Encephalitis in adults is associated with inpatient mortality in approximately 10

Background and Purpose:A national survey was conducted among members of the Neurohospitalist Society (NHS) to characterize updated practice patterns, perspectives, compensation, and career satisfaction of neurohospitalists in the U.S. Methods:Between March and May 2024, a 96-question online survey was distributed. Findings were compared to those from a similar NHS survey conducted in 2016. Results:143 neurohospitalists completed the survey (response rate 19%). 80% had some fellowship training, with vascular neurology (35%) and neurohospitalist (17%) being most common. 60% were ≤10 years out of completion of training, and 68% had ≤10 years of practice experience. 76% worked in academic medical centers and 24% in community hospitals. Cerebrovascular disease, seizure, and delirium/encephalopathy were the 3 most common neurological diagnoses seen in the inpatient setting. The most frequent work schedule (≥44%) was 7 days on/7 days off. The most common compensation model was base salary plus incentives (≥58%). For neurohospitalists working for academic medical centers, median total annual compensation was $299 250 (IQR $100 000). For neurohospitalists with non-academic employers, median total compensation was $367 000 (IQR $98 000). 70% of academic neurohospitalists and 53% of community neurohospitalists reported working with non-physician practitioners (NPPs). Although 64% of neurohospitalists reported having experienced burnout, 91% agreed that they find their clinical work personally rewarding. Conclusions:This survey, the largest to date among neurohospitalists, confirms that neurohospitalists remain a diverse, relatively young workforce with national presence. When compared to the 2016 survey, neurohospitalist compensation has increased.

The 2024 revised McDonald criteria for multiple sclerosis recognize the optic nerve as a topography for dissemination in space. Optical coherence tomography-derived inter-eye differences in peri-papillary retinal nerve fiber layer or ganglion cell-inner plexiform layer thicknesses (≥6μm or ≥4μm, respectively) are proposed for identifying unilateral optic nerve involvement. However, the value of combining inter-eye difference measures and optimal temporal-quadrant peri-papillary retinal nerve fiber layer inter-eye differences remains unclear. We investigated the diagnostic performance of combined inter-eye differences, optimal temporal-quadrant peri-papillary retinal nerve fiber layer inter-eye differences, and examined the effects of time, prior optic neuritis frequency, sex, and race on inter-eye differences. Retinal optical coherence tomography images from all study participants underwent rigorous quality control. Receiver operating characteristic analyses and area under the receiver operating characteristic curves (AUC) were used to determine optimal inter-eye differences of individual and combined measures to distinguish eyes with, from without, prior optic neuritis in people with multiple sclerosis. Mixed-effects models were used to assess impact of time, prior optic neuritis events, sex, and race on inter-eye differences. An independent multiple sclerosis cohort from a second center was examined for external validation. Among 1854 people with multiple sclerosis, optimal inter-eye difference thresholds for identifying unilateral optic nerve involvement were 6μm for peri-papillary retinal nerve fiber layer (AUC=0.80), 4μm for ganglion cell-inner plexiform layer (AUC=0.83), and 8μm for temporal-quadrant peri-papillary retinal nerve fiber layer (AUC=0.71) thicknesses. Peri-papillary retinal nerve fiber layer inter-eye differences ≥6μm or ganglion cell-inner plexiform layer inter-eye differences ≥4μm yielded 87.6% sensitivity, 70.0% specificity, and 64.0% positive predictive value. Concurrent inter-eye differences at lower thresholds (≥5μm peri-papillary retinal nerve fiber layer, ≥3μm ganglion cell-inner plexiform layer) reduced sensitivity to 72.5%, but improved specificity (86.6%) and positive predictive value (76.7%), while maintaining accuracy and negative predictive value. Temporal-quadrant peri-papillary retinal nerve fiber layer inter-eye differences did not improve diagnostic performance. Over a median of 5.1 years, ganglion cell-inner plexiform layer and peri-papillary retinal nerve fiber layer inter-eye differences remained stable. Prior optic neuritis counts and sex did not affect inter-eye differences. Although Black Americans had higher inter-eye differences than White Americans, optimal thresholds were comparable across races. The validation cohort comprising 254 people with multiple sclerosis confirmed these findings. In conclusion, concurrent peri-papillary retinal nerve fiber layer (≥5μm) and ganglion cell-inner plexiform layer inter-eye differences (≥3μm) improve unilateral optic nerve involvement detection versus either alone (≥6μm or ≥4μm, respectively), while temporal-quadrant peri-papillary retinal nerve fiber layer inter-eye differences offer limited benefit. Inter-eye differences remain stable longitudinally and unaffected by prior optic neuritis frequency.

