El papel de la tractografía en la localización del núcleo ventralis intermedius del tálamo y el haz dentatorrubrotalámico en el tratamiento del temblor / 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

Introducción: La diana habitual empleada para el tratamiento quirúrgico del temblor es el núcleo ventralis intermedius (Vim) del tálamo. Su localización es compleja, ya que no se puede visualizar con métodos de imagen convencionales, por lo que para el procedimiento quirúrgico se toman clásicamente medidas indirectas y se correlacionan con la clínica y neurofisiología intraoperatorias. Sin embargo, procedimientos ablativos actuales como la talamotomía por gamma-knife o por ultrasonidos (MRgFUS) hacen que sea preciso buscar otras alternativas para su localización. El objetivo del presente trabajo es comparar la localización indirecta del Vim mediante técnica esterotáctica con la realizada directamente por tractografía para el tratamiento del temblor.DiscusiónLa definición citoarquitectónica más empleada del Vim es la del atlas de Schaltenbrand-Wahren. Existe un límite claro entre el tálamo motor y el sensitivo; las neuronas del Vim responden a movimientos pasivos articulares y su actividad es sincrónica con el temblor periférico. Las coordenadas estereotácticas del Vim más frecuentemente utilizadas se basan en mediciones indirectas respecto a la línea intercomisural y el III ventrículo, las cuales dependen de variaciones interindividuales. Estudios recientes han propuesto el haz dentatorrubrotalámico como una diana óptima para el control del temblor, postulando que se asocia a una mejoría clínica; sin embargo, esto no ha sido corroborado por otros autores.ConclusionesLa visualización de la vía cerebelorrubrotalámica por tractografía puede ayudar a definir la localización del Vim. Esta técnica tiene limitaciones inherentes y sería necesaria una estandarización del método para lograr resultados más precisos. La posible mayor utilidad de la diana por tractografía, directa, sobre la indirecta queda por demostrar a largo plazo en pacientes con temblor. (AU)

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.DiscussionThe 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.ConclusionsVisualisation 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. (AU)

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.

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.

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

La estimulación cerebral profunda para las enfermedadespsiquiátricas que son refractarias a los distintostratamientos convencionales, se está realizandoactualmente debido en gran parte a los conocimientosadquiridos en la cirugía para los trastornos del movimiento,sobre todo la enfermedad de Parkinson (EP).La depresión, los trastornos obsesivo-compulsivos(TOC) y el síndrome de Gilles de la Tourette son problemascórtico-estriato-tálamo-corticales relacionados conlos circuitos límbicos de los ganglios basales.En esta revisión se analizan las distintas dianas quirúrgicaspara las diferentes patologías neuro-psiquiátricas.Para el TOC actualmente existen dos dianas,el complejo estriado ventral (VS)-núcleo accumbens(Nacc) y el núcleo subtalámico (NST). Para la depresiónrefractaria, el área subgenual (área 25 de Brodmann)y el VS/Nacc. Para el Tourette, el ventralis oralisinterno y centromediano parafascicularis (Voi, CM/Pf)del tálamo y el globo pálido interno (GPi). En la actualidadno existe una única diana específica en cualquierade las patologías, ya que los resultados clínicos tras laestimulación pueden considerarse similares. Por otrolado, una misma diana quirúrgica puede mejorar diferentespatologías (AU)

Deep brain stimulation (DBS) for psychiatricdisorders refractory to conventional treatments arecurrently been performed based in the knowledgmentobtained in the motor disorder surgery and mainly inParkinson´s disease. Depression, obsessive-compulsivedisorder (OCD) and Tourette syndrome, all of them arecortico-striato-thalamo-cortical pathological processinvolved in the limbic loop of the basal ganglia.This review describes the different targets in thesepathological neuro-psychiatric disorders. For OCDthere are currently two targets, ventral striatum (VS)Accumbens nucleus (Nacc) and the subthalamic nucleus(STN). In refractory depression the subgenual area (25Brodmann area) and VS/Nacc. For Tourette syndromethe ventralis oralis internus and centromedianum/parafascicularis of the thalamus (Voi and CM/Pf) andthe internal part of the globus pallidus (GPi). Currentlythere are no specific surgical target for each pathologicaldisorder because clinical results reported arevery similar after stimulation surgery. In other point,a selected surgical target also may improve differentpathologies (AU)

Changes in subthalamic activity during movement observation in Parkinson's disease: is the mirror system mirrored in the basal ganglia?

