Loss of muscle thickness can be demonstrated in a wide spectrum of neuromuscular disorders, while fasciculations are more frequent in amyotrophic lateral sclerosis (ALS). In the current study, we ...aimed to determine the sensitivity and specificity of quantitative sonographic assessment of muscle thickness and the presence of fasciculations for diagnosing various neuromuscular disorders. The thickness and the presence of fasciculations in eight muscles were determined by sonography in patients with myopathy (22), polyneuropathy (36), ALS (91), and spinal muscular atrophy (SMA) (31) and compared to normative values determined in 65 heathy control subjects. Reduced muscle thickness in at least one relaxed muscle showed 92-100% sensitivity for diagnosing a neuromuscular disease, with a specificity of 85% for differentiating patients from heathy controls (AUC = 0.90). Subtracting distal from proximal muscle thickness may differentiate between myopathy and polyneuropathy. Fasciculations in greater than or equal to1 proximal muscle showed good diagnostic accuracy (AUC = 0.87) for diagnosing ALS. Sonographic assessment of muscle thickness is a sensitive tool for diagnosing a wide spectrum of neuromuscular diseases, and may facilitate diagnosis even in patients with normal strength on neurological examination, while the presence of fasciculations in proximal muscles may facilitate ALS diagnosis.
Uric acid (UA) is considered to be one of the most important antioxidants in the blood. While high UA levels are found in many disease states, low UA levels are reported in many neurodegenerative ...diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). Various studies showed consistently that ALS patients have lower serum UA levels than healthy individuals, more prominently in cases with bulbar onset and longer disease duration. A systematic search of PubMed was conducted to retrieve published studies on UA levels in ALS patients. A meta-analysis was performed on published studies comparing UA levels between ALS patients and controls. This meta-analysis revealed highly statistically significant (
p
< 0.0001) lower UA levels and a very large size effect in 311 ALS patients compared to 515 controls as a group, as well as calculated for men and women separately. Many studies indicate that patients with neurodegenerative diseases, including ALS, have low UA levels. Our meta-analysis strengthens these findings in ALS patients, demonstrating highly statistically significant (
p
< 0.0001) lower UA levels in patients compared to controls, with very large total size effect, more prominent in men.
•Split hand index determined by sonography can aid in ALS and spinal muscular atrophy (SMA) diagnosis.•Split hand index determined by sonography is superior to abductor pollicis brevis/abductor ...digiti minimi and thenar index.•Thenar index determined by sonography is not useful for SMA diagnosis.
To explore the diagnostic accuracy of the split-hand index (SHI) for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) using sonographic assessment of muscle thickness.
We performed a prospective sonographic assessment of hand muscle thickness in 59 controls, 87 patients with ALS, and 33 patients with SMA. We determined the diagnostic accuracy of SHI for differentiating patients with ALS and SMA from controls.
Patients with ALS and SMA had significantly lower muscle thickness and SHI values compared with controls. SHI showed excellent diagnostic accuracy for differentiating ALS from controls, and good diagnostic accuracy for differentiating SMA from controls.
SHI determined by sonographic measurement of hand muscle thickness seems to be a promising tool for the diagnosis of ALS and may be added easily when performing neuromuscular ultrasound.
SHI determined by sonographic measurement of hand muscle thickness can differentiate between healthy subjects and patients with ALS and SMA.
Introduction
Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we have explored the association between fasciculation frequency ...in a single location—biceps brachii and brachialis muscles (BB), and disease burden and activity.
Methods
Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow‐up. The association between fasciculations frequency at the BB and ALS Functional Rating Scale—Revised (ALSFRS‐R) and manual muscle testing (MMT) scores was determined.
Results
High fasciculation frequency at the BB, where detection rate was the highest, was associated with shorter disease duration, greater muscle thickness, higher MMT scores, and faster rate of decline in ALSFRS‐R initially, and MMT subsequently.
