Downloaded from https://academic.oup.com/neurosurgery/advance-article-abstract/doi/10.1093/neuros/nyz039/5366465 by Departm of Anaesth. Cantonal Hospital St. Gallen Switz. user on 27 March 2019 RESEARCH-HUMAN-CLINICAL TRIALS Stereotactic Lesion in the Forel’s Field H: A Two-Years Prospective Open-Label Study on Motor and Nonmotor Symptoms, Neuropsychological Functions and Quality of Life in Parkinson Disease Fabio Godinho, MD, PhD ∗ ‡§ Michel Magnin, PhD¶ BACKGROUND: Stereotactic lesion in the Forel’s field H (campotomy) was proposed in ∗ 1963 to treat Parkinson disease (PD) symptoms. Despite its rationale, very few data on Paulo Terzian Filho, MD ‡ this approach have emerged. Additionally, no study has assessed its effects on nonmotor Paul Reis, MD symptoms, neuropsychological functions and quality of life. || Osmar Moraes, MD OBJECTIVE: To provide a prospective 2-yr assessment of motor, nonmotor, neuropsycho- Marivaldo Nascimento, MD# logical and quality of life variables after unilateral campotomy. Carlos Costa, MD∗∗ METHODS: Twelve PD patients were prospectively evaluated using the Unified Parkinson’s Maira Okada de Oliveira, Disease Rating Scale (UPDRS), the Dyskinesia Rating Scale and the Parkinson’s disease ∗∗ quality of life questionnaire (PDQ39) before campotomy, and after 6 and 24 mo. Nonmotor, PhD ‡‡ neuropsychiatric, neuropsychological and quality of life variables were assessed. The Maria Sheila Rocha, MD, impact of PD on global health was also rated. ∗∗ PhD RESULTS: A significant reduction in contralateral rest tremor (65.7%, P < .001), rigidity (87.8%, P < .001), bradykinesia (68%, P < .001) and axial symptoms (24.2%, P < .05) in ∗Department of Functional Neurosurgery, Hospital Santa Marcelina, São Paulo, offmedication condition led to a 43.9% reduction in UPSDRS III scores 2 yr after campotomy Brazil; ‡Division of Functional Neurosur- (P < .001). Gait improved by 31.9% (P < .05) and walking time to cover 7 m was reduced by gery, Institute of Psychiatry of Hospital 43.2% (P < .05). Pain decreased by 33.4% (P < .01), while neuropsychiatric and neuropsycho- das Clínicas, University of São Paulo, < Medicine School, São Paulo, Brazil; logical functions did not change. Quality of life improved by 37.8% (P .05), in line with a §Faculdade Santa Marcelina – Medicine 46.7% reduction of disease impact on global health (P < .001). ¶ School, São Paulo, Brazil; Centre de CONCLUSION: A significant 2-yr improvement of motor symptoms, gait performance and Recherche en Neurosciences de Lyon, NeuroPain lab, INSERM U 1028, UMR pain was obtained after unilateral campotomy without significant changes to cognition. 5292 – Lyon, Rhône-Alpes, France; QualityoflifemarkedlyimprovedinparallelwithasignificantreductionofPDburdenon || Department of Neurosurgery, Hospital global health. Santa Marcelina, São Paulo, Brazil; #De- partment of Anesthesiology, Hospital KEY WORDS: neuropsychological tests, pain, Parkinson disease, quality of life, subthalamus, stereotaxic ∗∗ Santa Marcelina, São Paulo, Brazil; De- techniques, Forel’s field H partment of Neurology, Hospital Santa Marcelina, São Paulo, Brazil; ‡‡Global Neurosurgery 0:1–10, 2019 DOI:10.1093/neuros/nyz039 www.neurosurgery-online.com Brain Health Institute, University of California-San Francisco, San Francisco, California ibers connecting basal ganglia struc- Many recent approaches confirmed that lesions Correspondence: tures to the cerebral cortex, thalamus extending into fiber tracts coursing in the Fabio Godinho, MD, PhD, and cerebellum have been very early vicinity of the subthalamic nucleus (STN) 592, Maestro Cardim, F Conj 1101, Bela Vista, targeted by different neurosurgical approaches and the pallidum gave better clinical results 1-3 4,5 São Paulo, Brazil – 01323-001. to control Parkinson disease (PD) symptoms. than lesions confined within these nuclei. E-mail: [email protected] Received, May 20, 2018. ABBREVIATIONS: AC, anterior commissure; ADL, activities of daily living; DBS, deep brain stimulation; D.im.e, Accepted, January 29, 2019. Dorsointermedius externus; FF, Forel’s Field H; L.po, Lateropolaris; PC, posterior commissure; PD, Parkinson disease; PPN, pedunculopontine tegmental nucleus; QoL, quality of life; SD, standard deviation; SEM, standard Copyright C 2019 by the errorofthemean;STN, subthalamic nucleus; V.im, Ventrointermedius; V.o.a, Ventro-oralis anterior thalamic Congress of Neurological Surgeons nucleus; V.o.p, Ventro-oralis posterior thalamic nucleus; VAS, visual analogue pain intensity scale; UDysRS, Unified Dyskinesia Rating Scale; UPDRS, Unified Parkinson’s Disease Rating Scale Supplemental digital content is available for this article at www.neurosurgery-online.com. NEUROSURGERY VOLUME 0 | NUMBER 0 | 2019 | 1 Downloaded from