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1.
Neurol Neurochir Pol ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742610

RESUMEN

INTRODUCTION: Unilateral gamma knife thalamotomy (GKT) is a treatment option for pharmacoresistant tremor of various aetiologies. There have been to date no randomised controlled trials performed to assess its safety and efficacy. Our aim was to summarise a two-year multimodal observation of patients with tremor caused by Parkinson's Disease (PD) or essential tremor (ET). MATERIAL AND METHODS: 23 patients with PD (n = 12) or ET (n = 11) were included. They underwent assessments before, V0 (n = 23), and 12 months, V12 (n = 23), and 24 months, V24 (n = 15), after unilateral GKT. Patients were assessed with psychological tests and acoustic voice analysis. Tremor assessment was performed with a digitising table using the Fahn-Tolosa-Marin rating scale (FTMRS). The Unified Parkinson's Disease rating scale part III (UPDRS-III) was also used in the PD group. Gait and balance was assessed using clinical tests, stabilometric platform, and treadmill. RESULTS: No side effects were observed in a two-year follow-up. There was no notable deterioration observed in the patients' psychological evaluation, speech, or assessment of gait and balance. The scores were significantly lower (p = 0.01) in parts A and B of FTMRS one year after GKT. In post hoc analysis, the scores did not differ significantly between V0 and V24. In FTMRS part C (activities of daily living), no significant change was observed. There was no significant difference in total UPDRS part III score or in score of UPDRS part III domains 3 and 4 ('tremor at rest' and 'action and postural tremor of hands') between measurements. CONCLUSIONS: UGKT may be a safe treatment modality if performed in an experienced centre. Tremor reduction may diminish over time, and UGKT did not lead to cognitive, gait or speech deterioration in a long-term observation.

2.
J Clin Med ; 12(21)2023 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-37959402

RESUMEN

The purpose of this case report is to describe the case of a patient with ankylosing spinal hyperostosis (ASH) and lumbar spine fracture complicated by ureteral injury mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation followed by the cervical spine fracture. A consecutive analysis and summary of the medical history, radiological documentation, operative procedure, complications, and outcomes were performed. A 59-year-old man presented with abdominal pain three weeks after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the L3/L4 level and features of ASH. Additionally, MRI scans demonstrated hyperintense fluid collection within L3/L4 intervertebral space communicating with both psoas major muscles, mimicking spondylodiscitis with osteomyelitis features and retroperitoneal abscess formation. An in situ instrumented lumbar fusion at the L2-L3-L5-S1 levels with implantation vertebral body replacement implant at the L3/L4 level was performed. Postoperative CT imaging revealed evidence of post-traumatic right ureteral injury. Following urological treatment covering nephrectomy and ureter ligation, the patient was maintained at a 2-year follow-up. After this period, the patient presented again with tetraparesis after sustaining a low-energy fall. The performed CT scans demonstrated a three-column fracture at the C5/C6 level. The combined anterior and posterior osteosynthesis at the C4-C5-C6-C7 levels was performed. This case report presents the rare clinical constellation regarding the lumbar spine fracture complicated by ureteral injury followed by a cervical spine fracture regarding the same patient. The potential injury of retroperitoneal structures, including the ureter after hyperextensive lumbar spine fracture, should be considered in ASH patients. In this case, one should be aware of the atypical clinical presentation regarding the observed spondylodiscitis- and osteomyelitis-like features.

