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The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and type of postoperative infections, the causative microorganisms and in-hospital mortality rates in a 4-year period, from the pre-pandemic year 2019 until 2022. A total of 4150 neurosurgical procedures were registered. In 2020 the total number of surgeries was reduced by 36% compared to 2019 OR = 0.689 (95% CI 0.566–0.834) p ≤ 0.001, transnasal/trans sphenoidal pituitary resections decreased by 53%, and spinal surgeries by 52%. The rate of neurosurgical infections increased from 3.5% in 2019 to 5.6% in 2020 (p = 0.002). Regarding the microorganisms that caused infections, gram positive cocci accounted for 43.5% of isolates, Klebsiella spp. and Pseudomonas spp. caused one third of the infections. No significant differences were found for in-hospital mortality nor patterns of resistance to antibiotics. The number of surgeries increased in the last two years, although the infection rate has returned to pre-pandemic levels. We observed a lower impact from subsequent waves of COVID-19 and despite an increase in the number of surgeries, the surgeries have not amounted to the full pre-pandemic levels.

Cryptococcal meningitis, one of the most severe infections affecting the central nervous system, often involves severe neurological sequels and high mortality.A retrospective review was performed, including 76 cases admitted in a 10-year period at a neurological referral center in Mexico City. From 68 isolates, 52 fungal specimens were identified as part of the Cryptococcus neoformans var. neoformans complex, 15 as C. neoformans var gattii complex, and one as Cryptococcus non-neoformans/gattii.Higher cryptococcal meningitis incidence and severity were found in HIV-infected men; other risk factors frequently observed were diabetes mellitus and labor exposure to poultry. The main clinical manifestations were subacute headache, cognitive alterations, and photophobia (exclusively in HIV patients). MRI was highly sensitive for pathologic findings such as meningeal enhancements and cryptococcomas, most of them associated to C. neoformans complex. Eleven patients developed severe brain vasculitis, as observed by transcranial Doppler. Hydrocephalus with intracranial hypertension was the most frequent complication.One-half of the population died, and the rest had neurological sequels, mainly neuropsychiatric manifestations and secondary headaches. These patients developed severe functional limitations in performing daily activities in an independent manner.

Introduction: Although citrulline is produced by nitric oxide (NO) synthase upon activation of the NMDA glutamate receptor, nitrite and nitrate (NOx) concentration is considered the best marker of NO synthesis, as citrulline is also metabolised by other enzymes. This study analyses the correlation between human cerebrospinal fluid NOx and citrulline concentrations in order to determine the extent to which citrulline reflects NO synthesis and glutamatergic neurotransmission. Methods: Participants were patients with acute neurological diseases undergoing lumbar puncture (n = 240). NOx and amino acid concentrations were determined by HPLC. Results: NOx concentrations did not vary significantly where infection (P = .110) or inflammation (P = .349) were present. Multiple regression analysis showed that NOx concentration was correlated with glutamine (r = −0.319, P

Resumen: Introducción: Aunque la citrulina es producida por la sintasa del óxido nítrico (NO) al activarse el receptor glutamatérgico NMDA, nitritos y nitratos (NOx) son considerados los mejores marcadores de síntesis del NO pues citrulina es también metabolizada por otras enzimas. En este estudio se realizó un análisis de correlaciones de concentraciones de citrulina y NOx en líquido cefalorraquídeo humano para evaluar la proporción en que la citrulina refleja la síntesis del NO y la neurotransmisión glutamatérgica. Métodos: Se incluyeron pacientes con trastornos neurológicos agudos a los que se realizó punción lumbar (n = 240). Se determinó la concentración de NOx y aminoácidos por HPLC. Resultados: NOx no fue diferente por la presencia de infección (p = 0,110) o inflamación (p = 0,349). La regresión múltiple mostró que NOx correlacionó con glutamina (r = -0,319, p

Antecedentes: Clostridioides difficile es un patógeno reemergente que causa diarrea nosocomial a nivel mundial, particularmente en países industrializados. Objetivo: Presentar una serie de casos clínicos de infección por Clostridioides difficile en un centro de referencia neurológico. Método: estudio retrospectivo y observacional de casos de infección por C. difficile (ICD) en el Instituto Nacional de Neurología de enero de 2016 a diciembre de 2018. Resultados: se incluyeron 16 pacientes con CDI durante el periodo de estudio. Todos ellos tuvieron el antecedente de terapia antimicrobiana de amplio espectro en las 6 semanas previas al inicio de los síntomas. Más de la mitad de la población afectada correspondió a mujeres. El principal diagnóstico de admisión fue enfermedad cerebrovascular, seguido de enfermedades infecciosas. Otros factores de riesgo (adicionales al uso de antimicrobianos) fueron inhibidores de bomba de protones, corticosteroides y obesidad. Conclusiones: los pacientes con afección neurológica son proclives al desarrollo de diarrea nosocomial debido a un conjunto de factores de riesgo, incluyendo uso concomitante de corticosteroides, inhibidores de bomba de protones, obesidad/diabetes (previos al uso de antibióticos de amplio espectro). Se requieren programas de gerencia de antibióticos para asegurar un uso racional de éstos y con ello disminuir el riesgo de diarrea nosocomial en esta población.

Clostridioides difficile has become the major cause of health care–associated diarrhea and a recognized causal agent of pseudomembranous colitis...

