Background: Transthyretin-mediated amyloidosis (ATTR) is a rare multisystemic disease involving the peripheral nervous system and heart. Autonomic and small fiber involvement is one of the hallmarks of ATTR, and many tools have been proposed to assess this aspect. Aim: The aim of this study was to investigate cutaneous and mixed nerve silent periods (CSP and MnSP) as instruments for small fiber assessment. Methods: A total of 21 ATTR patients, 20 healthy controls, and 18 asymptomatic carriers underwent a sensory conduction study from the right sural and non-dominant ulnar nerves. A motor conduction study from the right deep peroneal and non-dominant ulnar nerves, with their F waves, CSPs, and MnSPs, was performed. Results: The amplitudes of the sural and ulnar sensory nerves and of the peroneal and ulnar motor nerves were reduced in ATTR patients compared to the other groups. F waves from the ulnar and peroneal nerves showed no differences between the three groups. The CSP and MnSP latency, but not amplitude, were increased in both the ulnar and peroneal nerves of ATTR patients. Conclusions: ATTR patients showed axonal involvement of large sensory and motor nerve fibers and demyelinating features of small sensory fibers.

Recently, the endocannabinoid system has attracted growing attention from the scientific community for its involvement in homeostatic and pathological processes as they pertains to human physiology. Among the constituents of the endocannabinoid system, the molecule palmitoyl ethanolamide has particularly been studied for its ability to reduce several inflammatory processes involving the central nervous system. Here, we reviewed published literature and summarized the main targets of the palmitoyl ethanolamide, along with its unique possible mechanisms for restoring correct functioning of the central nervous system. Moreover, we have highlighted a less-known characteristic of palmitoyl ethanolamide, namely its ability to modulate the function of the neuromuscular junction by binding to acetylcholine receptors in different experimental conditions. Indeed, there are several studies that have highlighted how ultra-micronized palmitoyl ethanolamide is an interesting nutraceutical support for the treatment of pathological neuromuscular conditions, specifically when the normal activity of the acetylcholine receptor is altered. Although further multicentric clinical trials are needed to confirm the efficacy of ultra-micronized palmitoyl ethanolamide in improving symptoms of neuromuscular diseases, all the literature reviewed here strongly supports the ability of this endocannabinoid-like molecule to modulate the acetylcholine receptors thus resulting as a valid support for the treatment of human neuromuscular diseases.

Transthyretin-mediated amyloidosis (ATTR) is a systemic disease with protein precipitation in many tissues, mainly the peripheral nerve and heart. Both genetic (ATTRv, “v” for variant) and wild-type (ATTRwt) forms are known. Beyond the steric encumbrance, precipitated transthyretin seems to have a toxic effect. In this study carried out in men, we recruited 15 ATTRv patients, 7 ATTRv asymptomatic carriers, 14 ATTRwt patients and 10 young and 13 old healthy controls to evaluate the oxidative stress using FORD (Free Oxygen Radicals Defense) and FORT (Free Oxygen Radicals Test) analyses. ATTRv patients showed reduced FORD compared to ATTRwt and ATTRv asymptomatic carriers. FORD independently predicted the disease stage, with the early stages characterized by the highest consumption. These findings suggest a role for oxidative stress in the early stages of ATTRv.

Background: 3,4-diaminopyridine (3,4-DAP) can lead to clinical and electrophysiological improvement in myasthenic syndrome; it may thus represent a valuable therapeutic option for patients intolerant to pyridostigmine.Objective: to assess 3,4-diaminopyridine (3,4-DAP) effects and tolerability in patients with anti-AChR myasthenia gravis.Method: Effects were monitored electrophysiologically by repetitive nerve stimulation (RNS) and by standardized clinical testing (QMG score) before and after a single dose administration of 3,4-DAP 10 mg per os in 15 patients. Patients were divided according to their Myasthenia Gravis Foundation of America (MGFA) class into mild and severe.Results: No significant side effects were found, apart from transient paresthesia. 3,4-DAP had a significant effect on the QMG score (p = 0.0251), on repetitive nerve stimulation (p = 0.0251), and on the forced vital capacity (p = 0.03), thus indicating that it may reduce the level of disability and the decremental muscle response. When the patients were divided according to the MGFA classification, 3,4-DAP showed a positive effect in the severe group, either for the QMG score (p = 0.031) or for the RNS decrement (p = 0.031). No significant difference was observed in any of the outcome measures within the mild group (p > 0.05). A direct effect of 3,4-DAP on nicotinic ACh receptors (nAChRs) was excluded since human nAChRs reconstituted in an expression system, which were not affected by 3,4-DAP application.Conclusion: Our results suggest that 3,4-DAP may be a useful add-on therapy, especially in most severe patients or when immunosuppressive treatment has not yet reached its full effect or when significant side-effects are associated with anticholinesterase.

Background/Objectives: Hereditary transthyretin-mediated amyloidosis (ATTRv) is a rare disease characterized by the deposition of amyloid in the heart and peripheral nerves, particularly affecting small fibers. This study aims to evaluate autonomic cardiac involvement in ATTRv. Methods: Twelve patients with ATTRv and twelve sex- and age-matched healthy subjects underwent ¹²³I-mIBG scintigraphy to evaluate the early and late heart-to-mediastinum ratio (eH/M and lH/M), ^99mTc-HDP bone scan scintigraphy, and neurophysiological assessments. Data were analyzed in relation to functional cardiac and neurologic scales (NYHA and FAP scales). Results: Patients with ATTRv exhibited significant cardiac denervation, as demonstrated by the reduction in early and late H/M ratios compared to the control group (eH/M: 1.48 ± 0.08 vs. 1.89 ± 0.05, p < 0.001; lH/M: 1.39 ± 0.08 vs. 2.01 ± 0.05, p < 0.001). Values of eH/M and lH/M < 1.6 effectively differentiated patients with ATTRv from the healthy controls. Cardiac denervation correlated with interventricular septal thickness and the Perugini score but was not related to neurophysiological assessments or NYHA and FAP scales. Conclusions: Ultimately, ¹²³I-mIBG scintigraphy is an effective tool for assessing cardiac denervation in patients with ATTRv.

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.