Martín Sánchez-Aguilar

Effect of Rosuvastatin on Amnesia and Disorientation after Traumatic Brain Injury (NCT00329758)

Amnesia is a common sequela following traumatic brain injury (TBI), for which there is no current treatment. Pleiotropic effects of statins have demonstrated faster recovery of spatial memory after TBI in animals. We conducted a double-blind randomized clinical trial add-on of patients with TBI (16-50 years of age), with Glasgow Coma Scale (GCS) scores of 9-13, and intracranial lesions as demonstrated by computed tomography (CT) scan. We excluded those patients with recent head injury or severe disability; administration of known drugs as modifiers of statin metabolism; multisystemic trauma; prior use of mannitol, barbiturate, corticosteroids, indomethacin or calcium antagonists; surgical or isolated lesion in brainstem; allergy to statins; previous hepatopathy or myopathy; previous management in another clinic; or pregnancy. Each patient received the same treatment and was randomly allocated to receive either rosuvastatin (RVS) or placebo over a period of 10 days. The primary outcome measures assessed were amnesia and disorientation times using Galveston Orientation Amnesia Test. Additionally, we evaluated plasma levels of interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, and IL-6, as well as disability at 3 months. We analyzed eight patients with RVS and 13 controls with similar basal characteristics. Using Cox regression analysis, administration of RVS showed a reduction of amnesia time with a hazard ratio of 53.76 (95% confidence interval [CI], 1.58-1824.64). This was adjusted for early intubation, basal leukocytes, basal Marshall and Fisher score, change of IL-1beta levels, and lesion side. IL-6 values at day 3 were increased in the RVS group (p = 0.04). No difference was detected in disability at 3 months. While statins may reduce amnesia time after TBI, possibly by immunomodulation, further trials are needed in order to confirm this positive association.

Use of Statins for the Treatment of Spontaneous Intracerebral Hemorrhage: Results of a Pilot Study

BACKGROUND AND STUDY AIMS Spontaneous intracerebral hemorrhage (ICH) represents the most fatal kind of stroke, and there is still no treatment available that improves the outcome. Statins are cholesterol reducers, and during the last few years many additional effects have been demonstrated that might be neuroprotective. We designed a pilot clinical study in order to evaluate whether the administration of statins is associated with a better outcome. PATIENTS AND METHODS From August to December 2006 we carried out a prospective/retrospective non-randomized clinical study. The prospective group was treated with rosuvastatin (20 mg) and the retrospective control group was taken from our clinical records with a relation of 1:3. We included patients of both sexes, aged > or =15 years with proven ICH in CT-scan. Exclusion criteria were a history of neoplasm, head injury four weeks before admission, non-hypertensive reasons, brainstem hemorrhage, steroid administration, cranial surgery, initial hydrocephalus, and NIHSS > or =30. RESULTS We analyzed 18 patients treated with rosuvastatin and 57 controls with similar basic characteristics. The mortality rate during hospitalization was 1 (5.6%) patient in the statin group and 9 (15.8%) in the control group; the hazard ratio adjusted by the initial Glasgow Coma Scale (GCS), intubation, admission in intensive care unit, disruption into the subarachnoid space was 0.20 (95% CI 0.02-1.67). The odds ratio for NIHSS > or =15 at release was 0.04 (95% CI 0.003-0.93). CONCLUSIONS The use of statins during the acute phase of ICH could be associated with a better outcome. Further clinical trials are necessary to confirm a possible therapeutic effect and evaluate the toxicity of statins.

