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PubMed2004

[Preoperative adverse events during stereotactic microelectrode-guided deep brain surgery in Parkinson's disease].

OBJECTIVES: To evaluate the prevalence of adverse events and complications during surgery using deep brain electrodes, mainly in the treatment of Parkinsonism. To describe the adjustment of propofol to meet the needs of neurophysiological monitoring. PATIENTS AND METHODS: A prospective study of patients undergoing stereotactic microelectrode-guided deep brain surgery (stereotactic pallidotomy, implantation of electrodes in the thalamic or subthalamic neurons of the globus pallidus). After placement of a stereotactic frame and completion of a computed tomography scan of the head, the patients were transferred to the operating room. Monitoring included electrocardiography, pulse oximetry, arterial pressure (invasive), endtidal carbon dioxide pressure, and diuresis. Anesthesia was maintained by intermittent infusion of propofol. Variables recorded were age, sex, disease and time elapsed since diagnosis, surgical complications and their treatment, total dose of propofol, duration of surgery, and place of transfer for recovery. RESULTS: One hundred twenty-eight patients (50 women, 78 men) with a mean (+/- SD) age of 59.6 +/- 10.2 years underwent the procedure from 1996 through 2003. The mean time elapsed since diagnosis of the disease was 14 +/- 6.2 years. The propofol dose was 890.6 +/- 571.4 mg and duration of surgery was 8.3 +/- 2.4 hours. Adverse events were observed for 101 patients (78.9%). The most common complications involved hemodynamics: arterial hypertension (59.4%), bradycardia (18.0%), arterial hypotension (7.9%), and tachycardia (6.2%). Other more serious complications were pneumocephalus with clinical repercussions (3 cases), globus pallidus hematoma (2), air embolism (2), epileptic seizure (3), anisocoria (1), and dyspnea and/or airway obstruction (7). CONCLUSIONS: Deep brain stimulation requires surgery of long duration. Because of frequent episodes of arterial hypertension, which increases the risk of brain hemorrhage, and other less common but potentially dangerous complications, careful clinical monitoring is necessary during the procedure. The intermittent use of propofol does not interfere with neurophysiological monitoring.

Aged↗

PubMed2005

Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias.

The aim of this work was to study the role of subthalamo-pallidal synchronisation in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs) in a patient with Parkinson's disease and left surgery induced dyskinesias with double, bilateral deep brain stimulation electrode implants in the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied through coherence analysis. In the nuclei contralateral to the dyskinetic side of the body there was decreased STN-GPi coherence in the high beta range (20-30 Hz) and an enhanced coherence at low frequencies (<10 Hz). Despite the possible limitations arising from single-case observations, our findings suggest that parkinsonian dyskinesias are related to altered synchronisation between different structures of the basal ganglia. Firing abnormalities within individual basal ganglia nuclei are probably not enough to account for the complex balance between hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and altered interactions between nuclei should also be considered.

Deep Brain Stimulation↗

PubMed2007

[Surgery for Parkinson's disease].

Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason for this renewal in surgical treatment for PD is the "deep brain stimulation" (DBS) that replaced the previously used stereotactic lesions in most centers. DBS allows a focal specific electrical stimulation of basal ganglia target instead of an irreversible lesion. Mainly bilateral DBS of the nucleus subthalamicus is now an established surgical treatment for PD. But DBS of the Globus pallidus internus and of the thalamus should still be considered in selected patients. DBS is an efficient treatment for motor complication of PD that can no longer be controlled by drug treatment. Dyskinesia, bradykinesia, tremor and rigor can be improved by DBS and the medication can be reduced. It is still unclear, however, how the improvement in motor symptoms affects quality of life in the long term. Furthermore, patients with severe cognitive and psychiatric symptoms as well as patients with severe axial symptoms should not be operated since these symptoms may worsen after surgery.

Deep Brain Stimulation↗

PubMed2006

A technique for minimally altering anatomically based subthalamic electrode targeting by microelectrode recording.

