Combined thalamic and pallidal deep brain stimulation in diabetic hemiballism/hemichorea.

Hemiballism/hemichorea (HH) is a hyperkinetic movement disorder observed mostly in older adults with cerebrovascular diseases. Although the symptoms improve without any treatment, lesioning or DBS (deep brain stimulation) may be rarely required to provide symptomatic relief for patients with severe involuntary movements. HH is a rare complication of uncontrolled diabetes. There are only a few reported cases of diabetic HH that have been surgically treated. Thus, herein, we have reported the case of a 75-year-old female with type-II diabetes mellitus that presented with disabling involuntary limb movements of the left side, despite being treated conservatively for six months. DBS targeting the globus pallidus internus (GPi) and ventral intermediate (Vim) thalamic nucleus was performed. Complete resolution of symptoms was achieved with a combined stimulation of the thalamic Vim nucleus (at 1.7 mA) and GPi (at 2.4 mA). The combined stimulation of the Vim nucleus and GPi effectively resolved the diabetes-induced HH symptoms in our patient. Thus, although certain conclusions cannot be drawn due to the rarity of the surgically treated patients with HH, the combined stimulation is a novel treatment option for resistant HH.

Intracerebral hemorrhage after deep brain stimulation surgery guided with microelectrode recording: analysis of 297 procedures / Hemorragia intracerebral después de cirugía de estimulación cerebral profunda guiada por microrregistro: un análisis de 297 procedimientos

Objectives: Report the incidence of symptomatic and asymptomatic intracerebral hemorrhage (ICH) in patients submitted to deep brain stimulation (DBS) guided with microelectrode recording (MER) with further analysis of potential risk factors, both inherent to the patient and related to the pathology and surgical technique. Methods: We performed a retrospective observational study. 297 DBS procedures were concluded in 277 patients in a single hospital centre between January 2010 and December 2020. All surgeries were guided with MER. We analysed the incidence of symptomatic and asymptomatic ICH and its correlation to age, sex, diagnosis, hypertension and perioperative hypertension, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, and number of MER trajectories. Results: There were a total of 585 electrodes implanted in 277 patients. 16 ICH were observed, of which 6 were symptomatic and 10 asymptomatic, none of which incurred in permanent neurological deficit. The location of the hemorrhage varied between cortical and subcortical plans, always in relation with the trajectory or the final position of the electrode. The incidence of symptomatic ICH per lead-implantation was 1%, and the CT-scan demonstrated asymptomatic ICH in 1.7% more patients. Male patients or with hypertension are 2.7 and 2.2 times more likely to develop ICH, respectively. However, none of these characteristics has been shown to have a statistically significant association with the occurrence of ICH, as well as age, diagnosis, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, number of MER trajectories and perioperative hypertension. Conclusions: MER-guided DBS is a safe technique, with low incidence of ICH and no permanent deficits in our study. Hypertension and male sex seem to be risk factors for the development of ICH in this surgery. Nevertheless, no statistically significant factors were found for the occurrence of this complication.(AU)

Objetivos: Reportar la incidencia de hemorragia intracerebral (HIC) sintomática y asintomática en pacientes sometidos a estimulación cerebral profunda (ECP) guiada por microrregistro (MER), con el consecuente análisis de posibles factores de riesgo, tanto inherentes al paciente como relacionados con la patología y técnica quirúrgica. Métodos: Realizamos un estudio observacional retrospectivo. Se analizaron un total de 297 procedimientos de ECP realizados en 277 pacientes en un centro hospitalario entre enero de 2010 y diciembre de 2020. Todas las cirugías fueron guiadas con MER. Analizamos la incidencia de HIC, tanto sintomática como asintomática, y la correlación con edad, sexo, diagnóstico, hipertensión arterial e intraoperatoria, diabetes, dislipemia, medicación antiplaquetaria previa, diana anatómica y número de vías. Resultados: El número total de electrodos implantados fue de 585 en 277 pacientes. Se observaron 16 HIC, de las cuales 10 fueron asintomáticas y 6 sintomáticas y ninguna incurrió en déficit neurológico permanente. La localización de la hemorragia varió entre planos corticales y subcorticales, siempre en relación con el trayecto o posición final del electrodo. La incidencia de hemorragia sintomática fue de alrededor del 1 %, y la TC posoperatoria demostró hemorragia asintomática en un 1,7 % adicional de los pacientes. Los pacientes varones o los pacientes con hipertensión tienen 2,7 y 2,2 veces más probabilidades de desarrollar sangrado, respectivamente. Sin embargo, ninguna de estas características demostró una asociación estadísticamente significativa con la ocurrencia de hemorragia intracerebral, como la edad, el diagnóstico, la diabetes, la dislipidemia, la ingesta previa de medicamentos antiplaquetarios, el objetivo anatómico, el número de MER y las vías de HTA intraoperatorias. Conclusión: La ECP con MER es una técnica segura, con baja incidencia de HIC y sin déficits permanentes en nuestro estudio...(AU)

