Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in Parkinson’s disease

OBJECTIVE To determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) may modulate l-DOPA-induced dyskinesia (LID) in dyskinetic Parkinson's disease (PD) patients. LID is a severe motor complication in advanced PD patients. The neural mechanisms involved in LID are not clear, and it is apparent that both an excessive decrease in internal pallidus firing and a modification and overactivation of cortical motor and premotor areas are involved in its pathogenesis. METHODS Using low frequency 1Hz repetitive rTMS we investigated whether decrease of excitability of the supplementary motor area (SMA) may result in modification of LID in PD patients. Furthermore we tested whether it was possible to enhance and/or prolong the beneficial effects of the treatment with repeated sessions of stimulation. RESULTS We observed that 1Hz rTMS induced a transient reduction of dyskinesias. A single session of rTMS improved LID, while repeated sessions of stimulation failed to enhance and/or prolong the beneficial effects of the procedure, without causing motor deterioration or other adverse effects. CONCLUSIONS These results suggest that LID may depend on an increased excitability of the SMA. SIGNIFICANCE SMA rTMS is effective in reducing transiently LID, although cannot yet be considered clinically useful.

[1]  J A Obeso,et al.  Pathophysiology of levodopa-induced dyskinesias in Parkinson's disease: problems with the current model. , 2000, Annals of neurology.

[2]  S. Tsuji,et al.  Does transcranial magnetic stimulation improve the motor symptoms of Parkinson disease? , 2003, Journal of Neurology.

[3]  Erwan Bezard,et al.  Pathophysiology of levodopa-induced dyskinesia: Potential for new therapies , 2001, Nature Reviews Neuroscience.

[4]  M. Gentilucci,et al.  Planning and executing an action in Parkinson's disease , 1999, Movement disorders : official journal of the Movement Disorder Society.

[5]  Alexander Münchau,et al.  Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans , 2003, NeuroImage.

[6]  T. Paus,et al.  Repetitive Transcranial Magnetic Stimulation of the Human Prefrontal Cortex Induces Dopamine Release in the Caudate Nucleus , 2001, The Journal of Neuroscience.

[7]  S. Fahn Members of the UPDRS Development Committee. Unified Parkinson's Disease Rating Scale , 1987 .

[8]  G. Di Chiara,et al.  Cocaine and Amphetamine Increase Extracellular Dopamine in the Nucleus Accumbens of Mice Lacking the Dopamine Transporter Gene , 2001, The Journal of Neuroscience.

[9]  Sarah H Lisanby,et al.  Therapeutic application of repetitive transcranial magnetic stimulation: a review , 2001, Clinical Neurophysiology.

[10]  C. Civardi,et al.  Transcranial magnetic stimulation and Parkinson’s disease , 2002, Brain Research Reviews.

[11]  C. Weiller,et al.  Abnormal excitability of premotor-motor connections in de novo Parkinson's disease. , 2004, Brain : a journal of neurology.

[12]  J. Rothwell,et al.  Functional Connectivity of Human Premotor and Motor Cortex Explored with Repetitive Transcranial Magnetic Stimulation , 2002, The Journal of Neuroscience.

[13]  Idil Cavus,et al.  Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. , 2002, The American journal of psychiatry.

[14]  D J Brooks,et al.  Neuroimaging of dyskinesia. , 2000, Annals of neurology.

[15]  J. Dostrovsky,et al.  Neuronal recordings in Parkinson's disease patients with dyskinesias induced by apomorphine. , 2000, Annals of neurology.

[16]  D. Brooks,et al.  A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. , 2000, The New England journal of medicine.

[17]  C Caltagirone,et al.  High-frequency rTMS improves time perception in Parkinson disease , 2004, Neurology.

[18]  Paul Greengard,et al.  Loss of bidirectional striatal synaptic plasticity in L-DOPA–induced dyskinesia , 2003, Nature Neuroscience.

[19]  U Sabatini,et al.  Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia. , 1998, Brain : a journal of neurology.

[20]  S. Fahn Unified Parkinson's Disease Rating Scale , 1987 .

[21]  M. Hallett,et al.  Depression of motor cortex excitability by low‐frequency transcranial magnetic stimulation , 1997, Neurology.

[22]  S Fahn,et al.  The spectrum of levodopa-induced dyskinesias. , 2000, Annals of neurology.

[23]  O Rascol A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group , 2000 .

[24]  J. Hughes,et al.  Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. , 1992, Journal of neurology, neurosurgery, and psychiatry.

[25]  P. May,et al.  Quantitative Assessment of Neuroleptic‐Induced Extrapyramidal Symptoms: Clinical and Nonclinical Approaches , 1983, Clinical neuropharmacology.

[26]  D. Brooks,et al.  Core assessment program for intracerebral transplantations (CAPIT) , 1992, Movement disorders : official journal of the Movement Disorder Society.

[27]  L. Grégoire,et al.  Risk Factors for Peak Dose Dyskinesia in 100 Levodopa-treated Parkinsonian Patients , 1996, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[28]  C Caltagirone,et al.  rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease , 2005, Neurology.

[29]  J. Málly,et al.  Improvement in Parkinsonian symptoms after repetitive transcranial magnetic stimulation , 1999, Journal of the Neurological Sciences.

[30]  C. Marsden,et al.  Recent Developments in Parkinson's Disease , 1986 .

[31]  L. Tremblay,et al.  Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism , 1991, Brain Research.