The Korean ALS/MND research group was organized in February 2010 involving more than 50 neurologists from Korean neuromuscular centers. All of the physicians were Korean neurology specialists whose major field was neuromuscular disorders and who worked either in a university-based hospital or in a tertiary medical center in Korea.

The Korean ALS/MND research group consequently collected data on the management of patients with ALS between April and September 2010. For this purpose the Korean ALS/MND research group developed a questionnaire and conducted a survey by directly contacting patients or by interviewing the patients' primary caregivers.

All patients with ALS were carefully evaluated by an experienced neurologist for the presence of clinical and electromyographic evidence of ALS before being enrolled in the study. We used the El Escorial Criteria (ECC)13 and its revised form (the Airlie-House criteria) for the ALS diagnosis.14 We sought to enroll more patients with early-stage ALS in order to increase the diagnostic sensitivity. Thus, we included a "suspected" ALS category, which was dropped from the revised ECC, and included a "laboratory-supported probable ALS" category based on the results of the electrophysiological examination as a novel category for the revised ECC. The Pan-European ALS registry, which is the largest ALS database in the world, recommended and used these same criteria for their enrollment.15 According to these criteria, an ALS patient was classified as definite, probable, possible, laboratory-supported probable, or suspected ALS based on the impairment of upper motor neurons (UMNs) and/or lower motor neurons and on the number of involved regions (bulbar, cervical, thoracic, and lumbosacral). All patients or caregivers gave their informed consent to participate, and this study was approved by the ethics committees of the respective universities or institutions.

Before conducting the study, a task force team from the ALS/MND research group ("JS Bae, YH Hong, WK Baek, EH Shon, JY Cho, and B-J Kim") developed a registration questionnaire for patient enrollment by modifying data forms from the North American ALS CARE database (http://www.outcomes-umassmed.org/ALS/). The questionnaire was divided into a registration-completion form and a follow-up form. We measured a patient's disability using the ALS Functional Rating Scale (ALS-FRS).

After each patient visit, the data form was registered by the respective neurologist at the outpatient or inpatient department. If the patients could not visit the hospital due to having a poor general condition, a neurologist completed the form based on the information provided by the primary caregiver.

Data were analyzed using R software version 2.13.2 (R: A language and environment for statistical computing, Vienna, Austria). Student's t-test, the Wilcoxon rank-sum test, and analysis of variance were used to compare groups of continuous variables. Proportions were compared using the chi-square or Fisher's exact tests. In cases of multiple hypothesis testing, the p value was adjusted using a Bonferroni correction.

Our results show that the demographic and clinical features of Korean patients with ALS are similar to those of previous reports from other countries1,16 and a hospital-based study in Korea.11 The application rate of PEG was similar to that found in the ALS CARE database;7 however, respiratory support in Korea was primarily invasive (i.e., tracheostomy) rather than noninvasive (i.e., NIPPV).5 Considering the recent indications for these interventions, their recommendation rates tended to be low. In addition, application rates of these management procedures varied considerably among major centers. Given that quality of life and survival can be improved by NIPPV and PEG,5,6 the lower rate of adoption of these procedures in Korea may be due to the individual decisions of the respective neurologists, the environment of each hospital, or to patient personal or cultural preferences rather than by objective evidence-based guidelines.

The incidence of sporadic ALS in the 1990s was reported to be 1.5-2.7 per 100000 population/year (average 1.89 per 100000/year) in Europe and North America.17 The point prevalence is 2.7-7.4 per 100000 (average 5.2 per 100000) in Western countries. Although our study included most of the large centers that manage and follow patients with ALS in Korea, we could not estimate the aforementioned classical epidemiological parameters. However, some of our demographic findings were similar to those of previous reports.17 A consistent finding in previous reports is that there is a slight predilection toward males being affected by ALS, with a male : female ratio of about 1.5 : 1. We also found a slight male predominance among our patients. Nevertheless, more recent data suggest that the sex ratio might be approaching unity.1,17 Some reports have identified that the mean age at onset for sporadic ALS varies between 55 and 65 years, with a median age of onset of 64 years.16 Our findings also showed that the 50s and 60s were the most frequent ages for symptom onset.

Some limitations should be considered when investigating ALS epidemiology. Individuals with ALS who did not seek medical attention or who died prior to establishing the diagnosis, by definition, would not have been enrolled in any study. This is of particular concern among older patients with neurodegenerative disorders. For example, door-to-door surveys have shown that almost 40% of patients with Parkinson's disease remain undiagnosed even in countries with public healthcare systems.18 ALS is a less common disease that is even more difficult to diagnose than Parkinson's disease, and hence collecting epidemiological data is likely to be more inaccurate than for other neurodegenerative disorders.