OBJECT: Implantation of a subthalamic nucleus (STN) deep brain stimulation (DBS) electrode is increasingly recognized as an effective treatment for advanced Parkinson disease (PD). Despite widespread use of microelectrode recording (MER) to delineate the boundaries of the STN prior to stimulator implantation, it remains unclear to what extent MER improves the clinical efficacy of this procedure. In this report, the authors analyze a series of patients who were treated at one surgical center to determine to what degree final electrode placement was altered, based on readings obtained with MER, from the calculated anatomical target. METHODS: Subthalamic DBS devices were placed bilaterally in nine patients with advanced PD. Frame-based volumetric magnetic resonance images were acquired and then transferred to a stereotactic workstation to determine the anterior and posterior commissure coordinates and plane. The initial anatomical target was 4 mm anterior, 4 mm deep, and 12 mm lateral to the midcommissural point. The MERs defined the STN boundaries along one or more parallel tracks, refining the final electrode placement by comparison of results with illustrations in a stereotactic atlas. In eight of 18 electrodes, the MER results did not prompt an alteration in the anatomically derived target. In another eight placements, MER altered the target by less than 1 mm and two of 18 electrode positions differed by less than 2 mm. The anterior-posterior difference was 0.53 +/- 0.65 mm, whereas the medial-lateral direction differed by 0.25 +/- 0.43 mm. The ventral boundary of the STN defined by MER was 2 +/- 0.72 mm below the calculated target (all values are the means +/- standard deviation). All patients attained clinical improvement, similar to previous reports. CONCLUSIONS: In this series of patients, microelectrode mapping of the STN altered the anatomically based target only slightly. Because it is not clear whether such minor adjustments improve clinical efficacy, a prospective clinical comparison of MER-refined and anatomical targeting may be warranted.

Brain Mapping↗

PubMed2006

Neuroethics.

Neuroimaging, psychosurgery, deep-brain stimulation, and psychopharmacology hold considerable promise for more accurate prediction and diagnosis and more effective treatment of neurological and psychiatric disorders. Some forms of psychopharmacology may even be able to enhance normal cognitive and affective capacities. But the brain remains the most complex and least understood of all the organs in the human body. Mapping the neural correlates of the mind through brain scans, and altering these correlates through surgery, stimulation, or pharmacological interventions can affect us in both positive and negative ways. We need to carefully weigh the potential benefit against the potential harm of such techniques. This paper examines some of these techniques and explores the emerging ethical issues in clinical neuroscience.

Behavior Control↗

PubMed2005

Somatosensory evoked potential and clinical changes after electrode implant in basal ganglia of parkinsonian patients.

Median nerve somatosensory evoked potentials (SEPs) were recorded in three parkinsonian patients who underwent electrode implant in the subthalamic nucleus and/or globus pallidus for chronic deep brain stimulation (DBS). SEPs were evoked before surgery, in a medication-free condition, and after the functional stereotactic procedure, before beginning DBS. In order to evaluate the timing of the SEP changes after the electrode implant, in three further patients SEPs were recorded within the operating theater, before and immediately after the implantation. Patients' symptoms improved immediately after the electrode implant, and both N20 and N30 amplitudes increased in the postsurgical SEP recording. The clinical and neurophysiological effects observed after surgery, before commencing DBS, can be explained by microdamage in the target nucleus following the electrode implant. They occurred also in the patients studied in the operating theater, thus suggesting that they occur immediately after the stereotactic procedure. Our results suggest that the circuitries between the basal ganglia and the primary sensorimotor cortex may be modified not only by DBS but also by microdamage due to surgery and that they exert an important influence on SEP amplitude.

Basal Ganglia↗

PubMed2004

A mnemonic for Parkinson disease patients considering DBS: a tool to improve perceived outcome of surgery.

