Electroclinical Pattern Research Articles

P 125 Ring chromosome 20 Epilepsy syndrome in children Variable EEG- and electro-clinical pattern

Background Children with ring chromosome 20 epilepsy syndrome (rchr20es) typically show severe, drug-resistant focal epilepsies characterized by frontal semiology, high susceptibility for non-convulsive status epilepticus (NCSE) and epilepsy-associated cognitive and behavioral deteriorations. EEG has been reported to show frequent or continuous subclinical seizure patterns together with characteristic rhythmic theta waves (Caneveni et al. 1998). Here, we report on clinical and EEG data in four patients. Patients and methods Retrospective analysis of clinical and video-EEG-long-term-monitoring data of four patients (all female) with rchr20es. Age at onset of epilepsy ranged from 5 to 8 years, the number of antiepileptic drugs already used ranged from 6 to 10, and all four patients had suffered NCSE previously. Semiology: all four patients showed auras (epigastric: 2, fear: 2, visual: 1, somatosensory: 1) and seizures (hypermotor: 3, tonic: 3, dialeptic: 2, psychomotor: 2). Clinical epilepsy syndromes were frontal lobe epilepsies (n = 3) and frontal/ temporal lobe epilepsy (n = 1). EEG showed regional abnormalities in frontal (n = 4), temporal (n = 3) and parieto-occiptal (n = 1) areas, with subclinical seizure patterns and/ or EEG-status elements (with serial spikes, polyspikes, sharp waves, or spike wave complexes; n = 3), rhythmic theta (n = 2), 1–2 Hz slow sharp wave complexes (n = 1), spike wave complexes/low amplitude fast activity +high amplitude delta burst (n = 1), alpha/theta seizure activity (n = 1). MRI was essentially normal in all patients, with minor abnormalities in frontal (2) or temporal areas (2). Conclusion Consistent with the literature, our patients showed severe drug-resistant epilepsies with an electro-clinical complex of a fronto-temporal epilepsy with frequent, long-lasting or continuous subclinical seizure patterns and/or NCSE. Rhythmic theta as a “characteristic” EEG pattern was, however, only observed in 2/4 of our patients. Therefore, a rchr20es should be suspected in such patients also in the absence of this EEG feature. This information will help in an early identification of rchr20es, which is especially important since, without this specific diagnosis, many affected patients are considered candidates for pre-surgical diagnostics or even epilepsy surgery.

Hypothalamic hamartoma: Epileptogenesis beyond the lesion?

The discovery of intrinsic epileptogenicity of the hypothalamic hamartoma (HH) marked a new area in understanding the associated clinical syndrome, often manifesting as progressive epileptic encephalopathy. However, therapeutic procedures targeting the HH proved to be inefficient to cure seizures in up to 50% of cases, whereas in cases with partial improvement, the electroclinical patterns of persisting seizures suggest an involvement of distant cortical regions. The concept of kindling-like secondary epileptogenesis has been suggested as a possible underlying mechanism. Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10years. In two patients with HH ablation followed at a later time by a temporal lobectomy, only this second surgical step allowed complete seizure freedom. These findings suggest the existence of an independent, third stage of secondary epileptogenesis in human. In the Grenoble series, stereotactic intracerebral recordings (stereo electroencephalography [SEEG]) of five HH cases demonstrated that gelastic/dacrystic seizures were correlated with discharges within the HH, whereas other seizure types were related to discharges affecting cortical regions, which sometimes seemed to be triggered by HH. In the Marseille series, two cases explored by SEEG provided evidence of extended epileptogenicity outside the limits of the HH, forming complex epileptogenic networks, with HH still triggering clusters of neocortical seizures in the first, but not obligatory involved in spontaneous seizures in the second case. Taken together, our data argue for the existence of dynamic ictal network organization, with possible "kindling-like" relationships between the HH and the neocortex or widespread epileptogenesis. Despite the existence of secondary epileptogenesis, the epileptogenic zone could still be limited to the hamartoma, for which early surgical treatment should be pragmatically considered as a first surgical step.

