Molecular responses to ocean acidification in an Antarctic bivalve and an ascidian.

Southern Ocean organisms are considered particularly vulnerable to Ocean acidification (OA), as they inhabit cold waters where calcite-aragonite saturation states are naturally low. It is also generally assumed that OA would affect calcifying animals more than non-calcifying animals. In this context, we aimed to study the impact of reduced pH on both types of species: the ascidian Cnemidocarpa verrucosa sp. A, and the bivalve Aequiyoldia eightsii, from an Antarctic fjord. We used gene expression profiling and enzyme activity to study the responses of these two Antarctic benthic species to OA. We report the results of an experiment lasting 66 days, comparing the molecular mechanisms underlying responses under two pCO2 treatments (ambient and elevated pCO2). We observed 224 up-regulated and 111 down-regulated genes (FC ≥ 2; p-value ≤ 0.05) in the ascidian. In particular, the decrease in pH caused an upregulation of genes involved in the immune system and antioxidant response. While fewer differentially expressed (DE) genes were observed in the infaunal bivalve, 34 genes were up-regulated, and 69 genes were downregulated (FC ≥ 2; p-value ≤ 0.05) in response to OA. We found downregulated genes involved in the oxidoreductase pathway (such as glucose dehydrogenase and trimethyl lysine dioxygenase), while the heat shock protein 70 was up-regulated. This work addresses the effect of OA in two common, widely distributed Antarctic species, showing striking results. Our major finding highlights the impact of OA on the non-calcifying species, a result that differ from the general trend, which describes a higher impact on calcifying species. This calls for discussion of potential effects on non-calcifying species, such as ascidians, a diverse and abundant group that form extended three-dimensional clusters in shallow waters and shelf areas in the Southern Ocean.

Neonatal immune challenge influences the microbiota and behaviour in a sexually dimorphic manner.

There is comorbidity between anxiety disorders and gastrointestinal disorders, with both linked to adverse early life events. The microbiome gut-brain-axis, a bidirectional communication system, is plastic throughout the neonatal period and is a possible mediator of this relationship. Here, we used a well-established neonatal rodent immune activation model to investigate the long-term effect of neonatal lipopolysaccharide (LPS) exposure on adult behaviour and the relationship to microbiome composition. Wistar rats were injected with LPS (0.05 mg/kg) or saline (equivolume) on postnatal days 3 and 5. In adulthood, behavioural tests were performed to assess anxiety-like behaviour, and microbiota sequencing was performed on stool samples. There were distinctly different behavioural phenotypes for LPS-exposed males and females. LPS-exposed males displayed typical anxiety-like behaviours with significantly decreased social interaction (F(1,22) = 7.576, p = 0.009) and increased defecation relative to saline controls (F(1,23) = 8.623, p = 0.005). LPS-exposed females displayed a different behavioural phenotype with significantly increased social interaction (F(1,22) = 6.094, p = 0.018), and exploration (F(1,24) = 6.359, p = 0.015), compared to saline controls. With respect to microbiota profiling data, Bacteroidota was significantly increased for LPS-exposed females (F(1,14) = 4.931p = 0.035) and Proteobacteria was decreased for LPS-exposed rats of both sexes versus controls (F(1,30) = 4.923p = 0.035). Furthermore, alterations in predicted functional pathways for neurotransmitters in faeces were observed with a decrease in the relative abundance of D-glutamine and D-glutamate metabolism in LPS exposed females compared to control females (p < 0.05). This suggests that neonatal immune activation alters both later life behaviour and adult gut microbiota in sex-specific ways. These findings highlight the importance of sex in determining the impact of neonatal immune activation on social behaviour and the gut microbiota.

Maternal immune activation in mid-late gestation alters amphetamine sensitivity and object recognition, but not other schizophrenia-related behaviours in adult rats.

