Long-term stimulation of the subthalamic nucleus in hemiparkinsonian rats: neuroprotection of dopaminergic neurons

2004 ◽  
Vol 100 (4) ◽  
pp. 679-687 ◽  
Author(s):  
Satoshi Maesawa ◽  
Yoshiki Kaneoke ◽  
Yasukazu Kajita ◽  
Naotaka Usui ◽  
Nobuaki Misawa ◽  
...  

Object. The goal of this study was to evaluate the neuroprotective effects conferred by long-term electrical stimulation of the subthalamic nucleus (STN) against degeneration of dopaminergic neurons by assessing motor functional and immunohistological findings in hemiparkinsonian rats. Methods. In 13 of 25 rats, a concentric microelectrode was stereotactically implanted into the right STN under the guidance of extracellular microelectrode recording. After this had been done the animals were given an injection of 6-hydroxydopamine (6-OHDA) into the right striatum. Seven of the rats received continuous stimulation (frequency 130 Hz, intensity 80–100 µA) for 2 weeks (Group A); the other six did not receive any stimulation during this period (Group B). Twelve rats did not receive electrode implantation and underwent 6-OHDA injection only; these animals served as a control group (Group C). After 2 weeks, motor function in the rats was evaluated by conducting an amphetamine-induced rotation test. Finally, tyrosine hydroxylase—immunoreactive neurons in the pars compacta of the substantia nigra (SNc) were counted to evaluate the extent of degeneration of dopaminergic neurons. Ipsilateral rotation was significantly decreased in Group A, regardless of the effects of stimulation delivered during the test (p < 0.05). Rats in Group B demonstrated typical circling as did those in Group C, except that on stimulation Group B rats immediately stopped circling or changed direction. Tyrosine hydroxylase—immunoreactive neurons in the SNc were significantly preserved in the animals in Group A, whereas neurons in animals in Groups B and C were moderately depleted (p < 0.01). Conclusions. Acutely, STN stimulation improved rotation symmetry in rats with moderate SNc degeneration. When STN stimulation had been applied for the preceding 2 weeks, motor function was better and SNc neural degeneration was significantly milder. Subthalamic nucleus stimulation thus appears to protect dopaminergic neurons in this hemiparkinsonian model, in addition to improving motor function in these animals.

2002 ◽  
Vol 97 (3) ◽  
pp. 350-354 ◽  
Author(s):  
Takashiro Ohyama ◽  
Yoshichika Kubo ◽  
Hiroo Iwata ◽  
Waro Taki

Object. An interbody fusion cage has been introduced for cervical anterior interbody fusion. Autogenetic bone is packed into the cage to increase the rate of union between adjacent vertebral bodies. Thus, donor site—related complications can still occur. In this study a synthetic ceramic, β—tricalcium phosphate (TCP), was examined as a substitute for autograft bone in a canine lumbar spine model. Methods. In 12 dogs L-1 to L-4 vertebrae were exposed via a posterolateral approach, and discectomy and placement of interbody fusion cages were performed at two intervertebral disc spaces. One cage was filled with autograft (Group A) and the other with TCP (Group B). The lumbar spine was excised at 16 weeks postsurgery, and biomechanical, microradiographic, and histological examinations were performed. Both the microradiographic and histological examinations revealed that fusion occurred in five (41.7%) of 12 operations performed in Group A and in six (50%) of 12 operations performed in Group B. The mean percentage of trabecular bone area in the cages was 54.6% in Group A and 53.8% in Group B. There were no significant intergroup differences in functional unit stiffness. Conclusions. Good histological and biomechanical results were obtained for TCP-filled interbody fusion cages. The results were comparable with those obtained using autograft-filled cages, suggesting that there is no need to harvest iliac bone or to use allo- or xenografts to increase the interlocking strength between the cage and vertebral bone to achieve anterior cervical interbody fusion.


2002 ◽  
Vol 96 (4) ◽  
pp. 666-672 ◽  
Author(s):  
Tanya Simuni ◽  
Jurg L. Jaggi ◽  
Heather Mulholland ◽  
Howard I. Hurtig ◽  
Amy Colcher ◽  
...  

