Muscle hypertrophy following acquired neurogenic injury: systematic review and analysis of existing literature.

OBJECTIVES: Neurogenic muscle hypertrophy (NMH) is a rare condition characterized by focal muscle hypertrophy caused by chronic partial nervous injury. Given its infrequency, underlying mechanisms remain poorly understood. Inspired by two clinical cases, we conducted a systematic review to gain insights into the different aspects of NMH. METHODS: We systematically searched online databases up until May 30, 2023, for reports of muscle hypertrophy attributed to acquired neurogenic factors. We conducted an exploratory analysis to identify commonly associated features. We also report two representative clinical cases. RESULTS: Our search identified 63 reports, describing 93 NMH cases, to which we added our two cases. NMH predominantly affects patients with compressive radiculopathy (68.4%), negligible muscular weakness (93.3%), and a chronic increase in muscle bulk. A striking finding in most neurophysiological studies (60.0%) is profuse spontaneous discharges, often hindering the analysis of voluntary traces. Some patients exhibited features consistent with more significant muscle damage, including higher creatine phosphokinase levels, muscle pain, and inflammatory muscle infiltration. These patients are sometimes referred to in literature as "focal myositis." Treatment encompassed corticosteroid, Botulinum Toxin A, decompressive surgery, antiepileptic medications, and nerve blocks, demonstrating varying degrees of efficacy. Botulinum Toxin A yielded the most favorable response in terms of reducing spontaneous discharges. INTERPRETATION: This systematic review aims to provide a clear description and categorization of this uncommon presentation of an often-overlooked neurological disorder. Though questions remain about the underlying mechanism, evidence suggests that aberrant fiber overstimulation along with increased workload that promotes focal damage may result in muscle hypertrophy. This may serve as a guide for therapeutic interventions.

Overcoming therapeutic challenges: Successful management of a supposedly triple seronegative, refractory generalized myasthenia gravis patient with efgartigimod.

BACKGROUND AND PURPOSE: This study was undertaken to highlight neonatal Fc receptor inhibition (efgartigimod) as a valuable therapeutic option for patients with refractory seronegative myasthenia gravis (MG) and to emphasize the concept that seronegative MG is greatly constrained by the limitations of currently available diagnostic methods and therapeutic measures. METHODS: We describe the first refractory, generalized MG (gMG) patient successfully treated with efgartigimod after testing negative on standard autoantibody detection tests. RESULTS: Our patient presented with severe fluctuating bulbar and generalized weakness, resulting in multiple myasthenic crises requiring intubation. After a 28-year medical history of multiple failed lines of treatment, our patient was started on efgartigimod. Over five treatment cycles, a definite improvement in her clinical condition was observed (Myasthenia Gravis Foundation of America class: IIIb to IIb; MG-Activities of Daily Living score: 11 to 0; MG-Quality of Life 15 score: 30 to 0; Quantitative MG score: 28 to 6). Standard autoantibody detection tests failed to detect known pathogenic autoantibodies, but cell-based assay (CBA) identified autoantibodies against clustered adult acetylcholine receptor (AChR). CONCLUSIONS: In light of recent approvals of efgartigimod by the European Medicines Agency and US Food and Drug Administration exclusively for AChR-positive gMG forms, our case highlights evidence suggesting that such an approach might be shortsighted and could limit therapeutic options for patients with refractory seronegative gMG. Additionally, introducing more sensitive analytical techniques, exemplified by CBA, may help bridge the gap between seronegative and seropositive patients. This represents an urgent unmet need for gMG patients, as the antibody profile dramatically influences the therapeutic approach.

Reassessing the efficacy of bevacizumab in newly diagnosed glioblastoma: A systematic review and external pseudodata-based analysis.

Background: First-line use of bevacizumab for glioblastoma (GBM) was evaluated in 2 phase 3 randomized controlled trials (RCT), demonstrating an impact on progression-free survival but not overall survival (OS). However, the crossover events of these trials raised concerns regarding the reliability of this latter analysis. In this study, we conducted an external control-based reassessment of the bevacizumab efficacy in newly diagnosed GBM (ndGBM) against the standard Stupp protocol. Methods: A systematic review of the literature was conducted to identify the phase 3 RCTs in ndGBM incorporating the Stupp protocol as an arm. For the selected studies, we extracted individual patient survival pseudodata of the Stupp protocol arm by digitizing the Kaplan-Meier plots. A comprehensive pipeline was established to select suitable control studies as external benchmarks. Results: Among the 13 identified studies identified in our systematic review, 4 studies resulted as comparable with the AVAglio trial and 2 with the RTOG 0825. Pooled individual patient pseudodata analysis showed no differences in terms of OS when bevacizumab was added to the Stupp protocol. Conclusions: The external-controlled-based reassessment of the bevacizumab treatment in ndGBM confirmed its lack of efficacy in extending OS. Our study includes a summary table of individual patient survival pseudodata from all phase 3 RCTs in ndGBM employing the Stupp protocol and provides a pipeline that offers comprehensive guidance for conducting external control-based assessments in ndGBM.

