Heteroplasmia de la mutación del ADN mitocondrial m.3243A>G en la diabetes y sordera de herencia materna / Mitochondrial DNA heteroplasmy of the m.3243A>G mutation in maternally inherited diabetes and deafness

Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion ofmutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification ofMIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electrón chain transpon. We estimated the degree of heteroplasmy ofthe mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a femóle adult patient. For this purpose, PCR producís were inserted in a vector creatingplasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to créate a calibration curve used to interpólate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biológical sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.

Temblor ortostático como causa de inestabilidad postural en enfermedad de Parkinson: Caso clínico / Orthostatic tremor causing postural instability in Parkinson disease: Report of one case

Parkinson disease (PD) is a movement disorder characterized clinically by the variable combination of rigidity, bradykinesia, rest tremor and postural instability. Usually postural instability is a late-onset manifestation and is frequently associated with axial manifestations and with a poor prognosis. We report a 67-year-old female with orthostatic tremor as the etiology of her postural instability. The patient was treated with increasing doses of clonazepam, reaching 2 mg/day, and levodopa. There was an improvement of postural instability with a good response of parkinsonian symptoms.

Resección de lesiones cerebrales con asistencia de mapeo cortical intraoperatorio / Intraoperative cortical mapping in surgery for brain lesions

Introducción: Se ha demostrado que la resección extensa de tumores intracraneanos intra-axiales malignos mejora la sobrevida. Esto no siempre es posible dada la eventual ubicación de estos tumores en o cercanos a áreas elocuentes, como corteza motora primaria o de lenguaje. En estas circunstancias, el desafío es evitar secuelas neurológicas. Uno de los métodos para disminuir dicho riesgo es el mapeo cortical intraoperatorio (MCI). El presente trabajo describe la técnica de mapeo cortical intraoperatorio de áreas elocuentes, al igual que su factibilidad y complementariedad con otras técnicas de localización tumoral. Método: Se analizan 7 pacientes operados, portadores de lesiones cercanas a áreas elocuentes. Se utilizó neuronavegación y MCI (estimulación directa de corteza y registro de potenciales evocados somatosensoriales). Se analizó la localización, tamaño y tipo de la lesión, grado de resección y estado neurológico pre y postoperatorio. Resultados: En todos los pacientes el MCI fue efectivo en localizar corteza motora primaria. Hubo 6 pacientes en los que se pudo resecar el área tumoral no asociada a funcionalidad, logrando en 5 de ellos resección completa o superior al 90 por ciento. En un paciente la lesión correspondió a una malformación arteriovenosa profunda ubicada en corteza motora primaria en que el MCI permitió una vía de abordaje por corteza no elocuente para su resección completa. No hubo déficit neurológico agregado postoperatorio con seguimiento de 12 meses. Conclusión: El MCI es útil y localiza en forma efectiva, simple y reproducible áreas de corteza funcional, haciendo posible realizar resecciones extensas de tumores en áreas elocuentes. Esta técnica es complementaria a otros métodos de ubicación anatómica y fisiológica pudiendo contribuir a una cirugía más segura y efectiva.

Introduction: Extensive resection for malignant intraaxial intracranial tumors has been demonstrated to improve survival. This is not always possible due to potential tumor location in or next to eloquent brain regions, like primary motor cortex or speech areas. In this case, avoiding neurological deficits is challenging. One of the tools for minimizing that risk is intraoperative cortical mapping (ICM). This report describes the ICM technique of eloquent brain regions, feasibility and complementariness with other methods for tumor localization. Methods: Seven patients with brain lesions near eloquent regions operated on were analyzed. Frameless stereotaxis (neuronavigation) and intraoperative cortical mapping (direct cortical stimulation and monitoring of somatosensory evoked potentials) were used. The location, size, type of lesion, amount of resection, pre and postoperative neurological status were studied. Results: ICM was effective in localizing primary motor cortex in all patients. In 6 patients the tumor area without functionality was removed, achieving complete or greater than 90 percent resection in 5 of them. In one patient the lesion was a deep arteriovenous malformation located below the primary motor cortex. In this case ICM made feasible an approach from non-eloquent cortex to achieve total resection. No new postoperative deficit was found in a 12 month follow-up period. Conclusion: ICM is useful and localize functional cortical regions effectively, simply and reliably, making possible to perform extensive tumor resections in eloquent regions. This technique is complementary to other tools for anatomical or physiological localization and could contribute to a safer and more effective surgery.

Cell surface and gene expression regulation molecules in dystrophinopathy: mdx vs. Duchenne

Duchenne muscular dystrophy (DMD) is secondary to loss-of-function mutations in the dystrophin gene. The causes underlying the progression of DMD, differential muscle involvement, and the discrepancies in phenotypes among species with the same genetic defect are not understood. The mdx mouse, an animal model with dystrophin mutation, has a milder phenotype. This article reviews the available information on expression of signaling-related molecules in DMD and mdx. Extracellular matrix proteoglycans, growth factors, integrins, caveolin-3, and neuronal nitric oxide synthase expression do not show significant differences. Calcineurin is inconsistently activated in mdx, which is associated with lack of cardiomyopathy, compared to the permanent calcineurin activation in mdx/utrophin null mice that have a DMD-like cardiomyopathy. Levels of focal adhesion kinase (FAK) and extracellular regulated kinases (ERKs) differ among mdx and DMD. Further work is needed to identify the point of discrepancy in these signaling molecules' pathways in dystrophynopathies.

Investigación en Neurociencias Clínicas / Clinical Neurosciences Research

Being an academic neurosurgeon or neurologist is difficult everywhere. In Chile this is getting harder for several reasons. We review the process behind research grant applications for funding in Fondecyt, the Chilean government research funding agency. The number of grants proposals submitted and approved by academic neurologist and neurosurgeons has decreased dramatically in the last few years. The main cause for this decline is we compete with basic scientists who present their projects to the Neurology-Neurosurgery category instead of their own kind. This unequal competition does not occur for the majority of other medical specialties. Research done by clinicians is of the paramount importance for maintaining and developing academic Neurology and Neurosurgery in Chile. We should be allowed to compete with other clinical peers for research funding. We are optimistic that we will be able to follow the tradition of academic excellence of our predecessors.

Muscle cell outside and inside: the nascent approach of a clinician

Understanding muscle cell in disease and health is an unfinished process. Following the lead of Jaime Alvarez, I have had the opportunity of working on two complementary approaches to this field. One is the study of muscle cell surface molecules. Both synaptic muscle molecules, such as the asymmetric form of acetylcholinesterase, and extrasynaptic molecules, such as the extracellular matrix proteoglycans, are regulated by the motor nerve activity. This illustrates one of Jaime's teachings: cell phenotypes are a dynamic process that reflects the influence of other cells (Alvarez, 2001). Proteoglycans have many functions, including growth factor receptors. Studying them in muscular dystrophy will contribute to the comprehension of the muscle regeneration failure, characteristic of this disease. Muscle cells are highly dependent upon energy production, and the mitochondriae produce most of it. These organelles are unique in having their own genome. Mutations in these genes have recently been recognized as the cause of human disease and originally in muscle pathology. The physiopathology of these diseases is summarized here