Discussion
High fasciculation frequency at the BB as determined by sonography, is associated with less impairment at time of examination, and a more active disease with a more rapid progression.
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance ...mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis.
Background
In the current study, we aimed to determine normative values for muscle thickness and fasciculation prevalence in healthy subjects.
Methods
We performed a prospective study from October to ...December 2018 in 65 healthy subjects. All subjects underwent quantitative sonographic evaluation of muscle thickness and fasciculation prevalence in the following 8 muscles: Biceps brachii, abductor pollicis brevis, first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis.
Results
Subject ages ranged from 21 to 82 years, with 63% women. Normative values for muscle thickness were determined using the fifth percentile. Multivariate regression analysis showed that sex, age, body mass index, and hand dominance affected muscle thickness. Fasciculations were observed frequently only in distal muscles.
Conclusions
Normal values for muscle thickness were determined, and may enhance neuromuscular ultrasound sensitivity and serve as a basis for future studies. Larger series are needed to confirm these values.
•37 adults with SMA 2–3 treated with nusinersen, followed for up to 30 months of treatment.•Median MRC score increased from baseline to visits at 6 and 14 months, not afterwards.•The median rate of ...MRC score increase was 1.85 points per year.•Revised hammersmith scale median score increased only from baseline to 6 months.•Revised hammersmith scale's calculated annual rate of change was 0 points.
The effectiveness of nusinersen treatment in patients with spinal muscular atrophy (SMA) was established in clinical trials only for pediatric patients. Few cohort studies confirmed its benefit in adults up to 22 months of treatment. We report a longer-term observation of nusinersen treatment effects and safety in a large cohort of adult patients. Patients with SMA type 2 and 3 treated with nusinersen at Tel-Aviv Medical Center between March 2018 and September 2020 were prospectively recruited. Neurological impairment, motor, respiratory function, and side effects were recorded. We compared baseline measurements with those after 6, 14, and 26 months of treatment and calculated the annual rates of change. Overall, 37 patients were treated (21–64 years old). 16 completed 26 months, and 8 completed 30 months of treatment. The median score on the Medical Research Council strength scale increased from baseline to visits at 6 and 14 months (p ≤ 0.03), but not afterwards, with a median increase of 1.85 points per year. Revised Hammersmith Scale median score increased only from baseline to 6 months (p = 0.02), with a calculated annual rate of change of 0 points. No significant change was noticed in the respiratory function. The only side effect was post lumbar puncture headache. In conclusion, our study further supports the efficacy and safety of nusinersen treatment in adult patients with SMA2 and SMA3, with modest improvement in muscle strength, and stabilization of motor function over a relatively long period of observation.
•Sonography of contracted muscle thickness shows strong correlations with clinical scales.•Contracted muscle thickness shows better correlations with clinical measures than relaxed muscle.•Contracted ...muscle thickness measurement is more reliable than relaxed muscle measurement.
To compare the correlations of relaxed and contracted limb muscle thickness with clinical scales in patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).
Patients with ALS and SMA were prospectively recruited from December 2018 to November 2019. All patients underwent clinical assessment and sonographic muscle thickness measurement of eight relaxed muscles (biceps brachii, abductor pollicis brevis (APB), first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis), and four contracted muscles (biceps brachii, APB, quadriceps, and tibialis anterior).
91 patients with ALS and 31 patients with SMA were recruited. Contracted muscle thickness compared to relaxed muscle showed higher reliability and similar or better correlations with muscle strength and clinical scales, especially in ALS patients with hyperreflexia. Strong to very strong correlations with clinical scales were observed with multivariate analysis of relaxed and contracted muscle thickness (0.64–0.87).
Sonographic evaluation of contracted muscle thickness is an objective measure that correlates with disease burden. It is feasible, quick, valid and reliable, and may be superior to evaluation of relaxed muscles.
Sonographic evaluation of contracted muscle thickness is superior to evaluation of relaxed muscles.
PDF
