Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. RESULTS: Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Botulinum toxin therapy improves masseter spasticity in Amyotrophic Lateral Sclerosis.

Fifteen ALS patients, with troublesome symptoms linked to masseter spasticity, benefited from BoNT-A injections in each masseter. Based on the medical records of patients, the effect of the first injection was assessed one month later. We retrospectively collected information for 12 patients. Eight of them reported a beneficial effect after the injection for the following symptoms: trismus, tongue, lip and cheek biting, and jaw clonus. Five patients indicated that dental care was easier after injection. Our study showed that injections of BoNT-A unequivocally reduced masseter spasticity in ALS patients who subsequently enjoyed greater comfort in their daily living.

Type A competitiveness traits correlate with downregulation of c-Fos expression in patients with type 1 diabetes.

AIM: Type A personality has been associated with increased survival in people with type 1 diabetes (T1D). Systemic low-grade inflammation may play a critical role, as suggested in recent reports, although the links between the inflammatory circulating transcriptome and Type A remain unknown. This prompted our exploration of the potential associations between Type A personality and c-Fos gene expression, a candidate gene closely linked to inflammatory processes, in T1D. METHODS: Type A personality was assessed by Bortner questionnaire in patients with T1D, and two subscales - 'speed' and 'competitiveness' - were used to measure these specific dimensions of Type A. Expression of the c-Fos gene was assessed by a quantitative real-time polymerase chain reaction technique. RESULTS: This pilot study included 20 men with T1D. Multivariable analyses showed an independent inverse association between Type A competitiveness score and c-Fos expression, while a regression model adjusted for age, body mass index and HbA1c levels revealed a significant inverse relationship between c-Fos transcripts and Type A competitiveness (P = 0.003). CONCLUSION: This strong association between Type A competitiveness and reduced c-Fos expression is in line with recent data suggesting a psychobiological influence of the Type A profile in T1D via inflammatory pathways.

Electrically-induced muscle fatigue affects feedforward mechanisms of control.

OBJECTIVE: To investigate the effects of focal muscle fatigue induced by electromyostimulation (EMS) on Anticipatory Postural Adjustments (APAs) during arm flexions performed at maximal velocity. METHODS: Fifteen healthy subjects performed self-paced arm flexions at maximal velocity before and after the completion of fatiguing electromyostimulation programs involving the medial and anterior deltoids and aiming to degrade movement peak acceleration. APA timing and magnitude were measured using surface electromyography. RESULTS: Following muscle fatigue, despite a lower mechanical disturbance evidenced by significant decreased peak accelerations (-12%, p<.001), APAs remained unchanged as compared to control trials (p>.11 for all analyses). CONCLUSION: The fatigue signals evoked by externally-generated contractions seem to be gated by the Central Nervous System and result in postural strategy changes which aim to increase the postural safety margin. SIGNIFICANCE: EMS is widely used in rehabilitation and training programs for its neuromuscular function-related benefits. However and from a motor control viewpoint, the present results show that the use of EMS can lead to acute inaccuracies in predictive motor control. We propose that clinicians should investigate the chronic and global effects of EMS on motor control.

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Segmental somatosensory-evoked potentials as a diagnostic tool in chronic inflammatory demyelinating polyneuropathies, and other sensory neuropathies.

PURPOSE OF THE STUDY: Somatosensory-evoked potentials with segmental recordings were performed with the aim of distinguishing chronic inflammatory demyelinating polyneuropathy from other sensory neuropathies. PATIENTS AND METHODS: Four groups of 20 subjects each corresponded to patients with (1) possible sensory chronic inflammatory demyelinating polyneuropathy, (2) patients with sensory polyneuropathy of unknown origin, (3) patients with amyotrophic lateral sclerosis and (4) normal subjects. The patients selected for this study had preserved sensory potentials on electroneuromyogram and all waves were recordable in evoked potentials. Somatosensory-evoked potentials evaluations were carried out by stimulation of the posterior tibial nerve at the ankle, recording peripheral nerve potential in the popliteal fossa, radicular potential and spinal potential at the L4-L5 and T12 levels, and cortical at C'z, with determination of distal conduction time, proximal and radicular conduction time and central conduction time. RESULTS: In the group of chronic inflammatory demyelinating polyneuropathy, 80% of patients had abnormal conduction in the N8-N22 segment and 95% had abnormal N18-N22 conduction time. In the group of neuropathies, distal conduction was abnormal in most cases, whereas 60% of patients had no proximal abnormality. None of the patients in the group of amyotrophic lateral sclerosis had an abnormal N18-N22 conduction time. CONCLUSION: Somatosensory-evoked potentials with segmental recording can be used to distinguish between atypical sensory chronic inflammatory demyelinating polyneuropathy and other sensory neuropathies, at the early stage of the disease. Graphical representation of segmental conduction times provides a rapid and accurate visualization of the profile of each patient.

