Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Outcome Measures
2.3. Statistical Analysis
3. Results
4. Discussion
4.1. The Utility of the TUG Test to Identify Those at Risk for Falling
4.2. The Adult Myopathy Assessment Tool Endurance Subscale Can Also Detect Fall Risk in Those with SBMA
4.3. The Role of Weakness as a Risk Factor for Falling
4.4. Unexpected Study Findings
4.5. Study Limitations and Future Directions/Applications
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Kennedy, W.R.; Alter, M.; Sung, J.H. Progressive proximal spinal and bulbar muscular atrophy of late onset: A sex-linked recessive trait. Neurology 1968, 18, 671. [Google Scholar] [CrossRef] [PubMed]
- La Spada, A.R.; Wilson, E.M.; Lubahn, D.B.; Harding, A.E.; Fischbeck, K.H. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991, 352, 77–79. [Google Scholar] [CrossRef]
- Sobue, G.; Hashizume, Y.; Mukai, E.; Hirayama, M.; Mitsuma, T.; Takahashi, A. X-linked recessive bulbospinal neuronopathy. Brain 1989, 112, 209–232. [Google Scholar] [CrossRef]
- Sorarù, G.; D’Ascenzo, C.; Polo, A.; Palmieri, A.; Baggio, L.; Vergani, L.; Gellera, C.; Moretto, G.; Pegoraro, E.; Angelini, C. Spinal and bulbar muscular atrophy: Skeletal muscle pathology in male patients and heterozygous females. J. Neurol. Sci. 2008, 264, 100–105. [Google Scholar] [CrossRef] [PubMed]
- Jordan, C.L.; Lieberman, A.P. Spinal and bulbar muscular atrophy: A motoneuron or muscle disease? Curr. Opin. Pharmacol. 2008, 8, 752–758. [Google Scholar] [CrossRef]
- Querin, G.; Sorarù, G.; Pradat, P.-F. Kennedy disease (X-linked recessive bulbospinal neuronopathy): A comprehensive review from pathophysiology to therapy. Rev. Neurol. 2017, 173, 326–337. [Google Scholar] [CrossRef]
- Ferrante, M.A.; Wilbourn, A.J. The characteristic electrodiagnostic features of Kennedy’s disease. Muscle Nerve 1997, 20, 323–329. [Google Scholar] [CrossRef]
- Suzuki, K.; Katsuno, M.; Banno, H.; Takeuchi, Y.; Atsuta, N.; Ito, M.; Watanabe, H.; Yamashita, F.; Hori, N.; Nakamura, T.; et al. CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA. Brain 2007, 131, 229–239. [Google Scholar] [CrossRef]
- Dejager, S.; Bry-Gauillard, H.; Bruckert, E.; Eymard, B.; Salachas, F.; LeGuern, E.; Tardieu, S.; Chadarevian, R.; Giral, P.; Turpin, G. A comprehensive endocrine description of kennedy’s disease revealing androgen insensitivity linked to CAG repeat length. J. Clin. Endocrinol. Metab. 2002, 87, 3893–3901. [Google Scholar] [CrossRef]
- E Fernández-Rhodes, L.; Kokkinis, A.D.; White, M.J.; A Watts, C.; Auh, S.; O Jeffries, N.; A Shrader, J.; Lehky, T.J.; Li, L.; E Ryder, J.; et al. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: A randomised placebo-controlled trial. Lancet Neurol. 2011, 10, 140–147. [Google Scholar] [CrossRef]
- Atsuta, N. Natural history of spinal and bulbar muscular atrophy (SBMA): A study of 223 Japanese patients. Brain 2006, 129 Pt 6, 1446–1455. [Google Scholar] [CrossRef] [PubMed]
- Fratta, P.; Nirmalananthan, N.; Masset, L.; Skorupinska, I.; Collins, T.; Cortese, A.; Pemble, S.; Malaspina, A.; Fisher, E.M.; Greensmith, L.; et al. Correlation of clinical and molecular features in spinal bulbar muscular atrophy. Neurology 2014, 82, 2077–2084. [Google Scholar] [CrossRef] [PubMed]
- Rhodes, L.E.; Freeman, B.K.; Auh, S.; Kokkinis, A.D.; La Pean, A.; Chen, C.; Lehky, T.J.; Shrader, J.A.; Levy, E.W.; Harris-Love, M.; et al. Clinical features of spinal and bulbar muscular atrophy. Brain 2009, 132 Pt 12, 3242–3251. [Google Scholar] [CrossRef] [PubMed]
- Anagnostou, E.; Zachou, A.; Breza, M.; Kladi, A.; Karadima, G.; Koutsis, G. Disentangling balance impairments in spinal and bulbar muscular atrophy. Neurosci. Lett. 2019, 705, 94–98. [Google Scholar] [CrossRef]
- Rubenstein, L.Z.; Josephson, K.R. The epidemiology of falls and syncope. Clin. Geriatr. Med. 2002, 18, 141–158. [Google Scholar] [CrossRef]
- Facts About Falls. Centers for Disease Control and Prevention. 6 August 2021. Available online: https://www.cdc.gov/falls/facts.html (accessed on 10 May 2023).
