Philippe Paquier

Regional cerebral glucose metabolism in epilepsies with continuous spikes and waves during sleep.

Background: Epileptic syndromes with continuous spikes and waves during sleep (CSWS) represent a wide spectrum of epileptic conditions associated with cognitive dysfunctions that have the EEG pattern of CSWS as a common feature. Reported are the results of voxel-based analyses of brain glucose metabolism performed in a group of 18 children with CSWS. Methods: Voxel-based analyses of cerebral glucose metabolism were performed using statistical parametric mapping (SPM). First, each patient was compared with a control group and the influence of age, epileptic activity, and corticosteroid treatment on metabolic abnormalities was studied. Also, disease-related changes in the contribution of a brain area to the level of metabolic activity in another brain area were investigated using pathophysiologic interactions in groups of patients compared with the control group. Results: Individual SPM analyses identified three metabolic patterns: association of hypermetabolic and hypometabolic areas, hypometabolic areas only, and normal pattern. Age and intensity of awake interictal spiking did not significantly differ in patients showing focal hypermetabolism compared with the other ones. Treatment with corticosteroids was associated with absence of focal hypermetabolism. In the group of patients with hypermetabolic areas, analyses of pathophysiologic interactions showed disease-related altered functional connectivity between the parietal and frontal cortices. Conclusions: Cerebral metabolic patterns are heterogeneous among patients with CSWS. This metabolic heterogeneity could be related to the use of corticosteroid treatment before PET. The parietofrontal altered connectivity observed in patients with hypermetabolism is interpreted as a phenomenon of remote inhibition of the frontal lobes induced by highly epileptogenic and hypermetabolic posterior cortex.

Cognition in global aphasia: Indicators for therapy

Abstract In clinical practice we are frequently confronted with global aphasics who show communicative urge, whose mobility is such that they meet other people to communicate with, and who are motivated for language therapy. The regular methods for the assessment of language deficits are unsuited for these patients: the tasks are too complex; the instructions are too difficult and their performances show an invariable zero profile. Additionally, these methods do not throw any light on the associated neuropsychological deficits of memory, attention, visual and auditory non-verbal recognition, which are known to influence success with language-oriented treatment. We present the Global Aphasic Neuropsychological Battery (GANBA), which enables the clinician to assess attention and concentration, memory, intelligence, visual and auditory recognition and language comprehension for severely impaired aphasic patients. The results of 17 global aphasics are presented. The gravity of the associated cognitive disturb...

The pace of prosodic phrasing couples the listener's cortex to the reader's voice.

We studied online coupling between a readers voice and a listeners cortical activity using a novel, ecologically valid continuous listening paradigm. Whole‐scalp magnetoencephalographic (MEG) signals were recorded from 10 right‐handed, native French‐speaking listeners in four conditions: a female (Exp1f) and a male (Exp1m) reading the same text in French; a male reading a text in Finnish (Exp 2), a language incomprehensible for the subjects, and a male humming Exp1 text (Exp 3). The fundamental frequency (f0) of the readers voice was recorded with an accelerometer attached to the throat, and coherence was computed between f0 time‐course and listeners MEG. Similar levels of right‐hemisphere‐predominant coherence were found at ˜0.5 Hz in Exps 1–3. Dynamic imaging of coherent sources revealed that the most coherent brain regions were located in the right posterior superior temporal sulcus (pSTS) and posterior superior temporal gyrus (pSTG) in Exps 1–2 and in the right supratemporal auditory cortex in Exp 3. Comparison between speech rhythm and phrasing suggested a connection of the observed coherence to pauses at the sentence level both in the spoken and hummed text. These results demonstrate significant coupling at ∼0.5 Hz between readers voice and listeners cortical signals during listening to natural continuous voice. The observed coupling suggests that voice envelope fluctuations, due to prosodic rhythmicity at the phrasal and sentence levels, are reflected in the listeners cortex as rhythmicity of about 2‐s cycles. The predominance of the coherence in the right pSTS and pSTG suggests hemispherical asymmetry in processing of speech sounds at subsentence time scales. Hum Brain Mapp, 2013.

Acquired cognitive dysfunction with focal sleep spiking activity.

The syndrome of continuous spike‐waves during slow sleep (CSWS) is considered an epileptic encephalopathy in which the epileptiform abnormalities may contribute to progressive cognitive dysfunction. The characteristic electroencephalographic feature of the syndrome occurs during non‐REM sleep, and takes the form of continuous bilateral and diffuse slow spike‐waves that persist through all slow sleep stages. Using a case study design including clinical, neuropsychological, electroencephalographic, and positron emission tomography with 18F‐fluorodeoxyglucose (PET‐FDG) investigations, we describe the clinical and electroencephalographic findings in two patients who presented with nonsymptomatic epilepsy with unilateral spike‐waves during sleep. Both patients presented with a left unilateral motor neglect of the upper limb that was associated with unilateral CSWS activity over the right hemisphere, predominantly in the centrotemporal region. PET‐FDG studies during the active phase of CSWS showed right centrotemporal hypermetabolism in both cases. After treatment, a regression of the CSWS activity and an improvement of the cerebral FDG pattern were paralleled by a remission of the motor neglect. These cases demonstrate that the electroencephalographic pattern of CSWS in nonsymptomatic epilepsies is not necessarily diffuse and bilateral, and that focal unilateral CSWS activity can be associated with focal neuropsychological deficits. These findings add further evidence that the spectrum of clinical conditions associated with the electroencephalographic pattern of CSWS can include different forms of acquired cognitive disturbances that may be focal in nature.

