Focal non-motor seizures and subsequent focal motor seizures as the main clinical expression of GLUT-1 deficiency.

The seizure type most frequently described in GLUT1 deficiency is generalized (mainly absence). We report the case of a young boy who, as the main clinical manifestation presented with focal non-motor, and then focal motor seizures. At the age of 3 months episodes of face pallor/cyanosis and hypotonus lasting about 1 min, occurred. They were initially misdiagnosed as gastroesophageal reflux. These episodes disappeared spontaneously at 6 months of age. At 12 months, episodes similar to the previous ones reappeared. A few months later, a cluster of several episodes manifest as impaired responsiveness and vomiting occurred. The patient initially performed long-term video-EEG monitoring (LTVEM) however, no seizures were captured. During a second hospitalization for LTVEM, a focal to bilateral clonic seizure was recorded. Brain MRI was normal. Next Generation Sequencing (NGS) panel for genes associated with epilepsy showed a de novo mutation of SCL2A1 gene. The CSF showed glucose of 41 mg/dL, and the CSF/serum glucose ratio was equal to 0.46. The ketogenic diet was started with optimal efficacy in seizure control. Meal-sensitivity in childhood onset focal seizures may be associated with GLUT-1 deficiency syndrome that can be confirmed by biochemical analysis on blood and CSF following diagnostic genetic study.

Diagnosis of pediatric anti-NMDAR encephalitis at the onset: A clinical challenge.

BACKGROUNDS: To investigate the clinical and instrumental features at the onset addressing to the diagnosis of anti-NMDAR encephalitis. METHODS: Twenty children (age: 15 months-17 years; 7 males, 13 females) with initial suspected diagnosis of autoimmune encephalitis, observed between January 2008 and March 2018, were included. The final diagnosis was anti-NMDAR encephalitis in 7 children, other/probable autoimmune encephalitis in 7 children, and primary psychosis in the remaining 6 children. RESULTS: At the clinical onset, anxiety disorder was the main symptom that helped in distinguishing the group of psychotic children from children with non-infectious encephalitis (P = 0.05 OR = 0.001), while epileptic seizures strongly predicted anti-NMDAR encephalitis (P = 0.04 OR = 28.6). At the onset, anti-NMDAR encephalitis could be distinguished from other/probable autoimmune encephalitis for the presence of sleep/wake rhythm alteration (P = 0.05 OR = 15). Among the symptoms occurring during the hospitalization, movement disorders (P = 0.031 OR = 12) were predictive of non-infectious encephalitis rather than primary psychosis. More specifically, the occurrence of language impairment (P = 0.03 OR = 33), epileptic seizures (P = 0.04 OR = 28.6) and catatonia (P = 0.03, OR = 33), were predictive of anti-NMDAR encephalitis. Also at this stage, anxiety disorder (P = 0.03 OR = 0.033) was predictive of primary psychosis. CONCLUSION: Our findings suggest that at the clinical onset epileptic seizures and sleep/wake rhythm alteration represent the main features addressing to the diagnosis of anti-NMDAR encephalitis rather than primary psychosis and other/probable autoimmune encephalitis, while anxiety disorder could be a solid predictor of primary psychosis.

Improvement of quality of life in adolescents with epilepsy after an empowerment and sailing experience.

PURPOSE: Epilepsy in adolescents affects their psychological health, independence, and emotional adjustment. Psychological and self-management interventions might give benefits to adolescent with epilepsy in terms of quality of life, emotional well-being, and reduced fatigue. "Fondazione Tender To Nave Italia" promotes a project using sailing activities as an empowerment opportunity. The main aim of our study was to examine the empowerment effects on quality of life of adolescents with epilepsy attending sailing activities, and to compare the results perceived by adolescents and their parents. METHODS: Fifty-eight patients with a diagnosis of epilepsy were included in an empowerment project titled "Waves rather than spikes" from June 2013 to July 2018. Intellectual level was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria. Patients were administered Pediatric Quality of Life Inventory (PedsQL), adolescent and parent version. Behavioral data were collected by parent-report Child Behavior Checklist (CBCL). RESULTS: Thirty female and 28 male patients with a mean age of 15 years, referred to "Bambino Gesù Children's Hospital" in Italy, were included. Thirty-three (56.9%) patients had a history of refractory epilepsy; 34 (56.2%) received polytherapy, 19 (32.7%) monotherapy, and 5 (8.6%) were not taking antiepileptic drugs. Intellectual functioning was normal in 43 (74.1%), borderline in 9 (15.5%), and mildly impaired in 6 (10.3%). Results from PedsQL adolescent report revealed significant postintervention improvement for total score (p = 0.023) and in two domains: physical health (p = 0.0066) and emotional functioning (p = 0.015). Results from PedsQL parent report showed significant postintervention improvement for the domain of school functioning (p = 0.023). In the multivariate model, a low CBCL value was predicting a higher score in the health subscore difference between pre- and postempowerment activity (p = 000.8). CONCLUSION: Empowerments activities are crucial in order to reduce the burden of epilepsy in adolescents, and to improve quality of life. These are critical factors for a well-managed transition phase to adulthood.

Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study.

BACKGROUND AND PURPOSE: Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients' management was studied, focusing on the subgroup of Ab-negative-AE. METHODS: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). RESULTS: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second-line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first-line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00-1.04). CONCLUSIONS: In-house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab-positive-AE underestimation. Notwithstanding this limitation, our findings suggest that Ab-negative-AE and Ab-positive-AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab-negative-AE patients risk worse responses due to delayed and less aggressive treatments.

De novo Absence Status Epilepticus in a pediatric cohort: Electroclinical pattern in a multicenter Italian patients cohort.

PURPOSE: Absence Status epilepticus (AS) is a form of Non Convulsive Status Epilepticus defined as a prolonged, generalized and non-convulsive seizure, with an altered content of consciousness. We aim to describe a group of healthy children, who presented recurrent and unprovoked de novo AS as the only manifestation of their epilepsy, with an excellent response to antiepileptic drugs. METHOD: We retrospectively reviewed the electroclinical and genetic features of 13 pediatric patients, referring to our epilepsy centers from 2005 to 2019, on the following criteria: (1) regular psychomotor development, (2) one or more unprovoked AS as the only epileptic manifestation, (3) normal blood testing, (4) normal neuroimaging, (5) EEG recording, (6) available follow-up (1-14 years). RESULTS: Patients are 7 females and 6 males, aged 7-22, with a mean age at AS onset of 9,3 years. All of them started an antiepileptic therapy, with an excellent response to Valproic Acid (VPA) or Ethosuximide (ETS). 5 patients did not start the therapy immediately after the first AS and they presented recurrent AS (from 2 to 4 episodes). 10 of them performed aCGH, karyotype, NGS panel or Whole Exome Sequencing. CONCLUSIONS: We suggest that de novo AS may be a well-defined age-related and self-limited epilepsy syndrome, with a good prognosis and excellent response to therapy, but it comes with a high risk of relapsing if not adequately treated with antiepileptic drugs.

Midazolam vs diazepam in prolonged seizures in children: A pharmacoeconomic approach.

OBJECTIVE: A previous European cost-utility study reported that use of buccal midazolam in the community setting for the treatment of prolonged seizures (ie, seizures lasting ≥5 minutes) in children was associated with an overall €12 507 399 reduction in annual costs charged to the Italian national health service compared with rectal diazepam. We re-evaluated these findings by applying a more conservative approach. METHODS: The Italian Delphi panel reconvened to apply a more conservative assessment of available reports. A decision-tree model was used, allowing for different treatment pathways depending on whether or not a caregiver administers treatment, an ambulance is required for transport of the child to hospital, and an inpatient stay is required. Direct medical costs were derived from Italian healthcare system data. Estimates of the annual number of prolonged tonic-clonic seizures expected in the country were based on studies which assessed seizure duration using video-EEG recordings and medical records. RESULTS: Although drug acquisition costs were greater for buccal midazolam than for rectal diazepam, the acquisition cost difference was outweighed by larger cost savings resulting mostly from a reduction in hospital admissions. Assuming that 1.2% of tonic and/or clonic seizures occurring in children and adolescents over a 12-month period are prolonged, the annual nationwide reduction in costs from preferring buccal midazolam to rectal diazepam was estimated at €3 577 587.9. CONCLUSIONS: In this more conservative revised analysis, the high cost of buccal midazolam is still counteracted by greater cost savings compared with rectal diazepam, but cost reduction was less than previously estimated.

Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABAAR antibodies.

