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The gut-brain axis is a hot topic in Parkinson's disease. In an attempt to decipher its role in the disease pathogenesis, several animal models have been developed. Most of these models tried to reproduce Braak's hypothesis by showing that the pathological process could spread from the gut to the brain (bottom-up scenario). Interestingly, others groups showed that a top-down scenario could also occur and that 6-hydroxydopamine-induced nigrostriatal denervation was sufficient to induce significant changes in the gastrointestinal tract. Aside from this toxic approach, the article by O'Donovan and colleagues in this edition of Neurogastroenterology and Motility showed that bilateral nigral injection of adeno-associated virus (AAV)-alpha-synuclein in rats was accompanied by changes in the enteric nervous system and the gut microbiota, which occurred without any apparent brain-to-gut spread of human injected alpha-synuclein. Some changes observed in the gastrointestinal tract of animals injected with AAV-alpha-synuclein were in line with previous observations in Parkinson's disease patients, including increased expression of glial markers, swollen tyrosine hydroxylase-positive varicosities in the submucosal plexus, and decreases in Faecalibacterium and Lachnospiraceae. These findings suggest that, in addition to gut-brain pathways, the brain-to-gut communication may also be involved in Parkinson's disease pathophysiology. In this mini-review, we describe the strengths and limitations of the existing studies on the gut-brain axis in experimental models of parkinsonism and discuss an alternative hypothesis in which the central and enteric nervous system would evolve separately during disease progression., (© 2019 John Wiley & Sons Ltd.)

Lewy bodies and neurites, the pathological signatures found in the central nervous system of Parkinson's disease (PD) patients, are primarily composed of aggregated alpha-synuclein (aSyn). The observation that aSyn aggregates are also found in the enteric nervous system has prompted several studies aimed at developing a diagnostic procedure based on the detection of pathological aSyn in gastrointestinal (GI) biopsies. The existing studies, which have all used immunohistochemistry for the detection of pathological aSyn, have had conflicting results. In the current survey, we analyzed the seeding propensity of aSyn aggregates from GI biopsies. A total of 29 subjects participated to this study, 18 PD patients and 11 controls. For each patient, 2 to 4 GI biopsies were taken from the same site (antrum, sigmoid colon or rectum) and used to seed the aggregation of recombinant aSyn in an assay inspired from the protein misfolding cyclic amplification (PMCA) method. In a subset of patients and controls (14 and 3, respectively), one or two additional biopsies were analyzed by immunohistochemistry for the presence of phosphorylated aSyn histopathology (PASH) using antibodies against phosphorylated aSyn and PGP 9.5. Except for one subject, none of the control samples seeded aSyn aggregation in PMCA reaction. GI biopsies from patients with PD seeded aSyn aggregation in 10 out of 18 cases (7 from the sigmoid colon, 2 from the antrum and one from the rectum). There was good agreement between PMCA and immunohistochemistry results as, except for two cases, all PMCA-positive PD patients were also PASH-positive. Our findings show that the PMCA method we implemented is capable of detecting aSyn aggregates in routine GI biopsies. They also suggest that rectum biopsies do not contain sufficient amounts of aggregated aSyn to detect seeded assembly by PMCA. While encouraging, our findings indicate that further studies are needed to establish the diagnostic potential of the PMCA method we implemented to detect aSyn aggregates in upper GI biopsies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ceftriaxone is widely used to treat community-acquired CNS bacterial infections. French guidelines for meningitis in adults promote 75-100 mg/kg/day ceftriaxone without an upper limit for dosage, yet little is known about the pharmacology and tolerability of such regimens., Patients and Methods: A multicentre prospective cohort study was conducted in adult patients to assess the adverse drug reactions (ADRs) of high-dose ceftriaxone (i.e. daily dosage ≥4 g or ≥75 mg/kg) in CNS infections and to analyse their related factors. Drug causality was systematically assessed by an expert committee who reviewed the medical charts of all included patients., Results: A total of 196 patients were enrolled over a 31 month period. Median dosage and duration of ceftriaxone were 96.4 mg/kg/day (7 g/day) and 8 days, respectively. Nineteen ceftriaxone-related ADRs (mainly neurological) occurred in 17 patients (8.7%), with only one case of treatment discontinuation (biliary pseudolithiasis). In univariate analysis, older age, male gender, renal impairment and high trough ceftriaxone plasma concentration were associated with ceftriaxone-related ADRs., Conclusions: High-dose ceftriaxone for CNS infection administered as recommended by French guidelines in adults was well tolerated overall, suggesting these recommendations could be applied and generalized. In patients with advanced age or renal insufficiency, prescription should be done with caution and therapeutic drug monitoring could be useful., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD., Methods: A total of 43 PD patients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response)., Results: Colonic PASH was observed in 20/43 PD patients. No differences were observed in autonomic symptoms and testing between patients with and without PASH., Conclusions: Although frequent in PD, autonomic dysfunction is not related to colonic PASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

