Estimulación cerebral profunda: 12 años de experiencia y 250 pacientes intervenidos con un seguimiento de más de un año / Deep brain stimulation: 12 years experience and 150 patients treated with a follow-up of over a year

Introduction. Deep brain stimulation (DBS) is a widely accepted clinical technique. The main motor symptoms are significantly reduced. The success of the technique depends on the experience of the neurosurgeon, neurologist and neurophysiologist who carry it out. The presentation of extensive series is needed to confirm and further currently held knowledge. Aim. To demonstrate the clinical benefits of a long series of patients treated by a single group with a minimum follow-up of one year and to report new neurophysiological data. Patients and methods. The study examined a total of 250 patients with different diagnoses: most of them with Parkinson’s disease, tremor and dystonia. The nuclei that were chosen were located by magnetic resonance imaging, computerised axial tomography and neurophysiological registers. Neurophysiological exclusion criteria, such as reflex control of heart rate, sympathetic skin response and auditory startle reflex, are employed in order to exclude patients with Parkinson-plus. Results. The motor sub-scale (part III) of the Unified Parkinson’s Disease Rating Scale improves by 64% in the off-medication status with sub-thalamic stimulation at one year after surgery. One year after DBS, patients with dystonia show a significant decrease on the Burke-Fahn-Marsden dystonia scale. The improvement on the scales continues, with a mean descent of 65% in the second year after surgery. Conclusions. DBS is a suitable technique for the treatment of movement disorders. The neuronal activity of the sub-thalamus and the internal globus pallidus presents its own characteristics that reflect the motor symptoms of the patients. Surface electromyography proves to be useful for quantifying the patients’ improvement (AU)

Introducción. La estimulación cerebral profunda (ECP) es una técnica de gran aceptación clínica. Los principales síntomas motores se reducen significativamente. El éxito de la técnica radica en la experiencia del neurocirujano, neurólogo y neurofisiólogo que lo llevan a cabo. La presentación de series extensas es necesaria para confirmar y extender los actuales conocimientos. Objetivo. Demostrar los beneficios clínicos de una larga serie de pacientes intervenidos por un único grupo con un seguimiento mínimo de un año y presentar nuevos datos neurofisiológicos. Pacientes y métodos. Se han estudiado 250 pacientes con diversos diagnósticos; la mayoría con enfermedad de Parkinson, temblor y distonía. Los núcleos elegidos se localizan por resonancia magnética, tomografía axial computarizada y registros neurofisiológicos. Se utilizan criterios de exclusión neurofisiológicos, como el control reflejo de la frecuencia cardíaca, la respuesta simpaticocutánea y el reflejo de sobresalto auditivo, para excluir pacientes con Parkinson-plus. Resultados. La subescala motora (parte III) de la Unified Parkinson’s Disease Rating Scale mejora un 64% en situación off de medicación con la estimulación del subtálamo al año de la cirugía. Los pacientes con distonía muestran, un año después de la ECP, en la escala de distonía Burke-Fahn-Marsden, un descenso significativo. La mejoría en las escalas persiste, con un descenso medio del 65% en el segundo año después de la cirugía. Conclusiones. La ECP es una técnica apropiada para el tratamiento de los trastornos del movimiento. La actividad neuronal del subtálamo y del globo pálido interno presenta características propias que reflejan la sintomatología motora de los pacientes. La electromiografía superficial demuestra ser útil para cuantificar la mejoría de los pacientes (AU)

[Deep brain stimulation: 12 years' experience and 150 patients treated with a follow-up of over a year]. / Estimulación cerebral profunda: 12 años de experiencia y 250 pacientes intervenidos con un seguimiento de más de un año.

