Care of pharmaco-resistant absence seizures in childhood.

In childhood absence epilepsy, pharmaco-resistance occurs in 20-30% of patients. In that situation, glucose transporter type 1 deficiency has to be ruled out, especially if absences started before the age of four years and if neurological signs are present. If ethosuximide, valproate and lamotrigine have failed in monotherapy or in association, there are currently no valuable therapeutic options. The same rules apply for epilepsy with myoclonic absences. Importantly, arguments supporting that making the patient seizure-free will improve eventual associated cognitive deficits such as attention deficit are very weak. Therefore, limiting the cognitive side effects of the anti-epileptic drugs has always to be a priority when faced with typical refractory absences in childhood. In epilepsy with eyelid myoclonia, the majority of patients are pharmaco-resistant. However, absence seizures, if present, tend to be very brief, and seizures are limited in many patients to eyelid myoclonia that eventually do not affect their quality of life and are well attenuated by wearing blue lenses. Atypical absences occurring in the course a developmental and/or epileptic encephalopathy are often pharmaco-resistant. In that situation, characterizing the type of epilepsy syndrome and searching for a specific genetic or structural etiology are needed to offer the best therapeutic options to the patient.

Long-term outcome of developmental and epileptic encephalopathies.

Developmental and epileptic encephalopathies are conditions where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Usually they have multiple etiologies. Therefore, long-term outcome is related to both etiology-related factors and epilepsy-related factors-age at onset of epilepsy, type(s) of seizure(s), type of electroencephalographic abnormalities, duration of the epileptic disorder. This paper focuses on long-term outcome of six developmental and epileptic encephalopathies with onset from the neonatal period to childhood: early epileptic encephalopathy with suppression bursts, West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, epilepsy with myoclonic atonic seizures and epileptic encephalopathy with continuous spike and waves during slow-wave sleep including Landau-Kleffner syndrome. For each syndrome, definition, main etiologies if multiple, and long-term outcome are discussed.

Systematic review of international clinical guidelines for the promotion of physical activity for the primary prevention of cardiovascular diseases.

BACKGROUND: Cardiovascular diseases are the world's leading cause of morbidity and mortality. An active lifestyle is one of the cornerstones in the primary prevention of cardiovascular disease. An initial step in guiding primary prevention programs is to refer to clinical guidelines. We aimed to systematically review clinical practice guidelines on primary prevention of cardiovascular disease and their recommendations regarding physical activity. METHODS: We systematically searched Trip Medical Database, PubMed and Guidelines International Network from January 2012 up to December 2020 using the following search strings: 'cardiovascular disease', 'prevention', combined with specific cardiovascular disease risk factors. The identified records were screened for relevance and content. We methodologically assessed the selected guidelines using the AGREE II tool. Recommendations were summarized using a consensus-developed extraction form. RESULTS: After screening, 27 clinical practice guidelines were included, all of which were developed in Western countries and showed consistent rigor of development. Guidelines were consistent about the benefit of regular, moderate-intensity, aerobic physical activity. However, recommendations on strategies to achieve and sustain behavior change varied. Multicomponent interventions, comprising education, counseling and self-management support, are recommended to be delivered by various providers in primary health care or community settings. Guidelines advise to embed patient-centered care and behavioral change techniques in prevention programs. CONCLUSIONS: Current clinical practice guidelines recommend similar PA lifestyle advice and propose various delivery models to be considered in the design of such interventions. Guidelines identify a gap in evidence on the implementation of these recommendations into practice.

[Systematic follow-up of infants born preterm]. / Le suivi systématique des grands prématurés.

Advances in pediatric medicine have enabled a decrease in perinatal mortality, especially among infants born preterm (< 32 weeks gestational age) or low birth weight (< 1.500 g). However, this population is exposed to a greater risk of neurological sequelae. This is why the creation of specific follow-up program are mandatory to screen at-risk children to offer them a support able to minimize the impact of prematurity on their future neurological development.

Work stress and burnout among emergency physicians: a systematic review of last 10 years of research.

