Please confirm that you would like to log out of Medscape. If you log out, you will be required to enter your username and password the next time you visit. PLS usually affects adults GEF infants is usually sporadic.
According to Panzeri et al, “the protein encoded by the ALS2 gene, alsin, contains a number of cell signaling and protein trafficking domains. A unique locus for an autosomal dominant form of adult-onset PLS in a large French-Canadian family was mapped to chromosome 4ptel-4p16. This locus had not been implicated in ALS or in hereditary spastic parapareses, spinal muscular atrophy, or spinal and bulbar muscular atrophy. 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. These are considered first-order motor neurons, because they are connected directly to the muscles.
The somas of upper motor neurons reside in the brain, where they control the activity of lower motor neurons. Second-order motor neurons can be distinguished from higher-order motor neurons. Second-order motor neurons are upper motor neurons whose cell bodies reside primarily in the precentral gyrus or the primary motor cortex of the frontal lobe. These neurons are involved in planning and organizing motor activity and direct the second-order motor neurons. The somas of these third- and higher-order motor neurons reside in the brain, and their axons form associative or commissural projections within the brain. These should be distinguished from diseases in which primarily the axons of motor neurons are affected. ALS is the most common of the MNDs.
Therefore, not every MND is ALS. Patients with PLS occasionally have mild, nonspecific, and nonprogressive findings of denervation on electrodiagnostic testing. The severity of the denervation and reinnervation does not resemble that seen in ALS and does not justify these patients’ being classified as having ALS. These patients may be concerned that their PLS eventually could evolve into ALS. Clinical presentation ALS may present initially with signs of only upper or lower motor neuron involvement. Thus, a process that initially is considered PMA or PLS has the potential to be reclassified as ALS if sufficient signs of a combination of upper and lower motor neuron involvement develop over time.
Reports have described patients with 1 of the genes for familial ALS in whom only lower motor neuron involvement was seen during life and at autopsy. This position is supported by the World Federation of Neurology diagnostic criteria for ALS. Complications Dysfunction and disability accrue as PLS progresses. These are dealt with by the treating physician as they arise. The slow rate of progression of PLS provides most patients and families with time to adapt to the changes and identify resources for support. Conversely, the overall duration and magnitude of the burden placed on the family and caregivers is commensurately greater than it would be in a more rapidly progressing disease. Patients with early PLS may not be limited in these respects, but they should be reassessed as the disease progresses.
Patients and physicians should follow the specific laws of their jurisdictions regarding notification of licensing authorities and automobile insurers. Patients should be informed of these risks and counseled in accordance with the laws of their jurisdiction, taking their present and future condition into consideration. Such communications should be documented carefully. The term pathophysiology refers at this time to histologic consequences of unknown etiologic factors, which result, in turn, in the clinical manifestation of PLS. Five reports that include autopsy findings in 6 patients with PLS differ in the pathologic changes they describe. Two major factors may account for the different pathologic findings. First, uncertainties exist regarding the diagnosis in some of the series.
This is discussed below in regard to one of the patients in the series described by Pringle et al in 1992. Younger et al described 3 patients who had demyelination of the corticospinal tracts without gliosis or discernible loss of Betz cells in the precentral gyrus. The pathology in these patients appeared to affect the myelin sheath of the axon of the upper motor neuron or the axon itself rather than that of the upper motor neuron cell body. In contrast, histologic findings in 3 other patients were of involvement of the precentral gyrus and loss of Betz cells. 7 patients reported by Pringle et al showed cerebral atrophy that was most pronounced in the region of the precentral gyrus in 5 patients, was present only in the precentral region in 1 patient, and was most prominent in the frontoparietal region in another patient. 12 of 18 patients with PLS.