Deep brain stimulation of the globus pallidus internus or ventralis intermedius nucleus of thalamus for Holmes tremor.

Holmes tremor (HT) is a difficult-to-treat, very disabling symptomatic condition which characteristically appears weeks to years after a brain lesion. It features a unique combination of rest, action, and postural tremors. Pharmacotherapy is mostly not effective. Chronic deep brain stimulation (DBS) of ventralis intermedius nucleus (Vim) of thalamus has been described as being the best surgical approach in singular case series; various authors observe, however, cases with partial responses only; therefore, alternatives are still needed. We report ten patients with HT unresponsive to best medical therapy who underwent DBS in our center from March 2002 to June 2012. Based in our previous experience dealing with cases of unsatisfactory Vim intraoperative tremor control and in order to optimize surgical results, presurgical target planning included two Nuclei: Vim and posteroventral Globus pallidus internus (GPi) (Espinoza et al. 2010; Espinoza et al. Stereotact Funct Neurosurg 90(suppl 1):1-202, p 61, 2012). Definitive chosen target was decided after single-cell microelectrode recording, intraoperative test stimulation, thresholds for stimulation-induced adverse effects and best clinical response compared to baseline status. Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) was used to evaluate outcome. The electrode was implanted in the nucleus with the best tremor suppression achievement; on the other hand, GPi DBS was initially decided if one of the following conditions was present: (a) If Vim nucleus anatomy was grossly altered; (b) when intraoperative tremor control was unsatisfactory despite Vim high-intensity stimulation; or (c) if unaffordable side effects or even tremor worsening occurred during intraoperative macrostimulation. Seven patients received definitive Gpi DBS implantation, while three patients received Vim DBS. In all observed cases, we observed an improvement on the TRS. In two cases where Vim thalamic anatomy was altered by the pathological insult GPI was planned from the beginning, and same was true in two additional cases where the Gpi nucleus showed major alterations allowing only Vim planning. Over all cases, the average improvement in tremor was of 2.55 points on the TRS or a 64 % increase in measured results; with a minimum of 1 point (25 %) improvement in one case and a maximum of 4 points (100 % improvement) also in one case. All the results were sustained at 2 years follow-up. One case with predominant resting component, implanted in the GPi, achieved the maximum possible tremor reduction (from 4 to 0 points, meaning 100 % tremor reduction); in the nine resting cases, the average reduction was of 3 points (or 75 %). DBS demonstrated in this case series adequate tremor control in 10 patients unresponsive to medical therapy. Presurgical planning of two targets allowed choosing best optimal response. Gpi stimulation could be considered as an alternative target for cases in which thalamic anatomy is considerably altered or Vim intraoperative stimulation does not produce satisfactory results.

Deep brain stimulation in Latin America in comparison with the US and Europe in a real-world population: indications, demographics, techniques, technology, and adverse events.

OBJECTIVE: The aim of this study was to provide geographic comparisons of deep brain stimulation (DBS) procedures in Latin America with the US and Europe regarding primary indications, demographic information, clinical and device-related adverse events, technology used, and patient outcomes using the Medtronic Product Surveillance Registry data as of July 31, 2021. METHODS: Two thousand nine hundred twelve patients were enrolled in the registry (2782 received DBS and 1580 are currently active). Fourteen countries contributed 44,100 years of device experience to the registry. DBS centers in Latin America are located in Colombia (n = 3), Argentina (n = 1), Brazil (n = 1), and Mexico (n = 1). Fisher's exact test was used to compare the difference in proportions of categorical variables between regions. The Wilcoxon signed-rank test was used for the EQ-5D index score change from baseline to follow-up. RESULTS: The most common indication for DBS was Parkinson's disease across all regions. In Latin America, dystonia was the second most common indication, compared to essential tremor in other regions. There was a striking finding with respect to age-patients were an average of 10 years younger at DBS implantation in Latin America. This difference was most likely due to the greater number of patients with dystonia receiving the device implants. The intraoperative techniques were quite similar, showing the same level of quality and covering the main principles of the surgeries with some variations in the brand of frames, planning software, and microrecording systems. Rechargeable batteries were significantly more common in Latin America (72.37%) than in the US (6.44%) and Europe (9.9%). Staging of the DBS procedure differed, with only 11.84% in Latin America staging the procedure compared with 97.58% and 34.86% in the US and Europe, respectively. The EQ-5D score showed significant improvements in all regions during the first 6-12 months (p < 0.0001). However, the 24-month follow-up only showed an improvement in the scale for Latin America (p < 0.0001). CONCLUSIONS: DBS was performed in Latin America with similar indications, techniques, and technology as in the US and Europe. Important differences were found, with Latin America implementing more regular use of rechargeable devices, including younger patients at the time of surgery, and showing more sustained quality of life improvements at 24 months of follow-up. The authors hypothesize that these disparities stem from differences in resources among regions. However, more studies are needed to standardize DBS practice across the world to improve patients' quality of life and provide high-quality care.

Rapid differentiation of isobaric and positional isomers of structurally related glycosides from Phytolacca bogotensis.