3.
Int J Cancer ; 153(5): 1003-1015, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37338006

RESUMEN

High-grade gliomas are aggressive, deadly primary brain tumors. Median survival of patients with glioblastoma (GBM, WHO grade 4) is 14 months and <10% of patients survive 2 years. Despite improved surgical strategies and forceful radiotherapy and chemotherapy, the prognosis of GBM patients is poor and did not improve over decades. We performed targeted next-generation sequencing with a custom panel of 664 cancer- and epigenetics-related genes, and searched for somatic and germline variants in 180 gliomas of different WHO grades. Herein, we focus on 135 GBM IDH-wild type samples. In parallel, mRNA sequencing was accomplished to detect transcriptomic abnormalities. We present the genomic alterations in high-grade gliomas and the associated transcriptomic patterns. Computational analyses and biochemical assays showed the influence of TOP2A variants on enzyme activities. In 4/135 IDH-wild type GBMs we found a novel, recurrent mutation in the TOP2A gene encoding topoisomerase 2A (allele frequency [AF] = 0.03, 4/135 samples). Biochemical assays with recombinant, wild type (WT) and variant proteins demonstrated stronger DNA binding and relaxation activity of the variant protein. GBM patients carrying the altered TOP2A had shorter overall survival (median OS 150 vs 500 days, P = .0018). In the GBMs with the TOP2A variant we found transcriptomic alterations consistent with splicing dysregulation. luA novel, recurrent TOP2A mutation, which was found exclusively in four GBMs, results in the TOP2A E948Q variant with altered DNA binding and relaxation activities. The deleterious TOP2A mutation resulting in transcription deregulation in GBMs may contribute to disease pathology.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/patología , Neoplasias Encefálicas/metabolismo , Glioma/genética , Pronóstico , ADN , Isocitrato Deshidrogenasa/genética , Mutación
4.
Ann Otol Rhinol Laryngol ; 132(12): 1564-1572, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37096361

RESUMEN

BACKGROUND: No gold standard has been developed for the therapy of intracanalicular vestibular schwannomas (IVS). Options for treatment include a conservative approach, microsurgery, or radiosurgery. Although the efficacy of these treatment has been well-documented, little is known about the determinants of outcome in IVSs following radiosurgery. Therefore, we examined the results in relation to age, gender, tumor volume, distance to fundus, microcyst existence, and radiosensitivity in this group. In addition, we investigated possible predictors of facial nerve function and hearing preservation. METHODS: Ninety-four patients with unilateral IVS were included in the evaluation (52 women and 42 males). The patients were separated into younger and older age groups based on their median age (55 years). The median IVS volume was 138 mm3, microcysts were identified in 16 tumors, and 63 tumors were adjacent to the fundus. The data were analyzed using Statistica software package ver. 13.3. RESULTS: At final follow-up, a statistically significant decrease in tumor volume and no statistically significant decline in hearing were noted, but no differences between age groups were found. The sex had no effect on overall tumor growth control, facial nerve preservation, or hearing preservation. Localization of IVS close to the fundus and the presence of tumor microcysts had no effect on the control of tumor growth, preservation of hearing, and sparing of facial nerve following radiosurgery. Cochlear dose had no influence on hearing preservation. Higher tumor volume was associated with its pseudoprogression during early follow-up and a greater risk of hearing loss. CONCLUSIONS: Age, sex, tumor volume, proximity to the fundus, and the existence of a microcyst were not predictive of radiosensitivity nor preservation of facial nerve function and hearing, based on the findings. There was no effect of cochlear dose on hearing. Initial greater tumor volume was associated with an increased probability of tumor pseudoprogression.


Asunto(s)
Pérdida Auditiva , Neuroma Acústico , Radiocirugia , Masculino , Humanos , Femenino , Anciano , Persona de Mediana Edad , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Neuroma Acústico/complicaciones , Radiocirugia/efectos adversos , Radiocirugia/métodos , Pronóstico , Pérdida Auditiva/etiología , Pérdida Auditiva/cirugía , Audición , Resultado del Tratamiento , Estudios de Seguimiento
5.
Artículo en Inglés | MEDLINE | ID: mdl-36900887

