The role of tractography in the localization of the Vim nucleus of the thalamus and the dentato-rubro-thalamic tract for the treatment of tremor. / El papel de la tractografía en la localización del núcleo ventralis intermedius del tálamo y el haz dentatorrubrotalámico en el tratamiento del temblor.

INTRODUCTION: The ventralis intermedius (Vim) nucleus of the thalamus is the usual surgical target for tremor. However, locating the structure may be difficult as it is not visible with conventional imaging methods; therefore, surgical procedures typically use indirect calculations correlated with clinical and intraoperative neurophysiological findings. Current ablative surgical procedures such as Gamma-Knife thalamotomy and magnetic resonance-guided focused ultrasound require new alternatives for locating the Vim nucleus. In this review, we compare Vim nucleus location for the treatment of tremor using stereotactic procedures versus direct location by means of tractography. DISCUSSION: The most widely used cytoarchitectonic definition of the Vim nucleus is that established by Schaltenbrand and Wahren. There is a well-defined limit between the motor and the sensory thalamus; Vim neurons respond to passive joint movements and are synchronous with peripheral tremor. The most frequently used stereotactic coordinates for the Vim nucleus are based on indirect calculations referencing the mid-commissural line and third ventricle, which vary between patients. Recent studies suggest that the dentato-rubro-thalamic tract is an optimal target for controlling tremor, citing a clinical improvement; however, this has not yet been corroborated. CONCLUSIONS: Visualisation of the cerebello-rubro-thalamic pathway by tractography may help in locating the Vim nucleus. The technique has several limitations, and the method requires standardisation to obtain more precise results. The utility of direct targeting by tractography over indirect targeting for patients with tremor remains to be demonstrated in the long-term.

The role of tractography in the localisation of the Vim nucleus of the thalamus and the dentatorubrothalamic tract for the treatment of tremor.

INTRODUCTION: The ventralis intermedius (VIM) nucleus of the thalamus is the usual surgical target for tremor. However, locating the structure may be difficult as it is not visible with conventional imaging methods; therefore, surgical procedures typically use indirect calculations correlated with clinical and intraoperative neurophysiological findings. Current ablative surgical procedures such as Gamma-Knife thalamotomy and magnetic resonance-guided focused ultrasound require new alternatives for locating the VIM nucleus. In this review, we compare VIM nucleus location for the treatment of tremor using stereotactic procedures versus direct location by means of tractography. DISCUSSION: The most widely used cytoarchitectonic definition of the VIM nucleus is that established by Schaltenbrand and Wahren. There is a well-defined limit between the motor and the sensory thalamus; VIM neurons respond to passive joint movements and are synchronous with peripheral tremor. The most frequently used stereotactic coordinates for the VIM nucleus are based on indirect calculations referencing the mid-commissural line and third ventricle, which vary between patients. Recent studies suggest that the dentato-rubro-thalamic tract is an optimal target for controlling tremor, citing a clinical improvement; however, this has not yet been corroborated. CONCLUSIONS: Visualisation of the cerebello-rubro-thalamic pathway by tractography may help in locating the VIM nucleus. The technique has several limitations, and the method requires standardisation to obtain more precise results. The utility of direct targeting by tractography over indirect targeting for patients with tremor remains to be demonstrated in the long-term.

[Surgical targets in Psychiatric disorders. From movement to emotions]. / Dianas quirúrgicas en el tratamiento de enfermedades psiquiátricas.Desde el movimiento a las emociones.

Deep brain stimulation (DBS) for psychiatric disorders refractory to conventional treatments are currently been performed based on the knowledge obtained in the motor disorder surgery and mainly in Parkinson's disease. Depression, obsessive-compulsive disorder (OCD) and Tourette syndrome, all of them are cortico-striato-thalamo-cortical pathological process involved in the limbic loop of the basal ganglia. This review describes the different targets in these pathological neuro-psychiatric disorders. For OCD there are currently two targets, ventral striatum (VS) Accumbens nucleus (Nacc) and the subthalamic nucleus (STN). In refractory depression the subgenual area (25 Brodmann area) and VS/Nacc. For Tourette syndrome the ventralis oralis internus and centromedianum/parafascicularis of the thalamus (Voi and CM/Pf) and the internal part of the globus pallidus (GPi). Currently there are no specific surgical target for each pathological disorder because clinical results reported are very similar after stimulation surgery. In other point, a selected surgical target also may improve different pathologies.

