Clinical Neurophysiology 126 (2015) 1054–1061
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letters to the Editor Coincidence of non-convulsive epileptic seizures and electrical stimulation of thalamic anterior nuclei in an epileptic patient
A recent randomized, prospective study showed that deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduced frequency and intensity of epileptic seizures in medically refractory partial seizures, including secondarily generalized seizures (Fisher et al., 2010). Stimulation-associated transient seizures have been reported up to now in two patients (Fisher et al., 2010). In none of these cases a detailed description of the epileptic syndromes, of the electro-clinical semiology of stimulationassociated seizures and of the exact time-correlation between ANT-stimulation and seizures onset and duration was provided. Therefore, mechanisms behind the effects and even the causality remain unclear. A detailed analysis of such cases might establish whether stimulation-associated seizures depend on epileptic syndromes and/or on stimulation parameters, and might give insights into the mechanism of action of DBS. However, identification of stimulation-associated seizures can be difficult. Without an exact detection of stimulation intervals, irregularly-occurring and mild DBS-correlated seizures might be underestimated or misinterpreted as non-epileptic side-effects. We report the first case where the ANT-stimulation intervals were precisely resolved and demonstrate for the first time a coincidence between onphases of stimulation and habitual epileptic seizures, strongly suggesting a causal relationship. The female patient with non-lesional, medically refractory epilepsy of unclear etiology, developed bilateral convulsive and disabling daily focal tonic-dyscognitive seizures of upper body accompanied by falls since the age of 11 years. Seizure semiology, ictal electroencephalograms (EEGs) and positron emission tomography suggested a putative initiation of seizures in the left fronto-lateral and basal cortex (see Supplementary Information). In between tonic-dyscognitive seizures, the EEGs showed sharp–slow-waves or high-amplitude theta–delta waves in bilateral fronto-centro-temporal regions. The repetitive subclinical sharp–slow-wave bursts at 1–2 Hz occasionally lasted longer than tens of seconds. At age of 21, ANT-DBS was initiated. Quadripolar DBS-electrodes (Medtronic Model 3389, MedtronicÒ, Minneapolis, MN, USA), connected to a dual-channel programmable stimulation device (Model Activa PC, MedtronicÒ) were implanted bilaterally, paraventricularly in the ANT using a stereotactic technique (Supplementary Fig. S1). During DBS-therapy the patient was treated with eslicarbazepine acetate and phenytoin. Towards the end of DBS-therapy clobazam, zonisamid and temporary perampanel have been added to the medication (see Supplementary Information). Most upper and lateral located plots of each electrode (number 3 and 11, with a putative localization in the ANT, based on magnetic resonance imaging and neurosurgical implantation parameters) were chosen for
monopolar stimulation. A wide range of parameters were systematically tested during 11 months of stimulation: amplitudes between 3–7.5 V, cycles between 1 min on/5 min off and 20 s on/20 s off, frequency between 145–180 Hz and pulse-width between 90–120 ls. Mutism and avolition after onset of DBS were interpreted as disappointment of the patient, since her habitual tonic-dyscognitive seizures were not improved by ANT-DBS. We closely reanalyzed the patient’s scalp-EEGs towards the end of 11 months of DBS. Retrospectively and prospectively we could regularly identify the on-phases of stimulation cycles based on amplitude reductions of QRS-complexes in electrocardiograms (Fig. 1B; Supplementary Fig. S2, Video S1). The morphology of habitual bilateral frontocentro-temporal (sharp)-slow-wave discharges in EEGs was unaffected by ANT-DBS (Supplementary Fig. S2). We noticed a time-correlation between