Armin Schnider’s research while affiliated with University of Geneva and other places

Background and Purpose Functional neurological disorder (FND) is defined as the presence of neurological symptoms that are inconsistent with a neurological disease. We performed a single-center retrospective study aimed at determining the long-term outcome of FND patients receiving inpatient rehabilitation and the predictors of a good outcome. Methods A multidisciplinary graded exercise program was provided with one or two daily physiotherapy and occupational therapy sessions on 5 days each week, as well as weekly psychological support. Outcome was assessed using the motor part of the Functional Independence Measure scale (FIM; maximum score of 91) at admission, discharge, and follow-up, with the last assessment performed by phone interview. Results The 30 included patients were aged 43.6±14.7 years (mean±standard deviation), comprised 70% females, and received a mean of 4 weeks of rehabilitation. The admission FIM score (80.2±8.3) was significantly lower than the discharge FIM score (86.9±4.6; p<0.001, Wilcoxon signed-rank test). No notable difference was observed between discharge and follow-up FIM scores (85.5±8.5, p=0.54). The mean follow-up of the 36-month FIM scores at discharge and follow-up was dichotomized as a good outcome in cases where all items were scored ≥6 (functional independence). Binomial logistic regression showed that absence of a comorbid psychiatric disorder (p=0.039, odds ratio=10.7) was a predictive factor for a good outcome at follow-up. Other variables (e.g., sex and age) were not significant predictors of clinical outcome (all p≥0.058). Conclusions These results suggest inpatient intensive rehabilitation for motor FND is effective and produces favorable long-term results. Further studies with larger groups are warranted so that the management protocols can be standardized.

Introduction Event-related potential (ERP) studies have identified two time windows associated with recognition memory and interpreted them as reflecting two processes: familiarity and recollection. However, using relatively simple stimuli and achieving high recognition rates, most studies focused on hits and correct rejections. This leaves out some information (misses and false alarms) that according to Signal Detection Theory (SDT) is necessary to understand signal processing. Methods We used a difficult visual recognition task with colored pictures of different categories to obtain enough of the four possible SDT outcomes and analyzed them with modern ERP methods. Results Non-parametric analysis of these outcomes identified a single time window (470 to 670 ms) which reflected activity within fronto-central and posterior-left clusters of electrodes, indicating differential processing. The posterior-left cluster significantly distinguished all STD outcomes. The fronto-central cluster only distinguished ERPs according to the subject’s response: yes vs. no. Additionally, only electrophysiological activity within the posterior-left cluster correlated with the discrimination index (d’). Discussion We show that when all SDT outcomes are examined, ERPs of recognition memory reflect a single-time window that may reveal a bottom-up factor discriminating the history of items (i.e. memory strength), as well as a top-down factor indicating participants’ decision.

Background and objectives: Disorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is due to medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) - a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury. Methods: Participants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi and in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation. Results: Eighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = -0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus. Conclusion: Disorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.

1) Background: panic attack is often regarded as a benign disorder with variable physical and psychological symptoms. (2) Case Presentation: We here report the case of a 22-year-old patient known for an episode of motor functional neurological disorder a year earlier who presented a panic attack with hyperventilation causing severe hypophosphatemia and rhabdomyolysis, as well as mild tetraparesis. Electrolyte disturbances quickly resolved after phosphate substitution and rehy-dration. However, clinical signs suggesting a relapse of a motor functional neurological disorder appeared (improved walking with dual tasks). Diagnostic workup, including brain and spinal magnetic resonance imaging, as well as electroneuromyography and genetic testing for hypokalemic periodic paralysis, was unremarkable. Tetraparesis, lack of endurance, and fatigue eventually improved after several months. (3) Conclusions: the present case report highlights the intertwined relationship between a psychiatric disorder, leading to hyperventilation and acute metabolic disturbances , and functional neurological manifestations.

There is a general understanding that older adults suffering from a stroke have poorer outcomes and might benefit less from neurorehabilitation. This narrative review analyzes the conflicting evidence for the effect of aging on the success of neurorehabilitation after a stroke. While there is convincing evidence that functional outcomes are negatively impacted by age, functional gains made during rehabilitation are less clearly impacted, and the effect of age seems to be related to other factors such as prestroke independence and therapy intensity, as well as the population studied. There is no evidence that would justify withholding high-intensity neurorehabilitation on the sole basis of age.

