Primary Lateral Sclerosis

Definition

Primary Lateral Sclerosis (PLS) is characterized as being a rare, non-hereditary, idiopathic, slow, and progressive degeneration of the upper motor neuronsStatland, J. M., Barohn, R. J., Dimachkie, M. M., Floeter, M. K., & Mitsumoto, H. (2015). Primary lateral sclerosis. Neurologic Clinics, 33(4), 749-760. doi:10.1016/j.ncl.2015.07.007. PLS lies on a continuum of sporadic motor neuron disorders. This spectrum includes other disorders such as progressive muscular atrophy, which involves only lower motor neurons, as well as amyotrophic lateral sclerosis (ALS), characterized by both upper and lower motor neuron involvement. Many patients diagnosed with PLS continue to have high levels of independence for many years^{Gordon, P. H., Cheng, B., Katz, I. B., Pinto, M., Hays, A. P., Mitsumoto, H., & Rowland, L. P. (2006). The natural history of primary lateral sclerosis. Neurology, 66(5), 647-653. doi: 10.1212/01.wnl.0000200962.94777.71}.

Differential Diagnoses

(Statland et al, 2015); (Kuipers-Upmeijer et al, 2001); (Strong & Gordon, 2005)

As PLS is an upper motor neuron issue, there are several potential differential diagnosis. The 2 most likely upper motor neuron diseases that is associated with PLS are …

• Amyotrophic lateral sclerosis (Statland et al, 2015); (Strong & Gordon, 2005)

        - ALS presents with lower and/or upper motor deficits and has fast(er) progression; PLS is slower progression and typically only affects                upper motor neurons.
        - ALS is more commonly associated with stiffness then PLS (47% vs 4%)
        - Both ALS and PLS can be assoicated with cognitive issues but is not present in its ‘uncomplicated’ forms (Strong & Gordon, 2005).

• Hereditary spastic paraplegias (Strong & Gordon, 2005)

         - HSP has spasticity of the lower limbs; PLS is associated with spasticity as well and slight weakness but spasticity can affect                              speech (spastic dysarthria)
         - Complicated cases of HSP can result in dementia & mental retardation which may mimic cognitive issues possibly present in                              complicated cases of PLS.

Other potential, but less specific, differential considerations include (Statland et al, 2015)…

• Structural lesions, especially related to the spine (eg. cervical spondylmyelopathy)
• Infection (eg. HIV, syphilis)
• Demyelinating disease (eg. mutliple sclerosis)
• Metabolic / toxic (eg. vitamin E deficiency)
• Neurodegenerative (eg. Parkinsons and parkinson's-plus syndromes)

Special care must be taken when diagnosing as PLS can be misdiagnosed as the above examples, and many more (Kuipers-Upmeijer et al, 2001).

References

Gordon, P. H., Cheng, B., Katz, I. B., Pinto, M., Hays, A. P., Mitsumoto, H., & Rowland, L. P. (2006). The natural history of primary lateral sclerosis. Neurology, 66(5), 647-653. doi: 10.1212/01.wnl.0000200962.94777.71

Kuipers-Upmeijer, J., de Jager, A., Hew, J., Snoek, J., & van Weerden, T. (2001). Primary lateral sclerosis: Clinical, neurophysiological, and magnetic resonance findings. Journal of Neurology Neurosurgery and Psychiatry, 71(5), 615-620. doi:10.1136/jnnp.71.5.615

Singer, M. A., Statland, J. M., Wolfe, G. I., & Barohn, R. J. (2007). Primary Lateral Sclerosis. Muscle & Nerve, 35(3), 291-302. doi: 10.1002/mus.20728

Statland, J. M., Barohn, R. J., Dimachkie, M. M., Floeter, M. K., & Mitsumoto, H. (2015). Primary lateral sclerosis. Neurologic Clinics, 33(4), 749-760. doi:10.1016/j.ncl.2015.07.007

Strong, M. J., & Gordon, P. H. (2005). Primary lateral sclerosis, hereditary spastic paraplegia and amyotrophic lateral sclerosis: Discrete entities or spectrum? Amyotrophic Lateral Sclerosis, 6(1), 8-16. doi:10.1080/14660820410021267