Maria Grazia Pascarella

Lacosamide in absence status epilepticus

the role of LCM in patients withidiopathic generalized epilepsy presenting with absence statusepilepticus (ASE) is currently unknown.A 57-year-old woman came to be under our observation afterexperiencing confusion and drowsiness, immediately afterwaking up. Her family history was unremarkable. Apart frommild mental retardation and epilepsy, she had no other medicalproblems. Raretonic-clonic seizures,andepisodesoflost contactlasting for a few seconds or minutes had occurredmonthly sincethe age of 6 yearsold despite havingbeen treatedwith 2000 mg/day valproate(VPA),300 mg/daylamotrigine(LTG),3000mg/daylevetiracetam (LEV), 300 mg/day topiramate, 100 mg/day phe-nobarbital. The interictal EEG showed generalized spike-waveand polyspike-wave discharges at 3–4 Hz, lasting from 1 to 3 s.Brain MRI and genetic analysis (karyotypeand array-CGH) werenormal. After 6 h from the onset of confusion, the patient wasadmitted to our centre and at that timeshe was on 2000mg/dayVPA (plasma VPA was 87 mg/L, range 50–100 mg/L) and3000 mg/day LEV (plasma LEV was 25 mg/L, range 10–37 mg/L). A long-term video-EEG monitoring was performed and ASEwas diagnosed. In particular, she was slow, vague, inattentive,with no verbal contact and displayed rare, small myoclonictwitches of the eyelids and facial muscles.The ictal EEG revealeda continuous, generalized, 2.5–4Hz spike, polispike-wavepattern and brief trains of polispikes during confusional state(Fig. 1a). Intravenous (IV) diazepam (10 mg in bolus) induced arapid but transient effect (Fig. 1b), with ASE reappearing after5 min. The administration of IVdiazepam (10 mg bolus) was alsorepeated withouteffect.Wethereforeadministeredan IVloadingdose of200mgLCMoveraperiodof15 min,througha peripheralline, diluted in 50 ml of normal saline. During and at the end ofinfusion, the clinical picture and EEG pattern were unchanged(Fig. 1c). After 10 min, an additional 200 mg of LCM wasadministered for 15 min without effect (Fig. 1d). No adverseeffects were observed during the administration of LCM and noECG andlaboratoryvalues-changesweredocumented.After24 hthe ASE spontaneously resolved. The patient was then given2000 mg/day VPA and 100 mg/day LTG, while LEV was graduallydiscontinued. She has now been seizure-free during the 12months of follow-up.Althoughthe most commonly used bolus dose of LCM is 200–400 mg over 3–5 min,

Epileptic seizures, movement disorders, and breathing disturbances in Rett syndrome: diagnostic relevance of video-polygraphy.

Epileptic seizures, movement disorders and breathing disturbances may be observed in Rett syndrome, and correct diagnosis is mandatory for the management. We evaluated the usefulness of video-polygraphy in the differential diagnosis between epileptic and non-epileptic paroxysmal events in eight patients with Rett syndrome. Based on video analysis, myoclonic seizures were usually misdiagnosed as movement disorders and stereotypies; the events identified by parents as generalized tonic-clonic seizures included episodes of motor activity and breathing abnormality. Myoclonic seizures aggravated by inappropriate treatment were evident in four patients; hyperventilation and apnea during wakefulness were present in all patients, while central sleep apneas were present in one patient; sinus tachycardia and cardiac arrhythmias emerged in six patients; cortical myoclonus was disclosed in five patients. In Rett syndrome, video-polygraphy is essential in characterizing the clinical features of paroxysmal events, determining autonomic dysfunctions, documenting myoclonic motor phenomena, and evaluating the responses to the treatment of epilepsy.

Ictal video-polygraphic features of perioral myoclonia with absences

There have been few case reports of perioral myoclonia with absences (POMA) because of the lack of video-polygraphic recordings clarifying the electroencephalogram (EEG)-electromyogram (EMG) correlations. We describe one of the first video-polygraphic studies of POMA in a patient who underwent repeated and prolonged split-screen video-polygraphic recordings. The ictal EEG showed generalized and irregular discharges of spikes or multiple spikes and slow waves, while two concomitant EMG patterns appeared: (1) a rhythmic enhancement of the orbicularis oris and masseter muscles on both sides with minimal asymmetry corresponding to perioral movements, and (2) a progressive increment in muscular tone in the mylohyoideus muscle corresponding to oroalimentary automatisms. Myoclonic jerks were inconstantly time-locked to the spike component of the spike-wave complex. The evidence of a complex pattern of activation of the facial muscles suggests that the involvement of subcortical central pattern generators, related to masticatory activity, through the disinhibitory effect of the spike-wave discharge is a possible pathophysiological mechanism underlying POMA.

