Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with marked clinical heterogeneity, with an extremely variable time course from diagnosis to death or severe disability. The heterogeneity of ALS hinders the accurate prediction of endpoints and the development of novel therapies. Further identification of ALS prognostic factors will help to build a good survival prediction model, accurately predict survival time, and promote the development of ALS treatment.
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, and its pathogenesis includes glutamate excitotoxicity, oxidative stress injury, abnormal aggregation of neurofilaments, abnormal aggregation of intracellular calcium, neurotrophic factor deficiency, mitochondrial dysfunction, RNA metabolism disorder and immune dysfunction. This article reviews the effects of monocytes/macrophages, natural killer cells, astrocytes, microglia, CD4+ T cells, CD8+ T cells and the number and function of regulatory T cells on ALS.
Objective To detect risk factors of silent aspiration in patients with amyotrophic lateral sclerosis (ALS) and the diagnostic value of ALSFRS-R scale. Methods A total of 68 patients with ALS were recruited in our study. According to the results of Videofluoroscopic Swallowing Study (VFSS), patients were divided into the silent aspiration group (9 cases) and the non-silent aspiration group (59 cases). The muscle strength of neck and limb was assessed using the Medical Research Council score (MRC) scale, and the independent influencing factors of silent aspiration were assessed using Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of ALSFRS-R bulbar subscales and swallowing items for silent aspiration. Results The results of univariate analysis showed that compared with the non-silent aspiration group, cervical flexor muscle strength and right proximal upper limb muscle strength were decreased in the silent aspiration group (P<0.05), and the proportion of patients with bulbar onset was higher in the silent aspiration group (P<0.05). Multivariate Logistic regression analysis showed that patients with limb onset were less likely to have occult aspiration than those of bulbar onset (OR=0.001, 95%CI: 0.000-0.222, P=0.014). The higher the cervical flexor muscle strength was, the less the risk of occult aspiration was (OR=0.089, 95%CI: 0.010-0.814, P=0.032). The results of ROC curve showed that the ALSFRS-R bulbar subscales and swallowing items had limit clinical diagnostic value for ALS patients with silent aspiration, and the areas under the curve (AUC) were 0.774 (95%CI：0.741-0.924) and 0.781 (95%CI： 0.757-0.934), respectively (P<0.05). When the Youden index was the maximum, the optimal cut-off value of ALSFRS-R bulbar subscales was 11, and the sensitivity and specificity for the diagnosis of silent aspiration were 88.89% and 57.63%, respectively. The optimal cut-off value of ALSFRS-R swallowing items was 3, and the sensitivity and specificity for the diagnosis of silent aspiration were 77.78% and 67.80%, respectively. Conclusion For ALS patients with bulbar onset and poor cervical flexor muscle strength, attention should be paid to the screening of dysphagia and early clinical intervention. ALSFRS-R bulbar subscales and swallowing items have limited diagnostic value for silent aspiration, and new scales need to be developed to assess the risk of silent aspiration in ALS patients.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurons, resulting in progressive weakness and wasting of all voluntary muscles, culminating in respiratory failure. Neuroelectrophysiological detection plays an an essential role in early diagnosis of ALS, and can even detect subclinical dysfunction. Nerve conduction and needle electromyography, as standard neurophysiological detection method, are very important for early detection of lower motor neuron disease. Many emerging techniques for estimating the number of motor units have been proposed to increase diagnostic sensitivities and used to assess ALS progression.
