Involvement of the basal ganglia and cerebellar motor pathways in the preparation of self-initiated and externally triggered movements in humans.

The subthalamic nucleus (STN) is part of the cortico-basal ganglia (BG)-thalamocortical circuit, whereas the ventral lateral nucleus of the thalamus (VL) is a relay nucleus in the cerebello-dentato-thalamocortical (CTC) pathway. Both pathways have been implicated in movement preparation. We compared the involvement of the STN and VL in movement preparation in humans by recording local field potentials (LFPs) from seven patients with Parkinson's disease with deep-brain stimulation (DBS) electrodes in the STN and five patients with tremor and electrodes in VL. LFPs were recorded from DBS electrodes and scalp electrodes simultaneously while the patients performed self-paced and externally cued (ready, go/no-go) movements. For the self-paced movement, a premovement-related potential was observed in all patients from scalp, STN (phase reversal, five of six patients), and VL (phase reversal, five of five patients) electrodes. The onset times of the potentials were similar in the cortex, STN, and VL, ranging from 1.5 to 2 s before electromyogram onset. For the externally cued movement, an expectancy potential was observed in all patients in cortical and STN electrodes (phase reversal, six of six patients). The expectancy potential was recorded from the thalamic electrodes in four of five patients. However, phase reversal occurred only in one case, and magnetic resonance imaging showed that this contact was outside the VL. The cortico-BG-thalamocortical circuit is involved in the preparation of both self-paced and externally cued movements. The CTC pathway is involved in the preparation of self-paced but not externally cued movements, although the pathway may still be involved in the execution of these movements.

Electrophysiological features of myoclonus-dystonia.

Inherited myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonus and dystonia that often improves with alcohol. To examine the electrophysiologic characteristics of M-D, we studied 6 patients from 4 different families and 9 age-matched healthy subjects. Neurophysiological studies performed include electromyography (EMG)-electroencephalography (EEG) polygraphy, jerk-locked back-averaged EEG, somatosensory evoked potentials (SEP), long-latency reflex (LLR) to median and digital nerve stimulation, and transcranial magnetic stimulation studies with short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI). All 6 patients showed myoclonus and dystonia on clinical examination and EMG testing. The EMG burst durations ranged from 30.4 to 750.6 milliseconds (mean, 101.5 milliseconds). Jerk-locked back-averaged EEG failed to reveal any preceding cortical correlates. Median nerve SEP revealed no giant potential. No patients had exaggerated LLR to median or digital nerve stimulation. There was no significant difference in SICI, ICF, and LICI between M-D patients and normal subjects. Myoclonus in inherited M-D is likely of subcortical origin. Normal intracortical inhibition and facilitation suggest that the GABAergic circuits in the motor cortex are largely intact and that the mechanisms of myoclonus and dystonia are different from those for cortical myoclonus and other dystonic disorders.

Surgical management of tethered cord syndrome in adults: indications, techniques, and long-term outcomes in 60 patients.

OBJECT: The adult presentation of tethered cord syndrome (TCS) is well recognized but continues to pose significant diagnostic and management challenges. The authors performed a retrospective study of clinical outcomes after neurosurgical intervention in 60 adults with TCS. METHODS: All patients who underwent detethering surgery for caudal cord tethering at Toronto Western Hospital between August 1993 and 2004 were identified. Their clinical charts, operative records, and follow-up data were reviewed. Detethering procedures were performed in 62 patients (age range 17-72 years) for TCS of various origins. Long-term (mean 41.5 months) follow-up data were obtained in 60 patients. The tethering lesions were tight terminal filum in 29 patients, postrepair myelomeningocele in 15, lipomyelomeningocele/lipoma in nine, split cord malformation in four, and arachnoidal adhesions in three. Fifty-nine patients presented with progressive pain and/or neurological dysfunction. One patient underwent prophylactic sectioning of the terminal filum. Most patients (71%) had bladder dysfunction at presentation. Microsurgical release of the tethered cord was performed in each case while using multimodality intraoperative neurophysiological monitoring. The most common complication was cerebrospinal fluid leakage, which occurred in nine patients and was managed by reinforcement sutures in four patients, temporary external drainage in three, and the placement of a lumboperitoneal shunt in two. Infective complications included superficial wound infection in three patients, meningitis in one, and urinary tract infection in one. One patient who had undergone multiple previous intradural procedures experienced worsened foot weakness postoperatively. Another patient experienced temporary unilateral lower-limb numbness. At follow up, improvement was noted in the majority of patients presenting with back (78%) and leg (83%) pain. Improvement was more likely in patients with preoperative motor weakness than in those with sensory deficits. Overall, neurological status was improved or stabilized in 90% of patients. Subjective improvement in bladder function was noted in 50% of patients with bladder dysfunction at presentation. CONCLUSIONS: Surgery in adult patients with TCS is safe and effective for improving pain and neurological status in the majority of patients; however, patients who have undergone previous intradural detethering procedures in general fare less well, and considerable judgment is required in their management.

