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.

Clinical features, pathophysiology, and treatment of levodopa-induced dyskinesias in Parkinson's disease.

Dyskinetic disorders are characterized by excess of motor activity that may interfere with normal movement control. In patients with Parkinson's disease, the chronic levodopa treatment induces dyskinetic movements known as levodopa-induced dyskinesias (LID). This paper analyzed the pathophysiology, clinical manifestations, pharmacological treatments, and surgical procedures to treat hyperkinetic disorders. Surgery is currently the only treatment available for Parkinson's disease that may improve both parkinsonian motor syndrome and LID. However, this paper shows the different mechanisms involved are not well understood.

[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.

[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.

[Stereotactic radiation therapy]. / Radioterapia estereotáctica.

Stereotactic radiotherapy is a form of external radiotherapy that employs a system of three dimensional coordinates independent of the patient for the precise localisation of the lesion. It also has the characteristic that the radiation beams are conformed and precise, and converge on the lesion, making it possible to administer very high doses of radiotherapy without increasing the radiation to healthy adjacent organs or structures. When the procedure is carried out in one treatment session it is termed radiosurgery, and when administered over several sessions it is termed stereotactic radiotherapy. Special systems of fixing or immobilising the patient (guides or stereotactic frames) are required together with radiotherapy devices capable of generating conformed beams (lineal accelerator, gammaknife, cyberknife, tomotherapy, cyclotrons). Modern stereotactic radiotherapy employs intra-tumoural radio-opaque frames or CAT image systems included in the irradiation device, which make possible a precise localisation of mobile lesions in each treatment session. Besides, technological advances make it possible to coordinate the lesion's movements in breathing with the radiotherapy unit (gating and tracking) for maximum tightening of margins and excluding a greater volume of healthy tissue. Radiosurgery is mainly indicated in benign or malign cerebral lesions less than 3-4 centimetres (arteriovenous malformations, neurinomas, meningiomas, cerebral metastases) and stereotactic radiotherapy is basically administered in tumours of extracraneal localisation that require high conforming and precision, such as inoperable early lung cancer and hepatic metastasis.

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.

Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements.

A voluntary movement is accompanied by a series of changes in neuronal oscillatory activity in the subthalamic nucleus (STN). These changes can be recorded through electrodes implanted for deep brain stimulation to treat Parkinson's disease in the time interval between the surgery and the internalization of the connections to the batteries. Both baseline activity and movement-related changes are different in the 'on' and 'off' medication motor states. In the 'off' state a low frequency activity in the alpha-beta range (8-25 Hz) that dominates the spectrum is interrupted during the movement, while in the 'on' state baseline frequencies are higher and a peri-movement gamma increase (70-80 Hz) is usually observed. Similar changes have been described with electrocorticographic recordings over the primary motor cortex but the gamma increase was only present during contralateral movements. We compared ipsi- and contralateral movement-related changes in STN activity, using a time-frequency analysis of the recordings obtained simultaneously in both STN and the scalp (electroencephalography) during right and left hand movements. The movement-related changes observed in the STN in the 'on' and the 'off' states were similar to those described previously in terms of predominant frequency bands, but we found bilateral changes in the STN during movements of either hand. A contralateral earlier start of the beta STN changes was mostly observed when the moving hand corresponded to the less-affected side, irrespective of hand dominance. These results suggest that movement-related activity in the STN has, by and large, a bilateral representation and probably reflects cortical input.

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.

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.

Efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson's disease 4 years after surgery: double blind and open label evaluation.

