Encefalitis autoinmunes: Receptor anti-NMDA y nuevos inmunofenotipos / Autoimmune encephalitis. Anti-NMDA receptor and new immunophenotypes

Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

Autoimmune encephalitis: a review of diagnosis and treatment / Encefalites autoimunes: uma revisão sobre diagnóstico e tratamento

ABSTRACT Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

RESUMO As encefalites autoimunes (EAI) são a principal causa de encefalite não-infecciosa. As manifestações neurológicas são variadas, incluindo alterações comportamentais ou psiquiátricas, disautonomia, transtornos do movimento e epilepsia. Habitualmente a instalação dos sintomas ocorre em até 6 semanas, de forma aguda ou subaguda. As EAI podem ser desencadeadas por tumores, quadros infecciosos virais ou ainda apresentar etiologia criptogênica. Este artigo revisa as principais EAI, estratégias de diagnóstico e tratamento.

Diagnóstico etiológico en meningitis y encefalitis por técnicas de biología molecular / Etiologic diagnosis in meningitis and encephalitis molecular biology techniques

Introducción: El estudio etiológico de las infecciones del sistema nervioso central se ha realizado tradicionalmente con cultivos bacterianos y con reacción en cadena de la polimerasa (PCR) para virus herpes simple (VHS). Los cultivos bacterianos pueden disminuir su rendimiento en pacientes que hayan usado antibióticos previos a la toma de muestra, y el solicitar PCR solo para virus VHS reduce el diagnóstico etiológico a un solo agente. El objetivo de este trabajo fue determinar las causas infecciosas en meningitis y encefalitis en niños, utilizando conjuntamente la microbiología convencional y la biología molecular, con el fin de mejorar el diagnóstico etiológico de estas enfermedades. Pacientes y método: Se estudiaron 19 pacientes con sospecha de meningitis y encefalitis, de manera prospectiva, hospitalizados en el hospital Luis Calvo Mackenna en Santiago de Chile, entre el 1 de marzo de 2011 y el 30 de marzo de 2012. Luego de obtener el consentimiento informado, a las muestras de LCR se les realizó examen citoquímico, cultivo, PCR múltiple bacteriana (N. meningitidis, S. pneumoniae, H. influenzae) y PCR en tiempo real para HSV-1 y 2, VVZ, VEB, CMV, VHH-6 y enterovirus. Se recabaron datos clínicos y epidemiológicos desde la ficha clínica del paciente. Resultados: De los 19 pacientes analizados 2 (10%) fueron diagnosticados por métodos microbiológicos convencionales y 7 (37%) al adicionar biología molecular (p = 0,02). Tres pacientes presentaron meningitis por S. pneumoniae, uno por Enterobacter cloacae, 2 pacientes meningoencefalitis por VHS-1 y uno meningitis por VVZ. Conclusiones: La adición de la PCR a los métodos microbiológicos convencionales de diagnóstico en las infecciones del sistema nervioso central aumenta significativamente la probabilidad de detectar el agente causal. La incorporación rutinaria del diagnóstico molecular permitiría un manejo más oportuno y racional.

Introduction: The aetiological study of infections of the central nervous system has traditionally been performed using bacterial cultures and, more recently, using polymerase chain reaction (PCR) for herpes simplex virus (HSV). Bacterial cultures may not have good performance, especially in the context of patients who have received antibiotics prior to sampling, and a request for HSV only by PCR reduces the information to only one aetiological agent. The aim of this study is to determine the infectious causes of meningitis and encephalitis, using traditional microbiology and molecular biology to improve the aetiological diagnosis of these diseases. Patients and method: A prospective study was conducted on 19 patients with suspected meningitis, admitted to the Luis Calvo Mackenna Hospital in Santiago, Chile, from March 1, 2011 to March 30, 2012. After obtaining informed consent, the CSF samples underwent cytochemical study, conventional culture, multiplex PCR for the major producing bacterial meningitis (N. meningitidis, S. pneumoniae, H. influenzae), real-time single PCR for HSV-1 and 2, VZV, EBV, CMV, HHV-6 and enterovirus. Clinical and epidemiological data were also collected from the clinical records. Results: Of the 19 patients analysed, 2 were diagnosed by conventional methods and 7 by adding molecular biology (increase to 37%). Three patients had meningitis due to S. pneumoniae, one due to Enterobacter cloacae, 2 patients meningoencephalitis HSV-1, and one VZV meningitis. Conclusions: The addition of PCR to conventional diagnostic methods in CNS infections increases the probability of finding the causal agent. This allows a more adequate, timely and rational management of the disease.

