Pallidal and Thalamic Deep Brain Stimulation in the Treatment of Unilateral Dystonia: A Prospective Assessment.

BACKGROUND: The complexities of unilateral dystonia have led to exploring simultaneous (dual) globus pallidus internus (GPi) and motor ventral thalamus (Vim/Vop) deep brain stimulation (DBS), yet detailed assessments are lacking. OBJECTIVES: To assess the efficacy of GPi, Vim/Vop, and dual DBS in unilateral dystonia. METHODS: Three patients with unilateral dystonia (two idiopathic, one acquired), implanted with two DBS electrodes targeting ipsilateral Vim/Vop and GPi, were included. Three stimulation modalities were assessed. First, one electrode was activated, then the other, and finally, both electrodes were activated simultaneously. RESULTS: DBS yielded substantial symptomatic reductions in all three evaluated stimulation modalities. Patients exhibited varying responses regarding quality-of-life and depressive symptoms. Treatment satisfaction didn't align with clinical improvements, potentially affected by unrealistic expectations. CONCLUSIONS: This study contributes critical insights into GPi, Vim/Vop and simultaneous stimulation for unilateral dystonia. The safety of the procedure underscores the promise of this approach.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Dopaminergic Dependency of Cholinergic Pallidal Neurons.

We employed the whole-cell patch-clamp method and ChAT-Cre mice to study the electrophysiological attributes of cholinergic neurons in the external globus pallidus. Most neurons were inactive, although approximately 20% displayed spontaneous firing, including burst firing. The resting membrane potential, the whole neuron input resistance, the membrane time constant and the total neuron membrane capacitance were also characterized. The current-voltage relationship showed time-independent inward rectification without a "sag". Firing induced by current injections had a brief initial fast adaptation followed by tonic firing with minimal accommodation. Intensity-frequency plots exhibited maximal average firing rates of about 10 Hz. These traits are similar to those of some cholinergic neurons in the basal forebrain. Also, we examined their dopamine sensitivity by acutely blocking dopamine receptors. This action demonstrated that the membrane potential, excitability, and firing pattern of pallidal cholinergic neurons rely on the constitutive activity of dopamine receptors, primarily D2-class receptors. The blockade of these receptors induced a resting membrane potential hyperpolarization, a decrease in firing for the same stimulus, the disappearance of fast adaptation, and the emergence of a depolarization block. This shift in physiological characteristics was evident even when the hyperpolarization was corrected with D.C. current. Neither the currents that generate the action potentials nor those from synaptic inputs were responsible. Instead, our findings suggest, that subthreshold slow ion currents, that require further investigation, are the target of this novel dopaminergic signaling.

¿Psicosis luego de sobredosis por opioides? Lesión isquémica bilateral del globo pálido como causa orgánica insospechada / ¿Psychosis after opioid overdose? Bilateral globus pallidus ischaemic injury as an unsuspected organic cause

RESUMEN El abordaje de pacientes intoxicados que presentan antecedentes de patología psiquiátrica supone un reto en la atención médica. La presencia de una patología dual puede conducir a que algunos síntomas somáticos sean desestimados y no se consideren como manifestación de una posible patología grave subyacente. Se reporta el caso de una paciente que, durante su hospitalización debida a un episodio depresivo, presentó una sobredosis incidental de opioides. Al recuperarse de ella, sin embargo, presentó comportamiento desorganizado e ideas delirantes, inicialmente atribuidas a la depresión. Estudios ulteriores demostraron una causa orgánica grave subyacente: lesión isquémica bilateral del globo pálido. Se analiza el cuadro clínico a la luz de la literatura pertinente, abordando los temas de delirium, espectro clínico debido a las lesiones del globo pálido y finalizando con una breve descripción sobre la sobredosis y neurotoxicidad por opioides. Frente a síntomas no concordantes con la evolución usual de una descompensación psicopatológica o una intoxicación por drogas, debe ahondarse en la exploración de posibles causas orgánicas, objetivo para el cual se sugiere considerar estudios de neuroimágenes en todo paciente que experimente una sobredosis de opioides y que posteriormente presente graves manifestaciones de una alteración cognitiva.

