Jean-Michel Pignat's research while affiliated with Lausanne University Hospital and other places

At the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)-and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS.

Objective: To assess the economic impact of introducing the Swiss Diagnosis-Related Group (DRG)-financing system on the Acute Neurorehabilitation Unit (ANRU) of a University hospital in 2012 and to discuss the implications in 2020.Methods: A retrospective study using monocentric patient cohort and collecting anonymized data of consecutive patients admitted to the ANRU in 2012 and 2013. The characteristics, DRG A43Z, costs and revenues were retrieved from the hospital accounting system and allowed a comparison between the 2012 and 2013 groups of patients.Results: Forty-seven patients were included over the assessment period. In 2012, of the 23 patients admitted, 20 were coded A43Z, while in 2013, out of the 24 admissions, only eight had that specific code (p < .01). The average length of stay (LOS) increased from 45.5 days in 2012 to 49.5 days in 2013. Similarly, the average cost per patient increased by Swiss Franc (CHF) 19,994 over the two years, from CHF 183,634 in 2012 to CHF 194,629 in 2013. Finally, the average reimbursement per patient diminished by CHF 11,392, from CHF 193,153 in 2012 to CHF 181,760 in 2013.Conclusions: The negative impact on the cost–revenue balance is linked to both the increased cost of a longer stay and the decreased revenue due to less patients being coded A43Z. This study highlights the difficulties to justify funding of the complex care needed and to properly reflect patient burden in medico-administrative documents. Certainly, there is a need for a concerted effort to identify the services and resources needed within the DRG-system to guarantee the optimal management of acute neurorehabilitation.

Patients with acquired brain injury often suffer from pathological fatigue that differs from "normal" fatigue in that it appears more quickly and during non-demanding tasks, and recovery is not complete despite rest. It limits physical and cognitive activities, interferes with rehabilitation and return to work. The underlying mechanisms are poorly understood but appear to involve dysfunction of brain interactions. Current management combining physical reconditioning, cognitive compensatory strategies, and treatment of associated factors often leads to significant clinical improvement and promotes socio-professional reintegration. However, the effect remains insufficient in some patients, which underlines the importance of developing new therapeutic approaches based on a better understanding of the underlying neuronal deficits.

Background: Neurosensory stimulation is effective in enhancing the recovery process of severely brain-injured patients with disorders of consciousness. Multisensory environments are found in nature, recognized as beneficial to many medical conditions. Recent advances detected covert cognition in patients behaviorally categorized as un- or minimally responsive; a state described as cognitive motor dissociation (CMD). Objective: To determine effectiveness of a neurosensory stimulation approach enhanced by outdoor therapy, in the early phases of recovery in patients presenting with CMD. Methods: A prospective non-randomized crossover study was performed. A two-phase neurosensory procedure combined identical individually goal assessed indoor and outdoor protocols. All sessions were video-recorded and observations rated offline. The frequency of volitional behavior was measured using a behavioral grid. Results: Fifteen patients participated in this study. The outdoor group patients had statistically significant higher number of intentional behaviors than the indoor group on seven features of the grid. Additionally, for all items assessed, total amount of behaviors in the outdoor condition where higher than those in the indoor condition. Conclusions: Although preliminary, this study provides robust evidence supporting the effectiveness and appropriateness of an outdoor neurosensory intervention in patients with covert cognition, to improve adaptive goal-oriented behavior. This may be a step towards helping to restore functional interactive communication.

Disorders of consciousness (DOC) are a common consequence of severe brain injuries, and clinical evaluation is critical to provide a correct diagnosis and prognosis. The revised Motor Behavior Tool (MBT‐r) is a clinical complementary tool aiming to identify subtle motor behaviors that might reflect residual cognition in DOC. In this prospective study including 30 DOC patients in the early stage after brain injury, we show that the revised MBT‐r has an excellent inter‐rater agreement and has the ability to identify a subgroup of patients, underestimated by the Coma Recovery Scale‐Revised, showing residual cognition and a subsequent recovery of consciousness. This article is protected by copyright. All rights reserved.