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation / COVID-19 en la enfermedad de Parkinson tratada con fármacos o estimulación cerebral

Purpose: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. Methods: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. Results: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. Conclusion: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.(AU)

Objetivo: La COVID-19 ha afectado a toda la población, especialmente a aquellos con enfermedades crónicas, incluyendo a los pacientes con enfermedad de Parkinson (EP). La COVID-19 puede empeorar tanto los signos motores como los síntomas neuropsiquiátricos de los pacientes con EP. El objetivo de este estudio es evaluar diferentes aspectos del impacto de la COVID-19 en los pacientes con EP. Métodos: A través de un cuestionario virtual se evaluó a 647 pacientes con EP de acuerdo con sus presentaciones clínicas relacionadas con la EP y con la COVID-19, además de la historia médica previa durante la pandemia. Se compararon con un grupo de controles sanos de la misma edad que constaba de 673 individuos y una muestra de la población general de 1.215 individuos. Resultados: La prevalencia de la COVID-19 en pacientes con EP fue del 11,28%. La mortalidad fue del 1,23% entre los pacientes con EP. La prevalencia de COVID-19 en pacientes con EP con estimulación cerebral profunda fue del 18,18%. No se encontró una asociación significativa entre la duración de la enfermedad y la prevalencia de COVID-19. Se halló una prevalencia mayor de COVID-19 que fue estadísticamente significativa en pacientes con EP que tuvieron contacto directo con personas infectadas con SARS-CoV-2. No se encontró una asociación estadísticamente significativa entre el empeoramiento de los signos motores y la COVID-19. Los pacientes con EP y la población general podrían diferir en la prevalencia de algunos trastornos psicológicos, incluidos los trastornos de ansiedad y del sueño, y la COVID-19 podría afectar al estado psicológico. Conclusión: Los pacientes con EP posiblemente sigan protocolos preventivos más estrictos, lo que conduce a una menor prevalencia y gravedad de COVID-19 y de sus consecuencias en estos pacientes.(AU)

Essential Tremor: Update of Therapeutic Strategies. / Temblor esencial: actualización de las estrategias terapéuticas.

In the last decades there has been progress in the treatment of essential tremor (TE) especially in the surgical field and to a lesser extent in the pharmacological field. We carry out a review of the currently available treatments. The first intervention is the use of non-pharmacological and non-surgical strategies (general advice, occupational therapy, speech therapy, psychotherapy). With discrete advances, the pharmacological treatment is not very satisfactory. Only 30-60% of patients have a positive response, and in these the anti-tremor effectiveness is 40-60%. The first-line drugs are still propranolol and primidone. In cases with severe tremor we will consider a surgical option, the method of choice being thalamotomy using high-intensity focused ultrasound. In the future we must continue to study the pathophysiology of TE, develop drugs specifically designed for TE and improve the technology of available invasive techniques.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.

Intracerebral hemorrhage after deep brain stimulation surgery guided with microelectrode recording: analysis of 297 procedures.

OBJECTIVES: Report the incidence of symptomatic and asymptomatic intracerebral hemorrhage (ICH) in patients submitted to deep brain stimulation (DBS) guided with microelectrode recording (MER) with further analysis of potential risk factors, both inherent to the patient and related to the pathology and surgical technique. METHODS: We performed a retrospective observational study. 297 DBS procedures were concluded in 277 patients in a single hospital centre between January 2010 and December 2020. All surgeries were guided with MER. We analysed the incidence of symptomatic and asymptomatic ICH and its correlation to age, sex, diagnosis, hypertension and perioperative hypertension, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, and number of MER trajectories. RESULTS: There were a total of 585 electrodes implanted in 277 patients. 16 ICH were observed, of which 6 were symptomatic and 10 asymptomatic, none of which incurred in permanent neurological deficit. The location of the hemorrhage varied between cortical and subcortical plans, always in relation with the trajectory or the final position of the electrode. The incidence of symptomatic ICH per lead-implantation was 1%, and the CT-scan demonstrated asymptomatic ICH in 1.7% more patients. Male patients or with hypertension are 2.7 and 2.2 times more likely to develop ICH, respectively. However, none of these characteristics has been shown to have a statistically significant association with the occurrence of ICH, as well as age, diagnosis, diabetes, dyslipidaemia, antiplatelet drugs, anatomic target, number of MER trajectories and perioperative hypertension. CONCLUSIONS: MER-guided DBS is a safe technique, with low incidence of ICH and no permanent deficits in our study. Hypertension and male sex seem to be risk factors for the development of ICH in this surgery. Nevertheless, no statistically significant factors were found for the occurrence of this complication.

