Syndrome and outcome of antibody-negative limbic encephalitis.

BACKGROUND AND PURPOSE: The aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: The clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell-based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. RESULTS: Twelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short-term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm3 (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. CONCLUSIONS: Despite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy.

Understanding the effects of different HIV transmission models in individual-based microsimulation of HIV epidemic dynamics in people who inject drugs.

We investigated how different models of HIV transmission, and assumptions regarding the distribution of unprotected sex and syringe-sharing events ('risk acts'), affect quantitative understanding of HIV transmission process in people who inject drugs (PWID). The individual-based model simulated HIV transmission in a dynamic sexual and injecting network representing New York City. We constructed four HIV transmission models: model 1, constant probabilities; model 2, random number of sexual and parenteral acts; model 3, viral load individual assigned; and model 4, two groups of partnerships (low and high risk). Overall, models with less heterogeneity were more sensitive to changes in numbers risk acts, producing HIV incidence up to four times higher than that empirically observed. Although all models overestimated HIV incidence, micro-simulations with greater heterogeneity in the HIV transmission modelling process produced more robust results and better reproduced empirical epidemic dynamics.

Impaired health status and increased incidence of diseases in Toxoplasma-seropositive subjects - an explorative cross-sectional study.

The global seroprevalence of latent toxoplasmosis is estimated to be higher than 30%. The presence of slowly dividing parasites in tissue cysts located mainly in immunoprivileged organs was long considered asymptomatic. Recently, many studies have shown that latent Toxoplasma infections could have serious impacts on human health. Here we ran a cross-sectional study in a population of 1486 volunteers. The results showed that 333 infected subjects scored worse than 1153 controls in 28 of 29 health-related variables. Similarly, they reported higher rates of 77 of a list of 134 disorders reported by at least 10 participants of the study. Toxoplasmosis was associated most strongly with musculoskeletal (τ = 0·107, P < 0·0005), followed by neurological (τ = 0·088, P < 0·0005), immune (τ = 0·085, p < 0·0005), metabolic (τ = 0·079, P < 0·0005), respiratory (τ = 0·068, P = 0·0001), allergic (τ = 0·053, P = 0·004), digestive system (τ = 0·052, P = 0·004) and mental health disorders (τ = 0·050, P = 0·008). Results of the present cohort study, along with the previous data from many case-control studies or ecological studies suggest that latent toxoplasmosis represents a large and so far underrated public health problem.

Intensive care practices in brain death diagnosis and organ donation.

We conducted a multicentre study of 1844 patients from 42 Spanish intensive care units, and analysed the clinical characteristics of brain death, the use of ancillary testing, and the clinical decisions taken after the diagnosis of brain death. The main cause of brain death was intracerebral haemorrhage (769/1844, 42%), followed by traumatic brain injury (343/1844, 19%) and subarachnoid haemorrhage (257/1844, 14%). The diagnosis of brain death was made rapidly (50% in the first 24 h). Of those patients who went on to die, the Glasgow Coma Scale on admission was ≤ 8/15 in 1146/1261 (91%) of patients with intracerebral haemorrhage, traumatic brain injury or anoxic encephalopathy; the Hunt and Hess Scale was 4-5 in 207/251 (83%) of patients following subarachnoid haemorrhage; and the National Institutes of Health Stroke Scale was ≥ 15 in 114/129 (89%) of patients with strokes. Brain death was diagnosed exclusively by clinical examination in 92/1844 (5%) of cases. Electroencephalography was the most frequently used ancillary test (1303/1752, 70.7%), followed by transcranial Doppler (652/1752, 37%). Organ donation took place in 70% of patients (1291/1844), with medical unsuitability (267/553, 48%) and family refusal (244/553, 13%) the main reasons for loss of potential donors. All life-sustaining measures were withdrawn in 413/553 of non-donors (75%).

Intensive care medicine and organ donation: exploring the last frontiers?