INTRODUCTION: Deep brain stimulation (DBS) is a widely accepted clinical technique. The main motor symptoms are significantly reduced. The success of the technique depends on the experience of the neurosurgeon, neurologist and neurophysiologist who carry it out. The presentation of extensive series is needed to confirm and further currently held knowledge. AIM: To demonstrate the clinical benefits of a long series of patients treated by a single group with a minimum follow-up of one year and to report new neurophysiological data. PATIENTS AND METHODS: The study examined a total of 250 patients with different diagnoses: most of them with Parkinson's disease, tremor and dystonia. The nuclei that were chosen were located by magnetic resonance imaging, computerised axial tomography and neurophysiological registers. Neurophysiological exclusion criteria, such as reflex control of heart rate, sympathetic skin response and auditory startle reflex, are employed in order to exclude patients with Parkinson-plus. RESULTS: The motor sub-scale (part III) of the Unified Parkinson's Disease Rating Scale improves by 64% in the off-medication status with sub-thalamic stimulation at one year after surgery. One year after DBS, patients with dystonia show a significant decrease on the Burke-Fahn-Marsden dystonia scale. The improvement on the scales continues, with a mean descent of 65% in the second year after surgery. CONCLUSIONS: DBS is a suitable technique for the treatment of movement disorders. The neuronal activity of the sub-thalamus and the internal globus pallidus presents its own characteristics that reflect the motor symptoms of the patients. Surface electromyography proves to be useful for quantifying the patients' improvement.

Deep brain stimulation in the globus pallidus to treat dystonia: electrophysiological characteristics and 2 years' follow-up in 10 patients.

Deep brain stimulation (DBS) was applied in the internal segment of the globus pallidus (GPi) to treat dystonia in 10 patients. One year after surgery the Burke-Fahn-Marsden movement scores were significantly lower than preoperative values (P=0.01). Two years after surgery the mean decrease reached 65% (P=0.001) with no motor symptoms worsening. Single unity activity was recorded in the operating room: GPi cells discharged with tonic (n=19; 29%), irregular (n=32; 48%), or burst-like activity (n=15; 23%) and fired with a mean discharge rate of 39 Hz+/-22. Some neurons demonstrated an oscillatory activity with periods lasting several seconds. Pairs of pallidal cells (n=8) recorded simultaneously displayed discharge synchronization. Movement modulated 64.4% of the cells tested, with increases in firing in 89% of cells and decreases in firing in 10% of cells. GPi cells responded to flexion and extension movements and to several passive manipulations indicating an important sensory role in dystonia. GPi neurons fired in advance of the electromyography (EMG) when the surface EMG was recorded simultaneously with the neuronal activity. Spectral analysis of the co-contracting muscles during dystonia demonstrated prominent high peaks at a low frequency band (20 Hz) during involuntary and voluntary movements. The high amplitude EMG profile recorded at rest diminished to very low values with GPi stimulation, allowing an ease of voluntary contractions. We conclude that DBS in the GPi is a reliable surgical technique for dystonia. GPi cells discharge with distinct electrophysiological characteristics that may explain some of the symptoms in dystonia. EMG recording in the operating room helps to determine which DBS contacts produce the best benefit.

[Predictive clinical factors of response to subthalamic nucleus stimulation in Parkinson's disease]. / Factores clínicos predictivos de la respuesta a la estimulación subtalámica en la enfermedad de Parkinson.

INTRODUCTION: Subthalamic nucleus stimulation (SNE) is currently a reasonable treatment for patients with advanced Parkinson's disease (PD). Predictive factors for effective SNE have not yet been identified with precision. We have prospectively evaluated response to SNE in a series of patients with advanced PD to study the factors that influence clinical improvement after functional surgery. METHODS: We prospectively studied 20 patients with advanced PD (age: 59 +/-6.1; stage: 3.0+/-0.8) candidates for SNE. We studied these patients preoperatively and 6 months postoperatively according to Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol including timed tests. CONCLUSIONS: We found a negative correlation between age and Unified Parkinson Disease Rating Scale (UPDRS) improvement; however, age did not correlate with timed tests improvement. In addition, preoperative severity (UPDRS and Hoehn-Yahr) did not correlate with UPDRS and timed tests improvement. In summary, age is a negative predictor for effective SNE.

Pallidal stimulation relieves myoclonus-dystonia syndrome.

A patient with myoclonus-dystonia syndrome was treated by implanting electrodes in the internal segment of the globus pallidus (GPi) and applying deep brain stimulation. Surgery was done in two sessions. The most affected limb was treated first and the other limb one year later. Neuronal recordings showed that most pallidal neurones discharged in bursts at a relatively low firing rate (mean (SD), 46 (18) Hz) compared with cells in the GPi in patients with Parkinson's disease. Neurones modified the rate and mode of discharge with dystonic postures and rapid involuntary contractions of limb muscles. Neurological examination at 24 months after surgery showed a decline of 47.8% and 78.5% in the Burke-Fahn-Marsden and disability rating scales, respectively.