Objective To analyze the clinical characteristics and epidemiological status of amyotrophic lateral sclerosis (ALS). Methods A total of 110 ALS patients (62 males and 48 females) with a median age of 60 years of onset, were collected. The basic information, site of onset, diagnostic process, modified amyotrophic lateral sclerosis function score (ALSFRS-R), rate of disease progression (ΔFS), electrophysiology and pulmonary function were analyzed comprehensively. The patients were followed up by outpatient or telephone every 3 to 6 months to record changes of their condition, the application of non-invasive positive pressure ventilation (NIPPV), gastric tube, percutaneous gastrostomy (PEG) and the treatment of riluzole. Results Among 110 patients, limb onset accounted for 90 patients (81.8%). The delay diagnosis was 12 (7, 20) months. The misdiagnosis interval was 11 (7, 17) months, and the misdiagnosis rate was 81.3% (74 cases). The most misdiagnosed cases were cervical spondylosis and lumbar spondylosis. The ALSFRS-R score was 39 (36, 45) points, and the ΔFS was 0.6 (0.3, 1.0) points/month. The proportion of confirmed and suspected diagnosis was higher in patients with ball onset than that in patients with limb onset (90% vs. 83%, χ2=2.098, P<0.05). Compared with patients of rapid disease progression, the age of onset was younger in patients with moderate and slow disease progression. Compared with patients of slow disease progression, patients of rapid and moderate disease progression had shorter diagnostic delay. Results of EMG in 90 (81.8%) patients indicated that lower motor neuron lesion segment was greater than or equal to the clinically involved segment. The first pulmonary function examination indicated that 50% (45 cases) patients had restrictive ventilation dysfunction, and the forced vital capacity (FVC)<70% accounted for 17.8% (16 cases). After discharge, the treatment rate of riluzole was 85.6%, and the application rate of NIPPV and PEG was low. During the follow-up, 50 patients (45.5%) died, and the median survival time was 44.0 months. Median survival time was shorter in patients with onset age ≥60 years than that in patients under 60 years (36 months vs. 50 months, P<0.05). Survival time was shorter in patients with rapid disease progression than that in patients with moderate and slow disease progression (27 months vs. 32 months vs. 65 months, P<0.01). Conclusion A full and correct understanding of clinical features of ALS is helpful to make a reasonable diagnosis and treatment plan for patients and improve the prognosis.
Objective To compare the clinical effects of CT-guided and endoscopic surgical percutaneous gastrostomy in patients with amyotrophic lateral sclerosis (ALS). Methods The clinical data of 104 patients with ALS were retrospectively analyzed, including 48 patients underwent CT-guided percutaneous gastrostomy (CT-guided group) and 56 patients underwent endoscopic percutaneous gastrostomy (endoscopic group). The disease status, length of hospital stay, postoperative length of hospital stay, postoperative complications, and survival rates of six months and one year after surgery were compared between the two groups. Results There were no significant differences in age, disease course, dysphagia time, height, body weight and preoperative nutritional status between the two groups (P>0.05). The length of hospital stay and postoperative length of stay were shorter in the CT-guided group than those in the endoscopic group (P<0.05). There was no significant difference in the incidence of complications between the endoscopic group (19.6%) and the CT-guided group (8.3%, P>0.05). There was no significant difference in one-year survival rate between the endoscopic group and the CT-guided group (91.0% vs. 93.8%, Log-rank χ2=1.606, P>0.05). Conclusion CT-guided percutaneous gastrostomy shows its advantages in ALS, especially in shortening the length of hospital stay and postoperative length of hospital stay in ALS patients, and is worthy of widespread clinical application.
Objective To evaluate the functional status of the sensory system in patients with amyotrophic lateral sclerosis (ALS) by neuroelectrophysiological techniques. Methods According to the revised El Escorial diagnostic criteria, 66 patients with clinically confirmed and proposed limb-onset ALS were included and divided into the sensory symptom (sALS, n=13) group and without sensory symptom (nsALS, n=53) group according to the presence or absence of clinical sensory symptoms. Sixty healthy individuals were selected as the health control (HC) group. Sensory nerve conduction studies (SNCS) and skin sympathetic response (SSR) of bilateral upper and lower limbs were detected by Keypoint 4 electromyography evoked potential instrument. Pathway pain and sensation assessment system was used to conduct contact heat evoked potential (CHEP) detection of bilateral anterolateral leg and forearm volar side. Results (1) The abnormal rates of SNCS, SSR and CHEP in the ALS group were 0%, 21.2% (14/66) and 27.3% (18/66), respectively. The abnormal rates of SSR and CHEP in the sALS group were 30.8% (4/13) and 38.5% (5/13). The abnormal rates of SSR and CHEP in the nsALS group were 18.9% (10/53) and 24.5% (13/53). (2) Compared with the HC group, the latency of SSR in lower limbs was prolonged in the sALS group and the nsALS group, the latency of N wave in CHEP of upper and lower limbs was prolonged, and the amplitude of N-P wave was decreased (P<0.05). Compared with the nsALS group, the sALS group showed prolonged N wave latency and reduced N-P wave amplitude for anterolateral calf stimulation by CHEP detection (P<0.05). Conclusion ALS patients have small fiber damage in the sensory system.
