Brain anatomopathological findings in neonates with congenital heart disease.

INTRODUCTION: Neonates with congenital heart disease can develop neurological problems, which is why it is important to know the time and extent at which these lesions occur in order to elucidate their causes and implications. OBJECTIVE: To describe brain morphological alterations in autopsies of neonates with congenital heart disease. METHODS: The cases of neonates with congenital heart disease and complete autopsy registered in the pathology department from 2009 to 2019 were included. Descriptive statistics were used with the calculation of frequencies and percentages. RESULTS: Of a total of 21 patients, 61.9% were full-term males; median weight and age at admission were 2500 g and five days, respectively; mean hospital stay was seven days. The predominant heart disease was aortic arch pathology. Fifteen patients (71.3%) underwent surgery; 50% died of cardiogenic shock, 100% had hypoxic-ischemic brain lesions, 71% had incipient lesions, and 33.3%, parenchymal hemorrhage. CONCLUSIONS: There are various risk factors for neurological damage in patients with complex congenital heart disease, which is impossible to be entirely controlled. This study allows us to know, for the first time in our milieu, the changes in the central nervous system that could exist in these patients.

INTRODUCCIÓN: Los neonatos con cardiopatía congénita pueden desarrollar problemas neurológicos, por lo que es importante conocer el momento en el que ocurren dichas lesiones y su extensión, para dilucidar sus causas e implicaciones. OBJETIVO: Describir las alteraciones morfológicas cerebrales en autopsias de neonatos con cardiopatía congénita. MÉTODOS: Se incluyeron los casos de neonatos con cardiopatía congénita y autopsia completa registrados en un servicio de patología, de 2009 a 2019. Se utilizó estadística descriptiva con el cálculo de frecuencias y porcentajes. RESULTADOS: De 21 pacientes, 61.9 % fue a término del sexo masculino; las medianas del peso y edad al ingreso fueron 2500 g y cinco días, respectivamente; la media de la estancia hospitalaria fue siete días. La cardiopatía predominante fue la patología de arco aórtico. Quince pacientes (71.3 %) fueron sometidos a cirugía; 50 % falleció por choque cardiogénico, 100 % presentó lesiones hipóxico-isquémicas cerebrales; 71 %, lesiones incipientes; 33.3 %, hemorragia parenquimatosa. CONCLUSIONES: Existen diversos factores de riesgo para daño neurológico en los pacientes con cardiopatía congénita compleja, los cuales es imposible controlar en su totalidad. Este estudio permite conocer, por primera vez en nuestro medio, los cambios en el sistema nervioso central que podrían existir en estos pacientes.

[Effectiveness of pain neuroscience education in patients with fibromyalgia: Structured group intervention in Primary Care]. / Efecto de la educación en neurociencia del dolor en pacientes con fibromialgia: intervención grupal estructurada en atención primaria.

OBJECTIVE: To evaluate the effectiveness of a group intervention in Primary Care in patients with fibromyalgia (FM) based on pain neuroscience education (PNE). DESIGN: Pre-post study. LOCATION: Urban Primary Health Centre in Bilbao. PARTICIPANTS: Patients with FM (2010 American College of Rheumatology Diagnostic Criteria for fibromyalgia), ≥18 years. INTERVENTION: 5 weekly sessions (2hours each), and a reminder session one month later. MAIN MEASUREMENTS: Compliance with FM criteria, assessed using the WPI (Widespread Pain Index, number of pain areas) and the SS (severity of symptoms) questionnaires. An assessment was also made on the impact of FM on functional capacity (FIQ:≥20% and ≥50% reduction in the FIQ total score from baseline to after treatment, and proportion of patients with FIQ<39 at the end of the study). Assessments were made at baseline, one month following the 5th session, and during the 6- and 12-month follow-up. RESULTS: All the study evaluations were completed by 85/98 patients. A statistically significant improvement was observed in the 3 studied categories (WPI, SS, and FIQ) since the first visit, and was maintained until the final visit (12 months later). A total of 45 patients (53%, 95% CI: 42%-63%), more than those at baseline, scored FIQ<39 (no worse than mild functional impairment). One month following the 5th session there were 44 patients (52%, 95% CI: 41%-62%) that no longer met FM criteria and, at the end of follow-up, there were 56 patients (66%, 95% CI: 55%-75%). CONCLUSIONS: An intervention based on PNE has shown to be feasible in Primary Care, with results in the upper range of those published with other treatments for FM.

