Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy

René Günther; Claudia Diana Wurster; Isabell Cordts; Jan Christoph Koch; Christoph Kamm; Daniel Petzold; Elisa Aust; Marcus Deschauer; Paul Lingor; Albert Christian Ludolph; Andreas Hermann

doi:10.3389/fneur.2019.01098

Patient-Reported Prevalence of Non-motor Symptoms Is Low in Adult Patients Suffering From 5q Spinal Muscular Atrophy

Front Neurol. 2019 Nov 1:10:1098. doi: 10.3389/fneur.2019.01098. eCollection 2019.

Authors

René Günther^{1

2}, Claudia Diana Wurster³, Isabell Cordts⁴, Jan Christoph Koch⁵, Christoph Kamm⁶, Daniel Petzold¹, Elisa Aust¹, Marcus Deschauer⁴, Paul Lingor⁴, Albert Christian Ludolph^{3

7}, Andreas Hermann^{8

9}

Affiliations

¹ Department of Neurology, Technische Universität Dresden, Dresden, Germany.
² German Center for Neurodegenerative Diseases Dresden, Dresden, Germany.
³ Department of Neurology, Ulm University, Ulm, Germany.
⁴ Department of Neurology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany.
⁵ Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
⁶ Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany.
⁷ German Center for Neurodegenerative Diseases Ulm, Ulm, Germany.
⁸ Translational Neurodegeneration Section "Albrecht-Kossel", Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany.
⁹ German Center for Neurodegenerative Diseases Rostock, Rostock, Germany.

Abstract

Background: 5q spinal muscular atrophy (SMA) is an autosomal recessive lower motoneuron disease caused by deletion or mutations in the survival motor neuron 1 gene (SMN1) which results in reduced expression of full-length SMN protein. The main symptoms are caused by spinal motor neuron demise leading to muscle atrophy, and medical care mostly refers to motor symptoms. However, new insights of recent studies in severe SMA type I revealed disease involvement of several non-motor regions, for example cardiac, vascular, sensory nerve involvement, and thalamic lesions. Non-motor symptoms (NMS) were previously described in many neurodegenerative diseases i.e., Parkinson's disease and, importantly, also amyotrophic lateral sclerosis. Methods: We screened for NMS in 70 adult patients with SMA type II (SMAII) and type III (SMAIII) and 59 age/sex-matched healthy controls (controls) in a multicenter cross-sectional study including 5 different centers with specialized expertise in medical health care of motoneuron diseases. We used a self-rating questionnaire including 30 different items of gastrointestinal, autonomic, neuropsychiatric, and sleep complaints [NMS questionnaire (NMSQuest)], which is a validated tool in Parkinson's disease. Results: Total NMS burden was low in adult SMA (median: 3 items) and not significantly different compared to controls (median: 2 items). Total NMS of SMA patients did not correlate with disease severity scores. However, the items "swallowing difficulties," "falling," and particularly "swelling legs" were significantly more frequently reported in SMA. Neuropsychiatric symptoms were reported in a frequency comparable to controls and were not significantly increased in SMA. Conclusion: Patient-reported prevalence of NMS in adult SMA was low, which does not argue for a clinically relevant multisystemic disorder in SMAII/III. Importantly, adult SMA patients do not seem to suffer more frequently from symptoms of depression or adaptive disorders compared to controls. Our results yield novel information on previously underreported symptoms and will help to improve the medical guidance of these patients.

Keywords: NMSQuest; motor neuron disease (MND); multisystem disorder; non-motor symptoms; spinal muscular atrophy (SMA).