Prodromal Features Research Articles

Cognitive function in men with non-motor features of Parkinson’s disease

ObjectiveSubtle cognitive deficits can occur during the prodromal phase of Parkinson’s disease (PD), commonly in conjunction with hyposmia. However, little is known about the association between cognitive function and other...

Parkinson Disease-Related Brain Metabolic Patterns and Neurodegeneration in Isolated REM Sleep Behavior Disorder.

To elucidate the role of Parkinson disease (PD)-related brain metabolic patterns as a biomarker in isolated REM sleep behavior disorder (iRBD) for future disease conversion. This is a prospective cohort study consisting of 30 patients with iRBD, 25 patients with de novo PD with a premorbid history of RBD, 21 patients with longstanding PD on stable treatment, and 24 healthy controls. The iRBD group was longitudinally followed up. All participants underwent 18F-fluorodeoxyglucose (FDG) PET and were evaluated with olfaction, cognition, and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) at baseline. From FDG-PET scans, we derived metabolic patterns from the longstanding PD group (PD-RP) and de novo PD group with RBD (dnPDRBD-RP). Subsequently, we calculated the PD-RP and dnPDRBD-RP scores in patients with iRBD. We validated the metabolic patterns in each PD group and separate iRBD cohort (n = 14). The 2 patterns significantly correlated with each other and were spatially overlapping yet distinct. The MDS-UPDRS motor scores significantly correlated with PD-RP (p = 0.013) but not with dnPDRBD-RP (p = 0.076). In contrast, dnPDRBD-RP correlated with olfaction in butanol threshold test (p = 0.018) in patients with iRBD, but PD-RP did not (p = 0.21). High dnPDRBD-RP in patients with iRBD predicted future phenoconversion with all cutoff ranges from 1.5 to 3 SD of the control value, whereas predictability of PD-RP was only significant in a partial range of cutoff. The dnPDRBD-RP is an efficient neuroimaging biomarker that reflects prodromal features of PD and predicts phenoconversion in iRBD that can be applied individually. This study provides Class IV evidence that a de novo PD pattern on FDG-PET predicts future conversion to neurodegenerative disease in patients with iRBD.

Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation.

Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut-vagus-brain signaling or through blood-brain barrier permeability. Concepts regarding the gut-brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.

Constipation is Associated with Development of Cognitive Impairment in de novo Parkinson's Disease: A Longitudinal Analysis of Two International Cohorts.

Constipation is regarded as one of the prodromal features of Parkinson's disease (PD) and there is emerging evidence linking gastrointestinal dysfunction and cognitive impairment (CI) in PD. We explored whether constipation is associated with development of CI in two independent cohorts of de novo PD patients (n = 196 from the Non-motor International Longitudinal Study [NILS] and n = 423 from the Parkinson's Progression Markers Initiative [PPMI] study). Constipation was clinically defined using the Non-Motor Symptoms Scale (NMSS) item-21 [NILS] and Scales for Outcomes in PD-Autonomic (SCOPA-AUT) item-5 [PPMI]. We assessed baseline group differences (PD with or without constipation) in CI, global non-motor symptoms burden, motor dysfunction, and striatal dopaminergic denervation. Kaplan-Meier method estimated group differences in cumulative proportion of patients with incident CI over three years. In PPMI, we subsequently performed univariate and multivariate Cox survival analyses to evaluate whether constipation predicts incident mild cognitive impairment or dementia over a 6-year period, including constipation and other known predictors of CI as covariates. Patients with constipation had greater motor and global non-motor burden in both cohorts at baseline (p < 0.05). Kaplan-Meier plots showed faster conversion to CI in patients with constipation in both cohorts (p < 0.05). In PPMI, 37 subjects developed dementia during a mean follow-up of 4.9 years, and constipation was an independent predictor of dementia onset (hazard ratio = 2.311; p = 0.02). Constipation in de novo PD patients is associated with development of cognitive decline and may serve as a clinical biomarker for identification of patients at risk for cognitive impairment.