Background and Objectives:This study aims to assess whether adult patients with encephalitis from different racial and ethnic backgrounds exhibit significant differences in clinical presentation, diagnostic findings, and outcomes. Design and Methods:A retrospective cohort study was conducted by utilizing the electronic health records of encephalitis patients in the greater Houston and Baltimore areas. Patients were categorized by race/ethnicity into White or ethnic minority (including Black, Hispanic, and Asian patients). Data was analyzed for the presence of significant differences in clinical characteristics between the two groups. Results:Among 599 patients, 312 (52.1%) were White and 287 (47.9%) were of an ethnic minority. White patients were more often over sixty years-old upon presentation (43.1% vs 23.9%, P < 0.001) and more likely to present with memory deficits (36% vs 26.3%, P = 0.012). Ethnic minority patients more frequently presented with co-existing HIV (20.3% vs 3.4%, P < 0.001), severe organ dysfunction (44% vs 34.4%, P = 0.028), cerebrospinal fluid (CSF) pleocytosis (white blood cell count ≥5 cells/µL) (83.1% vs 69.3%, P < 0.001), and abnormal electroencephalogram (EEG) findings (84.3% vs 71.9%, P = 0.035). Ethnic minority patients also had worse outcomes on the Glasgow Outcome Scale (GOS) as defined by GOS <4 (59.3% vs 47.2%, P = 0.005). Binary logistic regression identified abnormal magnetic resonance imaging (MRI) and Glasgow Coma Scale (GCS) <13 as independent predictors of an adverse clinical outcome (GOS <4) with an adjusted odds ratio [95% confidence interval] (P value) of 1.609 [1.042-2.486] (P = 0.032) and 2.689 [1.675-4.317] (P < .001), respectively. Conclusion:Ethnic minority patients with encephalitis present at a younger age and are more likely to have co-existing HIV, severe initial organ dysfunction, CSF pleocytosis, abnormal EEG findings, and worse clinical outcomes. Abnormal MRI and GCS <13 are independent predictors of an unfavorable clinical outcome and may aid in risk stratification.

Abstract Background During evaluation for encephalitis, lumbar puncture (LP) plays a critical role in establishing a diagnosis. Repeat LP may be needed when the diagnosis remains in doubt, the specific etiology of encephalitis has not yet been identified, or to aid management decisions. However, findings on repeat LP have not been well characterized, potentially confounding interpretation. Here, we examine the clinical characteristics of patients with encephalitis who underwent repeat LP, the evolution of CSF parameters, and the indications for repeat LP during acute hospitalization. Methods This retrospective study analyzes LP and clinical data from 627 adults with all causes of encephalitis admitted between 2002 and 2022 across two hospital systems in Maryland and Texas. Results Of the 627 patients, 184 (29.3%) underwent repeat LP, with a median interval of 6 days between procedures, and more commonly among those with more severe presentations. Patients were more likely to undergo repeat LP in autoimmune than in infectious encephalitis (42/113 [37.2%] vs. 62/275 [22.5%], p=0.003). In infectious cases, CSF WBC counts decreased when repeat LP occurred ≥7 days after initial LP (p=0.016), whereas no decrease occurred in autoimmune cases. Repeat LP yielded a new diagnosis in 16/184 (8.6%). Among patients without initial pleocytosis, 51.4% developed pleocytosis on repeat LP, associated with worse outcomes. Diagnostic uncertainty was the most common indication. Conclusion Repeat lumbar punctures are performed in one-third of encephalitis hospitalizations and are more common in patients with autoimmune etiologies, severe disease, or diagnostic uncertainty. CSF dynamics differ between infectious and autoimmune etiologies.