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) has been described as an epileptic encephalopathy of unknown etiology affecting previously healthy children following febrile illness. Despite large investigations on autoimmune pathogenesis no membrane antibodies has been associated since now. CASE STUDY: We report a 13 years-old girl with negative history for neurological or autoimmune disease that developed at the sixth day of high fever a super-refractory status epilepticus. All investigations, including the most common antibodies related to immune-mediated encephalitis were negative. Seizures continued despite several therapeutic trials with anesthetics (midazolam, propofol) and antiepileptic agents as well as i.v. immunoglobulins but responded, at day 10 from the onset, to ketamine and high dose i.v. steroids. Due the high suspicion of autoimmune encephalitis we tested patient's CSF and plasma on mouse brain with positive response. We subsequently detected a high titre of GABAAR antibodies. After the resolution of the status epilepticus the patient achieved complete recovery of neurological functions. CONCLUSION: this is the first reported case of a FIRES-like condition due to autoimmune encephalitis mediated by GABAAR antibodies. Our case suggests that GABAAR antibodies should be investigated FIRES.

From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

BACKGROUND: Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). CASE REPORT: An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. CONCLUSIONS: Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE.

Effectiveness and tolerability of perampanel in children and adolescents with refractory epilepsies-An Italian observational multicenter study.

PURPOSE: To evaluate the efficacy and tolerability of Perampanel (PER) in children and adolescents with refractory epilepsies in daily clinical practice conditions. PATIENTS AND METHODS: This Italian multicenter retrospective observational study was performed in 16 paediatric epilepsy centres. Inclusion criteria were: (i) ≤18 years of age, (ii) history of refractory epilepsy, (iii) a follow-up ≥5 months of PER add-on therapy. Exclusion criteria were: (i) a diagnosis of primary idiopathic generalized epilepsy, (ii) variation of concomitant AEDs during the previous 4 weeks. Response was defined as a ≥50% reduction in monthly seizure frequency compared with the baseline. RESULTS: 62 patients suffering from various refractory epilepsies were included in this study: 53% were males, the mean age was 14.2 years (range 6-18 years), 8 patients aged <12 years. Mean age at epilepsy onset was 3.4 years and the mean duration of epilepsy was 10.8 years (range 1-16), which ranged from 2 seizures per-month up to several seizures per-day (mean number=96.5). Symptomatic focal epilepsy was reported in 62.9% of cases. Mean number of AEDs used in the past was 7.1; mean number of concomitant AEDs was 2.48, with carbamazepine used in 43.5% of patients. Mean PER daily dose was 7.1mg (2-12mg). After an average of 6.6 months of follow-up (5-13 months), the retention rate was 77.4% (48/62). The response rate was 50%; 16% of patients achieved ≥75% seizure frequency reduction and 5% became completely seizure free. Seizure aggravation was observed in 9.7% of patients. Adverse events were reported in 19 patients (30.6%) and led to PER discontinuation in 4 patients (6.5%). The most common adverse events were behaviour disturbance (irritability and aggressiveness), dizziness, sedation and fatigue. CONCLUSION: PER was found to be a safe and effective treatment when used as adjunctive therapy in paediatric patients with uncontrolled epilepsy.

Somatosensory system hyperexcitability in alternating hemiplegia of childhood.

BACKGROUND AND PURPOSE: Alternating hemiplegia of childhood (AHC) is a rare neurological disease characterized by recurrent paroxysmal attacks of hemiplegia. The aim of the study was to assess the recovery cycle of the somatosensory evoked potentials (SEPs) in a group of AHC patients. METHODS: Seven AHC patients and 10 control age-matched subjects (CS) were recruited. Right and left median nerve SEPs were recorded. The somatosensory system excitability was assessed by calculating the SEP changes after paired electrical stimuli. All patients were studied during the interictal phase, whilst four patients were studied also during the ictal phase. RESULTS: In AHC patients during the interictal phase, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30 responses showed a faster recovery than in CS. In AHC patients during the ictal phase, the cortical N20 recovery cycle was prolonged compared with the interictal phase. CONCLUSIONS: A shortened SEP recovery cycle in AHC during the interictal phase suggests multilevel somatosensory system hyperexcitability in AHC. A partial recovery of this phenomenon during the ictal phase possibly reflects a functional reset of the somatosensory system. Overall, there is a disinhibition of the somatosensory system in AHC, a functional change of brain function associated with a possible involvement of the Na(+) /K(+) channels. This abnormality and its partial recovery during the attacks might be linked to the pathophysiological and genetic mechanisms of the disease.