SUMMARY The approach to intoxicated patients with a previous history of psychopathological manifestations represents a challenge to medical care. The presence of a dual pathology can lead to somatic symptoms being dismissed and not considered as possible manifestations of a serious underlying pathology. We report the case of a patient who, during her hospitalization for a depressive episode, presented an incidental opioid overdose. Upon recovery, she presented disorganized behavior and delusions, initially attributed to her depression. Further studies demonstrated, however, a serious underlying organic cause: A bilateral ischaemic injury of the globus pallidus. The clinical picture is analyzed in the light of the relevant literature, addressing the issues of delirium, clinical spectrum of globus pallidus lesions and ending with a brief description of opioid overdoses and neurotoxicity. Faced with symptoms that are not consistent with the usual course of a psychopathological decompensation or drug intoxication, possible organic causes should be delved into. It is suggested that neuroimaging studies be considered in any patient who suffers from an opioid overdose and who later presents severe cognitive alterations.

Management of laryngopharyngeal reflux in Brazil: a national surveys / Manejo do refluxo laringofaríngeo no Brasil: pesquisa nacional

Abstract Introduction: Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking. Objective: To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists. Methods: A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies. Results: According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux. Conclusion: Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease.

Resumo Introdução: Estudos que avaliaram o manejo do refluxo laringofaríngeo por otorrinolaringologistas mostraram uma importante heterogeneidade em relação à definição, diagnóstico e tratamento, o que leva a discrepâncias no tratamento do paciente. Faltam informações sobre o conhecimento e as práticas atuais dos otorrinolaringologistas brasileiros sobre o refluxo laringofaríngeo. Objetivo: Investigar as tendências no manejo da doença do refluxo laringofaríngeo entre os otorrinolaringologistas brasileiros. Método: O questionário foi enviado por e-mail aos membros da Associação Brasileira de Otorrinolaringologia-Cirurgia de Cabeça e Pescoço. Esta pesquisa foi inicialmente conduzida pelo LPR Study Group of Young Otolaryngologists da International Federation of Otolaryngological Societies. Resultados: De acordo com os respondentes da pesquisa, a prevalência de refluxo laringofaríngeo foi estimada em 26,8% dos pacientes consultados e os sintomas mais comuns foram sensação de globus, pigarro, tosse e refluxo de ácido estomacal. Obstrução nasal, disfunção da trompa de Eustáquio, otite média aguda e crônica, nódulos nas pregas vocais e hemorragia foram considerados como não associados ao refluxo laringofaríngeo pela maioria dos respondentes. Cerca de 2/3 dos otorrinolaringologistas brasileiros basearam o diagnóstico de refluxo laringofaríngeo na avaliação dos sintomas e achados e na resposta positiva a testes terapêuticos empíricos. Inibidores de bomba de prótons uma ou duas vezes ao dia foi o esquema terapêutico mais usado. Somente 21,4% dos otorrinolaringologistas brasileiros já ouviram falar sobre refluxo laringofaríngeo não ácido e misto e o conhecimento sobre a utilidade do monitoramento de pH por impedância intraluminal multicanal foi mínimo; 30,5% dos respondentes não se consideraram tão bem informados sobre o refluxo laringofaríngeo. Conclusão: Embora os sintomas relacionados ao refluxo laringofaríngeo e as principais abordagens diagnósticas e terapêuticas referidas pelos otorrinolaringologistas brasileiros sejam consistentes com a literatura, a pesquisa identificou algumas limitações, como o conhecimento insuficiente do papel do refluxo laringofaríngeo em diversas condições otorrinolaringológicas e da possibilidade de refluxo não ácido ou misto em casos refratários. Estudos futuros são necessários para estabelecer recomendações internacionais para o manejo de doença do refluxo laringofaríngeo.

