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.
Highlights
5q-associated spinal muscular atrophy (SMA) is one of the most common neuromuscular diseases in childhood and is caused by homozygous deletion or less frequently other mutations in the survival motor neuron 1 gene (SMN1)
In contrast to amyotrophic lateral sclerosis (ALS), adult SMA type 2 (SMAII), and 3 (SMAIII) patients presented with a typical denervation pattern of the hand muscles [7]
Demographic and clinical characteristics of study populations are shown in Table 1. 57.1% of the patients were under nusinersen treatment to the time point of survey
Summary
5q-associated spinal muscular atrophy (SMA) is one of the most common neuromuscular diseases in childhood and is caused by homozygous deletion or less frequently other mutations in the survival motor neuron 1 gene (SMN1). SMA was originally thought to be a pure motoneuron disease (MND), but recent evidence suggests a multisystem involvement [4]. SMN is ubiquitously expressed, and SMN levels are reduced in different tissues in SMA animal models including spinal cord, brain, kidney, liver, heart and muscle [8]. A very recent study on health insurance data revealed numerous non-neuromuscular phenotypes which had been diagnosed in the cardiovascular, gastrointestinal, metabolic, reproductive, and skeletal systems in pre-diagnostic SMA [9]. Dysfunction of energy metabolism and increased levels of leptin were found in SMA type 1 to 3 patients, which was associated with disease severity and decreased motor function. It was hypothesized that neuronal degradation of hypothalamic cells or an increase in fat content by muscle remodeling could be the cause of the highly prevalent hyperleptinemia in SMA patients [17]
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