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BACKGROUND: Migraine is common and ranked as the first cause of disability in people under fifty. Despite significant advances in its pharmacological treatment, it often remains intractable. Neuromodulation is one option considered in the management of those patients. OBJECTIVE: To assess the safety and efficacy of neuromodulation in the treatment of intractable chronic migraine using the Abbott occipital nerve stimulator. METHODS: Recruitment took place in 18 centres in 6 countries. Patients over the age of 18 who had failed three or more preventative drugs, had at least moderate disability based on MIDAS or HIT-6 score and were implanted with an Abbott neurostimulator were included in the study. Patients were followed up for a maximum of 24 months. Data were collected on adverse events, headache relief, headache days, quality of life, migraine disability, satisfaction and quality of life. RESULTS: One hundred twelve patients were included, 79 female and 33 male, with 45 patients reaching the maximum follow-up of 24 months. At 3 months, 33.7% were satisfied or very satisfied with the procedure with 43.0% reporting improved or greatly improved quality of life. 67.5% indicated that they would undergo the procedure again with satisfaction peaking at 9 months when 49.3% were satisfied or very satisfied with the procedure. At 24 months, 46.7% of available patients were satisfied or very satisfied with the procedure-18% of enrolled patients. The adverse events were however frequent with incidences of 37%, 47% and 31% respectively for hardware-, biological and stimulation-related side effects. CONCLUSION: Neuromodulation can be beneficial for selected patients with intractable chronic migraine although frequent complications have been consistently reported across studies. Further research focusing on development of better hardware and technique optimisation and in particular reliable randomised trials with significantly longer follow-ups are warranted in this field.
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Terapia por Estimulação Elétrica/métodos , Neuroestimuladores Implantáveis , Transtornos de Enxaqueca/terapia , Nervos Espinhais , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Sistema de Registros , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The management of paediatric hydrocephalous remains challenging with the complication and revision rates being consistent in the literature. We hypothesise that the use of a fixed pressure gravitational valve for all de novo shunt insertions decreases the rate of functional revisions and that by implementing the routine use of gravitational valves in children, we would see a reduction in over-drainage and slit ventricle syndrome. METHODS: Retrospective data collection in a single centre, between February 2010 and August 2018. All patients undergoing fixed pressure gravitational Miethke valve insertion were included. We collected data on patients' demographics, reason for shunt insertion, type of valve and time to and reason for first revision. Data analysis was done with SPSS. RESULTS: A total of 235 patients were included in our study (124 males, 111 females), aged from 0 to 18.6 years (median 0.28). A total of 99 shunt revisions were documented, 30 of which secondary to ventricular catheter malfunction and 28 secondary to infection. The overall mechanical valve survival rates were 88.5%, 86.4% and 85.5% at 1, 2 and 5 years, respectively. Shunt revision due to over-drainage was documented in only 3 cases (1.3%). CONCLUSION: Our results are in agreement with existing literature regarding shunt failures secondary to all extrinsic factors to the valve (infection and mechanical failure). We have shown that the use of a Miethke fixed pressure valve for all de novo shunt insertions in paediatric hydrocephalus decreases the need for functional revisions with valve survival rates being superior to the ones described for other types.
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Derivações do Líquido Cefalorraquidiano , Hidrocefalia , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Criança , Feminino , Gravitação , Hospitais , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Masculino , Estudos Retrospectivos , Derivação VentriculoperitonealRESUMO
High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced factor (HIF) 1α and p53. Our evaluation of lead DIVERSet library compounds identified that JAG-6A, a compound that was significantly more potent than temozolomide or etoposide, was effective against HGG models in two-dimensional and three-dimensional systems; mediated this response by the potent inhibition of topoisomerase Iiα; remained effective under normoxic and hypoxic conditions; and displayed limited toxicity to non-neoplastic astrocytes. These data suggest that JAG-6A could be an alternative topoisomerase IIα inhibitor and used for the treatment of HGG.
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Cognitive deficits and psychiatric morbidities are commonly detected in dystonia. Psychiatric disturbances are of particular clinical concern as they not only contribute to poor quality of life and disease associated burden, but also exacerbate motor and cognitive symptoms. Bilateral deep brain stimulation of the globus pallidus internus improves motor symptoms in treatment-resistant dystonia, but its implications for non-motor manifestations are poorly understood. Improved prediction of cognitive and neuropsychiatric outcomes is important in deep brain stimulation (DBS) research and we aim to assess the latter through established assessment tools. We document the cognitive and neuropsychiatric profiles in 11 primary and 10 secondary dystonia patients attending our DBS clinic. We performed routine multidisciplinary assessments including a comprehensive battery of neuropsychometric tests and detailed neuropsychiatric evaluations. Post-operative assessment outcomes are reported for three patients in case series. The main cognitive deficit was on the Brixton test of spatial anticipation in primary dystonia. Background medical history included psychiatric illness in 38.1% of the patients with 76% of patients having mood abnormalities confirming elevated psychiatric morbidity in this population. Depressive illness was more prominent in primary, whereas clinically relevant histories in secondary dystonia were varied. Of the 21 patients three were able to perform on selected tests due to extensive limitations of their dystonia. No obvious alteration in intellectual functioning following DBS surgery relative to performance at the time of initial assessment was observed. The frequency of individual impairments suggests that difficulties associated with dystonia are likely to be of clinical relevance to cognitive functions in the majority of patients. In particular, current findings suggest that executive difficulties related to inductive processes and spatial learning may be a common in primary dystonias. Psychiatric disturbances demand recognition as a central aspect of dystonia as they contribute to overall disease burden, poor quality of life and exacerbated motor disabilities. The available evidence provides overwhelming suggestion that vulnerability to depression is inherent to the dystonia phenotype.