OBJECTIVE: The observation of a voluntary movement executed by another person is associated with an alpha and beta EEG desynchronization over the motor cortex, thought to reflect activity from the human "mirror neuron" system. The aim of our work was to study the changes in local field potentials (LFP) recorded from the subthalamic nucleus (STN) and their relationship with cortical activity, during movement observation. METHODS: Bilateral EEG and STN LFP recordings were acquired in 18 patients with Parkinson's disease, through surgically implanted electrodes for deep brain stimulation. Oscillatory changes during movement execution and movement observation were compared with two different control conditions (simple stimulus and rotating stimulus observation), in "off" and "on" motor states. Time-frequency transforms and event-related coherence were used for the analysis. RESULTS: Movement observation was accompanied by bilateral beta reduction in subthalamic power and cortico-STN coherence, which was smaller than the decrease observed during movement execution, but significant when compared with the two control conditions. CONCLUSIONS: Movement observation is accompanied by changes in the beta oscillatory activity of the STN, similar to those observed in the EEG. SIGNIFICANCE: These changes suggest that the basal ganglia might be engaged by the activity of the human mirror system.

[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.

What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

We have studied motor performance in a man with Parkinson's disease (PD) in whom thermolytic lesions of the left subthalamic and left globus pallidus nuclei interrupted the basal ganglia (BG)-thalamo-cortical motor circuit in the left hemisphere. This allowed us to study remaining motor capabilities in the absence of aberrant BG activity typical of PD. Movements of the left arm were slow and parkinsonian whereas movement speed and simple reaction times (RT) of the right (operated) arm were within the normal range with no obvious deficits in a range of daily life activities. Two main abnormalities were found with the right hand. (a) Implicit sequence learning in a probabilistic serial reaction time task was absent. (b) In a go/no-go task when the percent of no-go trials increased, the RT superiority with the right hand was lost. These deficits are best explained by a failure of the cortex, deprived of BG input, to facilitate responses in a probabilistic context. Our findings confirm the idea that it is better to stop BG activity than allowing faulty activity to disrupt the motor system but dispute earlier claims that interrupting BG output in PD goes without an apparent deficit. From a practical viewpoint, our observations indicate that the risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producing deficits that impair activities of daily life.

[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.

Radioterapia estereotáctica / Stereotactic radiation therapy

La radioterapia con técnica estereotáctica es unamodalidad de radioterapia externa que utiliza un sistemade coordenadas tridimensionales independientes delpaciente para la localización precisa de la lesión. Tambiénse caracteriza porque los haces de irradiación sonaltamente conformados, precisos y convergentes sobrela lesión que hacen posible la administración de dosismuy altas de radioterapia sin incrementar la irradiaciónde los órganos o estructuras sanas adyacentes. Cuandoel procedimiento se realiza en una sesión de tratamientose denomina radiocirugía y si se administra en variassesiones se denomina radioterapia estereotáctica. Seprecisa de sistemas de fijación e inmovilización del pacienteespeciales (guías o marcos estereotácticos) y dispositivosde radioterapia capaces de generar haces muyconformados (acelerador lineal, gammaknife, cyberknife,tomoterapia, ciclotrones). La radioterapia estereotácticamoderna utiliza marcas radioopacas intratumorales osistemas de imágenes de TAC incluidos en el dispositivode irradiación, que permiten una precisa localizaciónde las lesiones móviles en cada sesión de tratamiento.Además, los avances tecnológicos hacen posible coordinarlos movimientos de la lesión en la respiración con launidad de radioterapia (gaiting y tracking) de forma quepueden estrecharse al máximo los márgenes y por lo tantoexcluir un mayor volumen de tejido sanoLa radiocirugía está indicada principalmente en lesionescerebrales benignas o malignas menores de 3-4centímetros (malformaciones arteriovenosas, neurinomas,meningiomas, metástasis cerebrales) y la radioterapiaestereotáctica se administra fundamentalmenteen tumores de localización extracraneal que requieranuna alta conformación y precisión como cáncer precozde pulmón inoperable y metástasis hepáticas(AU)

Stereotactic radiotherapy is an external radiationmodality that uses a system of three dimensional referencesindependent of the patient to achive a preciselocation of the lesion. Stereotactic radiotherapy generatehighly conformal, precisely focused radiationbeams to administer very high doses of radiation withoutincreasing the radiation to healthy surroundingorgans or structures. When the procedure is carriedout in one treatment session the procedure is termedradiosurgery, and when the treatment is administeredin several fractions, the radiation modality is termedstereotactic radiotherapy. Special systems of patientimmobilization (guides or stereotactic frames) are requiredtogether with radiotherapy devices capable ofgenerating conformal beams (lineal accelerator, gammaknife,cyberknife, tomotherapy, cyclotrons). Modernstereotactic radiotherapy techniques employ intratumouralradio-opaque fiducials or CT image systemsincluded in the irradiation device, which make possiblea precise location of mobile lesions in each treatmentsession. Besides, technological advances permit breathingsynchronized radiation (gating and tracking) formaximum tightening of margins and excluding a greatervolume of healthy tissue.Radiosurgery is mainly indicated in benign or maligncerebral lesions less than 3-4 centimetres (arteriovenousmalformations, neurinomas, meningiomas,cerebral metastases) and stereotactic radiotherapy isbasically administered in tumours of extracraneal locationthat require high conformation and precision, suchas inoperable early lung cancer and liver metastasis(AU)

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.

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.

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 percent) and on (35.5 percent) 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...(AU)

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.