Circuitry models of Parkinson’s disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been ...the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.
Deep brain stimulation (DBS) surgery can significantly improve the quality of life for patients suffering from movement disorders, but the success of the procedure depends on the implantation ...accuracy of the DBS electrode array. Pre-operative surgical planning and navigation are based on the assumption that the brain tissue is rigid between the time of the acquisition of the pre-operative image set and the time of surgery. A shift of deep brain structures by only a few millimeters can potentially increase the number of required microelectrode and/or macroelectrode tracks and decrease implantation accuracy. We studied 25 subjects that underwent DBS surgery and analyzed brain shift between pre-operative and post-operative 3D MRI scans. Brain shift of up to 4 mm was observed in deep brain structures. On average, the recorded shift was in the direction of gravity, with deeper structures experiencing smaller shift than more superficial structures. The main conclusion of the study is that the brain shift is comparable to the size of the targets in deep brain stimulation surgery and should not be ignored. Techniques that minimize the amount of brain shift may therefore lead to increased accuracy of DBS lead implantation.
Thirty‐six patients with Parkinson's disease (PD) were randomized to either medical therapy (N = 18) or unilateral GPi pallidotomy (N = 18). The primary outcome variable was the change in total ...Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow‐up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug‐induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug‐induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS (p < 0.0001), “off” motor (p < 0.0001) and complications of therapy subscores (p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug‐induced dyskinesias. Ann Neurol 2003
Abstract Background Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of ...tardive dystonia are associated with different outcomes remains unknown. Methods We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Results Consistent with previous studies, deep brain stimulation improved the overall the Burke–Fahn–Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Conclusion Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia.
The authors describe the microelectrode recording and stimulation techniques used for localizing the caudal sensorimotor portion of the globus pallidus internus (GPi) and nearby structures (internal ...capsule and optic tract) in patients undergoing GPi pallidotomy.
Localization is achieved by developing a topographic map of the abovementioned structures based on the physiological characteristics of neurons in the basal ganglia and the microexcitable properties of the internal capsule and optic tract. The location of the caudal GPi can be determined by "form fitting" the physiological map on relevant planes of a stereotactic atlas. A sensorimotor map can be developed by assessing neuronal responses to passive manipulation or active movement of the limbs and orofacial structures. The internal capsule and optic tract, respectively, can be identified by the presence of stimulation-evoked movement or the patient's report of flashes or speckles of light that occur coincident with stimulation. The optic tract may also be located by identifying the neural response to flashes of light. The anatomical/physiological map is used to guide lesion placement within the sensorimotor portion of the pallidum while sparing nearby structures, for example, the external globus pallidus, nucleus basalis, optic tract, and internal capsule. The lesion location and size predicted by using physiological recording together with thin-slice high-resolution magnetic resonance imaging reconstructions of the lesion were confirmed in one patient on histological studies.
These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.
Recent studies have shown that fibroblast transplantation can modify the activity of basal ganglia networks in models of Parkinson＇s disease. To determine its effects on parkinsonian motor symptoms, ...we performed autologous dermal fibroblast transplantation into the internal pallidum （GPi） in two parkinsonian rhesus monkeys with stable levodopa- induced dyskinesias （LIDs）. Levodopa responses were assessed every week after transplantation for three months. A reduction of between 58% and 64% in total LIDs on the contralateral side was observed in both animals. No clear LID changes were observed on the ipsilateral side. These effects lasted the entire 3-month period in one monkey, but declined after 6-8 weeks in the other. The antiparkinsonian effects of levodopa did not diminish, The results of this pilot study indicate that fibroblast transplantation into the GPi may have beneficial effects on LIDs and warrant further investigation for potential therapeutic use.