Movement unpredictability and temporal constraints affect the integration of muscle fatigue information into forward models.

When performing self-paced movements in a fatigued state, internal models can predict the mechanical effects of muscle fatigue. Yet, it is unclear if this is still true when movements are submitted to additional constraints. The purpose of the present study was to investigate the Central Nervous System's (CNS) capacity to integrate fatigue signals into forward models' prediction processes when the movement to perform is unpredictable and temporally constrained. Participants had to perform two different focal movements, depending on the random presentation of color word-color associations (Stroop-like task). They had to trigger fast arm extensions and flexions in a standing posture at the presentation of congruent and incongruent colors, respectively. These movements involve the implementation of predictive mechanisms of control, namely Anticipatory Postural Adjustments (APAs), which have been shown to depend on arm peak acceleration. APA timing and magnitude were measured using surface electromyography. The experimental task was performed before and after a fatiguing protocol involving the prime mover of the flexion movement. According to the assumption that APAs are constructed upstream from the primary motor cortex (M1), up to 1.4s before movement onset on the basis of the processing of the relevant contextual-sensory information, the Stroop-like task aimed to prevent participants from predicting the movement to perform and to reduce movement preparation time. While the fatigue protocol resulted in significant alterations of arm flexion peak accelerations, APAs were not modified post-fatigue as compared to control trials. It is proposed that with unpredictable and temporally constrained movements, the CNS cannot incorporate fatigue signals in internal models' prediction processes to reweight the motor information contained in the efference copy. It is also suggested that APA implementation is based on predictive processes occurring in internal models located upstream from M1.

Impaired control of weight bearing ankle inversion in subjects with chronic ankle instability.

BACKGROUND: Previous studies have proposed that evertor muscle weakness represents an important factor affecting chronic ankle instability. For research purposes, ankle evertor strength is assessed by means of isokinetic evaluations. However, this methodology is constraining for daily clinical use. The present study proposes to assess ankle evertor muscle weakness using a new procedure, one that is easily accessible for rehabilitation specialists. To do so, we compared weight bearing ankle inversion control between patients suffering from chronic ankle instability and healthy subjects. METHODS: 12 healthy subjects and 11 patients suffering from chronic ankle instability conducted repetitions of one leg weight bearing ankle inversion on a specific ankle destabilization device equipped with a gyroscope. Ankle inversion control was performed by means of an eccentric recruitment of evertor muscles. Instructions were to perform, as slow as possible, the ankle inversion while resisting against full body weight applied on the tested ankle. RESULTS: Data clearly showed higher angular inversion velocity peaks in patients suffering from chronic ankle instability. This illustrates an impaired control of weight bearing ankle inversion and, by extension, an eccentric weakness of evertor muscles. INTERPRETATION: The present study supports the hypothesis of a link between the decrease of ankle joint stability and evertor muscle weakness. Moreover, it appears that the new parameter is of use in a clinical setting.

Mutations selected in the hepatitis C virus NS3 protease domain during sequential treatment with boceprevir with and without pegylated interferon alfa-2b.