Improving estimation of Parkinson\u2019s disease risk\u2014the enhanced PREDICT-PD algorithm

We previously reported a basic algorithm to identify the risk of Parkinson’s disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD and used tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as “intermediate” markers of prodromal PD in the absence of sufficient incident cases. We have now developed and tested an enhanced algorithm which incorporates the intermediate markers into the risk model. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort. The enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (93–609-fold difference between the 10th and 90th centiles vs 10–13-fold respectively). There was a greater increase in the risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.75 [95% CI 1.68–4.50; p < 0.001] versus 1.47 [95% CI 0.86–2.51; p = 0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R2 = 0.164, p = 0.005 vs R2 = 0.043, p = 0.17). Incorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm.

Sequence of clinical and neurodegeneration events in Parkinson's disease progression.

Dementia is one of the most debilitating aspects of Parkinson's disease. There are no validated biomarkers that can track Parkinson's disease progression, nor accurately identify patients who will develop dementia and when. Understanding the sequence of observable changes in Parkinson's disease in people at elevated risk for developing dementia could provide an integrated biomarker for identifying and managing individuals who will develop Parkinson's dementia. We aimed to estimate the sequence of clinical and neurodegeneration events, and variability in this sequence, using data-driven statistical modelling in two separate Parkinson's cohorts, focusing on patients at elevated risk for dementia due to their age at symptom onset. We updated a novel version of an event-based model that has only recently been extended to cope naturally with clinical data, enabling its application in Parkinson's disease for the first time. The observational cohorts included healthy control subjects and patients with Parkinson's disease, of whom those diagnosed at age 65 or older were classified as having high risk of dementia. The model estimates that Parkinson's progression in patients at elevated risk for dementia starts with classic prodromal features of Parkinson's disease (olfaction, sleep), followed by early deficits in visual cognition and increased brain iron content, followed later by a less certain ordering of neurodegeneration in the substantia nigra and cortex, neuropsychological cognitive deficits, retinal thinning in dopamine layers, and further deficits in visual cognition. Importantly, we also characterize variation in the sequence. We found consistent, cross-validated results within cohorts, and agreement between cohorts on the subset of features available in both cohorts. Our sequencing results add powerful support to the increasing body of evidence suggesting that visual processing specifically is affected early in patients with Parkinson's disease at elevated risk of dementia. This opens a route to earlier and more precise detection, as well as a more detailed understanding of the pathological mechanisms underpinning Parkinson's dementia.

Proactive C-L Psychiatry: Re-envisioning Psychiatric Care in Medical Settings

Proactive C-L Psychiatry: Re-envisioning Psychiatric Care in Medical Settings

REM sleep absence in patients referred to polysomnography for REM sleep behavior disorder.

Detection of REM sleep behavior disorder (RBD) with polysomnography (PSG) is relevant for the diagnosis of α-synucleinopathies. However, some patients referred for suspicion of RBD do not present REM sleep at PSG (NoREMSusRBD), rendering the study inconclusive. Our objective was to investigate disorders possibility associated with REM sleep absence in patients referred to PSG for investigation of RBD, in particular α-synucleinopathies. A sleep-lab database was revised to select NoREMSusRBD (n = 15) and patients: with no REM sleep referred for suspicion of other sleep disorder (NoREMSusOther, n = 28); referred for RBD suspicion with negative PSG (NegativeRBD, n = 24); α-synucleinopathies with no REM sleep (NoREMα, n = 23) and idiopathic RBD (iRBD, n = 26). NoREMSusRBD patients were compared with the other groups regarding PSG data and the emergence of prodromal features or established criteria for α-synucleinopathy. Severe Obstructive Sleep Apnea (OSA) was significantly more frequent in the NoREMsusRBD compared to the NoREMα and iRBD groups. No patient in the NoREMSusRBD developed a α-synucleinopathy (2 cases on the iRBD group). The prevalence of prodromal features in NoREMSusRBD (n = 7, 46.7%) was similar to that of iRBD (n = 18, 69.2%) and significantly higher than in the other groups. Apnea-Hypopnea Indices (AHI) were significantly higher in the NoREMSusRBD compared with iRBD and NoREMα. Our study suggests that the absence of REM sleep in NoREMSusRBD could be caused by OSA but does not exclude the possibility of underlying α- synucleinopathy, suggested by an increased prevalence of prodromal features. These data support the need for excluding OSA in patients suspected for RBD and recommends follow-up of NoREMSusRBD patients to uncover a possible α- synucleinopathy.

