Nathalie Kubis

Adaptive common carotid arteries remodeling after unilateral internal carotid artery occlusion in adult patients

OBJECTIVEnThis study was undertaken in human adults to examine modifications in common carotid internal diameter (ID), intima-media thickness (IMT), cross-sectional area (CSA) and wall shear stress (WSS) occurring both on the ipsilateral side of an internal carotid artery (ICA) occlusion and on the non-occluded contralateral side.nnnMETHODSnSeventeen patients with unilateral ICA occlusion had repeated echo-Doppler examinations during 1 year and were compared to 12 volunteers with control non-occluded common carotid arteries (CCA).nnnRESULTSnThe cause of ICA occlusion was atherosclerosis in nine patients, dissection in five, and undetermined in three. The results showed a significant reduction in ID on the occluded side (5.15 +/- 0.30 mm) compared with the non-occluded side (5.96 +/- 0.20 mm, P < 0.05) and with control arteries (5.55 +/- 0.10, P < 0.05). A significant reduction in blood flow was observed on the occluded side (404 +/- 58 ml/min) compared with the non-occluded side (703 +/- 51 ml/min, P < 0.0001) and with controls (567 +/- 27 ml/min, P < 0.0001). Wall cross-sectional area was found to be positively correlated to blood flow (r = 0.35, P < 0.01), without any significant difference in mean CSA between both sides. Interestingly, wall shear stress values were identical on both sides whatever the cause of ICA occlusion, and did not differ from those in controls.nnnCONCLUSIONSnOur results suggest that in humans, the internal diameter of the common carotid artery decreases in response to chronic decrease in blood flow, in order to maintain a constant wall shear stress even in pathological arteries.

Towards the therapeutic use of vascular smooth muscle progenitor cells

Recent advances in the development of alternative proangiogenic and revascularization processes, including recombinant protein delivery, gene therapy, and cell therapy, hold the promise of greater efficacy in the management of cardiovascular disease in the coming years. In particular, vascular progenitor cell-based strategies have emerged as an efficient treatment approach to promote vessel formation and repair and to improve tissue perfusion. During the past decade, considerable progress has been achieved in understanding therapeutic properties of endothelial progenitor cells, while the therapeutic potential of vascular smooth muscle progenitor cells (SMPC) has only recently been explored; the number of the circulating SMPC being correlated with cardiovascular health. Several endogenous SMPC populations with varying phenotypes have been identified and characterized in the peripheral blood, bone marrow, and vascular wall. While the phenotypic entity of vascular SMPC is not fully defined and remains an evolving area of research, SMPC are increasingly recognized to play a special role in cardiovascular biology. In this review, we describe the current approaches used to define vascular SMPC. We further summarize the data on phenotype and functional properties of SMPC from various sources in adults. Finally, we discuss the role of SMPC in cardiovascular disease, including the contribution of SMPC to intimal proliferation, angiogenesis, and atherosclerotic plaque instability as well as the benefits resulting from the therapeutic use of SMPC.

Recommandations françaises sur l’électroencéphalogramme

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patients bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre lÉpilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

Prognostic EEG patterns in patients resuscitated from cardiac arrest with particular focus on Generalized Periodic Epileptiform Discharges (GPEDs)

STUDY AIMSnWe assessed clinical and early electrophysiological characteristics, in particular Generalized Periodic Epileptiform Discharges (GPEDs) patterns, of consecutive patients during a 1-year period, hospitalized in the Intensive Care Unit (ICU) after resuscitation following cardiac arrest (CA).nnnPATIENTS AND METHODSnConsecutive patients resuscitated from cardiac arrest (CA) with first EEG recordings within 48hours were included. Clinical data were collected from hospital records, in particular therapeutic hypothermia. Electroencephalograms (EEGs) were re-analyzed retrospectively.nnnRESULTSnSixty-two patients were included. Forty-two patients (68%) were treated with therapeutic hypothermia according to international guidelines. Global mortality was 74% but not significantly different between patients who benefited from therapeutic hypothermia compared to those who did not. All the patients who did not have an initial background activity (36/62; 58%) died. By contrast, initial background activity was present in 26/62 (42%) and among these patients, 16/26 (61%) survived. Electroencephalography demonstrated GPEDs patterns in 5 patients, all treated by therapeutic hypothermia and antiepileptic drugs. One of these survived and showed persistent background activity with responsiveness to benzodiazepine intravenous injection.nnnCONCLUSIONnPatients presenting suppressed background activity, even when treated by hypothermia, have a high probability of poor outcome. Thorough analysis of EEG patterns might help to identify patients with a better chance of survival.

Recommandations françaises sur l’électroencéphalogramme [French guidelines on electroencephalogram]

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patients bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre lÉpilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

Tele-transmission of EEG recordings

EEG recordings can be sent for remote interpretation. This article aims to define the tele-EEG procedures and technical guidelines. Tele-EEG is a complete medical act that needs to be carried out with the same quality requirements as a local one in terms of indications, formulation of the medical request and medical interpretation. It adheres to the same quality requirements for its human resources and materials. It must be part of a medical organization (technical and medical network) and follow all rules and guidelines of good medical practices. The financial model of this organization must include costs related to performing the EEG recording, operating and maintenance of the tele-EEG network and medical fees of the physician interpreting the EEG recording. Implementing this organization must be detailed in a convention between all parties involved: physicians, management of the healthcare structure, and the company providing the tele-EEG service. This convention will set rules for network operation and finance, and also the continuous training of all staff members. The tele-EEG system must respect all rules for safety and confidentiality, and ensure the traceability and storing of all requests and reports. Under these conditions, tele-EEG can optimize the use of human resources and competencies in its zone of utilization and enhance the organization of care management.

Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in the Treatment of Dystonia.

Dystonias represent a heterogeneous group of movement disorders responsible for sustained muscle contraction, abnormal postures, and muscle twists. It can affect focal or segmental body parts or be generalized. Primary dystonia is the most common form of dystonia but it can also be secondary to metabolic or structural dysfunction, the consequence of a drug’s side-effect or of genetic origin. The pathophysiology is still not elucidated. Based on lesion studies, dystonia has been regarded as a pure motor dysfunction of the basal ganglia loop. However, basal ganglia lesions do not consistently produce dystonia and lesions outside basal ganglia can lead to dystonia; mild sensory abnormalities have been reported in the dystonic limb and imaging studies have shown involvement of multiple other brain regions including the cerebellum and the cerebral motor, premotor and sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive technique of brain stimulation with a magnetic field applied over the cortex allowing investigation of cortical excitability. Hyperexcitability of contralateral motor cortex has been suggested to be the trigger of focal dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or inhibitory lasting effects beyond the time of stimulation and protocols have been developed having either a positive or a negative effect on cortical excitability and associated with prevention of cell death, γ-aminobutyric acid (GABA) interneurons mediated inhibition and brain-derived neurotrophic factor modulation. rTMS studies as a therapeutic strategy of dystonia have been conducted to modulate the cerebral areas involved in the disease. Especially, when applied on the contralateral (pre)-motor cortex or supplementary motor area of brains of small cohorts of dystonic patients, rTMS has shown a beneficial transient clinical effect in association with restrained motor cortex excitability. TMS is currently a valuable tool to improve our understanding of the pathophysiology of dystonia but large controlled studies using sham stimulation are still necessary to delineate the place of rTMS in the therapeutic strategy of dystonia. In this review, we will focus successively on the use of TMS as a tool to better understand pathophysiology, and the use of rTMS as a therapeutic strategy.

Good prognosis of postpartum lower limb sensorimotor deficit: a combined clinical, electrophysiological, and radiological follow-up.

Postpartum lower limb motor and/or sensory deficit is an uncommon obstetrical complication. We aimed to identify its incidence, etiology, and precipitating factors, as well as the neurological prognosis by retrospectively analyzing the successive neurological evaluations, electrophysiological, and MRI data from all the consecutive patients with postpartum motor and/or sensory deficits of the lower limbs referred from the Lariboisière Obstetrical Department to the Lariboisière Neurophysiology Department, from January 2012 to June 2016, as well as data concerning labor and morphological characteristics of mother and baby. Thirteen patients (0.11% of the parturient women in the Lariboisière hospital) were included. Eight (62%) had lumbosacral plexopathy. Symptoms followed a first vaginal delivery in 10/13 patients (77%), in patients who were mostly overweight (mean patient BMI before pregnancy 25.6xa0±xa03.2xa0kg/m2). Labor duration was slightly longer than average (mean labor duration 8.9xa0±xa02.9xa0h). No other potentially precipitating factor was identified. Recovery was good in all patients, 7/11 (64%) made a rapid full recovery (mean recovery time 5xa0±xa02.5xa0weeks excluding one patient who had a normal neurological examination at 2xa0weeks but still complained of foot weakness that fully recovered in 1xa0year), and a minority (4/11, 36%) still complained of minor symptoms at time of follow-up, but showed marked improvement. New mothers presenting postpartum lower limb nerve injury should, therefore, be reassured.

Contribution of EEG in transient neurological deficits

Identification of stroke mimics and ‘chameleons’ among transient neurological deficits (TND) is critical. Diagnostic workup consists of a brain imaging study, for a vascular disease or a brain tumour and EEG, for epileptiform discharges. The precise role of EEG in this diagnostic workup has, however, never been clearly delineated. However, this could be crucial in cases of atypical or incomplete presentation with consequences on disease management and treatment. We analysed the EEG patterns on 95 consecutive patients referred for an EEG within 7xa0days of a TND with diagnostic uncertainty. Patients were classified at the discharge or the 3-month follow-up visit as: ‘ischemic origin’, ‘migraine aura’, ‘focal seizure’, and ‘other’. All patients had a brain imaging study. EEG characteristics were correlated to the TND symptoms, imaging study, and final diagnosis. Sixty four (67%) were of acute onset. Median symptom duration was 45xa0min. Thirty twoxa0% were ‘ischemic’, 14% ‘migraine aura’, 19% ‘focal seizure’, and 36% ‘other’ cause. EEGs were recorded with a median delay of 1.6xa0day after symptoms onset. Forty EEGs (42%) were abnormal. Focal slow waves were the most common finding (43%), also in the ischemic group (43%), whether patients had a typical presentation or not. Epileptiform discharges were found in three patients, one with focal seizure and two with migraine aura. Non-specific EEG focal slowing is commonly found in TND, and may last several days. We found no difference in EEG presentation between stroke mimics and stroke chameleons, and between other diagnoses.

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease

The pathophysiology of sporadic Alzheimer’s disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (−u200929%, Pu2009<u20090.001), collateral recruitment (−u200924%, Pu2009<u20090.001), capillary density (−u200922%; Pu2009<u20090.01) and arteriole density (−u200928%; Pu2009<u20090.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (Pu2009=u20090.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (Pu2009<u20090.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.