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ABSTRACT: Studies of deep brain stimulation for dystonia have shown significant motor improvement. However, patients' perceptions of surgery and its effects have been less studied. We aimed to explore perceptions of changes in life in patients with primary dystonia after deep brain stimulation. Thirteen patients underwent thematic interviews 8-60 months after pallidal deep brain stimulation. Interviews were transcribed verbatim and analyzed with grounded theory. Patients described a profound impact of dystonia on daily life. After surgery, physical changes with a more upright posture and fewer spasms translated into an easier, more satisfying life with greater confidence. Notwithstanding this positive outcome, the transition from a limited life before surgery to opportunities for a better life exhibited obstacles: The "new life" after deep brain stimulation was stressful, including concern about being dependent on the stimulator as well as having to deal with interfering side effects from deep brain stimulation. The whole coping process meant that patients had to quickly shift focus from struggling to adapt to a slowly progressive disorder to adjustment to a life with possibilities, but also with new challenges. In this demanding transition process, patients wished to be offered better professional guidance and support. Even though deep brain stimulation provides people with primary dystonia with a potential for better mobility and more confidence, patients experienced new challenges and expressed the need for support and counseling after surgery. Grounded theory is a useful method to highlight patients' own experience and contributes to a deeper understanding of the impact of deep brain stimulation on patients with dystonia.
Movement Disorders 05/2011; 26(11):2101-6. · 4.51 Impact Factor
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ABSTRACT: Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia.
Movement Disorders 05/2011; 26(10):1913-21. · 4.51 Impact Factor
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ABSTRACT: To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty-one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor.
Movement Disorders 07/2010; 25(10):1350-6. · 4.51 Impact Factor
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ABSTRACT: To evaluate pallidal DBS in a non-DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non-DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and "on" stimulation after a mean of 2.5 years (range 1-3) using the Burke-Fahn-Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 +/- 24 to 9 +/- 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia.
Movement Disorders 11/2009; 24(16):2415-9. · 4.51 Impact Factor
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Shen-Yang Lim,
Sean S O'Sullivan,
Katya Kotschet,
David A Gallagher,
Cameron Lacey,
Andrew D Lawrence,
Andrew J Lees,
Dudley J O'Sullivan,
Richard F Peppard,
Julian P Rodrigues,
Anette Schrag,
Paul Silberstein, Stephen Tisch,
Andrew H Evans
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ABSTRACT: Data regarding the effect of deep brain stimulation (DBS) surgery on the dopamine dysregulation syndrome (DDS), impulse control disorders (ICDs) and punding in Parkinson's disease (PD) are limited. We present a case series of 21 operated PD patients who had exhibited DDS, ICDs or punding at some stage during the disease. DDS remained unimproved or worsened post-operatively in 12/17 patients with pre-operative DDS (71%) (nine bilateral subthalamic nucleus [STN], one right-sided STN, two bilateral globus pallidus internus [GPi] DBS). DDS improved or resolved after bilateral STN DBS in 5/17 patients with pre-operative DDS. DDS apparently developed for the first time after bilateral STN DBS in two patients, although only after a latency of eight years in one case. One patient without reported pre-operative DDS or ICDs developed pathological gambling post-STN DBS. One patient had pathological gambling which resolved pre-operatively, and did not recur post-DBS. Thus, DDS, ICDs and punding may persist, worsen or develop for the first time after DBS surgery, although a minority of patients improved dramatically. Predictive factors may include physician vigilance, motor outcome and patient compliance.
Journal of Clinical Neuroscience 07/2009; 16(9):1148-52. · 1.25 Impact Factor
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ABSTRACT: The introduction of thalamotomy in 1954 led naturally to exploration of the underlying subthalamic area, with the development of such procedures as campotomy and subthalamotomy in the posterior subthalamic area. The most popular of these procedures was the subthalamotomy, which was performed in thousands of patients for various movement disorders. Today, in the deep brain stimulation (DBS) era, subthalamic nucleus DBS is the treatment of choice for Parkinson's disease, whereas thalamic and pallidal DBS are mainly used for nonparkinsonian tremor and dystonia, respectively. The interest in DBS in the posterior subthalamic area has been quite limited, however, with a total of 95 patients presented in 14 articles. During recent years, interest has increased, and promising results have been published concerning both Parkinson's disease and nonparkinsonian tremor. We reviewed the literature to investigate the development of surgery in the posterior subthalamic area from the lesional era to the present.
Neurosurgery 07/2009; 64(6):1029-38; discussion 1038-42. · 2.79 Impact Factor
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ABSTRACT: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.