BACKGROUND:Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature. METHODS:Retrospective series of patients with immune-related encephalitis and literature review. RESULTS:Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3. CONCLUSIONS AND RELEVANCE:Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.

Abstract Background Encephalitis in adults is associated with inpatient mortality in approximately 10% of patients but the cause and timing of death are unknown. Variables associated with inpatient mortality in 641 adults with encephalitis. 1p-value (statistically significant when <0.05) comparing the risk for mortality with each variable; 2N: total number of patients with data on analyzed variable; 3n: number of patients meeting criteria for the analyzed variable; 4BMI: body mass index, in kg/m2; 5CCI: Charlson comorbidity index score ≥3; 6Immunocompromise: defined as Human immunodeficiency virus (HIV) infection, recent chemotherapy (<1 month), solid organ or bone marrow transplantation, receiving ≥20 mg of prednisone or equivalent for >1 month, or congenital immunodeficiency; 7Acute presentation: if presenting within the first 5 days from symptom onset; 8Fever: temperature >38.4 °C; 9Focal neurological deficits: defined as acute-onset cranial nerve abnormalities or acute defects in sensorimotor abilities including aphasia and seizures; 10Psychiatric manifestations: behavioral (agitation, personality changes, combativeness), psychosis (delusions, paranoid ideas, hallucinations), mood disturbances (irritability, depression, anxiety), sleep disturbances (insomnia or hypersomnia), and catatonia; 11APACHE II score: Acute Physiology and Chronic Health Evaluation; 12SOFA score: Sequential Organ Failure Assessment score; 13GCS: Glasgow coma scale; 14Four score: eye response, motor response, brainstem reflexes, and respiration pattern; 15WBC: white blood cells; 16ICP: intracranial pressure, measured based on CSF opening pressure; 17CSF: cerebrospinal fluid; 18RBC: red blood cells. 19CT (Computed Tomography) scan abnormalities: hemorrhage, mass, or cerebral infarction; 20MRI (Magnetic Resonance Imaging) abnormalities: restricted diffusions, intraparenchymal lesions, demyelination, leukoencephalopathy, gliosis, ring enhancing lesions, or dural enhancement; 21EEG: electroencephalogram; 22ICU: intensive care unit. Methods We conducted a retrospective study across two tertiary healthcare systems in Texas and Maryland between 2002-2023. The causes of death were categorized according to the World Health Organization and National Center for Health Statistics into 3 groups: category 1, where encephalitis was the immediate cause of death; category 2, the underlying cause contributing to mortality but not directly responsible; or category 3, unrelated to the cause of death, acting independently. We also examined the timing of death from initial presentation, and the association of different variables with mortality. Distribution of causes of death per category in 45 adults with encephalitis 1Severe neurological impairment: including brain death; 2Sepsis/septic shock: included disseminated Cryptococcal, Staphylococcus aureus, and Streptococcus pneumoniae infections; 3HIV/AIDS: Human immunodeficiency virus/acquired immunodeficiency syndrome; 4CVID: Common variable immunodeficiency; 5Nosocomial bacteremia: in stem cell transplant patient with Mantle lymphoma; 6Malignancy: suspected AML (acute myeloid leukemia) and primary CNS (central nervous system) lymphoma; 7Multifactorial: included patients with multifactorial shock (2) and multiorgan failure (2). Results A total of 641 adults who had encephalitis were enrolled, 45 (7%) had inpatient mortality. Baseline factors associated with mortality included age, low BMI, presence of comorbidities, immunocompromised state, fever, psychiatric manifestations, memory deficits, mechanical ventilation, altered mental status, thrombocytopenia, hypoglycorrhachia, lymphocytic pleocytosis, HSV or VZV etiology of encephalitis, abnormal electroencephalogram and abnormal magnetic resonance imaging of the brain (p < 0.05). Encephalitis was the immediate cause of death (category I) in 62% of cases with a median time to death of 12 days, the underlying (category 2) in 13% with a median time to death of 12.5 days, and unrelated (category 3) in 25% with a median time to death of 27 days. Distribution of patients per category of death *Median timing of death, in days (range) Conclusion Encephalitis was the immediate or underlying cause of inpatient mortality in the majority of patients, particularly in the first 14 days. Evaluation of categories of death with timing of mortality Disclosures John Probasco, MD, Genentech: Study site investigator for multicenter study Rodrigo Hasbun, MD MPH FIDSA, Biomeriaux: Grant/Research Support|Biomeriaux: Honoraria