RESUMEN

BACKGROUND: Acute peripheral arterial ischemia is a rapidly developing loss of perfusion, resulting in ischemic clinical manifestations. This study aimed to assess the incidence of cardiovascular mortality in patients with acute peripheral arterial ischemia and either atrial fibrillation (AF) or sinus rhythm (SR). METHODS: This observational study involved patients with acute peripheral ischemia treated surgically. Patients were followed-up to assess cardiovascular mortality and its predictors. RESULTS: The study group included 200 patients with acute peripheral arterial ischemia and either AF (n = 67) or SR (n = 133). No cardiovascular mortality differences between the AF and SR groups were observed. AF patients who died of cardiovascular causes had a higher prevalence of peripheral arterial disease (58.3% vs. 31.6%, p = 0.048) and hypercholesterolemia (31.2% vs. 5.3%, p = 0.028) than those who did not die of such causes. Patients with SR who died of cardiovascular causes more frequently had a GFR <60 mL/min/1.73 m2 (47.8% vs. 25.0%, p = 0.03) and were older than those with SR who did not die of such causes. The multivariable analysis shows that hyperlipidemia reduced the risk of cardiovascular mortality in patients with AF, whereas in patients with SR, an age of ≥75 years was the predisposing factor for such mortality. CONCLUSIONS: Cardiovascular mortality of patients with acute ischemia did not differ between patients with AF and SR. Hyperlipidemia reduced the risk of cardiovascular mortality in patients with AF, whereas in patients with SR, an age of ≥75 years was a predisposing factor for such mortality.


Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Humanos , Anciano , Fibrilación Atrial/epidemiología , Corazón , Frecuencia Cardíaca , Insuficiencia Cardíaca/epidemiología , Resultado del Tratamiento
6.
Neuro Oncol ; 25(6): 1085-1097, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-36640127

RESUMEN

BACKGROUND: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes. METHODS: MDNA55-05 is an open-label, single-arm phase IIb study of MDNA55 in recurrent GBM (rGBM) patients with an aggressive form of GBM (de novo GBM, IDH wild-type, and nonresectable at recurrence) on their 1st or 2nd recurrence. MDNA55 was administered intratumorally as a single dose treatment (dose range of 18 to 240 ug) using convection-enhanced delivery (CED) with up to 4 stereo-tactically placed catheters. It was co-infused with a contrast agent (Gd-DTPA, Magnevist®) to assess distribution in and around the tumor margins. The flow rate of each catheter did not exceed 10µL/min to ensure that the infusion duration did not exceed 48 h. The primary endpoint was mOS, with secondary endpoints determining the effects of IL4R status on mOS and PFS. RESULTS: MDNA55 showed an acceptable safety profile at doses up to 240 µg. In all evaluable patients (n = 44) mOS was 11.64 months (80% one-sided CI 8.62, 15.02) and OS-12 was 46%. A subgroup (n = 32) consisting of IL4R High and IL4R Low patients treated with high-dose MDNA55 (>180 ug) showed the best benefit with mOS of 15 months, OS-12 of 55%. Based on mRANO criteria, tumor control was observed in 81% (26/32), including those patients who exhibited pseudo-progression (15/26). CONCLUSIONS: MDNA55 demonstrated tumor control and promising survival and may benefit rGBM patients when treated at high-dose irrespective of IL4R expression level.Trial Registration: Clinicaltrials.gov NCT02858895.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glioblastoma/patología , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Receptores de Interleucina-4/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Microambiente Tumoral
7.
Medicine (Baltimore) ; 101(38): e30348, 2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36197246