Involvement of human thalamus in the preparation of self-paced movement.

Cortical areas participating in the preparation of voluntary movements have been studied extensively. There is emerging evidence that subcortical structures, particularly the basal ganglia, also contribute to movement preparation. The thalamus is connected to both the basal ganglia and the cerebellar pathways, but its role in movement preparation has not been studied extensively in humans. We studied seven patients who underwent deep brain stimulation (DBS) electrode implantation in the thalamus for treatment of tremor (six patients) and myoclonus-dystonia (one patient). We recorded from the DBS contacts and scalp simultaneously, while patients performed self-paced wrist extension movements. Post-surgical MRI was used for precise localization of the DBS contacts in six patients. Back-averaging of the scalp recordings showed a slow negative movement-related potential (MRP) in all patients (onset 1846 +/- 189 ms prior to electromyography onset), whereas DBS electrode recordings showed pre-movement MRP in five out of seven patients. The thalamic MRP preceded both contralateral and ipsilateral wrist movements. There was no significant difference between the onset time of thalamic MRP (-2116 +/- 607 ms) and cortical MRP. Neither the scalp nor the thalamus showed pre-movement potentials with passive wrist extensions in two patients. In four patients with postoperative MRI who had thalamic MRP, the maximum amplitude or phase reversal occurred at contacts located in the ventral lateral nucleus. Frequency analysis was performed in the five patients with thalamic MRP. The medial frontocentral scalp contacts and the thalamic contacts with maximum MRP amplitude showed two discrete frequency bands in the alpha (mean peak 9 Hz) and beta (mean peak 17 Hz) range. Both frequency bands showed pre-movement event-related desynchronization (ERD). In the grand average, alpha and beta ERD in the scalp and beta ERD in the thalamus began 2.5-2.8 s prior to the onset of movement. However, the thalamic alpha ERD began considerably later, at 1.2 s before EMG onset. The beta band showed cortico-thalamic coherence from the beginning of the baseline period until approximately 0.5 s before the onset of movement. There was no cortico-thalamic coherence in the alpha band. Our findings suggest that the cerebellar thalamus is involved early in the process of movement preparation. Different cortico-subcortical circuits may mediate alpha and beta oscillations. During movement preparation, the motor thalamus and the supplementary motor area predominantly interact in the beta band.

Multi-modality neurophysiological monitoring during surgery for adult tethered cord syndrome.

During complex microneurosurgery performed in patients with tethered cord syndrome, the conus medullaris and the roots that innervate the lower limbs, bladder and bowel are potentially exposed to damage. The aim of multimodality intraoperative monitoring (IOM) is to reduce the risk of inadvertent injury of neural tissue. We simultaneously record tibial nerve somatosensory evoked potentials (SSEPs) from the scalp and free run electromyography (EMG) of limb muscles supplied by L2 to S2 roots, anal and urethral sphincters. We also identify critical neural structures in the operative field, including the conus and exiting nerve roots, with a nerve stimulator to evoke EMG. SSEPs assess the sensory pathways mainly mediated by the S1 roots. Continuous EMG provides the surgeon with immediate auditory feedback resulting from irritative discharges triggered by manipulation of nerve fibres. Microstimulation can distinguish the filum terminale, scar tissue and invasive tumors from functional neural tissue, thus minimizing the risk of iatrogenic injury. Overall multimodality IOM proves a valuable adjunct to microneurosurgery of the lumbosacral spine.