Maternal immune activation induced by Poly(I:C) administration is one of the most commonly used animal models of schizophrenia at present. Previous work from our team has demonstrated that some, but not all of the features often reported for maternal immune activation exposure in rodents can be observed in rats exposed to maternal immune activation at mid or late gestation. To determine whether previous findings in our laboratory were due to these time points simply being less sensitive neurodevelopmental periods for rats with regard to maternal immune activation effects, we aimed to investigate whether maternal immune activation at an often-reported sensitive period (mid-late gestation, day 14) resulted in more behavioural features reflective of face validity for schizophrenia. We examined the behavioural outcomes of mid-late maternal immune activation on a battery of behavioural tests aimed at assessing validity for positive, negative and cognitive symptoms of schizophrenia. We found that rats exposed to maternal immune activation, compared to controls, exhibited enhanced sensitivity to the locomotor-stimulating effects of amphetamine and reduced exploration of novel objects. These findings present a unique profile of effects, different to what has already been established for the same time point in rats, and different to what we had found at earlier and later time points. This work, among others in the literature, highlights the varying nature of models of maternal immune activation and we submit that it is essential for laboratories to characterise their models of maternal immune activation on behaviour rather than assuming that the effects from one laboratory apply in their own.

Ethical Use and Impact of Participatory Approaches to Research in Post-Disaster Environments: An Australian Bushfire Case Study.

This paper presents a case study of Beyond Bushfires, a large, multisite, mixed method study of the psychosocial impacts of major bushfires in Victoria, Australia. A participatory approach was employed throughout the study which was led by a team of academic investigators in partnership with service providers and government representatives and used on-site visits and multiple methods of communication with communities across the state to inform decision-making throughout the study. The ethics and impacts of conducting and adapting the approach within a post-disaster context will be discussed in reference to theories and models of participatory health research. The challenges of balancing local interests with state-wide implications will also be explored in the description of the methods of engagement and the study processes and outcomes. Beyond Bushfires demonstrates the feasibility of incorporating participatory methods in large, post-disaster research studies and achieving rigorous findings and multilevel impacts, while recognising the potential for some of the empowering aspects of the participatory experience to be reduced by the scaled-up approach.

Altered cerebral glucose metabolism normalized in a patient with a pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS)-like condition following treatment with plasmapheresis: a case report.

BACKGROUND: Pediatric autoimmune neuropsychiatric disorder after streptococcal infection (PANDAS) is a specific autoimmune response to group-A streptococcal infections in children and adolescents with a sudden onset of obsessive-compulsive disorders or tic-like symptoms. Cerebral metabolic changes of patients have not yet been observed. CASE PRESENTATION: We present a case of an 18-year old male with a PANDAS-like condition after developing tic-like symptoms and involuntary movements three weeks after cardiac surgery. The patient had suffered from pharyngotonsillitis before the symptoms started. The anti-streptolysin O (ASO) titer was elevated (805 kU/l). Antibiotic therapy did not improve his condition. Intravenous immunoglobulins and high-dose cortisone therapy had minor beneficial effects on his involuntary movements. 18F-Fluorodeoxyglucose positron emission tomography/ computer tomography (18F-FDG PET/CT) demonstrated pronounced hypermetabolism of the basal ganglia and cortical hypometabolism. The patient was treated with five cycles of plasmapheresis. A marked clinical improvement was observed after four months. Cerebral metabolic alterations had completely normalized. CONCLUSIONS: This is the first report of cerebral metabolic changes observed on FDG-PET/CT in a patient with a PANDAS-like condition with a normalization following immunomodulatory treatment. Cerebral FDG-PET/CT might be a promising tool in the diagnosis of PANDAS.

Late deviance detection in rats is reduced, while early deviance detection is augmented by the NMDA receptor antagonist MK-801.

One of the most robust electrophysiological features of schizophrenia is reduced mismatch negativity, a component of the event related potential (ERP) induced by rare and unexpected stimuli in an otherwise regular pattern. Emerging evidence suggests that mismatch negativity (MMN) is not the only ERP index of deviance detection in the mammalian brain and that sensitivity to deviant sounds in a regular background can be observed at earlier latencies in both the human and rodent brain. Pharmacological studies in humans and rodents have previously found that MMN reductions similar to those seen in schizophrenia can be elicited by N-methyl-d-aspartate (NMDA) receptor antagonism, an observation in agreement with the hypothesised role of NMDA receptor hypofunction in schizophrenia pathogenesis. However, it is not known how NMDA receptor antagonism affects early deviance detection responses. Here, we show that NMDA antagonism impacts both early and late deviance detection responses. By recording EEG in awake, freely-moving rats in a drug-free condition and after varying doses of NMDA receptor antagonist MK-801, we found the hypothesised reduction of deviance detection for a late, negative potential (N55). However, the amplitude of an early component, P13, as well as deviance detection evident in the same component, were increased by NMDA receptor antagonism. These findings indicate that late deviance detection in rats is similar to human MMN, but the surprising effect of MK-801 in increasing ERP amplitudes as well as deviance detection at earlier latencies suggests that future studies in humans should examine ERPs over early latencies in schizophrenia and after NMDA antagonism.