Cognitive impairment in patients with central nervous system tuberculosis.

INTRODUCTION: Tuberculosis (TB) in Mexico remains an important cause of morbidity and mortality; in the past 4 years, 110,681 cases of pulmonary tuberculosis and 1571 cases of tuberculous meningitis were reported. OBJECTIVE: To determine the neurocognitive sequelae, clinical presentation and neuroimaging alterations in patients with central nervous system tuberculosis. METHODS: A retrospective, analytical, and cross-sectional study was carried out from 2010 to 2019. Patients with central nervous system tuberculosis, with and without HIV/AIDS coinfection, were included. RESULTS: During the study period, 104 cases with a definitive or probable central nervous system tuberculosis diagnosis were included; 38% had HIV/AIDS coinfection, and 55%, various comorbidities (p = 0.0001); 49% had cognitive alterations, and 14% died. CONCLUSIONS: Although HIV/AIDS infection can contribute to cognitive decline in patients with tuberculous meningitis, no differences were observed between patients with and without HIV/AIDS. Cognitive sequelae showed improvement during follow-up with adequate management and therapeutic control of the patients.

INTRODUCCIÓN: La tuberculosis en México sigue siendo causa importante de morbimortalidad; en los últimos cuatro años, se reportaron 110 681 casos de tuberculosis pulmonar y 1571 casos de tuberculosis meníngea. OBJETIVO: Determinar las secuelas neurocognoscitivas, presentación clínica y alteraciones en los estudios de neuroimagen en pacientes con tuberculosis del sistema nervioso central. MÉTODOS: Se realizó un estudio retrospectivo, analítico y transversal de 2010 a 2019. Se incluyeron pacientes con tuberculosis del sistema nervioso central, con y sin coinfección por VIH/sida. RESULTADOS: Durante el periodo de estudio se incluyeron 104 casos con diagnóstico definitivo y probable de tuberculosis del sistema nervioso central; de acuerdo con los criterios de Marais, 38 % presentó coinfección por VIH/sida y 55 %, diversas comorbilidades (p = 0.0001); 49 % presentó alteraciones cognoscitivas y 14 % falleció. CONCLUSIONES: Aunque la infección por VIH/sida puede contribuir al deterioro cognitivo del paciente con tuberculosis meníngea, no se observaron diferencias entre pacientes con y sin VIH/sida. Las secuelas cognoscitivas mostraron mejoría en el seguimiento con el adecuado manejo y control terapéutico de los pacientes.

[Descriptive epidemiology and frequency variations of astrocytic tumors in the National Institute of Neurology and Neurosurgery of Mexico]. / Epidemiología descriptiva y cambios en la frecuencia de tumores astrocíticos en el Instituto Nacional de Neurología y Neurocirugía de México.

OBJECTIVE: To determine distribution, localization and frequency variations of astrocytic tumors (AT) in a Mexican Institute of neurology. MATERIALS AND METHODS: Institutional registries of AT from five decades were analyzed. AT/ Surgical discharges (SD) and AT/Central Nervous System Tumors (CNST) from 1995 to 2014 were compared. RESULTS: Two thousand two hundred and eighty-seven AT (1 356 men and 931 women) were analyzed. The most common glioma was glioblastoma multiforme (GBM), found in young adults with a higher frequency to that reported in other studies. Relation of AT/SD, as well as, relation of AT/CNST was similar between 1995 and 2014. CONCLUSIONS: In general, the frequency of AT worldwide, being higher in the subgroup of young adults with GBM. There was not significant variation in the frequency of AT during the time studied.

