Anna Luchetti

Epilepsy, Electroencephalographic Abnormalities, and Regression in Children With Autism:

The association of epilepsy and autism is recognized, and it has been reported at a percentage that varies between 8 and 42%, depending on age and diagnostic criteria. One third of autistic children undergo a regression of language and behavior between 2 and 3 years, and epileptiform abnormalities and epilepsy can be concomitant in an undetermined percentage of them. The aim of this study was to investigate the prevalence of epilepsy and paroxysmal abnormalities in a group of children with autism and to determine the percentage of regression course in this group. Forty-six patients with autism (mean age 7.8 ± 2.7 years; 34 boys and 12 girls) were consecutively examined, and clinical evaluation, assessment, and electroencephalographic (EEG) recordings were performed in all of them. Thirty-five percent showed paroxysmal abnormalities and epilepsy, 22% had only paroxysmal abnormalities without seizures, and 13% of the children suffered from epilepsy. Sixty-five percent had a normal EEG. No difference in regression rate was observed between patients with paroxysmal abnormalities and epilepsy and those with a normal EEG and without seizures. In the study group, the prevalence of epilepsy was in the low range of individuals with autism, and different types of epilepsy were observed. Autism with regression was not influenced by paroxysmal abnormalities and epilepsy. (J Child Neurol 2005;20:27—31).

Natalizumab treatment in pediatric multiple sclerosis: A case report

Pediatric multiple sclerosis (MS) with manifestations before 16 years of age occurs in 0.4-10.5% of whole MS population. The initial course of the disease is relapsing-remitting with a relapse rate generally higher than that of adults, less than 3% have a primary progressive form. Some recent reports have shown that Interferon beta (IFNbeta) has a strong effect in reducing the relapse rate in children with MS and is well tolerated. We report a 12-year-old girl with MS and a high relapse rate from the onset. Frequent magnetic resonance imaging (MRI) detected persisting inflammatory activity and increase of lesion burden. She continued to present acute relapses and progression of disability in spite of a treatment with IFNbeta-1a at different dosages and the addition of pulse IV steroid treatment. Then, we opted for Natalizumab treatment, recently approved as a monotherapy for patients with MS who experienced inadequate response to other disease modifying therapies and never used till now in pediatric MS. Our patient showed a complete response to Natalizumab with clinical and MRI suppression of disease activity.

The relationship between sleep and epilepsy: the effect on cognitive functioning in children

Aim  The purpose of this review was to examine the possible pathophysiological links between epilepsy, cognition, sleep macro‐ and microstructure, and sleep disorders to highlight the contributions and interactions of sleep and epilepsy on cognitive functioning in children with epilepsy.

Melatonin to prevent migraine or tension-type headache in children

We designed a 3-month open label trial of melatonin prophylaxis in children with primary headache. After a one month baseline period without receiving preventive drugs, all children received a 3-month course of melatonin, 3 mg, administered orally, at bedtime. A total of 22 children were enrolled (10 boys, mean age 12.2±2.6 years, age range 6–16 years), 13 had recurrent migraine without aura, 1 with aura and 8 had chronic tension-type headache. When the trial ended, 14 of the 21 subjects reported that the headache attacks had decreased by more than 50% in respect to baseline and 4 of them reported having no headache attacks. After receiving melatonin for one month one subject dropped out because of excessive daytime sleepiness. Our promising results warrant randomized placebo-controlled trials in children to assess the real effectiveness of melatonin in preventing primary headache.

A case with atypical childhood occipital epilepsy "Gastaut type": an ictal migraine manifestation with a good response to intravenous diazepam.