AIM OF THE STUDY: First, to provide a synthesis and analysis of available scientific literature regarding the level of work stress and burnout among emergency physicians. Second, to identify the effect of the specific work situation-related factors. METHODS: A systematic search was performed in NCBI PubMed and Embase. Comparative primary studies, both systematic review and cross-sectional, quantifying burnout in emergency physicians were included. Only studies published between 2011 and 2022 were retained. Synonym sets were compiled for the search key for 'burnout & stress', 'emergency', 'physician' and 'burnout & posttraumatic stress disorder'. RESULTS: Thirty-five papers were retained for further research. Emergency physicians scored significantly higher for all dimensions of burnout compared to other healthcare professions. Significant correlations for burnout were found with work characteristic and organizational factors. Critical incidents and aggression were identified as the most important acute work characteristics and organizational factors impacting emergency physician's mental wellbeing including the development of posttraumatic stress disorder. Moreover, personal factors such as age, personality, and coping strategies also play an important role in the development of burnout as well as work-related trauma. CONCLUSION: Available studies show that emergency physicians report higher scores of emotional exhaustion and depersonalization when compared to other healthcare professionals. Work characteristics contribute to this, but work-related traumatic incidents and aggression are important determinants. Personal characteristics such as age, personality type D, previous experiences and coping strategies seem to be determining factors likewise. Emergency physicians showed a high risk for developing burnout and work stress-related problems.

A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome.

Although deficiency of complex I of the mitochondrial respiratory chain is a frequent cause of encephalopathy in children, only a few mutations have been reported in each of its subunits. In the absence of families large enough for conclusive segregation analysis and of robust functional testing, it is difficult to unequivocally show the causality of the observed mutations and to delineate genotype-phenotype correlations, making additional observations necessary. We observed two consanguineous siblings with an early-onset encephalopathy, medulla, brainstem and mesencephalon lesions on brain magnetic resonance imaging and death before 8 months of age, caused by a complex I deficiency. We used a homozygosity mapping approach and identified a missense mutation in the NDUFV1 gene. The mutation, p.Arg386His, affects a highly conserved residue, contiguous to a cysteine residue known to coordinate an Fe ion. This observation adds to our understanding of complex I deficiency disease. It validates the important role of Arg386 and therefore supports the current molecular model of iron-sulfur clusters in NDUFV1.

A legal framework on advanced practice nursing in Belgium: what do we and don't we know?

OBJECTIVES: Presenting the Belgian new framework for Advanced Practice Nursing (APN) - 'Verpleegkundig Specialist [VS]'/"Infirmier de pratique avancée [IPA]" outlined in the Law of 22 April 2019, followed by a discussion of the lack of clarity, the current challenges and future opportunities. METHODS: The framework was analyzed by an expert in healthcare legislation and discussed by academics in Nursing Science and members of the board of directors of the Belgian Society of APN. RESULTS: Relevant paragraphs within this new law are"Article 46 §1. No one is allowed to carry the title of 'VS/IPA' who does not possess a bachelor in nursing mentioned in article 45 and who does not meet the requirements specified in this article. At the minimum, a master's degree in Nursing Sciences is also required. §2. Additional to the scope of practice of nursing as mentioned in article 46, the 'VS/IPA' perform, in the context of complex nursing care, medical interventions in order to maintain, improve or restore the health of the patient. Care is provided in the context of a specific target group of patients and in close concertation with the physician and potential other healthcare professionals. CONCLUSION: Although the legal recognition of the title of VS/IPA is a major breakthrough that will innovate healthcare, clarification is needed: How do VS/IPA distinguish themselves from other nursing functions, what is complex nursing care, which medical interventions can be performed, what is meant by specific target group of patients, what does 'in close concertation with the physician' entail, and will advisory power be possible?

Epileptic syndromes: differential treatment in infants, children, and adolescents.

This paper proposes therapeutic guidelines for the management of some epileptic syndromes in infants, children, and adolescents, based on available medical literature and clinical practice in the French Community of Belgium. The guidelines address both epileptic encephalopathies (West syndrome, Lennox-Gastaut syndrome, and Dravet syndrome) and idiopathic epilepsies (typical absence seizures, epilepsy with centro-temporal spikes and juvenile myoclonic epilepsy).

[Attention deficit disorder in childhood]. / Le déficit attentionnel chez l'enfant.