It is now well established that Parkinson's disease (PD) is not only a movement disorder of the CNS but also a gastrointestinal disorder affecting the enteric nervous system (ENS). The gut-brain axis is a bidirectional communication between the brain and the gastrointestinal tract, which comprises besides the CNS and the ENS, the intestinal epithelial barrier, the intestinal microbiota and the enteroendocrine systems. In this review, we present the clinical and pathological evidence suggesting that the gut-brain axis is dysfunctional in PD by discussing the possible role of gut microbiota, inflammation and permeability in the development of the disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Correct diagnosis of restless legs syndrome (RLS) is essential to patient care and treatment. Diagnosis is most often clinical and based on diagnostic criteria: the need to move the legs accompanied to varying degrees by unpleasant sensations, predominantly during the evening and improved by movement. In rare cases, clinical examination is insufficient and a polysomnography is necessary. Once a positive diagnosis has been made, a neurological examination and an assessment of iron status are required. The severity of the RLS must be evaluated to determine whether a specific treatment is necessary. Before treatment, it is essential to ensure that a definite diagnosis of RLS has been made and the phenotype characterised. This enables a personal treatment plan and limits the risk of augmentation syndrome., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Dysautonomic symptoms are frequent non-motor complaints in patients with Parkinson's disease. Numerous neuropathological studies have shown that Lewy bodies and neurites, the pathological hallmarks of Parkinson's disease, are widely distributed throughout the peripheral autonomic nervous systems and across end organs. However, few investigations integrally explored the symptoms and physiology of dysautonomia in Parkinson's disease. We, therefore, performed a comprehensive evaluation of the autonomic function in a prospective group of 45 patients with idiopathic Parkinson's disease. Autonomic components (pupillomotor, tear, salivary, cardiovascular, digestive, urinary, sexual, sudomotor functions and skin sensitivity) were evaluated using questionnaires and functional tests. Skin biopsy was performed for intraepidermal nerve fibre density quantification. In addition, all patients underwent polysomnography and a complete neuropsychological and neurological assessment. The analysis association of autonomic components showed that dysautonomic signs and symptoms were heterogeneously distributed among patients. Skin denervation as assessed by intraepidermal nerve fibre density quantification was only associated with quantitative thermal sensory testing (OR = 12.0, p = 0.02), constipation (OR = 5.5, p = 0.01) and ocular dryness symptoms (OR = 8.29, p = 0.04). Cognitive alteration was associated with cardiovascular symptoms (OR = 4.33, p = 0.03) and dysfunction (OR = 5.83, p = 0.02) as well as with constipation (OR = 5.38, p = 0.02). Axial motor impairment and rapid eye movement (REM) sleep behaviour disorder were not related to any of the autonomic complaint or dysfunction. Our results show that autonomic functions are affected in a heterogeneous pattern in Parkinson's disease, thereby suggesting that the progression of autonomic dysfunction follows an erratic rather than a stepwise progression.

Parkinson's disease (PD) is pathologically characterized by the presence of intraneuronal inclusions, termed Lewy bodies and Lewy neurites, whose main component is alpha-synuclein. Based on the topographic distribution of Lewy bodies and neurites established after autopsy from PD patients, Braak and coworkers hypothesized that PD pathology may start in the gastrointestinal tract then spread through the vagus nerve to the brain. This hypothesis has been reinforced by the discovery that alpha-synuclein may be capable of spreading transcellularly, thereby providing a mechanistic basis for Braak's hypothesis. This 'gut to brain' scenario has ignited heated debates within the movement disorders community and prompted a large number of studies in both humans and animals. Here, we review the arguments for and against the gut as the origin of PD. We conclude that the human autopsy evidence does not support the hypothesis and that it is too early to draw any definitive conclusions. We discuss how this issue might be further addressed in future research.