- Schell, W.E.; Mar, V.S.; Da Silva, C.P. Correlation of falls in patients with Amyotrophic Lateral Sclerosis with objective measures of balance, strength, and spasticity. NeuroRehabilitation 2019, 44, 85–93. [Google Scholar] [CrossRef]
- Shrader, J.A.; Kats, I.; Kokkinis, A.; Zampieri, C.; Levy, E.; Joe, G.O.; Woolstenhulme, J.G.; Drinkard, B.E.; Smith, M.R.; Ching, W.; et al. A randomized controlled trial of exercise in spinal and bulbar muscular atrophy. Ann. Clin. Transl. Neurol. 2015, 2, 739–747. [Google Scholar] [CrossRef]
- Harris-Love, M.O.; Fernandez-Rhodes, L.; Joe, G.; Shrader, J.A.; Kokkinis, A.; Kirschner, A.L.P.; Auh, S.; Chen, C.; Li, L.; Levy, E.; et al. Assessing function and endurance in adults with spinal and bulbar muscular atrophy: Validity of the adult myopathy assessment tool. Rehabil Res. Prac. 2014, 2014, 873872. [Google Scholar] [CrossRef]
- Montes, J.; Cheng, B.; Diamond, B.; Doorish, C.; Mitsumoto, H.; Gordon, P.H. The Timed Up and Go test: Predicting falls in ALS. Amyotroph. Lateral Scler. 2007, 8, 292–295. [Google Scholar] [CrossRef]
- Podsiadlo, D.; Richardson, S. The Timed “Up & Go”: A Test of Basic Functional Mobility for Frail Elderly Persons. J. Am. Geriatr. Soc. 1991, 39, 142–148. [Google Scholar] [CrossRef]
- Jacobson, G.P.; Newman, C.W.; Kartush, J.M. Handbook of Balance Function Testing; Singular Publishing Group, Inc.: San Diego, CA, USA, 1997. [Google Scholar]
- The National Isometric Muscle Strength (NIMS) Database Consortium. Muscular weakness assessment: Use of normal iso-metric strength data. Arch. Phys. Med. Rehabil. 1996, 77, 1251–1255. [Google Scholar] [CrossRef] [PubMed]
- Portney, L. Foundations of Clinical Research: Applications to Practice, Appleton and Lange, Norwalk Connecticut, 3rd ed.; Prentice Hall: Upper Saddle River, NJ, USA, 2015. [Google Scholar]
- Hosmer David, W.; Stanley, L. Applied Logistic Regression, 2nd ed.; John Wiley and Sons: New York, NY, USA, 2000. [Google Scholar]
- Pieterse, A.; Luttikhold, T.; de Laat, K.; Bloem, B.; van Engelen, B.; Munneke, M. Falls in patients with neuromuscular disorders. J. Neurol. Sci. 2006, 251, 87–90. [Google Scholar] [CrossRef] [PubMed]
- Shumway-Cook, A.; Brauer, S.; Woollacott, M. Predicting the Probability for Falls in Community-Dwelling Older Adults Using the Timed Up & Go Test. Phys. Ther. 2000, 80, 896–903. [Google Scholar] [CrossRef] [PubMed]
- Whitney, S.L.; Wrisley, D.M.; Marchetti, G.F.; Gee, M.A.; Redfern, M.S.; Furman, J.M. Clinical Measurement of Sit-to-Stand Performance in People with Balance Disorders: Validity of Data for the Five-Times-Sit-to-Stand Test. Phys. Ther. 2005, 85, 1034–1045. [Google Scholar] [CrossRef]