Patients considering deep brain stimulation (DBS) for Parkinson disease (PD) may be exposed to videotapes, media coverage, or literature which show dramatic improvements in PD symptoms after surgical intervention. Based on this information, patients may seek a medical center with expertise in DBS for an evaluation and assessment of their candidacy for surgery. If patients receive a device, they may be disappointed or despondent following surgery because of a failure to achieve a preconceived and unrealistic outcome. In order to address the important issue of patient misconception of potential outcome, we have introduced a simple mnemonic device. The device may be taught and then reviewed with patients and families both before and after surgery. Use of this mnemonic device may allow the patient and family the time necessary to alter the perception of perceived benefit. This education can help to ensure that outcome meets or exceeds expectation, and as a result they become a more satisfied and easy-to-manage DBS patient.

Deep Brain Stimulation↗

PubMed2006

Dopamine-dependent non-linear correlation between subthalamic rhythms in Parkinson's disease.

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.

Adult↗

PubMed2005

DBS therapy for the vegetative state and minimally conscious state.

Twenty-one cases of a vegetative state (VS) and 5 cases of a minimally conscious state (MCS) caused by various kinds of brain damage were evaluated neurologically and electrophysiologically at 3 months after brain injury. These cases were treated by deep brain stimulation (DBS) therapy, and followed up for over 10 years. The mesencephalic reticular formation was selected as a target in 2 cases of VS, and the CM-pf complex was selected as a target in the other 19 cases of VS and 5 cases of MCS. Eight of the 21 patients emerged from the VS, and became able to obey verbal commands. However, they remained in a bedridden state except for 1 case. Four of the 5 MCS patients emerged from the bedridden state, and were able to enjoy their life in their own home. DBS therapy may be useful for allowing patients to emerge from the VS, if the candidates are selected according to appropriate neurophysiological criteria. Also, a special neurorehabilitation system may be necessary for emergence from the bedridden state in the treatment of VS patients. Further, DBS therapy is useful in MCS patients to achieve consistent discernible behavioral evidence of consciousness, and emergence from the bedridden state.

Adolescent↗

PubMed2005

Somatotopic organization of the human periventricular gray matter.

The periventricular gray (PVG) matter is an established anatomical target for chronic deep brain stimulation (DBS) in the treatment of certain intractable pain syndromes. Data relating to the representation of pain and other somatosensory modalities within the PVG in humans are negligible. We examined the character and location of somatosensory responses elicited by electrical stimulation along the length of the PVG in a patient who underwent unilateral DBS for intractable nociceptive head pain. Consistent responses were obtained and indicated the presence of a somatotopic representation in this region. The contralateral lower limb was represented cranially, followed by the upper limb and trunk, with the face area located caudally, near the level of the superior colliculi. Bilateral representation was only observed in the forehead and scalp.

Adult↗

PubMed2006

Network modulation in the treatment of Parkinson's disease.

It has been proposed that deep brain stimulation (DBS) of the subthalamic nucleus (STN DBS) and dopaminergic therapy ameliorate the symptoms of Parkinson's disease through similar functional mechanisms. We examined this notion using PET to compare the metabolic effects of these treatment approaches. Nine Parkinson's disease patients (age 61.7 +/- 11.1 years) were scanned ON and OFF STN stimulation and nine others (age 60.0 +/- 9.3 years) were scanned ON and OFF an individual titrated intravenous levodopa infusion. The two treatment groups were matched for baseline disease severity as well as clinical response to therapy. Similarities and differences in the effects of treatment on regional metabolism were assessed using statistical parametric mapping (SPM). In addition, we used network analysis to assess the effect of therapy on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). We found that both STN DBS and levodopa therapy were associated with significant (P < 0.001) metabolic reductions in the putamen/globus pallidus, sensorimotor cortex and cerebellar vermis, as well as increases in the precuneus (BA 7). The metabolic effects of the two interventions differed in the STN and medial prefrontal cortex, with relative increases with stimulation in the former structure and decreases in the latter. Network quantification disclosed reductions in PDRP activity with both interventions, which correlated with clinical improvement (P < 0.05). The degree of network modulation by therapy did not differ significantly for the two treatment approaches (P > 0.6). These findings support the results of previous imaging studies indicating that effective symptomatic therapies for Parkinson's disease involve a common mechanism. The modulation of pathological brain networks is a critical feature of the treatment response in parkinsonism.

