Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy.

The aim of this multicentric, retrospective, and uncontrolled study was to evaluate the efficacy and safety of levetiracetam (LEV) in 81 children younger than 4 years with refractory epilepsy. At an average follow-up period of 9 months, LEV administration was found to be effective in 30% of patients (responders showing more than a 50% decrease in seizure frequency) of whom 10 (12%) became seizure free. This efficacy was observed for focal (46%) as well as for generalized seizures (42%). In addition, in a group of 48 patients, we compared the initial efficacy (evaluated at an average of 3 months of follow-up) and the retention at a mean of 12 months of LEV, with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Twenty-two patients (46%) were initial responders. After a minimum of 12 months of follow-up, 9 of 48 patients (19%) maintained the improvement, 4 (8%) of whom remained seizure free. A loss of efficacy was observed in 13 of the initial responders (59%). Maintained LEV efficacy was noted in patients with focal epilepsy and West syndrome. LEV was well tolerated. Adverse events were seen in 18 (34%) patients. The main side effects were drowsiness and nervousness. Adverse events were either tolerable or resolved in time with dosage reduction or discontinuation of the drug. We conclude that LEV is safe and effective for a wide range of epileptic seizures and epilepsy syndromes and, therefore, represents a valid therapeutic option in infants and young children affected by epilepsy.

Aicardi syndrome with favorable outcome: case report and review.

Aicardi syndrome is a congenital disorder characterized by severe psychomotor retardation, corpus callosum agenesis, chorioretinal lacunae, and early-onset infantile spasms. The prognosis is generally poor for children with the classical form. We report a peculiar case of Aicardi syndrome characterized by corpus callosum hypoplasia, brain malformations with subependymal heterotopias, extensive chorioretinal lacunae, seizures, and normal cognitive functions. Therefore, the clinical picture of the syndrome is broader than originally described. Cognitive disorders should not be considered inevitable and the prognosis not ineludibly poor.

Seizures and electroencephalographic findings in CDKL5 mutations: case report and review.

Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) have been detected in patients presenting with seizures in the first few months of life and Rett syndrome features. Twenty-seven cases have been detected to date. Generalized intractable seizures, as infantile spasms, and generalized tonic-clonic seizures and myoclonic seizures characterize the clinical picture of CDKL5 mutations. Here we report on a patient who presented with sleep-related hyperkinetic seizures. Our observation and review of the literature suggest that a broader polymorphic electroclinical pattern with both generalized and focal seizures may occur in patients with CDKL5 mutations. A screen for CDKL5 mutations is useful in patients, mainly females, with a history of early onset intractable seizures and becomes mandatory when idiopathic infantile spasms and/or atypical Rett syndrome features are also present.

Intractable reflex audiogenic seizures in Aicardi syndrome.

Aicardi syndrome (AS) is a rare disorder which includes the triad of total or partial agenesis of the corpus callosum, infantile spasms, and chorioretinal anomalies. Seizures and electroencephalogram findings observed in AS are polymorphic with both focal and generalized seizures. We first report on a patient affected by AS who presented with reflex audiogenic seizures specifically triggered by the starting tune of a popular television news. No other type of stimuli, either simple or complex, were able to precipitate the seizures in the patient. The severe cortical-subcortical lesions commonly observed in AS are associated with hyperexcitability of the cortices and may well account for the broad electroclinical patterns noted in this group of patients. From our report, the context of these patterns should be extended to include reflex audiogenic seizures.

Analgesic effect of watching TV during venipuncture.

AIMS: To assess the analgesic effect of passive or active distraction during venipuncture in children. METHODS: We studied 69 children aged 7-12 years undergoing venipuncture. The children were randomly divided into three groups: a control group (C) without any distraction procedure, a group (M) in which mothers performed active distraction, and a TV group (TV) in which passive distraction (a TV cartoon) was used. Both mothers and children scored pain after the procedure. RESULTS: Main pain levels rated by the children were 23.04 (standard deviation (SD) 24.57), 17.39 (SD 21.36), and 8.91 (SD 8.65) for the C, M, and TV groups, respectively. Main pain levels rated by mothers were 21.30 (SD 19.9), 23.04 (SD 18.39), and 12.17 (SD 12.14) for the C, M, and TV groups, respectively. Scores assigned by mothers and children indicated that procedures performed during TV watching were less painful (p<0.05) than control or procedures performed during active distraction. CONCLUSION: TV watching was more effective than active distraction. This was due either to the emotional participation of the mothers in the active procedure or to the distracting power of television.

Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry.

Survivors of retinoblastoma (Rb) are at high risk of dying from second malignant tumour. The occurrence of second malignant neoplasm (SMN) and related mortality in a cohort of 1111 cases from the Italian Retinoblastoma Registry was analysed, considering the possible role of both genetic and iatrogenic causes. Rb patients had a greater than 10-fold excess in overall mortality compared with the general population (standardized mortality ratio (SMR) 10.73, 95% CI 9.00-12.80). Their excess risk attributable to cancers other than Rb was 14.93 95% CI 10.38-21.49). Survivors of hereditary Rb had an SMR for all causes of 16.25 (95% CI 13.20-20.00), whereas their SMR for all cancers was 25.72 (95% CI 17.38-38.07). Survivors of unilateral sporadic Rb had an SMR of 4.12 from all cancers (95% CI 1.55-10.98) and a much higher excess for overall mortality (SMR 13.34, 95% CI 10.74-16.56). As expected, survivors of hereditary Rb had higher mortality from cancers of the bone (SMR 391.90, 95% CI 203.90-753.20) and soft tissue (SMR 453.00, 95% CI 203.50-1008.40), small intestine (SMR 1375.50, 95% CI 344.00-5499.70), nasal cavity (SMR 13.71, 95% CI 1.93-97.35) and cancers of the brain and central nervous system (SMR 41.14, 95% CI 13.2-127.55).

Efficacy and safety of levetiracetam: an add-on trial in children with refractory epilepsy.

The aim of this multicentric, prospective and uncontrolled study was to evaluate the efficacy and safety of levetiracetam in 110 children with refractory epilepsy, of whom 21 were less than 4 years old. After a median follow-up period of 7 months, levetiracetam administration was effective (responders with >50% decrease in seizure frequency) in 39% of children, of whom 10 (9%) became seizure-free. The efficacy was higher in patients with localization-related epilepsy (58% of responders) than in those with generalized epilepsy (37% of responders). Levetiracetam was well tolerated. The main side effects of somnolence and irritability occurred in 14% of patients. In one patient acute choreoathetosis occurred after few doses of levetiracetam. Overall, the adverse effects were not severe. Children younger than 4 years were particularly tolerant. In conclusion, the present study confirms that levetiracetam is effective and well tolerated as an add-on treatment in children with refractory epilepsy. Our preliminary data also indicate that levetiracetam may be a valid therapeutic option for epilepsy in infants and young children.

Efficacy and safety of topiramate in infants according to epilepsy syndromes.

Studies of the efficacy of topiramate (TPM) in infants and young children are few. Here we report an open, prospective, and pragmatic study of effectiveness of TPM in terms of epilepsy syndromes, in children aged less than 2 years. The median follow-up period was 11 months. We enrolled 59 children in the study: 22 affected by localization-related epilepsy (LRE), 23 by generalized epilepsy, six by Dravet's syndrome, and eight with unclassifiable epilepsy. TPM was effective (responders showed a decrease of more than 50% in seizure frequency) in 47% of patients, including 13% who were seizure-free at the last visit. TPM was more effective in localization-related epilepsy (48% of responders) than in generalized epilepsy (32% of responders). In the latter group, 19 patients suffered from infantile spasms. Four of six patients with cryptogenic infantile spasms became seizure-free. Of the 13 patients with symptomatic infantile spasms, only one was seizure-free. Results were poor for patients with Dravet's syndrome. In general, TPM was well tolerated. The most frequently reported adverse effects were drowsiness, irritability, hyperthermia, and anorexia. The present study concludes that TPM is effective for a broad range of seizures in infants and young children and represents a valid therapeutic option in this population.