Treatment with hepatitis C virus (HCV)-NS3-protease inhibitors lead to the selection of resistant variants. Viral kinetics and resistance profiles in patients who are re-treated with the same protease inhibitor are unknown. Viral kinetics and NS3-resistance mutations obtained by clonal sequencing of the NS3-protease were analyzed in nine HCV-genotype-1-infected nonresponder patients who were sequentially treated with boceprevir (400 mg t.i.d.) for 1 week, peginterferon-alfa-2b for 2 weeks and combination of the two for 2 weeks in varying order. In addition to predominant wild-type isolates, previously described boceprevir-resistant mutations (V36, T54, R155, A156, V170) were observed. Furthermore, two resistant mutations (Q41, F43) were detected for the first time in vivo. In three patients, mutations selected after initial treatment with boceprevir were re-selected during subsequent boceprevir exposure. However, mutational patterns after the first and second exposure to boceprevir were different in five patients. In one patient, a viral variant (V55A) known to reduce susceptibility to boceprevir was the predominant variant observed at baseline and throughout treatment and was associated with a shallow viral decline. Different resistance mutations were selected during treatment with boceprevir ± peginterferon. Sequential short-term dosing of boceprevir was not associated with accumulation of resistant variants but pre-existing variants may impair virologic response.

[Effects of unilateral fatigue of triceps surae on undisturbed stance]. / Effets d'une fatigue unilatérale du triceps surae sur la posture non-perturbée.

OBJECTIVE: Fatigue of lower limb presents various impacts on postural control. The purpose of this study was to explore the effects of a unilateral lower-limb muscle fatigue on undisturbed stance. METHODS: Nine healthy men performed until exhaustion a fatiguing exercise of the limb extensor muscles of one leg (exercised leg). Just before and after the fatiguing exercise, postural sway measures (centre of pressure) were recorded simultaneously from a double force platform and an in-shoe pressure system in quiet standing conditions. Maximal plantar pressure was computed from each sensor of the in-shoe system, before being averaged for the medial and lateral heel, the external mid-foot, the external and internal foreparts. RESULTS: In undisturbed stance, the fatiguing exercise induced postural destabilisation for the non-exercised leg (P < 0.001). Changes in antero-posterior mean position of the exercised leg were also observed reflecting a mean loading in a more rear foot stance (P < 0.01). The in-shoe system parameters revealed for the exercised foot, an increase of the maximal pressure value for the heel region (P < 0.05) and a decrease for the mid-foot and forepart (P < 0.05). For the non-exercised foot, the maximal pressure decreased only in forepart (P < 0.05). CONCLUSIONS: Unilateral triceps surae fatigue revealed an immediate destabilisation of undisturbed stance and the observed postural strategy appears similar to these developed by patients who presented pain pathology and/or sensory deficits in lower limb.

Peroneal reaction time measurement in unipodal stance for two different destabilization axes.

BACKGROUND: The variability of peroneal reaction time measurements is a major problem when using this parameter to control rehabilitation or proprioceptive training processes. In order to control peroneal reaction time values, some extrinsic factors should be considered. The purpose of this study was to measure peroneal reaction time in unipodal stance for two different destabilization axes. METHODS: The peroneal reaction time of 10 healthy subjects was measured from kinematic and electromyograhic data in an experimental study using an ankle destabilization device. FINDINGS: In a preliminary analysis, results showed that the destabilization axis orientation did not affect peroneal reaction time values (68.5 ms, standard deviation=9.5 ms and 71.5 ms, standard deviation=8 ms for destabilizations in the frontal plane and around the Henke's axis, respectively). However, the inter-trial variance of inversion velocity peaks explained between 40% and 49% of the peroneal reaction time variance. When trials were selected on the basis of homogeneous inversion velocity peaks, results showed that peroneal reaction time values for the peroneus brevis were shorter during inversion movements performed around the physiological Henke's tilting axis (63 ms, standard deviation=9 ms vs. 71 ms, standard deviation=8 ms). INTERPRETATION: Our findings evidenced that tilting axis orientation must be considered as an extrinsic factor that may influence peroneal reaction time. Moreover it also seems necessary to consider inversion speed values to adequately compare peroneal reaction time values.

Unilateral lower limb muscle fatigue induces bilateral effects on undisturbed stance and muscle EMG activities.

