Clinical Neurophysiology xxx (2014) xxx–xxx
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Case Report
Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report Francesca Cortese a,b,c,1, Manuela Rosa a,b,1, Mattia Arlotti a, Filippo Cogiamanian a, Gianluca Ardolino a, Paolo Rampini a, Giorgio Carrabba a, Marco Locatelli a, Vincenzo Levi b, Alberto Priori a,b,⇑ a b c
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Università degli Studi di Milano, Milan, Italy Dipartimento di Medicina, Scienze Chirurgiche e Biotecnologie, Univerisità la Sapienza di Roma, polo pontino, Latina, Italy
Although deep brain stimulation (DBS) surgery rarely leads to complications, when it does they can be serious (Fenoy and Simpson, 2014). In a recent study about DBS surgery complications in movement disorders, postoperative imaging demonstrated that asymptomatic intracerebral hemorrhage (ICH) occurs in 0.5% of patients, asymptomatic intraventricular hemorrhage in 3.4%, symptomatic ICH in 1.1%, and ischemic infarction in 0.4% (Fenoy and Simpson, 2014). Local field potentials (LFPs) are oscillatory bioelectrical signals arising from large neuronal ensembles around an electrode inserted into the central nervous system. LFP originating from deep human brain structures can be recorded through the electrodes used for DBS in various pathological conditions. For instance, in Parkinson’s disease (PD) LFP beta activity (13–30 Hz) is typically recorded in the off-medication state and when DBS is turned off. Levodopa treatment and DBS (Giannicola et al., 2010) both suppress beta activity and the degree of suppression correlates with motor improvement. Though recordings from the subthalamic nucleus (STN) are mainly used for experimental purposes they could be useful for monitoring DBS surgery: Chen and colleagues (Chen et al., 2006) showed that intra-operative LFP recordings help identifying the STN by disclosing specific beta activity. We report the case of a patient in whom LFP recordings disclosed abnormal STN activity before complications related to DBS became clinically and neuroradiologically evident. The patient was admitted for neurosurgery to implant bilateral DBS electrodes in the STN for PD (technique reported in detail elsewhere (Rampini et al., 2003)). PD first manifested about 13 years previously with bradykinesia and rigidity in the right limbs. In the ensuing years the neurological conditions progressively worsened. The patient had arterial hypertension under treatment with enalapril. The patient gave his informed consent to participate to a clinical study which was approved by hospital institutional
⇑ Corresponding author at: Università degli Studi di Milano, Centro Clinico per la Neurostimolazione, le Neurotecnologie ed i Disordini del Movimento, Fondazione IRCCS, Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milano 20122, Italy. E-mail address:
[email protected] (A. Priori). 1 The first two authors are in alphabetical order.
review board. Clinical study provided a LFP recording session (technique reported in detail elsewhere (Giannicola et al., 2010)) two days after surgery. Immediately after surgery a CT scan was performed: no surgical complications were detected (Fig. 1A). The recording session (about 48 h after surgery) showed that the mean LFP amplitude (calculated as the mean of the amplitude values recorded from 3 contact pairs) was clearly lower in the right than in left STN (1.22 ± 0.4 lVrms; 6.68 ± 0.25 lVrms) (Fig. 1B). Moreover the LFP value recorded for the right STN was in the lower limits of the normal LFP amplitude range (1.1 lVrms–7.2 lVrms). The mean impedance recorded from the macroelectrode contact pairs was almost symmetric (right = 8.58 ± 0.60 KO; left = 10.80 ± 0.52 KO). The day after the first recording session the patient started to complain of walking problems and tended to fall toward the left side. Neurological examination found a slight weakness in the left limbs, with mild pronation and distal weakness in the right upper limb, and a slight central left facial-nerve paralysis. There was an abnormal extensor plantar response (Babinski sign) on the left. Sensitivity, coordination and ocular motility were normal. The National Institutes of Health Stroke Scale (NIHSS) score was 3/42. The patient underwent a CT brain scan which showed a small hyperdense hemorrhagic area localized just caudally to the electrode apex and a slight hypodensity in the right cerebral peduncle and midbrain, extending through the right pons (Fig. 1A). The patient was therefore excluded from the planned study because of this complication, but a second LFP recording session was performed 7 days after DBS surgery. In the second recording session (about 168 h after surgery) the LFP amplitude recorded from the macroelectrode contact pairs decreased by 47.9% for the right STN (from 1.22 ± 0.4 lVrms to 0.56 ± 0.09 lVrms) whereas the left STN LFP amplitude remained almost unchanged (6.68 ± 0.25 lVrms and 6.98 ± 2.26 lVrms) (Fig. 1B). In both recording sessions spectral activity from the left STN peaked at around 15 Hz, whereas recordings from the right STN contained no peaks (Fig. 1C and D). In the second recording session, the mean electrode impedance for the contact pairs, also decreased for the right side (from 8.58 ± 0.60 KO to 3.40 ± 0.61 KO) whereas remained enough stable for the left (from 10.80 ± 0.52 KO to 10.63 ± 0.69 KO) (Fig. 1E-left). Electrode impedance significantly correlated with STN LFP amplitude value
http://dx.doi.org/10.1016/j.clinph.2014.08.013 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Cortese F et al. Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.08.013
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F. Cortese et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
Fig. 1. (A) Computed tomographic (CT) brain scan immediately, 3 days and 30 days after deep brain stimulation (DBS) surgery. Immediately after surgery (left) the scan is normal. Three days (center) after surgery, the scan shows a hyperdense hemorrhagic area in the right midbrain. In the scan obtained 30 days later, the lesion had disappeared (right). The CT slice was caudal to the right DBS electrode tip. (B) Local Field Potential (LFP) raw recordings from the right and left subthalamic nucleus (STN) (obtained through bipolar recordings from contacts 0–2) 2 days after surgery (top line) and 7 days (bottom line) after surgery. The recording signal was amplified (10.000) and filtered (1–100 Hz). Data were analyzed off-line with Matlab software (version 7.3, The Mathworks, Natick, MA, USA). The LFP amplitude in the right STN is lower in the second than in the first recording session. (C) LFP analysis in the frequency domain: mean power spectral density (PSD) recorded for session 1 (dotted line) and session 2 (continuous line) from the right and left STN. In the first and second recording sessions a well-defined spectral peak around 15 Hz appears in the left STN but not in the right STN. (D) LFP analysis in the time–frequency domain (logarithmic scale): time–frequency plots for LFP power in the recordings for session 1 (top) and session 2 (bottom) from the right and left STN. Red represents the maximum power value. Note the stable peak around 15 Hz in the left STN and the absence of any peaks in the right STN. (E) Impedance measurements. On the left, impedance in the right (black line) and left (gray line) STN in sessions 1 and 2. In the first recording session the mean impedance is only slightly lower in the right than in the left STN, whereas in the second session it is markedly reduced in the right STN. On the right, correlation between impedance and STN LFP Root Mean Squared (RMS) amplitude (p < 0.05) (Pearson’s correlation).