The main, universal problem for transplantation is organ scarcity. The gap between offer and demand grows wider every year and causes many patients in waiting list to die. In Spain, 90% of transplants are done with organs taken from patients deceased in brain death but this has a limited potential. In order to diminish organ shortage, alternative strategies such as donations from living donors, expanded criteria donors or donation after circulatory death, have been developed. Nevertheless, these types of donors also have their limitations and so are not able to satisfy current organ demand. It is necessary to reduce family denial and to raise donation in brain death thus generalizing, among other strategies, non-therapeutic elective ventilation. As intensive care doctors, cornerstone to the national donation programme, we must consolidate our commitment with society and organ transplantation. We must contribute with the values proper to our specialization and try to reach self-sufficiency by rising organ obtainment.

Transcranial Doppler ultrasound in the diagnosis of brain death. Is it useful or does it delay the diagnosis?

Transcranial Doppler ultrasound is able to demonstrate cerebral circulatory arrest associated to brain death, being especially useful in sedated patients, or in those in which complete neurological exploration is not possible. Transcranial Doppler ulstrasound is a portable, noninvasive and high-availability technique. Among its limitations, mention must be made of the absence of acoustic windows and false-negative cases. In patients clinically diagnosed with brain death, with open skulls or with anoxia as the cause of death, cerebral blood flow can be observed by ultrasound, since cerebral circulatory arrest is not always synchronized to the clinical diagnosis. The diagnostic rate is therefore time-dependent, and this fact that must be recognized in order to avoid delays in death certification. Despite its limitations, transcranial Doppler ulstrasound helps solve common diagnostic problems, avoids the unnecessary consumption of resources, and can optimize organ harvesting for transplantation.

Cranioplasty with bandaging. New forms of limitation of life support and organ donation.

Most of transplanted organs are obtained from brain death (BD) donors. In neurocritical patients with catastrophic injuries and decompressive craniectomy (DC), which show a dreadful development in spite of this treatment, DC could be a futile tool to avoid natural progress to BD. We propose if cranial compressive bandage (cranioplasty with bandage) could be an ethically correct practice, similar to other life-sustaining treatment limitation (LSTL) common methods. Based on a clinical case, we contacted with the Assistance Ethics Committee and some bioethics professionals asking them two questions: 1) Is ethically correct to perform a cranioplasty with bandage in those patients with LSTL indication? 2) Thinking in organ donation possibility, is this option preferable? Conclusions 1) Cranioplasty with bandage could be considered an ethically acceptable LSTL practice, similar to other procedures. 2) It facilitates organ donation for transplant, which provides value-added because of its own social good. 3) In these cases, it is necessary to know previous patient's will or, in absentia, to obtain family consent after a detailed procedure report.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Clinico-radiological related to early brain death factors.

OBJECTIVE: To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 h. DESIGN: A retrospective cohort study was made covering the period 2015-2017. SETTING: An adult Intensive Care Unit (ICU). PATIENTS/METHODS: Epidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD. RESULTS: A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD > 24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD > 24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD > 24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups. CONCLUSIONS: Early BD (>24 h) was associated to GCS < 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation.

Is there progressive cognitive dysfunction in Sjögren Syndrome? A preliminary study.

OBJECTIVE: The aim of this study was to determine the progression of cognitive dysfunction in primary Sjögren Syndrome (SS). METHODS: Twelve subjects with SS were compared with ten subjects with migraine and ten healthy controls on neuropsychological, mood and fatigue tests at baseline and 8 years later. RESULTS: At follow-up, SS subjects performed below subjects with migraine on the Continuous Performance Test (CPT) but did not differ on other tasks. Compared with controls, both clinical groups obtained lower scores on simple reaction time, patients with SS obtained lower scores on the Wisconsin Card Sorting Test (WCST) and patients with migraine performed below controls on the Benton's Judgment of Line Orientation Test (JOLO). Clinical groups did not differ on cognitive changes over time, except that migraine subjects improved on verbal fluency. Compared with baseline, both SS and migraine patients were more impaired on simple reaction time, Trail Making Test part B, Stroop and JOLO. However, they showed higher scores on verbal and visual memory, WCST and CPT reaction time. SS also showed higher levels of depression and fatigue than migraine and controls, with no significant changes over time. DISCUSSION: Preliminary evidence indicates some cognitive deficits in both SS and migraine following a pattern of fronto-subcortical dysfunction without a significant cognitive decline over time.

