PRIMARY LATERAL SCLEROSIS (PLS) AND PROGRESSIVE MUSCULAR ATROPHY (PMA)
The following is an excerpt from:
Mitsumoto H, Chad D, and Pioro E. Amyotrophic Lateral Sclerosis. Philadelphia: F.A. Davis Company, 1998.
Primary Lateral Sclerosis
In 1865, Charcot described a woman with "hysterical attacks" who had remitting, and, later, permanent "contractures" of the limbs. Autopsy examination showed sclerosis of the lateral columns and atrophic anterior roots, but normal cells in the gray matter of the spinal cord. The term "contracture" should be considered as an earlier term meaning spasticity with hyperreflexia. This case indicated a close association between paralysis and "contracture" and became one of defining descriptions of primary lateral sclerosis (PLS). The condition that is now recognized as PLS was described in 1875 by Heinrich Erb, a founder of German neurology. However, the term PLS always included a heterogenous group of diseases. Until recently, it has been generally agreed that PLS was not a disease separate from ALS.
Motor System Degeneration, Motor Neuron Disease, or ALS?
Sir William Gowers, a founder of British neurology, stated in his textbook, A Manual of Diseases of the Nervous System (the 3rd edition in 1899), that he never encountered a single case of PMA in which the pyramidal tracts were unaffected. He did not think Charcot's introduction of the term “ALS” to be very helpful because it implied that the primary lesion was degeneration of the pyramidal tracts and that atrophy of anterior horn cells was secondary, or deuteropathic. He felt that Charcot's distinction in effect gave a new name to an old disease. He concluded that PMA, PBP, and ALS were "essentially one disease." The clinical manifestations were determined by the timing, extent, and severity of the degeneration in the upper and lower segments of the motor pathway. Brain in 1933 introduced the term "motor neuron disease" so that all these apparently different conditions could be brought together in a single general category and used the terms “motor neuron disease” and “ALS” interchangeably.
A series of studies supported the opinion that PMA, PLS, and PBP were subsets of ALS. Swank and Putnam in 1943 analyzed 197 patients with ALS that was classified according to three types: the Charcot, or completely developed type; the atypical type (monoplegic, hemiplegic, or proximal involvement); and incomplete type (lateral sclerosis, amyotrophy, or bulbar palsy form). They considered PLS and PMA to be ALS that had yet to develop fully. Lawyer and Netsky in 1953 did a clinicopathologic analysis of 53 patients with ALS and concluded that motor neuron diseases form a group that includes PMA, PLS, ALS, and PBP. Mackay in 1963 reviewed 126 patients with ALS and concluded:
Regardless of the onset, the spastic forms nearly always become atrophic, the atrophic also spastic, while the spinal forms nearly always become bulbar, and the bulbar forms, if the patients live long enough, become also spinal. The entire group is, therefore, best regarded as a single degenerative disease, ALS, which constitutes a spectrum of atrophic process at one end, spastic at the other, and both in the center. With time, cases at each end of the spectrum move towards the center.
In 1970, Brownell and colleagues analyzed the extent of pathologic involvement in motor neuron disease and suggested that "for the time being, we retain the label of 'motor neurone disease'." They thought that 'classical' motor neuron disease was not well defined, but rather was a prominent band within a wide spectrum of subacute or chronic multiple system degenerations that show a predilection to certain parts of the motor system. Metcalf and Hirano in 1971 reported two members of a family with PMA and a third member with classic ALS, suggesting that PMA is only a clinical manifestation of ALS.
Diagnosis of motor neuron disease (MND) is a clinical matter. There is no single test to determine the diagnosis. Progressive muscular atrophy (PMA) is a MND characterized by progressive weakness and atrophy due to degeneration of lower motor neurons (LMN) in the spinal cord or in the brainstem. Amyotrophic lateral sclerosis (ALS), a far more common type of MND, includes degeneration of upper motor neurons (UMN) in the brain as well as degeneration of LMN. Interestingly some PMA patients continue to have a pure LMN syndrome throughout the natural history of the disease whereas others evolve to ALS.
From the Summer 2008 ALS Center Newsletter
Since Aran first described PMA in 1850, the relationship to and differentiation between PMA and ALS is still being debated. I studied the challenging topic of PMA. The results will be presented at the international symposium on ALS/MND in November.
The aim of the study was to investigate the proportion of patients with PMA who develop UMN signs in the disease course and to identify the outcome and clinical management in patients with PMA to find out how different they are from those of patients with ALS.
We identified 91 patients diagnosed with PMA and 871 patients with ALS using follow-up data after reviewing medical records of MND in the years 2000 to 2007 at the Eleanor and Lou Gehrig MDA/ALS research center, Columbia University.
Compared to ALS patients the PMA patients tended to have longer survival time, with a median survival time of 48.3 months vs. 36 months for ALS patients. Twenty (22%) of these PMA patients developed UMN signs during the follow-up period (up to 68.7 months). No convincing differences were found between the two groups in survival time. The use of percutaneous endoscopic gastrostomy (PEG) was 10% vs. 15%, while noninvasive ventilation (NIV) was used in 30% vs.60% of patients.
Though PMA was characterized by a longer survival than ALS, care and management required in these patients with PMA did not differ from patients with ALS. Thus PMA appears to be slowly progressive ALS, rather than a distinct entity.
It is a great honor for me to have an opportunity of fellowship to study motor neuron disease (MND) here at the Eleanor and Lou Gehrig MDA/ALS research center, Columbia University. I was impressed by the comprehensive care and management.
I would like to thank all members of ALS center for their help in conducting this study.
Woo-Kyung Kim, MD
Kangdong Sacred Heart Hospital
Dr. Woo-Kyung Kim’s paper was presented at the International ALS Symposium on ALS/MND in November 2008.
Hallym University, Korea
- Gordon PH, Cheng B, Katz IB, Pinto M, Hays AP, Mitsumoto H, Rowland LP. The natural history of primary lateral sclerosis. Neurology. 2006;66:647-653.
- Mitsumoto H, Uluğ AM, Pullman SL, et al. Quantitative Objective Markers for Upper and Lower Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis. Neurology 2007;17:1402-1410.
- Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008; 321:1218-21.