Photoparoxysmal responses in children with chromosomal aberrations.

Electroencephalographic (EEG) anomalies and epilepsy are commonly observed in the clinical picture of patients with chromosomal aberrations. However, no investigations have been performed on the relationship between chromosomal disorders and photoparoxysmal response (PPR). In this study, we evaluate the characteristics of PPRs elicited with intermittent photic stimulation during a routine electroencephalogram in children affected by chromosomal anomalies and correlated this with the clinical profile of the child. A review of the literature has also been performed. PPRs occurred in 14% (4/28) of patients. PPRs were brief (

Childhood absence epilepsy: evolution and prognostic factors.

PURPOSE: To evaluate how diagnostic criteria influence remission rates for patients with childhood absence epilepsy (CAE) and to assess clinical and EEG parameters as predictors of outcome. METHODS: One hundred nineteen patients were diagnosed with CAE, according to International League Against Epilepsy (ILAE) classification criteria. They were subsequently evaluated according to stricter diagnostic criteria. Sixty-two subjects fulfilled these criteria as group 2; 57 did not and constituted group 1. Diagnostic parameters that prevented patients of group 1 from entering group 2, and variables such as sex, familial history of generalized epilepsy, and personal history of febrile convulsions also were tested as prognostic factors for terminal remission. RESULTS: Compared with those in group 1, patients of group 2 had significantly higher rates of seizure control (95% vs. 77%), higher rates of terminal remission (82% vs. 51%), fewer generalized tonic-clonic seizures (8% vs. 30%), and shorter mean periods of treatment (2.2 vs. 3.8 years). Significantly fewer patients were receiving polytherapy in group 2 than in group 1 (11% vs. 47%), and fewer patients had seizure relapses at antiepileptic drug discontinuation (0 vs. 22%). CONCLUSIONS: Remission rates of patients with CAE are greatly influenced by the classification criteria used for selection. Stricter diagnostic criteria allow the definition of a homogeneous group of patients with excellent prognosis. Factors predicting unfavorable prognosis were generalized tonic-clonic seizures in the active stage of absences, myoclonic jerks, eyelid myoclonia or perioral myoclonia, and EEG features atypical for CAE.

Typical absence seizures associated with localization-related epilepsy: a clinical and electroencephalographic characterization.

INTRODUCTION: This paper describes the characteristics of patients with typical absence seizures associated with localization related epilepsy (LRE) and compares electroclinical features of absences occurring in these patients with those having childhood absence epilepsy (CAE). METHODS: Consecutive patients presenting with both LRE and typical absences in their epilepsy history were included in the study (Group 1). Clinical assessments and EEG investigations were conducted during the follow-up. Patients observed during the same period, but with typical absences fulfilling the CAE diagnostic criteria, were assigned to a second group (Group 2). RESULTS: Fourteen patients were included in Group 1. These patients had a mean age at their last visit of 11.3 years (range 7.2-16.8), with a mean follow-up period of 6.8 years. In all patients LRE was the first type of seizure to occur at median age of 4.95+/-2.1 years (range 1.9-8.8). Typical absences appeared at median age of 7.5+/-2.5 years (range 4.5-12.5), and were well controlled by therapy. Ictal EEG and semiology features of typical absences did not show any distinctive features when compared to those of Group 2 represented by 53 patients affected by CAE. However, age at onset was significantly higher in Group 1, as was the number of patients who underwent polytherapy, and the number with relapses after drug discontinuation. None of patients in Group 1 showed terminal remission. CONCLUSION: Although clinically heterogeneous and rare, the association of LRE with typical absences may be more than coincidental. In these patients, typical absences responded well to therapy, but terminal remission rates were lower than for CAE patients.

Post-ictal circulating levels of allopregnanolone in children with partial or generalized seizures.

