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The molecular mechanisms behind the rupture of intracranial aneurysms remain obscure. MiRNAs are key regulators of a wide array of biological processes altering protein synthesis by binding to target mRNAs. However, variations in miRNA levels in ruptured aneurysmal wall have not been completely examined. We hypothesized that altered miRNA signature in aneurysmal tissues could potentially provide insight into aneurysm pathophysiology. Using a high-throughput miRNA microarray screening approach, we compared the miRNA expression pattern in aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues (GEO accession number GSE161870). We found that the expression of 70 miRNAs was altered. Expressions of the top 10 miRNA were validated, by qRT-PCR and results were correlated with clinical characteristics of aSAH patients. The level of 10 miRNAs (miR-24-3p, miR-26b-5p, miR-27b-3p, miR-125b-5p, miR-143-3p, miR-145-5p, miR-193a-3p, miR-199a-5p, miR-365a-3p/365b-3p, and miR-497-5p) was significantly decreased in patients compared to controls. Expression of miR-125b-5p, miR-143-3p and miR-199a-5p was significantly decreased in patients with poor prognosis and vasospasm. The target genes of few miRNAs were enriched in Transforming growth factor-beta (TGF-ß) and Mitogen-activated protein kinases (MAPK) pathways. We found significant negative correlation between the miRNA and mRNA expression (TGF-ß1, TGF-ß2, SMAD family member 2 (SMAD2), SMAD family member 4 (SMAD4), MAPK1 and MAPK3) in aneurysm tissues. We suggest that miR-26b, miR-199a, miR-497and miR-365, could target multiple genes in TGF-ß and MAPK signaling cascades to influence inflammatory processes, extracellular matrix and vascular smooth muscle cell degradation and apoptosis, and ultimately cause vessel wall degradation and rupture.
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Aneurisma Intracraniano , MicroRNAs , Perfilação da Expressão Gênica , Humanos , RNA Mensageiro , Transdução de Sinais , Fator de Crescimento Transformador betaRESUMO
BACKGROUND: Deafferentiation pain following brachial plexus root avulsion has been documented to be severe enough to affect activities of daily living in patients. Microsurgical DREZotomy is known to alleviate the symptoms by decreasing the afferent signals transmitted from the spinal cord to sensory cortex. OBJECTIVES: To document and analyse the effectiveness of DREZotomy and to evaluate the role of 'sensory cortex' in the cause and relief of dysesthetic pain, using fMRI. MATERIALS AND METHODS: This was a prospective study conducted between 2010 and 2016 and included all patients who underwent DREZotomy for dysesthetic pain following traumatic brachial plexus injury (TBPI). Patients were evaluated both preoperatively and postoperatively with Visual Analogue Scale(VAS), Hospital Anxiety and Depression score (HADS) and SF36 questionnaire and effectiveness of surgery was assessed. Functional magnetic resonance imaging (fMRI) of the brain in resting state was performed before and after surgery and was also compared with controls. Patients underwent standard microsurgical DREZotomy from C5 to D1. Postoperative assessment was done at 6 weeks and 6 months following surgery. RESULTS: Our series had 18 patients aged between 22 and 63 years. RTA was the most common cause of injury. There was significant decrease in pain at 6 months follow up compared to pre-operative values as assessed by VAS, HADS, SF36 questionnaire. fMRI analysis revealed cluster activations in the sensory, motor cortex and in the right cingulate gyrus in the preoperative group which was higher than in normal controls. In the postoperative group, the size of the resting state activation was significantly reduced. CONCLUSION: DREZotomy is an effective procedure for TBPI patients. We hypothesize that these fMRI findings reflect the cortical reorganization that occurs not only after injury but also following successful surgery which explains the cause and relief of dyesthetic pain.