RESUMEN

This study evaluates the applicability of S100B levels, mean maximum velocity (Vmean) over time, pulsatility index (PI), intracranial pressure (ICP), and body temperature (T) for the prediction of the treatment of patients with traumatic brain injury (TBI). Sixty patients defined by the Glasgow Coma Scale score ≤ 8 were stratified using the Glasgow Coma Scale into 2 groups: favorable (FG: Glasgow Outcome Scale ≥ 4) and unfavorable (UG: Glasgow Outcome Scale < 4). The S100B concentration was at the time of hospital admission. Vmean was measured using transcranial Doppler. PI was derived from a transcranial Doppler examination. T was measured in the temporal artery. The differences in mean between FG and UG were tested using a bootstrap test of 10,000 repetitions with replacement. Changes in S100B, Vmean, PI, ICP, and T levels stratified by the group were calculated using the one-way aligned rank transform for nonparametric factorial analysis of variance. The reference ranges for the levels of S100B, Vmean, and PI were 0.05 to 0.23 µg/L, 30.8 to 73.17 cm/s, and 0.62 to 1.13, respectively. Both groups were defined by an increase in Vmean, a decrease in S100B, PI, and ICP levels; and a virtually constant T. The unfavorable outcome is defined by significantly higher levels of all parameters, except T. A favorable outcome is defined by S100B < 3 mg/L, PI < 2.86, ICP > 25 mm Hg, and Vmean > 40 cm/s. The relationships provided may serve as indicators of the results of the TBI treatment.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Presión Intracraneal , Velocidad del Flujo Sanguíneo , Temperatura Corporal , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/terapia , Circulación Cerebrovascular/fisiología , Escala de Coma de Glasgow , Humanos , Teofilina , Ultrasonografía Doppler Transcraneal
8.
Wideochir Inne Tech Maloinwazyjne ; 17(3): 450-456, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36187055

RESUMEN

Intracanalicular vestibular schwannomas (IVS) account for 8% of all vestibular schwannomas and their detection is still increasing due to high availability of magnetic resonance (MRI). Radiosurgery is one of several commonly acceptable methods of IVS treatment, but some risk may still exist with that treatment. The aim of this study is to analyze the clinical outcomes in tumor control and hearing preservation after radiosurgery of IVS. The retrospective analysis included 14 scientific papers available in the PubMed database. Assessment of tumor volume was performed based on gadolinium-enhanced T1-weighted scans. Hearing preservation was assessed using the Gardner-Robertson classification (GR class). Statistical analysis was performed using IBM SPSS Statistics 27. It was revealed that tumor growth control in IVS treated with radiosurgery was higher than in the wait-and-see strategy. The hearing preservation was similar in patients after wait and see and the surgical group. Radiosurgery was associated with low risk of facial nerve dysfunction.

9.
Biomed Rep ; 17(1): 58, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35719835

RESUMEN

Craniocerebral injury (CBI) is tissue damage caused by a sudden mechanical force. CBI can result in neurological, neuropsychological and psychiatric dysfunctions. Currently, the severity of CBI is assessed using the Glasgow Coma Scale, brain perfusion pressure measurements, transcranial Doppler tests and biochemical markers. This study aimed to determine the applicability of the S-100B protein levels and the time-averaged mean maximum cerebral blood flow velocity (Vmean) as a means of predicting the treatment outcomes of CBI in the first 4 days of hospitalization. The results validated the standard reference ranges previously proposed for the concentration of S-100B (0.05-0.23 µg/l) and the mean of cerebral blood flow velocity (30.9 to 74.1 cm/sec). The following stratification scheme was used to predict the success of treatment: Patients with a Glasgow Outcome Scale (GOS) score ≥4 or GOS <4 were stratified into 'favorable' and 'unfavorable' groups, respectively. The favorable group showed relatively constant levels of the S-100B protein close to the normal range and exhibited an increase in Vmean, but this was still within the normal range. The unfavorable group exhibited a high level of S-100B protein and increased Vmean outside of the normal ranges. The changes in the levels of S-100B in the unfavorable and favorable groups were -0.03 and -0.006 mg/l/h, respectively. Furthermore, the rate of decrease in the Vmean value in the unfavorable and favorable groups were -0.26 and -0.18 cm/sec/h, respectively. This study showed that constant levels of S-100B protein, even slightly above the normal range, associated with an increase in Vmean was indicative of a positive therapeutic outcome. However, additional research is required to obtain the appropriate statistical strength required for clinical practice.

