Unilateral subthalamotomy in Parkinson's disease: Cognitive, psychiatric and neuroimaging changes.

Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency.

Registro cerebral profundo y tiempo quirúrgico en la neurocirugía estereotáctica funcional para trastornos del movimiento / Deep brain recording and length of surgery in stereotactic and functional neurosurgery for movement disorders

OBJETIVO: Estudiar la duración de los registros cerebrales multiunitarios (RCM) en 20 años de neurocirugías en trastornos del movimiento, así como las veces en que fue necesario explorar todos los trayectos de los electrodos en las posiciones registradas simultáneamente (PRS) por grupos que usan registros cerebrales unitarios (RCU). MATERIAL Y MÉTODO: Análisis estadístico descriptivo retrospectivo de la duración de los RCM en 4.296 trayectos en 952 cirugías. Los criterios de exclusión fueron: trayectos con menos de 5 señales grabadas, o con señales con duración diferente de los 2 s habituales, o cuando existieron situaciones no usuales, ni relacionadas con los RCM, así como las primeras 20 cirugías de cada blanco quirúrgico, resultando así un total de 3.448 trayectos en 805 cirugías. Del total de 952 cirugías, se analiza además en cuántas de ellas fueron explorados todos los trayectos en las PRS de RCU. RESULTADOS: La media y su intervalo de confianza (p = 0,05) del tiempo por trayecto de RCM es 5,49 ± 0,16 min en cirugía en núcleo subtalámico; 8,82 ± 0,24 min en globo pálido medial o interno; y 18,51 ± 1,31 min en núcleo ventral intermedio del tálamo. Para la suma total de trayectos por cirugía, en el 75% de los casos el tiempo total es de menos de 39 min en núcleo subtalámico, casi 42 min en globo pálido medial o interno y menos de 1h y 17 min en núcleo ventral intermedio del tálamo. En solo el 4,2% de las cirugías fueron explorados todos los trayectos en las PRS de RCU. CONCLUSIONES: El impacto de los RCM en el tiempo quirúrgico es aceptable para esta guía en la localización objetiva de los blancos quirúrgicos, sin tener que usar varios electrodos simultáneos, no todos imprescindibles en la mayoría de los casos, con menor riesgo así para el paciente

OBJECTIVE: Our objectives were to study the length of multi-unit recordings (MURs) of brain activity in 20 years of movement disorder neurosurgeries and to determine the number of times in which it was necessary for the teams using single-unit recording (SUR) to explore all the electrode tracks in the simultaneously recorded sites (SRS). MATERIAL AND METHOD: This was a retrospective descriptive statistical analysis of MUR lengthon 4,296 tracks in 952 surgeries. The exclusion criteria were: tracks with fewer than 5 recorded signals, tracks that had a signal length different from the habitual 2 s, or there being unusual situations not related to the MUR, as well as the first 20 surgeries of each surgical target. This yielded a total of 3,448 tracks in 805 surgeries. We also determined the number of the total 952 surgeries in which all the tracks in the SURs of the SRS were explored. RESULTS: The mean and its confidence interval (P = .05) of time per MUR track were5.49 ± 0.16 min in subthalamic nucleus surgery, 8.82 ± 0.24 min in the medial or internalglobus pallidus) and 18.51 ± 1.31min in the ventral intermediate nucleus of the thalamus. For the total sum of tracks per surgery, in 75% of cases the total time was less than 39 min insubthalamic nucleus, almost 42 min in the medial or internal globus pallidus and less than1 h and 17min in ventral intermediate nucleus of the thalamus. All the tracks in the SURSRS were explored in only 4.2% of the surgeries. CONCLUSIONS: The impact of MUR on surgical time is acceptable for this guide in objective

Dystonia and tremor secondary to thalamic infarction successfully treated with thalamotomy of the ventralis intermedius nucleus.

BACKGROUND: Focal thalamic lesions have been associated with a variety of involuntary movements such as tremor, dystonia, and chorea-ballism. METHODS: We describe a patient with severe hyperkinesias of the right arm secondary to a thalamic infarction in the left postero-ventral region of the thalamus. RESULTS: The dystonia and tremor of the right upper limb were subsequently controlled with another surgical lesion of the ventralis intermedius nucleus of the thalamus. CONCLUSION: This observation suggests that ablative surgery might be applied to treat a movement disorder induced by the lesion of the same nucleus, which in addition lead to interesting pathophysiological conjectures.

The subthalamic nucleus and inhibitory control: impact of subthalamotomy in Parkinson's disease.