https://academic.oup.com/neurosurgery/advance-article-abstract/doi/10.1093/neuros/nyz039/5366465 by Departm of Anaesth. Cantonal Hospital St. Gallen Switz. user on 27 March 2019 GODINHO ET AL In addition, when high-frequency stimulation of the STN was Clinical, Neuropsychological and Neuropsychiatric used, the most effective contacts of quadripolar electrodes were Assessments located in the rostrodorsal part of the STN, close to the zona Primary outcomes were motor symptoms and QoL at 6 mo and incerta and the Forel’s Field H (FF).6 These data emphasize 2 yr after surgery (means ± SEM). Secondary outcomes were neuropsy- that functional modulation of subthalamic fibers is an important chological, neuropsychiatric and nonmotor symptoms. Evaluations were factor to achieve a satisfactory motor improvement in PD, using performed preoperatively, 6 and 24 mo after surgery using UPDRS either lesion or electrical stimulation. and Hoehn and Yahr (H&Y) scales, the CAPSIT-PD recommended Among the subthalamic fiber tracts, the FF and its vicinity by the core assessment program for intracerebral transplantation and comprise a complex bundle of pallidofugal, cerebellothalamic the Unified Dyskinesia Rating Scale (UDysRS). We assessed pain intensity through visual analogue pain intensity scale – VAS, the and pallidomesencephalic axons.7-9 Pallidothalamic fibers project overall nonmotor symptoms (nonmotor symptoms scale), fatigue severity predominantly onto Lateropolaris (L.po), Ventro-oralis anterior (fatigue severity scale) and sleep quality (SCOPA-sleep). Neuropsy- (V.o.a) and Ventro-oralis posterior (V.o.p) thalamic nuclei, while chiatric evaluation excluded dementia and other major psychiatric cerebellar fibers terminate preferentially into the Ventrointer- disorders using the Neuropsychiatric Inventory, Scales for Outcomes medius (V.im) and Dorsointermedius externus (D.im.e.) thalamic in PD – Psychiatric Complications (SCOPA-PC) and Beck Depression nuclei (Hassler nomenclature). These thalamic nuclei project to Inventory. The neuropsychological evaluation comprised tests recom- motor, premotor and supplementary motor cortical areas.10,11 As mended by the movement disorders society. QoL was estimated through to the pallidomesencephalic fibers, they project to mesencephalic the Brazilian version of PD QoL questionnaire – PDQ-39.16 The locomotor area and are likely involved in axial motor functions.12 subjective impact of PD on global health was rated preoperatively Despite these anatomical considerations, only one surgical team and at 2 years according to a 5-point Likert scale as follows: 1 – has reported results based on the direct approach of the FF in notatall,2–slightly,3–moderately,4–very,5–extremely.All 13-15 motor scales were performed in off and onmedication conditions, while PD patients during the last 5 decades. Using stereotactic nonmotor functions were evaluated only in onmedication condition. lesions centered at the FF (campotomy), significant reductions Adverse events were collected and reported according to the Medical 14 of tremor, rigidity and bradykinesia were reported. However, Dictionary for Regulatory Activities, version 17 (MedDRA 17.0 – 2014). no study so far analyzed the possible effects of campotomy on If no spontaneous complaints have occurred, an active inquiry was nonmotor symptoms, cognitive functions and quality of life performed. (QoL) in PD patients. In this study, we performed a compre- hensive and prospective evaluation of motor and nonmotor variables in 12 PD patients after unilateral campotomy followed- Surgical Procedure up for 2 yr. We hypothesized that reduction in motor symptoms Anatomical targeting was performed by fusing a stereotactic tomog- would result in significant improvement in QoL after surgery, raphy with a nonstereotactic volumetric 1.5T Magnetic Resonance = while neuropsychological and neuropsychiatric effects would be Imaging (MRI). The FF localization was estimated as following: X 7.5 limited or absent. mm from the lateral border of the third ventricle at the anterior commissure – posterior commissure level (AC–PC); Y = 1 mm posterior to the midcommissural point; Z = 1 mm inferior to the AC–PC METHODS level.17 Microelectrode recordings were performed using a set of 2 or 3 parallel tungsten microelectrodes (microTargetingR electrodes, FHC, Patients Greenville, Massachusetts). Recordings were started at 5 mm above the We enrolled 12 out of 19 right-handed patients with advanced PD anatomical target and performed every millimeter until recording spikes in this prospective open-label clinical trial. Data from 7 patients were from STN neurons. STN cell firings were used as an internal marker, excluded as they lived far away from our center and were followed-up not only to estimate the FF position