Objective: To determine whether REM sleep behavior disorder (RBD) in Parkinson disease (PD) is associated with lesions and dysfunctions of the autonomic nervous system by evaluating enteric phosphorylated α-synuclein histopathology (PASH) and permeability., Methods: A total of 45 patients with PD were included in this cross-sectional study. RBD was diagnosed on the basis of a standardized clinical interview and confirmed by polysomnography. For each patient, 5 biopsies were taken at the junction between the sigmoid and descending colon during the course of a rectosigmoidoscopy. For the detection of enteric PASH, 2 colonic biopsies were analyzed by immunohistochemistry with antibodies against phosphorylated α-synuclein and PGP9.5 in 43 patients (2 patients were excluded because only 1 biopsy was available). The paracellular permeability and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux, respectively, in the 3 remaining biopsies mounted in Ussing chambers., Results: Enteric PASH was more frequent in the subgroup of patients with PD with RBD compared to patients without RBD (18 of 28, 64.3%, vs 2 of 15, 13.3%, respectively, p < 0.01). No differences were observed in intestinal permeability between patients with PD with and without RBD., Conclusions: Patients with PD and RBD have a greater frequency of synuclein pathology in the enteric nervous system, suggesting that RBD is associated with widespread synuclein neuropathology., (© 2017 American Academy of Neurology.)

Study Objectives: Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS., Methods: Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases)., Results: Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 ± 1.8/y versus 3.8 ± 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes., Conclusion: Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS., (© 2016 Associated Professional Sleep Societies, LLC.)

Objectives: The Sudoscan™ system (Impeto Medical, Paris, France) has been recently proposed as a standardized, easy, painless tool for sudomotor function assessment. It is now used as an additional diagnostic tool in small fibre neuropathy. So far, no work has been published in children. The aim of this study was to measure electrochemical skin conductance (ESC) using the Sudoscan™ system in children in order to assess its feasibility and to provide normative values., Methods: 100 children were included in the study: 55 girls and 45 boys, age rank 2-17, mean 10.5 y. They were accompanying their brother or sister who came as outclinic patients in the Department of Paediatrics or the Department of Paediatric surgery of the University Hospital., Results: All subjects underwent the test. It was performed without any difficulty, except for some of the youngest who sometimes had some trouble in keeping calm for 3 min over the plates. 4 subjects who took the test were excluded from the analysis (2 diabetic patients and 2 having had previous chemotherapy). ESC was quite stable along childhood with an overall 80.1 μS value for hands and 81.9 μS for feet, very similar to what is observed in adults., Conclusion: Maturation process seems to occur early in life, in accordance to sudomotor control when assessed by sympathetic skin response, which is also recorded early in infancy., Significance: ESC measurement is a simple and easy-to-perform test that can be performed in the clinical setting in children in 5 min.

Objectives: Results from preclinical studies suggest that inhibition of glycogen synthase kinase (GSK-3) is a therapeutic option for tauopathies. The aim of the present study was therefore to determine the effects of sodium valproate (VPA), a GSK-3 inhibitor, on disease progression in progressive supranuclear palsy (PSP)., Patients and Methods: We performed a double-blind, randomized, placebo-controlled trial, in 28 PSP patients who received VPA (1500mg/day) or matching placebo for 24 months. The primary endpoint was the change from baseline in Progressive Supranuclear Palsy Rating Scale (PSPRS) at 12 and 24 months. Secondary endpoints evaluated the effects of VPA on cognitive and behavioral status (MMSE, Mattis Dementia Rating Scale, Wisconsin Card Sorting, Gröber and Buschke and Oral Denomination 80 tests), tolerability of treatment, and patient compliance., Results: There were no baseline differences between active treatment and placebo groups in age and clinical rating scores. PSPRS score at 12 months was significantly higher in the VPA than in the placebo group (60.8±20 versus 46.9±18.6 respectively, p=0.01), but was similar between the two groups at 24 months. No significant differences were observed between VPA and placebo groups for the secondary endpoints., Conclusion: Our results suggest that VPA is not effective as a disease-modifying agent in PSP., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Vincristine is an antimitotic agent used for treatment of leukemia, lymphomas, and cancers. Its main side effect is a dose-related, length-dependent (LD) axonal neuropathy., Methods: We performed electrodiagnostic (EDx) examinations in 17 children who had been treated with vincristine and who presented with the clinical picture of a peripheral neuropathy., Results: The mean dose of vincristine was 8.5 ± 4.0 mg/m(2) . Clinical motor symptoms were more frequent and more severe than sensory ones. Thirteen children presented with a motor deficit, 4 of whom could no longer walk. EDx examination showed an axonal neuropathy with a non-length-dependent (NLD) pattern in 9 children and an LD pattern in 8. A major motor predominance was encountered in 12 patients., Conclusions: The electrophysiological and clinical motor predominance described differs from the mainly sensory neuropathy reported in adults. Incomplete myelination due to young age may have resulted in greater sensitivity of some nerves to neurotoxic agents., (© 2015 Wiley Periodicals, Inc.)