Primary headache pathophysiology in children: the contribution of clinical neurophysiology.

Although primary headaches are very prevalent also in pediatric age, most neurophysiologic studies in these diseases concerned only the adulthood. The neurophysiologic investigation of the pathophysiological mechanisms subtending migraine and tension-type headache in children and adolescents could be particularly interesting, since during the developmental age the migrainous phenotype is scarcely influenced by many environmental factors that can typically act on adult headache patients. The neurophysiologic abnormality most frequently found in adult migraineurs, that is the reduced habituation of evoked potentials, was confirmed also in migraine children, although it was shown to involve also children with tension-type headache. Some studies showed abnormalities in the maturation of brain functions in migraine children and adolescents. While the visual system maturation seems slowed in young migraineurs, the psychophysiological mechanisms subtending somatosensory spatial attention in migraine children are more similar to those of healthy adults than to those of age-matched controls. There are some still unexplored fields that will have to be subjects of future studies. The nociceptive modality, which has been investigated in adult patients with primary headaches, should be studied also in pediatric migraine. Moreover, the technique of transcranial magnetic stimulation, not yet used in young migraineurs, will possibly provide further elements about brain excitability in migraine children.

Somatic mosaicism of PCDH19 mutation in a family with low-penetrance EFMR.

The occurrence of epilepsy with mental retardation limited to females (EFMR; MIM 300088) has been recently associated to mutations in the PCDH19 gene, located on chromosome X and encoding for protocadherin 19. EFMR shows a rare X-linked inheritance wherein affected females may be segregating a mutation through unaffected transmitting males (Fabisiak and Erickson Clin Genet 38(5):353-358, 1990; Juberg and Hellman J Pediatr 79:726-732, 1971; Ryan et al. Nat Genet 17(1):92-95, 1997). The description of a pedigree segregating PCDH19 mutations from unaffected mothers to patients (Depienne et al. Hum Mutat 32:E1959-1975, 2011; Dibbens et al. Neurology 76:1514-1519, 2011) complicates disease inheritance and genetic counseling. In the present study, we describe a PCDH19 mutation segregating from an asymptomatic mother to an EFMR patient. In order to correlate the healthy phenotype with the genotype of the transmitting mother, we quantified in a few tissues the level of the mutant allele by real-time PCR, disclosing a somatic mosaicism. This finding has a great impact on genetic counseling.

Evidence of different spinal pathways for the warmth evoked potentials.

OBJECTIVE: To investigate the presence of multiple spinothalamic pathways for warmth in the human spinal cord. METHODS: Laser evoked potentials to C-fiber stimulation (C-LEPs) were recorded in 15 healthy subjects after warmth stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels. This method allowed us to calculate the spinal conduction velocity (CV) in two different ways: (1) the reciprocal of the slope of the regression line was obtained from the latencies of the different C-LEP components, and (2) the distance between C5 and T10 was divided by the latency difference of the responses at the two sites. In particular, we considered the C-N1 potential, generated in the second somatosensory (SII) area, and the late C-P2 response, generated in the anterior cingulate cortex (ACC). RESULTS: The calculated CV of the spinal fibers generating the C-N1 potential (around 2.5m/s) was significantly different (p<0.01) from the one of the pathway producing the P2 response (around 1.4m/s). CONCLUSIONS: Our results suggest that the C-N1 and the C-P2 components are generated by two parallel spinal pathways. SIGNIFICANCE: Warmth sensation is subserved by parallel spinothalamic pathways, one probably reaching the SII area, the other the ACC.

Childhood refractory focal epilepsy following acute febrile encephalopathy.

BACKGROUND: We describe a group of previously normal children who developed severe focal epilepsy after an acute/sub-acute illness resembling encephalitis. METHODS: This is a retrospective study. An acute phase (encephalitis/encephalopathy period) and a chronic phase (chronic focal resistant epilepsy) were defined. RESULTS: Eight patients were enrolled. The median age at onset was 6.6 years (range 8 months-17.6 years). In the acute phase, fever was the first symptom in all cases and was associated with seizures and status epilepticus. All patients had focal seizures arising in both hemispheres. Seizure onset occurred in the frontal and temporal regions. EEGs showed slowing background activity associated with focal or diffuse slow waves with rare epileptiform abnormalities. Cerebrospinal fluid oligoclonal bands were observed in four out of six patients tested. MRI images showed bilateral peri-insular hyperintensity in four cases. Five patients received corticosteroids, and in four cases, they were given along with intravenous immunoglobulins. The median duration of the acute phase was 19 days (range 15-30 days). During the chronic phase, which followed the acute phase without interval, patients presented with drug-resistant focal seizures and neuropsychological deficits, which ranged from hyperactivity and attention deficits to short-term verbal memory deficit, pervasive developmental disorders, and language delay. CONCLUSION: Considering the clinical presentations, EEG findings, and the associated occurrence of non-specific immunological activations, a possible immune-mediated pathogenesis can be hypothesized, although firm conclusions cannot be drawn out.