Medical & Biological Engineering 11/2008; 47(1):21-8. · 1.76 Impact Factor
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ABSTRACT: Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in improving limb symptoms in Parkinson's disease. However, speech shows a variable response. Contact site and amplitude of stimulation have been suggested as possible factors influencing speech. In this double blind study, we assessed 14 patients post bilateral STN-DBS, without medication. Six conditions were studied in random order as follows: stimulation inside the STN at low voltage (2 V) and at high voltage (4 V); above the STN at 2 V and at 4 V, at usual clinical parameters, and off-stimulation. The site of stimulation was defined on the postoperative stereotactic MRI data. Speech protocol consisted of the assessment of intelligibility of the dysarthric speech, maximum sustained phonation, and a 1-minute monologue. Movement was assessed using the UPDRS-III. Stimulation at 4 V significantly reduced the speech intelligibility (P = 0.004) independently from the site of stimulation. Stimulation at 4 V significantly improved the motor function. Stimulation inside the nucleus was significantly more effective than outside the nucleus (P = 0.0006). The significant improvement in movement coupled with significant deterioration in speech intelligibility when patients are stimulated inside the nucleus at high voltage indicates a critical role for electrical stimulation parameters in speech motor control.
Movement Disorders 10/2008; 23(16):2377-83. · 4.51 Impact Factor
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08/2008: pages 401-414;
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ABSTRACT: The pedunculopontine nucleus (PPN) is a promising new target for deep brain stimulation (DBS) in parkinsonian patients with gait disturbance and postural instability refractory to other treatment modalities. This region of the brain is unfamiliar territory to most functional neurosurgeons. This paper reviews the anatomy of the human PPN and describes novel, clinically relevant methods for the atlas-based and MRI-based localization of the nucleus. These two methods of PPN localization are evaluated and compared on stereotactic MRI data acquired from a diverse group of 12 patients undergoing implantation of deep brain electrodes at sites other than the PPN. Atlas-based coordinates of the rostral and caudal PPN poles in relation to fourth ventricular landmarks were established by amalgamating information sourced from two published human brain atlases. These landmarks were identified on acquired T1 images and atlas-derived coordinates used to plot the predicted PPN location on all 24 sides. Images acquired using a specifically modified, proton-density MRI protocol were available for each patient and were spatially fused to the T1 images. This widely available and rapid protocol provided excellent definition between gray and white matter within the region of interest. Together with an understanding of the regional anatomy, direct localization of the PPN was possible on all 24 sides. The coordinates for each directly localized nucleus were measured in relation to third and fourth ventricular landmarks. The mean (SD) of the directly localized PPN midpoints was 6.4 mm (0.5) lateral, 3.5 mm (1.0) posterior and 11.4 mm (1.2) caudal to the posterior commissure in the anterior commissure-posterior commissure plane. For the directly localized nucleus, there was similar concordance for the rostral pole of the PPN in relation to third and fourth ventricular landmarks (P>0.05). For the caudal PPN pole, fourth ventricular landmarks provided greater concordance with reference to the anteroposterior coordinate (P<0.001). There was a significant difference between localization of the PPN poles as predicted by atlas-based coordinates and direct MRI localization. This difference affected mainly the rostrocaudal coordinates; the mean lateral and anteroposterior coordinates of the directly localized PPN poles were within 0.5 mm of the atlas-based predicted values. Our findings provide simple, rapid and precise methods that are of clinical relevance to the atlas-based and direct stereotactic localization of the human PPN. Direct MRI localization may allow greater individual accuracy than that afforded by atlas-based coordinates when localizing the human PPN and may be relevant to groups evaluating the clinical role of PPN DBS.
Brain 06/2008; 131(Pt 6):1588-98. · 9.46 Impact Factor
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ABSTRACT: The pedunculopontine nucleus (PPN) has recently been introduced as a new therapeutic target for deep brain stimulation (DBS) in patients suffering from Parkinson's disease (PD). In a recent case report it was demonstrated that alpha frequency oscillations appear in PPN after the administration of levodopa in PD, indicating a possible physiological role of these oscillations. Here we confirm this result and investigate the functional connectivity and reactivity of subcortical alpha activity by recording LFP activity from the PPN area and EEG in six patients with PD while at rest and in four of them while they performed ipsi- and contralateral self-paced joystick movements. Levodopa strongly promoted 7-11 Hz oscillatory synchronization in the region of PPN and coupling of this activity with similar activity in the cortical EEG. Such coupling was bidirectional. Moreover, the 7-11 Hz oscillatory synchronization in the PPN area increased about 3 s prior to self-paced movements, but only following levodopa treatment. These findings suggest that alpha oscillations in the PPN area may represent a physiological pattern of activity. The subcortical oscillations are coupled to cortical alpha activity and possibly allied to motor related attentional processes.