on-phases of stimulation cycles and habitual subclinical seizures at stimulations equal or above 3 V (Fig. 1A and B). Repetitive bursts of sharp–slow-waves occurred 12.6 ± 1.1 s after onset of ANT-DBS, which was similar to the time needed for ANT-DBS to affect neocortical temporal activity (Zumsteg et al., 2006). Electrical activity ceased 21.7 ± 5.5 s after the end of stimulation-on phases (Fig. 1A and B). In the densityspectral-array of a long-term video-EEG, several regularly-occurring periods with dominant delta frequencies, corresponding to bilateral anterior (sharp)–slow-wave series, were identified during ANT-stimulation phases (Fig. 1B). In video-EEG-recordings performed when the patient was reading aloud, EEG-discharges accompanied by interruption of reading flow were reproducibly documented during on-phases of stimulation cycles (Video S1). We discontinued the ANT-DBS at the patient’s request. Up to now she did not allow stimulation on different electrode plots. Whether DBS exerts its effects via inhibition of stimulated targets or by anterograde or retrograde propagation of stimuli to remote structures is a controversial matter. In epileptic patients low- and high frequency ANT-DBS influenced the frontal and temporal cortical activity, respectively (Kerrigan et al., 2004; Zumsteg et al., 2006). Therefore, it is possible that in our patient the highfrequency ANT-DBS propagated to the putative epileptogenic zone in the frontal cortex, where it induced or clustered epileptic discharges. Indubitably, the effects of ANT-DBS depend on localization of active plots and on stimulation parameters. In our patient, the selection of plots without interactions with the frontal cortex would have probably avoided the side-effects, but it is questionable if it would have had additional therapeutical consequences. Whether the stimulation-induced epileptic activity in our patient was related to generalized increased cortical excitability remains to be established by further studies in similar cases. Conflict of interest Dr. Rona and Dr. Gharabaghi report having received lecture fees and research funding from Medtronic, Inc. The other authors have no conflict of interest to disclose.
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Letters to the Editor / Clinical Neurophysiology 126 (2015) 1054–1061
(A)
FP2 – F4 F4 – C4 C4 – P4 P4 – O2 FP2 – F8 F8 – T8 T8 – P8 P8 – O2 FP1 – F3 F3 – C3 C3 – P3 P3 – O1 FP1 – F7 F7 – T7 T7 – P7 P7 – O1
FP2 – F4 F4 – C4 C4 – P4 P4 – O2 FP2 – F8 F8 – T8 T8 – P8 P8 – O2 FP1 – F3 F3 – C3 C3 – P3 P3 – O1 FP1 – F7 F7 – T7 T7 – P7 P7 – O1 FP2 − F4 F4 − C4 C4 − P4 P4 − O2 FP2 − F8 F8 − T8 T8 − P8 P8 − O2 FP1 − F3 F3 − C3 C3 − P3 P3 − O1 FP1 − F7 F7 − T7 T7 − P7 P7 − O1
FP2 − F4 F4 − C4 C4 − P4 P4 − O2 FP2 − F8 F8 − T8 T8 − P8 P8 − O2 FP1 − F3 F3 − C3 C3 − P3 P3 − O1 FP1 − F7 F7 − T7 T7 − P7 P7 − O1
4s
i
Frequency (Hz)
(B)
300 µV
10
* 0,5
ii FP1 - ref F3 - ref C3 - ref P3 - ref O1 - ref F7 - ref FT9 - ref T7 - ref P7 - ref
0
*
+ Time (min)
60
+
FP2 - ref F4 - ref C4 - ref P4 - ref O2 - ref F8 - ref FT10 - ref T8 - ref P8 - ref Fz - ref Cz - ref Pz - ref
250 µV
ECG
1s Fig. 1. ANT-DBS effects in routine and long-term scalp-EEGs. (A) Routine scalp-EEG. Stimulation on-phase, colorful underlined (duration: 68 s, including soft increment/ decrement of stimulation amplitudes). (B) Density spectral array (DSA) plot of a long-term scalp-EEG. (i), 60 min of a DSA plot of the Fz – common-average reference trace during wakefulness, tiredness. DSA: 0.5–17 Hz band frequency; 10 s analysis-segments; red, hyperintense, more dominant frequencies; blue, hypointense, less dominant frequencies. Blue squares, stimulation-on phases with corresponding DSA-hyperintensities. ANT-DBS correlated to DSA-hyperintensities in 11 out of 15 stimulation-cycles. (ii), corresponding scalp-EEG segments from stimulation-on (⁄) and stimulation-off (+) phases. DBS parameters: plots 3 and 11, 3 V (1A) and 3.5 V (1B), 160 Hz, pulse width 120 lS, cycling on/off 1 m/3 m, Soft Start/Stop 8 s.