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Aneurysmal subarachnoid hemorrhage (aSAH) occurs more often in postmenopausal women than in men. Estrogen plays an important role in vascular homeostasis. Our aim was to elucidate whether a drop in circulating estradiol in conjunction with variants of estrogen receptor genes have a role in female gender susceptibility to aSAH. A total of 709 subjects were enrolled (349 aSAH patients, 360 controls) and genotyped for rs2234693 or PvuII (intron 1, T>C) in the ESR1 gene and rs4986938 or AluI (exon 8, 1730G>A) of ESR2 gene by PCR-RFLP. Serum estradiol was estimated by ELISA. Estrogen receptor gene expression was studied by qRT-PCR. Logistic regression analysis indicated a significant recessive effect of the T allele of PvuII on aSAH in females, and this association remained statistically significant even after adjusting for confounders (OR 1.702, CI 95% 1.062, 2.726, P value = 0.027). ESR1 gene expression was significantly reduced (P value = 0.0089) in subjects carrying PvuII T allele. In postmenopausal women with TT genotype and low serum estradiol, the odds for developing aSAH were found to be 3.5-fold increase compared with premenopausal women (CI 95% 1.424-8.828, P value = 0.0074). However, this variant showed no significant association with aSAH in men. No significant difference was found in genotype and allelic distribution of AluI polymorphism in ESR2 gene, between patients and controls. We propose that the PvuII T allele could be a potential pharmacogenetic marker for strategizing personal medicine for preventing aSAH in postmenopausal women with low circulating estradiol. Further larger studies in other population are warranted.
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Receptor alfa de Estrogênio/genética , Variantes Farmacogenômicos , Hemorragia Subaracnóidea/genética , Adulto , Idoso , Estudos de Casos e Controles , Estradiol/sangue , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Pós-Menopausa , Medição de Risco , Fatores de Risco , Fatores Sexuais , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/diagnósticoRESUMO
OBJECTIVE: Intracranial fungal granuloma (IFG) remains an uncommon entity. The authors report a single-institute study of 90 cases of IFG, which is the largest study until now. METHODS: In this retrospective study, all cases of IFG surgically treated in the years 2001-2018 were included. Data were obtained from the medical records and the pathology, microbiology, and radiology departments. All relevant clinical data, imaging characteristics, surgical procedure performed, perioperative findings, and follow-up data were recorded from the case files. Telephonic follow-up was also performed for a few patients to find out their current status. RESULTS: A total of 90 cases consisting of 64 males (71.1%) and 26 (28.9%) females were evaluated. The mean patient age was 40.2 years (range 1-79 years). Headache (54 patients) was the most common presenting complaint, followed by visual symptoms (35 patients), fever (21 patients), and others such as limb weakness (13 patients) or seizure (9 patients). Cranial nerve involvement was the most common sign (47 patients), followed by motor deficit (22 patients) and papilledema (7 patients). The mean duration of symptoms before presentation was 6.4 months (range 0.06-48 months). Thirty patients (33.3%) had predisposing factors like diabetes mellitus, tuberculosis, or other immunocompromised status. A pure intracranial location of the IFG was seen in 49 cases (54.4%), whereas rhinocerebral or paranasal sinus involvement was seen in 41 cases (45.6%). Open surgery, that is, craniotomy and decompression, was performed in 55 cases, endoscopic biopsy was done in 30 cases, and stereotactic biopsy was performed in 5 cases. Aspergilloma (43 patients) was the most common fungal mass, followed by zygomycosis (13 patients), chromomycosis (9 patients), cryptococcoma (7 patients), mucormycosis (5 patients), and candida infection (1 patient). In 12 cases, the exact fungal phenotype could not be identified. Follow-up was available for 69/90 patients (76.7%). The mean duration of the follow-up was 37.97 months (range 3-144 months). The mortality rate was 52.2% (36/69 patients) among the patients with available follow-up. CONCLUSIONS: A high index of suspicion for IFG should exist for patients with an immunocompromised status and diabetic patients with rhinocerebral mass lesions. Early diagnosis, aggressive surgical decompression, and a course of promptly initiated antifungal therapy are associated with a better prognosis.
