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Targeting the Red Nucleus for Cerebellar Tremor

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Abstract

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

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References

  1. Hassler R. [Anatomy of the thalamus]. Arch Für Psychiatr Nervenkrankh Ver Mit Z Für Gesamte Neurol Psychiatr. 1950;184(3–4):249–56.

    CAS  Google Scholar 

  2. Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. 2009;8(1):67–81.

    Article  PubMed  Google Scholar 

  3. Dowsey-Limousin P. Postoperative management of Vim DBS for tremor. Mov Disord Off J Mov Disord Soc. 2002;17 Suppl 3:S208–11.

    Article  Google Scholar 

  4. Lyons KE, Pahwa R. Deep brain stimulation and tremor. Neurother J Am Soc Exp Neurother. 2008;5(2):331–8.

    Article  Google Scholar 

  5. Torres CV, Moro E, Lopez-Rios A-L, Hodaie M, Chen R, Laxton AW, et al. Deep brain stimulation of the ventral intermediate nucleus of the thalamus for tremor in patients with multiple sclerosis. Neurosurgery. 2010;67(3):646–51. discussion 651.

    Article  PubMed  Google Scholar 

  6. Berk C, Carr J, Sinden M, Martzke J, Honey CR. Thalamic deep brain stimulation for the treatment of tremor due to multiple sclerosis: a prospective study of tremor and quality of life. J Neurosurg. 2002;97(4):815–20.

    Article  PubMed  Google Scholar 

  7. Krystkowiak P, Martinat P, Cassim F, Pruvo JP, Leys D, Guieu JD, et al. Thalamic tremor: correlations with three-dimensional magnetic resonance imaging data and pathophysiological mechanisms. Mov Disord Off J Mov Disord Soc. 2000;15(5):911–8.

    Article  CAS  Google Scholar 

  8. Larochelle L, Bedard P, Boucher R, Poirier LJ. The rubro-olivo-cerebello-rubral loop and postural tremor in the monkey. J Neurol Sci. 1970;11(1):53–64.

    Article  CAS  PubMed  Google Scholar 

  9. Poirier LJ. Experimental and histological study of midbrain dyskinesias. J Neurophysiol. 1960;23:534–51.

    CAS  PubMed  Google Scholar 

  10. Cooper IS. A cerebellar mechanism in resting tremor. Neurology. 1966;16(10):1003–15.

    Article  CAS  PubMed  Google Scholar 

  11. Mostile G, Jankovic J. Alcohol in essential tremor and other movement disorders. Mov Disord Off J Mov Disord Soc. 2010;25(14):2274–84.

    Article  Google Scholar 

  12. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad hoc scientific committee. Mov Disord Off J Mov Disord Soc. 1998;13 Suppl 3:2–23.

    Google Scholar 

  13. Lefranc M, Le Gars D. Robotic implantation of deep brain stimulation leads, assisted by intra-operative, flat-panel CT. Acta Neurochir (Wien). 2012;54:1–6.

    Google Scholar 

  14. Bain PG, Findley LJ, Atchison P, Behari M, Vidailhet M, Gresty M, et al. Assessing tremor severity. J Neurol Neurosurg Psychiatry. 1993;56(8):868–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Diederich NJ, Verhagen Metman L, Bakay RA, Alesch F. Ventral intermediate thalamic stimulation in complex tremor syndromes. Stereotact Funct Neurosurg. 2008;86(3):167–72.

    Article  CAS  PubMed  Google Scholar 

  16. Hassan A, Ahlskog JE, Rodriguez M, Matsumoto JY. Surgical therapy for multiple sclerosis tremor: a 12-year follow-up study. Eur J Neurol Off J Eur Fed Neurol Soc. 2012;19:764–8.

    CAS  Google Scholar 

  17. Wishart HA, Roberts DW, Roth RM, McDonald BC, Coffey DJ, Mamourian AC, et al. Chronic deep brain stimulation for the treatment of tremor in multiple sclerosis: review and case reports. J Neurol Neurosurg Psychiatry. 2003;74(10):1392–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Fytagoridis A, Blomstedt P. Complications and side effects of deep brain stimulation in the posterior subthalamic area. Stereotact Funct Neurosurg. 2010;88(2):88–93.

    Article  CAS  PubMed  Google Scholar 

  19. Romanelli P, Brontë-Stewart H, Courtney T, Heit G. Possible necessity for deep brain stimulation of both the ventralis intermedius and subthalamic nuclei to resolve Holmes tremor. Case report. J Neurosurg. 2003;99(3):566–71.

    Article  PubMed  Google Scholar 

  20. Foote KD, Okun MS. Ventralis intermedius plus ventralis oralis anterior and posterior deep brain stimulation for posttraumatic Holmes tremor: two leads may be better than one: technical note. Neurosurgery. 2005;56(2 Suppl):E445. discussion E445.

    Article  PubMed  Google Scholar 

  21. Deuschl G, Raethjen J, Lindemann M, Krack P. The pathophysiology of tremor. Muscle Nerve. 2001;24(6):716–35.

    Article  CAS  PubMed  Google Scholar 

  22. Belhaj-Saïf A, Karrer JH, Cheney PD. Distribution and characteristics of poststimulus effects in proximal and distal forelimb muscles from red nucleus in the monkey. J Neurophysiol. 1998;79(4):1777–89.