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Letters to the Editor / Clinical Neurophysiology 126 (2015) 1054–1061
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.clinph.2014.08. 008. References Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010;51:899–908. Kerrigan JF, Litt B, Fisher RS, Cranstoun S, French JA, Blum DE, et al. Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. Epilepsia 2004;45:346–54. Zumsteg D, Lozano AM, Wennberg RA. Mesial temporal inhibition in a patient with deep brain stimulation of the anterior thalamus for epilepsy. Epilepsia 2006;47:1958–62.
⇑
I. Bucurenciu Kork Epilepsy Center, Kehl-Kork, Germany ⇑ Corresponding author. Address: Epilepsiezentrum Kork, Landstrasse 1, 77694 Kehl-Kork, Germany. Tel.: +49 7851842433; fax: +49 7851842600. E-mail address: [email protected] (I. Bucurenciu) A.M. Staack Kork Epilepsy Center, Kehl-Kork, Germany I. Hubbard Kork Epilepsy Center, Kehl-Kork, Germany S. Rona Department of Neurosurgery, Eberhard Karls University Hospital, Tübingen, Germany A. Gharabaghi Department of Neurosurgery, Eberhard Karls University Hospital, Tübingen, Germany B.J. Steinhoff Kork Epilepsy Center, Kehl-Kork, Germany Available online 2 September 2014
http://dx.doi.org/10.1016/j.clinph.2014.08.008 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report
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 corre-
lates 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 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 left 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 (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).
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Letters to the Editor Coincidence of non-convulsive epileptic seizures and electrical stimulation of thalamic anterior nuclei in an epileptic patient
A recent randomized, prospective study showed that deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) reduced frequency and intensity of epileptic seizures in medically refractory partial seizures, including secondarily generalized seizures (Fisher et al., 2010). Stimulation-associated transient seizures have been reported up to now in two patients (Fisher et al., 2010). In none of these cases a detailed description of the epileptic syndromes, of the electro-clinical semiology of stimulationassociated seizures and of the exact time-correlation between ANT-stimulation and seizures onset and duration was provided. Therefore, mechanisms behind the effects and even the causality remain unclear. A detailed analysis of such cases might establish whether stimulation-associated seizures depend on epileptic syndromes and/or on stimulation parameters, and might give insights into the mechanism of action of DBS. However, identification of stimulation-associated seizures can be difficult. Without an exact detection of stimulation intervals, irregularly-occurring and mild DBS-correlated seizures might be underestimated or misinterpreted as non-epileptic side-effects. We report the first case where the ANT-stimulation intervals were precisely resolved and demonstrate for the first time a coincidence between onphases of stimulation and habitual epileptic seizures, strongly suggesting a causal relationship. The female patient with non-lesional, medically refractory epilepsy of unclear etiology, developed bilateral convulsive and disabling daily focal tonic-dyscognitive seizures of upper body accompanied by falls since the age of 11 years. Seizure semiology, ictal electroencephalograms (EEGs) and positron emission tomography suggested a putative initiation of seizures in the left fronto-lateral and basal cortex (see Supplementary Information). In between tonic-dyscognitive seizures, the EEGs showed sharp–slow-waves or high-amplitude theta–delta waves in bilateral fronto-centro-temporal regions. The repetitive subclinical sharp–slow-wave bursts at 1–2 Hz occasionally