Estimulación cerebral profunda combinada del núcleo subtalámico y el globo pálido interno en la enfermedad de Parkinson / Combined subthalamic nucleus and globus pallidus internus deep brain stimulation in Parkinson’s disease

Introducción: La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) y el globo pálido interno (GPi) son los principales abordajes quirúrgicos en la enfermedad de Parkinson avanzada. La estimulación suele aplicarse de forma bilateral en la misma estructura cerebral. Sin embargo, cuando diferentes síntomas motores se presentan concomitantemente en el mismo paciente, la modulación simultánea de diferentes estructuras cerebrales puede ser una alternativa eficaz. Caso clínico: Presentamos un paciente con enfermedad de Parkinson avanzada en el que se realizó ECP combinada en NST y el GPi. La ECP del NST izquierdo controló de manera óptima la sintomatología del hemicuerpo derecho, mientras que las discinesias problemáticas que presentaba en el hemicuerpo izquierdo se redujeron con éxito mediante la estimulación del GPi derecho. Discusión. La estimulación combinada del NST/GPi puede considerarse un enfoque neuroquirúrgico adecuado cuando surge una sintomatología motora desafiante en pacientes con enfermedad de Parkinson avanzada.(AU)

Introduction: Subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) are the main surgical approaches for advanced Parkinson’s disease. Stimulation is usually applied bilaterally in the same brain structure. However, when various motor symptoms concomitantly present in the same patient, simultaneous modulation of different brain structures may be a suitable alternative. Case report: We present a patient with advanced Parkinson’s disease with a combined DBS neurosurgery. Left STN DBS optimally controlled the off right hemibody symptomatology while left side troublesome dyskinesias were successfully relieved by right GPi stimulation. Discussion: Combined STN/GPi stimulation can be considered a suitable approach when challenging motor symptomatology arises in advanced Parkinson’s disease patients.(AU)

Comparison of intraoperative imaging guided versus microelectrode recording guided deep brain stimulation for Parkinson's disease: A meta-analysis / Comparativa entre la cirugía guiada por imágenes y la estimulación cerebral profunda guiada por microelectrodos en el tratamiento de la enfermedad de Parkinson: un metaanálisis

Background Traditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD). Methods PubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site. Results Six studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were −0.45 (95% confidence interval, CI=−1.11 to 0.20), −0.18 (95% CI=−0.41 to 0.06), 3.40 (95% CI=−5.36 to 12.16), and 5.00 (95% CI=−1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques. Conclusions Both IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment (AU)

Antecedentes Tradicionalmente, la mayoría de los centros usaban los microelectrodos de registro (microelectrode recording [MER]) para mejorar la orientación en la cirugía mediante la estimulación cerebral profunda (deep brain stimulation [DBS]). En los últimos años, la DBS orientada mediante imágenes intraoperatorias (intraoperative imaging guided [IMG]) se ha convertido en una forma alternativa de verificar la colocación de los electrodos. Hoy en día, todavía existe controversia en torno al uso de MER o IMG para realizar una DBS. Este metaanálisis tiene como objetivo explorar la precisión de los electrodos, la eficacia clínica y la seguridad entre la DBS guiada mediante IMG y MER en el tratamiento de la enfermedad de Parkinson (EP). Métodos Se realizaron búsquedas en PubMed, Embase, Web of Science y Cochrane Library hasta marzo de 2021 para localizar estudios que informasen sobre comparaciones entre la DBS guiada mediante IMG y la guiada mediante MER en la EP. Se realizó un análisis de subgrupos para evaluar los efectos de una tecnología IMG y una ubicación DBS guiada diferentes. Resultados En nuestro análisis hemos incluido seis estudios con 478 pacientes. La diferencia media entre las dos técnicas de implantación en la precisión estereotáctica, los pasos del electrodo por trayectoria, el porcentaje de mejora de la escala unificada de clasificación de la enfermedad de Parkinson, parteIII, y la dosis diaria equivalente de levodopa fueron −0,45 (intervalo de confianza del 95% [IC 95%]: −1,11 a 0,20), −0,18 (IC 95%: −0,41 a 0,06), 3,40 (IC 95%: −5,36 a 12,16) y 5,00 (IC 95%: −1,40 a 11,39), respectivamente. No se observaron diferencias significativas en cada evento adverso y tiempo de operación/procedimiento entre las dos técnicas de implantación (AU)

Estimulación cerebral profunda subtalámica en un caso de enfermedad de Parkinson idiopática y esquizofrenia / Subthalamic deep brain stimulation in a case of idiopathic Parkinson’s disease and schizophrenia