Pelagic and benthic communities of the Antarctic ecosystem of Potter Cove: Genomics and ecological implications.

Molecular technologies are more frequently applied in Antarctic ecosystem research and the growing amount of sequence-based information available in databases adds a new dimension to understanding the response of Antarctic organisms and communities to environmental change. We apply molecular techniques, including fingerprinting, and amplicon and metagenome sequencing, to understand biodiversity and phylogeography to resolve adaptive processes in an Antarctic coastal ecosystem from microbial to macrobenthic organisms and communities. Interpretation of the molecular data is not only achieved by their combination with classical methods (pigment analyses or microscopy), but furthermore by combining molecular with environmental data (e.g., sediment characteristics, biogeochemistry or oceanography) in space and over time. The studies form part of a long-term ecosystem investigation in Potter Cove on King-George Island, Antarctica, in which we follow the effects of rapid retreat of the local glacier on the cove ecosystem. We formulate and encourage new approaches to integrate molecular tools into Antarctic ecosystem research, environmental conservation actions, and polar ocean observatories.

Pyrosequencing and de novo assembly of Antarctic krill (Euphausia superba) transcriptome to study the adaptability of krill to climate-induced environmental changes.

The Antarctic krill, Euphausia superba, has a key position in the Southern Ocean food web by serving as direct link between primary producers and apex predators. The south-west Atlantic sector of the Southern Ocean, where the majority of the krill population is located, is experiencing one of the most profound environmental changes worldwide. Up to now, we have only cursory information about krill's genomic plasticity to cope with the ongoing environmental changes induced by anthropogenic CO2 emission. The genome of krill is not yet available due to its large size (about 48 Gbp). Here, we present two cDNA normalized libraries from whole krill and krill heads sampled in different seasons that were combined with two data sets of krill transcriptome projects, already published, to produce the first knowledgebase krill 'master' transcriptome. The new library produced 25% more E. superba transcripts and now includes nearly all the enzymes involved in the primary oxidative metabolism (Glycolysis, Krebs cycle and oxidative phosphorylation) as well as all genes involved in glycogenesis, glycogen breakdown, gluconeogenesis, fatty acid synthesis and fatty acids ß-oxidation. With these features, the 'master' transcriptome provides the most complete picture of metabolic pathways in Antarctic krill and will provide a major resource for future physiological and molecular studies. This will be particularly valuable for characterizing the molecular networks that respond to stressors caused by the anthropogenic CO2 emissions and krill's capacity to cope with the ongoing environmental changes in the Atlantic sector of the Southern Ocean.

Parental experiences of their infant's hospitalization for cardiac surgery.

BACKGROUND: Parents are increasingly recognized as important partners in children's health care. Despite their involvement in care, parental experiences of their child's hospitalization have received little research attention. In this study we explored parents' perceptions of what they found difficult, what they would like to be different and what they found to be helpful during their infant's hospitalization and surgery for the treatment of congenital heart disease. METHODS: Structured interviews were conducted with 154 parents (91 mothers, 63 fathers) whose infant underwent cardiac surgery (at <3 months of age) 1 month post discharge from hospital. Thematic and frequency analyses were performed. RESULTS: Parents reported a range of difficulties from dealing with their baby's unfolding illness, surgery and recovery to the structural and systemic issues associated with the broader context of their experiences. In an effort to be near their baby, parents struggled to obtain the necessities for daily living at the hospital and negotiate transitions between their hospital and home lives throughout the admission. Domains parents identified for change included the availability of facilities and resources and the quantity and quality of information and emotional support. Parents reported relationships with hospital staff as the most common source of support during this challenging time. CONCLUSIONS: Opportunities to improve parents' experiences when their infant is in hospital exist at an organizational level as well as at the clinical level. The significance of parents' relationship with hospital staff indicates the potential for each professional to impact on families' experiences on a daily basis. The range of challenges indicates the scope and need for allied health services.

