als

Amyotrophic Lateral Sclerosis

Introduction

The brain is the most complex part of the human body. Brain along with the spinal cord constitutes our central nervous system which controls every part of our daily life from breathing, movements, memory, etc. The brain is made of three main parts: the forebrain (front part of the brain), midbrain, and hindbrain (the back part of the brain). The brain cells are called neurons (nerve cells). Motor neurons in the brain control important muscle activity, such as gripping, walking, speaking, swallowing, and breathing.

Grouped under motor neuron disease (MND), amyotrophic laterals sclerosis (ALS) is a rare condition that progressively damages motor neurons in the brain and spinal cord, stopping them from sending messages to muscles. The muscles gradually weaken, waste away, and twitch. Eventually the ability of the brain to start and control voluntary movement is lost. Symptoms are usually first noticed in the arms, hands, legs or swallowing muscles, which first lose their strength and then their ability to move. As the damage progresses, symptoms spread to other parts of the body and the condition becomes more debilitating.

Prevalence 

The prevalence of ALS is 6 per 100,000 of total population. The incidence is higher in people aged over 50 years. Only 10% of cases are familial (inherited from parents) while the remaining 90% are not. The male to female ratio is 2:1. [www.orpha.net]. According to Foundation for Research on Rare Diseases and Disorders [fRRDD], the frequency of ALS cases in India is 5 in 100,000. 

Cause of the disease

In a vast majority of cases of ALS, the cause is unknown. However, studies suggest that the involvement of multiple genes and environmental factors contribute to ALS in various cases [1]. Indeed, ALS is mainly a polygenic (multiple genes involved) disease (70%–90) and the heritable form (familial ALS – FALS, Inherited from parents) contributes to merely 30% of total ALS cases [2, 3].

Evidence shows that environmental factors such as intense physical activity, cigarette smoking, viral infections, and ingestion of non-protein amino acids play a role in ALS [4, 5, 6]. Dietary factor such as neurotoxin present in the seed of the tropical cycad plant, Cycus circinalis, is believed to have been the reason for increased incidence of ALS in West Pacific Guam [7].

Diagnosis 

The diagnosis is usually based on clinical history, physical examination, electromyography and exclusion of 'ALS-mimics' (e.g. multifocal motor neuropathy, Kennedy's disease and cervical spondylotic myelopathy) by appropriate investigations. The management of ALS is supportive, palliative, and multi-disciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.

Genetics

Genetics - the study of genes, heredity, and genetic variation - of affected individuals suggest that DNA variation in C9ORF72, TARDBP, FUS, and SOD1 genes account for 70% of all familial ALS cases [8]. 

Disease in the regional context

The first report from India on familial ALS, published in 2006, revealed the clinical profile and investigation results of two patients with FALS [9]. In 2008, another interesting study from India retrospectively analyzed 1153 patients of classical ALS over a period of 30 years and found that Indians appear to have a relatively younger age of onset and prolonged survival, suggesting a relatively slow course of ALS among Indian patients [10].

Historical information

ALS sometimes referred to as Lou Gehrig’s disease is named after US baseball player Lou Gehrig. His disease investigation was prompted by a sudden loss of his baseball performance resulting in a premature retirement and two years later death at an age of 37. However, the famous British physicist Stephen Hawking was diagnosed with ALS when he was 21, but continues to live beyond 70 under palliative care.

References 

1. Das K, Nag C, Ghosh M.  Familial, Environmental, and Occupational Risk Factors in Development of Amyotrophic Lateral Sclerosis. N Am J Med Sci. 2012;4:350-5.

2. Henriques A, Gonzalez De Aguilar JL: Can transcriptomics cut the gordian knot of amyotrophic lateral sclerosis? Curr Genomics. 2011;12:506-15

3. Stone N: Amyotrophic lateral sclerosis: a challenge for constant adaptation. J Neurosci Nurs. 1987; 19: 166–73.

4. Bastos AF, Orsini M, Machado D, et al.: Amyotrophic lateral sclerosis: one or multiple causes? Neurol Int. 2011; 3: e4.

5. Ferraiuolo L, De Bono JP, Heath PR, et al.: Transcriptional response of the neuromuscular system to exercise training and potential implications for ALS. J Neurochem. 2009; 109: 1714–24.

6. Köller H, et al.: Reversible ALS-like disorder in HIV infection. An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology. 2002; 59: 474

7. Mitchell JD: Amyotrophic lateral sclerosis: toxins and environment. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000;1:235-50.

8. Chen S, Sayana P, Zhang X, et al.: Genetics of amyotrophic lateral sclerosis: an update. Mol Neurodegener. 2013; 8: 28.

9. Nalini A, Yeshraj G, Veerendrakumar M. Familial amyotrophic lateral sclerosis: first report from India. Neurol India. 2006; 54:304-5.

10. Nalini A, Thennarasu K, Gourie-Devi M, Shenoy S, Kulshreshtha D. Clinical characteristics and survival pattern of 1,153 patients with amyotrophic lateral sclerosis: experience over 30 years from  India. J Neurol Sci. 2008; 272:60-70.

Contributor:

Praveen Raj MSc

MedGenome Labs Pvt Ltd 

258/A Bommasandra Hosur Road 

Bengaluru 560 099, India

Reviewer:

Pochi R. Subbarayan PhD

University of Miami, FL, USA