Clinico-radiological related to early brain death factors. / Factores clínico-radiológicos asociados con muerte encefálica precoz.

OBJECTIVE: To identify clinical and radiological factors associated to early evolution to brain death (BD), defined as occurring within the first 24 hours. DESIGN: A retrospective cohort study was made covering the period 2015-2017. SETTING: An adult Intensive Care Unit (ICU). PATIENTS/METHODS: Epidemiological, clinical and imaging (CT scan) parameters upon admission to the ICU in patients evolving to BD. RESULTS: A total of 166 patients with BD (86 males, mean age 62.7 years) were analyzed. Primary cause: intracerebral hemorrhage 42.8%, subarachnoid hemorrhage 18.7%, traumatic brain injury 17.5%, anoxia 9%, stroke 7.8%, other causes 4.2%. Epidemiological data: arterial hypertension 50%, dyslipidemia 34%, smoking 33%, antiplatelet medication 21%, alcoholism 19%, anticoagulant therapy 15%, diabetes 15%. The Glasgow Coma Score (GCS) upon admission was 3 in 68.8% of the cases in early BD versus in 38.2% of the cases in BD occurring after 24 h (p = 0.0001). Eighty-five patients presented supratentorial hematomas with a volume of 90.9 ml in early BD versus 82.7 ml in BD >24 h (p = 0.54). The mean midline shift was 10.7 mm in early BD versus 7.8 mm in BD >24 h (p = 0.045). Ninety-one patients presented ventriculomegaly and 38 additionally ependymal transudation (p = 0.021). Thirty-six patients with early BD versus 24 with BD >24 h presented complete effacement of basal cisterns (p = 0.005), sulcular effacement (p = 0.013), loss of cortico-subcortical differentiation (p = 0.0001) and effacement of the suprasellar cistern (p = 0.005). The optic nerve sheath measurements showed no significant differences between groups. CONCLUSIONS: Early BD (>24 h) was associated to GCS < 5, midline shift, effacement of the basal cisterns, cerebral sulci and suprasellar cistern, and ependymal transudation.

Prospective multicentre study of rectal carriage of multidrug-resistant Enterobacteriaceae among health-care workers in Spain.

OBJECTIVES: To investigate the rectal carriage of multidrug-resistant Enterobacteriaceae (colistin-resistant, extended-spectrum ß-lactamase (ESBL) -producers and/or carbapenemase-producers) among health-care workers (HCWs) from six Spanish hospitals. METHODS: Rectal swabs from 258 HCWs, employed in intensive care units, haematology wards and clinical microbiology laboratories from six hospitals in northern Spain were studied. They were cultured in selective media for Gram-negative resistant bacteria. Detection of antimicrobial resistance genes and multilocus sequence typing were performed by PCR and further sequencing. A questionnaire including data related to risk factors of colonization/infection by resistant bacteria (age, gender, chronic diseases, immunosuppressive therapies, invasive procedures or antimicrobial treatments) was given to each participant. RESULTS: No carbapenemase-producing Enterobacteriaceae were recovered. However, 8/258 HCWs (3.1%) were positive for ESBL-producing isolates. This rate was not higher than the colonization rate previously reported in Spain for healthy people in the community. Five isolates showed high-level resistance to colistin (MICs ranging from 8 to 128 mg/L) but all of them were negative for the mcr genes tested. No statistically significant risk factors for gut colonization by ESBL-producing or colistin-resistant Enterobacteriaceae were identified among the HCWs participating in the study. CONCLUSIONS: Our data suggest that working in hospitals does not represent a risk for rectal carriage of multidrug-resistant Enterobacteriaceae.