Object. Palliative neurosurgery has reemerged as a valid therapy for patients with advanced Parkinson disease (PD) that is complicated by severe motor fluctuations. Despite great enthusiasm for long-term deep brain stimulation (DBS) of the subthalamic nucleus (STN), existing reports on this treatment are limited. The present study was designed to investigate the safety and efficacy of bilateral stimulation of the STN for the treatment of PD. Methods. In 12 patients with severe PD, electrodes were stereotactically implanted into the STN with the assistance of electrophysiological conformation of the target location. All patients were evaluated preoperatively during both medication-off and -on conditions, as well as postoperatively at 3, 6, and 12 months during medication-on and -off states and stimulation-on and -off conditions. Tests included assessments based on the Unified Parkinson's Disease Rating Scale (UPDRS) and timed motor tests. The stimulation effect was significant in patients who were in the medication-off state, resulting in a 47% improvement in the UPDRS Part III (Motor Examination) score at 12 months, compared with preoperative status. The benefit was stable for the duration of the follow-up period. Stimulation produced no additional benefit during the medication-on state, however, when compared with patient preoperative status. Significant improvements were made in reducing dyskinesias, fluctuations, and duration of off periods. Conclusions. This study demonstrates that DBS of the STN is an effective treatment for patients with advanced, medication-refractory PD. Deep brain stimulation of the STN produced robust improvements in motor performance in these severely disabled patients while they were in the medication-off state. Serious adverse events were common in this cohort; however, only two patients suffered permanent sequelae.


2003 ◽  
Vol 99 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Takeo Goto ◽  
Kenji Ohata ◽  
Toshihiro Takami ◽  
Misao Nishikawa ◽  
Akimasa Nishio ◽  
...  

Object. The authors evaluated an alternative method to avoid postoperative posterior tethering of the spinal cord following resection of spinal ependymomas. Methods. Twenty-five patients with spinal ependymoma underwent surgery between 1978 and 2002. There were 16 male and nine female patients whose ages at the time of surgery ranged from 14 to 64 years (mean 41.8 years). The follow-up period ranged from 6 to 279 months (mean 112.4 months). In the initial 17 patients (Group A), the procedure to prevent arachnoidal adhesion consisted of the layer-to-layer closure of three meninges and laminoplasty. In the subsequently treated eight patients (Group B), the authors performed an alternative technique that included pial suturing, dural closure with Gore-Tex membrane—assisted patch grafting, and expansive laminoplasty. In Group A, postoperative adhesion was radiologically detected in eight cases (47%), and delayed neurological deterioration secondary to posterior tethering of the cord was found in five cases. In Group B, there was no evidence of adhesive posterior tethering or delayed neurological deterioration. A significant intergroup statistical difference was demonstrated for radiologically documented posterior tethering (p < 0.05, Fisher exact test). Moreover, patients with radiologically demonstrated posterior tethering suffered a significant delayed neurological functional deterioration (p < 0.01, Fisher exact test). Conclusions. This new technique for closure of the surgical wound is effective in preventing of postoperative posterior spinal cord tethering after excision of spinal ependymoma.


1999 ◽  
Vol 91 (4) ◽  
pp. 605-609 ◽  
Author(s):  
Petra M. Klinge ◽  
Georg Berding ◽  
Thomas Brinker ◽  
Wolfram H. Knapp ◽  
Madjid Samii

Object. In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus.Methods. Ten patients whose mean age was 67 ± 10 years (mean ± standard deviation [SD]) were compared with 10 healthy volunteers who were 25 ± 3 years of age. Global CBF and CVR were determined using 15O—H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt.Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 ± 8 compared with 61 ± 7 ml/100 ml/minute; mean ± SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 ± 7 compared with 44 ± 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 ± 21%, Group B = 37 ± 29%). After shunt placement, there was an increase in the CVR in Group A to 52 ± 37% after 7 days and to 68 ± 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 ± 18% (p < 0.05) after 7 days and returned to the preoperative level (39 ± 6%) 7 months after shunt placement.Conclusions. The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.


2002 ◽  
Vol 97 (5) ◽  
pp. 1070-1077 ◽  
Author(s):  
Alexandre Carpentier ◽  
Marc Polivka ◽  
Alexandre Blanquet ◽  
Guillaume Lot ◽  
Bernard George