Through the action of glycosyltransferases, a plant can biosynthetically assemble small different aglycons or 'templates' to various polysaccharides to produce numerous glycoconjugates differing in the type of the attached aglycon, the anomeric configuration of C-1 of the glycosylating sugar, the type of sugar and the different position of attachments of the sugar unit present in the polysaccharide chain. The position of attachments and the anomeric configuration of the different sugar present in the polysaccharide create the opportunity to generate molecules with either the same or very close molecular weights, which have relative structural similarity--forming isobaric and positional isomers. Although isomeric differentiation was once considered outside of the domain of mass spectrometry, this task can now be resolved using tandem mass spectrometry. In a standardized purified glycoconjugate fraction (SPT01) from Phytolacca bogotensis, we report conventional electrospray ionization mass spectrometry and collision-induced dissociation (CID) MS/MS parameters which favored the formation of characteristic product ions. This allowed us to suggest the type of sugar linkages present in a specific glycoconjugate. Ten new glycoconjugate are described from this plant and another twelve known saponins were structurally characterized using the automatic MSn acquisition mode. The differentiation of two pairs of positional isomers and four isobaric glycosides and the production of a library of 30 glycosides present in P. bogotensis were accomplished.

O-glycoside sequence of pentacyclic triterpene saponins from Phytolacca bogotensis using HPLC-ESI/multi-stage tandem mass spectrometry.

INTRODUCTION: The lack of pharmacopoeial methodologies for the quality control of plants used for therapeutic purposes is a huge problem that impacts directly upon public health. In the case of saponins, their great structural complexity, weak glycoside bonds and high polarity hinder their identification by conventional techniques. OBJECTIVE: To apply high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI/MS(n)) to identify the O-glycoside sequence of saponins from the roots of Phytolacca bogotensis. METHODOLOGY: Saponins were isolated by preparative HPLC and characterised by NMR spectroscopic experiments. Collision-induced dissociation (CID) of isolated saponins was performed producing typical degradation reactions that can be associated with several glycosidic bonds as empirical criteria. A method using solid-phase extraction (SPE) and HPLC/ESI-MS(n) for the characterisation of saponins and identification of novel molecules is described. RESULTS: Three saponins reported for the first time in P. bogotensis were isolated and characterised by NMR spectroscopy. Characteristic cross ring cleavage reactions have been used as empirical criteria for the characterisation of the glycosidic bonds most frequently reported for Phytolacca saponins. One new saponin was proposed on the basis of empirical criteria, and other five saponins were identified for the first time for P. bogotensis using HPLC-ESI/MS(n). CONCLUSION: Electrospray ionisation in combination with tandem mass spectrometry has been established as a powerful tool for the profiling of saponins from roots of P. bogotensis. CID proved to be a useful tool for the characterisation and identification of known and novel saponins from the plant family Phytolaccaceae and can be used for quality control purposes of crude plant extracts.

[Leishmania: role of P glycoprotein in drug resistance and reversion strategies]. / Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión.

Protozoan parasites are important causative agents of morbidity and mortality throughout the world--a problem further complicated by the emergence of drug resistance in these parasites. Mechanisms of drug resistance include the following: decreased uptake of the drug into the cell, loss of drug activation, alterations in the drug target, and over-expression of a well-known multiple drug transporter proteins. In this review, two critical components of resistance are stressed: (1) the role of ATP binding cassette proteins, such as P-glycoproteins, in mediating drug resistance in Leishmania and other protozoans, followed by development of cross-resistance to many structurally and functionally unrelated drugs, and (2) some concepts concerning the reversal mechanism of multidrug resistance by drugs and natural products. Several modulators or chemosensitizers alter the capacity of P-glycoproteins to maintain subtoxic intracellular drug concentrations. Calcium channel blockers such as verapamil act in this mode; however, high concentrations are required for an efficient and effective inhibition and, in addition, produce undesirable side effects. The discovery of new, natural product modulators of P-glycoproteins is stressed. This category of modulators offer potentially improved efficacy and lowered toxicity for the mammalian host.

Neurosurgical treatment for dystonia: long-term outcome in a case series of 80 patients.

INTRODUCTION: In this study, we assessed the outcomes of patients with dystonia who underwent surgery treatment following the same algorithm. PATIENTS AND METHODS: Eighty consecutive patients with dystonia were submitted to neurosurgical management by means of intrathecal pump implantation, pallidotomy or deep brain stimulation (GPi or VIM). These patients included 48 patients with primary dystonia and 32 patients with secondary dystonia. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to access pre- and post-operative outcomes. Patients were followed from 12 to 114 months. RESULTS: Mean improvement in BFMDRS score among patients with PrD was 87.54% and 42.21% for SeD. Hemidystonic patients in both groups (PrD, SeD) showed a mean improvement in BFMDRS of 71.05% with GPiDBS. Patients with SeD due to previous perinatal insults showed a mean improvement in BFMDRS of 41.9%, with better results in purely dyskinetic patients (mean improvement of 61.2%). CONCLUSION: Use of the proposed algorithm facilitated surgical decision planning, which translated in improved diagnostic rates, earlier interventions, appropriate management plans, and outcomes for both groups (PrD, SeD). Therefore, neuroimaging findings had a positive prognostic significance in the response to treatment in patients with primary dystonia compared with patients with secondary dystonia or distortion of basal ganglia anatomy. However, further studies in this line are warranted.