Estimulación cerebral profunda del globo pálido interno en el síndrome de distonía mioclónica: serie de 3 casos y revisión de la literatura / Deep brain stimulation of the internal globus pallidus in myoclonus-dystonia syndrome: a case series and review of the literature

RESUMEN INTRODUCCIÓN: La distonía mioclónica es un trastorno del movimiento con poca prevalencia, pero muy discapacitante, en el cual es frecuente la refractariedad al tratamiento médico. Cómo opción terapéutica se ha planteado la estimulación cerebral profunda, buscando con ello mejorar la función motora, la discapacidad y la calidad de vida de estos pacientes. MATERIALES Y MÉTODOS: Se presentan 3 pacientes con diagnóstico clínico de distonía mioclónica sin confirmación genética, que fueron llevados a estimulación cerebral profunda bilateral del globo pálido interno. RESULTADOS: Se evidenció una mejoría significativa en la evaluación de la escala unificada de mioclonías (80-90 %) y en la escala de distonía de Burke-Fahn-Marsden (tanto en movilidad como en discapacidad). La mejoría clínica se evidenció en los tres pacientes, en periodos de seguimiento que estuvieron entre los 6 meses y los 5 años luego de la estimulación cerebral profunda. DISCUSIÓN Y CONCLUSIONES: Los hallazgos en esta serie de 3 pacientes colombianos son consistentes con lo reportado en la literatura. Sin embargo, aportan información sobre el desenlace de pacientes sin genotipificación sometidos a estimulación cerebral profunda, dado que la eficacia de la intervención en pacientes con distonía sin confirmación genética aún no ha sido determinada, y depende de otros factores como la edad, el tiempo de evolución y el tipo de distonía.

ABSTRACT INTRODUCTION: Myoclonic dystonia is a movement disorder with low prevalence, but very disabling, where refractoriness to medical treatment is frequent. Deep brain stimulation has been proposed as a therapeutic option, seeking to improve motor function, disability and quality of life in these patients. MATERIALS AND METHODS: We present 3 patients with a clinical diagnosis of Myoclonic-Dystonia without genetic confirmation, who underwent bilateral deep brain stimulation of the Globus Pallidus Internus. RESULTS: A significant improvement was evidenced in the evaluation of the unified myoclonus scale (80-90 %) and in the Burke-Fahn-Marsden dystonia scale (both in mobility and in disability). The clinical improvement was evidenced in the 3 patients, in follow-up periods that were between 6 months and 5 years after deep brain stimulation. DISCUSSION AND CONCLUSIONS: Findings in this Colombian case series are consistent with that reported in the literature. However, the current description provides information on the outcome of patients without genotyping undergoing deep brain stimulation, considering that the efficacy of the intervention in these types of patients without genetic confirmation has not been determined and depends on other factors.

Elevation of GABA levels in the globus pallidus disinhibits the thalamic reticular nucleus and desynchronized cortical beta oscillations.

The external globus pallidus (GP) is a GABAergic node involved in motor control regulation and coordinates firing and synchronization in the basal ganglia-thalamic-cortical network through inputs and electrical activity. In Parkinson's disease, high GABA levels alter electrical activity in the GP and contribute to motor symptoms. Under normal conditions, GABA levels are regulated by GABA transporters (GATs). GAT type 1 (GAT-1) is highly expressed in the GP, and pharmacological blockade of GAT-1 increases the duration of currents mediated by GABA A receptors and induces tonic inhibition. The functional contribution of the pathway between the GP and the reticular thalamic nucleus (RTn) is unknown. This pathway is important since the RTn controls the flow of information between the thalamus and cortex, suggesting that it contributes to cortical dynamics. In this work, we investigated the effect of increased GABA levels on electrical activity in the RTn by obtaining single-unit extracellular recordings from anesthetized rats and on the motor cortex (MCx) by corticography. Our results show that high GABA levels increase the spontaneous activity rate of RTn neurons and desynchronize oscillations in the beta frequency band in the MCx. Our findings provide evidence that the GP exerts tonic control over RTn activity through the GP-reticular pathway and functionally contributes to cortical oscillation dynamics.

Management of laryngopharyngeal reflux in Brazil: a national survey.

INTRODUCTION: Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking. OBJECTIVE: To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists. METHODS: A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies. RESULTS: According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux. CONCLUSION: Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease.

Evolution of Globus Pallidus Targeting for Parkinson's and Dystonia Deep Brain Stimulation: A 15-Year Experience.