Object. Chordoma is a locally invasive tumor with a high tendency for recurrence for which radical resection is generally recommended. To assess the benefits of aggressive treatment of chordomas, the authors compared results in patients treated aggressively at the first presentation of this disease with results in patients who were similarly treated, but after recurrence. Methods. Among 36 patients with cervical chordomas who were treated at the authors' institution, 22 underwent primary aggressive treatment (Group A) and 14 were treated secondarily after tumor recurrence (Group B). Two cases were excluded from Group A because of unrelated early deaths and three from Group B because of insufficient pre- or postoperative data. Most tumors were located at the suboccipital level and only eight cases at a level below C-2. Radiotherapy and proton therapy were similarly conducted in both groups of patients. The actuarial survival rates were 80 and 65% at 5 and 10 years, respectively, in Group A patients and 50 and 0% at 5 and 10 years, respectively, in Group B patients (p = 0.049, log-rank test). The actuarial recurrence-free rates were 70 and 35% at 5 and 10 years, respectively, in Group A and 0% at 3 years in Group B (p < 0.0001, log-rank test). The numbers of recurrences per year were 0.15 in Group A and 0.62 in Group B (p > 0.05). All other parameters that were analyzed (patient age, delay before diagnosis, clinical symptoms, chondroid type of lesion, and histological features) did not prove to influence prognosis in a statistically significant manner. Conclusions. Aggressive therapy, combining as radical a resection as possible with radiotherapy, seems to improve the prognoses of suboccipital and cervical chordomas when applied at the patient's first presentation with the disease.


2005 ◽  
Vol 102 (6) ◽  
pp. 1122-1129 ◽  
Author(s):  
Naotaka Usui ◽  
Satoshi Maesawa ◽  
Yasukazu Kajita ◽  
Otone Endo ◽  
Shigenori Takebayashi ◽  
...  

Object. Deep brain stimulation (DBS) of subcortical nuclei such as the subthalamic nucleus (STN) or the substantia nigra pars reticulata (SNR) may provide an alternative therapy for intractable epilepsy. The authors attempted to evaluate the antiepileptic effects of DBS to these structures in an experimental seizure model. Methods. Three groups of rats were prepared. In the first two groups, the rats underwent unilateral implantation of stimulation electrodes in the STN (six rats) or the SNR (six rats). A control group received no electrodes (six rats). Kainic acid (KA) was systemically administered to induce limbic seizures, which started with focal seizures and became generalized secondarily. High-frequency electrical stimulation of the STN or SNR was begun immediately after KA administration, and changes on electroencephalography (EEG) and the magnitude of clinical seizures were evaluated. Results showed that STN stimulation significantly reduced the duration of generalized seizures on EEG, although the total duration of seizures (generalized plus focal seizures) was unchanged. The duration of focal seizures on EEG was prolonged by STN DBS, a result possibly due to the suppression of secondary generalization. In addition, STN DBS reduced the severity of clinical seizures. On the other hand, stimulation of the SNR demonstrated no effect. Conclusions. Unilateral STN DBS showed significant suppression of the secondary generalization of limbic seizures. Note, however, that SNR DBS was less effective, which implies that in addition to the nigral control of the epilepsy system, another antiepileptic mechanism such as antidromic stimulation of the corticosubthalamic pathway should be considered.


2002 ◽  
Vol 97 (2) ◽  
pp. 315-325 ◽  
Author(s):  
Sandeep Mittal ◽  
Jean-Pierre Farmer ◽  
Borhan Al-Atassi ◽  
Joanne Gibis ◽  
Eileen Kennedy ◽  
...  

Object. Selective posterior rhizotomy (SPR) is a well-recognized treatment for children with spastic cerebral palsy (CP). Few investigators have used quantitative outcome measures to assess the surgical results beyond 3 years. The authors analyzed data obtained from the McGill Rhizotomy Database to determine the long-term functional outcome of children who had undergone selective dorsal rhizotomy accompanied by intraoperative electrophysiological monitoring. Methods. The study population was composed of children with spastic CP who underwent SPR and were evaluated by a multidisciplinary team preoperatively, and at 6 months and 1 year postoperatively. Quantitative standardized assessments of lower-limb spasticity, passive range of motion, muscle strength, and ambulatory function were obtained. Of the 93 patients who met the entry criteria for the study, 71 completed the 3-year and 50 completed the 5-year assessments, respectively. Statistical analysis demonstrated significant improvements in spasticity, range of motion, and functional muscle strength at 1 year after SPR. The preoperative, 1-, 3-, and 5-year values for the global score of the Gross Motor Function Measure were 64.6, 70.8, 80, and 85.6, respectively. The greatest improvement occurred in the dimensions reflecting lower-extremity motor function, where the mean change was 10.1% at 1 year, 19.9% at 3 years, and 34.4% at the 5-year follow-up review in comparison with the baseline value. This was associated with a lasting improvement in alignment and postural stability during developmental positions, as well as increased ability to perform difficult transitional movements. Conclusions. The results of this study support the presence of significant improvements in lower-limb functional motor outcome 1 year after SPR, and the improvements persist at 3 and 5 years. The authors conclude that SPR in conjunction with intraoperative stimulation is valuable for permanently alleviating lower-limb spasticity while augmenting motor function.


1988 ◽  
Vol 69 (3) ◽  
pp. 393-398 ◽  
Author(s):  
Norihiko Tamaki ◽  
Kunio Shirataki ◽  
Noriaki Kojima ◽  
Yoshiteru Shouse ◽  
Satoshi Matsumoto

✓ Nine (15%) of 60 patients with repaired myelomeningocele exhibited late deterioration of neurological function with a tethered cord syndrome. Dense adhesions at the lowest laminae and at the site of previous repair were the most common findings at surgery. Postoperatively, 71% of the patients improved. Magnetic resonance (MR) imaging was performed in 29 of the 60 patients. Eight of these 29 patients exhibited a tethered cord syndrome. The MR images in all patients showed a low-lying conus fixed at the site of previous repair, irrespective of the presence or absence of a tethered cord syndrome. The MR images were classified into two groups depending upon the site of adhesions: Group A had potential sites of tethering at the ventral aspect of the last laminae and at the site of previous repair, and Group B showed the adhesion point only at the site of previous repair. Most patients with a tethered cord syndrome were found to be in Group A; conversely, most patients without the syndrome were in Group B. An enlarged low conus was seen in symptomatic patients more commonly than in those without this syndrome. It is concluded that the presence of adhesions specifically at the last laminae as well as a widened low-lying conus may be the cause of tethered cord syndrome in patients with repaired myelomeningoceles. A clear understanding of the tethering process and preoperative evaluation of potential sites of tethering, based on the MR findings, are very important for planning surgery. The release of adhesions at the lowest laminae by laminectomy appeared essential for improvement.


1978 ◽  
Vol 49 (6) ◽  
pp. 854-861 ◽  
Author(s):  
Lucio Palma ◽  
Nicola Di Lorenzo ◽  
Beniamino Guidetti

✓ The correlation existing in several human malignancies between lymphocytic infiltration and prolonged survival prompted this study. Two hundred selected patients who were operated on for glioblastoma were reviewed to investigate the incidence of the lymphocytic infiltration in the histological slides and its possible relevance to a better clinical course. The group that exhibited a definite lymphocytic infiltration (Group A, 11.5%) had a significantly longer preoperative history and postoperative survival (p < 0.01) than the other two groups that presented slight or no infiltration (Group B, 23%, and Group C, 65%, respectively). In addition, biopsies of 28 recidivous gliomas were reviewed to study the fate of this lymphocytic infiltration in relation to time and therapy, such as irradiation and steroids which are known to depress the immune response. The authors found that severe lymphocytic infiltration is a rare immunobiological reaction which significantly improves the prognosis of a malignant brain tumor and seems not to be influenced by time, local x-ray therapy, or steroids.


2000 ◽  
Vol 93 (5) ◽  
pp. 774-783 ◽  
Author(s):  
Maxwell Boakye ◽  
Sean C. Huckins ◽  
Nikolaus M. Szeverenyi ◽  
Bobby I. Taskey ◽  
Charles J. Hodge

Object. Functional magnetic resonance (fMR) imaging was used to determine patterns of cerebral blood flow changes in the somatosensory cortex that result from median nerve stimulation (MNS).Methods. Ten healthy volunteers underwent stimulation of the right median nerve at frequencies of 5.1 Hz (five volunteers) and 50 Hz (five volunteers). The left median nerve was stimulated at frequencies of 5.1 Hz (two volunteers) and 50 Hz (five volunteers). Tactile stimulation (with a soft brush) of the right index finger was also applied (three volunteers). Functional MR imaging data were transformed into Talairach space coordinates and averaged by group. Results showed significant activation (p < 0.001) in the following regions: primary sensorimotor cortex (SMI), secondary somatosensory cortex (SII), parietal operculum, insula, frontal cortex, supplementary motor area, and posterior parietal cortices (Brodmann's Areas 7 and 40). Further analysis revealed no statistically significant difference (p > 0.05) between volumes of cortical activation in the SMI or SII resulting from electrical stimuli at 5.1 Hz and 50 Hz. There existed no significant differences (p > 0.05) in cortical activity in either the SMI or SII resulting from either left- or right-sided MNS. With the exception of the frontal cortex, areas of cortical activity in response to tactile stimulation were anatomically identical to those regions activated by electrical stimulation. In the SMI and SII, activation resulting from tactile stimulation was not significantly different (p > 0.05) from that resulting from electrical stimulation.Conclusions. Electrical stimulation of the median nerve is a reproducible and effective means of activating multiple somatosensory cortical areas, and fMR imaging can be used to investigate the complex network that exists between these areas.


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