Publications by authors named "Eliane Roulet-Perez"

50 Publications

Structural brain abnormalities in epilepsy with myoclonic atonic seizures.

Epilepsy Res 2021 Sep 21;177:106771. Epub 2021 Sep 21.

Pediatric Neurology and Neurorehabilitation Unit, Woman-Mother-Child Department, Lausanne University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland. Electronic address:

Objective: Epilepsy with myoclonic atonic seizure (EMAS) occurs in young children with previously normal to subnormal development. The outcome ranges from seizure freedom with preserved cognitive abilities to refractory epilepsy with intellectual disability (ID). Routine brain imaging typically shows no abnormalities. We aimed to compare the brain morphometry of EMAS patients with healthy subjects several years after epilepsy onset, and to correlate it to epilepsy severity and cognitive findings.

Methods: Fourteen EMAS patients (4 females, 5-14 years) and 14 matched healthy controls were included. Patients were classified into three outcome groups (good, intermediate, poor) according to seizure control and cognitive and behavioral functioning. Individual anatomical data (T1-weighted sequence) were processed using the FreeSurfer pipeline. Cortical volume (CV), cortical thickness (CT), local gyrification index (LGI), and subcortical volumes were used for group-comparison and linear regression analyses.

Results: Morphometric comparison between EMAS patients and healthy controls revealed that patients have 1) reduced CV in frontal, temporal and parietal lobes (p = <.001; 0.009 and 0.024 respectively); 2) reduced CT and LGI in frontal lobes (p = 0.036 and 0.032 respectively); and 3) a neat cerebellar volume reduction (p = 0.011). Neither the number of anti-seizure medication nor the duration of epilepsy was related to cerebellar volume (both p > 0.62). Poor outcome group was associated with lower LGI. Patients in good and intermediate outcome groups had a comparable LGI to their matched healthy controls (p > 0.27 for all lobes).

Conclusions: Structural brain differences were detectable in our sample of children with EMAS, mainly located in the frontal lobes and cerebellum. These findings are similar to those found in patients with genetic/idiopathic generalized epilepsies. Outcome groups correlated best with LGI. Whether these anatomical changes reflect genetically determined abnormal neuronal networks or a consequence of sustained epilepsy remains to be solved with prospective longitudinal studies.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106771DOI Listing
September 2021

Phenotypic expansion of CACNA1C-associated disorders to include isolated neurological manifestations.

Genet Med 2021 10 23;23(10):1922-1932. Epub 2021 Jun 23.

Rare Diseases and Medical Genetic Unit, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.

Purpose: CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.

Methods: We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.

Results: Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.

Conclusion: We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.
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http://dx.doi.org/10.1038/s41436-021-01232-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488020PMC
October 2021

Neurologic assessment.

Handb Clin Neurol 2020 ;174:205-215

Pediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital, Lausanne, Switzerland. Electronic address:

Despite rapidly evolving technologies, an accurate and thorough clinical neurologic assessment is still crucial to understanding presenting symptoms and signs. It is the most exciting but also challenging part of the diagnostic puzzle, essential to establishing a rational working hypothesis and a consistent management plan. Flexibility, creativity, and social skills are needed to elicit the child's participation. History taking is of the utmost importance, requiring not only time and perseverance, but also knowledge and effective communication to obtain relevant and precise information. Understanding what is being tested and distinguishing the normal from the abnormal are indispensable in reaching a correct clinical interpretation. The clinician needs to tailor an individualized approach for each patient according to the chief complaint, clinical context, and the child's chronologic and developmental age. The questions about the nature, localization, and etiology must be addressed first and then summarized and developed into a reasonable diagnostic hypothesis and differential diagnosis. This chapter aims to guide the reader through a situation-related approach from history taking and neurologic examination to a systematic, step-by-step interpretation of the information and findings. It also provides some practical advice on how to avoid common pitfalls.
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http://dx.doi.org/10.1016/B978-0-444-64148-9.00015-6DOI Listing
July 2021

Acute monophasic erythromelalgia pain in five children diagnosed as small-fiber neuropathy.