Antecedentes: Las infecciones postoperatorias e intrahospitalarias, generan una mayor morbi-mortalidad e incrementan los costos de la atención. El abuso de antibióticos y la creciente prevalencia de infecciones posoperatorias por bacterias gram negativas, han llevado al empleo de regímenes alternativos de profilaxis antimicrobiana. Objetivos: Describir el comportamiento de las infecciones nosocomiales y comparar dos esquemas de profilaxis antimicrobiana pre-quirúrgica. Material y métodos: Estudio retrospectivo, en que se describen las tasas de infecciones nosocomiales, y su relación con dos esquemas de profilaxis prequirúrgica (EPP) de marzo a junio; EPP 1 (año 2017) y EPP2 (año 2018), así como con medidas adicionales a los EPP como uso de cloraprep /Lysol (2017) y lavado de manos (2018) durante esos periodos, a fin de evaluar la eficacia de los mismos. Resultados: El número de episodios de infecciones por cada 100 egresos, fue de 10.67 (2017) y de 11.42 (2018) sin diferencias estadísticas. La tasa de infección de catéter venoso central fue 17.4 vs 9.1 (p= 0.001), urosepsis de 10.75 vs 9.27 (p=0.03,) y bacteriemia de 2.59 a 1.88 (p=0.04,). Durante el esquema EPP1 hubo 125 episodios de infección, mientras EPP2, sólo 119, así como disminución en urosepsis, bacteriemia e infección del sitio de gastrostomía. Conclusiones: No hubo incremento significativo de infecciones en neuroquirúrgicos con ambos esquemas, ni en infecciones nosocomiales. Es importante mencionar que, el uso de cloraprep para la asepsia prequirúrgica y Lysol para descontaminación de superficies inertes, así como el mejoramiento en las técnicas de lavado de manos han sido determinantes para el control de infecciones nosocomiales.

The mechanisms underlying the immunopathology of tuberculous meningitis (TBM), the most severe clinical form of extrapulmonary tuberculosis (TB), are not understood. It is currently believed that the spread of Mycobacterium tuberculosis (Mtb) from the lung is an early event that occurs before the establishment of adaptive immunity. Hence, several innate immune mechanisms may participate in the containment of Mtb infection and prevent extrapulmonary disease manifestations. Natural killer (NK) cells participate in defensive processes that distinguish latent TB infection (LTBI) from active pulmonary TB (PTB). However, their role in TBM is unknown. Here, we performed a cross-sectional analysis of circulating NK cellCID="C008" value="s" phenotype in a prospective cohort of TBM patients ( n = 10 ) using flow cytometry. Also, we addressed the responses of memory-like NK cell subpopulations to the contact with Mtb antigens in vitro. Finally, we determined plasma levels of soluble NKG2D receptor ligands in our cohort of TBM patients by enzyme-linked immunosorbent assay (ELISA). Our comparative groups consisted of individuals with LTBI ( n = 11 ) and PTB ( n = 27 ) patients. We found that NK cells from TBM patients showed lower absolute frequencies, higher CD69 expression, and poor expansion of the CD45RO+ memory-like subpopulation upon Mtb exposure in vitro compared to LTBI individuals. In addition, a reduction in the frequency of CD56brightCD16- NK cells characterized TBM patients but not LTBI or PTB subjects. Our study expands on earlier reports about the role of NK cells in TBM showing a reduced frequency of cytokine-producing cells compared to LTBI and PTB.

We present the case of a patient with Guillain-Barre syndrome associated with Zika virus infection. The patient has been studied since July 2019 in Jalisco, western Mexico, where this year an increase in the number of dengue virus and Zika virus infections was reported. One week after multiple mosquito bites, our 32-year-old male patient had a 5 day nonspecific picture of fever, myalgias, headache, nausea, and vomiting without a rash or conjunctivitis. A week later he presented neurological manifestations that consisted of distal dysesthesia, proximal muscle weakness, and ascending areflexic paralysis of rapid progression; multiple cranial nerves were involved. He was hospitalized and treated with intravenous immunoglobulin. He required admission to the intensive care unit after respiratory failure. He was intubated, placed on mechanical ventilation, and underwent a tracheostomy. He evolved favorably, and 50 days after hospital admission, he walked without support, reaching level 2 on the Hughes disability scale.

IntroductionTuberculosis (TB) remains as an important concern of public health worldwide because the high prevalence and severe sequelae. Tuberculous meningitis (TBM) is the most lethal and disabling form.AimTo describe the clinical, laboratory, and neuroimaging characteristics of TBM on admission at neurological center in Mexico City.MethodsRetrospective cohort study at the third level neurological center from 2010 to 2016. Clinical follow-up was evaluated at hospital discharge, three months, and one-year either due to lack of follow-up or mortality, during the follow-up the adverse events were registered.ResultsOne-hundred and six patients were included, 74 (69.8%) males and 32 (30.2%) females. From these 31 (29.2%) were HIV-positive. The median age was 35.5 (IQR:28-51). Pulmonary TB was found in 25% of the population. Alcoholism was observed in a half of the patients while diabetes in 15%, the latter being significant (p=0.04). Abnormalities in neuroimaging were significant among our population (p=0.003). Only one-third of the population had a positive Lowenstein-Jensen culture. There were no differences in clinical outcomes between HIV positive and non-HIV patients.ConclusionOur study shows data to those described in the literature. The initiation of empirical treatment in all patients with a high clinical suspicion of tuberculosis mandatory to try to avoid severe neurological sequels.

In recent years, the increase in antimicrobial resistance (AMR) has been recognized as a real threat to human and animal health. It is a problem that has been given the highest priority, uniting nations in the fight against its causes and effects. Among the actions that have been implemented are: clinical and microbiological surveillance, promotion of rational and controlled use of antibiotics, AMR stewardship programs in hospitals, development of tools for rapid diagnosis of infectious diseases to establish prompt and adequate treatment, and radically improving vaccination strategies. The current COVID-19 pandemic has placed disproportionate demands on the healthcare infrastructure and economy worldwide, which will negatively impact on the availability of materials as well as the technical capacity for diagnosis, patient care, and treatment of both COVID-19 and non-COVID-19 patients. Disruptions to production and distribution chains will hamper the availability and usage of antibiotics, also interrupting several of the activities that have been implemented thus far to combat AMR, including detailed laboratory monitoring and reinforced vaccination programs. Here, we discuss the main aspects that should be considered with regard to AMR, that may be affected by the pandemic and propose some actions to counter them., Highlights • COVID-19 pandemic has placed disproportionate demands on the healthcare infrastructure worldwide. • Activities implemented so far to combat antimicrobial resistance are threatened. • Inappropriate and excessive use of antibiotics for the treatment of COVID-19 patients is noted. • Disruption of vaccination, diagnosis and treatment programs will trigger antimicrobial resistance.