Introducción La enfermedad de Parkinson (EP) y la esquizofrenia pueden coexistir. Los antipsicóticos bloquean los receptores D2 estriados, lo que inevitablemente agrava las manifestaciones de la EP. Caso clínico Presentamos el caso de un paciente con enfermedad de Parkinson idiopática y esquizofrenia, con pobre tolerancia a dosis mínimas de levodopa, que presentó una gran mejoría tras la estimulación cerebral profunda subtalámica bilateral (ECP-NST). La ECP-NST se consideró aquí, debido a la gravedad de este caso particular, como la única posibilidad de lograr una mejoría motora. Conclusiones El diagnóstico de EP idiopática se confirmó pese al tratamiento antidopaminérgico. La ECP-NST puede considerarse como una opción de tratamiento para las manifestaciones de la EP invalidantes, siempre y cuando la selección del paciente sea cuidadosa. (AU)

Introduction. Parkinson’s disease (PD) and schizophrenia can coexist. Antipsychotics block striatal D2 receptors, which inevitably aggravates the manifestations of PD.Case report. We report the case of a male patient with idiopathic Parkinson’s disease and schizophrenia, with poor tolerance to minimal doses of levodopa, who underwent a dramatic improvement after bilateral subthalamic deep brain stimulation (DBS-STN). DBS-STN was taken into consideration here, due to the severity of this particular case, as the only possible way to achieve motor improvement.Conclusions. The diagnosis of idiopathic PD was confirmed despite antidopaminergic treatment. DBS-STN can be considered a treatment option for disabling manifestations of PD, provided that a careful selection of patients is carried out. (AU)

Bilateral deep brain stimulation of the subthalamic nucleus: Targeting differences between the first and second side / Estimulación cerebral profunda bilateral del núcleo subtalámico: diferencias de posicionamiento entre el primer y el segundo lado

Introduction and objectives Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for drug-refractory Parkinson's disease (PD). However, the therapeutic success depends on the accuracy of targeting. This study aimed to evaluate potential accuracy differences in the placement of the first and second electrodes implanted, by comparing chosen electrode trajectories, STN activity detected during microelectrode recording (MER), and the mismatch between the initially planned and final electrode positions on each side. Materials and methods In this retrospective cohort study, we analyzed data from 30 patients who underwent one-stage bilateral DBS. For most patients, three arrays of microelectrodes were used to determine the physiological location of the STN. Final target location depended also on the results of intraoperative stimulation. The choice of central versus non-central channels was compared. The Euclidean vector deviation was calculated using the initially planned coordinates and the final position of the tip of the electrode according to a CT scan taken at least a month after the surgery. Results The central channel was chosen in 70% of cases on the first side and 40% of cases on the second side. The mean length of high-quality STN activity recorded in the central channel was longer on the first side than the second (3.07±1.85mm vs. 2.75±1.94mm), while in the anterior channel there were better MER recordings on the second side (1.59±2.07mm on the first side vs. 2.78±2.14mm on the second). Regarding the mismatch between planned versus final electrode position, electrodes on the first side were placed on average 0.178±0.917mm lateral, 0.126±1.10mm posterior and 1.48±1.64mm inferior to the planned target (AU)

Introducción y objetivos La estimulación cerebral profunda (ECP) del núcleo subtalámico (NST) es reconocida como un tratamiento para la enfermedad de Parkinson (EP) refractaria al tratamiento farmacológico. Sin embargo, el éxito de esta intervención depende de la precisión de la colocación de los electrodos. Este estudio tuvo como objetivo evaluar las posibles diferencias de precisión entre la colocación del primer y segundo electrodo, comparando las trayectorias elegidas para cada lado, la actividad del NST detectada durante el microrregistro (MER) y la discrepancia entre las posiciones inicialmente planeadas y las finales. Materiales y métodos En este estudio retrospectivo analizamos datos de 30 pacientes sometidos a ECP bilateral. En la mayoría de los casos se usaron tres conjuntos de microelectrodos para determinar la ubicación fisiológica del NST. El posicionamiento final del electrodo estuvo asimismo condicionado por los resultados de la estimulación intraoperatoria. Se comparó la elección de canales centrales vs. no centrales. El vector euclidiano del desvío se calculó a partir de las coordenadas planeadas inicialmente y la posición final de la punta del electrodo, según una tomografía computarizada realizada al menos un mes después de la cirugía. Resultados La trayectoria central se eligió en 70% de los casos en el primer lado y en el 40% de los casos en el segundo lado. La duración media de la actividad de alta calidad del NST registrada en el canal central fue mayor en el primer lado que en el segundo (3,07±1,85mm vs. 2,75±1,94mm), mientras que en el canal anterior hubo mejores registros de MER en el segundo lado (1,59±2,07mm en el primer lado vs. 2,78±2,14mm en el segundo) (AU)

