Amyotrophic lateral sclerosis
Citation, DOI & article data
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease and Charcot disease, is the most common form of motor neuron disease 1,4 resulting in progressive weakness and eventual death due to respiratory insufficiency. There is both upper motor neuron and lower motor neuron damage. 'Lateral sclerosis' indicates degeneration of the pyramidal tracts.
Amyotrophic lateral sclerosis typically is diagnosed in middle age. There is a recognized male predilection 1.
Both upper and lower motor neurons are affected, with decreased motor strength and wasting of the limb muscles, bulbar muscles, and diaphragm. There is a progressive loss of motor strength, with preservation of intellectual and sensory function. In the hands, the split hand sign or split hand plus sign may be characteristically seen.
El Escorial criteria for the diagnosis of amyotrophic lateral sclerosis 7:
- it requires the presence of
- signs of lower motor neuron (LMN) degeneration by clinical, electrophysiological or neuropathologic examination
- signs of upper motor neuron (UMN) degeneration by clinical examination
- progressive spread of signs within a region or to other regions
- together with the absence of
- electrophysiological evidence of other disease processes that might explain the signs of LMN and/or UMN degenerations
- neuroimaging evidence of other disease processes that might explain the observed clinical and electrophysiological signs
Amyotrophic lateral sclerosis is a relentlessly progressive neurological disorder characterized by the death of upper motor neurons (Betz cells in the cortex) and anterior horn cells with secondary Wallerian degeneration 2.
The majority of cases are sporadic and thus less well understood. In the familial form of amyotrophic lateral sclerosis several gene mutations have been identified (e.g. SOD1, TDP-43, FUS, and the hexanucleotide repeat expansion in C9ORF72) 5.
The earliest MR manifestation is hyperintensity on T2-weighted imaging in the corticospinal tracts, seen earliest in the internal capsule, as the fibers are most concentrated here. Eventually, the entire tract from motor strip to the spinal cord is affected by increased T2 signal and volume loss 3.
It is important to note that both of these features are present in varying degrees in normal control patients, and as such an appreciation of what is too much is essential if MRI is to be of benefit.
- T1: hyperintensity of the tongue may be seen in patients with bulbar involvement, known as the "bright tongue sign" 13
- T2: hyperintensity in the corticospinal tracts (specificity <70% and sensitivity <40%) 6
- GRE/SWI: hypointensity in the precentral gyrus bilaterally, known as the "motor band sign" 8,9
MR spectroscopy 2
- decreased NAA
- decreased glutamate
- increased choline
- increased myo-inositol
Treatment and prognosis
Amyotrophic lateral sclerosis typically progresses to death in 2-6 years, usually from respiratory complications 5. Few therapies have been shown to extend survival, including riluzole, a glutamate antagonist 10,11.
History and etymology
Amyotrophic lateral sclerosis is also known as Charcot disease in honor of French neurologist Jean-Martin Charcot (1825-1893) who diagnosed and described the first case in the nineteenth century (1865-1869) 12. It is also popularly known as Lou Gehrig disease, especially in North America, in honor of legendary New York Yankees first baseman Henry Louis (Lou) Gehrig (1903-1941), who was diagnosed with the disease in 1939.
- 1. Khader SM, Greiner FG. Neuroradiology case of the day. Amyotrophic lateral sclerosis. Radiographics. 19 (6): 1696-8. Radiographics (full text) - Pubmed citation
- 2. Chan S, Shungu DC, Douglas-Akinwande A et-al. Motor neuron diseases: comparison of single-voxel proton MR spectroscopy of the motor cortex with MR imaging of the brain. Radiology. 1999;212 (3): 763-9. Radiology (full text) - Pubmed citation
- 3. Cheung G, Gawel MJ, Cooper PW et-al. Amyotrophic lateral sclerosis: correlation of clinical and MR imaging findings. Radiology. 1995;194 (1): 263-70. Radiology (abstract) - Pubmed citation
- 4. Nelles M, Block W, Träber F et-al. Combined 3T diffusion tensor tractography and 1H-MR spectroscopy in motor neuron disease. AJNR Am J Neuroradiol. 2008;29 (9): 1708-14. doi:10.3174/ajnr.A1201 - Pubmed citation
- 5. Traynor BJ, Cleveland DW. Special Issue on amyotrophic lateral sclerosis. Exp. Neurol. 2014;262 Pt B: 73-4. doi:10.1016/j.expneurol.2014.08.020 - Free text at pubmed - Pubmed citation
- 6. Simon NG, Turner MR, Vucic S et-al. Quantifying disease progression in amyotrophic lateral sclerosis. Ann. Neurol. 2014;76 (5): 643-57. doi:10.1002/ana.24273 - Free text at pubmed - Pubmed citation
- 7. Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors. J. Neurol. Sci. 1995;124 Suppl: 96-107. Pubmed citation
- 8. Chakraborty S, Gupta A, Nguyen T, Bourque P. The "Motor Band Sign:" Susceptibility-Weighted Imaging in Amyotrophic Lateral Sclerosis. (2015) The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 42 (4): 260-3. doi:10.1017/cjn.2015.40 - Pubmed
- 9. Kwan JY, Jeong SY, Van Gelderen P, Deng HX, Quezado MM, Danielian LE, Butman JA, Chen L, Bayat E, Russell J, Siddique T, Duyn JH, Rouault TA, Floeter MK. Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology. (2012) PloS one. 7 (4): e35241. doi:10.1371/journal.pone.0035241 - Pubmed
- 10. Hinchcliffe M, Smith A. Riluzole: real-world evidence supports significant extension of median survival times in patients with amyotrophic lateral sclerosis. (2017) Degenerative neurological and neuromuscular disease. 7: 61-70. doi:10.2147/DNND.S135748 - Pubmed
- 11. Bensimon G, Bensimon LL, Bensimon MV, Bensimon. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. (1994) The New England journal of medicine. doi:10.1056/NEJM199403033300901 - Pubmed
- 12. Kumar DR, Aslinia F, Yale SH, Mazza JJ. Jean-Martin Charcot: the father of neurology. (2011) Clinical medicine & research. 9 (1): 46-9. doi:10.3121/cmr.2009.883 - Pubmed
- 13. Fox M & Cohen A. "Bright Tongue Sign" in ALS. Neurology. 2012;79(14):1520. doi:10.1212/wnl.0b013e31826d5ffc - Pubmed