Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model.

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation.

Antibody-mediated autoimmunity in symptom-based disorders: position statement and proceedings from an international workshop.

A 2-day closed workshop was held in Liverpool, United Kingdom, to discuss the results of research concerning symptom-based disorders (SBDs) caused by autoantibodies, share technical knowledge, and consider future plans. Twenty-two speakers and 14 additional participants attended. This workshop set out to consolidate knowledge about the contribution of autoantibodies to SBDs. Persuasive evidence for a causative role of autoantibodies in disease often derives from experimental "passive transfer" approaches, as first established in neurological research. Here, serum immunoglobulin (IgM or IgG) is purified from donated blood and transferred to rodents, either systemically or intrathecally. Rodents are then assessed for the expression of phenotypes resembling the human condition; successful phenotype transfer is considered supportive of or proof for autoimmune pathology. Workshop participants discussed passive transfer models and wider evidence for autoantibody contribution to a range of SBDs. Clinical trials testing autoantibody reduction were presented. Cornerstones of both experimental approaches and clinical trial parameters in this field were distilled and presented in this article. Mounting evidence suggests that immunoglobulin transfer from patient donors often induces the respective SBD phenotype in rodents. Understanding antibody binding epitopes and downstream mechanisms will require substantial research efforts, but treatments to reduce antibody titres can already now be evaluated.

Autonomic Nerve Involvement in Post-Acute Sequelae of SARS-CoV-2 Syndrome (PASC).

The novel SARS-CoV-2 virus and resulting COVID-19 global pandemic emerged in 2019 and continues into 2022. While mortality from COVID-19 is slowly declining, a subset of patients have developed chronic, debilitating symptoms following complete recovery from acute infection with COVID-19. Termed as post-acute sequelae of SARS-CoV-2 syndrome (PASC), the underlying pathophysiology of PASC is still not well understood. Given the similarity between the clinical phenotypes of PASC and postural orthostatic tachycardia syndrome (POTS), it has been postulated that dysautonomia may play a role in the pathophysiology of PASC. However, there have been only a few studies that have examined autonomic function in PASC. In this retrospective study, we performed an analysis of autonomic nerve function testing in PASC patients and compared the results with those of POTS patients and healthy controls. Our results suggest that a significant number of PASC patients have abnormal autonomic function tests, and their clinical features are indistinguishable from POTS.

Association between Temporomandibular Joint Disorder and Parkinson's Disease.

This study performed two different analyses using a large set of population data from the Korean National Health Insurance Service Health Screening Cohort to evaluate the interactional association between temporomandibular disorder (TMD) and Parkinson's disease (PD). Two nested case-control population-based studies were conducted on 514,866 participants. In Study I, 4455 participants with TMD were matched with 17,820 control participants, with a ratio of 1:4. In Study II, 6076 participants with PD were matched with 24,304 control participants, with a ratio of 1:4. Obesity, smoking, alcohol consumption, systolic, diastolic blood pressure, fasting blood glucose level, and total cholesterol were adjusted. The adjusted odds ratio (OR) for TMD was 1.43 (95% confidence interval (CI) = 1.02-2.00) in PD patients compared to non-PD patients in Study I (p < 0.001). The adjusted OR for PD was 1.56 (95% CI = 1.13-2.15) in TMD patients compared to non-TMD patients in Study II (p = 0.007). This study demonstrated that patients with TMD have a significantly higher risk of developing PD and, conversely, those with PD have a significantly higher risk of developing TMD.

Dysphagia in Myositis: A Study of the Structural and Physiologic Changes Resulting in Disordered Swallowing.

OBJECTIVES: Dysphagia in patients with myositis is associated with an increased risk of aspiration pneumonia. However, the pathophysiology of dysphagia is poorly understood. The aim of this study was to understand how myositis affects swallowing physiology on videofluoroscopic swallow study. DESIGN: This is a retrospective review of video fluoroscopic swallowing studies on 23 myositis patients with dysphagia from 2011 to 2016. Swallow studies were analyzed by timing of swallowing events and duration of swallowing events, diameter of upper esophageal sphincter opening, Modified Barium Swallow Impairment Profile, and Penetration-Aspiration Scale. The outcome measures for patients were compared with an archived videofluoroscopic swallow study from healthy, age-matched participants by Wilcoxon rank-sum tests. RESULTS: Patients with myositis had a shorter duration of upper esophageal sphincter opening (P < 0.0001) and laryngeal vestibule closure (P < 0.0001) than healthy subjects. The diameter of upper esophageal sphincter opening did not differ between groups. Patients with myositis presented with higher scores on the MBSIMP than healthy subjects, indicating great impairment particularly during the pharyngeal phase of swallowing, and a higher frequency of penetration and aspiration. CONCLUSIONS: Dysphagia in patients with myositis may be attributed to reduced endurance of swallowing musculature rather than mechanical obstruction of the upper esophageal sphincter.

Postural Orthostatic Tachycardia Syndrome (POTS): A critical assessment.

Although diagnostic criteria have been developed characterizing postural orthostatic tachycardia syndrome (POTS), no single set of criteria is universally accepted. Furthermore, there are gaps in the present criteria used to identify individuals who have this condition. The reproducibility of the physiological findings, the relationship of symptoms to physiological findings, the presence of symptoms alone without any physiological findings and the response to various interventions confuse rather than clarify this condition. As many disease entities can be confused with POTS, it becomes critical to identify what this syndrome is. What appears to be POTS may be an underlying condition that requires specific therapy. POTS is not simply orthostatic intolerance and symptoms or intermittent orthostatic tachycardia but the syndrome needs to be characterized over time and with reproducibility. Here we address critical issues regarding the pathophysiology and diagnosis of POTS in an attempt to arrive at a rational approach to categorize the syndrome with the hope that it may help both better identify individuals and better understand approaches to therapy.

Resolution of Postural Orthostatic Tachycardia Syndrome After CT-Guided, Percutaneous T2 Ethanol Ablation for Hyperhidrosis.

Postural orthostatic tachycardia syndrome is characterized by orthostatic intolerance. Orthostasis (or other mild physical stress) triggers a cascade of inappropriate tachycardia, lightheadedness, palpitations, and often fainting. The underlying defect is sympathetic dysregulation of the heart, which receives its sympathetic tone from the cervical and upper thoracic sympathetic ganglia. Primary hyperhidrosis is also thought to be the result of sympathetic dysregulation. We present the case of a patient treated with CT-guided, percutaneous T2 EtOH sympatholysis for craniofacial hyperhidrosis. The patient also suffered from postural orthostatic tachycardia syndrome for many years and was unresponsive to treatment. Immediately after sympatholysis, the patient experienced resolution of both craniofacial hyperhidrosis and postural orthostatic tachycardia syndrome.

The preoperative neurological evaluation.

Neurological diseases are prevalent in the general population, and the neurohospitalist has an important role to play in the preoperative planning for patients with and at risk for developing neurological disease. The neurohospitalist can provide patients and their families as well as anesthesiologists, surgeons, hospitalists, and other providers guidance in particular to the patient's neurological disease and those he or she is at risk for. Here we present considerations and guidance for the neurohospitalist providing preoperative consultation for the neurological patient with or at risk of disturbances of consciousness, cerebrovascular and carotid disease, epilepsy, neuromuscular disease, and Parkinson disease.