Colgajo axial de fascia temporoparietal (TPFF) para cobertura de dispositivo de estimulación cerebral profunda. Reporte de caso / Axial temporoparietal fascia flap (TPFF) for deep brain stimulation device coverage. Case report

Presentamos el caso de una paciente con enfermedad de Parkinson y extrusión del fijador craneal del electrodo de estimulación cerebral profunda. Luego del explante de todo el sistema, se realizó un colgajo axial de fascia temporoparietal (TPFF) para cobertura del trépano residual y en el segundo tiempo se utilizó el colgajo para cubrir el nuevo implante. La paciente no presentó complicaciones durante el seguimiento de 2 años

We present the case of a patient with Parkinson's disease and extrusion of the cranial fixation of the deep brain stimulation electrode. After explantation of the entire system, an axial flap of temporoparietal fascia (TPFF) was performed to cover the residual Burr hole, and in the second procedure, the flap was used to cover the new implant. The patient did not experience any complications during the 2-year follow-up period.

Evolución y tratamiento de la fase avanzada de una serie de pacientes con enfermedad de Parkinson LRRK2 / Progression and treatment of a series of patients with advanced LRRK2-associated Parkinson’s disease

Introducción: Las mutaciones en el gen LRRK2 se han relacionado tradicionalmente con unfenotipo benigno de la enfermedad de Parkinson (EP). En la fase avanzada, se ha descrito unarespuesta favorable a la estimulación cerebral profunda (ECP). Métodos: Retrospectivamente, hemos analizado las características clínicas y la evolución de14 pacientes con EP debida a mutaciones en LRRK2 (EP-LRRK2), 13 en G2019S y uno en I1371 V.Nueve de ellos, en fase avanzada, tuvieron una evolución media de 7, 2 a ̃nos hasta alcanzarla.Resultados: Siete pacientes fueron intervenidos de ECP subtalámica bilateral y dos recibierontratamiento con una terapia de infusión. Los pacientes portadores de la mutación G2019S mos-traron una excelente respuesta a la ECP, con una mejoría a los seis meses superior al 80% en laUnified Parkinson’s disease rating scale (UPDRS II y UPDRS III). Esta respuesta se ha mantenidoen el tiempo. El paciente con la mutación I1371 V mostraba un fenotipo grave de la enfermedad y su respuesta a la ECP ha sido moderada. Los pacientes con EP-LRRK2 en fase avanzadamostraron una afectación cognitiva predominantemente frontal con un deterioro significativodel lenguaje. Conclusiones: En nuestros pacientes con EP-LRRK2 hemos observado un fenotipo con una evolución más rápida a la fase avanzada de la enfermedad. Recalcamos la idoneidad de la ECPsubtalámica en estos casos.(AU)

Introduction: LRRK2 mutations have traditionally been associated with a benign phenotype ofParkinson’s disease (PD). Favourable responses to deep brain stimulation (DBS) are reported inthe advanced phase. Methods: We performed a retrospective analysis of the clinical characteristics and progressionof 13 patients with LRRK2-associated PD (13 with G2019S and one with I1371 V). Nine patientswere in the advanced phase, with a mean progression time of 7.2 years before reaching thisphase. Results: Seven patients underwent bilateral subthalamic DBS implantation, and two receivedinfusion treatment. Patients with mutation G2019S responded excellently to DBS, with UnifiedParkinson’s disease rating scale (UPDRS) II and III scores improving by 80% at six months. Thisresponse was sustained over time. The patient with mutation I1371 V had a severe phenotypeof the disease, and presented a moderate response to DBS. Patients with advanced LRRK2-associated PD showed predominantly frontal cognitive involvement, with significant languageimpairment. Conclusions: In these patients, progression was faster in the advanced stage of the disease.We emphasise the suitability of subthalamic DBS in the management of these patients.(AU)

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies? / ¿La estimulación cerebral profunda del núcleo subtalámico afecta el equilibrio estático en diferentes frecuencias?