10.
Biomed Res Int ; 2021: 2398488, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34734081

RESUMEN

The high frequency of traumatic brain injury imposes severe economic stress on health and insurance services. The objective of this study was to analyze the association between the serum S100B protein, the Gosling pulsatility index (PI), and the level of oxygen saturation at the tip of the internal jugular vein (SjVO2%) in patients diagnosed with severe TBI. The severity of TBI was assessed by a GCS score ≤ 8 stratified by Glasgow outcome scale (GOS) measured on the day of discharge from the hospital. Two groups were included: GOS < 4 (unfavorable group (UG)) and GOS ≥ 4 (favorable group (UG)). S100B levels were higher in the UG than in the FG. PI levels in the UG were also substantially higher than in the FG. There were similar levels of SjVO2 in the two groups. This study confirmed that serum S100B levels were higher in patients with unfavorable outcomes than in those with favorable outcomes. Moreover, a clear demarcation in PI between unfavorable and FGs was observed. This report shows that mortality and morbidity rates in patients with traumatic brain injury can be assessed within the first 4 days of hospitalization using the S100B protein, PI values, and SjVO2.


Asunto(s)
Lesiones Traumáticas del Encéfalo/clasificación , Lesiones Traumáticas del Encéfalo/mortalidad , Subunidad beta de la Proteína de Unión al Calcio S100/análisis , Adolescente , Adulto , Anciano , Femenino , Escala de Coma de Glasgow , Humanos , Venas Yugulares/fisiología , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Morbilidad , Oximetría , Saturación de Oxígeno/fisiología , Pronóstico , Flujo Pulsátil/fisiología , Subunidad beta de la Proteína de Unión al Calcio S100/sangre
12.
Clin Cancer Res ; 27(14): 3916-3925, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-33863808

RESUMEN

PURPOSE: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM). PATIENTS AND METHODS: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied. RESULTS: A total of 41 of 47 patients (mean age 56 ± 11.7) were evaluable for response. PFS was significantly shorter using standard RANO compared with iRANO (log-rank, P < 0.0001; HR = 0.3) and mRANO (P < 0.0001; HR = 0.3). In patients who died and had confirmed progression on standard RANO, no correlation was observed between PFS and OS (local, P = 0.47; central, P = 0.34). Using iRANO, a weak association was observed between confirmed PFS and OS via local site measurements (P = 0.017), but not central measurements (P = 0.18). A total of 24 of 41 patients (59%) were censored using iRANO and because they lacked confirmation of progression 3 months after initial progression. A strong correlation was observed between mRANO PFS and OS for both local (R2 = 0.66, P < 0.0001) and centrally determined reads (R2 = 0.57, P = 0.0007). CONCLUSIONS: No correlation between radiographic PFS and OS was observed for standard RANO or iRANO, but a correlation was observed between PFS and OS using the mRANO criteria. Also, the iRANO criteria was difficult to implement due to need to confirm progression 3 months after initial progression, censoring more than half the patients.


Asunto(s)
Glioblastoma/terapia , Inmunoterapia/métodos , Inmunotoxinas/farmacología , Subunidad alfa del Receptor de Interleucina-4/antagonistas & inhibidores , Recurrencia Local de Neoplasia/terapia , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias del Sistema Nervioso/tratamiento farmacológico , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
13.
Pol Przegl Chir ; 92(5): 1-5, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-33028729

RESUMEN

INTRODUCTION: Malignant gliomas (HGG) are the most common primary malignant brain tumors arising from glial cells. Between HGG, glioblastoma is the most common and the most malignant histological subtype with only a 27% 2-year survival rate. Current standard medical treatment of malignant gliomas is still not satisfactory, and may need some development and modification. We presented and discussed the achievements of the Department of Neurosurgery at Brodno Masovian Hospital in the treatment of malignant gliomas. MATERIAL AND METHODS: We step by step presented and discussed the policy in the treatment of malignant gliomas. We showed all steps starting from preparation of surgery (eg. neuroimaging) and finishing on the presentation the development of perioperative management - from intraoperative electrical stimulation mapping and monitoring which is nowadays already standard method to convection-enhanced delivery (CED) and gamma knife (GK) which are new and promising methods in the treatment of glioblastoma. RESULTS: All surgical methods described in this manuscript were introduced to achieve maximal and safe resection of malignant glioma. CED and GK are the last resort methods for patients with recurrent HGG. DISCUSSION: Department of Neurosurgery at Brodno Masovian Hospital deal with all types of brain tumors, including all types of high grade gliomas. As the first Department in Europe with close cooperation with the Department of Neurosurgery in San Francisco, we have started local infusions of drugs directly to the tumor in the real time of magnetic field, and we think that technology may change all approaches to the treatment of high grade gliomas.


