Thalamic Deep Brain Stimulation for Spasmodic Dysphonia: A Phase I Prospective Randomized Double-Blind Crossover Trial
Christopher R Honey, Marie T Krüger, Timóteo Almeida, Linda A Rammage, Mandeep S Tamber, Murray D Morrison, Anujan Poologaindran, Amanda Hu, Christopher R Honey, Marie T Krüger, Timóteo Almeida, Linda A Rammage, Mandeep S Tamber, Murray D Morrison, Anujan Poologaindran, Amanda Hu
Abstract
Background: Adductor spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. The current standard of care is repeated botulinum toxin injections to weaken the adductor muscles. We sought to ameliorate the underlying neurological cause of SD with a novel therapy-deep brain stimulation (DBS).
Objective: To assess the safety of DBS in SD through phase I trial, and to quantify the magnitude of any benefit.
Methods: Six patients had left ventral intermediate nucleus (Vim) thalamic DBS and were randomized to 3 mo blinded-DBS "on" or "off" followed by a crossover. Primary outcomes were quality of life and quality of voice during the blinded phase. Patients continued with open-DBS "on." Secondary outcomes were comparisons of pre- and 1-yr cognitive, mood, and quality of life. This trial was registered with ClinicalTrials.gov (NCT02558634).
Results: There were no complications. Every patient reported an improvement in quality of life (P = .07) and had an improvement in quality of their voice (P = .06) when their blinded DBS was "on" versus "off." The trend did not reach statistical significance with the small sample size. Secondary outcomes showed no difference in cognition, an improvement in mood, and quality of life at 1 yr.
Conclusion: This phase I randomized controlled trial confirmed that DBS can be performed safely in patients with SD. Blinded DBS produced a strong trend toward improved quality of life and objective quality of voice despite the small sample size. The cerebellar circuit, not the pallidal circuit, appears to be crucial for motor control of the vocal folds.
Keywords: Deep brain stimulation; Quality of life; Randomized control trial; Spasmodic dysphonia.
© Congress of Neurological Surgeons 2021.
Figures
References
- Blitzer A, Brin MF, Fahn S, Lovelace RE.. Clinical and laboratory characteristics of focal laryngeal dystonia: study of 110 cases. Laryngoscope. 1988;98(6 Pt 1):636-640.
- Nutt JG, Muenter MD, Aronson A, Kurland LT, Melton LJ 3rd. Epidemiology of focal and generalized dystonia in Rochester, Minnesota. Mov Disord. 1988;3(3):188-194.
- Brin MF, Blitzer A, Fahn S, Gould W, Lovelace RE.. Adductor laryngeal dystonia (spastic dysphonia): treatment with local injections of botulinum toxin (Botox). Mov Disord. 1989;4(4):287-296.
- Ludlow CL. Treatment for spasmodic dysphonia: limitations of current approaches. Curr Opin Otolaryngol Head Neck Surg. 2009;17(3):160-165.
- Paniello RC, Barlow J, Serna JS.. Longitudinal follow-up of adductor spasmodic dysphonia patients after botulinum toxin injection: quality of life results. Laryngoscope. 2008;118(3):564-568.
- Smith ME, Ford CN.. Resistance to botulinum toxin injections for spasmodic dysphonia. Arch Otolaryngol Head Neck Surg. 2000;126(4):533-535.
- Dedo HH. Recurrent laryngeal nerve section for spastic dysphonia. Ann Otol. 1976;85(4 Pt 1):451-459.
- Koufman JA, Rees CJ, Halum SL, Blalock D.. Treatment of adductor-type spasmodic dysphonia by surgical myectomy: a preliminary report. Ann Otol Rhinol Laryngol. 2006;115(2):97-102.
- Berke GS, Blackwell KE, Gerratt BR, Verneil A, Jackson KS, Sercarz JA.. Selective laryngeal adductor denervationreinnervation: a new surgical treatment for adductor spasmodic dysphonia. Ann Otol Rhinol Laryngol. 1999;108(3):227-231.
- Sanuki T, Yumoto E.. Long-term evaluation of type 2 thyroplasty with titanium bridges for adductor spasmodic dysphonia. Otolaryngol Head Neck Surg. 2017;157(1):80-84.
- Vidailhet M, Vercueil L, Houeto J-Let al. . Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005;352(5):459-467.
- Isaias IU, Alterman RL, Tagliati M.. Deep brain stimulation for primary generalized dystonia. Arch Neurol. 2009;66(4):465-470.
- Poologaindran A, Ivanishvili Z, Morrison MDet al. . The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits. J Neurosurg. 2018;128(2):575-582.
- Schulz KF, Altman DG, Moher D; CONSORT Group . CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ. 2010;340:c332.
- Dwan K, Li T, Altman DG, Elbourne D.. CONSORT 2010 statement: extension to randomised crossover trials. BMJ. 2019;366:l4378.
- Hogikyan ND, Sethuraman G.. Validation of an instrument to measure Voice-Related Quality of Life (V-RQOL). J Voice. 1999;13(4):557-569.
- Stewart CF, Allen EL, Tureen P, Diamond BE, Blitzer A, Brin MF.. Adductor spasmodic dysphonia: standard evaluation of symptoms and severity. J Voice. 1997;11(1):95-103.
- Morzaria S, Damrose EJ.. A comparison of the VHI, VHI-10, and V-RQOL for measuring the effect of botox therapy in adductor spasmodic dysphonia. J Voice. 2012;26(3):378-380.
- Dallapiazza RF, Lee DJ, De Vloo Pet al. . Outcomes from stereotactic surgery for essential tremor. J Neurol Neurosurg Psychiatry. 2019;90(4):474-482.
- Avecillas-Chasin JM, Poologaindran A, Morrison MD, Rammage LA, Honey CR.. Unilateral thalamic deep brain stimulation for voice tremor. Stereotact Funct Neurosurg. 2018;96(6):392-399.
- Kruger MT, Hu A, Honey CR.. Deep brain stimulation for spasmodic dysphonia: a blinded comparison of unilateral and bilateral stimulation in two patients. Stereotact Funct Neurosurg. 2020;98(3):200-205.
- Jurgens U. The neural control of vocalization in mammals: a review. J Voice. 2009;23(1):1-10.
- Simonyan K, Horwitz B.. Laryngeal motor cortex and control of speech in humans. Neuroscientist. 2011;17(2):197-208.
- Simonyan K, Ludlow CL.. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study. Cereb Cortex. 2010;20(11):2749-2759.
- Samargia S, Schmidt R, Kimberley TJ.. Shortened cortical silent period in adductor spasmodic dysphonia: evidence for widespread cortical excitability. Neurosci Lett. 2014;560:12-15.
- Hassler R. Architectonic organization of the thalamic nuclei. In: Schaltenbrand G, Walker AE, eds. Stereotaxy of the Human Brain. Anatomical, Physiological and Clinical Applications, ed 2. Stuttgart: Thieme; 1982:140-180.
- Ilinsky IA, Kultas-Ilinsky K.. Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disorders. Mov Disord. 2002;17(S3):S9-S14.
- Franca C, de Andrada DC, Teixeira MJet al. . Effects of cerebellar neuromodulation in movement disorders: a systematic review. Brain Stimul. 2018;11(2):249-260.
- Rumbach AF, Blitzer A, Frucht S, Simonyan K.. An open-label study of sodium oxybate in spasmodic dysphonia. Laryngoscope. 2017;127(6):1402-1407.
Source: PubMed