Multimodality intraoperative neurophysiologic monitoring findings during surgery for adult tethered cord syndrome: analysis of a series of 44 patients with long-term follow-up.

STUDY DESIGN: Prospective analysis of a consecutive series in which multimodality intraoperative neurophysiologic monitoring was used as an adjunct to microneurosurgery for adult tethered cord syndrome. The results of multimodality intraoperative neurophysiologic monitoring were compared with the "gold standard" (neurologic outcomes). OBJECTIVE: To assess the sensitivity, specificity, and positive and negative predictive values of multimodality intraoperative neurophysiologic monitoring in surgery for adult tethered cord syndrome. SUMMARY OF BACKGROUND DATA: Although intraoperative electrophysiologic techniques may help to minimize neural injury during spinal microneurosurgery, to our knowledge, no study has quantitatively evaluated the value of multimodality intraoperative neurophysiologic monitoring in the management of adult tethered cord syndrome. METHODS: Multimodality intraoperative neurophysiologic monitoring included posterior tibial nerve somatosensory evoked potentials (SSEPs), continuous electromyographic (EMG) monitoring of the L2 to S4 myotomes, and evoked EMG. Follow-up neurologic evaluations were performed for at least 1 year. RESULTS: A total of 44 consecutive patients, including 19 males and 25 females (aged 43 +/- 15 years), who underwent microsurgery for adult tethered cord syndrome were evaluated. After surgery, new neurologic deficits, including 1 transient and 1 permanent, developed in 2 patients. There was 1 patient who had persistent posterior tibial nerve SSEP amplitude reduction following microsurgical manipulation. In 1 patient, a transient posterior tibial nerve SSEP amplitude reduction prompted a change in microneurosurgical strategy. This patient awoke with no new postoperative neurologic deficits. For SSEPs, the sensitivity was 50% and specificity 100%. EMG bursts were recorded in 36 patients (82%). The 2 patients with postoperative neurologic worsening had EMG activity in the myotomes, where their new deficits presented. Continuous EMG had a sensitivity of 100% and a specificity of 19%. CONCLUSIONS: To our knowledge, this is the largest series to date reporting the use of multimodality intraoperative neurophysiologic monitoring in the surgical management of adult tethered cord syndrome. Posterior tibial nerve SSEPs have high specificity, but low sensitivity, for predicting new neurologic deficits. In contrast, continuous EMG showed high sensitivity and low specificity. Evoked EMG accurately identified functional neural tissue. The combined recording of SSEPs in concert with continuous and evoked EMGs may provide a useful adjunct to complex microsurgery for adult tethered cord syndrome.

Representation of facial muscles in human motor cortex.

Whether there is a projection from the primary motor cortex (M1) to upper facial muscles and how the facial M1 area is modulated by intracortical inhibitory and facilitatory circuits remains controversial. To assess these issues, we applied transcranial magnetic stimulation (TMS) to the M1 and recorded from resting and active contralateral (C-OOc) and ipsilateral orbicularis oculi (I-OOc), and contralateral (C-Tr) and ipsilateral triangularis (I-Tr) muscles in 12 volunteers. In five subjects, the effects of stimulating at different scalp positions were assessed. Paired TMS at interstimulus intervals (ISIs) of 2 ms were used to elicit short interval intracortical inhibition (SICI) and ISI of 10 ms for intracortical facilitation (ICF). Long interval intracortical inhibition (LICI) was evaluated at ISIs between 50 and 200 ms, both at rest and during muscle activation. The silent period (SP) was also determined. C-OOc and I-OOc responses were recorded in all subjects. The optimal position for eliciting C-OOc responses was lateral to the hand representation in all subjects and MEP amplitude markedly diminished when the coil was placed 2 cm away from the optimal position. For the I-OOc, responses were present in more scalp sites and the latency decreased with more anterior placement of the coil. C-Tr response was recorded in 10 out of 12 subjects and the I-Tr muscle showed either no response or low amplitude response, probably due to volume conduction. SICI and ICF were present in the C-OOc and C-Tr, but not in the I-OOc muscle. Muscle activation attenuated SICI and ICF. LICI at rest showed facilitation at 50 ms ISI in all muscles, but there was no significant inhibition at other ISIs. There was no significant inhibition or facilitation with the LICI protocol during muscle contraction. The SP was present in the C-OOc, C-Tr and I-OOc muscles and the mean durations ranged from 92 to 104 ms. These findings suggest that the I-OOc muscle response is probably related to the first component (R1) of the blink reflex. There is M1 projection to the contralateral upper and lower facial muscles in humans and the facial M1 area is susceptible to cortical inhibition and facilitation, similar to limb muscles.