Asunto(s)
Neoplasias Encefálicas/cirugía , Glioma/cirugía , Neurocirugia/normas , Procedimientos Neuroquirúrgicos/métodos , Centros Médicos Académicos , Adulto , Neoplasias Encefálicas/patología , Neoplasias del Tronco Encefálico/cirugía , Femenino , Glioma/patología , Humanos , Persona de Mediana Edad , Polonia
14.
J Neurosurg ; : 1-7, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33096525

RESUMEN

OBJECTIVE: The objective of this study was to assess the feasibility, accuracy, effectiveness, and safety of an MRI-compatible frameless stereotactic ball-joint guide array (BJGA) as a platform for cannula placement and convection-enhanced delivery (CED). METHODS: The authors analyzed the clinical and imaging data from consecutive patients with aromatic l-amino acid decarboxylase (AADC) deficiency who underwent infusion of adeno-associated virus (AAV) containing the AADC gene (AAV2-AADC). RESULTS: Eleven patients (7 females, 4 males) underwent bilateral MRI-guided BJGA cannula placement and CED of AAV2-AADC (22 brainstem infusions). The mean age at infusion was 10.5 ± 5.2 years (range 4-19 years). MRI allowed for accurate real-time planning, confirmed precise cannula placement after single-pass placement, and permitted on-the-fly adjustment. Overall, the mean bilateral depth to the target was 137.0 ± 5.2 mm (range 124.0-145.5 mm). The mean bilateral depth error was 0.9 ± 0.7 mm (range 0-2.2 mm), and the bilateral radial error was 0.9 ± 0.6 mm (range 0.1-2.3 mm). The bilateral absolute tip error was 1.4 ± 0.8 mm (range 0.4-3.0 mm). Target depth and absolute tip error were not correlated (Pearson product-moment correlation coefficient, r = 0.01). CONCLUSIONS: Use of the BJGA is feasible, accurate, effective, and safe for cannula placement, infusion MRI monitoring, and cannula adjustment during CED. The low-profile universal applicability of the BJGA streamlines and facilitates MRI-guided CED.

15.
J Neurosurg ; 134(6): 1751-1763, 2020 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-32915526

RESUMEN

Molecular biological insights have led to a fundamental understanding of the underlying genomic mechanisms of nervous system disease. These findings have resulted in the identification of therapeutic genes that can be packaged in viral capsids for the treatment of a variety of neurological conditions, including neurodegenerative, metabolic, and enzyme deficiency disorders. Recent data have demonstrated that gene-carrying viral vectors (most often adeno-associated viruses) can be effectively distributed by convection-enhanced delivery (CED) in a safe, reliable, targeted, and homogeneous manner across the blood-brain barrier. Critically, these vectors can be monitored using real-time MRI of a co-infused surrogate tracer to accurately predict vector distribution and transgene expression at the perfused site. The unique properties of CED of adeno-associated virus vectors allow for cell-specific transgene manipulation of the infused anatomical site and/or widespread interconnected sites via antero- and/or retrograde transport. The authors review the convective properties of viral vectors, associated technology, and clinical applications.


