Gait Function after High-Intensity Focused Ultrasound Thalamotomy for Essential Tremor: Searching for Technique Optimization.

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders in adults and may be highly disabling for some. Magnetic resonance image-guided high-intensity focused ultrasound (MRIgFUS) has been shown to control tremor efficaciously and with acceptable risk. To date, paresthesia and ataxia are the most common adverse effects (AE). Nevertheless, the impact of MRIgFUS thalamotomy on balance is not well established. METHODS: Thirty-two patients underwent MRIgFUS for ET and completed 6 months of follow-up. Tremor severity and functional disability were assessed using the Essential Tremor Rating Scale and the Quality of Life in Essential Tremor Questionnaire. The Berg Balance Scale (BBS) was applied to objectively measure balance status. RESULTS: All treatments were successful. The sonication target was 1-2 mm above the depth of the intercommissural line. Procedures lasted less the 2 h, with an average of 8 sonications per patient. Twenty-four patients were included in the tremor analysis. The hand tremor score was improved by 76% after 6 months of follow-up and 87% of patients self-reported marked improvement (≥75%). Disability scores showed marked improvement (78%), leading to a significant improvement in quality of life. At the final follow-up, 48% of the patients reported no side effects. When present, AE were generally transient and were considered mild in 96% of affected patients. Paresthesia and subjective feeling of unsteadiness were the most common persistent complaints (23% and 20%, respectively). Regarding objective ataxia, BBS scores remained stable throughout follow-up for most patients. Only 2 patients suffered a mild worsening of balance although no patients experienced moderate or severe ataxia. CONCLUSIONS: Subjective feeling of unsteadiness is one of the most frequent AE after MRIgFUS, although objective ataxia is infrequent and mild. Selecting the most appropriate lesion location and procedural parameters should increase treatment benefits while reducing side effects.

Ultrastructural Characterization of Human Oligodendrocytes and Their Progenitor Cells by Pre-embedding Immunogold.

Oligodendrocytes are the myelinating cells of the central nervous system. They provide trophic, metabolic, and structural support to neurons. In several pathologies such as multiple sclerosis (MS), these cells are severely affected and fail to remyelinate, thereby leading to neuronal death. The gold standard for studying remyelination is the g-ratio, which is measured by means of transmission electron microscopy (TEM). Therefore, studying the fine structure of the oligodendrocyte population in the human brain at different stages through TEM is a key feature in this field of study. Here we study the ultrastructure of oligodendrocytes, its progenitors, and myelin in 10 samples of human white matter using nine different markers of the oligodendrocyte lineage (NG2, PDGFRα, A2B5, Sox10, Olig2, BCAS1, APC-(CC1), MAG, and MBP). Our findings show that human oligodendrocytes constitute a very heterogeneous population within the human white matter and that its stages of differentiation present characteristic features that can be used to identify them by TEM. This study sheds light on how these cells interact with other cells within the human brain and clarify their fine characteristics from other glial cell types.

Epilepsy surgery beyond 50 years: Long-term seizure and cognitive outcomes.

INTRODUCTION: Surgery is a well-demonstrated effective treatment for patients with refractory epilepsy. However, there are scarce data about the efficacy in older patients. Endpoint was to evaluate the outcome of epilepsy surgery in pharmacorresistant patients operated in middle-late adulthood. METHODS: We conducted a retrospective observational study including patients who underwent a epilepsy surgery at age ≥ 50. Presurgical clinical data, type of surgery, and postsurgical seizure outcome and neurological complications, including neuropsychological assessment were analyzed. Minimum post-surgical follow-up was 1 year. RESULTS: We identified 38 patients (22 males, 17 females) out of 350 patients who underwent a resective surgery with curative intention in our Epilepsy Unit (12%). Median age at surgery was 56 years (50-69), with median epilepsy duration of 42 years (4-67). Neuroimaging showed focal epileptogenic lesions in 37 patients, mainly mesial temporal sclerosis (21). Presurgical neuropsychological evaluation was available in 38 patients: 35 had deficits, mostly in verbal or visual memory. Twenty-eight patients underwent standard temporal lobectomy with amygdalohippocampectomy, 7 lesionectomy and 4 lobectomy. Median follow-up was 4.46 years (1-9.75). A good outcome was achieved by 86.8% (28 Engel I; 5 Engel II); 5 patients were studied with SEEG, without any complications. None had postsurgical permanent neurological complications. From 22 patients with available post-surgical neuropsychological assessment, 16 scored lower than in pre-surgical one, mainly in memory domain. CONCLUSION: Surgical treatment of long-term refractory epilepsy in patients ≥50 years can be effective and safe. Post-surgical memory decline is a frequent side effect, but with a low impact in daily life.

Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic-clonic seizure during cortical stimulation in patients with focal epilepsy.

INTRODUCTION: Stimulation-evoked focal to bilateral tonic-clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. MATERIAL AND METHODS: In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. RESULTS: Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. CONCLUSIONS: The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS.

SOX2+ cell population from normal human brain white matter is able to generate mature oligodendrocytes.