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Granuloma/tratamento farmacológico , Granuloma/cirurgia , Hospedeiro Imunocomprometido/efeitos dos fármacos , Micoses/tratamento farmacológico , Micoses/cirurgia , Doenças do Sistema Nervoso/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Granuloma/imunologia , Granuloma/microbiologia , Cefaleia/tratamento farmacológico , Cefaleia/cirurgia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Micoses/imunologia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: Growing skull fracture (GSF) is a rare complication resulting from diastatic enlargement of a pediatric skull fracture. Orbitocranial GSF is a distinct variant with more complex management issues due to the displacement of the globe. This study aims to discuss surgical considerations in the management of GSF, with particular reference to orbitocranial variants. METHODS: We conducted a retrospective analysis of 7 children operated for GSFs at our institute from 2008 to 2015. RESULTS: Four boys and 3 girls were operated during this period. The mean age at initial trauma was 2 years, and most of them sustained falls. The most frequent symptoms of GSF were progressive scalp swelling and proptosis. The most common location was the orbitofrontal region. Duraplasty with cranioplasty was performed in 5 patients, while duraplasty alone was only required in 2 patients. A postoperative complication was noted in 1 patient and managed successfully. Good cosmetic results were obtained in all of the cases. CONCLUSIONS: Duraplasty is essential in the repair of GSF and should be followed by cranioplasty to prevent recurrent leptomeningeal herniation. We recommend the use of autologous bone from the surgical site for cranioplasty. Orbital roof repair is advisable for good visual and cosmetic outcome in orbitocranial variants of GSF.
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Traumatismos Craniocerebrais/complicações , Fraturas Cranianas , Pré-Escolar , Traumatismos Craniocerebrais/líquido cefalorraquidiano , Dura-Máter/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fraturas Cranianas/complicações , Fraturas Cranianas/diagnóstico , Fraturas Cranianas/etiologia , Fraturas Cranianas/cirurgiaRESUMO
PURPOSE: Intracranial aneurysms in children are rare compared to those in adults, and their causes, presentations, and outcomes also vary. Thus, they need to be studied intricately and as an independent entity. METHODS: We retrospectively reviewed intracranial saccular aneurysms in 44 children of <19 years of age who had been surgically treated during the last 30 years at our institute. We analyzed presentation, characteristics, size, multiplicity, cause, and eventual outcome, and compared these to the adult cases of aneurysms operated on during the same period. RESULTS: The commonest site of aneurysm was the internal carotid artery (ICA), in 47.7%. Follow-up was available for 38 (86.4%) children. The median duration of follow-up was 14 months (range 1-89 months). A favorable outcome was seen in 31 cases (81.6%) and an unfavorable outcome (including 1 death) in 7 (18.4%). CONCLUSION: Intracranial aneurysms in children present with subarachnoid hemorrhage in a good grade. ICA bifurcation aneurysms are the commonest sites of occurrence. Surgery is safe and effective, and children seem to have a better outcome.
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Gerenciamento Clínico , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Seguimentos , Humanos , Lactente , Masculino , Procedimentos Neurocirúrgicos/normas , Estudos RetrospectivosRESUMO
The issue of head injury in a noncontact sport like cricket is a matter of great debate and it carries more questions than answers. Recent incidents of fatal head injuries in individuals wearing a helmet have caused some to question the protective value of the helmet. The authors discuss the pattern, type of injury, incidents, and location of cranio-facio-ocular injuries in professional cricket to date. They evaluate the history of usage of the helmet in cricket, changes in design, and the protective value, and they compare the efficacy of various sports' helmets with injury profiles similar to those in cricket. The drop test and air cannon test are compared for impact energy attenuation performance of cricket helmets. A total of 36 cases of head injuries were identified, of which 5 (14%) were fatal and 9 (22%) were career-terminating events. Batsmen are the most vulnerable to injury, bearing 86% of the burden, followed by wicketkeepers (8%) and fielders (5.5%). In 53% of cases, the ball directly hit the head, while in 19.5% of cases the ball entered the gap between the peak and the faceguard. Ocular injuries to 3 wicketkeepers proved to be career-terminating injuries. The air cannon test is a better test for evaluating cricket helmets than the drop test. Craniofacial injuries are more common than popularly believed. There is an urgent need to improve the efficacy and compliance of protective restraints in cricket. A strict injury surveillance system with universal acceptance is needed to identify the burden of injuries and modes for their prevention.