[Tryptophan immunoadsorption for multiple sclerosis and neuromyelitis optica: therapy option for acute relapses during pregnancy and breastfeeding]. / Tryptophan-Immunadsorption bei Multipler Sklerose und Neuromyelitis optica : Therapieoption bei akuten Schüben in der Schwangerschaft und Stillphase.

BACKGROUND: Approximately 25 % of women with multiple sclerosis (MS) suffer clinically relevant relapses during pregnancy. Almost all disease-modifying drugs are contraindicated in pregnancy. High-dose glucocorticoids have some serious risks, especially within the first trimester. Tryptophan immunoadsorption (IA) provides a safe option to treat MS relapses during pregnancy. OBJECTIVES: In this case series we describe for the first time the use of tryptophan IA for MS and neuromyelitis optica (NMO) relapses during pregnancy and breastfeeding. PATIENTS AND METHODS: In this study a total of 9 patients were retrospectively analyzed of which 7 patients received IA treatment during pregnancy, 2 during breastfeeding and 4-6 tryptophan IA treatments were performed per patient with the single use tryptophan adsorber. Primary outcome was symptom improvement of the relapse. RESULTS: In this study four patients with MS and one with NMO relapse during pregnancy were treated with IA without preceding glucocorticoid pulse therapy. The MS patients showed improvement in the expanded disability status scale (EDSS) by at least one point, the NMO patient showed significant improvement in visual acuity and two pregnant patients with steroid-refractory relapses showed clinically relevant improvement after IA. Of the patients two suffered from steroid-refractory relapses during breastfeeding and relapse symptoms improved in both cases after treatment with IA. All treatments were well tolerated and no serious adverse events occurred. CONCLUSION: Tryptophan IA was found to be safe, well-tolerated and effective in the treatment of MS and NMO relapses during pregnancy and breastfeeding, sometimes without preceding glucocorticoid pulse therapy. A binding recommendation is limited without prospective clinical studies.

Volumetric assessment of optic nerve sheath and hypophysis in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a headache syndrome characterized by increased CSF pressure. Compression of the hypophysis and distension of the optic nerve sheath are reliable imaging signs. The purpose of the study was to validate, in patients with idiopathic intracranial hypertension, MR imaging-based volumetric measurements of the optic nerve sheath and hypophysis as an objective observation method for more accurate diagnosis and posttreatment follow-up. MATERIALS AND METHODS: Twenty-three patients with idiopathic intracranial hypertension as well as age-, sex-, and body mass index-matched controls underwent volumetric measurements of the optic nerve, optic nerve sheath, and hypophysis on high-resolution T2-weighted MR images by using a 7-cm surface coil, followed by correlation with CSF opening pressures and clinical symptom scores of visual disturbances and headache. RESULTS: Mean values of optic nerve sheath (341.86 ± 163.69 mm(3) versus 127.56 ± 53.17 mm(3), P < .001) and hypophysis volumes (554.59 ± 142.82 mm(3) versus 686.60 ± 137.84 mm(3), P < .05) differed significantly between healthy and diseased subjects. No significant differences between mean optic nerve volumes were observed. Receiver operating characteristic analysis showed optic nerve sheath volumes of >201.30 mm(3) (sensitivity, 86.96%; specificity, 91.30%) and hypophysis volumes of <611.21 mm(3) (sensitivity, 78.26%; specificity, 69.57%) to be indicative of idiopathic intracranial hypertension diagnosis. In patients with idiopathic intracranial hypertension, no correlations were found between optic nerve sheath and hypophysis volumes and CSF opening pressures or clinical scores of visual disturbances and headache. CONCLUSIONS: Semiautomated volumetric measurement of optic nerve sheath and hypophysis has the potential to more accurately diagnose and follow patients with idiopathic intracranial hypertension.

[Therapeutic apheresis for autoimmune encephalitis: a nationwide data collection]. / Therapeutische Apherese bei autoimmuner Enzephalitis: Eine bundesweite Datenerhebung.