Eur J Paediatr Neurol 2020 Sep 7;28:198-204. Epub 2020 Jul 7.

Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University of Lausanne, Lausanne, Switzerland.

The small-fiber polyneuropathies (SFN) are a class of diseases in which the small thin myelinated (Aδ) and/or unmyelinated (C) fibers within peripheral nerves malfunction and can degenerate. SFN usually begins in the farthest, most-vulnerable axons, so distal neuropathic pain and symptoms from microvascular dysregulation are common. It is well known in adults, e.g. from diabetes, human immunodeficiency virus, or neurotoxins, but considered extremely rare in children, linked mostly with pathogenic genetic variants in voltage-gated sodium channels. However, increasing evidence suggests that pediatric SFN is not rare, and that dysimmunity is the most common cause. Because most pediatric neurologists are unfamiliar with SFN, we report the diagnosis and management of 5 Swiss children, aged 6-11y, who presented with severe paroxysmal burning pain in the hands and feet temporarily relieved by cooling-the erythromelalgia presentation. Medical evaluations revealed autoimmune diseases in 3 families and 3/5 had preceding or concomitant infections. The standard diagnostic test (PGP9.5-immunolabeled lower-leg skin biopsy) confirmed SFN diagnoses in 3/4, and autonomic function testing (AFT) was abnormal in 2/3. Blood testing for etiology was unrevealing, including genetic testing in 3. Paracetamol and ibuprofen were ineffective. Two children responded to gabapentin plus mexiletine, one to carbamazepine, two to mexiletine plus immunotherapy (methylprednisolone/IVIg). All recovered within 6 months, remaining well for years. These monophasic tempos and therapeutic responses are most consistent with acute post-infectious immune-mediated causality akin to Guillain-Barré large-fiber polyneuropathy. Skin biopsy and AFT for SFN, neuropathic-pain medications and immunotherapy should be considered for acute sporadic pediatric erythromelalgia.
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http://dx.doi.org/10.1016/j.ejpn.2020.06.004DOI Listing
September 2020

Music processing deficits in Landau-Kleffner syndrome: Four case studies in adulthood.

Cortex 2020 08 15;129:99-111. Epub 2020 Apr 15.

Lyon Neuroscience Research Center, Inserm, CNRS, Lyon 1 University, Lyon, France.

Verbal-auditory agnosia and aphasia are the most prominent symptoms in Landau-Kleffner syndrome (LKS), a childhood epilepsy that can have sustained long-term effects on language processing. The present study provides the first objective investigation of music perception skills in four adult patients with a diagnosis of LKS during childhood, covering the spectrum of severity of the syndrome from mild to severe. Pitch discrimination, short-term memory for melodic, rhythmic and verbal information, as well as emotion recognition in music and speech prosody were assessed with listening tests, and subjective attitude to music with a questionnaire. We observed amusia in 3 out of 4 patients, with elevated pitch discrimination thresholds and poor short-term memory for melody and rhythm. The two patients with the most severe LKS had impairments in music and prosody emotion recognition, but normal perception of emotional intensity of music. Overall, performance in music processing tasks was proportional to the severity of the syndrome. Nonetheless, the four patients reported that they enjoyed music, felt musical emotions, and used music in their daily life. These new data support the hypothesis that, beyond verbal impairments, cerebral networks involved in sound processing and encoding are deeply altered by the epileptic activity in LKS, well after electrophysiological normalization.
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http://dx.doi.org/10.1016/j.cortex.2020.03.025DOI Listing
August 2020

Clinical Reasoning: Rapidly progressive gait disorder and cranial nerves involvement in a 9-year-old boy.

Neurology 2020 01;94(3):e330-e334

From the Division of Pediatrics (A.L., J.-B.A.), Pediatric Hematology Oncology Unit (C.A., M.B.-P.), Paediatric Infectious Diseases and Vaccinology Unit (S.A.), and Unit of Pediatric Neurology and Neurorehabilitation (C.P., E.R.-P., S.L.), Department Woman-Mother-Child, University Institute of Pathology (J.-P.B.), Department of Clinical Neurosciences, Service of Neurosurgery (M.M.), and Infectious Disease Service, Department of Medicine (S.A.), Lausanne University Hospital, Switzerland.

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http://dx.doi.org/10.1212/WNL.0000000000008826DOI Listing
January 2020

Childhood neurodegeneration associated with a specific UBTF variant: a new case report and review of the literature.

BMC Neurol 2020 Jan 13;20(1):17. Epub 2020 Jan 13.

Department woman-mother-child, Unit of Paediatric Neurology and Neurorehabilitation, Lausanne University Hospital (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland.

Background: A new monogenic neurodegenerative disease affecting ribosomal metabolism has recently been identified in association with a monoallelic UBTF putative gain of function variant (NM_001076683.1:c.628G>A, hg19). Phenotype is consistent among these probands with progressive motor, cognitive, and behavioural regression in early to middle childhood.

Case Presentation: We report on a child with this monoallelic UBTF variant who presented with progressive disease including regression, episodes of subacute deterioration during febrile illnesses and a remarkable EEG pattern with a transient pattern of semi-periodic slow waves.

Conclusions: This case further supports the phenotype-genotype correlation of neurodegeneration associated with UBTF c.628G>A. Moreover, it brings new insights into the clinical features and EEG that could possibly serve as diagnostic markers of this otherwise nonspecific phenotype.
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http://dx.doi.org/10.1186/s12883-019-1586-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958716PMC
January 2020

Cerebellar lesions in pediatric abusive head trauma.

Eur J Paediatr Neurol 2019 Jul 17;23(4):604-608. Epub 2019 May 17.

University Children's Hospital (Department of Pediatric Neurology and Developmental Medicine), Tübingen, Germany.

Pediatric abusive head trauma (AHT) or non accidental head trauma (NAHT) is a major cause of death from trauma in children under 2 years of age. Main etiological factor for non accidental head trauma is shaking a baby, causing brain injury by rotational head acceleration and deceleration. The consequent brain damage as shown by magnetic resonance imaging (MRI) is subdural haemorrhage and to a lesser extent parenchymal injuries of variable severity. Involvement of the cerebellum has very rarely been described. We report the clinical history and the development of cerebral magnetic resonance imaging findings in two children with serious brain injury following probable shaking who presented the typical "triad" with subdural haematoma, retinal haemorrhage and encephalopathy. We want to draw attention to cerebellar involvement characterized by cortico-subcortical signal alterations most prominent on T2w images following diffusion changes during the acute period. We discuss cerebellar involvement as a sign of higher severity of AHT which is probably underrecognized.
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http://dx.doi.org/10.1016/j.ejpn.2019.05.001DOI Listing
July 2019

Midazolam as a first-line treatment for neonatal seizures: Retrospective study.

Pediatr Int 2018 May;60(5):498-500

Unit of Pediatric Neurology and Neurorehabilitation, Mother-Woman-Child Department, Lausanne University Hospital, Lausanne, Switzerland.

Midazolam is commonly used to treat refractory seizures in newborns and as a first-line anti-epileptic drug in children. Its use as first-line treatment of neonatal seizures has not been investigated so far. We retrospectively studied the tolerability of midazolam in 72 newborn infants who received i.v. or i.n. midazolam as first-line treatment for seizures. No major side-effect exclusively due to midazolam was reported. The i.n. route was used for 20 patients (27.8%). Effectiveness could not be formally evaluated due to the absence of systematic electroencephalogram recording while midazolam was administered. In conclusion, midazolam was well-tolerated as a first-line abortive emergency treatment of neonatal seizure. The i.n. route offers a useful alternative to i.v. phenobarbital or phenytoin in emergency settings.
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http://dx.doi.org/10.1111/ped.13554DOI Listing
May 2018

[Pediatrics - New classification of seizures and epilepsies].

Rev Med Suisse 2018 Jan;14(588-589):74-75

Unité de neuropédiatrie et neuroréhabilitation pédiatrique, Département femme- mère-enfant, CHUV, 1011 Lausanne.

The International League Against Epilepsy published a new classification of epileptic seizures and epilepsies. It is more transparent and important notions like etiologies and comorbities have been added. The identification of seizures, epilepsies then epilepsy syndromes constitutes the three steps of this classification.
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January 2018

Childhood epilepsy with centro-temporal spikes (rolandic epilepsy) and written language.

Dev Med Child Neurol 2018 03 21;60(3):219. Epub 2017 Dec 21.

Pediatric Neurology and Neurorehabilitation Unit, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

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http://dx.doi.org/10.1111/dmcn.13658DOI Listing
March 2018

Periinsular anterior quadrantotomy: technical note.

J Neurosurg Pediatr 2018 02 8;21(2):124-132. Epub 2017 Dec 8.

1Department of Neurosurgery and.

Refractory frontal lobe epilepsy has been traditionally treated through a frontal lobectomy. A disconnective technique may allow similar seizure outcomes while avoiding the complications associated with large brain resections. The aim of this study was to describe a new technique of selective disconnection of the frontal lobe that can be performed in cases of refractory epilepsy due to epileptogenic foci involving 1 frontal lobe (anterior to the motor cortex), with preservation of motor function. In addition to the description of the technique, an illustrative case is also presented. This disconnective procedure is divided into 4 steps: the suprainsular window, the anterior callosotomy, the intrafrontal disconnection, and the frontobasal disconnection. The functional neuroanatomy is analyzed in detail for each step of the surgery. It is important to perform cortical and subcortical electrophysiological mapping to guide this disconnective procedure and identify eloquent cortices and intact neural pathways. The authors describe the case of a 9-year-old boy who presented with refractory epilepsy due to epileptogenic foci localized to the right frontal lobe. MRI confirmed the presence of a focal cortical dysplasia of the right frontal lobe. A periinsular anterior quadrant disconnection (quadrantotomy) was performed. The postoperative period was uneventful, and the patient was in Engel seizure outcome Class I at the 3-year follow-up. A significant cognitive gain was observed during follow-up. Periinsular anterior quadrantotomy may thus represent a safe technique to efficiently treat refractory epilepsy when epileptogenic foci are localized to 1 frontal lobe while preserving residual motor functions.
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http://dx.doi.org/10.3171/2017.8.PEDS17339DOI Listing
February 2018

Prenatal Brainstem Disruptions: Small Lesions-Big Problems.

Neuropediatrics 2017 10 1;48(5):350-355. Epub 2017 Jun 1.

Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States.

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http://dx.doi.org/10.1055/s-0037-1603516DOI Listing
October 2017

Instruction manual for the ILAE 2017 operational classification of seizure types.

Epilepsia 2017 04 8;58(4):531-542. Epub 2017 Mar 8.

The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, United Kingdom.

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. Illustration of the classification is enacted by tables, a glossary of relevant terms, mapping of old to new terms, suggested abbreviations, and examples. Basic and extended versions of the classification are available, depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categories of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can further be optionally characterized by whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it a focal impaired awareness seizure. Focal seizures are further optionally characterized by motor onset signs and symptoms: atonic, automatisms, clonic, epileptic spasms, or hyperkinetic, myoclonic, or tonic activity. Nonmotor-onset seizures can manifest as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which might then progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic. Generalized seizures engage bilateral networks from onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic, or tonic-clonic. Nonmotor (absence) seizures are typical or atypical, or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown onset may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms, or behavior arrest. This "users' manual" for the ILAE 2017 seizure classification will assist the adoption of the new system.
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http://dx.doi.org/10.1111/epi.13671DOI Listing
April 2017

Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology.

Epilepsia 2017 04 8;58(4):522-530. Epub 2017 Mar 8.

The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, United Kingdom.

The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of such a revision is to recognize that some seizure types can have either a focal or generalized onset, to allow classification when the onset is unobserved, to include some missing seizure types, and to adopt more transparent names. Because current knowledge is insufficient to form a scientifically based classification, the 2017 Classification is operational (practical) and based on the 1981 Classification, extended in 2010. Changes include the following: (1) "partial" becomes "focal"; (2) awareness is used as a classifier of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic, and secondarily generalized are eliminated; (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional; (5) atonic, clonic, epileptic spasms, myoclonic, and tonic seizures can be of either focal or generalized onset; (6) focal to bilateral tonic-clonic seizure replaces secondarily generalized seizure; (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic; and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change, but allows greater flexibility and transparency in naming seizure types.
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http://dx.doi.org/10.1111/epi.13670DOI Listing
April 2017

Procedural learning: A developmental study of motor sequence learning and probabilistic classification learning in school-aged children.

Child Neuropsychol 2016 6;22(6):718-34. Epub 2015 Jul 6.

a Paediatric Neurology and Neurorehabilitation Unit , University Hospital , Lausanne , Switzerland.

In this study, we investigated motor and cognitive procedural learning in typically developing children aged 8-12 years with a serial reaction time (SRT) task and a probabilistic classification learning (PCL) task. The aims were to replicate and extend the results of previous SRT studies, to investigate PCL in school-aged children, to explore the contribution of declarative knowledge to SRT and PCL performance, to explore the strategies used by children in the PCL task via a mathematical model, and to see whether performances obtained in motor and cognitive tasks correlated. The results showed similar learning effects in the three age groups in the SRT and in the first half of the PCL tasks. Participants did not develop explicit knowledge in the SRT task whereas declarative knowledge of the cue-outcome associations correlated with the performances in the second half of the PCL task, suggesting a participation of explicit knowledge after some time of exposure in PCL. An increasing proportion of the optimal strategy use with increasing age was observed in the PCL task. Finally, no correlation appeared between cognitive and motor performance. In conclusion, we extended the hypothesis of age invariance from motor to cognitive procedural learning, which had not been done previously. The ability to adopt more efficient learning strategies with age may rely on the maturation of the fronto-striatal loops. The lack of correlation between performance in the SRT task and the first part of the PCL task suggests dissociable developmental trajectories within the procedural memory system.
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http://dx.doi.org/10.1080/09297049.2015.1058347DOI Listing
February 2017

Erratum to: New Genes for Focal Epilepsies with Speech and Language Disorders.

Curr Neurol Neurosci Rep 2015 Aug;15(8):55

Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital, Parkville, Australia,

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http://dx.doi.org/10.1007/s11910-015-0578-5DOI Listing
August 2015

New genes for focal epilepsies with speech and language disorders.

Curr Neurol Neurosci Rep 2015 Jun;15(6):35

Department of Paediatrics, The University of Melbourne, The Royal Children's Hospital, Parkville, Australia,

The last 2 years have seen exciting advances in the genetics of Landau-Kleffner syndrome and related disorders, encompassed within the epilepsy-aphasia spectrum (EAS). The striking finding of mutations in the N-methyl-D-aspartate (NMDA) receptor subunit gene GRIN2A as the first monogenic cause in up to 20% of patients with EAS suggests that excitatory glutamate receptors play a key role in these disorders. Patients with GRIN2A mutations have a recognizable speech and language phenotype that may assist with diagnosis. Other molecules involved in RNA binding and cell adhesion have been implicated in EAS; copy number variations are also found. The emerging picture highlights the overlap between the genetic determinants of EAS with speech and language disorders, intellectual disability, autism spectrum disorders and more complex developmental phenotypes.
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http://dx.doi.org/10.1007/s11910-015-0554-0DOI Listing
June 2015

Verbal emotional memory in a case with left amygdala damage.

Neurocase 2016 28;22(1):45-54. Epub 2015 Apr 28.

a Pediatric Neurology and Neurorehabilitation Unit , University Hospital , Lausanne , Switzerland.

The amygdala nuclei appear to be critically implicated in emotional memory. However, in most studies, encoding and consolidation processes cannot be analyzed separately. We thus studied the verbal emotional memory in a young woman with a ganglioglioma of the left amygdala and analyzed its impact (1) on each step of the memory process (encoding, retrieval, and recognition) (2) on short- and long-term consolidation (1-hour and 1-week delay) and (3) on processing of valence (positive and negative items compared to neutral words). Results showed emotional encoding impairments and, after encoding was controlled for, emotional long-term consolidation. Finally, although the negative words were not acknowledged as emotionally arousing by the patient, these words were specifically poorly encoded, recalled, and consolidated. Our data suggest that separate cerebral networks support the processing of emotional versus neutral stimuli.
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http://dx.doi.org/10.1080/13554794.2015.1037843DOI Listing
September 2016

When should clinicians search for GLUT1 deficiency syndrome in childhood generalized epilepsies?

Eur J Paediatr Neurol 2015 Mar 11;19(2):170-5. Epub 2014 Dec 11.

Pediatric Neurology and Neurorehabilitation Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Unlabelled: GLUT1 deficiency (GLUT1D) has recently been identified as an important cause of generalized epilepsies in childhood. As it is a treatable condition, it is crucial to determine which patients should be investigated.

Methods: We analyzed SLC2A1 for mutations in a group of 93 unrelated children with generalized epilepsies. Fasting lumbar puncture was performed following the identification of a mutation. We compared our results with a systematic review of 7 publications of series of patients with generalized epilepsies screened for SLC2A1 mutations.

Results: We found 2/93 (2.1%) patients with a SLC2A1 mutation. One, carrying a novel de novo deletion had epilepsy with myoclonic-atonic seizures (MAE), mild slowing of head growth, choreiform movements and developmental delay. The other, with a paternally inherited missense mutation, had childhood absence epilepsy with atypical EEG features and paroxysmal exercise-induced dyskinesia (PED) initially misdiagnosed as myoclonic seizures. Out of a total of 1110 screened patients with generalized epilepsies from 7 studies, 2.4% (29/1110) had GLUT1D. This rate was higher (5.6%) among 303 patients with early onset absence epilepsy (EOAE) from 4 studies. About 50% of GLUT1D patients had abnormal movements and 41% a family history of seizures, abnormal movements or both.

Conclusion: GLUT1D is most likely to be found in MAE and in EOAE. The probability of finding GLUT1D in the classical idiopathic generalized epilepsies is very low. Pointers to GLUT1D include an increase in seizures before meals, cognitive impairment, or PED which can easily be overlooked.
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http://dx.doi.org/10.1016/j.ejpn.2014.11.009DOI Listing
March 2015

Lamotrigine can be beneficial in patients with Dravet syndrome.

Dev Med Child Neurol 2015 Feb 22;57(2):200-2. Epub 2014 Sep 22.

Austin Health, Melbourne, Vic., Australia.

Dravet syndrome, a severe infantile epilepsy syndrome, is typically resistant to anti-epileptic drugs (AED). Lamotrigine (LTG), an AED that is effective for both focal and generalized seizures, has been reported to aggravate seizures in Dravet syndrome. Therefore, LTG is usually avoided in Dravet syndrome. We describe two adults and a child with Dravet syndrome in whom LTG resulted in decreased seizure duration and frequency. This benefit was highlighted in each patient when LTG was withdrawn after 6 to 15 years, and resulted in an increased frequency of convulsive seizures together with longer seizure duration. A 25-year-old male required hospital admission for frequent seizures for the first time in 7 years, 6 weeks after ceasing LTG. Reintroduction of LTG improved seizure control, suggesting that in some patients with Dravet syndrome, LTG may be beneficial.
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http://dx.doi.org/10.1111/dmcn.12593DOI Listing
February 2015

Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

J Neurol Sci 2014 Jul 27;342(1-2):69-78. Epub 2014 Apr 27.

Neuropediatric Unit, Department of Pediatrics, Lausanne University Hospital, Lausanne, Switzerland.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel Ca(V)2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3 bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant Ca(V)2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.
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http://dx.doi.org/10.1016/j.jns.2014.04.027DOI Listing
July 2014

[Genetics of childhood epilepsies: for who? how? why?].

Rev Med Suisse 2014 Jan;10(412-413):110-1

Unité de Neuropédiatrie et Neuroréhabelitation Pédiatrique, CHUV, Lausanne.

Recent advances in genetics led to significant improvement in the field of childhood epilepsies diagnosis and physiopathology. Genetic testing is indicated by geneticist who is himself guided by the pediatric neurological approach. In rare circumstance, genetic etiology affects the clinical management. Cost remains the main limitation. Those new genetic tools are the first step toward a better understanding of seizure mechanism and therefore more efficient treatments.
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January 2014

Successful surgical resection in non-lesional operculo-insular epilepsy without intracranial monitoring.

Epileptic Disord 2013 Jun;15(2):148-57

Department of Neurology, Chisinau, Moldova.

Pre-operative assessment and surgical management of patients with non-lesional extratemporal epilepsy remain challenging due to a lack of precise localisation of the epileptic zone. In most cases, invasive recording with depth or subdural electrodes is required. Here, we describe the case of 6.5-year-old girl who underwent comprehensive non-invasive phase I video-EEG investigation for drug-resistant epilepsy, including electric source and nuclear imaging. Left operculo-insular epilepsy was diagnosed. Post-operatively, she developed aphasia which resolved within one year, corroborating the notion of enhanced language plasticity in children. The patient remained seizure-free for more than three years.
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http://dx.doi.org/10.1684/epd.2013.0581DOI Listing
June 2013

Functional independence within the self-memory system: new insights from two cases of developmental amnesia.

Cortex 2013 Jun 20;49(6):1463-81. Epub 2012 Nov 20.

University of Paris Descartes, Memory and Cognition Lab., Paris, France.

Neuropsychological and neuroimaging data suggest that the self-memory system can be fractionated into three functionally independent systems processing personal information at several levels of abstraction, including episodic memories of one's life (episodic autobiographical memory, EAM), semantic knowledge of facts about one's life (semantic autobiographical memory, SAM), and semantic knowledge of one's personality [conceptual self, (CS)]. Through the study of two developmental amnesic patients suffering of neonatal brain injuries, we explored how the different facets of the self-memory system develop when growing up with bilateral hippocampal atrophy. Neuropsychological evaluations showed that both of them suffered from dramatic episodic learning disability with no sense of recollection (Remember/Know procedure), whereas their semantic abilities differed, being completely preserved (Valentine) or not (Jocelyn). Magnetic resonance imaging, including quantitative volumetric measurements of the hippocampus and adjacent (entorhinal, perirhinal, and temporopolar) cortex, showed severe bilateral atrophy of the hippocampus in both patients, with additional atrophy of adjacent cortex in Jocelyn. Exploration of EAM and SAM according to lifetime periods covering the entire lifespan (TEMPAu task, Piolino et al., 2009) showed that both patients had marked impairments in EAM, as they lacked specificity, details and sense of recollection, whereas SAM was completely normal in Valentine, but impaired in Jocelyn. Finally, measures of patients' CS (Tennessee Self-Concept Scale, Fitts and Warren, 1996), checked by their mothers, were generally within normal range, but both patients showed a more positive self-concept than healthy controls. These two new cases support a modular account of the medial-temporal lobe with episodic memory and recollection depending on the hippocampus, and semantic memory and familiarity on adjacent cortices. Furthermore, they highlight developmental episodic and semantic functional independence within the self-memory system suggesting that SAM and CS may be acquired without episodic memories.
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http://dx.doi.org/10.1016/j.cortex.2012.10.003DOI Listing
June 2013

Long-term outcome after cognitive and behavioral regression in nonlesional epilepsy with continuous spike-waves during slow-wave sleep.

Epilepsia 2012 Jun 23;53(6):1067-76. Epub 2012 Apr 23.

Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.

Purpose: To present the long-term follow-up of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to nonlesional focal, mainly frontal, epilepsy with continuous spike-waves during slow wave sleep (CSWS).

Methods: Past medical and electroencephalography (EEG) data were reviewed and neuropsychological tests exploring main cognitive functions were administered.

Key Findings: After a mean duration of follow-up of 15.6 years (range, 8-23 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the active phase (AP) disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. Long-term outcome correlated best with duration of CSWS.

Significance: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence, as reported in adults with early destructive lesions of the frontal lobes. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.
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http://dx.doi.org/10.1111/j.1528-1167.2012.03465.xDOI Listing
June 2012
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