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.
Amyotrophic Lateral Sclerosis