BACKGROUND: The correlation between detection of autoantibodies and the pattern and severity of symptoms in patients with encephalitis was the crucial factor for the initiation of immune therapy. The elimination of autoantibodies using therapeutic apheresis by plasma exchange (PE) and immunoadsorption (IA) is a pathophysiologically guided therapeutic approach. The aim was to evaluate the current use of PE and for the first time also of IA for patients with autoimmune encephalitis. METHODS: A nationwide data collection was performed and the modified Rankin score (mRS) was used to evaluate the severity of neurological symptoms. RESULTS: Data of 31 treatment courses (30 patients and 1 relapse) were documented and 22 patients were positive for autoantibodies (NMDA-R, GABA, VGKC, Hu). In 23 cases PA was performed, tryptophan IA in 7 cases and in 1 patient both methods were applied. In 67 % of the treatment courses the mRS improved and the mean mRS of all patients was 3.2 before apheresis and 2.2 after apheresis (p < 0.05). All patients who were treated with IA improved clinically from a mean mRS of 3.9 before IA to 1.9 after IA (p < 0.01). CONCLUSIONS: For immune-mediated forms of encephalitis rapid elimination of autoantibodies with PA and IA seems to be an effective therapeutic option as part of a multimodal immune therapy and is already established in many clinics in Germany.

[Neurological manifestations in connective tissue disease]. / Neurologische Manifestationen bei Kollagenosen.

In connective tissue diseases, especially systemic lupus erythematosus and Sjögren's syndrome, diverse neurological symptoms and syndromes involving both the central and peripheral nervous system can occur at any stage of the disease. The pathogenesis is diverse. Prevalence figures in the literature vary considerably and the causal relationships are often uncertain. Very often connective tissue diseases must be considered in the differential diagnosis of conditions manifesting with unclear neurological symptoms. Both rheumatologists and neurologists should be familiar with the main neurological signs, symptoms and complications of connective tissue diseases and should recognize the importance of diagnostic testing.

IgA NMDA receptor antibodies are markers of synaptic immunity in slow cognitive impairment.

OBJECTIVE: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. METHODS: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. RESULTS: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. CONCLUSIONS: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.

Immune monitoring of Trichuris suis egg therapy in multiple sclerosis patients.

Initial clinical trials using Trichuris suis eggs (TSO) in autoimmune diseases such as inflammatory bowel disease, revealed a striking suppressive effect on the autoimmune response. Here, we analysed the effect of TSO therapy on the course of multiple sclerosis (MS), as a Th1/Th17-associated autoimmune disease. Different immunological parameters in four patients with secondary progressive MS were surveyed during a 6-month therapy with TSO, focusing on the modulation of T-cell Th1-Th2 balance as well as on the innate immune response. We are able to show a slight downregulation of the Th1-associated cytokine pattern, especially relevant in interleukin (IL)-2 (P < 0.05 after 2 months of therapy), with a temporary increase of Th2-associated cytokines such as IL-4. Furthermore, mild eosinophily and changes in CD4+ and CD8+T cells and natural killer (NK) CD56 bright cell numbers were observed. The findings observed in this group of patients suggest that TSO therapy has a moderate immunomodulatory impact in MS.

Olfactory bulb volume and olfactory function in patients with multiple sclerosis.

BACKGROUND: Some studies reported olfactory dysfunction in patients with multiple sclerosis (MS). There is no agreement about the most suitable testing method for measuring olfactory function (OF) in MS patients. Recent studies showed that olfactory bulb volume changes with the degree of olfactory dysfunction. We assessed olfactory bulb volume of MS patients with magnetic resonance imaging (MRI) and related it to the OF. MATERIAL AND METHODS: Volumetric measurements of the right and left olfactory bulb (OB) were performed by manual segmentation within 36 MS patients. Psychophysical testing of the orthonasal OF was performed using threshold-discrimination-identification (TDI) score in MS patients. RESULTS: Of all MS patients, 44.4% displayed olfactory dysfunction. The TDI score of all 36 MS patients, especially the score of the Identification subtest correlated strongly with neurological scores typical of MS. In patients with a decreased OB volume, there was a positive correlation between volumetry of the OB and OF. CONCLUSION: OB volumes may provide valuable information about MS patients with olfactory dysfunction. The TDI test and Identification subtest were very sensitive in detecting olfactory dysfunction in MS patients.

[Pathological changes of the chemosensory function in multiple sclerosis - an MRI study]. / Pathologische Veränderungen der Chemosensorik mittels Kernspintomografie bei Multipler Sklerose - eine MRT-Studie.