Endoscopic management of hydrocephalus due to neurocysticercosis

OBJECTIVE Hydrocephalus due to neurocysticercosis usually shows poor prognosis and shunt failure is a common complication. Neuroendoscopy has been suggested as treatment, but the indications remain unclear. METHODS A cohort of patients with clinical/radiological diagnosis of hydrocephalus due to NCC, treated between January 2002 and September 2006, were the subjects of the study. We excluded patients with tumors or those in whom diagnosis was not confirmed (histology/positive ELISA in CSF). Neuroendoscopy was offered as the first line of treatment. Shunt failure rate and Karnofsky index at 12 months were assessed. RESULTS Eighty-six patients (47 male) with a median age of 38 (9-79) were included in the study. Of them, 36.1% had a shunt before endoscopy and 97.7% had a Karnofsky index <80. We did not find the parasite in 18.6%, extraction was achieved in 79%, and in 87.2% an endoscopic third ventriculostomy (ETV) was performed. The median follow-up time was 43 months (1-72). Shunt failure was seen in 6.6% of patients with ETV in comparison to 27.2% in those without ETV. A hazard ratio of 0.22 (95% CI, 0.05-0.93) for shunt failure after ETV was calculated. At 12 months, 20.9% had a Karnofsky index <80. CONCLUSION Early extraction of parasite plus ETV might allow improving outcome and reducing shunt failure. Limitation of inflammatory stimulation by parasite antigens and improvement of CSF dynamics could be an explanation for these findings.

The role of statins in neurosurgery

Statins are drugs used to control cholesterol disorders and prevent cardiovascular diseases. Their denominated pleiotropic effects have demonstrated a broad action spectrum that might profit some neurological and neurosurgical diseases. These effects are correlated to dose and kind of statin. We accomplished a systematic review in PubMed and MEDLINE about studies of statins and main neurosurgical diseases. If statins are administered after subarachnoid hemorrhage, a significant lower incidence of vasospasm as well as delayed ischemic deficits and decreased mortality could be found; the results of a large multicenter trial are expected. In other complex diseases as intracerebral hemorrhage or traumatic brain injury, the evidence for positive effects of a treatment with statin increased. Additionally, promising experimental results indicate that high statin doses are able to promote cell death in tumor cells, especially in gliomas. Moreover, experimental and observational studies suggest the ability of statins to modulate the immune system, by that they can reduce incidence and severity of sepsis. The origin of these multiple effects from neuroprotection to tumoral apoptosis is not totally explained so far. Recent data in literature are discussed in this review. More trials in humans are urgently required to finally determine if statins could contribute to the current management of neurosurgical diseases.

Comparison of cerebrospinal fluid obtained by ventricular endoscopy and by lumbar puncture in patients with hydrocephalus secondary to neurocysticercosis

BACKGROUND Compare the differences between proteins, glucose, and morphological cellular counts from ventricular cerebrospinal fluid obtained by neuroendoscopy and lumbar puncture. METHODS This was a retrospective, transversal study. From January 2003 until June 2006, 30 neuroendoscopies were performed on patients with hydrocephalus secondary to NCC. Samples of CSF were extracted by lumbar puncture and ventricular neuroendoscopy, and their levels of glucose, proteins, number of leukocytes, and morphological differences (PMN including eosinophiles, monocytes, and lymphocytes) were subsequently measured and studied. Traumatic CSF results were excluded. Twenty-five patients with histopathologic confirmation of the NCC diagnosis were analyzed. The average age of the patients was 42 years (SD, 19.8 years) and female-male ratio was 10:15. RESULTS The differences in glucose values, between lumbar and ventricular CSF, were not statistically significant-lumbar, 45.28 mg/dL and ventricular, 53.92 mg/dL (P = .129). The differences in the protein values and leukocyte counts were statistically significant (P < .05) with the highest values found in lumbar CSF. The presence of monocytes was higher than that of PMNs in both fluids (P < .05). We did not find eosinophiles in any CSF. CONCLUSIONS We did not find differences in the glucose values as described by previous studies, but our findings showed differences in the values of proteins, PMN leukocytes, and monocytes. The presence of more monocytes could be explained by their incremented activation by the parasite antigen and chronicity of the disease. Translational trials with uniform criteria are needed to determinate the immune process in the several presentations of the disease in humans.

