This led to the development of the first animal model of ALS, the transgenic SOD1 mouse, in 1994. In December 1995, riluzole became the first FDA-approved drug for ALS. It was then approved in Europe in 1996 and in Japan in 1998. In 1996, the ALS Functional Rating Scale (ALSFRS) was first published; it was a 10-item questionnaire that measured the ability of people with ALS to perform activities of daily living. In 1999, the scale was changed to give more weight to respiratory symptoms. The resulting ALS Functional Rating Scale - Revised (ALSFRS-R) is a 12-item questionnaire that replaces the single question about breathing with a question each about dyspnea, orthopnea, and respiratory insufficiency.In 2006, it was discovered that the protein TDP-43 is a major component of the inclusion bodies seen in both ALS and frontotemporal dementia (FTD), which provided evidence that ALS and FTD are part of a common disease spectrum. This led to the discovery in 2008 that mutations in TARDBP, the gene that codes for TDP-43, are a cause of familial ALS. In 2011, noncoding repeat expansions in C9orf72 were found to be a major cause of ALS and FTD. Edaravone was approved to treat ALS in Japan and South Korea in 2015 and in the United States in 2017. As of 2017, it has not been approved to treat ALS in Europe. Diagnostic criteria
In the 1950s, electrodiagnostic testing (EMG and NCV) began to be used to evaluate clinically suspected ALS.
Of these, 9% are symptomatic, depending on the competence of the lower esophageal sphincter (LES). 95% of these are "sliding" hiatal hernias, in which the LES protrudes above the diaphragm along with the stomach, and only 5% are the "rolling" type (paraesophageal), in which the LES remains stationary, but the stomach protrudes above the diaphragm.Hiatal hernias are most common in North America and Western Europe and rare in rural African communities. Some have proposed that insufficient dietary fiber and the use of a high sitting position for defecation may increase the risk. References


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