Primary lateral sclerosis: disease, syndrome, both or neither?

Swash, Desai, and Misra [1] use two patients with uncommon, as the authors point out, for such cases to primary lateral sclerosis (PLS) as the foundation for a develop evidence of involvement of other parts of the history-based discussion of that elusive condition. They nervous system and thus place the case in another diagnosconclude that it is a form of motor neuron disease and tic category such as multiple sclerosis, amyotrophic lateral often turns into amyotrophic lateral sclerosis (ALS) before sclerosis, and spinal cord tumor.’’ That skeptical view death. Their inclusionary and exclusionary criteria for the confirms the label given by Swash et al. that this was the clinical diagnosis of PLS are the generally accepted ones. ‘‘era of doubt’’. However, there is no way to prove the diagnosis except by But we now have a paradox. The syndrome is defined autopsy, which has been performed in only 6 cases since and recognized clinically, but it is an unsatisfactory the ‘modern era’ started in 1977 with a report by C. Miller diagnosis-of-exclusion, and can be proven only at autopsy. Fisher [2–4]. It is reasonable to start in 1977 because, at There have been so few autopsy cases that there can be no the time of the earliest reports serological tests for syphilis reliable clinico-pathological correlation; we must rely on and viral infections were not available and B12 deficiency clinical series to define the variations of the syndrome. could not be identified; myelography and electromyogI believe the evidence indicates the following: raphy were not widely available before 1945. CT did not come until 1973 and MRI was even later. The syndrome was named by Erb [5]; in describing 10 1. PLS can be recognized anatomically as a disorder of previously published cases he used the term ‘spastic spinal the corticospinal tracts, implicating the upper motor paralysis’, but, in an aside, he said he had used ‘lateral neuron and sparing the lower motor neurons of sclerosis’ earlier. Four of the 10 cases were familial. Other brainstem and spinal cord; this pattern was seen in all neurology titans described 3 autopsy cases between 1902 6 modern autopsies. Neuronal cellular pathology was and 1910 [6–7]. Even with the limitations of diagnosis in not seen in the motor cortex in 3 of the 6 autopsies, those days there were few postmortem examinations. The but that failure does not exclude the possibility that the literature was then largely silent until the end of World primary disorder affected cortical motor neurons; War II when a new set of well-known neurologists another possibility is that the disease may sometimes reported series of living patients. Some authorities, howarise subcortically, in the corticospinal tracts. Also, the ever, disdained the clinically diagnosed cases. For inlack of visible change in the lower motor neurons of stance, in discussing a 1946 paper by Wechsler and Brody all 6 cases does not exclude the possibility that there [8], Merritt [9] stated: ‘‘The existence of primary lateral would have been symptoms of lower motor neuron sclerosis as a clinical entity has been doubted by most disease had the patients lived longer. modern neurologists. Although cases with symptoms and 2. PLS can be a form of ALS. In the autopsy series of signs limited to those which result from injury to the Brownell et al. [10], 3 patients had only upper motor pyramidal tract are not infrequently encountered, it is not neuron signs in life, but the anterior horn cells were affected at autopsy. Lawyer and Netsky [11] stated they had no such patients. Castaigne et al. [12] *Corresponding author. Tel.: 11-212-305-8551; fax: 11-212-305described two similar cases but the patients actually 6978. E-mail address: 1pr1@columbia.edu (L.P. Rowland) had lower motor neuron signs in life and should have