High resolution MR anatomy of the subthalamic nucleus: imaging at 9.4 T with histological validation.

Using conventional MRI the subthalamic nucleus (STN) is not clearly defined. Our objective was to define the anatomy of the STN using 9.4 T MRI of post mortem tissue with histological validation. Spin-echo (SE) and 3D gradient-echo (GE) images were obtained at 9.4 T in 8 post mortem tissue blocks and compared directly with corresponding histological slides prepared with Luxol Fast Blue/Cresyl Violet (LFB/CV) in 4 cases and Perl stain in 3. The variability of the STN anatomy was studied using internal reference points. The anatomy of the STN and surrounding structures was demonstrated in all three anatomical planes using 9.4 T MR images in concordance with LFB/CV stained histological sections. Signal hypointensity was seen in 6/8 cases in the anterior and medial STN that corresponded with regions of more intense Perl staining. There was significant variability in the volume, shape and location of the borders of the STN. Using 9.4 T MRI, the internal signal characteristics and borders of the STN are clearly defined and significant anatomical variability is apparent. Direct visualisation of the STN is possible using high field MRI and this is particularly relevant, given its anatomical variability, for planning deep brain stimulation.

Deep brain stimulation in the treatment of depression.

OBJECTIVE: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD). METHOD: A review of the literature on DBS in the treatment of MDD was conducted. RESULTS: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. CONCLUSION: DBS is a promising treatment for therapy-refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

Pallidal deep brain stimulation in the treatment of Meige syndrome.

BACKGROUND: Pallidal deep brain stimulation (DBS) of globus pallidus internus (Gpi) has emerged as an effective treatment for dystonia. The experience is however limited concerning focal dystonias and to date only a few cases of pallidal DBS in the treatment of Meige syndrome have been published. METHODS/RESULTS: We here present a patient with Meige syndrome in whom unilateral pallidal DBS failed to improve the axial symptoms, but bilateral stimulation resulted in a major improvement. The Burke-Fahn-Marsden score (BFM) improved by 71.5% and the patient's blepharospasm was abolished. CONCLUSIONS: The results suggest bilateral pallidal DBS may be an effective treatment for Meige syndrome.

Localization of beta and high-frequency oscillations within the subthalamic nucleus region.

Parkinsonian bradykinesia and rigidity are typically associated with excessive beta band oscillations in the subthalamic nucleus. Recently another spectral peak has been identified that might be implicated in the pathophysiology of the disease: high-frequency oscillations (HFO) within the 150-400 Hz range. Beta-HFO phase-amplitude coupling (PAC) has been found to correlate with severity of motor impairment. However, the neuronal origin of HFO and its usefulness as a potential target for deep brain stimulation remain to be established. For example, it is unclear whether HFO arise from the same neural populations as beta oscillations. We intraoperatively recorded local field potentials from the subthalamic nucleus while advancing DBS electrodes in 2 mm steps from 4 mm above the surgical target point until 2 mm below, resulting in 4 recording sites. Data from 26 nuclei from 14 patients were analysed. For each trajectory, we identified the recording site with the largest spectral peak in the beta range (13-30 Hz), and the largest peak in the HFO range separately. In addition, we identified the recording site with the largest beta-HFO PAC. Recording sites with largest beta power and largest HFO power coincided in 50% of cases. In the other 50%, HFO was more likely to be detected at a more superior recording site in the target area. PAC followed more closely the site with largest HFO (45%) than beta power (27%). HFO are likely to arise from spatially close, but slightly more superior neural populations than beta oscillations. Further work is necessary to determine whether the different activities can help fine-tune deep brain stimulation targeting.

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

A non-invasive method for fractionated stereotactic irradiation of brain tumors with linear accelerator.