Purpose To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. Materials and methods Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were ‘stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)’. These tests reported the centre of pressure data ‘ellipse area, perimeter, front/back and mediolateral standard deviations’. Results There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward–backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). Conclusion This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges (AU)

Propósito Investigar los efectos de la estimulación cerebral profunda del núcleo subtalámico bilateral (STN-DBS) con diferentes frecuencias de estimulación sobre el equilibrio estático. Materiales y métodos Se incluyó en el estudio a 20 pacientes (15 varones y 5 mujeres), con edades comprendidas entre 43 y 81 años (media: 60,05±7,4), que habían sido diagnosticados de enfermedad de Parkinson idiopática e intervenidos mediante cirugía STN-DBS. El equilibrio estático se evaluó con el sistema de rehabilitación TecnoBody en 4 frecuencias diferentes: 230, 130, 90 y 60Hz y sin estimulación. Las pruebas de equilibrio estático fueron: prueba estabilométrica, ojo cerrado/abierto bípedo comparado con estabilométrico, monopedal comparado con estabilométrico (pie derecho/izquierdo). Estas pruebas informaron el centro de datos de presión: área de elipse, perímetro, desviaciones estándar mediolateral y frontal/posterior. Resultados No hubo diferencias estadísticamente significativas entre los resultados de la prueba de equilibrio estático en cualquier frecuencia (p>0,05), pero los resultados fueron mejores con 90Hz. El resultado de la desviación estándar hacia adelante-atrás del ojo abierto bípedo comparado con el estabilométrico fue significativo entre la estimulación inactiva y 130Hz (p=0,04). La estimulación de diferente frecuencia afectó al porcentaje de categorías de equilibrio estático, sin significación estadística entre la estimulación inactiva y otras (todas p>0,05). Conclusión Este estudio mostró que STN-DBS no afectó negativamente al equilibrio estático. La estimulación de baja frecuencia mejoró el equilibrio estático. Los sistemas de posturografía darán resultados más precisos y cuantitativos en estudios similares con amplios rangos de frecuencia (AU)

Comparison of intraoperative imaging guided versus microelectrode recording guided deep brain stimulation for Parkinson's disease: A meta-analysis.

BACKGROUND: Traditionally, most centers would use microelectrode recording (MER) to refine targeting in deep brain stimulation (DBS) surgery. In recent years, intraoperative imaging (IMG) guided DBS has become an alternative way to verify lead placement. Currently, there is still controversy surrounding the necessity of MER or IMG for DBS. This meta-analysis aims to explore lead accuracy, clinical efficacy and safety between IMG and MER guided DBS for Parkinson's disease (PD). METHODS: PubMed, Embase, Web of Science, Cochrane Library were searched up to Mar, 2021 for studies reporting comparisons between IMG and MER guided DBS for PD. Subgroup analysis was conducted to assess effects of different IMG technology and DBS targeting site. RESULTS: Six studies, comprising of 478 patients were included in our analysis. The mean difference between the two implantation techniques in stereotactic accuracy, lead passes per trajectory, improvement% of Unified Parkinson's Disease Rating Scale part III and levodopa equivalent daily dose were -0.45 (95% confidence interval, CI=-1.11 to 0.20), -0.18 (95% CI=-0.41 to 0.06), 3.40 (95% CI=-5.36 to 12.16), and 5.00 (95% CI=-1.40 to 11.39), respectively. No significant differences were observed in each adverse event and operation/procedure time between the two implantation techniques. CONCLUSIONS: Both IMG and MER guided DBS offered effective control of motor symptoms for PD. Besides, IMG guided is comparable to MER guided DBS, in terms of safety, accuracy and efficiency. It is recommended for each hospital to select DBS guidance technology based on available resources and equipment.

Bilateral deep brain stimulation of the subthalamic nucleus: Targeting differences between the first and second side.

INTRODUCTION AND OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a recognized treatment for drug-refractory Parkinson's disease (PD). However, the therapeutic success depends on the accuracy of targeting. This study aimed to evaluate potential accuracy differences in the placement of the first and second electrodes implanted, by comparing chosen electrode trajectories, STN activity detected during microelectrode recording (MER), and the mismatch between the initially planned and final electrode positions on each side. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed data from 30 patients who underwent one-stage bilateral DBS. For most patients, three arrays of microelectrodes were used to determine the physiological location of the STN. Final target location depended also on the results of intraoperative stimulation. The choice of central versus non-central channels was compared. The Euclidean vector deviation was calculated using the initially planned coordinates and the final position of the tip of the electrode according to a CT scan taken at least a month after the surgery. RESULTS: The central channel was chosen in 70% of cases on the first side and 40% of cases on the second side. The mean length of high-quality STN activity recorded in the central channel was longer on the first side than the second (3.07±1.85mm vs. 2.75±1.94mm), while in the anterior channel there were better MER recordings on the second side (1.59±2.07mm on the first side vs. 2.78±2.14mm on the second). Regarding the mismatch between planned versus final electrode position, electrodes on the first side were placed on average 0.178±0.917mm lateral, 0.126±1.10mm posterior and 1.48±1.64mm inferior to the planned target, while the electrodes placed on the second side were 0.251±1.08mm medial, 0.355±1.29mm anterior and 2.26±1.47mm inferior to the planned target. CONCLUSION: There was a tendency for the anterior trajectory to be chosen more frequently than the central on the second side. There was also a statistically significant deviation of the second electrodes in the anterior and inferior directions, when compared to the electrodes on the first side, suggesting that another cause other than brain shift may be responsible. We should therefore factor this during planning for the second implanted side. It might be useful to plan the second side more anteriorly, possibly reducing the number of MER trajectories tested and the duration of surgery.