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Acidentes de Trânsito/estatística & dados numéricos , Lesões Encefálicas/prevenção & controle , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/prevenção & controle , Guias como Assunto , Dispositivos de Proteção da Cabeça , Acidentes de Trânsito/legislação & jurisprudência , Desenho de Equipamento , HumanosRESUMO
Fetus in fetu (FIF) is an extremely rare congenital anomaly in the pediatric age group. It is defined by the presence of an axial skeleton and well-formed internal organs in a fetiform mass. Only about 15 cases of intracranial FIF have been reported in the literature worldwide. We report a case of temporo-occipitocervical FIF. This 7-month-old female child presented to us with occipital swelling that she had had since birth. A soft swelling was palpable in the retroauricular region with extension into the neck. A few bony parts were palpable in the swelling. Imaging was suggestive of a multiseptate mass lesion in the right occipital region with intracranial, intraspinal and extracranial components. The patient underwent exploration and excision of the extracranial mass and retromastoid suboccipital craniectomy and decompression of the intracranial component. Different parts, such as a terminal ileum, cecum, appendix, femur, humerus and vertebral body, were identified within the mass. This case meets Willis' criteria as well as 4/5 criteria stated by Spencer for the diagnosis of this condition. To the best of our knowledge, this is the first reported case of temporo-occipitocervical FIF with a well-defined embryological spectrum. This also supports Spencer's hypothesis of abnormal twinning.
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Feto/anormalidades , Lobo Occipital/cirurgia , Teratoma/patologia , Anormalidades Congênitas/cirurgia , Craniotomia , Diagnóstico Diferencial , Feminino , Feto/cirurgia , Humanos , Lactente , Crânio/anormalidades , Crânio/cirurgia , Teratoma/cirurgiaRESUMO
Astroblastomas are extremely rare neuroepithelial tumors of uncertain histogenesis, affecting children and young adults, and constitute a new addition to the WHO 2000 classification of CNS tumors. We report the largest series of nine cases diagnosed in a single institute over the last 13 years and review published literature. Mean age at presentation was 12.8 years (range: 22 months to 27years). Seven out of nine cases were supratentorial (frontal/frontoparietal - three, parieto-occipital - three, parafalcine - one), one was intraventricular and another was optochaismatic/suprasellar. Five cases were high grade (anaplastic) astroblastomas with Ki-67 labeling index of 8-10%. Immunohistochemical and ultrastructural evidence suggesting origin from cells intermediate between ependymocytes and astrocytes is presented. The histogenetic origin of these tumors remains speculative. But the lack of Isocitrate dehydrogenase 1 (IDH1) mutation as detected by immunohistochemistry in this study, which is similar to ependymomas supports putative origin from ependymoglial cells. Out of the nine cases, recurrence was noted in one case, 12 months after gross total resection with progression to high grade in the recurrent tumor. There is no recommended treatment protocol due to the rarity of this entity and prognostic factors are yet to be established.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/ultraestrutura , Células Ependimogliais/ultraestrutura , Isocitrato Desidrogenase/genética , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/ultraestrutura , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Mutação , Neoplasias Neuroepiteliomatosas/etiologia , Adulto JovemRESUMO
Timely management of hydrocephalus in infants is critical as the initial treatment can have lifelong implications for survival and neurological outcome. In the developing countries, grossly enlarged heads are still not an uncommon occurrence. In extreme cases, there may be a spontaneous rupture of hydrocephalus either externally or internally, depending on the status of the sutures. Here, the successful management of a rare complication of spontaneous rupture of hydrocephalus in an infant is discussed. The management of the present case provides a novel approach to deal with this dreaded complication. Though the neurological outcome remains guarded in such cases, they need to be tackled cautiously to address the hydrocephalus and esthetic appearance of the infant.
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Ventrículos Cerebrais/patologia , Hidrocefalia/complicações , Fraturas Cranianas/etiologia , Humanos , Lactente , Masculino , Ruptura Espontânea/etiologia , Fraturas Cranianas/cirurgiaRESUMO
Dermoid cysts of posterior fossa are uncommon benign lesions. They differ from other lesions found in the infra tentorial compartment by virtue of their associated conditions. Due to their association with dermal sinus tracts, intracranial infection is a potential threat following infection of the cyst. Due to their embryologic origin, these cysts may also be associated with other congenital anomalies. In this article we detail our eleven-year-experience with posterior fossa dermoid cysts in fifteen patients. Despite the morbid presentation with severe life-threatening complications, the overall outcome was excellent. Implications of the various associations are discussed.
