Muscle & Nerve最新文献

Electrical Interference (EI: radiated electromagnetic and/or power line interference) is a common problem in clinical neurophysiology with many causes and thus various conceivable solutions. Although newer digitized electrodiagnostic (EDX) systems have markedly reduced EI issues, it remains a possible impediment in achieving high quality studies. So that the electrodiagnostic medicine consultant (EMC) can problem solve EI, this monograph details the fundamental functional concepts and terminology of electronic amplification and recording electrodes from a practical perspective. This information is then utilized in a proposed standard operating protocol (SOP) to help the EMC address a wide variety of EI sources. Three major EI sources are considered: the EDX system/operator error, the environment, and the patient. The first is a thorough assessment of the recording electrodes from the perspective of clean electrodes, security of attachment, appropriate gel application, proper lead connections to both the patient and instrument, and similarity of electrode composition. Second is how adverse environmental conditions are mitigated through isolating the EDX instrument from nearby large generator sources, unplugging unnecessary equipment, keeping the amplifier close to the patient along with short and braided electrode leads, and utilize filtering (both 60 Hz and total bandwidth) with appropriate caution to avoid unwanted signal distortion. Third, the patient and EMC interaction must be considered. Specifically, all electronic devices that can be removed should be powered down and relocated as far as feasible from the EDX system, including digital watches, cell phones, TENS units, and other such devices. A systematic application of the above proposed protocol should solve the majority of EI issues.

Introduction/aims: Risdiplam was the first orally administered drug approved to treat spinal muscular atrophy (SMA). Efficacy in adults is based on short-term observational studies. This longitudinal study aimed to examine risdiplam's efficacy and safety in adults over a long period of follow-up.

Methods: All eligible SMA patients ≥ 16 years old, followed at the Muscular Dystrophy Association Hellas Neuromuscular Diseases Unit between April 2021 and December 2023, were included. We prospectively evaluated motor function, muscle strength, and pulmonary function before and after 6, 12, 18, 24, and 30 months of treatment. Laboratory assessments and patient-reported adverse events were recorded.

Results: Overall, 14 patients (18-57 years, 93% treatment-naive) received risdiplam for a median period of 28.5 months (range 6-30). There were statistically significant improvements in the Hammersmith Functional Motor Scale-Expanded (mean difference [MD] 1.5 [95%CI 0.49-2.42]), Revised Upper Limb Module (MD 1.6 [95%CI 0.54-2.73]), Motor Function Measurement-32 (MD 2.7[95%CI 1.52-3.93]), Medical Research Council scores of the upper (MD 3 [95%CI 0.8-5.2]), and lower (MD 1.7 [95%CI 0.1-3.3]) limbs (all p ≤ 0.05). Eighty-two percent of patients achieved a clinically meaningful improvement (CMI) in at least one scale. Overall, CMI occurred earlier in type 3 patients. SMA functional rating scale and respiratory function tests remained stable over time. Fifty-seven percent of patients did not report any adverse events. None discontinued treatment.

Discussion: Risdiplam treatment over 30 months resulted in overall CMI in most treated adult SMA type 2 or 3 patients. Outpatient drug administration and overall patient management proved feasible and safe. Larger studies are warranted.

Introduction: A 20 kDa fragment at the N-terminus of titin is highly excreted in the urine of patients with Duchenne muscular dystrophy (DMD), making urine titin a prominent biomarker for muscle breakdown. This N-terminal fragment is presumed to be a product of degradation by a protein-degrading enzyme, calpain 3; however, whether calpain 3 is required remains unclear. We aimed to determine whether urine titin elevation occurs in the absence of calpain 3.

Methods: We measured urine titin by ELISA in two genetically confirmed limb-girdle muscular dystrophy type R1(LGMDR1) patients, 11 other LGMD patients, and five healthy controls. Five Capn3-/- and nine wild-type mice were also examined.

Results: Urine titin in LGMDR1 patients was ~100-fold higher than in controls (median 112.3 vs. 1.3 pmol/mg Cr, p < 0.0001), with no difference between LGMDR1 and other LGMD subtypes. Similarly, urine titin levels in Capn3-/- mice were more than four times higher than normal (p < 0.01).

Discussion: These results suggest the involvement of other protein-degrading enzymes leading to the production of the N-terminal fragment.

