Emotion recognition in amyotrophic lateral sclerosis in a dynamic environment.

OBJECTIVE: The aim of our study was to measure the ability of ALS patients to process dynamic facial expressions as compared to a control group of healthy subjects and to correlate this ability in ALS patients with neuropsychological, clinical and neurological measures of the disease. METHODS: Sixty-three ALS patients and 47 healthy controls were recruited. All the ALS patients also underwent i) the Geneva Emotion Recognition Test (GERT) in which ten actors express 14 types of dynamic emotions in brief video clips with audio, ii) the Edimburgh Cognitive and Behavioral ALS Screen (ECAS) test; iii) the ALS Functional Rating Scale Revised (ALSFRS-R) and iv) the Medical Research Council (MRC) for the evaluation of muscle strength. All the healthy subjects enrolled in the study underwent the GERT. RESULTS: The recognition of irritation and pleasure was significantly different between ALS patients and the control group. The amusement, despair, irritation, joy, sadness and surprise had been falsely recognized differently between the two groups. Specific ALS cognitive impairment was associated with bulbar-onset phenotype (OR = 14,3889; 95%CI = 3,96-52,16). No association was observed between false emotion recognition and cognitive impairment (F(1,60)=,56,971, p=,45,333). The number of categorical errors was significantly higher in the ALS patients than in the control group (27,66 ± 7,28 vs 17,72 ± 5,29; t = 8723; p = 0.001). CONCLUSIONS: ALS patients show deficits in the dynamic processing of a wide range of emotions. These deficits are not necessarily associated with a decline in higher cognitive functions: this could therefore lead to an underestimation of the phenomenon.

Neuromuscular magnetic stimulation counteracts muscle decline in ALS patients: results of a randomized, double-blind, controlled study.

The aim of the study was to verify whether neuromuscular magnetic stimulation (NMMS) improves muscle function in spinal-onset amyotrophic lateral sclerosis (ALS) patients. Twenty-two ALS patients were randomized in two groups to receive, daily for two weeks, NMMS in right or left arm (referred to as real-NMMS, rNMMS), and sham NMMS (sNMMS) in the opposite arm. All the patients underwent a median nerve conduction (compound muscle action potential, CMAP) study and a clinical examination that included a handgrip strength test and an evaluation of upper limb muscle strength by means of the Medical Research Council Muscle Scale (MRC). Muscle biopsy was then performed bilaterally on the flexor carpi radialis muscle to monitor morpho-functional parameters and molecular changes. Patients and physicians who performed examinations were blinded to the side of real intervention. The primary outcome was the change in the muscle strength in upper arms. The secondary outcomes were the change from baseline in the CMAP amplitudes, in the nicotinic ACh currents, in the expression levels of a selected panel of genes involved in muscle growth and atrophy, and in histomorphometric parameters of ALS muscle fibers. The Repeated Measures (RM) ANOVA with a Greenhouse-Geisser correction (sphericity not assumed) showed a significant effect [F(3, 63) = 5.907, p < 0.01] of rNMMS on MRC scale at the flexor carpi radialis muscle, thus demonstrating that the rNMMS significantly improves muscle strength in flexor muscles in the forearm. Secondary outcomes showed that the improvement observed in rNMMS-treated muscles was associated to counteracting muscle atrophy, down-modulating the proteolysis, and increasing the efficacy of nicotinic ACh receptors (AChRs). We did not observe any significant difference in pre- and post-stimulation CMAP amplitudes, evoked by median nerve stimulation. This suggests that the improvement in muscle strength observed in the stimulated arm is unlikely related to reinnervation. The real and sham treatments were well tolerated without evident side effects. Although promising, this is a proof of concept study, without an immediate clinical translation, that requires further clinical validation.

Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment.

BACKGROUND: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (µm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. OBJECTIVE: To analyze the possible beneficial effects of µm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. METHOD: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with µm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. RESULTS: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. CONCLUSION: According to our observations, µm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.

Effects of visual deprivation on primary motor cortex excitability: a study on healthy subjects based on repetitive transcranial magnetic stimulation.

We investigated whether rapid changes in visual input or dark adaptation modify primary motor cortex (M1) excitability in healthy subjects. Repetitive transcranial magnetic stimulation (rTMS), consisting of 10 stimuli delivered at 5 Hz at 120% of the resting motor threshold, was delivered over the M1 in 14 healthy volunteers. They were instructed to relax under eyes-open (EO) and eyes-closed (EC) resting conditions. Two experimental sessions were performed. In the first session, subjects were tested under both EO and EC conditions in order to determine whether short visual deprivation affected M1 excitability as tested through changes in the motor-evoked potential (MEP) amplitude during rTMS. In the second session, rTMS was delivered both under EO conditions with room lights on and after 30 min of blindfolding to evaluate the effects of prolonged visual deprivation on M1 excitability. Short-term visual deprivation lasting 2.5 s left the MEP facilitation unchanged during the 5-Hz rTMS trains, while 30 min of blindfolding significantly reduced MEP facilitation. Short-term visual deprivation did not significantly affect M1 excitability, whereas dark adaptation reduced rTMS-induced MEP facilitation, modulating motor cortical excitability.

