[Show abstract][Hide abstract] ABSTRACT: The syndrome of malignant migrating partial seizures in infancy was first reported in 1995, and is now included among the childhood epilepsy syndromes in development in the proposal of the revision of the International League Against Epilepsy (ILAE) classification of the epilepsies and epilepsy syndromes. The main clinical features are seizure onset in the first 6 months of life, occurrence of almost continuous migrating polymorphous focal seizures, combined with multifocal ictal electroencephalography (EEG) discharges, and progressive deterioration of psychomotor development. Etiology is so far unknown. Seizures are markedly drug resistant and outcome is generally severe. Based on age at onset, migrating partial seizures in infancy (MMPEI) may be placed between early epileptic encephalopathies (early myoclonic encephalopathy [EME] and early infantile epileptic encephalopathy [EIEE]) and infantile spasms.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the video-polygraphic features and the long-term outcome of epilepsy in two patients with startle epilepsy associated with infantile hemiplegia (SEIH).
Two patients (patient 1: a 14-year-old girl; patient 2: a 17 year-and-half-year-old girl), with hemiparesis and moderate mental retardation, underwent a full clinical and neurophysiological examination with video-polygraphic monitoring and recording of startle-evoked seizures. The follow-up was 9 years from epilepsy onset in patient 1, and 8 years from epilepsy onset in patient 2.
Firstly, video-polygraphic recordings of startle-evoked seizures, triggered by unexpected auditory stimuli, showed tonic asymmetrical postures with ictal EEG characterized by an abrupt and diffuse electrodecremental pattern or a seizure discharge predominant over the vertex and anterior regions controlateral to the posturing limbs. Electromyogram recording showed a prevalent involvement of proximal muscles with a concomitant tachycardia and apnoea. In particular, in patient 1 ictal heart rate was high, with persisting tachycardia for 60-120 s after the end of seizures. Secondly, a high seizure frequency persisted throughout the course of the disease, as seizures were medically refractory to all currently available anti-epileptic drugs.
The long-term outcome of epilepsy in SEIH, with constantly high seizure frequency, suggests an early surgical intervention, avoiding years with unsuccessful drug treatments and poor quality of life.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess bone mineral density (BMD) in a large population of children, adolescents, and young adults with epilepsy alone or in association with cerebral palsy and/or mental retardation.
Ninety-six patients were enrolled in the study. The group comprised 50 males and 46 females, aged between 3 and 25 years (mean age 11 years). The control group consisted of 63 healthy children and adolescents (23 males, 40 females), aged between 3 and 25 years (mean age 12.1 years). Patients underwent a dual-energy x-ray absorptiometry (DEXA) scan of the lumbar spine (L1-L4) and the z scores were calculated for each patient; the t score was considered for patients 18 years of age or older.
Abnormal BMD was found in 56 patients (58.3%), with values documenting osteopenia in 42 (75%) and osteoporosis in 14 (25%). A significant difference emerged between epileptic patients and the control group in BMD, z score, and body mass index (BMI) (p = <0.001). Lack of autonomous gait, severe mental retardation, long duration of antiepileptic treatment, topiramate adjunctive therapy, and less physical activity significantly correlated with abnormal BMD.
This study detected abnormal BMD in more than half of a large pediatric population with epilepsy with or without cerebral palsy and/or mental retardation. The clinical significance of these findings has yet to be clarified.
[Show abstract][Hide abstract] ABSTRACT: 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.
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 patient's 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).
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.
ZNS effectively reduced seizure frequency in this pediatric population with both partial and generalised crypto/symptomatic refractory epilepsy. Its overall tolerability was good.
Epilepsy research 01/2009; 83(2-3):112-6. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 enrollment 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.
[Show abstract][Hide abstract] ABSTRACT: Mutations in the LGI1 gene are linked to autosomal dominant lateral temporal epilepsy (ADTLE) in about half of the families tested, suggesting that ADLTE is genetically heterogeneous. Recently, the Lgi1 protein has been found associated with different protein complexes and two distinct molecular mechanisms possibly underlying ADLTE have been hypothesized: the one recognizes Lgi1 as a novel subunit of the presynaptic Kv1 potassium channel implicated in the regulation of channel inactivation, the other suggests that Lgi1 acts as a ligand that selectively binds to the postsynaptic receptor ADAM22, thereby regulating the glutamate-AMPA neurotransmission. Both mechanisms imply that LGI1 mutations result in alteration of synaptic currents, though of different types. Since their protein products have been found associated with Lgi1, the Kv1 channel subunit genes KCNA1, KCNA4, and KCNAB1 and ADAM22 can be considered strong candidates for ADLTE. We sequenced their coding exons and flanking splice sites in the probands of 9 carefully ascertained ADLTE families negative for LGI1 mutations. We failed to detect any mutation segregating with the disease, but identified several previously unreported polymorphisms. An association study of four non-synonymous variants (three found in ADAM22, one in KCNA4) in a population of 104 non-familial lateral temporal epilepsy cases did not show any modification of susceptibility to this disorder. Altogether, our results suggest that neither ADAM22 nor any of the three Kv1 channel genes are major causative genes for ADLTE.