A population scale analysis of rare SNCA variation in the UK Biobank

Parkinson's disease (PD) is a complex neurodegenerative disease with a variety of genetic and environmental factors contributing to disease. The SNCA gene encodes for the alpha-synuclein protein which plays a central role in PD, where aggregates of this protein are one of the pathological hallmarks of disease. Rare point mutations and copy number gains of the SNCA gene have been shown to cause autosomal dominant PD, and common DNA variants identified using Genome-Wide Association Studies (GWAS) are a moderate risk factor for PD. The UK Biobank is a large-scale population prospective study including ~500,000 individuals that has revolutionized human genetics. Here we assessed the frequency of SNCA variation in this cohort and identified 30 subjects carrying variants of interest including duplications (n = 6), deletions (n = 6) and large complex likely mosaic events (n = 18). No known pathogenic missense variants were identified. None of these subjects were reported to be a PD case, although it is possible that these individuals may develop PD at a later age, and whilst three had known prodromal features, these did not meet defined clinical criteria for being considered ‘prodromal’ cases. Seven of the 18 large complex carriers showed a history of blood based cancer. Overall, we identified copy number variants in the SNCA region in a large population based cohort without reported PD phenotype and symptoms. Putative mosaicism of the SNCA gene was identified, however, it is unclear whether it is associated with PD. These individuals are potential candidates for further investigation by performing SNCA RNA and protein expression studies, as well as promising clinical trial candidates to understand how duplication carriers potentially escape PD.

Prevalence and severity of neuropsychiatric symptoms in the prodromal stages of dementia with Lewy bodies and Alzheimer’s disease

AbstractBackgroundThere has been minimal investigation into the prodromal features dementia with Lewy bodies (DLB) and how they may differ from prodromal features of Alzheimer’s disease (AD).MethodThe data analyzed for this investigation were collected as part of a large, prospective longitudinal study conducted by the National Alzheimer’s Coordinating Center (NACC database is funded by NIA/NIH Grant U01 AG016976). We identified 110 non‐demented participants who converted to DLB at a subsequent visit. Participants were age and sex matched to 220 non‐demented participants who later converted to AD. We examined between group differences in the prevalence of symptoms on the Neuropsychiatric Inventory Questionnaire (NPI‐Q) at time of dementia diagnosis and in the 1‐3 years preceding conversion to dementia using Chi‐Square or Fisher Exact Test analyses.ResultsFor the DLB and AD groups, 82% were male and the average age at the time of dementia diagnosis was 75.4 years (SD=7.9). There was no significant difference in education between the two groups. The DLB group was significantly less culturally diverse than the AD group (See Table 1). Nighttime behaviors and hallucinations were significantly more common in the DLB group compared to the AD group at all time points during the prodromal phase and at the time of dementia diagnosis. There was no significant difference in the informant’s report of motor symptoms in the prodromal phases between the two groups (See Table 2).ConclusionThe DLB group demonstrated a significantly higher prevalence of nighttime behaviors and hallucinations than the AD group in both the prodromal phase and at the time of dementia diagnosis. These findings support the occurrence of core clinical features of DLB during the prodromal phase of the disease [1]; however, there was no significant difference in the informant’s report of motor symptoms within the prodromal phases, which warrants a comparison utilizing more objective motor data. Reference: 1. McKeith IG, Boeve BF, Dickson DW, et al.; Dementia with Lewy Bodies Consortium. Diagnosis and management of Dementia with Lewy Bodies: Fourth consensus report of the DLB Consortium. Neurol. 2017;89:1‐13.

Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer’s Disease

Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD. Modest neuron-specific transgenic Rab5 expression inducing hyperactivation of Rab5 comparable to that in AD brain reproduces AD-related Rab5-endosomal enlargement and mistrafficking, hippocampal synaptic plasticity deficits via accelerated AMPAR endocytosis and dendritic spine loss, and tau hyperphosphorylation via activated glycogen synthase kinase-3β. Importantly, Rab5-mediated endosomal dysfunction induces progressive cholinergic neurodegeneration and impairs hippocampal-dependent memory. Aberrant neuronal Rab5-endosome signaling, therefore, drives a pathogenic cascade distinct from β-amyloid-related neurotoxicity, which includes prodromal and neurodegenerative features of AD, and suggests Rab5 overactivation as a potential therapeutic target.

A patient with papilloedema

A 45-year-old Jordanian man had 2 weeks of gradual onset headache, neck stiffness and loss of vision. The headache was occipital with pulsatile tinnitus and exacerbated by coughing, sneezing and...

Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank

ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether...

Assessing self-reported clinical high risk symptoms: The psychometric properties of the polish version of the prodromal questionnaire-brief and a proposal for an alternative approach to scoring.

Psychotic-like experiences (PLEs) might occur in the general population as low-risk individual differences or prodromal features, requiring quick detection and early intervention. The aims of this study were to conduct a mini-systematic review of the prognostic abilities of the Prodromal Questionnaire-Brief (PQ-B), describe the PLEs distribution for the first time in a Polish population, assess PQ-B reliability and propose an innovative scoring approach based on cluster analysis. Five hundred and twenty eight (334 female) adult volunteers underwent screening with the PQ-B, 49% also underwent the early psychosis screening test PRIME, to verify the tests' psychometric properties, to compare the prognostic accuracy of the PQ-B to the more restrictive PRIME, and to the detected types of possible diagnosis in the general population. Almost 70% of respondents met the prognostic criteria of the PQ-B while only 30.6% met the PRIME criteria. Both tests proved reliable (α > .835) and valid (rho >.710; P < .001). A cluster analysis identified three different sub-groups detected with the PQ-B: healthy individuals without PLE; healthy with low-distressing PLEs; and possibly prodromal subjects reporting less frequent but more distressing PLEs and no worries about their own mental state. Also in systematic reviews, authors of different adaptations have observed that the PQ-B has too low specificity and postulated the need for higher cut-offs. Study provides evidence of good reliability and sensitivity of the PQ-B in assessing PLEs among the general population, but emphasizes that straightforward quantitative scoring criteria are still unclear. A more qualitative approach might be useful for differentiating true prodromal subjects from clinically low-risk individual differences.

Diet pattern and prodromal features of Parkinson disease.

To assess the relationship between diet pattern and prodromal Parkinson disease (PD) features. These analyses include 47,679 participants from the Nurses' Health Study and the Health Professionals Follow-up Study. Since 1986, both cohorts have collected dietary information every 4 years and calculated scores for adherence to different diet patterns, including the alternate Mediterranean diet (aMED) and the Alternative Healthy Eating Index (AHEI). In 2012, participants responded to questions regarding constipation and probable REM sleep behavior disorder. For a subset of 17,400 respondents to the 2012 questionnaire, 5 additional prodromal features of PD were assessed in 2014 to 2015. We used multinomial logistic regression to estimate the association between baseline (1986) diet pattern score quintiles and number of prodromal features (0, 1, 2, or ≥3) in 2012 to 2015. Additional analyses investigated the association between long-term adherence to these dietary patterns over 20 years and prodromal features suggestive of PD. In a comparison of extreme aMED diet quintiles, the odds ratio for ≥3 vs 0 features was 0.82 (95% confidence interval [CI] 0.68-1.00, false discovery rate [FDR]-adjusted p trend = 0.03) at baseline and 0.67 (95% CI 0.54-0.83, FDR-p trend < 0.001) for long-term diet; results were equally strong for the association with AHEI scores. Higher adherence to these diets was inversely associated with individual features, including constipation, excessive daytime sleepiness, and depression. The inverse association between these diet patterns and prodromal PD features is consistent with previous findings and suggests that adherence to a healthy diet may reduce the occurrence of nonmotor symptoms that often precede PD diagnosis.