Landau‐Kleffner syndrome: 50 years after

In 1957, William L. Landau and Frank R. Kleffner described an intriguing childhood disorder combining an epileptic disturbance and an acquired language regression, which they termed ‘‘Syndrome of acquired aphasia with convulsive disorder in children’’ (Landau & Kleffner, 1957). Although the authors did not specifically study aspects of electroencephalography (EEG) during sleep, they suspected that persistent convulsive discharges resulted in the functional ablation of brain areas concerned with linguistic communication. Their publication subsequently led to the introduction of the eponym LandauKleffner syndrome (LKS), and was classified as a landmark article reprinted in the 50th anniversary issue of Neurology in 1998. In 1971, Patry and collaborators from the group of Carlo Alberto Tassinari introduced the notion of encephalopathy related to electrical status epilepticus during slow sleep (ESES), a condition defined by diffuse and continuous spike–waves occupying at least 85% of slow-wave sleep time (Patry et al., 1971). The authors did not make reference to LKS in their first paper. Hence, in 1989 the International League Against Epilepsy (ILAE) recognized LKS and epilepsy with continuous spikewaves during slow-wave sleep (CSWS) as distinct epileptic syndromes of childhood (undetermined whether focal or generalized) (Commission, 1989). However, it became evident from subsequent observations discussed, in particular, at the Venice Colloquium on CSWS in 1993 (Beaumanoir et al., 1995), that LKS and epilepsy with CSWS share sufficient characteristics to be classified within the same group of epileptic syndromes. In 2001, the ILAE Task Force on Classification and Terminology proposed to classify LKS and epilepsy with CSWS among the epileptic encephalopathies in which the epileptiform abnormalities may contribute to progressive dysfunction (Engel, 2001). Since the third edition of the textbook on epileptic syndromes of infancy and childhood, ESES and CSWS have been considered as synonymous, and LKS as a particular presentation of epilepsy with CSWS where acquired aphasia is the core symptom (Tassinari et al., 2002). Finally, in 2006, the ILAE Task Force stated that there is insufficient evidence for mechanistic differences between LKS and CSWS to warrant considering them separate syndromes (Engel, 2006). Therefore, LKS and epilepsy with CSWS encompass epileptic conditions having in common cognitive or behavioral impairment acquired during childhood and strong activation of interictal epileptiform activity during sleep. This spectrum of disorders has been enlarged to include atypical forms of rolandic epilepsy (i.e., idiopathic partial epilepsies of childhood) and epilepsies associated with cerebral lesions (e.g., neuronal migration disorders or perinatal cerebral infarct). In 2007, the international neurologic community celebrated the 50th anniversary of the seminal study by Landau and Kleffner. An international symposium was held in Alden-Biesen, Belgium, from 2–4 November 2007. Symposium participants presented state-of-the-art findings on acquired epileptic aphasia and related disorders, focusing on the developments during the last 10–15 years in the fields of neurophysiology, neuropsychology, functional neuroimaging, pathophysiology, and treatment. The Organizing Committee (Willem F. Arts, MD, PhD; Edgard De Wijngaert, MSc; Pierre Maquet, MD, PhD; Philippe F. Paquier, PhD; and Patrick Van Bogaert, MD, PhD) positioned the electroencephalographic phenomenon of CSWS centrally in the program, with several CSWS-related clinical pictures revolving around it. The symposium was officially held under the auspices of the ILAE. Drs. Landau, Kleffner, and Tassinari actively participated in the debates. Significant advances were made in the delineation of the epileptic syndromes with CSWS with respect to other epileptic syndromes and developmental disorders of childhood, in the elucidation of pathophysiologic mechanisms leading to cognitive deterioration, and in therapeutic approaches. The Symposium also cast light on the many issues that need to be addressed in future research. For example, the etiology of LKS is still unknown, the occurrence of impaired sleep–related plasticity as a consequence of Address correspondence to Dr. Patrick Van Bogaert, Department of Pediatric Neurology, ULB-H pital Erasme, 808 Route de Lennik, 1070 Brussels, Belgium. E-mail: pvanboga@ulb.ac.be

Perceptual accent rating and attribution in psychogenic fas: Some further evidence challenging whitaker’s operational definition