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Fossa Craniana Posterior/patologia , Cisto Dermoide/complicações , Neoplasias Infratentoriais/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Fossa Craniana Posterior/cirurgia , Cisto Dermoide/patologia , Cisto Dermoide/cirurgia , Feminino , Seguimentos , Humanos , Lactente , Neoplasias Infratentoriais/patologia , Neoplasias Infratentoriais/cirurgia , Síndrome de Klippel-Feil/cirurgia , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Background: Autonomic nervous system (ANS) is invariably affected by craniovertebral junction (CVJ) anomalies. The usual presentation is sudden after trivial trauma. When symptomatic, most of this autonomic dysfunction is clearly elicited clinically with bedside tests. Nonetheless, ANS functionality in relatively less symptomatic or asymptomatic patients is not known as no studies exist. Methodology: We performed a longitudinal prospective study of 40 less symptomatic patients who underwent surgery with conventional autonomic function tests (AFT) in pre- and post-operative periods. Correlation of its association with such anomalies is studied. Results: All 40 had both pre- and post-operative clinical follow-up, pre-operative AFT, whereas only 22 patients had follow-up AFT. The mean age for the group was 32 years and male: female ratio was 2.3:1. Mean Nurick's grade was 1.8, whereas Barthel's index was 83.75%. Clinical improvement was seen in almost 98% at follow-up. Orthostatic test showed a significant association with Nurick's grade. Barthel's index was significantly associated with degree of compression. The mean follow-up was 17.4 months. Most conventional AFTs were significantly decreased in the preoperative period (P ≤ 0.01). Both parasympathetic and sympathetic tone improved on follow-up with better improvement later. Overall clinical involvement of ANS was seen in 22.5% whereas subclinical involvement in the form of AFT impairment was seen in 100%. Conclusion: There is a definite involvement of subclinical ANS in all patients of CVJ anomalies irrespective of their symptomatology. Knowing the extent of involvement in the preoperative period can help prognosticate, prioritize regarding surgery as well as correlate with the extent of improvement.
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Objective: The aim of this study was to study mechanism, risk factors, and prognosis of patients with vertebral artery dissection (VAD) from acute cervical spine trauma (CST). Methods: A total of 149 consecutive patients were chosen from 2014 to 2019 from our institute data base, and their records were retrospectively studied. Morphology of fracture and subluxation were studied in detail with respect to the presence or absence of VAD. Results: Patients were divided in subsets of axial spine injury and subaxial spine injury. Subgroup and group analysis was performed and computerized tomography angiogram, MR angiogram and T1/T2 axial scans were studied to identify VAD, an incidence of 14.1% was found. Patients having infarcts in posterior circulation were also identified. Conclusion: There is a significant contribution of biomechanics of CST and evolution of VAD. This is an important consideration to prevent significant morbidity and mortality. Hence, a diagnostic algorithm which can be applied in any hospital setup is the need of the hour.
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Context Endothelial nitric oxide synthase ( eNOS) gene polymorphisms are found to predict predisposition to aneurysmal rupture and development of vasospasm in a patient of subarachnoid hemorrhage (SAH). eNOS gene polymorphisms are also found to predict invasiveness of malignant cells. Studies are not available in literature to describe the effect of eNOS gene polymorphisms and correlation between aneurysm and carcinoma. This study aims to investigate whether positive cancer history influences clinical outcome following SAH and eNOS gene polymorphisms. Materials and Methods The eNOS gene polymorphisms were analyzed in seven consecutive patients (mean age, 52.28 ± 20 years) with a diagnosis of invasive systemic tumors from 2011 to 2017. The eNOS 4a/4b eNOS -786T> eNOS 894G > T polymorphisms of the eNOS gene were determined by polymerase chain reaction and restriction fragment length polymorphism. Results Seven patients of aneurysmal SAH in association with malignancies were studied for eNOS polymorphisms expression and outcome. Three patients had carcinoma cervix: one patient of carcinoma breast and one each of transitional cell carcinoma of urinary bladder, spindle cell carcinoma of left kidney, and untreated patient of atypical pituitary (adenoma). A genotype study of eNOS gene polymorphisms in these patients shows common polymorphisms are involved in the determination of disease progression in malignancies and aneurysmal SAH. Conclusion Patients who expressed 4ab, eNOS -786T > TT/CC/TC, eNOS 894G > T GG/GT polymorphisms did better than patients who expressed only 4bb, though both were associated with poor prognosis.
