Brain-actuated functional electrical stimulation elicits lasting arm motor recovery after stroke.

Brain-computer interfaces (BCI) are used in stroke rehabilitation to translate brain signals into intended movements of the paralyzed limb. However, the efficacy and mechanisms of BCI-based therapies remain unclear. Here we show that BCI coupled to functional electrical stimulation (FES) elicits significant, clinically relevant, and lasting motor recovery in chronic stroke survivors more effectively than sham FES. Such recovery is associated to quantitative signatures of functional neuroplasticity. BCI patients exhibit a significant functional recovery after the intervention, which remains 6-12 months after the end of therapy. Electroencephalography analysis pinpoints significant differences in favor of the BCI group, mainly consisting in an increase in functional connectivity between motor areas in the affected hemisphere. This increase is significantly correlated with functional improvement. Results illustrate how a BCI-FES therapy can drive significant functional recovery and purposeful plasticity thanks to contingent activation of body natural efferent and afferent pathways.

Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.

Cognitive-motor dual-task interference modulates mediolateral dynamic stability during gait in post-stroke individuals.

Gait asymmetry and dynamic balance impairments observed in post-stroke individuals increase their risk of fall. Moreover, walking while performing a cognitive task (i.e. dual-task) disturbs the control of balance in post-stroke individuals. Here we investigated the mediolateral dynamic stability in twenty-two community-dwelling participants (12 post-strokes and 10 healthy controls) while walking in single-task (normal gait) and four different dual-tasks (cognitive-motor interference). Positions of the extrapolated center of mass and mediolateral widths of both margin of stability and base of support were extracted from 35 marker trajectories. Post-stroke participants presented larger margin of stability and base of support than controls during single-task (both p < 0.01), with a larger margin of stability on the non-paretic side than on the paretic side at ipsilateral foot-strike (p < 0.05). No significant effect of the dual-task was found between groups. In post-stroke participants, dual-task induced slight modification of the mediolateral stability strategy, as the margin of stability was not different between the two limbs at foot-strike, and significantly reduced the performance in every cognitive task. Post-stroke participants increased their dynamic stability in the frontal plane in single-task by extending their base of support and mainly relying on their non-paretic limb. Under cognitive-motor interference (dual-task), post-stroke participants prioritized dynamic stability over cognitive performance to ensure a safe locomotion. Thus, rehabilitation programs should consider both dynamic balance and dual-task training, even at a chronic delay following stroke, to reduce the risk of fall in post-stroke individuals.

Principles of proportional recovery after stroke generalize to neglect and aphasia.

BACKGROUND AND PURPOSE: Motor recovery after stroke can be characterized into two different patterns. A majority of patients recover about 70% of initial impairment, whereas some patients with severe initial deficits show little or no improvement. Here, we investigated whether recovery from visuospatial neglect and aphasia is also separated into two different groups and whether similar proportions of recovery can be expected for the two cognitive functions. METHODS: We assessed 35 patients with neglect and 14 patients with aphasia at 3 weeks and 3 months after stroke using standardized tests. Recovery patterns were classified with hierarchical clustering and the proportion of recovery was estimated from initial impairment using a linear regression analysis. RESULTS: Patients were reliably clustered into two different groups. For patients in the first cluster (n = 40), recovery followed a linear model where improvement was proportional to initial impairment and achieved 71% of maximal possible recovery for both cognitive deficits. Patients in the second cluster (n = 9) exhibited poor recovery (<25% of initial impairment). CONCLUSIONS: Our findings indicate that improvement from neglect or aphasia after stroke shows the same dichotomy and proportionality as observed in motor recovery. This is suggestive of common underlying principles of plasticity, which apply to motor and cognitive functions.

Memory in time: electrophysiological comparison between reality filtering and temporal order judgment.