Magnetic resonance neurography (MRN) is increasingly used in clinical practice for the evaluation of patients with a wide spectrum of peripheral nerve disorders. This review article discusses the technical aspects of MRN highlighting the core sequences performed for clinical care. A robust, high-resolution, heavily T2-weighted fluid-sensitive sequence performed on a 3.0 Tesla magnet system remains the main workhorse MRN sequence. In specific clinical scenarios, adjunct techniques such as diffusion-weighted imaging can be added to a protocol for disease characterization. In addition, gadolinium-based contrast material can also be administered for the purposes of image optimization (suppress adjacent vascular signal) and disease characterization. Technical modifications to field of view and planes of imaging can be made based on the clinical question and discussion with the radiologist(s). On fluid-sensitive MRN sequences, a normal peripheral nerve exhibits iso- to minimally hyperintense signal relative to skeletal muscle with a predictable trajectory, preserved "fascicular" architecture, and tapered caliber from proximal to distal. Peripheral nerve abnormalities on MRN include alterations in signal, caliber, architecture, diffusion characteristics as well as enhancement and provide information regarding the underlying etiology. Although some MRN findings including nerve hyperintensity and long-segmental enlargement are nonspecific, there are certain diagnoses that can be made with high certainty based on imaging including benign peripheral nerve tumors, high-grade peripheral nerve injury, and intraneural ganglia. The purpose of this article is to familiarize a neuromuscular clinician with fundamentals of MRN acquisition and interpretation to facilitate communication with the neuromuscular radiologist and optimize patient care.

Introduction: Motor recovery following nerve injury is dependent on time required for muscle reinnervation. This process is imperfect, however, and recovery is often incomplete. At the neuromuscular junction (NMJ), macrophage signaling aids muscle reinnervation. Tacrolimus (FK506) treatment speeds functional recovery through unknown mechanisms. This study investigated whether macrophages were required for FK506 neuroenhancing effects.

Methods: Wildtype (WT) mice and mice with impaired macrophage recruitment to injury sites (Ccr2 ^-/- ) were injected subcutaneously with either saline or FK506 for 3 days prior to sciatic nerve transection and immediate repair and then daily for 4 weeks. Functional recovery was assessed by grid walk and muscle force. Morphometric NMJ and macrophage analyses were conducted in extensor digitorum longus muscles.

Results: FK506-injected WT mice showed increased proportions of fully reinnervated NMJs and terminal Schwann cells/NMJ (p < 0.05), improved recovery of tetanic muscle force (p < 0.05), and improved grid walking (p < 0.05) relative to controls. Ccr2 ^-/- mice showed no enhancements in recovery; Ccr2 ^-/- mice treated with FK506 did not differ from controls on any tested metric. We also observed at the NMJ of WT mice increased macrophage numbers with FK506 treatment and increased macrophages expressing FK506 binding protein, FKBP52, after nerve injury.

Discussion: These results show that macrophages are required for FK506-mediated improvements in NMJ reinnervation and muscle function. These data implicate macrophages in the mechanism underlying FK506-mediated enhancement of motor recovery after nerve injury. Enhanced knowledge of the neuroenhancing mechanism of FK506 may identify new clinically relevant therapeutic targets.

Introduction/aims: Literature on the role of gastrostomy and noninvasive ventilation (NIV) in primary lateral sclerosis (PLS) is limited. We aim to investigate whether PLS patients develop dysphagia requiring feeding tubes or respiratory failure necessitating NIV.

Methods: We conducted a retrospective study of PLS patients with a definite diagnosis followed at our center (1994-2024). Patients with marked dysphagia (score < 3 on Question 3 of the ALSFRS-R) received a recommendation for gastrostomy and were divided into two groups: G1/G2 (accepted/declined gastrostomy). We investigated NIV indications due to respiratory failure and compared these patients (G3) to those without respiratory impairment (G4). Demographic, clinical, and neurophysiological data were collected and compared.

Results: Forty-eight patients had a definite diagnosis of PLS. Gastrostomy was recommended to 18 (37.5%), yet only 7 patients (38.9%-G1) consented. The median time to gastrostomy was 77 months. Total survival and survival post-gastrostomy recommendation were not different between G1 and G2. Six PLS patients (12.5%-G3) developed respiratory failure and initiated NIV (median of 63 months). At 63 months, G3 had significantly lower median forced vital capacity (65% vs. 99%; p < 0.001) and phrenic nerve amplitude (0.43 vs. 0.75 mV; p = 0.039), but a greater ALSFRS-R slope (0.34 vs. 0.14; p = 0.046) and shorter survival (35 vs. 94.9 months; p = 0.009) compared to G4.

Discussion: Dysphagia requiring gastrostomy was common in our PLS cohort, but survival after gastrostomy recommendation did not differ between groups. Patients who developed respiratory impairment may represent a distinct group with faster disease progression and shorter survival. Our findings may contribute to a deeper understanding and improved management of PLS.

Introduction/aims: Neuromuscular ultrasound (NMUS) is gaining prominence as a valuable tool for diagnosing neuromuscular disorders at the point of care. Neuromuscular disorder diagnostic criteria guidelines have begun incorporating NMUS findings. As interest grows, fellowship programs must consider incorporating training into their curricula. This study evaluated the current state of NMUS training, potential barriers, and interest in training across Canadian neuromuscular fellowship programs.

Methods: A 23-question online survey was developed and distributed via email to all 10 neuromuscular fellowship program directors across Canada.

