Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson’s disease

Objective: To investigate cognitive and behavioural effects of bilateral lead implants for high frequency stimulation (HFS) of the subthalamic nucleus in patients with Parkinson’s disease; and to discriminate between HFS and the effects of surgical intervention on cognitive function by carrying out postoperative cognitive assessments with the stimulators turned on or off. Methods: Motor, cognitive, behavioural, and functional assessments were undertaken in 20 patients with Parkinson’s disease before implantation and then at three, six, and 12 months afterwards. Nine patients were also examined 18 months after surgery. Postoperative cognitive assessments were carried out with stimulators turned off at three and 18 months, and turned on at six and 12 months. Results: Cognitive assessment showed a significant postoperative decline in performance on tasks of letter verbal fluency (across all postoperative assessments, but more pronounced at three months) and episodic verbal memory (only at three months, with stimulators off). At three, six, and 12 months after surgery, there was a significant improvement in the mini-mental state examination and in a task of executive function (modified Wisconsin card sorting test). On all postoperative assessments, there was an improvement in parkinsonian motor symptoms, quality of life, and activities of daily living while off antiparkinsonian drugs. A significant postoperative decrease in depressive and anxiety symptoms was observed across all assessments. Similar results were seen in the subgroup of nine patients with an 18 month follow up. Following implantation, three patients developed transient manic symptoms and one showed persistent psychic akinesia. Conclusions: Bilateral HFS of the subthalamic nucleus is a relatively safe procedure with respect to long term cognitive and behavioural morbidity, although individual variability in postoperative cognitive and behavioural outcome invites caution. Stimulation of the subthalamic nucleus does not per se appear to impair cognitive performance in patients with Parkinson’s disease and may alleviate the postpoperative decline in verbal fluency.

[1]  W W Zung,et al.  Self-rating depression scale in an outpatient clinic. Further validation of the SDS. , 1965, Archives of general psychiatry.

[2]  M. Torricelli,et al.  Effects of Dexamethasone and Dexamethasone plus Naltrexone on Pituitary Response to GnRH and TRH in Normal Women , 1999, Hormone Research in Paediatrics.

[3]  A. Lozano,et al.  Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation , 1999, Neurology.

[4]  B. Milner,et al.  Interhemispheric differences in the localization of psychological processes in man. , 1971, British medical bulletin.

[5]  Guy Vingerhoets,et al.  Cognitive outcome after unilateral pallidal stimulation in Parkinson’s disease , 1999, Journal of neurology, neurosurgery, and psychiatry.

[6]  Antonio Daniele,et al.  Transient mania with hypersexuality after surgery for high frequency stimulation of the subthalamic nucleus in Parkinson's disease , 2002, Movement disorders : official journal of the Movement Disorder Society.

[7]  A. Tröster,et al.  Unilateral pallidal stimulation for Parkinson's disease: Neurobehavioral functioning before and 3 months after electrode implantation , 1997, Neurology.

[8]  H. Nelson.  A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[9]  E. Moro,et al.  Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease , 1999, Neurology.

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

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

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

[13]  Bezerra Ml,et al.  Transient acute depression induced by high-frequency deep-brain stimulation. , 1999 .

[14]  J. Saint-Cyr,et al.  Neuropsychological consequences of chronic bilateral stimulation of the subthalamic nucleus in Parkinson's disease. , 2000, Brain : a journal of neurology.

[15]  P. Pollak,et al.  Transient acute depression induced by high-frequency deep-brain stimulation. , 1999, The New England journal of medicine.

[16]  L. Defebvre,et al.  Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease , 2001, Journal of Neurology.

[17]  J. Rothwell,et al.  The impact of deep brain stimulation on executive function in Parkinson's disease. , 2000, Brain : a journal of neurology.

[18]  R. Grossman,et al.  Neuropsychological outcome following unilateral pallidotomy. , 1999, Brain : a journal of neurology.

[19]  P. Rubé,et al.  L’examen Clinique en Psychologie , 1959 .

[20]  F. L. Wells.  The Measurement and Appraisal of Adult Intelligence , 1958 .

[21]  A. Bentivoglio,et al.  Long-term follow up of subthalamic nucleus stimulation in Parkinson's disease. , 2002, Neurology.

[22]  A L Benabid,et al.  Neuropsychological changes between “off” and “on” STN or GPi stimulation in Parkinson’s disease , 2000, Neurology.

[23]  M. Lezak.  Neuropsychological assessment, 3rd ed. , 1995 .

[24]  Arthur L. Benton,et al.  Word fluency and brain damage , 1967 .

[25]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

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

[27]  A L Benabid,et al.  Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: A consecutive series of 62 patients , 1999, Annals of neurology.

[28]  E. Tolosa,et al.  Effects of bilateral subthalamic stimulation on cognitive function in Parkinson disease. , 2001, Archives of neurology.

[29]  T. Aziz,et al.  Neuropsychological, neurological and functional outcome following pallidotomy for Parkinson's disease. A consecutive series of eight simultaneous bilateral and twelve unilateral procedures. , 1998, Brain : a journal of neurology.

[30]  S. Lajic,et al.  How Can Molecular Biology Contribute to the Management of Congenital Adrenal Hyperplasia? , 2000, Hormone Research in Paediatrics.

[31]  J. Speelman,et al.  Quality of life in patients with Parkinson's disease: development of a questionnaire. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[32]  Anthony E. Lang,et al.  Neuropsychological Outcome of GPi Pallidotomy and GPi or STN Deep Brain Stimulation in Parkinson's Disease , 2000, Brain and Cognition.

[33]  J. Saint-Cyr,et al.  Neuropsychological consequences of posteroventral pallidotomy for the treatment of Parkinson's disease , 1998, Neurology.

[34]  Diane C. Tsai.  Recent Developments in Parkinson's Disease , 1986, The Yale Journal of Biology and Medicine.

[35]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[36]  A L Benabid,et al.  Subthalamic nucleus or internal pallidal stimulation in young onset Parkinson's disease. , 1998, Brain : a journal of neurology.

[37]  Patricia Limousin,et al.  Deep brain simulation of the globus pallidus pars interna in advanced Parkinson's disease. , 2000 .

[38]  A L Benabid,et al.  Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease. , 2000, Neurology.

[39]  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.