Chromosome 18 aberrations and epilepsy: a review.

Epilepsy is commonly observed in patients with chromosomal aberrations. We evaluated epilepsy and electroencephalographic (EEG) features in a group of patients carrying aberrations of chromosome 18. Fourteen patients were recruited: five with an 18p deletion syndrome (18pDS); six with an 18q deletion syndrome (18qDS); two with trisomy 18p syndrome; and one with a 45,XY,t(17-18) (cen-q11.2) karyotype. Patients with 18pDS had neither epilepsy nor EEG anomalies; four patients with 18qDS had epilepsy with partial seizures occurring during infancy or early childhood. Partial seizures were also present in both patients with trisomy 18p. By contrast, mixed seizures were observed in the patient carrying a translocation between chromosomes 17 and 18. Our data and a re-evaluation of the literature suggest that epilepsy is infrequent in patients with 18pDS. Conversely, partial seizures and focal EEG anomalies may be observed in those with patients with 18qDS. Our observations suggest that the haplo-insufficiency of genes located on the long arm of chromosome 18 is more likely to be associated with epilepsy, than is haplo-insufficiency of genes located on the short arm. While further EEG/clinical investigations are needed to validate these observations, this study indicates a possible relationship between chromosome 18 genes and epilepsy.

Color vision in epileptic adolescents treated with valproate and carbamazepine.

OBJECTIVE: The aims of our study were to evaluate whether deficits in color vision exist in epileptic adolescents, to study if monotherapy with valproic acid (VPA) and carbamazepine (CBZ) can affect color vision, and to determine the possible relationship between abnormal color vision tests and AEDs dosage and their serum concentrations. PATIENTS: We examined 45 epileptic patients before the beginning of therapy and after 1 year of VPA or CBZ monotherapy and 40 sex- and age-matched healthy controls. METHODS: Color vision was evaluated with Farnsworth Munsell 100 (FM100) hue test and achromatic and short-wavelength automated perimetry (SWAP). STATISTICAL ANALYSIS: To evaluate intergroup differences we used ANOVA with Scheffe's post hoc test, when appropriate. Repeated measures ANOVA was used to evaluate the intragroup modifications of total error score (TES) and perimetric threshold during the follow-up. Pearson's correlation test was performed to correlate chromatic sense and perimetric data and AEDs dosage and serum concentrations. RESULTS: Before the beginning of therapy, there were no differences in central color vision and SWAP between controls and epileptic patients. After 1 year, patients treated with VPA or CBZ showed a deficit in FM100 hue test and SWAP parameters while no significant deficit was found in achromatic perimetry. In particular, with the FM100 hue test a higher number of errors was found in both groups of patients (CBZ patients: 166.00 +/- 27.72 TES; VPA patients: 151.19 +/- 44.09, P < 0.001) in comparison with controls (controls: 109.29 +/- 24.73) and baseline values (CBZ patients: 110.65 +/- 22.9; VPA patients 107.43 +/- 21.70). With SWAP patients of both groups showed significant variation of foveal threshold (controls: 21.07 +/- 2.01 dB; CBZ patients: 19.35 +/- 1.32, P < 0.001; VPA patients: 18.88 +/- 1.89, P < 0.001), full-field mean threshold perimetric sensitivity (controls: 18.50 +/- 1.24 dB; CBZ patients: 16.60 +/- 1.47, P < 0.001; VPA patients: 16.23 +/- 1.55, P < 0.001) and mean threshold perimetric sensitivity of the three evaluated subareas of the visual field (area 1 controls: 21.01 +/- 1.15; CBZ patients: 19.45 +/- 1.74, P = 0.001; VPA patients: 18.25 +/- 1.61, P < 0.001; area 2 controls: 18.40 +/- 1.43; CBZ patients: 16.07 +/- 1.58, P +/- 0.001; VPA patients: 16.13 +/- 1.46, P = 0.001; area 3 controls: 17.20 +/- 1.49; CBZ patients: 14.28 +/- 1.51, P < 0.001; VPA patients: 14.31 +/- 2.90, P = 0.001). CONCLUSIONS: Our study demonstrates that treatment with VPA or CBZ can affect significantly both central and paracentral color vision after a short treatment period.