- Nocera, J.R.; Stegemöller, E.L.; Malaty, I.A.; Okun, M.S.; Marsiske, M.; Hass, C.J. Using the Timed Up & Go Test in a Clinical Setting to Predict Falling in Parkinson’s Disease. Arch. Phys. Med. Rehabil. 2013, 94, 1300–1305. [Google Scholar] [CrossRef]
- Steffen, T.M.; Hacker, T.A.; Mollinger, L. Age- and Gender-Related Test Performance in Community-Dwelling Elderly People: Six-Minute Walk Test, Berg Balance Scale, Timed Up & Go Test, and Gait Speeds. Phys. Ther. 2002, 82, 128–137. [Google Scholar] [CrossRef]
- Schoene, D.; Wu, S.M.-S.; Mikolaizak, A.S.; Menant, J.C.; Smith, S.T.; Delbaere, K.; Lord, S.R. Discriminative Ability and Predictive Validity of the Timed Up and Go Test in Identifying Older People Who Fall: Systematic Review and Meta-Analysis. J. Am. Geriatr. Soc. 2013, 61, 202–208. [Google Scholar] [CrossRef]
- Heje, K.; Andersen, G.; Buch, A.; Andersen, H.; Vissing, J. High-intensity training in patients with spinal and bulbar muscular atrophy. J. Neurol. 2019, 266, 1693–1697. [Google Scholar] [CrossRef]
- Preisler, N.; Andersen, G.; Thøgersen, F.; Crone, C.; Jeppesen, T.D.; Wibrand, F.; Vissing, J. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease). Neurology 2009, 72, 317–323. [Google Scholar] [CrossRef]
- Pol, F.; Khajooei, Z.; Hosseini, S.M.; Taheri, A.; Forghany, S.; Menz, H.B. Foot and ankle characteristics associated with fear of falling and mobility in community-dwelling older people: A cross-sectional study. J. Foot Ankle Res. 2022, 15, 86. [Google Scholar] [CrossRef]
- Horlings, C.G.; Carpenter, M.G.; Küng, U.M.; Honegger, F.; Wiederhold, B.; Allum, J.H. Influence of virtual reality on postural stability during movements of quiet stance. Neurosci. Lett. 2009, 451, 227–231. [Google Scholar] [CrossRef] [PubMed]
- Cattagni, T.; Scaglioni, G.; Laroche, D.; Van Hoecke, J.; Gremeaux, V.; Martin, A. Ankle muscle strength discriminates fallers from non-fallers. Front. Aging Neurosci. 2014, 6, 336. [Google Scholar] [CrossRef]
- Whipple, R.H.; Wolfson, L.I.; Amerman, P.M. The relationship of knee and ankle weakness to falls in nursing home residents: An isokinetic study. J. Am. Geriatr. Soc. 1987, 35, 13–20. [Google Scholar] [CrossRef]
- Fukagawa, N.K.; Wolfson, L.; Judge, J.; Whipple, R.; King, M. Strength is a major factor in balance, gait, and the occurrence of falls. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 1995, 50, 64–67. [Google Scholar] [CrossRef] [PubMed]
- Clemson, L.; Singh, M.A.F.; Bundy, A.; Cumming, R.G.; Manollaras, K.; O’loughlin, P.; Black, D. Integration of balance and strength training into daily life activity to reduce rate of falls in older people (the LiFE study): Randomised parallel trial. BMJ 2012, 345, e4547. [Google Scholar] [CrossRef] [PubMed]
