Medicinal cannabis in neurodegenerative disorders: an open label, dose finding, safety and efficacy study.

Aim: Currently, there exist no curative treatments for neurodegenerative disorders. Recently, there has been a resurgence of interest in the use of medicinal cannabis to improve neurological conditions. Methods: A 12-month, open label, dose-finding, safety and efficacy study was conducted including 48 subjects with a variety of neurodegenerative disorders. Results: In our participants, we observed a reduction in pain, improved sleep, enhanced well-being and less agitation. Conclusion: Our findings suggest that medicinal cannabis might be useful in patients with neurodegenerative disorders in controlling pain, enhancing sleep, reducing difficult behaviors, controlling unusual and complex symptoms when other treatments have failed - this offers medicinal cannabis a role in palliation.

Two New Families and a Literature Review of ELOVL4-Associated Spinocerebellar Ataxia Type 34.

Autosomal dominant variants in ELOVL4 cause spinocerebellar ataxia type 34 (SCA34; ATX-ELOVL4), classically associated with a skin condition known as erythrokeratoderma. Here, we report a large Italian-Maltese-Australian family with spinocerebellar ataxia. Notably, while there were dermatological manifestations (eczema), erythrokeratoderma was not present. Using a next-generation sequencing panel, we identified a previously reported ELOVL4 variant, NM_022726.4: c.698C > T p.(Thr233Met). The variant was initially classified as a variant of uncertain significance; however, through segregation studies, we reclassified the variant as likely pathogenic. We next identified an individual from another family (Algerian-Maltese-Australian) with the same ELOVL4 variant with spinocerebellar ataxia but without dermatological manifestations. We subsequently performed the first dedicated literature review of ELOVL4-associated ataxia to gain further insights into genotype-phenotype relationships. We identified a total of 60 reported cases of SCA34 to date. The majority had gait ataxia (88.3%), limb ataxia (76.7%), dysarthria (63.3%), and nystagmus (58.3%). Of note, skin lesions related to erythrokeratoderma were seen in a minority of cases (33.3%). Other extracerebellar manifestations included pyramidal tract signs, autonomic disturbances, retinitis pigmentosa, and cognitive impairment. For brain MRI data, cerebellar atrophy was seen in all cases (100%), whereas the hot cross bun sign (typically associated with multiple system atrophy type C) was seen in 32.4% of cases. Our family study and literature review highlight the variable phenotypic spectrum of SCA34. Importantly, it shows that erythrokeratoderma is not found in most cases and that, while a dermatological assessment may be helpful in these patients, SCA34 diagnosis should be considered irrespective of dermatological manifestations.

Electroencephalography in young onset dementia.

BACKGROUND: Young onset dementia (YOD) is a major diagnostic and management problem. METHODS: We set out to explore if electroencephalography (EEG) might be useful in the diagnosis of young onset Alzheimer's disease (YOAD) and young onset frontotemporal dementia (YOFTD). The ARTEMIS project is a 25-year prospective study of YOD based in Perth, Western Australia. 231 participants were included: YOAD: n = 103, YOFTD: n = 28, controls: n = 100. EEGs were performed prospectively, with 30-minute recording time for each subject, without knowledge of diagnosis or other diagnostic data. RESULTS: 80.9% of patients with YOD had abnormal EEGs (P < 0.00001). Slow wave changes were more frequent in YOAD that YOFTD (P < 0.00001), but no difference in the frequency of epileptiform activity (P = 0.32), with 38.8% of YOAD and 28.6% of YOFTD patients having epileptiform activity. Slow wave changes were more generalized in YOAD (P = 0.001). Slow wave changes and epileptiform activity were not sensitive to the diagnosis of YOD, but highly specific (97-99%). The absence of slow wave changes and epileptiform activity had a 100% negative predictive value and likelihood radio 0.14 and 0.62 respectively, meaning that those without slow wave changes or epileptiform activity had low probability of having YOD. No relationship was established between EEG findings and the patient's presenting problem. Eleven patients with YOAD developed seizures during the study, and only one with YOFTD. CONCLUSIONS: The EEG is highly specific for the diagnosis of YOD with the absence of slow wave changes and epileptiform phenomena making the diagnosis unlikely, with 100% negative predictive value and with low probability for the dementia diagnosis.