Background Coccidioidal meningitis is a life-threatening condition and a diagnostic challenge in cases of chronic meningitis. It is associated to severe complications, like basal arachnoiditis, hydrocephalus, and secondary vasculitis. Objective To present a 20-year retrospective clinical series of coccidioidal meningitis cases at a Mexican neurological referral center. Results The clinical records of 11 patients, predominantly males, were retrieved. Weight loss and night sweats were observed in 64 % of cases. Neurological signs included intracranial hypertension in 91 % of cases, altered alertness and meningeal syndrome in 72 %, and neuropsychiatric symptoms in 64 %. Mean CSF glucose levels were 30 ± 25 mg/dL, and pleocytosis ranged from 0 to 2218 cells/mm3. The diagnosis was confirmed by coccidioidal antigen latex agglutination in 91 % of cases. Radiological findings were hepatomegaly in 55 % of cases and pneumonia in 45 %. Neuroimaging findings included leptomeningitis in 73 % of cases, pachymeningitis in 45 %, and vascular involvement in 91 %. Less common findings included spinal cord lesion and mycotic aneurism, found in 18 % of cases. A molecular coccidioidal DNA test confirmed the predominance of Coccidioides immitis, detected in 64 % of cases. With respect to the clinical outcome, 46 % of patients died. The survivors suffered from sequels like chronic headache, cognitive alterations, and depression. Conclusions Coccidioidal meningitis is an entity with high mortality rates. More than one half of patients suffered disseminated disease. Although meningeal signs are not frequent in chronic meningitis, more than two-thirds of our patients showed mild nuchal rigidity. In addition, cerebral and cerebellar volume loss, associated with cognitive impairment and depression, was often observed in surviving patients during the clinical-radiological follow-up.

Background In previous studies of pneumococcal meningitis in adults within general hospitals or national cohorts, the most common predisposing conditions were otitis media, sinusitis, pneumonia, immunosuppression, alcoholism, and diabetes. The epidemiology of pneumococcal meningitis is changing because of the use of vaccines in childhood, and antibiotic resistance has increased. Methods We retrospectively reviewed the cases of patients with diagnoses of pneumococcal meningitis proved by an inflammatory cerebrospinal fluid (CSF) with a positive culture, treated during a period of 14 years at an adult neurosurgical neurologic referral center. Our aim was to define their clinical course, predisposing conditions, antimicrobial susceptibilities, and outcome. Results We reviewed the cases of 30 patients, 17 men and 13 women, with a mean age of 36.7 years. Fourteen patients (46.6%) had previous neurosurgery, 12 patients (40%) had CSF fistula, 8 had remote head trauma, and 8 also presented recurrent meningitis. Resistance to ceftriaxone or vancomycin was less than 5%, and penicillin resistance was 53%. Eight patients (26.7%) had died. An increased risk of death was associated with coma at admission, septic shock, upper gastrointestinal bleeding, mechanical ventilation, thrombocytopenia, and a low CSF opening pressure. Conclusions We conclude that patients with pneumococcal meningitis treated at neurosurgical neurologic centers have different predisposing conditions with severe disease and high mortality, thus prompting us to recommend aggressive pneumococcal vaccination in patients with CSF leaks and severe head trauma. Prospective studies to identify which neurosurgical patients may benefit in the long term from a pneumococcal vaccine are urgently needed.

Background Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. Aim To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. Methods A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. Results 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. Conclusions In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.

OBJECTIVEThe coronavirus disease 2019 (COVID-19) pandemic has forced the modification of surgical practice worldwide. Medical centers have been adapted to provide an efficient arrangement of their economic and human resources. Although neurosurgeons are not in the first line of management and treatment of COVID-19 patients, they take care of patients with neurological pathology and potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, the authors describe their institutional actions against the pandemic and compare these actions with those in peer-reviewed publications.METHODSThe authors conducted a search using the MEDLINE, PubMed, and Google Scholar databases from the beginning of the pandemic until July 11, 2020, using the following terms: “Neurosurgery,” “COVID-19/SARS-CoV-2,” “reconversion/modification,” “practice,” “academy,” and “teaching.” Then, they created operational guidelines tailored for their institution to maximize resource efficiency and minimize risk for the healthcare personnel.RESULTSAccording to the reviewed literature, the authors defined the following three changes that have had the greatest impact in neurosurgical practice during the COVID-19 pandemic: 1) changes in clinical practices; 2) changes in the medical care setting, including modifications of perioperative care; and 3) changes in the academic teaching methodology.CONCLUSIONSThe Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez” is one of the major referral centers for treating highly complex neurosurgical pathologies in Mexico. Its clinical and neurosurgical practices have been modified with the implementation of specific interventions against the spread of COVID-19. These practical and simple actions are remarkably relevant in the context of the pandemic and can be adopted and suited by other healthcare centers according to their available resources to better prepare for the next event.