INTRODUCTION: Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) is a neurosteroid with a potent modulating activity on the gamma-aminobutyric acid (GABA)(a) receptor complex. It plays a key role in the epileptogenesis of partial seizures. Serum allopregnanolone concentrations significantly increase in the postcritical phase. In the present study we investigated the post-ictal serum allopregnanolone levels in children with partial seizures and generalized seizures, respectively. PATIENTS AND METHODS: Three groups of subjects were included in the study. Group 1 consisted of 18 children affected by complex partial seizures. Group 2 consisted of 11 children presenting with generalized epilepsy. Group 3 consisted of 20 healthy age-matched subjects. Serum allopregnanolone levels were assayed in the inter-ictal phase and within 30 min after an epileptic event. RESULTS: The data we obtained suggest that circulating allopregnanolone level significantly increases in the post-ictal phase. However, we found no significant differences in the post-ictal serum allopregnanolone concentrations between patients with partial seizures and those with generalized seizures. CONCLUSIONS: Further studies are needed to establish if allopregnanolone is a reliable circulating marker of epileptic seizures. However, our observations seem to indicate that post-ictal circulating allopregnanolone level is not useful in differentiating focal and generalized epilepsy events.

Non-progressive leukoencephalopathy with bilateral anterior temporal cysts: a case report and review of the literature.

A newly described disease is characterized by anterior bilateral temporal lobe cysts associated with multilobar leukoencephalopathy and a non-progressive clinical course. We report a patient with bilateral anterior temporal lobe cystic changes associated with a non-progressive neurological disorder, microcephaly, spasticity, mental retardation, and sensorineural deafness. From the literature, 12 other patients have shown a similar phenotype. The common neuroradiological findings in these patients have been bilateral anterior temporal lobe cystic changes and non-progressive leukoencephalopathy. By contrast, variability in the clinical phenotype has been observed, ranging from severe neuromotor handicap with mental retardation and microcephaly to spasticity in the lower limbs associated with normal cognitive function. The pathological basis of the defect remains to be defined.

Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study.

This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy.

Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12.

Epilepsy, together with mental retardation, represents a common manifestation of chromosomal aberrations. Specific electroencephalographic (EEG) and epileptic patterns have been described in several chromosomal disorders, such as Angelman's syndrome, Miller-Dieker syndrome, Wolf-Hirschhorn syndrome, and ring 20 syndrome. A peculiar electroclinical pattern has also been identified in trisomy 12p syndrome. We report three patients with a pericentric inversion of chromosome 12, with breakpoints localized to p11-q13 and affected by epilepsy or EEG anomalies. Two suffered from epilepsy, which, in the clinical course, was mainly characterized by complex partial seizures with a semiology related to the temporal lobe. In one patient, myoclonic absences, head drop, and massive jerky attacks were also present. In both patients, generalized 3 Hz bursts were registered, together with multifocal and focal paroxysmal activity, which were most prominent in the temporoparietal and temporal areas, respectively. In the other patient, who had no epilepsy, EEG showed bioccipital paroxysmal activity. In all patients, the clinical picture was characterized by the presence of moderate mental retardation and behavioral disorders. The incidence of epilepsy or EEG anomalies among patients with a pericentric inversion of chromosome 12 remains to be ascertained. However, the present study confirms that chromosome 12 anomalies can be associated with epilepsy. Although myoclonic absence-like episodes can occasionally be part of the epileptic phenotype, the electroclinical pattern in pericentric inversion of chromosome 12 seems to be more polymorphic when compared with that observed in trisomy 12p syndrome.

Electroencephalographic and epileptic patterns in X chromosome anomalies.

Although epilepsy and mental retardation are commonly observed in individuals with chromosomal aberrations, the identification of EEG/epileptic profiles in those with specific chromosome anomalies remains difficult. A few syndromes seem to show peculiar clinical and EEG associations. The authors report an electroclinical investigation on a group of patients carrying X chromosome anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1 with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the patients with Klinefelter's syndrome, in one patient with an X-autosomal rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG anomalies were detected in the other patients. Epilepsy may be associated with Klinefelter's syndrome. In addition, the authors found that an electroclinical pattern, represented by paroxysmal activity in the posterior regions (temporo-parieto-occipital areas) with complex partial seizures and easily controlled by antiepileptic drugs, may be present in patients with triple X syndrome. In contrast, gross X-autosomal rearrangements are associated with polymorphic EEG/epileptic findings. Although further studies are needed to validate these observations, they clearly confirm the strict relationship between X chromosome anomalies and epilepsy.

Hot water epilepsy and focal malformation of the parietal cortex development.

Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. HWE is considered to be a geographically specific epileptic syndrome since it mainly occurs in the Indian community. Spontaneous seizures may also occur later in life. The seizure pattern includes complex partial attacks. Although the pathogenesis of HWE is still unknown, temporal lobe has been thought to take part in the epileptogenesis. This paper reports on a 4-year-old girl who, at the age of 6 months, experienced complex partial seizures triggered by bathing in hot water. Non-provoked seizures intercritical EEG showed isolated spikes and spike-and-waves in the left parietal region. Brain MRI detected a left parietal focal cortical dysplasia. This is the second patient with HWE in whom a cortical malformation has been observed. The observation present here and data reported in the literature seem to indicate that the sensory cortex might also be involved in triggering seizures precipitated by a bath in hot water. Moreover, the authors believe that MRI examination should be considered for this group of patients.

Craniofacial dyssynostosis: case report and review.

Craniofacial dyssynostosis (CFD) is a rare disorder related to premature closure of the lambdoid suture and the posterior part of the sagittal suture. Epilepsy, mental retardation, abnormalities of the corpus callosum, and short stature have been reported. We studied a patient with CFD, hydronephrosis, and partially empty sella turcica; the latter two features are reported for the first time. We discuss the brain anomalies and their neurologic sequelae, which are part of the CFD phenotype.

Factors associated with poor control in partial complex epilepsy.

To evaluate the predictive factors of response to anticonvulsant therapy in children with complex partial epilepsy, we studied prospectively 74 children and adolescents suffering from this type of epilepsy. All children were prospectively followed for at least 2 years after the beginning of anticonvulsant therapy. At the end of follow-up, the children were subdivided into two groups according to the frequency of seizures: group A, children who were seizure free in the last year, and group B, children with at least six seizures in the previous year. Children with a poor response to anticonvulsant therapy had a more frequent personal history of neonatal seizures, an interval of less than 6 months between the first and the second seizures, and persistent abnormal electroencephalograms than the seizure-free patients and were often treated with polytherapy.

Epilepsy in neurofibromatosis 1.

Neurofibromatosis 1 is the most common neurocutaneous disease. Neurologic manifestations are mainly represented by tumors such as optic gliomas, focal areas of high T2-weighted signal known as unidentified bright objects, and mental retardation or learning disabilities. The prevalence of seizures has been reported to range from 3.8 to 6%. In the present study, we evaluated prevalence, type, and etiology of epilepsy in a neurofibromatosis 1 population. A retrospective analysis of 198 patients affected by neurofibromatosis 1 was performed. Fourteen patients (7%) were found to be epileptic. Every patient underwent electroencephalographic examination and neuroimaging investigations. Thirteen were submitted to magnetic resonance imaging (MRI) study and one to computed tomographic (CT) scanning. Single-photon emission computed tomographic and positron emission tomographic studies were performed in a few selected cases. Seizures were partial in 12 of these (85%) and generalized in 2 (15%). In nine (64%), epilepsy was secondary to brain lesions: five of these had cerebral tumors (three with epilepsy as the fist symptom), three had cortical malformation, and one had mesial temporal sclerosis. Seizures were controlled rapidly in eight (57%) and drug resistant in four (29%). Two patients were lost at follow-up. All patients with uncontrolled seizures had severe mental retardation, and three of these had malformations of cortical development. Our observations and our re-evaluation of the literature indicate that patients with neurofibromatosis 1 have an increased risk of epilepsy related to intracranial masses and cytoarchitectural abnormalities, and seizures can represent the first symptom of a tumor or cortical malformation. Brain MRI and, in selected cases, functional studies appear to be useful in patients with neurofibromatosis 1 who present with seizures, especially if associated with mental retardation.

Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy: a practical approach.

In epileptic patients, treated with anticonvulsant drugs (AEDs), the question when and how an attempt should be made to withdraw therapy is a crucial point in the management of these patients. In recent years, many studies have identified the main risk factors for seizure recurrence after discontinuation of AEDs. Patients are more likely to have recurrences if there is a definite symptomatic aetiology, two or more different types of seizures, an abnormal neurological examination and a seizure onset at adolescence or later. In contrast, abnormal EEG has not been proved as a risk factor for recurrence. Moreover, the classification of epilepsy syndromes is another important predictor of the outcome for these patients. In practice, most authors suggest that medication is discontinued after a seizure-free period of two years. In this review we analyse data from the literature and we suggest a practical approach for safe anticonvulsant withdrawal, although the decision should always be made individually, weighing risks and benefits.

Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia.

Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.

Inter-ictal and post-ictal circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in epileptic children.