Objective: The aim of this study is to evaluate the evolution of GPi DBS targeting. Methods: This retrospective, single-center study included patients implanted with GPi DBS leads for dystonia or PD during the years 2004 to 2018 at the University of Florida Fixel Institute for Neurological Diseases. Each patient underwent a high-resolution targeting study on the day prior to the surgery, which was fused with a high resolution CT scan that was acquired on the day of the procedure. Intraoperative target location was selected using a digitized 3D Schaltenbrand-Bailey atlas. All patients underwent a high-resolution head CT scan without contrast approximately one month after lead implantation and accurate measurement of neuroanatomical lead position was acquired after fusion of pre-operative and post-operative image studies. Results: We analyzed 253 PD patients with 352 leads and 80 dystonia patients with 141 leads. During 15 years of follow-up, lead locations in the PD group migrated more laterally (ß = 0.09, p < 0.0001), posteriorly [slope (ß) = 0.04, p < 0.05], and dorsally (ß = 0.07, p < 0.001), whereas leads in the dystonia group did not significantly change position aside from a trend in the dorsal direction (ß = 0.06, p = 0.053). Conclusion: The evolving target likely results from multiple factors including improvements in targeting techniques and clinical feedback intraoperatively and post-operatively. Our demonstrates the potential importance of a systematic post-operative DBS lead measurement protocol to ensure quality control and to inform and optimize DBS programming.

Successful Unilateral Surgical Approach to Internal Globus Pallidus and Ventral Intermediate Nucleus of the Thalamus in 3 Cases of Myoclonus-Dystonia Syndrome.

Surgical approaches of internal globus pallidus (GPi) and ventral intermediate thalamic nucleus (Vim) have been used to treat different movement disorders. Three subjects with myoclonus-dystonia syndrome were surgically treated, one of them with GPi and Vim stimulation, while radiofrequency ablation of these structures was performed in the other 2 subjects. Surgical approach of both targets was performed simultaneously on each subject. Mean follow-up was of 33.3 months (22-48 months), the Unified Myoclonus Rating Scale action myoclonus (AM), functional tests (FT), patient questionnaire (PQ) sub-scores, and the Unified Dystonia Rating Scale (UDRS) were used during assessments. Improvement in all scales were seen 6 months after surgery (AM: 74%, FT: 60%, PQ: 63%, UDRS: 65%), and this benefit persisted throughout follow-up (AM: 61%, FT:62%, PQ: 65%, UDRS: 86%). No adverse events were noticed. Simultaneous unilateral procedures of GPi and Vim by either stimulation or ablation techniques improve both motor and functional scores in myoclonus-dystonia syndrome.

Cerebral blood flow in dystonia due to pantothenate kinase-associated neurodegeneration.

BACKGROUND AND PURPOSE: The aim of this study was to look for deviations of cerebral perfusion in patients suffering from pantothenate kinase-associated neurodegeneration, where the globus pallidus is affected by severe accumulation of iron. MATERIAL AND METHODS: Under resting conditions, cerebral blood flow was measured by the magnetic resonance imaging technique of arterial spin labelling in cortical areas and basal ganglia in eight pantothenate kinase-associated neurodegeneration patients and 14 healthy age-matched control subjects and correlated to T2* time of these areas and - in patients - to clinical parameters. RESULTS: Despite highly significant differences of T2* time of the globus pallidus (20 vs 39 ms, p < 0.001), perfusion values of this nucleus were nearly identical in both groups (32 ± 3.3 vs 31 ± 4.0 ml/min/100 g) as well as in total brain gray matter (both 62 ± 6.7 resp. ±10.3 ml/min/100 g), putamen (41 ± 5.4 vs 40 ± 6.1 ml/min/100 g), in selected cortical regions, and the cerebellum. Correlations between perfusion and T2* time to clinical data did not reach significance (p > 0.05). CONCLUSION: The absence of any obvious deviations of perfusion in the group of patients during a resting condition does not support the view that (non-functional) vascular pathology is a major pathogenic factor in pantothenate kinase-associated neurodegeneration in the younger age group. The findings underline the value of the arterial spin technique to measure cerebral blood flow in areas of disturbed susceptibility.

Reduction of dopaminergic transmission in the globus pallidus increases anxiety-like behavior without altering motor activity.