Electrical status epilepticus during sleep in Mowat–Wilson syndrome

AimMowat–Wilson Syndrome (MWS) is a genetic rare disease. Epilepsy is present in 70–75% of Patients and an age-dependent electroclinical pattern has been described. Up to date, there are studies with overnight sleep EEGs, probably because of the severe intellectual disability (ID) and hyperactivity of these Patients.Our purpose was to verify the hypothesis that MWS Patients might have electrical status epilepticus in slow wave sleep (ESES pattern). MethodsA retrospective analysis of anamnestic and electrographic data was performed on 7 consecutive MWS Patients followed between 2007 and 2016. Only Patients with at least one overnight sleep EEG were included in the study. ResultsFive out of 7 Patients had overnight sleep EEG studies and were included in this study. All of them had an anterior ESES pattern with spike-and-wave index>85%. The architecture of sleep was abnormal. An ESES related regression of cognitive and motor functions with impact on daily activities (ESES-related syndrome) was demonstrated in 3 out of 5 (60%) Patients. In two Patients marked improvement of cognitive and motor performances was observed when the epileptiform activity during sleep was successfully controlled or it was spontaneously reduced. ConclusionsThe clinical significance of the ESES pattern is hard to assess in MWS Patients due to severe ID, but changing in behaviour or in motor and cognitive functions should mandate sleep EEG investigation and, if ESES is present, an appropriate treatment should be tried. Furthermore, overnight sleep EEG recordings, if regularly performed in the follow up, might help to understand if ESES pattern hampers the cognitive and communicative profile in MWS.

Childhood absence epilepsy and benign epilepsy with centro-temporal spikes: a narrative review analysis

Recent studies have shown a possible coexistence of absence seizures with other forms of epilepsy. The purpose of this study was to ascertain the possible contemporary or subsequent presence of childhood absence epilepsy (CAE) and benign epilepsy with centro-temporal spikes (BECTS) in pediatric epileptic patients. A PubMed systematic search indexed for MEDLINE, PubMed and EMBASE was undertaken to identify studies in children including articles written between 1996 and 2015. Retrospective studies, meta-analysis and case reports were included. The list of references of all the relevant articles was also studied. The date of our last search was December 2015. Review of the literature revealed 19 cases, 8 females and 11 males, reporting a consecutive or contemporary coexistence of CAE and BECTS within the same patients. Patient's age ranged between 4 and 12 years. Three out of 19 patients presented concomitant features of both syndromes, whereas 16 patients experienced the two syndromes at different times. BECTS and CAE may be pathophysiologically related, and the two epileptic phenotypes may indicate a neurobiological continuum. Further studies are needed to elucidate a probable genetic or functional link between partial and primarily generalized electro-clinical patterns in idiopathic childhood epilepsies.

Congenital disorders of glycosylation presenting as epileptic encephalopathy with migrating partial seizures in infancy.

Epilepsy is commonly observed in congenital disorders of glycosylation (CDG), but no distinctive electroclinical pattern has been recognized. We aimed at identifying a characteristic clinical presentation that might help targeted diagnostic work-up. Based on the initial observation of an index case with CDG and migrating partial seizures, we evaluated 16 additional children with CDG and analysed their clinical course, biochemical, genetic, electrographic, and imaging findings. Four of 17 consecutively observed children with CDG (three females, one male) were first referred between the first and fourth month of life, after early onset of migrating partial seizures. All four patients manifested developmental delay, microcephaly, and multi-organ involvement. Magnetic resonance imaging disclosed cerebral and cerebellar atrophy. Isoelectrofocusing of transferrin, enzymatic studies, and lipid-linked oligosaccharide analysis indicated CDG-I. Genetic testing demonstrated either homozygous or compound heterozygous variants involving the ALG3 gene in patients 1 and 3, the RFT1 gene in patient 2, and the ALG1 gene in patient 4. At last follow-up, patients 1 and 2 were 5 and 3(1/2) years old. Patients 3 and 4 had died due to respiratory failure during pneumonia and refractory status epilepticus respectively. Children with migrating partial seizures and concomitant multisystem involvement should be investigated for CDG.

Characteristic phasic evolution of convulsive seizure in PCDH19-related epilepsy.