OBJETIVO: Determinar distribución, localización y cambios de la frecuencia de tumores astrocíticos (TA) en un instituto mexicano de neurología. MATERIAL Y MÉTODOS: Se revisaron los registros institucionales de TA de cinco décadas. Se compararon las relaciones TA/egresos quirúrgicos (EQ) y TA/total de tumores del sistema nervioso central (TSNC) de 1995 a 2014. RESULTADOS: Se analizaron 2 287 TA (1 356 en hombres y 931 en mujeres). El glioma más común fue el glioblastoma multiforme (GBM), que estuvo presente en adultos jóvenes con una frecuencia mayor a la reportada en otros estudios. La relación TA/EQ y TA/TNSC fue similar entre 1995 y 2014. CONCLUSIONES: En general, la frecuencia de TA atendidos en el Instituto es similar a la reportada internacionalmente. No obstante, los casos de TA en el subgrupo de adultos jóvenes con GBM son más frecuentes (40%) que las incidencias reportadas en otros estudios (menores al 5%). No se encontró variación significativa en la frecuencia de TA durante las últimas dos décadas.

Neurologic emergencies in HIV-negative immunosuppressed patients. / Urgencias neurológicas en el paciente inmunosuprimido no VIH.

HIV-negative immunosuppressed patients comprise a heterogeneous group including transplant patients, patients undergoing treatment with immunosuppressors, uremic patients, alcoholics, undernourished patients, diabetics, patients on dialysis, elderly patients, and those diagnosed with severe or neoplastic processes. Epileptic seizures, focal neurologic signs, and meningoencephalitis are neurologic syndromes that require urgent action. In most of these situations, neuroimaging tests are necessary, but the findings can be different from those observed in immunocompetent patients in function of the inflammatory response. Infectious disease is the first diagnostic suspicion, and the identification of an opportunistic pathogen should be oriented in function of the type and degree of immunosuppression. Other neurologic emergencies include ischemic stroke, cerebral hemorrhage, neoplastic processes, and pharmacological neurotoxicity. This article reviews the role of neuroimaging in HIV-negative immunodepressed patients with a neurologic complication that requires urgent management.

Management of pediatric central nervous system emergencies: a review for general radiologists. / Manejo de los casos de urgencia del sistema nervioso central pediátricos para radiólogos generales.

TEACHING OBJECTIVES: To review the most common and most important diseases and disorders of the central nervous system (CNS) in pediatric emergencies, discussing the indications for different imaging tests in each context. DISCUSSION: In pediatric patients, acute neurologic symptoms (seizures, deteriorating level of consciousness, focal neurologic deficits, etc.) can appear in diverse clinical situations (trauma, child abuse, meningoencephalitis, ischemia…). It is important to decide on the most appropriate neuroimaging diagnostic algorithm for each situation and age group, as well as to know the signs of the most typical lesions that help us in the etiological differential diagnosis. Pediatric patients' increased vulnerability to ionizing radiation and the possible need for sedation in studies that require more time are factors that should be taken into account when indicating an imaging test. It is essential to weigh the risks and benefits for the patient and to avoid unnecessary studies.

[Arachnoid cysts: Embriology and pathology]. / Quistes aracnoideos: embriología y anatomía patológica.

There is still great controversy surrounding the origin of the arachnoid cyst. The most accepted theory in the case of congenital cysts explains how they are formed from an anomalous development of the arachnoid membrane, which is unfolded allowing the accumulation of cerebrospinal fluid inside and creating a cyst. This theory seems to explain the origin of convexity and sylvian cistern arachnoid cysts, whereas those in other locations might be due to other mechanisms. In the anatomopathological analysis, the arachnoid cyst wall can be seen as having few differences from normal, although thickened due to an increase quantity of collagenous material. A description of the embryological development of the arachnoid layer and cyst formation is presented, describing the main anatomopathological findings.

[Giant racemose subarachnoid and intraventricular neurocysticercosis: A case report]. / Neurocisticercosis racemosa subaracnoidea gigante y ventricular: a propósito de un caso.

Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.