A new technique for fractionated stereotactic irradiation of intracranial lesions is described. The treatment is based on a versatile, non-invasive interface for stereotactic localization of the brain target imaged by computed tomography (CT), angiography or magnetic resonance tomography (MRT), and subsequent repetitive stereotactic irradiation of the target using a linear accelerator. The fractionation of the stereotactic irradiation was intended to meet the requirements of the basic principles of radiobiology. The radiophysical evaluation using phantoms, and the clinical results in a small number of patients, demonstrated a good reproducibility between repeated positionings of the target in the isocenter of the accelerator, and a high degree of accuracy in the treatment of brain lesions.

Influence of previous treatment on outcome after glycerol rhizotomy for trigeminal neuralgia.

The aim of the present study was to evaluate the influence of previous treatment on outcome and sensory disturbance after a retrogasserian glycerol injection for trigeminal neuralgia. Ninety-nine patients with trigeminal neuralgia underwent a retrogasserian glycerol rhizotomy. Fifty-three of those patients experienced recurrent pain after the previous treatment. At the 1 year follow-up, the outcome was excellent or good in 83% of patients with no previous treatment, compared with 60 and 75% in those patients with earlier glycerol injections or radiofrequency lesions, respectively. Quantitatively assessed, the sensory impairment was most pronounced in patients who had earlier radio-frequency lesions compared with patients not treated previously. The occurrence of dysesthesia was more frequent in patients who had been surgically treated earlier. A review of the literature showed that the concentration of the glycerol preparation used probably is of great importance in terms of pain relief and sensory sequelae.

A comparative study on ventriculographic and computerized tomography-guided determinations of brain targets in functional stereotaxis.

Thalamic, pallidal, and hypothalamic targets were determined in 16 patients by a stereotactic computerized tomography (CT) study using a noninvasive technique with Laitinen's Stereoadapter. At surgery, the Stereoadapter was remounted to the head and the stereotactic CT coordinates were transferred to the Stereoguide without radiography. Air ventriculography was then carried out. The positions of the anterior and posterior commissures (AC and PC), the length of the intercommissural (IC) line, the width of the third ventricle, and the stereotactic coordinates of the target were measured on the ventriculograms and compared to the stereotactic CT measurements. The study showed that the width of the third ventricle was significantly larger on the ventriculograms than on the stereotactic CT scans, whereas the length of the IC line was not significantly different. The differences in the coordinates of the target and of the AC and PC were statistically significant only for the anteroposterior (y) coordinate. Both commissures as well as the surgical target lay, on average, 1.0 mm more anteriorly on the ventriculograms than on the stereotactic CT study. It is concluded that air ventriculography may cause slight anterior displacement of the midbrain structures. The surgical coordinates of the targets based on the stereotactic CT study with the Stereoadapter were on average as accurate as those obtained with ventriculography; therefore, ventriculography may become superfluous in functional stereotaxis.

A 10-year follow-up review of patients who underwent Leksell's posteroventral pallidotomy for Parkinson disease.

OBJECT: The clinical condition of patients with Parkinson disease (PD) who had undergone posteroventral pallidotomy (PVP) between 1985 and 1990 was evaluated at a mean of 10 years postsurgery. These patients were part of a larger series described in the first paper on Leksell's PVP that was published in 1992. METHODS: Thirteen consecutive patients who had undergone pallidotomy at the University Hospital of Northern Sweden were tracked. Hospital and clinic records that had been updated regularly by the patients' various neurologists, geriatricians, and other clinicians were reviewed. Emphasis was placed on assessing the evolution of PD symptoms after surgery, and changes in the general health and social condition of the patients. The mean follow-up duration was 10.5 years (range 3-13.5 years). Five patients underwent a total of seven subsequent surgeries for their PD, 4 months to 11 years after the initial pallidotomy. The mean Hoehn and Yahr stage was 3 at the first surgery and 3.7 at the last follow-up review (p < 0.005). Dosages of levodopa and dopamine agonists were increased in all patients, without recurrence or induction of dyskinesias contralateral to the pallidotomy. Contralateral tremor, if it was initially controlled by surgery, remained improved. However, most patients exhibited a gradual recurrence of akinesia and an increase in gait freezing. Cognitive decline and presentation with diseases unrelated to PD were not uncommon. CONCLUSIONS: The long-term effect of PVP on dyskinesias was not only curative but also appeared to be prophylactic. Contralateral tremor was improved in the majority of patients, although additional surgeries for PD were needed in some patients. Further progression of axial and akinetic symptoms, and an eventual decline in cognition together with other concomitant illnesses, contributed to increased disability in several patients.