Therapeutic efficacy of unilateral subthalamotomy in Parkinson's disease: results in 89 patients followed for up to 36 months.

BACKGROUND: Stereotactic thermocoagulative lesions of the subthalamic nucleus (STN) have been shown to induce significant motor improvement in patients with Parkinson's disease (PD). PATIENTS AND METHODS: 89 patients with PD were treated with unilateral subthalamotomy. 68 patients were available for evaluations after 12 months, 36 at 24 months and 25 at 36 months. RESULTS: The Unified Parkinson's Disease Rating Scale (UPDRS) motor scores improved significantly contralaterally to the lesion in the "off" and "on" states throughout the follow-up, except for the "on" state at the last evaluation. Axial features and signs ipsilateral to the lesion progressed steadily throughout the study. Levodopa daily doses were significantly reduced by 45%, 36% and 28% at 12, 24 and 36 months post-surgery. 14 patients (15%) developed postoperative hemichorea-ballism which required pallidotomy in eight. These 14 patients had significantly higher dyskinesia scores (levodopa induced) preoperatively than the entire cohort. CONCLUSION: Unilateral subthalamotomy was associated with significant and sustained motor benefit contralateral to the lesion. Further work is needed to ascertain what factors led to severe, persistent chorea-ballism in a subset of patients. Subthalamotomy may be considered an option in circumstances when deep brain stimulation is not viable.

[Critical review of the subthalamic stimulation in Parkinson's disease]. / Revisión crítica de la estimulación subtalámica en la enfermedad de Parkinson.

The authors critically review subthalamic nucleus (STN) stimulation for Parkinson's disease (PD) at long follow-up (3-5 years). Subthalamic stimulation induce a significant improvement during the "off" medication in the assessment motor score UPDRS (Unified Parkinson Disease Rating Scale) 3-5 years after surgery. Results show that the benefits obtained in tremor, rigidity, bradykinesia, dyskinesias induced by medication and levodopa reduction are significantly maintained during long term. The improvement in other clinical signs as gait and postural stability at long follow-up are not maintained comparing with the benefits obtained one year after surgery. A high percentage of patients show a cognitive disturbance during the follow-up period that may be correlated with the disease progression. The conclusion is that bilateral STN stimulation is an effective treatment for PD patients at long term but it should be considered earlier in the course of PD.

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.

Bilateral subthalamotomy in Parkinson's disease: initial and long-term response.

We conducted an open label pilot study of the effect of bilateral subthalamotomy in 18 patients with advanced Parkinson's disease. In seven patients, the first subthalamotomy pre-dated the second by 12-24 months ('staged surgery'). Subsequently, a second group of 11 patients received bilateral subthalamotomy on the same day ('simultaneous surgery'). Patients were assessed according to the CAPIT (Core Assessment Program for Intracerebral Transplantation) protocol, a battery of timed motor tests and neuropsychological tests. Evaluations were performed in the 'off' and 'on' drug states before surgery and at 1 and 6 months and every year thereafter for a minimum of 3 years after bilateral subthalamotomy. Compared with baseline, bilateral subthalamotomy induced a significant (P < 0.001) reduction in the 'off' (49.5%) and 'on' (35.5%) Unified Parkinson's Disease Rating Scale (UPDRS) motor scores at the last assessment. A blind rating of videotape motor exams in the 'off' and 'on' medication states preoperatively and at 2 years postoperatively also revealed a significant improvement. All of the cardinal features of Parkinson's disease as well as activities of daily living (ADL) scores significantly improved (P < 0.01). Levodopa-induced dyskinesias were reduced by 50% (P < 0.01), and the mean daily levodopa dose was reduced by 47% at the time of the last evaluation compared with baseline (P < 0.0001). Dyskinesias occurred intraoperatively or in the immediate postoperative hours in 13 patients, but were generally mild and short lasting. Three patients developed severe generalized chorea that gradually resolved within the next 3-6 months. Three patients experienced severe and persistent postoperative dysarthria. In two, this coincided with the patients exhibiting large bilateral lesions also suffering from severe dyskinesias. No patient exhibited permanent cognitive impairment. The motor benefit has persisted for a follow-up of 3-6 years. This study indicates that bilateral subthalamotomy may induce a significant and long-lasting improvement of advanced Parkinson's disease, but the clinical outcome was variable. This variability may depend in large part on the precise location and volume of the lesions. Further refinement of the surgical procedure is mandatory.