Dysphagia in Amyotrophic Lateral Sclerosis: Impact on Patient Behavior, Diet Adaptation, and Riluzole Management.

This retrospective study aimed to investigate the clinical features associated with deteriorated swallow in amyotrophic lateral sclerosis (ALS) patients with spinal and bulbar onset, describe the modification of diet and liquid intake, and assess the impact of dysphagia on the use of riluzole. One hundred forty-five patients were observed periodically every 3-6 months. They underwent routinely fiberoptic endoscopic evaluation of swallowing (FEES) and spirometry; dysphagia severity was classified according to the Penetration Aspiration Scale and the Pooling score (P-score) integrated with other parameters such as sensation, collaboration, and age (P-SCA score). During a mean follow-up period of about 2 years, the percentage of ALS patients suffering from dysphagia increased to 85 (rising from 35 to 73% in patients with spinal onset and from 95 to 98% in those with bulbar onset). Also, 8% of patients with dysphagia by FEES did not perceive the disorder. The frequency of normal and semi-solid diets decreased over time, while that of pureed diets and percutaneous endoscopic gastrostomy (PEG) prescription increased. Forty-four percent of dysphagic patients refused thickeners or PEG. A significant difference was observed in the mortality rate between patients untreated with riluzole and patients treated with riluzole oral suspension (p < 0.05). Disease duration mainly impacted on the frequency of dysphagia in spinal onset patients, appearing very early in those with bulbar onset. Riluzole oral suspension would allow the safe administration in dysphagic ALS patients to avoid tablet crushing and consequent dispersion in food, common practices that are inconsistent with the safe and effective use of the drug.

Laryngeal Sensitivity in Patients with Amyotrophic Lateral Sclerosis.

Recent studies have shown the involvement of the sensory nervous system in patients with amyotrophic lateral sclerosis (ALS). The aim of our study was to investigate the correlation between the laryngeal sensitivity deficit and the type of ALS onset (bulbar or spinal) in a large series of 114 consecutive ALS patients. Participants were subdivided into two groups, bulbar and spinal ALS, according to the clinical onset of disease and submitted to a clinical and instrumental evaluation of swallowing, including a fiber-optic endoscopic evaluation of swallowing with sensory testing. Dysphagia severity was scored using the Penetration-Aspiration Scale (PAS) and the Pooling score (P-score). In addition, three patients with laryngeal sensitivity deficit were submitted to a laryngeal biopsy to assess the status of the sensory innervation. All patients showed a normal glottal closure during phonation and volitional cough. Fifty-six subjects (49%), 14 spinal- and 42 bulbar-onset ALS, showed dysphagia at the first clinical observation (PAS score >1; P-score >5). Dysphagia resulted more frequently in bulbar-onset ALS (P < 0.01). Thirty-eight (33%) patients had a sensory deficit of the larynx. The sensory deficit of the larynx was significantly more frequent in bulbar-onset ALS (P < 0.01). The sensory deficit of the larynx among dysphagic patients was also significantly more frequent in bulbar-onset ALS (P = 0.02). Several abnormalities were found in all three subjects who underwent a laryngeal biopsy: in one patient, no intraepidermal fiber was found; in the other two, the fibers showed morphological changes. Our observations are important to consider for assessment and management of dysphagia in patients with ALS.

Neuromuscular function after muscle fatigue in Charcot-Marie-Tooth type 1A patients.

INTRODUCTION: The effect of recovery time on neuromuscular function after a fatiguing task was compared in both the upper and lower limbs between patients with Charcot-Marie-Tooth type 1A (CMT1A) and healthy individuals. METHODS: Torque of elbow flexors and knee extensors and surface electromyography (sEMG) data of biceps brachii and vastus lateralis were recorded from 8 CMT1A patients and 8 matched, healthy individuals during maximal voluntary contraction (MVC) before (pre-fatigue MVC), 10 s after (10-s post-fatigue MVC), and 10 min after (10-min post-fatigue MVC) a fatiguing task at 80% MVC until exhaustion. RESULTS: Only in the lower limb, torque and root mean square of sEMG (RMS) during pre-fatigue MVC were lower (P < 0.05) in patients (91.93 ± 45.95 Nm, 0.11 ± 0.07 mV) than in controls (161.06 ± 75.5 Nm, 0.24 ± 0.16 mV). In the 10-min post-fatigue MVC, muscle-fiber conduction velocity (MFCV) and RMS, expressed as a percentage of pre-fatigue MVC, were lower (P < 0.05) in patients (MFCV 90.3 ± 6.91%, RMS 84.50 ± 9.89%) than in controls (MFCV 100.87 ± 5.1%, RMS 92.71 ± 11.84%). CONCLUSIONS: CMT1A patients are not only weaker than healthy individuals in the knee extensors, but they also have impaired neuromuscular recovery after fatigue.