Brain Amyloid in Sporadic Young Onset Alzheimer's Disease.

Background: Controversy exists as to the role of the amyloid-ß (Aß) peptide in the pathophysiology of Alzheimer's disease (AD). Objective: To clarify the effect of age on Aß deposition in sporadic AD by exploring the degree of amyloid burden in patients with sporadic young onset AD (YOAD). Methods: Patients were diagnosed with YOAD with dementia starting before the age of 65 years (N = 42; males = 20, females = 22). A cross-sectional analysis of amyloid binding using positron emission tomography (PET) imaging was performed using the C-Pittsburgh Compound B (PiB). The global standardized uptake value ratios (gSUVR) were examined using the Wilcoxon two-sample test, as were the cognitive scores between disease and healthy control populations. Differences in PiB retention in different anatomical areas were compared using the Kruskal-Wallis test. The contrast in APOE genotyping between groups was calculated with Fisher's Exact Test. Results: Women had a median gSUVR = 2.68±0.73 and 73% had at least one APOE ɛ4 allele. Men had gSUVR = 2.37±0.54, with 80% having at least one APOE ɛ4 allele. The gSUVRs were significantly higher than the control populations for men and women and had significantly greater frequency of APOE ɛ4. Men and women analyzed together had significantly greater amyloid burden and APOE ɛ4 allele frequencies than controls, but no differences existed between them in gSUVR nor in the anatomical distribution of amyloid uptake. Conclusion: Men and women with YOAD have greater amyloid uptake than controls and have more APOE ɛ4 alleles. Our findings suggest that the Aß peptide is operational in young onset dementia and driven by the APOE ɛ4 allele.

A global online study of haematopoietic stem cell transplantation in multiple sclerosis and other neurodegenerative disorders.

Background: The objective of this study was to understand the uptake of hemopoietic stem cell transplantation (HSCT) in neuroimmunological disorders like multiple sclerosis (MS). Method: An independent University affiliated research organization conducted a global online survey of people having had HSCT, examining demographics, treatment protocol, and effectiveness. Results: Of 271 participants, useful data were available in 223; women aged 35-54 accounted for 73.5%. Most had a household income greater than US$50,000, and the majority of participants were from Australia and the United States. Nearly 94.6% of people suffer from MS. Most had their treatment in Russia (38.7%) and 78.1% had nonmyeloablative transplants. Nearly half of the participants spent between US$50,000 to US$74,999. There were 54.5% of neurologists who did not support their patients having HSCT. Around 85.5% of participants believed HSCT helped them manage their disease from weeks to years after transplantation, and treatment was recommended by 9.5% of participants. The average reduction in Expanded Disability Status Score after transplantation was 1.2 (95% CI: 0.97-1.41; N = 197; p < 0.01; t: 10.7, df: 196). Conclusion: Participants were supportive of HSCT despite the costs and would recommend it to others. The data suggest some benefit in minimizing disability in MS and provides justification for large randomized controlled trials.

Stochasticity, Entropy and Neurodegeneration.

We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders.

Guillain-Barre syndrome complicating Neisseria meningitidis infection.

Guillain-Barré Syndrome (GBS)-an immune-mediated condition-is the most common cause of acute flaccid paralysis, since the elimination of poliomyelitis. We present a case of GBS as a rare complication of meningococcal meningitis based on clinical features, nerve conduction studies and magnetic resonance imaging (MRI) findings. GBS has rarely been described after meningitis. This case is unique in that our findings show that GBS may be observed after meningococcal meningitis.

Alzheimer's disease, Huntington's disease and cancer.