    PubMed  Google Scholar 

  23. Pacheco-Calderón R, Carretero-Guillén A, Delgado-García JM, Gruart A. Red nucleus neurons actively contribute to the acquisition of classically conditioned eyelid responses in rabbits. J Neurosci Off J Soc Neurosci. 2012;32(35):12129–43.

    Article  Google Scholar 

  24. Nieoullon A, Vuillon-Cacciuttolo G, Dusticier N, Kerkérian L, André D, Bosler O. Putative neurotransmitters in the red nucleus and their involvement in postlesion adaptive mechanisms. Behav Brain Res. 1988;28(1–2):163–74.

    Article  CAS  PubMed  Google Scholar 

  25. Brittain J-S, Jenkinson N, Holland P, Joundi RA, Green AL, Aziz TZ. Development of Holmes’ tremor following hemi-cerebellar infarction. Mov Disord Off J Mov Disord Soc. 2011;26(10):1957–9.

    Article  Google Scholar 

  26. Nieuwenhuys R, Voogd J, Huijzen CV, van Huijzen C, Voogd J. The human central nervous system. Berlin: Springer; 2008.

    Google Scholar 

  27. Foltynie T, Zrinzo L, Martinez-Torres I, Tripoliti E, Petersen E, Holl E, et al. MRI-guided STN DBS in Parkinson’s disease without microelectrode recording: efficacy and safety. J Neurol Neurosurg Psychiatry. 2011;82:358–63.

    Article  CAS  PubMed  Google Scholar 

  28. Bejjani BP, Dormont D, Pidoux B, Yelnik J, Damier P, Arnulf I, et al. Bilateral subthalamic stimulation for Parkinson’s disease by using three-dimensional stereotactic magnetic resonance imaging and electrophysiological guidance. J Neurosurg. 2000;92(4):615–25.

    Article  CAS  PubMed  Google Scholar 

  29. Blomstedt P, Sandvik U, Linder J, Fredricks A, Forsgren L, Hariz MI. Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor. Acta Neurochir (Wien). 2011;153(12):2329–35.

    Article  Google Scholar 

  30. Carrillo-Ruiz JD, Velasco F, Jimènez F, Castro G, Velasco AL, Hernández JA, et al. Bilateral electrical stimulation of prelemniscal radiations in the treatment of advanced Parkinson’s disease. Neurosurgery. 2008;62(2):347–57. discussion 357–359.

    Article  PubMed  Google Scholar 

  31. Grover PJ, Pereira EAC, Green AL, Brittain J-S, Owen SLF, Schweder P, et al. Deep brain stimulation for cluster headache. J Clin Neurosci Off J Neurosurg Soc Australas. 2009;16(7):861–6.

    Google Scholar 

  32. Rodriguez-Oroz MC, Rodriguez M, Leiva C, Rodriguez-Palmero M, Nieto J, Garcia-Garcia D, et al. Neuronal activity of the red nucleus in Parkinson’s disease. Mov Disord. 2008;23(6):908–11.

    Article  PubMed  Google Scholar 

  33. Hicks TP, Onodera S. The mammalian red nucleus and its role in motor systems, including the emergence of bipedalism and language. Prog Neurobiol. 2012;96(2):165–75. Février.

    Article  PubMed  Google Scholar 

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Conflict of Interest

The authors declare no conflicts of interest.

There are no financial issues relative to the research or funding sources.

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Authors and Affiliations

  1. Department of Neurosurgery, Amiens University Hospital, Amiens, France

    M. Lefranc & D. Le Gars

  2. Department of Clinical Neurophysiology, Amiens University Hospital, Amiens, France

    P. Merle & J.-M. Macron

  3. Department of Neurology, Amiens University Hospital, Amiens, France

    M. Tir & P. Krystkowiak

  4. EA 4559, Laboratoire de Neurosciences Fonctionnelles et Pathologie, Jules Verne University of Picardy, Amiens, France

    P. Krystkowiak

  5. Department of Anaesthesiology, Amiens University Hospital, Amiens, France

    D. Montpellier

  6. Department of Neurosurgery, Amiens University Hospital, Amiens, France

    J.-M. Constant

  7. Laboratory of Experimental Neurology, Erasme Hospital, Brussels, Belgium

    M. Manto

  8. INSERM U1105, Groupe de Recherches sur l’Analyse Multimodale de la Fonction Cérébrale, Amiens, France

    M. Lefranc

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  1. M. Lefranc
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Correspondence to M. Lefranc.

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Pre-operative clinical status of the patient and intra-operative findings. (M4V 28,413 kb)

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Lefranc, M., Manto, M., Merle, P. et al. Targeting the Red Nucleus for Cerebellar Tremor. Cerebellum 13, 372–377 (2014). https://doi.org/10.1007/s12311-013-0546-z

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  • DOI: https://doi.org/10.1007/s12311-013-0546-z

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