Effects of apomorphine on flexor reflex and periodic limb movement.

It has been suggested that periodic leg movements (PLM) and spinal flexor reflex (FR) share common mechanisms. Although dopaminergic agents improve PLM in humans and strongly influence spinal FR circuitry in animal studies, its effects on FR have not been documented in humans. We describe a 65-year-old man with PLM after overnight withdrawal of dopaminergic agents. The electromyographic pattern of spontaneous PLM closely resembled that of the FR elicited by medial plantar nerve stimulation. Thirty minutes after subcutaneous injection of apomorphine, both PLM and FR were completely abolished. These findings demonstrate that dopaminergic agents can suppress exaggerated FR in humans, and support the hypothesis of common mechanisms for PLM and FR.

Two phases of short-interval intracortical inhibition.

Short-interval intracortical inhibition (SICI) is a widely used method to study cortical inhibition, and abnormalities have been found in several neurological and psychiatric disorders. Previous studies suggested that SICI involves two phases and the first phase may be explained by axonal refractoriness. Our objectives are to further investigate the mechanisms of the two phases of SICI. SICI was studied in 11 normal volunteers by a paired transcranial magnetic stimulation (TMS) paradigm applied to the left motor cortex with a subthreshold conditioning stimulus (80% resting motor threshold for rest condition and 95% active motor threshold for active condition) followed by a suprathreshold test stimulus at interstimulus intervals (ISIs) of 1-4.5 ms in steps of 0.5 ms. Motor-evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. Three different test stimulus intensities adjusted to produce 0.2, 1 and 4 mV MEPs at rest were studied with the target muscle relaxed and during 20% maximum contraction. Maximum inhibition was observed at ISIs of 1 ms and 2.5 ms for the rest condition and the difference among ISIs was reduced with voluntary contraction. SICI increased with larger test MEP amplitude and decreased with voluntary contraction. At test MEP of 0.2 mV, some subjects showed facilitation and this is likely related to short-interval intracortical facilitation. For rest SICI, the correlation between adjacent ISIs was much higher from 3 to 4.5 ms than from 1 to 2.5 ms or between 1 and 2.5 ms. There was no correlation between SICI at different test MEP amplitudes. We conclude that maximum SICI at ISIs of 1 and 2.5 ms are mediated by different mechanisms. SICI at 1 ms cannot be fully explained by axonal refractoriness and synaptic inhibition may be involved. SICI is a complex phenomenon and inhibition at different ISIs may be mediated by different inhibitory circuits.

Exploring the connectivity between the cerebellum and motor cortex in humans.

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5-7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICF. The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex.

Short and long latency afferent inhibition in Parkinson's disease.