- Bird, M.-L.; Hill, K.D.; Robertson, I.; Ball, M.J.; Pittaway, J.K.; Williams, A.D. The Association between seasonal variation in vitamin D, postural sway, and falls risk: An observational cohort study. J. Aging Res. 2013, 2013, 751310. [Google Scholar] [CrossRef]
- Bok, S.-K.; Lee, T.H.; Lee, S.S. The effects of changes of ankle strength and range of motion according to aging on balance. Ann. Rehabil. Med. 2013, 37, 10–16. [Google Scholar] [CrossRef]
- Lombardi, V.; Bombaci, A.; Zampedri, L.; Lu, C.-H.; Malik, B.; Zetterberg, H.; Heslegrave, A.J.; Rinaldi, C.; Greensmith, L.; Hanna, M.G.; et al. Plasma pNfH levels differentiate SBMA from ALS. J. Neurol. Neurosurg. Psychiatry 2019, 91, 215–217. [Google Scholar] [CrossRef]
- Dahlqvist, J.R.; Oestergaard, S.T.; Poulsen, N.S.; Thomsen, C.; Vissing, J. Refining the spinobulbar muscular atrophy phenotype by quantitative MRI and clinical assessments. Neurology 2019, 92, E548–E559. [Google Scholar] [CrossRef]
- Dahlqvist, J.R.; Fornander, F.; Bsc, J.d.S.B.; Oestergaard, S.T.; Poulsen, N.S.; Vissing, J. Disease progression and outcome measures in spinobulbar muscular atrophy. Ann. Neurol. 2018, 84, 754–765. [Google Scholar] [CrossRef]
- Shrader, J.A.; Sansare, A.; Niemic, A.C.; Jimenéz-Silva, R.; Woolstenhulme, J.G.; Joe, G.O.; Jacobs, U.; Kokkinis, A.; Fischbeck, K.; Grunseich, C.; et al. Evaluation of Sensory and Motor Function in Spinal and Bulbar Muscular Atrophy Using Quiet Stance and Reactive Postural Control. Neurol. Int. 2025, 17, 79. [Google Scholar]
- Hijikata, Y.; Hashizume, A.; Yamada, S.; Inagaki, T.; Ito, D.; Hirakawa, A.; Suzuki, K.; Atsuta, N.; Tsuboi, T.; Hattori, M.; et al. Biomarker-based analysis of preclinical progression in spinal and bulbar muscular atrophy. Neurology 2018, 90, E1501–E1509. [Google Scholar] [CrossRef] [PubMed]
- Ahmadiahangar, A.; Javadian, Y.; Babaei, M.; Heidari, B.; Hosseini, S.; Aminzadeh, M. The role of quadriceps muscle strength in the development of falls in the elderly people, a cross-sectional study. Chiropr. Man. Ther. 2018, 26, 31. [Google Scholar] [CrossRef]
- Kwofie, M.K.; Shastri, U.D.; Gadsden, J.C.; Sinha, S.K.; Abrams, J.H.; Xu, D.; Salviz, E.A. The effects of ultrasound-guided adductor canal block versus femoral nerve block on quadriceps strength and fall risk: A blinded, randomized trial of volunteers. Reg. Anesth. Pain Med. 2013, 38, 321–325. [Google Scholar] [CrossRef] [PubMed]
Measure | Unit | Mean ± SD | p-Value | Effect Size | 95% CI | |
---|---|---|---|---|---|---|
Fallers (n = 18) | Non-Fallers (n = 32) | |||||
Demographics | ||||||
Age | years | 58.0 ± 9.4 | 53.7 ± 8.6 | 0.12 | −0.48 d | [−1.15, 0.07] |
Disease duration | years | 18.7 ± 11.1 | 13.8 ± 7.6 | 0.11 | 0.23 r | [0.02, 0.46] |
Body mass index | 27.7 ± 3.24 | 28.6 ± 5.42 | 0.48 | |||