Results: Seven (70%) programs responded to the survey. There was general agreement among programs on the value of NMUS, however, only one (14.3%) program reported they would consider recent graduates to be competent in NMUS. Critical barriers to incorporation of NMUS training included lack of a formalized curriculum, faculty expertise and time, and equipment. Two (28.6%) programs reported that accessibility of equipment and one (14.3%) that faculty expertise was not a barrier to NMUS training. Two (28.6%) programs have local NMUS training options available to fellows (in only one program is NMUS training mandatory). All programs expressed interest in additional training opportunities, and three (43%) programs reported taking steps toward incorporating NMUS training into their curricula.

Discussion: NMUS training is in its infancy in Canada, with several common barriers identified across programs. There is universal interest in further NMUS training opportunities for fellows, highlighting the importance of a common approach to addressing the educational gap to support development of formalized NMUS training mechanisms in Canada.

Introduction/aims: Tofacitinib, a first-generation Janus kinase (JAK) 1/3 inhibitor, is commonly used for treating ulcerative colitis and rheumatoid arthritis. However, its role in myasthenia gravis (MG) remains unclear. This study aimed to evaluate the immunomodulatory effects of tofacitinib on experimental autoimmune myasthenia gravis (EAMG) and peripheral blood mononuclear cells (PBMCs) from patients with MG.

Methods: Flow cytometry, enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot were used to evaluate the effects of tofacitinib on T helper (Th) cell profiles, humoral immune responses, and the JAK-signal transducer and activator of transcription (STAT) pathway proteins.

Results: In vivo, tofacitinib significantly ameliorated EAMG severity in rats, reducing the proportions of Th1, Th17 and memory B cells, and anti-acetylcholine receptor (AChR) antibodies levels, while increasing the proportions of regulatory T (Treg) cells. In vitro, tofacitinib administration resulted in a significant decrease in the proportions of Th1 and IgG-secreting B cell, and a significant upregulation of Treg cells in mononuclear cells (MNCs) from EAMG rats, which was consistent with findings in PBMCs from MG patients. Further analysis revealed that tofacitinib inhibited CD4⁺ T cell differentiation into Th1 by decreasing phosphorylated STAT1 levels, while promoting Treg differentiation via increased phosphorylated STAT5 levels in MNCs from EAMG rats.

Discussion: Tofacitinib modulates Th cell profiles and humoral immune responses by targeting the JAK-STAT pathway, suggesting its potential as a therapeutic candidate for MG. Further clinical studies are warranted to evaluate the efficacy and safety of tofacitinib in MG patients.

Introduction/aims: A previous randomized controlled trial showed that guided self-help acceptance and commitment therapy plus standard medical care (ACT+SMC) was superior to standard medical care alone (SMC) for improving quality of life (QoL) and mood at 9-weeks post randomization in a sample of people with muscle disorders (MD). This follow-up study evaluated whether these effects were maintained in the longer term alongside individual patterns of response.

Methods: The original study was a two-arm parallel group randomized controlled trial, which compared ACT+SMC to SMC. The primary outcome of QoL was assessed with the Individualized Neuromuscular Quality of Life Questionnaire. We recruited people with different MDs from UK National Health Service clinics and patient registries. In this follow-up study, we re-administered all outcome measures to participants at 6 months post randomization.

Results: Questionnaires were completed by 109 participants (70.3% of the original sample). At six months, the adjusted group difference in QoL continued to favor ACT+SMC, which was significant with moderate effect size. Improvements in secondary outcomes of mood and aspects of psychological flexibility also favored ACT+SMC. Reliable improvement was evident in 33.9% of the ACT+SMC group and 5.7% of the SMC group. Reliable deterioration was uncommon following ACT+SMC (1.8% of participants.) DISCUSSION: The beneficial impacts of guided self-help ACT for QoL and mood were maintained in the longer-term. A third of participants showed response to this brief intervention, and negative individual outcomes were very rare. As is common in psychological interventions, there was a considerable group of non-responders.

Introduction: Extrapolated reference values (E-Ref) procedure is a new method for determining the cutoff value without collecting the control data. We tried to apply this method to determine the cutoff value for the distal motor latency of the median nerve (median DML). During this process, we found two pitfalls of the E-Ref method. First, the E-Ref procedure did not correctly work when the DML values measured with 0.1 ms accuracy frequently took on tie values. Second, the result was influenced by the proportion of abnormal values. This study investigated these issues.

Methods: Data of the median DML were extracted from our laboratory database. To solve the problem of tie values, we tried a wider post-smoothing window in the original E-Ref method. We also devised a modified method conducting pre-smoothing. To see the effect of the proportion of abnormal data, we simulated many datasets having different proportion of abnormal data.

Results: In total, 1016 DML values were identified. False deflections due to tie values were often identified as the E-Ref point using the original methods even using a wider window, resulting in unrealistically low values. Modified method was free from this drawback. For all methods, the E-Ref value increased as the proportion of abnormal values increased.

Discussion: The problem of tie values, a pitfall of the E-Ref method, might be solved by pre-smoothing the data. The E-Ref value is influenced by the proportion of the normal data, and datasets containing less than 20% abnormal data may achieve appropriate results.