Neurodegenerative disorders and cancer are two of the most common groups of conditions in our world. Some studies have proposed that neurodegenerative disorders may be protective of the development of cancer. We tested this hypothesis using two neurodegenerative disorders with different molecular pathophysiology - Alzheimer's disease (AD) and Huntington's disease (HD) - to see if the inverse relationship between cancer and neurodegeneration was generalizable. Five-year cancer incidence was determined in two large datasets: AD using the C-Path Online Date Repository (CODR) database (n = 6383) and HD using the ENROLL-HD database (n = 2608). Cancer incidence was determined in the populations and compared to normal population data for Australia, United Kingdom and the United States of America. Age-sex standardized rates of cancer were determined and expressed as 95% confidence intervals. We describe an age-sex standardized cancer rate of 1179.6/per 100,000 population to 1253.7/per 100,000 population in normal populations. The rate in AD was 815.2/per 100,000 population (95% CI 813.32-817.5/per 100,000 population) and for HD 1296.6/per 100,000 population (95% CI 1288-1308.2/per 100,000 population). We conclude that patients with AD have a reduced age-sex standardized rate of developing cancer not shared with HD, a finding that hints at different molecular mechanisms.

The Clinical Spectrum of Young Onset Dementia Points to Its Stochastic Origins.

BACKGROUND: Dementia is a major global health problem and the search for improved therapies is ongoing. The study of young onset dementia (YOD)-with onset prior to 65 years-represents a challenge owing to the variety of clinical presentations, pathology, and gene mutations. The advantage of the investigation of YOD is the lack of comorbidities that complicate the clinical picture in older adults. Here we explore the origins of YOD. OBJECTIVE: To define the clinical diversity of YOD in terms of its demography, range of presentations, neurological examination findings, comorbidities, medical history, cognitive findings, imaging abnormalities both structural and functional, electroencephagraphic (EEG) data, neuropathology, and genetics. METHODS: A prospective 20-year study of 240 community-based patients referred to specialty neurology clinics established to elucidate the nature of YOD. RESULTS: Alzheimer's disease (AD; n = 139) and behavioral variant frontotemporal (bvFTD; n = 58) were the most common causes with a mean age of onset of 56.5 years for AD (±1 SD 5.45) and 57.1 years for bvFTD (±1 SD 5.66). Neuropathology showed a variety of diagnoses from multiple sclerosis, Lewy body disease, FTD-MND, TDP-43 proteinopathy, adult-onset leukoencephalopathy with axonal steroids and pigmented glia, corticobasal degeneration, unexplained small vessel disease, and autoimmune T-cell encephalitis. Non-amnestic forms of AD and alternative forms of FTD were discovered. Mutations were only found in 11 subjects (11/240 = 4.6%). APOE genotyping was not divergent between the two populations. CONCLUSION: There are multiple kinds of YOD, and most are sporadic. These observations point to their stochastic origins.

Making the Right Connections: Maximizing Lexical Generalization in Lexical Impairments in Primary Progressive Aphasia and Alzheimer's Disease.

Purpose Positive intervention effects following lexical retrieval interventions are increasingly reported with people with progressive language impairments; however, generalization of therapy gains are less frequently evident and less well understood. This study sought to explore the impact of specific therapy ingredients on generalization outcomes. Method Twelve participants with progressive lexical retrieval deficits (four each with semantic variant primary progressive aphasia, logopenic variant primary progressive aphasia, and Alzheimer's disease, amnestic presentation) and their family members participated in a 6-week intervention that aimed to increase access to different word classes (nouns, verbs, and adjectives) through a strategic self-cueing approach. Generalization was actively facilitated through strategy practice in connected speech. Repeated baselines of picture naming and connected speech were conducted prior to intervention and repeated immediately post and at 6 weeks following intervention. Results All three diagnostic groups showed significant improvements in naming performance post-intervention for all word classes and for both treated and untreated items, demonstrating consistent treatment effectiveness and generalization at the word level. No changes in the informativeness or efficiency of connected speech were found. Conclusions Despite heterogeneity across participants, widespread evidence of both treatment effects and generalization to untreated items was found for all diagnostic groups and word classes. The consistent within-level generalization across all groups is explored here in relation to optimization of strategy use through incorporation of cognitive scaffolds, strategic practice at the connected speech level, and the inclusion of family members. The absence of across-level generalization to connected speech is also explored. Supplemental Material https://doi.org/10.23641/asha.14219771.