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.

Targeting the basal ganglia for deep brain stimulation in Parkinson's disease.

The revitalization of surgery for Parkinson's disease (PD) has fueled discussion about the best methodology to define the target. Placement of electrodes for deep brain stimulation (DBS) requires the usual stereotactic technique but the argument is mainly centered on whether or not microrecording neuronal activity is necessary. We compared the accuracy of calculating the coordinates X (medio-lateral) and Y (rostro-caudal) considered by the classic stereotactic method, i.e., definition of the AC-PC intercomissural line by MRI and a digitized version of the Schaltenbrand's atlas, with final electrode placement according with microrecording and microstimulation in 21 patients. For both the globus pallidum internum (GPi) (n = 21) and the subthalamic nucleus (STN) (n = 36) there was, respectively, a 43% and 45% mismatching of more than 3 mm between the theoretic coordinates and the final site of electrode location. This applies to both the X and Y planes. Accuracy was not improved in patients (n = 11) in whom the bilateral procedure was undertaken in a single day. We conclude that proper electrode positioning of the STN and GPi requires fine electrophysiologic assessment.

Bilateral deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is rapidly becoming the preferred surgical choice for the treatment of advanced Parkinson's disease (PD). We report initial results in 15 patients after 12 months and in nine patients evaluated between 30 and 36 months postoperatively. Our experience confirms the robust antiparkinsonian effect of DBS of the STN in advanced PD. The severity of "off" episodes, as assessed by the Unified Parkinson Disease Rating Scale (UPDRS), was drastically reduced by 74% at 12 months, and dyskinesia scores (Dyskinesia Rating Scale) decreased. The levodopa daily dose was reduced by 55% at 12 months. A double-blind assessment to determine the effect of stimulation performed in nine patients at 3 months in the "off" medication condition was very significant (p<0.05). Nine patients have been followed for 3 years with maintained efficacy in the UPDRS "off" score and the dyskinesia score. The experience of other groups using a similar technique is reviewed. The overall assessment indicates a high antiparkinsonian effect of DBS of the STN even in advanced patients. The existence of a learning curve for this procedure should be taken into account when initial results are evaluated.

Pathophysiologic basis of surgery for Parkinson's disease.

Dopamine depletion induces a series of changes in the basal ganglia motor circuit that underlie the origin of the cardinal features of Parkinson's disease. It has now been established that hyperactivity of the subthalamic nucleus (STN) is an essential feature of the parkinsonian state. This leads to increased excitatory driving onto the globus pallidum internum (GPi) and substantia nigra reticulata (SNr) which, in turn, overinhibits the motor projections to the thalamus and brainstem. The STN and GPi have become the preferred targets for surgery to treat PD. In keeping with the classic pathophysiologic model, physiologic and neuroimaging studies in patients have shown that lesioning or functional blockades (by deep brain stimulation, or DBS) of these nuclei increased cortical activation, in parallel with clinical improvements of bradykinesia. Neuronal recording during surgery has also shown tremor-related activity in both the STN and GPi. However, the pathophysiologic model of the basal ganglia needs further refinement to provide a more detailed explanation of the origin of both tremor and rigidity in Parkinson's disease and to explain the antidyskinetic effect of surgery of the GPi and STN.

Consequences of nigrostriatal denervation on the gamma-aminobutyric acidic neurons of substantia nigra pars reticulata and superior colliculus in parkinsonian syndromes.