A 40-year-old, non-aphasic, right-handed, and polyglot (L1: French, L2: Dutch, and L3: English) woman with a 12-year history of addiction to opiates and psychoactive substances, and clear psychiatric problems, presented with a foreign accent of sudden onset in L1. Speech evolved toward a mostly fluent output, despite a stutter-like behavior and a marked grammatical output disorder. The psychogenic etiology of the accent foreignness was construed based on the patient’s complex medical history and psychodiagnostic, neuropsychological, and neurolinguistic assessments. The presence of a foreign accent was affirmed by a perceptual accent rating and attribution experiment. It is argued that this patient provides additional evidence demonstrating the outdatedness of Whitaker’s (1982) definition of foreign accent syndrome, as only one of the four operational criteria was unequivocally applicable to our patient: her accent foreignness was not only recognized by her relatives and the medical staff but also by a group of native French-speaking laymen. However, our patient defied the three remaining criteria, as central nervous system damage could not conclusively be demonstrated, psychodiagnostic assessment raised the hypothesis of a conversion disorder, and the patient was a polyglot whose newly gained accent was associated with a range of foreign languages, which exceeded the ones she spoke.

Acquired auditory agnosia in childhood and normal sleep electroencephalography subsequently diagnosed as Landau-Kleffner syndrome: A report of three cases

Aimu2002 We report three cases of Landau–Kleffner syndrome (LKS) in children (two females, one male) in whom diagnosis was delayed because the sleep electroencephalography (EEG) was initially normal.

Regional changes in cerebral glucose metabolism induced by status epilepticus in patients with partial epilepsy

In 1990, the World Health Organization (WHO) estimated that about 50 million people worldwide are afflicted with epilepsy. A disproportionately high number live in developing countries. Prevalence in industrialized countries lies between 5 and 8 per 1,000 population. I n the developing countries where prevalence has been studied it may be up to 6 times higher. Most epilepsy sufferers in industrialized countries receive medical treatment, and are able to live a normal life. The treatment gap (percentage ofpeople who should, but do not, receive treatment) in developing countries is dismal and may reach 80-90%. Most people with epilepsy in developing countries do not lead a normal life. On the basis of her research and work with epilepsy in Africa for over 30 years, the author determined possible reasons for the high prevalence of epilepsy and the poor attendance at available medical facilities in developing countries. From the beginning of history, epilepsy has impressed people as mysterious and frightening. Traditional treatment and attitude towards the afflicted is closely linked to the socio-cultural make up of the population and often leads to additional suffering. All the aforementioned factors have to be taken into consideration if preventive measures and medical treatment are to be successful in developing countries.

Acquired epileptic opercular syndrome related to a heterozygous deleterious substitution in GRIN2A.

Epileptic encephalopathies with continuous spike-and-waves during sleep (CSWS) are characterized by cognitive or language impairment, and are occasionally associated with pathogenic variants of the GRIN2A gene. In these disorders, speech dysfunction could be either related to cerebral dysfunction caused by the GRIN2A deleterious variant or intense interictal epileptic activity. Here, we present a patient with apraxia of speech, clearly linked to severity of epilepsy, carrying a GRIN2A variant. A 6-year-old boy developed acute regression of expressive language following epileptic seizures, leading to complete mutism, at which time EEG revealed CSWS. MEG showed bilateral superior parietal and opercular independent CSWS onsets and PET with fluorodeoxyglucose demonstrated significant increase in relative glucose metabolism in bilateral superior parietal regions. Corticosteroids induced a regression of CSWS together with impressive improvement in speech abilities. This case supports the hypothesis of a triggering role for epileptic discharges in speech deterioration observed in children carrying a deleterious variant of GRIN2A. When classic antiepileptic drugs fail to control epileptic activity, corticosteroids should be considered. Multimodal functional neuroimaging suggests a role for opercular and superior parietal areas in acquired epileptic opercular syndrome. [Published with video sequences on www.epilepticdisorders.com].

Short-term perspectives of parents and teachers on school reintegration of childhood brain tumour survivors

ABSTRACT Objective: To discover short-term changes in perspectives of parents and teachers of childhood brain tumour survivors on school reintegration, in order to reveal similarities and differences between them over time. Methods: Semi-structured interviews were conducted with parents and teachers of five children at the start and the end of a 1-year period following the child’s school re-entry. Results: Thematic analysis of data resulted in three main themes: ‘the child’s performance and wellbeing’, ‘the school’s attitude and approach’ and ‘communication and working together’. Parental concerns about child-specific changes and the school’s approach to the child could either decrease or increase over time. Teachers remained focused on assessing their pupil’s learning potential and finding ways of appropriate support. Their different perspectives on communication and working together became more pronounced. Conclusions: This study emphasizes the importance of clear communication and collaboration, coordinated follow-up and availability of healthcare professionals during the child’s school reintegration.