Attention deficit disorder, eventually associated with hyperactivity (ADD +/- H), is nowadays viewed as a syndrome often of unknown etiology but probably not unique, with important genetic influence and associated environmental factors. The cognitive model proposing ADHD as a result of impaired inhibitory control which makes the child less flexible to changing circumstances suffers from poor sensibility and specificity. As studies aimed to make genotype-phenotype correlations were disappointing, recent genetic researches tend to correlate the genotype to an endophenotype defined from neuro-imaging data with encouraging preliminary results. Treatment with methylphenidate has long been considered as a first choice for disabling forms of ADHD, but recent data do not show evidence for superiority of methylphenidate compared to non pharmacological approach at long-term. Evaluation and treatment of each suspected case of ADHD need to be tailored with special concern for associated conditions as psycho-affective troubles or learning difficulties.

Opsoclonus in a child with neuroborreliosis: Case report and review of the literature.

Opsoclonus consists of massive erratic rapid eye jerks. They may occur in isolation or in association with myoclonus and ataxia, i.e., opsoclonus-myoclonus syndrome (OMS). We report the case of a 9-year-old girl who suffered from headaches for several days and was shown to have opsoclonus and left peripheral facial palsy. Work-up excluded the diagnosis of neuroblastoma, but CSF analysis showed aseptic meningitis, and serology for Borrelia burgdorferi (Lyme) was positive. The outcome was favorable with complete regression of symptoms after treatment with ceftriaxone 2g/day for 3 weeks. Although rare, the diagnosis of Lyme neuroborreliosis must be raised in the presence of isolated opsoclonus, particularly if the clinical picture is incomplete and if other features, such as peripheral facial palsy and pleocytosis in the CSF, are present.

[Intraoperative MRI and epilepsy surgery]. / IRM opératoire et chirurgie de l'épilepsie.

Intraoperative imaging, in particular intraoperative MRI, is a developing area in neurosurgery and its role is currently being evaluated. Its role in epilepsy surgery has not been defined yet and its use has been limited. In our experience with a compact and mobile low-field intraoperative MRI system, a few epilepsy surgeries have been performed using this technique. As the integration of imaging and functional data plays an important role in the planning of epilepsy surgery, intraoperative verification of the surgical result may be highly valuable. Therefore, teams that have access to intraoperative MRI should be encouraged to use this technique prospectively to evaluate its current relevance in epilepsy surgery.

Cardiofaciocutaneous (CFC) syndrome associated with muscular coenzyme Q10 deficiency.

The cardiofaciocutaneous (CFC) syndrome is characterized by congenital heart defect, developmental delay, peculiar facial appearance with bitemporal constriction, prominent forehead, downslanting palpebral fissures, curly sparse hair and abnormalities of the skin. CFC syndrome phenotypically overlaps with Noonan and Costello syndromes. Mutations of several genes (PTPN11, HRAS, KRAS, BRAF, MEK1 and MEK2), involved in the mitogen-activated protein kinase (MAPK) pathway, have been identified in CFC-Costello-Noonan patients. Coenzyme Q10 (CoQ10), a lipophilic molecule present in all cell membranes, functions as an electron carrier in the mitochondrial respiratory chain, where it transports electrons from complexes I and II to complex III. CoQ10 deficiency is a rare treatable mitochondrial disorder with various neurological (cerebellar ataxia, myopathy, epilepsy, mental retardation) and extraneurological (cardiomyopathy, nephropathy) signs that are responsive to CoQ10 supplementation. We report the case of a 4-year-old girl who presented a CFC syndrome, confirmed by the presence of a pathogenic R257Q BRAF gene mutation, together with a muscular CoQ10 deficiency. Her psychomotor development was severely impaired, hindered by muscular hypotonia and ataxia, both improving remarkably after CoQ10 treatment. This case suggests that there is a functional connection between the MAPK pathway and the mitochondria. This could be through the phosphorylation of a nuclear receptor essential for CoQ10 biosynthesis. Another hypothesis is that K-Ras, one of the proteins composing the MAPK pathway, might be recruited into the mitochondria to promote apoptosis. This case highlights that CoQ10 might contribute to the pathogenesis of CFC syndrome.

The epileptic syndromes with continuous spikes and waves during slow sleep: definition and management guidelines.

The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong activation of the interictal epileptiform discharges during NREM sleep--whatever focal or generalized--and not related to another factor than the presence of CSWS. The type of syndrome will be defined according to the neurological and neuropsychological deficit. These syndromes have to be classified among the localization-related epileptic syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for work-up and treatment are proposed.

SolCos model-based individual reminiscence for older adults with mild to moderate dementia in nursing homes: a randomized controlled intervention study.