A 38-year-old male presented to the hospital with headache, fever, and meningeal signs. He had undergone a surgical review of a ventriculoperitoneal shunt system one month earlier. A head computed tomography scan showed hydrocephalus. His medical history included a human immunodeficiency virus infection identified four years before and resolved cryptococcal meningitis, which had necessitated the implantation of the shunt system. Ventricular cerebrospinal fluid (CSF) was obtained, which showed inflammation and, in culture, grew a Gram-negative bacillus identified as multidrug-resistant Klebsiella oxytoca. The shunt was removed and a ventricular drain was installed. Treatment with meropenem and amikacin was established without a response; the CSF white blood cell count continued to increase, with cultures remaining positive. The patient's clinical condition deteriorated to stupor. With informed consent, intraventricular (ITV) treatment with tigecycline was initiated at a dose of 5 mg every 24 h and, three days later, the CSF cultures were negativized. Tigecycline levels in the CSF were quantified by liquid chromatography with ultraviolet detection and showed peak concentrations achieved at two hours after the dose of between 178 and 310 μg/mL. After 11 days of treatment with ITV tigecycline and eight negative CSF cultures, a new CSF shunt was installed. During follow-up review 10 months later, the patient reported he was working. The dose of tigecycline used in this study produced levels 15 to 20 times the minimum inhibitory concentration of the bacteria for up to six hours with adequate tolerance.

Made available in DSpace on 2018-11-27T11:27:10Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-04-01 To present a retrospective study from patients with spinal cysticercosis (SC), diagnosed within the last 30 years in Mexican and Indian neurological referral centers. This is a retrospective and comparative study of the clinical and radiological profile between Mexican and Indian patients with spinal neurocysticercosis during a 30-year period and a review of the literature during the same period. Twenty-seven SC patients were included: 19 from Mexico and 8 from India. SC presented predominantly with motor symptoms (21/27 patients): paraparesis and paraplegia were the most common signs; one-third of patients presented sphincter dysfunction. Imaging studies showed that parasites in vesicular stage were more frequent in patients from Mexico, while degenerative stages predominated in India. Association of subarachnoid cysticerci and hydrocephalus was observed only in Mexican patients. Despite the limitations of this study, the collected information supports the existence of differences in the clinical and radiological traits of SC patients between Asian and Latin-American hospitals. The possible biological factors that may underlie these differences are discussed. Inst Nacl Neurol & Neurocirug, Dept Neuroinfectol, Mexico City, DF, Mexico Hop La Pitie Salpetriere, Dept Neurol, Paris, France Univ Nacl Autonoma Mexico, Dept Immunol, Inst Invest Biomed, Mexico City 04510, DF, Mexico Univ Estadual Paulista, Arcatuba, Brazil Natl Inst Mental Hlth & Neurosci, Bangalore 560029, Karnataka, India Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Infect Dis, Insurgentes 3877, Mexico City 14269, DF, Mexico Univ Estadual Paulista, Arcatuba, Brazil

objective Some neurocysticercosis cysts may remain hidden despite novel MRI sequences. This study evaluates the diagnostic value of gadodiamide (GDD)-contrasted MRI cisternography in selected cases of neurocysticercosis. methods We included patients aged 18–65 years with a probable diagnosis of subarachnoid cysticercosis in whom previous neuroimaging studies failed to demonstrate the presence of cysts. One millilitre of GDD was administered intrathecally as a contrast agent with subsequent performance of MRI. results Fourteen patients were included. Optimal contrast diffusion was achieved in nine patients, and partial diffusion was achieved in 4. Intracranial vesicles were identified in 10 patients, with the presence of more than 60 basal subarachnoid vesicles being revealed in all, with five cysts in the fourth ventricle in four patients and a floating cyst in the lateral ventricle in one. In one case, intrathecal GDD demonstrated spinal cysticercosis. No adverse events were reported after intrathecal GDD administration. conclusions Intrathecal GDD administration is useful for the diagnosis of subarachnoid and intraventricular neurocysticercosis and can be used to improve diagnostic accuracy in selected cases.

Currently, AIDS is the worldwide leading cause of death among 15- to 59-year-old individuals. This trend has had particularly harsh social and economic consequences in sub-Saharan Africa, where more than half of global AIDS deaths take place. In the United States, an estimated 1.2 million people are infected with HIV. In 2012, a worldwide estimate of 1.7 million deaths due to AIDS-related causes was reported.About 10% to 12% of all AIDS patients will develop intracranial tumors. Differential diagnosis should rule out brain tumors such as central nervous system lymphoma and gliomas, as well as infectious processes such as toxoplasmosis, tuberculosis, and cryptococcosis.A 27-year-old homosexual man was referred to our care center after 2 months of disabling left frontal headache. Upon AIDS diagnosis, the patient was given abacavir (ABC), lamivudine (3TC), and efavirenz (EFV), but he discontinued the treatment after 9 months and failed to attend follow-up appointments. Three years later, the patient returned to the hospital and received ABC, 3TC, and lopinavir/ritonavir (LPV/r). On admission, computed tomographic scan reported multiple contrast-enhancing lesions compatible with meningiomas. The patient underwent uncomplicated surgical resection of the frontal basal lesion originating in the left olfactory bulb. No new neurological deficits were reported during the postoperative stay.According to a literature revision, it is likely that associated meningiomas are more aggressive in AIDS patients. Severe immunosuppression and the HIV-Tat protein may be involved in the pathogenesis of tumoral growth.

Objectives To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection. Design A search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.” Setting Only papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included. Sample We included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included. Main outcome measures Demographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection. Results The retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed. Conclusions Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.

Anton syndrome, or cortical blindness, consists of an objective blindness in the presence of an intact anterior visual pathway, with the patient expressing a denial of blindness; it is a peculiar form of visual anosognosia. Those patients with this syndrome often show an inappropriate affect and confabulate to conceal their visual loss. The common pathologic process in Anton syndrome is an ischemic event of the occipital circulation, and the most frequent causes are cerebral infarctions in aged patients with vascular risk factors, while hypertensive encephalopathy, eclampsia, hypoperfusion, trauma, tumors, and bacterial meningitis are common in children. Herein we report two patients with Anton-Babinski syndrome related to tuberculous meningitis, cared for at a single center. A search in the literature did not render any similar cases previously reported. The patients had no previous history of vascular risk factors, and the presentation of tuberculous meningitis was atypical: in the context of a rapidly evolving headache, one of the patients had visual changes and mental confusion; the other patient presented with stupor caused by acute hydrocephalus. Ischemic events were documented by imaging studies, and cerebrospinal fluid was inflammatory with positive polymerase chain reaction (PCR) for Mycobacteriumtuberculosis and high adenosine deaminase levels. Antituberculous drugs wereadministered and both patients stabilized; one patient showed no significant visual recovery, while the other was able to walk unassisted but had severe and incapacitating neuropsychiatric sequels at 3 years of follow-up.