We report the history of a 14‐year‐old girl with atypical childhood occipital epilepsy “Gastaut type” whose first generalized tonic–clonic seizure was preceded by migraine without aura and followed by a status migrainosus. This status lasted for 3 days despite standard analgesic therapy. An EEG recording revealed an occipital status epilepticus during her migraine complaints. Seven minutes after intravenous administration of 10 mg diazepam under continuous EEG recording, a suppression of the epileptiform discharges over the right occipital was seen, while the headache subsided 3 min later. After precise questioning about the circumstances that possibly could have led to these events, it appeared that she had played for hours with a play station on the new color TV and she had visited an exhibition of Matisse and Bonnard with bright colors and contrast‐rich text. Standardized extensive intermittent photic stimulation (IPS), 2 days after the status migrainosus, evoked besides asymmetrical right‐sided driving, green spots in her left visual field, while in the EEG sharp waves were recorded over the right parietotemporal region. After further IPS with 20 Hz (eye closure), she started complaining of a light pulsating headache right occipitally and in the EEG right parietotemporal sharp‐waves were seen. This lasted for about 10 min. Later, an interictal routine EEG was normal except for some theta over the right temporooccipital area. The most likely diagnosis is an atypical form of occipital epilepsy “Gastaut type.” We would therefore advocate recording EEGs with photic stimulation in patients with atypical migraneous features.

Lacosamide in pediatric and adult patients: comparison of efficacy and safety.

PURPOSE This multicenter, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in pediatric and adult patients with uncontrolled epilepsy. METHOD This study was carried out between September 2010 and December 2011 at 16 Italian and 1 German neurologic centers. Lacosamide was added to the baseline therapy at a starting dose of 1 mg/kg/day in patients aged <16 years (group A) and 100 mg daily in subjects aged 16 and older (group B), and titrated to the target dose, ranging from 3 to 12 mg/kg/day or from 100 to 600 mg daily, respectively. After completing the titration period, patients entered a 12-month maintenance period and they were followed up at 3, 6 and 12 months. The primary assessment of efficacy was based on the change from baseline in seizure frequency per 28 days and was evaluated at 3, 6 and 12 months as follows: number and proportion of 100% responders, 50% responders, non-responders and worsening patients. Safety evaluation was also performed at 3, 6 and 12 months. RESULTS A total of 118 patients (59 group A, 59 group B) with uncontrolled generalized and focal epilepsy were enrolled. Patient mean±SD age was 15.9±6.80 years and the age range was 4-38 years. At 3-month evaluation, of 118 treated patients 56 subjects (47.4% group A; 47.4% group B; p=0.8537) experienced at least a 50% reduction in seizure frequency. At 6 and 12-month follow-up, the 50% responders were 57 (52.5% group A; 44.1% group B; p=0.4612) and 51 (47.4% group A; 39% group B; p=0.4573), respectively. Thirty-five subjects (30.5% group A; 28.8% group B; p=1) experienced side effects during the treatment period. The most common adverse events were dyspepsia for group A and dizziness for group B. CONCLUSION Lacosamide may be a useful and safe pharmacological treatment option for both pediatric and adult patients with uncontrolled seizures.

Reduced NREM sleep instability in benign childhood epilepsy with centro-temporal spikes

OBJECTIVE To analyze sleep architecture and NREM sleep instability by means of the cyclic alternating pattern (CAP) in children with benign epilepsy with rolandic spikes (BERS). METHODS Ten children with BERS, drug free at the time of the study and 10 age-matched normal controls were included in this study. Sleep was visually scored for sleep architecture and CAP using standard criteria. RESULTS Sleep architecture in BERS showed only few significant differences vs. controls with a reduction of total sleep time, sleep efficiency, and REM sleep percentage. CAP analysis revealed several significant differences: reduced total CAP rate, mainly in sleep stage 2, and reduced EEG slow oscillations and arousals during stages N1 and N2. CONCLUSIONS Sleep architecture is not importantly affected in BERS but CAP analysis reveals a decrease of NREM instability, mainly in sleep stage 2. Since there is a spindle-related spike activation in BERS, we speculate that the decrease of CAP and of EEG slow oscillations and arousals might be linked with the inhibitory action of spindling activity and spikes on arousals. SIGNIFICANCE CAP analysis discloses sleep structure abnormalities in children with BERS not shown by the classical sleep scoring. Spike activity and CAP A1 subtypes seem to be mutually exclusive probably because centro-temporal spikes disturb the physiological synchronization mechanisms needed for the generation of slow-wave components of CAP.

Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog–Scott syndrome due to a novel FGD1 gene mutation (R408Q)

Mutations of the FGD1 gene are responsible for a significant proportion of patients with Aarskog–Scott syndrome (AAS), an X‐linked disorder characterized by short stature, brachydactyly, urogenital abnormalities, and a typical dysmorphic facial appearance. Although mental retardation does not occur significantly in AAS, this condition has been described associated with various degrees of mental impairment and/or behavioral disorders in some patients. In particular, attention deficit hyperactivity disorder (ADHD) is reported as a common characteristic of AAS. However, AAS/ADHD reported patients have been only clinically described, and diagnosis never has been confirmed on molecular basis. We present here a unique case of a 16‐years‐old patient presenting with ADHD, lower intelligence quotient, and dysmorphic features. Although the clinical features were not completely typical of AAS, genetic analysis demonstrated a novel FGD1 missense mutation (R408Q). The case we report confirms the highly variable expressivity of AAS and first documents that the FGD1 gene may play a role in ADHD susceptibility. We suggest that FGD1 analysis may be adequate in ADHD patients who exhibit dysmorphic features suggestive of AAS, also in the absence of the full phenotypical spectrum.

Zonisamide in children and young adults with refractory epilepsy : An open label, multicenter Italian study

PURPOSE To report on the first multicenter Italian experience with zonisamide as an add-on drug for refractory generalised or partial epilepsy in children, adolescents and young adults. METHODS The patients were enrolled in a prospective, add-on, open-label treatment study from eight Italian centres for children and adolescent epilepsy care. Eighty-two young patients (45 males, 37 females), aged between 3 and 34 years (mean 13.1 years), all affected by partial (47) or generalised (35) refractory epilepsy, were enrolled in the study. ZNS was added to the baseline therapy at a starting dose of 1 mg/kg/day twice daily. This dose was increased by 2 mg/kg every 1-2 weeks over a period of up 3 months, according to the patients response and tolerability, up to a maximum dose of 12 mg/kg. ZNS was given at the mean daily dose of 5.7/mg/kg/24 h (range 1-12 mg/kg). RESULTS After a mean follow-up period of 11.9 months (range 2-64 months), 9 patients (10.9%) were seizure-free. The number of seizures decreased by 50-99% in 31 cases (37.8%), by 25-49% in 5 cases (6.1%), remained the same in 29 cases (35.4%) and increased in 8 cases (9.7%). After 15 months of follow-up, 61 patients (74.4%) were still taking ZNS, while the remaining 21 (25.6%) had stopped. Twenty-two patients (26.8%) reported adverse effects while taking ZNS. They generally appeared during the first weeks of treatment, and were mild to moderate. The most frequent adverse effects were irritability and a reduced appetite. CONCLUSION ZNS effectively reduced seizure frequency in this pediatric population with both partial and generalised crypto/symptomatic refractory epilepsy. Its overall tolerability was good.

All-night EEG power spectral analysis of the cyclic alternating pattern at different ages

OBJECTIVE To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP) in the whole sleep of pre-school and school age children compared to normal young adults. METHODS Fourteen pre-school age and 18 school age children and 16 adults were included in this study. Each participant underwent a polysomnographic overnight recording, after an adaptation night; sleep stages and CAP were scored following standard criteria. Average spectra were obtained for each CAP condition from the signal recorded from C3/A2 or C4/A1, separately in sleep stage 2 and slow-wave sleep (SWS), for each subject. RESULTS The analysis of the relative power density in the three groups showed that in sleep stage 2 and in SWS, CAP A1, A2, A3 subtypes had a significantly higher power in all frequency ranges in pre-school children than in adults, while school children differed mainly for the lower frequencies (<7 Hz). For non-CAP, pre-school and school children differed from adults at almost all frequencies analyzed. Generally, A1, A2 and A3 showed clear spectral differences in the three different groups of subjects with pre-school age children showing slightly less evident differences. CONCLUSIONS CAP subtypes are characterized by clearly different spectra at different ages and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This study shows that pre-school children have a different structure of sleep, especially from the microstructural (CAP) point of view: the differences are evident for all the CAP components and for non-CAP in almost all the frequency bands. This finding might be associated to the age-related delta decline in the 0-3 Hz frequency reported in children of the same age. SIGNIFICANCE Our data seem to provide information not available before and useful for the understanding of the impact of CAP on the sleep EEG neurophysiological dynamics at different ages. This type of information is crucial for a more adequate interpretation of data provided by a growing number of studies analyzing CAP in groups of pediatric patients.