OBJECTIVE:We aimed to determine the clinical and prognostic significance of hypoglycorrhachia in adults with encephalitis. METHODS:We conducted an IRB-approved, retrospective chart review of adult patients diagnosed with encephalitis from Greater Houston and Baltimore regions from 2005 to 2022 based on the 2013 International Encephalitis Consortium criteria. Data was collected on demographics, presenting symptoms, diagnostic findings, and clinical outcomes. Hypoglycorrhachia was defined as a cerebrospinal fluid (CSF) to serum glucose ratio ≤ 0.6. Patients were dichotomized based on presence or absence of hypoglycorrhachia. RESULTS:Of 556 patients (47.5 % infectious, 15.6 % seropositive autoimmune, 36.9 % unknown etiology), 69.8 % had hypoglycorrhachia (n = 388). Patients with hypoglycorrhachia were more often immunocompromised and presented with fever, headache, nausea, and neck stiffness (p < 0.05), while patients without hypoglycorrhachia more frequently presented with seizures, memory deficits, and psychiatric symptoms (p < 0.05). Hypoglycorrhachia was associated with CSF pleocytosis (CSF white blood cell level ≥ 5 cells/μL), a higher CSF protein level (p < 0.05), and infectious etiology. Absence of hypoglycorrhachia was associated with seropositive autoimmune etiology, greater use of immunotherapies, higher intensive care unit (ICU) admission rates, and longer hospitalization (p < 0.05). Prevalence rates and etiology distribution of patients with hypoglycorrhachia were comparable to those in a subset of patients with concomitant CSF/serum glucose collection. CONCLUSIONS:Hypoglycorrhachia is strongly associated with bacterial and fungal etiologies and their clinical features, while absence of hypoglycorrhachia is linked to higher ICU admission rates and prolonged hospitalization, likely due to autoimmune encephalitis. The CSF/serum glucose ratio captures greater variability in serum glucose levels yet reliably rules out absolute hypoglycorrhachia when >0.6, regardless of concomitant collection.