Gait aid use | % | 83.3 | 43.8 | 0.01 * | 0.34 φ | |
Strength | ||||||
L Hip Ext | % predicted | 88.5 ± 28.6 | 97.0 ± 30.9 | 0.34 | 0.28 r | [−0.30, 0.90] |
R Hip Ext | % predicted | 88.2 ± 28.0 | 101.9 ± 41.0 | 0.37 | 0.13 r | [−0.17, 0.89] |
L Knee Ext | % predicted | 31.7 ± 13.7 | 41.2 ± 25.1 | 0.25 | 0.17 r | [0.01, 0.42] |
R Knee Ext | % predicted | 29.2 ± 11.9 | 41.3 ± 25.3 | 0.14 | 0.21 r | [0.02, 0.45] |
L Ankle DF | % predicted | 34.4 ± 16.4 | 43.3 ± 20.3 | 0.14 | 0.21 r | [0.02, 0.45] |
R Ankle DF | % predicted | 38.0 ± 14.8 | 43.9 ± 20.3 | 0.34 | 0.14 r | [0.01, 0.40] |
L Ankle PF | % predicted | 41.9 ± 19.3 | 52.8 ± 25.8 | 0.10 | 0.48 d | [−0.10, 1.10] |
R Ankle PF | % predicted | 42.0 ± 18.6 | 56.4 ± 27.7 | 0.03 * | 0.61 d | [0.06, 1.20] |
Total LE | % predicted | 49.3 ± 14.1 | 58.8 ± 22.5 | 0.07 | 0.51 d | [−0.01, 1.04] |
Balance | ||||||
MCT LatBLR | ms | 143.8 ± 13.3 | 144.8 ± 15.6 | 0.94 | 0.02 r | [0.01, 0.38] |
mCTSIB Foam Eyes Closed | deg/s | 3.98 ± 1.85 | 3.35 ± 1.82 | 0.21 | 0.19 r | [0.01, 0.44] |
Function | ||||||
TUG | s | 11.78 ± 5.65 | 9.15 ± 4.48 | 0.02 * | 0.34 r | [0.09, 0.56] |
AMAT functional | (max 21 pts) | 13.94 ± 4.14 | 15.63 ± 3.23 | 0.15 | 0.45 d | [−0.18, 1.22] |
AMAT endurance | (max 24 pts) | 12.28 ± 2.76 | 15.09 ± 3.53 | 0.01 ** | 0.38 r | [0.13, 0.60] |
Biomarkers | ||||||
Creatinine | mg/dL | 0.468 ± 0.15 | 0.531 ± 0.18 | 0.18 | 0.19 r | [0.01, 0.46] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Shrader, J.A.; Niemic, A.C.; Jiménez-Silva, R.; Woolstenhulme, J.G.; Joe, G.O.; Jacobs, U.; Sansare, A.; Kokkinis, A.; Fischbeck, K.; Grunseich, C.; et al. Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy. Neurol. Int. 2025, 17, 80. https://doi.org/10.3390/neurolint17060080
Shrader JA, Niemic AC, Jiménez-Silva R, Woolstenhulme JG, Joe GO, Jacobs U, Sansare A, Kokkinis A, Fischbeck K, Grunseich C, et al. Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy. Neurology International. 2025; 17(6):80. https://doi.org/10.3390/neurolint17060080
Chicago/Turabian StyleShrader, Joseph A., Allison C. Niemic, Rafael Jiménez-Silva, Joshua G. Woolstenhulme, Galen O. Joe, Uma Jacobs, Ashwini Sansare, Angela Kokkinis, Kenneth Fischbeck, Chris Grunseich, and et al. 2025. "Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy" Neurology International 17, no. 6: 80. https://doi.org/10.3390/neurolint17060080
APA StyleShrader, J. A., Niemic, A. C., Jiménez-Silva, R., Woolstenhulme, J. G., Joe, G. O., Jacobs, U., Sansare, A., Kokkinis, A., Fischbeck, K., Grunseich, C., & Zampieri, C. (2025). Identifying Clinical Measures Related to Falls in Ambulatory Patients with Spinal and Bulbar Muscular Atrophy. Neurology International, 17(6), 80. https://doi.org/10.3390/neurolint17060080