Protocadherin 19 mutations in girls with infantile-onset epilepsy.

OBJECTIVE: To explore the causative role of PCDH19 gene (Xq22) in female patients with epilepsy. METHODS: We studied a cohort of 117 female patients with febrile seizures (FS) and a wide spectrum of epilepsy phenotypes including focal and generalized forms with either sporadic or familial distribution. RESULTS: PCDH19 screening showed point mutations in 13 probands (11%). Mean age at seizure onset was 8.5 months; 8 patients (62%) presented with FS, 4 (33%) with cluster of focal seizures, and 1 with de novo status epilepticus (SE). Subsequent seizure types included afebrile tonic-clonic, febrile, and afebrile SE, absences, myoclonic, and focal seizures. Seven patients (54%) had a clinical diagnosis consistent with Dravet syndrome (DS); 6 (46%) had focal epilepsy. In most patients, seizures were particularly frequent at onset, manifesting in clusters and becoming less frequent with age. Mental retardation was present in 11 patients, ranging from mild (7; 64%) to moderate (1; 9%) to severe (3; 27%). Five patients (38%) had autistic features in association to mental retardation. Mutations were missense (6), truncating (2), frameshift (3), and splicing (2). Eleven were new mutations. Mutations were inherited in 3 probands (25%): 2 from apparently unaffected fathers and 1 from a mother who had had generalized epilepsy. CONCLUSIONS: PCDH19 is emerging as a major gene for infantile-onset familial or sporadic epilepsy in female patients with or without mental retardation. In our cohort, epileptic encephalopathy with DS-like features and focal epilepsy of variable severity were the associated phenotypes and were equally represented.

The abnormal recovery cycle of somatosensory evoked potential components in children with migraine can be reversed by topiramate.

The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 (P = 0.03) and N30 (P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.

Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria.

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5. METHODS: Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14 months to 13 years, were evaluated by two clinical geneticists, classified using a severity score system based on the evaluation of 22 different clinical signs and compared with 128 classic Rett and 25 Zappella variant MECP2-mutated patients, evaluated by the same clinical geneticists. Clinical features were compared with previously described CDKL5 mutated patients. Both the statistical and the descriptive approach have been used to delineate clinical diagnostic criteria. RESULTS: All girls present epilepsy with onset varying from 10 days to 3 months. Patients may present different type of seizures both at onset and during the whole course of the disease; multiple seizure types may also occur in the same individual. After treatment with antiepileptic drugs patients may experience a short seizure-free period but epilepsy progressively relapses. Typical stereotypic hand movements severely affecting the ability to grasp are present. Psychomotor development is severely impaired. In the majority of cases head circumference is within the normal range both at birth and at the time of clinical examination. CONCLUSION: For the practical clinical approach we propose to use six necessary and eight supportive diagnostic criteria. Epilepsy with onset between the first week and 5 months of life, hand stereotypies, as well as severe hypotonia, are included among the necessary criteria.

Correlation between abnormal brain excitability and emotional symptomatology in paediatric migraine.

We investigated a possible correlation between brain excitability in children with migraine and tension-type headache (TTH) and their behavioural symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The mismatch negativity (MMN) and P300 response were recorded in three successive blocks to test the amplitude reduction of each response from the first to the third block (habituation). MMN and P300 habituation was significantly lower in migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). In migraineurs, but not in TTH patients, significant positive correlations between the P300 habituation deficit and the CBCL scores were found (P < 0.05), meaning that the migraineurs with the most reduced habituation showed also the worst behavioural symptomatology. To the best of our knowledge, this is the first study showing a correlation between neurophysiological abnormality and emotional symptomatology in migraine, suggesting a role of the latter in producing the migrainous phenotype.

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.