Autosomal malignant osteopetrosis. From diagnosis to therapy.

Osteopetrosis is a heterogeneous family of rare human genetic disorders due to markedly decreased bone resorption. It is one among disorders causing osteosclerosis of the trabecular bone and/or hyperostosis of the cortical bone. Four types of human osteopetrosis have been clearly defined, but patients with atypical symptoms are frequent, suggesting that there are additional forms. The most severe expression of this condition in its malignant form is inherited as an autosomal recessive disorder and it is usually fatal before school age. It presents with failure to thrive, severe hepatosplenomegaly, pancytopenia and nerve compression leading to blindness and deafness during infancy. The case of a 2-month-old female child with severe hepatosplenomegaly, failure to thrive, nystagmus, pancytopenia, gengival hyperplasia, optic atrophy, absent evoked visual potential and increased bone density within the total skeleton, is reported. Diagnosis of autosomal recessive malignant osteopetrosis was established by transiliac bone biopsy. She underwent bone marrow transplantation, but died soon afterwards. This rare and mortal disorder of bone formation requires early diagnosis and immediate pharmacological treatment, consisting in administration of vitamin D, in order to enhance bone resorption and of prednisone to improve hematological indexes and, if possible, bone marrow transplantation in order to ameliorate quality of life and survival.

Serum levels of chitotriosidase as a marker of disease activity and clinical stage in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease characterized by T-lymphocyte activation and lymphocyte migration into involved organs, usually the lungs. The amounts of a number of biochemical markers, such as angiotensin converting enzyme (ACE) activity, increase in the serum of patients with sarcoidosis. Chitotriosidase is an enzyme secreted by activated macrophages able to catalyze the hydrolysis of both chitin and chitin-like substrates. Chitotriosidase is involved in defense against, and in degradation of chitin-containing pathogens such as fungi, nematodes, and insects. METHODS: Forty-three patients affected by chronic sarcoidosis, in active (23 patients) or inactive (20 patients) phase, were studied. Serum levels of chitotriosidase and ACE activity were evaluated and compared with those of 32 healthy subjects. Serum chitotriosidase concentration and ACE activity were also correlated with radiographic stage of disease. RESULTS: Individuals with chronic sarcoidosis have higher serum chitotriosidase concentrations and ACE activity than those of normal subjects. Sarcoidosis patients in the active phase of the disease had significantly higher chitotriosidase and ACE levels than those in the inactive phase. In contrast to serum ACE activity, a significant relationship between serum levels of chitotriosidase and the four radiographic stages of the disease was observed. CONCLUSION: Although the data need to be validated by further investigation, the observations made in this study seem to indicate that serum chitotriosidase concentrations may be a useful marker for monitoring sarcoidosis disease activity and prognosis.

Facial hemangioma and malformation of the cortical development: a broadening of the PHACE spectrum or a new entity?

Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.

Malformations of cortical development in neurofibromatosis type 1.

The authors report three patients with neurofibromatosis type 1 and different types of malformations of cortical development: Patient 1 had a possible transmantle cortical dysplasia involving the right temporoinsuloparieto-occipital areas; Patient 2 had a periventricular band of heterotopic gray matter with an overlying pachygyric cerebral cortex; and Patient 3 had a left perisylvian polymicrogyria. Because all of these lesions result from different pathogenetic mechanisms, neurofibromin may play a role during several stages of cortical development.

Magnetoencephalographic and electroencephalographic evaluation in patients with cryptogenetic partial epilepsy.