Introduction The cerebrovascular complications in neurocysticercosis (NC) are uncommon. However, their pathophysiology remains unknown, but may be likely related to chronic inflammatory processes in the subarachnoid space (basal meningitis). Alterations of inflammatory cytokines in cerebrospinal fluid and sera correlate with vasospasm in SAH; these inflammatory mediators in NC may induce aneurysm formation. Case reports A 7-year retrospective study in a neurological referral center (Instituto Nacional de Neurologia y Neurocirugia), showed 3 cases of subarachnoid hemorrhage (SAH) among the 267 NC patients admitted during the study period. The clinical status, cerebrospinal fluid parameters, and clinical outcome were retrieved to compare them with previous NC-related SAH reported patients. Six of 15 patients showed aneurysm. These aneurysms were found within foci of inflammation and fibrosis surrounding the parasites. Conclusions We found that, in contrast with the ominous prognosis of SAH for ruptured congenital aneurysm, cases associated with NC may have a more benign course. However with limited clinical information provided by previous reports, we only propose a possible direct relationship between chronic inflammation and NC as an inference because of the limited evidence available.

BACKGROUND: Tuberculosis (TB) remains an important public health problem in developing countries. OBJECTIVE: To evaluate the clinical presentation, management, and long-term outcome in 6 patients with tuberculous brain abscesses (TBA), an uncommon form of central nervous system (CNS) TB. METHODS: A search of medical records of a single referral neurological center in Mexico City from 2002 to 2007 retrieved 149 patients with CNS TB; 6 of them (4%) met Whitener's criteria for TBA and were included in this review. RESULTS: Five of six patients had a previous history of TB. Three patients were referred to our center under antituberculous treatment (ATT) for pulmonary and lymph node TB, and two patients were receiving ATT for TB meningitis at diagnosis of TBA. All presented with symptoms of intracranial hypertension and hemiparesis. On imaging studies, 3 patients had a single, deep multiloculated lesion and another three had separated lesions, all patients underwent surgery and received long courses of ATT. One patient died after surgery and the rest recovered with moderate to severe neurological sequelae. The residual lesions in 5 patients resolved in follow-up CT or MRI studies at a mean time of 10 months. CONCLUSIONS: Early surgery confirms the diagnosis of TBA. Some patients may require additional surgical procedures if enlargement or recurrence of the lesion occurs. No evidence of drug resistance was found in our cases, and we found only two reports of TBA with primary resistance to ATT in a selective literature review. TBA does not seem to be a consequence of drug resistance. Sequelae are common, and long-term ATT with close clinical and imaging follow-up is mandatory.

Citrulline and nitric oxide (NO) are synthesized by NO synthase (NOS) in a 1:1-stoichiometry. In this study, we determined by HPLC arginine and citrulline concentrations by fluorescence detection and nitrate levels by UV absorbance detection in the cerebrospinal fluid (CSF) from patients with acute hydrocephalus that underwent ventricular drainage. We found increased citrulline concentration (50.6 ± 17.2 versus 20.9 ± 2.0 μM) and decreased arginine/citrulline molar ratio (0.42 ± 0.11 versus 1.12 ± 0.16) in hydrocephalus patients, while arginine and nitrate concentrations and citrulline/nitrate molar ratio remained with little change. Citrulline has been determined as a marker of NOS activity in some studies, but it remains to be determined the extent at which this statement holds true, since other biochemical pathways also regulate the concentration of this amino acid. Our results suggest that citrulline is primarily synthesized from NOS in acute hydrocephalus. The evaluation of sample deproteinization by addition of methanol for the analysis of amino acids in CSF is also reported.

Background There are few reports on the outcome of surgical treatment of TGN without vascular compression. Methods Between 1984 and 2004, 668 patients underwent MVD for TGN. In 21 patients (3.1%), vascular compression was absent. The surgical strategy in these cases involved the following: (1) dissection and exposure of the entire trigeminal nerve root; (2) slight neurapraxia with bipolar tips at the trigeminal nerve root; and (3) isolation of trigeminal nerve with Teflon sponge fragments. Results The patients' (female/male, 20:1) ages ranged from 33 to 77 years. Their right side was the most frequently involved (61.9%). Their mean duration of pain before treatment was 7.6 years (range = 1-20 years). At surgical exploration, vascular compression or anatomical abnormalities were absent in 15 patients (71.4%), arachnoidal thickening was present in 5 (23.8%), and fiber dissociation of the trigeminal nerve was present in 1 (4.8%). Mean follow-up after surgery was 17.7 months (range = 4-65 months). Immediate relief from pain occurred in all 21 patients. On Kaplan-Meier analysis, recurrence was maintained at 14.8% for 12, 24, and 36 months, increasing to 43.2% at 48 months. Permanent hypoesthesia was present in 6 patients (28.6%), whereas loss of corneal reflex was observed transiently in 1 (4.8%). Motor function of the trigeminal nerve was intact in all patients. No other complication was found. Conclusion The proposed surgical plan of standard MVD plus slight trigeminal nerve root neurapraxia is a safe and effective management option for TGN without vascular compression.