To examine the effects of nigrostriatal denervation on the substantia nigra pars reticulata (SNpr), one of the main outputs of the basal ganglia, we used quantitative in situ hybridization to analyze the messenger RNA coding for Mr 67,000 glutamic acid decarboxylase (GAD67 mRNA) in the SNpr neurons from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP), and their respective controls. In MPTP-intoxicated monkeys, the expression of GAD67 mRNA was increased in the SNpr neurons, and the increase was reversed by L-dopa treatment. There were no differences in the level of GAD67 mRNA between PD patients who had been treated with L-dopa and control subjects. Combined with the previously reported increased expression of GAD67 mRNA in the internal segment of the pallidum of MPTP-intoxicated monkeys, these data suggest that the gamma-aminobutyric acid (GABAergic) activity of the output system of the basal ganglia is globally increased by nigrostriatal denervation. We also analyzed the level of GAD67 mRNA expression in the superior colliculus, a structure that receives the inhibitory influence of the GABAergic neurons of the SNpr and that is involved in eye movement control. GAD67 mRNA expression was reduced in both MPTP-intoxicated monkeys, whether or not they received L-dopa therapy, and PD patients, compared to their respective controls. This decrease may result from the hyperactivity of the inhibitory nigrotectal pathway, but also from other influences since it was not corrected by L-dopa therapy. These changes may account for the slight ocular motor and visuospatial cognitive impairment occurring in PD, even after L-dopa therapy.

Consequence of nigrostriatal denervation and L-dopa therapy on the expression of glutamic acid decarboxylase messenger RNA in the pallidum.

To examine the consequences of nigrostriatal denervation and L-dopa treatment on the basal ganglia output system, we analyzed, by quantitative in situ hybridization, the messenger RNA coding for glutamic acid decarboxylase (Mr 67,000) (GAD67 mRNA) in pallidal cells from patients with Parkinson's disease (PD), monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) receiving or not receiving L-dopa, and their respective control subjects. In MPTP-treated monkeys, the expression of GAD67 mRNA was increased in cells from the internal pallidum, and this effect was abolished by L-dopa treatment. There were no differences in the levels of GAD67 mRNA between patients with PD, who were all treated with L-dopa, and control subjects. These results indicate that the level of GAD67 mRNA is increased in the cells of the internal pallidum after nigrostriatal dopaminergic denervation and that this increase can be reversed by L-dopa therapy.

Deep brain stimulation of the globus pallidus pars interna in advanced Parkinson's disease.

Pallidotomy is now widely performed for the treatment of advanced Parkinson's disease (PD). Preliminary reports of the effect of globus pallidus pars interna deep brain stimulation (GPi DBS) have also been promising. We have analyzed a cohort of 22 consecutive patients enrolled in a multicenter study. Surgery was bilateral in 17 and unilateral in five patients. At 6-month follow-up, the bilaterally GPi-implanted patients demonstrated a marked improvement when examined after drug withdrawal ("off") and under optimal medication ("on") using the Unified Parkinson's Disease Rating Scale (UPDRS). The benefit induced by the stimulation in the "off" medication condition in the total motor score was 31% and in the activities of daily living (ADL) scores was 39%. During the "on" medication period, the reduction in the total "on" dyskinesias score was 66% and in the ADL score was 32%. A similar pattern of improvement was seen in the group of patients with unilateral GPi stimulation, although a second cohort of 12 patients not included in the multicenter study showed greater improvements in "on" motor functioning. Although the effect of DBS is predominantly reversible, electrode insertion alone resulted in measurable clinical effects in the absence of stimulation. Thus, at 6-month follow-up, the benefit observed without stimulation was up to 44% in the "on" dyskinesias score and 29% in timed tapping scores undertaken in the "off" medication state. Complications among 34 patients from all centers included perioperative infection (n=3), hardware fracture (n=2), and premature battery failure (n=3). These results show a positive antiparkinsonian effect of pallidal DBS. No specific complications were observed with bilateral procedures.

A brief history of pallidotomy.

A large number of surgical procedures involving the globus pallidus and ansa lenticularis were performed from 1939 to the late 1950s for alleviation of rigidity and tremor, two of the main symptoms of Parkinson's disease. Several groups reported beneficial effects using a wide array of techniques and targets within the pallidum and its projections. Over time, pallidal targets lying in the ventral and posterior portions of the internal pallidum were considered to be the most effective. Based on anatomic studies, surgical misadventures, and empirical observations, there was an abrupt shift regarding the favored target to treat parkinsonian tremor to the thalamus, and most neurosurgeons abandoned pallidotomy in the 1960s. With the advent of L-dopa and the realization of its striking clinical benefits in the mid 1960s, within 5 to 10 years, virtually all surgery for Parkinson's disease ceased. We are now witnessing a rediscovery of pallidotomy as patients with Parkinson's disease are experiencing the shortcomings of medical therapy. In this article, we examine the evolution of pallidotomy and discuss the reasons for the renewed interest in this procedure.