Orbitofrontal reality filtering (ORF) denotes a little known but vital memory control mechanism, expressed at 200-300ms after stimulus presentation, that allows one to sense whether evoked memories (thoughts) refer to present reality and can be acted upon, or not. Its failure induces reality confusion evident in confabulations that patients act upon and disorientation. In what way ORF differs from temporal order judgment (TOJ), that is, the conscious knowledge about when something happened in the past, has never been explored. Here we used evoked potential analysis to compare ORF and TOJ within a combined experimental task and within a comparable time frame, close to the experienced present. Seventeen healthy human subjects performed an experiment using continuous recognition tasks that combined the challenges of ORF and TOJ. We found that the two mechanisms dissociated behaviorally: subjects were markedly slower and less accurate in TOJ than ORF. Both mechanisms evoked similar potentials at 240-280ms, when ORF normally occurs. However, they rapidly dissociated in terms of amplitude differences and electrical source from 310 to 360ms and again from 530 to 560ms. We conclude that the task of consciously ordering memories in the immediate past (TOJ) is effortful and slow in contrast to sensing memories' relation with the present (ORF). Both functions invoke similar early electrocortical processes which then rapidly dissociate and engage different brain areas. The results are consistent with the different consequences of the two mechanisms' dysfunction: while failure of ORF has a known clinical manifestation (reality confusion as evident in confabulation and disorientation), the failure of TOJ, as tested here, has no such known clinical correlate.

Frontal tDCS modulates orbitofrontal reality filtering.

Orbitofrontal reality filtering denotes a memory control mechanism necessary to keep thought and behavior in phase with reality. Its failure induces reality confusion as evident in confabulation and disorientation. In the present study, we explored the influence of orbitofrontal transcranial direct current stimulation (tDCS) on reality filtering. Twenty healthy human subjects made a reality filtering task, while receiving cathodal, anodal, or sham stimulation over the frontal pole in three sessions separated by at least 1week. Computational models predicted that this montage can produce polarity-specific current flow across the posterior medial orbitofrontal cortex (OFC). In agreement with our hypothesis, we found that cathodal tDCS over the frontal pole specifically impaired reality filtering in comparison to anodal and sham stimulation. This study shows that reality filtering, an orbitofrontal function, can be modulated with tDCS.

Do irrelevant sounds impair the maintenance of all characteristics of speech in memory?

Several studies have shown that maintaining in memory some attributes of speech, such as the content or pitch of an interlocutor's message, is markedly reduced in the presence of background sounds made of spectrotemporal variations. However, experimental paradigms showing this interference have only focused on one attribute of speech at a time, and thus differ from real-life situations in which several attributes have to be memorized and maintained simultaneously. It is possible that the interference is even greater in such a case and can occur for a broader range of background sounds. We developed a paradigm in which participants had to maintain the content, pitch and speaker size of auditorily presented speech information and used various auditory distractors to generate interference. We found that only distractors with spectrotemporal variations impaired the detection, which shows that similar interference mechanisms occur whether there are one or more speech attributes to maintain in memory. A high percentage of false alarms was observed with these distractors, suggesting that spectrotemporal variations not only weaken but also modify the information maintained in memory. Lastly, we found that participants were unaware of the interference. These results are similar to those observed in the visual modality.

[Functional weakness of movement]. / Trouble du mouvement d'origine fonctionnelle.

The diagnosis of functional paresis is evoked when a patient presents with symptoms and signs incompatible with current anatomical and physiological knowledge. A broad assessment, including imaging and motor evoked potentials at rest, remains necessary; the rate of false diagnosis being estimated at 4%. The mechanisms of hysteria remain still dubious but various studies suggest that functional paresis is different from simulation by conscious, voluntary inhibition. The long-term prognosis is bad. The treatment includes cognitive-behavioral therapy and rehabilitation to develop a positive attitude.

Masticatory function and bite force in stroke patients.

Orofacial functions are frequently affected by stroke, but little is known on the nature and extent of the impairment of mastication, which is investigated in this observational study. Thirty-one stroke patients, aged 69.0 ± 12.7 yrs, presenting with a hemi-syndrome with facial palsy, were recruited. Chewing efficiency, maximum bite and restraining lip forces were tested. Stroke severity (National Institutes of Health Stroke Scale) and dental state were recorded. The control group was similar in age, gender, and dental state (n = 24). The chewing efficiency was significantly lower in the stroke group (p ≤ 0.0001) and was related to both the dental state and the lip forces measured with small and medium-sized labial plates. The maximum bite force proved to be not significantly different between sides or groups (n.s.), whereas lip force was significantly lower in the stroke group (p ≤ 0.05). Chewing efficiency is severely affected by stroke; thus, rehabilitation protocols should aim to restore the strength and co-ordination of the orofacial muscles.

Peripheral dysgraphia characterized by the co-occurrence of case substitutions in uppercase and letter substitutions in lowercase writing.

