Prognosis of amyotrophic lateral sclerosis patients after tracheostomy invasive ventilation in Korea.

Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [≥80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.

Amyotrophic Lateral Sclerosis with a Priority Request for a Postmortem Kidney Donation to a Relative.

The patient was 57 years old when he was diagnosed with amyotrophic lateral sclerosis (ALS) at 1 year after developing bulbar symptoms. At 58 years old, he stated that he was considering donating his kidney to his son suffering from diabetic nephropathy. We confirmed the patient's intentions through repeated interviews before his death at 61 years old. Nephrectomy was performed 30 min after his cardiac death. Organ donation spontaneously proposed by an ALS patient should be considered in order to meet the requests of patients who want their families and other patients to live longer, thereby imparting a beneficial legacy through their deaths.

Remimazolam Sedation and Neuraxial Anesthesia in a Patient with Amyotrophic Lateral Sclerosis Undergoing an Open Colectomy: A Case Report.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving the upper and lower motor neurons. Perioperative management of patients with ALS can be challenging due to the risk of hemodynamic instability, aspiration, and ventilatory failure. We discuss a 58-year-old male patient with ALS who underwent open abdominal surgery under regional anesthesia utilizing a remimazolam infusion for sedation. While various sedation agents have been used successfully in patients with ALS, remimazolam, a new short-acting benzodiazepine with unique pharmacologic properties and reversible anxiolysis, provides amnesia while avoiding ventilatory depression.

Misdiagnosis in Amyotrophic Lateral Sclerosis.

The symptoms of amyotrophic lateral sclerosis (ALS) can mimic those of compressive neuropathies, such as carpal and cubital tunnel syndromes, especially early in a patient's clinical course. We surveyed members of the American Society for Surgery of the Hand and found that 11% of active and retired members have performed nerve decompression surgeries on patients later diagnosed with ALS. Hand surgeons are commonly the first providers to evaluate patients with undiagnosed ALS. As such, it is important to be aware of the history, signs, and symptoms of ALS to provide an accurate diagnosis and prevent unnecessary morbidities, such as nerve decompression surgery, which invariably results in poor outcomes. The major "red flag" symptoms warranting further work-up include weakness without sensory symptoms, profound weakness and atrophy in multiple nerve distributions, progressively bilateral and global symptoms, presence of bulbar symptoms (such as tongue fasciculations and speech/swallowing difficulties), and, if surgery is performed, failure to improve. If any of these red flags are present, we recommend neurodiagnostic testing and prompt referral to a neurologist for further work-up and treatment.

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: outcomes of a dedicated anesthesia and surgery protocol.

BACKGROUND: Patients requiring percutaneous endoscopic gastrostomy (PEG) for amyotrophic lateral sclerosis (ALS) related dysphagia represent a clinical challenge. Diminished pulmonary function and aspiration risks can lead to anesthesia-related complications, and gastric displacement from hemidiaphragm elevation may preclude safe gastric access. This study reports the efficacy and outcomes of a dedicated anesthesia/surgery management protocol for ALS patients undergoing PEG. METHODS: In 2013, a PEG placement protocol for ALS patients was developed emphasizing efficient pre-operative evaluation, rapidly metabolized anesthetic agents, and minimization of opioid use. Outcomes were analyzed retrospectively. Preoperative weight loss, pulmonary function tests, total analgesia, procedural time, and 90-day morbidity and mortality were recorded. RESULTS: From 2013-2019, 67 ALS patients (mean age 65.3 years, 52.2% female) received a PEG under the protocol. Mean percentage weight loss 6 months before PEG was 9.3 ± 5.1% with 38.8% of patients meeting criteria for severe malnutrition. Mean anesthesia time (propofol induction to anesthesia emergence) was 34.5 ± 10.8 min and mean operative time (endoscope insertion to dressing placement) was 16.4 ± 8.2 min. Regional anesthesia with liposomal bupivacaine was performed in 76.1%. All attempts at PEG placement were successful. With a mean follow-up of 6.1 ± 6.8 months, all PEGs were functional and there were no surgical site complications. Thirty-day readmission rate was 7.0% and 90-day mortality was 22.4% (46.7% occurring within 30 days). Mean time from surgery to death was 8.8 ± 7.8 months. CONCLUSIONS: Protocols for optimizing PEG may help overcome challenges present in the ALS patient population. Despite patient comorbidities, protocol implementation and dedicated team members resulted in a high procedural success rate and low complication rate. Further study is warranted to optimize the timing of PEG placement in relation to ALS disease progression and determine the utility of regional anesthesia during PEG placement.

Perioperative management of patients with amyotrophic lateral sclerosis: A narrative review.