[Neuroimaging of Langerhans cell histiocytosis in the central nervous system of children]. / Neuroimagen de la histiocitosis de células de Langerhans en el sistema nervioso central pediátrico.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the accumulation within tissues of anomalous dendritic cells similar to Langerhans cells. The clinical presentation varies, ranging from the appearance of a single bone lesion to multisystemic involvement. Central nervous system (CNS) involvement, manifesting as diabetes insipidus secondary to pituitary involvement, has been known since the original description of the disease. Two types of CNS lesions are currently differentiated. The first, pseudotumoral lesions with infiltration by Langerhans cells, most commonly manifests as pituitary infiltration. The second, described more recently, consists of neurodegenerative lesions of the CNS associated with neurologic deterioration. This second type of lesion constitutes a complication of the disease; however, there is no consensus about the cause of this complication. Our objective was to describe the radiologic manifestations of LCH in the CNS in pediatric patients.

Effect of iron deficiency on the expression of insulin-like growth factor-II and its receptor in neuronal and glial cells.

INTRODUCTION: Many studies have demonstrated that iron deficiency modifies the normal function of the central nervous system and alters cognitive abilities. When cellular damage occurs in the central nervous system, neuroprotective mechanisms, such as the production of neurotrophic factors, are essential in order for nervous tissue to function correctly. Insulin-like growth factor II (IGF- II) is a neurotrophic factor that was recently shown to be involved in the normal functioning of cognitive processes in animal models. However, the impact of iron deficiency on the expression and function of this molecule has not yet been clarified. METHODS: Mixed primary cell cultures from the central nervous system were collected to simulate iron deficiency using deferoxamine. The expression of IGF-I, IGF-II, IGF-IR, and IGF-IIR was determined with the western blot test. RESULTS: We observed increased expression of IGF-II, along with a corresponding decrease in the expression of IGF-IIR, in iron-deficient mixed primary cell cultures. We did not observe alterations in the expression of these proteins in isolated microglia or neuronal cultures under the same conditions. We did not detect differences in the expression of IGF-I and IGF-IR in iron-deficient cultures. CONCLUSIONS: In vitro iron deficiency increases the expression of IGF-II in mixed glial cell cultures, which may have a beneficial effect on brain tissue homeostasis in a situation in which iron availability is decreased.

Non-perinatal listeriosis: Changes in frequency, clinical spectrum and prognostic factors.

INTRODUCTION: Listeria monocytogenes infection is a severe disease affecting mainly aged people and patients with immune depression. The incidence of listeriosis seems to be increasing. In the present study cases of listeriosis from two hospitals are analyzed with the aims of studying changes in its incidence, clinical forms of presentation and possible factors associated with mortality. METHODS: Retrospective multicentric study of patients with culture-proven listeriosis in two university hospitals in Madrid between 1977 and 2021. Epidemiological and clinical variables, as well as factors for immune depression, complementary studies and treatments were registered. Factors associated with mortality were analyzed. RESULTS: A total of 194 cases of listeriosis were analyzed. The incidence of listeriosis among in-patients increased through the study period, with a significant drop in the number of cases in 2020. The most common clinical presentations were isolated bacteriemia (37.1%) and central nervous system involvement (CNS) (36.6%). Symptoms of gastroenteritis occurred in 21% of cases. Other focal infections were present in 16.5% of patients, the most frequent were spontaneous bacterial peritonitis (8.2%), cholecystitis (2.1%), respiratory infection (1.5%) and vascular prothesis infection (1.5%). In-hospital mortality was 24.7%. Independent factors associated with mortality at admission were age (Odds Ratio [OR] 1.027, 95% confidence interval [IC95%] 1.003-1.056) and a diagnosis of a solid tumor (OR 3.525, IC95% 1.652-7.524). CONCLUSIONS: This study confirms an increasing incidence of listeriosis in our millieu. The most common clinical presentations were isolated bacteriemia and central nervous system involvement. In-hospital mortality was associated with age and the diagnosis of a solid tumor.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Streptococcus bovis infection of the central nervous system in adults: Report of 4 cases and literature review.