UNLABELLED: Magnetoencephalography (MEG) has been applied for more than 20 years to the localization of the epileptic focus in partial epilepsies, but correlation with electroencephalographic (EEG) data in homogeneous groups of patients is scarce. OBJECTIVE: The aim of our work was to use EEG and MEG for the study of a group of adults and children affected by cryptogenetic partial epilepsy. METHODS: We analyzed the traces obtained from electroencephalographic and magnetoencephalographic recordings of 10 patients of ages ranging from 7 to 38 years affected by cryptogenetic partial epilepsy. We evaluated the presence of commonly detected or uniquely detected spikes, and, whenever possible, we used MEG for localization of the epileptic focus. RESULTS: Three patients showed no epileptic activity during the EEG and MEG sessions. Overall agreement between EEG and MEG (presence of concordant spikes with the same localization shown by both techniques) was obtained in five patients. In one patient the spikes detected by EEG and MEG were different, and in another patient interictal activity was demonstrated exclusively by EEG. CONCLUSIONS: EEG in this series was not inferior to MEG in terms of spike detection. Combination of EEG and MEG is feasible, better than each technique alone, and may be useful for non-invasive diagnosis and monitoring of pediatric and adult patients with partial epilepsies.

Posterior knee pain: primary symptom of a small non-occlusive venous clot.

A healthy 9 year old girl presented with severe posterior knee pain and a small segmental non-occlusive popliteal venous thrombosis. The case is relevant for its unique presentation and symptoms. Lack of recanalisation persisted at one year follow up.

Serum leptin levels in girls with precocious puberty.

Few data are available regarding leptin levels in children with different pubertal stages or with precocious puberty (PP). The aim of this study was to assess the changes in serum leptin levels in patients with PP. We studied 20 girls with PP, with Tanner stage II-III; the age at the beginning of pubertal signs ranged from 4.2 to 7.1 yr; all the girls had an advantaged bone age. Controls were subdivided in two groups: group 1: 20 pre-pubertal girls with the same chronological age of the patients, without any signs of pubertal development (Tanner stage I); group 2: 20 additional girls with the same bone age, pubertal stage and body mass index (BMI) of the girls with PP. Serum leptin levels in females with PP are similar to those found in subjects with normal puberty (9.0 +/- 0.8 vs 9.1 +/- 0.9 ng/ml; ns) and different from subjects with the same chronological age without activation of puberty (5.6 +/- 0.9 ng/ml, p < 0.001). In all groups leptin levels correlated significantly with BMI (girls with PP: r = 0.5 1, p < 0.02; control group 1 girls: r = 0.71; p < 0.0001; control group 2 girls: r = 0.49; p < 0.02), there was no significant relationship between leptin and activation of hypothalamic-pituitary-gonadal axis. Our results indicate that the serum leptin levels in the girls with PP are not significantly different from levels in healthy girls at a similar stage of pubertal development, suggesting that the relationship between serum leptin levels and BMI is also present in this pathological situation.

Anticardiolipin, glutamic acid decarboxylase, and antinuclear antibodies in epileptic patients.

To explore the hypothesis that raised anticardiolipin antibodies, glutamic acid decarboxylase, and antinuclear antibodies may be associated with epilepsy and/or pharmacoresistance, we studied titers in 74 epileptic patients and 50 controls. Epileptic patients were divided into two groups according to their response to anticonvulsant therapy. Group I included 52 children (30 females and 22 males with a mean age+/-SD of 7.0+/-2.4 years) suffering from different types of epilepsy who were treated with various anticonvulsants. Group II included 22 children (10 females and 12 males with a mean age of 6.2+/-3.6 years) suffering from therapy resistant epilepsy. We found that the prevalence of anticardiolipin antibodies was significantly higher in epileptic patients than in controls, while there was no significant difference between patients who were seizure free and those with uncontrolled epilepsy. No significant difference was found in glutamic acid decarboxylase antibodies between epileptic children and controls, and between patients who were seizure free and those with uncontrolled epilepsy. A significant difference in the incidence of antinuclear antibodies was found between epileptic children and controls, while no difference was found between well-controlled and drug-resistant epilepsy. In conclusion, the prevalence of anticardiolipin and antinuclear antibodies was higher in patients with epilepsy than in controls. There was no significant difference in serum glutamic acid decarboxylase antibodies between epileptic children and controls, and between patients who were seizure free and those with uncontrolled epilepsy.