PCDH19-related epilepsy is a genetic disorder that was first described in 1971, then referred to as "epilepsy and mental retardation limited to females". PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video-EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19-related epilepsy. To do this, ictal video-EEG recordings of 26 convulsive seizures in three girls with PCDH19-related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: "jerk", "reactive", "mild tonic", "fluttering", "mild clonic", and "postictal". Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic-clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19-related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19-related epilepsy when occurring in clusters with or without high fever in girls. [Published with video sequences online].

Electroclinical phenotype in Rubinstein–Taybi syndrome

ObjectiveRubinstein–Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated.The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. Patients and methodsElectroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. ResultsEEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. ConclusionThe specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients.

Multiplex families with epilepsy

To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies.

Ictal epileptic headache in adult life: Electroclinical patterns and spectrum of related syndromes.

Both headache and epilepsy are frequent paroxysmal disorders that often co-occur or are related in numerous ways. Although ictal epileptic headache has become the focus of several studies, this remains a very rare and not well-known phenomenon. Electroclinical features, pathophysiology, and syndromic context are heterogeneous. We investigated the electroclinical and neuroimaging findings in a population of adult patients with ictal epileptic headache. We retrospectively examined 8800 EEG recordings of almost 4800 patients admitted to our video-EEG laboratory from 2010 to 2013 with a history of well-documented epilepsy. We selected patients who reported headache closely related to a seizure documented by video-EEG or 24-hour ambulatory EEG. We analyzed ictal electroclinical features of headache, and we defined the related epileptic syndromes. We identified five patients with ictal epileptic headache. Two patients described tension headache during an epileptic seizure. In three patients, the headache was accompanied by other "minor" neurological symptoms mimicking a migrainous aura. In all cases, the headache stopped with the end of the epileptic activity. Three patients had a history of partial symptomatic epilepsy with cerebral lesions (low grade glioma, astrocytoma, porencephalic cyst) in the left posterior regions, whereas two patients were affected by idiopathic generalized epilepsy. This study confirms the rarity of ictal epileptic headache. To date, well-documented video-EEG cases remain as exceptional reports, especially in cases of idiopathic generalized epilepsies. Moreover, we confirm the main involvement of posterior regions in patients with ictal epileptic headache affected by partial symptomatic epilepsies.

Panayiotopoulos syndrome and diffuse paroxysms as the first EEG manifestation at clinical onset: a study of nine patients.

To present a retrospective study of nine children with Panayiotopoulos syndrome associated with diffuse spikes and waves as the sole EEG manifestation at onset. Charts of children with typical clinical criteria of Panayiotopoulos syndrome, electroclinically followed between February2000 and February2012, were reviewed. Among 150 patients who met the electroclinical criteria of Panayiotopoulos syndrome, we identified nine children who presented with the typical clinical manifestations but who, on EEG, only had diffuse paroxysms at onset that continued along the course of the syndrome. In three, in addition to the diffuse paroxysms, focal spikes appeared later. From a clinical point of view, other features were otherwise unremarkable. Diffuse spike-and-wave discharges were observed in all patients when awake and during sleep (100%). Later, three children also had focal spikes during sleep, which were occipital in one, frontal in one, and temporo-occipital in the remaining patient. Spikes were activated by sleep in all three cases. During disease evolution, no particular electroclinical pattern was observed. Two patients who received clobazam and carbamazepine, respectively, did not respond well to the drugs and valproic acid was added with excellent seizure control. Outcome was good. We present evidence that patients with Panayiotopoulos syndrome may have diffuse discharges at onset as the sole EEG manifestation, which last throughout the course of the syndrome. In some, focal paroxysms developed later. The course was benign. In our group of patients, clinical features and evolution were similar to those of typical cases of Panayiotopoulos syndrome.