Allopregnanolone belongs to a group of neuroactive steroid hormones, or neurosteroids, synthesized and acting within the brain and is as a potent endogenous positive modulator of GABA(A) receptor complex. Administration of allopregnanolone protects rats against pentylentetrazol, bicuculline, kainic acid, and picrotoxin-induced seizures. We investigated serum allopregnanolone levels in children with active epilepsy at pubertal Tanner's stage I (n=52). Blood specimens were collected at least 12 h after a seizure (inter-ictal). In a subgroup of patients (n=11), specimens were also collected within 30 min from a seizure attack (post-ictal). Healthy age-matched children (n=18) served as controls. Serum allopregnanolone was measured by radioimmunoassay using a polyclonal antiserum. The inter-ictal serum allopregnanolone levels in the epileptic children were not statistically different from those detected in the control group, whereas post-ictal levels were significantly higher than the inter-ictal ones (P=0.0001). In this subgroup of patients allopregnanolone levels decreased to the basal values during the following 12 h. Serum allopregnanolone levels may therefore reflect changes in neuronal excitability, and allopregnanolone appears to be a reliable circulating marker of epileptic seizures. It is possible that increased post-ictal serum levels of allopregnanolone may play a role in modulating neuronal excitability and may represent an endogenous mechanism of seizure control.

Schinzel-Giedion syndrome: a further cause of West syndrome.

Schinzel-Giedion syndrome (SGS) is a rare disorder with a likely autosomal recessive pattern of inheritance which is characterized by several facial dysmorphisms, midface hypoplasia, multiple skeletal anomalies including short and sclerotic skull base, short neck, and post-axial polydactyly. Cardiac and urogenital malformations are also present. Thirty-three cases have been described so far. We report on a boy affected by SGS in whom a long-term EEG follow-up showed a progressive deterioration of the background bioelectric activity ending, at the age of 19 months, with a hypsarrhythmic pattern clinically correlated with severe and refractory infantile spasms. EEG deterioration and neuroradiological findings, which showed progressive brain atrophy, confirm the neurodegenerative nature of SGS. We also re-evaluated all the published cases and found that 33% of patients with SGS experienced neonatal seizures and another 25% developed West syndrome in the following months. The seizures appeared extremely refractory to several anticonvulsive treatments. In conclusion, we believe that SGS should be included among the causes of secondary West syndrome.

von Willebrand factor and its propeptide in children with diabetes. Relation between endothelial dysfunction and microalbuminuria.

It has been shown that patients with insulin-dependent diabetes mellitus have elevated von Willebrand factor (vWF) plasma concentrations. Plasma fibrinogen, vWF, and its propeptide concentrations have been evaluated in 102 children with insulin-dependent diabetes mellitus to determine whether an increase of vWF and its propeptide levels precedes and may predict the development of persistent microalbuminuria. The patients have been divided into two groups according to the presence or absence of microalbuminuria at the end of follow-up. They have been followed up for at least 8 y. Control group consisted of 80 age- and sex-matched healthy volunteers. At the beginning of the study there was no significant difference in fibrinogen, vWF, and its propeptide levels between patients and control subjects. During the follow-up, a significant increase of plasma vWF and its propeptide has been observed in the group of patients who later developed microalbuminuria but not in those who remained normoalbuminuric. This increase started 3 y and become statistically significant (p < 0.01) 2 y before the onset of microalbuminuria, persisting until the end of the study. During the entire follow-up plasma values of fibrinogen persisted in the normal range. In conclusion, an increase in plasma concentration of vWF and its propeptide precedes microalbuminuria and, therefore, can be useful to identify children with insulin-dependent diabetes mellitus at risk to develop incipient nephropathy later in life.

Linear scleroderma associated with progressive brain atrophy.

Linear scleroderma (LS) is characterized by scleroatrophic lesions affecting limbs and legs, unilaterally. Neurological involvement may be associated with ipsilateral facial and skull involvement in disorders referred to clinically as LS 'en coup de sabre', and Parry-Romberg syndrome. We report a child with LS presenting with a severe neurological disorder characterized by epilepsy, progressive mental deterioration and a rapid process of atrophy involving the ipsilateral cerebral hemisphere, but not associated with an overlying facial structure involvement. Functional brain studies showed a reduction in the diameter of the left internal carotid and of the left middle cerebral artery. Our observations suggest that neuroimaging studies should be considered in all patients with linear scleroderma, and such studies become necessary when neurological symptoms occur.