Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease or Charcot disease, is the most common form of motor neuron disease 1,4 resulting in progressive weakness and eventual death due to respiratory insufficiency.
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 muscles of the face, limbs, 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.
- 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.
- 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
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- measurements and ratios
- midbrain to pons area ratio (for PSP)
- Magnetic Resonance Parkinsonism Index (MRPI) (for PSP)
- frontal horn width to intercaudate distance ratio (FH/CC) (for Huntington disease)
- intercaudate distance to inner table width ratio (CC/IT) (for Huntington disease)
- scoring systems
- measurements and ratios
- typical/classical Alzheimer disease
- variant (e.g. posterior cortical atrophy)
- chronic traumatic encephalopathy (CTE)
- corticobasal degeneration
- frontotemporal lobar degeneration (FTLD) (not all are tau)
- Pick disease
- progressive supranuclear palsy (PSP)
- Alzheimer disease
- cerebral amyloid angiopathy (CAA)
- transthyretine-associated cerebral amyloidosis
- neuronal intranuclear hyaline inclusion disease (NIHID)
- TDP-43 proteinopathies
- spinocerebellar ataxias
- Huntington disease
- hereditary spastic paraplegia
- clinically unclassifiable parkinsonism (CUP)
- Unverricht-Lundborg disease
prion diseases (not always included as neurodegenerative)
- Creutzfeldt-Jakob disease (sporadic, variant, familial, and iatrogenic)
- fatal familial insomnia
- Gerstmann-Straussler-Scheinker disease
- variably protease-sensitive prionopathy