High-frequency stimulation of the subthalamic nucleus silences subthalamic neurons: a possible cellular mechanism in Parkinson's disease.

The subthalamic nucleus participates in the control of movement and is considered a surgical target in the treatment of parkinsonian symptoms. Using the rat brain in vitro slice technique we show that sustained high-frequency (>100 Hz) electrical stimulation (i.e., 'tetanic stimulation') of the nucleus, as used in humans to treat Parkinson's disease, silenced subthalamic neurons. Two main cell types were identified. 'Tonic cells' (68%) showed delayed inward rectification, fired continuously, switched to bursting and stopped firing when strongly depolarized with injected current. Tetanic stimulation of the nucleus induced a steady depolarization (approximately 18 mV) that triggered action potentials at a high rate followed by bursts and finally (approximately 25 s) totally silenced tonic cells. The control tonic activity was recovered rapidly (<10 s) after ending stimulation. 'Phasic cells' (25%) discharged a single initial brief burst of action potentials both when depolarized by prolonged current injection and tetanic stimulation and did not show inward rectification. An infrequent cell type called 'phasic-tonic' (7%) showed a mixed discharge. We suggest that the silencing effect of tetanic stimulation is not a frequency-dependent presynaptic depression and could result from the gradual inactivation of Na+-mediated action potentials. These findings suggest that the remission of parkinsonian symptoms by treatment with high-frequency electrical stimulation of the subthalamic nucleus in humans may primarily reside on its capacity to suppress the action potential activity of subthalamic neurons.

Further supporting evidence of beneficial subthalamic stimulation in Parkinson's patients.

Twenty-two patients with Parkinson's disease were treated by implanting electrodes in the subthalamic nucleus. The follow-up evaluation was conducted at one (22 patients) and two years (9 patients). Significant improvement in the Unified PD Rating Scale scores was found. Tremor diminished 100% in the on drug/on stimulation and 70% off drug/on stimulation state. Rigidity decreased by 68% in the on drug/on stimulation and by 52% in off drug/on stimulation state. Subthalamic stimulation is reliable.

Subthalamic neuron activity related to tremor and movement in Parkinson's disease.

Single cell activity recorded in the subthalamic nucleus (STN) of Parkinson's patients and the effect of tremor, passive and voluntary movement upon the same cells are described. Three types of cells were distinguished by the pattern of discharge: tonic, phasic and rhythmic. They all demonstrated high mean firing rates (65, 59 and 69 Hz, respectively). Simultaneous recordings of muscle activity and tremor helped in defining cell activity. The implantation of the definitive stimulating electrode in the patients was based on the number of STN cells related to tremor, active and passive movements (mean = 68%) along the track chosen. Cells were related to tremor (n = 21; 11%), modified the discharge with differences in the amplitude of tremor (n = 4), and changed the rate and pattern when tremor stopped spontaneously or artificially (n = 6). Movement-related cells (n = 97; 51%) showed a cyclic activity correlated with phases of the movement, or modified the firing rate along the performance of the movement. Tremor and movement-related cells (n = 11; 6%) revealed an interesting sensory-motor integrative function.

[Neuronal activity in the subthalamic nucleus in Parkinson disease]. / Actividad neuronal en el núcleo subtalámico en la enfermedad de Parkinson.

INTRODUCTION: The subthalamic nucleus has been demonstrated to be involved in Parkinson's disease. Electrical stimulation of this nucleus at high frequency was proved to revert most symptoms and is used as the most advanced alternative therapy. The technique requires the recording of single cell activity as an important step in locating spatially the limits of the nucleus together with magnetic resonance imaging and ventriculography. OBJECTIVES: To study the electrophysiological properties of single cells in the subthalamus. This information is important to recognize the nucleus in the operating room so as to implant the definitive stimulating electrode. PATIENTS AND METHODS: Twelve patients with Parkinson's disease were implanted with bilateral electrodes in the subthalamic nucleus. Several neurological tests were applied during one year to study the clinical results. RESULTS: Single cell activity was recorded in both hemispheres. Three types of cells were recognized based on the mode of discharge: tonic, phasic and rhythmic. The track chosen to implant the definitive electrode was based on the higher number of cells recorded and on the response to tremor and passive or voluntary movements. The neurological tests applied demonstrated a diminution of the symptoms. CONCLUSION: The subthalamic nucleus plays an important role in handling motor and sensory information. Stimulation of the nucleus at high frequency reveals an amelioration of Parkinson's symptoms during the one year period of study.

