics of delta (slow wave activity (SWA) 0.5-4.0 Hz) and sigma activity (12.0-16.0 Hz) during sleep. METHODS: In order to define more accurately the relationship between synchronizing mechanisms (spindles and delta activities) and IEDs during sleep in BECRS, we have performed overnight continuous EEG polysomnography studies in 9 patients (mean age 7.4 +/- 2.5 years). The temporal series of SWA and sigma values, derived from spectral analysis, have been obtained from a spike-free derivation lead. The IEDs count has been performed on the most active lead. Relationships between sigma and SWA and time series of IEDs were tested by means of correlation techniques after data normalization. RESULTS: Our results revealed a significant higher correlation between IEDs and sigma activity with respect to SWA in all the subjects, in total sleep time. The same analysis limited to NREM sleep highlights the better correlation between sigma and IEDs. CONCLUSIONS: Data suggest that during sleep of BECRS patients, IEDs are more sensitive to the promoting action of the spindle-generating mechanism than to the SWA-producing one.

A quantified analysis of sleep electroencephalography in anorectic adolescents.

BACKGROUND: Previous studies on sleep characteristics in anorexia nervosa have led to controversial results. This may be due to either the heterogeneity of the samples studied or to an intrinsic inadequacy of the scoring criteria. To obtain a more detailed analysis we have investigated sleep characteristics in a group of adolescents affected by anorexia nervosa using spectral analysis techniques. METHODS: After a baseline night, the sleep-electroencephalograms of 10 adolescent anorectic girls (age +/- SD = 14 +/- 2 years) and 10 age-matched control subjects were recorded and processed by a fast Fourier transformation routine. RESULTS: Anorectics showed an increased number of awakenings and wakefulness after sleep onset and a reduction of sleep efficiency and slow-wave sleep. Spectral analysis results revealed a significant reduction in the power spectral values of slow-wave activity (SWA; 0.5-4.5 Hz) band in all NREM-REM cycles of sleep and in the undisturbed and stable stage 4. Moreover the anorectic group was characterized by a concentration of SWA in the first NREM-REM cycle with an abrupt decay in the second part of the night. A positive correlation (r2 = .58, p < .01) between body mass index and the amount of SWA was found. CONCLUSIONS: Sleep of anorectic patients seems to be characterized by a weakness of SWA producing mechanisms. The positive correlation between body mass index and the amount of SWA appears to be consistent with the neurobiological consequences of the malnutrition state.

Electrical status epilepticus during sleep (ESES). Different clinical syndromes: towards a unifying view?

'Electrical status epilepticus during sleep' (ESES) is a typical childhood process of generalization of paroxysmal activity. Notwithstanding a number of intermediate forms, three syndromes included in the 1989 ILAE classification can be considered as prototypes: the 'continuous spike-waves during sleep' (CSWS syndrome), the 'acquired aphasia with convulsive disorder in children' (L-Kl syndrome) and the 'benign epilepsy of childhood with rolandic spikes' (BECRS), which can be considered as the benign end of the spectrum. The pathognomonic clinical and EEG features of these conditions are described. They can probably be considered, in a unifying view, to be based on a common pathogenetic factor. They are associated with neuropsychological and/or mental disturbances with differences probably due to the idiopathic or symptomatic origin of the underlying epileptic condition, the cortical area of the primary focal paroxysmal activity, the patient's age and the severity and duration of the paroxysmal dysfunction. Possible hypotheses on the physiopathogeneses of ESES and correlated neuropsychological disorders are summarized. Short cycles (3-4 weeks) of relatively high daily doses of diazepam (DZP) (0.5 mg/kg body weight) following a rectal DZP bolus of 1 mg/kg b.w. seem to be effective in the majority of ESES conditions. The somewhat underestimated problem of neuropsychological disorders correlated with ESES in BECRS is also considered.

[Aplasia and hypoplasia of the optic nerve. Comparison of 2 cases]. / Aplasia ed ipoplasia del nervo ottico. Comparazione di due casi.