PP01.5 – 3005: Clinical and cytogenetic features of 3 cases with ring chromosome 20 syndrome

Objective Ring chromosome 20 syndrome (R20) has an almost constant association with refractory epilepsy and intellectual and behavioral disabilities. Though early diagnosis is usually difficult and rarely made, Particular electroclinical patterns have been found to be very helpful for the R20 diagnosis that is usually difficult and rarely early made. Here, we present the clinical, EEG and cytogenetic correlations in three patients with R20. Methods Three patients, aged 17, 13 and 4 years, respectively, were studied by video-EEG monitoring (VEEG) for drug-resistant seizures. Brain MRI was normal; standard EEGs showed anterior epileptiform activity with one-sided predominance, correlating to some ictal clinical features; intellectual and behavioral problems increased with age and disease course. VEEG as a part of presurgical evaluation was considered because of drug-resistant epilepsy. Results All three patients presented an electroclinical pattern consistent with frontal epilepsy. They also had subclinical or “subtle” clinical episodes, both awake and in sleep, corresponding to nonconvulsive status epilepticus (NCSE). The epilepsy started earlier (age 3 years) in the youngest patient with more severe epilepsy. The seizures started later (age 7 and 9 years, respectively) and were rarer in the older patients, who also showed mild cognitive and behavioral disability. Due to the particular electroclinical picture R20 was suspected and cytogenetic analysis was performed. It revealed R20 mosaic karyotype, at 10%, 25% and 40%, respectively. Conclusion The presented cases show again that the diagnosis of R20 syndrome is usually delayed and is based on the very helpful and characteristic for the syndrome electroclinical NCSE pattern and the overall “frontal” seizure appearance. Our cases add further evidence for the genotype-phenotype correlation in the syndrome, since the degree of mosaicism reflects the age of epilepsy onset, the severity and refractoriness of the seizures, and the severity of the associated intellectual and behavioral disabilities.

Behavioral and Movement Disorders due to Long-Lasting Myoclonic Status Epilepticus Misdiagnosed as ADHD in a Patient With Juvenile Myoclonic Epilepsy: Electroclinical Findings and Related Hemodynamic Changes.

Epilepsy and attention-deficit/hyperactivity disorder (ADHD) likely share common underlying neural mechanisms, as often suggested by both the evidence of electroencephalography (EEG) abnormalities in ADHD patients without epilepsy and the coexistence of these 2 conditions. The differential diagnosis between epilepsy and ADHD may consequently be challenging. In this report, we describe a patient presenting with a clinical association of "tics" and behavioral disorders that appeared 6 months before our first observation and had previously been interpreted as ADHD. A video-EEG evaluation documented an electroclinical pattern of myoclonic status epilepticus. On the basis of the revised clinical data, the EEG findings, the good response to valproate, the long-lasting myoclonic status epilepticus, and the enduring epileptic abnormalities likely causing behavioral disturbances, the patient's symptoms were interpreted as being the expression of untreated juvenile myoclonic epilepsy. The EEG-functional magnetic resonance imaging study revealed, during clinical generalized spike-and-wave and polyspike-and-wave discharges, positive blood oxygen level-dependent (BOLD) signal changes bilaterally in the thalamus, the prefrontal cortex (Brodmann area 6, supplementary motor area) and the cerebellum, and negative BOLD signal changes in the regions of the default mode network. Such findings, which are typical of BOLD changes observed in idiopathic generalized epilepsy, may also shed light on the anatomofunctional network underlying ADHD.

Seizures and EEG features in 74 patients with genetic-dysmorphic syndromes.

Epilepsy is one of the most common findings in chromosome aberrations. Types of seizures and severity may significantly vary both between different conditions and within the same aberration. Hitherto specific seizures and EEG patterns are identified for only few syndromes. We studied 74 patients with defined genetic-dysmorphic syndromes with and without epilepsy in order to assess clinical and electroencephalographic features, to compare our observation with already described electro-clinical phenotypes, and to identify putative electroencephalographic and/or seizure characteristics useful to address the diagnosis. In our population, 10 patients had chromosomal disorders, 19 microdeletion or microduplication syndromes, and 32 monogenic syndromes. In the remaining 13, syndrome diagnosis was assessed on clinical grounds. Our study confirmed the high incidence of epilepsy in genetic-dysmorphic syndromes. Moreover, febrile seizures and neonatal seizures had a higher incidence compared to general population. In addition, more than one third of epileptic patients had drug-resistant epilepsy. EEG study revealed poor background organization in 42 patients, an excess of diffuse rhythmic activities in beta, alpha or theta frequency bands in 34, and epileptiform patterns in 36. EEG was completely normal only in 20 patients. No specific electro-clinical pattern was identified, except for inv-dup15, Angelman, and Rett syndromes. Nevertheless some specific conditions are described in detail, because of notable differences from what previously reported. Regarding the diagnostic role of EEG, we found that--even without any epileptiform pattern--the generation of excessive rhythmic activities in different frequency bandwidths might support the diagnosis of a genetic syndrome.

