Personality profile and health-related quality of life in adults with previous continuous spike-waves during slow sleep syndrome.

INTRODUCTION: Epilepsy with continuous spike-waves during slow sleep syndrome (CSWSS) is characterized by various seizure types, a characteristic EEG pattern and neuropsychological disorders. The main purpose of this study was to evaluate the long-term outcome of CSWSS occurred in childhood and to evaluate the variables that could influence the quality of social adaptation and the personality profile. MATERIAL AND METHODS: This is a prospective study on 24 young adults with previous CSWSS (median age 24.5 yrs) who were enrolled between January and July 2011 at the G. Gaslini Children's Hospital, Genoa, Italy. Patients were divided into two groups: twelve with previous spike-wave index (SWI > 85%) defined as typical CSWSS (T-CSWSS) and twelve with previous SWI = 50-85% defined as atypical CSWSS (A-CSWSS). All the subjects were submitted to Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Psychological General Well-Being Index (PGWBI), and to a structured interview. RESULTS: A correlation was observed with the severity of EEG abnormalities expressed by the SWI and outcome. The T-CSWSS group showed a significantly lower perceived well-being. Similarly in the T-CSWSS group the percentage of MMPI-2 clinical scales with T-scores ≥65 was higher than in the A-CSWSS group. Finally, a significant lower schooling in the T-CSWSS group was observed. CONCLUSION: There seem to be two forms of the same disease, with similar onset and clinical evolution but a different outcome regarding the social and psychological conditions. The outcome of the social adaptation and of the personality consciousness was related with the severity of the EEG abnormalities: more favorable in patients with less intense SWI activity (A-CSWSS) compared those with a more severe EEG impairment (T-CSWSS).

Symptoms of anxiety and depression and family's quality of life in children and adolescents with epilepsy.

INTRODUCTION: We studied children and adolescents with epilepsy (CAWE) and their families to evaluate symptoms of anxiety and depression, quality of life (QoL), and their correlations with epilepsy characteristics. MATERIAL AND METHODS: The study included 326 (52.5% females) 8 to 18years old CAWE. Anxiety and depression were assessed with the "Self-administered psychiatric scales for children and adolescents" (SAFA), and family's QoL with the parents' report "Impact of Epilepsy on QoL" (IEQoL). RESULTS: The CAWE exhibiting abnormal (T≥70) scores were 8.0% in the anxiety scale, 9.2% in the depression scale, and 4.6% in both scales. Social anxiety was the predominant anxiety symptom, while irritable mood and desperation were the most frequent symptoms of depression. Depressive symptoms were associated with parents' complaint of higher worries about the child's condition and future and lower well-being of the family. Severity and duration of the epilepsy and polypharmacy were independent from abnormal scores of anxiety and depression, but were associated with parents' worries about the child's condition and family's well-being. CONCLUSIONS: Anxiety and depression in CAWE are independent from the characteristics of the disease but are correlated to the lower well-being of the family. A search of these emotional problems is recommended for better care of the patients and their families.

Early-Onset Shapiro Syndrome Variant Treated with Pizotifen: A Case Report.

Shapiro Syndrome is a rare entity defined by the triad of recurrent spontaneous hypothermia, hyperhidrosis, and agenesis of the corpus callosum. Fewer than 100 cases have been reported so far and there are only few cases without a complete agenesis of corpus callosum ("Shapiro Syndrome Variant"). In this article, we report the clinical, electroencephalographic, and neuroimaging data of a patient with early-onset Shapiro Syndrome Variant. The case study describes a 4-year-old patient with episodes characterized by generalized hyperhidrosis, hypotonia, impaired consciousness, and hypothermia with onset before the first year of age. We captured an event during which the EEG showed rhythmic low- to medium-voltage theta waves without clear epileptiform activity. Brain MRI was normal and Shapiro Syndrome Variant was hypothesized. We started treatment with pizotifen, and after 2 years, the patient showed a reduction in frequency and duration of episodes. Shapiro Syndrome, although rare, should be considered in the differential diagnosis in patients with neurovegetative symptoms which suggest epileptic attacks at first. Our case is of particular interest to specialists because Shapiro SyndromeVariant is a rare syndrome and our patient had a very early onset of symptoms.In addition, we report our experience with pizotifen therapy, which produced a good response.