Amyotrophic lateral sclerosis, or motor neuron disease, is an uncommon progressive neurological disorder. Professionals working in the perioperative field may encounter patients with amyotrophic lateral sclerosis only rarely. The relevant published literature on amyotrophic lateral sclerosis is broad in scope, but a contemporary review focused on the perioperative period is absent. This structured narrative review seeks to provide a summary of the contemporary management of patients and then focuses on eliciting if there are perioperative management considerations specific to amyotrophic lateral sclerosis that can be optimised. A comprehensive structured narrative literature review, including grey literature searching, indicated worsening ventilatory failure is of prime concern but that patients may present with a broad range of neurological symptoms, and that cardiovascular and cognitive dysfunction specific to amyotrophic lateral sclerosis may exist and be occult. Exacerbation of neuromuscular weakness during the perioperative period is multifaceted and requires the application of a high standard of the core principles of surgical and anaesthetic management of neuromuscular disease. Standard perioperative approaches require rigorous attention and potential exists for significant alteration. There is a potential high risk of postoperative increased morbidity from neurological decline and mortality from pulmonary complications. A meticulous approach to planning preoperative assessment, shared decision-making, intraoperative and postoperative care is required.

Slow vital capacity as a useful indicator of the prognosis after percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis.

OBJECTIVES: Forced vital capacity (FVC) is recommended as a respiratory function test in patients with amyotrophic lateral sclerosis (ALS). However, in ALS associated with orofacial palsy, FVC may be an unreliable test. Slow vital capacity (SVC) is an easier and more reliable test even in cases with bulbar symptoms. However, it remains unclear whether respiratory function tests using SVC and FVC are associated with prognosis after percutaneous endoscopic gastrostomy (PEG) placement. This study aimed to confirm whether both SVC and FVC are related to prognosis after PEG placement in patients with ALS. MATERIALS AND METHODS: We conducted this retrospective observational cohort study of 69 consecutive patients diagnosed with sporadic ALS who underwent PEG placement between July 2007 and February 2020. We analyzed the association with mortality 6 months after PEG placement and evaluated long-term prognosis. RESULTS: Forty-four patients met the inclusion criteria. In cases with decreased SVC (p < .01) and FVC (p < .01), a significant difference was observed in mortality 6 months after PEG placement, with an optimal cut-off of SVC ≤57.4% (sensitivity, 0.828; specificity, 0.867) and FVC ≤57.3% (sensitivity, 0.828; specificity, 0.867). Multivariate analysis showed that onset age ≥ 65 years (p < .05), SVC ≤57.4% (p < .01), and FVC ≤57.3% (p < .01) were associated with survival after PEG placement. CONCLUSIONS: SVC, like FVC, is an important prognostic factor after PEG placement in patients with ALS, and there is a possibility that evaluation using SVC can complement respiratory function testing even in cases where the evaluation of FVC is limited.

[Gastrostomy tubes in patients with amyotrophic lateral sclerosis: indications, safety and experience in a tertiary care centre]. / Sondas de gastrostomía en pacientes con esclerosis lateral amiotrófica: indicaciones, seguridad y experiencia en un centro de tercer nivel.

AIM: The aim of this study is the clinical characterisation of patients diagnosed with amyotrophic lateral sclerosis (ALS), who were indicated for the placement of a gastrostomy tube (G-Tube) in the period 2007-2017 in the Complejo Asistencial Universitario de Salamanca, and to find possible associated prognostic factors. MATERIAL AND METHODS: It is a descriptive study of clinical cases. RESULTS: Between 2007 and 2017, 139 cases of ALS were assessed and a G-Tube was indicated in 29 of them. Of these 29, on two occasions it was not performed, one due to the patient refusing and the other because of clinical deterioration. Of the total number of G-Tubes, 21 were placed by endoscopy, four by interventional radiology and two by surgery. The main indications were: in 10 cases, for severe dysphagia; in eight cases, for weight loss >10%; and in nine cases, for reduced forced vital capacity <50%. Immediate complications (first 24 hours) included: two intraprocedural desaturations, one ostomy infection, one abdominal pain, one paralytic ileus and one respiratory failure resulting in death. Late complications (first month) include pneumonia, intestinal ischaemia, cellulitis and poor control of secretions. The main cause of death was respiratory failure. The median time elapsed between G-Tube placement and death was 7.89 months. An improvement in analytical nutritional parameters was observed, without showing statistical significance, as a prognostic factor. CONCLUSION: G-Tube placement is an effective and safe procedure to ensure enteral nutrition in ALS patients.