Adult↗

PubMed2005

Effect of GPi DBS on functional imaging of the brain in dystonia.

Five patients with idiopathic dystonic conditions, treated successfully with deep brain stimulation (DBS) of the globus pallidus internus (GPi), were studied using single-photon emission tomography (SPET) in order to evaluate brain perfusion in the presence and absence of DBS. Comparison was made between the "on" and "off" DBS scans on an individual basis and also as part of a group analysis. Whilst the individual data suggested great regional variation in cerebral perfusion between individuals, the results of the group analysis revealed several topographically similar areas of the brain where relative hyperperfusion in the absence of DBS was common to all patients. Based on these results we postulate on possible mechanisms for this phenomenon.

Adult↗

PubMed2006

Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson's disease.

The pathophysiology of levodopa-induced dyskinesias (LID) in Parkinson's disease is not well understood. We have recorded local field potentials (LFP) from macroelectrodes implanted in the subthalamic nucleus (STN) of 14 patients with Parkinson's disease following surgical treatment with deep brain stimulation. Patients were studied in the 'Off' medication state and in the 'On' motor state after administration of levodopa-carbidopa (po) or apomorphine (sc) that elicited dyskinesias in 11 patients. The logarithm of the power spectrum of the LFP in selected frequency bands (4-10, 11-30 and 60-80 Hz) was compared between the 'Off' and 'On' medication states. A peak in the 11-30 Hz band was recorded in the 'Off' medication state and reduced by 45.2% (P < 0.001) in the 'On' state. The 'On' was also associated with an increment of 77. 6% (P < 0.001) in the 4-10 Hz band in all patients who showed dyskinesias and of 17.8% (P < 0.001) in the 60-80 Hz band in the majority of patients. When dyskinesias were only present in one limb (n = 2), the 4-10 Hz peak was only recorded in the contralateral STN. These findings suggest that the 4-10 Hz oscillation is associated with the expression of LID in Parkinson's disease.

Action Potentials↗

PubMed2006

Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease.

Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is evident as oscillatory local field potential (LFP) activity. To test whether such synchronization may contribute to bradykinesia and rigidity, we sought correlations between the suppression of synchronization at 8-35 Hz in STN and the reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication from STN deep-brain stimulation electrodes in nine PD patients. LFP power was calculated over the frequencies of the most prominent spectral peak within the 8-35 Hz frequency band on each of 17 sides (off medication), and over the frequencies of any peak in the 60-90 Hz band, if present (seven sides, on medication). Levodopa-induced reduction of LFP power over these two frequency ranges was then correlated with improvement in motor impairment as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak activity in the 8-35 Hz band with levodopa positively correlated with the improvement in the contralateral hemibody motor UPDRS score with levodopa (r = 0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r = 0.835, P < 0.001), but not tremor. A trend for negative correlations was found between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that positive correlations were relatively frequency-specific. Our results support a link between levodopa-induced improvements in bradykinesia and rigidity and reductions in population synchrony at frequencies < 35 Hz in the region of the STN in patients with PD.

Action Potentials↗

PubMed2006

Bursting activity of neurons in the human anterior thalamic nucleus.

Single unit microelectrode recordings were obtained under local anesthesia in 5 patients who underwent placement of deep brain stimulation electrodes in the anterior thalamic nucleus for control of intractable epilepsy. Of the 261 neurons recorded, 145 were in the anterior nucleus (AN), with the remainder ventral to AN in nucleus cucularis and dorsal dorsomedian nucleus (DM). 126 of the 261 neurons fired in bursts, and of these, 74 cells were analyzed in greater detail to characterize their bursting pattern. The bursts in 70% of the bursting neurons were characterized as low-threshold calcium spike (LTS) mediated bursts, on the basis of their intraburst firing pattern. The bursts of the remainder, although similar to LTS bursts, did not fulfil all of the criteria for an LTS burst and were termed atypical bursting cells. LTS and atypical bursting cells were found both within AN and in the nucleus cucularis and dorsal DM. The LTS bursting observed in these patients may be due to the altered electrophysiological state of the patients studied since LTS bursting in thalamus is usually only observed during sleep. This study describes for the first time the properties of this nucleus in humans and may be important in furthering our knowledge of thalamic mechanisms of epileptogenesis.