Lewy pathology has been described in neurons of the enteric nervous system in nearly all Parkinson's disease (PD) patients at autopsy. The enteric nervous system not only contains a variety of functionally distinct enteric neurons but also harbors a prominent component of glial cells, the so-called enteric glial cells, which, like astrocytes of the central nervous system, contribute to support, protect, and maintain the neural network. A growing body of evidence supports a role for enteric glial cells in the pathophysiology of gastrointestinal disorders such as inflammatory bowel disease and chronic constipation. We have recently shown that enteric glial cell dysfunction occurs in PD. In the present review, we discuss the possible implications of enteric glia in PD-related gut dysfunction as well as in disease initiation and development., (© 2014 International Parkinson and Movement Disorder Society.)

Functional and morphological alterations of the intestinal epithelial barrier (IEB) have been consistently reported in digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. There is mounting evidence that Parkinson's disease (PD) is not only a brain disease but also a digestive disorder. Gastrointestinal involvement is a frequent and early event in the course of PD, and it may be critically involved in the early development of the disease. We therefore undertook the present survey to investigate whether changes in the IEB function and/or morphology occur in PD. Colonic biopsies were performed in 31 PD patients and 11 age-matched healthy controls. The para- and transcellular permeability were evaluated by measuring sulfonic acid and horseradish peroxidase flux respectively, in colonic biopsies mounted in Ussing chambers. The expression and localization of the two tight junctions proteins ZO-1 and occludin were analyzed by Western blot and immunofluorescence, respectively. The para- and transcellular permeability were not different between PD patients and controls. The expression of occludin, but not ZO-1, was significantly lower in colonic samples from PD patients as compared to controls and the cellular distribution of both proteins was altered in colonic mucosal specimens from PD patients. Our findings provide evidence that the IEB is morphologically altered in PD and further reinforce the potential role of the gastrointestinal tract in the initiation and/or the progression of the disease.

Obstructive sleep apnea (OSA) and short sleep duration are individually associated with an increased risk for hypertension (HTN). The aim of this multicenter cross-sectional study was to test the hypothesis of a cumulative association of OSA severity and short sleep duration with the risk for prevalent HTN. Among 1,499 patients undergoing polysomnography for suspected OSA, 410 (27.3%) previously diagnosed as hypertensive and taking antihypertensive medication were considered as having HTN. Patients with total sleep time (TST) <6 h were considered to be short sleepers. Logistic regression procedures were performed to determine the independent association of HTN with OSA and sleep duration. Considering normal sleepers (TST ≥6 h) without OSA as the reference group, the odds ratio (OR) (95% confidence intervals) for having HTN was 2.51 (1.35-4.68) in normal sleepers with OSA and 4.37 (2.18-8.78) in short sleepers with OSA after adjustment for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, daytime sleepiness, poor sleep complaint, time in bed, sleep architecture and fragmentation, and study site. The risk for HTN appeared to present a cumulative association with OSA severity and short sleep duration (p<0.0001 for linear trend). The higher risk for HTN was observed in short sleepers with severe OSA (AHI ≥30) (OR, 4.29 [2.03-9.07]). In patients investigated for suspected OSA, sleep-disordered breathing severity and short sleep duration have a cumulative association with the risk for prevalent HTN. Further studies are required to determine whether interventions to optimize sleep may contribute to lower BP in patients with OSA.

