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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 5  |  Page : 1155-1156

Commentary: Amyotrophic lateral sclerosis: Ongoing search for prognostic biomarkers of longevity

Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi, India

Date of Web Publication6-Sep-2017

Correspondence Address:
Sanjay Pandey
Department of Neurology, Academic block, Room no 507, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi - - 110 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/neuroindia.NI_7_17

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How to cite this article:
Pandey S, Sarma N. Commentary: Amyotrophic lateral sclerosis: Ongoing search for prognostic biomarkers of longevity. Neurol India 2017;65:1155-6

How to cite this URL:
Pandey S, Sarma N. Commentary: Amyotrophic lateral sclerosis: Ongoing search for prognostic biomarkers of longevity. Neurol India [serial online] 2017 [cited 2022 Dec 3];65:1155-6. Available from: https://www.neurologyindia.com/text.asp?2017/65/5/1155/214063

Charcot in 1974 first described amyotrophic lateral sclerosis (ALS).[1] The term consists of two parts, “amyotrophy"meaning atrophy of the muscles and “lateral sclerosis"meaning hardening of lateral column of spinal cord on palpation in autopsy specimens.[1] There is degeneration of both upper and lower motor neurons resulting in weakness, muscle atrophy, fasciculations, spasticity, and brisk deep tendon reflexes. Uncommon presentation of ALS has been reported associated with other neurological conditions and the current issue describes a patient with spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS), which is very rare.[2]

Epidemiology of amyotrophic lateral sclerosis

ALS has an incidence of 1.5 to 2.7/100,000/year and a prevalence of 3 to 5/100,000.[3] The average age of onset is between 55 and 65 years according to the Western literature; however, the same has been found to be a decade earlier in the Indian population.[4] There is a male preponderance with a ratio of approximately 1.5:1.[5] An increased risk of development of ALS has been observed in the rural population, possibly due to a link between the exposure to chemicals such as pesticides and the development of neuronal injury.[4] Western literature has found an increased risk among army veterans and in soccer players; however, there is no documented evidence of exercise being a risk factor for ALS.[5] Although there is lack of definite evidence regarding the presence of a causal relationship, smoking appears to increase the risk of ALS.[5]

Clinical presentation

The clinical hallmark of ALS is the presence of both upper motor neuron and lower motor neuron features in bulbar and spinal cord regions of innnervation. The predominant form of presentation is the ‘limb onset’ type seen in approximately 70%, followed by the ‘bulbar onset’ type seen in 25% and the ‘isolated respiratory involvement’ type seen in 5% of the cases.[6] Irrespective of the region of presentation, the disease spreads over time to other body regions. Other rare forms of presentation include weight loss, muscle cramps and fasciculations in the absence of weakness, and a frontal-type of cognitive loss.[6]

Associated cognitive dysfunction

Up to 40% of patients with ALS have mild cognitive change, and an approximately 5–14% of them have associated frontotemporal dementia (FTD).[5] Postmortem studies have indicated a pathological link between the two conditions.[5] Patients who have concomitant ALS and FTD have a shorter survival than those with ALS alone.[5]

Genetics and pathophysiology

Approximately 10% ALS cases are inherited as a dominant trait and the gene C9orf72 accounts for approximately 40–50% of the cases detected in North America.[5] Mutations associated with the superoxide dismutase (SOD1) gene have been found in nearly 20% of familial ALS patients. The main neurotransmitter implicated in the pathophysiology of ALS is glutamate. Glutamate is an excitatory neurotransmitter and acts on NMDA (N-methy- D-aspartic acid) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, resulting in neurodegeneration.


The El Escorial criteria (EEC) for diagnosis divided the motor system into four regions: bulbar cervical, thoracic, and lumbosacral.[5] It defined five categories of diagnostic certainty for ALS –definite, clinically probable, clinically probable with laboratory support, clinically possible, and clinically suspected ALS. For a definitive diagnosis to be established, the criteria demanded clinical demonstration of both upper motor and lower motor signs in atleast three regions. Electrophysiologic evidence of LMN involvement in isolation was considered under the laboratory support category. The Awaji Shima criteria simplified the EEC by reducing the categories of diagnostic certainty to three categories –clinically definite, probable, and possible.[5] However, the fundamental difference between the Awaji Shima criteria and the EEC is that the former also considers the fasciculation potentials in the absence of fibrillation and positive sharp wave potentials to be signs of active denervation.[7]

Neuroimaging plays a supportive role in the diagnosis.[8] T2-weighted magnetic resonance imaging shows nonspecific hyperintensity of corticospinal tracts in patients with ALS. Magnetic resonance spectroscopy show a reduced N-acetyl aspartate-to-creatine ratio, which can act as a sensitive marker to distinguish patients of ALS from those of progressive muscular atrophy.[7] Diffusion tensor imaging, which detects fractional anisotropy, can delineate motor and extramotor pathway involvement in ALS.[7] Functional imaging, including fluorodeoxyglucose positron emission tomography, shows widespread motor and extramotor involvement.


Other than riluzole, which shows only a modest benefit in survival, there is a dearth of effective disease-modifying therapies in ALS. Novel therapies that show promise include antisense oligonucleotides and virus-delivered gene therapies. Currently, a phase 2 study is ongoing testing the efficacy of bone marrow-derived mesenchymal cells in patients with ALS.


ALS is a devastating disease; 50% of the patients succumb within the first 30 months of symptom onset, while 20% continue suffering from the disease for 5–10 years from its onset.[8] Poor markers for survival include an older age at onset, the ‘bulbar onset’ of disease, and an early respiratory muscle involvement, whereas the ‘limb onset’ disease and a younger age at onset of the disease portray a better prognosis.[6] Certain subtypes such as the ‘flail limb’ variant of ALS have a slower disease progression.[6] There is an urgent need for the detection of prognostic biomarkers of longevity.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

Rowland LP, Shneider NA. Amyotrophic lateral sclerosis. N Engl J Med 2001;344:1688-700.  Back to cited text no. 1
Singh RK, Sonkar KK, Bhoi S, Kalita J, Misra UK. Spinocerebellar ataxia type 2 associated with amyotrophic lateral sclerosis, Neurol India 2017;65:1153-5.  Back to cited text no. 2
Al-Chalabi A, Hardiman O. The epidemiology of ALS: A conspiracy of genes, environment and time. Nat Rev Neurol 2013;9:617-28.  Back to cited text no. 3
Das K, Nag C, Ghosh M. Familial, environmental, and occupational risk factors in development of amyotrophic lateral sclerosis. North Am J Med Sci 2012;4:350-5.  Back to cited text no. 4
[PUBMED]  [Full text]  
Salameh JS, Brown RH Jr, Berry JD. Amyotrophic lateral sclerosis: Review. Semin Neurol 2015;35:469-76.  Back to cited text no. 5
Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. Amyotrophic lateral sclerosis. Lancet 2011;377:942-55.  Back to cited text no. 6
Dengler R. Diagnostic criteria of amyotrophic lateral sclerosis. Romanian J Neurol 2010;9:165-71.  Back to cited text no. 7
Talbot K. Motor neuron disease: The bare essentials. Pract Neurol 2009;9:303-9.  Back to cited text no. 8

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