Paediatric epilepsy surgery in the posterior cortex: a study of 62 cases.

Past surgical series have emphasized the diagnostic complexity of posterior cortex epilepsy. Available data are sparse, especially in children, and most published series report a high number of surgical failures and post-operative neurological deficits. In this article, we present a paediatric cohort of 62 children who underwent surgery for drug resistant posterior cortex epilepsy before the age of 16 years with a mean post-operative follow-up of 6.94 years (range: 2-16). Mean age at epilepsy onset was 3.2 years and 28 children (45%) had onset before 1 year of age. The mean age at surgery was 7.9 years (range: 1-16). Daily seizures were present in 63% of children. MRI was positive in 58 cases (93.5%) and invasive stereo-EEG was judged mandatory in 24/62 (39%) of patients. Surgery was confined to the parietal lobe in 11 children, the occipital lobe in 8, the occipito-parietal region in four, the occipito-temporal region in 18, and involved both the temporal and parietal lobes in the remaining 21. Following surgery, 53 subjects (85.5%) remained seizure-free and among those who underwent a SEEG procedure, 75% achieved seizure freedom. Focal cortical dysplasia was the most frequent histopathological diagnosis (50%), followed by tumoural (24%) and gliotic lesions (14.5%). An older age at epilepsy onset, the presence of a rather restricted epileptogenic area, and a complete resection of the epileptogenic zone were predictive of a favourable surgical outcome. These results demonstrate that a good surgical outcome is possible in children with drug resistant posterior cortex epilepsy. Accurate analysis of the chronology of ictal semiology and electrophysiological features, viewed in the context of the complete electroclinical pattern, provides a topographical orientation for posterior cortex epilepsy and, together with the presence of a lesion detectable on imaging, may improve the rate of surgical success of posterior cortex epilepsy at paediatric age.

A Novel Mutation in STXBP1 Gene in a Child With Epileptic Encephalopathy and an Atypical Electroclinical Pattern

Mutations in STXBP1 gene, encoding the syntaxin binding protein 1, have been recently described in Ohtahara syndrome, or early infantile epileptic encephalopathy with suppression-burst pattern, and in other early-onset epileptic encephalopathies. A 3-year-old boy affected by epileptic encephalopathy started at 8 months of age is described. Focal epilepsy was characterized by drug resistance seizures with multifocal interictal and ictal electroencephalographic (EEG) features and variable EEG focus. Direct sequencing of the STXBP1 gene showed a novel de novo mutation (c.751G>A), leading to a p.Ala251Thr substitution. Based on reported data, treatment with vigabatrin was attempted and patient became immediately seizure free for 4 months. The present case further expands the clinical spectrum of "STXBP1-related encephalopathy" suggesting molecular analysis of STXBP1 in early onset epileptic encephalopathies of unknown etiology (with onset within the first year of life). In addition, the case provides valuable suggestions on seizures treatment in STXBP1 mutated subjects.

113. Neurophysiology in neonatal stroke undergoing therapeutic hypotermia: An illustrative case

Therapeutic hypothermia (TH) is at present standard of cure in hypoxic ischemic encephalopathy but its role is debated in ischemic stroke. We report EEG monitoring and EP in a neonate with stroke due to internal carotid thrombosis who underwent TH. Case Report: A female infant born at 38 GA, BW 2730 gr (10°ile), was recruited for TH at 3 h of life, because of Sarnat 2 plus pH < 7 and BE −19.6. Video-EEG monitoring, from 7th hour of life, demonstrated electroclinical seizure pattern, controlled with high doses of Phenobarbital. MRI, done in 1st day, showed left ischemic lesion in the territory of the middle and anterior cerebral arteries; MRI angiography showed internal carotid thrombosis. It was decided to continue TH with continuous EEG monitoring. SEP, at 4th day, showed a left absence of N2; VEP, 10th day, were minimally abnormal. Follow-up at 9 months: right hemiparesis and good relationship; no seizures. Our case confirms the utility of neurophysiology in neonatal stroke: EEG has a crucial role in detection and monitoring of seizures; unilateral involvement of SEP may suggest stroke. The preliminary follow up data are in favour of use of TH in case of massive stroke.