A novel super-resolution reconstruction (SRR) framework in magnetic resonance imaging (MRI) is proposed. Its purpose is to produce images of both high resolution and high contrast desirable for ...image-guided minimally invasive brain surgery. The input data are multiple 2-D multislice inversion recovery MRI scans acquired at orientations with regular angular spacing rotated around a common frequency encoding axis. The output is a 3-D volume of isotropic high resolution. The inversion process resembles a localized projection reconstruction problem. Iterative algorithms for reconstruction are based on the projection onto convex sets (POCS) formalism. Results demonstrate resolution enhancement in simulated phantom studies, and ex vivo and in vivo human brain scans, carried out on clinical scanners. A comparison with previously published SRR methods shows favorable characteristics in the proposed approach.
The centromedian nucleus (CM) of the thalamus is an important site with anatomical connections to different cortical and subcortical motor areas; however, its role in tremor disorders is not clear, ...although deep brain stimulation (DBS) of the CM has been described to be effective in the treatment of parkinsonian tremor. We report a case of a patient with medication-refractory essential tremor (ET) who had excellent tremor suppression with DBS of the CM. The CM and the nearby region should be explored as a potential target for the treatment of ET and other forms of tremor.
Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14 patients with Parkinson's disease submitted to surgery. Three hundred and fifty neurones were recorded and assessed for ...their response to passive and active movements. Thirty-two per cent were activated by passive and active movement of the limbs, oromandibular region and abdominal wall. All neurones with sensorimotor responses were in the dorsolateral region of the STN. Arm-related neurones were lateral (≥14 mm plane) to leg-related neurones, which were found more medially (≤12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (~13 mm plane) and ventral to the arm and leg. Two hundred neurones were adequately isolated for `off-line' analysis. The mean frequency of discharge was 33 ± 17 Hz (13–117 Hz). Three types of neuronal discharges were distinguished: irregular (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically differentiated on the basis of their mean firing frequency and the coefficient of variation of the interspike interval. Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded. The majority (84%) of these were sensitive to movement and were located in the dorsolateral region of the STN. Cross power analysis (n = 16) between the rhythmic neuronal activity and tremor in the limbs showed a peak frequency of 5 Hz (4–8 Hz). Neuronal activity of the subtantia nigra pars reticulata was recorded 0.5–3 mm below the STN. Eighty neurones were recorded `on-line' and 27 were isolated for `off-line' analysis. A tonic pattern of discharge characterized by a mean firing rate of 71 ± 28 Hz (35–122 Hz) with a mean coefficient of variation of the interspike interval of 0.85 ± 0.29 ms was found. In only three neurones (11%) was there a response to sensorimotor stimulation. The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys.
With the expanding indications and increasing number of patients undergoing deep brain stimulation (DBS), postoperative MR imaging is becoming even more important in guiding clinical care and ...practice-based learning; important safety concerns have recently emerged, however. Although phantom model studies have driven conservative recommendations regarding imaging parameters, highlighted by 2 recent reports describing adverse neurological events associated with MR imaging in patients with implanted DBS systems, the risks of MR imaging in such patients in clinical practice has not been well addressed. In this study, the authors capitalized on their large experience with serial MR imaging (3 times per patient) to use MR imaging itself and clinical outcomes to examine the safety of MR imaging in patients who underwent staged implantation of DBS electrodes for Parkinson disease, tremor, and dystonia.
Sixty-four patients underwent staged bilateral lead implantations between 1997 and 2006, and each patient underwent 3 separate MR imaging sessions subsequent to DBS placement. The first of these was performed after the first DBS placement, the second occurred prior to the second DBS placement, and third was after the second DBS placement. Follow-up was conducted to examine adverse events related either to MR imaging or to DBS-induced injury.
One hundred and ninety-two MR images were obtained, and the mean follow-up time was 3.67 years. The average time between the first and second, and second and third MR imaging sessions was 19.4 months and 14.7 hours, respectively. Twenty-two MR imaging-detected new findings of hemorrhage were documented. However, all new findings were related to acute DBS insertion, whereas there were no new findings after imaging of the chronically implanted electrode.
Although potential risks of MR imaging in patients undergoing DBS may be linked to excessive heating, induced electrical currents, disruption of the normal operation of the device, and/or magnetic field interactions, MR imaging can be performed safely in these patients and provides useful information on DBS lead location to inform patient-specific programming and practice-based learning.
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