The aim of our study was to investigate two inter-related hypotheses about the role of the subthalamic nucleus. First that the subthalamic nucleus plays a role in adjusting response thresholds and speed-accuracy trade-offs and second that it is involved in reactive and proactive inhibition and conflict resolution. These were addressed by comparing the performance of 10 patients with Parkinson's disease treated with right subthalamotomy and 12 patients with left subthalamotomy, to 14 unoperated patients with Parkinson's disease and 23 age-matched healthy control participants on a conditional stop signal task and applying the drift diffusion model. Unilateral subthalamotomy significantly improved Parkinson's disease motor signs. Patients with right subthalamotomy had significantly faster Go reaction times with their contra-lesional hand than the unoperated patients and did not differ from the control participants, indicating their speed of response initiation was 'normalized'. However, operated patients made significantly more discrimination errors than unoperated patients and controls, suggesting that subthalamotomy influenced speed-accuracy trade-offs. This was confirmed by the drift diffusion model, revealing that while the unoperated patients had significantly lower drift rate and higher response thresholds than the control participants, the response thresholds for the operated groups did not differ from the controls and the patients with right subthalamotomy had a significantly higher drift rate than unoperated patients and similar to that of controls. The drift diffusion model further established that unlike the control participants, operated patients failed to show context-dependent strategic modulation of response thresholds. The patients with right subthalamotomy could not engage in late phase, fast inhibition of the response and showed minimal proactive inhibition when tested with the contra-lesional hand. These results provide strong evidence that the subthalamic nucleus is involved in response inhibition, in modulating the rate of information accumulation and the response threshold and influencing the balance between speed and accuracy of performance. Accordingly, the subthalamic nucleus can be considered a key component of the cerebral inhibitory network.

[Deep brain recording and length of surgery in stereotactic and functional neurosurgery for movement disorders]. / Registro cerebral profundo y tiempo quirúrgico en la neurocirugía estereotáctica funcional para trastornos del movimiento.

OBJECTIVE: Our objectives were to study the length of multi-unit recordings (MURs) of brain activity in 20 years of movement disorder neurosurgeries and to determine the number of times in which it was necessary for the teams using single-unit recording (SUR) to explore all the electrode tracks in the simultaneously recorded sites (SRS). MATERIAL AND METHOD: This was a retrospective descriptive statistical analysis of MUR length on 4,296 tracks in 952 surgeries. The exclusion criteria were: tracks with fewer than 5 recorded signals, tracks that had a signal length different from the habitual 2s, or there being unusual situations not related to the MUR, as well as the first 20 surgeries of each surgical target. This yielded a total of 3,448 tracks in 805 surgeries. We also determined the number of the total 952 surgeries in which all the tracks in the SURs of the SRS were explored. RESULTS: The mean and its confidence interval (P=.05) of time per MUR track were 5.49±0.16min in subthalamic nucleus surgery, 8.82±0.24min in the medial or internal globus pallidus) and 18.51±1.31min in the ventral intermediate nucleus of the thalamus. For the total sum of tracks per surgery, in 75% of cases the total time was less than 39min in subthalamic nucleus, almost 42min in the medial or internal globus pallidus and less than 1h and 17min in ventral intermediate nucleus of the thalamus. All the tracks in the SUR SRS were explored in only 4.2% of the surgeries. CONCLUSIONS: The impact of MUR on surgical time is acceptable for this guide in objective localization for surgical targets, without having to use several simultaneous electrodes (not all indispensable in most of the cases). Consequently, there is less risk for the patient.

Deficits in inhibitory control and conflict resolution on cognitive and motor tasks in Parkinson's disease.

Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.

Cognitive and neuropsychiatric effects of subthalamotomy for Parkinson's disease.

Since the advent of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD), subsequent cognitive and neuropsychiatric effects of this procedure have become well-chronicled. Yet, thermolitic lesion of the subthalamic nucleus (STN) is still a valid option when DBS cannot be applied, and little has been published regarding its impact on cognition and mood. We examined the cognitive and neuropsychiatric functions of 10 consecutive patients with advanced PD undergoing simultaneous bilateral subthalamotomies. With 24 months of follow-up, the patients, three of whom were on anticholinergics prior to surgery, showed no deterioration in cognitive assessments including verbal fluency. Hypoactive behaviors (depression and apathy) showed lasting improvement, while hyperactive behaviors (euphoria and disinhibition) transiently increased after surgery. Improvement in hypoactive behaviors correlated with improvement in hypokinetic movements, and enhanced hyperactive behaviors followed the course of post-operative hyperkinetic movements. Such correlations may support the role of the STN in modulating limbic connections between the basal ganglia and frontal cortex. The results of this proof-of-concept pilot study suggest the need for larger, long-term, randomized controlled studies to assess motor, neuropsychiatric, behavioral and radiologic correlations after subthalamotomies.

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms.

A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

Anatomic and neurophysiological methods for the targeting and lesioning of the subthalamic nucleus: Cuban experience and review.