The study investigated the effects of an unilateral ankle muscle fatigue onto independent postural control parameters including the trajectories of the estimated resultant CoP (CoPres) and his components: the centre of gravity (CG) and CoP-CG trajectories. Nine healthy men realized series of 10 toe-lift immediately followed by 10 knee flexions until exhaustion with one (Ex) leg. Maximal isometric voluntary contractions, postural sway measures of each leg, and muscular activities of the ankle muscles were recorded before and immediately after the fatiguing exercise. As expected, the latter induced a decrease in maximal voluntary peak force associated with a greater variability of the relative contribution of each leg on the CoPres, enhanced all postural parameters of the non-exercised leg. A significant decreased of the tibialis anterior EMG activity for the Ex leg and an increased one for the NoEx leg. Finally, following unilateral fatigue, the body sway destabilisation seemed to occur only along the medio-lateral (ML) axis. The enhanced and greater variability of the variance along ML axis might be explained by the recourse at the loading-unloading strategy choice and suggests a central attempt to compensate for pain sensation.

[Primary lateral sclerosis: the era of international diagnosis criteria]. / La sclérose latérale primitive : l'avènement de critères consensuels internationaux.

Since Charcot's first description, primary lateral sclerosis (PLS) remains a rare clinical syndrome, a neuropathological phenotype of motor system degeneration. In turn, PLS has been described as belonging to the large spectrum of motoneuron diseases or to the diverse degenerative diseases of the nervous system. Clinically, it is characterized by progressive pyramidal involvement in patients who present insidiously progressive gait disorders and, on examination, have relatively symmetrical lower limb weakness, increased muscle tone, pathologic hyper-reflexia, and exaggerated extensor plantar responses. Pinprick, light touch, and temperature sensations are preserved. Viewed in another way, PLS mimicks progressive hereditary spastic paraparesis (HSP) and the "central" phenotype of amyotrophic lateral sclerosis (ALS). PLS is considered "idiopathic" and, depending on the presence or absence of similarly affected family members, the syndrome of idiopathic HSP and ALS are labeled "hereditary" or "apparently sporadic". The juvenile form of PLS and early age at onset in cases of HSP complicate our understanding of the relationship between these two disorders. Guidelines for diagnosis and genetic counseling have been published for HSP and ALS. Recently, since the first international workshop, guidelines for diagnosis of PLS propose a classification system, e.g. for heterogeneous HSP into "pure PLS", complicated or "plus PLS", symptomatic PLS and upper motor neuron-dominant ALS. However, when reviewing known cases of PLS drawn from the literature, rigorous retrospective application of these new PLS criteria raises an unanswered question: does pure PLS exist?

[Parkinson disease and amyotrophic lateral sclerosis. Tauopathies, TDP-43 and SOD mutations]. / Syndromes parkinsoniens et sclérose latérale amyotrophique Tauopathies, TDP-43 et mutations SOD.

In addition to a large number of clinical descriptions of atypical cases, recent pathological, biochemical and genetic studies challenge the view that amyotrophic lateral sclerosis (ALS) is a disorder restricted to the pyramidal motor system. Relations between ALS, Parkinson disease, fronto-temporal dementia, progressive supranuclear paralysis, and cortico-basal degeneration have now been identified. We propose a review of the topic and discuss the contribution of various clinical and pathological features leading to consider motoneuron diseases as neurodegenerative processes included in a broad spectrum of tauopathies.

The effects of an ankle destabilization device on muscular activity while walking.

Chronic Ankle Instability sprain causes are unclear and many factors or mechanisms may contribute to recurrence of this injury. The aim of the study was to investigate how an ankle destabilization device affects the EMG patterns of the ankle muscles during ankle stabilization against inversion. The left foot was equipped with a mechanical device mounted under the heel of the shoe. This mechanical device induces subtalar joint destabilization necessitating the control of ankle muscles. Surface electrodes were placed over the tibialis anterior, the peroneus longus, the peroneus brevis, the gastrocnemius lateral, and the gastrocnemius medial. Nine healthy subjects (mean age 37+/-12 yr; mean mass 68+/-17 kg; mean height 1.73+/-0.7 m) were instructed to walk normally along a tape fixed on the floor. The ankle destabilization device altered the walking pattern of all subjects. More specifically, the walking pattern is disturbed resulting in higher amplitude of the EMG activity of the peroneal muscles and the Tibialis Anterior and anticipatory reactions in the peroneal muscles. The results suggest that the ankle destabilization device could be beneficial for rehabilitation programs especially during the training of walking. Using this material may help to a specific reinforcement of muscles involved in anti-inversion ankle movement.