Background: Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol). Our study conceptually builds on preclinical experiments highlighting a pleiotropic mechanism of action that includes downregulation of PMP22. The primary objective was to assess safety and tolerability of PXT3003. The secondary objective aimed at an exploratory analysis of efficacy of PXT3003 in CMT1A, to be used for designing next clinical development stages (Phase 2b/3)., Methods: 80 adult patients with mild-to-moderate CMT1A received in double-blind for 1 year Placebo or one of the three increasing doses of PXT3003 tested, in four equal groups. Safety and tolerability were assessed with the incidence of related adverse events. Efficacy was assessed using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and the Overall Neuropathy Limitations Scale (ONLS) as main endpoints, as well as various clinical and electrophysiological outcomes., Results: This trial confirmed the safety and tolerability of PXT3003. The highest dose (HD) showed consistent evidence of improvement beyond stabilization. CMTNS and ONLS, with a significant improvement of respectively of 8% (0.4% - 16.2%) and 12.1% (2% - 23.2%) in the HD group versus the pool of all other groups, appear to be the most sensitive clinical endpoints to treatment despite their quasi-stability over one year under Placebo. Patients who did not deteriorate over one year were significantly more frequent in the HD group., Conclusions: These results confirm that PXT3003 deserves further investigation in adults and could greatly benefit CMT1A-diagnosed children, usually less affected than adults., Trial Registration: EudraCT Number: 2010-023097-40. ClinicalTrials.gov Identifier: NCT01401257. The Committee for Orphan Medicinal Products issued in February 2014 a positive opinion on the application for orphan designation for PXT3003 (EMA/OD/193/13).

Enteric glial cells (EGCs) are in many respects similar to astrocytes of the central nervous system and express similar proteins including glial fibrillary acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have been reported during brain damage or central nervous system degeneration. As in Parkinson's disease (PD) the enteric neurons accumulate α-synuclein, and thus are showing PD-specific pathological features, we undertook the present survey to study whether the enteric glia in PD become reactive by assessing the expression and phosphorylation levels of GFAP in colonic biopsies. Twenty-four PD, six progressive supranuclear palsy (PSP), six multiple system atrophy (MSA) patients, and 21 age-matched healthy controls were included. The expression levels and the phosphorylation state of GFAP were analyzed in colonic biopsies by western blot. Additional experiments were performed using real-time PCR for a more precise analysis of the GFAP isoforms expressed by EGCs. We showed that GFAPκ was the main isoform expressed in EGCs. As compared to control subjects, patients with PD, but not PSP and MSA, had significant higher GFAP expression levels in their colonic biopsies. The phosphorylation level of GFAP at serine 13 was significantly lower in PD patients compared to control subjects. By contrast, no change in GFAP phosphorylation was observed between PSP, MSA and controls. Our findings provide evidence that enteric glial reaction occurs in PD and further reinforce the role of the enteric nervous system in the initiation and/or the progression of the disease. We showed that GFAP is over-expressed and hypophosphorylated in the enteric glial cells (EGCs) of Parkinson's disease (PD) patients as compared to healthy subjects and patients with atypical parkinsonism (MSA, multiple system atrophy and PSP, progressive supranuclear palsy). Our findings provide evidence that enteric glial reaction occurs in PD but not in PSP and MSA and further reinforce the role of the enteric nervous system in the pathophysiology of PD., (© 2014 International Society for Neurochemistry.)

The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Guillain-Barré syndrome (GBS) has some specific characteristics in children., Methods: In this study we reviewed the clinical, laboratory, electrophysiological, and prognosis features of the 19 children diagnosed with GBS at Nantes University Hospital from 2000 to 2011., Results: Gait disturbance and leg pain were the most frequent presenting symptoms. Electrophysiological examinations revealed significant abnormalities even when performed within the first week after onset. Decreased distal CMAP amplitude was noted in 89% of cases. The pattern indicated an acute inflammatory demyelinating polyneuropathy in 95% of cases and acute motor axonal neuropathy in the remaining 5%. About two-thirds of the children were treated with intravenous immunoglobulin. After >1 year of follow-up, 17 patients had complete recovery., Conclusion: Gait disorder, leg pain, a high rate of distal conduction block, and a good prognosis are among the main specific features of GBS in childhood., (© 2013 Wiley Periodicals, Inc.)