lasted longer than tens of seconds. At age of 21, ANT-DBS was initiated. Quadripolar DBS-electrodes (Medtronic Model 3389, MedtronicÒ, Minneapolis, MN, USA), connected to a dual-channel programmable stimulation device (Model Activa PC, MedtronicÒ) were implanted bilaterally, paraventricularly in the ANT using a stereotactic technique (Supplementary Fig. S1). During DBS-therapy the patient was treated with eslicarbazepine acetate and phenytoin. Towards the end of DBS-therapy clobazam, zonisamid and temporary perampanel have been added to the medication (see Supplementary Information). Most upper and lateral located plots of each electrode (number 3 and 11, with a putative localization in the ANT, based on magnetic resonance imaging and neurosurgical implantation parameters) were chosen for
monopolar stimulation. A wide range of parameters were systematically tested during 11 months of stimulation: amplitudes between 3–7.5 V, cycles between 1 min on/5 min off and 20 s on/20 s off, frequency between 145–180 Hz and pulse-width between 90–120 ls. Mutism and avolition after onset of DBS were interpreted as disappointment of the patient, since her habitual tonic-dyscognitive seizures were not improved by ANT-DBS. We closely reanalyzed the patient’s scalp-EEGs towards the end of 11 months of DBS. Retrospectively and prospectively we could regularly identify the on-phases of stimulation cycles based on amplitude reductions of QRS-complexes in electrocardiograms (Fig. 1B; Supplementary Fig. S2, Video S1). The morphology of habitual bilateral frontocentro-temporal (sharp)-slow-wave discharges in EEGs was unaffected by ANT-DBS (Supplementary Fig. S2). We noticed a time-correlation between on-phases of stimulation cycles and habitual subclinical seizures at stimulations equal or above 3 V (Fig. 1A and B). Repetitive bursts of sharp–slow-waves occurred 12.6 ± 1.1 s after onset of ANT-DBS, which was similar to the time needed for ANT-DBS to affect neocortical temporal activity (Zumsteg et al., 2006). Electrical activity ceased 21.7 ± 5.5 s after the end of stimulation-on phases (Fig. 1A and B). In the densityspectral-array of a long-term video-EEG, several regularly-occurring periods with dominant delta frequencies, corresponding to bilateral anterior (sharp)–slow-wave series, were identified during ANT-stimulation phases (Fig. 1B). In video-EEG-recordings performed when the patient was reading aloud, EEG-discharges accompanied by interruption of reading flow were reproducibly documented during on-phases of stimulation cycles (Video S1). We discontinued the ANT-DBS at the patient’s request. Up to now she did not allow stimulation on different electrode plots. Whether DBS exerts its effects via inhibition of stimulated targets or by anterograde or retrograde propagation of stimuli to remote structures is a controversial matter. In epileptic patients low- and high frequency ANT-DBS influenced the frontal and temporal cortical activity, respectively (Kerrigan et al., 2004; Zumsteg et al., 2006). Therefore, it is possible that in our patient the highfrequency ANT-DBS propagated to the putative epileptogenic zone in the frontal cortex, where it induced or clustered epileptic discharges. Indubitably, the effects of ANT-DBS depend on localization of active plots and on stimulation parameters. In our patient, the selection of plots without interactions with the frontal cortex would have probably avoided the side-effects, but it is questionable if it would have had additional therapeutical consequences. Whether the stimulation-induced epileptic activity in our patient was related to generalized increased cortical excitability remains to be established by further studies in similar cases. Conflict of interest Dr. Rona and Dr. Gharabaghi report having received lecture fees and research funding from Medtronic, Inc. The other authors have no conflict of interest to disclose.