Asunto(s)
Convección , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/terapia , Adenoviridae/genética , Animales , Humanos , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Resultado del Tratamiento
16.
Neurol Neurochir Pol ; 54(3): 220-231, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32557526

RESUMEN

INTRODUCTION: Vector-based intracerebral gene therapies are being used to treat specific neurodegenerative conditions such as Parkinson's Disease (PD). This review presents a basis for central nervous system (CNS) gene therapy treatments of neurodegenerative diseases such as PD, as well as the need for novel skill sets and health delivery strategies within the clinical neurosciences (neurology and neurosurgery) to meet future demand for such therapies. STATE OF THE ART: Preclinical vector-based gene therapy approaches have been translated into clinical trials for PD and other neurodegenerative conditions. Unfortunately, such trials, and parallel efforts using other therapeutics, have yet to provide a breakthrough. Image-guided convection enhanced delivery (CED) optimises the parenchymal distribution of gene therapies applied within the CNS, and may ultimately provide such a breakthrough. CLINICAL IMPLICATIONS: Currently, image-guided CED and gene therapy are not part of training programmes for most neurosurgeons and neurologists. As a result, few medical centres and hospitals have sufficiently experienced teams to participate in gene transfer clinical trials for PD or other neurological conditions. If CNS gene therapies prove to be efficacious for PD and/or other conditions, the demand for such treatments will overwhelm the available number of experienced clinical neuroscience teams and treatment centres. FUTURE DIRECTIONS: Expanded indications and demand for CNS gene therapies will require a worldwide educational effort to supplement the training of clinical neuroscience practitioners. Initially, a limited number of Centres of Excellence will need to establish relevant educational training requirements and best practice for such therapeutic approaches. Advanced technologies, including robotics and artificial intelligence, are especially germane in this regard, and will expand the treatment team's capabilities while assisting in the safe and timely care of those afflicted.


Asunto(s)
Enfermedad de Parkinson , Inteligencia Artificial , Sistema Nervioso Central , Terapia Genética , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia
17.
Acta Neurol Scand ; 141(5): 415-422, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31922606

RESUMEN

OBJECTIVE: According to the literature, gamma knife surgery (GKS) is a promising method for intracanalicular vestibular schwannoma (IVS) management, providing excellent tumor growth control rates (91%-100%) and good hearing preservation rates (41%-76%), but this evidence originates primarily from a small series of patients. The aim of this study was to present the outcomes of GKS in the largest group of patients with IVS studied to date, with particular emphasis on the long-term outcomes of treatment. METHODS: The study included 136 consecutive patients with unilateral IVS, who underwent GKS in 2011-2015. Mean age of the patients was 54 ± 12.6 years. All patients were operated on with a 192-source cobalt-60 gamma knife unit. All patients had complete follow-up documentation and the mean duration of the follow-up was 52 ± 13.8 months (6-83 months). Neurological status (facial and trigeminal nerve), hearing and instability/dizziness presence were determined prior to GKS, immediately after the procedure, and during the follow-up visits. RESULTS: Tumor growth control was obtained in 124/136 (~91.2%) patients. Hearing improvement was observed in 32/136 (23.5%) patients, and there was a distinct cluster of 9 patients (6.6%) regaining serviceable hearing after GKS, whereas in 36 patients (26.5%) was stable. Four patients developed facial nerve dysfunction, including 3 periodic hemifacial spasm and 1 partial paresis, which resolved spontaneously within 12 months of GKS. None of the operated patients showed new, debilitating neurological deficits, including trigeminal sensory disturbances or hydrocephalus. CONCLUSIONS: GKS is a highly effective treatment for IVS, associated with low morbidity and good tumor growth control.