Hypoplasia and aplasia of the optic nerve are congenital anomalies characterized respectively by a marked volume reduction (very small papilla, often identifiable only as a rosy-yellowish area from which the retinal vessels emerge) and by the absence of the optic disk (absence of the nerve and mainly of its vessels) and of the visual functions. These anomalies are often associated with malformations of the central nervous system and of the ocular structures. The defects originate in the embryonal period due to the arrested development of the mesodermal component towards the head of the optic nerve. The aim of this study is to try to interpret the different clinical manifestations of the disease by observing two cases (a female and a male) with a clinical picture of aplasia and hypoplasia of the optic nerve respectively. Both cases presented the following clinical characteristics: developmental defects of the optic nerve, severe microcephaly, positive IgG antibodies against CMV. The association of the optic nerve defect with microcephaly is due to the embryogenic origin of the optic vescicle by prosencephalon. The resulting clinical picture is probably the outcome of an interfering process that the authors have presumed in CMV intrauterine infection, after having excluded the most frequent teratogenic agents (maternal diabetes, tabagism, intake of alcohol ad drugs). Moreover, the different degree of ocular involvement and the different time of onset of the intrauterine pathogenic insult in the two cases could account for the different clinical pictures.

Early-onset progressive encephalopathy with migrant, continuous myoclonus.

Three unusual cases of focal continuous myoclonus with onset during the first months of life, lasting from dozens of minutes to hours, are reported. During disease evolution, prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occur. Subsequently, a progressive encephalopathy with hypotonia and ataxia appears. A net worsening of the neurological condition is observed after the age of 4-5 years. Cortical atrophy is shown by CCT and MRI. Neurometabolic screening is not contributory. Repeated polygraphic recordings show continuous and segmental myoclonic jerks, localized in different muscles, at frequencies ranging between 0.5-1 c/s and 6-8 c/s. Moreover action myoclonus is recorded. During the first period of disease the EEG does not show any paroxysmal activity. As to the classification, this syndrome corresponds to an early onset progressive encephalopathy of unknown origin, similar in some aspects to Alper's disease. Another problem is the interpretation of the myoclonic phenomena. Some important aspects suggest a cortical origin of the diverse myoclonic phenomena observed in these cases.

Occlusion of unilateral carotid artery in Down syndrome.

The association between moyamoya phenomena and Down syndrome (DS) is reported in the literature. This paper reports a case of DS, which at age 9 presented right hemiparesis, secondary to the occlusion of the left internal carotid artery; cerebral angiography (CAG) showed a collateral circulation that mimicks the moyamoya phenomenon. Clinical recovery was almost complete; a second CAG after 15 months showed a persistent occlusion of the left internal carotid artery and an opacification of the left middle cerebral artery from abnormal vessels; but the collateral circulation is not enhanced. This case proves that in DS cerebrovascular occlusions may present moyamoya-like phenomena. These differ however from the true moyamoya disease in a number of aspects: the arterial occlusion is unilateral, the evolution is favorable and revascularization does not occur through the peculiar abnormal vessels of the moyamoya syndrome.

Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test.

The effects of rapid rectal diazepam introduction (DZP test) were investigated in 43 patients (age range 5 months-14 years) with electrical status epilepticus (ESE) undergoing EEG monitoring. A remission of the paroxysmal activity was obtained in 58% of cases, a negative response in 42%, particularly in hypsarrhythmic patterns. DZP test responders were aged over 12 months with organized paroxysmal EEG patterns, in particular with ESE during sleep (ESES). The patients who responded to the DZP test underwent short cycles (3-4 weeks) of relatively high dosage DZP (0.5-0.75 mg/kg). The response to treatment was positive in 64%, particularly in ESES conditions. 56% of responders to the DZP test but not to DZP therapy (five out of nine patients) presented a significant mental retardation; maturational factors were also likely to be present.

SPECT and epilepsy with continuous spike waves during slow-wave sleep.

Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using 99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion.

Hyperkinetic behaviour, attention deficit disorder, conduct disorder and instabilité psychomotrice: identity, analogies, and misunderstandings. Commentary to Gordon's paper (Brain Dev 1994; 15: 169-72).

'Hyperkinetic behaviour', 'attention deficit disorder' and 'conduct disorder' with antisocial aspects or delinquency are concepts frequently superimposed. They can be traced back to the classic nosological entity, 'instabilité psychomotrice', still used in French psychiatric nosography. In this paper, the different components of the condition are analyzed (emotional, attentional, posturo-motoric and behavioural) both in normal subjects and in cases of mild encephalopathies, and for different age groups. A criticism is advanced towards the undifferentiated approach to the problem in the most current literature.

Electrical status epilepticus in childhood: treatment with short cycles of high dosage benzodiazepine (preliminary note).

A treatment of electrical status epilepticus during childhood with relatively high doses of benzodiazepines (BZ) in short cycles (3 weeks) is proposed for subjects shown to be responsive to BZs (diazepam bolus test: DZP test). This treatment gave positive results in 7 out of 8 patients responsive to the DZP test (87%).