Abstract
Purpose
Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis.
Methods
Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded.
Results
A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns.
Conclusion
We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baltadzhieva R, Gurevich T, Korczyn AD (2005) Autonomic impairment in amyotrophic lateral sclerosis. Curr Opin Neurol 18:487–493
Coon EA, Fealey RD, Sletten DM, Mandrekar JN, Benarroch EE, Sandroni P, Low PA, Singer W (2017) Anhidrosis in multiple system atrophy involves pre- and postganglionic sudomotor dysfunction. Mov Disord 32:397–404
Fealey RD, Low PA, Thomas JE (1989) Thermoregulatory sweating abnormalities in diabetes mellitus. Mayo Clin Proc 64:617–628
Figueroa JJ, Dyck PJ, Laughlin RS, Mercado JA, Massie R, Sandroni P, Dyck PJ, Low PA (2012) Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy. Neurology 78:702–708
Guttmann L (1947) The management of the quinizarin sweat test. Overseas Postgrad Med J 1:69–82
Hachiya Y, Arai H, Hayashi M, Kumada S, Furushima W, Ohtsuka E, Ito Y, Uchiyama A, Kurata K (2005) Autonomic dysfunction in cases of spinal muscular atrophy type 1 with long survival. Brain Dev 27:574–578
Hassan A, Mittal SO, Hu WT, Josephs KA, Sorenson EJ, Ahlskog JE (2021) Natural history of “pure” primary lateral sclerosis. Neurology 96:e2231–e2238
Itoh T, Sobue G, Ken E, Mitsuma T, Takahashi A, Trojanowski JQ (1992) Phosphorylated high molecular weight neurofilament protein in the peripheral motor, sensory and sympathetic neuronal perikarya: system-dependent normal variations and changes in amyotrophic lateral sclerosis and multiple system atrophy. Acta Neuropathol 83:240–245
Kennedy PG, Duchen LW (1985) A quantitative study of intermediolateral column cells in motor neuron disease and the Shy-Drager syndrome. J Neurol Neurosurg Psychiatry 48:1103–1106
Kihira T, Yoshida S, Yoshimasu F, Wakayama I, Yase Y (1997) Involvement of Onuf’s nucleus in amyotrophic lateral sclerosis. J Neurol Sci 147:81–88
Konno H, Yamamoto T, Iwasaki Y, Iizuka H (1986) Shy-Drager syndrome and amyotrophic lateral sclerosis. Cytoarchitectonic and morphometric studies of sacral autonomic neurons. J Neurol Sci 73:193–204
Low PA (1993) Autonomic nervous system function. J Clin Neurophysiol 10:14–27
Low PA (1993) Composite autonomic scoring scale for laboratory quantification of generalized autonomic failure. Mayo Clin Proc 68:748–752
Low PA (2004) Evaluation of sudomotor function. Clin Neurophysiol 115:1506–1513
Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ (1983) Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol 14:573–580
Mitsumoto H, Chiuzan C, Gilmore M, Zhang Y, Simmons Z, Paganoni S, Kisanuki YY, Zinman L, Jawdat O, Sorenson E, Floeter MK, Pioro EP, Fernandes Filho JAM, Heitzman D, Fournier CN, Oskarsson B, Heiman-Patterson T, Maragakis N, Joyce N, Hayat G, Nations S, Scelsa S, Walk D, Elman L, Hupf J, McHale B, group Ps (2020) Primary lateral sclerosis (PLS) functional rating scale: PLS-specific clinimetric scale. Muscle Nerve 61:163–172
Nubling GS, Mie E, Bauer RM, Hensler M, Lorenzl S, Hapfelmeier A, Irwin DE, Borasio GD, Winkler AS (2014) Increased prevalence of bladder and intestinal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 15:174–179
Paganoni S, De Marchi F, Chan J, Thrower SK, Staff NP, Datta N, Kisanuki YY, Drory V, Fournier C, Pioro EP, Goutman SA, Atassi N, Jeon M, Caldwell S, McDonough T, Gentile C, Liu J, Turner M, Denny C, Felice K, Green M, Scarberry S, Abu-Saleh S, Nefussy B, Hastings D, Kim S, Swihart B, Arcila-Londono X, Newman DS, Silverman M, Genge A, Salmon K, Elman L, McCluskey L, Almasy K, Gotkine M, Goslin K, Cummings A, Edwards EK, Rivner M, Bouchard K, Quarles B, Kwan J, Jaffa M, Baloh R, Allred P, Walk D, Maiser S, Manousakis G, Ferment V, Fernandes JAM Jr, Thaisetthawatkul P, Heimes D, Phillips M, Sams L, Kahler M, Corcoran A, Larriviere DG, Chotto S, Juba G, Group NPRS (2020) The NEALS primary lateral sclerosis registry. Amyotroph Lateral Scler Frontotemporal Degener 21:74–81
Piccione EA, Sletten DM, Staff NP, Low PA (2015) Autonomic system and amyotrophic lateral sclerosis. Muscle Nerve 51:676–679
Rocchi C, Greco V, Urbani A, Di Giorgio A, Priori M, Massa R, Bernardi G, Marfia GA (2011) Subclinical autonomic dysfunction in spinobulbar muscular atrophy (Kennedy disease). Muscle Nerve 44:737–740
Takahashi H, Oyanagi K, Ikuta F (1993) The intermediolateral nucleus in sporadic amyotrophic lateral sclerosis. Acta Neuropathol 86:190–192
Toepfer M, Folwaczny C, Klauser A, Riepl RL, Muller-Felber W, Pongratz D (1999) Gastrointestinal dysfunction in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:15–19
Turner MR, Barohn RJ, Corcia P, Fink JK, Harms MB, Kiernan MC, Ravits J, Silani V, Simmons Z, Statland J, van den Berg LH, Mitsumoto H, Delegates of the 2nd International PLSC (2020) Primary lateral sclerosis: consensus diagnostic criteria. J Neurol Neurosurg Psychiatry 91:373–377
Funding
No funding was received to assist with the preparation of this manuscript. The authors have no relevant financial or non-financial interests to disclose.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This research study was conducted retrospectively from data obtained for clinical purposes. We consulted extensively with the IRB of Mayo Clinic, which determined that our study did not need ethical approval. An IRB official waiver of ethical approval was granted from the IRB of Mayo Clinic.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Rashed, H.R., Staff, N.P., Milone, M. et al. Autonomic impairment in primary lateral sclerosis. Clin Auton Res (2024). https://doi.org/10.1007/s10286-024-01039-y
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10286-024-01039-y