PURPOSE: To examine possible causes for olfactory and gustatory dysfunction in MS patients in a prospective study with MRI. MATERIALS AND METHODS: 30 MS patients (21 women, 11 men, 22 - 65 years, Ø 42 years) were examined by MRI. The olfactory bulb (OB) and olfactory brain volume was correlated with the number and volume of MS lesions in the olfactory brain and the non-olfactory brain. Olfactory testing was performed using the Threshold-Discrimination-Identification Test (TDI), and gustatory function was tested using the Taste-Strips-Test (TST). RESULTS: 33 % of the MS patients displayed olfactory dysfunction (8 % of the control group), and 17 % displayed gustatory dysfunction (5 % of the control group). There was a correlation between the olfactory brain volume and the number (r = -0.38, p < 0.05) and volume (r = -0.38, p < 0.05) of MS lesions in the olfactory brain. The olfactory brain volume correlated with the number of MS lesions in the non-olfactory brain (r = -0.48, p < 0.05). The volume of the left OB correlated with the volume of MS lesions in the olfactory brain (r = -0.42, p < 0.05), the number (r = 0.37, p < 0.05) and volume (r = 0.4, p < 0.05) of lesions in the left part of the olfactory brain and with the TST score (r = -0.45, p < 0.05). The TST score correlated with the volume of lesions in the left (r = -0.45, p < 0.05) and right part (r = -0.53, p < 0.05) of the olfactory brain. The TST score correlated with the number of lesions in the non-olfactory brain (r = -0.48, p < 0.05). CONCLUSION: The correlation between a higher number and volume of MS lesions in the olfactory brain with a decreased OB and olfactory brain volume could help to explain olfactory and gustatory dysfunction in MS patients. Just the left OB correlated with the number and volume of lesions in the olfactory brain. Manual segmentation was a suitable method for measuring OB and olfactory brain volume.

Anesthetic management of a pregnant woman with Gorham-Stout disease.

Gorham-Stout disease is a rare disorder of bone loss and proliferation of lymphatic and vascular tissue (lymphangiomatosis). A 30-year-old nulliparous woman with Gorham-Stout disease presented at 8weeks of gestation with a fused cervical spine. At 31weeks she developed basilar invagination and neurological symptoms that were managed with a neck brace. Anesthetic considerations were those of airway compromise, development of severe preeclampsia and Kasabach-Merritt coagulopathy. Elective tracheostomy was declined. She presented two days before a planned cesarean delivery at 35weeks in preterm labor. A semi-urgent cesarean delivery under spinal anesthetic proceeded uneventfully, with an otolaryngologist present in case a surgical airway was required. Mother and baby were discharged home after three days. Maternal postpartum recovery was complicated by episodes of respiratory compromise and critical bone loss in the cervical spine, necessitating further surgical reinforcement.

Retrospective analysis of NMDA receptor antibodies in encephalitis of unknown origin.

BACKGROUND: Anti-NMDA-receptor (NMDAR) encephalitis is a severe disorder that occurs in association with antibodies to the NR1 subunit of the NMDAR and results in a characteristic syndrome. OBJECTIVE: To determine in a single institution setting whether patients previously diagnosed with encephalitis of unknown origin had anti-NMDAR encephalitis. METHODS: Charts of 505 patients aged 18 to 35 years admitted to the intensive care unit (ICU) during a 5-year period were retrospectively reviewed for criteria of encephalitis of unknown etiology. These included encephalitic signs with psychiatric symptoms (agitation, paranoid thoughts, irritability, or hallucinations); seizures; CSF inflammation; and exclusion of viral or bacterial infection. Archived serum and CSF samples of patients fulfilling these criteria were examined for NMDAR antibodies. Follow-up visits allowed the analysis of the natural disease course and estimation of prognosis. RESULTS: Seven patients (all women) fulfilled the indicated criteria; 6 of them had NMDAR antibodies. Ovarian teratomas were detected in 2 patients, in one 3 years after the onset of encephalitis. Outcome was favorable in all patients. One patient without teratoma improved spontaneously along with disappearance of NMDAR antibodies. CONCLUSIONS: Anti-NMDAR encephalitis represented 1% of all young patients' admissions to the ICU. Six of 7 cases with the indicated clinical criteria had anti-NMDAR encephalitis. NMDAR antibodies should be tested in all patients with encephalitis who fulfill these criteria.