Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a rare, terminal neurodegenerative disorder characterized by the progressive loss of motor neurons that control voluntary muscle movements. It is the most common form of motor neuron disease. Early symptoms include muscle stiffness, twitches, weakness, and muscle wasting. The condition progresses to the loss of abilities such as eating, speaking, moving, and eventually breathing. Approximately 15% of individuals with ALS develop frontotemporal dementia, while 50% experience minor cognitive or behavioral difficulties. ALS is categorized into limb-onset or bulbar-onset based on the initial symptoms.
1918: Description of Flail Leg Syndrome
In 1918, Pierre Marie and his student Patrikios first described flail leg syndrome, a regional variant of ALS.
1933: Coining of Motor Neurone Disease Term
In 1933, British neurologist Russell Brain coined the term 'motor neurone disease' to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease.
1938: Lou Gehrig Diagnosed with ALS
In 1938, American baseball player Lou Gehrig was diagnosed with ALS, which led to the disease being commonly known as 'Lou Gehrig's disease' in the United States.
1969: First EMG/NCS Diagnostic Criteria for ALS
In 1969, Edward H. Lambert published the first EMG/NCS diagnostic criteria for ALS, which included four key findings supporting the diagnosis.
1994: Introduction of El Escorial Criteria
The El Escorial diagnostic criteria for ALS were introduced in 1994 and revised in 1998, primarily for research purposes to include/exclude patients and stratify them for trials.
1998: Revision of El Escorial Criteria
In 1998, the El Escorial diagnostic criteria for ALS were revised to improve their application in research and clinical trials.
November 2004: ALS Fact Sheet Archived
In November 2004, an 'Amyotrophic Lateral Sclerosis Fact Sheet' was archived, incorporating public domain text and other references about ALS.
2006: NIV Prolongs Survival in ALS
A 2006 randomized controlled trial found that non-invasive ventilation (NIV) prolongs survival by about 48 days and improves the quality of life for ALS patients, although its benefits vary based on bulbar function.
2006: Proposal of Awaji Criteria
In 2006, the Awaji criteria were proposed to use EMG and NCV tests for earlier diagnosis of ALS.
August 2014: Ice Bucket Challenge Goes Viral
In August 2014, the 'Ice Bucket Challenge' went viral online to raise money for ALS research. Participants filmed themselves pouring a bucket of ice water on themselves and nominated others to do the same, raising significant funds for various ALS organizations.
2015: Large Cohort Study on NIV
Results from a 2015 large cohort study suggested that NIV may prolong survival in ALS patients with bulbar weakness, leading to recommendations that NIV be offered to all ALS patients despite potential tolerance issues.
2015: Racial and Regional Differences in ALS Prevalence
In 2015, ALS prevalence in the United States varied by race and region, with whites having a higher prevalence (5.4 per 100,000) compared to blacks (2.3 per 100,000). The Midwest had the highest regional prevalence, possibly due to its higher proportion of white residents.
2015: Age-related ALS Prevalence
In 2015, the prevalence of ALS in the United States was lowest in the 18–39 age group and highest in the 70–79 age group. It was noted that ALS incidence decreases dramatically after age 80.
2015: ALS Epidemiology in 2015
In 2015, the prevalence of ALS in the United States was 5.2 people per 100,000, with higher rates observed in whites, males, and older individuals. Epidemiological studies indicated significant variation in ALS incidence and prevalence across different regions and ethnic groups.
2016: Mexiletine Trial for ALS Cramps
In 2016, a randomized controlled trial demonstrated that mexiletine is effective for treating cramps in ALS patients.
2017: Review on Mexiletine for ALS Cramps
A 2017 review concluded that mexiletine is safe and effective for treating cramps in ALS, based on a randomized controlled trial conducted in 2016.
2019: Introduction of Gold Coast Criteria
The Gold Coast criteria for ALS diagnosis were introduced in 2019, representing the most recent advancements in diagnostic criteria.
April 2023: Approval of Tofersen for SOD1-Associated ALS
In April 2023, Tofersen (Qalsody), an antisense oligonucleotide, was approved for the treatment of SOD1-associated ALS in the United States. Studies indicated a trend towards slowing disease progression and a significant reduction in neurofilament light chain, a biomarker for neuronal damage.
2023: Biomarkers Studied for ALS Diagnosis
In 2023, researchers continued to study various biomarkers for ALS, although none were in general medical use at the time. The diagnosis of ALS remained primarily dependent on clinical assessments by physicians after ruling out other diseases.
April 2024: Withdrawal of Relyvrio
In April 2024, the manufacturer withdrew AMX0035 (Relyvrio) following the completion of the Phase 3 PHOENIX trial, which did not show substantial benefits for ALS patients.
2040: Projected Increase in ALS Cases
The number of ALS cases worldwide is projected to increase by 69% from 222,801 in 2015 to 376,674 in 2040, primarily due to global population aging, especially in developing countries.