The authors present the case of a 59-year-old woman with an 8 months history of lancinating pain and hyphestesia on the right side of the face along with hearing impairment. She had poor tolerance to carbamazepine. A non-enhancing cystic image was observed at the right cerebellopontine angle on magnetic resonance imaging. The patient underwent surgery. Through a right retromastoid minicraniectomy and under microscopic magnification the VII and VIII cranial nerve complex was found involved by multiple adhesions around a cysticercus. After the cyst was removed a loop of the anteroinferior cerebellar artery was identified compressing the V right nerve at its root entry zone. Decompression was performed by the insertion of a Teflon implant. The postoperative course was uneventful and trigeminal neuralgia (TN) disappeared after surgery. Five previous cases of cranial nerve hyperactive dysfunction syndromes, four of trigeminal neuralgia and one of hemifacial spasm associated to cerebellopontine angle cysticercosis are briefly commented. We suggest that in some of these cases microvascular compression was probably present, and during surgery of cerebellopontine angle cysticercus by either trigeminal neuralgia or hemifacial spasm, vascular compression must be carefully searched and treated when found.

OBJECTIVE AND IMPORTANCE: We report an unusual case of basal ganglia granulomas caused by Candida albicans that surrounded the proximal segment of a nonfunctional cerebrospinal fluid shunt in a previously healthy patient. CLINICAL PRESENTATION: A 22-year-old woman had undergone ventriculoatrial cerebrospinal fluid shunt placement for posttraumatic hydrocephalus 3 years previously. One year later, a shunt revision was followed by wound dehiscence with local infection at the neck level. She received oral administration of antibiotics for 3 months until the wound closed. Twelve weeks before admission, the patient experienced pulmonary emboli. She received anticoagulants, and the distal segment of the shunt was removed. Five weeks after shunt removal, she presented with headache and left-sided hemiplegia caused by right basal ganglia inflammatory masses. INTERVENTION: A stereotactic brain biopsy was performed, and the shunt remnants were removed. Microscopically, the lesions were acutely and chronically inflamed. C. albicans grew in tissue and in shunt hardware cultures. The patient was treated with 1.1 g of intravenously administered amphotericin B and orally administered ketoconazole; she recovered completely. CONCLUSION: C. albicans brain granulomas occur rarely in immunocompetent patients. Despite the large size of the lesions and severe brain edema, the absence of an underlying disease contributed to complete resolution after shunt removal and antifungal therapy.

Background Neurological complications may be present clinically in up to 39% of patients infected with HIV or AIDS. Some reports have shown different profiles of neurological illness related to geographic variations and the population studied. Methods This retrospective study describes the neurological manifestations of patients with AIDS seen between 1990 and 1998 at a single neurological referral hospital in Mexico City. Results One hundred forty-nine patients were included, 133 males (89%) and 16 females (10.7%). The average age was 33.8 years (9 to 75 years). Upon admission, only 50 patients (33.6%) were known to be seropositive to HIV-1. In 75 patients (50.3%), the neurological illness was definitory of AIDS and also was its first recognized clinical manifestation. The most common infection problems were brain toxoplasmosis (32.2%), meningeal cryptococcosis (21.5%), tuberculosis (8.7%), and AIDS-dementia complex (8.7%). There were eight (5.4%) cases of ischemic cerebrovascular disease and four (2.7%) neoplasms. Two primary brain lymphomas and single cases of astrocytoma and oligodendroglioma, progressive multifocal leukoencephalopathy (PML), aseptic meningitis, acute encephalitis, transverse myelitis, myopathy, and cranial neuropathy were also seen. Conclusions In comparison with other studies of neurological complications of AIDS, opportunistic infections amenable to treatment in our population were more common. A high case fatality rate was observed, as was a large proportion of patients in whom the neurological illness was the first manifestation of HIV infection or AIDS due to denied, unknown, or unrecognized risk factors for HIV infection.

Klebsiella pneumoniae liver abscess syndrome (KLAS) is an emerging infection characterized by primary monomicrobial liver abscess, bacteremia and metastatic complications. KLAS is endemic in Taiwan but additional cases has also been described in other world regions. It’s caused by strains of K. pneumonia serotype K1, rmpA, magA positive, displaying hypermucoviscosity. We present the case of a previously healthy 69 years old patient who developed fever, liver abscess,septic shock, bacteremia, and pneumonia. In cultures grew hypermucoviscous phenotype of K. pneumonia characterized by positive “string test”. The patient responded favourably to antibiotic therapy with ceftriaxone, meropenem, amykacin and percutaneous drainage of the abscess. Increased awareness about this globally emerging infection by physicians could allow earlier detection and optimal treatment.

✓ In a prospective open study, 15 patients with hydrocephalus secondary to cysticercosis who required insertion of a ventriculoperitoneal (VP) shunt were treated with 50 mg of prednisone given orally three times a week. Treatment began in the 1st postoperative week, with isoniazid and pyridoxine administered daily as antituberculous chemoprophylaxis. The drug regimen was continued with close follow up for 24 months. Clinical status, Karnofsky performance status (KPS) scores, and postoperative course in the prednisone-treated group were compared with 30 control patients with hydrocephalus due to cysticercosis. The control patients were matched by age and sex, underwent surgical shunting in the same period, and were followed routinely by the neurosurgery staff. Lumbar cerebrospinal fluid (CSF) was studied at 2, 16, and 32 weeks postoperatively in the prednisone group. At 24-month follow up two (13%) of 15 patients in the prednisone group and 18 (60%) of 30 patients in the control group required surgical shunt revisions for symptomatic shunt obstruction (p = 0.002). Follow-up studies of CSF performed at 32 weeks in the prednisone group revealed improvement of abnormal values with statistically significant differences for glucose (p < 0.02). Serial imaging studies in the prednisone group revealed persistence of cysticercal cysts with no change in size. Mean initial KPS scores were similar in both groups. At the end of the follow-up period, the mean KPS score was significantly higher in the prednisone group (p = 0.003). Prednisone and chemoprophylactic drugs were well tolerated. These results suggest that in selected patients with hydrocephalus secondary to cysticercosis, intermittent long-term prednisone therapy after VP shunting may reduce shunt malfunction and improve the functional status of the patients.

