Familial clustering of primary lateral sclerosis and amyotrophic lateral sclerosis: Supplementary evidence for a continuum

Abstract

Background and purpose: Primary lateral sclerosis (PLS) is a motor neuron disorder characterized by a pure upper motor neuron degeneration in the bulbar and spinal regions.The key difference with amyotrophic lateral sclerosis (ALS) is the lower motor neuron system integrity. Despite important literature on this disease, the pathophysiology of PLS remains unknown, and the link with ALS still balances between a continuum and a separate entity from ALS.Methods: We report nine families in which both PLS and ALS cases occurred, in general among first-degree relatives. Results:The patients with PLS and ALS had a typical disease presentation. Genetic studies revealed mutations in SQSMT1, TBK1, and TREM2 genes in two PLS patients and one ALS patient. Conclusions:These results strongly support a phenotypic continuum between PLS and ALS.

Reply to the letter from Gazulla et al.

“…Although we agree with the comments of these authors, we would like to mention several findings in favour of a continuum between PLS and ALS [1]. First, continuum does not mean progression from one side of the spectrum to the other in all cases but just different phenotypes of the same phenomenon.…”

“…First, continuum does not mean progression from one side of the spectrum to the other in all cases but just different phenotypes of the same phenomenon. Secondly, we stress the relevant literature supporting that PLS is associated with other motor neuron disorders, whether ALS, spinal muscular atrophy and frontotemporal lobar dementia, in the same family [1][2][3]. Moreover, many genes linked to ALS (C9orf72, FIG4, OPTN, UBQLN2) have also been found mutated in PLS patients [4].…”

“…Data are available to researchers on reasonable request by directly contacting the corresponding authors. Philippe Corcia 1,2 Christian Lunetta 3,4 Philippe Couratier 5…”

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We read with great interest the letter of Drs Gazulla and collaborators, who suggested that the continuum between primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) is not straightforward [1]. They indicated that PLS can be associated with other central nervous system disorders related to known or unknown rare mutations.

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Familial clustering of primary lateral sclerosis and amyotrophic lateral sclerosis: Supplementary evidence for a continuum

“…Dear Editor, In their article, Corcia et al describe a series of nine patients suffering from primary lateral sclerosis (PLS) coming from different family clusters, in which every individual had a first-or second-degree relative affected by amyotrophic lateral sclerosis (ALS). The authors concluded from their results that adult onset PLS might be an inherited disease, and that there was a continuum between PLS and ALS, as both diseases coexisted in the reported kinships [1].…”