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Letters to the Editor / Clinical Neurophysiology 126 (2015) 1054–1061
(A)
FP2 – F4 F4 – C4 C4 – P4 P4 – O2 FP2 – F8 F8 – T8 T8 – P8 P8 – O2 FP1 – F3 F3 – C3 C3 – P3 P3 – O1 FP1 – F7 F7 – T7 T7 – P7 P7 – O1
FP2 – F4 F4 – C4 C4 – P4 P4 – O2 FP2 – F8 F8 – T8 T8 – P8 P8 – O2 FP1 – F3 F3 – C3 C3 – P3 P3 – O1 FP1 – F7 F7 – T7 T7 – P7 P7 – O1 FP2 − F4 F4 − C4 C4 − P4 P4 − O2 FP2 − F8 F8 − T8 T8 − P8 P8 − O2 FP1 − F3 F3 − C3 C3 − P3 P3 − O1 FP1 − F7 F7 − T7 T7 − P7 P7 − O1
FP2 − F4 F4 − C4 C4 − P4 P4 − O2 FP2 − F8 F8 − T8 T8 − P8 P8 − O2 FP1 − F3 F3 − C3 C3 − P3 P3 − O1 FP1 − F7 F7 − T7 T7 − P7 P7 − O1
4s
i
Frequency (Hz)
(B)
300 µV
10
* 0,5
ii FP1 - ref F3 - ref C3 - ref P3 - ref O1 - ref F7 - ref FT9 - ref T7 - ref P7 - ref
0
*
+ Time (min)
60
+
FP2 - ref F4 - ref C4 - ref P4 - ref O2 - ref F8 - ref FT10 - ref T8 - ref P8 - ref Fz - ref Cz - ref Pz - ref
250 µV
ECG
1s Fig. 1. ANT-DBS effects in routine and long-term scalp-EEGs. (A) Routine scalp-EEG. Stimulation on-phase, colorful underlined (duration: 68 s, including soft increment/ decrement of stimulation amplitudes). (B) Density spectral array (DSA) plot of a long-term scalp-EEG. (i), 60 min of a DSA plot of the Fz – common-average reference trace during wakefulness, tiredness. DSA: 0.5–17 Hz band frequency; 10 s analysis-segments; red, hyperintense, more dominant frequencies; blue, hypointense, less dominant frequencies. Blue squares, stimulation-on phases with corresponding DSA-hyperintensities. ANT-DBS correlated to DSA-hyperintensities in 11 out of 15 stimulation-cycles. (ii), corresponding scalp-EEG segments from stimulation-on (⁄) and stimulation-off (+) phases. DBS parameters: plots 3 and 11, 3 V (1A) and 3.5 V (1B), 160 Hz, pulse width 120 lS, cycling on/off 1 m/3 m, Soft Start/Stop 8 s.
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Letters to the Editor / Clinical Neurophysiology 126 (2015) 1054–1061
Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.clinph.2014.08. 008. References Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, et al. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010;51:899–908. Kerrigan JF, Litt B, Fisher RS, Cranstoun S, French JA, Blum DE, et al. Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy. Epilepsia 2004;45:346–54. Zumsteg D, Lozano AM, Wennberg RA. Mesial temporal inhibition in a patient with deep brain stimulation of the anterior thalamus for epilepsy. Epilepsia 2006;47:1958–62.
⇑
I. Bucurenciu Kork Epilepsy Center, Kehl-Kork, Germany ⇑ Corresponding author. Address: Epilepsiezentrum Kork, Landstrasse 1, 77694 Kehl-Kork, Germany. Tel.: +49 7851842433; fax: +49 7851842600. E-mail address: [email protected] (I. Bucurenciu) A.M. Staack Kork Epilepsy Center, Kehl-Kork, Germany I. Hubbard Kork Epilepsy Center, Kehl-Kork, Germany S. Rona Department of Neurosurgery, Eberhard Karls University Hospital, Tübingen, Germany A. Gharabaghi Department of Neurosurgery, Eberhard Karls University Hospital, Tübingen, Germany B.J. Steinhoff Kork Epilepsy Center, Kehl-Kork, Germany Available online 2 September 2014
http://dx.doi.org/10.1016/j.clinph.2014.08.008 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Abnormal local field potentials precede clinical complications after DBS surgery for Parkinson’s disease: A case report
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 corre-
lates 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 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 left 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 (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).
