Search Results (4)

Amyotrophic lateral sclerosis (ALS) is a progressive disease of both upper motor neurons (UMNs) and lower motor neurons (LMNs) leading invariably to decline in motor function. The clinical exam is foundational to the diagnosis of the disease, and ordinal severity scales are used to track its progression. However, the lack of objective biomarkers of disease classification and progression delay clinical trial enrollment, muddle inclusion criteria, and limit accurate assessment of drug efficacy. Ultimately, biomarker evidence of therapeutic target engagement will support, and perhaps supplant, more traditional clinical trial outcome measures. Electrophysiology tools including nerve conduction study and electromyography (EMG) have already been established as diagnostic biomarkers of LMN degeneration in ALS. Additional understanding of the motor manifestations of disease is provided by motor unit number estimation, electrical impedance myography, and single-fiber EMG techniques. Dysfunction of UMN and non-motor brain areas is being increasingly assessed with transcranial magnetic stimulation, high-density electroencephalography, and magnetoencephalography; less common autonomic and sensory nervous system dysfunction in ALS can also be characterized. Although most of these techniques are used to explore the underlying disease mechanisms of ALS in research settings, they have the potential on a broader scale to noninvasively identify disease subtypes, predict progression rates, and assess physiologic engagement of experimental therapies. Full article

Objective: Motor unit number estimation (MUNE) methods are crucial for estimating lower motor neuron loss in motor neuron diseases. The MScanFit MUNE (MScanFit) is a novel method that estimates MUNE values from compound motor action potential (CMAP) scans, demonstrating high sensitivity and reproducibility in detecting motor unit loss in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we aimed to characterize the pattern of motor unit loss in the hand intrinsic muscles of SMA patients compared to ALS patients and healthy controls (HC) using MScanFit MUNE. Methods: Patients diagnosed with ALS, adult SMA patients, and HC were prospectively enrolled. MScanFit examinations were performed on the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. To focus on the different patterns of motor neuron degeneration in the intrinsic hand muscles, the ratio of CMAP amplitude of APB to ADM (CMAP ratio) and the ratio of MUNE values of APB to those of the ADM muscle (MUNE ratio) were calculated. Results: The study included 46 ALS patients, 16 SMA patients, and 23 HC. MScanFit MUNE revealed distinct patterns of motor unit degeneration in SMA patients, notably more severe in the ADM than in the APB muscle, indicating a “reverse” split-hand phenomenon. Both CMAP and MUNE ratios demonstrated high diagnostic accuracy in distinguishing ALS from SMA, with the MUNE ratio performing better. Conclusions: MScanFit MUNE is a valuable tool for exploring distinct patterns of motor neuron degeneration in patients with different types of motor neuron diseases. Full article

Background: Vascularized nerve grafts (VNGs) have been proposed as a superior alternative to free nerve grafts (FNGs) for complex nerve defects. A greater regenerative potential has been suggested by clinical and experimental studies, but conclusive evidence is still lacking. Methods: In this experimental study, 10 adult male Wistar rats received a non-vascularized orthotopic sciatic nerve graft on their right side, and a vascularized orthotopic sciatic nerve graft nerve on their left side. Functional outcome following nerve regeneration was evaluated through electrodiagnostic studies, target muscles weight and histomorphology, and data of VNGs and FNGs were compared. Results: The results of this study showed a significant difference in the motor unit number of Gastrocnemius Medialis (GM) estimated by MUNE in the VNG side compared to the FNG side. No other significant differences in axonal regeneration and muscle reinnervation were evident at either electrodiagnostic, histomorphology studies or muscle weight. Conclusions: This experimental model showed slight differences in nerve regeneration between VNGs and FNGs, but cannot support a high clinical advantage for VNGs. The results of this study show that VNGs are not strongly superior to FNGs in the rat model, even in avascular beds. Clinical advantages of VNGs are likely to be limited to extensive and thick nerve defects and can only be assessed on experimental model with bigger animals. Also, we showed that the MUNE technique provided a reliable and reproducible evaluation of functional outcomes in the rat sciatic nerve and defined a reproducible protocol for functional evaluation of muscle reinnervation. Full article

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O⁻²) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. Results and Discussion: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS. Full article