Experimental Neurology 06/2008; 211(1):59-66. · 4.70 Impact Factor
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ABSTRACT: Deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for primary generalized dystonia. However, the physiological mechanisms of improvement are not fully understood. Cortical activity in response to pallidal stimulation was recorded in 6 patients with primary generalized dystonia >6 months after bilateral GPi DBS. Scalp electroencephalogram was recorded using 60 surface electrodes during 10 Hz bipolar pallidal DBS at each electrode contact pair. Anatomical position of the electrode contacts in relation to the GPi, medial medullary lamina and globus pallidus externus (GPe) was determined from the postoperative stereotactic MRI. In all six patients an evoked potential (EP) was observed with average onset latency of 10.9 ms +/- 0.77, peak latency 26.6 ms +/- 1.6, distributed mainly over the ipsilateral hemisphere, maximal centrally. The mean amplitude of this potential was larger with stimulation in posteroventral GPi than in GPe (3.36 microV vs. 0.50 microV, P < 0.0001). The EP was absent in one patient-side, ipsilateral to a previous thalamotomy. Low frequency GPi stimulation produces an EP distributed centrally over the ipsilateral hemisphere. The latency and distribution of the EP are consistent with stimulation of pallidothalamic neurons projecting to the sensorimotor cortex. Because the EP is larger and more consistently present with stimulation of posteroventral GPi than GPe, it may provide a physiological tool to identify contacts within the optimal surgical target.
Movement Disorders 02/2008; 23(2):265-73. · 4.51 Impact Factor
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ABSTRACT: To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia.
We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions.
The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF.
After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia.
Experimental Neurology 08/2007; 206(1):80-5. · 4.70 Impact Factor
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ABSTRACT: Dystonia is an involuntary movement disorder characterized by muscle contractions causing abnormal postures and spasms, affecting part or all of the body. Dystonia may be primary where an abnormal gene, most commonly DYT1, may be identified, or secondary to structural brain lesions or heredodegenerative disorders. The underlying defect is believed to be abnormal basal ganglia modulation of cortical motor pathways, and various motor and sensory physiological abnormalities have been demonstrated. The failure of medical treatment in many patients with the more severe and generalized forms of dystonia has led to renewed interest in neurosurgical treatment approaches. In recent years, deep brain stimulation (DBS) of globus pallidus internus (GPi) has emerged as an effective treatment for dystonia, particularly patients with primary generalized dystonia, where remarkable improvement may occur. In contrast to Parkinson's disease, the beneficial effects of DBS in dystonia are not immediate but progressive over weeks to months. Physiological and imaging studies in dystonia patients with GPi DBS have demonstrated both short and long-term effects of GPi DBS on motor cortex and subcortical circuits including progressive normalization of spinal and brainstem excitability after GPi DBS which correlate with clinical improvement. These effects, in light of existing physiological data in dystonia, suggest that GPi DBS acts primarily by major modification of basal ganglia output to brainstem, thalamus, and cortex resulting in neural reorganization, which may explain the characteristic progressive improvement in dystonia after GPi DBS.
IEEE Transactions on Neural Systems and Rehabilitation Engineering 07/2007; 15(2):166-72. · 3.44 Impact Factor
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Chiung Chu Chen,
Vladimir Litvak,
Thomas Gilbertson,
Andrea Kühn,
Chin Song Lu,
Shih Tseng Lee,
Chon Haw Tsai, Stephen Tisch,
Patricia Limousin,
Marwan Hariz,
Peter Brown
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ABSTRACT: Excessive synchronization of neuronal activity at around 20 Hz is a common finding in the basal ganglia of patients with untreated Parkinson's disease (PD). Correlative evidence suggests, but does not prove, that this spontaneous activity may contribute to slowness of movement in this condition. Here we investigate whether externally imposed synchronization through direct stimulation of the region of the subthalamic nucleus at 20 Hz can slow motor performance in a simple unimanual tapping task and whether this effect is frequency selective. Tapping rates were recorded on 42 sides in 22 patients with PD after overnight withdrawal of medication. Tapping was performed without stimulation and during bilateral stimulation at 20 Hz, 50 Hz and 130 Hz. We found that tapping rates were slowed by 8.2+/-3.2% (p=0.014) during 20-Hz stimulation in subjects with relatively preserved baseline function in the task. This effect was frequency selective. The current data provide proof of the principle that excessive beta synchrony within the basal ganglia-cortical loop may contribute to the slowing of movements in Parkinson's disease.
