Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Anti-NMDAR encephalitis misdiagnosed as Hashimoto's encephalopathy.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-defined autoimmune disorder. Hashimoto's encephalopathy (HE) is a still controversial entity, lacking definite diagnostic criteria. We described a 14-year-old-girl presenting with a clinical picture consistent with the diagnosis of anti-NMDAR encephalitis, confirmed by NMDAR antibody testing. Four years earlier, she had presented a similar episode of acute encephalopathy diagnosed as HE. Anti-NMDAR encephalitis and HE share similar clinical features so that the differential diagnosis can be difficult if specific antibodies are not tested. The correct diagnosis of anti-NMDAR encephalitis is crucial to plan the appropriate management and follow-up, namely in term of oncological screening, since it can be paraneoplastic in origin. We suggest to re-evaluate the clinical history of all subjects with previous HE diagnosis in order to evaluate the possible diagnosis of anti-NMDAR encephalitis and plan the appropriate management of these patients.

An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy.

OBJECTIVE: To conduct an open-label, add-on trial on safety and efficacy of levetiracetam in severe myoclonic epilepsy of infancy (SMEI). PATIENTS AND METHODS: SMEI patients were recruited from different centers according to the following criteria: age > or =3 years; at least four tonic-clonic seizures/month during the last 8 weeks; previous use of at least two drugs. Levetiracetam was orally administrated at starting dose of approximately 10 mg/kg/day up to 50 to 60 mg/kg/day in two doses. Treatment period included a 5- to 6-week up-titration phase and a 12-week evaluation phase. Efficacy variables were responder rate by seizure type and reduction of the mean number per week of each seizure type. Analysis was performed using Fisher exact and Wilcoxon tests. RESULTS: Twenty-eight patients (mean age: 9.4 +/- 5.6 years) entered the study. Sixteen (57.1%) showed SCN1A mutations. Mean number of concomitant drugs was 2.5. Mean levetiracetam dose achieved was 2,016 mg/day. Twenty-three (82.1%) completed the trial. Responders were 64.2% for tonic-clonic, 60% for myoclonic, 60% for focal, and 44.4% for absence seizures. Number per week of tonic-clonic (median: 3 vs 1; p = 0.0001), myoclonic (median: 21 vs 3; p = 0.002), and focal seizures (median: 7.5 vs 3; p = 0.031) was significantly decreased compared to baseline. Levetiracetam effect was not related to age at onset and duration of epilepsy, genetic status, and concomitant therapy. Levetiracetam was well tolerated by subjects who completed the study. To date, follow-up ranges 6 to 36 months (mean, 16.2 +/- 13.4). CONCLUSION: Levetiracetam add-on is effective and well tolerated in severe myoclonic epilepsy of infancy. Placebo-controlled studies should confirm these findings.

Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy.

OBJECTIVE: To identify cryptic chromosomal deletions involving SCN1A in patients with severe myoclonic epilepsy of infancy (SMEI). METHODS: Thirty-nine patients with SMEI and without SCN1A point mutations and their parents were typed with 14 intragenic SCN1A polymorphisms to identify hemizygosity. The parental origin and the extent of genomic deletions were determined by fluorescence in situ hybridization analysis using genomic clones encompassing chromosome 2q24.3-q31.1. Deletion breakpoints were more finely mapped by typing single-nucleotide polymorphisms and microsatellite markers. RESULTS: We identified three patients with SMEI who had genomic deletions encompassing the SCN1A locus. Deletion size was between 607 kb and 4.7 Mb. Deletions originated de novo from paternal chromosome in all subjects. One patient had central precocious puberty and palatoschisis. Genotype-phenotype correlations suggest that these clinical features are due to genes centromeric to SCN1A. CONCLUSIONS: Patients with severe myoclonic epilepsy of infancy (SMEI) lacking SCN1A point mutations should be investigated for cryptic chromosomal deletions involving SCN1A. Clinical features other than epilepsy could be associated with SMEI as a consequence of deletions in contiguous genes.

Hashimoto's encephalopathy with selective involvement of the nucleus accumbens: a case report.

Hashimoto's encephalopathy (HE) is an acute or subacute relapsing disorder usually affecting euthyroid patients with evidence of autoimmune thyroiditis. The neurological manifestations are non-specific, with subacute cognitive impairment, movement disorders, generalized seizures, focal neurological symptoms such as stroke-like episodes, or psychiatric disturbances. Autoimmune phenomena are likely to play an etiological role. Magnetic resonance imaging (MRI) findings are usually normal or show non-specific changes. We report the case of an 11-year-old girl with autoimmune thyroiditis who presented acutely with a complex neuropsychiatric disorder in association with MRI evidence of focal involvement of the nucleus accumbens (NA). The NA, a ventral striate nucleus, is part of a complex dopaminergic network. Lesions to the NA result in several psychiatric symptoms, such as attention-deficit hyperactivity disorders. In this patient, we observed alternating phases of stupor and hyperkinetic-anxious behavior, with marked instability. The pathogenetic mechanism and the anatomic and functional correlations are briefly discussed.

Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy.

OBJECTIVES: SCN1A mutations were recently reported in several patients with severe myoclonic epilepsy in infancy (SMEI). The authors analyzed SCN1A mutations in 93 patients with SMEI and made genotype-phenotype correlation to clarify the role of this gene in the etiology of SMEI. METHODS: All patients fulfilled the criteria for SMEI. The authors analyzed all patients for SCN1A mutations using denaturing high performance liquid chromatography. If a patient's chromatogram was abnormal, the authors sequenced the gene in the patient and both parents. RESULTS: SCN1A mutations were identified in 33 patients (35%). Most mutations were de novo, but were inherited in three patients. Parents carrying the inherited mutations had either no symptoms or a milder form of epilepsy. A greater frequency of unilateral motor seizures was the only clinical difference between patients with SCN1A mutations and those without. Truncating mutations were more frequently associated with such seizures than were missense mutations. The percentage of cases with family history of epilepsy was significantly higher in patients with SCN1A mutations. CONCLUSIONS: Unilateral motor seizures may be a specific clinical characteristic of SMEI caused by SCN1A mutations. Ten percent of SCN1A mutations are inherited from an asymptomatic or mildly affected parent, suggesting that SMEI is genetically heterogeneous. The increased frequency of familial epilepsy indicates that other genetic factors may contribute to this disorder.

Mesial temporal sclerosis--a late complication in four allogeneic pediatric recipients with persistent seizures after an acute episode of cyclosporine-A neurotoxicity.

Mesial temporal sclerosis (MTS) is a common finding in patients with intractable temporal lobe epilepsy (TLE). In this report, we retrospectively reviewed the neuroimaging results of four children who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and who developed recurrent, partial, intractable seizures following a first event caused by cyclosporine-A (CSA) neurotoxicity. Neuroradiologic findings of MTS were demonstrated in all these patients. We suggest that MTS may be a consequence of CSA neurotoxicity, which induces repeated seizures, associated with other predisposing conditions, as well as being a consequence of the underlying disease and its treatment, and of severe graft-versus-host disease (GvHD).

Severe neurologic complications after hematopoietic stem cell transplantation in children.

OBJECTIVE: To describe and evaluate the incidence and risk factors of severe neurologic events (SNE) in pediatric recipients of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) for hematologic or nonhematologic diseases. METHODS: Retrospective analysis of 272 consecutive children admitted to the G. Gaslini Children's Research Institute and given HSCT (70 from unrelated donors, 115 from related donors, and 87 autologous) between June 1985 and January 2001. RESULTS: Thirty-seven children (13.6%) developed SNE after a median of 90 days (range, 5 days to 8.8 years) after HSCT. Cyclosporine A (CSA) neurotoxicity was the most frequent SNE (n = 21), followed by irradiation or chemotherapy injury (n = 7), CNS infections (n = 7), cerebrovascular events (n = 3), and immune-mediated etiology SNE (n = 2). Eleven patients (30%) died because of the neurologic complications. Type of HSCT, treatment with total body irradiation (TBI), acute graft-vs-host disease (GvHD), GvHD >grade 2, and treatment with CSA were associated with a significant increased risk of SNE. CONCLUSIONS: Severe neurologic complications are frequent (14%) among children receiving HSCT, causing 8.5% of deaths after transplant. Transplant from allogeneic donor, especially if unrelated, the development of severe acute GvHD grade >2, and the use of TBI in the preparative regimen are the main risk factors for such complications.

An Italian severe Salla disease variant associated with a SLC17A5 mutation earlier described in infantile sialic acid storage disease.

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15-bp deletion in exon 6 on one of the alleles. This mutation is the same described in French-Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum).

Benign parasomnias and nocturnal frontal epilepsy: differential diagnosis in a case report.

We report the case of a 13-year-old boy who complained of complex motor episodes during sleep characterized by sudden arousal followed by deambulation associated with automatic movements and vocalization. His family history included both epileptic and psychiatric disorders. The patient himself presented psychopathologic traits and adaptive difficulties. In support of an epileptic origin of these phenomena were the stereotyped fashion in which they appeared and their responsiveness to carbamazepine. We classified the present case as a nocturnal frontal epilepsy with variable manifestations that can be classified as paroxysmal arousals, paroxysmal dystonia, and epileptic nocturnal wanderings. It was possible to differentiate such events from the most common parasomnias on the basis of videopolysomnographic studies.