Abstract Background Encephalitis involves symptoms like reduced consciousness and seizures, diagnosed via lumbar puncture and brain imaging. Increased intracranial pressure (ICP) and its effect is well described in meningitis/ventriculitis and serve as poor prognostic factors. Data on ICP in encephalitis is limited, highlighting the need for further research.Table 1.Demographic, Clinical Characteristics, and Initial Presentations of 647 Adults with Encephalitis by Opening Pressure Measurement Status and DegreeAbbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; GCS, Glasgow Coma Scale; MAP, Mean Arterial Pressure; qSOFA, Quick Sequential Organ Failure Assessment. Methods Retrospective study at University of Texas and Johns Hopkins, 2002-2023, on 647 patients over 17 years old with encephalitis. Data analyzed via SPSS software.Table 2.Laboratory Findings, Etiology, and Imaging Results in Encephalitis Patients by Opening Pressure Measurement Status and DegreeAbbreviations: CSF, cerebral spinal fluid; CT, computed tomography; EEG, electroencephalogram; HSV, herpes simplex virus; MRI, magnetic resonance imaging; PMN, polymorphonuclear leukocyte; RBC, red blood cell; VZV, varicella zoster virus; WBC, white blood cell. Results Our study had 647 patients, with ICP measured in 298 (46%). Patients were categorized by ICP levels: < 30mmHg (242) and ≥30mmHg (56). Demographics such as gender, race, and age showed no variance across ICP. Comorbidity profiles were similar, though immunocompromised patients more frequently had ICP measurement (p=0.010). Symptoms like photophobia were uniformly distributed, but seizures and fever were more common in those measured for ICP (p=0.007 & p=0.013). Nuchal rigidity was higher in those with ICP ≥30mmHg (31% vs. 15%, p=0.031). Blood and cerebrospinal fluid analyses did not differ across groups. The leading etiologies identified were viral (32.9%) and autoimmune (18.1%), with no cause specifically linked to elevated ICP. Neuroimaging was more likely to be abnormal in patients with ICP measured (65% vs. 53%, p=0.004). Those with abnormal EEGs were more likely to have ICP measured (82% vs. 74%, p=0.050), but abnormal EEGs were less common in patients with ICP >30mmHg (p=0.008). No differences were found in given treatments like vancomycin, acyclovir, or steroids between ICP groups. ICU admission, vasopressor support, and ventilation needs were comparable, though patients with higher ICP had longer median hospital stays (12 days vs. 10 days, p=0.012) and mechanical ventilation (1.5 days vs. 0 days, p=0.005). Mortality and readmission rates showed no differences, but patients with higher ICP had worse Glasgow Outcome Scale (GOS) scores (61% vs. 46%, p=0.045).Table 3.Management Approaches and Outcomes in Encephalitis Patients Categorized by Opening Pressure LevelsAbbreviations: ICU, intensive care unit; GOS, Glasgow outcome scale. Conclusion This retrospective study on ICP in encephalitis across two centers emphasizes presentation variability and the need for standardized diagnostic and management protocols. Noted differences include ventilation duration, hospital stays, and GOS in patients with higher ICP.Figure 1.Breakdown of 647 cases of encephalitis, categorized by their determined etiologies and ICP measurements. The chart illustrates the distribution across three groups: OP not measured, OP <30mmHg, and OP ≥30mmHg, detailing the total number of cases alongside the percentages for each etiological category, including viral, bacterial, autoimmune, and unknown origins.CMV; Cytomegalovirus, EBV; Epstein-Barr Virus, HSV; Herpes Simplex Virus, JCV; JC Virus, MTB; Mycobacterium tuberculosis NMDA; N-Methyl-D-Aspartate, T. pallidum; Treponema pallidum, VGKC; Voltage-Gated Potassium Channel, WNV; West Nile Virus. Disclosures John Probasco, MD, Genentech: Study site investigator for multicenter study Rodrigo Hasbun, MD MPH FIDSA, Biomeriaux: Grant/Research Support|Biomeriaux: Honoraria

This case of encephalomyelitis in a previously healthy 21-year-old man who developed opsoclonus-myoclonus demonstrates the diagnostic utility of clinically validated metagenomic next-generation sequencing (mNGS), followed by appropriate confirmation, in complex cases of encephalitis. In this patient, an extensive diagnostic workup was negative for infectious, inflammatory, demyelinating, autoimmune, and paraneoplastic etiologies. However, clinically validated mNGS of the CSF identified human pegivirus (HPgV) as a potential causative agent. A 5-day course of IV immunoglobulins (IVIg) led to the resolution of the opsoclonus-myoclonus. HPgV identification provided clinical and pathophysiologic insights: (1) a possible link between HPgV and CNS pathology, including brainstem neurotropism similar to other flaviviruses; (2) expansion of the opsoclonus-myoclonus differential to include HPgV; and (3) potential immune-mediated CNS involvement, suggested by the favorable response to IVIg. Although promising, broader mNGS use remains limited by biologic, technical, and logistic challenges.