Leksell's posteroventral pallidotomy in the treatment of Parkinson's disease.

Between 1985 and 1990, the authors performed stereotactic posteroventral pallidotomies on 38 patients with Parkinson's disease whose main complaint was hypokinesia. Upon re-examination 2 to 71 months after surgery (mean 28 months), complete or almost complete relief of rigidity and hypokinesia was observed in 92% of the patients. Of the 32 patients who before surgery also suffered from tremor, 26 (81%) had complete or almost complete relief of tremor. The L-dopa-induced dyskinesias and muscle pain had greatly improved or disappeared in most patients, and gait and speech volume also showed remarkable improvement. Complications were observed in seven patients: six had a permanent partial homonymous hemianopsia (one also had transient dysphasia and facial weakness) and one developed transitory hemiparesis 1 week after pallidotomy. The results presented here confirm the 1960 findings of Svennilson, et al., that parkinsonian tremor, rigidity, and hypokinesia can be effectively abolished by posteroventral pallidotomy, an approach developed in 1956 and 1957 by Lars Leksell. The positive effect of posteroventral pallidotomy is believed to be based on the interruption of some striopallidal or subthalamopallidal pathways, which results in disinhibition of medial pallidal activity necessary for movement control.

Stereotactic localization of small subcortical brain tumors for open surgery.

A noninvasive, computed tomography (CT) stereoadapter was used for stereotactic localization of small brain tumors in 16 patients scheduled for open surgery. The stereotactic CT study was carried out 1 day to 3 months before surgery. On the day of surgery, the adapter was remounted on the patient's head. The tumor in relation to the adapter, as shown on the CT study, was drawn on the scalp of the patient. The tumor could be found and removed through a small bone opening and a minimal cortical incision.

Controversies in pallidal surgery.

Posteroventral pallidotomy (PVP) has gained a worldwide acceptance after its reintroduction by Laitinen et al. in 1992 (56) and many studies have since been published. A review of the recent literature reveals that there is variation in the clinical indications for this procedure, the surgical technique used and the assessment of results. There is no uniform practice in the choice of the anatomical target point within the globus pallidus, the imaging of the target structure, the intraoperative assessment of the physiological target and the mode of evaluation of the surgical results. Although some neurosurgeons advocate that the lesion should be in the lateral pallidum, the majority insist it should be in the medial pallidum. It is shown here that, as long as the lesion is made at the posterior and ventral parts of the globus pallidus, it will necessarily include aspects of both medial and lateral posteroventral pallidum. There is a common agreement on the effectiveness of pallidal surgery on the L-dopa induced dyskinesias, but, its long-term effects on tremor, akinesia, freezing of the gait and other genuine parkinsonian symptoms need more extensive evaluation. The assessment of the outcome of pallidal surgery in terms of the patient's disability, quality of life and coping abilities following surgery seems to have been neglected.

The side-effects and complications of posteroventral pallidotomy.

The side-effects and complications of posteroventral pallidotomy are analysed in 138 consecutive patients who underwent 152 pallidotomies. Transient side-effects, lasting less than three months, appeared in 18% of the patients, that is, 16.5% of the surgical procedures. Long term complications, lasting more than 6 months, were noted in 10% of the patients, that is, 9.2% of the surgical procedures. Sixteen complications occurred alone or in various combinations in 14 patients and included fatigue and sleepiness (2), worsening of memory (4), depression (1), aphonia (1), dysarthria (3), scotoma (1), slight facial and leg paresis (2) and delayed stroke (2). Complications such as dysarthria and paresis could be attributed to MR- or CT-verified pallidal lesions lying too medially and encroaching on the internal capsule. Two of the patients with deterioration in memory had some memory impairment before surgery, and the aphonic patient had dysphonia preoperatively. The study suggests that stereotactic MRI and careful impedance monitoring and macro-stimulation of the posteroventral pallidum area should be sufficient for minimizing the risk of complications; the stereotactic lesion should be centered within the posterior ventral pallidum without involvement of internal capsule. It is concluded that pallidotomy is a safe procedure if performed on cognitively alert patients, and it seems that both the incidence and especially the severity of complications are lower for posteroventral pallidotomy than for thalamotomy.