Does subthalamic nucleus deep brain stimulation affect the static balance at different frequencies?

PURPOSE: To investigate the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) with different stimulation frequencies on static balance. MATERIALS AND METHODS: Twenty patients (15 males and 5 females), aged between 43 and 81 (mean: 60.05±7.4) years, who had been diagnosed with idiopathic Parkinson's disease (PD) and undergone STN-DBS surgery were included in the study. Static balance was assessed with TecnoBody Rehabilitation System at four different frequencies: 230, 130, 90 and 60Hz and off-stimulation. Static balance tests were 'stabilometric test, stabilometric compared bipedal closed/opened eye, stabilometric compared mono pedal (right/left foot)'. These tests reported the centre of pressure data 'ellipse area, perimeter, front/back and mediolateral standard deviations'. RESULTS: There were no statically differences between the static balance test results at any frequency (p>0.05), but results were found better at 90Hz. Stabilometric compared bipedal opened eye forward-backward standard deviation result was significant between off-stimulation and 130Hz (p=0.04). Different frequency stimulation affected the static balance categories percentage with no statistical significance between off-stimulation and others (all p>0.05). CONCLUSION: This study showed that STN-DBS did not affect the static balance negatively. Low-frequency (LF) stimulation improved the static equilibrium. Posturography systems will give more precise and quantitative results in similar studies with wide frequency ranges.

Progression and treatment of a series of patients with advanced LRRK2-associated Parkinson's disease.

INTRODUCTION: LRRK2 mutations have traditionally been associated with a benign phenotype of Parkinson's disease (PD). Favourable responses to deep brain stimulation (DBS) are reported in the advanced phase. METHODS: We performed a retrospective analysis of the clinical characteristics and progression of 13 patients with LRRK2-associated PD (13 with G2019S and 1 with I1371V). Nine patients were in the advanced phase, with a mean progression time of 7.2 years before reaching this phase. RESULTS: Seven patients underwent bilateral subthalamic DBS implantation, and 2 received infusion treatment. Patients with mutation G2019S responded excellently to DBS, with Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores improving by 80% at 6 months. This response was sustained over time. The patient with mutation I1371V had a severe phenotype of the disease, and presented a moderate response to DBS. Patients with advanced LRRK2-associated PD showed predominantly frontal cognitive involvement, with significant language impairment. CONCLUSIONS: In these patients, progression was faster in the advanced stage of the disease. We emphasise the suitability of subthalamic DBS in the management of these patients.

Hacia una definición fisiológica positiva de los núcleos cerebrales profundos en humanos / Towards a positive physiological definition of the deep brain nuclei in humans

Introducción: El registro con microelectrodos en la estimulación cerebral profunda (ECP) ha demostrado una gran utilidad. Es posible mejorar su eficiencia caracterizando las propiedades de los potenciales de acción extracelulares (PAE). Pacientes y métodos: Hemos analizado registros de nueve pacientes operados por epilepsia o agresividad bajo anestesia general. Se han determinado las propiedades de los PAE de los núcleos talámicos centromediano, ventral intermedio, ventrocaudal e hipotalámico posteromedial. Resultados: Hemos analizado 706 células talámicas y 142 hipotalámicas. La proporción de tipos celulares resultó específica de cada núcleo celular. El tipo celular más frecuente fue P1P2N1 (59,5%), seguido por N1P1N2 (23,1%). La primera fase del PAE es altamente variable. Las propiedades de las fases del PAE de la misma morfología difieren altamente entre núcleos. Conclusiones: Hemos demostrado que diversos núcleos cerebrales profundos tienen propiedades específicas de la morfología de los PAE. Esto permitirá una mejora en la localización de estos núcleos durante la ECP.(AU)

Introduction: Using microelectrodes for recording purposes in deep brain stimulation (DBS) has proven to be very useful. Their efficiency can be improved by characterising the properties of extracellular action potentials (EAPs). Patients and methods: We analysed the records of nine patients who underwent surgery for epilepsy or aggressiveness under general anaesthesia. The properties of the EAPs of the centromedian, ventral intermediate, ventrocaudal and posteromedial hypothalamic nuclei of the thalamus have been determined. Results: We have analysed 706 thalamic and 142 hypothalamic cells. The proportion of cell types was found to be specific to each cell nucleus. The most frequent cell type was P1P2N1 (59.5%), followed by N1P1N2 (23.1%). The first phase of the EAP is highly variable. The properties of the EAP phases of the same morphology differ greatly from one nucleus to another. Conclusions: We have shown that several deep brain nuclei have properties that are specific to the morphology of the EAPs. This will allow for improved localisation of these nuclei during DBS.(AU)

