What is primary lateral sclerosis (PLS)?

Updated: Sep 06, 2019
  • Author: Carmel Armon, MD, MSc, MHS; Chief Editor: Nicholas Lorenzo, MD, MHCM, CPE, FAAPL  more...
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Answer

Primary lateral sclerosis (PLS) is a progressive, degenerative disease of upper motor neurons characterized by progressive spasticity (ie, stiffness). It affects the lower extremities, trunk, upper extremities, and bulbar muscles (usually in that order). [1, 2] The major clinical challenge that the presentation of PLS poses is distinguishing it from the more common form of motor neuron disease, amyotrophic lateral sclerosis (ALS), [3, 4] from hereditary spastic paraparesis (HSP), [5] and from nondegenerative conditions that may present similarly early in their course. (See Differentials.)

PLS usually affects adults and is usually sporadic. A rare, hereditary variant affecting infants and children (JPLS) was mapped to the gene ALS2 (alsin) on chromosome 2q33.2. According to Panzeri et al, "the protein encoded by the ALS2 gene, alsin, contains a number of cell signaling and protein trafficking domains. The structure of alsin predicts that it functions as a guanine nucleotide exchange factor (GEF). GEFs regulate the activity of members of the Ras superfamily of GTPases." [6] At least 10 deletion mutations and 1 missense mutation of the alsin gene have been shown to cause JPLS. [6] (See Etiology.)

A unique locus for an autosomal dominant form of adult-onset PLS in a large French-Canadian family was mapped to chromosome 4ptel-4p16.1. This locus had not been implicated in ALS or in hereditary spastic parapareses, spinal muscular atrophy, or spinal and bulbar muscular atrophy. [7]

A genetically mediated PLS look-alike, progressive familial paraparesis (hereditary spastic paraparesis), is a separate condition with a more limited clinical extent and a more benign course.

Go to Amyotrophic Lateral Sclerosis, Amyotrophic Lateral Sclerosis in Physical Medicine and Rehabilitation, and Emergent Treatment of Amyotrophic Lateral Sclerosis for complete information on these topics.


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