TITLE: Sondas de gastrostomía en pacientes con esclerosis lateral amiotrófica: indicaciones, seguridad y experiencia en un centro de tercer nivel.Objetivo. El objetivo es la caracterización clínica de los pacientes diagnosticados de esclerosis lateral amiotrófica (ELA) a los que se les indicó la colocación de una sonda de gastrostomía (SG) en el período 2007-2017 en el Complejo Asistencial Universitario de Salamanca, y encontrar posibles factores pronósticos asociados. Material y métodos. Es un estudio descriptivo de casos clínicos. Resultados. Entre 2007 y 2017 se evaluaron 139 ELA y se indicó SG en 29 casos. De esos 29, en dos ocasiones no se llevó a cabo, en una ocasión por negativa del paciente y en otra por deterioro clínico. Del total de SG, 21 se colocaron por endoscopia; cuatro, por radiología intervencionista; y dos, por cirugía. Las principales indicaciones fueron: en 10 casos, por disfagia grave; en ocho, por pérdida ponderal > 10%; y en nueve, por disminución de la capacidad vital forzada menor de 50%. Entre las complicaciones inmediatas (primeras 24 horas) se observaron: dos desaturaciones intraprocedimiento, una infección de la ostomía, un dolor abdominal, un íleo paralítico y una insuficiencia respiratoria con fallecimiento. Entre las complicaciones tardías (primer mes): una neumonía, una isquemia intestinal, una celulitis y un mal control de las secreciones. La principal causa de fallecimiento fue la insuficiencia respiratoria. La mediana de tiempo desde la colocación de la SG hasta el fallecimiento fue de 7,89 meses. Se constató mejoría de los parámetros analíticos nutricionales, sin demostrarse significación estadística, como factor pronóstico. Conclusión. La colocación de una SG es un procedimiento eficaz y seguro para asegurar la nutrición enteral en los pacientes con ELA.

Combined Spinal-Epidural for Loop Ileostomy in a Patient With End-Stage Amyotrophic Lateral Sclerosis: A Case Report.

Anesthesia can be a challenge for patients with amyotrophic lateral sclerosis (ALS). This progressive neurological disease is associated with a high risk of aspiration and postoperative ventilatory failure. Our patient was a 72-year-old man with ALS, quadriplegia, bulbar symptoms, dysphagia, and dysarthria who underwent palliative exploratory laparotomy and loop ileostomy creation. He received a single-shot spinal anesthetic at L4-L5 and a thoracic T11-12 epidural. He tolerated the procedure well with no perioperative pulmonary complications or worsening of his ALS. To reduce the risks of general anesthesia, we chose a neuraxial approach.

A phase I/IIa clinical trial of autologous hematopoietic stem cell transplantation in amyotrophic lateral sclerosis.

OBJECTIVE: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients. METHODS: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). RESULTS: Eight of the 11 ALS patients enrolled received the established immunoablative protocol. The procedure was well tolerated and side effects were those expected. One patient died 4 months after the conditioning regimen and another patient underwent tracheotomy just before T3 for a sudden respiratory failure, but he is still alive 4 years after the procedure without being ventilated any more. A third patient died 10 months after conditioning. In the other cases, there was no statistical difference in all functional measures and QoL pre- and post-treatment; however, a transitory slopes' reduction of ALSFRS-R and seated SVC% after the conditioning procedures was reported. Moreover, although not statistically significant, trends of reduction of CD4 + and increment of CD8 + were found. CONCLUSIONS: aHSCT was overall well tolerated, but it was not followed by any significant modification in disease progression. Considering the negative results of this small trial, further studies aimed to evaluate the possible efficacy of the aHSCT using a higher-intensity regimen should be carefully and with caution evaluated.

Long-term outcomes after surgery to prevent aspiration for patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons selectively. In particular, weakness in respiratory and swallowing muscles occasionally causes aspiration pneumonia and choking, which can be lethal. Surgery to prevent aspiration, which separates the trachea and esophagus, can reduce the associated risks. Central-part laryngectomy (CPL) is a relatively minimally invasive surgery to prevent aspiration. No studies have been conducted on the long-term outcomes of surgery to prevent aspiration in patients with ALS. This case series aimed to determine the long-term outcomes of surgery to prevent aspiration and the use of a continuous low-pressure aspirator in patients with ALS by evaluating the frequency of intratracheal sputum suctions performed per day, intra- and postoperative complications, oral intake data, and satisfaction of patients and their primary caregiver to predict improvement in patients' quality of life (QOL). METHODS: We report a case series of six patients with ALS who underwent CPL along with tracheostomy to prevent aspiration between January 2015 and November 2018. We evaluated their pre- and postoperative status and administered questionnaires at the time of last admission to the patients and their primary caregivers. RESULTS: The mean follow-up period after CPL was 33.5 months. Aerophagia was a common postoperative complication. The use of a continuous low-pressure aspirator resulted in reduced frequency of intratracheal sputum suctions. All cases avoided aspiration pneumonia. Oral intake was continued for 2-4 years after the tracheostomy and CPL. The satisfaction levels of the patient and primary caregiver were high. CONCLUSION: Our case series suggests that the use of a continuous low-pressure aspirator in patients undergoing CPL improves oral intake and reduces the frequency of intratracheal sputum suctions, which improves the QOL of patients with ALS and their families and caregivers. CPL and continuous low-pressure aspiration should be considered as a management option for ALS with significant bulbar and respiratory muscle weakness/dysfunction.

