Percutaneous endoscopic gastrostomy using the introducer method with ultra-slim endoscopy in amyotrophic lateral sclerosis patients with respiratory compromise: A safe technique.

BACKGROUND AND AIM: Percutaneous endoscopic gastrostomy (PEG) placement is recommended in patients with amyotrophic lateral sclerosis (ALS), but the procedure is considered high risk. In this study, we aimed to compare the outcome of ALS patients with and without PEG. The success of the procedure and complications of PEG insertion were also explored. METHODS: Patients with ALS who met the criteria for enteral feeding support were consecutively recruited. Patients who consented had PEG insertion using the modified technique of introducer method with transoral ultra-slim endoscopy. RESULTS: A total of 64 patients were recruited, of which 36 (56%) patients consented to PEG. The median age of all patients was 65 years and 59% were male. There was no difference in demographic and clinical characteristics between patients who agreed to a PEG and those who did not. The mortality rate at 6 and 12 months was lower in the PEG cohort compared with non-PEG, but this was not statistically significant (6 months: 28.6% vs 32.2%, P = 0.561; 12 months: 38.9% vs 50.0%, P = 0.374). Amongst the PEG cohort, 61% were stratified high risk and 31% moderate risk. Thirty-one percent of them required long-term home noninvasive ventilation. All patients (100%) underwent successful PEG insertion at single attempt using the modified approach. The complications reported over a period of 6 months were infected PEG site (17%), dislodged gastrostomy tube (14%), and minor bleeding (8%). CONCLUSION: In ALS patients with moderate to high risk of PEG insertion, the introducer technique utilizing ultra-slim endoscopy guidance was well tolerated and safe.

Mutation analysis of SOD1, C9orf72, TARDBP and FUS genes in ethnically-diverse Malaysian patients with amyotrophic lateral sclerosis (ALS).

Recent studies have identified SOD1, FUS, TARDBP and C9orf72 as major ALS-related genes in both European and Asian populations. However, significant differences exist in the mutation frequencies of these genes between various ancestral backgrounds. This study aims to identify the frequency of mutations in the common causative ALS genes in a multi-ethnic Malaysian cohort. We screened 101 Malaysian ALS patients including 3 familial and 98 sporadic cases for mutations in the coding regions of SOD1, FUS, and TARDBP by Sanger sequencing. The C9orf72 hexanucleotide repeat expansion was screened using the repeat-primed polymerase chain reaction assay. Mutations were found in 5.9% (6 of 101) of patients including 3.0% (3 of 101) of patients with the previously reported SOD1 missense mutations (p.V48A and p.N87S) and 3.0% (3 of 101) of patients with the C9orf72 repeat expansion. No mutations were found in the FUS and TARDBP genes. This study is the first to report the mutation frequency in an ethnically diverse Malaysian ALS population and warrants further investigation to reveal novel genes and disease pathways.

A model incorporating ultrasound to predict the probability of fast disease progression in amyotrophic lateral sclerosis.

OBJECTIVE: We aimed to develop a model to predict amyotrophic lateral sclerosis (ALS) disease progression based on clinical and neuromuscular ultrasound (NMUS) parameters. METHODS: ALS patients were prospectively recruited. Muscle fasciculation (≥2 over 30-seconds, examined in biceps brachii-brachialis (BB), brachioradialis, tibialis anterior and vastus medialis) and nerve cross-sectional area (CSA) (median, ulnar, tibial, fibular nerve) were evaluated through NMUS. Ultrasound parameters were correlated with clinical data, including revised ALS Functional Rating Scale (ALSFRS-R) progression at one year. A predictive model was constructed to differentiate fast progressors (ALSFRS-R decline ≥ 1/month) from non-fast progressors. RESULTS: 40 ALS patients were recruited. Three parameters emerged as strong predictors of fast progressors: (i) ALSFRS-R slope at time of NMUS (p = 0.041), (ii) BB fasciculation count (p = 0.027) and (iii) proximal to distal median nerve CSA ratio < 1.22 (p = 0.026). A predictive model (scores 0-5) was built with excellent discrimination (area under curve: 0.915). Using a score of ≥ 3, the model demonstrated good sensitivity (81.3%) and specificity (91.0%) in differentiating fast from non-fast progressors. CONCLUSION: The current model is simple and can predict the probability of fast disease progression. SIGNIFICANCE: This model has potential as a surrogate biomarker of ALS disease progression.