Epilepsy Research 08/2008; 80(1):1-8. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autosomal dominant lateral temporal epilepsy (ADTLE) is a genetically transmitted epileptic syndrome characterized by focal seizures with predominant auditory symptoms likely originating from the lateral region of the temporal lobe. Mutations in coding region or exon splice sites of the leucine-rich, glioma-inactivated 1 (LGI1) gene account for about 50% of ADLTE families. De novo LGI1 mutations of the same kind have also been found in about 2.5% of non-familial cases with idiopathic partial epilepsy with auditory features (IPEAF). In both conditions, mutations in the LGI1 promoter region have not been reported. We sequenced the minimal promoter region of LGI1 in the probands of 16 ADLTE families and in 104 sporadic IPEAF patients and no mutations clearly linked to the disease were found. However, two polymorphisms, -500G>A and -507G>A, with potential functional implications were identified and analysed in the cohort of sporadic IPEAF patients but their frequencies did not differ from those found in a control population of similar age, gender and geographic origin. We also analysed in our study population the GABA(B) receptor 1 c.1465G>A and the prodynorphin promoter 68-bp repeat polymorphisms, previously associated with temporal lobe epilepsy. None of these polymorphisms showed a significant association with IPEAF, whereas a tendency towards association with the prodynorphin low expression (L) alleles was found in the small group of ADLTE index cases, in agreement with previous studies suggesting that this polymorphism is a susceptibility factor in familial forms of temporal lobe epilepsy.
[Show abstract][Hide abstract] ABSTRACT: Epilepsy and electroencephalographic (EEG) anomalies are common in subjects carrying chromosomal aberrations. We report clinical and EEG investigations on 13 patients carrying chromosome 2 anomalies, including two patients with inversions, six with translocations, two with partial duplications and three with interstitial deletion syndromes. Epilepsy and/or EEG anomalies were found in one patient with a chromosome 2 translocation, in both of those carrying partial duplications and in all three with interstitial deletion syndromes. No epilepsy or EEG anomalies were detected in the remaining patients. CONCLUSIONS: Epilepsy may be associated with chromosome 2 aberrations. Gross rearrangements involving the long arm of chromosome 2 might be more often associated with epilepsy than those involving the short arm. The association of epilepsy with chromosome 2 duplications is less clear. In particular, our observations and a review of the literature appear to suggest that a strict relationship between epilepsy and interstitial deletions involving the 2q24-q31 region. In the latter disorder tonic and focal seizures occur early in life. Generalized and focal myoclonic jerks tend to appear in infancy and are subsequently followed by seizures mixed in type. Seizures usually persist up to late childhood and are drug resistant. Further studies are necessary to better define the electroclinical patterns of patients carrying deletions in 2q24-q31. These may help to direct systematic study of this--probably underestimated--cause of severe epilepsy.
Epilepsy Research 04/2008; 79(1):63-70. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Our aim was to evaluate bone mineral densitometry in patients with Angelman syndrome with or without antiepileptic therapy. Eighteen patients (9 females, 9 males), aged 4.0-24.3 years (mean age, 10.1 years), and two control groups consisting of 18 epileptic and 24 healthy patients, underwent dual-energy X-ray absorptiometry at the lumbar spine (L(1)-L(4)), and z score was evaluated for each patient; the t score was considered for patients aged > or = 18 years. Abnormal bone mineral density was present in 8/18 (44.5%) of patients with Angelman syndrome, in 7/18 (38.9%) of the epileptic group, and in none of the healthy controls. Furthermore, a significant difference regarding mean age of patients (6 versus 15 years, P = 0.008, by Fisher exact test), and mean length of drug treatment (3.5 versus 11.1 years, P = 0.005 by Fisher exact test), appeared in the group with Angelman syndrome. Most of these patients (94.4%) were receiving antiepileptic drugs, mainly valproic acid, for many years. In conclusion, our study revealed osteopenia in almost half the children and young patients with Angelman syndrome. Dual-energy X-ray absorptiometry should be performed in all patients with Angelman syndrome, particularly if they are treated with antiepileptic drugs.