Transventricular Neuroendoscopic Exploration and Biopsy of the Basal Cisterns in Patients with Basal Meningitis and Hydrocephalus

BACKGROUND Management of communicating hydrocephalus associated with infectious meningitis and arachnoiditis of the basal cisterns can be challenging if no microorganism or pathological diagnosis is established. The purpose of our series is to elucidate the efficacy of endoscopic basal cistern exploration, biopsy, and endoscopic third ventriculostomy (ETV) in patients with basal cistern meningitis and hydrocephalus. METHODS Between 2005 and 2010, all patients who underwent transventricular endoscopic exploration biopsy and biopsy of the basal cisterns were analyzed and prospectively followed up. Particular attention was given to neuroendoscopic findings, sensitivity of biopsy, and the role of ETV. RESULTS Twenty-four patients, ranging in age from 2 to 63 years, underwent transventricular endoscopic biopsy and exploration of the basal cisterns. All patients had negative cerebrospinal fluid analysis obtained by lumbar puncture. Successful ETV, exploration, dissection, and biopsy of the basal cisterns were performed successfully in all patients with a flexible neuroendoscope. Neuroendoscopic findings included: unusually thick Liliequist membrane, moderate to severe adhesive arachnoiditis, inflammatory and cotton-like exudates, granulations, and narrow subarachnoid space. Definitive histopathological diagnosis from the basal cisterns specimen was obtained in 79% of patients. There were no complications related to the procedure. At 15 months of follow-up, 70% of the patients with hydrocephalus did not require a ventriculoperitoneal shunt. CONCLUSIONS Endoscopic transventricular basal cisterns exploration is feasible with a flexible neuroendoscope. It is a viable alternative in the management of patients with basal cistern meningitis and arachnoiditis without histopathological diagnosis. It yields to an accurate diagnosis in 79% of the patients. ETV is a good alternative in the management of intracisternal extraventricular obstructive hydrocephalus.

Análisis de factores asociados al fracaso del tratamiento médico del absceso hepático amebiano

INTRODUCTION To identify the laboratory and ultrasound factors that could predict the response to medical treatment of amoebic liver abscess. MATERIAL AND METHOD Retrospective study of patients diagnosis with amoebic liver abscess in Hospital Central in San Luis Potosí, Mexico. We included patients greater than 15 years of both sexes. We excluded those with probable pyogenic abscess, immunosupression, history of abdominal or biliary surgery, abdominal neoplasm abdominal or sepsis. We identified patients with good response to medical treatment and patients who needed the abscess drained. We studied the ultrasound findings, plasma levels of albumin, alkaline phosphatase and bilirubin. RESULTS We analysed 45 patients, 31 had a good response (controls) and 14 needed drainage (cases). The medians of the variables with statistical significance in bivariate analysis were: albumin 2.65 g/dl and 1.7 g/dl (p < 0.001); alkaline phosphatase 133 U and 259 U (p = 0.02) and diameter of absences 5.9 cm and 9.95 cm (p < 0.001), controls and cases respectively. By logistic regression the diameter of the abscess showed a determination coefficient of 0.447 (p < 0.05) and OR = 14.85 (95% CI, 2.11-104.9) for drain if it was > or = 8 cm. CONCLUSIONS A diameter bigger than 8 cm in hepatic amoebic abscess is associated with failure of medical treatment. Low albumin could be related to malnutrition and increased alkaline phosphatase with extrinsic compression of extrahepatic conducts due to big abscesses.Resumen Introduccion Identificar los factores de laboratorio y ultrasonograficos que pudieran predecir la respuesta al tratamiento medico del absceso hepatico amebiano. Material y metodo Se realizo un estudio retrospectivo de pacientes con diagnostico de absceso hepatico amebiano en el Hospital Central de San Luis Potosi, Mexico. Se incluyo a los pacientes mayores de 15 anos de ambos sexos. Se excluyo a los sujetos con sospecha clinica de absceso piogeno, inmunosupresion o con antecedentes de cirugia abdominal o biliar o neoplasia abdominal. Se identifico a los pacientes que respondieron favorablemente al tratamiento medico y aquellos que requirieron de intervencion para el drenaje del absceso. Se estudiaron los hallazgos ultrasonograficos, concentraciones sericas de albumina, fosfatasa alcalina y bilirrubinas. Resultados Se analizo a 45 pacientes, 31 respondieron al tratamiento (controles) y 14 requirieron intervencion (casos). Las medianas de las variables con significacion estadistica en el analisis bivariable fueron: concentraciones de albumina de 2,65 y 1,7 g/dl (p Conclusiones Un diametro > 8 cm del absceso hepatico amebiano se relaciono con fracaso del tratamiento medico. La asociacion con hipoalbuminemia probablemente se relaciona con desnutricion, mientras que valores elevados de fosfatasa alcalina pueden deberse a compresion extrinseca de los conductos extrahepaticos por abscesos de gran tamano.

