The Silent Period for Small Fiber Sensory Neuropathy Assessment in a Mixed Cohort of Transthyretin-Mediated Amyloidosis.

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.

Effects of Skin Stimulation on Sensory-Motor Networks Excitability: Possible Implications for Physical Training in Amyotrophic Lateral Sclerosis.

Background: Many different trials were assessed for rehabilitation of patients with amyotrophic lateral sclerosis (ALS), with non-unique results. Beside the effects on muscle trophism, some of the encouraging results of physical training could be ascribed to the modulation of cortical excitability, which was found hyperexcited in ALS. Objective: The effects of tactile skin stimulation in the modulation of the sensory-motor integrative networks in healthy subjects were assayed through the paired associative stimulation (PAS) protocol. Methods: In total, 15 healthy subjects were enrolled. In the standard PAS session, the average amplitude of the motor evoked potential (MEP) after 10 stimuli of transcranial magnetic stimulation (TMS) was measured at the baseline and after the PAS protocol (0, 10, 20, 30, and 60 min). In the skin stimulation session, the average amplitude of the MEP was measured before and after 10 min of skin stimulation over the hand. Subsequently, each subject underwent the PAS stimulation and the measure of the average amplitude of the MEP (0, 10, 20, 30, and 60 min). Results: The tactile skin stimulation on healthy subjects increases the PAS-induced sensory-motor network hyperexcitability in healthy subjects. Conclusion: Skin stimulation should be avoided in the physiotherapeutic approaches for patients with ALS, given the possible hyperexciting effects on the already upmodulated sensory-motor networks. They can be taken into account for diseases characterized by downregulation of cortical and transcortical networks.

Heteronymous H reflex in temporal muscle as sign of hyperexcitability in ALS patients.

OBJECTIVE: The stimulation of the masseteric nerve elicits a homonymous and a heteronymous H reflex in the masseter muscle and in the temporalis one. The presence of the H reflex may be considered a sign of upper motor neuron (UMN) involvement in amyotrophic lateral sclerosis (ALS) patients. The aim of this study was to evaluate the presence of the heteronymous H reflex in patients with ALS and compare it with normal subjects. METHODS: We enrolled 36 ALS patients and 52 healthy subjects. We stimulated the masseteric nerve in the infratemporal fossa and recorded the muscle responses ipsilaterally to the stimulation. RESULTS: The heteronymous temporalis H reflex was elicitable in 88.9% of ALS patients and in none of the controls. CONCLUSION: The heteronymous H reflex does not disappear when the stimulation intensity is increased. It can be used as sign of UMN involvement and may prove useful in patients with suspected MND/ALS with purely lower motor neurons (LMN) signs and no signs of UMN involvement. SIGNIFICANCE: The heteronymous H reflex is present far more often in ALS patients than in healthy people. It is a simple test that may be used to detect UMN involvement in patients in whom the only evident signs are LMN impairment, improving diagnosis of ALS.

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.

Repetitive transcranial magnetic stimulation for chronic neuropathic pain in patients with bladder pain syndrome/interstitial cystitis.

AIMS: To evaluate the efficacy, safety, and tolerability of repetitive Transcranial Magnetic Stimulation (rTMS) associated with standard drug therapies for neuropathic pain that does not respond to pharmacological treatment alone in patients with Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC). Secondary goals were to assess the effects of rTMS on Lower Urinary Tract Symptoms (LUTS) and Quality of Life (QOL). METHODS: Fifteen patients with BPS/IC were enrolled in this randomized, double-blind, sham stimulation-controlled, crossover study. Patients were treated for 2 weeks with either real-rTMS (for five consecutive days in 20-min sessions) or sham-rTMS (for five consecutive days in 20-min sessions). After a 6-week washout period, the patients who had previously undergone real-rTMS underwent sham-rTMS, and vice versa. Patients were rated at each visit by means of questionnaires on pain, urinary disturbances, depression, and QOL. RESULTS: The statistical analysis revealed significant effects of real-rTMS, when compared with sham-rTMS, on pain (in the VAS, Functional Neuropathic Pelvic Pain, Neuropathic Pain Symptom Inventory, McGill questionnaire, and Central Sensitization Inventory), urinary LUTS (in the Overactive Bladder Questionnaire score, bladder emptying, and daily urinary frequency), and QOL (in the subscores of the SF-36 related to physical pain and to emotional status). No serious adverse events were reported during the study. CONCLUSIONS: The results of this study show that rTMS applied with an H-coil over the M1 in the area corresponding to the pelvic region in patients with BPS/IC appears to improve chronic pelvic pain (CPP) and associated urinary disorders.

Partial block by riluzole of muscle sodium channels in myotubes from amyotrophic lateral sclerosis patients.

Denervated muscles undergo fibrillations due to spontaneous activation of voltage-gated sodium (Na(+)) channels generating action potentials. Fibrillations also occur in patients with amyotrophic lateral sclerosis (ALS). Riluzole, the only approved drug for ALS treatment, blocks voltage-gated Na(+) channels, but its effects on muscle Na(+) channels and fibrillations are yet poorly characterized. Using patch-clamp technique, we studied riluzole effect on Na(+) channels in cultured myotubes from ALS patients. Needle electromyography was used to study fibrillation potentials (Fibs) in ALS patients during riluzole treatment and after one week of suspension. Patients were clinically characterized in all recording sessions. In myotubes, riluzole (1 µM, a therapeutic concentration) reduced Na(+) current by 20%. The rate of rise and amplitude of spikes evoked by depolarizing stimuli were also reduced. Fibs were detected in all patients tested during riluzole treatment and riluzole washout had no univocal effect. Our study indicates that, in human myotubes, riluzole partially blocks Na(+) currents and affects action potentials but does not prevent firing. In line with this in vitro finding, muscle Fibs in ALS patients appear to be largely unaffected by riluzole.