Animal studies have shown that sequenced patterns of neuronal activity may be replayed during sleep. However, the existence of such replay in humans has not yet been directly demonstrated. Here we studied patients who exhibit overt behaviors during sleep to test whether sequences of movements trained during the day may be spontaneously reenacted by the patients during sleep. We recruited 19 sleepwalkers (who displayed complex and purposeful behaviors emerging from non REM sleep), 20 patients with REM sleep behavior disorder (who enacted their dreams in REM sleep) and 18 healthy controls. Continuous video sleep recordings were performed during sleep following intensive training on a sequence of large movements (learned during a variant of the serial reaction time task). Both patient groups showed learning of the intensively trained motor sequence after sleep. We report the re-enactment of a fragment of the recently trained motor behavior during one sleepwalking episode. This study provides, to our knowledge, the first evidence of a temporally-structured replay of a learned behavior during sleep in humans. Our observation also suggests that the study of such sleep disorders may provide unique and critical information about cognitive functions operating during sleep.

Objectives: The video-polysomnographic criteria of REM sleep behavior disorder (RBD) have not been well described. We evaluated the between-night reproducibility of phasic and tonic enhanced muscle activity during REM sleep as well as the associated behaviors and vocalizations of the patients., Methods: Fifteen patients with clinical RBD underwent two consecutive video-polysomnographies. The amount of excessive phasic and tonic chin muscle activity during REM sleep was measured in 15 patients in 3-sec mini-epochs. The time spent with motor (minor, major, complex, and scenic) or vocal (sounds, mumblings, and comprehensible speeches) events was measured in 7 patients during REM sleep., Results: There was a good between-night agreement for tonic (Spearman rho = 0.55, p = 0.03; Kendall tau = 0.48, p = 0.01) but not for phasic (rho = 0.47, p = 0.1; tau = 0.31, p = 0.1) excessive chin muscle activity. On the video and audio recordings, the minor RBD behaviors tended to occur more frequently during the second night than the first, whereas the patients spoke longer during the first than the second night., Conclusion: The excessive tonic activity during REM sleep is a reliable marker of RBD. It could represent the extent of dysfunction in the permissive atonia systems. In contrast, the more variable phasic activity and motor/vocal events could be more dependent on dream content (executive systems).

Rapid eye movements and complex visual dreams are salient features of human rapid eye movement sleep. However, it remains to be elucidated whether the eyes scan dream images, despite studies that have retrospectively compared the direction of rapid eye movements to the dream recall recorded after having awakened the sleeper. We used the model of rapid eye movement sleep behaviour disorder (when patients enact their dreams by persistence of muscle tone) to determine directly whether the eyes move in the same directions as the head and limbs. In 56 patients with rapid eye movement sleep behaviour disorder and 17 healthy matched controls, the eye movements were monitored by electrooculography in four (right, left, up and down) directions, calibrated with a target and synchronized with video and sleep monitoring. The rapid eye movement sleep behaviour disorder-associated behaviours occurred 2.1 times more frequently during rapid eye movement sleep with than without rapid eye movements, and more often during or after rapid eye movements than before. Rapid eye movement density, index and complexity were similar in patients with rapid eye movement sleep behaviour disorder and controls. When rapid eye movements accompanied goal-oriented motor behaviour during rapid eye movement sleep behaviour disorder (e.g. grabbing a fictive object, hand greetings, climbing a ladder), which happened in 19 sequences, 82% were directed towards the action of the patient (same plane and direction). When restricted to the determinant rapid eye movements, the concordance increased to 90%. Rapid eye movements were absent in 38-42% of behaviours. This directional coherence between limbs, head and eye movements during rapid eye movement sleep behaviour disorder suggests that, when present, rapid eye movements imitate the scanning of the dream scene. Since the rapid eye movements are similar in subjects with and without rapid eye movement sleep behaviour disorder, this concordance can be extended to normal rapid eye movement sleep.