To overcome this challenge, several population-based registries were established in the early 1990s to prospectively survey the epidemiology of ALS in defined geographical regions.8,15 The ALS CARE database, which is a clinical registry using a simple questionnaire, is another distinct multicenter-based registry in North America.9,10 These approaches have been considered as alternatives that can substitute for population-based epidemiological research and are now widely used. In fact, our study was originally planned as a framework to establish a nationwide ALS registry in Korea. This registry can be used to identify ALS epidemiological information in Korea.

Nutritional support might be one of the most commonly overlooked aspects of ALS patient care. In fact, malnutrition increases the relative risk of death by almost eightfold in patients with ALS.19 Severe malnutrition is also associated with muscle atrophy, muscle weakness, and diaphragmatic weakness.20-22 Therefore, aggressive nutritional care is essential for patients with ALS. Our results showed that about 20% of patients were underweight, as evaluated by the body mass index. We did not evaluate whether special nutritional support was adopted for these 20% of patients. It is reasonable to assume that lengthy evaluation and management is not widely practiced and might be difficult in the Korean hospital and insurance system. Some hospitals in Western countries provide multidisciplinary clinics for ALS care, and this approach has been reported to improve the quality of life in patients with ALS.23 Physicians caring for patients with ALS should recognize this problem as early as possible, since correcting it can influence the overall outcome.

PEG was recommended in the American Academy of Neurology guidelines for patients with symptomatic dysphagia to minimize the procedural risk when forced vital capacity has not yet declined to <50% of the predicted value.4 According to our results, PEG was performed in 18.1% of patients. This percentage is slightly higher than that of the ALS CARE database (16% of patients received PEG).7 It remains uncertain whether physicians do not recommend PEG because of a lack of evidence of sufficient benefit, physician bias, a center's lack of resources, potential complications of the procedure, or simply that patients are reluctant to undergo such a procedure. However, one report demonstrated a marked variability in the use of PEG among ALS clinics. That report suggested that certain factors bias a clinic or physician toward the increased use of PEG.6 Although there was some positive impact, the ALS CARE database suggests that PEG does not affect survival.7 However, PEG may have been performed too late to show survival benefits.6 Therefore, a future workup is needed to clarify this issue.

NIPPV has been associated with improved survival in patients with ALS and has been widely recommended.24-26 It can also improve patient symptoms27 and health-related quality of life.28,29 However, it appears that a considerable proportion of patients do not receive NIPPV, even in Western countries. Numerous reasons for this have been proposed, including physician attitudes,30 cost,31 caregiver burden,4 and the complete paralysis and loss of communication that ultimately occurs in these patients.32 Compared to the ALS CARE database, our results showed that a relatively small proportion of patients with ALS received NIPPV (16%5 vs. 9.5%). In addition, according to the ALS CARE database, NIPPV has become the most widely used form of ventilator support for patients with ALS in North America, with only 2% receiving invasive mechanical ventilation. However, our data show that 11% of patients underwent a tracheostomy, indicating that invasive respiratory support is still the most common procedure in Korea. In contrast, the application rate of NIPPV was remarkably variable, even among large ALS centers in Korea. However, one possible explanation for this finding is the atypically high proportion of patients with lower diagnostic certainty in our data: 36.5% of patients did not meet the criteria of clinically definite or probable ALS. Furthermore, about 20% of patients were possible or suspected ALS, and clinicians might be more conservative in their therapeutic practice when the diagnosis is uncertain.

We did not analyze other modalities requiring supportive management, such as depression, sleep disturbances, spasticity, or sialorrhea. The ALS CARE database emphasizes the importance of those additional management procedures and demonstrated significant changes following their application.7

This is the first nationwide, multicenter study of the demographic and clinical findings of ALS in Korea, and is the first to provide information on how often NIPPV and PEG are used for this devastating disease in Korea. This study has revealed that supportive management for patients with ALS remains insufficient and is usually introduced by subjective experience rather than objective guidelines. These findings highlight the unmet clinical need, and give physicians tools to better understand the guidelines, evaluate an appropriate patient population, and implement (when possible) to improve overall care and benefit for ALS patients.

One of the most important outcomes of the ALS CARE database project is a favorable change in physician behavior. According to recent reports, physicians were influenced to provide supportive care for patients with ALS behavior after collecting data for this registry.7,9,10 The Korean ALS/MND research group designed and established a nationwide ALS registry as a prospective longitudinal database,12,33 and it has been operated and used as a prospective multicenter cooperative hospital-based registry of Korean ALS. It is thus now possible to evaluate both basic information regarding the current status of ALS diagnosis/treatment and the favorable effects of the treatment procedures.