Digital subtraction angiography (DSA) was performed in 24 adults with tuberculous meningitis (TBM) and results were correlated with 24 admission and 16 follow-up CT examinations. 19 MRI studies and clinical outcome at a mean follow-up of 44 weeks. DSA was abnormal in 11 patients. Abnormal DSA was associated with advanced clinical stages of the Medical Research Council classification, admission CT with hydrocephalus or gyral cortical enhancement. MRI disclosed brain infarcts not seen on initial CT in 8 cases. Of seven patients who died, 4 had abnormal and 3 normal DSA. Among patients who survived, those with normal DSA had a better functional outcome by Karnofsky scores. During follow-up infarcts were evident in 16 patients. Abnormal DSA in relation to brain infarcts had a sensitivity of 0.56, specificity 0.75, positive predictive value 0.82 and negative predictive value 0.46. A single arteriogram does not predict the outcome in patients with TBM and its value is limited in the assessment of vascular complications of TBM. Angiography in TBM is justified only in specific clinical trials to assess new therapeutic modalities against infarcts.

BACKGROUND With the progression of acquired immunodeficiency virus (AIDS) and human immunodeficiency virus (HIV) infection to endemic areas of cysticercosis, the simultaneous diagnosis of both diseases is an expected event. METHODS Among 91 patients with AIDS or HIV infection studied from 1987 to 1993 at a neurologic reference center in Mexico City, 2 patients with AIDS and neurocysticercosis were found. Five previously reported cases were jointly reviewed. RESULTS The first patient presented with increased intracranial pressure of rapid progression. A single giant cyst was surgically excised and cysticercus was confirmed on histopathologic examination. The second patient had brain toxoplasmosis and concurrent neurocysticercosis as an incidental finding. CONCLUSIONS Neurocysticercosis in HIV infection/AIDS may appear as a life-threatening condition or as an incidental finding. All reported cases have been found in advanced stages of HIV infection. Management must be individualized depending on the clinical form of cysticercosis, stage of HIV infection, and coexisting opportunistic conditions. Surgery may be lifesaving and some patients apparently responded to cysticidal drugs.

A 35-year-old female agricultural worker presented with a 4 month history of productive cough, fever, and left subcostal pain, followed by progressive paraparesis and urinary incontinence. 10 years previously, she had been treated for a skin infection on her back at another centre for 3 years, without further follow-up. Examination showed more than one irregular scars, hyperpigmented papules, and few skin sinuses with scanty purulent discharge, without erythema, on the middle and left side of the upper back. The patient was afebrile and did not have palpable cervical or supraclavicular lymphadenopathy. We heard no rales, rhonchi, or substantial wheezing. The patient had fl accid paraplegia with complete sensory loss at T4 level and urinary sphincter incontinence. Laboratory tests showed a leucocyte count of 9·1 cells per μL, a normal liver enzyme profi le, a C-reactive protein concentration of 59·1 mg/dL (normal range 0–0·5 mg/dL), and no evidence of venereal disease or HIV. Protein concentration in her cerebrospinal fl uid was 800 mg/dL, glucose was 32 mg/dL, and no cells were present. Cerebrospinal fl uid stains, bacterial culture, and PCR for Mycobacterium tuberculosis were negative. Chest radiography showed a paravertebral mass with a fragmentary pattern of osseous patchy destruction and periosteal reaction (fi gure, A). Spiral CT showed a left paravertebral extensive osteolytic lesion involving vertebral bodies and costovertebral unions (fi gure, B). T2-weighted MRI (fi gure, C–E) showed widespread hyperintense lesions that infi ltrated vertebral bodies without involvement of intersomatic spaces (arrow), pleural thickening, and lung consolidation of the left lower lobe (asterisks). Gram stain and modifi ed acid-fast stain (Kinyoun) of sinus discharge showed variably Gram-positive and faintly acid-fast positive, slender, non-branching fi lamentous bacilli, consistent with a diagnosis of Nocardia sp. Intravenous amikacin, co-trimoxazole, and an orthopaedic corset were indicated. Surgery for debridement was off ered, but the patient did not choose to have the procedure. The patient attended our neurological care centre 2 months after discharge and showed a discrete amelioration of neurological symptoms, but did not return for further follow-up. Initially, diff erential diagnosis included extramedullary neoplasms and granulomatous infections (aspergillosis, histoplasmosis, tuberculosis, chromomycosis, blastomycosis, coccidiodomycosis, botryomycosis, sporotrichosis, frambesia, and syphilis). Gadolinium MRI is especially useful because it could help the practitioner to diff erentiate between vertebral intraosseous abscesses, meningeal involvement, subligamentous spread, and paraspinal abscess.

The review highlights the recent advances in the pathogenesis, diagnosis and treatment of AIDS-related primary CNS lymphoma (AIDS-PCNSL).The incidence of AIDS-PCNSL has decreased in the era of highly active antiretroviral therapy (HAART). The prognosis has improved and this most probably in relation both with the HAART-induced immunologic status recovery and subsequently the possibility to use more aggressive treatment strategies. Immunomodulatory effect of HAART seems also to have an indirect antitumor activity on the disease.The treatment strategy for AIDS-PCNSL in the HAART era tends to become similar to that of the immunocompetent population. In the absence of randomized trials devoted to AIDS-PCNSL, most current national comprehensive cancer network guidelines recommend the use of high-dose methotrexate-based chemotherapy combined or not with whole-brain radiotherapy as initial treatment in addition to HAART. The objective for the future would be that prognosis of AIDS-PCNSL catch up with that of the immunocompetent patients with special attention to systemic and neurocognitive tolerance of the treatments.