The globus pallidus (GP) plays an important role in the flow of information between input and output structures of the basal ganglia (BG) circuit. In addition to participating in motor control, the GP may also be involved in cognitive and emotional functions related to the symptoms of patients with Parkinson's disease (PD). Since the GP receives dopaminergic innervation from the substantia nigra pars compacta (SNc), it is important to determine whether a local dopamine (DA) deficit in the GP is related not only to motor but also to the cognitive and emotional alterations of PD. The aim of this study was to examine the effects of lesions in the GP (induced by 6-OHDA) on anxiety, depression and ambulation in rats. Such lesions are known to reduce dopaminergic innervation in this brain structure. Additionally, the effect on DA receptors in the GP was tested by local administration of the dopamine agonist PD168,077, antagonist haloperidol and psychostimulant amphetamine. Experimental anxiety was evaluated with the elevated plus maze (EPM), burying behavior test (BBT) and social interaction test, while depressive-like behavior was assessed with the sucrose preference test. Rats with unilateral and bilateral lesions showed a higher level of anxiety than intact animals in both the EPM and BBT, an effect also obtained after intrapallidal injection of haloperidol. The administration of methamphetamine or PD-168.077 caused the opposite effect. The dopaminergic lesions in the GP did not affect sucrose preference, social interaction or ambulation. These results show that dopamine in the GP, acting through D2 or D4 receptors, may be involved in the manifestation of anxiety, a non-motor symptom of PD that often appears before motor symptoms.

Intrinsic Connectivity of the Globus Pallidus: An Uncharted Marker of Functional Prognosis in People With First-Episode Schizophrenia.

There is growing evidence suggesting that abnormalities in cortical-basal ganglia circuitry may play a significant role in determining outcomes in schizophrenia. The globus pallidus (GP), a critical structure within this circuitry, unique in its role as a mediator of competing inputs through the striatum, has not been well characterized in schizophrenia. The following study examined functional interactions of the GP in individuals with first-episode schizophrenia (FES). To probe the large-scale intrinsic connectivity of the GP, resting-state fMRI scans were obtained from patients with FES and sex and age-matched healthy controls. Participants with FES were also evaluated after 6 months via the Strauss-Carpenter Outcomes Scale to assess overall functional trajectory. The GP was parcellated to generate seeds within its substructures, and connectivity maps were generated. Our FES cohort showed significantly lower functional connectivity between the left GP interna and a network of regions including the dorsolateral prefrontal cortex, caudate, and cerebellum at baseline. In addition, FES participants with lower overall scores of functioning at 6 months showed significantly decreased connectivity between the GP interna and the dorsal anterior cingulate and bilateral insula, all regions important for motivational salience. These results provide novel evidence for unique abnormalities in functional interactions of the GP with key prefrontal cortical regions in FES. Our findings also suggest that reduced prefrontal-pallidal connectivity may serve as a predictor of early functional outcome.

Morphometric Study of the Internal Globus Pallidus Using the Robert, Barnard, and Brown Staining Method.

BACKGROUND: The globus pallidus internus (Gpi) is a major target in functional neurosurgery. Anatomical studies are crucial for correct planning and good surgical outcomes in this region. The present study described the anatomical coordinates of the Gpi and its relationship with other brain structures and compared the findings with those from previous anatomical studies. METHODS: We obtained 35 coronal and 5 horizontal brain specimens from the Department of Anatomy and stained them using the Robert, Barnard, and Brown technique. After excluding defective samples, 60 nuclei were analyzed by assessing their distances to the anatomical references and the trajectories to these nuclei. RESULTS: The barycenter of the Gpi was identified at the level of the mammillary bodies and 1 cm above the intercommissural plane. Thereafter, the distances to other structures were found. The mean ± standard deviation distance was 15.62 ± 2.66 mm to the wall of the third ventricle and 17.02 ± 2.69 mm to its midline, 4.74 ± 1.12 mm to the optic tract, 2.51 ± 0.8 mm and 13.56 ± 2 mm to the internal and external capsule, and 21.3 ± 2.44 mm to the insular cortex. The cortical point of entry should be located 22.03 ± 4.34 mm to 48.74 ± 4.44 mm from the midline. CONCLUSION: The Gpi has less variability in distance to closer anatomical references, such as the optic tract and internal capsule. Distant locations showed a more inhomogeneous pattern. Anatomical studies such as ours are important for the development of new therapeutic approaches and can be used as a basis for new research involving volumetric and specific group analyses.

Deep Brain Stimulation Surgery for Parkinson Disease Coexisting With Communicating Hydrocephalus: A Case Report.