WHAT IS KNOWN ON THE SUBJECT?: To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes resulting in effects on behaviour and well-being as an alternative for medication. Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We have provided individual standardized reminiscence therapy to residents with dementia. The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers. In comparison with a control group who received usual care, residents who received the reminiscence therapy showed significant less depressive symptoms. Moreover, residents were, in general, attentive, open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes. ABSTRACT: Aim To investigate the effect of a standardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms (primary outcome), cognition and behaviour (secondary outcomes) for older people with mild to moderate dementia, performed by trained nursing home volunteers as facilitators. Background Because of limited pharmacological treatment options for older adults with dementia relevant physical, sensory, psychological or social interventions offer alternative opportunities. Method Randomized controlled trial (ISRCTN74355073) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively. Eighteen nursing home volunteers were trained to perform the reminiscence therapy. Various assessment scales were measured pre- and post-sessions. Results Linear regression analysis showed an impact on depressive symptoms. However, no impact was identified on cognition and behaviour. Facilitators experienced the sessions as useful and pleasant, and study participants were, in general, attentive, open and collaborative. Discussion Study results showed that organizing standardized individual reminiscence therapy with nursing home volunteers was feasible and study participants' attention and participation were overall good. Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes.

Prophylaxis of the epilepsies: should anti-epileptic drugs be used for preventing seizures after acute brain injury?

In many circumstances antiepileptic drugs are used in patients who have never presented any clinical epileptic seizures. These substances are administered on the assumption of a potential risk for the patients of developing acute or delayed chronic seizures after brain injuries such as trauma, stroke, hemorrages or even neurosurgical interventions. The aim of this paper is to propose therapeutic guidelines for the management of this prophylactic attitude in epilepsy based on basic research and clinical practice in the French community in Belgium. We will distinguish between the prevention of acute (early onset-provoked) seizures and a delayed truly post-lesional (unprovoked) epilepsy. Some therapeutic goals can be achieved under the former circumstances whereas in the latter situation we all agree for the absence of any coherent antiepileptic prophylactic behaviour.

Effect of movement rate on corticokinematic coherence.

AIMS OF THE STUDY: This study investigates the effect of movement rate on the coupling between cortical magnetoencephalographic (MEG) signals and the kinematics of repetitive active finger movements, i.e., the corticokinematic coherence (CKC). MATERIAL AND METHODS: CKC was evaluated in ten right-handed healthy adults performing repetitive flexion-extension of the right-hand fingers in three different movement rate conditions: slow (∼1 Hz, duration: 11 min), medium (∼2 Hz, duration: 5 min) and fast (∼3 Hz, duration: 3 min). Neuromagnetic signals were recorded with a whole-scalp-covering MEG (Elekta Oy) and index acceleration was monitored with a 3-axis accelerometer. Coherent sources were estimated on the time-course of the cross-correlogram using equivalent current dipole (ECD) modeling. RESULTS: Significant coherence was found at movement frequency or its first harmonics in all subjects and movement conditions. ECDs clustered at the primary sensorimotor cortex contralateral to hand movements. Movement rate had no effect on the coherence levels and the location of coherent sources. CONCLUSIONS: This study demonstrates that the movement rate does not affect coherence levels and CKC source location during active finger movements. This finding has direct implications for CKC functional mapping applications and studies investigating the pathophysiology of central nervous disorders affecting proprioceptive pathways.

Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileum.