OBJECTIVES: A number of neurodegenerative diseases progress with a loss of myelin, which makes them candidate diseases for the development of cell-replacement therapies based on mobilisation or isolation of the endogenous neural/glial progenitor cells, in vitro expansion, and further implantation. Cells expressing A2B5 or PDGFRA/CNP have been isolated within the pool of glial progenitor cells in the subcortical white matter of the normal adult human brain, all of which demonstrate glial progenitor features. However, the heterogeneity and differentiation potential of this pool of cells is not yet well established. METHODS: We used diffusion tensor images, histopathology, and immunostaining analysis to demonstrate normal cytoarchitecture and the absence of abnormalities in human temporal lobe samples from patients with mesial temporal sclerosis. These samples were used to isolate and enrich glial progenitor cells in vitro, and later to detect such cells in vivo. RESULTS: We have identified a subpopulation of SOX2+ cells, most of them co-localising with OLIG2, in the white matter of the normal adult human brain in vivo. These cells can be isolated and enriched in vitro, where they proliferate and generate immature (O4+) and mature (MBP+) oligodendrocytes and, to a lesser extent, astrocytes (GFAP+). CONCLUSION: Our results demonstrate the existence of a new glial progenitor cell subpopulation that expresses SOX2 in the white matter of the normal adult human brain. These cells might be of use for tissue regeneration procedures.

The dentate nucleus and its projection system in the human cerebellum: the dentate nucleus microsurgical anatomical study.

BACKGROUND: Neurosurgical management of cerebellar lesions remains challenging. Thus, it is important to have sound knowledge of the microsurgical anatomy of the cerebellum and dentate nucleus (DN) and to define different types of exposure in a variety of surgical interventions. OBJECTIVE: To examine the anatomy of the DN from a neurosurgical viewpoint using fiber tracking techniques. METHODS: Ten formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under × 6 to × 40 magnification. Anatomic images were created with 3-dimensional diffusion tensor imaging. The relationships of the DN to tentorium and suboccipital and lateral surfaces of the cerebellum and its spatial positioning relative to different surgical approaches in the cerebellum and fourth ventricle were examined. The fiber tracts terminating at and surrounding the DN were defined. RESULTS: The DN is at greater risk of being injured in the transvermian and supratonsillar approaches to the cerebellum and fourth ventricle, with lesser risk in the telovelar and subtonsillar approaches. Superior approaches are safer compared with other approaches. CONCLUSION: The DN represents an important anatomic structure in surgical interventions involving the posterior fossa, particularly in the elderly because of the common occurrence of atrophy-related problems in this age group. Functionally and anatomically, the DN is closely related to the superior and middle cerebellar peduncles. The inferior cerebellar peduncle poses positional risks because it follows an anterior and superior course relative to the DN. The telovelar approach is a safer procedure for interventions involving the pathological lesions of the fourth ventricle floor.

[Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations]. / Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía.

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It́s recommended a one week treatment with antiepileptic drugs in patients who didnt have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient.

Control de las crisis epilépticas durante el postoperatorio inmediato de los tumores cerebrales supratentoriales: recomendaciones del Grupo de Neurocirugía Funcional y Estereotáctica de la Sociedad Española de Neurocirugía / Primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors: Group for the Study of Functional-Sterotactic Neurosurgery of The Spain Society of Neurosurgery recommendations

Con la finalidad de proponer una serie de recomendaciones del tratamiento médico antiepiléptico, en el perioperatorio de los tumores cerebrales supratentoriales, se realiza una revisión de la literatura enfocada sobre todo a la profilaxis primaria de las crisis epilépticas precoces acaecidas en el postoperatorio inmediato. Se concluye que es recomendable pautar profilaxis primaria antiepiléptica poscirugía durante una semana en los pacientes con tumor cerebral supratentorial que no han presentado crisis epilépticas. Si las crisis aparecen durante la evolución de la enfermedad, es necesario pautar un tratamiento a largo plazo. Dadas las características de estos pacientes, se recomienda usar un fármaco antiepiléptico con presentación por vía intravenosa y un perfil bajo de interacciones. El levetiracetam, seguido del valproato, parecen ser los más adecuados. Dichas recomendaciones deben considerarse como una guía general de manejo, pudiendo ser modificadas, incluso de manera significativa, por las circunstancias propias de cada caso clínico (AU)

Our review of the literature is basically focused on the primary prophylaxis of early seizures after surgery of cerebral supratentorial tumors, with the aim of suggesting several recommendations in medical antiepileptic treatment to avoid this kind of seizures which occur immediately after surgery. In conclusion, it is recommended to provide criteria for prophylaxis of early seizures after surgery of cerebral supratentorial tumors. It's recommended a one week treatment with antiepileptic drugs in patients who didn't have seizures jet, starting immediately after the surgical treatment. If seizures appear during progress of the disease, a large period treatment will be needed. Preferred antiepileptic treatment is intravenous and with a low interactions profile. Levetiracetam, followed by valproic acid seem to be most appropriated drugs due to their properties and protective effects, particularly for our patients requirements. These recommendations are considered a general proposal to effective clinical management of early seizures after surgery, not taking into account the single circumstances of our patients. Always, clinical features of the patients could modify even significantly these guides in the benefit of each patient (AU)