We report a successful bilateral globus pallidus internus-deep brain stimulation (GPi-DBS) for a Parkinson disease (PD) patient with idiopathic normal pressure hydrocephalus (INPH) and an unusually long anterior commissure-posterior commissure (AC-PC) line. A 54-year-old man presented with a history of 3 months of severe shuffling gait, rigidity, slow movements of the left side limbs, and difficulty managing finances. A brain MRI revealed marked ventriculomegaly (Evans index = 0.42). The patient was diagnosed with INPH and a ventriculoperitoneal shunt was placed. Cognitive impairment improved, but walking disturbances, slowness, and rigidity persisted. Then treatment with levodopa was added, and the patient experienced a sustained improvement. He was diagnosed with PD. After 7 years, the patient developed gait freezing and severe levodopa-induced dyskinesia. The patient underwent bilateral GPi-DBS. We used MRI/CT fusion techniques for anatomical indirect targeting. Indirect targeting is based on standardized stereotactic atlas and on a formula-derived method based on AC-PC landmarks. The AC-PC line was 40 mm (the usual length is between 19 and 32 mm). Intraoperative microelectrode recording was a non-expendable test, but multiple recordings were avoided to reduce the surgical risk of ventricular involvement. There was a 71% decrease in the UPDRS III score during the on-stimulation state (28 to 8). The patient's dyskinesias resolved dramatically with a UdysRS of 15 (88% improvement) during the on-stimulation condition. The observed motor benefits and the improvement of his daily activities have persisted 6 months after surgery. Deep brain stimulation surgery in PD with ventriculomegaly is a challenge. This procedure can result in a greater chance of breaching the ventricle, with risks of intraventricular hemorrhage and migration of cerebrospinal fluid into the brain parenchyma with target displacement. Furthermore, clinical judgment is paramount when recent onset of shuffling gait coexists with ventriculomegaly because the most common dilemma is differentiating between PD and INPH. For these reasons, neurologists and surgeons may refuse to operate on PD patients with ventriculomegaly. However, DBS should be considered for PD patients with motor complications when responsiveness to levodopa is demonstrated, even in the context of marked ventriculomegaly.

Estimulación cerebral profunda del globo pálido interno en pacientes con síndrome de Gilles de la Tourette / Deep brain stimulation of internal globus pallidus in Tourette syndrome

RESUMEN INTRODUCCIÓN: El síndrome de Gilles de la Tourette es un trastorno neuropsiquiátrico caracterizado por tics y comorbilidades que comienza en la infancia. La estimulación cerebral profunda (ECP), aceptada como tratamiento para otros trastornos, se reserva para casos severos y pacientes con farmacorresistencia, aunque sigue permaneciendo en terreno experimental para esta patología. El objetivo de este trabajo es analizar la bibliografía científica actual acerca de la ECP del globo pálido interno en la reducción de tics y comorbilidades asociadas a este Síndrome. MATERIAL Y METODOS: Se ha realizado una revisión sistemática de varios artículos científicos consultando (entre febrero y marzo de 2017) las bases de datos MedLine, PubMed, Scopus, Web of Science y Cochrane. Se ha limitado la búsqueda a todos aquellos artículos publicados entre 2012 y 2017, escritos en inglés y realizados en humanos; se excluyeron revisiones, cartas al editor o aquellos que no se centrasen en el tema de estudio. RESULTADOS: En general, los resultados obtenidos muestran mejoras significativas en casi la totalidad de pacientes, pero, la carencia de estudios controlados aleatorizados con muestras mayores, la falta de resultados fiables, la ausencia de uniformidad en los protocolos y el desconocimiento de la fisiopatología y del área ideal a estimular, hacen que la aplicación de esta técnica no goce de evidencia científica suficiente para ser aceptada como parte del tratamiento de este síndrome hipercinético.