OBJECTIVE: To evaluate the long term (4 years) efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease. METHODS: We performed a double blind crossover evaluation of the efficacy of DBS of the STN in the "off" medication condition in 10 patients with Parkinson's disease. Assessments included the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor) and two timed tests (arm tapping and walking). Open evaluation of the effect of stimulation in the off and on drug states preoperatively and at 1 and 4 years postoperatively was also conducted. The latter assessment included the UPDRS parts II (activities of daily living) and III (dyskinesia scale and global assessment) as judged by the patient and examiner. The mean amount of levodopa daily dose at base line, 1 year, and 4 years after surgery was compared. RESULTS: A significant (p<0.04) effect of stimulation was observed in the overall group regarding both the UPDRS motor and the timed tests. Open evaluation also showed a significant benefit of STN DBS with respect to preoperative assessment in both the motor and activities of daily living scales, dyskinesia scale, and in global assessment. Levodopa daily dose was reduced by 48% and 50% at 1 and 4 years, respectively. There was no difference between the 1 and 4 years evaluations in any of the parameters evaluated. Complications due to stimulation were minor. CONCLUSIONS: DBS of the STN provides a significant and persistent anti-parkinsonian effect in advanced Parkinson's disease 4 years after surgery.

[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.

[Primary low-grade non-Hodgkin's B lymphoma mimicking meningioma]. / Linfoma dural primario no Hodgkin B de bajo grado simulando un meningioma.

Primary dural lymphomas are rare. Usually they present themselves as diffuse lesions and are infrequently well-delimited. We present a 44 year old male, who was admitted into our Centre after a generalised seizure. Neuroimage studies (CT scan, MRI and angiography) were performed, demonstrating a right hemispheric well-delimited extra-axial mass, being diagnosed initially as meningioma. The patient underwent surgery with radical scission of the mass and dural margins. Histopathological diagnosis was Non-Hodgkin B-Cell lymphoma (marginal B-Cell lymphoma), which nowadays is considered as MALT lymphoma (Mucosa Associated Lymphoid Tissue). Studies directed to establish tumour extension didn't demonstrate the existence of another lesions in the organism.

[Discrepancy between imaging and neurophysiology in deep brain stimulation of medial pallidum and subthalamic nucleus in Parkinson's disease]. / Discrepancia entre imagen y neurofisiología en estimulación cerebral profunda en el globo pálido medial y núcleo subtalámico en la enfermedad de Parkinson.

OBJECTIVE: The objective of this work is to assess the discrepancy in distance between the target chosen by magnetic resonance imaging (MRI) and the final electrode placement after intraoperative microrecording in patients submitted to deep brain stimulation (DBS) for alleviating the Parkinson's disease (PD). METHODS: Thirty patients with PD and motor complications were operated with stereotactic surgery by MRI and microrecording. In 19 patients, the target chosen was the subthalamic nucleus (STN) and in 11 others the target was globus pallidus internus (GPi). In this work it is considered that the electrode has a current field below usual parameters of 1.5 mm radius. Consequently, when the distance error between the final physiological target and the MRI target, is between 1.5 and 3 mm was considered as partial discrepancy and distances of 3 mm or more were considered as total discrepancy. RESULTS: Partial discrepancy for STN and GPi were in 25 and 33% of the cases respectively and total discrepancy was 57 and 42% for each nucleus. The average distance error between both targets, final and image, for X stereotactic coordinate (mediolateral distance) was 1.54 mm for STN and 0.8 mm for GPi. The average distance for Y coordinate (anteroposterior distance) was 2.3 mm for STN and 2.2 mm for GPi. CONCLUSION: There is a significant discrepancy between the final physiological target after microrecording and the target chosen by MRI during surgery for alleviating PD that may induce variations or absence of clinical efficacy in parkinsonian patients submitted to the DBS surgery. Authors suggest the necessity of the microelectrode recording in order to reach the surgical target with the best clinical condition.

The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.

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 (> or =14 mm plane) to leg-related neurones, which were found more medially (< or =12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (approximately 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 substantia 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.

[Intracranial hemorrhage from an arteriovenous malformation (AVM) in a tuberous sclerosis patient]. / Hemorragia intraparenquimatosa por una malformación arteriovenosa en una paciente con esclerosis tuberosa.

We describe a previously diagnosed tuberous sclerosis patient that arrived to the hospital with an intracerebral hemorrhage whose origin was an arteriovenous malformation (AVM). A craniectomy was performed and the hematoma was evacuated with the alleviation of the patient. Although the association between tuberous sclerosis and intracerebral hemorrhage is known in the literature it has never been described associated with an AVM.

[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.

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.

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.

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.