Nueva mutación en el gen KMT2B como causa de distonía generalizada de inicio temprano: reporte de caso / Early-onset generalized dystonia caused by a new mutation in the KMT2B gene: Case report

La distonía por mutación en el gen KMT2B es un subtipo recientemente descrito del inicio focal de la enfermedad en los miembros inferiores que, posteriormente, evoluciona a una forma generalizada con compromiso cervical y orofaríngeo, disartria, trastorno secundario de la deglución y discapacidad intelectual. Se describe el caso de una escolar de 10 años de edad, sin antecedentes de consanguinidad ni historia familiar de enfermedad neurológica, que presentó alteración de la marcha y distonía de inicio focal, de curso progresivo a una forma generalizada que afectó sus músculos orofaciales y bulbares con alteración significativa del lenguaje y la deglución. Los estudios metabólicos y sistémicos, incluidas las neuroimágenes, no evidenciaron anormalidades. Se hizo una secuenciación genómica completa y se identificó una nueva variante, probablemente patogénica heterocigota, en el gen KMT2B, la c.1205delC, p.(Pro402Hisfs*5), que causa desplazamiento en el marco de lectura. Este hallazgo explica el fenotipo de la paciente y la distonía de inicio temprano autosómica dominante. Se reporta una nueva mutación heterocigota del gen KMT2B como causa de distonía generalizada de inicio temprano, no reportada en la literatura especializada hasta el momento. El diagnóstico de esta afección tiene implicaciones en el tratamiento y el pronóstico de los pacientes, porque las estrategias terapéuticas tempranas pueden prevenir su rápido deterioro y un curso más grave de la enfermedad.

Introduction: KMT2B-related dystonia is a recently described subtype of focal-onset dystonia in the lower limbs, evolving into a generalized form with cervical, oropharyngeal involvement, dysarthria, swallowing disorder and intellectual disability. Clinical case: We describe the case of a 10-year-old female patient, without a history of consanguinity or neurological disease. She manifested abnormal gait and dystonia with focal onset and progressive course with evolution into generalized dystonia, affecting orofacial and bulbar muscles, significant alteration of language and swallowing. Metabolic and systemic studies, including neuroimaging, were found to be normal. A complete genomic sequencing study was performed identifying a new, probably pathogenic, heterozygous variant in the KMT2B gene, c.1205delC, p. (Pro402Hisfs*5), causing displacement in the reading frame, a finding that explains the patient's phenotype and it is associated to autosomal dominant childhood-onset dystonia-28. Conclusion: We report a new heterozygous mutation in the KMT2B gene as a cause of generalized early-onset dystonia not reported in the literature until the date. The diagnosis of this pathology has implications for the treatment and prognosis of patients, given that therapeutic strategies implemented early can prevent the fast deterioration and severe course of this disease.

Neuromodulación del núcleo talámico anterior como opción terapéutica para epilepsia de difícil control / Neuromodulation of the anterior thalamic nucleus as a therapeutic option for difficult-to-control epilepsy

La estimulación cerebral profunda (ECP) consiste en la estimulación eléctrica de las estructuras subcorticales mediante el implante de electrodos conectados a un generador de impulsos. El tálamo, al ser una estructura que posee múltiples conexiones con diversas partes del sistema nervioso central, es un target adecuado para la ECP. El núcleo talámico anterior (NA) sirve como un sitio de relevo importante para el sistema límbico al recibir aferencias desde el hipocampo y los cuerpos mamilares y enviar eferencias hacia el giro del cíngulo, formando así el circuito de Papez. Debido a estas conexiones, el NA constituye una vía idónea para la propagación de la actividad epileptogénica. La ECP-NA tiene excelentes resultados en el control de las crisis parciales complejas. La gran mayoría de pacientes con ECP-NA han demostrado una reducción significativa en la frecuencia de sus crisis de más del 50% (AU)

Deep brain stimulation (DBS) consists of the electrical stimulation of the subcortical structures by implanting electrodes connected to a pulse generator. The thalamus, being a structure that has multiple connections with various parts of the central nervous system, is a suitable target for DBS. The anterior thalamic nucleus (ANT) serves as an important relay site for the limbic system by receiving input from the hippocampus and mammillary bodies, and sending input to the cingulate gyrus; thus forming the Papez circuit. Due to these connections, the ANT constitutes an ideal route for the propagation of epileptogenic activity. ANT-DBS has excellent results in the control of complex partial seizures. The vast majority of patients with ANT-DBS have shown a significant reduction in the frequency of their seizures of more than 50% (AU)