Intraoperative electroneurography-guided intercostal nerve cryoablation for pain control after thoracoabdominal aneurysm open surgical repair.

BACKGROUND: Postoperative pain after thoracoabdominal (TAAA) or thoracic (TAA) aortic aneurysm open surgical repair may be debilitating and induce limitations in mobilization resulting in a longer length of stay, higher rate of pulmonary adverse events, readmissions, and a higher risk of mortality. Commonly employed analgesic strategies do not completely solve this issue and have their own drawbacks. Cryoablation of intercostal nerves has been proposed as an appealing alternative to address the postoperative pain. METHODS: Between 2020 and 2021, data of all consecutive patients undergoing TAA or TAAA aortic aneurysms open repair with electroneurography-guided cryoablation of intercostal nerves were collected. Postoperative pain was recorded using patient-reported 0-10 numeric rating scale (NRS). Need for adjunctive opioid drugs and postoperative complications were also recorded. Narcotic usage was calculated as morphine milligram equivalents (MMEs) per day. RESULTS: A total of 15 patients (8 males, mean age 61.1-year-old) underwent open surgical repair for TAAA (13 cases) or TAA (2 cases) and received intercostal nerve cryoablation. There were no intraoperative deaths and cases of spinal cord ischemia. Overall, 70 intercostal nerves underwent electroneurography-guided cryoablation, with a mean of 4.6 nerves per patient. On the first day after extubating, mean NRS was 4.6 and the MMEs calculated was 6.7, decreasing over the days. There was one case of pneumonia and atelectasis requiring bronchoscopy. There were no reported bowel complications. The mean postoperative length of stay was 16 days and in the intensive care unit stay was 6.5 days. CONCLUSIONS: Electroneurography-guided cryoablation of intercostal nerves is a safe and reproducible technique which can be used in addition to systemic pain management for TAA and TAAA open repair.

Intraoperative neurophysiologic monitoring in thoracoabdominal aortic aneurysm surgery can provide real-time feedback for strategic decision making.

OBJECTIVES: Despite the introduction of several adjuncts to improve spinal perfusion, spinal cord ischemia (SCI) remains a devastating complication of thoracoabdominal aortic aneurysm (TAAA) repair. Our aim was to assess the effects on clinical outcome of interventions triggered by motor evoked potentials (MEP) alerts. Furthermore, we want to assess whether a multimodal intraoperative neurophysiologic monitoring (IONM) protocol is helpful for stratifying patients according to the risk of SCI at the end of the vascular phase of surgery. METHODS: We prospectively studied one-hundred consecutive patients who underwent TAAA repair. We applied a multimodal IONM including MEP, somatosensory evoked potentials (SEP) and peripheral nerve monitoring techniques. Signal deteriorations were classified as reversible/irreversible according to whether they recovered or not at the end of monitoring (EOM), set at the end of the vascular phase of surgery. Significant MEP changes drove a series of corrective measures aimed to improve spinal perfusion. RESULTS: The rate of immediate postoperative motor deficits consistent with SCI was significantly higher with irreversible MEP deteriorations compared to reversible ones. The interpretation of MEP findings at the EOM led to the development of risk categories for SCI, based on the association between MEP results and motor outcome. CONCLUSIONS: Our data seem to justify interventions made to reverse MEP deterioration in order to improve the clinical outcome. A multimodal IONM protocol could improve MEP interpretation at the end of the vascular phase of surgery, supporting the surgeon in their decision-making, before concluding vascular maneuvers.

Hereditary spastic paraplegia is a novel phenotype for germline de novo ATP1A1 mutation.

Dominant mutations in ATP1A1, encoding the alpha-1 isoform of the Na+ /K+ -ATPase, have been recently reported to cause an axonal to intermediate type of Charcot-Marie-Tooth disease (ie, CMT2DD) and a syndrome with hypomagnesemia, intractable seizures and severe intellectual disability. Here, we describe the first case of hereditary spastic paraplegia (HSP) caused by a novel de novo (p.L337P) variant in ATP1A1. We provide evidence for the causative role of this variant with functional and homology modeling studies. This finding expands the phenotypic spectrum of the ATP1A1-related disorders, adds a piece to the larger genetic puzzle of HSP, and increases knowledge on the molecular mechanisms underlying inherited axonopathies (ie, CMT and HSP).