title: The effect of dopaminergic therapy on intraoperative microelectrode recordings for subthalamic deep brain stimulation under GA: can we operate on patients 'on medications'?
abstract: OBJECTIVE
  Microelectrode recording (MER) plays an important role in target refinement in deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD). Traditionally, patients were operated on in the 'off-medication' state to allow intraoperative assessment of the patient response to direct STN stimulation. The development of intraoperative microelectrode recording (MER) has facilitated the introduction of general anaesthesia (GA). However, the routine withdrawal of dopaminergic medications has remained as standard practice. This retrospective review examines the effect of continuing these medications on intraoperative MER for subthalamic DBS insertion under GA and discusses the clinical implication of this approach.
  
  
  METHODS
  Retrospective review of PD patients who had bilateral STN DBS insertion was conducted. A cohort of seven patients (14 STN microelectrodes) between 2012 and 2013, who inadvertently underwent the procedure while 'on medication', was identified. This 'on-medication' group was compared to all other patients who underwent the same procedure between 2012 and 2013 and had their medications withdrawn preoperatively, the 'off-medication' group, n = 26 (52 STN DBS). The primary endpoint was defined as the number of microelectrode tracks required to obtain adequate STN recordings. A second endpoint was the length of MERs that was finally used to guide the DBS lead insertion. The Reduction of the levo-dopa equivalent daily dose (LEDD) was also examined as a surrogate marker for clinical outcome 12 months postoperatively for both groups. For the on-medication group further analysis of the clinical outcome was done relying on the change in the motor examination at 12 months following STN DBS using the following parameters (Hoehn and Yahr scale, the number of waking hours spent in the OFF state as well as the duration of dyskinesia during the ON periods).
  
  
  RESULTS
  The on-medication group was statistically comparable in all baseline characteristics to the off-medication group, including age at operation 57 ± 9.9 years vs. 61.5 ± 9.2 years, p = 0.34 (mean ± SD); duration of disease (11.6 ± 5 years vs. 11.3 ± 4 years, p = 0.68); gender F:M ratio (1:6 vs. 9:17, p = 0.40). Both groups had similar PD medication regimes preoperatively expressed as levodopa equivalent daily dose (LEDD) 916 mg (558-1850) vs. 744 mg (525-3591), respectively, p = 0.77. In the on-medication group, all seven patients (14 STN electrodes) had satisfactory STN recording from a single brain track versus 15 out of 26 patients (57.7 %) in the off-medication group, p = 0.06. The length of MER was 4.5 mm (3.0-5.5) in the on-medication group compared to 3.5 mm (3.0-4.5) in the off-medication group, p = 0.16. The percentage of reduction in LEDD postoperatively for the on-medication group was comparable to that in the off-medication group, 62 % versus 58 %, respectively, p > 0.05. All patients in the on-medication group had clinically significant improvement in their PD motor symptoms as assessed by the Hoehn and Yahr scale; the number of hours (of the waking day) spent in the OFF state dropped from 6.9 (±2.3) h to 0.9 (±1.6) h; the duration of dyskinesia during the ON state dropped from 64 % (±13 %) of the ON period to only 7 % (±12 %) at 12 months following STN DBS insertion.
  
  
  CONCLUSIONS
  STN DBS insertion under GA can be performed without the need to withdraw dompaminergic treatment preoperatively. In this review the inadvertent continuation of medications did not affect the physiological localisation of the STN or the clinical effectiveness of the procedure. The continuation of dopamine therapy is likely to improve the perioperative experience for PD patients, avoid dopamine-withdrawal complications and improve recovery. A prospective study is needed to verify the results of this review.
authors.affiliation: Divisions of Neurosurgery, University Hospital Birmingham, Birmingham, UK. mohammedjamil80@yahoo.com.
authors.forename: Mohammed J
authors.initials: MJ
authors.lastname: Asha
authors.affiliation: Divisions of Neurosurgery, University Hospital Birmingham, Birmingham, UK.
authors.forename: Jamilla
authors.initials: J
authors.lastname: Kausar
authors.affiliation: Divisions of Neuroanaesthesia, University Hospital Birmingham, Birmingham, UK.
authors.forename: Hari
authors.initials: H
authors.lastname: Krovvidi
authors.affiliation: Divisions of Neurophysiology, University Hospital Birmingham, Birmingham, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Shirley
authors.affiliation: Divisions of Neurosurgery, University Hospital Birmingham, Birmingham, UK.
authors.forename: Anwen
authors.initials: A
authors.lastname: White
authors.affiliation: Divisions of Neurosurgery, University Hospital Birmingham, Birmingham, UK.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chelvarajah
authors.affiliation: Department of Statistics, Wolfson Computer Laboratory, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Hodson
authors.affiliation: Department of Neurology, School of Clinical and Experimental Medicine, College of Medicine, University of Birmingham, Birmingham, UK.
authors.forename: Hardev
authors.initials: H
authors.lastname: Pall
authors.affiliation: Divisions of Neurosurgery, University Hospital Birmingham, Birmingham, UK.
authors.forename: Rosalind D
authors.initials: RD
authors.lastname: Mitchell
mesh_terms: D000368:Aged; D000768:Anesthesia, General; D000978:Antiparkinson Agents / Q000494:pharmacology; D000075202:Contraindications; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D020531:Subthalamic Nucleus / Q000187:drug effects*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: DBS; Dopaminergic therapy; MER; STN