Malignant migrating partial seizures in infancy.

A previously unreported epileptic condition characterised by onset before 6 months of age, nearly continuous electroencephalographic seizures involving multiple independent areas originating in both hemispheres, no identifiable cause, and poor outcome has been described by Coppola et al. We report three cases presenting the same clinical and EEG pictures. They show a peculiar epileptic condition unlike the other early epileptogenic encephalopathies, so they may represent a new infantile epileptic syndrome.

Distribution of epileptiform discharges during nREM sleep in the CSWSS syndrome: relationship with sigma and delta activities.

PURPOSE: The EEG pattern of epilepsy with continuous spike-waves during slow wave sleep (CSWSS) is characterized by an almost continuous activation of spike-and-slow-wave complexes during nREM sleep with a marked reduction of EEG abnormalities during REM sleep and the awake state. Experimental studies indicate that normal sleep oscillations that during nREM sleep lead to the appearance of spindles and delta waves on scalp EEG might develop into paroxysmal synchronization. Spectral analysis enables the quantitative description of the dynamics of delta (Delta Activity, DA, 0.5-4.5 Hz) and sigma activity (SA, 12-16 Hz) and can be used to assess the relationship between SA, DA and epileptiform discharges (EDs) during sleep. METHODS: We analyzed the EDs distribution during sleep in five children affected by CSWSS. We used a model of the evolution of power of DA and SA to which the time series of EDs could be fitted. RESULTS: We found a high and positive correlation between EDs and SA. DA resulted negatively correlated with EDs. CONCLUSION: Our data suggest that neural mechanisms involved in the generation of sleep spindles facilitate EDs production in the CSWSS syndrome. Such a mechanism seems to be an age related phenomenon shared by other epileptic syndromes of childhood.

Epilepsy associated with infantile hemiparesis: predictors of long-term evolution.

To study the evolution of epilepsy associated with infantile hemiparesis (IH) in relation to age and identification of factors predictive of pharmacoresistance. Thirty-four children with epilepsy and associated IH were followed for a period of 13 years and 3 months (range 5-19 years). All the patients underwent clinical evaluation and EEG, CT and/or MRI. Disease course was evaluated from the time of diagnosis of epilepsy to end of follow-up by differentiating the cases with severe pharmacoresistance from those with favourable outcome. Several possible prognostic factors were identified predicting evolution toward intractable epilepsy. Univariate statistical analysis by calculating odds ratio (OR) with 95% confidence interval (CI) and multivariate analysis by logistic regression were performed. Eleven cases presented severe epilepsy evolving toward pharmacoresistance; duration of epilepsy was always longer than 8 years. Twenty-three cases (seven with severe epilepsy and 16 with mild epilepsy) evolved toward remission; in these patients epilepsy duration was shorter (2-7 years) and a complete remission was obtained within 12 years of age. Significant prognostic factors associated with pharmacoresistance included: non-vascular causes, cortical lesions, mixed and frequent seizures during the first two years of epilepsy. Our results show that surgical treatment could be considered in cases with unfavourable prognostis factors.

Early-onset progressive encephalopathy with migrant, continuous myoclonus.

Three unusual cases of focal continuous myoclonus with onset during the first months of life, lasting from dozens of minutes to hours, are reported. During disease evolution, prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occur. Subsequently, a progressive encephalopathy with hypotonia and ataxia appears. A net worsening of the neurological condition is observed after the age of 4-5 years. Cortical atrophy is shown by CCT and MRI. Neurometabolic screening is not contributory. Repeated polygraphic recordings show continuous and segmental myoclonic jerks, localized in different muscles, at frequencies ranging between 0.5-1 c/s and 6-8 c/s. Moreover action myoclonus is recorded. During the first period of disease the EEG does not show any paroxysmal activity. As to the classification, this syndrome corresponds to an early onset progressive encephalopathy of unknown origin, similar in some aspects to Alper's disease. Another problem is the interpretation of the myoclonic phenomena. Some important aspects suggest a cortical origin of the diverse myoclonic phenomena observed in these cases.

Occlusion of unilateral carotid artery in Down syndrome.

The association between moyamoya phenomena and Down syndrome (DS) is reported in the literature. This paper reports a case of DS, which at age 9 presented right hemiparesis, secondary to the occlusion of the left internal carotid artery; cerebral angiography (CAG) showed a collateral circulation that mimicks the moyamoya phenomenon. Clinical recovery was almost complete; a second CAG after 15 months showed a persistent occlusion of the left internal carotid artery and an opacification of the left middle cerebral artery from abnormal vessels; but the collateral circulation is not enhanced. This case proves that in DS cerebrovascular occlusions may present moyamoya-like phenomena. These differ however from the true moyamoya disease in a number of aspects: the arterial occlusion is unilateral, the evolution is favorable and revascularization does not occur through the peculiar abnormal vessels of the moyamoya syndrome.

Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test.

The effects of rapid rectal diazepam introduction (DZP test) were investigated in 43 patients (age range 5 months-14 years) with electrical status epilepticus (ESE) undergoing EEG monitoring. A remission of the paroxysmal activity was obtained in 58% of cases, a negative response in 42%, particularly in hypsarrhythmic patterns. DZP test responders were aged over 12 months with organized paroxysmal EEG patterns, in particular with ESE during sleep (ESES). The patients who responded to the DZP test underwent short cycles (3-4 weeks) of relatively high dosage DZP (0.5-0.75 mg/kg). The response to treatment was positive in 64%, particularly in ESES conditions. 56% of responders to the DZP test but not to DZP therapy (five out of nine patients) presented a significant mental retardation; maturational factors were also likely to be present.

SPECT and epilepsy with continuous spike waves during slow-wave sleep.

Ten cases of epilepsy with continuous spike waves in slow-wave sleep (CSWS) were evaluated using single photon emission computed tomography (SPECT); in eight patients the EEG paroxysmal abnormalities showed a predominant localization. SPECT carried out using 99mTc-HMPAO allows study of cerebral blood flow (CBF); the examination was performed during phases of drowsiness and the results compared to the EEG data. In four cases SPECT revealed areas of low CBF in sites corresponding to those of the prevalent EEG discharges; in two cases the areas of hypoperfusion did not correspond to those indicated by the EEG; lastly, in four cases SPECT results were negative. The areas of hypoperfusion were predominantly located in the frontal, temporal, and parietal regions. Furthermore, the percentage of positive SPECT results was significantly higher (five cases out of six) in the group in which the CSWS phase was prolonged for at least 1 year, compared to the group in which this phase lasted less than 1 year. Thus, in this type of epilepsy, SPECT reveals focal cortical areas of decreased CBF which correlated generally to the predominant sites of EEG abnormalities. A longer duration of the CSWS phase seems to be associated with a more significant cortical disorder, documented by the presence of areas of hypoperfusion.

Familial white matter hypoplasia, agenesis of the corpus callosum, mental retardation and growth deficiency: a new distinctive syndrome.

We have observed in two different families two pairs of male siblings born from normal, non-consanguineous parents having the same syndrome, characterized by severe cerebral white matter hypoplasia, agenesis or extreme hypoplasia of the corpus callosum, mental retardation, failure to thrive and minor midline facial abnormalities. This seems to be a previously unreported genetic syndrome.

[The clinical use of dynamic EEG in childhood]. / Uso clinico dell'EEG dinamico in età evolutiva.

A-EEG is an important recent technologic innovation in EEG recording that facilitates long-term monitoring. The system consists of a miniature cassette tape recorder and a video play-back unit, which permits the taped EEG to be reviewed (Brain Spy CH24, Micromed). Because it is extremely lightweight and portable, the system permits unrestricted activity during recording. On the other hand, this predisposes the recording to more artifacts than are seen in routine recordings. We examined 103 patients, aged 3 months-24 years, between July 1988 and July 1990. Patients were divided into three groups: group 1 included 61 subjects with evidence of epilepsy and clinically definite seizures; group 2 included 29 patients with recurrent episodes that were not clearly epileptic (suspected "pseudo epileptic"); group 3 included 13 subjects with psychiatric disorders. We found that the clinical utility of A-EEG in epileptic children was: 1) obtain better clinical and EEG characterization and circadian distribution of seizures in 17 cases (28%); 2) quantify epileptiform generalized abnormalities and their variations during the sleep in 6 cases (10%); 3) verify the efficacy of specific drug treatment such as Bzd and ACTH in 12 cases (20%). The role of A-EEG in non-epileptic children with pseudoseizures was to establish the epileptic or non epileptic nature of some ictal events by detecting EEG seizure patterns in 11 cases (38%). As to regard the group 3, A-EEG has permitted to study sleep architecture and REM sleep measures, especially in depressed children compared to normal children. We discuss advantages, drawbacks and clinical applications of A-EEG in child neurology and psychiatry vs conventional EEG.