Actividad neuronal en el núcleo subtalámico en la enfermedad de Parkinson / Neuronal activity in the subthalamic nucleus in Parkinson's disease

Introducción. Se ha demostrado que el núcleo subtalámico se halla afectado en la enfermedad de Parkinson. Ha podido demostrarse una disminución de la mayoría de los síntomas tras la estimulación eléctrica de este núcleo a alta frecuencia, y dicha técnica se utiliza como la terapia alternativa más avanzada. La técnica precisa del registro de la actividad de una célula única como paso importante en la localización espacial de los límites del núcleo, junto con la resonancia magnética y la ventriculografía. Objetivos. Estudiar las propiedades electrofisiológicas de células individuales del subtálamo. Esta información es importante para reconocer el núcleo en el quirófano con el fin de implantar el electrodo definitivo. Pacientes y métodos. Se implantaron electrodos bilaterales en el núcleo subtalámico de 12 pacientes con enfermedad de Parkinson. Se aplicaron varias pruebas neurológicas para el estudio de los resultados clínicos durante un año. Resultados. Se registró actividad celular individual en ambos hemisferios. Se reconocieron tres tipos de células basándose en el modo de descarga: tónica, fásica y rítmica. El camino elegido para implantar el electrodo definitivo se basó en el número más alto de células registradas y en la respuesta al temblor y a los movimientos pasivos o voluntarios. Conclusiones. El núcleo subtalámico desempeña un importante papel en el manejo de la información sensorial y motora. La estimulación de alta frecuencia del núcleo reveló la disminución de los síntomas parkinsonianos durante el período de un año que duró el estudio (AU)

Different discharge properties of rat facial nucleus motoneurons.

In this paper, we describe two types of putative facial motoneuron based on their electrophysiological properties and on their firing frequency adaptation as recorded in rat brainstem slices. Type I motoneurons (n = 33, 61%) were characterized by a sustained spike firing during depolarizing current injections and a marked depolarizing sag (inward rectification) during hyperpolarizing pulses. The time-course and voltage-dependence of the inward rectification together with the finding that it was blocked by Cs+ are consistent with the involvement of a Na+ -and K+ -mediated Q current. Type II motoneurons (n = 21, 39%) were identified by a fast spike firing adaptation. Type II cells showed a less pronounced inward rectification with hyperpolarizing current pulses and a higher discharge rate than type I cells during depolarizing current pulses. These distinct discharge properties imply the activation of a Ca2+ -dependent K+ current, because when carbachol was added to the bath, or the slice was exposed to a Ca2+ -free solution, a decrease was noticed in the firing frequency adaptation. The two types of motoneuron were further differentiated by the initial delay of the first spike, observed only in type I cells, which was blocked by bath application of 4-aminopyridine, indicating the presence of a K+ -mediated A current. The addition of 4-aminopyridine to the bath also increased the firing rate due to a decrease of the post-spike afterhyperpolarization. However, the two types of motoneuron were not morphologically differentiated. Facial motoneurons exhibited rhythmic membrane potential oscillations (8-20 Hz) at depolarized membrane potentials or during the silence following spike frequency adaptation. It is suggested that the intrinsic properties of these two types of facial motoneuron may be relevant in the government of distinct facial muscle activities. The fact that their discharge rate and the level of spike frequency adaptation were modified by altering some K+ currents suggests a potential plasticity in the modulation of motoneuron firing activities depending upon functional motor needs.

Frequency potentiation in the medial cortex of young turtle brains in vitro.