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Autologous dentritic cell immunotherapy has been proven effective in treating tumors outside the central nervous system. Current evidence from phase I and II trials suggest a similar efficacy for central nervous system tumors as well and that an active immune response against these tumors can be generated. We aim to review the literature to identify the types of immune responses against gliomas found to be generated by dendritic cell vaccinations and the types of immune cells subsequently infiltrating the glioma microenvironment. A systematic review of the literature was performed by searching the online databases PubMEd, Google Scholar, and EMBASE with use of the keywords intratumoral, infiltration, lymphocytic, vaccination and gliomas. Seven studies reporting lymphocytic infiltration of gliomas microenvironment were identified. Three studies (42.8%) reported presence of tumor infiltrating lymphocytes in 50%, 50% and 28.6% of included patients respectively in the post-vaccination specimens that were not present in the pre-vaccination samples. The remaining 4 (57.2%) reported an up to 6-fold increase in the number of pre-existing lymphocytes following vaccination. Present data indicate that tumor infiltration by lymphocytes can be induced by dentritic cell immunotherapy and that this may positively affect clinical outcome. It still remains unclear which factors influence the above reaction and therefore prediction of response to treatment is still not possible.
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Glioblastoma/imunologia , Glioblastoma/terapia , Linfócitos do Interstício Tumoral/imunologia , Microambiente Tumoral/imunologia , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Células Dendríticas/imunologia , Citometria de Fluxo , Glioma/imunologia , Glioma/terapia , Humanos , Imunoterapia , Camundongos , VacinaçãoRESUMO
BACKGROUND: Rapid growth in cerebral cavernous malformation is rare. A review of the literature revealed 4 patients with known cerebral cavernous malformations who later developed a high-grade glioma at the same site. All 4 patients were females, ranging in age from 25 to 71 years, with imaging confirming rapid growth in the lesion. CASE DESCRIPTION: We present the case of a 71-year-old patient with known multiple cavernomas over many years in whom one lesion showed rapid expansion in size. Histological examination revealed the coexistence of a glioblastoma within the cavernoma. CONCLUSIONS: We conclude that, although rare, rapid expansion of an existing cavernoma should be considered suspicious for the development of other malignant tumors, and propose adding chronic inflammation in the surrounding brain caused by microbleeds and hemosiderin deposition from the cavernoma to the list of possible causes.
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Neoplasias Encefálicas/complicações , Glioma/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso/complicações , Neoplasias Primárias Múltiplas/complicações , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Feminino , Glioma/diagnóstico , Hemangioma Cavernoso/diagnóstico , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnósticoRESUMO
BACKGROUND: Deep brain stimulation (DBS) has been a major advance in the treatment of dystonias. Outcomes are, however, less predictable for secondary dystonias, predominantly due to progression of disease or specific brain lesions. There are few cases reported of globus pallidus internus (GPi)-DBS for posttraumatic dystonia. We describe the successful use of unilateral GPi-DBS in a patient with hemidystonia following penetrating head injury. To our knowledge, this is the first description of the use of DBS following penetrating head injury. CASE DESCRIPTION: We present the case of a 47-year-old man with phasic hemidystonia. At the age of 3 years he suffered a penetrating head injury from a welding needle. The patient developed dystonic and phasic right-sided movements. Preoperative Burke-Fahn-Marsden score was 26. Magnetic resonance imaging showed a linear encephalomalacic track extending from the cortex in the left parieto-occipital region, traversing just superolateral to the left trigone into the left thalamus and ending in the region of left cerebral peduncle and subthalamic nucleus. There was no left GPi lesion. A left GPi-DBS electrode was inserted. At 6 months' follow-up, the patient's arm was more relaxed and his spasms lessened in their severity and frequency. Although the Burke-Fahn-Marsden score of 21 had improved modestly by 20%, pain and comfort levels had significantly improved with 50% improvement in visual analog scale score, translating in better quality of life. There were no complications. The clinical benefit persists at 5 years post surgery. CONCLUSION: Selected patients with posttraumatic hemidystonia, including following penetrating head injury, represent one group of secondary dystonias that might benefit from DBS surgery.