Background:Encephalitis is characterized by brain parenchymal inflammation caused by infection or autoimmunity. There are limited recent data on how immunocompromised patients with encephalitis differ from the general encephalitis population. Methods:This retrospective study of 2 large medical institutions compares clinical characteristics and outcomes of immunocompromised and immunocompetent patients with all-cause encephalitis. Results:Of the 657 patients, 151 (23%) were immunocompromised. Immunocompromised patients were more likely to have an infectious etiology, comorbidities, inflammatory cerebrospinal fluid (CSF) profile, abnormal neuroimaging, and worse clinical outcomes as assessed by discharge Glasgow Outcome Scale (GOS) and in-hospital mortality (all P < .05). The most commonly identified etiologies in immunocompromised patients were herpes simplex virus (HSV) and varicella zoster virus. HSV accounted for similar proportions in the immunocompromised (18%) and immunocompetent (14%) groups, though it was more commonly associated with a CSF neutrophilia in the immunocompromised group (P = .001). Strikingly, >10% of immunocompromised patients with encephalitis had autoimmune causes, two-thirds of which were checkpoint inhibitor associated. Factors associated with poor GOS on discharge differed, with poorer outcomes in the infectious group associated with immunocompromised state and poorer outcomes in the autoimmune group associated with immunocompetent state. Conclusions:Immunocompromised patients with encephalitis have differing causes, atypical clinical presentations, higher in-hospital mortality, and distinct factors associated with poor outcome as compared with immunocompetent patients. While HSV and opportunistic infections cause encephalitis in the immunocompromised, the diagnosis of autoimmune encephalitis should also be considered and can be checkpoint inhibitor associated.

This case of encephalomyelitis in a previously healthy 21-year-old man who developed opsoclonus-myoclonus demonstrates the diagnostic utility of clinically validated metagenomic next-generation sequencing (mNGS), followed by appropriate confirmation, in complex cases of encephalitis. In this patient, an extensive diagnostic workup was negative for infectious, inflammatory, demyelinating, autoimmune, and paraneoplastic etiologies. However, clinically validated mNGS of the CSF identified human pegivirus (HPgV) as a potential causative agent. A 5-day course of IV immunoglobulins (IVIg) led to the resolution of the opsoclonus-myoclonus. HPgV identification provided clinical and pathophysiologic insights: (1) a possible link between HPgV and CNS pathology, including brainstem neurotropism similar to other flaviviruses; (2) expansion of the opsoclonus-myoclonus differential to include HPgV; and (3) potential immune-mediated CNS involvement, suggested by the favorable response to IVIg. Although promising, broader mNGS use remains limited by biologic, technical, and logistic challenges.

BACKGROUND:Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, an absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥5 cells/µL), to inform timely diagnosis and management of encephalitis. METHODS:This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. RESULTS:Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis (37/59, 62.7%). Notably, the group without pleocytosis comprised similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; P > .05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had an absence of pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs 71.1% in patients with pleocytosis; P < .001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CONCLUSIONS:CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit an absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

AbstractObjectiveEncephalitis is a serious and potentially life‐threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.MethodsThis was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high‐level categories: behavior, psychosis, mood, sleep disturbances, and catatonia.ResultsIn our cohort of 642 patients, 318 (49.6%) had psychiatric symptoms at the time of initial presentation, including 78.2% with autoimmune etiologies and 35.2% with viral etiologies (P < 0.001). Those with psychiatric symptoms were younger (median age 47.5 vs. 51.5; P < 0.001), and more likely to have a history of documented psychiatric disorders, as well as longer lengths of hospital stay, and poorer discharge outcomes. Of patients initially admitted to a psychiatric service (n = 28), most had autoimmune causes, although 3 out of 28 (10.7%) had herpes viral infections; admission to a psychiatric service was associated with substantially longer interval to initiation of antivirals and immunotherapy. Autoimmune and infectious etiologies differed in the spectrum and frequency of psychiatric manifestations.InterpretationPsychiatric symptoms are common across etiologies of encephalitis and are associated with longer lengths of hospital stay and worse clinical outcomes. Specific patterns and dimensionality of psychiatric symptoms distinguish autoimmune from infectious causes.