Combined early treatment in hemiplegic attacks related to CACNA1A encephalopathy with brain oedema: Blocking the cascade?

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs. Case description We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma. Discussion Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.

Antiepileptic drugs in Rett Syndrome.

PURPOSE: We investigated drugs most often used to treat epilepsy in Rett Syndrome and their efficacy in a large cohort of Italian patients. METHODS: This is a multi-centre retrospective study. Data of 165 Rett subjects were collected from the patients' files, and hospital charts. The efficacy of antiepileptic drugs (AEDs) was classified as follows: not effective; decrease in seizure frequency ≥50% for at least 6 months; seizure-free for at least 2 years. Phenotypic and genetic categorization of patients was performed and it was considered in AEDs efficacy evaluation. RESULTS: There were 130 epileptic patients.Sodium valproate (VPA) was the most commonly administered AED (44.3%) at seizure onset, followed by Carbamazepine (CBZ) (25.4%) and Phenobarbital (PB) (13%). Monotherapy was the first treatment option in most patients. VPA and CBZ proved to be equally effective in Rett patients who presented seizures within the typical age range (4-5 years), while Lamotrigine (LTG) was effective for patients in whom epilepsy started later. Overall, the frequency of side effects was low and the most often observed ones were restlessness and somnolence. CONCLUSION: Our study suggests that LTG, VPA and CBZ can be used as drugs of first choice in Rett Syndrome. The association of four drugs should be avoided since it did not result in any significant clinical improvement.

The perceived burden of epilepsy: Impact on the quality of life of children and adolescents and their families.

PURPOSE: The assessment of the quality of life (QoL) is relevant for a comprehensive treatment of patients with epilepsy. In children and adolescents, an impact of epilepsy on the QoL of the entire family is expected. METHODS: We asked 293 parents of children and adolescents with epilepsy, included in an observational study on treatment satisfaction, to evaluate the impact of the disease on several aspects of the QoL of the whole family using a specifically organized questionnaire (IEQoL). RESULTS: The degree of parents' concerns about epilepsy and the severity of the disease correlated with a deterioration of QoL in both the children and the family. This involved all aspects of QoL (conflicts within the family, job, leisure activities, peer relationship, economy) although to a different degree. Parents frequently admitted increased apprehensiveness, even when not justified by the low severity of the disease. There was general agreement between parents and their adolescent children, although in a few cases adolescents overrated their school and daily performance in respect to the parents, suggesting a tendency to overlook their problems. CONCLUSION: Epilepsy impairs all aspects of QoL, although at different degree, both in children/adolescents and in their families. Parental apprehensiveness appears to have a role on this, and it may not reflect the severity of the disease.

Early classification of childhood focal idiopathic epilepsies: is it possible at the first seizure?

PURPOSES: To evaluate the possibility of early syndrome classification of idiopathic partial epilepsies in children at the first seizure. PATIENTS AND METHODS: In this observational study we prospectively evaluated 298 patients, aged between 1 month and 17 years and consecutively referred for the first unprovoked focal seizure. The whole cohort included 133 patients; the final analysis was carried out on 107 (59 males) individuals. Age at the first seizure ranged between 2.3 and 13.0 years. Clinical and EEG data of all patients were independently reviewed by two medical doctors. Patients were followed-up for at least 5 years, with a mean period of follow-up of 6.9 years. RESULTS: After the first seizure, a specific syndrome could be diagnosed in eighty (74.7%) children. In particular, Childhood Epilepsy with Centro-Temporal Spikes (CECTS) 42.9% of cases, Panayiotopoulos Syndrome (PS) 28.9%, idiopathic childhood occipital epilepsy of Gastaut (ICOE-G) 2.8%. Unclassified cases were 25.4%. At the end of the follow-up, the diagnosis was confirmed in 72 of 80 children (90%): BCECTS 89% of patients, PS 90% and ICOE-G 100%: among the unclassified cases, in 11 patients (40.7%) the diagnosis did not change, whereas 16 patients (59.3%) evolved into other syndromes or into atypical forms. CONCLUSIONS: At the onset an initial diagnosis is possible in the majority of cases; epilepsy syndromes can be identified at the time of the initial diagnosis and at follow up this diagnosis has not to be revised in 90% of the cases.

Congenital segmental lymphedema in tuberous sclerosis complex with associated subependymal giant cell astrocytomas treated with Mammalian target of rapamycin inhibitors.

Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy.

RORB gene and 9q21.13 microdeletion: report on a patient with epilepsy and mild intellectual disability.

Copy number variants represent an important cause of neurodevelopmental disorders including epilepsy, which is genetically determined in 40% of cases. Epilepsy is caused by chromosomal imbalances or mutations in genes encoding subunits of neuronal voltage- or ligand-gated ion channels or proteins related to neuronal maturation and migration during embryonic development. Here, we report on a girl with mild intellectual disability and idiopathic partial epilepsy. Array-CGH analysis showed a 1.040 Mb de novo interstitial deletion at 9q21.13 band encompassing only four genes, namely RORB, TRPM6, NMRK1, OSTF1, two open reading frames (C9orf40, C9orf41), and a microRNA (MIR548H3). RORB encodes a nuclear receptor highly expressed in the retina, cortex, and thalamus. We hypothesize its role in producing the phenotype of our patient and compare this case with other ones previously reported in the literature to better identify a genotype-phenotype correlation.

Epileptic encephalopathy with continuous spike and wave during sleep associated to periventricular leukomalacia.

Periventricular leukomalacia is the most common type of brain injury in premature infants. Our aim is to describe the frequency and the features of epilepsy in a single-center population of 137 children with periventricular leukomalacia. Forty-two of the 137 (31%) patients presented epilepsy. Twelve percent of these patients presented West syndrome, whereas 19% showed a pattern of continuous spike-waves during slow sleep syndrome. In the latter group, outcome was frequently unfavorable, with a greater number of seizures and more drug resistance. A significant association was found between epilepsy and neonatal seizures, spastic tetraplegia, and mental retardation. Although less common than in other forms of brain injury, epilepsy is nevertheless a significant complication in children with periventricular leukomalacia. The fairly frequent association with continuous spike-waves during slow sleep syndrome deserves particular attention: electroencephalographic sleep monitoring is important in order to provide early treatment and prevent further neurologic deterioration.

Anti-glutamic acid decarboxylase limbic encephalitis without epilepsy evolving into dementia with cerebellar ataxia.

OBJECTIVES: To expand the spectrum of the clinical presentation of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis and to improve the recognition of this entity. DESIGN: Case study. SETTING: University hospital. PATIENT: An 11-year-old-girl with progressive mood and behavioral disorder, speech impairment, and short-term memory impairment who manifested cerebellar ataxia with nystagmus during the disease course. INTERVENTIONS: Blood and cerebrospinal fluid analysis including autoantibodies, electroencephalography, brain and spinal magnetic resonance imaging, and cognitive and neuropsychological assessment were performed. High-dose methylprednisolone sodium succinate pulses, cycles of intravenous immunoglobulins, mycophenolate mofetil, and rituximab as well as antipsychotics and benzodiazepine were administered. RESULTS: Diagnosis of anti-glutamic acid decarboxylase antibodies-related limbic encephalitis was made. The clinical features during the first months of disease included only mood, behavioral, and memory impairment. After 5 months, despite immunotherapies, cerebellar ataxia with nystagmus appeared with brain magnetic resonance imaging evidence of cerebral atrophy. No clinical or infraclinical seizures were recorded during follow-up. CONCLUSIONS: Anti-glutamic acid decarboxylase antibodies-related limbic encephalitis can present with only behavioral or neuropsychological symptoms without any epileptic disorder. Moreover, cerebellar ataxia related to anti-glutamic acid decarboxylase antibodies can be observed in patients with limbic encephalitis during the disease course.

Satisfaction with antiepileptic drugs in children and adolescents with newly diagnosed and chronic epilepsy.

PURPOSE: To assess incidence, indicators and outcome of satisfaction with antiepileptic drugs in children. METHODS: Multicenter, observational, open, prospective survey of children and adolescents with epilepsy with three-month follow-up. Included were patients aged 3-17 years with newly diagnosed ("new diagnosis") or chronic epilepsy ("old diagnosis") requiring treatment start or change. Satisfaction was assessed with the Hedonic Visual Scale or direct questions, depending on patient's age. Quality of life of adolescents (QOLIE-48) and of caregivers (SF-36) and predictors of (dis)satisfaction were also assessed. RESULTS: 293 patients completed the study. Most had generalized idiopathic epilepsy, and a disease lasting <12 months. Newly diagnosed patients were 60.8%. Patients declaring satisfaction were 70.6% at one month and 75.8% at three months. Compared to old diagnosis, new diagnosis carried a higher satisfaction rate and improved satisfaction at end of follow-up. Independent predictors of dissatisfaction were an old diagnosis, adverse events and SF-36 score. The latter remained the only independent predictor of persisting dissatisfaction when adjusting for the presence of and the interaction with adverse events. CONCLUSIONS: About one-fourth of children and adolescents with epilepsy are dissatisfied with treatment. Chronic epilepsy, adverse events, and parents/caregivers with poor quality of life predict dissatisfaction.

A clinical and genetic study of 33 new cases with early-onset absence epilepsy.

PURPOSE: To investigate the electroclinical features and the outcome of patients with typical absences starting before the 3 years of life. METHODS: We reviewed the clinical data of patients with absences started before 3 years observed over a 15-year period. Mutation analysis of SLC2A1 (GLUT-1) gene was performed when possible. Their clinical features were compared with those of subjects with a diagnosis of childhood absence epilepsy (CAE). RESULTS: Among 33 children with absence epilepsy starting before 3 years of life, there were 20 boys and 13 girls. Mean seizure onset was at 28.0 ± 8.3 (range: 8-36) months of life. Two children displayed borderline intellectual functioning at long-term follow-up. Twenty-eight (85%) patients showed excellent response to therapy. Three subjects evolved into a different form of idiopathic generalized epilepsy (IGE). No SLC2A1 mutation was identified in 20 (60.6%) patients tested. The main clinical features of patients with early-onset absences did not differ from those of CAE except for increased prevalence of males (p=0.002) and longer treatment duration (p=0.001) in the former. CONCLUSIONS: Strong similarities in the electroclinical features and outcome between children with early-onset absences and those with CAE support the view that these conditions are part of the wide spectrum of IGE.

Focal leptomeningeal enhancement and corticopial calcifications underlying a parietal convexity lipoma: a rare association of findings in 2 pediatric epileptic patients.

We present the unusual neuroimaging findings of focal cerebral leptomeningeal enhancement in association with corticopial calcifications, underlying a parietal convexity lipoma in 2 pediatric patients with normal psychomotor development, unremarkable physical findings, and recent onset of epilepsy. To our knowledge, this clinical and neuroradiological association has not been previously reported and shows overlapping features with Sturge-Weber syndrome without facial nevus and encephalocraniocutaneous lipomatosis, thus possibly representing an extremely rare variant within the spectrum of these congenital neurocutaneous disorders.

Epilepsy in Rett syndrome: clinical and genetic features.

Epilepsy often occurs in Rett syndrome and is considered a major problem. The aim of this study was to define the clinical features of epilepsy and the correlation between seizures and both genotype and clinical phenotype in the Rett population. One hundred sixty-five patients with Rett syndrome referred to four Italian centers were recruited. All patients underwent video/EEG monitoring and molecular analysis of the MECP2 gene or, in negative cases, of the CDKL5 and FOXG1 genes. The frequency of epilepsy was 79%. Drug-resistant epilepsy occurred in 30% of all our patients with Rett syndrome and in 38% of those with epilepsy. Our findings demonstrate that epilepsy differs among the various phenotypes and genotypes with respect to age at onset, drug responsiveness, and seizure semiology. The Hanefeld and preserved speech variants represent the extremes of the range of severity of epilepsy: the preserved speech variant is characterized by the mildest epileptic phenotype as epilepsy is much less frequent, starts later, and is less drug resistant than what is observed in the other phenotypes. Another important finding is that seizure onset before 1 year of age and daily frequency are risk factors for drug resistance. Thus, this study should help clinicians provide better clinical counseling to the families of patients with Rett syndrome.