Patients with peripheral dysgraphia due to impairment at the allographic level produce writing errors that affect the letter-form and are characterized by case confusions or the failure to write in a specific case or style (e.g., cursive). We studied the writing errors of a patient with pure peripheral dysgraphia who had entirely intact oral spelling, but produced many well-formed letter errors in written spelling. The comparison of uppercase print and lowercase cursive spelling revealed an uncommon pattern: while most uppercase errors were case substitutions (e.g., A - a), almost all lowercase errors were letter substitutions (e.g., n - r). Analyses of the relationship between target letters and substitution errors showed that errors were neither influenced by consonant-vowel status nor by letter frequency, though word length affected error frequency in lowercase writing. Moreover, while graphomotor similarity did not predict either the occurrence of uppercase or lowercase errors, visuospatial similarity was a significant predictor of lowercase errors. These results suggest that lowercase representations of cursive letter-forms are based on a description of entire letters (visuospatial features) and are not - as previously found for uppercase letters - specified in terms of strokes (graphomotor features).

Comparison of real-time PCR assays for detection, quantification, and differentiation of campylobacter jejuni and campylobacter coli in broiler neck skin samples.

We tested the use of multiplex real-time PCR for detection and quantification of Campylobacter jejuni and Campylobacter coli on broiler carcass neck skin samples collected during 2008 from slaughterhouses in Switzerland. Results from an established TaqMan assay based on two different targets (hipO and ceuE for C. jejuni and C. coli, respectively) were corroborated with data from a newly developed assay based on a single-nucleotide polymorphism in the fusA gene, which allows differentiation between C. jejuni and C. coli. Both multiplex real-time PCRs were applied simultaneously for direct detection, differentiation, and quantification of Campylobacter from 351 neck skin samples and compared with culture methods. There was good correlation in detection and enumeration between real-time PCR results and quantitative culture, with real-time PCR being more sensitive. Overall, 251 (71.5%) of the samples were PCR positive for Campylobacter, with 211 (60.1%) in the hipO-ceuE assays, 244 (69.5%) in the fusA assay, and 204 (58.1%) of them being positive in both PCR assays. Thus, the fusA assay was similarly sensitive to the enrichment culture (72.4% positive); however, it is faster and allows for quantification. In addition, real-time PCR allowed for species differentiation; roughly 60% of positive samples contained C. jejuni, less than 10% C. coli, and more than 30% contained both species. Real-time PCR proved to be a suitable method for direct detection, quantification, and differentiation of Campylobacter from carcasses, and could permit time-efficient surveillance of these zoonotic agents.

Masseter muscle thickness in hospitalised stroke patients.

The aim of the study was to investigate the thickness of the masseter muscles in stroke patients when compared to a control group (CG). Hospitalised stroke patients (18 men, 13 women; age 69.0 +/- 12.7 years) were compared to a CG (13 men, 11 women; age 68.8 +/- 10.8 years) composed to correspond to in age, gender and dental state. The thickness of the masseter muscle was recorded by means of a real-time ultrasound scanner on both sides, twice under contraction and twice in relaxed condition. In the stroke patients, the thickness of the masseter muscle of the affected side (aff) was smaller than the one of the non-affected side (non-aff) both, under contraction (aff 13.1 +/- 2.4 mm; non-aff 13.8 +/- 2.3 mm, P

[Expansion of the sphere of crisis: the question of the intrusiveness of the disease]. / Extension du domaine de la crise: la question de l'intrusion de la maladie.

The passage to ambulatory care of a patient with a long hospital stay due to a wrenching disease is not something obvious. The doctor and the care staff will have to take up the challenge of dealing with an important amount of care. The quality of life of the patient and his caregivers is influenced by the neuropsychiatric disorders, the illness intrusiveness and the depression that come along with them. The chronic disease intruding causes a crisis in their lives. In order to better evaluate these factors we are using the Illness Intrusiveness Rating Scale developed by Devins. This article addresses the high complexity of clinical situations handled in an environment of rehabilitation care with the support of the consultants, nurses and doctors, of the liaison psychiatry.

Dopaminergic modulation of rapid reality adaptation in thinking.