A survey on patients' disease perception and the impact of the COVID-19 pandemic on persons living with amyotrophic lateral sclerosis in Malaysia.

Aim: To investigate the patients' perception of their disease, its management and the impact of the COVID-19 pandemic on persons living with amyotrophic lateral sclerosis (ALS) in Malaysia. Patients & methods: An online survey comprising 42 questions was conducted on ALS patients during the peak of the COVID-19 pandemic. Results: Responses were received from 37/60 (62%) participants with ALS directly or through their caregivers. During the COVID-19 pandemic, two-thirds of patients were negatively impacted by the sudden disruption to their hospital appointments, rehabilitation sessions and reduced social interactions. Conclusion: This study provided insight into patients' perception of their care and management of ALS in Malaysia which will facilitate in implementing changes that can improve care to persons living with this devastating illness.

The utility of ALS staging systems in a multi-ethnic patient cohort.

Objective: To compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using prospective data from a multi-ethnic cohort of ALS patients. Methods: The stages of disease were determined prospectively based on existing definitions. The two systems were compared for timing of stages using box plots, correspondence using chi-square tests and association using Spearman's rank correlation. Results: The distribution of stages differed between the two systems. The proportions of disease stages of the King's staging system were more evenly distributed whereas in MiToS, there was greater weight seen at the later stages of disease. At the early stages, patients moved consecutively in the MiToS staging system but not in the King's staging system where patients tended to skip stages to reach later stages. Both systems had good correlation (Spearman's rho = 0.869) and the King's stage 4 most frequently corresponded to MiToS stage 2. Conclusion: We found the King's staging was helpful in determining the stages of disease burden, whereas both were helpful in determining the time to functional dependence with MiToS further refining the levels of dependence.

Natural history and clinical features of ALS in Malaysia.

OBJECTIVE: Studies from multiethnic populations are rarely reported but do indicate differences in phenotypic presentation and survival in amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the natural history of a cohort of ALS patients from a multiethnic population. Methods: Data from ALS patients presenting to our multidisciplinary ALS clinic were prospectively collected from January 2015 to June 2020 as part of an ongoing hospital-based patient registry. Kaplan-Meier and Cox regression model were performed to identify potential prognostic factors. Results: A total of 144 ALS patients were recruited. We estimated the crude ALS incidence as 0.53 per 100,000 for 2019 but rises to 2 per 100,000 in patients aged 60-74 years. The majority of patients were of Chinese ethnicity (59.7%), followed by Malay (24.3%), Indian (11.1%), and others (4.9%). Malaysian Indians had a significantly steeper ALSFRS-R slope at diagnosis (p = 0.040). We found a worse prognosis in patients with bulbar-onset (HR = 1.915, p = 0.019), older age (HR = 1.052, p = 0.000), and who were fast-progressors (HR = 1.274, p = 0.000). In contrast, a higher body mass index (HR = 0.921, p = 0.007) and a longer time to diagnosis (HR = 0.967, p = 0.006), noninvasive ventilation (HR = 0.820, p = 0.000) and percutaneous endoscopic gastrostomy insertion (HR = 0.823, p = 0.000) were associated with better survival. On multivariate analysis, diagnostic delay and slow disease progression were associated with better survival. Conclusions: In our cohort, diagnostic delay and a slow disease progression were significantly associated with better survival in ALS. We also found ethnic variation with Chinese preponderance and more rapid disease progression in patients of Indian descent.