Caterina Cerminara

Early control of seizures improves long-term outcome in children with tuberous sclerosis complex

Epilepsy associated with tuberous sclerosis complex (TSC) is characterized by early onset and intractable seizures in the majority of children. There is a solid evidence of clinical efficacy of vigabatrin in interrupting infantile spasms associated with TSC. Due to an early diagnosis we were able to start vigabatrin at the very early onset of seizures in 10 children, who subsequently underwent a long-term neurodevelopmental follow-up. At the final evaluation, a seizure free status was achieved in 50% of patients; 30% of individuals had a normal or borderline mental development, with no patients developing severe mental retardation and/or autism. Early control of seizures has a crucial role in preventing subsequent epileptic encephalopathy, and in reducing the cognitive/behavioural consequences of seizures, but does not guarantee for a normal mental outcome in children with TSC.

Neonatal status epilepticus vs recurrent neonatal seizures: clinical findings and outcome.

Background: Although most children with status epilepticus have a good prognosis, its effects on newborns are unclear. Objective: We compare the neurodevelopmental consequences of recurrent seizures and status epilepticus in newborns. Methods: One hundred six newborns with video-EEG–confirmed seizures, consecutively admitted to the neonatal intensive care unit of the University of Parma between January 1999 and December 2004, were enrolled in the study. Fifty-one were preterm and 55 were full-term newborns. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes or recurrent seizures lasting a total of >30 minutes without definite return to the baseline neurologic condition of the newborn between seizures. Neurologic outcome was assessed at 24 months of corrected age. Results: Thirty-six newborns had a normal outcome, 20 died, and 50 presented an adverse outcome. All but 1 of the 26 subjects with neonatal status epilepticus had an adverse outcome. Birth weight, severely abnormal cerebral ultrasound scans, and status epilepticus were independent predictors of abnormal outcome. Depending on gestational age (GA), neonatal status epilepticus seems to be a risk factor of adverse outcome in full-term newborns (GA ≥ 37 weeks: odds ratio [OR] 20.312, 95% CI 2.417 to 170.679, p = 0.006), and a risk factor of epilepsy in early preterm and full-term newborns (GA ≤ 29 weeks: OR 10.500, 95% CI 1.211 to 91.026, p = 0.033; GA ≥ 37 weeks: OR 6.517, 95% CI 1.321 to 32.148, p = 0.021). Conclusion: Newborns with status epilepticus are at high risk of severe neurologic disability and postneonatal epilepsy. This is particularly evident in early preterm and full-term infants.

Lamotrigine-induced seizure aggravation and negative myoclonus in idiopathic rolandic epilepsy

The authors describe a paradoxical reaction to lamotrigine (LTG) treatment in a patient with idiopathic rolandic epilepsy characterized by seizure deterioration, the appearance of new seizure type, and transient cognitive impairment. This phenomenon was present at a low dose after a slow titration and promptly reverted on LTG discontinuation. This rare event may have similarities with carbamazepine-induced seizure worsening caused by the Na++ channel inhibitory effect of the two antiepileptic drugs.

Current management for epilepsy in tuberous sclerosis complex

Purpose of reviewThis article reviews the most significant advances in the field of epilepsy associated with tuberous sclerosis complex, with emphasis on new advances in the knowledge of the pathophysiological mechanisms of epileptogenicity, progress in identifying the epileptogenic zone, and the rationale for surgical management in individuals with intractable seizures. Recent findingsAdvances in our understanding of the mechanisms and genetics underlying infantile spasms and catastrophic epilepsy associated with tuberous sclerosis complex may facilitate more effective interventions. Early effective seizure control could significantly reduce the adverse developmental effects of chronic epilepsy in tuberous sclerosis. Vigabatrin is the first choice in the short-term treatment of infantile spasms. Some individuals, however, develop seizures that remain highly intractable. The factors that influence the intractability of epilepsy associated with tuberous sclerosis complex remain poorly understood. Multimodality neuroimaging has improved detection of epileptogenic foci, allowing an increased number of individuals to be evaluated for resective surgery. Epilepsy surgery is often associated with significant improvement of the neurologic outcome. SummaryEpilepsy in tuberous sclerosis seems to arise from the interaction between multiple areas, all of which have increased excitability and reduced inhibition. Understanding the mechanisms of epileptogenesis might increase the availability of development of a more specific and efficacious treatment. New evidence suggests that it is possible to noninvasively identify children with tuberous sclerosis who are highly likely to become seizure free following surgical treatment.