Dopamine has long held a prominent role in the interpretation of schizophrenia and other psychoses. Clinical studies on confabulation and disorientation, disorders marked by a confusion of reality in thinking, indicated that the ability to keep thinking in phase with reality depends on a process suppressing the interference of upcoming memories that do not refer to ongoing reality. A host of animal studies and a recent clinical study suggested that this suppression might correspond to the phasic inhibition of dopaminergic neurons in response to the absence of expected outcomes. In this study, we tested healthy subjects with a difficult version of a memory paradigm on which confabulating patients had failed. Subjects participated in three test sessions, in which they received in double-blind, randomized fashion L-dopa, risperidone, or placebo. We found that l-dopa, in comparison with risperidone, impaired performance in a highly specific way, which corresponded to the pattern of patients with reality confusion. Specifically, they had an increase of false positive responses, while overall memory performance and reaction times were unaffected. We conclude that dopaminergic transmission influences the ability to rapidly adapt thinking to ongoing reality.

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02).

BACKGROUND: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.

[Constraint-induced movement therapy in neurological rehabilitation: which modality to choose? Our experience in rehabilitation in Geneva]. / La thérapie par contrainte en rééducation neurologique: quelles modalités choisir? Notre expérience dans le service de neurorééducation à Genève.

OBJECTIVE: The purpose of constraint-induced movement therapy (CIMT) is to stimulate the use of the affected upper arm following stroke and to improve the integration of the arm in activities of daily living. CIMT consists of restraining the unaffected arm to limit its use, combined with a training program based on the shaping principle. We aimed to explore how this method can be used in practice by studying 4 patients after stroke. METHOD: We investigated 4 patients, 2 with chronic disability (10 and 17 months after the stroke), and 2 with subacute disability (1 month after the stroke). Patients underwent 3 weeks of treatment, with evaluations before, immediately after, 3 months and 1 year after the training. The following scales were used: Wolf Motor Function Test (WFMT), Fugl-Meyer Assessment (FMA), and motor activity log (MAL). RESULTS: Four patients showed enhanced function (improved WFMT and FMA scores) at 3 months and 3 patients at one year and better use of the paretic limb in daily activities (MAL score). Two patients in the subacute phase showed better speed of movement (WFMT score). CONCLUSION: The efficacy of CIMT seems to be confirmed by the literature and our observations. It is superior to the usual treatment but concerns only a few patients. The scheme of treatment is still not clear, but many studies recommend the use of a glove 90% of the day for 2 or 3 weeks, with 3 to 6 hours per day of intensive therapy.

Paradoxical switching to a barely-mastered second language by an aphasic patient.

Polyglot speakers who become aphasics are not necessarily affected to the same extent in each language. In some cases there is a mixing of the different languages or a switching between languages and in very rare cases the switch is to the language seldom if ever used in everyday live. We report a French-speaking aphasic, who switched paradoxically from his mother tongue (French) to a second language (German) which he had learned at school but barely mastered and hardly ever spoke, and kept using German most of the time. We tried to understand the mechanism responsible for that phenomenon by reviewing the actual hypothesis of multi-language organization. We concluded, in line with previous reports, that our case used his metalinguistic knowledge to compensate for his inability to access his linguistic skills.

[Ischemic, an uncommon complication of Biermer disease (pernicious anemia)]. / L'accident ischémique cérébral, une complication rare de la maladie de Biermer.

INTRODUCTION: Stroke in a young adult justifies an extensive etiologic workup. OBSERVATION: We present a 44-year-old women victim of a frontal ischemic stroke. Extensive evaluation was normal, except for high plasma level of homocysteine in the context of pernicious anemia, otherwise asymptomatic. DISCUSSION: Hyperhomocysteinemia is a known marker, and probably risk factor for stroke, fostering atherosclerosis and thrombosis. It can be found among individuals suffering from homocystinuria, in individuals homozygous for the MHTFR T allele but also when there is deficiency of vitamin B12 or folic acid. Although it is very seldom ascribed, pernicious anemia would be a cause of stroke, possibly though hyperhomocysteinemia.

The prognosis of agenesis of the corpus callosum might mostly be favourable.

The post-natal development of 6 patients with complete agenesis of the corpus callosum was assessed. The diagnosis of agenesis of the corpus callosum had been suspected prenatally in 3 cases. In the remaining 3 cases diagnostic neuro-imaging was performed because of partial seizures (n = 2) and pendular nystagmus (n = 1). The neurological examination was normal in all patients with the exception of nystagmus in one. The neuro-developmental outcome was found to be normal in all 6 patients. In conclusion, these data suggest that good outcome is predominant in agenesis of the corpus callosum.