OBJECTIVES: To describe the clinical features, history and association with intestinal disease in central nervous system (CNS) S. bovis infections. METHODS: Four cases of S. bovis CNS infections from our institution are presented. Additionally a systematic literature review of articles published between 1975 and 2021 in PubMed/MEDLINE was conducted. RESULTS: 52 studies with 65 cases were found; five were excluded because of incomplete data. In total 64 cases were analyzed including our four cases: 55 with meningitis and 9 with intracranial focal infections. Both infections were frequently associated with underlying conditions (70.3%) such as immunosuppression (32.8%) or cancer (10.9%). In 23 cases a biotype was identified, with biotype II being the most frequent (69.6%) and S. pasteurianus the most common within this subgroup. Intestinal diseases were found in 60.9% of cases, most commonly neoplasms (41.0%) and Strongyloides infestation (30.8%). Overall mortality was 17.1%, with a higher rate in focal infection (44.4% vs 12.7%; p=0.001). CONCLUSIONS: CNS infections due to S. bovis are infrequent and the most common clinical form is meningitis. Compared with focal infections, meningitis had a more acute course, was less associated with endocarditis and had a lower mortality. Immunosuppression and intestinal disease were frequent in both infections.

Risk stratification for CNS infection: A potential tool to avoid unwarranted lumbar punctures - An observational study.

OBJECTIVE: Central nervous system (CNS) infection poses a diagnostic challenge especially in elderly patients who frequently exhibit atypical symptoms. Our study aimed to identify patients with a low risk of CNS infection, in whom lumbar puncture (LP) could be avoided. METHODS: Observational study of consecutive adult patients who underwent a LP in the emergency room (ER) of Hospital Universitari Vall d'Hebron between January 2017 and December 2021. We performed a univariate and multivariate analysis to identify factors associated with non-CNS infection. These factors were used to create a combined variable, and its diagnostic positive predictive value and specificity to detect patients without CNS infections were calculated. RESULTS: We included 489 patients of which 77 (15.7%) were diagnosed with CNS infection. Median age was 62 years (IQR 41-78) and 240 (49.1%) were male. In the multivariate analysis, variables associated with non-CNS infection were female sex (OR 1.89; 95% CI 1.12-3.20), age older than 80 years (OR 3.14; 95% CI 1.20-8.19), previous cognitive impairment (OR 3.91; 95% CI 1.18-13.01), and clinical presentation without meningitis triad (fever, headache and neck stiffness) (OR 4.12; 95% CI 1.72-9.85). A composite variable encompassing age older than 80, cognitive impairment, and the absence of the meningitis triad was used as a diagnostic tool to identify patients with non-CNS infection, exhibiting a 98% positive predictive value and 99% specificity. CONCLUSIONS: This study identifies factors associated with a low risk of CNS infection. Thus, a more precise clinical approach could help clinicians to detect patients who would not benefit from a LP.

[Lung-brain interaction in the mechanically ventilated patient]. / Interacción pulmón-cerebro en el paciente ventilado mecánicamente.

Patients with acute lung injury or acute respiratory distress syndrome (ARDS) admitted to the ICU present neuropsychological alterations, which in most cases extend beyond the acute phase and have an important adverse effect upon quality of life. The aim of this review is to deepen in the analysis of the complex interaction between lung and brain in critically ill patients subjected to mechanical ventilation. This update first describes the neuropsychological alterations occurring both during the acute phase of ICU stay and at discharge, followed by an analysis of lung-brain interactions during mechanical ventilation, and finally explores the etiology and mechanisms leading to the neurological disorders observed in these patients. The management of critical patients requires an integral approach focused on minimizing the deleterious effects over the short, middle or long term.

[Fusarium meningoencephalitis in the late puerperium: A case report]. / Meningoencefalitis por Fusarium en puerperio tardío: reporte de caso.