Action Potentials↗

PubMed2006

Referrals for movement disorder surgery: under-representation of females and reasons for refusal.

OBJECTIVE: Referral of movement disorder patients for deep brain stimulation surgery was examined to determine whether referred patients were representative of gender proportions in our population, and reasons why patients do not proceed to surgery. METHODS: Demographic information on referrals to the surgical program was retrospectively reviewed from our database and from a detailed chart review. RESULTS: Although almost equal numbers of movement disorder patients are male and female, of the 91 patients referred for surgery, only 31% were female. Sixty-one percent of referred patients did not undergo surgery. Of these, the majority were denied for medical reasons, including cognitive decline (21%), psychiatric concerns (5%) and neurological reasons (42%). CONCLUSIONS: Almost one-third of patients referred for movement disorder surgery were denied for medical reasons. This underscores the importance of evaluation of all potential patients by a multidisiplinary team to fully assess suitablity for stereotactic surgery. Interestingly, women were under-represented in those referred. In order that all appropriate patients have the opportunity to consider surgery, education of both physicians and patients, and different strategies to approach females regarding surgery may allow more patients to benefit from this treatment.

Deep Brain Stimulation↗

PubMed2006

Different mechanisms may generate sustained hypertonic and rhythmic bursting muscle activity in idiopathic dystonia.

Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. In 5 dystonic patients with mobile involuntary movements, rhythmic EMG bursts in the contralateral muscles were coherent with the oscillations in the pallidal LFPs at the burst frequency. In contrast, no significant coherence was seen between EMG and LFPs either for the sustained activity separated out from the compound EMGs in those 5 cases, or in the EMGs in 3 other cases without mobile involuntary movements and rhythmic EMG bursts. In comparison with the resting condition, in both active and passive movements, significant modulation in the GPi LFPs was seen in the range of 8-16 Hz. The finding of significant coherence between GPi oscillations and rhythmic EMG bursts but not sustained tonic EMG activity suggests that the synchronized pallidal activity may be directly related to the rhythmic involuntary movements. In contrast, the sustained hypertonic muscle activity may be represented by less synchronized activity in the pallidum. Thus, the pallidum may play different roles in generating different components of the dystonic symptom complex.

Adult↗

PubMed2005

GABAergic interneurons in human subthalamic nucleus.

The subthalamic nucleus (STN) is considered a homogeneous structure composed essentially of projection neurons that exert a profound glutamate-mediated excitatory influence upon the main output structures of the basal ganglia. It is currently the most efficient target for deep brain stimulations designed to alleviate symptoms of Parkinson's disease. STN neurons were analyzed by applying stereological methods and single/double-immunostaining procedures to postmortem material obtained from normal individuals. Besides a multitude of closely packed projection neurons ( approximately 24.7 mum in diameter), the human STN (mean volume, 174.5 +/- 20.4 mm3; total neuronal density, 239.5 +/- 31.9 x 10(3)) contained smaller neurons (approximately 12.2 microm), which displayed glutamic acid decarboxylase (GAD)(65/67) immunoreactivity and shared the morphological features of interneurons described in Golgi studies of primate STN. These putative gamma-aminobutyric acid (GABA)ergic interneurons accounted for 7.5% of the total neuronal population of the STN. Although present throughout the nucleus, they were significantly more numerous in its posterior-ventral-medial sector, which belongs to the limbic/associative functional territory. Many projection neurons located dorsolaterally in the STN showed parvalbumin immunoreactivity and others lying ventromedially displayed calretinin immunostaining, but none of the GAD-positive interneurons expressed these calcium-binding proteins. Although less abundant than projection neurons, GABAergic interneurons might play a important role in the intrinsic organization of the STN. The morphological and chemical heterogeneity of the human STN reported here might have important implications in the functional organization of the basal ganglia.

Adult↗