Asunto(s)
Neuroma Acústico/cirugía , Radiocirugia/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Audición , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Radiocirugia/efectos adversos , Resultado del Tratamiento
18.
J Neurol Sci ; 400: 97-103, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-30909114

RESUMEN

BACKGROUND: We present our operative experience of patients with movement disorders who developed intracerebral hemorrhage (ICH), which was identified on intraprocedural stereotactic computed tomography (CT) imaging performed immediately after deep brain stimulation (DBS) lead placement and prior to the implantation of further components of the DBS hardware. METHODS: Patients who underwent DBS lead implantation from January 2009 through December 2017 were included in the present study. Most of the surgeries were performed in a staged fashion. All patients were operated using identical surgical and intraprocedural imaging techniques, and no microelectrode recordings were done. Leksell Stereotactic G frame and neuronavigation software was utilized for all surgeries. Intraprocedural stereotactic CT was performed to confirm the precise position of the implanted DBS lead and to rule out any hemorrhagic complications. RESULTS: Overall, 222 patients underwent 322 DBS lead implantations during 316 stereotactic procedures. Six patients exhibited early ICH recognized on intraprocedural stereotactic CT performed immediately after DBS lead placement; in addition, two patients developed delayed ICH due to large venous infarction. Four patients with ICH were asymptomatic. The ICH rate was 2.5% per electrode and 3.6% per patient; the permanent deficit rate was 1.2% per electrode and 1.8% per patient. The death rate due to ICH in our cohort was 0.6% per electrode and 0.9% per patient. CONCLUSIONS: Intraprocedural stereotactic CT can not only visualize the implanted DBS lead in the stereotactic space but also rule out early ICH. Identified predisposing factors for development of ICH include patient's age, hypertension, and previous antiplatelet therapy. Careful planning of stereotactic trajectories plays a paramount role in reducing the rate of ICH in DBS surgery.


Asunto(s)
Hemorragia Cerebral/diagnóstico por imagen , Estimulación Encefálica Profunda/efectos adversos , Complicaciones Intraoperatorias/diagnóstico por imagen , Monitorización Neurofisiológica Intraoperatoria/métodos , Técnicas Estereotáxicas/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Hemorragia Cerebral/etiología , Estimulación Encefálica Profunda/métodos , Electrodos Implantados , Femenino , Humanos , Complicaciones Intraoperatorias/etiología , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/cirugía , Estudios Retrospectivos
20.
J Neurol Sci ; 383: 153-157, 2017 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-29246604

RESUMEN

BACKGROUND: The aim of the present study was to report the short-term as well long-term results of bilateral pallidal stimulation in 6 consecutive patients for severe debilitating craniocervical dystonia (Meige syndrome) using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). METHODS: We evaluated 6 consecutive patients with the diagnosis of intractable long-standing craniocervical dystonia. The formal objective assessment included the motor and disability BFMDRS scores. The BFMDRS assessment was performed before and after it roughly annually up to 60months when bilateral pallidal stimulation was switched on and compared to baseline BFMDRS scores. We present short-term (3months postoperatively) follow-up as well long-term (from 6 to 60months) results. Baseline BFMDRS scores and subsequent follow-up BFMDRS scores were compared with the use of a Wilcoxon signed-rank test for matched pairs. A two-tailed probability level of 5% (p<0.05) was considered significant. RESULTS: Bilateral GPi DBS improved the BFMDRS total movement score by 65% at short-term follow-up and by 53% at long-term follow-up when compared to baseline scores. Subscores for eyes at short-term follow-up were reduced by 78%, for mouth by 58%, and for speech/swallowing by 49%. This improvements for individual subscores were maintained at long-term follow-up and were as follows for eyes by 67%, mouth by 50% and speech/swallowing by 39%. The BFMDRS disability score was reduced by 48% at short-term follow-up and by 55% at long-term follow-up when compared to baseline scores. CONCLUSION: Our results showed that bilateral GPi DBS in craniocervical dystonia is effective and safe. Phasic dystonic movements like blepharospasm or oromandibular dystonia responded very fast and favorable to pallidal stimulation reducing disabilities.


Asunto(s)
Estimulación Encefálica Profunda , Globo Pálido , Síndrome de Meige/terapia , Anciano , Estimulación Encefálica Profunda/métodos , Femenino , Estudios de Seguimiento , Globo Pálido/fisiopatología , Humanos , Masculino , Síndrome de Meige/fisiopatología , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
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