Background: Fusarium infection in the central nervous system is a rare pathology generally reported in patients with hematological malignancies. Clincal case: A patient with Fusarium meningoencephalitis during the late postpartum period is presented. The patient's main symptom was holocranial headache with poor response to analgesics, adding dysarthria and blurred vision. Initially, it was classified as aseptic meningitis due to the absence of bacterial isolation, however, 8 weeks after the onset of the symptoms, Fusarium development was obtained in cerebrospinal fluid cultures. Targeted treatment with liposomal amphotericin and voriconazole was established, with partial improvement at first; however, at 16 weeks from the onset of the clinical picture, the patient presented sudden deterioration of alertness, an ischemic area was found in the occipital lobe by imaging study, which quickly led the patient to a fatal outcome. Conclusion: Despite the fact that in recent years Fusarium spp infection has been detected more frequently in the population, the treatment is still not well established, making management of the Central Nervous System a challenge.

Introducción: la infección por Fusarium en el sistema nervioso central es una patología rara, reportada generalmente en pacientes con neoplasias hematológicas. Caso clínico: se presenta una paciente con meningoencefalitis por Fusarium durante el periodo de puerperio tardío. El síntoma principal de la paciente fue cefalea holocraneana con baja respuesta a analgésicos, agregándose disartria y visión borrosa. De manera inicial, se catalogó como meningitis aséptica por ausencia de aislamiento bacteriano, no obstante, a las 8 semanas posterior al inicio del cuadro se obtuvo desarrollo de Fusarium en los cultivos de líquido cefalorraquídeo. Se estableció tratamiento dirigido con anfotericina liposomal y voriconazol, con mejoría parcial en un inicio; sin embargo, la paciente a las 16 semanas desde el inicio del cuadro clínico presentó deterioro súbito del estado de alerta, se evidenció zona isquémica en el lóbulo occipital por estudio de imagen, lo que rápidamente llevó a la paciente a un desenlace fatal. Conclusión: a pesar de que en los últimos años la infección por Fusarium spp se ha detectado con mayor frecuencia en la población, el tratamiento aún no se encuentra bien establecido ocasionando que sea un reto el manejo en Sistema Nervioso Central.

Scedosporium boydii finding in an immunocompromised patient and review of the literature.

BACKGROUND: Scedosporiasis is an emerging mycosis that has gained importance in recent years due to its worldwide prevalence. It is caused by species of the Scedosporium apiospermum complex. These species can cause opportunistic infections in immunocompromised patients and, occasionally, in immunocompetent patients as well. The high intrinsic antifungal resistance make these infections difficult to manage. AIMS: The objective of this study was to interpret the mycological findings in a transplant patient, together with the images obtained in the radiological studies, in order to provide an early and effective antifungal therapy. METHODS: The mycological analysis of samples taken from a heart transplant patient with radiological images suggesting a fungal infection was performed. Computed tomography scan of the head and thorax showed space-occupying lesions in both the frontal lobe and cerebellum, and multiple pulmonary nodules. The nodules were punctured and the samples obtained were analyzed according to the procedures for mycological analysis. The identity of the isolates was confirmed by nucleotide sequencing. Eventually, the antifungal susceptibility was studied. RESULTS: The fungal isolates obtained, whose identity was confirmed by sequencing, belonged to the species Scedosporium boydii. Injured tissues were surgically removed and a treatment with amphotericin B and voriconazole-minimum inhibitory concentration (MIC) 0.5µg/mL and ≥0.5µg/mL respectively - was administered. CONCLUSIONS: Although the patient died due to complications of a Klebsiella pneumoniae sepsis refractory to treatment, the progression of the fungal disease, although slow, was favourable in the early phases of the treatment due to a correct diagnosis and the antifungal susceptibility test carried out. Clinical cases of this nature highlight the need to increase the epidemiological study of these microorganisms, as well as the proper treatment of the diseases caused, in order to achieve early diagnoses that reduce the morbidity and mortality of patients.

Primary central nervous system vasculitis: A diagnostic and therapeutic challenge. A series of 7 patients.