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Background: Craniovertebral junction (CVJ) anomalies involve mosaic interaction of multifaceted neurovascular and bony elements. Most of them present late in the course of illness usually as acute presentations following trivial trauma. Knowing subclinical autonomic dysfunction in such anomalies when managed medically can not only indicate progression but also provide en route to early intervention for better outcomes, especially in relatively asymptomatic patients. Materials and Methods: We conducted a 6-year longitudinal prospective study including 40 consecutive patients of CVJ anomalies with clinical, radiological, and heart rate variability (HRV) parameters and found their correlation in preoperative and follow-up period. Results: Twenty-eight patients were male and the rest were female. The mean age was 32 years with the least age being 8 years and maximum age being 75 years old. Mean Nurick's grade and Barthel's index were 1.8 and 83.75, respectively. 38% had severe-to-moderate compression. The mean follow-up was 17.4 months. Both sympathetic and parasympathetic oscillator HRV indices were significantly affected in the preoperative period (P ≤ 0.001) with no association with Nurick's grade or degree of compression although there was association with grade of Barthel's index. Poincare plots showed "fan," "complex," or "torpedo" patterns in 36 patients. Forty patients had both preoperative and follow-up clinical grade whereas 22 patients HRV tests in the above periods. None of the HRV indices showed significant improvement at follow-up. Nonetheless both sympathetic and parasympathetic did improve at follow-up with sympathetic tone registering better scores. Poincare plots showed improvement toward "comet" patterns in all patients. Conclusion: HRV indices not only help in prognosticating but may also help in predicting outcomes.
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Rosai-Dorfman disease is a rare non-neoplastic lymphoproliferative condition. It commonly affects individuals between third and fifth decades, most common presentation being in the form of massive painless cervical lymphadenopathy with fever, weight loss and malaise. Isolated intracranial involvement is rare seen in less than 5% of patients with extranodal involvement. We present a patient with isolated contiguous cranio-spinal involvement who presented to us with remitting symptoms.
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Histiocitose Sinusal/patologia , Quadriplegia/patologia , Transtornos da Visão/patologia , Adulto , Craniectomia Descompressiva , Feminino , Forame Magno , Histiocitose Sinusal/complicações , Humanos , Quadriplegia/etiologia , Resultado do Tratamento , Transtornos da Visão/etiologiaRESUMO
BACKGROUND: Cerebral vasospasm can complicate aneurysmal subarachnoid hemorrhage (aSAH), contributing to cerebral ischemia. We explored the role of remote ischemic preconditioning (RIPC) in reducing cerebral vasospasm and ischemia and improving outcomes after aSAH. MATERIALS AND METHODS: Patients with ruptured cerebral aneurysm undergoing surgical clipping and meeting the trial criteria were randomized to true RIPC (n = 13) (inflating upper extremity blood pressure cuff thrice to 30 mmHg above systolic pressure for 5 min) or sham RIPC (n = 12) (inflating blood pressure cuff thrice to 30 mmHg for 5 min) after ethical approval. A blinded observer assessed outcome measures-cerebral vasospasm and biomarkers of cerebral ischemia. We also evaluated the feasibility and safety of RIPC in aSAH and Glasgow Outcome Scale-Extended (GOSE). RESULTS: Angiographic vasospasm was seen in 9/13 (69%) patients; 1/4 patients (25%) in true RIPC group, and 8/9 patients (89%) in sham RIPC group (P = 0.05). Vasospasm on transcranial Doppler study was diagnosed in 5/25 (20%) patients and 1/13 patients (7.7%) in true RIPC and 4/12 patients (33.3%) in sham RIPC group, (P = 0.16). There was no difference in S100B and neuron-specific enolase (NSE) levels over various time-points within groups (P = 0.32 and 0.49 for S100B, P = 0.66 and 0.17 for NSE in true and sham groups, respectively) and between groups (P = 0.56 for S100B and P = 0.31 for NSE). Higher GOSE scores were observed with true RIPC (P = 0.009) unlike sham RIPC (P = 0.847) over 6-month follow-up with significant between group difference (P = 0.003). No side effects were seen with RIPC. CONCLUSIONS: RIPC is feasible and safe in patients with aSAH and results in a lower incidence of vasospasm and better functional outcome.
