Maria Cristina Scaduto

Epilepsy and EEG paroxysmal abnormalities in autism spectrum disorders

The occurrence of epilepsy in autism is variable; nevertheless, EEG paroxysmal abnormalities (PA) are frequently recorded in patients with autism, although the influence of epilepsy and/or EEG PA on the autistic regression has not been clarified yet. We examine a large sample of 345 inpatients with autism, divided into three groups: (1) patients without epilepsy and EEG PA; (2) patients with EEG PA but no seizures; (3) patients with epilepsy including febrile convulsions. The prevalence of epilepsy (24.9%) and EEG PA (45.5%) was higher than that reported in the general population. The significant differences among the three groups concerned autistic regression (comparison between groups 1 and 2, p<0.05; comparison between groups 1 and 3, p<0.01), cerebral lesions (comparison between groups 1 and 2, p<0.05; between groups 1 and 3, p<0.001), and symptomatic autism (comparison between groups 1 and 2 as much as comparison between groups 1 and 3, p<0.001), which were prevalent in groups 2 and 3; while severe/profound mental retardation was more frequent in group 3 compared to group 1 (p<0.01). Focal epilepsy (43.0%) and febrile convulsions (33.7%) were frequent in the third group with epilepsy. EEG PA were mainly localized in temporal and central areas (31.4%). Only 2.6% of patients had subcontinuous/continuous EEG PA during sleep. Seizures and EEG PA were not related to autistic regression. EEG PA occurred mainly in childhood, while epilepsy tended to occur (p<0.001) as age increased. The age at onset of seizures had two peaks: between 0 and 5 and between 10 and 15 years with no difference between idiopathic and symptomatic cases. In 58.5% of subjects aged > or = 20 years, epilepsy including febrile seizures occurred at some point of their lives, while cases with only EEG PA were less frequent (9.7%). The relationship among autism, EEG PA and epilepsy should be clarified and investigated. In autism, seizures and EEG PA could represent an epiphenomenon of a cerebral dysfunction independent of apparent lesions.

Epilepsy in patients with pervasive developmental disorder not otherwise specified.

Data on epilepsy in pervasive developmental disorder not otherwise specified are few and scanty. Seventy-seven patients with pervasive developmental disorder not otherwise specified were compared with 77 with autistic disorder, matched for age and sex. The 2 groups were divided into 3 subgroups each: A, without electroencephalography (EEG) paroxysmal abnormalities or epilepsy; B, with EEG paroxysmal abnormalities without epilepsy; and C, with epilepsy. Mild mental retardation (P < .01), pathological neurological examination (P < .05), cerebral lesions (P < .01), abnormal EEG background activity (P < .001), and associated genetic pathologies (P < .01) were more common in pervasive developmental disorder not otherwise specified. Familial antecedents for epilepsy prevailed in subgroup C (P < .01). Epilepsy occurred in 35.1% of patients with pervasive developmental disorder not otherwise specified, with no statistically significant difference compared with autistic disorder. The mean age of seizure onset was earlier (2 years 8 months) in pervasive developmental disorder not otherwise specified (P < .000). Seizure outcome was better in autistic disorder. Genetic diseases and cerebral lesions should be investigated in pervasive developmental disorder not otherwise specified to clarify the etiological and clinical features.

Epilepsy, Intelligence, and Psychiatric Disorders in Patients With Cerebellar Hypoplasia

The cerebellum is involved in motor and cognitive functions and behavior. Its role in controlling epileptic seizures has been demonstrated in the literature. Genetic factors can enhance epilepsy susceptibility when the cerebellum is damaged. We examined the occurrence and features of epilepsy, intelligence, and psychiatric disorders in 28 patients with cerebellar hypoplasia. We compared patients with (10; 35.7%) and without (18; 64.3%) epilepsy. The statistical evaluation showed a significant prevalence of familial antecedents for seizures in patients with epilepsy (P < .01); cerebral associated lesions and type of cerebellar hypoplasia did not influence the occurrence of epilepsy, which was partial in 80% of cases. Profound mental retardation prevailed in patients with epilepsy (P < .05). Both mental retardation (75%) and pervasive developmental disorders (17.8%) prevailed in our cases with respect to the general population (P < .000). Cerebellar hypoplasia in our sample seems to be an important risk factor for the occurrence of epilepsy, mental retardation, and psychiatric disorders. (J Child Neurol 2003; 18: 1—4).

Is cognitive behavioural therapy an effective complement to antidepressants in adolescents? A meta-analysis

Calati R, Pedrini L, Alighieri S, Alvarez MI, Desideri L, Durante D, Favero F, Iero L, Magnani G, Pericoli V, Polmonari A, Raggini R, Raimondi E, Riboni V, Scaduto MC, Serretti A, De Girolamo G. Is cognitive behavioural therapy an effective complement to antidepressants in adolescents? A meta-analysis. Objective: Evidence on effectiveness of combined treatments versus antidepressants alone in adolescents consists on a few studies in both major depressive and anxiety disorders. A meta-analysis of randomised 12-week follow-up studies in which antidepressant treatment was compared to combined treatment consisting of the same antidepressant with cognitive behavioural therapy has been performed. Methods: Data were entered into the Cochrane Collaboration Review Manager software and were analysed within a random effect framework. A quality assessment has been performed through Jadad Scale. Results: Higher global functioning at the Childrens Global Assessment Scale was found in the combined treatment group (p < 0.0001) as well as higher improvement at the Clinical Global Impressions Improvement Scale (p = 0.04). No benefit of combined treatment was found on depressive symptomatology at the Childrens Depression Rating Scale – Revised. Conclusion: Combined treatment seems to be more effective than antidepressant alone on global functioning and general improvement in adolescents with major depressive and anxiety disorders.