Prognostic indications of the failure to treat amoebic liver abscesses

Abstract Objectives: To identify the variables that predict the failure to treat amoebic liver abscesses. Methods: We prospectively carried out a case–control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure. Results: Of 40 patients with amoebic liver abscess, 24 (mean age: 36·7±11·2 years) responded to medical treatment and 16 (41·8±11·6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P<0·05) on the bivariate analysis. The highest (>99%) sensitivity and negative predictive value were observed for an abscess volume >500 ml and diameter >10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter. Conclusions: The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy.

Hypocalcaemia as a prognostic factor of early mortality in moderate and severe traumatic brain injury

Abstract Objectives: Our main objective was to evaluate whether serum hypocalcaemia on the third day [defined as < 2·1 mmol/l (8·5 mg/dl)] is a prognostic factor for early mortality after moderate and severe traumatic brain injury (TBI). Methods: We developed an ambispective comparative case control study. We evaluated clinical profiles from included patients from January 2005 to July 2009 and we prospectively recruited additional patients from August 2009 to July 2011. Patients were between 1 and 89 years old and had a Glasgow Coma Scale of 3–12 points following TBI. Results: We calculated an Odds Ratio of 5·2 (Confidence Intervals 95%: 4·48 to 6·032) for hypocalcaemia on day three, which was associated with death. Retrospectively (January 2005 to July 2009) we compiled data from 81 patients. Prospectively (August 2009 to July 2011) we recruited 41 patients. The adjusted variables in the logistic regression final model were: serum calcium on day three (Odds Ratio 3·5, Confidence Intervals 95%: 1·12 to 13·61, P < 0·028) and anisocoria (Odds Ratio 8·24, Confidence Intervals 95%: 1·3 to 67·35, P < 0·019) obtaining an adjusted R2 of 0·22 (P < 0·005). Discussion: The serum levels of calcium on day three could be useful for the prediction of mortality in patients with moderate and severe TBI.

Amoebic toxic colitis: analysis of factors related to mortality

Abstract Background: Toxic or fulminant colitis due to Entamoeba histolytica infrequently presents but is very serious. Unfortunately, there are numerous contradictory factors related to mortality. Methods: We analyzed several cases of E. histolytica infection to determine the factors related to mortality. We included patients >15 years of age who were histopathologically diagnosed with amoebic toxic colitis and treated from January 2000 through December 2006. We evaluated demographic, clinical, laboratorial, surgical, and histopathological characteristics. Results: We examined 24 patients and recorded 12 deaths (50%). Twenty patients underwent surgery within a mean time of 24 hours (range: 8–120 hours). Tenesmus and intestinal perforation were determined to be statistically significant (P<0·05) by univariate analysis. Three models of logistic regression were able to determine three statistically significant factors that affected mortality: (1) tenesmus and a lymphocyte count <1·5×103 cell/μl; 2) depth of invasion beyond the mucosa and a lymphocyte count <1·5×103 cell/μl; 3) time spent with symptoms and perforation. Conclusions: The mortality rate determined in this study is similar to previously reported series. A low lymphocyte count, significant depth of invasion, and intestinal perforation were determined to be the factors related to increased mortality, while tenesmus and limited amount of time spent with symptoms were associated with survival. Quick diagnosis and appropriate treatment are important factors that reduce mortality.