[Pre- and postoperative quantitative measures of facial sensitivity in tic douloureux]. / Mesures quantitatives pré et post-opératoires de la sensibilité faciale dans le tic douloureux.

Electrical stimulation was used for quantitative assessment of facial sensibility before, during and after percutaneous electrocoagulation of the Gasserian ganglion in 19 patients with tic douloureux. A portable stimulator was of a constant current type, which generated rectangular monophasic pulses of 0,2 ms in length and 100 Hz in frequency. The bipolar electrode consisted of saline-soaked felt discs with a surface of 1 cm2 and an interpolar distance of 1 cm. The thresholds for perception and pain were measured over six regions of each side of the face. Additionally, maximal pain tolerance was measured in the painful area and its corresponding healthy area. Shortlasting intravenous anesthesia with Brietal was given before each electrocoagulation. As soon as the patient began to react to speech, the threshold for pain was measured in the painful and the corresponding healthy area. Preoperatively, the measurements showed that the average threshold for perception was 2,5 mA and for pain 3,5 mA. The average maximal pain tolerance was 10,8 mA. There were no differences between the painful and the healthy sides. Electrocoagulations were stopped when the thresholds for pain in the trigger area had become twice as high as that on the contralateral side. The postoperative measurements showed that the average thresholds for perception and pain had doubled, measuring 4,8 and 8,0 mA, respectively. The average pain tolerance had risen from 10,8 to 22,5 mA. A marked rise of both thresholds was also seen in the ipsilateral areas adjacent to the trigger zone. There was good correlation between a heavy sensory deficit and a favourable clinical result.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. METHODS: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. RESULTS: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2%±20.15% off-medication and 16.9%±21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6%±5.5% and 4.5%±8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. CONCLUSION: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.

Parkinsonian impairment correlates with spatially extensive subthalamic oscillatory synchronization.

The local strength of pathological synchronization in the region of the subthalamic nucleus (STN) is emerging as a possible factor in the motor impairment of Parkinson's Disease (PD). In particular, correlations have been repeatedly demonstrated between treatment-induced suppressions of local oscillatory activity in the beta frequency band and improvements in motor performance. However, a mechanistic role for beta activity is brought into question by the difficulty in showing a correlation between such activity at rest and the motor deficit in patients withdrawn from medication. Here we recorded local field potential (LFP) activity from 36 subthalamic regions in 18 patients undergoing functional neurosurgery for the treatment of PD. We recorded directly from the contacts of the deep brain stimulation (DBS) electrodes as they were introduced in successive 2 mm steps, and assessed phase coherence as a measure of spatially extended, rather than local, oscillatory synchronization. We found that phase coherence in the beta frequency band correlated with the severity of Parkinsonian bradykinesia and rigidity, both in the limbs and axial body. Such correlations were frequency and site specific in so far as they were reduced when the lowermost contact of the DBS electrode was above the dorsal STN. Correlations with limb tremor occurred at sub-beta band frequencies and were more lateralized than those between beta activity and limb bradykinesia and rigidity. Phase coherence could account for up to ∼25% of the variance in motor scores between sides and patients. These new data suggest that the strength of spatially extended oscillatory synchronization, as well as the strength of local synchronization, may be worthwhile incorporating into modelling studies designed to inform surgical targeting, post-operative stimulation parameter selection and closed-loop stimulation regimes in PD. In addition, they strengthen the link between pathological synchronization and the different motor features of Parkinsonism.