Posterior Fossa Malformations and Epilepsy

The association between posterior fossa malformations and epilepsy is rarely reported in the literature. We describe 54 cases with posterior fossa malformations, according to embryogenesis classification, divided into two groups on the basis of presence or absence of epilepsy. Epilepsy occurred in 22 cases (40.7%) and was not related to the type of posterior fossa malformation or to supratentorial cerebral lesions associated with the malformation. Familial antecedents for epilepsy and/or febrile convulsions influenced the presence of epilepsy in patients with posterior fossa malformations (P < .01). Epilepsy was mainly partial (77.3%); benign partial/generalized epilepsies and febrile convulsions occurred in 27.3% of cases. Seizures disappeared for 2 or more years at the end of follow-up in 36.4% of patients. Good epilepsy prognosis was not related to the age at onset of seizures, familial antecedents for epilepsy and/or febrile convulsions, supratentorial associated lesions, or age of patients at the last observation. Profound mental retardation prevailed in patients with epilepsy (P <.01), as did pathologic electroencephalograms (EEG) (P <.0001), with paroxysmal abnormalities (P <.001) and asymmetry (P < .01). In our 54 cases of posterior fossa malformation, we identified two risk factors for epilepsy: familial antecedents for epilepsy and/or febrile convulsions and the involvement of the cerebellum in the malformation. (J Child Neurol 1999;14:113-117).

Cerebellar hypoplasia, continuous spike-waves during sleep, and neuropsychological and behavioral disorders

We describe 3 patients with different degrees of cerebellar hypoplasia and continuous spike-waves during sleep: the more extensive the cerebellar hypoplasia, the more compromised the neuropsychological abilities and behavior. Cerebellar hypoplasia is a risk factor for epilepsy and/or neuropsychological and psychiatric disorders. Epilepsy is also strongly associated with familial antecedents for seizures, as previously reported. The cerebellum is implicated in controlling epileptic seizures and in regulating motor, cognitive, and emotional functions with a topographic organization. The association between cerebellar hypoplasia and continuous spike-waves during sleep has never been reported. We suggest that continuous spike-waves during sleep may further compromise neuropsychological and behavioral features that are associated with cerebellar hypoplasia.

Neuropsychiatric phenotype in a child with pseudohypoparathyroidism

Pseudohypoparathyroidism (PHP) is a rare heterogeneous genetic disease characterized by end-organ resistance to parathyroid hormone. In adulthood, heterogeneous neurological and psychiatric disorders have been reported which are associated with hypoparathyroidism in general and with PHP in particular, while for childhood, data are scanty. We report a case of a boy with PHP type 1b, in whom neurological signs at the onset prevailed, characterized by tic-like dyskinesias associated with a series of heterogeneous not well-defined neurological and behavioral features, describing the diagnostic work-up performed and the follow-up. We suggest that the diagnostic hypothesis of PHP might be considered when dealing with a child with tic-like dyskinesias, especially if associated with a series of heterogeneous not well-defined neurological and behavioral features. In these cases, treatment with calcitriol and calcium has to be started as soon as possible to achieve a prompt and persistent clinical improvement.

Neuropsychological implications of adjunctive levetiracetam in childhood epilepsy

Introduction: Levetiracetam (LEV) is an effective antiepileptic drug also used in childhood and adolescence. Literature data regarding the long-term effects of LEV in childhood epilepsy and based on extensive neuropsychological evaluations using standardized tools are still scanty. Our study aimed to address this topic. Materials and Methods: We studied 10 patients with epilepsy characterized by focal or generalized seizures (4 boys, 6 girls; mean age: 10 years 8 months; range: 6 years 2 months - 16 years 2 months), treated with adjunctive LEV during a follow-up of 12 months. In 6 patients electroencephalogram (EEG) showed continuous spike and waves during sleep. Using standardized tools, we performed seriated assessments of cognitive and behavioral functioning in relation to seizure and EEG outcome. Results: Six patients completed the trial after 12 months of treatment; 1 patient dropped out of the study after 9 months, 3 patients after 6 months. Adjunctive LEV was effective on seizures in 3/10 patients and on EEG in 2/10 patients, and was well tolerated in all examined cases. Overall, no worsening of cognitive or behavioral functions has been detected during the period of the study; even at 6 and 12 months from baseline, an improvement in patients’ abstract reasoning has been found, that was not related to seizure or EEG outcome. Conclusions: In our population of children and adolescents, LEV had no adverse cognitive or behavioral effects, short- or long-term. We found an improvement of abstract reasoning, regardless of seizure and EEG outcome.

Methyl-CpG-binding Protein 2 (MECP2) Gene Mutations in an Italian Sample of Patients with Pervasive Developmental Disorder and Mental Retardation

Methyl-CpG-binding protein 2 (MECP2) gene mutations have been identified in girls with Rett syndrome and in boys with heterogeneous neuropsychiatric disorders. Because of the limited or inconsistent data reported in literature, the role of methyl-CpG-binding protein 2 gene in the pathogenesis of mental retardation and pervasive developmental disorders needs further study. We scanned methyl-CpG-binding protein 2 gene in 99 Italian patients with pervasive developmental disorder or with nonsyndromal mental retardation. Four methyl-CpG-binding protein 2 gene mutations were found: 2 in 4 girls with Rett disorder, the others in 2 girls with mental retardation. The wide phenotypic spectrum and the variants of methyl-CpG-binding protein 2 gene, which may play an important role in gene regulation and neurodevelopment, justify the literatures interest particularly in girls.