[Show abstract][Hide abstract] ABSTRACT: A child had the characteristic clinical and EEG pattern of migrating partial seizures in infancy with left temporal lobe atrophy, hippocampal sclerosis and cortical-subcortical blurring. Seizures were drug-resistant, with recurring episodes of status epilepticus. The child developed microcephaly with arrest of psychomotor development. Focal brain lesions, in the context of migrating partial seizures, have not been previously reported.[Published with video sequences].
Epileptic disorders: international epilepsy journal with videotape 07/2007; 9(2):145-8. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and tolerability of levetiracetam or oxcarbazepine as monotherapy in children with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS). Twenty-one children (11 males, 10 females), aged between 5 and 13 years (mean 10.5 years), and 18 (10 M, 8 F), aged between 3.3 and 14 years (mean 8.4 years), were randomised to receive monotherapy with levetiracetam or oxcarbazepine, respectively. LEV was titrated up to 20-30 mg/kg/once or twice a day, and OXC up to 20-35 mg/kg once or twice a day. Thirty-nine consecutive children (21 males, 18 females), aged between 3.3 and 14 years (mean 10.7 years), were recruited into the study. Twenty-one were randomised on LEV (11 male, 10 female; mean age 10.5 years), and 18 on OXC (10 male, 8 female; mean age 8.4 years). After a mean follow-up period of 18.5 months (range 12-24 months), 19 out of 21 patients (90.5%) on levetiracetam, and 13 out of 18 (72,22%) on oxcarbazepine did not have further seizures. Mean serum level of LEV was 4.1 microg/ml (range 1.3-9.0), and of OXC was 15.2 microg/ml (range 4.2-27.5). Adverse side effects on LEV were reported in 3 children (14.3%), represented by mild and transient decreased appetite (2) and cephalalgia (1). They were reported on OXC in 2/18 (11.1%), including headache (1), and sedation (1). These preliminary data from an open, parallel group study suggest that levetiracetam and oxcarbazepine may be potentially effective and well tolerated drugs for children with BECTS who require treatment.
Brain and Development 07/2007; 29(5):281-4. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Almost ten years have passed since the identification of Kv7.2 and Kv7.3, the genes altered in benign familial neonatal seizures (BFNS), a familial autosomal dominant focal epilepsy of the newborn. Despite the rarity of the disease, clinical and genetic data have been gathered from more than 50 BFNS-affected families; these studies reveal that each family harbours a specific disease-causing mutation, and that the mutation-induced functional changes range from a subtle alteration in channel behaviour to a complete ablation of channel function. Prompted by the recent identification of peculiar gating changes in Kv7.2 subunits caused by novel mutations responsible for BFNS, in the present work we attempt to link, whenever possible, the specific genetic defect with the clinical evolution of the disease in the affected families on one side, and, on the other, with the functional defects revealed by expression studies. Such genotype-phenotype correlations may provide clues on the pathogenesis of the wide variety of neuropsychiatric manifestations often associated to BFNS, and should foster our attempts to gain more detailed functional information which might help to elucidate the pathogenetic mechanisms of the disease.
[Show abstract][Hide abstract] ABSTRACT: This study was performed to evaluate carnitine deficiency in a large series of epilepsy children and adolescents treated with old and new antiepileptic drugs with or without ketogenic diet. Plasma free carnitine was determined in 164 epilepsy patients aged between 7 months and 30 years (mean 10.8 years) treated for a mean period of 7.5 years (range 1 month-26 years) with old and new antiepileptic drugs as mono or add-on therapy. In 16 patients on topiramate or lamotrigine and in 11 on ketogenic diet, plasma free carnitine was prospectively evaluated before starting treatment and after 3 and 12 months, respectively. Overall, low plasma levels of free carnitine were found in 41 patients (25%); by single subgroups, 32 out of 84 patients (38%) taking valproic acid and 13 of 54 (24%) on carbamazepine, both as monotherapy or in combination, showed low free carnitine levels. A higher though not statistically significant risk of hypocarnitinemia resulted to be linked to polytherapy (31.5%) versus monotherapy (17.3%) (P=.0573). Female sex, psychomotor or mental retardation and abnormal neurological examination appeared to be significantly related with hypocarnitinemia, as well. As to monotherapy, valproic acid was associated with a higher risk of hypocarnitinemia (27.3%) compared with carbamazepine group (14.3%). Neither one of the patients on topiramate (10), lamotrigine (5) or ketogenic diet (11) developed hypocarnitinemia during the first 12 months of treatment. Carnitine deficiency is not uncommon among epilepsy children and adolescents and is mainly linked to valproate therapy; further studies are needed to better understand the clinical significance of serum carnitine decline.