Memory disorders are common in clinical practice. This review focuses on the rehabilitation of anterograde amnesia, the inability to learn and retrieve new information, in non-degenerative brain disease. Diverse mnemonic strategies may be helpful in learning specific pieces of information. Their success also depends on the severity of associated cognitive failures, in particular, executive dysfunction. However, unless transfer to everyday activities is specifically trained, such strategies are of limited value in promoting independence in daily life. External memory aids are often necessary to allow for independent living. Learning to use them requires intact capacities such as procedural learning or conditioning. This review further discusses the rehabilitation of confabulation, that is, the emergence of memories of events that never happened. The rehabilitation of memory disorders needs to be tailored to patients’ individual capacities and needs.

Virtual reality (VR) is seen by some as a tool that may greatly improve, or even revolutionize cognitive rehabilitation. VR offers distinct advantages compared to classic rehabilitation using paper-and-pencil or computer-based training, such as immersion, the feeling of presence, embodiment of virtual players, ecological and multisensory stimulation. We here review recent clinical studies examining the effects of VR training in patients with stroke-induced cognitive deficits. Several trials reported evidence that VR training improves general cognition compared to standard cognitive training. However, the evidence remains controversial, as some of these studies had a high risk of bias. Regarding mood, there is some indication that immersive training improves depression scores in stroke patients, but the number of studies examining mood changes is very low. Finally, in the domain of spatial cognition the development of specific intervention techniques such as virtual prism adaptation provide avenues for clinical interventions, though well-controlled clinical trials are lacking. Together, the available evidence suggests that VR has the potential to improve rehabilitation particularly in domains requiring repetitive training in an immersed, ecological setting, or when a mismatch between body frames and the environment is created. Controlled clinical studies are required to examine the specific advantages of VR compared to classic interventions.

Though motivational value is a recognized trigger of approach and avoidance behavior, less is known about the potential of reward to capture attention. We here explored whether positive or negative reward modulates the characteristic deficit of patients with left spatial neglect to disengage attention from an ipsilesional distracter. We built our study on recent observations showing that the disengagement deficit is exaggerated for distracters with target-defining features, indicating that task-relevance captures attention. Patients with left neglect and matched healthy controls were asked to react to lateralized, colored targets preceded by a peripheral cue. Crucially, the cue either possessed the color of the target and was thus task-relevant, or was followed by a positive, negative, or neutral symbolic reward. Neglect patients only exhibited a disengagement deficit when cues were task-relevant or were followed by a negative reward. This finding indicates that attentional selection is driven by task-relevance and negative reward, possibly through interactions between limbic and attention networks.

Patients with early Alzheimer’s disease (AD) have difficulty in learning new information and in detecting novel stimuli. The underlying physiological mechanisms are not well known. We investigated the electrophysiological correlates of the early (< 400 ms), automatic phase of novelty detection and encoding in AD. We used high-density EEG Queryin patients with early AD and healthy age-matched controls who performed a continuous recognition task (CRT) involving new stimuli (New), thought to provoke novelty detection and encoding, which were then repeated up to 4 consecutive times to produce over-familiarity with the stimuli. Stimuli then reappeared after 9–15 intervening items (N-back) to be re-encoded. AD patients had substantial difficulty in detecting novel stimuli and recognizing repeated ones. Main evoked potential differences between repeated and new stimuli emerged at 180–260 ms: neural source estimations in controls revealed more extended MTL activation for N-back stimuli and anterior temporal lobe activations for New stimuli compared to highly familiar repetitions. In contrast, AD patients exhibited no activation differences between the three stimulus types. In direct comparison, healthy subjects had significantly stronger MTL activation in response to New and N-back stimuli than AD patients. These results point to abnormally weak early MTL activity as a correlate of deficient novelty detection and encoding in early AD.

Objective: Return-to-work is often the most important objective of working-age patients with acquired brain injury, but is often difficult to achieve. There is a lack of evidence for effective treatment. This study aimed to assess the benefit of a multidisciplinary neurorehabilitation in a daytime hospital on return-to-work after an acquired brain injury. Design: Retrospective case-control study. Patients: Acquired brain injury patients between 18 and 65 years of age. Methods: Two periods, before (n = 82 patients) and after (n = 89 patients) the implementation of a daytime hospital in our neuro-rehabilitation unit were compared. Patients followed in the daytime hospital received intensive, interdisciplinary, coordinated, individual and group-level physical, cognitive, and vocational rehabilitation. During the control period, patients received outpatient neurorehabilitation with less intensive treatment without interdisciplinary coordination. The main outcome was the proportion of patients returning to > 50% of their premorbid work activity. Results: Fifty-five percent of patients were able to resume more than 50% of their premorbid work level in the daytime hospital period vs 41% in the control period (p = 0.076). Conclusion: Intensive and coordinated outpatient neurorehabilitation may facilitate return-to-work after an acquired brain injury.