Prion disease in Indigenous Australians.

BACKGROUND: Indigenous Australians are at increased risk of developing dementia - Alzheimer disease and mixed dementia diagnoses are the most common. While prion diseases have been reported in Indigenous peoples of Papua New Guinea and the United States, the occurrence and phenotype of prion disease in Indigenous Australians is hitherto unreported. AIM: To report the incidence rate and clinical phenotype of Creutzfeldt-Jakob disease (CJD) in Indigenous Australians. METHOD: Crude sporadic CJD (sCJD) incidence rates and indirect age standardisation of all CJD were assessed to calculate the standardised mortality ratio (SMR) of the Indigenous Australian population in comparison to the all-resident Australian population, along with analysis of clinical phenotypes. RESULTS: We report an illustrative case of an Indigenous Australian from regionally remote Western Australia dying from typical 'probable' sCJD 2 months after disease onset, with Australian National CJD Registry (ANCJDR) surveillance overall demonstrating eight Indigenous Australians dying from sCJD (five post-mortem confirmed, three classified as 'probable') with a clinical phenotype similar to non-indigenous people, including median age at death of 61 years (interquartile range IQR = 16 years) and median duration of illness of 3 months (IQR = 1.6 months). Indigenous Australians with sCJD were geographically dispersed throughout Australia. The calculated overall crude annual rate of sCJD in Indigenous Australians compared to the remainder of the Australian population was not significantly different (0-3.87/million for Indigenous Australians; 0.94-1.83/million for non-indigenous). The overall indirect age-standardised CJD mortality ratio for the indigenous population for the years 2006-2018 was 1.49 (95% CI, 0.75-2.98), also not significantly different to the all-resident Australian population. CONCLUSION: CJD occurs in Indigenous Australians with clinical phenotype and occurrence rates similar to non-Indigenous Australians. These findings contrast with a previous report where the incidence rate of CJD in a non-Australian indigenous population was reported to be decreased.

CYLD is a causative gene for frontotemporal dementia - amyotrophic lateral sclerosis.

Frontotemporal dementia and amyotrophic lateral sclerosis are clinically and pathologically overlapping disorders with shared genetic causes. We previously identified a disease locus on chromosome 16p12.1-q12.2 with genome-wide significant linkage in a large European Australian family with autosomal dominant inheritance of frontotemporal dementia and amyotrophic lateral sclerosis and no mutation in known amyotrophic lateral sclerosis or dementia genes. Here we demonstrate the segregation of a novel missense variant in CYLD (c.2155A>G, p.M719V) within the linkage region as the genetic cause of disease in this family. Immunohistochemical analysis of brain tissue from two CYLD p.M719V mutation carriers showed widespread glial CYLD immunoreactivity. Primary mouse neurons transfected with CYLDM719V exhibited increased cytoplasmic localization of TDP-43 and shortened axons. CYLD encodes a lysine 63 deubiquitinase and CYLD cutaneous syndrome, a skin tumour disorder, is caused by mutations that lead to reduced deubiquitinase activity. In contrast with CYLD cutaneous syndrome-causative mutations, CYLDM719V exhibited significantly increased lysine 63 deubiquitinase activity relative to the wild-type enzyme (paired Wilcoxon signed-rank test P = 0.005). Overexpression of CYLDM719V in HEK293 cells led to more potent inhibition of the cell signalling molecule NF-κB and impairment of autophagosome fusion to lysosomes, a key process in autophagy. Although CYLD mutations appear to be rare, CYLD's interaction with at least three other proteins encoded by frontotemporal dementia and/or amyotrophic lateral sclerosis genes (TBK1, OPTN and SQSTM1) suggests that it may play a central role in the pathogenesis of these disorders. Mutations in several frontotemporal dementia and amyotrophic lateral sclerosis genes, including TBK1, OPTN and SQSTM1, result in a loss of autophagy function. We show here that increased CYLD activity also reduces autophagy function, highlighting the importance of autophagy regulation in the pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.