Sensory abnormalities have been reported in Parkinson's disease and may contribute to the motor deficits. Peripheral sensory stimulation inhibits the motor cortex, and the effects depend on the interstimulus interval (ISI) between the sensory stimulus and transcranial magnetic stimulation (TMS) to the motor cortex. Short latency afferent inhibition (SAI) occurs at an ISI of approximately 20 ms, and long latency afferent inhibition (LAI) at an ISI of approximately 200 ms. We studied SAI and LAI in 10 Parkinson's disease patients with the aim of assessing whether sensorimotor processing is altered in Parkinson's disease. Patients were studied on and off medication, and the findings were compared with 10 age-matched controls. Median nerve and middle finger stimulation were delivered 20-600 ms before TMS to the contralateral motor cortex. The motor evoked potentials were recorded from the relaxed first dorsal interosseous (FDI) muscle. SAI was normal in Parkinson's disease patients off dopaminergic medications, but it was reduced on the more affected side in Parkinson's disease patients on medication. LAI was reduced in Parkinson's disease patients compared with controls independent of their medication status. LAI reduced long interval intracortical inhibition in normal subjects but not in Parkinson's disease patients. The different results for SAI and LAI indicate that it is likely that separate mechanisms mediate these two forms of afferent inhibition. SAI probably represents the direct interaction of a sensory signal with the motor cortex. This pathway is unaffected by Parkinson's disease but is altered by dopaminergic medication in Parkinson's disease patients and may contribute to the side effects of dopaminergic drugs. LAI probably involves other pathways such as the basal ganglia or cortical association areas. This defective sensorimotor integration may be a non-dopaminergic manifestation of Parkinson's disease.

Las variaciones de la velocidad de conducción nerviosa en función de la temperatura no dependen de la edad / Temperature related nerve conduction velocity is not age-dependent

En 14 sujetos normales (edad x =48,1 ñ 23,9 años, rango 9-83) se estudiaron las variaciones de la velocidad de conducción del nervio sural (VC) en relación con las variaciones de la temperatura. Se analizaron los valores individuales de Q10 y b en función de la edad y no mostraron correlación (r - 0,31 y 0, 25, respectivamente). En el grupo de sujetos jóvenes (n = 7, edad x = 26,7 ñ 10,6 años, rango 9-47) se obtuvieron los valores Q10 - 1,36 y b 1,21 m/s/-C y en el grupo de sujetos de edad avanzada (n = 7, edad x = 72,0 ñ 8,9 años, rango 60-83) Q10 = 1,36 y b = 1,32 m/s/-C, valores similares al total de la muestra. En conclusión, las variaciones de la VC en función de la temperatura no dependen de la edad

Conducción nerviosa digital / Digital nerve conduction

Se describe un método que permite estudiar la conducción nerviosa digital, selectivamente el ramo digital palmar radial del dedo medio, en forma directa (D) por estimulando en la tercera falange (PIII) y registro en la primera falange (PI) e indirectamente (Di) estimulando en PIII y PI y registrando en la muñeca (W). En 20 controles la velocidad de conducción (en m/s) y la amplitud (en micronV) promedio para cada segmento fue PI-W 56 ñ 3,5, 20 ñ 7,9, PIII-W 53 ñ 3,1, 8 ñ 7,53, D 46 ñ 3,7, 20 ñ 10 y Di 47 ñ 4,1; la relación de las amplitudes registradas en W al estimular PI y PIII fue aproximadamente 3 a 1. El método podría ser particularmente útil en la evaluación de la severidad y en el diagnóstico precoz del síndrome del túnel del carpo y en las polineuropatías tipo dyiung back

Consideraciones sobre neuropatías perifericas diabéticas y alcoholicas y el uso de gangliosidos / Diabetic and alcoholic peripheral neuropathies and their treatment with gangliosides

Se estudiaron 19 pacientes con polineuropatía, 11 diabéticos y 8 alcohólicos. El ensayo consistió en la administración de 20 mg diarios de gangliósidos de corteza cerebral bovina por vía intramuscular durante 30 días. Se realizó la evaluación clínica y electrofisiológica de los pacientes previa y posteriormente al tratamiento. Se encontró mejoría de la sintomatología en la diabetes moderna (5 casos de un total de 6) y en el alcoholismo (7 casos de 8), mientras que en la diabetes severa mejoró un caso de 5. Con estos datos no es posible descartar el efecto placebo. Los estudios neurofisiológicos no demonstraron cambios significativos. Un solo pacientes presentó efectos colaterales: urticaria y blafaritis alérgica, que desaparecieron al suspender la medicación. La tolerancia local y general fue excelente