Does limited EMG denervation in early primary lateral sclerosis predict amyotrophic lateral sclerosis?

Objective: We assessed whether a cohort of patients with primary lateral sclerosis (PLS) and limited electromyography (EMG) motor unit denervation changes evolve into amyotrophic lateral sclerosis (ALS) with prolonged follow-up. Methods: We initially ascertained all PLS patients diagnosed at Mayo Clinic-Rochester (1990-2016). Of 64 total cases, 43 had normal EMGs ("pure" PLS) during the first 4 years after symptom onset and were the focus of a prior publication, documenting absence of evolution to ALS. The remaining 21 patients had limited motor unit changes on EMG needle examination (denervation and most with fibrillation or fasciculation potentials) but insufficient to raise a strong suspicion of ALS; these 21 patients were followed to determine whether they evolved into ALS. Results: Of these 21 patients, the median follow-up was 7 years' disease duration (range: 4-27 years; IQR 5-8.5). They included 11 females (52%) with median onset-age of 57 years (range: 42-72 years). Two patients (10%) subsequently met revised El Escorial criteria for ALS after 7 and 13 years, respectively. The remainder had stable EMG changes with a persistent PLS phenotype. Among these remaining 19 patients, the PLS course was somewhat more aggressive than our previously reported series of 43 patients devoid of EMG denervation. The paraparetic variant was more common than the hemiparetic and bulbar variants, similar to "pure" PLS. Conclusions: Among PLS patients with definite but limited EMG denervation, 2/21 (10%) later developed ALS. The patients in this series had a more progressive clinical course compared to our previously reported pure PLS cases.

Percutaneous gastrostomy in amyotrophic lateral sclerosis: a review.

Amyotrophic lateral sclerosis (ALS) causes dysphagia and consequent poor nutrition. Sometimes enteral feeding is offered. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for enteral nutrition of these patients. This systematic review addresses the role of PEG and other enteral feeding techniques in maintaining ALS patients' survival and quality of life and in identifying prognostic factors for survival, in order to optimize their usefulness. We also evaluated the mortality of enteral feeding in the first 30 days after each procedure and its complications. Studies were retrieved from Pubmed, Google Scholar, and Cochrane databases, using the relevant keywords, and by hand search. The inclusion criteria were prospective and retrospective designs of studies of people with clinically diagnosed ALS in whom gastrostomy or nasogastric enteral feeding were used in management, published in English. Studies with sample sizes <40, or which focused on a specific gastrostomy technique utilizing less than 30 subjects were excluded in order to avoid small sample bias. We conclude that PEG is safe and probably prolongs survival in non-malnourished ALS patients. However, older age at onset, marked loss of weight or reduced body mass index from symptomatic onset, and marked respiratory dysfunction negatively influence the outcome after PEG insertion. The currently available evidence does not meaningfully address the impact of PEG on quality of life in ALS. The literature about other enteral feeding techniques is insufficient for reliable conclusions. The optimum time for PEG insertion and preferences for specific gastrostomy techniques also require more investigation.

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease).

Circulating myomiRs in Muscle Denervation: From Surgical to ALS Pathological Condition.

ALS is a fatal neurodegenerative disease that is associated with muscle atrophy, motoneuron degeneration and denervation. Different mechanisms have been proposed to explain the pathogenesis of the disease; in this context, microRNAs have been described as biomarkers and potential pathogenetic factors for ALS. MyomiRs are microRNAs produced by skeletal muscle, and they play an important role in tissue homeostasis; moreover, they can be released in blood circulation in pathological conditions, including ALS. However, the functional role of myomiRs in muscle denervation has not yet been fully clarified. In this study, we analyze the levels of two myomiRs, namely miR-206 and miR-133a, in skeletal muscle and blood samples of denervated mice, and we demonstrate that surgical denervation reduces the expression of both miR-206 and miR-133a, while miR-206 but not miR-133a is upregulated during the re-innervation process. Furthermore, we quantify the levels of miR-206 and miR-133a in serum samples of two ALS mouse models, characterized by different disease velocities, and we demonstrate a different modulation of circulating myomiRs during ALS disease, according to the velocity of disease progression. Moreover, taking into account surgical and pathological denervation, we describe a different response to increasing amounts of circulating miR-206, suggesting a hormetic effect of miR-206 in relation to changes in neuromuscular communication.