Factors determining recurrence in transient global amnesia.

BACKGROUND: Aetiology of transient global amnesia (TGA) remains uncertain, though many have been proposed, including ischaemic, migrainous or epileptic pathologies. METHODS: We attempted to determine risk factors for TGA, as well as prognostic factors that may cause recurrence. We evaluated clinical history, family history and magnetic resonance diffusion-weighted imaging (DWI) studies of 93 prospective patients with TGA. Patients were followed from 2004 to 2016. Fifteen of 93 (16%) patients experienced a recurrence of TGA. RESULTS: Among precipitating events, physical activities inducing Valsalva-like manoeuvres were most common, followed by emotional stress. Eighty-four patients had possible comorbidities or risk factors for TGA, though no single risk factor was ubiquitous. Risk factors associated with recurrence were head injury (isolated vs. recurrent, 16.7% vs. 53.5%, p < 0.01), depression (isolated vs. recurrent, 15.4% vs 46.7%, p = 0.01) and family history of dementia (isolated vs. recurrent, 20.5% vs. 46.7%, p = 0.03). Of 15 patients with confirmed recurrent TGA, two developed dementia and four subjective memory impairment. DWI lesions were observed in 24 patients and were located anywhere within the hippocampus. CONCLUSIONS: DWI lesions were not significantly associated with outcomes (recurrence, subjective memory impairment, dementia). We have found that depression, previous head injury and family history of dementia may predict TGA recurrence.

Revisiting Criteria for Psychosis in Alzheimer's Disease and Related Dementias: Toward Better Phenotypic Classification and Biomarker Research.

BACKGROUND: Psychotic symptoms are common in Alzheimer's disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. OBJECTIVE: To establish research criteria for the diagnosis of psychosis in AD. METHODS: The International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. RESULTS: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. CONCLUSION: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Profiling sentence repetition deficits in primary progressive aphasia and Alzheimer's disease: Error patterns and association with digit span.

The use of sentence repetition tasks to distinguish dementia syndromes, particularly variants of primary progressive aphasia (PPA), is receiving growing attention. Impaired sentence repetition is a core feature of logopenic variant PPA, although the underlying cognitive mechanisms of this impairment and its significance as a diagnostic criterion remain poorly understood. Sentence repetition abilities of 12 people with dementia, using an adapted error classification schema, were analyzed, along with digit span abilities, a measure frequently used to assess working memory capacity, to explore error patterns and correlations. Participants with semantic variant PPA showed the greatest performance on sentence repetition and digit span in comparison to the logopenic variant PPA and Alzheimer's disease participants. Sentence repetition errors were characterized by middle omissions for semantic variant PPA, ending omissions and phonological errors for logopenic variant PPA, and ending omissions and unrelated word substitutions for Alzheimer's disease. Significant correlations were found between sentence repetition and digit span abilities. Findings are discussed in relation to working memory capacity theories, specifically, the dual-component model.

Determining stability in connected speech in primary progressive aphasia and Alzheimer's disease.

PURPOSE: Using connected speech to assess progressive language disorders is confounded by uncertainty around whether connected speech is stable over successive sampling, and therefore representative of an individual's performance, and whether some contexts and/or language behaviours show greater stability than others. METHOD: A repeated measure, within groups, research design was used to investigate stability of a range of behaviours in the connected speech of six individuals with primary progressive aphasia and three individuals with Alzheimer's disease. Stability was evaluated, at a group and individual level, across three samples, collected over 3 weeks, involving everyday monologue, narrative and picture description, and analysed for lexical content, fluency and communicative informativeness and efficiency. RESULT: Excellent and significant stability was found on the majority of measures, at a group and individual level, across all genres, with isolated measures (e.g. nouns use, communicative efficiency) showing good, but greater variability, within one of the three genres. CONCLUSION: Findings provide evidence of stability on measures of lexical content, fluency and communicative informativeness and efficiency. While preliminary evidence suggests that task selection is influential when considering stability of particular connected speech measures, replication over a larger sample is necessary to reproduce findings.