Intravenous lacosamide in seizure emergencies: Observations from a hospitalized in-patient adult population

PURPOSE to evaluate the efficacy and safety of intravenous (IV) lacosamide (LCM) in the treatment of seizure clusters (SC) and status epilepticus (SE) in hospitalized adult patients. METHODS we prospectively analyzed treatment response, seizure outcome, and adverse effects of IV LCM in 38 patients with seizure emergencies (15 with SC, 23 with SE) during a hospital stay. The loading dose of IV LCM was 200-400mg and the maintenance dose was 200-400mg daily. Response to IV LCM was evaluated within 20min, 4h and 24h of LCM infusion. RESULTS an acute anti-seizure effect after IV LCM was especially evident when it was first used - (SC) or second line (established SE) treatment. In particular, 87% of SC patients (13/15) and 80% of established SE (8/10) demonstrated response to LCM treatment, while no patients with super-refractory SE (0/8) responded to IV LCM according to our criteria. The loading of IV LCM was well tolerated, with mild adverse effects (2/38 temporary dizziness). In most patients, during and after administration of the loading dose of IV LCM a temporary (30min-1h) sedation was observed. No ECG and laboratory values-changes were documented in any of the patients. CONCLUSIONS LCM is an effective and well-tolerated treatment when used to treat SC in hospitalized adult patients. As add-on therapy, it may be useful to stop seizure activity in patients with focal SE not responding to first/second-line intravenous AEDs.

New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic–clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies.

Partial Trisomy 18q and Epileptic Spasms Induced by Eating Associated With Bilateral Opercular Dysplasia

In2007,wedescribedtheclinicalandvideo-polygraphicfeaturesofa patient with reflex periodic spasms triggered by eating [d’Orsietal.,2007].Thepatientwasa30-year-old,right-handedmanwithsevereasphyxiaatbirthandsignificantintellectualdisability.Fromthe age of 25, he began to experience generalized tonic–clonicseizures,atonicdropattacksandeating-inducedrepetitiveepilepticspasmscharacterizedbysuddenheadandupperlimbsdropping.Inparticular, during the longer spasms (at least 1sec) the ictalpolygraphy showed a diffuse slow wave complex prevalent onanterior regions with an activation in crescendo-decrescendo onthe neck and the right sternocleidomastoideus muscles. Subse-quently, chromosome analysis, fluorescence in situ hybridization(FISH), and array comparative genomic hybridization (array-CGH) were performed. The array-CGH was carried out usingthe GenomeARRAY slide (TechnoGenetics Srl-Bouty Spa, Italy),containing 5,380 BAC clones, with a genomic resolution ofabout 0.5Mb, and increasing to 0.25Mb in the subtelomericregions. These studies revealed the presence of a partialtrisomy of chromosome 18 in the 18 q12.2q22.3 region (partialtrisomy 18q; see Fig. 1). The parents had normal karyotypes andarray-CGH.The relationship between chromosomal 18 anomalies and epi-lepsy was evaluated in a previous review [Grosso et al., 2005], andpartial seizures and focal EEG abnormalities were observed inpatients with 18 qDS, trisomy 18p and translocation betweenchromosome17and18.Epilepsyonsetinpatientscarryingtrisomy18p is usually during infancy, and focal seizures remitted in themajority. EEG pattern disclosed symmetric or asymmetric parox-ysmal activity in posterior regions associated with generalizedspikes and spike and waves, while brain MRI showed agenesis ofthe splenium and thin of corpus callosum.Toourknowledge,nopreviouscaseshavebeenreportedregardingthe relationship between partial trisomy 18q and epilepsy, andour patient expands the clinical spectrum and genomic character-izationoftrisomy18.Infact,fromaclinicalpointofviewageseizureonset (25 years) and seizure semiology (epileptic spasms inducedbyeating)differentiateourcasefromothersreportedintheliterature-[Grosso et al., 2005]. In addition, genetic testing based on array-CGH and FISH have revealed additional material on chromosome18, specificallya partialduplication of the longarm of chromosome18 (trisomy of 18q12.2q22.3 region), not previously associatedwith epileptic phenotype. Deletion of genes located in the distalportion of 18q seems to be important in conferring susceptibilityfor the clinical features, including epilepsy [Strathdee et al., 1995].Deletion of the long arm of the chromosome 18 is associated withepilepsy witha frequency ranging from 10% [Wilson et al., 1979] to31%[Strathdeeetal.,1995].Notablythepatientshavebeenreportedin the literature with partial duplication of the short arm of chro-mosome 18 and epilepsy, but no previous cases have been reported

Fear as nonconvulsive status epilepticus of frontal origin: EEG-SPECT correlation

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The epilepsy phenotype in adult patients with intellectual disability and pathogenic copy number variants

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Brain SPECT imaging of ictal smile seizure.

PURPOSE To characterize the electroclinical features of epilepsy associated with intellectual disability and pathogenic copy number variations (CNVs) METHODS: we prospectively investigated 61 adult patients with epilepsy and intellectual disability or other neurodevelopmental disorders. We performed high resolution SNP-Array analysis in order to detect clinical relevant chromosomal microdeletions and microduplications. An ordinal logistic regression model was fitted with 34 demographic, clinical and EEG-related variables in order to identify the epilepsy phenotype of patients with pathogenic CNVs. RESULTS chromosome microarray analysis identify non-polymorphic CNVs in 33 patients analyzed: 11 had an established pathogenic microdeletion/microduplication, 22 were carriers of CNVs of unknown clinical significance. Univariate analysis revealed a significant association between pathogenic CNVs and 3 electroclinical variables considered, specifically atypical absence seizures (p<0.05), tonic seizures (p<0.05), epileptic spasms (p<0.01). CONCLUSIONS high resolution SNP-Array analysis should be evaluated in adult patients with intellectual disability and epilepsy with peculiar electroclinical features, specifically atypical absence seizures, tonic seizures, and epileptic spasms, resembling a Lennox-Gastaut syndrome without a clear structural lesion.