114. Movement disorder and EEG patterns in anti-NMDAr antibodies encephalitis

Our aim was to investigate clinical picture, differential diagnosis between epileptic seizures and movement disorder and the significance of EEG patterns in paediatric anti- N-methyl- d -aspartate receptor (NMDAr) antibodies encephalitis. We reviewed clinical history, time course of the disease and EEG records. Clinical suspicion was confirmed by cell-based assay for detection of NMDAr antibodies in the serum and CSF in 3 and in serum in 1 of the patients. Four patients had the diagnosis of anti-NMDAr antibodies encephalitis in our Institution between 2007 and 2012 (the last three since 2011). All presented with movement disorders, epileptic seizures or seldom psychiatric disturbance, rapidly associated to abnormal sleep-wake cycle, hyporesponsivity and catatonia, followed by autonomic nervous system imbalance. In the acute phase epileptic seizures were clinically suspected in all patients but the EEG showed clear electro-clinical patterns in only one patient, one other receiving antiepileptic treatment before EEG recording had electrical seizure patterns. EEG recordings showed some similarities between the four subjects in the corresponding disease phases. Extensive diagnostic testing failed to detect neoplasms in all. All patients showed a marked improvement at follow up. Anti NMDAr antibodies encephalitis is increasingly recognised in the paediatric population. With respect to adults, movement disorder, seizures and rapid development of hyporesponsivity predominate at onset over discrete psychiatric symptoms. EEG features although not specific might help to suspect the disease in the early stages and aid in the differentiation between epileptic and non epileptic manifestations, with implications for treatment.

Extrarolandic electroclinical findings in the evolution of adult-onset Rasmussen's encephalitis

Rasmussen's encephalitis (RE) is a rare immunomediated disorder characterized by unilateral hemispheric atrophy, drug-resistant focal epilepsy, and progressive neurological deficits. Its onset typically occurs in childhood, though it has also been reported in adult age (A-RE) with atypical clinical features. The aim of this study was to describe the electroclinical features in a group of seven patients with A-RE.We retrospectively studied seven women aged 23–43years (mean: 32.1years) with a diagnosis of RE according to commonly accepted diagnostic criteria. All the patients were clinically evaluated and underwent prolonged video-EEG monitoring, laboratory investigations, and high-resolution MRI follow-up.All the patients displayed an ictal electroclinical pattern whose evolution varied. We identified an early phase characterized by polymorphic ictal electroclinical manifestations (temporal semiology in five cases, frontal in one, and parietal in the remaining case) and a late phase clinically characterized by viscerosensitive phenomena followed by somatosensitive signs, experiential symptoms, and motor signs in all the cases. In the late phase, the ictal EEG pattern was characterized by monomorphic, pseudorhythmic, repetitive slow-wave theta activity over the frontal and central regions, with ipsilateral propagation and/or secondary spreading to contralateral perisylvian structures. Patients were treated with a combination of AEDs and immunotherapy (steroids and IVIg); epilepsy surgery was performed in 3 cases.Our results show that A-RE is characterized by early and late clinical- and EEG-different features which may reflect a progressive involvement of a specific “extrarolandic” network in the advanced phase of the disease and may suggest that the electroclinical expression of RE varies according to the different stages of the pathological process.

Epilepsy in Mowat‐Wilson syndrome: Is it a matter of GABA?