BACKGROUND AND PURPOSE Stent retrievers have revolutionized endovascular treatment of acute ischemic stroke (AIS). Animal studies showed that mechanical thrombectomy (MT) may cause endothelial injury and intimal layer edema. Using transcranial color‐coded duplex‐sonography (TCCS) we observed postprocedural hemodynamic changes in the treated vessel. METHODS We studied AIS patients with large intracranial artery occlusion in whom MT with stent retrievers was performed. Only those with complete recanalization (modified TICI‐2b or 3) as assessed by postprocedural digital subtraction angiography (DSA) and in whom early control TCCS was performed were retained. Patients treated with intra‐arterial thrombolysis or stenting were excluded. RESULTS In 31 patients treated within a time period of 4 years (29 with middle cerebral artery [MCA] and 2 with basilar artery [BA] occlusion), postacute stroke brain‐DSA confirmed complete recanalization without residual stenosis or vasospasm. However, in 27 (17 men, mean age 66.3 years) of them TCCS (mean 3.4 days after MT) showed very segmental acceleration of blood flow velocities in the affected arteries (MCA maximum peak systolic velocity [PSVmax] at least >35% as compared to the contralateral side at the same depth; BA PSVmax >40% as compared to velocities at different depths of the same vessel). None showed clinical deterioration. TCCS follow‐up (mean 20 days) showed normalization in 14 of 16 cases. CONCLUSION Our TCCS study provides preliminary evidence of focal acceleration of blood flow velocities after MT. Without residual stenosis or vasospasm, this may be a sign of endothelial layer disruption/intimal injury. Further studies are needed to confirm our results.

Background Patients who experience severe brain injuries are at risk of secondary brain damage, because of delayed vasospasm and edema. Traditionally, many of these patients are kept on prolonged bed rest in order to maintain adequate cerebral blood flow, especially in the case of subarachnoid hemorrhage. On the other hand, prolonged bed rest carries important morbidity. There may be a clinical benefit in early mobilization and our hypothesis is that early gradual mobilization is safe in these patients. The aim of this study was to observe and quantify the changes in sympathetic activity, mainly related to stress, and blood pressure in gradual postural changes by the verticalization robot (Erigo®) and after training by a lower body ergometer (MOTOmed-letto®), after prolonged bed rest of minimum 7 days. Methods Thirty patients with severe neurological injuries were randomized into 3 groups with different protocols of mobilization: Standard, MOTOmed-letto® or Erigo® protocol. We measured plasma catecholamines, metanephrines and blood pressure before, during and after mobilization. ResultsBlood pressure does not show any significant difference between the 3 groups. The analysis of the catecholamines suggests a significant increase in catecholamine production during Standard mobilization with physiotherapists and with MOTOmed-letto® and no changes with Erigo®. Conclusions This preliminary prospective randomized study shows that the mobilization of patients with severe brain injuries by means of Erigo® does not increase the production of catecholamines. It means that Erigo® is a well-tolerated method of mobilization and can be considered a safe system of early mobilization of these patients. Further studies are required to validate our conclusions. Trial registrationThe study was registered in the ISRCTN registry with the trial registration number ISRCTN56402432. Date of registration: 08.03.2016. Retrospectively registered.

The initial stages of reading are characterised by parallel and effortless access to letters constituting a word. Neglect dyslexia is an acquired reading disorder characterised by omission or substitution of the initial or the final letters of words. Rarely, the disorder appears in a'pure’ form that is, without other signs of spatial neglect. Neglect dyslexia is linked to damage involving the inferior parietal lobe and regions of the temporal lobe, but the precise anatomical basis of the pure form of the disorder is unknown. Here, we show that pure neglect dyslexia is associated with decreased structural connectivity between the inferior parietal and lateral temporal lobe. We examined patient DM, who following bilateral occipito-parietal damage presented left neglect dyslexia together with right visual field loss, but no signs of spatial neglect. DM's reading errors were affected by word length and were much more frequent for pseudowords than for existing words. Most errors were omissions or substitutions of the first or second letter, and the spatial distribution of errors was similar for stimuli presented left or right of fixation. The brain lesions of DM comprised the inferior and superior parietal lobule as well as the cuneus and precuneus of the left hemisphere, and the angular gyrus and lateral occipital cortex of the right hemisphere. Diffusion tensor imaging revealed bilateral decrease of fibre tracts connecting the inferior parietal lobule with the superior and middle temporal cortex. These findings suggest that parieto-temporal connections play a significant role for the deployment of attention within words during reading.