Please cite this article in press as: Cortese F et al. Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.08.013
F. Cortese et al. / Clinical Neurophysiology xxx (2014) xxx–xxx
(r = 0.658; p = 0.0014) (Fig. 1E-right). Seven days after DBS implantation, in the afternoon, the patient underwent surgery under general anesthesia to insert the high-frequency stimulator in a submuscular pouch under the pectoralis major muscle. After hospital discharge the patient started a rehabilitation program. One month later the patient had fully recovered from the hemiparesis. CT brain scan no longer showed the hemorrhagic hyperdensity or the hypodensity in the midbrain, pons and cerebral peduncle (Fig. 1A), even though we didn’t perform additional techniques to detect any possible residual structural changes (i.e., Perfusional TC). This case report is unusual and novel for two reasons. First, DBS-related complications occurring 72 h after DBS surgery are quite rare events: surgical complications commonly manifest during surgery or in the ensuing hours and are already demonstrated by postoperative imaging (3–4 h after surgery) (Fenoy and Simpson, 2014). Second, though a previous report (Novak et al., 2006) has described abnormal intraoperative single unit recordings in DBS-related ischemia, none have reported LFP changes associated with a brain lesion or suggesting a DBS-related complication. We conjecture that in our patient a stunning phase causing LFP recording abnormalities preceded a phase characterized by further LFP changes and clinical manifestations. As well as a small hemorrhagic hyperdensity, the CT scan identified a slight hypodensity in the right cerebral peduncle and midbrain and extending through the pons that probably reflected edema because it caused only mild neurological deficits and was fully reversible 30 days after the event. A technically important finding was that as a variable for diagnosing a possible DBS complication, LFP electrode impedance proved less sensitive than LFP amplitude. In fact, in the first recording session – one day before the patient’s hemiparesis began – electrode impedance was only slightly lower in the right than in the left STN. Conversely, the LFP recordings already showed reduced amplitude in the right side unaccompanied by the typical spectral oscillatory pattern. We could hypothesize that, in the early stunning phase, neuronal apraxia impairs neuronal oscillatory activity thus leading to abnormal LFP recordings. Afterwards, brain
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edema and bleeding alter also tissue conductivity and ultimately reduce impedance. In conclusion, our case report underlines that early asymmetry in LFP recordings after DBS surgery should alert neurologists to possible DBS-related complications, occurring in proximity to the electrode’s apex. Even though CT scan remains quickest and the most useful method for detecting the hemorrhage, our study suggest that LFP recording could be useful not only for scientific purpose but also to detect some kinds of preclinical surgical complications (in particular the ones occurring near the electrode’s apex). Being a quick and safe method it can be repeated several times a day, if available, especially in patients at risk as patients with comorbidities or with advanced age. Acknowledgement This study was supported by Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena (Milan, Italy), Università degli Studi di Milano (Italy), Ministero della Sanità (Italy), Ministero dell’Università e della Ricerca Scientifica e Tecnologica (Italy). Conflict of Interest: None of the authors have potential conflicts of interest to be disclosed. References Chen CC, Pogosyan A, Zrinzo LU, Tisch S, Limousin P, Ashkan K, et al. Intra-operative recordings of local field potentials can help localize the subthalamic nucleus in Parkinson’s disease surgery. Exp Neurol 2006;198:214–21. Fenoy AJ, Simpson Jr RK. Risks of common complications in deep brain stimulation surgery: management and avoidance. J Neurosurg 2014;120:132–9. Giannicola G, Marceglia S, Rossi L, Mrakic-Sposta S, Rampini P, Tamma F, et al. The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson’s disease. Exp Neurol 2010;226:120–7. Novak KE, Nenonene EK, Bernstein LP, Vergenz S, Medalle G, Prager JM, et al. Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson’s disease. Mov Disord 2006;21:1477–83. Rampini PM, Locatelli M, Alimehmeti R, Tamma F, Caputo E, Priori A, et al. Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. J Neurosurg Sci 2003;47:33–9.
Please cite this article in press as: Cortese F et al. Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report. Clin Neurophysiol (2014), http://dx.doi.org/10.1016/j.clinph.2014.08.013