Peduncular Hallucinosis and Autonomic Dysfunction in Anti-Aquaporin-4 Antibody Syndrome.

Neuromyelitis optica is a rare, severe inflammatory demyelinating disease of the central nervous system, previously described as affecting only the optic nerve and spinal cord. Since the discovery of a highly specific autoantibody, anti-aquaporin-4, lesions are now recognized outside these regions. We report a man with severe, debilitating symptoms resulting from a symptomatic lesion within the diencephalon, manifesting with abnormal circadian rhythms, autonomic dysfunction, behavioral disturbance, and complex visual hallucinations. The patient reported seeing nonexistent small people and animals, streaks of color across people's faces, movement of objects and facial features, water cascading down walls, bright spots, and writing appearing as hieroglyphics. His centrally driven sick sinus syndrome required insertion of a permanent cardiac pacemaker. We have been able to suppress his disease activity with methotrexate for 30 months. We review the literature on patients with positive anti-aquaporin-4 serology and dysregulation of hypothalamic function, to provide evidence that the clinical manifestations can include complex visual phenomena.

The Nature and Natural History of Posterior Cortical Atrophy Syndrome: A Variant of Early-onset Alzheimer Disease.

A prospective longitudinal evaluation of 12 patients over a 16-year interval using clinical neurological and imaging data to determine whether posterior cortical atrophy syndrome (PCA) related to early-onset Alzheimer disease (AD) and to examine its natural history. Our 12 patients had a median age of onset of 56 years (range, 48 to 63 y) and were followed for a median of 6 years (range, 3 to 9 y). Patients either presented with complex visual phenomena or developed them with time. Six patients underwent flurodeoxyglucose and Pittsburgh investigational compound B imaging which showed a mismatch between metabolic activity and amyloid deposition with reduced metabolism in parieto-occipital regions on flurodeoxyglucose positron emission tomography and diffuse neocortical uptake of amyloid without occipital predominance. All patients progressively deteriorated using a quality of life and total functional capacity assessments and this change is similar to the natural history of other early-onset AD variants (typical amnestic presentation, logopenic, and frontal). Two patients had neuropathologic assessments and were shown to have AD using standard pathologic criteria. Of interest, 5 of our 12 patients had occupations strongly dependent on visuospatial functioning. PCA is a syndrome that is most likely a variant of early-onset AD and our correlative clinical, structural, functional, and amyloid imaging data, along with neuropathologic studies in 2 patients, support this concept. The natural history of PCA shows progression with time and this trajectory seems to reflect that of other variants of early-onset AD.

Anti-N-methyl-D-aspartate receptor encephalitis with an imaging-invisible ovarian teratoma: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is a recently discovered disease entity of paraneoplastic limbic encephalitis. It largely affects young women and is often associated with an ovarian teratoma. It is a serious yet treatable condition if diagnosed early. Its remedy involves immunotherapy and surgical removal of the teratoma of the ovaries. This case of anti-N-methyl-D-aspartate receptor encephalitis involves an early surgical intervention with bilateral oophorectomy, despite negative imaging evidence of a teratoma. CASE PRESENTATION: A 25-year-old white woman with anti-N-methyl-D-aspartate receptor encephalitis presented with behavioral changes and seizures that were confirmed to be secondary to anti-N-methyl-D-aspartate receptor encephalitis. She required an admission to our intensive care unit for ventilator support and received a number of immunological therapies. Multiple imaging investigations showed no evidence of an ovarian teratoma; she had a bilateral oophorectomy 29 days after admission. Ovarian histology confirmed the presence of a teratoma with neuronal cells. A few days after the operation she began to show signs of improvement and, apart from mild short-term memory loss, she returned to normal function. CONCLUSIONS: Our patient is an example of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis, in which the teratoma was identified only microscopically. Her case highlights that even with negative imaging evidence of a teratoma, ovarian pathology should still be considered and explored.