The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from the ileum of 17 pigs was studied by intracellular recording. In 77% of the neurones, electrical stimulation of a fibre tract evoked fast excitatory postsynaptic potentials (fEPSPs) with an amplitude of 6 +/- 5 mV (mean +/- S.D.) and lasting 49 +/- 29 ms. The nicotinic nature of the fEPSPs was demonstrated by superfusing hexamethonium (20 microM). High-frequency stimulation (up to 20 Hz, 3 seconds) did not result in a rundown of the fEPSPs, and did not evoke slow excitatory or inhibitory postsynaptic potentials. The effects of neurotransmitters, possibly involved in these excitatory responses, were investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 +/- 9 mV, duration 7.0 +/- 7.2 seconds) as did 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) application (10 mM; 14 +/- 10 mV, duration 4.1 +/- 2.8 seconds) in 76% of the cells. The fast nicotinic response to acetylcholine was sometimes (6/27) followed by a slow muscarinic depolarisation (8 +/- 4 mV; duration 38.7 +/- 10.8 seconds). Immunostaining revealed 5-hydroxytryptamine hydrochloride (5-HT)- and calcitonin gene-related peptide (CGRP)-positive neuronal baskets distributed around and in close vicinity to Dogiel type II neuronal cell bodies. Microejection of 5-HT (10 mM) resulted in a fast nicotinic-like depolarisation (12 +/- 6 mV, duration 3.0 +/- 1.3 seconds) in 4 of 8 neurones tested, whereas microejection of CGRP (20 mM) gave rise to a slow muscarinic-like depolarisation (6 +/- 2 mV, duration 56.0 +/- 27.5 seconds) in 8 of 12 neurones tested. In conclusion, myenteric Dogiel type II neurones in the porcine ileum receive diverse synaptic input. Mainly with regard to the prominent presence of nicotinic responses, these neurones behave contrary to their guinea pig counterparts.

High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2.

OBJECTIVE: To characterize the nature of CACNA1A mutations in episodic ataxia type 2 (EA2), to search for mutations in sporadic cases, and to delineate better the clinical spectrum. BACKGROUND: EA2 is an autosomal dominant disorder characterized by recurrent acetazolamide-responsive attacks of cerebellar ataxia. The mutated gene, CACNA1A, located on chromosome 19, encodes the alpha1A subunit of a voltage-dependent calcium channel. So far, only three CACNA1A mutations have been identified-in two EA2 families and in one sporadic case. These three mutations disrupted the reading frame and led to truncated proteins. Interestingly, distinct types of CACNA1A mutations have been identified in familial hemiplegic migraine (missense mutations) and spinocerebellar ataxia type 6 (SCA-6) progressive cerebellar ataxia (expanded CAG repeats). However, except for SCA-6, these genotype-phenotype correlations relied on the analysis of very few families. METHODS: To characterize CACNA1A mutations, eight familial and seven sporadic EA2 patients were selected. All 47 exons of CACNA1A were screened by a combination of single-strand conformer polymorphism and sequencing analysis. In addition, the length of the CAG repeat has been determined in all patients. RESULTS: Seven new mutations were detected in four multiple case families and three sporadic cases. Six of them lead most likely to truncated or aberrant proteins. CAG repeat sizes were in the normal range. CONCLUSION: These data clearly establish the specificity of EA2 mutations compared with SCA-6 and familial hemiplegic migraine. Detailed clinical analysis of the mutation carriers showed the highly variable penetrance and expression of this disorder: Several of the carriers did not show any clinical symptom; others displayed atypical or permanent neurologic symptoms (such as recurrent, transient diplopia or severe, permanent, and isolated cerebellar ataxia).

N-methyl-D-aspartate receptor activation by guanidinosuccinate but not by methylguanidine: behavioural and electrophysiological evidence.

Levels of methylguanidine (MG) and guanidinosuccinate (GSA) are known to be highly increased in uraemic patients. In the present work, the effects of these uraemic guanidino compounds on the excitatory amino acid system were investigated in vivo and in vitro. It was found that convulsions induced by intracerebroventricular GSA injection in mice were antagonized by N-methyl-D-aspartate (NMDA) receptor blockade, whereas those induced by MG were not significantly altered. Application of GSA (between 25 and 10,000 microM) to mouse spinal cord neurones in primary dissociated cell cultures, evoked depolarizing, inward whole-cell currents in a dose-dependent fashion and with reversal potential at 0 mV; MG did not produce such effects. GSA-induced whole-cell currents were caused by NMDA receptor activation since NMDA receptor antagonists (2-amino-5-phosphonovalerate, Mg2+ and ketamine) blocked GSA-evoked whole-cell currents completely and reversibly, whereas co-application of a non-NMDA receptor antagonist (6-cyano-7-nitroquinoxaline-2,3-dione) did not affect GSA-induced current. Evoked field potentials in CA1 region of rat hippocampal slices were completely abolished by GSA, and this effect was antagonized by NMDA receptor blockade. All data were consistent with selective agonist action of GSA upon the NMDA-type glutamate receptor. In view of the results presented here, it should be examined whether NMDA receptors contribute to the neurological complications of renal failure through GSA-induced inappropriate or excessive activation of NMDA receptors.