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Neurological Sciences

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01-03-2022 | Amyotrophic Lateral Sclerosis | Original Article

Rate-dependent depression is impaired in amyotrophic lateral sclerosis

Authors: Xiajun Zhou, Ze Wang, Zhi Lin, Ying Zhu, Desheng Zhu, Chong Xie, Nigel A. Calcutt, Yangtai Guan

Published in: Neurological Sciences | Issue 3/2022

Abstract

Objective

We investigated rate-dependent depression (RDD) of the Hoffman reflex (H-reflex) in patients with amyotrophic lateral sclerosis (ALS), a degenerative disease with ventral horn involvement.

Patients and methods

In this case–control study, we enrolled 27 patients with ALS and 30 matched healthy control subjects. Clinical and electrophysiological assessments, as well as RDD in response to various stimulation frequencies (0.5 Hz, 1 Hz, 3 Hz and 5 Hz), were compared between groups. Multiple clinical and electrophysiological factors were also explored to determine any underlying associations with RDD.

Results

The ALS group showed a significant loss of RDD across all frequencies compared to the control group, most notably following 1 Hz stimulation (19.1 ± 20.3 vs. 34.0 ± 13.7%, p = 0.003). Among factors that might influence RDD, the enlargement of the motor unit potential (MUP) showed a significant relationship with RDD following multifactor analysis of variance (p = 0.007) and Pearson correlation analysis (ρ = − 0.70, p < 0.001), while various upper motor neuron manifestations were not correlated with RDD values (p > 0.05).

Conclusion

We report a loss of RDD in patients with ALS. The strong correlation detected between the RDD deficit and increased MUP suggests that RDD is a sensitive indicator of underlying spinal disinhibition in ALS.

Trial registration

ChiCTR2000038848, 10/7/2020 (retrospectively registered), http://www.chictr.org.cn/.

Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH (2017) Amyotrophic lateral sclerosis. Nat Rev Dis Primers 3:17071. https://doi.org/10.1038/nrdp.2017.71CrossRefPubMed

Misra UK, Kalita J (1998) A study of H reflex in amyotrophic lateral sclerosis. Neurol India 46:119–122PubMed

Ishikawa K, Ott K, Porter RW, Stuart D (1966) Low frequency depression of the H wave in normal and spinal man. Exp Neurol 15:140–156. https://doi.org/10.1016/0014-4886(66)90039-2CrossRefPubMed

Nielsen J, Petersen N, Ballegaard M, Biering-Sorensen F, Kiehn O (1993) H-reflexes are less depressed following muscle stretch in spastic spinal cord injured patients than in healthy subjects. Exp Brain Res 97:173–176. https://doi.org/10.1007/BF00228827CrossRefPubMed

Aymard C, Katz R, Lafitte C, Lo E, Penicaud A, Pradat-Diehl P, Raoul S (2000) Presynaptic inhibition and homosynaptic depression: a comparison between lower and upper limbs in normal human subjects and patients with hemiplegia. Brain 123(Pt 8):1688–1702. https://doi.org/10.1093/brain/123.8.1688CrossRefPubMed

Sabatier MJ, Wedewer W, Barton B, Henderson E, Murphy JT, Ou K (2015) Slope walking causes short-term changes in soleus H-reflex excitability. Physiol Rep 3:e12308. https://doi.org/10.14814/phy2.12308CrossRefPubMedPubMedCentral

Lamy JC, Wargon I, Mazevet D, Ghanim Z, Pradat-Diehl P, Katz R (2009) Impaired efficacy of spinal presynaptic mechanisms in spastic stroke patients. Brain 132:734–748. https://doi.org/10.1093/brain/awn310CrossRefPubMed

Marshall AG, Lee-Kubli C, Azmi S et al (2017) Spinal disinhibition in experimental and clinical painful diabetic neuropathy. Diabetes 66:1380–1390. https://doi.org/10.2337/db16-1181CrossRefPubMedPubMedCentral

Lee-Kubli C, Marshall AG, Malik RA, Calcutt NA (2018) The H-reflex as a biomarker for spinal disinhibition in painful diabetic neuropathy. Curr Diab Rep 18:1. https://doi.org/10.1007/s11892-018-0969-5CrossRefPubMedPubMedCentral

10.

Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Mot Neuron Disord 1:293–299. https://doi.org/10.1080/146608200300079536CrossRef

11.

Makary MM, Weerasekara A, Rodham H et al (2021) Comparison of two clinical upper motor neuron burden rating scales in ALS using quantitative brain imaging. ACS Chem Neurosci 12:906–916. https://doi.org/10.1021/acschemneuro.0c00772CrossRefPubMed

12.

Bohannon RW, Smith MB (1987) Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 67:206–207CrossRef

13.

Nandedkar SD, Barkhaus PE, Stålberg EV, Neuwirth C, Weber M (2018) Motor unit number index: guidelines for recording signals and their analysis. Muscle Nerve 58:374–380. https://doi.org/10.1002/mus.26099CrossRefPubMed

14.

Jerath N, Kimura J (2019) F wave, A wave, H reflex, and blink reflex. Handb Clin Neurol 160:225–239. https://doi.org/10.1016/B978-0-444-64032-1.00015-1CrossRefPubMed

15.

Mekhael W, Begum S, Samaddar S, Hassan M, Toruno P, Ahmed M, Gorin A, Maisano M, Ayad M, Ahmed Z (2019) Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury. J Physiol 597:2201–2223. https://doi.org/10.1113/JP276952CrossRefPubMedPubMedCentral

16.

Toda T, Ishida K, Kiyama H, Yamashita T, Lee S (2014) Down-regulation of KCC2 expression and phosphorylation in motoneurons, and increases the number of in primary afferent projections to motoneurons in mice with post-stroke spasticity. PLoS ONE 9:e114328. https://doi.org/10.1371/journal.pone.0114328CrossRefPubMedPubMedCentral

17.

Sabbahi M, Etnyre B, Al-Jawayed IA, Hasson S, Jankovic J (2002) Methods of H-reflex evaluation in the early stages of Parkinson’s disease. J Clin Neurophysiol 19:67–72. https://doi.org/10.1097/00004691-200201000-00009CrossRefPubMed

18.

Pivik RT, Mercier L (1981) Spinal motoneuronal excitability in hyperkinesis: H-reflex recovery function and homosynaptic depression during wakefulness. J Clin Neuropsychol 3:215–236. https://doi.org/10.1080/01688638108403127CrossRefPubMed

19.

Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y (2003) Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424:938–942. https://doi.org/10.1038/nature01868CrossRefPubMed

20.

Sánchez-Brualla I, Boulenguez P, Brocard C, Liabeuf S, Viallat-Lieutaud A, Navarro X, Udina E, Brocard F (2018) Activation of 5-HT receptors restores KCC2 function and reduces neuropathic pain after spinal cord injury. Neuroscience 387:48–57. https://doi.org/10.1016/j.neuroscience.2017.08.033CrossRefPubMed

21.

Lee-Kubli CA, Calcutt NA (2014) Altered rate-dependent depression of the spinal H-reflex as an indicator of spinal disinhibition in models of neuropathic pain. Pain 155:250–260. https://doi.org/10.1016/j.pain.2013.10.001CrossRefPubMed

22.

Boulenguez P, Liabeuf S, Bos R, Bras H, Jean-Xavier C, Brocard C, Stil A, Darbon P, Cattaert D, Delpire E, Marsala M, Vinay L (2010) Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury. Nat Med 16:302–307. https://doi.org/10.1038/nm.2107CrossRefPubMed

23.

Fuchs A, Ringer C, Bilkei-Gorzo A, Weihe E, Roeper J, Schutz B (2010) Downregulation of the potassium chloride cotransporter KCC2 in vulnerable motoneurons in the SOD1-G93A mouse model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 69:1057–1070. https://doi.org/10.1097/NEN.0b013e3181f4dcefCrossRefPubMed

24.

Branchereau P, Martin E, Allain AE, Cazenave W, Supiot L, Hodeib F, Laupenie A, Dalvi U, Zhu H, Cattaert D (2019) Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks. Elife 8:e51402. https://doi.org/10.7554/eLife.51402CrossRefPubMedPubMedCentral

25.