Brain and Development 08/2006; 28(6):358-65. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberous sclerosis complex (OMIM 191100) is a multiorgan disease commonly associated with epilepsy refractory to anticonvulsants. Individual reports indicate that seizures in children with tuberous sclerosis might benefit from a ketogenic diet. We studied the effects of the diet introduced at 3.5 years of age in three boys with tuberous sclerosis and refractory partial seizures.
On admission a classical LCT ketogenic diet was initiated and patients were followed for 12 months. Antiepileptic drugs were maintained unless adverse effects required reduction.
Two patients became seizure-free within 2 months on the diet. In the third patient drop attacks decreased significantly. On follow-up the diet was well accepted and without adverse effects.
The ketogenic diet should be considered as a treatment option for children with tuberous sclerosis and partial seizures refractory to anticonvulsants. Our data support the need for further studies in larger cohorts to confirm the effectiveness of the ketogenic diet in this entity.
European Journal of Paediatric Neurology 06/2006; 10(3):148-51. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mutational analysis of potassium (KCNQ2, KCNQ3), sodium (SCN1A, SCN2A), and chloride (CLCN2) ion channels was performed in three children with typical features of the recently described syndrome of migrating partial seizures in infancy. Mutational analysis was performed by PCR and automatic sequencing. The coding regions, including the exon-intron boundaries, were amplified in the patients using appropriate primers sets. No mutations associated to migrating partial seizures have been found. Mutational screening of CLCN2 gene, revealed a homozygous mutation G2003C (exon 17), leading to a Ser/Thr substitution at the codon 668, in two of the three patients. The same variation has been found in 38 out of 100 control alleles. The identification of the genetic basis of this new epileptic encephalopathy requires further studies that might be enforced by familial cases.
Brain and Development 04/2006; 28(2):76-9. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two patients with typical tuberous sclerosis complex (TSC) associated with cervical or dorsal-lumbar hydrosyringomielia are described for the first time. Syringomielic cavities are small in extension in both cases, leading to significant clinical symptoms as bilateral pes cavus and scoliosis in one patient only. So far, tuberous sclerosis had not been reported to involve primarily the spinal cord, and other factors directly linked to syringomiely are not present in both these patients.
European Journal of Paediatric Neurology 02/2006; 10(1):37-40. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Atypical antipsychotic agents, specifically those with a high hyposerotonergic activity such as clozapine and clothiapine, have been associated with de novo obsessive-compulsive symptoms. We report the case of a 16-year-old adolescent male with severe mental impairment and disruptive behaviour who developed a compulsive head and body turning disorder on clothiapine. Such a symptom had to be distinguished from epileptic partial seizures; it promptly disappeared with the drug discontinuation.
Brain and Development 10/2004; 26(6):409-11. · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to verify the clinical efficacy of melatonin (MLT) in children, adolescents and young adults with wake-sleep disorder and mental retardation, most of them on chronic anticonvulsant therapy for epileptic seizures, by means of a randomized, double-blind, placebo-controlled cross-over trial. Twenty-five patients (16 males, nine females), aged from 3.6 to 26 years (mean 10.5 years), all affected with mental retardation mostly with epileptic seizures, were randomized to oral synthetic fast-release MLT or placebo. Melatonin was initiated at the daily dose of 3 mg, at nocturnal bedtime. In case of inefficacy, MLT dose could be titrated up to 9 mg the following 2 weeks at increments of 3 mg/week, unless the patient was unable to tolerate it. The analysis of all the sleep logs disclosed a significant treatment effect of melatonin on sleep latency (P = 0.019). Melatonin was well tolerated in all patients and no side effects were reported. In conclusion, our study supports the efficacy of MLT in young patients with mental disabilities and epileptic seizures in improving the wake-sleep disorders such as time to fall asleep. Overall, MLT appeared to influence the seizure frequency poorly, though there may be occasional seizure worsening or improving. Such a dual effect requires further studies in young epileptic patients.
Brain and Development 10/2004; 26(6):373-6. · 1.67 Impact Factor