Mild Parkinsonian Signs in a Community Ambulant Population.

Mild parkinsonian signs (MPS) are common in the older adult and associated with a wide range of adverse health outcomes. There is limited data on the prevalence of MPS and its significance. To determine the prevalence of MPS in the community ambulant population and to evaluate the relationship of MPS with prodromal features of Parkinson's disease (PD) and cognition. This cross-sectional community-based study involved participants aged ≥50 years. Parkinsonian signs were assessed using the modified Unified Parkinson's Disease Rating Scale (mUPDRS) and cognition using the Montreal Cognitive Assessment (MoCA). Premotor symptoms of PD were screened using a self-reported questionnaire. Linear regression was used to assess the association of MPS with premotor symptoms of PD and cognitive impairment. Of 392 eligible participants, MPS was present in 105 (26.8%). Mean age of participants with MPS was 68.8±6.9 years and without MPS was 66.1±5.9 years (p < 0.001). Multivariate analysis revealed that MoCA scores were significantly lower in the MPS group (β= -0.152, 95% CI = -0.009, -0.138, p < 0.05). A significant correlation between the presence of REM sleep behavior disorder (RBD) and total MPS scores (β= 0.107, 95% CI = 0.053, 1.490, p < 0.05) was also found. Neither vascular risk factors nor other premotor symptoms were significantly associated with MPS. MPS is common and closely related to cognitive impairment and increasing age. Presence of RBD is predictive of higher MPS scores. This study highlights the necessity of other investigations or sensitive risk markers to identify subjects at future risk of PD.

Metabolic syndrome does not influence the phenotype of LRRK2 and GBA related Parkinson\u2019s disease

In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pressure, demographic, cognitive, motor, olfactory and affective information enabling the assessment of each component of MS and the construction of the MDS prodromal probability score. The number of metabolic components and their levels were compared between participants who were separated based on disease state and genetic status. One hundred and four idiopathic PD, 40 LRRK2-PD, 70 GBA-PD, 196 healthy non-carriers, 55 LRRK2-NMC and 97 GBA-NMC participated in this study. PD groups and non manifesting carriers (NMC) did not differ in the number of metabolic components (p = 0.101, p = 0.685, respectively). LRRK2-PD had higher levels of triglycerides (p = 0.015) and higher rates of prediabetes (p = 0.004), while LRRK2-NMC had higher triglyceride levels (p = 0.014). NMC with probability rates for prodromal PD above 50% had higher frequencies of hypertriglyceridemia and prediabetes (p < 0.005, p = 0.023 respectively). While elevated triglycerides and prediabetes were more frequent among LRRK2 carriers, MS does not seem to influence GBA and LRRK2-PD phenotype.

Where in the World Did You Get That Rash?

1. Panteha Eshtiaghi, HBSc* 2. Miriam Weinstein, MD, FRCPC† 1. *Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada 2. †Hospital for Sick Children, Toronto, Ontario, Canada * Abbreviations: ACD: : allergic contact dermatitis CD: : cercarial dermatitis CL: : cutaneous leishmaniasis CLM: : cutaneous larva migrans DF: : dengue fever HFMD: : hand, foot, and mouth disease HSV: : herpes simplex virus KD: : Kawasaki disease PCR: : polymerase chain reaction PR: : pityriasis rosea RT-PCR: : reverse transcriptase polymerase chain reaction The challenge to diagnose cutaneous eruptions and lesions in patients who have spent time in foreign countries is increasingly common. With the advent of increased global travel, foreign adoptions, immigration, and refugee seekers, rashes that were once relegated to the realm of the exotic and likely to show up in a tropical diseases clinic may now present to a general pediatrician. Furthermore, the pediatric traveler is at increased risk for dermatoses. (1) It behooves the practitioner to be aware of these skin findings, to be able to recognize them and distinguish them from other skin conditions. After completing this article, readers should be able to: 1. Identify and classify rashes by main morphologic patterns. 2. Develop a broad differential diagnosis and diagnostic approach for a rash in a returned pediatric traveler based on initial morphology, history, epidemiology, and other clinical features. 3. Consider both infectious and noninfectious causes of skin disorders presenting in a patient with a travel history. 4. Outline the basic investigations and principles of management for travel-acquired and non–travel-acquired dermatologic illnesses. 5. Discuss …