INTRODUCTION: Primary central nervous system vasculitis (PCNSV) is a rare disease affecting medium- and small-calibre blood vessels of the central nervous system. OBJECTIVE: The aim of this study was to analyse clinical findings and diagnostic aspects, with special attention to histopathological findings, as well as the treatments used and treatment response in patients diagnosed with PCNSV at our hospital. PATIENTS AND METHODS: We conducted a retrospective descriptive analysis of patients with a diagnosis of PCNSV at discharge from our centre and meeting the 1988 Calabrese criteria. To this end, we analysed the hospital discharge records of Hospital General Universitario de Castellón between January 2000 and May 2020. RESULTS: We analysed a series of 7 patients who were admitted with transient focal alterations and other less specific symptoms such as headache or dizziness; diagnosis was based on histological findings in 5 cases and on suggestive arteriographic findings in the remaining 2. Neuroimaging results were pathological in all cases, and CSF analysis detected alterations in 3 of the 5 patients who underwent lumbar puncture. All patients received initial treatment with megadoses of corticosteroids followed by immunosuppressive treatment. Progression was unfavourable in 6 cases, with fatal outcomes in 4. CONCLUSIONS: Despite the diagnostic challenge of PCNSV, it is essential to attempt to reach a definitive diagnosis using such tools as histopathology and/or arteriography studies, in order to promptly establish appropriate treatment and thus reduce the morbidity and mortality of this condition.

Hypertrophic pachymeningitis due to IgG4-related disease (RD-IgG4). A case report.

INTRODUCTION: Hypertrophic pachymeningitis (HP) is a clinico-radiological entity characterized by a thickening of the dura mater that may be focal or diffuse and manifested by a variety of neurological syndromes. Aetiologically, it is classified as infectious, neoplastic, autoimmune, and idiopathic. Many of these formerly idiopathic cases have been shown to fall into the spectrum of IgG4-related disease. OBJECTIVE: To describe the case of a patient attended for neurological involvement due to hypertrophic pachymeningitis with initial diagnosis of inflammatory myofibroblastic tumour and final diagnosis of IgG4-related disease. CASE: A 25-year-old woman with neurological symptoms of 3 years' evolution characterized initially by right hypoacusis, evolving with headache and diplopia. Magnetic resonance imaging (MRI) of the encephalon showed pachymeningeal thickening with involvement of vasculo-nervous structures in the tip of the cerebellum, cavernous sinus, ragged foramen, and optic chiasm. The patient presented for consultation with the result of an incisional biopsy that reported a proliferative lesion combining fibrous elements of fascicular or swirling arrangement with collagenized streaks with dense, lymphoplasmacytic infiltrate and some macrophages, with negative staining for ALK 1, with a diagnosis of inflammatory myofibroblastic tumour. Due to suspicion of IgG4-related disease (IgG4-RD) the biopsy was sent for review and pertinent complementary studies were requested. BIOPSY REVIEW: Non storiform fibrosis, predominantly lymphoplasmacytic infiltrate, histiocytes, and polymorphonuclear infiltrate in sectors, without granulomas or atypia. Staining for germs negative. Immunohistochemistry with 50-60 IgG4+/HPF cells and range of 15%-20%, CD68+ in histiocytes, CD1a-, S100-. The patient presented deterioration of visual acuity due to ophthalmic nerve involvement, so glucocorticoid treatment was started in pulses and rituximab with regression of symptoms and imaging improvement of the lesions. CONCLUSION: HP is a clinical imaging syndrome with variable symptoms and aetiologies that poses a diagnostic challenge. In this case the initial diagnosis was inflammatory myofibroblastic tumour, which is a neoplasm of variable behaviour, locally aggressive, and can metastasize; it is one of the main differential diagnoses of IgG4-related disease because they share anatomopathological features, including storiform fibrosis. IgG4-RD is an immune-mediated condition that can have single or multiple involvement. Its diagnosis is complex when it presents with single organ involvement or in non-typical organs (CNS, meninges) in which data are scarce, as in the case of our patient with single organ involvement of the CNS. Although there are classification criteria to guide non-specialists in the diagnosis, the sum of the clinical picture, imaging, laboratory, pathological anatomy, and immunohistochemistry will always be evaluated together for a definitive diagnosis.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients.