Eliane Roulet-Perez

Impact of severe epilepsy on development: recovery potential after successful early epilepsy surgery.

Purpose:  Epilepsy surgery in young children with focal lesions offers a unique opportunity to study the impact of severe seizures on cognitive development during a period of maximal brain plasticity, if immediate control can be obtained. We studied 11 children with early refractory epilepsy (median onset, 7.5 months) due to focal lesion who were rendered seizure‐free after surgery performed before the age of 6 years.

Glut-1 deficiency syndrome masquerading as idiopathic generalized epilepsy

To report the case of a child with short absences and occasional myoclonias since infancy who was first diagnosed with an idiopathic generalized epilepsy, but was documented at follow‐up to have a mild phenotype of glucose transporter type 1 deficiency syndrome. Unlike other reported cases of Glut‐1 DS and epilepsy, this child had a normal development as well as a normal head growth and neurological examination. Early onset of seizures and later recognized episodes of mild confusion before meals together with persistent atypical EEG features and unexpected learning difficulties led to the diagnosis. Seizure control and neuropsychological improvements were obtained with a ketogenic diet.

Anti-N-Methyl-d-Aspartate (NMDA) Receptor Encephalitis Mimicking a Primary Psychiatric Disorder in an Adolescent

Anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis likely has a wider clinical spectrum than previously recognized. This article reports a previously healthy 16-year-old girl who was diagnosed with anti-NMDA receptor encephalitis 3 months after onset of severe depression with psychotic features. She had no neurological manifestations, and cerebral magnetic resonance imaging (MRI) was normal. Slow background on electroencephalogram and an oligoclonal band in the cerebrospinal fluid prompted the search for anti-NMDA receptor antibodies. She markedly improved over time but remained with mild neuropsychological sequelae after a trial of late immunotherapy. Only a high index of suspicion enables recognition of the milder forms of the disease masquerading as primary psychiatric disorders.

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

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).

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

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.

Sign language in Landau‐Kleffner syndrome

This article reviews the history of sign language (SL) and the rationale for its use in children with profound auditory agnosia due to Landau‐Kleffner syndrome (LKS), illustrated by studies of children and adults followed for many years and rare cases from the literature. The reasons that SL was successful and brought some children out of isolation while it could not be implemented in others are discussed. The nowadays earlier recognition and treatment of LKS and better awareness of the crucial need to maintain communication have certainly improved the outcome of affected children. Alternatives to oral language, even for less severe cases, are increasingly accepted. SL can be learned at different ages with a clear benefit, but the ambivalence of the patients and their families with the world and culture of the deaf may sometimes explain its refusal or limited acceptance. There are no data to support the fear that SL learning may delay or prevent oral language recovery in children with LKS. On the contrary, SL may even facilitate this recovery by stimulating functionally connected core language networks and by helping speech therapy and auditory training.

Status epilepticus in fragile X syndrome

Epilepsy is frequent in fragile X syndrome (FXS), the most common cause of inherited mental retardation. Status epilepticus (SE), however, seems exceptional in FXS, particularly as an initial epileptic manifestation. To our knowledge, SE was reported in only four FXS patients. We report the clinical features and electroencephalography (EEG) findings of five children with FXS, who presented with SE as their initial seizure.

ISOLATED FACIAL AND BULBAR PARESIS: A PERSISTENT MANIFESTATION OF NEONATAL MYASTHENIA GRAVIS

The differential diagnosis of congenital facial and bulbar paresis in toddlers includes myotonic dystrophy, congenital myopathies, congenital myasthenic syndromes, Moebius syndrome, and 22q11 deletion syndrome. We report on a 6-year-old boy with a history of neonatal hypotonia and severe feeding difficulties followed by persistent isolated facial and bulbar paresis of unknown etiology. When he was 3 years old, his mother was diagnosed with myasthenia gravis (MG) and we concluded that his condition was a rare and persistent manifestation of neonatal MG. ### Case reports. The boy presented with neonatal hypotonia and poor spontaneous movements without respiratory distress or arthrogryposis. Sucking was absent; he was tube fed for 2 weeks. His tone progressively improved; he walked at 13 months but prominent facial weakness and feeding difficulties persisted. He was referred to us at 30 months with severe dysarthria. There was no complaint of fatigue or weakness. At age 5 his weight was 10 kg (<p3), his height was 86 cm (p3), and he had no ptosis or ophthalmoplegia. He had facial weakness, a constantly open mouth, and a high arched palate (figure). The soft palate was immobile and speech was extremely nasal and dysarthric. The tongue was normal. He could not whistle or blow his cheeks. Limb muscle strength and …

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

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.

Visual impairment due to a dyskinetic eye movement disorder in children with dyskinetic cerebral palsy

‘Normal MRI neuroimaging and acute dancing eyes syndrome’ SIR–Dancing eyes syndrome DES (otherwise known as opsoclonus myoclonus syndrome) is a disabling neurological condition characterized by acute or subacute onset of eye opsoclonus, myoclonus, ataxia, and irritability. Although eye signs often resolve, significant cognitive and motor sequelae are typical. DES is often associated with neuroblastoma tumours, although non-specific infectious illnesses may also herald onset. Postinfectious and paraneoplastic associations have supported the theories that DES is immune-mediated.1 This hypothesis is also supported by the use of immune modulating therapies, although a controlled trial to determine the most effective therapies has not been undertaken. The clinical characteristics of DES suggest the involvement of cerebellar and brainstem neural circuits, however, more widespread neural dysfunction is possible. Antineuronal antibody studies have demonstrated antibodies directed against components of the cerebellum in one study,2 although a further study showed inconsistent findings of anti-neuronal antibodies in acute DES.3 The exact disease localization remains unknown due to the lack of pathological studies. Neuroimaging is considered to be normal by most paediatric neurologists. However, two case reports on this disorder have described focal inflammatory lesions in the pons and cerebellar vermis, respectively. 4,5 In view of this discrepancy, we examined retrospectively the brain MRI of 10 sequential patients (7 females, 3 males; mean age 32 months [SD 19], range 12 to 60 months) presenting with acute DES at Great Ormond Street Hospital, UK between 1995 and 2000. All patients had MRI within 4 weeks of disease onset. Four patients had an associated neuroblastoma and six were postinfectious without evidence of neuroblastoma (despite extensive investigation). T1and T2-weighted images were reviewed in all 10 patients. Two neuroradiologists were blinded to the clinical details and purpose of the study. Both independently reported no abnormalities in all 10 images. We conclude that acute MR neuroimaging is usually normal in DES using conventional techniques, and that novel approaches are required to understand the pathogenesis of the disorder. Neuroimaging may still play an important role, possibly using MR spectroscopy techniques in acute DES, or regional volumetric analysis of chronic DES. Further immunological investigation is required to see whether cell mediated or humoral immunity is primarily involved in DES pathogenesis. Collaboration is likely to be important in future investigations of this rare but disabling condition.