Levetiracetam in juvenile myoclonic epilepsy: long‐term efficacy in newly diagnosed adolescents

The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6‐month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12‐month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.

Attention and executive functions profile in childhood absence epilepsy

Childhood absence epilepsy (CAE) has been associated with executive functions and attention deficits. To clarify the issue of neurocognitive impairments in CAE, we investigated whether specific executive functions and attention deficit patterns were present in a well-defined group of children with CAE who were taking valproic acid. Participants included 15 children with CAE and 15 healthy controls aged 8-15 years and matched for sex, age and IQ. We compared the performances of the two groups in the following neuropsychological domains: planning and problem solving (TOL), verbal fluency (FAS and CAT), verbal short-term memory (DSF), verbal working memory (DSB), visuospatial memory (Corsi Block Tapping Test) and sustained and divided attention (TMT-A and TMT-B). No differences were found between the two groups on measures of intellectual functioning, verbal short-term memory and visuospatial memory. By contrast, significant differences were found in total time of planning task, phonological and category fluency and sustained and divided attention. Future studies that systematically examine different aspects of attention and executive functions are needed to outline a clear and specific neuropsychological profile in CAE.

Epilepsy secondary to tuberous sclerosis: lessons learned and current challenges

BackgroundIn tuberous sclerosis complex (TSC), a substantially increased risk of developing epilepsy is present as a result of a disruption of a TSC gene expression in the brain and secondary abnormal cellular differentiation, migration, and proliferation. Dysregulated excitation probably has its roots in the disruption of GABAergic interneuron development. There is an age-dependent electroclinical expression of seizures, and epilepsy is often quite severe and unremitting.DiscussionThe majority of patients (>60%) who are candidates for surgery remain seizure-free after tuberectomy. During the recent years technical advances in the localization of the epileptogenic zone during the recent years have lead to a 63% of Engel class I status after surgery compared with a previous 52%. In medically refractory patients not suitable for surgery, vagus nerve stimulation has proved efficacy in significantly reducing seizure frequency in more than 50% of cases. New evidence suggests that mTOR inhibitors may be helpful in the management of intractable epilepsy for individuals with TSC.

A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy

Purpose:  To evaluate the potential efficacy of levetiracetam as an antiabsence agent in children and adolescents with newly diagnosed childhood or juvenile absence epilepsy.

Levetiracetam in absence epilepsy

The aim of the study was to assess the efficacy, tolerability, and safety of levetiracetam therapy in children and adolescents with absence epilepsy. Twenty‐one participants (11 male, 10 female) with typical absence seizures were enrolled in this prospective study from seven centres in Italy. The mean age and age range at time of enrolment into the study were 8 years 9 months (SD 0.9) and 5 years 1 month to 13 years respectively. All patients were carefully evaluated at 6 months from baseline, and 12 patients were also re‐evaluated at 12 months after the beginning of therapy with levetiracetam. At the 6‐month evaluation, out of 21 patients studied, 11 were seizure free and one showed ‘decreased’ seizures (more than 50% reduction in seizures). A less than 50% reduction in seizures was observed in nine patients. At the 12‐month evaluation, 10 patients were completely seizure free and two were seizure free with some anomalies in electroencephalograms. Two patients who had shown no improvement at 6 months had decreased seizures at the second follow‐up. Our results suggest that monotherapy with levetiracetam could be effective and well tolerated in patients with childhood absence epilepsy and juvenile absence epilepsy. Prospective, large, long‐term double‐blind studies are needed to confirm these findings.

Attention-Deficit Hyperactivity Disorder (ADHD) and Tuberous Sclerosis Complex

The neurobiological basis of attention-deficit hyperactivity disorder (ADHD) in tuberous sclerosis complex is still largely unknown. Cortical tubers may disrupt several brain networks that control different types of attention. Frontal lobe dysfunction due to seizures or epileptiform electroencephalographic discharges may perturb the development of brain systems that underpin attentional and hyperactive functions during a critical early stage of brain maturation. Comorbidity of attention-deficit hyperactivity disorder (ADHD) with mental retardation and autism spectrum disorders is frequent in children with tuberous sclerosis. Attention-deficit hyperactivity disorder (ADHD) may also reflect a direct effect of the abnormal genetic program. Treatment of children with tuberous sclerosis complex with combined symptoms of attention-deficit hyperactivity disorder (ADHD) and epilepsy may represent a challenge for clinicians, because antiepileptic therapy and drugs used to treat attention-deficit hyperactivity disorder (ADHD) may aggravate the clinical picture of each other.