Martin E, Cazenave W, Allain AE, Cattaert D, Branchereau P (2020) Implication of 5-HT in the dysregulation of chloride homeostasis in prenatal spinal motoneurons from the G93A mouse model of amyotrophic lateral sclerosis. Int J Mol Sci 21:1107. https://doi.org/10.3390/ijms21031107CrossRefPubMedCentral

26.

Modol L, Mancuso R, Ale A, Francos-Quijorna I, Navarro X (2014) Differential effects on KCC2 expression and spasticity of ALS and traumatic injuries to motoneurons. Front Cell Neurosci 8:7. https://doi.org/10.3389/fncel.2014.00007CrossRefPubMedPubMedCentral

27.

Huynh W, Simon NG, Grosskreutz J, Turner MR, Vucic S, Kiernan MC (2016) Assessment of the upper motor neuron in amyotrophic lateral sclerosis. Clin Neurophysiol 127:2643–2660. https://doi.org/10.1016/j.clinph.2016.04.025CrossRefPubMed

28.

Babu S (2020) Upper motor neuron burden measurement in motor neuron diseases: does one scale fit all? Muscle Nerve 61:431–432. https://doi.org/10.1002/mus.26836CrossRefPubMed

29.

Chang YX, Zhao Y, Pan S, Qi ZP, Kong WJ, Pan YR, Li HR, Yang XY (2019) Intramuscular injection of adenoassociated virus encoding human neurotrophic factor 3 and exercise intervention contribute to reduce spasms after spinal cord injury. Neural Plast 2019:3017678. https://doi.org/10.1155/2019/3017678CrossRefPubMedPubMedCentral

30.

Swash M, Czesnik D, de Carvalho M (2019) Muscular cramp: causes and management. Eur J Neurol 26:214–221. https://doi.org/10.1111/ene.13799CrossRefPubMed

31.

Mazzini L, Balzarini C, Gareri F, Brigatti M (1997) H-reflex changes in the course of amyotrophic lateral sclerosis. Electroencephalogr Clin Neurophysiol 104:411–417. https://doi.org/10.1016/s0168-5597(97)00071-3CrossRefPubMed

32.

de Carvalho M, Swash M (2016) Lower motor neuron dysfunction in ALS. Clin Neurophysiol 127:2670–2681. https://doi.org/10.1016/j.clinph.2016.03.024CrossRefPubMed

33.

Fukushima Y, Yamashita N, Shimada Y (1982) Facilitation of H-reflex by homonymous Ia-afferent fibers in man. J Neurophysiol 48:1079–1088. https://doi.org/10.1152/jn.1982.48.5.1079CrossRefPubMed

34.

Andrews JA, Shefner JM (2019) Clinical neurophysiology of anterior horn cell disorders. Handb Clin Neurol 161:317–326. https://doi.org/10.1016/B978-0-444-64142-7.00057-6CrossRefPubMed

35.

Amendola J, Durand J (2008) Morphological differences between wild-type and transgenic superoxide dismutase 1 lumbar motoneurons in postnatal mice. J Comp Neurol 511:329–341. https://doi.org/10.1002/cne.21818CrossRefPubMed

36.

Howells J, Matamala JM, Park SB, Garg N, Vucic S, Bostock H, Burke D, Kiernan MC (2018) In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis. J Physiol 596:5379–5396. https://doi.org/10.1113/JP276624CrossRefPubMedPubMedCentral

37.

Caress JB, Ciarlone SL, Sullivan EA, Griffin LP, Cartwright MS (2016) Natural history of muscle cramps in amyotrophic lateral sclerosis. Muscle Nerve 53:513–517. https://doi.org/10.1002/mus.24892CrossRefPubMed

Title: Rate-dependent depression is impaired in amyotrophic lateral sclerosis
Authors: Xiajun Zhou
Ze Wang
Zhi Lin
Ying Zhu
Desheng Zhu
Chong Xie
Nigel A. Calcutt
Yangtai Guan
Publication date: 01-03-2022
Publisher: Springer International Publishing
Keywords: Amyotrophic Lateral Sclerosis
Mood Disorders
Affective Disorder
Published in: Neurological Sciences / Issue 3/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-021-05596-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Rate-dependent depression is impaired in amyotrophic lateral sclerosis

Abstract

Objective

Patients and methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Patients and methods

Results

Conclusion

Trial registration

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