Genética de las distonías / Genetic classification of dystonia

RESUMEN Con el avance de la secuenciación genética y otras técnicas se ha logrado avanzar de manera significativa en la detección de formas monogénicas de la distonía así como en la contribución de varios factores genéticos en la génesis de esta condición.

SUMMARY With the refinement of genetic sequencing and many other techniques, monogenic forms of dystonia as well as various genetic contributions and epigenetic factors are now available to guide the clinician in the pursue of an accurate diagnosis of this condition.

Genética de las distonías / Genetic classification of dystonia

Con el avance de la secuenciación genética y otras técnicas se ha logrado avanzar de manera significativa en la detección de formas monogénicas de la distonía así como en la contribución de varios factores genéticos en la génesis de esta condición.

SUMMARY With the refinement of genetic sequencing and many other techniques, monogenic forms of dystonia as well as various genetic contributions and epigenetic factors are now available to guide the clinician in the pursue of an accurate diagnosis of this condition.

Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión / Leishmania: role of P glycoprotein in drug resistance and reversion strategies

Actualmente, los parásitos protozoarios son uno de los principales agentes causantes de morbilidad y mortalidad en el mundo, un problema complicado, además, por la aparición de resistencia a medicamentos en estos organismos. La resistencia a medicamentos observada en parásitos protozoarios se debe a diferentes mecanismos como la disminución de la entrada del medicamento a la célula por cambios en el transportador requerido, la pérdida de la activación del medicamento por parte del hospedero, las alteraciones en el blanco del medicamento y la expresión exagerada del transportador múltiple de medicamentos o glicoproteína P (Pgp). En esta revisión, nos centramos en: 1) el papel de las glicoproteínas P (Pgp) de la familia de proteínas ABC (ATP binding cassette) como los transportadores de múltiples medicamentos en la mediación de resistencia en protozoarios, especialmente en Leishmania, y en el desarrollo de resistencia cruzada para medicamentos estructural y funcionalmente no relacionados, y 2) en algunos conceptos relacionados con los mecanismos moduladores que podrían revertir la resistencia a medicamentos por fármacos y productos naturales. Numerosos moduladores o quimiosensibilizadores son conocidos por alterar la capacidad de las glicoproteínas P para mantener concentraciones intracelulares subtóxicas del medicamento; algunos ejemplos incluyen los bloqueadores de los canales de calcio como el verapamilo; sin embargo, se requieren altas concentraciones para una inhibición eficiente y duradera, las cuales producen efectos adversos indeseables. Por tanto, se necesitan más investigaciones relacionadas con los moduladores naturales para Pgp, los cuales podrían presentar menor toxicidad para el hospedero

Estandarización del método de la bolsa de aire para su utilización en la evaluación in vivo de sustancias con actividad leishmanicida / Standarization of the air pouch method to be used in the evaluation in vivo of leishmanicide substances

La evaluación de sustancias con actividad Leishmanicida in vivo, actualmente se realiza en modelos animales (ratones o hámster), previo aislamiento y cultivo de los parásitos de Leishmania ssp. y suposterior inoculación y producción de infección en el animal. En este estudio se adaptó la técnica de ®Bolsa de aire¼ descrita por Edwars y colaboradores en 1981, inoculando promastigotes de Leishmania Viannia panamensis (cepa MHOM/CO/87/UA140) vía subcutánea en el espacio interescapular en hámster dorados (Mesocricetus auratus) machos, con el fin de estandarizar un método adecuado para la evaluación in vivo de la actividad leishmanicida de sustancias de origen natural, sintético o hemisintético. En los días 30, 60 y 90 post-inoculación, a cada reactivo biológico se le realizó frotis y aspirado para cultivo en medio NNN para determinar la presencia de infección; en el día 90 a los animales se les aplico la eutanasia, y se tomaron biopsias del sitio de inoculación. Las muestras se procesaron y colorearon con los métodos de Hematoxilina - Eosina y Giemsa. Los aspectos éticos relacionados con el manejo y cuidado de los hámster contaron con la aprobación del ”Comité deÉtica de Animales de Experimentación” de la Universidad de Antioquia y del Ministerio de Salud. La “bolsa de aire” se formo en todos los especímenes, encontrándose permeable, revestida por varias hileras de células simulando el revestimiento articular y a su alrededor se encontraron macrófagos, linfocitos y polimorfonucleares. Sin embargo, no se logro el establecimiento de la infección en los animales en estudio, debido posiblemente a varios factores entre los cuales se puede mencionar la patogenicidad de la cepa del parásito utilizado, la vía y sitio de inoculación y la respuesta inmunologica del Hámster.