Turtle brains have a relatively primitive cortex. Glutamate receptors in the cortex of turtles include N-methyl-D-aspartate (NMDA) and DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). Our aim was to determine whether the medial cortex in turtles, like the cortex and hippocampus in mammals exhibits frequency potentiation, a non-lasting form of synaptic plasticity, and, if so, to identify the involved receptors. Our results indicate that (1) the medial cortex exhibits this phenomenon with septal stimulation at 2 Hz, the frequency with maximum power spectral density in the electrocorticogram of turtles, showing an increase in both the excitatory postsynaptic potential and the evoked potential amplitudes; (2) the frequency potentiation of the medial cortex in turtles is mediated by AMPA type glutamate receptors; (3) the dynamics of frequency potentiation development in turtles show a number of differences from that in mammals. In summary, the cortex in this group of reptiles exhibits a functional trait of the cortex in mammals that is related to learning and memory; this trait, frequency potentiation, may have appeared as an independent specialization in both groups.

Nucleus basalis of Meynert cell responses in awake monkeys.

Extracellular cell activity was recorded in the intermediate and posterior subdivisions of the nucleus basalis of Meynert (NBM) of awake monkeys to determine cell characteristics and the motor and sensory participation. Animals were trained to move a lever by elbow flexion-extensions to receive a reward. Cell activity was recorded when the animal was at rest and executing the task. The electromyogram of the upper limb, contralateral to the recording site, was recorded simultaneously with NBM neuron activity. The effect of visual, auditory, and tactile stimuli were also studied after performance of the learned task. A moderate number of cells responded to the reward (16%), while a higher percentage of them was associated with unexpected, unspecific stimuli (22%). Firing rates correlated positively with limb movement (30%). Visual (34%) and auditory (15%) responses were also found. No NBM cell responded to tactile stimulation. Considering these findings and the anatomical projections over the cortex, the NBM role ion complex integrative processes in discussed.

Polymodal sensory and motor convergence in substantia nigra neurons of the awake monkey.

Responses of substantia nigra (SN) pars compacta (SNc) and reticulata (SNr) neurons to sensory stimulation and movement were investigated in awake Macaca fascicularis. Concern was assigned to polysensory and sensory/motor convergence on the same cell, which were found in 12% and 9% of the neurons, respectively. Others were modality specific (35%) or unresponsive (44%). The convergence lends support to the notion that SN plays an important role in sensory-motor integration.

Activity in monkey substantia nigra neurons related to a simple learned movement.

Single cell activity was recorded in the pars compacta (SNc) and pars reticulata (SNr) of the substantia nigra (SN) in 4 unanesthetized Macaca fascicularis to determine the motor role of the nucleus. Animals were trained to perform a simple task that involved moving a lever by elbow flexion-extensions, in the horizontal plane using the hand contralateral to the recording site. Two monkeys learnt to execute the task on both sides. Electromyograms (EMG) of limb muscles were recorded simultaneously with SN neurons. Discharge rate modulation related to specific movement phases was present in 35% of the neurons. A significant positive correlation of the discharge rate with movement velocity and amplitude was found in SNc and SNr neurons. Some SNr cells discharged in anticipation of the EMG, suggesting a participation of the nucleus in the preparation of movement. The activity of SNr neurons was also related to movement of the left and right upper limb. In conclusion, the SN seems to play an important role in the control of specific motor mechanisms, probably modulating movement velocity, amplitude and direction, with little participation of somatosensory feedback. The involvement of the SNr in the coordination of bilateral arm activity is discussed.

Monkey pulvinar units related to motor activity and sensory response.

Single neuron activity in the pulvinar (Pu) was recorded in unanesthetized Macaca irus to investigate the sensory-motor role of this nucleus. A cylinder cemented to the skull allowed microelectrode penetrations. The head was immobilized during recording. Animals were trained to move a lever (push-pull). Electromyographs (EMGs) of several limb muscles were recorded together with Pu unit activity. The effect of active and passive limb movements was studied. Pu responses were also recorded during stimulation with flashes and clicks. A high percentage of units (65%) modified their discharge rate with limb movements. Firings showed a rate modulation in relation to specified movement phases, which were characteristic of each individual unit. Firing rates correlated with movement parameters, strongly with velocity and amplitude, and less with force. Firing rate modulation depth correlated better than mean rate changes with movement parameters, implying that dynamic information is well represented while static parameters are less important. Most of the movement-related units showed visual or auditory responses. A visuo-auditory and motor response was demonstrated in a few cells. The results suggest a participation of the Pu in motor-control.