Parkinson prodromal features in a large cohort of Gaucher carriers

Some case series have suggested that psychotic features could occur even before the onset of motor symptoms of Parkinson's Disease (PD). Our aim was to investigate a possible association between psychotic symptoms and prodromal Parkinson's disease in a population-based cohort, the Hellenic Longitudinal Investigation of Aging and Diet study.This cross-sectional study included participants aged ≥65 years without dementia or PD. We defined psychotic symptoms as the presence of at least one new hallucinatory or delusional feature, assessed with the Neuropsychiatric Inventory scale and the Columbia University Scale for Psychopathology in Alzheimer's Disease, exhibited only at follow-up and not present at baseline visit. We calculated the probability of prodromal PD (pPD) for every participant, according to the 2019 International Parkinson and Movement Disorders Society research criteria for prodromal PD.Participants who developed psychotic manifestations over a three-year follow up (20 of 914) had 1.3 times higher probability of pPD score (β [95%CI]: 1.3 [0.9-1.5], p=0.006) compared to non-psychotic subjects. This association was driven mostly by depressive symptoms, constipation and subthreshold parkinsonism (p<0.05).Our data indicate that emerging psychotic features evolve in parallel with the probability of pPD. This is the first study that provides evidence for the presence of psychotic experiences in pPD. The association detected needs to be confirmed in longitudinal studies.

N-Methyl-D-Aspartate(NMDA) Receptor and Voltage-Gated Potassium Channel (VGKC) Antibody-Associated Encephalitides Presenting as First Episode Acute Psychosis.

Aim: Acute psychosis is not an uncommon presenting feature in immune-mediated encephalitides. Most patients improve if properly diagnosed and treated expediently with immunotherapy. Our study aimed to describe the frequency, clinical spectrum, and long-term outcomes in patients presenting with acute psychosis who have anti-N-methyl-D-aspartate (NMDA) receptor or anti-voltage-gated potassium channel (VGKC) encephalitis. Method: We recruited patients aged 16–50 years presenting with less than 1 month of psychotic and neurological symptoms including cognitive dysfunction, seizures, abnormal movements, and/or autonomic dysfunction. Results: Between September 2011 and October 2013, 60 patients with first episode acute psychosis were screened; 15 were recruited and included for analyses. Four (26.7%) patients were diagnosed with anti-NMDA receptor encephalitis and 1 (6.7%) with anti-VGKC encephalitis. We found that the mean serum white blood cell (WBC) count (12.8 × 109/L ± 4.8 vs. 7.9 × 109/L ± 2.6; p = 0.05) and cerebrospinal fluid WBC count (106 cells/µl ± 101 vs. 8.5 cells/µl ± 18.9; p = 0.05) were higher in positive cases. Certain prodromal features such as fever, headache, confusion, facial dyskinesia, and hypersalivation were also more likely to be present in positive cases. Patients with autoimmune encephalitis also tended to be more unwell, with the majority requiring intensive care, had lower global assessment of functioning scores (30 ± 10 vs. 53.7 ± 21.2, p = 0.09), and were not well enough to complete standard psychiatric and cognitive assessments at presentation. Conclusion: Autoimmune encephalitis is not uncommon in patients with acute psychosis. Elevated WBC counts, certain prodromal features, and a more severe illness at presentation should prompt appropriate evaluation.