We have read with interest the latest advances regarding ZEB2 gene function in neuroembryology and its connections with epilepsy (McKinsey et al., 2013; Van den Berghe et al., 2013). Zinc finger E-box binding homeobox 2 (ZEB2, MIM#60580), also annotated as ZFHX1B and SIP1, is a member of the two-handed zinc finger/homeodomain transcription factors. Its role during development has been confirmed by invalidation in mice, which revealed arrest of embryonic development with severe neural plate and somatogenesis defects, as well as migratory failure of neural crest cells (Van de Putte et al., 2003). In humans, deletions or mutations of ZEB2 cause the Mowat-Wilson syndrome (MWS), which is characterized by a distinctive facial appearance, intellectual disability, and variable other features including agenesis of the corpus callosum and Hirschsprung disease (Mowat et al., 2003). Epilepsy is one of the main features of MWS, with a prevalence of about 70–75%. We recently delineated the electroclinical phenotype of epilepsy in MWS. In these patients, epilepsy is usually characterized by frontal lobe and atypical absence seizures, often preceded by fever-triggered seizures; in addition, we observed an age-dependent electroencephalography (EEG) pattern with frequent diffuse frontal dominant spike and wave discharges during the awake state and a near to continuous spike and wave activity during slow sleep (Cordelli et al., 2013). Some authors suggested that epilepsy in MWS could be the result of cerebral malformations (Engenheiro et al., 2008). Instead, we noticed that MRI did not disclose any cortical malformations clearly associated with epilepsy and that the electroclinical pattern (which was present irrespective of magnetic resonance imaging [MRI] findings) suggested an age-related disorder with a genetic, rather than a structural-malformative, etiology. Meanwhile, McKinsey and Van den Berghe et al. demonstrated the influence of ZEB2 on the neurogenesis of cortical γ-aminobutyric acid (GABA)ergic interneurons. Their studies highlight that the lack of ZEB2 prevents the repression of NKX2-1 homeobox transcription factor, the expression of which provokes the differentiation of the progenitors in striatal interneurons rather than cortical ones. Deficit of GABAergic inhibition is supposed to underlie most forms of seizures, including focal and absence seizures (Yalçın, 2012). However, results of GABAergic inhibition are brain-area and inhibitory-pathway specific. In fact, within one brain region, at a given time of life, some modifications in these circuitries will appear as proepileptic and others as antiepileptic (Bernard et al., 2000). Therefore, the switch between cortical and striatal GABAergic interneurons determined by mutations of ZEB2 could suggest a mechanism for the epilepsy observed in MWS, as proposed by McKinsey and Van den Berghe. From our point of view, that is the one of the clinicians, we strongly support this hypothesis, as the age-related electroclinical pattern we have detected in vivo is reminiscent of the idea of a genetic form of epilepsy and is scarcely influenced by brain macroanatomy. In conclusion, we feel that these observations could be of high importance in understanding how epilepsy is determined in patients with MWS. New interesting scenarios in terms of treatment are now opened. The authors declare no conflict of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

FXTAS

Fragile X-associated tremor ataxia syndrome (FXTAS) is defined by FMR1 premutation, cerebellar ataxia, intentional tremor, and middle cerebellar peduncle (MCP) hyperintensities. We delineate the clinical, neurophysiologic, and morphologic characteristics of FXTAS. Clinical, morphologic (brain MRI, (123)I-ioflupane SPECT), and neurophysiologic (tremor recording, nerve conduction studies) study in 22 patients with FXTAS, including 4 women. A total of 43% of patients had no family history of fragile X syndrome (FXS), which contrasts with previous FXTAS series. A total of 86% of patients had tremor and 81% peripheral neuropathy. We identified 3 electroclinical tremor patterns: essential-like (35%), cerebellar (29%), and parkinsonian (12%). Two electrophysiologic patterns evocative of non-length-dependent (56%) and length-dependent sensory neuropathy (25%) were identified. Corpus callosum splenium (CCS) hyperintensity was as frequent (68%) as MCP hyperintensities (64%). Sixty percent of patients had parkinsonism and 47% abnormal (123)I-ioflupane SPECT. Unified Parkinson's Disease Rating Scale motor score was correlated to abnormal (123)I-ioflupane SPECT (p = 0.02) and to CGG repeat number (p = 0.0004). Scale for the assessment and rating of ataxia correlated with dentate nuclei hyperintensities (p = 0.03) and CCS hyperintensity was a marker of severe disease progression (p = 0.04). We recommend to include in the FXTAS testing guidelines both CCS hyperintensity and peripheral neuropathy and to consider them as new major radiologic and minor clinical criterion, respectively, for the diagnosis of FXTAS. FXTAS should also be considered in women or when tremor, MCP hyperintensities, or family history of FXS are lacking. Our study broadens the spectrum of tremor, peripheral neuropathy, and MRI abnormalities in FXTAS, hence revealing the need for revised criteria.