Objective: Cefepime neurotoxicity usually occurs in patients with renal impairment. The aim of this study was to evaluate the neurotoxicity of cefepime administered by continuous intravenous infusion during treatment of nosocomial infections in neurological patients with normal renal function. Methods: This was an open pilot study of neurological patients with infections caused by cefepime sensitive bacteria. Patients had baseline neurological assessment and electroencephalogram (EEG). Cefepime plasma concentrations were determined 48 hours after infusion was initiated and at end of treatment (EOT). Results: Eleven patients were included. These were diagnosed with a brain tumor (9), cerebrovascular disease (1) and polyneuropathy (1). Infections were surgical site infection in 5, clinically defined nosocomial pneumonia in 4, and bacterial meningitis associated to postoperative CSF fistula in 2. Gram-negative organisms were isolated in 10 patients. Cefepime dose was 2 g/day in 9 patients and 4 g/day in 2. Mean cefepime plasma concentration at 48h was 13.6 ± 2.0 µg/mL (range 4.6 to 24.5 µg/mL), at EOT was 11.9 ± 1.8 µg/mL (range 3.0 to18.9 µg/mL ). EEG interpreted by two experts showed at baseline alpha background rhythm in 5 and theta-alpha rhythm in 6 patients. On EEG at EOT background rhythm was alpha in 4 and theta-alpha in 7, one patient presented isolated sharp and slow wave activity. No mental status changes or seizures occurred and all infections resolved. Conclusion: Significant EEG change was observed in 1of 11 patients. A preserved mental status may correlate with cefepime safety in neurological patients with normal renal function during cefepime treatment.

The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO x ) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO x /HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naive patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.

In disease-endemic areas, severe cysticercal meningitis (SCM) is characterized by intense inflammatory cerebrospinal fluid (CSF) and negative bacterial and fungal cultures. There have been no systematic studies of SCM. We characterized patients with SCM and compare them with neurocysticercosis (NC) patients with mild CSF abnormali- ties by conducting a nine-year retrospective review at a neurological referral center. Two groups of patients were com- pared: group A, those with severe CSF pleocytosis > 1,000 cells/mm 3 (n = 12), and group B, those with CSF pleocytosis ≤ 1,000 cells/mm 3 (n = 126). All patients had positive CSF results in an enzyme-linked immunosorbent assay for cysticer- cal antigens and negative CSF cultures for bacteria, fungi, and mycobacteria. Intracranial hypertension, meningeal signs, CSF hypoglycorrachia, and a longer clinical course of NC were more frequently seen in group A. It is likely that SCM often goes unrecognized. Its correct identification may reduce morbidity and risks of unnecessary surgery in patients with chronic NC and CSF shunts. Clinical manifestations of neurocysticercosis (NC), the invasion of the central nervous system by the metacestode of Taenia solium , are variable and closely associated with the topography, number and stage of parasites, and the intensity of the immuno-inflammatory response. These factors pro- duce pleomorphic clinical, radiological, and cerebrospinal fluid (CSF) inflammatory changes. 1 The most severe forms of NC occur when parasites are located in the subarachnoid space at the base of the brain or in the ventricular system. 2,3 Subarachnoid locations seem to be more frequent in Latin America, and soft tissue locations seem to be more common in Asia and Africa. 4 Cysticercal meningitis is a term without well-defined diag- nostic criteria. When parasites lodge in the subarachnoid space at the base of the brain, a mild or moderate CSF inflam- matory profile (< 500 cells/mm 3 ) is observed. 4-8 In some cases, cellularity is higher, reaching ≥ 1,000 cells/mm 3 . This condition presents a diagnostic challenge because of the need to discrim- inate this entity from acute superimposed bacterial meningitis, especially if a CSF shunt has been previously placed. The first medical approach for these patients is generally to remove the shunt on the basis of the possibility of a bacterial infection, which unnecessarily exposes the patient to the risks of surgery with an increase in morbidity and costs. In this report, we describe a series of patients with severe cysticercal meningitis (SCM). We compared their clini- cal, radiological, and CSF inflammatory characteristics with another group of patients with subarachnoid parasites who had a less intense CSF inflammatory reaction.

Background Highly active antiretroviral therapy (HAART) restores the inflammatory immune response in AIDS patients and it may unmask previous subclinical infections or paradoxically exacerbate symptoms of opportunistic infections. Up to 25% of patients receiving HAART develop immune reconstitution inflammatory syndrome (IRIS). We describe six patients with IRIS central nervous system (CNSIRIS) manifestations emphasizing the relevance of CSF cultures and neuroimaging in early diagnosis and management. Methods Patients with CNSIRIS were identified among hospitalized HIV-infected patients that started HAART from January 2002 through December 2007 at a referral neurological center in Mexico. Results One-hundred and forty-two HIV-infected patients with neurological signs were hospitalized, 64 of which had received HAART, and six (9.3%) developed CNSIRIS. Five patients were male. Two cases of tuberculosis, two of cryptococcosis, one of brain toxoplasmosis, and one possible PML case were found. IRIS onset occurred within 12 weeks of HAART in five patients. Anti-infective therapy was continued. In one case, HAART was temporarily suspended. In long-term follow-up the clinical condition improved in all patients. Conclusions CNSIRIS associated to opportunistic infections appeared in 9% of patients receiving HAART. Interestingly, no cases of malignancy or neoplasm IRIS-related were found. Frequent clinical assessment and neuroimaging studies supported diagnosis and treatment. Risk factors were similar to those found in other series.

Background: Only five cases of infection of the central nervous system attributable to intracranial permanent devices (e.g., coils, cyanacrylate) have been described. Methods: Case report and review of the pertinent English-language literature. Case Report: A case of perianeurysmal abscess, cavernous sinus syndrome, and bacterial meningitis after coil placement in an intracranial aneurysm is presented. Among the possible sources of infection, both intrinsic and extrinsic factors are discussed. Medical management was successful, and removal of the implanted devices was not required. Conclusions: Even if central nervous system infection in interventional procedures is a rare entity, particular circumspection in the handling of endovascular devices and excluding from treatment patients with a simultaneous infection may further decrease the possibility of this complication.