Experimental Neurology 06/2007; 205(1):214-21. · 4.70 Impact Factor
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Current Biology 12/2006; 16(22):R952-3. · 9.65 Impact Factor
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ABSTRACT: A pathophysiological feature of dystonia is reduced inhibition at various levels of the nervous system, which may be detected in clinically unaffected body parts. Chronic deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an effective treatment for primary torsion dystonia (PTD), although its mechanism of action and impact on inhibitory abnormalities in dystonia are unknown. We sought to understand the effect of GPi DBS on brainstem excitability in patients with PTD. We measured the blink reflex from orbicularis oculi in response to paired electrical stimulation of the supraorbital nerve at interstimulus intervals of 500 and 1,000 milliseconds in 10 patients with PTD before and at intervals of 1, 3, and 6 months after bilateral GPi DBS and in 10 healthy subjects. Patients were clinically evaluated using the Burke-Fahn-Marsden dystonia rating scale. We found R2 inhibition was significantly decreased in PTD patients compared with control subjects and progressively increased after GPi DBS, which correlated with clinical improvement in dystonia. We conclude that GPi DBS for PTD results in functional reorganization of the nervous system, which includes a long-term increase in brainstem inhibition.
Movement Disorders 11/2006; 21(10):1650-5. · 4.51 Impact Factor
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ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly effective treatment for Parkinson's disease (PD). However, therapeutic efficacy is limited by difficulties in consistently and correctly targeting this nucleus. Increasing evidence suggests that there is abnormal synchronization of beta frequency band activity (approximately 20 Hz) in the STN of PD patients, as reflected in the oscillatory nature of the local field potential (LFP). We hypothesized that an increase in the power of the LFP beta activity may provide intra-operative confirmation of STN targeting in patients undergoing STN implantation for the treatment of advanced PD. Accordingly, we recorded LFPs from the four contacts of DBS electrodes as the latter were advanced in 2 mm steps from a point 4-6 mm above the intended surgical target point in the STN, to a point 4 mm below this. Contacts were configured to give three bipolar recordings of LFPs. These were analyzed on 16 sides in 9 patients. The power in the 13-35 Hz band recorded at the lowest contact pair underwent a steep but focal increase during electrode descent. The depth of the peak beta activity showed excellent agreement with the level of the intra-operative clinical stun effect (k coefficient = 0.792). The depth of peak beta activity also showed 100% specificity and 100% sensitivity for placement within STN in comparison to pre- and Post-operative stereotactic MRI. Functional physiological localization of STN by the on-line spectral analysis of LFPs is quick to perform and may provide information directly relevant to the position of the electrode contact actually used for DBS.
Experimental Neurology 04/2006; 198(1):214-21. · 4.70 Impact Factor
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ABSTRACT: Five parkinsonian subjects with chronic bilateral stimulation of the subthalamic nucleus and five sex- and age-matched healthy controls grasped, lifted, and held an instrumented object. The grip-lift task was either performed at self-determined speed or in response to an auditory cuing signal. Parkinsonian subjects performed the task with subthalamic nucleus stimulation switched ON and OFF. In Parkinson's disease, stimulation of the subthalamic nucleus and the presentation of auditory timing cues improved akinesia of both the grasp and lift components of the task. The finding that auditory timing cues improve akinesia in the absence of subthalamic nucleus stimulation suggests that the basal ganglia are less involved in the control of movements made in response to environmental cues. However, subthalamic nucleus stimulation caused parkinsonian subjects to apply excessive grip forces, regardless of whether the movement was made under self-determined or externally guided speed conditions. This implies that subthalamic nucleus stimulation produces a generalized upregulation in the gain of all components of a movement without the subtlety of focused control that is required to normalize performance.
Movement Disorders 03/2006; 21(2):166-72. · 4.51 Impact Factor
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ABSTRACT: Subthalamic nucleus stimulation dramatically improves parkinsonian symptoms, notably the tremor. The occurrence of a tremor in the first 6 months after the surgical procedure in patients without tremor preoperatively is much less common. We report on the cases of 3 patients who developed such modification of their parkinsonian symptomatology. Physiopathological hypotheses are discussed.
Movement Disorders 09/2005; 20(8):1066-9. · 4.51 Impact Factor