Infección por Mycoplasma neumoniae: microangeitis cerebral, síndrome de Bickerstaff y anemia hemolítica autoinmune / Mycoplasma pneumoniae infection: cerebral microangeitis, bickerstaff syndrome and autoimmune hemolytic anemia

Mycoplasma pneumoniae produce 10 to 20 percent of atypical pneumonia, and secondarily affects by autoimmune mechanisms the central and peripheral nervous system. This presentation prospects to understand others pathologies than pneumonia, originated by mycoplasma pneumonia, like hemorrhagic cerebral microvasculitis, Bickerstaff syndrome and autoimmune hemolytic anemia expressed by an adolescent. They were an immunomimetic manifestation of this bacteria, same days after pulmonary box. The microvasculitis shows blood in the CSF, retinal hemorrhages and special MR imaging s. Protuberancia! syndrome was identified by a multidirectional nystagmus, facial diplegia, involvement of the sixth cranial nerve and quadriplegia with pyramidal signs. The autoimmune hemolytic anemia was the last complication. Generally all these syndromes have been isolated described in relation to this bacterial infection. In this case they occurred simultaneously. The cerebral vasculitis took a special way, apparently not described before with these characteristics. Our conclusions are that mycoplasma pneumoniae can affect simultaneously different parenchyma expressing immunomimetic responses.

El Mycoplasma neumoniae es una bacteria productora del 10 al 20 por ciento de las neumonías atípicas, que secundariamente y por patomecanismos inmunomiméticos afecta al sistema nervioso central y periférico. Con esta presentación se busca dar significado a las variadas alteraciones que originó una neumonía por mycoplasma en un adolescente, que además presentó una micro vasculitis cerebral hemorrágica, un síndrome de Bickerstaffy una anemia hemolítica autoimune, como expresión de una respuesta inmunomimética desencadenada por la bacteria, días después de cuadro pulmonar. La microvasculitis produjo presencia de sangre en el LCR, hemorragias retinianas y una RM con imágenes características. El síndrome rombencefálico se identificó por un nistagmus multidireccional, diplejia facial, compromiso del sexto par y cuadriparesia con signos piramidales, que secuencial mente se complicaron con una anemia hemolítica autoimune. Todos estos síndromes han sido descritos aisladamente en relación a esta infección bacteriana, sin embargo, en este caso se produjeron simultáneamente y la vasculitis cerebral tomó un modo especial, al parecer no descrito antes con esas características. Se concluye que el mycoplasma neumoniae puede afectar con respuestas inmunomiméticas diversos parénquimas simultáneamente.

Cytomegalovirus Ventriculoencephalitis after Unrelated Double Cord Blood Stem Cell Transplantation with an Alemtuzumab-containing Preparative Regimen for Philadelphia-positive Acute Lymphoblastic Leukemia

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.

Aracnoiditis y encefalitis cortical tuberculosa en un paciente con VIH / Arachnoiditis and tuberculuos cortical encephalitis in an HIV+ patient

La infección por VIH es uno de los mayores factores de riesgo para tuberculosis. Presentamos el caso de un paciente de 30 años que ingresó al hospital con datos neurológicos caracterizados por cefalea, alteración del alerta, crisis convulsivas, signos meníngeos y fiebre, a quien subsecuentemente se le diagnosticó VIH y neuroinfección. Los datos clínicos, el examen del líquido cefalorraquídeo y la neuroimagen sustentaron el diagnóstico de neurotuberculosis. La resonancia magnética de cráneo reveló aracnoiditis generalizada de predominio basal, así como encefalitis cortical. Los hallazgos de imagen desempeñan un papel fundamental en el diagnóstico integral de la tuberculosis del sistema nervioso central.

HIV infection is a major risk factor for tuberculosis. We describe the case of a 30-year-old male presenting with headache, compromised mental status, seizures, neck stiffness and fever that was subsequently diagnosed with HlV and neuroinfection. Clinical data, cerebrospinal fluid and brain imaging supported a diagnosis of neurotuberculosis. Cranial magnetic resonance imaging showed diffuse arachnoidal enhancement, mainly at the basal cisterns and cortical encephalitis. Such imaging findings play a key role in the diagnosis of central nervous system tuberculosis.

