Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.

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Critical period plasticity in local cortical circuits.

Role of interictal epileptiform abnormalities in cognitive impairment

Background Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. Methods We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at doses ranging from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses — one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. Results Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive s...

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A comparison of rectal diazepam gel and placebo for acute repetitive seizures.

Encephalopathy with electrical status epilepticus during sleep or ESES is an age-dependent and self-limited syndrome whose distinctive features include a characteristic age of onset (with a peak around 4-5 years), heterogeneous seizures types (mostly partial motor or unilateral seizures during sleep and absences or falls while awake), a typical EEG pattern (with continuous and diffuse paroxysms occupying at least 85% of slow wave sleep) and a variable neuropsychological regression consisting of IQ decrease, reduction of language (as in acquired aphasia or Landau-Kleffner syndrome), disturbance of behaviour (psychotic states) and motor impairment (in the form of ataxia, dyspraxia, dystonia or unilateral deficit). Despite the long-term favourable outcome of epilepsy and status epilepticus during sleep (SES), the prognosis is guarded because of the persistence of severe neuropsychological and/or motor deficits in approximately half of the patients. No specific treatment has been advocated for this syndrome, but valproate sodium, benzodiazepines and ACTH have been shown to control the seizures and the SES pattern in many cases, although often only temporarily. Subpial transection is proposed in some instances as in non-regressive acquired aphasia. Recent data support the concept that ESES syndrome may include a large subset of developmental or acquired regressive conditions of infancy.

Encephalopathy with electrical status epilepticus during slow sleep

Background: Although so-called “benign” epilepsy with centrotemporal spikes (BECTS) always has an excellent prognosis with regard to seizure remission, behavioral problems and cognitive dysfunctions may sometimes develop in its course. To search for clinical or EEG markers allowing early detection of patients prone to such complications, the authors conducted a prospective study in a cohort of unselected patients with BECTS. Methods: In 35 children with BECTS, academic, familial, neurologic, neuropsychological, and wake and sleep EEG evaluations were repeated every 6 to 12 months from the beginning of the seizure disorder up to complete recovery. Results: In 25 of 35 patients (72%), behavioral and intellectual functioning remained unimpaired. In 10 of 35 patients (28%), educational performance and familial maladjustment occurred. These sociofamilial problems were correlated with impulsivity, learning difficulties, attention disorders, and minor (7/35 cases, 20%) or serious (3/35 cases, 8%) auditory–verbal or visual–spatial deficits. Worsening phases started 2 to 36 months after onset and persisted for 9 to 39 months. Occurrence of atypical evolutions was significantly correlated with five qualitative and one quantitative interictal EEG pattern: intermittent slow-wave focus, multiple asynchronous spike-wave foci, long spike-wave clusters, generalized 3-c/s “absence-like” spike-wave discharges, conjunction of interictal paroxysms with negative or positive myoclonia, and abundance of interictal abnormalities during wakefulness and sleep. Clinical deterioration was not linked with seizure characteristics or treatment. Conclusion: Different combinations of at least three of six distinctive interictal EEG patterns and their long-lasting (≥6-month) persistence seem to be the hallmarks of patients with BECTS at risk for neuropsychological impairments.

EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy

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).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1469-8749.2001.tb00229.x

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

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.

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

'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.

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

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.

Treatment of status epilepticus in children

THE recent article by Sheila Wallace about the drug management of epilepsy (DMCN, 34, 1018-1021) is very comprehensive. However, it may be useful to add a note concerning electrical status epilepticus (ESE), given its particular pathophysiological, clinical and therapeutic peculiarities, and in view of the fact that it has seldom been considered in detail, even in a recent review article on non-convulsive status epilepticus'. ESE occurs most frequently in childhood, although it is occasionally found in the adult (petit ma1 status or absence status). It is the common denominator of several childhood epilepsy syndromes, such as infantile myoclonic epilepsy, West syndrome and related forms, LennoxGastaut syndrome and related forms, Landau-Kleffner syndrome and related forms, and electrical status epilepticus during sleep (ESES). These conditions differ in seizure type and EEG expression according to developmental factors and the type and severity of the basic cerebral damage. The aim of this annotation is to offer a dynamic and unifying perspective for these ESE conditions typical of the developmental age. Although hetereogeneous, "0 they have some features in common; these need to be considered as risk factors which may require specific therapeutic strategies. Even though there is no pathophysiological explanation as yet, there are clinical reasons why ESE should be W

Maurizio De Negri

Papers

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

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

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

Treatment of status epilepticus in children

Electrical Status Epilepticus in Childhood: Neuropsychological Impairment and Therapeutic Management