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Academias e Institutos/história , Neurociências/história , Neurocirurgia/história , Psiquiatria/história , História do Século XX , História do Século XXI , Índia , Neurociências/educação , Neurociências/organização & administração , Psiquiatria/educação , Psiquiatria/organização & administraçãoRESUMO
INTRODUCTION: Diagnosis of the rupture of an intracranial aneurysm (IA) relies on sophisticated neuro-imaging studies, and molecular biomarkers to identify an IA or predict its rupture are still unavailable. OBJECTIVE: Our objective was to determine the plasma microRNA (miRNA) expression profile in patients with ruptured IA presenting as aneurysmal subarachnoid hemorrhage (aSAH) and identify potential biomarkers of aneurysmal rupture. METHODS: Plasma miRNA profiling was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) in 20 patients with aSAH and 20 age- and sex-matched healthy controls. Eight differentially expressed miRNAs were validated by qPCR in a larger cohort of 88 patients with aSAH and 110 healthy controls. A receiver operating characteristic (ROC) curve was constructed to evaluate the overall performance of the miRNA-based assay. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to determine the potential pathway of miRNA-target genes. RESULTS: The miRNA profiles were clearly distinct in patients compared with controls. Validation studies showed that three upregulated miRNAs (miR-15a-5p, miR-34a-5p, miR-374a-5p) and five downregulated miRNAs (miR-146a-5p, miR-376c-3p, miR-18b-5p, miR-24-3p, miR-27b-3p) could distinguish patients with aSAH from healthy controls with high predicted probability (0.865 and 0.995, respectively). Further, the expression levels of the eight candidate miRNAs were significantly dysregulated only in aSAH cases and not in patients with SAH due to other causes. Plasma miR-146a-5p and miR-27b-3p were associated with clinical outcomes in patients with aSAH. Functional analysis of the eight differentially expressed miRNA showed that the target genes involved in signaling pathways were related to inflammation. CONCLUSIONS: Our study determined the plasma miRNA signature of ruptured IAs and identified eight candidate miRNAs that could be useful biomarkers for this condition. We hypothesize that these differentially expressed miRNAs may play pivotal roles in IA pathology.
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Aneurisma Roto/etiologia , Biomarcadores , MicroRNA Circulante , Suscetibilidade a Doenças , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/patologia , MicroRNAs/genética , Adulto , Idoso , Aneurisma Roto/diagnóstico , Biologia Computacional/métodos , Gerenciamento Clínico , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Interferência de RNA , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/metabolismoRESUMO
BACKGROUND: The response of the brain to obstetric brachial plexus palsy (OBPP) is not clearly understood. We propose that even a peripheral insult at the developmental stage may result in changes in the volume of white matter of the brain, which we studied using corpus callosum volumetry and resting-state functional magnetic resonance imaging (rsfMRI) of sensorimotor network. OBJECTIVE: To study the central neural effects in OBPP. METHODS: We performed an MRI study on a cohort of 14 children who had OBPP and 14 healthy controls. The mean age of the test subjects was 10.07 ± 1.22 yr (95% confidence interval). Corpus callosum volumetry was compared with that of age-matched healthy subjects. Hofer and Frahm segmentation was used. Resting-state fMRI data were analyzed using the FSL software (FMRIB Software Library v5.0, Oxford, United Kingdom), and group analysis of the sensorimotor network was performed. RESULTS: Statistical analysis of corpus callosum volume revealed significant differences between the OBPP cohort and healthy controls, especially in the motor association areas. Independent t-test revealed statistically significant volume loss in segments I (prefrontal), II (premotor), and IV (primary sensory area). rsfMRI of sensorimotor network showed decreased activation in the test hemisphere (the side contralateral to the injured brachial plexus) and also decreased activation in the ipsilateral hemisphere, when compared with healthy controls. CONCLUSION: OBPP occurs in an immature brain and causes central cortical changes. There is secondary corpus callosum atrophy which may be due to retrograde transneuronal degeneration. This in turn may result in disruption of interhemispheric coactivation and consequent reduction in activation of sensorimotor network even in the ipsilateral hemisphere.