Giant intradiploic epidermoid tumor of the occipital bone: case report.

The authors describe a case of a giant intradiploic epidermoid cyst of the occipital bone with an intracranial extension in the posterior fossa and no signs of neurological involvement. The lesion started as a painless lump under the scalp. Roentgenographic and computed tomographic findings led to a correct diagnosis, and the complete removal of the cyst was accomplished, despite its large size. The total removal of these cysts is associated with a good prognosis.

Stereotactic targeting of the globus pallidus internus in Parkinson's disease: imaging versus electrophysiological mapping.

OBJECTIVE: The reintroduction of pallidotomy for the treatment of Parkinson's disease (PD) has generated various opinions regarding the ideal anatomic or physiological location of the target within the globus pallidus. The role of microelectrode recording guidance in pallidotomy for the treatment of advanced PD is presently under debate. The purpose of this study was twofold. The first goal was to determine the degree of accuracy in the targeting of the globus pallidus internus (GPi) with magnetic resonance imaging (MRI), by comparing these results with the final placement of the thermolytic lesions (as defined by electrophysiological assessment). The second goal was to ascertain the somatotopic arrangement of the GPi in PD. METHODS: The analysis involved 50 patients with PD who underwent microrecording-guided pallidotomy. The theoretical coordinates for lesioning were calculated after definition of the intercommissural line by MRI. The actual placement of the lesions was determined after mapping of the GPi by microrecording, using stimulation to identify the sensorimotor region and its somatotopic organization. RESULTS: In most cases, the lesions were placed posterior and lateral to the targets chosen by MRI. Mapping by microrecording revealed differences of 2.3 +/- 1.55 mm and 3 +/- 1.9 mm in the mediolateral and anteroposterior coordinates, respectively. The actual lesion overlapped the theoretical target for only 45% of the patients. The somatotopic organization of the GPi was analyzed. Most of the units with sensorimotor activity or tremor-related activity were in the lateral portion of the nucleus. Upper limb and axial units were in the most lateral region and mainly in the ventral one-third of the nucleus. Lower limb responses were recorded mainly in the dorsal one-third of the nucleus. Tremor-related cells were found throughout the sensorimotor region of the nucleus. CONCLUSION: These results indicate that lesion targeting based on MRI alone is not sufficiently accurate to guarantee placement of the lesion in the sensorimotor region of the GPi.

[Surgical treatment for Parkinson's disease]. / Servicio de Neurocirugía, Departamento de Neurociencias. Clinica Universitaria. Universidad de Navarra. Pamplona, USA.

In the past years there has been an increasing interest in the surgical therapies for Parkinson's disease. This renewed interest is related to differents factors. First, pharmacological treatments are still unable to alter substantially the progression of the disease and after a few years they generally cause motor complications and dyskinesias. Secondly, the great advances in the surgical techniques, especially with the improvement of stereotactic surgery, have decreased morbidity in recent years. Finally, the introduction of deep brain stimulation, now allows surgical treatment without damaging brain structures. In this review, different surgical treatments are summarized. Ablative surgery, deep brain stimulation and reinervation therapies are described.

[Surgery of the subthalamic nucleus in Parkinson's disease]. / Cirugía del núcleo subtalámico en la enfermedad de Parkinson.

INTRODUCTION AND DEVELOPMENT: The subthalamic nucleus (STN) plays a crucial part in the pathophysiology of Parkinsonism. Its inactivation improves all the main signs and symptoms of Parkinson's disease. Surgery of the STN in patients with the disease is effective and the benefit/risk relationship very favorable. Although the dyskinesias are not a definite limitation, it seems most reasonable to use techniques of deep cerebral stimulation until greater experience has been obtained with subthalamotomy. The long term efficacy is being studied and preliminary data indicate that the clinical benefit obtained is maintained in the long term. CONCLUSIONS: More studies are necessary to determine the mechanism of action of surgery on the STN. The potential neuroprotector effect of subthalamic surgery requires more extensive study.