Anti-N-methyl-D-aspartate-receptor encephalitis in a four-year-old girl.

Anti-N-methyl-D-aspartate-receptor encephalitis is a recently identified autoimmune disorder. We report on a 4-year-old girl presenting with seizures after nonspecific viral-like symptoms, progressing to severe aphasia, upper limb dyskinesias, fluctuation in consciousness, and inability to walk. Anti-N-methyl-D-aspartate-receptor encephalitis should be included in the differential diagnosis of acute/subacute encephalitis in children.

Epilepsy associated with supratentorial brain tumors under 3 years of life.

OBJECTIVE: To investigate the clinical features and outcome of epilepsy in children under 3 years of age with supratentorial brain tumors. METHODS: Patients under 3 years with primary supratentorial hemispheric brain tumors were collected during a 10-year period through a database including demographic and clinical features, neuroimaging, tumor location, developmental outcome, pharmacological and surgical treatment, and tumor histology. Postoperative outcome was assessed according to Engel classification. RESULTS: Among 28 children evaluated, twenty (71.4%) suffered from epilepsy. Mean age at seizure onset was 18.7 months (range: 1-60). In fifteen (75%) children, epilepsy was an early manifestation or the presenting symptom of the tumor; seizures were focal in 8 (53.3%) and generalized in 7 (46.7%) individuals. Three (15%) children presented with an epileptic encephalopathy and continuous spike-waves during sleep. Of the five children with epilepsy onset after surgery, four had focal seizures. Post-surgical follow-up ranged from 4 to 10 years (mean: 7.6+/-3.74). The outcome of epilepsy was generally good, with most children (76.4%) being seizure free (Engel I) or showing >90% improvement in seizure frequency (Engel II) after surgery. However, in about 20% of the cases, epilepsy persisted despite surgery and different AEDs regimen. Best epilepsy outcome was observed in patients with low-grade tumors (p<0.01) and without neurological deficits after surgery (p<0.001). CONCLUSIONS: Epilepsy is a common and early symptom in infants with brain tumors. Its outcome is negatively influenced by high tumor malignancy and by the persistence of neurological deficits after surgery. Treatment of these patients needs a multidisciplinary approach.

Epilepsia partialis continua in type 1 diabetes: evolution into epileptic encephalopathy with continuous spike-waves during slow sleep.

Hyperglycemic status may be rarely complicated by Epilepsia partialis continua (EPC) that usually responds to metabolic normalization. Anti-glutamic acid decarboxylase antibodies (GAD-Ab) play a pivotal role in the autoimmune process that leads to clinical onset of type 1 diabetes mellitus (T1DM). GAD-Ab have been recently reported in association with rare forms of refractory epilepsy, with or without association to T1DM. Here we describe a young patient who developed EPC five months after T1DM onset; GAD-Ab were detected in his cerebrospinal fluid with evidence of oligoclonal bands. His epileptic disorder evolved over time into drug-resistant epilepsy with continuous spike-waves during slow sleep and severe behavioral impairment. The role of both metabolic imbalance and GAD autoimmunity is discussed.

Clinical and electroencephalographic features in patients with CDKL5 mutations: two new Italian cases and review of the literature.

Clinical features and electroencephalographic findings of two patients affected by a previously unreported cyclin-dependent kinase-like 5 (CDKL5) gene mutation are described. Both patients had the Hanefeld variant phenotype with early-onset seizures, but different degrees of clinical severity. In fact, patient 1 was not drug-resistant and is responding to a single drug. On the contrary, patient 2, like most reported cases, has severe epilepsy, exhibits electroencephalographic changes, and is drug resistant. We suggest that the pseudoperiodic patterns observed on the EEGs for these cases represent this genetic form of epilepsy, though differing in frequency, voltage, and associated patterns. This is in agreement with data reported by other authors indicating that no unique pattern can be identified in subjects with CDKL5 mutations. Thus, a CDKL5 investigation should be performed in developmentally delayed patients with early-onset seizures, including drug-resistant subjects with severe EEG changes, as well as in patients with milder, drug-responsive forms of epilepsy.