Stress-induced neuroinflammation: mechanisms and new pharmacological targets

Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO) and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2), another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ2 and its peroxisome proliferator-activated nuclear receptor PPARγ, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA) glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NFκB). In the case of inducible NO synthase (iNOS), release of the cytokine TNF-α also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-α activation and release, inhibitors of NFκB, specific inhibitors of iNOS and COX-2 activities and PPARγ agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders.

Dengue infection in patients presenting with neurological manifestations in a dengue endemic population / Infección de dengue en pacientes que se presentan con manifestaciones neurológicas en una población con dengue endémico

The evaluation of the contribution of neurological dengue in suspected central nervous system (CNS) viral infections is essential to better understand the impact of neurological dengue on morbidity and mortality in dengue endemic regions such as Jamaica. For this study, 401 cases of suspected viral CNS infections were investigated for evidence of dengue infection. The frequency of neurological dengue among these CNS cases was found to be 13.5% (54/401). Fifty-three cases were confirmed serologically by haemagglutination inhibition assay (HI) and IgM antibody (ELISA) and the virus was isolated in one case only. Clinical manifestations among dengue positive CNS cases included encephalitis in 51.8% (28/54), meningitis in 33.3% (18/54), seizures in 11.1% (6/54) and acute flaccid paralysis/Guillain-Barré syndrome in 3.7% (2/54). The clinical diagnosis of dengue neurological infection corresponded with laboratory confirmation in 22.2% (12/54) of cases only. Deaths occurred in 3.7% (2/54) of cases and were associated with patients with dengue neurological infection. The high risk of dengue among patients with suspected viral CNS infections in this study supports the need for an increased index of suspicion of dengue in patients presenting with neurological manifestations in dengue endemic countries.

La evaluación de la contribución del dengue neurológico en las infecciones virales sospechadas del sistema nervioso central (SNC) resulta esencial para un mejor entendimiento del impacto del dengue neurológico en la morbilidad y mortalidad en regiones donde el dengue es endémico tales como Jamaica. Para este estudio 401 casos de infecciones virales sospechadas del SNC fueron investigados en busca de evidencia de infección por dengue. Se haló entonces que la frecuencia del dengue neurológico entre estos casos de SNC, fue de 13.5% (54/401). Cincuenta y tres casos fueron confirmados por serología mediante ensayos de inhibición de hemaglutinación (IH) y ELISA para la detección de anticuerpos IgM, siendo el virus aislado sólo en un caso. Las manifestaciones clínicas entre los casos que resultaron positivos al dengue, incluyeron encefalitis en 51.8 % (28/54), meningitis en 33.3% (18/54), convulsiones en 11.1% (6/54) y parálisis facial aguda/síndrome Barré Guillain en 3.7% (2/54). El diagnóstico clínico de infección neurológica por dengue estuvo en correspondencia con la confirmación del laboratorio sólo en el 22.2% (12/ 54) de los casos. Se produjeron muertes en el 3.7% (2/54) de los casos, las cuales estuvieron asociadas con pacientes con infección neurológica por dengue. El alto riesgo de dengue entre los pacientes con sospecha de infecciones virales de SNC en este estudio, apunta a la necesidad de aumentar el índice de sospecha de dengue en pacientes que se presentan con manifestaciones neurológicas en países donde el dengue es endémico.

Clinical outcome in measles patients hospitalized with complications

Measles is a highly communicable viral illness and is common cause of childhood mortality and morbidity. Keeping in view the high prevalence of measles in the developing world, we carried out this study to look into the complicated measles cases and clinical outcome in patients admitted in children ward of Ayub Teaching Hospital. Detailed history and physical examination of all the hospitalized patients with complication of measles were recorded in a proforma. Immunization and nutritional status of each admitted patient was assessed and the clinical outcome of measles was compared with demographic profile. One hundred thirty six hospitalized patients with complications of measles were studied. There was 60.3% male and 57.3% of patients were vaccinated against measles. Malnourished patients were 71.35% and had longer hospital stay [>5 days]. Pneumonia [39.7%] and diarrhoea [38.2%] were the commonest complications. Seven children died and encephalitis [57.1%] was the commonest cause of death. The most common complications of measles are pneumonia and diarrhoea with dehydration requiring admission. Malnutrition results in more complications and longer hospital stay. Mortality is significantly associated with encephalitis

Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease

Inflammation, a self-defensive reaction against various pathogenic stimuli, may become harmful self-damaging process. Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis. In the central nervous system, microglia, the resident innate immune cells play major role in the inflammatory process. Although they form the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines (IL-1beta, TNF-alpha, IL-6), NO, PGE

Hemiplejía aguda infantil asociada a infección por enterovirus / Acute hemiplegía of childhood associated with enteroviral infection

El ictus isquémico en la infancia es una entidad in frecuente, en el 50 por ciento de los casos no existe una causa identificable. Sin embargo, con el advenimiento de nuevas técnicas diagnósticas se han podido conocer más afecciones causales.Presentamos el caso de una paciente de 9 años conhemiplejía aguda izquierda, con estudios de neuro imágenes poco significativos y en la cual el análisis del líquido cefalorraquídeo por método de reacciónen cadena de polimerasa (PCR) para ARN viral, fue positivo para enterovirus.La encefalitis focal por enterovirus constituye una entidad neurológica rara en la infancia. Se ha implicado a un probable proceso vasculítico secundario a la infección viral como causa de la isquemia cerebral.Sin embargo, es un diagnóstico etiológico pocas veces pensado y que debería incluirse en el diagnóstico diferencial de hemiplejía aguda infantil.

Clinical profile and outcome of Dengue fever cases.

Dengue fever is on rise globally. In India, Dengue epidemics are expanding geographically, even into the rural areas. Dengue can present with varied manifestations. The mortality rate has been brought down with high index of suspicion, strict monitoring and proper fluid resuscitation. Herewith, we are presenting clinical features and outcome of Dengue cases seen in and around Hubli (North Karnataka).

Encefalitis carcinomatosa / Carcinomatous encephalitis

We report a case of carcinomatous encephalitis in a patient with lung adenocarcinoma and confusional syndrome. This is a rare form of brain metastases. We discuss its clinical picture, the importance of suspecting it after a normal computed tomography scan and the miliary typical images at magnetic resonance.

Se comunica un caso de encefalitis carcinomatosa, en un paciente con diagnóstico de adenocarcinoma de pulmón y síndrome confusional. Esta entidad es poco conocida en relación a otras afecciones neurológicas relacionadas al cáncer. Se discute su presentación clínica, se destaca la necesidad de sospecharla aun luego de obtener una tomografía computada normal y sus típicas imágenes miliares en resonancia magnética.

Herpes simplex acute encephalitis in children

to determine the incidence of HSV as a cause of acute sporadic viral encephalitis in Syria, and to describe any significant clinical, laboratory, and radiological findings that may help to indicate the causative agent of encephalitis. Materials and this was a prospective study which included 95 patients [69.5% male, 30.5% female] aged between 2 months and 12 years [average 3.4 years] who were admitted to Children University from September 1, 1998 to August 30, 2000 with a possible diagnosis of encephalitis. Laboratory, biological, and radiological investigations were done. the percentage of herpetic encephalitis was 35.7% [34 children]. The important clinical findings were: fever [97%], altered mental state [97%], seizures [88%], and focal neurological signs [47%]. Cerebrospinal fluid pleocytosis was present in 97% [lymphocytes= 90%] with mild elevation in CSF protein [47%], and normal CSF glucose. Electroencephalogram showed abnormal findings in 79%. CT scan showed abnormal findings in 87%. the study demonstrated that HSV is a significant causative agent of acute sporadic encephalitis in Syria. There was no statistical difference between the two groups of Herpes [HSE] and non-Herpes [Non-HSE] except that localized convulsions, severe deterioration in level of consciousness, localized neurological signs, morbidity, and mortality were higher in the HSE group

Neurological complications of measles.

