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 yearsGordon, 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.

Epidemiology

Approximately 2-5% of adults in neuromuscular clinics will be diagnosed with PLSSinger, 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. The age of onset ranges from a mean age of 45.4-53.7 years, though a juvenile form of PLS has been described as well. Although the difference is not pronounced, there is a slight male predominance over females in being diagnosed with PLS.

Etiology

The exact cause of adult-onset PLS remains unknownSinger, 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. PLS is a diagnosis of exclusion, meaning that individuals are diagnosed with the condition when their progressive upper motor neuron dysfunctions cannot be explained by any other possible cause.

Prognosis

A distinctive clinical feature of PLS is that it has a very slow progression, leading it to be considered to have a more benign prognosis in comparison to ALSSinger, 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. The longevity of individuals with PLS is unclear, but it has been estimated to be 7.9 years or longer. Individuals with PLS and minimal EMG changes appear to have a decreased ability to ambulate independently in comparison to those without EMG changes. Nonetheless, patients may still be able to ambulate without aids after several years of being diagnosed. It is common for patients to be diagnosed with PLS but later diagnosed with ALS instead. Due to their similar course of progression, misdiagnosis can occur. A detailed spectrum of PLS categories have been detailedSinger, 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.20728Gordon, 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).