Enfermedad de Refsum / Refsum's disease

La enfermedad de Refsum es un defecto congénito del metabolismo graso que se hereda en forma autosómica recesiva. Aunque es una entidad infrecuente, el mecanismo fisiopatológico ha sido intensivamente estudiado y se demostró la acumulación en tejidos de ácido fitánico. Presentamos el segundo caso comunicado en la Argentina, un joven varón con los hallazgos típicos de degeneración tapetorretiniana, neuropatia periférica crónica y ataxia moderada. El ácido fitánico correspondió al 10,3% del total de los ácidos grasos séricos. El conocimiento y diagnóstico de este trastorno metabólico es particularmente importante puesto que se ha comprobado que la progresión natural puede ser detenida mediante la eliminación de alimentos ricos en ácido fitánico de la dieta de los enfermos

Síndrome de Charcot-Marie-Tooth / Charcot-Marie-Tooth syndrome

El síndrome de Charcot-Marie-Tooth (sCMT) comprende un grupo de neuropatías periféricas hereditarias cuya ubicación nosográfica no es precisa. En nuesta serie de 25 pacientes la distribución de los casos fue claramente bimodal en relación con la velocidad de conducción nerviosa motora: un grupo a) presentó conducciones severamente reducidas y un grupo b) presentó conducciones normales o ligeramente reducidas (exceptuando un paciente con valores intermedios). El grupo b) pudo subdividirse en 1) pacientes con alteraciones sensitivas (clínicas o neurofisiológicas) y 2) pacientes sin alteraciones de la sensibilidad. Los tres grupos a, b1 y b2 corresponden a las formas hipertrófica, neuronal (y neuronal "plus" cuando se agregan alteraciones del SNC) y espinal. Las neuropatías hereditarias sensitivomotoras o motoras tipo sCMT deben tenerse en cuenta cuando no hay causas evidentes de polineuropatía en el primer caso y cuando la presentación es atípica en el segundo

Neuropatia axonal proximal paraneoplásica: neuropatía asociada al cancer / Proximal axonal paraneoplastic neuropathy: neuromyopathy associated with cancer

Un paciente de 68 años de edad se presentó con pérdida de fuerza de cuatro meses de evolución en músculos de la cintura pelviana y un mes de evolución en músculos de la cintura escapular. Clínicamente mostró atrofia proximal de los 4 miembros y arreflexia en miembros inferiores. El decaimiento del estado general y los estudios de laboratorio fueron sugestivos de un proceso maligno. La EMG reveló cambios típicamente "miogénicos" y fasciculaciones; la condicción nerviosa sensitiva mostró alteraciones compatibles con polineuropatía axonal. Mas tarde se comprobó la presencia de un adenocarcinoma de colon por biopsia operatoria. La debilidad y atrofia proximal y el EMG con "patrón miogénico" han originado una interpretación confusa de este cuadro poco frecuente, una polineuropatía axonal a predominio proximal, que, a diferencia de la polimiositis se asocia al cáncer y no tiene tratamiento

Potenciales evocados somatosensitivos corticales y espinales de los nervios tibial y mediano en pacientes con insuficiencia renal cronica y transplante renal / Cortical and spinal somatosensory potentials of tibial and median nerves in patients with chronic renal insufficiency and renal transplantations

Se realizaron potenciales evocados somatosensitivos corticales y espinogramas de los nervios tibial y mediano en 14 pacientes con enfermedad renal: 3 en tratamiento médico, 9 en hemodiálisis y 2 con trasplante renal. La conducción nerviosa central (CC) del nervio mediano (N20-N14) no demostró alteraciones significativas. La CC del tibial (O-N22) estuvo prolongada en 8 casos, 7 en hemodiálisis y uno en tratamiento médico. Las CCs de los pacientes con trasplante renal fueron normales. La conmbinación CC mediano normal y CC tibial aumentada sugiere alteración de laq conducción medular. Postulamos que el mismo factor metabólico que produce la disminución de la conducción periférica por una alteración metabólica no-estructural rápidamente reversible tras el trasplante renal podría atravesar la barrera hematoencefálica y producir el mismo efecto a nivel medular