OBJECTIVE: To develop a method to place a lesion precisely in the subthalamic nucleus (STN) and evaluate its effectiveness. METHODS: A retrospective study of targeting data collected during stereotactic planning to lesion the STN in 31 patients with Parkinson's disease and of results in more than 50 procedures was performed. The targeting method was based on computed tomographic imaging together with semimicroelectrode recording digital processing and electrical stimulation. Two statistical methods were used to correlate initial with final target coordinates and assess the efficacy of the targeting procedure. RESULTS: The anatomic target based on computed tomographic imaging data showed electrical activity in the subthalamus in the first pass in 82% of the procedures. In the remaining 18%, the STN was an average of 1.93 mm away from the nearest trajectory that recorded the STN (range, 1.41-2.24 mm). The average number of trajectories per procedure was 7.2; the location of the first trajectory relative to the center of the nucleus determined by electrical and physiological means (P < 0.01, analysis of variance, Student's t test) was as follows: in the lateral direction, 1.25 +/- 1.15 mm; in the anteroposterior direction, 1.53 +/- 1.31 mm; and in the vertical direction, 0.67 +/- 0.51 mm. The average number of tracts necessary to lesion the STN was two. CONCLUSION: The combination of computed tomographic imaging, semimicroelectrode recording, and microstimulation provides an effective method to identify the STN lesion in parkinsonian patients. The method used for anatomic localization and electrophysiological mapping of the subthalamus was found to be effective in reaching the sensorimotor region of the nucleus. We carried out an accurate determination of the subthalamus location and its volume in the lesioning.

Personal-compputer-based system for three-dimensional anatomic-physiological correlations during stereotactic and functional neurosurgeryç

This paper describes the automatic three-dimensional (3D) graphic possibilities that are supplied by the Neurosurgical Deep Recording System (NDRS) to facilitate anatomic-physiological targeting during stereotactic and functional neurosurgery using depth recording. This software has been developed to substitute the complex electronic equipment ordinarily used for deep brain electrical recording, display and processing by a personal computer. It may also help to improve on-line graphic analysis, automatic management of the recorded information and flexibility to implement different forms of signal analysis. It can automatically show a 2D or 3D representation of the electrode track, with the electrophysiological findings superimposed as well as the corresponding sagittal, coronal and axial views of a brain atlas using automatic scaling. The NDRS has already successfully been applied during more than 300 neurosurgeries in Spain and Cuba, enabling improved targeting accuracy and safety(AU)

Immunological study in Parkinson's disease patients with intracerebral allografts

Immunological response was characterized in 15 patients with Parkinso's disease intracerebrally transplanted: seven in unilateral and eight in bilateral hemisphere with fetal mesencephalic cells by stereotactical technique. The phenotypic distribution of mononuclear cells in CSF and PB was investigated using monoclonal antibodies. The total protein, albumin and IgG in CSF and albumin, IgA, IgM and IgG Concentration in serum were also analyzed, before and after evolution. A general decrease in CD2+ cells was found in patients with unilateral neurotransplantation during the first semester following trasplant. A small increase in the proportion of CSF CD8+ cells was observed in the first month and in the fourth month in PB. In patients with bilateral intracerebral allografts a decrease in CD2+ and CD4+ cells was found during the first and fourth month. The intrathecal synthesis of IgG during the fourth month was observed in both patients. Results are discussed taking into account the immunosupressor treatment(AU)

Ablative surgery for Parkinson's disease

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Surgical treatment of Parkinson's disease

Summary. At present there are major surgical approaches to Parkinson's disease (PD): (1). Ablative surgery (i.e. pallidotomy, thalamotomy); (2) deep brain stimulation (DBS) of the thalamus, internal globus pallidus (GPi) and subthalamic nucleus (STN); and (3) grafting fetal mesencephalic cells into the striatum. The aim of pallidotomy and DBS is to reduce the excessive inhibitory output from the GPi and substantia nigra reticulata (SNr). Pallidotomy and DBS of the STN or GPi aim to reverse the pathophysiological consequences of dopamine deficiency in PD, and should be considered entirely symptomatic treatments. The ideal candidates for pallidotomy are young patients in good general health in whom dyskinesias are the main reasons for disability. Patients with severe bilateral problems uncontrollable with present pharmacological tools are candidates for DBS. Grafting aims to repair the nigrostriatal pathway and restore dopaminergic function in the striatum. In the future implants containing not only dopaminergic cells but also growth factors and a variety of other substances could become a method to not only functionally compensate the biochemical abnormalities of PD but also to arrest its progression. At present, grafting of dopaminergic cells is perhaps best suited for patients with young-onset PD (less than 45 years old) who are at high risk of developing complications within a short time of begining pharmacological treatment and in whom the idea of making lesions or implanting electrodes into the brain for decades seems less appealing. Consideration of surgery in any given patient should be weighed against the risks (about 1 per cent mortality and 2-6 per cent of severe morbidity-hemiplegia, cognitive deficit, speech problems, etc.) associated with these techniques. The development of better imaging methods and the growing expertise of multidisciplinary teams will undoubtedly make surgery for PD safer and more effective in the future(AU)