OBJECTIVE: To study the clinical features and course of neurological complications of measles. DESIGN: Prospective study. SETTING: Neurology Unit, Teaching Hospital, Kandy. PATIENTS: 10 patients admitted with neurological complications of measles during an outbreak. MEASUREMENTS: Assessment of clinical features and the neurological investigations. RESULTS: 6 had CSF IgM antibodies confirming a recent measles infection. 7 patients had encephalitis and 3 had myelitis. Complications had appeared 5 to 14 days after appearance of the rash. All patients with encephalitis had depressed level of consciousness (Glasgow coma scale 2 to 11) with seizures, 3 patients had lateralising signs, and assisted ventilation was required in 4. Cranial CTs were either normal or showed mild cerebral oedema. CSF analysis showed either normal or mildly raised protein without a cellular reaction. EEG in all 7 revealed diffuse delta activity. During the follow up period of 1 to 12 weeks, all showed a gradual improvement, except one who succumbed to respiratory complications of assisted ventilation. All others were left with some residual disability when last seen. Three patients with myelitis had symmetrical paraparesis. CSF protein was 60 to 80 mg/ml without a cellular reaction. All three improved without residual disability. CONCLUSIONS: Measles encephalitis is a life threatening complication. All three myelitis patients recovered completely within 5 to 8 weeks.

Experience of human rabies in north India.

Rabies is one of the most common causes of human encephalitis in developing countries. This study shows the diagnosis of rabies among suspected human rabies encephalitis cases by Seller stain, Flourescent stain as well as mouse inoculation test. Out of 71 postmortem brain specimens, 26 were diagnosed as rabies positive. Negri bodies were demonstrated in 18 (25.4%) brain saples by Seller stain. Flourescent antibody technique could detect rabies antigen in 21 (29.6%) samples. Rabies virus could be isolated in 15 (42.9%) of the 35 samples by intracerebral inoculation in 15 (42.9%) of the 35 samples of intracerebral inoculation in newborn Swiss albino mice. Of the 26 confirmed cases, 61.5% occurred during the months of June to August and history of dog bite was present in 9 (34.6%) cases.

Polymerase chain reaction for the laboratory diagnosis of aseptic meningitis and encephalitis

A protocol for testing cerebrospinal fluid specimens using a range of PCR assays for the diagnosis of central nervous system infection was developed and used to test prospectively 383 specimens. PCR assays were used for the detection of adenovirus, Borrelia burgdorferi, enteroviruses, Epstein Barr virus, cytomegalovirus, herpes simplex virus, human herpes virus type 6, JC virus, Leptospira interrogans, Listeria monocytogenes, lymphocytic choriomeningitis virus, measles virus, mumps virus, Mycobacterium sp., Mycoplasma pneumoniae, Toxoplasma gondii and varicella zoster virus. Of the 383 specimens tested in this study, 46 (12.0 percent) were found to be positive. The microorganisms detected were CMV, enterovirus, Epstein Barr virus, herpes simplex virus, human herpes virus type 6, JC virus, L. monocytogenes, Mycobacterium genus, Toxoplasma gondii and varicella zoster virus. The introduction of the PCR protocol described has improved the diagnosis of a range of central nervous system infections in our laboratory. We believe however that further evaluation of these assays in immunocompromised patients is necessary to better determine the predictive value of positive PCR results in these patient groups

Complicaciones neurologicas del transplante renal / Neurological complications of renal tranplants

Los avances en las técnicas quirúrgicas y nuevos esquemas inmunosupresores han mejorado la sobrevida de los injertos renales. Estos cambios se han visto acompañados por complicaciones infecciosas, neoplásicas y neurológicas. En este trabajo se revisaron las complicaciones neurológicas de los 542 pacientes que recibieron un trasplante renal (donante vivo o cadavérico) en el CEMIC desde 1970 hasta 1996. 43 pacientes presentaron complicaciones neurológicas (8 por cento); 8 meningitis (1.5 por ciento); 8 síndrome confusional agudo (1.5 por ciento); 7 encefalitis (1.3 por ciento), 7 accidente cerebro vascular (1.3 por ciento); 6 convulsiones (1.1 por ciento); 3 tumores (0.5 por ciento); 3 lesión de nervio femoral (0.5 por ciento); 1 lipomatosis epidural (0.1 por ciento). Los agentes etiológicos más comunes de las meningitis fueron Cryptococcus neoformans, Listeria monocytogenes y Mycobacterium tuberculosis. Las encefalitis presentaron las mayores dificultades diagnósticas. Para el diagnóstico de las complicaciones descriptas, se requirió de un alto nivel de sospecha clínica, repetidos estudios bacteriológico y de imágenes.