SUMMARY INTRODUCTION: Gilles de la Tourette syndrome is a neuropsyquiatric disorder characterized by tics and comorbidities which starts during the infancy. Deep brain Stimulation, accepted as treatment for other diseases, it is reserved for severe cases and pharmacoresistant patients, even though it still remains on the experimental field for this pathology. The main aim of this review is to analyse the current scientific bibliography about Deep brain Stimulation of the Globus Pallidus Internus on the reduction of tics and associated comorbidities from Gilles de la Tourette Syndrome. MATERIAL AND METHODS: A systematic review of several scientific articles was done checking (February-March, 2017) MedLine, PubMed, Scopus, Web of Science and Cochrane databases. We have restricted the search to all those articles published from 2012 to 2017, written in English and done with humans, excluding those which were reviews, letters to the editor or not focussed on the subject of the study. RESULTS: In general, the outcomes shows significant improvements in almost the totality of patients but the lack of randomised controlled trials with higher samples, the shortage of reliable results and the lack of awareness of the physiopathology and the ideal target to stimulate, don't allow this technique to enjoy scientific evidence enough to be accepted as part of the treatment for this hyperkinetic disorder.

Control temprano de los factores de mal pronóstico en el abordaje de los pacientes con eventos cerebrovasculares isquémicos / Early control of the factors of poor prognosis in the approach of patients with ischemic cerebrovascular events

RESUMEN OBJETIVO: Describir aspectos generales en relación con los eventos cerebrovasculares (ECV) isquémicos, así como los principales factores pronósticos que se han relacionado con el desenlace y la recuperación funcional posterior al evento cerebrovascular. MATERIALES Y MÉTODOS: Se realizó una revisión narrativa utilizando bases de datos (PubMed, Science Direct, MEDLINE), plataformas virtuales (National Institutes of Health) y publicaciones del Acta Neurológica Colombiana. RESULTADOS: Ser mujer, la edad avanzada, la inatención (negligencia), la gravedad del compromiso cognitivo y de la función ejecutiva, la desnutrición, y comorbilidades como la neumonía se asocian con un peor pronóstico en los 90 días posteriores al evento. Las alteraciones en la esfera mental (delirio), alteración de la conciencia, hemiplejia o parálisis de la mirada conjugada y el origen cardioembólico del ECV son algunos de los factores asociados con la mortalidad. La lateralidad hemisférica es una variable importante a tener en cuenta para valorar el pronóstico y la discapacidad funcional residual posevento; sin embargo, la evidencia actual es poco concluyente y algo contradictoria en relación con su rol como factor pronóstico. CONCLUSIONES: Es importante un diagnóstico temprano y una intervención adecuada de los pacientes afectados con ECV isquémico, así como el control precoz de los factores modificables de mal pronóstico. Entre los no modificables, la lateralidad hemisférica podría ser más bien un criterio de selección para un programa de rehabilitación específico y personalizado, pues indudablemente existe un compromiso cognitivo y del lenguaje que difiere sustancialmente en relación con la ubicación topográfica de la lesión.

SUMMARY OBJETIVE: To describe general aspects related to acute ischemic stroke (AIS), as well as to know the main prognostic factors that have been related to the outcome and functional recovery after the AIS. MATERIALS AND METHODS: A narrative review was performed using databases (PubMed, Science-Direct, MEDLINE), virtual platforms (National Institutes of Health) and publications of the Colombian Neurological Record. RESULTS: Being female, advanced age, inattention (neglect), severity of cognitive and executive function impairment, malnutrition, and comorbidities such as pneumonia are associated with a worse prognosis in the 90 days after the event. Alterations in the mental sphere (delirium), altered consciousness, hemiplegia or paralysis of the conjugate gaze and the cardioembolic origin of the AIS are some of the factors that are associated with higher mortality. Hemispheric laterality is an important variable to consider in assessing the prognosis and residual functional disability post-event; however the current evidence is inconclusive and somewhat contradictory. CONCLUSIONS: Early diagnosis and adequate intervention of patients with AIS and early control of modifiable factors of poor prognosis are important. Among the non-modifiable, hemispheric laterality may be more a selection criterion for a specific and personalized rehabilitation program, since there is undoubtedly a cognitive and language compromise that differs substantially in relation to the topographical location of the ischemic lesion.

Deep brain stimulation outcomes in patients implanted under general anesthesia with frame-based stereotaxy and intraoperative MRI.

OBJECTIVEThe authors' aim in this study was to evaluate placement accuracy and clinical outcomes in patients who underwent implantation of deep brain stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI after induction of general anesthesia.METHODSThirty-three patients with movement disorders (27 with Parkinson's disease) underwent implantation of unilateral or bilateral deep brain stimulation systems (64 leads total). All patients underwent the implantation procedure with standard frame-based techniques under general anesthesia and without microelectrode recording. MR images were acquired immediately after the procedure and fused to the preoperative plan to verify accuracy. To evaluate clinical outcome, different scales were used to assess quality of life (EQ-5D), activities of daily living (Unified Parkinson's Disease Rating Scale [UPDRS] part II), and motor function (UPDRS part III during off- and on-medication and off- and on-stimulation states). Accuracy was assessed by comparing the coordinates (x, y, and z) from the preoperative plan and coordinates from the tip of the lead on intraoperative MRI and postoperative CT scans.RESULTSThe EQ-5D score improved or remained stable in 71% of the patients. When in the off-medication/on-stimulation state, all patients reported significant improvement in UPDRS III score at the last follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points and 23.5%, respectively). There was improvement or stability in the UPDRS II scores for 68% of the Parkinson's patients. For 2 patients, the stereotactic error was deemed significant based on intraoperative MRI findings. In these patients, the lead was removed and replaced after correcting for the error during the same procedure. Postoperative lead revision was not necessary in any of the patients. Based on findings from the last intraoperative MRI study, the mean difference between the tip of the electrode and the planned target was 0.82 mm (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y-axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral implantation, accuracy was further evaluated comparing the first implanted side and the second implanted side. There was a significant mediolateral (x-axis) difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57 mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).CONCLUSIONSFrame-based DBS implantation under general anesthesia with intraoperative MRI verification of lead location is safe, accurate, precise, and effective compared with standard implantation performed using awake intraoperative physiology. More clinical trials are necessary to directly compare outcomes of each technique.

Unilateral thalamic and pallidal deep brain stimulation for idiopathic hemidystonia: results of individual and combined stimulations. Case report.

Pallidal stimulation has been the usual surgical treatment for dystonia in the last decades. The continuous investigation of the physiopathology and the motor pathways involved leads to the search for complementary targets to improve results. The authors present the case of a 37-year-old woman who had suffered from idiopathic hemidystonia with hyperkinetic and hypokinetic movements for 11 years, and who was treated with deep brain stimulation. A brief literature review is also provided. The globus pallidus internus and the ventral intermediate/ventral oral posterior complex of the thalamus were stimulated separately and simultaneously for 3 months and compared using the Burke-Fahn-Marsden Dystonia Rating Scale and the Global Dystonia Severity Rating Scale, with a 3.5-year follow-up. The synergism of multiple-target stimulation resulted in a complete improvement of the mixed dystonic symptoms.

Degeneración hepatocerebral adquirida reporte de caso y revisión de la literatura / Acquired hepatocerebral degeneration. case report and literature review

Acquired hepatocerebral degeneration also termed acquired hepatolenticular degeneration, cirrhosis-related Parkinsonism o pseudo-Wilson is a rare, progressive and chronic neurological syndrome that occurs in patients with chronic liver disease, particularly in those with surgically or spontaneously induced portosystemic shunts. The clinical features of this pathological entity include extrapyramidal signs, ataxia, cognitive decline and neuropsychiatric changes, such as delirium, apathy, lethargy and emotional instability. Brain Magnetic Resonance Imaging classically shows symmetrical T1-weighted hyperintensities in the globus pallidus, substantia nigra and periaqueductal gray matter. Although its pathogenesis is not completely elucidated, it is postulated that the excess manganese accumulation and deposition in the basal ganglia, leading to dysfunctional dopaminergic system in this anatomical location, would have a key role in triggering the disease. Orthotopic liver transplantation is the mainstay of treatment and is considered effective by reducing motor and cognitive alterations. Other therapeutic alternatives that have reported symptomatic improvement are the use of bromocriptine or levodopa and portosystemic shunts occlusion. In this article, we report a case of a 63-year-old woman with clinical manifestations over the course of one year, characterized by cognitive decline, chorea, gait and language disturbances. She was examined with plasma levels of copper and ceruloplasmin, which excluded the possibility of Wilson´s Disease, its main differential diagnosis. Neuroimaging revealed T1-weighted hyperintensity in the pallidum, confirming suspected diagnosis of acquired hepatocerebral degeneration.